Phase of the CELL CYCLE following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
The period of the CELL CYCLE preceding DNA REPLICATION in S PHASE. Subphases of G1 include "competence" (to respond to growth factors), G1a (entry into G1), G1b (progression), and G1c (assembly). Progression through the G1 subphases is effected by limiting growth factors, nutrients, or inhibitors.
The process by which a DNA molecule is duplicated.
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
The interval between two successive CELL DIVISIONS during which the CHROMOSOMES are not individually distinguishable. It is composed of the G phases (G1 PHASE; G0 PHASE; G2 PHASE) and S PHASE (when DNA replication occurs).
A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.
A key regulator of CELL CYCLE progression. It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21.
Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.
A 50-kDa protein that complexes with CYCLIN-DEPENDENT KINASE 2 in the late G1 phase of the cell cycle.
A large family of regulatory proteins that function as accessory subunits to a variety of CYCLIN-DEPENDENT KINASES. They generally function as ENZYME ACTIVATORS that drive the CELL CYCLE through transitions between phases. A subset of cyclins may also function as transcriptional regulators.
A cyclin subtype that has specificity for CDC2 PROTEIN KINASE and CYCLIN-DEPENDENT KINASE 2. It plays a role in progression of the CELL CYCLE through G1/S and G2/M phase transitions.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
A family of cell cycle-dependent kinases that are related in structure to CDC28 PROTEIN KINASE; S CEREVISIAE; and the CDC2 PROTEIN KINASE found in mammalian species.
The period of the CELL CYCLE following DNA synthesis (S PHASE) and preceding M PHASE (cell division phase). The CHROMOSOMES are tetraploid in this point.
A unique DNA sequence of a replicon at which DNA REPLICATION is initiated and proceeds bidirectionally or unidirectionally. It contains the sites where the first separation of the complementary strands occurs, a primer RNA is synthesized, and the switch from primer RNA to DNA synthesis takes place. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
A family of basic helix-loop-helix transcription factors that control expression of a variety of GENES involved in CELL CYCLE regulation. E2F transcription factors typically form heterodimeric complexes with TRANSCRIPTION FACTOR DP1 or transcription factor DP2, and they have N-terminal DNA binding and dimerization domains. E2F transcription factors can act as mediators of transcriptional repression or transcriptional activation.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
Product of the retinoblastoma tumor suppressor gene. It is a nuclear phosphoprotein hypothesized to normally act as an inhibitor of cell proliferation. Rb protein is absent in retinoblastoma cell lines. It also has been shown to form complexes with the adenovirus E1A protein, the SV40 T antigen, and the human papilloma virus E7 protein.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
An antiviral antibiotic produced by Cephalosporium aphidicola and other fungi. It inhibits the growth of eukaryotic cells and certain animal viruses by selectively inhibiting the cellular replication of DNA polymerase II or the viral-induced DNA polymerases. The drug may be useful for controlling excessive cell proliferation in patients with cancer, psoriasis or other dermatitis with little or no adverse effect upon non-multiplying cells.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
An E2F transcription factor that interacts directly with RETINOBLASTOMA PROTEIN and CYCLIN A and activates GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis. E2F1 is involved in DNA REPAIR and APOPTOSIS.
A nucleoside that substitutes for thymidine in DNA and thus acts as an antimetabolite. It causes breaks in chromosomes and has been proposed as an antiviral and antineoplastic agent. It has been given orphan drug status for use in the treatment of primary brain tumors.
A quiescent state of cells during G1 PHASE.
Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.
Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types.
Established cell cultures that have the potential to propagate indefinitely.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.
A transcription factor that possesses DNA-binding and E2F-binding domains but lacks a transcriptional activation domain. It is a binding partner for E2F TRANSCRIPTION FACTORS and enhances the DNA binding and transactivation function of the DP-E2F complex.
A ubiquitously expressed regulatory protein that contains a retinoblastoma protein binding domain and an AT-rich interactive domain. The protein may play a role in recruiting HISTONE DEACETYLASES to the site of RETINOBLASTOMA PROTEIN-containing transcriptional repressor complexes.
A cyclin subtype that is transported into the CELL NUCLEUS at the end of the G2 PHASE. It stimulates the G2/M phase transition by activating CDC2 PROTEIN KINASE.
A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.
The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Enzyme activated in response to DNA DAMAGE involved in cell cycle arrest. The gene is located on the long (q) arm of chromosome 22 at position 12.1. In humans it is encoded by the CHEK2 gene.
A genus of ascomycetous fungi of the family Schizosaccharomycetaceae, order Schizosaccharomycetales.
Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each.
A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.
Proteins obtained from the species Schizosaccharomyces pombe. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.
Genes that code for proteins that regulate the CELL DIVISION CYCLE. These genes form a regulatory network that culminates in the onset of MITOSIS by activating the p34cdc2 protein (PROTEIN P34CDC2).
Nucleoproteins, which in contrast to HISTONES, are acid insoluble. They are involved in chromosomal functions; e.g. they bind selectively to DNA, stimulate transcription resulting in tissue-specific RNA synthesis and undergo specific changes in response to various hormones or phytomitogens.
Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms.
Compounds that inhibit cell production of DNA or RNA.
A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3.
A group of cell cycle proteins that negatively regulate the activity of CYCLIN/CYCLIN-DEPENDENT KINASE complexes. They inhibit CELL CYCLE progression and help control CELL PROLIFERATION following GENOTOXIC STRESS as well as during CELL DIFFERENTIATION.
Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.
Geminin inhibits DNA replication by preventing the incorporation of MCM complex into pre-replication complex. It is absent during G1 phase of the CELL CYCLE and accumulates through S, G2,and M phases. It is degraded at the metaphase-anaphase transition by the ANAPHASE-PROMOTING COMPLEX-CYCLOSOME.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
3-Hydroxy-4-oxo-1(4H)-pyridinealanine. An antineoplastic alanine-substituted pyridine derivative isolated from Leucena glauca.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Deoxyribonucleic acid that makes up the genetic material of fungi.
A family of structurally-related proteins that were originally identified by their ability to complex with cyclin proteins (CYCLINS). They share a common domain that binds specifically to F-BOX MOTIFS. They take part in SKP CULLIN F-BOX PROTEIN LIGASES, where they can bind to a variety of F-BOX PROTEINS.
Cyclin-dependent kinase 4 is a key regulator of G1 PHASE of the CELL CYCLE. It partners with CYCLIN D to phosphorylate RETINOBLASTOMA PROTEIN. CDK4 activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P16.
The origin recognition complex is a multi-subunit DNA-binding protein that initiates DNA REPLICATION in eukaryotes.
Proteins found in any species of fungus.
A subclass of dual specificity phosphatases that play a role in the progression of the CELL CYCLE. They dephosphorylate and activate CYCLIN-DEPENDENT KINASES.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A minichromosome maintenance protein that is a key component of the six member MCM protein complex. It is also found in tightly-bound trimeric complex with MINICHROMOSOME MAINTENANCE COMPLEX COMPONENT 6 and MINICHROMOSOME MAINTENANCE COMPLEX COMPONENT 7.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
A minichromosome maintenance protein that is a key component of the six member MCM protein complex. It is also found in tightly-bound trimeric complex with MINICHROMOSOME MAINTENANCE COMPLEX COMPONENT 4 and MINICHROMOSOME MAINTENANCE COMPLEX COMPONENT 6.
The temporal order in which the DNA of the GENOME is replicated.
Elements of limited time intervals, contributing to particular results or situations.
A cell line derived from cultured tumor cells.
A group of PROTEIN-SERINE-THREONINE KINASES which activate critical signaling cascades in double strand breaks, APOPTOSIS, and GENOTOXIC STRESS such as ionizing ultraviolet A light, thereby acting as a DNA damage sensor. These proteins play a role in a wide range of signaling mechanisms in cell cycle control.
Either of the two longitudinally adjacent threads formed when a eukaryotic chromosome replicates prior to mitosis. The chromatids are held together at the centromere. Sister chromatids are derived from the same chromosome. (Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.
Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.
Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.
Structures within the nucleus of fungal cells consisting of or containing DNA, which carry genetic information essential to the cell.
A minichromosome maintenance protein that is a key component of the six member MCM protein complex. It contains a NUCLEAR LOCALIZATION SIGNAL, which provide targeting of the protein complex. In addition, acetylation of this protein may play a role in regulating of DNA replication and cell cycle progression.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
A minichromosome maintenance protein that is a key component of the six member MCM protein complex. It contains a NUCLEAR LOCALIZATION SIGNAL which may provide targeting of the protein complex and an extended N-terminus which is rich in SERINE residues.
Transport proteins that carry specific substances in the blood or across cell membranes.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
An E2F transcription factor that interacts directly with RETINOBLASTOMA PROTEIN and CYCLIN A. E2F2 activates GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis.
That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants.
An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.
Regulatory signaling systems that control the progression of the CELL CYCLE through the G1 PHASE and allow transition to S PHASE when the cells are ready to undergo DNA REPLICATION. DNA DAMAGE, or the deficiencies in specific cellular components or nutrients may cause the cells to halt before progressing through G1 phase.
A broadly expressed type D cyclin. Experiments using KNOCKOUT MICE suggest a role for cyclin D3 in LYMPHOCYTE development.
A cyclin D subtype which is regulated by GATA4 TRANSCRIPTION FACTOR. Experiments using KNOCKOUT MICE suggest a role for cyclin D2 in granulosa cell proliferation and gonadal development.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A widely-expressed cyclin A subtype that functions during the G1/S and G2/M transitions of the CELL CYCLE.
The rate dynamics in chemical or physical systems.
Complexes of enzymes that catalyze the covalent attachment of UBIQUITIN to other proteins by forming a peptide bond between the C-terminal GLYCINE of UBIQUITIN and the alpha-amino groups of LYSINE residues in the protein. The complexes play an important role in mediating the selective-degradation of short-lived and abnormal proteins. The complex of enzymes can be broken down into three components that involve activation of ubiquitin (UBIQUITIN-ACTIVATING ENZYMES), conjugation of ubiquitin to the ligase complex (UBIQUITIN-CONJUGATING ENZYMES), and ligation of ubiquitin to the substrate protein (UBIQUITIN-PROTEIN LIGASES).
Regulatory signaling systems that control the progression through the CELL CYCLE. They ensure that the cell has completed, in the correct order and without mistakes, all the processes required to replicate the GENOME and CYTOPLASM, and divide them equally between two daughter cells. If cells sense they have not completed these processes or that the environment does not have the nutrients and growth hormones in place to proceed, then the cells are restrained (or "arrested") until the processes are completed and growth conditions are suitable.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
An E3 ubiquitin ligase primarily involved in regulation of the metaphase-to-anaphase transition during MITOSIS through ubiquitination of specific CELL CYCLE PROTEINS. Enzyme activity is tightly regulated through subunits and cofactors, which modulate activation, inhibition, and substrate specificity. The anaphase-promoting complex, or APC-C, is also involved in tissue differentiation in the PLACENTA, CRYSTALLINE LENS, and SKELETAL MUSCLE, and in regulation of postmitotic NEURONAL PLASTICITY and excitability.
A cyclin subtype that is specific for CYCLIN-DEPENDENT KINASE 4 and CYCLIN-DEPENDENT KINASE 6. Unlike most cyclins, cyclin D expression is not cyclical, but rather it is expressed in response to proliferative signals. Cyclin D may therefore play a role in cellular responses to mitogenic signals.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
An alkylating agent in cancer therapy that may also act as a mutagen by interfering with and causing damage to DNA.
A family of proteins that share the F-BOX MOTIF and are involved in protein-protein interactions. They play an important role in process of protein ubiquition by associating with a variety of substrates and then associating into SCF UBIQUITIN LIGASE complexes. They are held in the ubiquitin-ligase complex via binding to SKP DOMAIN PROTEINS.
An E2F transcription factor that represses GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis. E2F4 recruits chromatin remodeling factors indirectly to target gene PROMOTER REGIONS through RETINOBLASTOMA LIKE PROTEIN P130 and RETINOBLASTOMA LIKE PROTEIN P107.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
A cyclin B subtype that colocalizes with MICROTUBULES during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.
DNA present in neoplastic tissue.
A family of structurally related proteins that were originally discovered for their role in cell-cycle regulation in CAENORHABDITIS ELEGANS. They play important roles in regulation of the CELL CYCLE and as components of UBIQUITIN-PROTEIN LIGASES.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
The portion of chromosome material that remains condensed and is transcriptionally inactive during INTERPHASE.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in fungi.
A DNA-dependent DNA polymerase characterized in E. coli and other lower organisms. It may be present in higher organisms and has an intrinsic molecular activity only 5% of that of DNA Polymerase I. This polymerase has 3'-5' exonuclease activity, is effective only on duplex DNA with gaps or single-strand ends of less than 100 nucleotides as template, and is inhibited by sulfhydryl reagents. EC
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
An E2F transcription factor that interacts directly with RETINOBLASTOMA PROTEIN and CYCLIN A. E2F3 regulates GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
A diverse class of enzymes that interact with UBIQUITIN-CONJUGATING ENZYMES and ubiquitination-specific protein substrates. Each member of this enzyme group has its own distinct specificity for a substrate and ubiquitin-conjugating enzyme. Ubiquitin-protein ligases exist as both monomeric proteins multiprotein complexes.
A family of proteins that were originally identified in SACCHAROMYCES CEREVISIAE as being essential for maintaining the structure of minichromosomes00. They form into a protein complex that has helicase activity and is involved in a variety of DNA-related functions including replication elongation, RNA transcription, chromatin remodeling, and genome stability.
Cyclin-dependent kinase 6 associates with CYCLIN D and phosphorylates RETINOBLASTOMA PROTEIN during G1 PHASE of the CELL CYCLE. It helps regulate the transition to S PHASE and its kinase activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P18.
The functional hereditary units of FUNGI.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Nocodazole is an antineoplastic agent which exerts its effect by depolymerizing microtubules.
The phase of cell nucleus division following METAPHASE, in which the CHROMATIDS separate and migrate to opposite poles of the spindle.
A single-stranded DNA-binding protein that is found in EUKARYOTIC CELLS. It is required for DNA REPLICATION; DNA REPAIR; and GENETIC RECOMBINATION.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
The clear constricted portion of the chromosome at which the chromatids are joined and by which the chromosome is attached to the spindle during cell division.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
Any DNA sequence capable of independent replication or a molecule that possesses a REPLICATION ORIGIN and which is therefore potentially capable of being replicated in a suitable cell. (Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
The degree of replication of the chromosome set in the karyotype.
A negative regulator of the CELL CYCLE that undergoes PHOSPHORYLATION by CYCLIN-DEPENDENT KINASES. It contains a conserved pocket region that binds E2F4 TRANSCRIPTION FACTOR and interacts with viral ONCOPROTEINS such as POLYOMAVIRUS TUMOR ANTIGENS; ADENOVIRUS E1A PROTEINS; and PAPILLOMAVIRUS E7 PROTEINS.
A continuous cell line of high contact-inhibition established from NIH Swiss mouse embryo cultures. The cells are useful for DNA transfection and transformation studies. (From ATCC [Internet]. Virginia: American Type Culture Collection; c2002 [cited 2002 Sept 26]. Available from
High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.
Cellular DNA-binding proteins encoded by the c-myc genes. They are normally involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Elevated and deregulated (constitutive) expression of c-myc proteins can cause tumorigenesis.

The yeast ser/thr phosphatases sit4 and ppz1 play opposite roles in regulation of the cell cycle. (1/4298)

Yeast cells overexpressing the Ser/Thr protein phosphatase Ppz1 display a slow-growth phenotype. These cells recover slowly from alpha-factor or nutrient depletion-induced G1 arrest, showing a considerable delay in bud emergence as well as in the expression of the G1 cyclins Cln2 and Clb5. Therefore, an excess of the Ppz1 phosphatase interferes with the normal transition from G1 to S phase. The growth defect is rescued by overexpression of the HAL3/SIS2 gene, encoding a negative regulator of Ppz1. High-copy-number expression of HAL3/SIS2 has been reported to improve cell growth and to increase expression of G1 cyclins in sit4 phosphatase mutants. We show here that the described effects of HAL3/SIS2 on sit4 mutants are fully mediated by the Ppz1 phosphatase. The growth defect caused by overexpression of PPZ1 is intensified in strains with low G1 cyclin levels (such as bck2Delta or cln3Delta mutants), whereas mutation of PPZ1 rescues the synthetic lethal phenotype of sit4 cln3 mutants. These results reveal a role for Ppz1 as a regulatory component of the yeast cell cycle, reinforce the notion that Hal3/Sis2 serves as a negative modulator of the biological functions of Ppz1, and indicate that the Sit4 and Ppz1 Ser/Thr phosphatases play opposite roles in control of the G1/S transition.  (+info)

p27 is involved in N-cadherin-mediated contact inhibition of cell growth and S-phase entry. (2/4298)

In this study the direct involvement of cadherins in adhesion-mediated growth inhibition was investigated. It is shown here that overexpression of N-cadherin in CHO cells significantly suppresses their growth rate. Interaction of these cells and two additional fibroblastic lines with synthetic beads coated with N-cadherin ligands (recombinant N-cadherin ectodomain or specific antibodies) leads to growth arrest at the G1 phase of the cell cycle. The cadherin-reactive beads inhibit the entry into S phase and the reduction in the levels of cyclin-dependent kinase (cdk) inhibitors p21 and p27, following serum-stimulation of starved cells. In exponentially growing cells these beads induce G1 arrest accompanied by elevation in p27 only. We propose that cadherin-mediated signaling is involved in contact inhibition of growth by inducing cell cycle arrest at the G1 phase and elevation of p27 levels.  (+info)

Leukemia translocation protein PLZF inhibits cell growth and expression of cyclin A. (3/4298)

The PLZF gene was identified by its fusion with the RARalpha locus in a therapy resistant form of acute promyelocytic leukemia (APL) associated with the t(11;17)(q23;q21) translocation. Here we describe PLZF as a negative regulator of cell cycle progression ultimately leading to growth suppression. PLZF can bind and repress the cyclin A2 promoter while expression of cyclin A2 reverts the growth suppressed phenotype of myeloid cells expressing PLZF. In contrast RARalpha-PLZF, a fusion protein generated in t(11;17)(q23;q21)-APL activates cyclin A2 transcription and allows expression of cyclin A in anchorage-deprived NIH3T3 cells. Therefore, cyclin A2 is a candidate target gene for PLZF and inhibition of cyclin A expression may contribute to the growth suppressive properties of PLZF. Deregulation of cyclin A2 by RARalpha-PLZF may represent an oncogenic mechanism of this chimeric protein and contribute to the aggressive clinical phenotype of t(11;17)(q23;q21)-associated APL.  (+info)

Interleukin-6 dependent induction of the cyclin dependent kinase inhibitor p21WAF1/CIP1 is lost during progression of human malignant melanoma. (4/4298)

Human melanoma cell lines derived from early stage primary tumors are particularly sensitive to growth arrest induced by interleukin-6 (IL-6). This response is lost in cell lines derived from advanced lesions, a phenomenon which may contribute to tumor aggressiveness. We sought to determine whether resistance to growth inhibition by IL-6 can be explained by oncogenic alterations in cell cycle regulators or relevant components of intracellular signaling. Our results show that IL-6 treatment of early stage melanoma cell lines caused G1 arrest, which could not be explained by changes in levels of G1 cyclins (D1, E), cdks (cdk4, cdk2) or by loss of cyclin/cdk complex formation. Instead, IL-6 caused a marked induction of the cdk inhibitor p21WAF1/CIP1 in three different IL-6 sensitive cell lines, two of which also showed a marked accumulation of the cdk inhibitor p27Kip1. In contrast, IL-6 failed to induce p21WAF1/CIP1 transcript and did not increase p21WAF1/CIP1 or p27kip1 proteins in any of the resistant lines. In fact, of five IL-6 resistant cell lines, only two expressed detectable levels of p21WAF1/CIP1 mRNA and protein, while in three other lines, p21WAF1/CIP1 was undetectable. IL-6 dependent upregulation of p21WAF1/CIP1 was associated with binding of both STAT3 and STAT1 to the p21WAF1/CIP1 promoter. Surprisingly, however, IL-6 stimulated STAT binding to this promoter in both sensitive and resistant cell lines (with one exception), suggesting that gross deregulation of this event is not the unifying cause of the defect in p21WAF1/CIP1 induction in IL-6 resistant cells. In somatic cell hybrids of IL-6 sensitive and resistant cell lines, the resistant phenotype was dominant and IL-6 failed to induce p21WAF1/CIP1. Thus, our results suggest that in early stage human melanoma cells, IL-6 induced growth inhibition involves induction of p21WAF1/CIP1 which is lost in the course of tumor progression presumably as a result of a dominant oncogenic event.  (+info)

Caffeine can override the S-M checkpoint in fission yeast. (5/4298)

The replication checkpoint (or 'S-M checkpoint') control prevents progression into mitosis when DNA replication is incomplete. Caffeine has been known for some time to have the capacity to override the S-M checkpoint in animal cells. We show here that caffeine also disrupts the S-M checkpoint in the fission yeast Schizosaccharomyces pombe. By contrast, no comparable effects of caffeine on the S. pombe DNA damage checkpoint were seen. S. pombe cells arrested in early S phase and then exposed to caffeine lost viability rapidly as they attempted to enter mitosis, which was accompanied by tyrosine dephosphorylation of Cdc2. Despite this, the caffeine-induced loss of viability was not blocked in a temperature-sensitive cdc2 mutant incubated at the restrictive temperature, although catastrophic mitosis was prevented under these conditions. This suggests that, in addition to S-M checkpoint control, a caffeine-sensitive function may be important for maintenance of cell viability during S phase arrest. The lethality of a combination of caffeine with the DNA replication inhibitor hydroxyurea was suppressed by overexpression of Cds1 or Chk1, protein kinases previously implicated in S-M checkpoint control and recovery from S phase arrest. In addition, the same combination of drugs was specifically tolerated in cells overexpressing either of two novel S. pombe genes isolated in a cDNA library screen. These findings should allow further molecular investigation of the regulation of S phase arrest, and may provide a useful system with which to identify novel drugs that specifically abrogate the checkpoint control.  (+info)

Regulation of the start of DNA replication in Schizosaccharomyces pombe. (6/4298)

Cells of Schizosaccharomyces pombe were grown in minimal medium with different nitrogen sources under steady-state conditions, with doubling times ranging from 2.5 to 14 hours. Flow cytometry and fluorescence microscopy confirmed earlier findings that at rapid growth rates, the G1 phase was short and cell separation occurred at the end of S phase. For some nitrogen sources, the growth rate was greatly decreased, the G1 phase occupied 30-50% of the cell cycle, and cell separation occurred in early G1. In contrast, other nitrogen sources supported low growth rates without any significant increase in G1 duration. The method described allows manipulation of the length of G1 and the relative cell cycle position of S phase in wild-type cells. Cell mass was measured by flow cytometry as scattered light and as protein-associated fluorescence. The extensions of G1 were not related to cell mass at entry into S phase. Our data do not support the hypothesis that the cells must reach a certain fixed, critical mass before entry into S. We suggest that cell mass at the G1/S transition point is variable and determined by a set of molecular parameters. In the present experiments, these parameters were influenced by the different nitrogen sources in a way that was independent of the actual growth rate.  (+info)

Immunologic proliferation marker Ki-S2 as prognostic indicator for lymph node-negative breast cancer. (7/4298)

BACKGROUND: Proper treatment of lymph node-negative breast cancer depends on an accurate prognosis. To improve prognostic models for this disease, we evaluated whether an immunohistochemical marker for proliferating cells, Ki-S2 (a monoclonal antibody that binds to a 100-kd nuclear protein expressed in S, G2, and M phases of the cell cycle), is an accurate indicator of prognosis. METHODS: We studied 371 Swedish women with lymph node-negative breast cancer; the median follow-up time was 95 months. The fraction of tumor cells in S phase was assessed by flow cytometry, and tumor cell proliferation was measured immunohistochemically with the monoclonal antibodies Ki-S2 and Ki-S5 (directed against the nuclear antigen Ki-67). A combined prognostic index was calculated on the basis of the S-phase fraction, progesterone receptor content, and tumor size. RESULTS: In multivariate analyses that did or did not (263 and 332 observations, respectively) include the S-phase fraction and the combined prognostic index, the Ki-S2 labeling index (percentage of antibody-stained tumor cell nuclei) emerged as the most statistically significant predictor of overall survival, disease-specific survival, and disease-free survival (all two-sided P<.0001). In the risk group defined by a Ki-S2 labeling index of 10% or less, life expectancy was not statistically significantly different from that of age-matched women without breast cancer, whereas the group with a high Ki-S2 labeling index had an increased risk of mortality of up to 20-fold. CONCLUSIONS: Cellular proliferation is a major determinant of the biologic behavior of breast cancer. Prognosis is apparently best indicated by the percentage of cells in S through M phases of the cell cycle. Measurement of the Ki-S2 labeling index of a tumor sample may improve a clinician's ability to make an accurate prognosis and to identify patients with a low risk of recurrence who may not need adjuvant therapy.  (+info)

Fus3p and Kss1p control G1 arrest in Saccharomyces cerevisiae through a balance of distinct arrest and proliferative functions that operate in parallel with Far1p. (8/4298)

In Saccharomyces cerevisiae, mating pheromones activate two MAP kinases (MAPKs), Fus3p and Kss1p, to induce G1 arrest prior to mating. Fus3p is known to promote G1 arrest by activating Far1p, which inhibits three Clnp/Cdc28p kinases. To analyze the contribution of Fus3p and Kss1p to G1 arrest that is independent of Far1p, we constructed far1 CLN strains that undergo G1 arrest from increased activation of the mating MAP kinase pathway. We find that Fus3p and Kss1p both control G1 arrest through multiple functions that operate in parallel with Far1p. Fus3p and Kss1p together promote G1 arrest by repressing transcription of G1/S cyclin genes (CLN1, CLN2, CLB5) by a mechanism that blocks their activation by Cln3p/Cdc28p kinase. In addition, Fus3p and Kss1p counteract G1 arrest through overlapping and distinct functions. Fus3p and Kss1p together increase the expression of CLN3 and PCL2 genes that promote budding, and Kss1p inhibits the MAP kinase cascade. Strikingly, Fus3p promotes proliferation by a novel function that is not linked to reduced Ste12p activity or increased levels of Cln2p/Cdc28p kinase. Genetic analysis suggests that Fus3p promotes proliferation through activation of Mcm1p transcription factor that upregulates numerous genes in G1 phase. Thus, Fus3p and Kss1p control G1 arrest through a balance of arrest functions that inhibit the Cdc28p machinery and proliferative functions that bypass this inhibition.  (+info)

TY - JOUR. T1 - Suppression of replication fork progression in low-dose-specific p53-dependent S-phase DNA damage checkpoint. AU - Shimura, T.. AU - Toyoshima, M.. AU - Adiga, S. K.. AU - Kunoh, T.. AU - Nagai, H.. AU - Shimizu, N.. AU - Inoue, M.. AU - Niwa, O.. PY - 2006/9/28. Y1 - 2006/9/28. N2 - The S-phase DNA damage checkpoint is activated by DNA damage to delay DNA synthesis allowing time to resolve the replication block. We previously discovered the p53-dependent S-phase DNA damage checkpoint in mouse zygotes fertilized with irradiated sperm. Here, we report that the same p53 dependency holds in mouse embryonic fibroblasts (MEFs) at low doses of irradiation. DNA synthesis in p53 wild-type (WT) MEFs was suppressed in a biphasic manner in which a sharp decrease below 2.5 Gy was followed by a more moderate decrease up to 10 Gy. In contrast, p53-/- MEFs exhibited radioresistant DNA synthesis below 2.5 Gy whereas the cells retained the moderate suppression above 5 Gy. DNA fiber analysis ...
The Mre11-Rad50-Nbs1 (MRN) complex has many biological functions: processing of double-strand breaks in meiosis, homologous recombination, telomere maintenance, S-phase checkpoint, and genome stability during replication. In the S-phase DNA damage checkpoint, MRN acts both in activation of checkpoint signaling and downstream of the checkpoint kinases to slow DNA replication. Mechanistically, MRN, along with its cofactor Ctp1, is involved in 5 resection to create single-stranded DNA that is required for both signaling and homologous recombination. However, it is unclear whether resection is essential for all of the cellular functions of MRN. To dissect the various roles of MRN, we performed a structure-function analysis of nuclease dead alleles and potential separation-of-function alleles analogous to those found in the human disease ataxia telangiectasia-like disorder, which is caused by mutations in Mre11. We find that several alleles of rad32 (the fission yeast homologue of mre11), along with
Cells were treated with either UVA or TMP/UVA. a Sequential IP demonstrates association of early-replicating Alu sequences with DONSON and late-replicating Satellite 3 sequences with FANCM. LINE-1 elements replicate throughout the S phase and are found in all fractions. Representative blot (n = 3). b DONSON interaction with the H3K4me3 euchromatin mark is more frequent in early S phase cells than in late S phase, while there is little interaction with the H3K9me3 heterochromatin mark in either stage. Sorted early and late S phase cells were examined by PLA. Scored nuclei: PLA between GFP-D: H3K4me3 of early S phase = 67, late S phase = 64, PLA between GFP-D: H3K9me3 of early S phase = 70, late S phase = 85, from three biological replicates. Data are mean ± s.e.m. c FANCM interaction with H3K9me3 heterochromatin mark is biased toward late S phase, while there is low interaction frequency with H3K4me3 in either stage. Scored nuclei: PLA between FANCM: H3K4me3 of early S phase = 64, late S phase = ...
CDC25A plays a role in the unperturbed cell cycle (Ben-Yehoyada et al., 2007); to address the concern that the CDC25A siRNA was slowing down replication, which would affect the result, we pulsed cells with BrdU after 48 h of CDC25A siRNA transfection and chased the cells for 8 h. Flow cytometric analysis revealed that the progression through S phase at these time points was largely unaffected by the lower cellular concentration of CDC25A (Fig. S3 E). Thus, repression of DNA damage after CDC25A depletion is not caused by markedly slowed progression through S phase or G1-phase arrest.. Finally, we asked whether CDC25A accumulation could be an important determinant of the proliferative capability of cells depleted for CHK1 because coknockdown of CDC25A with CHK1 abolished the majority of DNA damage. Importantly, TIG-3-tert cells depleted for CHK1 proliferated very poorly, whereas this phenotype was partly rescued by codepletion of CDC25A. In fact, cells depleted for both CDC25A and CHK1 ...
BioAssay record AID 609847 submitted by ChEMBL: Cell cycle arrest in human HeLaS3 cells assessed as accumulation at S phase at 150 uM after 48 hrs using propidium iodide staining by flow cytometry (Rvb = 19.62%).
PR-Set7/SET8 is a histone H4-lysine 20 methyltransferase required for normal cell proliferation. However, the exact functions of this enzyme remain to be determined. In this study, we show that human PR-Set7 functions during S phase to regulate cellular proliferation. PR-Set7 associates with replication foci and maintains the bulk of H4-K20 mono- and trimethylation. Consistent with a function in chromosome dynamics during S phase, inhibition of PR-Set7 methyltransferase activity by small hairpin RNA causes a replicative stress characterized by alterations in replication fork velocity and origin firing. This stress is accompanied by massive induction of DNA strand breaks followed by a robust DNA damage response. The DNA damage response includes the activation of ataxia telangiectasia mutated and ataxia telangiectasia related kinase-mediated pathways, which, in turn, leads to p53-mediated growth arrest to avoid aberrant chromosome behavior after improper DNA replication. Collectively, these data ...
To achieve faithful replication of the genome once in each cell cycle, reinitiation of S phase is prevented in G(2) and origins are restricted from refiring within S phase. We have investigated the block to rereplication during G(2) in fission yeast. The DNA synthesis that occurs when G(2)/M cyclin-dependent kinase (CDK) activity is depleted has been assumed to be repeated rounds of S phase without mitosis, but this has not been demonstrated to be the case. We show here that on G(2)/M CDK depletion in G(2), repeated S phases are induced, which are correlated with normal G(1)/S transcription and attainment of doublings in cell size. Mostly normal mitotic S-phase origins are utilized, although at different efficiencies, and replication is essentially equal across the genome. We conclude that CDK inhibits reinitiation of S phase during G(2), and if G(2)/M CDK is depleted, replication results from induction of a largely normal S-phase program with only small differences in origin usage and efficiency ...
In Saccharomyces cerevisiae, a single cyclin-dependent kinase, Cdc28, regulates both G1/S and G2/M phase transitions by associating with stage-specific cyclins. During progression through S phase and G2/M, Cdc28 is activated by the B-type cyclins Clb1-6. Because of functional redundancy, specific roles for individual Clbs have been difficult to assign. To help genetically define such roles, strains carrying a cdc28(ts) allele, combined with single CLB deletions were studied. It is assumed that by limiting the activity of the kinase, these strains would be rendered more sensitive to loss of individual Clbs. By this approach, a novel phenotype associated with CLB5 mutation was observed. Homozygous cdc28-4(ts) clb5 diploids are not viable at room temperature. Cells are defective in spindle positioning, leading to migration of undivided nuclei into the bud. Occasionally, misplaced spindles are observed in cdc28-4 clb5 haploids; additional deletion of CLB6 causes full penetrance. Thus, CLB5 brings ...
numerous post-translational modifications lead to stabil- In contrast to the key role of p53 in maintenance of the isation of the p53 protein and activation of its DNA-induced G1 arrest, no specific roles for p53 or p21 sequence-specific DNA binding [9,30]. Only then can p53 have been implicated in the control of the intra-S-phase efficiently stimulate transcription of cell-cycle inhibitors checkpoint. This is perhaps not so surprising as the such as p21 (Figure 2). Furthermore, the p21 protein has to S-phase checkpoint, manifested by a decreased rate of accumulate to levels sufficiently high to inhibit the CDK- DNA synthesis after generation of DSBs, is by definition a containing complexes, before cell-cycle progression transient phenomenon [5]. The absence of the mainte- becomes efficiently blocked. Although p53 has recently nance component during S phase, contrary to the G1 and been described binding to 5′ untranslated region of CDK4 G2 checkpoints, might be beneficial for the cells by ...
ABSTRACTAims:Breast cancer is the major diagnosed cancer and the leading reason of cancer related death among women, and the tumor size is one of the risk factors. Therefore, it is significant to reveal the principle of breaking the subtle homeostasis of cell cycle and sustaining chronic proliferati
Duplication of a cells genetic material is of paramount importance. This task must be completed accurately, efficiently and occur once and only once within any given cell cycle. Origin firing, which occurs according to a temporal program, results in the establishment of bidirectional replication forks. As replication forks traverse the chromosomal landscape, their stability is threatened by endogenous obstacles such as heavily transcribed tRNAs, protein-DNA complexes and replication slow zones. In addition, fork stability can also be threatened by genotoxic agents. During S phase, in response to genotoxin-induced stress, the cell activates the intra-S phase checkpoint. The intra-S phase checkpoint is comprised of three major groups of proteins: sensors, adaptors and effectors. Sensor proteins detect problems at the replication fork and elicit a phosphorylation cascade that is mediated by adaptor proteins and results in the activation of effector kinases. Together, these proteins act to ...
Faithful duplication and segregation of undamaged DNA is critical to the survival of all organisms and prevention of oncogenesis in multicellular organisms. To ensure inheritance of intact DNA, cells rely on checkpoints. Checkpoints alter cellular processes in the presence of DNA damage preventing cell cycle transitions until replication is completed or DNA damage is repaired. Several checkpoints are specific to S-phase. The S-M replication checkpoint prevents mitosis in the presence of unreplicated DNA. Rather than outright halting replication, the S-phase DNA damage checkpoint slows replication in response to DNA damage. This checkpoint utilizes two general mechanisms to slow replication. First, this checkpoint prevents origin firing thus limiting the number of replication forks traversing the genome in the presence of damaged DNA. Second, this checkpoint slows the progression of the replication forks. Inhibition of origin firing in response to DNA damage is well established, however when this thesis
To maintain genome stability, DNA replication occurs only once in each cell cycle. This is achieved by the cell cycle-dependent licensing control that permits assembly of prereplication complexes (pre-RCs) at replication origins only once per cell cycle (Mendez and Stillman, 2003; Diffley, 2004; Nishitani and Lygerou, 2004; Blow and Dutta, 2005; Arias and Walter, 2007). On exit from metaphase, the minichromosome maintenance (MCM) 2-7 complex is recruited to replication origins to establish pre-RCs. Once replication is activated by the Cdks and Cdc7/Dbf4 kinase, pre-RCs are disassembled and the reassociation of MCM proteins with origins is not permitted until the completion of mitosis.. Regulation of Cdt1 activity during the cell cycle is critical for the prevention of reassembly of pre-RCs within a single cell cycle (Blow and Dutta, 2005; Arias and Walter, 2007). When cells enter S phase, Cdt1 is ubiquitinated and degraded (Nishitani et al., 2001; Li et al., 2003; Zhong et al., 2003; Arias and ...
Mechanisms for the initiation signal that delays the MI division.We address three possible mechanisms for the earlier start of the MI division in initiation mutants. The first hypothesis is that WT cells have a longer S phase because of the presence of recombination initiation proteins and that this results in a normal delay of the MI division. Cha et al. (4) showed that premeiotic S phase is shorter in spo11 mutants than in WT cells (4). This is consistent with the view that the shorter S phase results in the earlier timing of the MI division observed in spo11 mutants. The same authors, however, also showed that rec102 mutants had normal timing of premeiotic S phase (4). This is something of a paradox, since rec102 mutants clearly begin the MI division earlier than WT cells. We observe no significant differences in the timing of S phase (measured in three different ways) between WT cells and rec102, rec104, rec114, and spo11 mutants (Table 1). We note that the exact time at which 50% of cells ...
In the absence of Rif1, this mid‐S‐phase architecture is not formed, allowing Cdc7 kinase to gain access in early‐S‐phase to the origins that would normally not be activated until mid‐S‐phase. This would explain the increased Cdc7‐dependent phosphorylation of the target proteins and hyper‐loading of Cdc45 and PCNA onto chromatin in Rif1‐depleted cells at early‐S‐phase (Figure 1). As a result of loss of mid‐S replication domains, replication timing domain structures may undergo genome‐wide alteration. It should be noted that replication timing is generally more centred to mid‐S in the absence of Rif1, although mid‐S replication foci pattern is lost and all the replication foci appear to adopt the early‐S‐like pattern (Supplementary Figure S9). This effect of Rif1 on replication timing is similar to what we observed in fission yeast rif1Δ mutant, where some early‐firing origins are delayed and late‐firing/dormant origins are fired earlier (Hayano et al, ...
Clinical experience has shown that mammary carcinomas can be classified according to their type of progression into slow-growing and fast-growing ones, where the terms
A stochastic model for interpreting BrdUrd DNA FCM-derived data is proposed. The model is based on branching processes and describes the progression of the DNA distribution of BrdUrd-labelled cells through the cell cycle. With the main focus on estimating the S phase duration and its variation, the DNA replication rate is modelled by a piecewise linear function, while assuming a gamma distribution for the S phase duration. Estimation of model parameters was carried out using maximum likelihood for data from two different cell lines. The results provided quite a good fit to the data, suggesting that stochastic models may be a valuable tool for analysing this kind of data.
Cyclin-dependent Kinase Inhibitor (CKI); Inhibitor Of Cdc28-Clb Kinase Complexes That Controls G1/S Phase Transition, Preventing Premature S Phase And Ensuring Genomic Integrity; Phosphorylated By Clb5/6-Cdk1 And Cln1/2-Cdk1 Kinase Which Regulate Timing Of Sic1p Degradation; Phosphorylation Targets Sic1p For SCF(CDC4)-dependent Turnover; Functional Homolog Of Mammalian Kip1
The precise replication of the genome and the continuous surveillance of its integrity are essential for survival and the avoidance of various diseases. Cells respond to DNA damage by activating a complex network of the so-called checkpoint pathways to delay their cell-cycle progression and repair t …
In this study we show that CPS and nordihydrocapsiate (CPT) inhibit early and late events in T cell activation, including CD69, CD25 and ICAM-1 cell surface expression, progression to the S phase of the cell cycle and proliferation in response to TCR and CD28 co-engagement ...
TY - JOUR. T1 - p107 inhibits G1 to S phase progression by down-regulating expression of the F-box protein Skp2. AU - Rodier, Geneviève. AU - Makris, Constantin. AU - Coulombe, Philippe. AU - Scime, Anthony. AU - Nakayama, Keiko. AU - Nakayama, Keiichi I.. AU - Meloche, Sylvain. PY - 2005/1/3. Y1 - 2005/1/3. N2 - Cell cycle progression is negatively regulated by the pocket proteins pRb, p107, and p130. However, the mechanisms responsible for this inhibition are not fully understood. Here, we show that overexpression of p107 in fibroblasts inhibits Cdk2 activation and delays S phase entry. The inhibition of Cdk2 activity is correlated with the accumulation of p27, consequent to a decreased degradation of the protein, with no change of Thr187 phosphorylation. Instead, we observed a marked decrease in the abundance of the F-box receptor Skp2 in p107-overexpressing cells. Reciprocally, Skp2 accumulates to higher levels in p107-/- embryonic fibroblasts. Ectopic expression of Skp2 restores p27 ...
Cells divide with remarkable fidelity, allowing complex organisms to develop and possess longevity. Checkpoint controls contribute by ensuring that genome duplication and segregation occur without error so that genomic instability, associated with developmental abnormalities and a hallmark of most human cancers, is avoided. S-phase checkpoints prevent cell division while DNA is replicating. Budding yeast Mec1p and Rad53p, homologues of human checkpoint kinases ATM/ATR and Chk2, are needed for this control system. How Mec1p and Rad53p prevent mitosis in S phase is not known. Here we provide evidence that budding yeasts avoid mitosis during S phase by regulating the anaphase-promoting complex (APC) specificity factor Cdc20p: Mec1p and Rad53p repress the accumulation of Cdc20p in S phase. Because precocious Cdc20p accumulation causes anaphase onset and aneuploidy, Cdc20p concentrations must be precisely regulated during each and every cell cycle. Catastrophic mitosis induced by Cdc20p in S phase ...
1. Kotsantis P, Petermann E, Boulton SJ. Mechanisms of Oncogene-Induced Replication Stress: Jigsaw Falling into Place. Cancer Discov. 2018;8(5):537-55. doi: 10.1158/2159-8290.CD-17-1461 29653955. 2. Gaillard H, García-Muse T, Aguilera A. Replication stress and cancer. Nat Rev Cancer. 2015;15(5):276-89. doi: 10.1038/nrc3916 25907220. 3. Heller R, C., Kang S, Lam W, M., Chen S, Chan C, S., Bell S, P. Eukaryotic origin-dependent DNA replication in vitro reveals sequential action of DDK and S-CDK kinases. Cell. 2011;146(1):80-91. doi: 10.1016/j.cell.2011.06.012 21729781. 4. Sheu YJ, Stillman B. Cdc7-Dbf4 phosphorylates MCM proteins via a docking site-mediated mechanism to promote S phase progression. Mol Cell. 2006;24(1):101-13. doi: 10.1016/j.molcel.2006.07.033 17018296. 5. Tanaka S, Nakato R, Katou Y, Shirahige K, Araki H. Origin association of Sld3, Sld7, and Cdc45 proteins is a key step for determination of origin-firing timing. Curr Biol. 2011;21(24):2055-63. doi: 10.1016/j.cub.2011.11.038 ...
Molecular cloning and characterisation of a human nuclear protein designated BM28 is reported. On the amino acid level this 892 amino acid protein, migrating on SDS-gels as a 125 kDa polypeptide, shares areas of significant similarity with a recently defined family of early S phase proteins. The members of this family, the Saccharomyces cerevisiae Mcm2p, Mcm3p, Cdc46p/Mcm5p, the Schizosaccharomyces pombe Cdc21p and the mouse protein P1 are considered to be involved in the onset of DNA replication. The highest similarity was found with Mcm2p (42% identity over the whole length and higher than 75% over a conservative region of 215 amino acid residues), suggesting that BM28 could represent the human homologue of the S. cerevisiae MCM2. Using antibodies raised against the recombinant BM28 the corresponding antigen was found to be localised in the nuclei of various mammalian cells. Microinjection of anti-BM28 antibody into synchronised mouse NIH3T3 or human HeLa cells presents evidence for the ...
TY - JOUR. T1 - SU9516, a cyclin-dependent kinase 2 inhibitor, promotes accumulation of high molecular weight E2F complexes in human colon carcinoma cells. AU - Yu, Bo. AU - Lane, Maureen E.. AU - Wadler, Scott. PY - 2002/10/1. Y1 - 2002/10/1. N2 - The E2F family plays a critical role in the expression of genes required for entry into and progression through S phase. E2F-mediated transcription is repressed by the tumor suppressor retinoblastoma protein (pRb), which results in sequestration of E2F in a multiprotein complex that includes pRb. Derepression of E2F results from a series of complex phosphorylation events mediated by cyclin D/cdk4 and cyclin E/cdk2. We have employed a novel 3-substituted indolinone compound, 3-[1-(3H-imidazol-4-yl)-meth-(Z)-ylidene]-5-methoxy-1,3-dihydro-indol-2-one (SU9516), which selectively inhibits cdk2 activity (Lane et al., Cancer Res 2001;61:6170-7) to investigate these events. Electrophoretic mobility gel shift assays were performed on SU9516-treated and ...
Progression through S phase of the eukaryotic cell cycle is regulated by the action of the cyclin dependent protein kinase 2 (CDK2) in association with cyclin A. CDK2/cyclin A phosphorylates numerous substrates. Substrate specificity often employs a dual recognition strategy in which the sequence flanking the phospho-acceptor site (Ser.Pro.X.Arg/Lys) is recognized by CDK2, while the cyclin A component of the complex contains a hydrophobic site that binds Arg/Lys.X.Leu (RXL or KXL) substrate recruitment motifs. To determine additional sequence specificity motifs around the RXL sequence, we have performed X-ray crystallographic studies at 2.3 A resolution and isothermal calorimetry measurements on complexes of phospho-CDK2/cyclin A with a recruitment peptide derived from E2F1 and with shorter 11-mer peptides from p53, pRb, p27, E2F1, and p107. The results show that the cyclin recruitment site accommodates a second hydrophobic residue either immediately C-terminal or next adjacent to the ...
Progression through S phase of the eukaryotic cell cycle is regulated by the action of the cyclin dependent protein kinase 2 (CDK2) in association with cyclin A. CDK2/cyclin A phosphorylates numerous substrates. Substrate specificity often employs a dual recognition strategy in which the sequence flanking the phospho-acceptor site (Ser.Pro.X.Arg/Lys) is recognized by CDK2, while the cyclin A component of the complex contains a hydrophobic site that binds Arg/Lys.X.Leu (RXL or KXL) substrate recruitment motifs. To determine additional sequence specificity motifs around the RXL sequence, we have performed X-ray crystallographic studies at 2.3 A resolution and isothermal calorimetry measurements on complexes of phospho-CDK2/cyclin A with a recruitment peptide derived from E2F1 and with shorter 11-mer peptides from p53, pRb, p27, E2F1, and p107. The results show that the cyclin recruitment site accommodates a second hydrophobic residue either immediately C-terminal or next adjacent to the ...
Muktadir S. Hossain completed his Ph.D. at the University of Tokyo, Japan in 2004 where he showed that quiescent (G0) phase cells of multicellular eukaryotes like mammals and insects require DNA topoisomeras II enzyme for the re-entry into the cell cycle, whereas the unicellular eukaryotes like yeast do not. The title of his Ph.D. dissertation is Requirement for DNA topoisomerase II during the G0-to-S phase transition in mammalian and insect cells. In the University of Tokyo as a Ph.D. student, he participated in the isolation of temperature-sensitive mutants of the pathogenic bacterium, Staphylococcus aureus. In the University of Tokyo as a Ph.D. student, he also showed that the DNA double-strand break-inducing drugs that are used to treat cancner can induce myogenic differentiation in cultured cells of the fruit fly, Drosophila melanogaster. In the University of Tokyo as a Research Assistant, he established the larvae of the silk moth, Bombyx mori as animal model to study purified toxins ...
Traversing the cell-division cycle may require more than a single exposure to growth factor. Jones and Kazlauskas suggest that the G0 to S interval may be divided into two phases, each requiring stimulation of distinct signaling events by growth factor. Serum-arrested fibroblast cells could be driven into S phase either by continuous long exposure to platelet-derived growth factor (PDGF) or by two shorter pulses of PDGF at distinct times. The first segment of the G1 phase required activation of the Erk pathway and c-Myc; the latter part of G1 required phosphatidylinositol-3-kinase activity. An analysis of growth factors that stimulate either receptor tyrosine kinases or G protein-coupled receptors revealed that exposure to different combinations of these agents in the first and second phases of the interval could also promote progression to S phase. The authors propose that the earlier biochemical events may cause accumulation of proteins that are required by the later signaling events to ...
The p53 oncosuppressor protein is a critical mediator of the response to injury in mammalian cells and is mutationally inactivated in the majority of lung malignancies. In this analysis, the effects of p53-deficiency were investigated in short-term primary cultures of murine bronchiolar Clara cells. Clara cells, isolated from gene-targeted p53-deficient mice, were compared to cells derived from wild type littermates. p53 null cultures displayed abnormal morphology; specifically, a high incidence of multinucleation, which increased with time in culture. Multinucleated cells were proficient in S phase DNA synthesis, as determined by BrdU incorporation. However, multinucleation did not reflect altered rates of S phase synthesis, which were similar between wild type and p53-/- cultures. Nucleation defects in p53-/- Clara cells associated with increased centrosome number, as determined by confocal microscopy of pericentrin-stained cultures, and may highlight a novel role of p53 in preserving genomic
Synchronized VSMCs were obtained by the method of double-thymidine block,colchicine treatment and serum starvation . Synchronized growth was monitored by flow cytometry. All the synchronized VSMCs distribution ration were 89.22% (±3.54%) at G0 phase, (66.74±7.16%) at G1/S phase, (63.24±4.06)% at S phase and (51.64±11.18)% at G2/M phase. The expression of ORC1 mRNA and CyclinA in a quiescent stage of VSMC was not significantly found, After synchronized, peaked(50.4%) at G2/M of CyclinA, and decreased(1.03%) at G2/M of ORC1, CyclinA in preventing the ORC1 from bind during G2/Mphase. The expression of ORC1 protein and CyclinA had a same change as ORC1 mRNA and CyclinA in different cell cycles of VSMC by flow cytometry (P,0.001). ...
Fingerprint Dive into the research topics of Staphylococcus aureus gyrase-quinolone-DNA ternary complexes fail to arrest replication fork progression in vitro: Effects of salt on the DNA binding mode and the catalytic activity of S. aureus gyrase. Together they form a unique fingerprint. ...
Chromosome replication is a key event in the eukaryotic cell division cycle. During S phase the entire genome must be faithfully duplicated with the minimum of errors. The many thousands of replication forks involved in this process must be co-ordinated to ensure that despite the very large quantities of DNA involved, no section of DNA is left unreplicated and no section of DNA is replicated more than once. Cells achieve this by having a distinct stage that occurs prior to S phase when replication origins are licensed for replication. At the onset of S phase, replication forks are initiated only at these licensed replication origins. As initiation occurs at each origin, the licence is removed, thereby ensuring that it fires only once in each cell cycle. Mistakes made in this process may cause irreversible genetic modifications that could ultimately lead to the cells becoming cancerous. Many early stage cancer cells have lost the ability to correctly down-regulate the licensing system, ...
p21CDKN1A does not interfere with loading of PCNA at DNA replication sites, but inhibits subsequent binding of DNA polymerase delta at the G1/S phase transition.
The p110α and p110β catalytic subunits of phosphoinositide 3-kinase (PI3K) regulate cell cycle events. Marqués et al. found that NIH 3T3 cells overexpressing p110β, but not p110α, divided more rapidly than control cells, whereas cells expressing a catalytically inactive p110β point mutant (Lys805→Arg; K805R) divided more slowly than control cells or cells expressing a catalytically inactive p110α mutant. Specifically, S phase progression was accelerated in cells overexpressing p110β and slowed in cells expressing the K805R mutant, suggesting a role for p110β in DNA elongation. Individual DNA fibers were isolated from synchronously dividing NIH 3T3 cells treated with inhibitors specific for p110α (PIK75) or for p110β (TGX221) and subsequently incubated with bromodeoxyuridine (BrdU). In DNA fibers from TGX221-treated cells, the BrdU-labeled sections were shorter in length and closer together compared with those from PIK75-treated cells, implying that replication fork progression was ...
Plays a role in viral genome replication by driving entry of quiescent cells into the cell cycle. Stimulation of progression from G1 to S phase allows the virus to efficiently use the cellular DNA replicating machinery to achieve viral genome replication. E7 protein has both transforming and trans-activating activities. Induces the disassembly of the E2F1 transcription factor from RB1, with subsequent transcriptional activation of E2F1-regulated S-phase genes. Interferes with host histone deacetylation mediated by HDAC1 and HDAC2, leading to transcription activation. Plays also a role in the inhibition of both antiviral and antiproliferative functions of host interferon alpha. Interaction with host TMEM173/STING impairs the ability of TMEM173/STING to sense cytosolic DNA and promote the production of type I interferon (IFN-alpha and IFN-beta ...
BioAssay record AID 461873 submitted by ChEMBL: Cell cycle arrest in human HeLa cells assessed as increase in S phase accumulation at 10 uM after 24 hrs by FACS analysis.
E, CAL120 cells were either untreated or pretreated with gemcitabine for 24 hours followed by treatment with AZD7762 and /or MK-1775 for an additional 2 hours (top) or 8 hours (bottom), before lysis. Western blot analysis of Cyclin B1, CDK1 (phospho-Y15 and total) expression, and β-tubulin as loading control. F, induction of the intra-S-phase checkpoint was not affected by WEE1 inhibition. CAL120 cells were pulse-labeled with 10 μmol/L BrdU for 30 minutes, washed (W), and then treated with 1 μmol/L camptothecin (CPT) for 30 minutes. After CPT removal (0 hours), BrdU-labeled S-phase cells (BrdU+ , indicated by boxed area) were monitored at the indicated time points in the absence (iii) or presence of MK-1775 (iv) or AZD7762 as a positive control (v). Control cells (ctr) were not exposed to CPT and cultured in the absence (i) or presence of MK-1775 (ii). Arrowheads indicate delayed S-phase progression.. ...
Fidelity of histone gene regulation, and ultimately of histone protein biosynthesis, is obligatory for packaging of newly replicated DNA into chromatin. Control of histone gene expression within the 3‐dimensional context of nuclear organization is reflected by two well documented observations....
The end of the S phase of the cell cycle leads to G2 phase, which in turns leads to the M phase or mitosis. During G2 phase, there must be an increasing amount of molecules needed for M phase. G2 phase has been traditionally regarded as a transitional phase between S and M phases. However, during G2 phase, it is checked if any error occurred during DNA replication and if the DNA has been completely replicated. If something went wrong during S phase, M phase does not start until the errors are repaired. It is of great importance the detection of errors before M phase starts, otherwise they will be inherited by the daughter cells. During G2 phase, cell increases the size, and centrosomes of animal cells, duplicated during S phase too, are positioned at opposite locations of the cytoplasm for starting the polymerization of the mitotic spindle during M phase. ...
TY - JOUR. T1 - Rapid cell cycle analysis. II. Phase durations and dispersions from computer analysis of RC curves.. AU - Gray, J. W.. AU - Bogart, E.. AU - Gavel, D. T.. AU - George, Y. S.. AU - Moore, D. H.. PY - 1983/9. Y1 - 1983/9. N2 - In this paper, we present a procedure for the rapid, quantitative estimation of the G1, S, and G2 + M phase durations and dispersions and the growth fraction for asynchronously growing cell populations. In this procedure, the cell population is pulse-labelled with a radioactive DNA precursor at the beginning of the analysis and then sampled periodically. The samples are dispersed, stained with a DNA specific dye, and processed through a cell sorter where cells from mid-S phase and G1 phase are sorted. The radioactivity per cell (RC) is determined for each sorted sample. In addition, the variation in the rate of incorporation of the radioactive DNA precursor across S phase is determined and the fractions of cells in the G1, S, and G2 + M phase are estimated ...
Replication times for all important chromosome bands, of both types R and Q (277 structures) are analysed. - The R-bands form a group of structures whose DNA replicates during the early S-phase, while
Over the following 36 h, we quantified by movement cytometry the charge of EdU nucleotide analogue incor poration from the cells and their total DNA content material, which allowed us to assign cells to G0G1, S, and G2M phases with the cell cycle. When compared to cells transfected using a management non targeting microRNA, cells transfected with miR 29 contained fewer cells in G0G1 and much more cells in S phase at twenty and 24 h submit transfec tion. At 28 and 32 h right after trans fection, cells transfected with miR 29 contained fewer cells in S phase and much more cells in G2M phase than these transfected with the handle. miR 29 overexpression thus hastens re entry into the cell cycle from a quiescent state. To more discover the results of miR 29 expression around the cell cycle, we transfected miR 29 or perhaps a detrimental manage microRNA into asynchronously cycling fibroblasts.. Forty eight hrs publish transfection, miR 29 transfection led to extra cells in G2M. As anticipated ...
Flow-cytometric analysis was used to examine the cell cycle characteristics of BMKs from each of the three genotypes ( Fig. 4A), and the data shown are representative of three independently derived cultures from each genotype. LSL-K-rasG12D BMKs infected with Ad-Cre displayed a higher percentage of cells in G1 and S phases (40.8% and 15.2%, respectively) than control cells (33.4% and 11.5%, respectively). We believe that this is indicative of an increased rate of exit from G2-M and increased cellular proliferation, as supported by data obtained from daily cell counts in LSL-K-rasG12D BMKs (see Fig. 4C and below). Importantly, Ad-Cre-infected Rac1flox/flox BMKs displayed similar growth kinetics to LSL-K-rasG12D BMKs (39.6% of cells in the G1 phase and 13.5% in the S phase compared with controls at 34.9% in the G1 phase and 11.6% in the S phase). Thus, in BMK cells, loss of Rac1 function alone is not lethal and is compatible with proliferation. In contrast, following Ad-Cre infection, ...
When does DNA replication happen? A. During the G1 phase of the cell cycle B. During the S phase of the cell cycle C. During the G2 phase of the cell...
Components and dynamics of DNA replication complexes in S. cerevisiae: Redistribution of MCM proteins and Cdc45p during S phase ...
To examine helicase function, we analyzed DNA unwinding in the absence of polymerase progression by treating cells with hydroxyurea (HU) to deplete the nucleotide pool, which inhibits the DNA polymerase and leads to formation of ssDNA (12). In Xenopus, this response is dependent on MCM2-7 function (13). We measured formation of ssDNA ahead of the polymerase by detection of BrdU-substituted DNA and acute accumulation of RPA at replication sites (fig. S6). In control cells treated with HU, 75% of cells in S phase showed formation of ssDNA and recruitment of RPA to these ssDNA patches at replication sites (Fig. 2B). This response was dramatically reduced when we depleted Asf1 (a and b) (Asf1 knockdown), which indicated that impaired replication reflects a DNA unwinding defect and implied that DNA in chromatin cannot be properly unwound by the replicative helicase. This could reflect a direct effect of Asf1 on DNA unwinding and fork progression or indirect effects, involving DNA damage at the ...
Dates: 7 - 10 May 2018 Registration: 26 Mar 18 Abstract: 12 Feb 18 Event webpage: Aim:There has been tremendous progress in the past few years regarding our understanding of DNA replication in eukaryotes, both yeast and mammals. Many important questions in the field are poised to be answered within the next decade. These include understanding DNA replication at the biochemical and three-dimensional protein structure levels. In addition, studies using high throughput technologies at the cellular and organismal levels are poised to answer how accurate replication of the genome is ensured by controlling origin firing in space and time.Several human diseases, including cancer, have already been linked to DNA replication stress, a term that refers to perturbations in DNA replication. Thus, a better understanding of how cells respond to DNA replication stress will help us understand disease development and responses to therapy. By bringing ...
Malignant proliferation is the fundamental trait of tumor cells. The initiation of DNA replication represents a key process for cell proliferation, and has a marked impact on tumorigenesis and progression (19,21). The factors that promote DNA replication are organized in multiprotein complexes that coordinately help to recognize regions of origin, unwind DNA and promote replisome formation (21). The data in this study showed that SIX1 could modulate the expression of several genes related to DNA replication, thus accelerating G1 to S phase progression, promoting the proliferation of cervical cancer cells in vitro, and promoting the growth of cervical cancer in vivo.. The expression of SIX1 was closely correlated with the progression of cervical cancer as shown by our data. High levels of SIX1 expression were observed in almost all regions that developed intraepithelial neoplasia, suggesting that SIX1 might play an important role in tumorigenesis and progression of cervical cancer. Our data ...
Colchicine, vinblastine, and vincristine inhibit the mitogenic stimulation of lymphocytes by concanavalin A as measured by the incorporation of [3H]thymidine and the appearance of blast cells. The inhibitory effect of colchicine could not be accounted for by diminution in cell viability or by metaphase arrest of mitosis in the stimulated cells. Moreover, the inhibition of [3H]thymidine incorporation was not due to blockage of thymidine transport or inhibition of DNA synthesis inasmuch as addition of colchicine had no effect on cells in the S phase of the cell cycle. The time of inhibition was correlated with the kinetics of cellular commitment to lectin activation and the kinetic data indicated that colchicine blocks stimulation early in the sequence of events following addition of the mitogen. These findings support the hypothesis that cytoplasmic microtubular function plays a role in the commitment of resting cells to undergo mitotic division. ...
As its role in tumor progression emerges, the PI3K/PKB (Akt) pathway presents an appealing cancer therapeutic target. Recent studies have investigated the mechanisms underlying the tumor-promoting effects of this pathway. PKB triggers a network that positively regulates G1/S cell cycle progression t …
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Wet-lab validated real-time PCR primer assays for your biological pathway of interest. Select your gene target of interest using an interactive pathway map, and select your plate.
Tweet. End Sociable. Related posts:. 1The Institute of Science in Society raises serious concerns about the Cauliflower Mosaic Viral Promoter found in commercial GMOS. A recently released study by Podevain and du Jardin in 2012…. A major consequence of mutant p53 degradation in tumor cells after glucose deprivation is the loss of a critical check on the autophagic process that results in increased autophagy and leads to cell death (Fig. 1). Importantly, wild type p53 has been previously demonstrated to protect cells from glucose deprivation through induction of a reversible G1/S phase cell cycle arrest, suggesting that normal tissues will respond to glucose shortage differently than tumors harboring mutant p53.1. fig ft0fig mode=article f1. Taken together, these findings strongly indicate that some tumor-promoting forms of mutant p53 can be targeted for autophagic degradation through glucose restriction. These exciting results could be tested in the clinic by randomizing patients with tumors ...
Above the next 36 h, we quantified by movement cytometry the fee of EdU nucleotide analogue incor poration through the cells and their overall DNA content, which allowed us to assign cells to G0G1, S, and G2M phases of your cell cycle. Inhibitors,Modulators,Libraries When compared to cells transfected using a manage non focusing on microRNA, cells transfected with miR 29 contained fewer cells in G0G1 and even more cells in S phase at twenty and 24 h publish transfec tion. At 28 and 32 h right after trans fection, cells transfected with miR 29 contained fewer cells in S phase and much more cells in G2M phase than people transfected with all the control. miR 29 overexpression as a result hastens re entry to the cell cycle from a quiescent state. To additional check out the results of miR 29 expression within the cell cycle, we transfected miR 29 or maybe a negative control microRNA into asynchronously cycling fibroblasts.. Forty eight hours post transfection, miR 29 transfection led to extra cells ...
CDK2 is a catalytic subunit of the cyclin-dependent protein kinase complex, and is essential for cell cycle G1S phase transition. This protein is coexpressed and copurified with CyclinA.
Precise coordination of the S and M phases of the eukaryotic cell cycle is critical not only for normal cell division, but also for effective growth arrest under conditions of stress. When damaged, a cell must communicate signals to both the mitotic
Scientists refer to the stages of a cells growth and development as the cell cycle. All nonreproductive system cells are constantly in the cell cycle, which has four parts. The M, G1, G2 and S phases are the four stages of the cell cycle; all stages besides M are said to be a part of the overall interphase ...
MITOSIS: The division of chromosomes in the nucleus. S phase: duplication of DNA. (to form two complete copies of each chromosome).
Wellbutrin (bupropion) is an energizer used to treat significant depressive issue and occasional full of feeling issue. This medication works by obstructing the reuptake of norepinephrine and dopamine in the mind, in this way adjusting particular normal s
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If you have a question about this talk, please contact Kathryn Gooch.. Abstract not available. This talk is part of the Seminars at the Department of Biochemistry series.. ...
G4S於1993年進入台灣市場。累積百年經營歷史的G4S,將符合國際高標準的保全服務,帶進本地市場,不僅通過ISO9001的國際認證,並且獲得大型的台灣企業與外商公司的認可,成為全台知名的保全公司品牌。. 經過二十多年的耕耘,G4S「台灣士瑞克保全集團」,先後設立了多家法人公司,取得各項安全服務的營業許可,將不同安全領域的軟硬體以及人力派遣服務,整合成最佳組合提供給客戶。. ...
In 2020 Sandling made his directorial feature film debut with PHASE. Filmed remotely, in isolation entirely via Zoom, PHASE is ... "PHASE". RICHARD SANDLING. July 3, 2020. "SHORT FILMS". RICHARD SANDLING. January 14, 2020. "MASH UPS". RICHARD SANDLING. ...
The biggest benefit of digital media on children is the ability to expose children to the world during their "Why?" phase. ...
"Bartosz Frankowski » J1 League 2016 1. Phase". Retrieved 23 April 2021. "Bartosz Frankowski » Premier League ...
Phase 2 of the project includes the remaining infrastructure not included in Phase-1: track, signalling, telecommunications, ... Phase I Package 2 covers construction of four of the five stations. In April 2009, $38 million worth of design contracts for ... "ADIF participation in phase 2". Archived from the original on 8 January 2011. Retrieved 29 May 2011. "Adjudicado al consorcio ... The 6.79 billion riyal (US$1.8 billion) design and construction contract for Phase I Package 1 - Civil Works for the project ...
"Phase Velocity". Microwaves 101. 2010-03-30. Archived from the original on 2012-01-14. Retrieved 2012-01-25. "CommScope Heliax ... which has a phase value of -45 degrees. At higher frequencies, the reactive terms usually dominate R and G, and the cable ... since it may cause multiple modes with different phase velocities to propagate, interfering with each other. The outer diameter ...
An NGO, PHASE Nepal provides many health care facilities and training programs to six VDCs: Kolti, Wai, Kotila, Pandusain, ... Currently PHASE Nepal is working on several projects in this district including community health and education, livelihood, ... "Project Area: Bajura". PHASE Nepal. "Districts of Nepal". Statoids. Martadi. ...
Phase II will also include the electronics upgrade of Phase I, until the entire active fleet is outfitted with the new ... The actual SLEP modifications are planned to be conducted in two phases. Phase I. Over a period of several years electronics ... Phase II. Buoyancy box replacement will be conducted at the Textron Marine and Land Systems facility in New Orleans, LA, where ...
"Creative Commons License , Eclipse Phase". Retrieved 24 February 2021. CS1 maint: discouraged parameter (link) "Licensing Fate ... Eclipse Phase by Posthuman Studios (CC BY-NC-SA 3.0) Fate by Fantastic Adventures in Tabletop Entertainment (OGL and CC-BY 3.0 ...
"Artists :: Phase One :: Vera Molnar". Retrieved 2016-06-05. "Vera Molnar , Database of Digital Art". Dada.compart- ...
The first phase of the project was to span across 82 acres with the flats being priced between Rs 20 lakh and Rs 80 lakh. There ... The first 450 units were to be sold over by December 2007 and the entire project, comprising five phases, was expected to be ... The developers have missed numerous deadlines since 2008; 2013 not even half of the first phase work was completed. Salim Group ... "Focus: West Bengal". Changing Phase. Frontline, Vol 24, Issue 2, 27 Jan-9 Feb 2007. Retrieved 26 March 2007. CS1 maint: ...
Beysens, D.; Steyer, A.; Guenoun, P.; Fritter, D.; Knobler, C. M. (1991). "How does dew form?". Phase Transitions. 31 (1-4): ...
It is found in Southern Africa and shows classic gregarious behaviour with phase polymorphism on crowding. "With its drought- ... London 7: 162 OSF: Locustana (retrieved 2 February 2018) Uvarov, B.P. (1966). "Phase polymorphism". Grasshoppers and Locusts ( ... arise following the end of droughts and are characterised by the dramatic increase in the density of the solitary phase adult ...
CS1 maint: discouraged parameter (link) Thompson-Smith, Oliver (26 November 2013). "Introducing: Ghost Town". Phase Magazine. ...
"Phase One". Retrieved 2018-02-10. LLC, Advanced Kernels. "Blurate: Custom Image Manipulation". www.blurate. ...
Phase 1.1. Core Requirements Held in Gaithersburg, Maryland on April 26, 1988." National Bureau of Standards (NEL), ...
... and structural phase transitions. Phase equilibrium has been considered within the context of their physical similarities, with ... that is particles coexist with equal chemical potential in two distinct structural phases. The role of the ordered phase as an ... Equilibrium phase transitions (e.g. order/disorder), an equation of state, and the kinetics of colloidal crystallization have ... Structural defects have been directly observed in the ordered solid phase as well as at the interface of the solid and liquid ...
"Phase One X". Ice District. ICE District JV Inc. Retrieved 1 May 2016. Kent, Gordon. "Stantec Tower in Edmonton set to be ... Phase One started after the Ice District announcement 2014-2016. It has A new Office tower, and attractions along with Rogers ... The next Phase X will is from 2017-2020. This includes Stantec Tower, and the JW Marriott Edmonton Ice District & Residences ... "Phase One". Ice District. ICE District JV Inc. Retrieved 1 May 2016. Ramsay, Caley (6 September 2015). "After lengthy delay, ...
Flight phase. The risk is greatest when the exposure comes during a time of high workload: takeoffs, critical or emergency ... These include passenger exposure to laser light, pilot distraction during cruising or other non-critical phases of flight, and ... during a critical phase of flight such as landing or takeoff. It is far less likely, though still possible, that a visible or ... especially when they are in a critical phase of flight: takeoff, approach, landing, and emergency maneuvers. There are four ...
1994.CS1 maint: others in cite AV media (notes) (link) Kempster, Chris (1994). "Purple Phase". Retrieved 20 June 2020. CS1 ...
Phase 1. Benthic Characterization Study. Vol. 2 - Final Report. Prepared for the U.S. Department of the Interior, Minerals ... Jones, N. S., (1990). The Cumacea of the Atlantic phase of the Balgim Cruise. Cahier Biologie Marine 31: 75-85. Jones, N. S. ...
There are three phases of using wikis for collaborative writing: Phase 1. Crisis of Authority Users experience challenges due ... Phase 2. Crisis of Relationship Collaborative learning emerges and group communication is improved. Phase 3. Resolution of ... The internet is now entering a new phase, Web 3.0 or the Semantic Web, which is characterized by the greater interconnectivity ... All aspects of this phase of the VMT project were described in "Translating Euclid." Finally, "Constructing Dynamic Triangles ...
Phase IIIA. Road network. Archived 2015-04-14 at the Wayback Machine Report on Indian Ports. Archived 2012- ...
"Phase II". Sun Hung Kai Properties. Retrieved 20 January 2007. "Official website (for phase II)". Sun Hung Kai. Archived from ... The flats were sold in three phases. It consists of ten blocks of high-rise buildings surrounded by a terrace of green plants ... "Official website (for phase III)". Sun Hung Kai Properties. Retrieved 20 January 2007. "Hong Kong Property" (PDF). Press ...
"DAM :: Artists :: Phase One :: Joan Truckenbrod :: Biography". Digital Art Museum. DAM Projects GmbH, Berlin (Germany). ...
An NGO, PHASE Nepal provides many health care facilities and training programs to Ryale, a VDC of Kavrepalanchok District. ... Currently PHASE Nepal is working on several projects in this district including community health and education, livelihood, ... The main aim of PHASE Nepal is to provide awareness to the local people and help to know about sanitation, livelihood, hygiene ... "Project Area: Kavrepalanchok". PHASE Nepal. "Saping Siddhi Ganesh Temple". Retrieved May 31, 2018. "Saping Siddhi Ganesh Temple ...
a. Phase Training. "Leadership training". RAF Air Cadets. Archived from the original on 9 December 2010. "Air Cadet Junior ...
Sciretta, Peter (October 28, 2014). "Watch: All Of Your Marvel Phase 3 Questions Answered By Marvel Head Kevin Feige". /Film. ... Zalben, Alex; Horowitz, Josh (April 12, 2015). "Marvel's Movie Future: Here's Everything You Need To Know Through... Phase 4 ... as part of Phase Three of the MCU. The film received praise for Brolin's performance, visual effects, action sequences, and ... Infinity War is part of Phase Three of the MCU. Select footage from the film was screened in various cities during the film's ...
Phase 1. Phase 2. Phase 3. Kalinga Vihar. Gopabandhu Nagar. Madhusudan Nagar. TISCO Colony. Saraswati Colony. Kalyani Nagar. Co ...
An NGO, PHASE Nepal, provides many healthcare facilities and training programs in two VDCs: Phulpingkot and Hagam. Many people ... Following is the data obtained from the PHASE Nepal website: Central/regional/zonal hospitals: 0 District hospitals: 1 Primary ... Ekta Boarding High School "Project Area: Sindhupalchowk". PHASE Nepal. Copernicus (2015). EMSR125: Earthquake in Nepal. ...
"Phase II". Montini Catholic High School Web Site. Archived from the original on 28 May 2012. Retrieved 17 November 2011. "Phase ... Phase III of the Capital Campaign was begun in the summer of 2010 and was slated for completion by 2016. The school year is ... Phase I of the Capital Campaign, construction of the West Wing, was completed in 2003. The West Wing contains the 300 Corridor ... Phase II of the Capital Campaign, demolition of Dominic Hall and construction of an Academic and Administrative Center, was ...
Phase transitions[edit]. Main article: Phase transition. When a substance undergoes a phase transition (changes from one state ... a molecule in the liquid phase gains enough kinetic energy to break away from the liquid phase and enter the gas phase. ... The term phase is sometimes used as a synonym for state of matter, but there can be several immiscible phases of the same state ... Crystal phases[edit]. A single material may have several distinct solid states capable of forming separate phases. Water is a ...
... the final phases of the war/, [as adj.] /phase two of the development is in progress./ ∎ a stage in a persons psychological ... phase / fāz/ • n. 1. a distinct period or stage in a process of change or forming part of somethings development: / ... the work is being phased over a number of years , [as adj.] (phased) a phased withdrawal of troops. ∎ (phase something in/out) ... reaching corresponding phases at the same time) or out of phase. In the latter case the difference in phase - the phase ...
Phase 1 LS Approaches. Enhance cancer registry reporting including bi-directional reporting. Several states are currently ... For Phase 2, this strategy could potentially be used to facilitate identification of relatives who might be at risk. ...
Other articles where Clonic phase is discussed: epilepsy: Generalized-onset seizures: Following the tonic stage, clonic ( ...
During this phase the corpus luteum secretes oestrogens and progesterone, which prepare the uterine wall to receive a ... Source for information on luteal phase: A Dictionary of Biology dictionary. ... luteal phase The phase of the oestrous cycle (menstrual cycle in women) that occurs after ovulation. ... luteal phase The phase of the oestrous cycle (menstrual cycle in women) that occurs after ovulation. During this phase the ...
... 2 - 3 October 2018, King of Prussia, United States ... This highly rated industrial PTC course has been conducted 53 times since 1996 (formerly under the name "Practical Phase- ...
Project phases Phase 2 01.01.2014 - 31.12.2017 (Completed) Phase 1 01.04.2012 - 30.06.2014 (Completed) ... Current phase Swiss budget CHF 1200000 Swiss disbursement to date CHF 1324110 ...
The g1 phase, gap 1 phase, or growth 1 phase, is the first of four phases of the cell cycle that takes place in eukaryotic cell ... G1 phase ends when the cell moves into the S phase of interphase. It takes 30-40 percentage time of a cell cycle. G1 phase ... The G1/S checkpoint is the point between G1 phase and the S phase in which the cell is cleared for progression into the S phase ... S phase. The duration of each phase, including the G1 phase, is different in many different types of cells. In human somatic ...
Penalty Phase is a 1986 American made-for-television thriller drama film directed by Tony Richardson and starring Peter Strauss ... CS1 maint: discouraged parameter (link) Penalty Phase at IMDb v t e. ... Penalty Phase looks at problems of a judge". The New York Times. Retrieved 26 November 2015. CS1 maint: discouraged parameter ...
This permits the expression of the pupil-plane phase aberrations φ {\displaystyle \varphi } to the image plane Fourier phase as ... New Brown Dwarf Binaries from Kernel Phase Interferometry [2] Ireland 2013 : Phase errors in diffraction-limited imaging: ... This equation can be used for model-fitting as it represents the interpretation of a sub-space of the Fourier phase that is ... In order to extract kernel-phases from an image, some requirements must be met: Images are nyquist-sampled (at least 2 pixels ...
See an archive of all morning phase stories published on the New York Media network, which includes NYMag, The Cut, Vulture, ... Rosen: Becks Morning Phase Is Expertly Made, But a Terminal Bummer. Its not clear what exactly Beck is bummed out about, but ... You Can Now Stream Becks Morning Phase. Like our forefathers intended. By Amanda Dobbins @media (min-width: 0px) and (max- ...
Boiling: …that has been confining near-boiling water in deep, narrow conduits beneath a geyser. As steam or gas bubbles begin to form in the conduit, hot water spills from the vent of the geyser, and the pressure is lowered on the water column below. Water at depth then exceeds its…
Honeymoon Phase. In a person who has type 1 diabetes (T1D), immune cells destroy the insulin-producing beta cells in the ... However, right after the time of diagnosis, some people experience a "honeymoon phase" in which their existing beta cells still ... by JDRF have shown promise in preserving the function of these existing beta cells in people with T1D past the honeymoon phase. ...
At phase two we could focus on two areas *Increasing our understanding of phase one user groups. This includes: *Identifying ... Covered in phase one e.g. ADHD Delirium, dementia, and amnesia and other cognitive disorders Alzheimers disease Covered in ... Sexual disorder , , disease or disability become exaggerated or faked F7: Mental retardation (covered in phase 1 as ... F0: Organic, including symptomatic, mental disorders (convered in phase one and other categories. Exceptions includes Delirium ...
review recent advances of dense synaptic assembly formation via phase separation and discuss implications of phase separation ... and present some challenges and opportunities of phase separation in synaptic biology. Phase separation is emerging as a ... Here we review recent developments showing how phase separation can build dense synaptic molecular clusters, highlight unique ... features of such condensed clusters in the context of synaptic development and signaling, discuss how aberrant phase-separation ...
... and the United Kingdom saw promising results in 19 of 30 patients in Phase II \[…\] ... Phase I studies prove the safety of a therapy, while Phase II studies must prove the treatment is both safe and effective. ... The study is the first gene therapy trial in any disease to get past Phase I FDA trials to be accepted for publication in a ... The next step in proving gene therapys merit is a pivotal Phase III trial, said Dr. French Anderson, a gene therapy expert at ...
Pandion announces first subject dosed in phase 1 trial of PT101, an IL-2 mutein Fc fusion therapy for autoimmune disease. By ... Harbour BioMed announces completion of phase 1 study in China of HBM9161, an anti-FcRn antibody. By PBR Staff Writer ... Impel NeuroPharma enrolls last patient in phase 3 migraine trial of INP104. *Clinical Trials ... based on the results of the positive Phase 3 RELAY study. ...
Liver Genomic Responses to Ciguatoxin: Evidence for Activation of Phase I and Phase II Detoxification Pathways following an ... Glycine conjugation, a phase II detoxification process, is catalyzed ...". Abstract - Add to MetaCart Glycine conjugation, a ... Induction of phase II enzymes is an important mechanism of chemo-prevention. In our search for novel cancer chemopreventive ... Induction of phase II enzymes is an important mechanism of chemo-prevention. In our search for novel cancer chemopreventive ...
Project H.M., Phase I Project H.M., Phase I * facebook * twitter ...
Remark: Illicit opioid use has been considered the second phase of the nations current opioid epidemic with one drug in ...
Media in category "Solid phase extraction". The following 6 files are in this category, out of 6 total. ... Retrieved from "" ...
Questcor announced it would commence a phase II study (n~210) to evaluate its marketed drug, H.P. Acthar in an additional ... QCOR) announced it would commence a phase II study (n~210) to evaluate its marketed drug, H.P. Acthar in an additional ...
Biotech, COVID-19 Vaccine, GSK, News, Phase 3 Study, SNY GSK Kick Starts Late-Stage Study With Medicago-Partnered COVID-19 ... Biotech, Covid-19, LLY, News, Phase 3 Study, Health Care Eli Lilly Reports More Positive Data From Combination Antibody Drug In ... Alzheimers disease, Biotech, News, Phase 3 Study, SAVA, FDA Cassava Sciences To Start Two Pivotal Trials With Simufilam In ... Biotech, Diabetes, LLY, News, Phase 3 Study, Health Care Eli Lillys Tirzepatide Reduces A1C And Body Weight, Late-Stage ...
Compiled by Dexter Perkins (University of North Dakota) and John Brady (Smith College) Standard phase diagrams are graphical ... representations of the equilibrium relationships between minerals (or others phases). ... ... Standard phase diagrams show how phases or phase assemblages change as a function of temperature, pressure, phase composition, ... Other Phase Diagrams. The above examples are of phase diagrams commonly used by geologists. Phase diagrams are also useful in ...
... Spyrian 12/15/2015 225 .heroes-blog p {padding: 5px 0px 5px 0px;} When Heroes of the Storm ... Despite this first phase of matchmaking improvements, its still possible for new or low MMR players to be mixed in with ... In addition to keeping an eye on the changes weve made with this first phase of matchmaking improvements, were looking ...
Phase II - Degraded Plant Condition Potential At-Risk Maps and Information. No changes from Phase I. The following are the ... Resource Assessment - Home‎ , ‎Phase II - Home‎ , ‎Phase II - Model Results by Resource Concern‎ , ‎ ... potential at-risk maps produced during the Arkansas Resource Assessment - Phase I. The NRCS definition of the natural resource ...
... but I just noticed that the HapMap project has made its phase 3 data available through its browser (the data were previously ... HapMap phase 3 data available for browsing. This will probably only be of interest to population genetics afficianados, but I ... Phase 3 has data on about 1.5 million genetic markers for 1,115 individuals from 11 populations. Thats substantially fewer ... The breakdown of the analysed samples in the phase 3 HapMap data-set is below the fold... ...
Next up is Pharmachems Phase 2 Carb Controller, derived from white kidney beans. The company got the thumbs up from Canadas ... which is valuable information to consumers as it reflects the true efficacy of Phase 2 and its intended use."​ ...
Alloy Phase Diagram International Commission (APDIC) 2018 Best Paper Award: Journal of Phase Equilibria and Diffusion (November ... Investigation on the Phase Diagram of LiCl-KCl-NdCl3 Pseudo-Ternary System Sajal Ghosh, Rajesh Ganesan, R. Sridharan… (November ... and other kinetic properties of phases. It features critical phase diagram evaluations on scientifically and industrially ... Journal of Phase Equilibria and Diffusion. Coverage. Volume 19 / 1998 - Volume 39 / 2018. Print ISSN. 1547-7037. Online ISSN. ...
  • Also, the term phase is sometimes used to refer to a set of equilibrium states demarcated in terms of state variables such as pressure and temperature by a phase boundary on a phase diagram . (
  • However, the state of matter and phase diagram usages are not commensurate with the formal definition given above and the intended meaning must be determined in part from the context in which the term is used. (
  • As shown in the diagram for iron alloys, several phases exist for both the solid and liquid states. (
  • A phase diagram of water, with temperature on the horizontal axis increasing to the left, and pressure on the vertical axis increasing downwards. (
  • It shows the commonly known phases of water (ice, liquid, vapor) as well as the more exotic high-pressure phases Ice II, Ice III and Ice V. As pressure increases, the diagram shows Vanilla Ice (Ice VI) transitioning to David Bowie & Queen. (
  • It features critical phase diagram evaluations on scientifically and industrially important alloy systems, authored by international experts, as well as critically reviewed basic and applied research results, and a survey of current literature. (
  • Pseudosections are a type of phase diagram that shows the fields of stability of different equilibrium mineral assemblages for a single bulk-rock composition. (
  • A new nomenclature for the crystalline phases present in a sequence of structural phase transitions occurring as a function of temperature and/or pressure is defined as a first step in presenting a unified and informative notation for the various phases appearing in a phase diagram. (
  • Discussion of the thermodynamic phase diagram of a substance has often been facilitated by use of a simple notation assigned to each phase in the diagram. (
  • The Journal of Phase Equilibria and Diffusion (JPED) focuses on the crystallographic, chemical, diffusion, and other kinetic properties of phases. (
  • The Phase 1a stage of the study was completed in November of 2019. (
  • The first phase of the programme included various beneficiary-specific and regional initiatives and ran from 2016 to 2019. (
  • The second phase of the programme (worth €41 million between 2019 and 2022) keeps building on the results of the phase I and broadens the thematic areas to new topics crucial for the region - freedom of expression and media. (
  • Phase I of the Horizontal Facility begun on 24 May 2016 and lasted until 24 May 2019. (
  • HAYWARD, Calif. , May 19, 2011 /PRNewswire/ -- Metabolex, Inc., a biopharmaceutical company focused on the discovery and development of proprietary new medicines for the treatment of metabolic diseases, announced today that it has initiated a Phase 2 clinical trial of arhalofenate (MBX-102), its product candidate for the management of hyperuricemia in patients with gout. (
  • MENLO PARK, Calif., July 07, 2020 (GLOBE NEWSWIRE) -- CohBar, Inc. ( CWBR ), a clinical stage biotechnology company developing mitochondria based therapeutics to treat chronic diseases and extend healthy lifespan, today announced that it has resumed the Phase 1b stage of its Phase 1a/1b clinical trial of CB4211, its lead candidate for the treatment of nonalcoholic steatohepatitis (NASH) and obesity. (
  • Previously, in July 2018, CB4211 entered a Phase 1a/1b clinical trial which includes a potential activity readout relevant to NASH and obesity. (
  • The company's lead compound, CB4211, is in the Phase 1b stage of a Phase 1a/1b clinical trial for NASH and obesity. (
  • In the United States, which is both the largest drug maker and the largest single drug market in the world, the next step is the clinical trial process, which has three main phases. (
  • Aveo Pharmaceuticals has initiated a Phase I clinical trial to evaluate the safety, tolerability and recommended dose of SCH900105, its novel, highly potent antibody to hepatocyte growth factor, administered intravenously in patients with relapsed or refractory solid tumors or lymphoma. (
  • Ranibizumab: Phase III clinical trial results. (
  • In the ensuing, recently completed phase 1 clinical trial, healthy volunteers took daily dosages of PRI-002 for 4 weeks. (
  • NEW DELHI, Aug 28 (Reuters) - India will begin deploying its first locally made supersonic combat aircraft next year and gradually phase out its ageing fleet of Russian fighters, defence officials said on Friday. (
  • Defense Secretary Mark Esper, shown here testifying during a House Armed Services Committee hearing on Washington, D.C., in February, issued a memo last week saying the Department of Defense's stop-movement order will be phased out gradually. (
  • The purpose of this website is to provide a comprehensive introduction to heterogeneous phase equilibria in the geosciences. (
  • To support teaching and learning, this site contains the essential background information needed to understand phase equilibria, links to related resources, examples of worked problems, and teaching activities. (
  • This site provides a comprehensive development of the fundamental principles of heterogeneous phase equilibria. (
  • The material found in this site is appropriate for upper division undergraduate and graduate students and for professional colleagues in the broader geoscience community who need to apply heterogeneous phase equilibria (e.g. construction of phase diagrams, thermobarometry, PTt paths, modeling of melt systems) in their own education and research projects. (
  • This module was developed to aggregate and organize the resources and practical experiences of guest authors and editors who are experts in the field of heterogeneous phase equilibria, and who regularly teach this subject using web-based instructional resources, thermodynamic databases, and modern thermodynamic modeling programs ( List of Participants ). (
  • The Teaching Phase Equilibria workhshop was convened in March 2007 at Montana State University to create the on-line curriculum goals of the workshop that led to this module included making significant progress in creating an on-line resource that effectively help the geoscience community. (
  • So, phase equilibria are plotted on T-X diagrams instead of P-T diagrams. (
  • Researchers at the MD Anderson Cancer Clinic in Texas, as well as centers in California, Canada, and the United Kingdom saw promising results in 19 of 30 patients in Phase II FDA trials. (
  • The study is the first gene therapy trial in any disease to get past Phase I FDA trials to be accepted for publication in a scientific journal. (
  • Astellas Pharma Plc (OTCMKTS: ALPMY) has reported positive topline results from two Phase 3 trials, SKYLIGHT 1 and SKYLIGHT 2, evaluating an oral non-hormonal compound, fezolinetant, for treating moderate to severe vasomotor symptoms (VMS), specifically hot flashes associated with. (
  • Are 3 Failed Phase 3 Trials Enough? (
  • But after three failed phase 3 trials, we can only hope that the quest is over, as it appears the NExUS between ESCAPE and MISSION is failure. (
  • Phase I trials are the first stage of testing in human subjects. (
  • Phase I trials also include dose-ranging, also called dose escalation, studies so that the appropriate dose for therapeutic use can be estimated. (
  • Although Phase I trials typically use healthy human volunteers, there are circumstances in which real patients are used, such as patients who have terminal cancer or are infected with HIV and lack other treatment options. (
  • Once the initial safety of the drug candidate has been confirmed in Phase I trials, Phase II trials are performed on larger groups (20 to 300), this time of patients. (
  • Phase II trials are designed to assess how well the drug works on the disease in question, as well as to continue Phase I safety assessments in a larger group of volunteers and patients. (
  • Although the pivotal phase III trials (MARINA and ANCHOR) used monthly injections of ranibizumab for 2 years, the ongoing PIER, PrONTO, and SAILOR trials are investigating less frequent dosing regimens, and preliminary results from the PrONTO study suggest that fewer injections will most likely result in visual acuity improvements similar to the results from the phase III trials. (
  • In December 2005, Genentech submitted a Biologics License Application to the FDA for the use of ranibizumab in the treatment of neovascular wet AMD based on 1-year clinical efficacy and safety data from the two pivotal phase III trials, ANCHOR and MARINA, and the phase I-II FOCUS trial. (
  • As about two thirds of therapeutic interventions that enter Phase III fail to reproduce success observed in Phase II trials. (
  • Reducing false-positives in Phase II trials, the authors say, is ethically attractive because, for example, it reduces the occurrence of failure in Phase III, and can limit the number of patient-volunteers exposed to unsafe and ineffective drugs. (
  • Introducing randomization in Phase II studies, for example, roughly doubles the number of patients in trials because the trials now require comparator arms. (
  • These and other extra "burdens" in Phase II trials, the ethicists say, are not morally equivalent to those found in Phase III trials because risks of drug administration in confirmatory trials are ethically justified by clinical "equipoise", or a state of collective uncertainty about whether experimental treatment is preferable to standard care, and therefore plausibly claim therapeutic value for subjects. (
  • luteal phase The phase of the oestrous cycle (menstrual cycle in women) that occurs after ovulation. (
  • However, data show that 6-10% of women who are fertile demonstrate an inadequate luteal phase, which confirms the need for a better understanding of normal variations in the menstrual cycle and in variations that could be pathologic. (
  • The following mechanisms can cause an inadequate endometrial response to hormonal stimulation during the luteal phase. (
  • A deficiency results in low-to-absent progesterone production and a luteal phase defect. (
  • however, a 1991 symposium hypothesized that luteal phase deficiency (LPD) occurs in 3-10% of infertile patients, and healthy women have deficient luteal phase production of progesterone on a sporadic basis. (
  • Luteal phase deficiency affects women of all races. (
  • Luteal phase deficiency affects only women. (
  • Luteal phase deficiency primarily affects women during their reproductive years. (
  • Some phase diagrams (those for 1-component diagrams) depict relationships involving multiple phases having the same composition (for example, the relationships between the vapor, liquid and solid forms of H 2 O). Other diagrams (such as the one shown on the right), depict the relationships between a number of compounds having different compositions. (
  • This wide range allows, in theory, for data to be stored in multiple phases in the chalcogenide structure, just like multi-level cell (MLC) flash does today. (
  • Standard phase diagrams are graphical representations of the equilibrium relationships between minerals (or others phases). (
  • Standard phase diagrams show how phases or phase assemblages change as a function of temperature, pressure, phase composition, or combinations of these variables. (
  • Standard phase diagrams may include many reactions but, depending on its composition, a particular rock may only experience a few (or none) of them. (
  • This is a diverse collection of phase diagrams, intended to be used by instructors when teaching petrology or mineralogy classes. (
  • Download binary phase diagrams. (
  • Ternary igneous phase diagrams are triangular diagrams that show melting relationships involving three chemical components. (
  • Some of the diagrams available here involve only a few components and a few phases. (
  • Phase diagrams that show many reactions that take place in a single chemical system are termed 'petrogentic grids. (
  • The above examples are of phase diagrams commonly used by geologists. (
  • Phase diagrams are also useful in other fields, including chemistry and engineering. (
  • So, before we dive into our first phase of really talking about the commitment aspect of the work and the project partners, I'd really - David - I'd love to hear from you. (
  • Today, this podcast will feature again Mr. David Ellsworth, our State Expert Advisor for Ohio, who's going to join us and discuss about phase four, the Implementation phase. (
  • [a] Mutually immiscible liquid phases are formed from water (aqueous phase), hydrophobic organic solvents, perfluorocarbons ( fluorous phase ), silicones, several different metals, and also from molten phosphorus. (
  • Emerging evidence indicates that liquid-liquid phase separation, the formation of a condensed molecular assembly within another diluted aqueous solution, is a means for cells to organize highly condensed biological assemblies (also known as biological condensates or membraneless compartments) with very broad functions and regulatory properties in different subcellular regions. (
  • Therefore, it seems that the early addition of aqueous suppressant treatment, particularly fixed combination timolol / dorzolamide , improves AGV outcomes by leading to a greater IOP reduction, a higher success rate, and a lower frequency of the hypertensive phase. (
  • The Aqueous Phase Ammonia Removal and Destruction System (APARDS) Phase I Program rigorously demonstrated the feasibility of each sub-process, and an integrated system was developed that removed and destroyed ammonia from a simulated bioreactor effluent. (
  • This activity is a small-group activity that makes students learn the subject matter of aqueous solutions (colloids, suspensions) and phase changes by writing a children's book. (
  • The next step in proving gene therapy's merit is a pivotal Phase III trial, said Dr. French Anderson , a gene therapy expert at the University of Southern California Keck School of Medicine. (
  • The FDA and Cassava Sciences agree on key elements of a pivotal Phase 3 program for simufilam, which would include two. (
  • Here we review recent developments showing how phase separation can build dense synaptic molecular clusters, highlight unique features of such condensed clusters in the context of synaptic development and signaling, discuss how aberrant phase-separation-mediated synaptic assembly formation may contribute to dysfunctional signaling in psychiatric disorders, and present some challenges and opportunities of phase separation in synaptic biology. (
  • Here, we will emphasize the importance of phases, how phases are derived from some prior knowledge of structure and look briefly at phasing methods (direct, molecular replacement and heavy-atom isomorphous replacement). (
  • Given recent advances in phasing methods, those new to protein crystallography may be forgiven for asking `what problem? (
  • Along the way, we will meet some of the heroes of protein crystallography such as Perutz, Kendrew, Crick, Rossmann and Blow who established many of the phasing methods in the UK. (
  • In most phasing methods the aim is to preserve isomorphism, such that the only structural change upon heavy-atom substitution is local and there are no changes in unit-cell parameters or orientation of the protein in the cell. (
  • During G1 phase, the cell grows in size and synthesizes mRNA and protein that are required for DNA synthesis. (
  • In order for the cell to continue through the G1-pm, there must be a high amount of growth factors and a steady rate of protein synthesis, otherwise the cell will move into G0 phase. (
  • is widespread in identifying the various phases in metals and alloys. (
  • The section begins with an explanation of the stages along that continuum -- the five phases of retirement planning and the key aspects of good planning to be carried out during each phase. (
  • Doctors call these groups phases instead of stages. (
  • The phase 1 trial of PRI-002 completed two stages: single administrative dose (SAD) and multiple administrative dose (MAD). (
  • denoting each aspect of the moon): from French phase , based on Greek phasis 'appearance,' from the base of phainein 'to show. (
  • In magick, the position and phase of the Moon is considered to be one of the deciding factors in when to celebrate, or when to use magick. (
  • phases, for example, are commonly used to designate, respectively, the disordered (Cu-type) and the ordered (CsCl-type) phases of the Cu-Zn alloy. (
  • Such notations are immediately understandable to workers familiar with the given metal or alloy since they refer to specific experimental conditions for observing these phases and to a definite set of experimental results (twinning appearance, mechanical properties etc . (
  • The overarching goal of this project Fire Safety Challenges of Tall Wood Buildings Phase 2 (involving five tasks) is to quantify the contribution of CLT building elements (wall and/or floor-ceiling assemblies) in compartment fires and provide data to allow comparison of the performance of CLT systems against other building systems commonly used in tall buildings. (
  • Some patterns of sudden change have been identified as phase transitions, similar to those known from the physics of phase changes. (
  • Nedelsky, N. B. & Taylor, J. P. Bridging biophysics and neurology: aberrant phase transitions in neurodegenerative disease. (
  • A systematic nomenclature for a sequence of several solid-state phase transitions was, however, not considered in the document. (
  • It is uninformative to the reader with only a general knowledge of the field of phase transitions, since it does not summarize any specific crystallographic or physical information. (
  • and MBX-8025, which has completed a Phase 2 trial in patients with dyslipidemia. (
  • Anderson said Onyx Pharmaceuticals , the company that sponsored the study, plans a Phase III trial soon that, if successful, could result in the FDA approving gene therapy as a viable treatment. (
  • Sanofi SA (NASDAQ: SNY) and Regeneron Pharmaceuticals Inc (NASDAQ: REGN) revealed that they're stopping a Phase 3 cervical cancer trial early after Libtayo showed cutting the risk of death by 31% over chemotherapy. (
  • Almost 60% of patients with biopsy-confirmed nonalcoholic steatohepatitis and liver fibrosis showed resolution of NASH after treatment with semaglutide ,according to a phase 2, double-blind, randomized, placebo-controlled trial published in the New England Journal of Medicine and presented at the 2020 American Association for the Study of Liver Diseases (AASLD) meeting. (
  • The scientists say that many trial reforms being considered to raise Phase II positive predictibility (reduction of late-phase attrition) have repercussions for human subjects, as well as the capacity of the research enterprise to "execute its social mission. (
  • These include establishing the upper and lower bounds on evidence needed to initiate Phase III studies, limiting nontherapeutic risks for trial patient-subjects, and consideration of the potential knowledge-value of decisively negative Phase III results. (
  • Based on the efficacy or toxic effects of the drug / treatment in a Phase -II trial the outcome of the development process could be decided, i.e if a Phase -III trial would be required. (
  • anti-PDL1) in a randomized Phase 2 trial in patients with soft tissue sarcoma. (
  • The randomized, open label Phase 2 trial will evaluate CMB305 and atezolizumab in patients with locally advanced, relapsed, or metastatic synovial sarcoma or myxoid/round-cell liposarcoma, two types of sarcoma that tend to express NY-ESO-1 broadly. (
  • The next phase of the trial consists of vaccinating Ebola workers on the front lines. (
  • Instead, the military commission proceedings are bogged down in a pre-trial phase, as it has been for the past three years. (
  • Passing this stage of testing in humans means that the candidate drug can now proceed to a phase 2 trial to evaluate its effectiveness in people with Alzheimer's disease. (
  • Prosecutors Wednesday wrapped up their portion of the penalty phase trial for Floyd Eugene Maestas, 52, who was convicted last week by a 12-member jury of killing Donna Lou Bott, 72, in 2004. (
  • The Phase Angle Calibrator makes use of an op amp filter circuit called the all-pass circuit, which takes a sine-wave input and produces a constant amplitude phase-shifted sine wave output. (
  • The output signal is amplitude modulated at the phase modulation frequency to transpose the optical phase shift into a low frequency electronic phase shift, which is measured using a digital time interval counter. (
  • selecting a predetermined frequency from the amplitude modulated output to produce a signal which is representative of shifts in said phase difference, wherein said predetermined frequency is a harmonic of the modulation frequency. (
  • 2. A method of detecting shifts in phase difference of interfering light waves as defined in claim 1, wherein the step passing the output through an amplitude modulator comprises the step of amplitude modulating the output to provide a low frequency signal having a phase shift which corresponds to the shift in the phase difference of the interfering light waves. (
  • Even at equilibrium molecules are constantly in motion and, once in a while, a molecule in the liquid phase gains enough kinetic energy to break away from the liquid phase and enter the gas phase. (
  • So instead of quitting the rat race entirely and collecting a Social Security check, he scaled back his hours under the school's phased retirement program. (
  • More and more companies are beginning to offer phased retirement programs as a way to hold trained and loyal employees. (
  • About 16 percent of large companies have a phased retirement program, according to the consulting firm Watson Wyatt. (
  • Whether it's through scaling back work hours, overseeing particular projects, or working as a mentor, phased retirement programs can differ among employers. (
  • For example, the Florida Board of Regents oversees the phased retirement program at the University of Central Florida in Orlando, where John O'Hara has worked for two decades. (
  • O'Hara began his phase retirement in January, after meeting the eligibility requirement of at least 10 years of service at the school. (
  • Private companies also offer phased retirement in a variety of forms. (
  • Varian Medical Systems in Palo Alto, Calif., which manufactures cancer therapies, has offered phased retirement for its employees for the last 20 years. (
  • Whereas the follicular phase of the menstrual cycle can vary in length, the secretory phase lasts approximately 14 days, correlating with the life span of the corpus luteum. (
  • Phase transition in postsynaptic densities underlies formation of synaptic complexes and synaptic plasticity. (
  • Bernevig, B. A., Hughes, T. L. & Zhang, S.-C. Quantum spin Hall effect and topological phase transition in HgTe quantum wells. (
  • Confusion caused by the lack of a unified notation procedure led the Commission on Crystallographic Nomenclature to establish a Working Group on Phase Transition Nomenclature. (
  • Left to equilibration, many compositions will form a uniform single phase, but depending on the temperature and pressure even a single substance may separate into two or more distinct phases. (
  • A multiplicity of terminologies may be found in the crystallographic and other literature of the condensed state for distinguishing individual members of a sequence of crystalline phases that form as a function of temperature and/or pressure. (
  • The Working Group was charged with studying the multiple nomenclature in current use for naming the sequence of phases that a material may form as a function of temperature and/or pressure and with making such recommendations as may be appropriate. (
  • G1 phase and the other subphases of the cell cycle may be affected by limiting growth factors such as nutrient supply, temperature, and room for growth. (
  • In humans, the normal physiological temperature is around 37 °C (98.6 °F). G1 phase is particularly important in the cell cycle because it determines whether a cell commits to division or to leaving the cell cycle. (
  • By 2016 1 , to provide data on and an understanding of the role of particle formation in limiting the action of gas-phase active phosphorous-based fire retardants added to polymers. (
  • Within each phase, the properties are uniform but between the two phases properties differ. (
  • The Welchel phase-rotation FFT is a new form of the fast Fourier transform (FFT) that replaces data movement at runtime with equivalent multiplications by precomputed constants. (
  • from Kevin Cowtan's Book of Fourier ( ), the importance of phases in carrying structural information is beautifully illustrated. (
  • The method relies on a discrete model of the instrument's pupil plane and the corresponding list of baselines to provide corresponding vectors φ {\displaystyle \varphi } of pupil plane errors and Φ {\displaystyle \Phi } of image plane Fourier Phases. (
  • This permits the expression of the pupil-plane phase aberrations φ {\displaystyle \varphi } to the image plane Fourier phase as a linear transformation described by the matrix A {\displaystyle A} : Φ = Φ 0 + A ⋅ φ {\displaystyle \Phi =\Phi _{0}+A\cdot \varphi } Where Φ 0 {\displaystyle \Phi _{0}} is the theoretical Fourier phase vector of the object. (
  • This equation can be used for model-fitting as it represents the interpretation of a sub-space of the Fourier phase that is immune to the instrumental phase errors to the first order. (
  • Porvair Sciences announce Microlute™ CP - a new generation of Solid Phase Extraction (SPE) 96-well microplates and cartridges that take SPE to a new level of performance by enhancing the reproducibility of analyte extraction and recovery from biological, environmental and chemical samples. (
  • Retrieved on November 27, 2020 from (
  • Complexes of cyclin that are active during other phases of the cell cycle are kept inactivated to prevent any cell-cycle events from occurring out of order. (
  • These complexes then activate S-Cdk complexes that move forward with DNA replication in the S phase. (
  • The other outcome measures included best corrected visual acuity, complications, and hypertensive phase frequency. (
  • Three Phases of Water main content. (
  • This chapter introduces and discusses activities in the Microsoft® Solutions Framework (MSF) Developing Phase as they are performed in a migration project. (
  • A simple description is that a phase is a region of material that is chemically uniform, physically distinct, and (often) mechanically separable. (
  • Distinct phases may also exist within a given state of matter. (
  • A mixture can separate into more than two liquid phases and the concept of phase separation extends to solids, i.e., solids can form solid solutions or crystallize into distinct crystal phases. (
  • Not all organic solvents are completely miscible, e.g. a mixture of ethylene glycol and toluene may separate into two distinct organic phases. (
  • In a system consisting of ice and water in a glass jar, the ice cubes are one phase, the water is a second phase, and the humid air is a third phase over the ice and water. (
  • Illicit opioid use has been considered the second phase of the nation's current opioid epidemic with one drug in particular contributing to this increase. (
  • AbbVie Inc (NYSE: ABBV) announces data from the second Phase 3 study, U-ACCOMPLISH, evaluating upadacitinib in patients with moderate to severe ulcerative colitis. (
  • POTTEIGER: Well, some friends of mine and I are working on this website called and the idea is that we've really reached the second phase of this movement here, at least that's what a lot of people in Boston feel. (
  • The second phase of the programme will cover actions in Albania, Bosnia and Herzegovina, Kosovo*, Montenegro, North Macedonia, Serbia as well as Turkey and the regional dimension of the programme will be strengthened. (
  • This second phase of testing may last from several months to two years. (
  • The second phase was the dangerous one for Rita, and during a certain luncheon at Romanos her fate hung in the balance. (
  • This second phase of the Provincial Maternal-Child Health Investment Project will support governmental efforts to improve access to basic health services for the uninsured population by expanding the Maternal Child Health Insurance Program ("Plan Nacer") at the provincial level. (
  • The methods and apparatus of the present invention provide as a specific embodiment, a dual wavelength phase modulation system which allows the clinical application of time resolved spectroscopy in a commerically feasible embodiment. (
  • The present invention to provides methods and apparatus for studying photon migration using signal modulation techniques such as time, frequency and phase modulation. (
  • Typical uses include: Finding the phase angle between voltage and current to determine the phase shift and impedance of a loudspeaker over its frequency range. (
  • Finding the phase shift between the input and output of a tube amplifier to establish the HF (high frequency) and LF (low frequency) cutoff points needed to avoid instability in feedback amplifiers. (
  • is the phase angle, and f is the frequency. (
  • In this embodiment, an open-loop, all-fiber-optic gyroscope provides an output signal comprising the phase difference of two light waves which are counterpropagating within the gyroscope, and which are phase modulated at a selected frequency. (
  • Eli Lilly and Company announced that a U.S. Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) voted 6-5 that CYRAMZA (ramucirumab) plus erlotinib demonstrated a favorable benefit/risk profile for patients with untreated metastatic EGFR-positive non-small cell lung cancer (NSCLC), based on the results of the positive Phase 3 RELAY study. (
  • Eli Lilly And Co (NYSE: LLY) have announced topline results from two Phase 3 studies, SURPASS-3 and SURPASS-5, evaluating Tirzepatide in adults with type 2 diabetes. (
  • Travere Therapeutics Inc (NASDAQ: TVTX) share gains after announcing positive interim results from the ongoing Phase 3 DUPLEX study evaluating sparsentan in focal segmental glomerulosclerosis (FSGS), a rare kidney condition that often leads to end-stage kidney disease. (
  • However, right after the time of diagnosis, some people experience a "honeymoon phase" in which their existing beta cells still function and the body is able to produce its own insulin. (
  • It is time to phase out the use of codeine as a pain reliever because of its significant risks and ineffectiveness as an analgesic, states an editorial in CMAJ (Canadian Medical Association Journal) (pre-embargo link only) . (
  • When it comes time for the Phase 2 rollout, SHA will have 226 clinics in 181 communities and that includes mass immunization sites in Wakaw, Birch Hills, Cudworth, Middle Lake, and Rosthern. (
  • Next time you're drinking a glass of ice water, stop and think about this: At a single moment, you're experiencing water in all three phases. (
  • A phase angle meter is useful in audio work to determine the phase angle between a reference signal and a phase shifted signal, both having identical time periods. (
  • For a migration project, the Developing Phase is the time when you build the solution components, code, and infrastructure, as well as prepare the documentation. (
  • In human somatic cells, the cell cycle lasts about 18 hours, and the G1 phase takes up about 1/3 of that time. (
  • This project really builds upon a previous Healthy Communities model used by NACDD and was modified to consist of six phases that really are a crucial part of the inclusive healthy community change processes that are focused on improving the health and well-being of people with disabilities. (
  • Because phase boundaries relate to changes in the organization of matter, such as a change from liquid to solid or a more subtle change from one crystal structure to another, this latter usage is similar to the use of "phase" as a synonym for state of matter. (
  • At equilibrium, evaporation and condensation processes exactly balance and there is no net change in the volume of either phase. (
  • He's going to talk to us about some of the successes implemented in Adams and Marion Counties, Ohio, just so that our listeners get a feel for the types of policies, systems, and environmental change strategies that our local communities and their coalitions implemented through this phased process. (
  • For example, recent anecdotal information indicates that very small changes to a gas-phase active phosphorus FR additive can change its effectiveness by more than an order of magnitude, but the industry researchers do not yet have a credible hypothesis as to why. (
  • And boffins at IBM Research in Zurich, Switzerland, think they have come up with a new encoding technique that will allow for multi-level cell (MLC) phase change memory to be commercialized at some point in the not too distant future. (
  • Phase change memory is based on an interesting goop called chalcogenide compounds, which are used in rewriteable CD, DVD, and Blu-Ray disks. (
  • Large changes in resistor value produce very little change in phase angle as you approach 0 or 180 degrees. (
  • This phase lasts from the day you retire until you are 70 years old. (
  • This phase begins at age 70 and lasts as long as you are able-bodied and high-functioning. (
  • These phases are: Phase one is the Commitment phase, phase two is the Assessment and Training phase, phase three is the Prioritization and Planning phase, phase four is Implementation, phase five is Evaluation, and phase six is Communication and Dissemination. (
  • This Implementation phase is really the phase where the community coalitions work to implement the strategies that were outlined and described in the community action plans that they all developed. (
  • This highly rated industrial PTC course has been conducted 53 times since 1996 (formerly under the name "Practical Phase-Transfer Catalysis), of which 32 were conducted in-house at process R&D departments for pharmaceuticals, agrochemicals, flavors & fragrances, dyes & pigments and a variety of commodity, specialty and fine organic chemical manufacturers. (
  • F0: Organic, including symptomatic, mental disorders (convered in phase one and other categories. (
  • Equilibrium phase relationships between calcite, quartz, wollastonite and CO 2 . (
  • Penalty Phase is a 1986 American made-for-television thriller drama film directed by Tony Richardson and starring Peter Strauss. (
  • T]he glucose metabolism claim emphasizes a 'carbohydrate-rich meal' which is valuable information to consumers as it reflects the true efficacy of Phase 2 and its intended use. (
  • We began working on Alleghany Park in 2004 and development of the third phase will complete the 95-acre park," said Grayslake Park District Executive Director Kristin Splitt. (
  • This phase occurs during the final years of the accumulation phase and should begin when you reach 50 years old or are 15 years away from retiring, whichever happens first. (
  • Patients in the chronic phase typically have less than 10% blasts in their blood or bone marrow samples. (
  • The following are the potential at-risk maps produced during the Arkansas Resource Assessment - Phase I. The NRCS definition of the natural resource concern and the input layers and land use designation weights that were used for modeling the natural resource concern within the Degraded Plant Condition Resource Concern are listed to the right of each map. (
  • This study was a double blind, placebo-controlled single ascending dose and multiple ascending dose assessment of safety, tolerability, and pharmacokinetics in healthy adults, to select the most appropriate dose for the Phase 1b stage. (
  • Questcor Pharmaceuticals, Inc. ( QCOR ) announced it would commence a phase II study (n~210) to evaluate its marketed drug, H.P. Acthar in an additional indication. (
  • Just a week after acing Phase 3 study evaluating radioligand therapy in prostate cancer, Novartis AG (NYSE: NVS) is licensing the rights to develop and commercialize treatments based on a library of radioligand compounds from iTheranostics, a subsidiary of Sofie. (
  • Humanigen Inc (NASDAQ: HGEN) has reported topline data from Phase 3 study evaluating its lead drug candidate, lenzilumab, in patients hospitalized with COVID-19. (
  • Eli Lilly and Co (NYSE: LLY) has announced new data from BLAZE-1 Phase 3 study, evaluating the combination of bamlanivimab (LY-CoV555) 700 mg and etesevimab (LY-CoV016) 1400 mg in COVID-19 patients. (
  • Caladrius Biosciences Inc (NASDAQ: CLBS), a penny-stock clinical-stage biopharmaceutical company announced after Wednesday's market close it will discontinue an ongoing Phase 3 study. (
  • In this phase the effectiveness and safety of the experimental study drug or treatment is evaluated by controlled studies. (
  • The study drug or experimental treatment is tested on a larger group of people ( 100- 300) compared to a phase I study. (
  • so this introduction to the CCP4 Study Weekend attempts to give an overview of phasing for those new to the field. (
  • Having established the safety and individual immunologic activity of LV305 and G305 in prior studies, Immune Design initiated a new Phase 1B study of the product candidate CMB305 earlier this year. (
  • This book gives physical chemists a broader view of potential biological applications of their techniques for the study of nucleic acids in the gas phase. (
  • Cancer chemopreventive activity mediated by 4′-bromoflavone, a potent inducer of phase II detoxification enzymes. (
  • Induction of phase II enzymes is an important mechanism of chemo-prevention. (
  • Water in a closed jar with an air space over it forms a two phase system. (
  • Fig. 1: Basic principles of phase separation illustrated by a simple two-component system. (
  • In order to aid in the development and application of new compounds that are likely to be used in fire-retarded high-volume thermoplastics, this project will determine the gas-phase mechanism of the most promising replacement moiety (phosphorus), as well as the existing bromine-antimony system. (
  • We're also … in the process of implementing an online scheduling system, mostly to support phase two where we'll see much larger vaccine, but we're trying to approach it in a multi-factorial way, but again, we're still learning," said Livingstone after problems with accessing appointments and awareness of their availability were identified with the pop-up clinics which were held in the North Central zone in late January. (
  • Within the cell cycle, there is a stringent set of regulations known as the cell cycle control system that controls the timing and coordination of the phases to ensure a correct order of events. (
  • This nomenclature specifies in a compact but intuitive manner the essential crystallographic and physical characteristics of each phase in the sequence. (
  • During this phase the corpus luteum secretes oestrogens and progesterone, which prepare the uterine wall to receive a fertilized egg. (
  • This is the lite version of the equipment sizing app and provides the optimum two-phase separator design for various process conditions. (