• Ad5 is one of the mostly used gene therapy vectors to date. (metu.edu.tr)
  • Therefore, understanding the functions of E4orf3 is very important for developing efficient and safe adenovirus vectors. (metu.edu.tr)
  • Schematic of the adenovirus genome and adenovirus-based vectors. (genemedi.com)
  • These findings should provide valuable information for gene therapy using Ad vectors in neonates and infants. (hindawi.com)
  • i) Neonates and infants have immature immune systems, making it possible to circumvent the immune reactions against gene delivery vectors and transgene products that reduce therapeutic efficiency in adults. (hindawi.com)
  • Adenovirus (Ad) vectors are among the most commonly used viral vectors in gene therapy clinical trials because they have the following advantages. (hindawi.com)
  • iv) They can deliver transgene into the nuclei of not only dividing cells but also nondividing cells with the highest efficiency among the gene delivery vectors. (hindawi.com)
  • On the other hand, Ad vectors also have a number of disadvantages, including their low transduction efficiency in cells lacking coxsackievirus-adenovirus receptor (CAR) and their induction of innate immune responses. (hindawi.com)
  • Ad vectors have been used in gene therapy clinical trials of adult patients with various diseases, including several types of cancers and cardiac diseases, and promising results have been reported [ 9 , 10 ]. (hindawi.com)
  • 2023). Updates and New Perspectives on Adenoviral Gene Therapy and Vaccine Vectors. (leibniz-liv.de)
  • One of the main vectors used to carry modified genes into cells is the virus. (familymednews.com)
  • Commonly used vectors include adenoviruses, adeno-associated viruses, retroviruses and the herpes simplex virus. (familymednews.com)
  • Adenoviral vectors are capable of efficient gene transfer, but use of these vectors during donor organ preservation may be less efficient due to the low temperature. (unipv.it)
  • Recombinant adeno-associated viruses (AAV) are one of the leading vectors for gene therapy applications that deliver gene-editing enzymes, antibodies, and RNA interference molecules to eliminate viral reservoirs that fuel persistent infections. (biomedcentral.com)
  • Thus, over the past few decades, extensive efforts to optimize AAV vectors for gene therapy applications have focused on capsid engineering with approaches such as directed evolution and rational design. (biomedcentral.com)
  • So far, the approved AAV-based drugs and most clinical trials utilizing AAV vectors aim to supplement a defective gene with a new, working copy [ 3 ], but many studies have investigated AAV for the delivery of non-self therapeutic genes. (biomedcentral.com)
  • c production of replication incompetent AAV vectors via transient plasmid transfection into 293 producer cells that express adenovirus type 5 E1 genes. (biomedcentral.com)
  • pAd1129-01 is a shuttle plasmid designed for constructing E3-deleted and bipartite (dicistronic) recombinant adenovirus vectors. (od260.com)
  • One amino acid change in the receptor-binding domain of fiber and 6 amino acid pattern is the result of a mutation of the Bam HI restriction variations in E4 ORF 6/7 were identified between 2 site at 0.93 map units of the genome. (cdc.gov)
  • provide evidence that the rapid divergence of Ad7d to a Particularly interesting were the distinctive patterns of cir- novel genome type Ad7l could have been due to viral culating genome types during the Ad7 epidemic in Korea strategies involving multiple sequence changes in E4. (cdc.gov)
  • Genetic variations between the Ad7d and Ad7l genome types have been studied by analyzing the sequences of hexon, E3, fiber, and E4 ORF 6/7 peptides. (cdc.gov)
  • Top panel: a simplified map of the adenovirus serotype 5 genome showing the early genes (E1-E4) and the region from which the major late transcript is produced. (genemedi.com)
  • Without integration into host genome, adenovirus genome remains in an episomal state, which guarantees the low risk of mutation (Fig. 8). (genemedi.com)
  • It also exhaustively introduces the concrete mechanism of invading GC cells and the viral genome composition of adenovirus and herpes simplex virus type 1 (HSV-1). (frontiersin.org)
  • The highest Ad vector genome copy numbers and transgene expression were found in the neonatal liver. (hindawi.com)
  • The human papillomavirus (HPV) E2 protein is a multifunctional protein essential for the control of virus gene expression, genome replication and persistence. (microbiologyresearch.org)
  • a genome organization of wild type AAV2 depicting its ssDNA genome and the 7 viral RNAs expressed from 2 genes Rep (Black boxes) and Cap (Grey boxes) and via the p5, p19 or p40 promoters. (biomedcentral.com)
  • In a genome-wide screen for putative tumor suppressor genes, the EBF3 locus on the human chromosome 10q26.3 was found to be deleted or methylated in 73% of the examined cases of brain tumors. (aacrjournals.org)
  • It contains the sequence encompassing psn 27885-32795 in the Ad5 genome including the E3 region and the entire fiber gene. (od260.com)
  • When you construct a recombinant adenovirus genome in E. coli using cosmid technology, you are almost sure that every colony carries a full-size genome, and not a smaller plasmid that lost chuncks of the adenovirus genome by DNA recombination. (od260.com)
  • Both of them are flanking both ends of the recombinant adenovirus genome contained in your cosmid. (od260.com)
  • Because the PacI site is immediately flanking the start of the adenovirus genome, the DNA ends generated by PacI resemble the most the ends obtained from deproteinised virion DNA and might therefore be more efficient in promoting virus replication. (od260.com)
  • The virus N protein is another protein that has a critical role for genome packaging. (ajmb.org)
  • The authors evaluated the entire genome of a 40-year old man and compared it to several databases of disease-related gene variants. (blogspot.com)
  • Here, based on significant liver contribution to the catabolism of the branched chain amino acid leucine, we develop a liver-directed adeno-associated virus (AAV8) gene therapy for MSUD. (nature.com)
  • A first-generation Ad vector containing a cytomegalovirus (CMV) promoter-driven luciferase expression cassette was administered to neonatal mice on the second day of life via retro-orbital sinus. (hindawi.com)
  • Adenovirus is often used as a viral vector to produce vaccines with replication ability and vaccines with replication defects. (medicaltrend.org)
  • In order to produce a replication-deficient vector, the two early genes E1A and E1B of adenovirus were replaced with transgene (the insertion antigen of the target pathogen) expression cassette, thereby preventing the virus from replicating in the host cell. (medicaltrend.org)
  • In addition, by genetically depleting the E3 and E4 genes of the adenovirus vector, the host cell-mediated elimination of adenovirus-infected cells and the instability of the transgene can be prevented. (medicaltrend.org)
  • Gene therapy using an adenovirus vector: A new gene is injected into an adenovirus vector, which is used to introduce the modified DNA into a human cell. (familymednews.com)
  • Incubation with an adenoviral vector encoding for E. coli beta-galactosidase was performed for 1 h at three different temperatures: 4 degrees C, 10 degrees C and 37 degrees C. Transgene expression was assessed by histochemical staining for beta-galactosidase in transduced cells and by evaluation of beta-galactosidase activity in organ cultures. (unipv.it)
  • The success of AAV as a gene delivery vector is due to several characteristics, including its nonpathogenic nature, its good safety profile, and its ease of production to clinical grade. (biomedcentral.com)
  • Synthetic genes of RBD and N were cloned separately in pET28a + expression vector. (ajmb.org)
  • Gene delivery of antiviral therapeutics to anatomical sites where viruses accumulate and persist is a promising approach for the next generation of antiviral therapies. (biomedcentral.com)
  • For example, the common cold is caused by a wide variety of respiratory viruses, most commonly rhinovirus, but also coronaviruses, adenoviruses, and other virus serotypes [ 13 ]. (breathinglabs.com)
  • CF stands for Carrier Free (CF). We typically add Bovine Serum Albumin (BSA) as a carrier protein to our recombinant proteins. (bio-techne.com)
  • They were transferred into Escherichia coli ( E. coli ) BL21 DE3 host cell, and expression of recombinant proteins was induced with IPTG. (ajmb.org)
  • The recombinant proteins were purified by column chromatography and approved by Western blotting. (ajmb.org)
  • Animal immunization was performed with each of the recombinant proteins individually and in combination of the two. (ajmb.org)
  • According to the present study, recombinant proteins, either RBD alone or in combination with N adequately stimulated the immune response, and the raised antibodies could neutralize the virus in in vitro test. (ajmb.org)
  • The adenoviral genes required for proper AAV packaging are provided in the pHelper plasmid (E2A, E4 and VA RNA) or in the 293 packaging cells (E1). (ecceterra.fr)
  • Si ricorda che il superamento dei valori soglia (almeno 2 su 3) è requisito necessario ma non sufficiente al conseguimento dell'abilitazione. (unipv.it)
  • Through immunoprecipitation of YY1-bound chromatin from affected individuals' cells with antibodies recognizing both ends of the protein, we show that YY1 deletions and missense mutations lead to a global loss of YY1 binding with a preferential retention at high-occupancy sites. (unimi.it)
  • The neutralization test exhibited produced antibodies' potency to bind the virus proteins. (ajmb.org)
  • Hexon and penton structures form the capsid of AdV, and fiber protein mediates the binding of the virion to the cell surface and is a major determinant of viral tropism. (genemedi.com)
  • Evidence that the Adenovirus Single-Stranded DNA Binding Protein Mediates the Assembly of Biomolecular Condensates to Form Viral Replication Compartments. (leibniz-liv.de)
  • Adenovirus transcription is a two-phase event, early and late, occurring before and after viral DNA replication, respectively (Figure. (genemedi.com)
  • Life cycle of adenovirus is separated by DNA replication process into two distinct phases: the early and late, occurring before and after viral DNA replication, respectively. (genemedi.com)
  • To prevent infected cell lysis, recombinant replication deficiency virus has been developed as a gene delivery tool to replace wild-type adenovirus (recombinant AdV in "application" part). (genemedi.com)
  • Using cell-based assays, we show that co-expression of L1 and E2 results in enhanced transcription and virus origin-dependent DNA replication. (microbiologyresearch.org)
  • Upon co-expression in keratinocytes, L1 reduces nucleolar association of E2 protein, and when co-expressed with E1 and E2, L1 is partially recruited to viral replication factories. (microbiologyresearch.org)
  • A Single Amino Acid Switch in the Adenoviral DNA Binding Protein Abrogates Replication Center Formation and Productive Viral Infection. (leibniz-liv.de)
  • Adipocyte commitment of 3T3-L1 cells is required to support human adenovirus 36 productive replication concurrent with altered lipid and glucose metabolism. (leibniz-liv.de)
  • The Marek's Disease Virus Unique Gene MDV082 Is Dispensable for Virus Replication but Contributes to a Rapid Disease Onset. (leibniz-liv.de)
  • Viral DNA Binding Protein SUMOylation Promotes PML Nuclear Body Localization Next to Viral Replication Centers. (leibniz-liv.de)
  • ii) an attenuated, replication-defective orthopoxvirus (Modified Vaccinia virus Ankara), encoding for the neoantigens gene. (biosafety.be)
  • As a consequence, the synthesis and release of Th1- (T helper 1) and Th2- (T helper 2) type cytokines, and other inflammatory mediators from T-cells and mast cells are blocked and the expression of signals essential for the activation of inflammatory T-lymphocytes is inhibited. (medindex.am)
  • Description: The AAV Helper Free System produces recombinant AAV containing your gene of interest without the need to use a helper adenovirus. (ecceterra.fr)
  • This gene encodes one of three GA-binding protein transcription factor subunits which functions as a DNA-binding subunit. (wikipedia.org)
  • This subunit also shares identity with a subunit constituting the transcription factor E4TF1, responsible for expression of the adenovirus E4 gene. (wikipedia.org)
  • NAC-type plant-specific transcription factor genes encode proteins that play important roles in abiotic stress responses, as well as regulation of plant development. (metu.edu.tr)
  • In the current study, expression profiles of wheat NAC-type transcription factor genes, TaNAC69-1 and TtNAMB-2, were examined under drought, salt, cold, and heat stress conditions in wheat. (metu.edu.tr)
  • However, the binding rate of the transcription factor PPARγ to its target genes Acc, Adipoq, Lpin1 and Glut4 was enhanced, and thus increased the protein expression of P-FoxO1, PPARγ2, ACC, LPIN1, GLUT4 and ADIPOQ. (biomedcentral.com)
  • In this study, structural and functional aspects of adenovirus type 5 (Ad5) E4orf3 protein were analyzed by biophysical and biochemical methods. (metu.edu.tr)
  • In humans, 57 adenovirus serotypes have been identified and further divided into 7 subgroups (A-G). Most adenovirus-based vaccines are prepared using adenovirus type 5 (Ad5). (medicaltrend.org)
  • The human papillomavirus type 18 (HPV18) E2 gene product is a repressor of the HPV18 regulatory region in human keratinocytes. (microbiologyresearch.org)
  • A novel interaction between the human papillomavirus type 16 E2 and E1^E4 proteins leads to stabilization of E2. (microbiologyresearch.org)
  • This study aims to investigate the molecular mechanism of Adenovirus type 36 (Ad36) in adipocyte differentiation and glucolipid metabolism. (biomedcentral.com)
  • Differential Regulation of Cellular FAM111B by Human Adenovirus C Type 5 E1 Oncogenes. (leibniz-liv.de)
  • Human Adenovirus Type 5 Infection Leads to Nuclear Envelope Destabilization and Membrane Permeability Independently of Adenovirus Death Protein. (leibniz-liv.de)
  • Outbreak of Acute Respiratory Illness Associated with Human Adenovirus Type 4 at the U.S. Coast Guard Academy, 2019. (cdc.gov)
  • The neonatal heart exhibited the second highest levels of transgene expression among the organs examined. (hindawi.com)
  • There was an approximately 1500-fold difference in the transgene expression levels between the adult liver and heart, while the neonatal liver exhibited only an approximately 30-fold higher level of transgene expression than the neonatal heart. (hindawi.com)
  • In addition, non-replicating mRNAs can be used to produce RNA-related vaccines that involve mRNA sequences encoding pathogen-specific proteins (antigens) in host cells. (medicaltrend.org)
  • Cosmids are really great tools to construct recombinant adenoviruses because their minimum sizes (~39 kb) accommodates the 36 kb adenovirus genomes almost perfectly. (od260.com)
  • Such vaccines do not include other protein sequences that induce self-amplification of the inserted mRNA sequence. (medicaltrend.org)
  • The adenovirus sequences are flanked by two SfiI sites, which generate non-symmetrical sticky ends suitable for directional cloning with the other AdenoQuick2.0 plasmids (pAd1127, pAd1128, pAd1130, and their derivatives). (od260.com)
  • A 1.9 kb XbaI fragment encoding gp19K membrane protein and the adenovirus "death" protein (ADP, 11.6K) was deleted, and replaced with a multiple cloning site. (od260.com)
  • BACKGROUND: Although a human adenovirus (HAdV) vaccine is available for military use, officers-in-training are not routinely vaccinated. (cdc.gov)
  • Because of its chromosomal localization and ability to form heterodimers with other polypeptides, this gene may play a role in the Down syndrome phenotype. (wikipedia.org)
  • Conserved E1B-55K SUMOylation in different human adenovirus species is a potent regulator of intracellular localization. (leibniz-liv.de)
  • However, some of its proteins possess oncogenic potential and their presence comprises safety risks. (metu.edu.tr)
  • Comparison of the structure and DNA-binding properties of the E2 proteins from an oncogenic and a non-oncogenic human papillomavirus. (microbiologyresearch.org)
  • This work pinpoints E2 as a key protein in the initiation of HPV-induced cervical cancer and identifies the SAC as a target for oncogenic pathogens. (docksci.com)
  • For most serotypes, adenovirus infection is mediated by the high-affinity binding of the fiber-knob region to a receptor of target cell, named as the coxsackie-Ad receptor (CAR), which mainly determines the viral tropism [44]. (genemedi.com)
  • Infection process of adenovirus. (genemedi.com)
  • Protein-Protein Interactions Facilitate E4orf6-Dependent Regulation of E1B-55K SUMOylation in HAdV-C5 Infection. (leibniz-liv.de)
  • E1B-55K is a phosphorylation-dependent transcriptional and post-transcriptional regulator of viral gene expression in HAdV-C5 infection. (leibniz-liv.de)
  • SCID results from mutations in any of more than 15 known genes. (medscape.com)
  • Considering the effect of mutations in NA gene on the resistance to NAIs, it is important to monitor the possible emergence and dissemination of multidrug-resistant variants in the human population due to amino acid changes at NA gene as well as to develop novel NAIs. (ophrp.org)
  • Compared to their presence in strains of Ad7d, 2 restriction isolated in Korea during nationwide outbreaks from 1995 to fragments (8,400 and 2,650 bp) are lost in strains of Ad7l, 2000, the genetic variabilities of Ad7d and Ad7l were stud- which contain a new fragment equal in length to the sum ied by sequence analysis of hexon, fiber, E3, and E4 open of those 2 fragments. (cdc.gov)
  • Genomic and phylogenetic analysis of two guinea pig adenovirus strains recovered from archival lung tissue. (leibniz-liv.de)
  • Objective: The transfer of recombinant genes to donor organs may allow for novel therapeutic approaches to the challenges of acute and chronic rejection. (unipv.it)
  • As an autosomal recessive monogenic disease, MSUD represents an ideal target for liver-directed gene therapy since clinical OLT data suggests that incomplete restoration of liver BCKD enzyme activity (representing 9-13% of body BCKD activity 10 ) is fully therapeutic. (nature.com)
  • This constitutes a strong rationale for testing liver gene transfer as a therapeutic option for MSUD. (nature.com)
  • Bughio, F., M. Umashankar, J. Wilson, and F. Goodrum, 'Human Cytomegalovirus UL135 and UL136 Genes Are Required for Postentry Tropism in Endothelial Cells. (arizona.edu)
  • Methods: Gene transfer to human endothelial cells, porcine vascular smooth muscle cells and cultured rat thoracic aortas was examined. (unipv.it)
  • Hancock, M. H., J. Mitchell, F. D. Goodrum, and J. A. Nelson, 'Human Cytomegalovirus miR-US5-2 Downregulation of GAB1 Regulates Cellular Proliferation and Expression through Modulation of Epidermal Growth Factor Receptor Signaling Pathways. (arizona.edu)
  • In particular, we will discuss the modifications in intrinsic and extrinsic apoptotic pathways caused by proteins encoded by HPV early genes. (mdpi.com)
  • Apoptosis-inducing factor (AIF), named for its involvement in cell death pathways, is a mitochondrial protein that regulates metabolic homeostasis. (biomedcentral.com)
  • result suggests fiber and E4 ORF 6/7 peptides participate in the evolution of Ad7. (cdc.gov)
  • Fiber and E4 ORF 6/7 peptides were chosen for study because of close proximity to a mutation site at 0.93 map units, and hexon and E3 peptides were chosen because of their reported genetic heterogeneities. (cdc.gov)
  • The aggregation of both amyloid beta (Abeta) peptides extracellularly and Tau proteins intracellularly plays key roles in the pathological consequences of AD, which lead to cholinergic neurodegeneration and eventually death. (inra.fr)
  • Rak, M. A., J. Buehler, S. Zeltzer, J. Reitsma, B. Molina, S. Terhune, and F. Goodrum, 'Human Cytomegalovirus UL135 Interacts with Host Adaptor Proteins To Regulate Epidermal Growth Factor Receptor and Reactivation from Latency. (arizona.edu)
  • Desogestrel binds intracellular progesterone receptors in progesterone responsive tissue and the resultant complex interacts with DNA and results in either gene transcription or gene repression. (medindex.am)
  • Phylogenetic trees based on hexon, fiber, and E4 sug- early region 4 (E4) (unpub. (cdc.gov)
  • Subsequently, the interaction of E4orf3 with four different proteins, DNA-PK, Aup1, E1B-55 kDa and E4orf6 was analyzed in detail by GST-pulldown technique. (metu.edu.tr)
  • CAR receptor-fiber-knob adenovirus interaction and internalization process [46]. (genemedi.com)
  • This phenotype is associated with interaction of E2 with the Mitotic Checkpoint Complex (MCC) proteins Cdc20, MAD2 and BUBR1. (docksci.com)
  • RESULTS: Six risk genes for SCZ (LINC01795, DDHD2, SBNO1, KCNG2, SEMA7A, and RUFY1) involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response. (inra.fr)
  • In gene therapy for congenital disorders, treatments during neonate and infant stages are promising. (hindawi.com)
  • Radical treatment during neonate or infant stage is required for these patients, and gene therapy is a promising candidate for such treatment. (hindawi.com)
  • There are several advantages to gene therapy in neonates and infants. (hindawi.com)
  • With the advances in BMT and gene therapy, patients now have a better likelihood of developing a functional immune system in a previously lethal genetic disease. (medscape.com)
  • What is Gene Therapy? (familymednews.com)
  • Home » Health Problems » What is Gene Therapy? (familymednews.com)
  • Gene therapy is a form of therapy that involves inserting one or more corrective genes that have been designed in the laboratory, into the genetic material of a patient's cells to cure a genetic disease. (familymednews.com)
  • Gene therapy is still in the experimental stages and its use is therefore not yet widespread. (familymednews.com)
  • One of the first hurdles of gene therapy is successful introduction of the corrected gene into the human cells. (familymednews.com)
  • Here we show efficacy of gene therapy for MSUD demonstrating its potential for clinical translation. (nature.com)
  • Human Gene Therapy. (wustl.edu)
  • Once introduced, the gene needs to be incorporated into the genetic material of those cells. (familymednews.com)
  • Immunoblot analysis was used to determine relative protein quantities within cells. (biomedcentral.com)
  • Recombinant Human IFN-beta Protein Binding Activity Recombinant Human IFN‑ beta (Catalog # 8499-IF) exhibits anti-viral activity in HeLa human cervical epithelial carcinoma cells infected with encephalomyocarditis (EMC) virus. (bio-techne.com)
  • Description: Luciferase (firefry) expression stable cell line in Hela cells with Blasticidin marker. (ecceterra.fr)
  • Up on invasion, the Receptor Binding Domain (RBD) of Spike protein plays a crucial role in the entry of the virus into the host cell. (ajmb.org)
  • The expression of the new gene or genes can then alter the DNA or RNA transcript used to synthesis proteins and therefore correct the disease. (familymednews.com)
  • Archival gene expression data revealed a modest elevation of AIF transcript levels in subsets of pancreatic tumor specimens, suggesting a possible role in disease progression. (biomedcentral.com)
  • A liver-specific promoter for firefly luciferase expression conferred a more than 100-fold higher luciferase expression in the liver relative to the other organs. (hindawi.com)
  • The binding rate of FoxO1, PPARγ and its target gene promoter was detected using ChIP. (biomedcentral.com)
  • While the use of a ubiquitous promoter fully and sustainably rescued the disease (long-term survival, normal phenotype and correction of biochemical abnormalities), liver-specific expression of BCKDHA led to partial, though sustained rescue. (nature.com)
  • Expression cassettes inserted into the multiple cloning site should contain a promoter and poly(A) signal, but no intron or splice site. (od260.com)
  • Description: Pre-made optional inducible lentiviral shRNA expression particles under human H1 promoter, containing a hairpin insert that should not knockdown any known human or mouse gene. (cell-ess.com)
  • The expression of cyclin-dependent kinase inhibitors was profoundly affected with early activation and then repression of p21 cip1/waf1 and persistent activation of both p27 kip1 and p57 kip2 , whereas genes involved in cell survival and proliferation were suppressed. (aacrjournals.org)
  • They include the major genes that are present in all PV, namely the early genes E1 and E2 as well as the late genes L1 and L2. (creative-biolabs.com)
  • Besides the major ORF, additional early genes such as E4 and the viral oncogenes E6 and E7 are present in many PV, and E5 is encoded in, for example, genital Alpha-PV types. (creative-biolabs.com)
  • If the treatment is successful, the new gene will make a functional protein. (familymednews.com)
  • GA-binding protein alpha chain is a protein that in humans is encoded by the GABPA gene. (wikipedia.org)
  • Adenovirus-based vaccines can induce antibody-mediated and T-cell- mediated immune responses. (medicaltrend.org)
  • KIR3DS1 directs NK cell-mediated protection against human adenovirus infections. (leibniz-liv.de)
  • In RNA vaccines, mRNA is used as a template for the endogenous synthesis of the target pathogenic protein (antigen). (medicaltrend.org)
  • This study was designed to examine the effect of temperature on the efficiency of adenovirus-mediated gene transfer. (unipv.it)
  • 0.001 vs. 10 degrees C). Conclusions: The present study demonstrates that the efficiency of adenovirus-mediated gene transfer is significantly reduced at lower temperatures. (unipv.it)
  • Although macrophages play a role in inflammation and repair, their specific roles are related to the expression and function of their surface receptors [ 4 - 6 ]. (thno.org)
  • The need for cold preservation of donor organs may render efficient adenovirus-mediated gene transfer more difficult in the transplantation setting. (unipv.it)