We identified a lipid synthesis enzyme [acetyl CoA carboxylase 1 (ACC1)] as a synthetic lethal target in mutant IDH1 (mIDH1), but not mIDH2, cancers. (lu.se)
In response to DNA damage, a synthetic lethal relationship exists between the cell cycle checkpoint kinase MK2 and the tumor suppressor p53. (nature.com)
Here, we describe the concept of augmented synthetic lethality (ASL): depletion of a third gene product enhances a pre-existing synthetic lethal combination. (nature.com)
Delivery of siRNA-peptide nanoplexes co-targeting MK2 and XPA to pre-existing p53-deficient tumors in a highly aggressive, immunocompetent mouse model of lung adenocarcinoma improves long-term survival and cisplatin response beyond those of the synthetic lethal p53 mutant/MK2 combination alone. (nature.com)
The concept has now been extended to embrace synthetic lethal drug sensitivity, such as that observed with PARP inhibitors in combination with DNA-damaging chemotherapy in a variety of BRCA defective tumors 10 . (nature.com)
Because BRCA mutations are observed in fewer than 10% of cancer patients (cBioPortal: 6.7%) 11 , 12 , 13 the identification of additional genes that share synthetic lethal sensitivity relationships with mutated oncogenes or tumor suppressors would greatly enhance the implementation of tumor cell-specific synthetic lethal sensitivity to improve an anticancer therapeutic response. (nature.com)
A second line of research is aimed at identifying synthetic lethal genetic interactions that can exploited for cancer therapy. (cancer.gov)
Doses2
However, we know that radiation at high doses can be lethal. (cdc.gov)
Very rarely you may experience increased sensitivity to pain despite the fact that you are taking increasing doses of these tablets (hyperalgesia). (who.int)
Tumor2
Isolated EOC tumor cells obtained at surgery were investigated for their sensitivity to seven standard cytotoxic drugs and nine TKIs using a short‑term fluorescent microculture cytotoxicity assay (FMCA). (spandidos-publications.com)
One example is the conserved Drosophila tumor-suppressor protein Lethal giant larvae (Lgl). (biologists.com)
Toxin3
Anthrax toxin is composed of a cell-binding protein, known as protective antigen (PA), and two enzyme components, called edema factor (EF) and lethal factor (LF). (wikipedia.org)
Anthrax toxin is a mixture of three protein components: (i) protective antigen (PA), (ii) edema factor (EF), and (iii) lethal factor (LF). (wikipedia.org)
The former combination is called edema toxin, and the latter combination is called lethal toxin. (wikipedia.org)
Humans4
Kinetoplastid parasites cause lethal diseases in humans and animals. (gla.ac.uk)
Non Lethal Projectiles such as tear gas canisters use a chemical mechanism to cause visual disruption, pain and cognitive confusion among a target group of humans to disorient them. (pharmiweb.com)
Non Lethal Projectiles provide an alternative to the use of conventional ammunition, the application of which often results in death or serious permanent disabilities to humans. (pharmiweb.com)
Botulinum toxin's median lethal dose (LD50) has been determined across several animal species but not in humans. (medscape.com)
Fatalities4
Also, in conflict areas where military personnel are involved in peacekeeping missions, non lethal projectiles greatly reduce human fatalities. (pharmiweb.com)
Although there have also been fatalities reported resulting from the use of non lethal projectiles, a big reason of this has been lack of enough training for personnel specialized weapons with non lethal projectiles. (pharmiweb.com)
Moreover, efforts are underway to further reduce the number of unwanted fatalities through better design of non lethal projectiles. (pharmiweb.com)
Thus the growing need for crowd control, violent crime reduction and the increasing sensitivity of nations to human fatalities at the hands of law enforcement is driving the market for non lethal projectiles. (pharmiweb.com)
Genes2
SL originally described a relationship between two genes, where alteration of either gene alone results in viable cells, but alteration (mutation, loss, or inhibition) of both genes simultaneously was lethal. (nature.com)
The laboratory uses CRISPR/Cas9-based screening approaches to identify genes that modulate cellular sensitivity to radiotherapy and chemotherapy. (cancer.gov)
Species2
In addition, we have shown that amphibian species differed in their sensitivity to direct flooding effects and indirect changes in the fish community and wetland-specific conductance, which led to variable responses across the community. (usgs.gov)
Yet BoNT-A sensitivity varies among different species. (medscape.com)
Evidence3
They discussed ways to identify and address suicide risk, the evidence base for suicide prevention, access to lethal means, impact of media and the value of partnerships. (aap.org)
Although supporters of lethal injection believe the prisoner dies painlessly, there is mounting evidence that prisoners may have experienced excruciating pain during their executions.This should not be surprising given that corrections agencies have not taken the steps necessary to ensure a painless execution. (hrw.org)
We provide evidence that the primary effects of flooding on the amphibian community were through indirect mechanisms via changes in the composition of the sympatric fish community that may have had lethal (i.e. through direct predation) or non-lethal (i.e. through direct or indirect competitive interactions) effects. (usgs.gov)
Vivo1
Frequency analysis of cytolytic T cell precursors (CTL-P) generated in vivo during lethal rabies infection of mice. (uni-muenchen.de)
Enhances1
TLK activity is regulated by the DNA damage response and their depletion provokes innate immune signaling and enhances cellular sensitivity to DNA damaging agents. (cancer.gov)
Mutation1
Last, functional analysis in Xenopus oocytes revealed that the I321T mutation might reduce GluCl3 sensitivity to abamectin, but also suggested that all three T. urticae Rdls are affected by abamectin. (ugent.be)
Food allergies1
While these are very real and very lethal reactions to food allergies, not all autoimmune responses are that immediate. (foodzie.com)
Factor1
Individual sensitivity to radiation is also a factor. (cdc.gov)
Suicide1
Suicide is death caused by an act of self-harm that is intended to be lethal. (msdmanuals.com)
Reduce2
City staff have created a list of non-lethal deer management techniques that allow residents to reduce deer impacts on their property. (a2gov.org)
Reduce youth access to lethal means like firearms. (aap.org)
Behavior1
They viewed the boys behavior as an expression of primitive violence a lethal masculinity straight from The Lord of the Flies. (freerepublic.com)
Temperature2
We bridge this gap by identifying the key measures of heat stress, considering both air temperature and near-surface humidity, in characterizing the climate sensitivity of electricity demand at a national scale. (ufz.de)
Our results establish that air temperature is a necessary but not sufficient variable for adequately characterizing the climate sensitivity of cooling load, and that near-surface humidity plays an equally important role. (ufz.de)
Drug5
Because cancer therapeutics often target DNA synthesis or repair, we asked if mutational signatures make useful markers of drug sensitivity. (nature.com)
Signatures of prior exposures to DNA damaging agents - including chemotherapy - tend to associate with drug resistance, while signatures of deficiencies in DNA repair tend to predict sensitivity towards particular therapeutics. (nature.com)
Because mutational signatures describe the state of the DNA repair machinery of a cancer cell, they may be able to serve as a drug sensitivity marker. (nature.com)
Oklahoma's three-drug protocol was copied by Texas, which in 1982 was the first state to execute a man by lethal injection. (hrw.org)
Even when permitted by statute to consider other drug options, they have not revised their choice of lethal drugs, despite new developments in and knowledge about anesthesia and lethal chemical agents. (hrw.org)
Assessment1
This intimate partner violence (IPV) risk assessment is an 11-item version of the Danger Assessment (DA) that was designed to be user-friendly for first responders and to maximize sensitivity. (ojp.gov)
High4
At very high levels approaching lethal levels the curve become asymptotic. (whale.to)
The high sensitivity and low specificity should be considered carefully when determining whether the Lethality Screen is appropriate for particular areas of practice with IPV survivors and/or perpetrators. (ojp.gov)
Non Lethal Projectiles such as rubber or plastic bullets or pellets cause high physical impact on targets, which may also cause physical injuries of a temporary nature. (pharmiweb.com)
Finally, the trap is constructed entirely out of high temper stainless steel wire, so unlike other gopher traps, The Gophinator will not lose power or trigger sensitivity due to rust. (wildlifecontrolsupplies.com)
Combination1
a lethal combination that could significantly increase morbidity and mortality rates during extreme heat events. (ufz.de)
Cancer1
Breast cancer is one of the commonest and most lethal malignancies in women worldwide. (karger.com)
Requires1
Interference can be reduced by using MS3-based quantification, but this reduces sensitivity and requires specialized instrumentation. (biorxiv.org)
Local1
The local response to lethal infection with rabies virus was used as a model system that is not accessible to analysis by secondary activation in vitro. (uni-muenchen.de)
Standard1
In the standard method of lethal injection used in the United States, the prisoner lies strapped to a gurney, a catheter with an intravenous line attached is inserted into his vein, and three drugs are injected into the line by executioners hidden behind a wall. (hrw.org)
Results1
This increased sensitivity results in ~65% more proteins quantified compared to TMTPro-MS3 and even slightly outperforms TMTPro-MS2. (biorxiv.org)
Effect1
Blood cyanide concentrations were generally higher in males than in females, which may explain the higher sensitivity of males to the lethal effect of methacrylonitrile. (nih.gov)
Read1
Considering these aspects of the Non Lethal Projectiles, the study of the trends and forecasts of the Non Lethal Projectiles market becomes an important read. (pharmiweb.com)
Form1
More palatable to the general public, lethal injection has become the most prevalent form of execution in the United States. (hrw.org)
Police1
Video has repeatedly shown that these lethal police tactics could be avoided, while polls are highlighting America's call for widespread, systematic changes to a criminal justice system that has failed to attain the level of transparency and accountability necessary in a democratic society. (brookings.edu)
Pain2
In emergency situations where force in required to be used, Non Lethal Projectiles fired from special guns or deployed by human force inflict pain on impact with targets. (pharmiweb.com)
Non Lethal Projectiles inflict enough pain or have enough impact on the human targets so as to temporarily incapacitate them, or restrain them from fleeing and or retaliating. (pharmiweb.com)
General1
Con ese fin, se examinan los estudios sobre el riesgo de contaminación y la prevalencia de los patógenos en general, así como los estudios recientes sobre el Covid-19 y sus reflejos individuales y psicosociales. (bvsalud.org)
State1
The history of lethal injection executions in the United States reveals no such care on the part of state legislators and corrections officials. (hrw.org)