gebhart/patrepeval huggingface dataset:
VarScan 2: Somatic mutation and copy number alteration discovery in cancer by exome sequencing (2012)

Cancer is a disease driven by genetic variation and mutation. Exome sequencing can be utilized for discovering these variants and mutations across hundreds of tumors. Here we present an analysis tool, VarScan 2, for the detection of somatic mutations and copy number alterations (CNAs) in exome data from tumor-normal pairs. Unlike most current approaches, our algorithm reads data from both samples simultaneously; a heuristic and statistical algorithm detects sequence variants and classifies them by somatic status (germline, somatic, or LOH); while a comparison of normalized read depth delineates relative copy number changes. We apply these methods to the analysis of exome sequence data from 151 high-grade ovarian tumors characterized as part of the Cancer Genome Atlas (TCGA). We validated some 7790 somatic coding mutations, achieving 93% sensitivity and 85% precision for single nucleotide variant (SNV) detection. Exome-based CNA analysis identified 29 large-scale alterations and 619 focal events per tumor on average. As in our previous analysis of these data, we observed frequent amplification of oncogenes (e.g., CCNE1, MYC) and deletion of tumor suppressors (NF1, PTEN, and CDKN2A). We searched for additional recurrent focal CNAs using the correlation matrix diagonal segmentation (CMDS) algorithm, which identified 424 significant events affecting 582 genes. Taken together, our results demonstrate the robust performance of VarScan 2 for somatic mutation and CNA detection and shed new light on the landscape of genetic alterations in ovarian cancer.
Ras‐effector interactions, the problem of specificity (1995)

Ras plays the role of a molecular switch in many cellular signalling pathways. The Raf-kinase has been identified as the direct target molecule of Ras in mammalian cells. However, in recent reports other proteins have been characterised as putative Ras effectors which have neither a functional nor a structural relationship to each other. In addition it has been shown that also other members of the Ras family like Rap and R-Ras can interact with some of these proteins. To address the problem of specificity and of biological relevance of the interactions, they have to be carefully quantified and the cellular localisation of the proteins involved taken into account.
Effect of initiation factor eIF-5A depletion on protein synthesis and proliferation of Saccharomyces cerevisiae. (1994)

Eukaryotic translation initiation factor eIF-5A (formerly eIF-4D) is thought to function in protein synthesis by promoting synthesis of the first peptide bond because it stimulates methionyl-puromycin formation in vitro. eIF-5A is encoded by two genes (TIF51A and TIF51B) in Saccharomyces cerevisiae; the protein and its hypusine modification are essential for cell viability. To analyze the factor's function in vivo, we expressed from the repressible GAL promoter a functional but unstable eIF-5A fusion protein (R-eIF-5A) with an NH2-terminal arginine which is subject to rapid turnover through the NH2-terminal end rule proteolytic pathway. When the conditional mutant strain is shifted from galactose to glucose medium, the rapid disappearance of R-eIF-5A protein occurs within one generation, causing an immediate inhibition of cell growth. However, eIF-5A-depleted cells synthesize protein at about 70% of the wild type rate and exhibit only a slight change in polysome profiles reflecting a subtle defect in a late step of translation initiation. These results suggest that the activity of eIF-5A may not be absolutely essential for general protein synthesis. Rather, eIF-5A may be selectively required for translation of certain mRNAs and/or may be involved in some other aspect of cell metabolism.
Binding of ethidium bromide to double-stranded ribonucleic acid (1973)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBinding of ethidium bromide to double-stranded ribonucleic acidR. J. Douthart, J. P. Burnett, F. W. Beasley, and B. H. FrankCite this: Biochemistry 1973, 12, 2, 214–220Publication Date (Print):January 1, 1973Publication History Published online1 May 2002Published inissue 1 January 1973https://pubs.acs.org/doi/10.1021/bi00726a006https://doi.org/10.1021/bi00726a006research-articleACS PublicationsRequest reuse permissionsArticle Views355Altmetric-Citations62LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Accelerated aging in the tumor microenvironment (2011)

Cancer is thought to be a disease associated with aging. Interestingly, normal aging is driven by the production of ROS and mitochondrial oxidative stress, resulting in the cumulative accumulation of DNA damage. Here, we discuss how ROS signaling, NFκB- and HIF1-activation in the tumor microenvironment induces a form of "accelerated aging," which leads to stromal inflammation and changes in cancer cell metabolism. Thus, we present a unified model where aging (ROS), inflammation (NFκB) and cancer metabolism (HIF1), act as co-conspirators to drive autophagy ("self-eating") in the tumor stroma. Then, autophagy in the tumor stroma provides high-energy "fuel" and the necessary chemical building blocks, for accelerated tumor growth and metastasis. Stromal ROS production acts as a "mutagenic motor" and allows cancer cells to buffer-at a distance-exactly how much of a mutagenic stimulus they receive, further driving tumor cell selection and evolution. Surviving cancer cells would be selected for the ability to induce ROS more effectively in stromal fibroblasts, so they could extract more nutrients from the stroma via autophagy. If lethal cancer is a disease of "accelerated host aging" in the tumor stroma, then cancer patients may benefit from therapy with powerful antioxidants. Antioxidant therapy should block the resulting DNA damage, and halt autophagy in the tumor stroma, effectively "cutting off the fuel supply" for cancer cells. These findings have important new implications for personalized cancer medicine, as they link aging, inflammation and cancer metabolism with novel strategies for more effective cancer diagnostics and therapeutics.
Deletion of heart‐type cytochrome c oxidase subunit 7a1 impairs skeletal muscle angiogenesis and oxidative phosphorylation (2012)

Oxidative metabolism is needed for sustained skeletal muscle function. A key component of such metabolism is cytochrome c oxidase, the 13-subunit terminal complex of the mitochondrial electron transport chain. We used mice null for one of the two isoforms of Cox subunit 7a, heart/skeletal muscle-specific Cox7a1, to examine the cellular and functional responses of muscle adaptation in response to mitochondrial dysfunction. Specifically we determined if deletion of Cox7a1 would (1) limit exercise capacity, and (2) alter genes responsible for skeletal muscle capillarity and mitochondrial biogenesis. Sixteen male mice (Cox7a1 null mice, n = 8, and littermate controls, n = 8) performed incremental and run-to-exhaustion treadmill tests. The hindlimb muscles for both groups were analysed. The results indicated that capillary indices were reduced (by 30.7–44.9%) in the Cox7a1 null mice relative to controls. In addition, resting ATP levels and Cox specific activity were significantly reduced (>60%) in both glycolytic and oxidative muscle fibre types despite an increase in a major regulator of mitochondrial biogenesis, PGC-1β. These changes in the skeletal muscle resulted in exercise intolerance for the Cox7a1 null mice. Thus, our data indicate that deletion of the Cox7a1 isoform results in reduced muscle bioenergetics and hindlimb capillarity, helping to explain the observed impairment of muscle structure and function.
Synthesis of enantiopure α-deuteriated Boc-L-amino acids (1996)

An alternative scheme for the synthesis of enantiopure α-deuteriated amino acids from a common intermediate is presented. Methyl bis(methylsulfanyl)methylene[2,2-2H2]glycinate was prepared in a mixture of MeOD and D2O with a catalytic amount of Na2CO3 and attached to (2R)-bornane-10,2-sultam. Alkylation of the corresponding enolate provided intermediates which after careful purification were first deprotected on nitrogen and then cleaved from the auxiliary to give deuteriated α-amino acids of very high purity ( > 99% ee and > 98% D). These were directly converted into the corresponding Boc-L-[2-2H]-Ala, -Leu, -Phe and -(O-Bzl)Tyr derivatives, suitable for application in peptide synthesis. Boc-[2,2-2H2]Gly was also prepared.
Degenerate four-wave mixing spectroscopy based on two-dimensional femtosecond pulse shaping (2004)

We report noncollinear, degenerate four-wave mixing experiments that employ a new device based on two-dimensional femtosecond pulse shaping that delays and modulates all incident fields. Heterodyne detection is easily implemented due to the full phase stability of the device.
Imitation learning for locomotion and manipulation (2007)

Decision making in robotics often involves computing an optimal action for a given state, where the space of actions under consideration can potentially be large and state dependent. Many of these decision making problems can be naturally formalized in the multiclass classification framework, where actions are regarded as labels for states. One powerful approach to multiclass classification relies on learning a function that scores each action; action selection is done by returning the action with maximum score. In this work, we focus on two imitation learning problems in particular that arise in robotics. The first problem is footstep prediction for quadruped locomotion, in which the system predicts next footstep locations greedily given the current four-foot configuration of the robot over a terrain height map. The second problem is grasp prediction, in which the system must predict good grasps of complex free-form objects given an approach direction for a robotic hand. We present experimental results of applying a recently developed functional gradient technique for optimizing a structured margin formulation of the corresponding large non-linear multiclass classification problems.
Fly pushing : the theory and practice of Drosophila genetics (1996)

The basics of doing a cross isolating new variants mapping synthesizing specific genotypes analysis of mutations I - characteristics of the allele analysis of mutations II - mosiacs you're on your own.
Risk Factors for Vascular Dementia and Alzheimer Disease (2004)

Alzheimer disease and vascular cognitive impairment are important causes of cognitive decline in the elderly. It has now been shown that vascular risk factors have measurable negative effects on the brain and are associated with cognitive impairment. We review vascular factors that might be responsible to cognitive decline in Alzheimer disease and vascular cognitive impairment and the corresponding interventions that might prevent cognitive impairment as we age.
Ser45 plays an important role in managing both the equilibrium and transition state energetics of the streptavidin—biotin system (2000)

The contribution of the Ser45 hydrogen bond to biotin binding activation and equilibrium thermodynamics was investigated by biophysical and X-ray crystallographic studies. The S45A mutant exhibits a 1,700-fold greater dissociation rate and 907-fold lower equilibrium affinity for biotin relative to wild-type streptavidin at 37 degrees C, indicating a crucial role in binding energetics. The crystal structure of the biotin-bound mutant reveals only small changes from the wild-type bound structure, and the remaining hydrogen bonds to biotin retain approximately the same lengths. No additional water molecules are observed to replace the missing hydroxyl, in contrast to the previously studied D128A mutant. The equilibrium deltaG degrees, deltaH degrees, deltaS degrees, deltaC degrees(p), and activation deltaG++ of S45A at 37 degrees C are 13.7+/-0.1 kcal/mol, -21.1+/-0.5 kcal/mol, -23.7+/-1.8 cal/mol K, -223+/-12 cal/mol K, and 20.0+/-2.5 kcal/mol, respectively. Eyring analysis of the large temperature dependence of the S45A off-rate resolves the deltaH++ and deltaS++ of dissociation, 25.8+/-1.2 kcal/mol and 18.7+/-4.3 cal/mol K. The large increases of deltaH++ and deltaS++ in the mutant, relative to wild-type, indicate that Ser45 could form a hydrogen bond with biotin in the wild-type dissociation transition state, enthalpically stabilizing it, and constraining the transition state entropically. The postulated existence of a Ser45-mediated hydrogen bond in the wild-type streptavidin transition state is consistent with potential of mean force simulations of the dissociation pathway and with molecular dynamics simulations of biotin pullout, where Ser45 is seen to form a hydrogen bond with the ureido oxygen as biotin slips past this residue after breaking the native hydrogen bonds.
The Mammalian Gastric Parietal Cell In Vitro (1984)

To summarize the metabolic status of the parietal cell: There does not seem to be a close relationship between cellular ATP levels and acid secretion. Acid secretion is absolutely dependent on oxygen, and oxygen consumption will increase in direct proportion to the rate of acid secretion. However, the absolute rate of respiration is not closely related to the formation of acid in the subtissue systems. Acid formation can be driven directly by addition of ATP in permeabilized glands, even under apparent anoxic conditions. This correlates well with the presence of the gastric (H+, K+)-ATPase in the parietal cell. If ATP is the main source of energy for the acid secretion, it is quite possible that the relevant ATP pool is compartmentalized and that the content in this pool has a high turnover rate, whereas the ATP used for other cellular functions would be spared. A pure redox mechanism in the gastric mucosa is not possible. However, it remains to be shown that a redox component is not involved in the secretory process. The acid formation measured by AP accumulation in the gastric glands is not an indication of secretory rate. Thus even though ATP appears to restore acid formation in permeabilized glands, this effect has been mainly studied in nonstimulated systems. A detailed study over the energy requirement in the permeabilized resting cell remains to be done. In the mammals we only have information so far about the piglet and the rabbit in terms of substrate preference. The differences between the two could either be due to species or age difference. In both mammals and amphibia, there is no evidence to suggest that acid secretion results in an increase in oxygen consumption purely due to a state IV to III transition of mitochondrial respiration. Rather, increased Krebs-cycle activity would appear to be the major metabolic result of stimulation.
Neurotoxins Affecting Neuroexocytosis (2000)

Nerve terminals are specific sites of action of a very large number of toxins produced by many different organisms. The mechanism of action of three groups of presynaptic neurotoxins that interfere directly with the process of neurotransmitter release is reviewed, whereas presynaptic neurotoxins acting on ion channels are not dealt with here. These neurotoxins can be grouped in three large families: 1) the clostridial neurotoxins that act inside nerves and block neurotransmitter release via their metalloproteolytic activity directed specifically on SNARE proteins; 2) the snake presynaptic neurotoxins with phospholipase A(2) activity, whose site of action is still undefined and which induce the release of acethylcholine followed by impairment of synaptic functions; and 3) the excitatory latrotoxin-like neurotoxins that induce a massive release of neurotransmitter at peripheral and central synapses. Their modes of binding, sites of action, and biochemical activities are discussed in relation to the symptoms of the diseases they cause. The use of these toxins in cell biology and neuroscience is considered as well as the therapeutic utilization of the botulinum neurotoxins in human diseases characterized by hyperfunction of cholinergic terminals.
Ground Vehicle Navigation Using Magnetic Field Variation (2012)

The Polish versions of both measures show satisfactory psychometric properties, being suitable for the evaluation of the levels of empowerment in nurses, midwives and patients. Med Pr. 2020;71(5):551-68.
A Novel Reaction Medium: Perfluorocarbon Fluids (1993)

The use of perfluorocarbon (PFC) fluids such as perfluorinated alkanes and alkylamines as inert medium for organic reactions is demonstrated with advantages summarized. PFC fluids have been found to be very useful in organic reactions where a medium is needed for refluxing and for separating a low boiling component, or where an extremely nonpolar/inert medium is required for reactions carried out under vigorous conditions. The PFC fluids are not miscible with most organic compounds and therefore offer good separatory properties that common organic solvents do not have.
Role of Chitin and Chitinase/Chitinase-Like Proteins in Inflammation, Tissue Remodeling, and Injury (2011)

The 18 glycosyl hydrolase family of chitinases is an ancient gene family that is widely expressed from prokaryotes to eukaryotes. In mammals, despite the absence of endogenous chitin, a number of chitinases and chitinase-like proteins (C/CLPs) have been identified. However, their roles have only recently begun to be elucidated. Acidic mammalian chitinase (AMCase) inhibits chitin-induced innate inflammation; augments chitin-free, allergen-induced Th2 inflammation; and mediates effector functions of IL-13. The CLPs BRP-39/YKL-40 (also termed chitinase 3-like 1) inhibit oxidant-induced lung injury, augments adaptive Th2 immunity, regulates apoptosis, stimulates alternative macrophage activation, and contributes to fibrosis and wound healing. In accord with these findings, levels of YKL-40 in the lung and serum are increased in asthma and other inflammatory and remodeling disorders and often correlate with disease severity. Our understanding of the roles of C/CLPs in inflammation, tissue remodeling, and tissue injury in health and disease is reviewed below.
Advanced glycation end product in familial amyloidotic polyneuropathy (FAP) (2000)

The immunoreactivity for the AGE antibody suggests that AGE may be involved in fibril formation in FAP.
Unmasking the chemistry of DNA cleavage by the esperamicins: modulation of 4'-hydrogen abstraction and bistranded damage by the fucose-anthranilate moiety (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTUnmasking the chemistry of DNA cleavage by the esperamicins: modulation of 4'-hydrogen abstraction and bistranded damage by the fucose-anthranilate moietyDonna F. Christner, Bruce L. Frank, John W. Kozarich, JoAnne Stubbe, Jerzy Golik, Terrence W. Doyle, Ira E. Rosenberg, and Bala KrishnanCite this: J. Am. Chem. Soc. 1992, 114, 23, 8763–8767Publication Date (Print):November 1, 1992Publication History Published online1 May 2002Published inissue 1 November 1992https://pubs.acs.org/doi/10.1021/ja00049a002https://doi.org/10.1021/ja00049a002research-articleACS PublicationsRequest reuse permissionsArticle Views102Altmetric-Citations53LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Candidate reference method for total thyroxine in human serum: use of isotope-dilution liquid chromatography-mass spectrometry with electrospray ionization. (2002)

This well-characterized LC/MS-ESI method for total serum thyroxine with a theoretically sound approach, demonstrated good accuracy and precision, and low susceptibility to interferences qualifies as a candidate reference method. Use of this reference method as an accuracy base may reduce the apparent biases in routine methods along with the high interlaboratory imprecision.
PET/CT today and tomorrow. (2004)

Combined PET/CT scanners represent an important evolution in technology that is helping to bring molecular imaging to the forefront in cancer diagnosis, staging, and therapy monitoring.
DNA sequences and quaternary cyclic codes (2002)

There is a need to find generalized or universal tags for multiplex genome analysis. We use sets of reverse complement cyclic codes to generate DNA codes that can be used for DNA tags. These tags are placed on DNA chips and connect with the capture tags floating in a solution. The capture tags attach themselves to these generalized codes and give us much information about an individual strand. We show that the reverse complement cyclic and shortening cyclic codes are suitable for this application. We found theoretical bounds of parameters for these codes and the parameters and the generator polynomials of these codes for length up to 41.
Genomic profiling of short- and long-term caloric restriction effects in the liver of aging mice (2001)

We present genome-wide microarray expression analysis of 11,000 genes in an aging potentially mitotic tissue, the liver. This organ has a major impact on health and homeostasis during aging. The effects of life- and health-span-extending caloric restriction (CR) on gene expression among young and old mice and between long-term CR (LT-CR) and short-term CR (ST-CR) were examined. This experimental design allowed us to accurately distinguish the effects of aging from those of CR on gene expression. Aging was accompanied by changes in gene expression associated with increased inflammation, cellular stress, and fibrosis, and reduced capacity for apoptosis, xenobiotic metabolism, normal cell-cycling, and DNA replication. LT-CR and just 4 weeks of ST-CR reversed the majority of these changes. LT-CR produced in young mice a pattern of gene expression that is a subset of the changes found in old LT-CR mice. It is possible that the early changes in gene expression, which extend into old age, are key to the life- and health-span-extending effects of CR. Further, ST-CR substantially shifted the "normo-aging" genomic profile of old control mice toward the "slow-aging" profile associated with LT-CR. Therefore, many of the genomic effects of CR are established rapidly. Thus, expression profiling should prove useful in quickly identifying CR- mimetic drugs and treatments.