gebhart/patrepeval huggingface dataset:
Evaluating potential drug targets through human loss-of-function genetic variation (2019)

Abstract Human genetics has informed the clinical development of new drugs, and is beginning to influence the selection of new drug targets. Large-scale DNA sequencing studies have created a catalogue of naturally occurring genetic variants predicted to cause loss of function in human genes, which in principle should provide powerful in vivo models of human genetic “knockouts” to complement model organism knockout studies and inform drug development. Here, we consider the use of predicted loss-of-function (pLoF) variation catalogued in the Genome Aggregation Database (gnomAD) for the evaluation of genes as potential drug targets. Many drug targets, including the targets of highly successful inhibitors such as aspirin and statins, are under natural selection at least as extreme as known haploinsufficient genes, with pLoF variants almost completely depleted from the population. Thus, metrics of gene essentiality should not be used to eliminate genes from consideration as potential targets. The identification of individual humans harboring “knockouts” (biallelic gene inactivation), followed by individual recall and deep phenotyping, is highly valuable to study gene function. In most genes, pLoF alleles are sufficiently rare that ascertainment will be largely limited to heterozygous individuals in outbred populations. Sampling of diverse bottlenecked populations and consanguineous individuals will aid in identification of total “knockouts”. Careful filtering and curation of pLoF variants in a gene of interest is necessary in order to identify true LoF individuals for follow-up, and the positional distribution or frequency of true LoF variants may reveal important disease biology. Our analysis suggests that the value of pLoF variant data for drug discovery lies in deep curation informed by the nature of the drug and its indication, as well as the biology of the gene, followed by recall-by-genotype studies in targeted populations.
Selective tissue targeting of synthetic nucleic acid drugs (2019)

Antisense oligonucleotides (ASOs) are chemically synthesized nucleic acid analogs designed to bind to RNA by Watson-Crick base pairing. Following binding to the targeted RNA, the ASO perturbs RNA function by promoting selective degradation of the targeted RNA, altering RNA intermediary metabolism, or disrupting function of the RNA. Most antisense drugs are chemically modified to enhance their pharmacological properties and for passive targeting of the tissues of therapeutic interest. Recent advances in selective tissue targeting have resulted in a newer generation of ASO drugs that are more potent and better tolerated than previous generations, spawning renewed interest in identifying selective ligands that enhance targeted delivery of ASOs to tissues.
Modeling the Impact of Dilution on the Microbial Degradation of Dispersed Oil in Marine Environments (2019)

Dispersants aid the breakup of crude oil masses and increase the available interfacial surface area for bacteria to degrade insoluble hydrocarbons in the marine environment. However, this common view neglects key aspects of the microscale interactions between bacteria and oil droplets, particularly the encounters between these elements that are required for degradation to occur. This chapter discusses a biophysical model for hydrocarbon consumption of suspended oil droplets under conditions of rapid dilution that occur in natural environments. Based on the model, which includes typical biological growth parameters, dilution is found to produce an effective delay in the onset of biodegradation by approximately a week. The steady and rapid reduction in oil concentration, due to dilution, is found to outpace the production of oil-degrading bacteria that results from colonization of degrading oil droplets, maintaining the process in an encounter-limited state. This mechanistic model provides a baseline for better understanding of microscale biodegradation in dilute oil environments and can help inform the design of mitigation strategies in marine systems.
Evaluation of CD4+ cells infiltration as a prognostic factor in cervical intraepithelial neoplasia 2 (2022)

CD4<sup>+</sup> TIL infiltration in intertumoral lesions was related with CIN2 regression. Our findings suggest CD4<sup>+</sup> TIL infiltration may be useful for the triage of CIN2 patients.
Correlating reticle pinhole defects to wafer printability for the 90-nm node lithography using advanced RET (2004)

For the 90nm-lithography node, understanding the impact of various reticle pinhole defects on wafer printability is essential to optimize wafer yield and to create the best quality reticle defect specification. In this study, a new programmed pinhole test reticle was designed by UMC, TCE and KLA-Tencor based on UMC's process requirements for its 193nm lithography. The reticle was manufactured and inspected on KLA-Tencor's high-resolution reticle inspection system in die to database mode by TCE. The reticle was then printed on a wafer by UMC to characterize the printability impact of programmed pinhole defects. The programmed pinhole test reticle, "193PTM", consists of two IC background patterns - poly gate and contact with programmed pinholes at various locations. The pinhole size ranges from 20nm to 75nm in 5nm increments on the wafer. By comparing the high-resolution pattern inspection results to the wafer print data, we have established the correlation and the appropriate mask specifications based on wafer application guidelines.
Desenlace y calidad asistencial de los pacientes con un infarto agudo de miocardio (2007)

We report the crystal structure of a 58 nucleotide fragment of 23S ribosomal RNA bound to ribosomal protein L11. This highly conserved ribonucleoprotein domain is the target for the thiostrepton family of antibiotics that disrupt elongation factor function. The highly compact RNA has both familiar and novel structural motifs. While the C-terminal domain of L11 binds RNA tightly, the N-terminal domain makes only limited contacts with RNA and is proposed to function as a switch that reversibly associates with an adjacent region of RNA. The sites of mutations conferring resistance to thiostrepton and micrococcin line a narrow cleft between the RNA and the N-terminal domain. These antibiotics are proposed to bind in this cleft, locking the putative switch and interfering with the function of elongation factors.
[Effects of vagal tone on Kent bundle conduction in patients with Wolff-Parkinson-White syndrome]. (1993)

These data evidence a vagal influence on the conduction in the resting Kent bundle; the vagal effect appears, however, less marked than the sympathetic one.
TOLERANCE INDUCTION TO MULTIPLE MINOR HISTOINCOMPATIBLE CELLS BY ACTIVATED B CELLS IS ASSOCIATED WITH PREFERENTIAL ACTIVATION OF Th2 CELLS1 (1994)

C3H/HeH or C57BL/6 mice were injected with resting or Escherichia coli lipopolysaccharide (LPS)-stimulated splenic B cells from adult B10.BR mice. Animals were grafted with tail skin grafts from B10.BR mice 36 hr later. Spleen cells were removed from these mice 7 days after grafting and challenged in tissue culture with irradiated B10.BR spleen cells or BALB/c cells. LPS blasts, but not naive B cells, induced an antigen-specific reduction in proliferation and IL-2 production from stimulated C3H/HeJ cells. The response obtained from C57BL/6 spleen responder cells was increased by this treatment. IL-4 production was either unchanged (C57BL/6) or enhanced (C3H/HeJ). Modification of the C3H/HeJ anti-B10.BR response by B blasts was not blocked by CTLA-4 Ig, although the increased response seen using MHC-incompatible (C57BL/6) spleen cells was inhibited by CTLA-4 Ig. B10.BR, but not BALB/c, skin graft survival in vivo was enhanced in C3H/HeJ recipients of B10.BR B blasts. In addition, in lymph nodes draining the graft site of C3H/HeJ mice injected with B10.BR LPS blasts, mRNA for IL-4 was detected by polymerase chain reaction. When similar studies were performed with B10.BR immune C3H/HeJ or C57BL/6 mice, no enhancement of graft survival in vivo, or decrease in proliferation/IL-2 production in vitro, was seen following prechallenge with B10.BR LPS blasts.
Fast source optimization by clustering algorithm based on lithography properties (2015)

Lithography is a technology to make circuit patterns on a wafer. UV light diffracted by a photomask forms optical images on a photoresist. Then, a photoresist is melt by an amount of exposed UV light exceeding the threshold. The UV light diffracted by a photomask through lens exposes the photoresist on the wafer. Its lightness and darkness generate patterns on the photoresist. As the technology node advances, the feature sizes on photoresist becomes much smaller. Diffracted UV light is dispersed on the wafer, and then exposing photoresists has become more difficult. Exposure source optimization, SO in short, techniques for optimizing illumination shape have been studied. Although exposure source has hundreds of grid-points, all of previous works deal with them one by one. Then they consume too much running time and that increases design time extremely. How to reduce the parameters to be optimized in SO is the key to decrease source optimization time. In this paper, we propose a variation-resilient and high-speed cluster-based exposure source optimization algorithm. We focus on image log slope (ILS) and use it for generating clusters. When an optical image formed by a source shape has a small ILS value at an EPE (Edge placement error) evaluation point, dose/focus variation much affects the EPE values. When an optical image formed by a source shape has a large ILS value at an evaluation point, dose/focus variation less affects the EPE value. In our algorithm, we cluster several grid-points with similar ILS values and reduce the number of parameters to be simultaneously optimized in SO. Our clustering algorithm is composed of two STEPs: In STEP 1, we cluster grid-points into four groups based on ILS values of grid-points at each evaluation point. In STEP 2, we generate super clusters from the clusters generated in STEP 1. We consider a set of grid-points in each cluster to be a single light source element. As a result, we can optimize the SO problem very fast. Experimental results demonstrate that our algorithm runs speed-up compared to a conventional algorithm with keeping the EPE values.
Correction: Corrigendum: A pan-cancer proteomic perspective on The Cancer Genome Atlas (2015)

Nature Communications 5: Article number: 3887 (2014); Published 29 May 2014; Updated 28 Jan 2015 This Article contains an error in the Author contributions section that has resulted in incorrect credit for supervision of the network analysis. The correct Author contributions section is as follows: R.A.
Assessment of systemic genetic damage in pediatric inflammatory bowel disease (2020)

The etiology of distal site cancers in inflammatory bowel disease (IBD) is not well understood and requires further study. We investigated whether pediatric IBD patients' blood cells exhibit elevated levels of genomic damage by measuring the frequency of mutant phenotype (CD59-/CD55-) reticulocytes (MUT RET) as a reporter of PIG-A mutation, and the frequency of micronucleated reticulocytes (MN-RET) as an indicator of chromosomal damage. IBD patients (n = 18 new-onset disease, 46 established disease) were compared to age-matched controls (constipation or irritable bowel syndrome patients from the same clinic, n = 30) and young healthy adults age 19-24 (n = 25). IBD patients showed no indication of elevated MUT RET relative to controls (mean ± SD = 3.1 ± 2.3 × 10<sup>-6</sup> vs. 3.6 ± 5.6 x 10<sup>-6</sup> , respectively). In contrast, 59 IBD patients where %MN-RET measurements were obtained, 10 exceeded the upper bound 90% tolerance interval derived from control subjects (i.e., 0.42%). Furthermore, each of the 10 IBD patients with elevated MN-RET had established disease (10/42), none were new-onset (0/17) (p = .049). Interestingly, each of the subjects with increased chromosomal damage was receiving anti-TNF based monotherapy at the time blood was collected (10/10, 100%), whereas this therapy was less common (20/32, 63%) among patients that exhibited ≤0.42% MN-RET (p = .040). The results clearly indicate the need for further work to understand whether the results presented herein are reproducible and if so, to elucidate the causative factor(s) responsible for elevated MN-RET frequencies in some IBD patients.
Radiative recombination lifetime measurements of InGaN single quantum well (1996)

We present results from a time-resolved study of radiative recombination in InGaN quantum wells. The sample was grown by atmospheric pressure metal-organic chemical-vapor deposition. Time-resolved photoluminescence measurements were performed from 7 K up to room temperature. The low temperature radiative lifetime was measured to be on the order of 250 ps at a generated carrier density of 1012 cm−2. The time-resolved measurements show a bimolecular recombination characteristic. At 300 K, we observed a lifetime of 130 ps which, to the best of our knowledge, is the longest lifetime reported for any III–V nitride at room temperature.
Distributed Sensors for Wildfire Early Warnings (2022)

Wildfires cause immense damage and loss of life. They are exacerbated by climate change effects and will be getting worse each year for some time to come. One way to deal with them is to have better means of early detection. Fires produce significant changes in the physical and chemical makeup of the local atmosphere that, in practice, can be detected by air quality monitors. This paper describes a sensor array that measures trace levels of fire produced emissions that is coupled to computation and communication equipment that is low power and low cost. The emission arrays are calibrated and deployed in controlled fire detection situations. Evaluations illustrate some important characteristics of detecting fire emissions including: 1] sensing CO and Particulates together reduce ambiguity of signals; and 2] fire emission signatures for relatively close fires produce rapid spikes in concentrations of emissions. Most importantly, the details of this work indicate that an individual sensor node consisting of only a CO and particle detector can provide an early indication of a wildfire. Additionally, the low-cost CO and particle sensors used in this study show a correlation of greater than 0.9 R 2 with FRM reference monitors. The results are encouraging that very low-cost arrays could substantially contribute to an early warning system for detection of wildland fires thereby improving response times for mitigation measures.
The Insect Brain as a Model System for Low Power Electronics and Edge Processing Applications (2019)

The insect brain is a great model system for low power electronics: insects carry out multisensory integration and are able to change the way the process information, learn, and adapt to changes in their environment with a very limited power budget. This context-dependent processing allows them to implement multiple functionalities within the same network, as well as to minimize power consumption by having context-dependent gains in their first layers of input processing. The combination of low power consumption, adaptability and online learning, and robustness makes them particularly appealing for a number of space applications, from rovers and probes to satellites, all having to deal with the progressive degradation of their capabilities in remote environments. In this work, we explore architectures inspired in the insect brain capable of context-dependent processing and learning. Starting from algorithms, we have explored three different implementations: a spiking implementation in a neuromorphic chip, a custom implementation in an FPGA, and finally hybrid analog/digital implementations based on cross-bar arrays. For the latter, we found that the development of novel resistive materials is crucial in order to enhance the energy efficiency of analog devices while maintaining an adequate footprint. Metal-oxide nanocomposite materials, fabricated using ALD with processes compatible with semiconductor processing, are promising candidates to fill in that role.
Acyloxymethylzinc Reagents:  Preparation, Reactivity, and Solid-State Structure of This Novel Class of Cyclopropanating Reagents (2001)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTAcyloxymethylzinc Reagents: Preparation, Reactivity, and Solid-State Structure of This Novel Class of Cyclopropanating ReagentsAndré B. Charette, André Beauchemin, and Sébastien FrancoeurView Author Information Département de Chimie, Université de Montréal Québec, Canada H3C 3J7 Cite this: J. Am. Chem. Soc. 2001, 123, 33, 8139–8140Publication Date (Web):July 27, 2001Publication History Received11 April 2001Published online27 July 2001Published inissue 1 August 2001https://pubs.acs.org/doi/10.1021/ja0109287https://doi.org/10.1021/ja0109287rapid-communicationACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views2198Altmetric-Citations63LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Chemical reactions,Cyclopropanation,Hydrocarbons,Reagents,Zinc Get e-Alerts
Super-resolution in position and velocity estimation for short-range MM-wave radar (2016)

Recently developed super-resolution algorithms have demonstrated performance approaching fundamental estimation-theoretic bounds. These algorithms have significant potential for applications such as vehicular situational awareness using low-cost, short-range millimeter wave radar sensors. In this paper, we show that such algorithms can approach single-sensor estimation-theoretic bounds for range and Doppler estimation. We also investigate, under a simple 2D model, the limits of position and radial velocity estimation performance of one shot estimation and provide insights for array design.
A Systematic Method to Characterize the Soft-Failure Susceptibility of the I/Os on an Integrated Circuit Due to Electrostatic Discharge (2019)

In this paper, we present a methodology to characterize the I/O pins of a logic IC such as an application processor or ASIC with respect to soft-failure susceptibility due to electrostatic discharge. With the IC in a functional system, variable stress pulses are injected while the interface under test operates in real-world use cases. This test methodology enables the extraction of the IC behavior during ESD-like stress on a pin-by-pin basis. This characterization is intended to be performed during the validation stages of component development, making it possible to provide system developers with valuable information about potential modes of failure. This early detection of potential soft errors and their sensitivities can then be used to design for soft-failure robustness from the very beginning of system hardware and software design.
Alterations in the Pituitary-Thyroid Axis and 5′- Deiodinase Activity in Mice with Muscular Dystrophy* (1985)

Mice with hereditary muscular dystrophy have reduced levels of serum T3. To determine possible causes of T3 deficits, we evaluated pituitary thyrotroph ultrastructure by electron microscopy, thyroid gland morphology by light microscopy, and T4 to T3 conversion by measuring iodothyronine 5'-deiodinase activity. Differences were not evident between dystrophic and normal littermates in either the structure of pituitary thyrotrophs or thyroid tissues. Dystrophic mice, however, had only 50% the normal hepatic 5'-deiodinase activity. Cerebral 5'-deiodinase, which does not appear to contribute significantly to serum T3, was similar in normal and dystrophic mice. Submandibular gland concentrations of nerve growth factor and epidermal growth factor are reduced in dystrophic mice but can be increased by T4 treatment. To distinguish whether growth factor deficits are due to reductions in serum T3 or to deficiencies in T4 5'-deiodinase activity and subsequent T3 utilization within the salivary gland, we measured submandibular deiodinase activity. Gland homogenates were active in the deiodinase assay, but no differences were detected between normal and dystrophic mice. In order to evaluate tissue responses to reductions in circulating T4, we treated mice with methimazole. Structural analyses revealed that thyrotrophs in dystrophic mice were less stimulated than thyrotrophs in similarly treated normal littermates. Likewise, thyroid follicular cells appeared less active, and thyroid weights increased only 40-50% as much as in normals. Liver 5'-deiodinase activity decreased in both normal and dystrophic mice. Cerebral 5'-deiodinase activity increased more than 4-fold in normal females but only 2-fold in dystrophic females; 2- to 3-fold increases occurred in both normal and dystrophic males. In summary, the structure of pituitary and thyroid glands in dystrophic mice is similar to that of tissues from normal littermates, but hepatic conversion of T4 to T3 is reduced. When challenged by methimazole-induced reductions in serum T4, pituitary and cerebral tissues in dystrophic mice respond abnormally.
Cyano(ethoxycarbonothioylthio)methyl Benzoate:  A Novel One-Carbon Radical Equivalent (2005)

[reaction: see text] Cyano(ethoxycarbonothioylthio)methyl benzoate 3 has been prepared and shown to be an excellent one-carbon radical equivalent that can be applied for the introduction of an acyl unit via xanthate transfer radical addition to olefins. The corresponding adducts can be further elaborated. A rare 1,5-nitrile translocation was also observed during the study.
Interactive Code Generation via Test-Driven User-Intent Formalization (2022)

Large language models (LLMs) have shown great potential in automating significant aspects of coding by producing natural code from informal natural language (NL) intent. However, when interacting with LLMs, users have no guarantees that the code suggestions produced correctly satisfy the intent they provided. In fact, it is hard to define a notion of correctness since natural language can be ambiguous and lacks a formal semantics. In this paper, we propose the workflow of {\it interactive test-driven code generation}, which leverages lightweight user feedback to (a) formalize the user intent using generated tests that can be useful for debugging, and (b) produce an improved set of code suggestions by pruning and ranking candidate code suggestions. We describe a language-agnostic abstract algorithm and a concrete implementation TiCoder. We perform an automated evaluation of TiCoder on the \emph{MBPP} and \emph{HumanEval} code generation benchmarks. Our results are promising with using the OpenAI Codex LLM: our best algorithm improves the \passk{1} code generation accuracy (in absolute percentages) between $22.49\%$ to $37.71\%$ for MBPP and between $24.79\%$ to $53.98\%$ for HumanEval using between 1 to 5 simulated user queries.