gebhart/patrepeval huggingface dataset:
Extension of a minimal T cell Determinant allows relaxation of the requirement for particular residues within the determinant (1991)

The determinant recognized by a class II restricted helper T cell clone raised against a peptide corresponding to the C-terminal 24 residues of the heavy chain of influenza virus hemagglutinin (HA) was examined in detail. The sequence 309VKQNTLKL316 was identified as the minimal determinant for T cell activation but its stimulatory capacity was augmented by extension at either end. Sets of peptide analogs, in which each residue within the minimal determinant was replaced in turn by every one of the other naturally occurring amino acids, revealed either an absolute requirement for the native residue or a very limited degree of replaceability, at seven of the eight positions. Only the N-terminal residue 309V could be replaced with almost any other amino acid without loss of reactivity; in fact, substitution at this position with residues containing bulky side groups enhanced the response. The reactivity of the clone with analogs of the longer peptide 307KYVKQNTLKL316, which induces maximal levels of stimulation, revealed a very different pattern of replaceability for certain residues; in particular, the requirement for a lysine at position 310 was no longer apparent. This study presents a complete analysis of the importance of each individual residue to the integrity of a T cell determinant and provides evidence that the critical requirement for a particular amino acid at a given location may be overridden by N-terminal extension of the minimal determinant. These findings indicate that, within different homologs of the native sequence, particular residues may assume quite different roles.
Novel molecular signatures of sensitivity to Lapatinib in breast cancer cells using an adaptive approach (2007)

C135 Genome-scale analyses of human breast tumors have already established that these cells manifest a variety of molecular defects at various levels, ranging from the genome to the proteome, which influence response to therapy. It is now evident that improved individualization of patient treatment is essential to design effective therapies. Genomic technologies have enabled predicting patient response to drugs, a priori, from their genome-scale molecular profiles (DNA, mRNA and protein), and identifying the concomitant molecular markers. However, most such studies have used cancer cells originating in disparate types of tissues, thus restricting the efficacy of therapy. It is difficult to extend these approaches to model sensitivity of specific tumor types, primarily because the sample sizes are significantly smaller.  We have developed a novel computational approach based on adaptive linear splines that can overcome this limitation, and can comprehensively model responses from all cell-lines for a given tumor type. We measured the response to Lapatinib (GW572016, dual inhibitor of EGFR and ErbB2) of a well-characterized model system of 40 breast cancer cell-lines, and applied the above adaptive method to identify molecular signatures of response. This proof-of-concept study indeed revealed ErbB2 and its amplicon, the prime targets of Lapatinib, as top predictors. In addition, it identified new markers that are biologically significant, and showed high accuracy (≥ 90%) in predicting response of new samples. Furthermore, this new technique enabled identification of candidate markers for a much more restricted data set, the ErbB2-negative cells, for the first time to our knowledge. Statistical tests indicate that many of these markers may be used clinically. Application of this method to multiple other datasets indicates that our adaptive approach holds promise for ab initio determination of clinically applicable molecular markers.  (Supported by funds form NIH/NCI U54 CA112970 and GlaxoSmithKline)
Atomic Resolution Structures of the Core Domain of Avian Sarcoma Virus Integrase and Its D64N Mutant (1999)

ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionORIGINAL ARTICLEThis notice is a correctionAtomic Resolution Structures of the Core Domain of Avian Sarcoma Virus Integrase and Its D64N MutantJacek Lubkowski, Zbigniew Dauter, Fan Yang, Jerry Alexandratos, George Merkel, Anna Marie Skalka, and Alexander WlodawerCite this: Biochemistry 1999, 38, 45, 15060Publication Date (Web):October 23, 1999Publication History Published online23 October 1999Published inissue 1 November 1999https://pubs.acs.org/doi/10.1021/bi995092nhttps://doi.org/10.1021/bi995092ncorrectionACS PublicationsCopyright © 1999 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views248Altmetric-Citations4LEARN 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 PDF (9 KB) Get e-Alertsclose Get e-Alerts
Sigmatropic Rearrangement-Based Synthesis of 4-Alkenyl-1,3-dithiol-2-ones (2019)

A series of conjugated 4-alkenyl-1,3-dithiol-2-ones have been prepared by microwave-assisted rearrangement of S-(4-acyloxy-2-alkynyl)- O-ethyl xanthates in moderate to good yields. The synthetic approach is based on a combination of [3,3] and [1,5] sigmatropic rearrangements as well as the intermediacy of a reactive betaine that induces the ionic elimination of the acyloxy group. The [1,5] sigmatropic rearrangement was confirmed by a deuterium-labeling experiment.
ChemInform Abstract: ASYMMETRIC OXYGENATION OF CHIRAL IMIDE ENOLATES. A GENERAL APPROACH TO THE SYNTHESIS OF ENANTIOMERICALLY PURE α‐HYDROXY CARBOXYLIC ACID SYNTHONS (1985)

Abstract Die Hydroxylierung der chiralen Enolate aus den Oxazolidinen (I), (V), (VIII) bzw. (XI) mit dem Oxidans (IV) erfolgt in hohem Maß diastereoselektiv unter Bildung der Haupt‐Diastereomeren (II), (VI), (IX) bzw. (XII).
Sensors for Predicting Caviar Maturity in Farmed Sturgeon to Optimize Yield (2012)

Declining wild sturgeon populations around the world have led to a significant increase in the production of farm-raised caviar, but sturgeon farmers face difficult challenges to produce eggs of sufficient size and firmness to yield high-quality caviar. Females reach sexual maturity at about seven years and the eggs are examined by biopsy in late autumn for color and size. The exact time of harvest to produce optimum quantity and quality of caviar cannot be predicted based on egg size or color at the time of biopsy because of individual variation in the rate of egg growth and development. The overall goal of this research is to conduct the preliminary work on sensor development and maturity prediction to give sturgeon farmers better methods to optimize the quantity and quality of harvested caviar. During the ovarian cycle, eggs sequester the yolk precursor vitellogenin, a glycolipophosphoprotein secreted into the bloodstream by the liver. Changes in the concentration of circulating vitellogenin reflect development and growth of the eggs. The total calcium concentration in the plasma of sturgeon is highly correlated with vitellogenin concentration. Total calcium can be measured directly in the laboratory by atomic absorption spectrophotometry or by inductively coupled plasma mass spectrometry. For our research we chose a simple diagnostic assay commercially available for measurement of free calcium and most bound calcium in fluid samples. A miniature sensor platform using micro-pumps and micro-valves was designed to run the assay, with a complete testing cycle of less than 3 minutes. Calibration was done using standards made with calcium chloride in distilled water over the approximate range of physiological concentrations of total calcium in blood plasma. Preliminary tests were conducted on calcium chloride standards and on plasma from an immature female white sturgeon and a vitellogenic female green sturgeon. The sensor estimates differed somewhat from the known concentrations for the calcium standards, but were generally consistent with our expectations for blood plasma. The sensor was able to measure most of the total calcium in plasma and, thus, distinguish vitellogenic fish. Additional tests will be conducted with white sturgeon to determine the relationships between plasma calcium and egg development.
Directed vertical alignment liquid crystal display with fast switching (2006)

We describe a directed vertical alignment (VA) display mode based on a nematic liquid crystal (LC) doped with a chiral dopant and confined between two substrates, one of which is pretreated, say, by unidirectional rubbing or photoalignment. The design allows one to eliminate umbilical defects that appear during switching of the conventional VA cells and thus to obtain better contrast. Switching is ∼30% faster than for VA cells when optimized concentration of a chiral dopant is added and LC molecules at one of the substrates are slightly tilted from the cell normal due to the unidirectional surface treatment.
Control-Based Performance Improvements of a Single-Phase Induction Machine with a Large Air Gap and a Copper-Coated Solid Rotor (2019)

This paper demonstrates that, within the context of a rotary anode X-ray tube drive, step function commutation of a single phase induction machine with a phase-shift capacitor offers reduced losses compared to block commutation and rivals the losses achievable with sinusoidal commutation but with significantly less control effort. The start-up behavior resulting from these three different voltage waveforms using the original capacitor value are analyzed by means of 2D-/3D-FEM parameter extraction for an equivalent circuit model and corresponding laboratory tests.
Discovery of AG-270, a First-in-Class Oral MAT2A Inhibitor for the Treatment of Tumors with Homozygous MTAP Deletion (2021)

The metabolic enzyme methionine adenosyltransferase 2A (MAT2A) was recently implicated as a synthetic lethal target in cancers with deletion of the methylthioadenosine phosphorylase (<i>MTAP</i>) gene, which is adjacent to the <i>CDKN2A</i> tumor suppressor and codeleted with <i>CDKN2A</i> in approximately 15% of all cancers. Previous attempts to target MAT2A with small-molecule inhibitors identified cellular adaptations that blunted their efficacy. Here, we report the discovery of highly potent, selective, orally bioavailable MAT2A inhibitors that overcome these challenges. Fragment screening followed by iterative structure-guided design enabled >10 000-fold improvement in potency of a family of allosteric MAT2A inhibitors that are substrate noncompetitive and inhibit release of the product, <i>S</i>-adenosyl methionine (SAM), from the enzyme's active site. We demonstrate that potent MAT2A inhibitors substantially reduce SAM levels in cancer cells and selectively block proliferation of <i>MTAP</i>-null cells both in tissue culture and xenograft tumors. These data supported progressing <b>AG-270</b> into current clinical studies (ClinicalTrials.gov NCT03435250).
Barrier-free absorbance modulation for super-resolution optical lithography (2015)

Absorbance-Modulation-Optical Lithography (AMOL) enables super-resolution optical lithography by simultaneous illumination of a photochromic film by a bright spot at one wavelength, λ1 and a node at another wavelength, λ2. A deep subwavelength region of the transparent photochromic isomer is created in the vicinity of the node. Light at λ1 penetrates this region and exposes an underlying photoresist layer. In conventional AMOL, a barrier layer is required to protect the photoresist from the photochromic layer. Here, we demonstrate barrier-free AMOL, which considerably simplifies the process. Specifically, we pattern lines as small as 70nm using λ1 = 325nm and λ2 = 647nm. We further elucidate the minimum requirements for AMOL to enable multiple exposures so as to break the diffraction limit.
WS3-4Time-Evolving Volume Data Mining (2001)

This paper presents a 3D field topology analysis scheme to locate time-intervals of interest from a very large time-evolving volume dataset, and to design a proper color/opacity transfer functions for each of snapshot volumes belonging to the extracted time-intervals. Feasibility study of the present scheme is performed with a large scale 4D simulated dataset from atomic collision research.
Construction of genomic libraries of Cryptosporidium parvum and identification of antigen-encoding genes. (1991)

Genomic libraries have been constructed from bovine C. parvum DNA in the lambda ZAP and lambda DASH vectors. Based on an estimated genome size of 2 x 10(4) kilobases (kb), each recombinant library contains greater than 10 genomic equivalents. The average recombinant size for the lambda ZAP library is 2.1 kb and for the lambda DASH library is 14 kb. We have identified genes to major antigens recognized by hyperimmune bovine antiserum. These recombinants are currently being purified and characterized. Limited DNA sequence analysis of random C. parvum clones confirms suggestions that the genome is quite AT-rich. The DNA sequence of random lambda ZAP fusion proteins has identified a potential ATPase, a structural protein and a DNA-binding protein.
Efflux-mediated tolerance to cationic biocides, a cause for concern? (2022)

<b>Abstract</b>With an increase in the number of isolates resistant to multiple antibiotics, infection control has become increasingly important to help combat the spread of multi-drug-resistant pathogens. An important component of this is through the use of disinfectants and antiseptics (biocides). Antibiotic resistance has been well studied in bacteria, but little is known about potential biocide resistance genes and there have been few reported outbreaks in hospitals resulting from a breakdown in biocide effectiveness. Development of increased tolerance to biocides has been thought to be more difficult due to the mode of action of biocides which affect multiple cellular targets compared with antibiotics. Very few genes which contribute towards increased biocide tolerance have been identified. However, the majority of those that have are components or regulators of different efflux pumps or genes which modulate membrane function/modification. This review will examine the role of efflux in increased tolerance towards biocides, focusing on cationic biocides and heavy metals against Gram-negative bacteria. As many efflux pumps which are upregulated by biocide presence also contribute towards an antimicrobial resistance phenotype, the role of these efflux pumps in cross-resistance to both other biocides and antibiotics will be explored.
Development Direction of Smart Factory for Mass Customization Based On Investigating Adidas SpeedFactory Closure (2020)

아디다스 스피드팩토리가 공식 폐쇄되었으나, 그 원인과 배경에 대해서는 알려진 바가 극히 적다. 본 연구는 이론적 고찰을 통해 스마트 팩토리 분석 프레임워크를 제안하고, 이를 스피드팩토리에 적용하여 스마트 팩토리 정책방향을 제언하였다. 스피드팩토리는 대량 맞춤 체계를 적용하고자 하였고, 그 과정에서 희생되는 생산 효율성의 저하를 생산 인력 감축과 물류비용 절감으로 상쇄하겠다고 밝혔다. 그러나, 실상 스피드팩토리에서는 맞춤형 신발은 전혀 생산하지 않았다. 이는 생산자, 소비자, 공급 사슬 측면의 대량 맞춤을 위한 요건이 갖춰지지 않았기 때문이다. 분석을 통해 얻을 수 있는 정책적 시사점은 다음과 같다. 첫째, 스마트 팩토리는 맞춤형 생산과 효율성 향상을 별개의 목표로 설정해야 한다. 둘째, 중장기적 관점에서 대량 맞춤을 위한 기반 기술들을 조화롭고 균형있게 육성해야 한다. 셋째, 생산 반영 가능 맞춤형 디자인에 대한 투자와 연구개발이 필요하다.
Comprehensible Video Thumbnails (2015)

Abstract We present the Comprehensible Video Thumbnail; an automatically generated visual précis that summarizes salient objects and their dynamics within a video clip. Salient moving objects are detected within clips using a novel stochastic sampling technique that identifies, clusters and then tracks regions exhibiting affine motion coherence within the clip. Tracks are analyzed to determine salient instants at which motion and/or appearance changes significantly, and the resulting objects arranged in a stylized composition optimized to reduce visual clutter and enhance understanding of scene content through classification and depiction of motion type and trajectory. The result is an object‐level visual gist of the clip, obtained with full automation and depicting content and motion with greater descriptive power that prior approaches. We demonstrate these benefits through a user study in which the comprehension of our video thumbnails is compared to the state of the art over a wide variety of sports footage.
Analysis of p16 (CDKN2/MTS-1/INK4A) alterations in primary sporadic uveal melanoma. (1999)

p16 inactivation by HD or methylation occurs in 27% of uveal melanomas, representing the most common molecular genetic alteration identified thus far in uveal melanoma.
Abstract 18666: A Carbon Monoxide (CO) Scavenging Agent Reverses CO-Induced Mitochondrial Inhibition in vitro and in vivo (2016)

Introduction: There are 50,000 cases of carbon monoxide (CO) poisoning per year in the United States alone. Even with current therapy, 1/3 of moderate-severely poisoned patients have cardiac dysfun...
Effects of charge, size, and shape-asymmetry on the phase behavior of model electrolytes (2002)

Monte Carlo simulations have been conducted to investigate the phase behavior of 2:1 hard-core electrolyte models. Two distinct cases have been considered: In the first, both bivalent cations and monovalent anions are spherical. In the second, bivalent cations are modeled as rigid dimers composed of two tangent hard spheres, each carrying a positive charge at the center. Critical temperatures and densities have been calculated as a function of the size asymmetry between positive and negative ions. The simulated critical temperature and critical density are strongly influenced by size asymmetry and by the shape of the ions. Changes in the critical constants are traced back to ground-state energy configurations of small ionic clusters. The trends observed in simulations for the critical temperature and density as a function of size asymmetry are shown to contradict the predictions of available theoretical formalisms.
Surface-specific ordering of reverse micelles in confinement (2010)

We have applied holographic X-ray diffraction from fluid-filled channel arrays for model-independent density reconstruction of spherical AOT/water/isooctane reverse micelles (average diameter σ≃12–13 nm) confined between planar surfaces. We find the confinement-induced ordering of the reverse micelles to strongly depend on the surface potential of the confining surfaces: for hydrophilic surfaces we find diffuse monolayers centered at 13 ± 3 nm away from the solid–fluid interface, while for hydrophobic surfaces we observe close-packed monolayers at the solid–fluid interface.
Chapter 13 Responsive paraCEST MRI Contrast Agents and Their Biomedical Applications (2017)

Magnetization transfer (MT) eﬀects in tissues broadly classifysaturation transfer eﬀects arising from protons in macromoleculesand semisolid components, the saturation of which is transferred tothewater pool via spin exchange and/or cross relaxation [1, 2]. A keyfeature of theseMT eﬀects is that they are broadbandwith respect tothe frequency oﬀset for the saturation, which may be a result of thebroad dipolar spectra that are characteristic of rigid components.In addition, it has been reported that MT eﬀects are generallyasymmetric around the water resonance, thereby complicating theirelimination by a simple symmetrization or subtraction techniquein evaluating chemical exchange saturation transfer (CEST) eﬀects.Such interferences have been reported when in vivo CEST eﬀectswere measured [3-5], which can result in the false identiﬁcation ofCEST eﬀects and incorrect interpretations regarding metabolic andpathologic processes.
Development of the Dried Spot Sample Preparation Methodology and Applications to XRMF Analysis (1997)

The dried spot method has significant potential for trace elemental analysis using x-ray fluorescence. Small sample size coupled with spatially resolved excitation offers increased sensitivity for aqueous solutions. The primary limitation in applying this method to routine analyses is that much of the method development and fundamental aspects have not been investigated. We have studied the effects of a number of parameters on the quantitative capabilities of the dried spot method. These include thin-film substrates, drying methods, and solution composition. The small sample size offers opportunities for the analysis of a wide array of sample types including highly radioactive specimens.
Spray‐dried lipid‐hyaluronan‐polymethacrylate microparticles for drug delivery in the peritoneum (2008)

Application of controlled release technology to the peritoneum would allow for sustained drug levels. However, some polymeric systems either create adhesions, or rapidly exit the peritoneum; neither result is desirable. Here we have produced particles based on sphyngomyelin, a phospholipid that occurs naturally in the peritoneum, along with hyaluronic acid and the polymethacrylate Eudragit E100 (to modulate drug release). Particles with a low proportion of E100 (5% (w/w); "high SPM") release albumin rapidly over 2 days, then more slowly; increasing the E100 to 20% (w/w; high "E100") slowed drug release markedly. When injected in the murine peritoneum, high SPM particles were disseminated as free particles, without forming collections. There was a mild inflammatory response but no formation of adhesions. High E100 particles formed collections in all animals, with an intense inflammatory response. Even so, there were very few adhesions. These results suggest that microparticulate formulations can be produced that have acceptable drug-releasing properties and are suitable for use in the peritoneum from the standpoint of biocompatibility.
Investigation and Remediation of the 2006 Nixa, Missouri, Collapse Sinkhole (2009)

The August 2006 collapse of a sinkhole beneath a residential structure in Nixa, Missouri, offered a new opportunity to investigate such features. Investigation of the roughly 60 ft (18 m) diameter by 75 ft (23 m) deep sink suggested factors that may be precursors of such catastrophic events and provided an opportunity to document a common approach to remediating collapse subsidence events. A review is presented here of the site conditions, the initial emergency response, site investigation and remedial planning, and the final actions taken. In addition, several potential indicators or contributing factors are identified that may allow others in karst terranes to identify future potential hazard areas. These factors include subsurface drainage features, tree roots and macropores, and unique storm-water drainage conditions. Lessons learned during the response to the sinkhole collapse are presented that should prove helpful to others if they need to prepare for, or respond to, similar incidents.