gebhart/patrepeval huggingface dataset:
An MHC-restricted antibody-based chimeric antigen receptor requires TCR-like affinity to maintain antigen specificity (2016)

Chimeric antigen receptors (CARs) are synthetic receptors that usually redirect T cells to surface antigens independent of human leukocyte antigen (HLA). Here, we investigated a T cell receptor-like CAR based on an antibody that recognizes HLA-A*0201 presenting a peptide epitope derived from the cancer-testis antigen NY-ESO-1. We hypothesized that this CAR would efficiently redirect transduced T cells in an HLA-restricted, antigen-specific manner. However, we found that despite the specificity of the soluble Fab, the same antibody in the form of a CAR caused moderate lysis of HLA-A2 expressing targets independent of antigen owing to T cell avidity. We hypothesized that lowering the affinity of the CAR for HLA-A2 would improve its specificity. We undertook a rational approach of mutating residues that, in the crystal structure, were predicted to stabilize binding to HLA-A2. We found that one mutation (DN) lowered the affinity of the Fab to T cell receptor-range and restored the epitope specificity of the CAR. DN CAR T cells lysed native tumor targets <i>in vitro</i>, and, in a xenogeneic mouse model implanted with two human melanoma lines (A2+/NYESO+ and A2+/NYESO-), DN CAR T cells specifically migrated to, and delayed progression of, only the HLA-A2+/NY-ESO-1+ melanoma. Thus, although maintaining MHC-restricted antigen specificity required T cell receptor-like affinity that decreased potency, there is exciting potential for CARs to expand their repertoire to include a broad range of intracellular antigens.
Research Resource: Progesterone Receptor Targetome Underlying Mammary Gland Branching Morphogenesis (2013)

Progesterone (P 4 )-activated progesterone receptors (PRs) play an essential role in driving pregnancy-associated mammary ductal side-branching morphogenesis and alveologenesis. However, the global cistromic and transcriptome responses that are required to elicit P 4 -dependent branching morphogenesis have not been elucidated. By combining chromatin immunoprecipitation followed by deep sequencing to identify genome-wide PR-binding sites in PR-positive luminal epithelial cells with global gene expression signatures acutely regulated by PRs in the mammary gland, we have identified a mammary epithelial PR targetome associated with active P 4dependent branching morphogenesis in vivo. We demonstrate that P 4 -induced side-branching is initiated by epithelial cell rearrangement into a multilayered epithelium that sprouts laterally from quiescent ducts via a mechanism requiring P 4 -dependent activation of Rac-GTPase signaling. We identify effectors of Rac-GTPases as direct transcriptional targets of PRs, and we demonstrate that disruption of the P 4 -activated Rac-GTPase signaling axis is sufficient to eliminate P 4 -dependent side-branching. Our data reveal that the molecular mediators of P 4 -dependent ductal side-branching overlap with those implicated in breast cancer.
Periscope (2004)

A system for efficient 3D visualization of Web search results is presented. The system, called Periscope1, uses a novel approach for adaptive and customizable visualization of complex data. The whole process is divided into a number of interactive steps. At each step, the system can automatically choose the best method of presenting search results. The user can also select a specific presentation method to focus on certain properties of the result obtained. After analyzing the current search result, the user can narrow or broaden the search query and repeat the procedure.
Cyclic polysiloxanes from the hydrolysis of dichlorosilane (1983)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCyclic polysiloxanes from the hydrolysis of dichlorosilaneDietmar Seyferth, Christian Prud'homme, and Gary H. WisemanCite this: Inorg. Chem. 1983, 22, 15, 2163–2167Publication Date (Print):July 1, 1983Publication History Published online1 May 2002Published inissue 1 July 1983https://pubs.acs.org/doi/10.1021/ic00157a014https://doi.org/10.1021/ic00157a014research-articleACS PublicationsRequest reuse permissionsArticle Views736Altmetric-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
Triazaspirodimethoxybenzoyls as Selective Inhibitors of Mycobacterial Lipoamide Dehydrogenase, (2010)

Mycobacterium tuberculosis (Mtb) remains the leading single cause of death from bacterial infection. Here we explored the possibility of species-selective inhibition of lipoamide dehydrogenase (Lpd), an enzyme central to Mtb's intermediary metabolism and antioxidant defense. High-throughput screening of combinatorial chemical libraries identified triazaspirodimethoxybenzoyls as high-nanomolar inhibitors of Mtb's Lpd that were noncompetitive versus NADH, NAD(+), and lipoamide and >100-fold selective compared to human Lpd. Efficacy required the dimethoxy and dichlorophenyl groups. The structure of an Lpd-inhibitor complex was resolved to 2.42 A by X-ray crystallography, revealing that the inhibitor occupied a pocket adjacent to the Lpd NADH/NAD(+) binding site. The inhibitor did not overlap with the adenosine moiety of NADH/NAD(+) but did overlap with positions predicted to bind the nicotinamide rings in NADH and NAD(+) complexes. The dimethoxy ring occupied a deep pocket adjacent to the FAD flavin ring where it would block coordination of the NADH nicotinamide ring, while the dichlorophenyl group occupied a more exposed pocket predicted to coordinate the NAD(+) nicotinamide. Several residues that are not conserved between the bacterial enzyme and its human homologue were predicted to contribute both to inhibitor binding and to species selectivity, as confirmed for three residues by analysis of the corresponding mutant Mtb Lpd proteins. Thus, nonconservation of residues lining the electron-transfer tunnel in Mtb Lpd can be exploited for development of species-selective Lpd inhibitors.
In Vitro and in Vivo Function of the C-Terminus of Escherichia Coli Single-Stranded DNA Binding Protein (1996)

We constructed several deletion mutants of Escherichia coli single-stranded DNA binding protein (EcoSSB) lacking different parts of the C-terminal region. This region of EcoSSB is composed of two parts: a glycine and proline-rich sequence of approximately 60 amino acids followed by an acidic region of the last 10 amino acids which is highly conserved among the bacterial SSB proteins. The single-stranded DNA binding protein of human mitochondria (HsmtSSB) lacks a region homologous to the C-terminal third of EcoSSB. Therefore, we also investigated a chimeric protein consisting of the complete sequence of the human mitochondrial single-stranded DNA binding protein (HsmtSSB) and the C-terminal third of EcoSSB. Fluorescence titrations and DNA-melting curves showed that the C-terminal third of EcoSSB is not essential for DNA-binding in vitro. The affinity for single-stranded DNA and RNA is even increased by the removal of the last 10 amino acids. Consequently, the nucleic acid binding affinity of HsmtSSB is reduced by the addition of the C-terminus of EcoSSB. All mutant proteins lacking the last 10 amino acids are unable to substitute wild-type EcoSSB in vivo. Thus, while the nucleic acid binding properties do not depend on an intact C-terminus, this region is essential for in vivo function. Although the DNA binding properties of HsmtSSB and EcoSSB are quite similar, HsmtSSB does not function in E.coli. This failure cannot be overcome by fusing the C-terminal third of EcoSSB to HsmtSSB. Thus differences in the N-terminal parts of both proteins must be responsible for this incompatibility. None of the mutants was defective in tetramerization. However, mixed tetramers could only be formed by proteins containing the same N-terminal part. This reflects structural differences between the N-terminal parts of HsmtSSB and EcoSSB. These results indicate that the region of the last 10 amino acids, which is highly conserved among bacterial SSB proteins, is involved in essential protein-protein interactions in the E.coli cell.
Antiknock Antagonists (1951)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAntiknock AntagonistsH. K. LivingstonCite this: Ind. Eng. Chem. 1951, 43, 3, 663–671Publication Date (Print):March 1, 1951Publication History Published online1 May 2002Published inissue 1 March 1951https://pubs.acs.org/doi/10.1021/ie50495a029https://doi.org/10.1021/ie50495a029research-articleACS PublicationsRequest reuse permissionsArticle Views57Altmetric-Citations5LEARN 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 options Get e-Alerts
Managed Pressure Drilling Resolves Pressure Depletion Related Problems in the Development of the HPHT Kristin Field (2008)

Abstract Depletion of the Kristin HPHT field (911 bar, 172° C / 13,213 psi, 342° F) is occurring, challenging the drilling of future increased recovery wells. The main concern is uncertainty of the reservoir pressures in development areas of the producing intervals. Initially, the operational window range for the bottomhole pressure (BHP) varied from a pore pressure of 1.97 SG to a fracture pressure of 2.14-2.16 SG. With depletion, the difference has become narrower since fracture pressure is decreasing. This paper describes the need to implement managed pressure drilling (MPD) techniques in the Kristin field to overcome the problems related to a narrow drilling window. MPD is a technique that allows the use of lower-density drilling fluid, minimizing the overbalance pressure. Thus, BHP can be easily controlled and changed by applying surface-back pressure using a closed and pressurized circulation system and an automated choke. Circulating and static BHP can be increased rapidly, by applying back pressure at surface, if a higher than expected reservoir pressure is encountered. Conversely, BHP can rapidly be reduced, by reducing surface back pressure, should losses be seen down hole. The paper will discuss the use of a drilling fluid with a density giving a hydrostatic pressure lower than the original pore pressure to facilitate drilling operations and allow better control of the BHP for drilling future wells in the Kristin Field. The Kristin development wells may be the first wells globally to use MPD techniques in a harsh weather offshore environment on a floating drilling installation. The paper will also discuss some of the new equipment which has been designed to allow the implementation of MPD techniques in a harsh weather offshore environment from a semi submersible rig.
Electrospun Sb/C Fibers for a Stable and Fast Sodium-Ion Battery Anode (2013)

Sodium-ion batteries (SIBs) are considered a top alternative to lithium-ion batteries (LIBs) for large-scale renewable energy storage units due to their low cost and the abundance of sodium-bearing precursors in the earth's mineral deposits. However, the development of anode materials for SIBs to date has been mainly limited to carbonaceous materials with minimal research devoted to high capacity alloy-based materials. In this study, an antimony (Sb)/carbon (C) electrode with ~30 nm Sb nanoparticles (NPs) uniformly encapsulated in interconnecting one-dimensional (1D) 400 nm carbon fibers (denoted as SbNP@C) was fabricated using a simple and scalable electrospinning method. This binder-free, current collector-free SbNP@C electrode demonstrated high capacity and stable long-term cycling performance at various current densities. The SbNP@C electrode showed an initial total capacity of 422 mAh/gelectrode and retained 350 mAh/gelectrode after 300 deep charge-discharge cycles under 100 mA/gSb. Moreover, because of the efficient 1D sodium-ion transport pathway and the highly conductive network of SbNP@C, the electrode preserved high overall capacities even when cycled at high currents, extending its usability to high power applications.
Induction of Proneurotrophins and Activation of p75<sup>NTR</sup>-Mediated Apoptosis via Neurotrophin Receptor-Interacting Factor in Hippocampal Neurons after Seizures (2008)

Seizure-induced damage elicits a loss of hippocampal neurons mediated to a great extent by the p75 neurotrophin receptor (NTR). Proneurotrophins, which are potent apoptosis-inducing ligands for p75(NTR), were increased in the hippocampus, particularly in astrocytes, by pilocarpine-induced seizures; and infusion of anti-pro-NGF dramatically attenuated neuronal loss after seizures. The p75(NTR) is expressed in many different cell types in the nervous system, and can mediate a variety of different cellular functions by recruiting specific intracellular binding proteins to activate distinct signaling pathways. In this study, we demonstrate that neurotrophin receptor-interacting factor (NRIF) mediates apoptotic signaling via p75(NTR) in hippocampal neurons in vitro and in vivo. After seizure-induced injury, NRIF(-/-) mice showed an increase in p75(NTR) expression in the hippocampus; however, these neurons failed to undergo apoptosis in contrast to wild-type mice. Treatment of cultured hippocampal neurons with proneurotrophins induced association of NRIF with p75(NTR) and subsequent translocation of NRIF to the nucleus, which was dependent on cleavage of the receptor. Neurons lacking NRIF were resistant to p75(NTR)-mediated apoptosis in vitro and in vivo. In addition, we demonstrate some mechanistic differences in p75(NTR) signaling in hippocampal neurons compared with other cell types. Overall, these studies demonstrate the requirement for NRIF to signal p75(NTR)-mediated apoptosis of hippocampal neurons and that blocking pro-NGF can inhibit neuronal loss after seizures.
Improvement In The Corrosion Rate And Mechanical Properties Of Low Carbon Steel Through Deep Cryogenic Treatment. (2013)

Abstract- Exploration of the benefit of cryotreatment for achieving improvement in corrosion rate of mild steel is a topic of current research interest. This study is concerned with the effect of deep cryogenic treatment at temperature of-193 0 C on the corrosion rate and mechanical properties. A series of corrosion rate tests have been carried out to cryotreated samples. The specimen were divided into two groups, the first group was subjected to conventional heat treatment process at a temperature of 950 0 C for about 1 hour and the other group was subjected to deep cryogenic treatment for about 36 hours at a temperature of-193 0 C, followed by tempering at 150 0 C for about 1 hour to both the groups. The results have shown that after DCT the corrosion rate and mechanical properties of the samples were all improved. The changes in microstructure due to (DCT) were clearly noticeable, the grain boundaries were no longer visible and the microstructure consists of baninite, martensite and retained austenite.
Selective cleavage of the allyl and (allyloxy)carbonyl groups through palladium-catalyzed hydrostannolysis with tributyltin hydride. Application to the selective protection-deprotection of amino acid derivatives and in peptide synthesis (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSelective cleavage of the allyl and (allyloxy)carbonyl groups through palladium-catalyzed hydrostannolysis with tributyltin hydride. Application to the selective protection-deprotection of amino acid derivatives and in peptide synthesisO. Dangles, F. Guibe, G. Balavoine, S. Lavielle, and A. MarquetCite this: J. Org. Chem. 1987, 52, 22, 4984–4993Publication Date (Print):October 1, 1987Publication History Published online1 May 2002Published inissue 1 October 1987https://pubs.acs.org/doi/10.1021/jo00231a027https://doi.org/10.1021/jo00231a027research-articleACS PublicationsRequest reuse permissionsArticle Views3957Altmetric-Citations234LEARN 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
A fast string searching algorithm (1977)

An algorithm is presented that searches for the location, “ i l” of the first occurrence of a character string, “ pat ,” in another string, “ string .” During the search operation, the characters of pat are matched starting with the last character of pat . The information gained by starting the match at the end of the pattern often allows the algorithm to proceed in large jumps through the text being searched. Thus the algorithm has the unusual property that, in most cases, not all of the first i characters of string are inspected. The number of characters actually inspected (on the average) decreases as a function of the length of pat . For a random English pattern of length 5, the algorithm will typically inspect i /4 characters of string before finding a match at i . Furthermore, the algorithm has been implemented so that (on the average) fewer than i + patlen machine instructions are executed. These conclusions are supported with empirical evidence and a theoretical analysis of the average behavior of the algorithm. The worst case behavior of the algorithm is linear in i + patlen , assuming the availability of array space for tables linear in patlen plus the size of the alphabet.
Different requirements for <i>EDS1</i> and <i>NDR1</i> by disease resistance genes define at least two <i>R</i> gene-mediated signaling pathways in <i>Arabidopsis</i> (1998)

The Arabidopsis genes EDS1 and NDR1 were shown previously by mutational analysis to encode essential components of race-specific disease resistance. Here, we examined the relative requirements for EDS1 and NDR1 by a broad spectrum of Resistance (R) genes present in three Arabidopsis accessions (Columbia, Landsberg-erecta, and Wassilewskija). We show that there is a strong requirement for EDS1 by a subset of R loci (RPP2, RPP4, RPP5, RPP21, and RPS4), conferring resistance to the biotrophic oomycete Peronospora parasitica, and to Pseudomonas bacteria expressing the avirulence gene avrRps4. The requirement for NDR1 by these EDS1-dependent R loci is either weak or not measurable. Conversely, three NDR1-dependent R loci, RPS2, RPM1, and RPS5, operate independently of EDS1. Another RPP locus, RPP8, exhibits no strong exclusive requirement for EDS1 or NDR1 in isolate-specific resistance to P. parasitica, although resistance is compromised weakly by eds1. Similarly, resistance conditioned by two EDS1-dependent RPP genes, RPP4 and RPP5, is impaired partially by ndr1, implicating a degree of pathway cross-talk. Our results provide compelling evidence for the preferential utilization of either signaling component by particular R genes and thus define at least two disease resistance pathways. The data also suggest that strong dependence on EDS1 or NDR1 is governed by R protein structural type rather than pathogen class.
Recovering 3-D shape and reflectance from a small number of photographs (2003)

There are computer graphics applications for which the shape and reflectance of complex objects, such as faces, cannot be obtained using specialized equipment due to cost and practical considerations. We present an image based technique that uses only a small number of example images, and assumes a parametric model of reflectance, to simultaneously and reliably recover the Bidirectional Reflectance Distributions Function (BRDF) and the 3-D shape of non-Lambertian objects. No information about the position and intensity of the light-sources or the position of the camera is required. We successfully apply this approach to human faces, accurately recovering their 3-D shape and BRDF. We use the recovered information to efficiently and accurately render photorealistic images of the faces under novel illumination conditions in which the rendered image intensity closely matches the intensity in real images. The accuracy of our technique is further demonstrated by the close resemblance of the skin BRDF recovered using our method, to the one measured with a method presented in the literature and in which a 3-D scanner was used.
Improving Connection Pooling Persistence Systems (2009)

Server-sided applications often use a persistence system for storing and managing their data in a database. Such a system has become complex and includes but is not limited to a database system, drivers, connection pools, query languages, the mapping between application logic and a database data model and it involves the optimization of resources. One important resource is the connection from applications to the database system since acquiring a connection is a very expensive operation. This paper introduces monitoring facilities for the use or misuse of connections in a persistence system. In particular, it explains how the monitoring can take place in order to configure connection pooling for optimal performance. The implemented solution uses conventional programming methods as well as an aspect-oriented approach. The described facilities are integrated into the development of an enterprise-scale system implementing a communications middleware.