gebhart/patrepeval huggingface dataset:
T Cell Activation by Antibody-Like Immunoreceptors: The Position of the Binding Epitope within the Target Molecule Determines the Efficiency of Activation of Redirected T Cells (2007)

Recombinant TCRs confer specificity to T cells and trigger their activation. Receptors with Ab-derived binding domains have the advantages of MHC-independent Ag recognition and of targeting a variety of chemically different molecules. We explored the impact of the position of a defined epitope within the target molecule on the efficacy of receptor-mediated T cell activation. T cells were grafted with recombinant immunoreceptors that recognize either the membrane distal N or the proximal A3 domain of carcinoembryonic Ag (CEA). Upon binding to isolated, solid-phase immobilized CEA, receptor-mediated T cell activation correlates with the binding efficiency, irrespectively, of the epitope position. Upon binding to CEA expressed on the cell membrane, in contrast, the A3 epitope mediates more efficiently T cell activation than the N epitope, although the N epitope is bound with higher affinity. The CEA N epitope when expressed in a more membrane proximal position, however, activated receptor grafted T cells with higher efficiency than in the distal position. The position of the targeted epitope within the molecule obviously has major impact on the efficacy of T cell activation independently of the binding efficiency of the immunoreceptor.
Peptide-Mediated Interference with Influenza A Virus Polymerase (2007)

The assembly of the polymerase complex of influenza A virus from the three viral polymerase subunits PB1, PB2, and PA is required for viral RNA synthesis. We show that peptides which specifically bind to the protein-protein interaction domains in the subunits responsible for complex formation interfere with polymerase complex assembly and inhibit viral replication. Specifically, we provide evidence that a 25-amino-acid peptide corresponding to the PA-binding domain of PB1 blocks the polymerase activity of influenza A virus and inhibits viral spread. Targeting polymerase subunit interactions therefore provides a novel strategy to develop antiviral compounds against influenza A virus or other viruses.
A fast shaded-polygon renderer (1986)

Image rendering is the performance bottleneck in many computer-graphics systems today because of its computation-intensive nature. Described here is a one-chip VLSI implementation of a shaded-polygon renderer which provides an affordable solution to the bottleneck. The chip takes advantage of a unique extension to Bresenham's vector drawing algorithm [1] to interpolate four axes (for Red, Green, Blue and Z) across a polygon, in addition to the X and Y values. Its inherent accuracy and ease of high-speed hardware implementation distinguish this new algorithm from interpolation with incrementing fractions (DDA).This chip was designed as part of a workstation primarily for mechanical engineering CAD applications. The pipelining and internal bandwidth possible on the chip allows rendering speeds of over twelve-thousand, 1000-pixel, shaded polygons per second, suitable for interactive manipulation of solids. Described in this paper is the derivation of the new algorithm and its implementation in a pipelined, polygon-rendering chip.
Structural analysis of the regulatory elements of the type-II procollagen gene. Conservation of promoter and first intron sequences between human and mouse (1992)

Transcription of the type-II procollagen gene (COL2A1) is very specifically restricted to a limited number of tissues, particularly cartilages. In order to identify transcription-control motifs we have sequenced the promoter region and the first intron of the human and mouse COL2A1 genes. With the assumption that these motifs should be well conserved during evolution, we have searched for potential elements important for the tissue-specific transcription of the COL2A1 gene by aligning the two sequences with each other and with the available rat type-II procollagen sequence for the promoter. With this approach we could identify specific evolutionarily well-conserved motifs in the promoter area. On the other hand, several suggested regulatory elements in the promoter region did not show evolutionary conservation. In the middle of the first intron we found a cluster of well-conserved transcription-control elements and we conclude that these conserved motifs most probably possess a significant function in the control of the tissue-specific transcription of the COL2A1 gene. We also describe locations of additional, highly conserved nucleotide stretches, which are good candidate regions in the search for binding sites of yet-uncharacterized cartilage-specific transcription regulators of the COL2A1 gene.
Basicity of substituted 2-phenyl-1,1,3,3- tetramethylguanidines and other bases in acetonitrile solvent (1989)

A series of 30 phenyl substituted derivatives of 2-phenyl-1,1,3,3-tetramethylguanidine was synthesized and the pK a value of each was measured in acetonitrile using a conventional, general purpose glass electrode. The slope of the Hammett relationship, for the para and meta substituted compounds, ρ = 2.18 ± 0.16, is significantly lower than ρ = 2.85 ± 0.06 found for anilines in water, even though the phenyl ring is attached directly to the basic centre in both cases. The influence of electronic and steric effects on the basicity of the compounds is discussed. The solvent effect on the basicity is also discussed, by comparison of the pK a values in acetonitrile and water. The mean value of [Formula: see text] is slightly higher than the value previously observed for ammonia and aliphatic amines, [Formula: see text]. Additionally, the pKa values were measured for seven other cyclic bases, including 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and 1,5-diazabicyclo[4.3.0]non-5-ene (DBN). Keywords: 2-phenyl-1,1,3,3-tetramethylguanidines, pK a measurements.
Clinical applications of resting state functional connectivity (2010)

During resting conditions the brain remains functionally and metabolically active. One manifestation of this activity that has become an important research tool is spontaneous fluctuations in the blood oxygen level dependent (BOLD) signal of fMRI. The identification of correlation patterns in these spontaneous fluctuations has been termed resting state functional connectivity (fcMRI) and has the potential to greatly increase the translation of fMRI into clinical care. In this article we review the advantages of the resting state signal for clinical applications including detailed discussion of signal to noise considerations. We include guidelines for performing resting state research on clinical populations, outline the different areas for clinical application, and identify important barriers to be addressed to facilitate the translation of resting state fcMRI into the clinical realm.
Examination of the substrate specificity of heparin and heparan sulfate lyases (1990)

We have examined the activities of different preparations of heparin and heparan sulfate lyases from Flavobacterium heparinum. The enzymes were incubated with oligosaccharides of known size and sequence and with complex polysaccharide substrates, and the resulting degradation products were analyzed by strong-anion-exchange high-performance liquid chromatography and by oligosaccharide mapping using gradient polyacrylamide gel electrophoresis. Heparinase (EC 4.2.2.7) purified in our laboratory and a so-called Heparinase I (Hep I) from a commercial source yielded similar oligosaccharide maps with heparin substrates and displayed specificity for di- or trisulfated disaccharides of the structure----4)-alpha-D-GlcNp2S(6R)(1----4)-alpha-L-IdoAp2S( 1----(where R = O-sulfo or OH). Oligosaccharide mapping with two different commercial preparations of heparan sulfate lyase [heparitinase (EC 4.2.2.8)] indicated close similarities in their depolymerization of heparan sulfate. Furthermore, these enzymes only degraded defined oligosaccharides at hexosaminidic linkages with glucuronic acid:----4)-alpha-D-GlcNpR(1----4)-beta-D-GlcAp(1----(where R = N-acetamido or N-sulfo). The enzymes showed activity against solitary glucuronate-containing disaccharides in otherwise highly sulfated domains including the saccharide sequence that contains the antithrombin binding region in heparin. A different commercial enzyme, Heparinase II (Hep II), displayed a broad spectrum of activity against polysaccharide and oligosaccharide substrates, but mapping data indicated that it was a separate enzyme rather than a mixture of heparinase and heparitinase/Hep III. When used in conjunction with the described separation procedures, these enzymes are powerful reagents for the structural/sequence analysis of heparin and heparan sulfate.
Nominal and Effective Dosimetry of Silica Nanoparticles in Cytotoxicity Assays (2008)

Because of their small size and large specific surface area (SA), insoluble nanoparticles are almost not affected by the gravitational force and are generally formulated in stable suspensions or sols. This raises, however, a potential difficulty in in vitro assay systems in which cells adhering to the bottom of a culture vessel may not be exposed to the majority of nanoparticles in suspension. J. G. Teeguarden et al., 2007, Toxicol. Sci. 95, 300-312 have recently addressed this issue theoretically, emphasizing the need to characterize the effective dose (mass or number or SA dose of particles that affect the cells) which, according to their model based on sedimentation and gravitation forces, might only represent a very small fraction of the nominal dose. We hypothesized, in contrast, that because of convection forces that usually develop in sols, the majority of the particles may reach the target cells and exert their potential toxicity. To address this issue, we exposed three different cell lines (A549 epithelial cells, EAHY926 endothelial cells, and J774 monocyte-macrophages) to a monodisperse suspension of Stöber silica nanoparticles (SNP) in three different laboratories. Four different end points (lacticodehydrogenase [LDH] release, LDH cell content, tetrazolium salt (MTT), and crystal violet staining) were used to assess the cell response to nanoparticles. We found, in all cell lines and for all end points, that the cellular response was determined by the total mass/number/SA of particles as well as their concentration. Practically, for a given volume of dispersion, both parameters are of course intimately interdependent. We conclude that the nominal dose remains the most appropriate metric for in vitro toxicity testing of insoluble SNP dispersed in aqueous medium. This observation has important bearings on the experimental design and the interpretation of in vitro toxicological studies with nanoparticles.
Ag(I)-Catalyzed Michael Additions of β-Ketoesters to Nitroalkenes in Water: Remarkable Effect of Water as a Reaction Medium on Reaction Rates (2006)

AgOTf-PPh3 complex-catalyzed Michael additions of β-ketoesters to nitroalkenes in water were performed. The system promotes the reaction efficiently only in water, and interestingly the reaction does not proceed well in organic solvents. In addition, this ­reaction system could be applied to catalytic asymmetric synthesis in water.
A dynamic processor allocation policy for multiprogrammed shared-memory multiprocessors (1993)

We propose and evaluate empirically the performance of a dynamic processor-scheduling policy for multiprogrammed shared-memory multiprocessors. The policy is dynamic in that it reallocates processors from one parallel job to another based on the currently realized parallelism of those jobs. The policy is suitable for implementation in production systems in that: We have evaluated our scheduler and compared it to alternatives using a set of prototype implementations running on a Sequent Symmetry multiprocessor. Using a number of parallel applications with distinct qualitative behaviors, we have both evaluated the policies according to the major criterion of overall performance and examined a number of more general policy issues, including the advantage of “space sharing” over “time sharing” the processors of a multiprocessor, and the importance of cooperation between the kernel and the application in reallocating processors between jobs. We have also compared the policies according to other criteia important in real implementations, in particular, fairness and respone time to short, sequential requests. We conclude that a combination of performance and implementation considerations makes a compelling case for our dynamic scheduling policy.
Programming Windows With MFC (1996)

A definitive book for developers who want to understand and profit from the advances inherent in C++ and the Microsoft Foundation Class (MFC) library, this book explores the basics and, for the first time, gives authoritative coverage of OLE and ActiveX.
Oral-resident natural Th17 cells and γδ T cells control opportunistic Candida albicans infections (2014)

Oropharyngeal candidiasis (OPC) is an opportunistic fungal infection caused by Candida albicans. OPC is frequent in HIV/AIDS, implicating adaptive immunity. Mice are naive to Candida, yet IL-17 is induced within 24 h of infection, and susceptibility is strongly dependent on IL-17R signaling. We sought to identify the source of IL-17 during the early innate response to candidiasis. We show that innate responses to Candida require an intact TCR, as SCID, IL-7Rα(-/-), and Rag1(-/-) mice were susceptible to OPC, and blockade of TCR signaling by cyclosporine induced susceptibility. Using fate-tracking IL-17 reporter mice, we found that IL-17 is produced within 1-2 d by tongue-resident populations of γδ T cells and CD3(+)CD4(+)CD44(hi)TCRβ(+)CCR6(+) natural Th17 (nTh17) cells, but not by TCR-deficient innate lymphoid cells (ILCs) or NK cells. These cells function redundantly, as TCR-β(-/-) and TCR-δ(-/-) mice were both resistant to OPC. Whereas γδ T cells were previously shown to produce IL-17 during dermal candidiasis and are known to mediate host defense at mucosal surfaces, nTh17 cells are poorly understood. The oral nTh17 population expanded rapidly after OPC, exhibited high TCR-β clonal diversity, and was absent in Rag1(-/-), IL-7Rα(-/-), and germ-free mice. These findings indicate that nTh17 and γδ T cells, but not ILCs, are key mucosal sentinels that control oral pathogens.
Selective Itk Inhibitors Block T-Cell Activation and Murine Lung Inflammation (2004)

Nonreceptor protein tyrosine kinases including Lck, ZAP-70, and Itk play essential roles in T-cell receptor (TCR) signaling. Gene knockout studies have revealed that mice lacking these individual kinases exhibit various degrees of immunodeficiency; however, highly selective small molecule inhibitors of these kinases as potential immunosuppressive agents have not been identified. Here we discovered two novel compounds, BMS-488516 and BMS-509744, that potently and selectively inhibit Itk kinase activity. The compounds reduce TCR-induced functions including PLCgamma1 tyrosine phosphorylation, calcium mobilization, IL-2 secretion, and T-cell proliferation in vitro in both human and mouse cells. The inhibitors suppress the production of IL-2 induced by anti-TCR antibody administered to mice. BMS-509744 also significantly diminishes lung inflammation in a mouse model of ovalbumin-induced allergy/asthma. Our findings represent the first description of selective inhibitors to probe human Itk function and its associated pathway, and support the hypothesis that Itk is a therapeutic target for immunosuppressive and inflammatory diseases.
N‐Methyl‐d‐aspartate receptor subunit‐ and neuronal‐type dependence of excitotoxic signaling through post‐synaptic density 95 (2010)

NMDA receptors (NMDARs) mediate excitatory synaptic transmission during repetitive or prolonged glutamate release, playing a critical role in synaptic plasticity or cell death, respectively. Evidence indicates that a major pathway of NMDAR signaling to cell death in cortical and hippocampal neurons requires the scaffolding protein post-synaptic density 95 (PSD-95) and activation of neuronal nitric oxide synthase. However, it is not known if this PSD-95-dependent pathway contributes to excitotoxicity in other brain regions. It is also unclear whether the neuroprotective effects of Tat-NR2B9c, a membrane-permeant peptide that disrupts PSD-95/NMDAR binding, correlate with uncoupling NR2B- and/or NR2A-type NMDARs from PSD-95. In this study, we used cultured hippocampal and striatal neurons to test the potency of Tat-NR2B9c on uncoupling NR2 subunits from PSD-95 and protecting against NMDA-induced excitotoxicity. We found that the concentration of Tat-NR2B9c required to dissociate 50% of PSD-95 was fourfold lower for NR2B than NR2A in cultured hippocampal and striatal neurons, and that this concentration correlated tightly with protection against NMDA-induced toxicity in hippocampal neurons without altering NMDAR current. In contrast, NMDAR signaling to cell death in cultured striatal neurons occurred independently of the NR2B/PSD-95 interaction or neuronal nitric oxide synthase activation. These results will facilitate development of neuronal type-specific protective therapies.
Azo Derivatives of the Pyrimidines (1932)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
CW periodically poled LiNbO 3 optical parametric oscillator model with strong idler absorption (1999)

An analytical model is described for predicting the gain and performance of cw, singly resonant, optical parametric oscillators with strong idler absorption, strong pump depletion and thermally induced dephasing. Pump and signal beam focusing effects are included by using the Guha, Wu and Falk h<SUB>sm</SUB> parameters. It is shown that significant parametric gain can be generated with an idler absorption- length product exceeding 10, and in some cases idler absorption is seen to enhance the pump depletion by impeding back conversion. The model accurately predicts current experimental results with weak idler absorption, and greatly over predicts the performance with high idler absorption. This difference is believed to be due to thermally induced focus that strongly disturbs the resonant optical cavity for the signal. Shorter crystal lengths, with resonant pump enhancement, offers a possible solution.
Nucleosomes in serum of patients with benign and malignant diseases (2001)

High quantities of mono- and oligonucleosomes circulate in the blood of patients with malignant tumors. For their direct quantification in serum, we modified the Cell Death Detection(plus)-ELISA for its application in liquid materials. We examined sera samples from 590 persons, including 418 patients with malignant tumors, 109 patients with benign diseases and 63 healthy persons. We also observed the kinetics of the concentration of nucleosomes in serum samples from 20 patients undergoing chemotherapy and from 16 patients undergoing radiotherapy. Sera of patients with malignant tumors contained considerably higher concentrations of nucleosomes (mean = 350 arbitrary units [AU], median = 190 AU) compared with those of healthy persons (mean = 36 AU, median = 24 AU; p = 0.0001) and patients with benign diseases (mean = 264 AU, median = 146 AU; p = 0.072). Concerning the follow-up investigations, the concentration of nucleosomes in serum increased 24-72 hr after the first application of chemotherapy and 6-24 hr after the start of radiotherapy. A subsequent decrease was often correlated with regression of the tumor. In patients undergoing chemotherapy, an increase in the baseline values of circulating nucleosomes >50%, which were determined before each new therapeutic cycle, was correlated with progression of disease; all patients with disease regression showed a decrease >50% of the baseline values. In patients undergoing radiotherapy, an early decrease of the nucleosomal concentration (< or = 1 day after the initial peak during therapy) to low minimum levels (< or = 100 AU) correlated with good clinical outcome; a late decrease (>1 day) to higher minimum levels (>100 AU) was associated with a worse clinical outcome. Thus, the concentration of nucleosomes in serum might be a useful tool for monitoring the biochemical response during antitumor therapy, especially for the early estimation of therapeutic efficacy.
Pivotal Roles of T-Helper 17-Related Cytokines, IL-17, IL-22, and IL-23, in Inflammatory Diseases (2013)

T-helper 17 (Th17) cells are characterized by producing interleukin-17 (IL-17, also called IL-17A), IL-17F, IL-21, and IL-22 and potentially TNF- α and IL-6 upon certain stimulation. IL-23, which promotes Th17 cell development, as well as IL-17 and IL-22 produced by the Th17 cells plays essential roles in various inflammatory diseases, such as experimental autoimmune encephalomyelitis, rheumatoid arthritis, colitis, and Concanavalin A-induced hepatitis. In this review, we summarize the characteristics of the functional role of Th17 cells, with particular focus on the Th17 cell-related cytokines such as IL-17, IL-22, and IL-23, in mouse models and human inflammatory diseases.
Ultracompact corner-mirrors and T-branches in silicon-on-insulator (2002)

In this letter, we have designed and fabricated low-loss ultrasmall corner mirrors and T-branches on thin silicon-on-insulator material system. The measured performance of the devices agrees with simulations using finite-difference time-domain calculations. These devices demonstrate the potential of this high-refractive-index-contrast material system for high-density planar optical integrated circuits.
Cytokine release assays for the prediction of therapeutic mAb safety in first-in man trials — Whole blood cytokine release assays are poorly predictive for TGN1412 cytokine storm (2015)

The therapeutic monoclonal antibody (mAb) TGN1412 (anti-CD28 superagonist) caused near-fatal cytokine release syndrome (CRS) in all six volunteers during a phase-I clinical trial. Several cytokine release assays (CRAs) with reported predictivity for TGN1412-induced CRS have since been developed for the preclinical safety testing of new therapeutic mAbs. The whole blood (WB) CRA is the most widely used, but its sensitivity for TGN1412-like cytokine release was recently criticized. In a comparative study, using group size required for 90% power with 5% significance as a measure of sensitivity, we found that WB and 10% (v/v) WB CRAs were the least sensitive for TGN1412 as these required the largest group sizes (n = 52 and 79, respectively). In contrast, the peripheral blood mononuclear cell (PBMC) solid phase (SP) CRA was the most sensitive for TGN1412 as it required the smallest group size (n = 4). Similarly, the PBMC SP CRA was more sensitive than the WB CRA for muromonab-CD3 (anti-CD3) which stimulates TGN1412-like cytokine release (n = 4 and 4519, respectively). Conversely, the WB CRA was far more sensitive than the PBMC SP CRA for alemtuzumab (anti-CD52) which stimulates FcγRI-mediated cytokine release (n = 8 and 180, respectively). Investigation of potential factors contributing to the different sensitivities revealed that removal of red blood cells (RBCs) from WB permitted PBMC-like TGN1412 responses in a SP CRA, which in turn could be inhibited by the addition of the RBC membrane protein glycophorin A (GYPA); this observation likely underlies, at least in part, the poor sensitivity of WB CRA for TGN1412. The use of PBMC SP CRA for the detection of TGN1412-like cytokine release is recommended in conjunction with adequately powered group sizes for dependable preclinical safety testing of new therapeutic mAbs.