gebhart/patrepeval huggingface dataset:
Functional characterization of the human tumor necrosis factor receptor p75 in a transfected rat/mouse T cell hybridoma. (1992)

We investigated the biological role of the human tumor necrosis factor p75 (hTNF-R75), making use of the species specificity of TNF responses in murine (m) T cell lines. Several TNF-mediated activities on mouse T cells, such as cytokine induction or proliferation, showed a 100-500-fold difference in specific biological activity between mTNF and hTNF. After transfection of hTNF-R75 cDNA in a rat/mouse T cell hybridoma (PC60), however, the 100-fold lower specific biological activity of hTNF was converted to the same specific biological activity as mTNF. The TNF-mediated induction of granulocyte/macrophage colony-stimulating factor was strongly synergized by the addition of interleukin 1. In the presence of the latter cytokine, ligand-competing monoclonal antibodies against hTNF-R75 (utr-1, utr-2, utr-3) were agonistic on transfected PC60 cells. This agonistic activity was further enhanced by crosslinking with sheep anti-murine immunoglobulin antibodies. These data provide direct evidence for a functional role of TNF-R75, without ligand-dependent TNF-R55 involvement, in the induction of cytokine secretion in T cells.
PD-1 Inhibitor MK-3475 Again Shows Promise in Advanced Melanoma (2013)

The PD-1 inhibitor MK-3475 is continuing to show activity and long-term responses in patients with metastatic melanoma, according to results presented at the International Congress of the Society for Melanoma Research.
Interaction of calpastatin with calpain: a review (2004)

Calpastatin is a multiheaded inhibitor capable of inhibiting more than one calpain molecule. Each inhibitory domain of calpastatin has three subdomains, A, B, and C; A binds to domain IV and C binds to domain VI of the calpains. Crystallographic evidence shows that binding of C to domain VI involves hydrophobic interactions at a site near the first EF-hand in domain VI. Sequence homology suggests that binding of A to calpain domain IV also involves hydrophobic interactions near the EF1-hand of domain IV. Neither subdomain A nor C have inhibitory activity without subdomain B, but both increase the inhibitory activity of B. Subdomain B peptides have no inhibitory activity unless they contain at least 13 amino acids, and inhibitory activity increases with the number of amino acid residues, suggesting that inhibition requires interaction over a large area of the calpain molecule. Although subdomain B inhibition kinetically is competitive in nature, subdomain B does not seem to interact with the active site of the calpains directly, but may bind to domain III of the calpains and act to block access to the active site. It is possible that subdomain B binds to calpain only after it has been activated by Ca2+.
Coherent spatial and temporal occlusion generation (2009)

A vastly growing number of productions from the entertainment industry are aiming at 3D movie theatres. These productions use a two-view format, primarily intended for eye-wear assisted viewing in a well defined environment. To get this 3D content into the home environment, where a large variety of 3D viewing conditions exists (e.g different display sizes, display types, viewing distance), we need a flexible 3D format that can adjust the depth effect. Such a format is the image plus depth format in which a video frame is enriched with depth information of all pixels in the video. This format can be extended with an additional layer for occluded video and associated depth, that contains what is behind objects in the video. To produce 3D content in this extended format, one has to deduce what is behind objects. There are various axes along which this occluded data can be obtained. This paper presents a method to automatically detect and fill the occluded areas exploiting the temporal axis. To get visually pleasing results, it is of utmost importance to make the inpainting globally consistent. To do so, we start by analyzing data along the temporal axis and compute a confidence for each pixel. Then pixels from the future and the past that are not visible in the current frame are weighted and accumulated based on computed confidences. These results are then fed to a generic multi-source framework that computes the occlusion layer based on the available confidences and occlusion data.
Design and modification of EGF4KDEL 7Mut, a novel bispecific ligand-directed toxin, with decreased immunogenicity and potent anti-mesothelioma activity (2009)

These data show that EGF4KDEL 7Mut is a promising new anti-mesothelioma agent that was developed to specifically address the obstacles facing clinical utility of targeted toxins.
Killer Cell Inhibitory Receptor Recognition of Human Leukocyte Antigen (HLA) Class I Blocks Formation of a pp36/PLC-γ Signaling Complex in Human Natural Killer (NK) Cells (1996)

The killer cell inhibitory receptors (KIR) of human natural killer (NK) cells recognize human leukocyte antigen class I molecules and inhibit NK cell cytotoxicity through their interaction with protein tyrosine phosphatases (PTP). Here, we report that KIR recognition of class I ligands inhibits distal signaling events and ultimately NK cell cytotoxicity by blocking the association of an adaptor protein (pp36) with phospholipase C-gamma in NK cells. In addition, we demonstrate that pp36 can serve as a substrate in vitro for the KIR-associated PTP, PTP-1C (also called SHP-1), and that recognition of class I partially disrupts tyrosine phosphorylation of NK cell proteins, providing evidence for KIR-induced phosphatase activity.
Genetic characteristics of patients with congenital hyperinsulinism (2018)

Identification of the cause of congenital hyperinsulinism helps guide management decisions. Use of therapies with limited benefit and significant potential risks should be avoided.
SEL, a Selective Enrichment Broth for Simultaneous Growth of Salmonella enterica , Escherichia coli O157:H7, and Listeria monocytogenes (2008)

Multipathogen detection on a single-assay platform not only reduces the cost for testing but also provides data on the presence of pathogens in a single experiment. To achieve this detection, a multipathogen selective enrichment medium is essential to allow the concurrent growth of pathogens. SEL broth was formulated to allow the simultaneous growth of Salmonella enterica, Escherichia coli O157:H7, and Listeria monocytogenes. The results were compared to those obtained with the respective individual selective enrichment broths, Rappaport-Vassiliadis (RV) for S. enterica, modified E. coli broth with 20 mg of novobiocin/liter for E. coli O157:H7, and Fraser broth for L. monocytogenes, and a currently used universal preenrichment broth (UPB). The growth of each pathogen in SEL inoculated at 10(1) or 10(3) CFU/ml was superior to that in the respective individual enrichment broth, except in the case of RV, in which Salmonella cells inoculated at both concentrations grew equally well. In mixed-culture experiments with cells of the three species present in equal concentrations or at a 1:10:1,000 ratio, the overall growth was proportional to the initial inoculation levels; however, the growth of L. monocytogenes was markedly suppressed when cells of this species were present at lower concentrations than those of the other two species. Further, SEL was able to resuscitate acid- and cold-stressed cells, and recovery was comparable to that in nonselective tryptic soy broth containing 6% yeast extract but superior to that in the respective individual selective broths. SEL promoted the growth of all three pathogens in a mixture in ready-to-eat salami and in turkey meat samples. Moreover, each pathogen was readily detected by a pathogen-specific immunochromatographic lateral-flow or multiplex PCR assay. Even though the growth of each pathogen in SEL was comparable to that in UPB, SEL inhibited greater numbers of nontarget organisms than did UPB. In summary, SEL was demonstrated to be a promising new multiplex selective enrichment broth for the detection of the three most prominent food-borne pathogens by antibody- or nucleic acid-based methods.
Identification of a new malaria susceptibility locus (Char4) in recombinant congenic strains of mice (2001)

The genetic component of susceptibility to malaria is complex, both in humans and in the mouse model of infection. Two murine loci on chromosomes 8 (Pchr/Char2) and 9 (Char1) have previously been mapped in F(2) crosses, and play an important role in regulating blood parasitemia and survival to infection with Plasmodium chabaudi. These loci explain only part of the interstrain phenotypic variance, and their penetrance and expressivity vary in different inbred strains. Novel loci regulating response to P. chabaudi infection were investigated by using an alternative strategy based on a newly derived set of AcB/BcA recombinant congenic strains bred from malaria-susceptible A/J (A) and resistant C57BL/6J (B6). One of the AcB strains, AcB55, is shown to be highly resistant to infection despite 83% susceptible A genomic composition, including susceptibility alleles at Char1 and Pchr/Char2. Early onset of parasite clearance in AcB55 is associated with lower peak parasitemia and absence of mortality. Linkage analysis in an informative (AcB55 x A)F(2) population, using peak parasitemia as a quantitative trait, located a new B6-derived resistance locus on chromosome 3 (lod score = 6.57) that we designate Char4. A second, suggestive linkage on chromosome 10 (lod score = 2.53) shows additive effect with Char4 on peak parasitemia. Char4 maps to a small congenic B6 fragment in AcB55 that should facilitate the search for candidate genes. Our findings provide an entry point for parallel association studies in humans between the syntenic 4q21-4q25 region and susceptibility to disease in endemic areas of malaria.
Phenotypic Drug Susceptibility Assay for Influenza Virus Neuraminidase Inhibitors (2004)

A flow cytometric (fluorescence-activated cell sorter [FACS]) assay was developed for analysis of the drug susceptibilities of wild-type and drug-resistant influenza A and B virus laboratory strains and clinical isolates for the neuraminidase (NA) inhibitors oseltamivir carboxylate, zanamivir, and peramivir. The drug susceptibilities of wild-type influenza viruses and those with mutations in the hemagglutinin (HA) and/or NA genes rendering them resistant to one or more of the NA inhibitors were easily determined with the FACS assay. The drug concentrations that reduced the number of virus-infected cells or the number of PFU by 50% as determined by the FACS assay were similar to those obtained with the more time-consuming and labor-intensive virus yield reduction assay. The NA inhibition (NAI) assay confirmed the resistance patterns demonstrated by the FACS and virus yield assays for drug-resistant influenza viruses with mutations in the NA gene. However, only the FACS and virus yield assays detected NA inhibitor-resistant influenza viruses with mutations in the HA gene but not in the NA gene. The FACS assay is more rapid and less labor-intensive than the virus yield assay and just as quantitative. The FACS assay determines the drug susceptibilities of influenza viruses with mutations in either the HA or NA genes, making the assay more broadly useful than the NAI assay for measuring the in vitro susceptibilities of influenza viruses for NA inhibitors. However, since only viruses with mutations in the NA gene that lead to resistance to the NA inhibitors correlate with clinical resistance, this in vitro assay should not be used in the clinical setting to determine resistance to NA inhibitors. The assay may be useful for determining the in vivo susceptibilities of other compounds effective against influenza A and B viruses.
Altered balance between excitatory and inhibitory inputs onto CA1 pyramidal neurons from SV2A‐deficient but not SV2B‐deficient mice (2012)

Synaptic vesicle protein 2 (SV2) is a glycoprotein that exists in three isoforms, SV2A, SV2B, and SV2C. SV2A knockout (KO) mice and SV2A/SV2B double KO (DKO) mice, but not SV2B KO animals, start to experience severe seizures and weight loss 7 days after birth and die at about postnatal day (P)14-P23. Because excitatory and inhibitory inputs play a major role in controlling neuronal excitability in the hippocampus, we examined the effects of SV2A and/or SV2B deletions on glutamatergic and GABA(A) neurotransmission in hippocampal CA1 pyramidal neurons. Spontaneous and miniature excitatory and inhibitory postsynaptic currents (sEPSCs, mEPSCs, sIPSCs, and mIPSCs, respectively) were recorded using the whole-cell patch-clamp technique in slices from P6-P14 mice. The frequency of sEPSCs was increased in SV2A KO and SV2A/SV2B DKO mice, but their amplitude was unchanged. Such changes were not observed in SV2B KOs. On the contrary, the frequency and amplitude of sIPSCs were decreased in SV2A KO and SV2A/SV2B DKO mice but not in SV2B KO animals, as reported previously for the CA3 region. Kinetic parameters of sIPSCs and sEPSCs were unchanged. Importantly, no changes were observed in any genotype when examining mEPSCs and mIPSCs. We conclude that action potential- and Ca(2+) -dependent glutamatergic and GABAergic synaptic transmission are differentially altered in the hippocampus of SV2A-deficient mice, whereas the mechanism of exocytosis itself is not changed. The altered balance between these major excitatory and inhibitory inputs is probably a contributing factor to seizures in SV2A KO and SV2A/SV2B DKO mice.
Keratinocyte conditioned medium stimulates type IV collagenase synthesis in cultured human keratinocytes and fibroblasts (1995)

We have previously shown that conditioned medium from cultured human keratinocytes stimulates proliferation of a variety of cell types involved in wound healing, as well as re-epithelialization of wounds in human skin in vitro. We now present evidence for an autocrine/paracrine control of the synthesis of type IV collagenases in human keratinocytes and fibroblasts. During wound healing, keratinocytes migrate over the wound bed, an activity coupled with lysis of basement membranes, and hence requiring the presence of collagenases. Collagenases are also needed for the production and remodelling of the granulation tissue. In order to study the autocrine/paracrine control of collagenase production in keratinocytes and fibroblasts, we stimulated these cells in culture with conditioned medium from cultured keratinocytes. Protease synthesis was determined by affinity labelling with 3H-diisopropylfluorophosphoridate (DFP) and by zymography. Keratinocyte-conditioned medium was found to increase the expression of 72 and 92 kDa type IV collagenase in human keratinocytes, and the 72 kDa collagenase in human fibroblasts, indicating that an autocrine/paracrine control mechanism is involved in collagenase production in these cell types during wound healing. This increased expression of collagenases could be partly responsible for the stimulated healing seen in wounds treated with sheets of cultured keratinocytes.
Cervical Inflammation and Immunity Associated With Hormonal Contraception, Pregnancy, and HIV-1 Seroconversion (2014)

HC use, pregnancy, and young age alter cervical immunity in different ways known to increase risk of HIV, for example, through increased levels of pro-inflammatory cytokines or decreased levels of SLPI. Higher levels of RANTES may be one factor underlying a possible association between DMPA use and risk of HIV acquisition.
Major Histocompatibility Complex: Interaction with Peptides (2011)

Abstract T‐cell‐specific immunity functions in a major histocompatibility complex (MHC)‐dependent manner. MHC molecules present antigenic peptides on the surface of cells to be recognised by specific T‐cells. MHC class I and class II molecules possess highly similar structural features used to load peptides. Specifically, both contain peptide‐binding grooves formed by two α‐helices and eight β‐strands. In the peptide‐binding groove, specific amino acids compose pockets that accommodate the corresponding side chains of the anchor residues of the presented peptides. Peptide‐binding preferences exist among different alleles of both of MHC I and MHC II molecules, which are mainly dependent on amino acid polymorphisms in the peptide‐binding grooves of MHC chains. Aside from the common binding of peptides to MHC molecules, the currently determined structures of post‐translationally modified peptides to MHC molecules demonstrate that the modified groups have important roles in the peptide–MHC interaction. The illumination of the binding features of peptides to MHC molecules has aided our understanding of T‐cell‐specific immunity and the development of T‐cell epitope‐related vaccines. Key Concepts: MHC I and class II molecules fold into a highly similar conformations featuring a peptide‐binding groove to present T‐cell epitopes. Peptide‐binding grooves of MHC I molecules are composed of two α‐helices and eight β‐strands formed by one heavy chain, while MHC II uses two domains from different chains to construct the peptide‐binding groove. Peptides bind to MHC molecules through primary and secondary anchor residues protruding into the pockets in the peptide‐binding grooves. Peptide preferences are dependent on the amino acids polymorphisms comprising the anchor pockets, which are related to the various alleles of MHC. The conformations of peptides presented by MHC I molecules are length‐dependant. The modified groups of post‐translationally modified peptides have important roles in the peptide–MHC interaction. MHC is called HLA, human leucocyte antigen, in human; H‐2 in mice.
ChemInform Abstract: Synthesis and Bioactivity of Novel Bis(heteroaryl)piperazine (BHAP) Reverse Transcriptase Inhibitors: Structure‐Activity Relationships and Increased Metabolic Stability of Novel Substituted Pyridine Analogues. (1997)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Rapid isoelectric trapping in a micropreparative‐scale multicompartment electrolyzer (2007)

A multicompartmental electrolyzer called membrane-separated wells for isoelectric focusing and trapping (MSWIFT) has been developed and tested for micropreparative-scale isoelectric trapping separations. In the MSWIFT, the length of the heat conduction path from the center of the compartments to the wall is less than 1 mm. The compartments are made from 99.8% nonporous alumina that has a high heat conductivity and a high specific heat capacity, leading to adequate Joule heat dissipation even at power loads as high as 5 W. The length of any compartment parallel to the electric field (the intermembrane distance) can be selected to be multiples of 1.5 mm, leading to compartment volumes that are multiples of about 60 muL. A maximum of 20 (1.5 mm long) separation compartments can be readily assembled in the current version of MSWIFT. The MSWIFT has been used to desalt samples, isolate small ampholytic components (amino acids, peptides, and dyes), prefractionate complex protein mixtures and enrich minor components; these separations were achieved in 20-60 min.
A second thrombospondin gene in the mouse is similar in organization to thrombospondin 1 but does not respond to serum. (1991)

A second, expressed thrombospondin (TSP) gene, Thbs2, has been identified in the mouse. The exon/intron organization of Thbs2 is highly conserved in comparison with Thbs1 in that exon size and the pattern of interruption of the reading frame by introns are preserved, but there is a marked divergence in coding sequence, primarily in the first 7 exons. On the other hand, the DNA and translated amino acid sequences of exons coding for the type I, II, and III repeats in the two TSPs are far better conserved. Thbs2 is located on chromosome 17, band A3, whereas Thbs1 was found on chromosome 2, band F. In marked contrast to Thbs1, the Thbs2 gene is not induced by serum in NIH 3T3 cells; promoter sequences in the two genes are also very different. It is therefore likely that the two TSPs perform related but distinct functions.
A best-first language processing model integrating the unification grammar and Markov language model for speech recognition applications (1993)

A language processing model is proposed in which the grammatical approach of unification grammar and the statistical approach of Markov language models are properly integrated in a word lattice chart parsing algorithm with different best-first parsing strategies. This model has been successfully implemented in experiments on Mandarin speech recognition although it is language-independent. Test results show that significant improvements in both correct rate of recognition and computation speed can be achieved. A correct rate of 93.8% and 5 s per sentence on an IBM PC/AT, as compared with 73.8% and 25 s using unification grammar alone and 82.2% and 3 s using a Markov language model alone, was achieved. This high performance is due to the effective rejection of noisy word hypothesis interferences; that is, the unification-based grammatical analysis eliminates all illegal combinations, while the Markovian probabilities of constituents combined with the considerations on constituent length indicate the correct direction of processing.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
ProxylessNAS: Direct Neural Architecture Search on Target Task and Hardware (2018)

Neural architecture search (NAS) has a great impact by automatically designing effective neural network architectures. However, the prohibitive computational demand of conventional NAS algorithms (e.g. $10^4$ GPU hours) makes it difficult to \emph{directly} search the architectures on large-scale tasks (e.g. ImageNet). Differentiable NAS can reduce the cost of GPU hours via a continuous representation of network architecture but suffers from the high GPU memory consumption issue (grow linearly w.r.t. candidate set size). As a result, they need to utilize~\emph{proxy} tasks, such as training on a smaller dataset, or learning with only a few blocks, or training just for a few epochs. These architectures optimized on proxy tasks are not guaranteed to be optimal on the target task. In this paper, we present \emph{ProxylessNAS} that can \emph{directly} learn the architectures for large-scale target tasks and target hardware platforms. We address the high memory consumption issue of differentiable NAS and reduce the computational cost (GPU hours and GPU memory) to the same level of regular training while still allowing a large candidate set. Experiments on CIFAR-10 and ImageNet demonstrate the effectiveness of directness and specialization. On CIFAR-10, our model achieves 2.08\% test error with only 5.7M parameters, better than the previous state-of-the-art architecture AmoebaNet-B, while using 6$\times$ fewer parameters. On ImageNet, our model achieves 3.1\% better top-1 accuracy than MobileNetV2, while being 1.2$\times$ faster with measured GPU latency. We also apply ProxylessNAS to specialize neural architectures for hardware with direct hardware metrics (e.g. latency) and provide insights for efficient CNN architecture design.