gebhart/patrepeval huggingface dataset:
The proteasome inhibitor MG132 promotes accumulation of the steroidogenic acute regulatory protein (StAR) and steroidogenesis (2001)

StAR, a protein synthesized in the cytoplasm and subsequently imported into mitochondria, regulates the rate-determining step in steroidogenesis, the transport of cholesterol from the outer to the inner mitochondrial membrane. The active form of StAR is the 37 kDa pre-protein, which has a short half-life. To determine whether proteasomes participate in the turnover of StAR, we incubated primary cultures of preovulatory rat granulosa cells and immortalized human granulosa cells in the presence of MG132, a specific inhibitor to proteasome catalysis. This treatment caused accumulation of StAR in unstimulated cells. Moreover, incubation of the cells with MG132 in the presence of forskolin (FK), luteinizing hormone/chorionic gonadotropin or follicular stimulating hormone augmented the accumulation of both the 37 kDa cytoplasmic protein and the 30 kDa mature mitochondrial protein, compared to cells incubated with FK or the gonadotropic hormones alone. Concomitantly, progesterone production was enhanced. In contrast no elevation in the 37 kDa StAR intracellular levels or progesterone production was observed following incubation of the cells with the cysteine protease inhibitor E-64. The increase of the 37 kDa StAR protein was evident after 15 min and 30 min of incubation with MG132 (143% and 187% of control values, respectively) with no significant elevation of the 30 kDa protein. Accumulation of the intermediate mitochondrial 32 kDa protein was evident after 1-2 h and the accumulation of the 30 kDa protein was evident only after 4 h of incubation with MG132. In contrast, no elevation in adrenodoxin, a component of the cytochrome P450scc enzyme system, was found. These data suggest that StAR protein is either directly or indirectly degraded by the proteasome which may explain, in part, its short half-life. Moreover, it seems that the cytosolic 37 kDa protein, which is responsible for the steroidogenic activity of StAR, is the primary proteasomal substrate and that the inhibition of its degradation by MG132 causes the up-regulation of progesterone production.
A Local-Pair Mechanism for High-Temperature Superconductivity at the Di- and Trivalent Sites (2000)

The \\( p/d \\) hybridization that primarily characterizes copper leads to local moments, lacking of the pair-breaking variety, both at di- and trivalent sites. Support for the negative-U model is extracted from the author&amp;amp;apos;s earlier work on the metal-insulator transition. A more magnetically oriented model, like the resonant valence band model which we have recently associated with our observations in d1 TiOCl etc., does not really seem suited to the geometry and electronic conditions in the copper oxides present. However it is suggested that TiB2, La3S4 and the Chevrel phases might be open to treatment by such a model. Comment it also made about how the superconductivity of PdHx and Ba(Pb/Bi)O3 might be seen in the light of the present model, and attention is directed once again to what might be happening in the pressure-quenched CuCl and CdS.
Chronic endothelin receptor antagonist treatment of young spontaneously hypertensive rats (1995)

Endothelins are not involved in the development of hypertension or vascular hypertrophy and remodelling in young SHR.
Histopathological Features of L-Asparaginase-Induced Liver Disease (2003)

We studied the histopathological changes of liver in four patients who developed hepatomegaly and abnormal liver chemistry tests 2 to 20 days following administration of L-asparaginase as a part of a combination chemotherapy regimen for treatment of acute lymphoblastic leukemia. The severity of the liver disease due to L-asparaginase was unpredictable. One patient developed acute fulminant hepatic failure and required liver transplantation. The most consistent pathological change, observed in all four cases, was diffuse steatosis. Other changes included patchy hepatocyte necrosis, mixed inflammatory cell infiltrates in the portal tracts, and variable degrees of hepatocellular, or canalicular cholestasis, or a combination of these.
Comparative Patch‐clamp Studies with Freshly Dissociated Rat Hippocampal and Striatal Neurons on the NMDA Receptor Antagonistic Effects of Amantadine and Memantine (1996)

Patch- and concentration-clamp techniques were used to compare the effects of the uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists (+)-MK-801 (dizocilpine, (+)-5-methyl-10, 11-dihydro-5H-dibenzocyclohepten-5, 10-imine maleate), ketamine, memantine (1-amino-3,5-dimethyladamantane) and amantadine (1-amino-adamantane) on agonist-induced inward currents in freshly dissociated rat hippocampal and striatal neurons. In hippocampal neurons, ketamine (5 microM), menantine (10 microM) and amantadine (100 microM) selectively antagonized inward current responses to NMDA (500 microM plus glycine 5 microM) in a voltage-dependent manner without affecting responses to (s)-alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (100 microM) or gamma-aminobutyric acid (10 microM). The NMDA receptor antagonistic effect of all four agents was typical of open channel blockade. The kinetics of blockade/unblockade was inversely related to antagonist affinity. In hippocampal neurons amantadine was the least potent NMDA receptor antagonist (IC50 18.6 +/- 0.9 microM) and showed the fastest blocking kinetics, whereas (+)-MK-801 was the most potent (IC50 0.12 +/- 0.01 microM) and showed the slowest blocking kinetics. Memantine (IC50 1.04 +/- 0.26 microM) and ketamine (IC50 0.43 +/- 0.10 microM) were almost equipotent and had similar, intermediate blocking kinetics. In striatal neurons recorded under identical conditions (+)-MK-801, ketamine and memantine were 3- to 4-fold less potent whereas amantadine was somewhat more potent than on hippocampal neurons. This could offer an explanation for the better clinical profile of amantadine in Parkinson's disease, as therapeutically relevant concentrations of amantadine are likely to be more active in the striatum whereas memantine is likely to be more active in other structures.
Nonintrusive precision instrumentation of microcontroller software (2005)

Debugging, testing, and profiling microcontroller programs are notoriously difficult. The lack of supporting software such as an operating system, a narrow interface to the hardware chip, and delicately timed sequences of code present significant challenges which can be exacerbated by the presence of additional debugging or profiling code. In this paper we present a solution to the precision instrumentation problem for microcontroller code that is based upon our open, flexible simulator framework, Avrora. Our simulator preserves all timing and behavior of the instrumented program while allowing precision measurement of application-specific quantities.
Optimal humanization of 1B4, an anti-CD18 murine monoclonal antibody, is achieved by correct choice of human V-region framework sequences (1993)

The murine anti-CD18 mAb 1B4 has been humanized using CDR grafting. Three VH (Gal, Jon, and New) and two VL (Rei and Len) human frameworks, whose selection was based exclusively on their sequence identity with m1B4, were used to construct five human gamma 4/kappa recombinant antibodies: Gal/Rei, Gal/Len, Jon/Rei, and New/Rei, and a "hemichimeric" antibody pairing the VH of m1B4 with grafted Rei. Each of these h1B4 constructs completely inhibited the binding of m1B4 to activated human leukocytes with avidities (IC50) ranging from 1.5 to 8.0 nM, compared to 0.5 nM for m1B4. Replacement of three VH residues in the best VH framework, Gal, with the corresponding m1B4 "packing" (nonsolvent exposed) residues gave an h1B4 (mutant Gal/Rei) with the same avidity as m1B4. Avidity correlated with overall percent identity between the human and murine VH frameworks and, in particular, with conservation of "packing" residues. Rei and Len VL frameworks proved to be interchangeable. Further characterization showed that the Gal/Rei prototype was equipotent to m1B4 in blocking adhesion of polymorphonuclear leukocytes and monocytes to human vascular endothelium in vitro, and polymorphonuclear leukocyte extravasation into C5a-injected rabbit or monkey skin sites. Dual-label immunofluorescence microscopy of bone marrow cells with Gal/Rei h1B4 and m1B4 demonstrated that the fine specificity of the combining sites had not been altered by humanization. Reduced immunogenicity was demonstrated in rhesus monkeys that tolerated weekly treatment with h1B4 for 6 wk, whereas m1B4 induced profound anaphylaxis at 3 wk. Anti-1B4 titers in h1B4-treated rhesus were 50 to 66% lower and developed 1 wk later than in m1B4-treated monkeys. Crucially, the anti-h1B4 antibodies were anti-idiotypic while the anti-m1B4 antibodies were directed against constant and framework regions. We conclude that sequence identity searches are sufficient to identify suitable human frameworks for CDR-grafting of m1B4, yielding functionally equivalent humanized antibodies that are tolerated better in primates.
ENDOTOXINS AND DISEASE MECHANISMS (1987)

In this chapter, current concepts about the mechanisms of action of endotoxin are reviewed. Particular attention is focused upon endotoxin-induced production of soluble mediators from macrophages and mononuclear cells and on the potential contribution of these mediators to endotoxin shock. In many cases, the interrelationships between these mediators as primary and/or secondary consequences of endotoxin stimulation of mononuclear phagocytes are discussed. Final comments address the relevance of these mediators to the therapy of endotoxin shock.
Mapping segmental and sequence variations among laboratory mice using BAC array CGH (2005)

We used arrays of 2069 BACs (1303 nonredundant autosomal clones) to map sequence variation among Mus spretus (SPRET/Ei and SPRET/Glasgow) and Mus musculus (C3H/HeJ, BALB/cJ, 129/J, DBA/2J, NIH, FVB/N, and C57BL/6) strains. We identified 80 clones representing 74 autosomal loci of copy number variation (|log(2)ratio| >/= 0.4). These variant loci distinguish laboratory strains. By FISH mapping, we determined that 63 BACs mapped to a single site on C57BL/6J chromosomes, while 17 clones mapped to multiple chromosomes (n = 16) or multiple sites on one chromosome (n = 1). We also show that small ratio changes (Delta log(2)ratio approximately 0.1) distinguish homozygous and heterozygous regions of the genome in interspecific backcross mice, providing an efficient method for genotyping progeny of backcrosses.
Free hemoglobin concentration in severe sepsis: methods of measurement and prediction of outcome (2012)

Free hemoglobin is an important new predictor of survival in severe sepsis.
Nondefective spleen necrosis virus-derived vectors define the upper size limit for packaging reticuloendotheliosis viruses. (1986)

We constructed a nondefective retrovirus vector based on spleen necrosis virus (SNV), a replication-competent reticuloendotheliosis virus. We introduced different DNA sequences into this vector and studied the ability of the resulting viruses to replicate in chicken embryo fibroblasts. The replication efficiency of SNV-derived viruses decreased with increasing virus size. Viruses larger than 9.4 kilobases (kb) were rapidly overgrown by replication-competent deletion mutants. The size restriction for the efficient replication of nondefective SNV-derived viruses prevented the production of viruses larger than 10.0 kb. Analysis of the kinetics of virus particle release indicated that the size restriction occurred during virus encapsidation.
Adipocyte P2 gene: developmental expression and homology of 5'-flanking sequences among fat cell-specific genes. (1986)

We have isolated the mouse gene encoding adipocyte P2, aP2, the differentiation-dependent adipocyte protein homologous to myelin P2. The aP2 gene is present in a single copy in the mouse and is present in single or few copies in species from human to Drosophila. The entire gene spans 4 kilobases and consists of four exons encoding 25, 57, 34, and 16 amino acids; the overall exon structure is similar to the gene encoding liver fatty acid binding protein. A plasmid vector was constructed containing the entire aP2 gene with flanking sequences, modified by linker insertion. When this gene is stably introduced into 3T3-F442A cells, it is expressed only upon adipose differentiation, with a time course of induction very similar to that of the endogenous aP2 gene. We have compared the DNA sequence of the 5'-flanking region of the aP2 gene to the promoter regions of two other genes activated during adipocyte differentiation, glycerol-3-phosphate dehydrogenase and adipsin, and find a 13-base region of homology (Formula: see text) present in multiple copies in the 5'-flanking region of each gene. An adjacent 15-base sequence is present only in glycerol-3-phosphate dehydrogenase and aP2 genes. Both of these elements share homology with putative viral enhancer core sequences. These results indicate that the aP2 gene contains sequence information necessary for differentiation-dependent expression in fat cells; common elements shared by adipocyte-specific genes may play a role in this process.
Data structure aware garbage collector (2015)

Garbage collection may benefit greatly from knowledge about program behavior, but most managed languages do not provide means for the programmer to deliver such knowledge. In this work we propose a very simple interface that requires minor programmer effort and achieves substantial performance and scalability improvements. In particular, we focus on the common use of data structures or collections for organizing data on the heap. We let the program notify the collector which classes represent nodes of data structures and also when such nodes are being removed from their data structures. The data-structure aware (DSA) garbage collector uses this information to improve performance, locality, and load balancing. Experience shows that this interface requires a minor modification of the application. Measurements show that for some significant benchmarks this interface can dramatically reduce the time spent on garbage collection and also improve the overall program performance.
Enrichment of Anti-Glomerular Antigen Antibody-Producing Cells in the Kidneys of MRL/MpJ-Fas lpr Mice (2004)

Lupus nephritis is characterized by immune complex deposition and infiltration of inflammatory cells into the kidney including Ab-producing cells (AbPCs). Although AbPCs play a central role in the pathogenesis of immune complex glomerulonephritis in lupus, the specificity and pathogenic role of AbPCs infiltrating into the kidneys in lupus are poorly understood. To characterize AbPCs present in lupus kidneys, we isolated AbPCs from diseased MRL/MpJ-Faslpr (MRL/lpr) mouse kidneys. ELISPOT assays, using glomerular Ag (GA) extracts as Ag, demonstrated significant enhancement of anti-GA AbPCs in the kidneys as compared in peripheral blood or spleen of the same mouse. We isolated hybridomas with anti-GA specificity from MRL/lpr mouse kidneys. All the anti-GA mAbs had polyreactive binding to ssDNA, dsDNA, and IgG (i.e., rheumatoid factor), but not to histones or Sm. Sequence analysis of anti-GA Abs suggested the occurrence of somatic mutations and amino acid replacement in complementarity-determining regions with a high replacement to silent ratio resulting in charged amino acids. Intravenous administration of the monoclonal anti-GA Abs into BALB/c mice resulted in graded deposition in glomeruli paralleling their ELISA anti-GA reactivity. These results suggest that AbPCs infiltrating the kidneys in MRL/lpr mice accumulate as a result of Ag selection and likely play a pathologic role in lupus nephritis.
Multiple Cytokines and Acute Inflammation Raise Mouse Leptin Levels: Potential Role in Inflammatory Anorexia (1997)

Several inflammatory cytokines, most notably tumor necrosis factor (TNF) and IL-1, induce anorexia and loss of lean body mass, common manifestations of acute and chronic inflammatory conditions. In C57BL/6 female mice, the administration of TNF, IL-1, and, to a lesser extent, leukemia inhibitory factor (LIF), produced a prompt and dose-dependent increase in serum leptin levels and leptin mRNA expression in fat. IL-10, IL-4, ciliary neurotrophic factor, and IL-2, cytokines not known to induce anorexia or decrease food intake, had no effect on leptin gene expression or serum leptin levels. After administration of Escherichia coli lipopolysaccharide (LPS), leptin gene expression and leptin levels were increased. These findings suggest that leptin levels may be one mechanism by which anorexia is induced during acute inflammatory conditions.
Generation of mutant mice by pronuclear injection of circular plasmid expressing Cas9 and single guided RNA (2013)

CRISPR/Cas mediated genome editing has been successfully demonstrated in mammalian cells and further applications for generating mutant mice were reported by injecting humanized Cas9 (hCas) mRNA and single guide RNA into fertilized eggs. Here we inject the circular plasmids expressing hCas9 and sgRNA into mouse zygotes and obtained mutant mice within a month. When we targeted the Cetn1 locus, 58.8% (10/17) of the pups carried the mutations and six of them were homozygously mutated. Co-injection of the plasmids targeting different loci resulted in the successful removal of the flanked region in two out of three mutant pups. The efficient mutagenesis was also observed at the Prm1 locus. Among the 46 offspring carrying CRISPR/Cas plasmid mediated mutations, only two of them carried the hCas9 transgene. The pronuclear injection of circular plasmid expressing hCas9/sgRNA complex is a rapid, simple, and reproducible method for targeted mutagenesis.
Research through design as a method for interaction design research in HCI (2007)

For years the HCI community has struggled to integrate design in research and practice. While design has gained a strong foothold in practice, it has had much less impact on the HCI research community. In this paper we propose a new model for interaction design research within HCI. Following a research through design approach, designers produce novel integrations of HCI research in an attempt to make the right thing: a product that transforms the world from its current state to a preferred state. This model allows interaction designers to make research contributions based on their strength in addressing under-constrained problems. To formalize this model, we provide a set of four lenses for evaluating the research contribution and a set of three examples to illustrate the benefits of this type of research.
A novel Krüppel-associated box containing the SSX gene (SSX3) on the human X chromosome is not implicated in t(X;18)-positive synovial sarcomas (1996)

The human synovial sarcoma-specific translocation t(X;18) results in the fusion of the SYT gene on chromosome 18 with either one of the Krüppel-associated box (KRAB) containing SSX1 or SSX2 genes on the X chromosome, depending on the exact location of the breakpoint within band Xp11.2. Screening of a testis cDNA library yielded several SSX-positive clones. Subsequent sequence analysis revealed that one third of these clones represent an SSX gene that differs from both SSX1 and SSX2. This novel member of the family of KRAB containing SSX genes, which we designated SSX3, is 90% homologous to SSX1 and 95% homologous to SSX2 at the cDNA level. Somatic cell hybrid analysis indicated that SSX3 maps within Xp11.2 --> p11.1, the region that also harbors the SSX1 and SSX2 genes. However, we conclude from our RT-PCR data and from results reported in the literature that SSX3 does not act as a fusion partner to SYT in any of the 44 independent synovial sarcomas thus far tested.
Mechanisms of Defibrillation (2010)

Electrical shock has been the one effective treatment for ventricular fibrillation for several decades. With the advancement of electrical and optical mapping techniques, histology, and computer modeling, the mechanisms responsible for defibrillation are now coming to light. In this review, we discuss recent work that demonstrates the various mechanisms responsible for defibrillation. On the cellular level, membrane depolarization and electroporation affect defibrillation outcome. Cell bundles and collagenous septae are secondary sources and cause virtual electrodes at sites far from shocking electrodes. On the whole-heart level, shock field gradient and critical points determine whether a shock is successful or whether reentry causes initiation and continuation of fibrillation.
Nucleotide−Surface Interactions in DNA-Modified Au−Nanoparticle Conjugates: Sequence Effects on Reactivity and Hybridization (2008)

We report a systematic study of the base-dependent behavior of oligonucleotides linked to Au NP surfaces. Ten 15mer sequences were designed to investigate the effect of oligonucleotide sequence and high-affinity nucleotide location relative to the nanoparticle surface. The nucleotide position was varied within the sequence to be proximal, midway, or distal to the 5′ thiol. High-affinity motifs of adenine, guanine, and cytosine were placed in polythymine sequences, with a homobase oligonucleotide of thymine as a control sequence. Oligonucleotide reactivity toward the NPs and the extent of hybridization of the conjugates varied with sequence. Chemical treatment of the NP surface to remove nonspecific adsorption removed sequence-dependent effects on the hybridization. The behavior of the conjugates can be explained by nonspecific adsorption, where A- and C-containing oligonucleotides have a higher affinity for the NP surface.
Isocochliodinol and neocochliodinol, bis(3-indolyl)benzoquinones from Chaetomium spp. (1983)

Two kinds of bis (3-indolyl)-dihydroxybenzoquinones, isocochliodinol and neocochliodinol, were isolated from Chaetomium murorum and C. amygdalisporum, respectively, and their structures were determined.