gebhart/patrepeval huggingface dataset:
An Ultrastructural Basis for the Shape Changes Induced in Platelets by Chilling (1967)

Abstract Blood platelets normally circulate in the form of flat discs. Under conditions which promote aggregation, platelets transform from discs to irregular spheres and become sticky. Exposure of platelets to low temperature for brief periods causes similar shape changes. The present study demonstrates that the alterations induced in platelets by chilling are related to disappearance of a marginal bundle of microtubules, which has recently been described in platelets. Rewarming platelets which have previously been chilled results in recovery of both the marginal band of tubules and platelet disc shape. Thus the bundle of microtubules in platelet hyaloplasm appears intimately associated with disc shape of unaltered cells. Factors which influence platelet shape changes may do so by acting on the supporting marginal band of microtubules.
The changing virtual machine environment: Interfaces to real hardware, virtual hardware, and other virtual machines (1979)

One can envision future uses of virtual machines that will exploit a proliferation of multiple, interconnected real and virtual machines. While the interconnections may be local or commhnications-based, the logical view can remain the same. VM/370 attached processor support <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">48</sup> can be viewed as a first step—for large systems and in a tightly-coupled context. Multiple logical and real systems (large or small) are appropriate and fertile fields for future experimentation and investigation.
Golden Mandarin(II)-an intelligent Mandarin dictation machine for Chinese character input with adaptation/learning functions (2002)

Golden Mandarin (II) is an intelligent single-chip based real-time Mandarin dictation machine for the Chinese language with a very large vocabulary for the input of unlimited Chinese texts into computers using voice. This dictation machine can be installed on any personal computer, in which only a single chip Motorola DSP 96002D is used, with a preliminary character correct rate around 95% at a speed of 0.6 sec per character. Various adaptation/learning functions have been developed for this machine, including fast adaptation to new speakers, on-line learning the voice characteristics, task domains, word pattern and noise environments of the users, so the machine can be easily personalized for each user. These adaptation/learning functions are the major subjects of the paper.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Iterative High-Throughput Polymorphism Studies on Acetaminophen and an Experimentally Derived Structure for Form III (2002)

Three crystal forms of acetaminophen were prepared and characterized using a newly developed high-throughput crystallization platform, CrystalMax. The platform consists of design software, robotic sample dispensing and handling, and high-throughput microanalytics and is capable of running thousands of crystallizations in parallel using several different methods to drive supersaturation and subsequent crystallization. Additionally, structural models of the elusive third form of acetaminophen will be discussed on the basis of powder X-ray diffraction data. One structure suggested has a bilayer motif, held together by O-H...O(H) hydrogen bonds, and helps explain the difficulty associated with preparing this form from solution.
Revealing Interaction Mode Between HIV‐1 Reverse Transcriptase and Diaryltriazine Analog Inhibitor (2008)

HIV-1 reverse transcriptase is a key enzyme playing an important role in the HIV-1 life cycle for the replication of the RNA genome into DNA form. Lys103Asn (K103N) mutant frequently is observed in HIV-1 reverse transcriptase. Therefore, a series of novel non-nucleoside reverse transcriptase inhibitors were designed and synthesized. In vitro experimental results show that diaryltriazine analogs have potent anti-HIV activity with moderate to high selectivity. In order to design anti-HIV drug, docking and molecular dynamics simulation were used to investigate the binding mode between ligand and HIV-1 reverse transcriptase. The results suggest that the analogs might have a similar interaction mechanism with HIV-1 reverse transcriptase. Then comparative molecular field analysis and comparative molecular similarity indices analysis were used to construct quantitative structure-activity models. These models were evaluated by eight test set compounds. These models are helpful in making quantitative prediction of their activity for new lead compounds before resorting in vitro and in vivo experimentation.
Rate of antigen degradation by the ubiquitin-proteasome pathway influences MHC class I presentation (1995)

The effect on MHC class I Ag presentation of enhancing a protein's rate of degradation by the ubiquitin-proteasome pathway was investigated. In extracts of mouse B-lymphoblasts and reticulocytes, as in rabbit reticulocytes, proteins with acidic or basic N-termini are conjugated to ubiquitin and degraded by the 26S proteasome very rapidly. We found that the rate of MHC class I presentation of microinjected beta-galactosidase was enhanced when this antigenic protein was modified with such a destabilizing amino-terminal residue. This enhanced presentation was inhibited by blocking potential ubiquitination sites on the protein through methylation of amino groups and by peptide aldehyde inhibitors of the proteasome. Furthermore, in B lymphoblast cell extracts, the rapid degradation of these beta-galactosidase constructs required ATP and ubiquitin and was blocked by inhibitors of proteasomes. Their rates of degradation in extracts correlated with their rates of class I Ag presentation in vivo. These results indicate that ubiquitin conjugation is a key rate-limiting step in Ag presentation and provide further evidence for a critical role of ubiquitin and the 26S proteasome in generating MHC class I-presented peptides.
Monolayer metallic nanotube interconnects: promising candidates for short local interconnects (2005)

Mono- or bi-layer metallic single-wall carbon nanotube interconnects have lateral capacitances more than four times smaller than those of copper interconnects. The resistance and time-of-flight of these monolayer nanotubes would be larger than that of copper interconnects. For short lengths, however, driver resistance is quite dominant, and latency is determined by interconnect capacitance. Monolayer nanotube interconnects are therefore promising candidates for local interconnects. The average capacitance per unit length of these nanotube interconnects can be 50% smaller than that of copper interconnects and that leads to significant saving in power dissipation.
Percutaneous Ablation of Hepatic Tumors (2010)

The liver is a common site of both primary and secondary malignancy resulting in significant morbidity and mortality. Careful patient evaluation and triage allows for optimal utilization of all oncologic therapies, including radiation, systemic chemotherapy, surgery, transarterial therapies, and ablation. Although the role of interventional oncologists in the management of hepatic malignancies continues to evolve, the use of percutaneous ablation therapies has proven to be an effective and minimally invasive modality for treatment. Percutaneous ablation therapies have diversified from direct ethanol injection to multiple modalities including radiofrequency ablation (RFA), cryoablation, acetic acid injection, laser ablation, microwave ablation, high-intensity focused ultrasound, and irreversible electroporation. RFA is the most commonly utilized modality for hepatic interventions and has proven efficacy in both hepatocellular carcinoma and colorectal carcinoma metastases. Although tumor size remains a challenge, combination therapies and new device innovations continue to allow for improved ablation zones and more durable results.
Rabies virus quasispecies: Implications for pathogenesis (1998)

Passage of the mouse-adapted rabies virus strain CVS-24 (where CVS is challenge virus standard) in BHK cells results in the rapid selection of a dominant variant designated CVS-B2c that differs genotypically and phenotypically from the dominant variant CVS-N2c present in mouse-brain- or neuroblastoma-cell-passaged CVS-24. The glycoprotein of CVS-B2c has 10 amino acid substitutions compared with that of CVS-N2c. Because CVS-B2c can be reproducibly selected in BHK cells, it is likely to be a conserved minor subpopulation of CVS-24. CVS-N2c is more neurotropic in vitro and in vivo than CVS-B2c, which replicates more readily in nonneuronal cells in vitro and in vivo. These characteristics appear to be relevant to the pathogenicity of the two variants. CVS-N2c is more pathogenic for adult mice than CVS-B2c. In contrast, CVS-B2c is more pathogenic for neonatal mice. These differences in pathogenicity are reflected in the selection pattern when mixtures of CVS-N2c and CVS-B2c were used to infect neonatal and adult mice. Although CVS-N2c was highly selected in adult mice, no selection for either variant was seen in neonates, suggesting that certain aspects of development, such as maturation of the nervous and immune systems, may contribute to the selection process. We speculate that the existence of different variants within a rabies virus strain may facilitate the virus in overcoming barriers to its spread, both within the host and between species.
The semantics of power and ARM multiprocessor machine code (2009)

We develop a rigorous semantics for Power and ARM multiprocessor programs, including their relaxed memory model and the behaviour of reasonable fragments of their instruction sets. The semantics is mechanised in the HOL proof assistant. This should provide a good basis for informal reasoning and formal verification of low-level code for these weakly consistent architectures, and, together with our x86 semantics, for the design and compilation of high-level concurrent languages.
Cytokine responses to the native and recombinant forms of the major surface glycoprotein of Pneumocystis carinii (1997)

Pneumocystis carinii is a major opportunistic pathogen and leading cause of morbidity in patients with AIDS. The major surface glycoprotein (MSG) of P. carinii, represented by a family of related proteins encoded by unique genes, is highly immunogenic and contains T cell-protective epitopes. We undertook the present study to define the CD4 T helper (Th) response by cytokine secretion to native MSG and a recombinant form of the protein, MSG-B. Spleen cells were collected from Lewis rats and restimulated with both native MSG and MSG-B. Within 24 h, the CD4 cells secreted high levels of interferon-gamma (IFN-gamma) in response to both types of antigen, indicative of a Th1 response; however, after 72h of incubation, only the native MSG stimulated secretion of IL-4 (Th2 response) from the cells. We then investigated whether the presence of IL-4 could alter the predominant Th1 phenotype by the CD4 cells in response to MSG and MSG-B. Cells cultured with native MSG and IL-4 produced low levels of IFN-gamma and elevated levels of IL-4. Interestingly, cells incubated with MSG-B and IL-4 reduced production of IFN-gamma, but were not stimulated to produce increased levels of IL-4. The presence of anti-IFN-gamma antibody in the MSG- or MSG-B-stimulated cultures did not effect the expression of IFN-gamma mRNA, suggesting that the generation of Th1 cells in response to MSG or MSG-B was not dependent on IFN-gamma. We conclude that native MSG, which contains multiple forms of this antigen, and recombinant MSG elicit different cytokine responses in vitro. These data are not only important to studies of MSG, but may also be relevant to the role of MSG in the immunopathogenesis of P. carinii infection in vivo.
Molecular Detection ofAnaplasma Platysin Dogs Using Polymerase Chain Reaction and Reverse Line Blot Hybridization (2003)

Several polymerase chain reactions (PCRs) and a reverse line blot hybridization (RLB) method were used to identify Anaplasma platys in dogs held in a kennel in Italy. Whereas PCR techniques confirmed the presence of A. platys, the RLB method not only correlated the results obtained by PCR but also ruled out the presence of other species such as Ehrlichia canis or E. chaffeensis. There was no correlation between infection status and age or breed of the dogs. Polymerase chain reaction performed on the Rhipicephalus sanguineus ticks collected from those dogs showed that they were also infected with A. platys. Sequences obtained from some samples and compared with those within the GenBank also confirmed the presence of A. platys.
T cells in peripheral blood after gluten challenge in coeliac disease (2005)

In vivo gluten challenge is a simple safe method that allows relevant T cells to be analysed and quantified in peripheral blood by ELISPOT, and should permit comprehensive high throughput mapping of gluten T cell epitopes in large numbers of individuals with CD.
Microfluidic Single-Cell mRNA Isolation and Analysis (2006)

Single-cell gene expression analysis holds great promise for studying diverse biological systems, but methodology to process these precious samples in a reproducible, quantitative, and parallel fashion remains challenging. Here, we utilize microfluidics to isolate picogram and subpicogram mRNA templates, as well as to synthesize cDNA from these templates. We demonstrate single-cell mRNA isolation and cDNA synthesis, provide quantitative calibrations for each step in the process, and measure gene expression in individual cells. The techniques presented here form the foundation for highly parallel single-cell gene expression studies.
Atypical mRNA fusions in PML‐RARA positive, RARA‐PML negative acute promyelocytic leukemia (2010)

Reciprocal RARA-PML transcripts are not detected in approximately 25% of patients with PML-RARA positive acute promyelocytic leukemia (APL), but the reasons for this are poorly understood. We studied 21 PML-RARA positive/RARA-PML negative cases by bubble PCR and multiplex long template PCR to identify the genomic breakpoints. Additional RT-PCR analysis was performed based on the DNA findings. Three cases were found to have complex rearrangements involving a third locus: the first had a PML-CDC6-RARA forward DNA fusion and expressed a chimeric PML-CDC6-RARA mRNA in addition to a PML-RARA. The other two had HERC1-PML and NT_009714.17-PML genomic fusion sequences at their respective reciprocal breakpoints. Six patients were falsely classified as RARA-PML negative due to deletions on chromosome 15 and/or 17, or alternative splicing leading to atypical RARA-PML fusion transcripts, which were not identified by conventional RT-PCR assays. This study demonstrates that the frequency of RARA-PML expression has been underestimated and highlights remarkable complexity at chromosomal breakpoint regions in APL even in cases with an apparently simple balanced t(15;17)(q24;q12).
Getting away with murder: how does the BCL‐2 family of proteins kill with immunity? (2013)

The adult human body produces approximately one million white blood cells every second. However, only a small fraction of the cells will survive because the majority is eliminated through a genetically controlled form of cell death known as apoptosis. This review places into perspective recent studies pertaining to the BCL-2 family of proteins as critical regulators of the development and function of the immune system, with particular attention on B cell and T cell biology. Here we discuss how elegant murine model systems have revealed the major contributions of the BCL-2 family in establishing an effective immune system. Moreover, we highlight some key regulatory pathways that influence the expression, function, and stability of individual BCL-2 family members, and discuss their role in immunity. From lethal mechanisms to more gentle ones, the final portion of the review discusses the nonapoptotic functions of the BCL-2 family and how they pertain to the control of immunity.
Adherence of streptococcus pyogenes, Escherichia coli, and Pseudomonas aeruginosa to fibronectin-coated and uncoated epithelial cells (1983)

The relationship between the variability in the fibronectin (Fn) content on human buccal epithelial cells and the capacity of the cells to bind gram-positive (Streptococcus pyogenes) or gram-negative (Escherichia coli or Pseudomonas aeruginosa) bacteria was investigated. Adhesion experiments performed with mixtures of epithelial cells and mixed suspensions of either S. pyogenes and E. coli or S. pyogenes and P. aeruginosa exhibited three major populations of buccal cells: one of these was able to bind S. pyogenes (gram positive) but neither of the gram-negative bacteria; a second population was able to bind the gram-negative but not the gram-positive bacteria; and a third was able to bind various numbers of both types of organisms. Further adhesion experiments performed with a mixture of epithelial cells and a mixed suspension of S. pyrogens, E. coli, and fluoresceinconjugated methacrylate beads coated with immune immunoglobulin G directed against Fn revealed that the epithelial cells recognizing the gram-positive bacteria were rich in Fn, whereas those recognizing the gram-negative organisms were poor in Fn. Immunoelectron microscopy confirmed that cells of S. pyogenes bound to epithelial cells coated with Fn, whereas cells of E. coli bound to epithelial cells lacking Fn. These results suggest that Fn on the surfaces of epithelial cells may modulate the ecology of the human oropharyngeal cavity, especially with respect to the colonization of these surfaces by pathogenic gram-negative or gram-positive bacteria.
Canine reaginic antibody. Characterization of the spontaneous anti-ragweed and induced anti-dinitrophenyl reaginic antibodies of the atopic dog. (1971)

Anti-2,4-dinitrophenyl reaginic antibody has been induced in the atopic dog and compared with anti-ragweed reaginic antibody of spontaneous canine atopic hypersensitivity. Immunization of an atopic dog with ragweed hypersensitivity with dinitrophenylated ragweed pollen produced a high and sustained level of canine reaginic anti-DNP antibody. The induced and spontaneous forms of canine reaginic antibodies were shown to be identical in heat lability, sulfhydryl sensitivity, molecular size, charge, in their ability to remain fixed at passively-sensitized dermal sites for a prolonged period, and in their capacity to sensitized homologous white blood cells from normal donors for an immunospecific release of histamine. The induced anti-DNP and spontaneous anti-ragweed reaginic antibodies were physically separated and immunochemically differentiated from six other classes of canine immunoglobulins: γ2a, γ2b, γ2c, γ1, γA and γM, and shown to be members of a distinct class of canine immunoglobulins analogous to human γE (IgE). A high incidence of spontaneous atopic hypersensitivity has been observed in the progeny of the atopic dog.
Increased cytokine secretion by human bone marrow cells after menopause or discontinuation of estrogen replacement. (1995)

Studies on circulating human mononuclear cells and rodents have suggested that cytokines such as interleukin-1 (IL-1) and IL-6 may be paracrine mediators of postmenopausal bone loss. However, the assumption that the concentration of these cytokines is increased in the local bone microenvironment of postmenopausal women is still unproved. To address this question, we aspirated bone marrow from the iliac crest of 40 women during surgery for localized breast cancer and analyzed cytokine release in short term cultures. Cytokine levels in the cell supernatants from premenopausal (n = 12) and late postmenopausal (n = 18) subjects were not significantly different. Bone marrow cells from women who had discontinued estrogen replacement within 1 month before aspiration (n = 5) secreted significantly more IL-1 alpha, tumor necrosis factor-alpha, IL-6, prostaglandin E2, and granulocyte-macrophage colony-stimulating factor than bone marrow cells from either premenopausal or late postmenopausal subjects. Increased levels of IL-6, prostaglandin E2, and granulocyte-macrophage colony-stimulating factor were also observed in cultures from women who were within 5 yr of natural menopause (n = 5). Our data show that estrogen withdrawal is associated with an increased potential of human bone marrow cells to release bone-resorbing cytokines and strengthen the hypothesis that these cytokines may play a role in the accelerated bone resorption after menopause.
Varicella-Zoster Virus (VZV)-Specific Cytotoxicity after Immunization of Nonimmune Adults with Oka Strain Attenuated VZV Vaccine (1992)

Cytotoxic, proliferative, and serum IgG antibody responses to varicella-zoster virus (VZV) were measured monthly in 29 young adults for 3 months following primary immunization with the Oka strain attenuated VZV vaccine. No subjects had lymphocytes stimulated to VZV-specific cytotoxicity at study entry although lymphocytes from 2 subjects proliferated when stimulated by VZV antigen. The percentages of subjects with positive major histocompatibility complex class II-restricted cytotoxic responses at 1, 2, and 3 months after immunization were 54%, 69%, and 66%, respectively. Correlations between cytotoxic, proliferative, and antibody responses were highest in the first month after immunization; lower but still statistically significant after the second month; and not apparent by the third month. The data suggest that antibody and cell-mediated immune responses to VZV immunization develop in parallel after immunization, but these effector mechanisms are independently regulated by 3 months after immunization.
Nintedanib in patients with idiopathic pulmonary fibrosis: Combined evidence from the TOMORROW and INPULSIS® trials (2016)

Nintedanib has a beneficial effect on slowing disease progression in patients with IPF.
Identification of a Novel Family of Sequence Repeats among Prokaryotes (2002)

The rapid increase in genomic sequences provides new opportunities for comparative genomics. In this report, we describe a novel family of repeat sequences that is present in Bacteria and Archaea but not in Eukarya. The repeat loci typically consisted of repetitive stretches of nucleotides with a length of 25 to 37 bp alternated by nonrepetitive DNA spacers of approximately equal size as the repeats. The nucleotide sequences and the size of the repeats were highly conserved within a species, but between species the sequences showed no similarity. Due to their characteristic structure, we have designated this family of repeat loci as SPacers Interspersed Direct Repeats (SPIDR). The SPIDR loci were identified in more than forty different prokaryotic species. Individual species such as Mycobacterium tuberculosis contain one SPIDR locus, while other species such as Methanococcus jannaschii contained up to 20 different loci. The number of repeats in a locus varies greatly from two repeats to several dozens of repeats. The SPIDR loci were flanked by a common 300-500-bp leader sequence, which appeared to be conserved within a species but not between species. The SPIDR locus of M. tuberculosis is extensively used for strain typing. The finding of SPIDR loci in other prokaryotes, including the pathogens Salmonella, Campylobacter, and Pasteurella may extend this surveillance to other species.
Tryptase inhibitors - review of the recent patent literature. (2002)

The past several years has seen research increasingly focused around the inhibition of tryptase, a mast cell protease implicated in a myriad of pro-inflammatory responses. Although few compounds have reached the clinic, several monobasic and multibasic small molecules have emerged as promising candidates as a treatment for asthma and other allergic and inflammatory disorders. This summary reviews recent patent activity of tryptase inhibitors and briefly outlines recent tryptase inhibitor literature and clinical updates.