gebhart/patrepeval huggingface dataset:
Reduction of plasma urate levels following treatment with multiple doses of pegloticase (polyethylene glycol–conjugated uricase) in patients with treatment‐failure gout: Results of a phase II randomized study (2008)

Pegloticase, administered in multiple doses, was effective in rapidly reducing and maintaining plasma urate levels at <or=6 mg/dl in most patients in whom conventional therapy had been unsuccessful due to lack of response, intolerability, or contraindication.
Phase I study of REGN421 (R)/SAR153192, a fully-human delta-like ligand 4 (Dll4) monoclonal antibody (mAb), in patients with advanced solid tumors. (2013)

2502 Background: Dll4, a Notch receptor ligand, may have a role in tumor angiogenesis and is an emerging anticancer target. REGN421 (R) is a fully human IgG 1 mAb that binds human Dll4 and disrupts Notch-mediated signaling. Methods: Primary objectives of the dose escalation (3+3 design) trial were to determine safety and a recommended phase II dose (RP2D) of R in patients (pts) with advanced cancer. R was given IV at doses of 0.25, 0.5, 1, 2 and 4mg/kg every 3 weeks (Q3W) or 0.75, 1, 1.5, and 3mg/kg every 2 weeks (Q2W). Secondary objectives were PK, immunogenicity, and antitumor activity. Results: 53 pts (M/F=22/31, ECOG 0/1=18/35) were enrolled; 31 pts were treated Q3W at doses of 0.25 - 4 mg/kg; 22 pts were treated Q2W at doses of 0.75 - 3 mg/kg. Two DLTs occurred: Grade 3 (Gr3) nausea (0.5mg/kg Q3W) and Gr3 abdominal pain (1 mg/kg Q2W). A maximum tolerated dose was not reached on either schedule. Grade 3/4 AEs occurred in 29 pts; nausea, abdominal pain, dyspnea, hypoxia, and hypertension (HTN) were reported in ≥ 5%. Most frequent treatment related AEs were fatigue (30%), headache (26%), HTN (26%), and nausea (15%). Six treatment related SAEs (all reversed off treatment) were reported in 4 patients: BNP increase (0.25mg/kg, Gr1), troponin I increase (4mg/kg, Gr3), right ventricular dysfunction (1.5mg/kg, Gr3), left ventricular dysfunction (3mg/kg, Gr3) and 2 events of pulmonary HTN (1.5mg/kg, Gr 3, and 3mg/kg Gr3). Laboratory abnormalities (≥ Gr3) were neutropenia (3) and anemia (2), and elevated ALP (7), ALT (3), bilirubin (3), AST (2), and decreased albumin (1). Anti-tumor activity included 2 PRs (NSCLC BAL-type with a beta-catenin mutation and ovarian cancer [OvCa]), and 16 pts with SD (3 pts had SD &gt; 6 months). Two of 8 pts with OvCa had CA125 responses. R had non-linear target-mediated PK without accumulation. The half-life of R at 3mg/kg Q2W was 7 days. No immunogenicity was observed. Conclusions: REGN421 had an acceptable safety profile, and RP2Ds of 4mg/kg Q3W and 3mg/kg Q2W. Responses and prolonged SD were noted in OvCa pts and other solid tumors. Dose escalation has concluded and disease specific expansion cohorts are ongoing. Clinical trial information: NCT00871559.
Electrical conductivity of polymers containing carbon black (1988)

Abstract Changes in volume resistivity with temperature of carbon‐black‐filled polymers and a random copolymer of styrene and butyl methacrylate were measured. For polystyrene containing 20 wt % carbon black, of surface area 24 m 2 /g, the resistivity changes abruptly from 10 13 to 10 6 ohm‐cm above 150°C. Poly(butyl methacrylate) did not show well‐defined changes in resistivity on heating. The random copolymer containing 16.7 or 28.6 wt % carbon black, of surface area 24 m 2 /g, showed a resistivity exceeding 10 13 ohm‐cm, that decreased to about 10 7 ohm‐cm on heating above 120°C. This Copolymer containing 16.7 wt % carbon black, of surface area 625 m 2 /g, shows a resistivity of about 108 ohm‐cm that decreases sharply to 10 3 ohm‐cm by 150°C. Decreases in resistivity on increasing the temperature in the quiescent state are correlated with the observation of a yield stress at low shear rates in rheological studies. It is suggested that carbon black agglomerates at elevated temperature and forms an independent conductive network that prevents flow.
Optimal spatial requirements for the location of basic residues in peptide substrates for the cyclic AMP-dependent protein kinase. (1980)

The specificity of the cyclic AMP-dependent protein kinase was examined using two series of dodecapeptides as substrates. One series consisted of peptides of the general sequence (Gly)x-Arg-Arg-(Gly)y-Ala-Ser-Leu-Gly in which x + y = 6. The other series consisted of peptides of the sequence (Gly)x-Lys-Arg-(Gly)y-Ala-Ser-Leu-Gly in which x + y was again equal to 6. The peptides Gly-Gly-Gly-Gly-Gly-Gly-Gly-Arg-Arg-Ser-Leu-Gly and Gly-Gly-Gly-Gly-Gly-Gly-Gly-Lys-Arg-Ser-Leu-Gly were also examined. In the series in which the adjacent arginines were located various distances from the serine, the substrate for which the enzyme clearly exhibited optimal kinetic constants contained one amino acid residue between the basic residues and serine. Direct binding studies of N alpha-[3H]acetyl peptides to catalytic subunit of cyclic AMP-dependent protein kinase revealed a correlation between binding affinity and the ability to serve as substrate for the enzyme. In the second series in which the adjacent basic amino acids were Lys-Arg, optimal kinetic constants were again obtained when these residues were separated from serine by a single amino acid. This latter result was surprising in view of phosphorylation site sequences in the known physiologically significant protein substrates for the kinase, since those containing Lys-Arg all contain two amino acids between these residues and serine.
Visual impairment following stroke: do stroke patients require vision assessment? (2008)

of patients referred with a suspected visual difficulty, only 8% had normal vision status confirmed on examination. Ninety-two per cent had visual impairment of some form confirmed which is considerably higher than previous publications and probably relates to the prospective, standardised investigation offered by specialist orthoptists. However, under-ascertainment of visual problems cannot be ruled out.
Induction of murine T-helper-cell responses to the filarial nematode Brugia malayi (1993)

The purpose of this study was to examine the murine T-helper-cell (Th) cytokine response to the human filarial parasite Brugia malayi. In the first 14 days following intraperitoneal inoculation of live microfilariae into BALB/c mice, filarial antigen-driven splenic lymphoid cells produced gamma interferon (IFN-gamma) and little or no interleukin-5 (IL-5). After this time, IL-5 production increased (to 10 to 12 ng per 5 x 10(6) cells) coincident with a marked diminution in IFN-gamma generation. A single subcutaneous immunization with soluble microfilarial antigens also induced an IFN-gamma but no IL-5 response, whereas immunization three times elicited a predominant Th2-like reaction characterized by IL-4 and IL-5 production by CD4+ lymph node lymphocytes and a 10-fold increase in serum immunoglobulin E. The importance of IL-10 in establishing the balance between parasite-specific Th1 and Th2 responses was demonstrated by the ability of neutralizing monoclonal antibody to this cytokine to increase IFN-gamma production by splenic and lymph node cells from mice chronically exposed to live microfilariae or immunized multiple times with soluble filarial antigens.
Toward realistic soft-tissue modeling in medical simulation (1998)

Most of today's medical simulation systems are based on geometric representations of anatomical structures that take no account of their physical nature. Representing physical phenomena and, more specifically, the realistic modeling of soft tissue will not only improve current medical simulation systems but will considerably enlarge the set of applications and the credibility of medical simulation, from neurosurgery planning to laparoscopic-surgery simulation. To achieve realistic tissue deformation, it is necessary to combine deformation accuracy with computer efficiency. On the one hand, biomechanics has studied complex mathematical models and produced a large amount of experimental data for accurately representing the deformation of soft tissue. On the other hand, computer graphics has proposed many algorithms for the real-time computation of deformable bodies, often at the cost of ignoring the physics principles. The author surveys existing models of deformation in medical simulation and analyze the impediments to combining computer-graphics representations with biomechanical models. In particular, the different geometric representations of deformable tissue are compared in relation to the tasks of real-time deformation, tissue cutting, and force-feedback interaction. Last, the author inspects the potential of medical simulation under the development of this key technology.
Stem Cells as Vectors to Deliver HSV/tk Gene Therapy for Malignant Gliomas (2009)

The prognosis of patients diagnosed with malignant gliomas including glioblastoma multiforme (GBM) is poor and there is an urgent need to develop and translate novel therapies into the clinic. Neural stem cells display remarkable tropism toward GBMs and thus may provide a platform to deliver oncolytic agents to improve survival. First we provide a brief review of clinical trials that have used intra-tumoral herpes simplex virus thymidine kinase (HSV/tk) gene therapy to treat brain tumors. Then, we review recent evidence that neural stem cells can be used to deliver HSV/tk to GBMs in animal models. While previous clinical trials used viruses or non-migratory vector-producing cells to deliver HSV/tk, the latter approaches were not effective in humans, primarily because of satellite tumor cells that escaped surgical resection and survived due to low efficiency delivery of HSV/tk. To enhance delivery of HSV/tk to kill gliomas cells, recent animal studies have focused on the ability of neural stem cells, transduced with HSV/tk, to migrate efficiently and selectively to regions occupied by GBM cells. This approach holds the promise of targeting GBM cells that have infiltrated the brain well beyond the original site of the tumor epicenter.
Suppression of boron penetration by polycrystalline Si1−x−yGexCy in metal–oxide–semiconductor structures (1999)

A polycrystalline Si1−x−yGexCy layer grown by rapid thermal chemical vapor deposition has been used as a thin intermediate layer on top of the thin gate oxide in a metal–oxide–semiconductor structure with boron-doped polycrystalline silicon as the gate electrode. Although boron readily penetrated through the Si1−x−yGexCy and accumulated in it, boron penetration across the gate oxide into the substrate was greatly suppressed compared to that in structures without Si1−x−yGexCy layer. Our work suggests that the addition of carbon reduced the chemical potential of boron in polycrystalline Si1−x−yGexCy, compared to that in polycrystalline silicon or polycrystalline Si1−xGex. We have also observed no gate depletion effects with the use of poly-Si1−x−yGexCy layers in both p+ and n+ gate doping.
MUC1 peptide epitopes associated with five different H‐2 class I molecules (1997)

We have previously described the induction of murine CD8+ major histocompatibility complex (MHC) class I-restricted cytotoxic T cells (CTL) recognizing the 20-amino acid repeat region of the human mucin 1 (MUC1) variable number of tandem repeats region (VNTR), a mucin greatly increased in expression in breast cancer and proposed as a target for immunotherapy. In that study, CTL could detect MUC1 peptides associated with the MHC of all nine strains examined, and we now report the different epitopes presented by five different MHC class I molecules. The epitopes were defined in CTL assays using peptide-pulsed phytohemagglutinin blasts or MHC class I-transfected L cells as targets; in addition, peptide binding assays and T cell proliferation studies were performed. Within the 20-amino acid VNTR, nine potential epitopes could be defined. The epitopes for the four MHC class I molecules [Kb (three epitopes), Dd, Ld and Kk] were closely related, all containing the amino acids PDTRPAP. For Db, three epitopes were identified, all containing APGSTAP. Most of the epitopes did not contain a consensus motif for the particular MHC class I allele, and bound with low 'affinity', compared with known high-affinity peptides. CD8+ T cell proliferation also occurred to the same MHC class I-presented epitopes. Finally, when conventional anchor residues were introduced into the peptides, peptide binding increased, whereas CTL recognition was either retained (Kb) or lost (Db) depending on the epitope.
Sequencing analysis of a 40·2 kb fragment of yeast chromosome X reveals 19 open reading frames including URA2 (5′ end), TRK1, PBS2, SPT10, GCD14, RPE1, PHO86, NCA3, ASF1, CCT7, GZF3, two tRNA genes, three remnant delta elements and a Ty4 transposon (1996)

The complete sequence of a 40247 bp DNA segment located on the left arm of chromosome X of Saccharomyces cerevisiae has been determined and analysed. The sequence encodes the 5' coding region of the URA2 gene and 18 open reading frames of at least 100 amino acids. Ten of these correspond to known genes, whereas eight correspond to new genes. In addition, the sequence contains a tRNA-Ala gene, a tRNA-Asp gene, a Ty4 transposable element and three delta elements.
Antibody to a conserved antigenic target is protective against diverse prokaryotic and eukaryotic pathogens (2013)

Microbial capsular antigens are effective vaccines but are chemically and immunologically diverse, resulting in a major barrier to their use against multiple pathogens. A β-(1→6)-linked poly-N-acetyl-d-glucosamine (PNAG) surface capsule is synthesized by four proteins encoded in genetic loci designated intercellular adhesion in Staphylococcus aureus or polyglucosamine in selected Gram-negative bacterial pathogens. We report that many microbial pathogens lacking an identifiable intercellular adhesion or polyglucosamine locus produce PNAG, including Gram-positive, Gram-negative, and fungal pathogens, as well as protozoa, e.g., Trichomonas vaginalis, Plasmodium berghei, and sporozoites and blood-stage forms of Plasmodium falciparum. Natural antibody to PNAG is common in humans and animals and binds primarily to the highly acetylated glycoform of PNAG but is not protective against infection due to lack of deposition of complement opsonins. Polyclonal animal antibody raised to deacetylated glycoforms of PNAG and a fully human IgG1 monoclonal antibody that both bind to native and deacetylated glycoforms of PNAG mediated complement-dependent opsonic or bactericidal killing and protected mice against local and/or systemic infections by Streptococcus pyogenes, Streptococcus pneumoniae, Listeria monocytogenes, Neisseria meningitidis serogroup B, Candida albicans, and P. berghei ANKA, and against colonic pathology in a model of infectious colitis. PNAG is also a capsular polysaccharide for Neisseria gonorrhoeae and nontypable Hemophilus influenzae, and protects cells from environmental stress. Vaccination targeting PNAG could contribute to immunity against serious and diverse prokaryotic and eukaryotic pathogens, and the conserved production of PNAG suggests that it is a critical factor in microbial biology.
Web search for a planet: the google cluster architecture (2003)

Amenable to extensive parallelization, Google's web search application lets different queries run on different processors and, by partitioning the overall index, also lets a single query use multiple processors. to handle this workload, Googless architecture features clusters of more than 15,000 commodity-class PCs with fault tolerant software. This architecture achieves superior performance at a fraction of the cost of a system built from fewer, but more expensive, high-end servers.
Nano-PPUF: A Memristor-Based Security Primitive (2012)

CMOS devices have been used to build hardware security primitives such as physical unclonable functions. Since MOS devices are relatively easy to model and simulate, CMOS-based security primitives are increasingly prone to modeling attacks. We propose memristor-based Public Physical Unclonable Functions (nano-PPUFs), they have complex models that are difficult to simulate. We leverage sneak path currents, process variations, and computationally intensive SPICE models as features to build the nano-PPUF. With just a few hundreds of memristors, we construct a time-bounded authentication protocol that will take several years for an attacker to compromise.
Remote ischaemic pre-conditioning in cardiac surgery: benefit or not? (2014)

peer reviewed
A Lactobacillus acidophilus Strain of Human Gastrointestinal Microbiota Origin Elicits Killing of Enterovirulent Salmonella enterica Serovar Typhimurium by Triggering Lethal Bacterial Membrane Damage (2005)

The human gastrointestinal microbiota produces antagonistic activities against gastrointestinal bacterial pathogens. We undertook a study to investigate the mechanism(s) by which a Lactobacillus acidophilus strain of human microbiota origin antagonizes the gram-negative enteroinvasive pathogen Salmonella enterica serovar Typhimurium. We showed that the cell-free culture supernatant of L. acidophilus strain LB (LB-CFCS) induced the following effects in S. enterica SL1344: (i) a decrease in intracellular ATP that paralleled bacterial death, (ii) the release of lipopolysaccharide, (iii) permeabilization of the bacterial membrane, and (iv) an increase in the sensitivity of Salmonella to the lytic action of sodium dodecyl sulfate. Finally, we showed using two mutant strains of Salmonella, PhoP MS7953s and PmrA JKS1170, that the two-component regulatory systems PhoP-PhoQ and PmrA-PmrB that regulate the mechanisms of resistance to antibacterial agents in Salmonella did not influence the anti-Salmonella effect of LB-CFCS.
Refractory status epilepticus during pregnancy secondary to cavernous angioma (2008)

First-time seizure and status epilepticus during pregnancy have been previously reported as the initial manifestation of intracranial cavernous hemangioma. We report a woman with no history of seizures who presented with refractory status epilepticus at 10 weeks gestation. Cranial MRI revealed a right frontal cavernous hemangioma. The seizures remained refractory to conventional anticonvulsant medications and 48 h of general anesthetic. Termination of the pregnancy resulted in almost immediate resolution of the seizures. The dramatic response of the seizures to termination of the pregnancy suggests that hormonal factors were primarily responsible for the precipitous presentation in this patient.
The effects of extracellular pH on immune function (2001)

The effect of alterations in extracellular pH on cellular and humoral immune function is reviewed. Because acidic pH predominates at inflammatory loci and other sites of immune activity, most studies to date focus on the effect of acidic rather than alkaline pH. Investigations on polymorphonuclear leukocytes demonstrate mainly inhibition of chemotaxis, respiratory activity, and bactericidal capacity at reduced pH. Evidence of impaired lymphocyte cytotoxicity and proliferation at acidic pH is also beginning to emerge. Many of the clinical acidoses are accompanied similarly by immunodeficiency. Studies on macrophages and eosinophils are few and inconclusive. A small number of studies demonstrate acid-induced activation of complement proteins and the alternative complement pathway, plus increased antibody-binding to leukocytes at lowered pH. A differential effect of acidic pH on humoral and cellular immunity may, therefore, exist. Increasing recognition of the significance of extracellular pH in relation to immune function warrants further studies in this presently incomplete but rewarding field.
Immobilized Ru Clusters in Nanosized Mesoporous Zirconium Silica for the Aqueous Hydrogenation of Furan Derivatives at Room Temperature (2013)

Ru lonesome tonight? Immobilized ruthenium clusters (50 Ru atoms) in nanosized mesoporous zirconium silica were synthesized by using an impregnation method starting from an aqueous solution of RuCl3. The Ru cluster catalysts were thermally stable at 500 °C and showed remarkable activity for the hydrogenation of furan derivatives in water at room temperature under 5 bar hydrogen pressure.
The yeast α-factor receptor: structural properties deduced from the sequence of theSTE2gene (1985)

The STE2 gene of the yeast Saccharomyces cerevisiae encodes a component of the receptor for the oligopeptide pheromone alpha-factor. We have cloned and determined the nucleotide sequence of the STE2 gene. A sequence involved in the control of cell-type expression of the STE2 gene was found 5' of an open reading frame that could encode a protein of 431 amino acids. The predicted STE2 protein contains seven hydrophobic segments, suggesting that the alpha-factor receptor is an integral membrane protein. No extensive homology at the primary sequence level was detected between the predicted STE2 protein and other available protein sequences.
LOK Is a Novel Mouse STE20-like Protein Kinase That Is Expressed Predominantly in Lymphocytes (1997)

We have identified a new gene, designated lok (lymphocyte-oriented kinase), that encodes a 966-amino acid protein kinase whose catalytic domain at the N terminus shows homology to that of the STE20 family members involved in mitogen-activated protein (MAP) kinase cascades. The non-catalytic domain of LOK does not have any similarity to that of other known members of the family. There is a proline-rich motif with Src homology region 3 binding potential, followed by a long coiled-coil structure at the C terminus. LOK is expressed as a 130-kDa protein, which was detected predominantly in lymphoid organs such as spleen, thymus, and bone marrow, in contrast to other mammalian members of the STE20 family. LOK phosphorylated itself as well as substrates such as myelin basic protein and histone IIA on serine and threonine residues but not on tyrosine residues, establishing LOK as a novel serine/threonine kinase. When coexpressed in COS7 cells with the known MAP kinase isoforms (ERK, JNK, and p38), LOK activated none of them in contrast to PAK- and GCK-related kinases. These results suggest that LOK could be involved in a novel signaling pathway in lymphocytes, which is distinct from the known MAP kinase cascades.
Influence of bombesin on thresholds for feeding and reward in the rat (1999)

Bombesin's purported role in satiety mechanisms prompted this investigation of its effects on thresholds for stimulation-induced feeding and self-stimulation in the rat. Single electrodes were implanted in the lateral hypothalamus and the ability of each electrode to support self-stimulation and stimulation-induced feeding was evaluated at four current levels between 80 and 320 microA. The frequency thresholds associated with each current value were assessed following four intraperitoneal doses of bombesin, 2, 4, 8, and 16 micrograms/kg, as well as a saline dose. Bombesin increased the thresholds for stimulation-induced feeding at doses known to reduce food intake without influencing self-stimulation thresholds. From these findings we conclude that (1) the effects of peripheral bombesin on stimulation-induced feeding are analogous to its effects on normal feeding and (2) the data provide additional evidence for a pharmacological dissociation between stimulation-induced feeding and reward.