gebhart/patrepeval huggingface dataset:
Polyethylene glycol precipitation for recovery of pathogenic viruses, including hepatitis A virus and human rotavirus, from oyster, water, and sediment samples (1988)

Polyethylene glycol 6000 precipitation was found to be an effective concentration method that enhanced the chances for detecting human virus pathogens in environmental samples. Percent recoveries from eluates of fresh and estuarine waters with 8% polyethylene glycol 6000 averaged 86 for hepatitis A virus, 77 for human rotavirus Wa, 87 for simian rotavirus SA11, and 68 for poliovirus. Percent recoveries of 97, 40, 97 and 105, respectively, for the same viruses were obtained from oyster eluates by the same procedure. Percent recoveries of 97 for hepatitis A virus and 78 for human rotavirus Wa were obtained from sediment eluates containing 2 M NaNO3 with a final concentration of 15% polyethylene glycol 6000. The polyethylene glycol method was shown to be more effective than the organic flocculation method for recovery of hepatitis A virus and rotaviruses Wa and SA11, but not of poliovirus 1 in laboratory studies. In field trials, hepatitis A virus or rotavirus or both were recovered from 12 of 18 eluates by polyethylene glycol, compared with recovery from 9 of 18 eluates by organic flocculation from fresh and estuarine waters subject to pollution.
Quantitative evaluation of vimentin expression in tumour stroma of colorectal cancer (2007)

Recent studies have identified vimentin, a type III intermediate filament, among genes differentially expressed in tumours with more invasive features, suggesting an association between vimentin and tumour progression. The aim of this study, was to investigate whether vimentin expression in colon cancer tissue is of clinical relevance. We performed immunostaining in 142 colorectal cancer (CRC) samples and quantified the amount of vimentin expression using computer-assisted image analysis. Vimentin expression in the tumour stroma of CRC was associated with shorter survival. Overall survival in the high vimentin expression group was 71.2% compared with 90.4% in the low-expression group (P=0.002), whereas disease-free survival for the high-expression group was 62.7% compared with 86.7% for the low-expression group (P=0.001). Furthermore, the prognostic power of vimentin for disease recurrence was maintained in both stage II and III CRC. Multivariate analysis suggested that vimentin was a better prognostic indicator for disease recurrence (risk ratio=3.5) than the widely used lymph node status (risk ratio=2.2). Vimentin expression in the tumour stroma may reflect a higher malignant potential of the tumour and may be a useful predictive marker for disease recurrence in CRC patients.
Characterization of polyisobutylene‐based model urethane networks (1986)

Abstract Polyisobutylene‐based model urethane networks have been prepared by crosslinking liquid α, ω‐di(hydroxyl)polyisobutylenes, i.e., PIB‐diols carrying exactly two CH 2 OH functions, F n = 2.0 ± 0.1, and rather narrow molecular weight distributions, M w / M n = 1.5−1.6, with tritriphenylmethyl isocyanate \documentclass{article}\pagestyle{empty}\begin{document}$$\rm{HC}\ (\hskip-6pt\hbox{---}p\rm{C}_6\rm{H}_4\hbox{---}\rm{NCO})_3$$\end{document} . Networks prepared with M n = 1400 and 7500 PIB‐diols, and with 90/10 and 80/20 mixtures of these PIB‐diols (bimodal networks), have been characterized by extraction, by the Flory–Rehner swelling method, and by the Mooney–Rivlin equilibrium modulus method, and tested by stress–strain measurements. M c values of the M n = 1400 PIB‐diol network obtained by swelling (1550) and by equilibrium modulus studies (1500) were in excellent agreement with the M n of the prepolymer. Also the C 2 parameter was negligible in comparison to C 1 , suggesting the absence of interchain entanglements. This is the first hydrocarbon‐based polyurethane network that exhibits a negligible C 2 value by stress–strain measurements of unswollen samples. The M c values of the M n = 7500 PIB‐diol were also in good agreement with the M n of the prepolymer; however, C 2 was larger than C 1 , indicating interchain entanglements. Evidence for strain‐induced toughening was observed with both networks prepared with the M n = 1400 and 7500 PIB‐diols. The ultimate properties of the two bimodal networks did not show improvement over those of the individual constituents; however, the M n 's of the constituents were not very different.
Estimating Divergence Functionals and the Likelihood Ratio by Convex Risk Minimization (2010)

We develop and analyze <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">M</i> -estimation methods for divergence functionals and the likelihood ratios of two probability distributions. Our method is based on a nonasymptotic variational characterization of <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">f</i> -divergences, which allows the problem of estimating divergences to be tackled via convex empirical risk optimization. The resulting estimators are simple to implement, requiring only the solution of standard convex programs. We present an analysis of consistency and convergence for these estimators. Given conditions only on the ratios of densities, we show that our estimators can achieve optimal minimax rates for the likelihood ratio and the divergence functionals in certain regimes. We derive an efficient optimization algorithm for computing our estimates, and illustrate their convergence behavior and practical viability by simulations.
Photoaffinity Labeling in Target- and Binding-Site Identification (2015)

Photoaffinity labeling (PAL) using a chemical probe to covalently bind its target in response to activation by light has become a frequently used tool in drug discovery for identifying new drug targets and molecular interactions, and for probing the location and structure of binding sites. Methods to identify the specific target proteins of hit molecules from phenotypic screens are highly valuable in early drug discovery. In this review, we summarize the principles of PAL including probe design and experimental techniques for in vitro and live cell investigations. We emphasize the need to optimize and validate probes and highlight examples of the successful application of PAL across multiple disease areas.
The use of synthetic oligonucleotides as hybridization probes. II. Hybridization of oligonucleotides of mixed sequence to rabbit β-globin DNA (1981)

Two oligonucleotides 14-bases long were synthesized, one complementary to rabbit beta-globin DNA (R beta G14A) and the other with the same sequence except for a single base change (T for C) (R beta G14B). Hybridization conditions were established such that R beta G14A would hybridize to globin DNA while R beta G14B would not. We also synthesized a mixture of 13-base long oligonucleotides (R beta G13Mix), representing eight of the possible coding sequences for amino acids 15-19 of rabbit beta-globin. One of the eight is complementary to globin DNA. R beta G13Mix was found to hybridize specifically to globin DNA under conditions where oligonucleotides forming single base pair mismatches do not. Furthermore, R beta G13Mix was shown to hybridize specifically to colonies containing a plasmid with a globin DNA insert. These results are discussed with respect to a general procedure for screening recombinant clones for those containing DNA coding for a protein of known amino acid sequence.
A putative mechanism of demyelination in multiple sclerosis by a proteolytic enzyme, calpain (1999)

In autoimmune demyelinating diseases such as multiple sclerosis (MS), the degradation of myelin proteins results in destabilization of the myelin sheath. Thus, proteases have been implicated in myelin protein degradation, and recent studies have demonstrated increased expression and activity of a calcium-activated neutral proteinase (calpain) in experimental allergic encephalomyelitis, the corresponding animal model of MS. In the present study, calpain activity and expression (at translational and transcriptional levels) were evaluated in white matter from human patients with MS and Parkinson's and Alzheimer's diseases and compared with that of white matter from normal controls. Western blot analysis revealed that levels of the active form of calpain and calpain-specific degradation products (fodrin) were increased by 90.1% and 52.7%, respectively, in MS plaques compared with normal white matter. Calpain translational expression was up-regulated by 462.5% in MS plaques compared with controls, although levels of the specific endogenous inhibitor, calpastatin, were not altered significantly. At the transcriptional level, no significant changes in calpain or calpastatin expression were detected by reverse transcription-PCR. Using double immunofluorescent labeling, increased calpain expression was observed in reactive astrocytes, activated T cells, and activated mononuclear phagocytes in and adjacent to demyelinating lesions. Calpain activity and translational expression were not increased significantly in white matter from patients with Parkinson's or Alzheimer's diseases compared with that of normal controls. Because calpain degrades all major myelin proteins, the increased activity and expression of this proteinase may play a critical role in myelinolysis in autoimmune demyelinating diseases such as MS.
Immune Parameters That Distinguish Multiple Sclerosis Patients from Patients with Other Neurological Disorders at Presentation (2015)

We found no signature cytokines or profiles thereof in MS patients at presentation. Only IND patients presented with a clear Th1 cytokine polarization in serum and CSF. The parameters that distinguished MS patients from patients with other neurological disorders were IgG intrathecal synthesis, the IgG index and its correlation with CSF IL-4 levels.
Spatial structure of media noise in film disks (1986)

Measurements of the spatial structure of media noise across the track direction are made using new techniques involving computer processing of digitized transient read signal waveforms. Images of media noise having spatial resolution much finer than available head widths are obtained, and are used to study the scaling of media noise with read head width. Results are presented for two types of metal film disks and a particulate disk. Uniformly DC erased media noise is found to decrease less rapidly with decreasing head width for the metal film disks than for the particulate disk, in which it scales approximately as the square root of head width. A strip of excess noise is found at the edges of written tracks on the metal film disks but not the particulate disk.
Inhibition of activated protein C by recombinant alpha 1-antitrypsin variants with substitution of arginine or leucine for methionine358. (1990)

alpha 1-Antitrypsin (alpha 1-AT) was recently identified as a major physiologic plasma inhibitor of activated protein C. The reaction with activated protein C of recombinant alpha 1-AT containing amino acid substitutions at the reactive center was studied. The substitution of Arg358 for Met, as observed in a patient with a severe bleeding disorder with the mutant alpha 1-AT Pittsburgh, increased the association rate constant for activated protein C from 1.1 x 10(1) to 4.9 x 10(4) M-1 s-1. The association rate constant of activated protein C with protein C inhibitor, a native plasma serpin that contains Arg354 at the reactive site, is 6 x 10(3) M-1 s-1 in the absence of heparin. Plasma containing 4 microM [Arg358]alpha 1-AT inhibited activated protein C activity by greater than 95% in 15 s, and the inhibited activated protein C was shown by immunoblotting to exist as activated protein C-inhibitor complexes. In controls 50% loss of activated protein C activity in normal plasma occurred in 19 min. Double-substituted [Pro357,Met358]alpha 1-AT----[Ala357,Arg358]alpha 1-AT had similar reactivity toward activated protein C as the single-substituted [Arg358]alpha 1-AT. Thus, replacement of the reactive center Met358 of alpha 1-AT by Arg358, analogous to Arg354 of protein C inhibitor, results in an activated protein C inhibitor that is more potent than either of the native inhibitors. Comparison of the association rate constant of the [Arg358]alpha 1-AT for activated protein C to that for thrombin (4 x 10(4) versus 3 x 10(5) M-1 s-1) suggests that thrombin would be more effectively inhibited than activated protein C, thereby giving an explanation for bleeding rather than thrombosis in the alpha 1-AT Pittsburgh patient.
Improving the pharmacokinetic properties of biologics by fusion to an anti-HSA shark VNAR domain (2012)

Advances in recombinant antibody technology and protein engineering have provided the opportunity to reduce antibodies to their smallest binding domain components and have concomitantly driven the requirement for devising strategies to increase serum half-life to optimise drug exposure, thereby increasing therapeutic efficacy. In this study, we adopted an immunization route to raise picomolar affinity shark immunoglobulin new antigen receptors (IgNARs) to target human serum albumin (HSA). From our model shark species, Squalus acanthias, a phage display library encompassing the variable binding domain of IgNAR (VNAR) was constructed, screened against target, and positive clones were characterized for affinity and specificity. N-terminal and C-terminal molecular fusions of our lead hit in complex with a naïve VNAR domain were expressed, purified and exhibited the retention of high affinity binding to HSA, but also cross-selectivity to mouse, rat and monkey serum albumin both in vitro and in vivo. Furthermore, the naïve VNAR had enhanced pharmacokinetic (PK) characteristics in both N- and C-terminal orientations and when tested as a three domain construct with naïve VNAR flanking the HSA binding domain at both the N and C termini. Molecules derived from this platform technology also demonstrated the potential for clinical utility by being available via the subcutaneous route of delivery. This study thus demonstrates the first in vivo functional efficacy of a VNAR binding domain with the ability to enhance PK properties and support delivery of multifunctional therapies.
IL-2 and IL-15 exhibit opposing effects on Fas mediated apoptosis. (2004)

It has been shown that IL-2 and IL-15 can have opposing effects on life and death of T cells. However, the role of IL-2 and IL-15 in regulating the fate of other cell types is less clear. In the present study, we examined the impact of IL-2 and IL-15 on life and death of pre-B cells using the BAF-B03 line. We showed that BAF-B03 cells constitutively expressed the private IL-2R alpha chain and IL-15R alpha chain, and the shared IL-2R beta chain and gamma c chain. Stimulation of BAF-B03 cells in vitro with IL-2 and IL-15 induced vigorous cell proliferation in a dose-dependent fashion. Titration of IL-2 and IL-15 in the assay showed that the mitotic effects of IL-2 and IL-15 were remarkably similar. However, the sensitivities of BAF-B03 cells to Fas mediated apoptosis after IL-2 and IL-15 stimulation were strikingly different. Cells cultured in IL-2 readily underwent apoptotic cell death upon cross-linking of the Fas receptor whereas cells cultured in IL-15 were extremely resistant to Fas triggered cell death. The anti-apoptotic effect of IL-15 in this model was associated with increased expression of Bcl-xL. FLIP expression, however, was comparable between IL-2 and IL-15 stimulated cells. We conclude that IL-2 and IL-15 have diametrically opposite effect on the fate of BAF-B03 cells, although both cytokines share similar receptor structure and exhibit similar mitotic activities.
Cutting Edge: CD8+CD122+ Regulatory T Cells Produce IL-10 to Suppress IFN-γ Production and Proliferation of CD8+ T Cells (2005)

We recently identified CD8+CD122+ regulatory T cells that directly control CD8+ and CD4+ cells without intervention of APCs. In this study, we investigated the effector mechanism of CD8+CD122+ regulatory T cells by using an in vitro regulation system. The profile of cytokine expression revealed that IL-10 was predominantly produced by CD8+CD122+ cells, whereas other cytokines were similarly expressed in CD8+CD122+ cells and CD8+CD122- cells. Suppression of both proliferation and IFN-gamma production by CD8+CD122- cells by CD8+CD122+ cells was blocked by adding anti-IL-10 Ab to the culture but not by adding anti-TGF-beta Ab. When IL-10 was removed from the conditioned medium from CD8+CD122+ cells, the conditioned medium no longer showed regulatory activity. Finally, CD8+CD122+ cells from IL-10-deficient mice had no regulatory activity in vitro and reduced regulatory activity in vivo. Our results clearly indicate that IL-10 is produced by CD8+CD122+ cells and mediates the regulatory activity of these cells.
Vagal nerve stimulation increases right ventricular contraction and relaxation and heart rate (1996)

The present experiments suggest that vagal nerve stimulation releases vasoactive intestinal peptide (VIP) or a "VIP-like substance' that significantly increases right ventricular contraction, relaxation, and heart rate.
EEG dipole source localization (1998)

Considers using inverse solutions for determining source locations. Dipole source localization using EEGs recorded from the scalp is widely used to make estimates of the locations of sources of electrical activity in the brain. Such information can be very useful for both clinical and research applications. For example, in clinical applications, accurate information about the location of an epileptic focus (source) in the brain can be used to plan surgery for its removal. Likewise, information about the regions of the brain that process various signals (e.g., an auditory tone) can provide valuable research information about the functioning of the brain. It is necessary to assume a model of the source and a model of the head in order to estimate the location of a source. Once these models are selected, an inverse solution can be calculated for the location of the source in the head model. This source is then assumed to represent the actual source. The accuracy with which a source can be located by this method is affected by a number of factors including source-modeling errors, head-modeling errors, measurement-location errors, and EEG noise. This article presents a review of the research dealing with the effects of these factors on localization accuracy.
Factors Affecting the Gelation Properties of Hydrolyzed Sunflower Proteins (1997)

ABSTRACT The effects of temperature and several chemicals on gelation time and strength of gels formed by heating (pH 8) 5% solutions of trypsin hydrolyzed sunflower proteins were studied by dynamic rheological methods. The storage modulus reached a maximum at 80°C. Ca 2 Cl (and NaCl at &gt; 0.2M) accelerated gelation and weakened the gel. NaCOCH 3 Na 2 SO 4 and NaSCN decreased the storage modulus. Urea decreased gelstrength and at high concentrations slowed gelation. Time for gelation diminished and gel strength increased with increasing mercaptoethanol concentration up to 0.1M. Propylene glycol at 5–20% concentrations accelerated gelation and at 5% also increased gel strength. Trypsin hydrolyzed sunflower proteins could be useful in products requiring strong gels at high temperatures.
Rhenium-188 - A Generator-Derived Radioisotope for Cancer Therapy (1998)

Rhenium-188 (188Re) is an important therapeutic radioisotope which is obtained on demand as carrier-free sodium perrhenate by saline elution of the tungsten-188/rhenium-188 generator system. With a half-life of 16.9 hours and emission of a high energy beta particle (maximal energy of 2.12 MeV) and a gamma photon (155 keV, 15%) for imaging, 188Re can be provided at reasonable costs for routine preparation of radiopharmaceuticals for cancer treatment.
Gel electrophoretic analysis of Zymomonas mobilis glycolytic and fermentative enzymes: identification of alcohol dehydrogenase II as a stress protein (1991)

The 13 major enzymes which compose the glycolytic and fermentative pathways in Zymomonas mobilis are particularly abundant and represent one-half of the soluble protein in exponential-phase cells. One- and two-dimensional polyacrylamide gel electrophoresis maps were developed for 12 of these enzymes. Assignments were made by comigration with purified proteins, comparison with overexpressed genes in recombinant strains, and Western blots (immunoblots). Although most glycolytic enzymes appeared resistant to turnover and accumulated in stationary-phase cells, the protein levels of pyruvate kinase, alcohol dehydrogenase I, and glucokinase declined. Alcohol dehydrogenase II was identified as a major stress protein and was induced both by exposure to ethanol and by elevated temperature (45 degrees C). This enzyme, encoded by the adhB gene, is expressed from tandem promoters which share partial sequence identity with the Escherichia coli consensus sequence for heat shock proteins.
Electric field effects on excitons in gallium nitride (1996)

Electric-field effects on Wannier exciton are observed in GaN thin films. Using both absorption and photocurrent measurements, we have studied the excitonic Franz-Keldysh effect in thin epitaxial GaN films at temperatures between 80 and 300 K. We have measured the Stark shift, quenching, and broadening of the exciton peak with applied field. These results are compared with theoretical calculations from the literature. The physics of exciton ionization at varying temperatures is discussed, which explains the interplay between absorption and photocurrent. \textcopyright{} 1996 The American Physical Society.
Increased Osteoclast Development After Estrogen Loss: Mediation by Interleukin-6 (1992)

Osteoclasts, the cells that resorb bone, develop from hematopoietic precursors of the bone marrow under the control of factors produced in their microenvironment. The cytokine interleukin-6 can promote hematopoiesis and osteoclastogenesis. Interleukin-6 production by bone and marrow stromal cells is suppressed by 17 beta-estradiol in vitro. In mice, estrogen loss (ovariectomy) increased the number of colony-forming units for granulocytes and macrophages, enhanced osteoclast development in ex vivo cultures of marrow, and increased the number of osteoclasts in trabecular bone. These changes were prevented by 17 beta-estradiol or an antibody to interleukin-6. Thus, estrogen loss results in an interleukin-6-mediated stimulation of osteoclastogenesis, which suggests a mechanism for the increased bone resorption in postmenopausal osteoporosis.
Programmed Cell Death 1-Directed Immunotherapy for Enhancing T-Cell Function (2013)

T-cell exhaustion is a unique state that appears during many chronic infections and cancer and is characterized by loss of proliferative capacity and effector function. Complex mechanisms are involved in this T-cell dysfunction but an inhibitory receptor, PD-1, has been identified as a major regulator of T-cell exhaustion. Blockade of the PD-1 pathway can reinvigorate exhausted T cells, resulting in better control of chronic infections and cancer. Notably, recent clinical studies have revealed that PD-1-directed immunotherapy is highly effective in cancer patients, demonstrating that PD-1 is a promising therapeutic target in humans. In this review, we summarize our current understanding of the epigenetic regulation of PD-1 expression in T cells and discuss potential combination therapy with PD-1 blockade toward developing more effective treatment for chronic infections and cancer.