gebhart/patrepeval huggingface dataset:
IFN-α Skews Monocyte Differentiation into Toll-Like Receptor 7-Expressing Dendritic Cells with Potent Functional Activities (2003)

IFN-alpha is an important cytokine for the generation of a protective T cell-mediated immune response to viruses. In this study, we asked whether IFN-alpha can regulate the functional properties of dendritic cells (DCs). We show that monocytes cultured in the presence of GM-CSF and IFN-alpha can differentiate into DCs (IFN-alpha-derived DCs (IFN-DCs)). When compared with DCs generated in the presence of GM-CSF and IL-4 (IL-4-derived DCs), IFN-DCs exhibited a typical DC morphology and expressed, in addition to DC markers CD1a and blood DC Ag 4, a similar level of costimulatory and class II MHC molecules, but a significantly higher level of MHC class I molecules. After maturation with CD40 ligand, IFN-DCs up-regulated costimulatory, class I and II MHC molecules and expressed mature DC markers such as CD83 and DC-lysosome-associated membrane protein. IFN-DCs were endowed with potent functional activities. IFN-DCs secreted large amounts of the inflammatory cytokines IL-6, IL-10, TNF-alpha, IL-1beta, and IL-18, and promoted a Th1 response that was independent of IL-12p70 and IL-18, but substantially inhibited by IFN-alpha neutralization. Furthermore, immature IFN-DCs induced a potent autologous Ag-specific immune response, as evaluated by IFN-gamma secretion and expansion of CD8(+) T cells specific for CMV. Also, IFN-DCs expressed a large number of Toll-like receptors (TLRs), including acquisition of TLR7, which is classically found on the natural type I IFN-producing plasmacytoid DCs. Like plasmacytoid DCs, IFN-DCs could secrete IFN-alpha following viral stimulation or TLR7-specific stimulation. Taken together, these results illustrate the critical role of IFN-alpha at the early steps of immune response to pathogens or in autoimmune diseases.
Reversal of corticosteroid‐induced diabetes mellitis with supplemental chromium (1999)

These data demonstrate that corticosteroid treatment increases chromium losses and that steroid-induced diabetes can be reversed by chromium supplementation. Follow-up, double-blind studies are needed to confirm these observations.
Disease‐specific biomarker discovery by aptamers (2009)

RNA and DNA aptamers developed by an in vitro selection process, Systematic Evolution of Ligands by EXponential enrichment (SELEX), comprise a novel class of high-affinity and specific capture agents, which can be easily modified for cytometry and in vivo applications. A novel application of this technique (Cell SELEX) explores the expression of cell surface epitopes that differ between two given cell types or between healthy and diseased cells. Using whole cells as targets, aptamer libraries can be identified that bind to biomarkers expressed by target cells and not by any other cells. Aptamers have been developed that specifically interact with cell surface epitopes of trypanosomes or distinguish between the differences in molecular signature of somatic and cancer cells. Aside from its use for target cell identification by image and flow cytometry and laser-scanning microscopy, aptamers can be used for ligand-mediated purification and identification of their binding proteins in target cell membranes. In this review, we discuss an approach for the development of aptamers targeting parasite-derived surface proteins of Trypanosoma and Plasmodium.
Studies by e.p.r. spectroscopy of carbon monoxide oxidases from Pseudomonas carboxydovorans and Pseudomonas carboxydohydrogena (1983)

E.p.r. spectra were obtained at 8-120 K for carbon monoxide oxidases isolated from the carboxydotrophic bacteria Pseudomonas carboxydovorans and Pseudomonas carboxydohydrogena. Spectra from the two enzymes are extremely similar to one another. Under appropriate conditions each enzyme shows signals from Mo(V) atoms in two different chemical environments, as well as showing signals from two distinct iron-sulphur centres, presumed to be [2Fe-2S] clusters, and weak FADH X free-radical signals. Parameters of most of the signals were measured, and they show considerable similarities to those of the corresponding signals from xanthine oxidase and related enzymes. Though the signals from carbon monoxide oxidases appear and disappear under reducing and oxidizing conditions, we have so far failed to demonstrate the kinetic competence of any of them. It seems likely that this was due to the presence in the enzyme preparation examined of high amounts of desulpho carbon monoxide oxidase together with another non-functional form of the enzyme giving a stable 'Resting' Mo(V) e.p.r. signal.
Crystallization and preliminary X-ray crystallographic analysis of the curli transporter CsgG (2013)

Gram-negative bacteria have eight known protein secretion systems. The type-VIII secretion system, also known as the curli biosynthesis system, is responsible for the formation of aggregative fibres known in Escherichia coli as curli. Curli are extracellular proteinaceous fibres primarily involved in bacterial biofilm formation and attachment to nonbiotic surfaces. The secretion of curli subunits depends on a dedicated lipoprotein, CsgG, which is found to form an oligomeric secretion channel in the outer membrane. A nonlipidated mutant of CsgG was expressed and crystallized in a soluble form. The crystals diffracted to 3.15 Å resolution and belong to space group P1 with a unit cell containing a predicted 16 molecules per asymmetric unit.
Urinary kidney injury molecule-1: a sensitive quantitative biomarker for early detection of kidney tubular injury (2005)

Sensitive and specific biomarkers are needed to detect early kidney injury. The objective of the present work was to develop a sensitive quantitative urinary test to identify renal injury in the rodent to facilitate early assessment of pathophysiological influences and drug toxicity. Two mouse monoclonal antibodies were made against the purified ectodomain of kidney injury molecule-1 (Kim-1), and these were used to construct a sandwich Kim-1 ELISA. The assay range of this ELISA was 50 pg/ml to 5 ng/ml, with inter- and intra-assay variability of <10%. Urine samples were collected from rats treated with one of three doses of cisplatin (2.5, 5, or 7.5 mg/kg). At one day after each of the doses, there was an approximately three- to fivefold increase in the urine Kim-1 ectodomain, whereas other routinely used biomarkers measured in this study [plasma creatinine, blood urea nitrogen (BUN), urinary N-acetyl-beta-glucosaminidase (NAG), glycosuria, proteinuria] lacked the sensitivity to show any sign of renal damage at this time point. When rats were subjected to increasing periods (10, 20, 30, or 45 min) of bilateral ischemia, there was an increasing amount of urinary Kim-1 detected. After only 10 min of bilateral ischemia, Kim-1 levels on day 1 were 10-fold higher (5 ng/ml) than control levels, whereas plasma creatinine and BUN were not increased and there was no glycosuria, increased proteinuria, or increased urinary NAG levels. Thus urinary Kim-1 levels serve as a noninvasive, rapid, sensitive, reproducible, and potentially high-throughput method to detect early kidney injury in pathophysiological studies and in preclinical drug development studies for risk-benefit profiling of pharmaceutical agents.
A Sandwiched-Culture Technique for Evaluation of Heterologous Protein Production in a Filamentous Fungus (1999)

Aspergillus niger is known for its efficient excretion machinery. However, problems have often arisen in obtaining high amounts of heterologous proteins in the culture medium. Here we present a quick method using sandwiched colonies to evaluate transgenic strains for secretion of heterologous proteins. Expressing the ABH1 hydrophobin of Agaricus bisporus in A. niger, we showed that low production levels of the heterologous protein are probably due to extracellular proteolytic degradation of the protein.
Extracellular histones promote thrombin generation through platelet-dependent mechanisms: involvement of platelet TLR2 and TLR4 (2011)

The release of histones from dying cells is associated with microvascular thrombosis and, because histones activate platelets, this could represent a possible pathogenic mechanism. In the present study, we assessed the influence of histones on the procoagulant potential of human platelets in platelet-rich plasma (PRP) and in purified systems. Histones dose-dependently enhanced thrombin generation in PRP in the absence of any trigger, as evaluated by calibrated automated thrombinography regardless of whether the contact phase was inhibited. Activation of coagulation required the presence of fully activatable platelets and was not ascribable to platelet tissue factor, whereas targeting polyphosphate with phosphatase reduced thrombin generation even when factor XII (FXII) was blocked or absent. In the presence of histones, purified polyphosphate was able to induce thrombin generation in plasma independently of FXII. In purified systems, histones induced platelet aggregation; P-selectin, phosphatidylserine, and FV/Va expression; and prothrombinase activity. Blocking platelet TLR2 and TLR4 with mAbs reduced the percentage of activated platelets and lowered the amount of thrombin generated in PRP. These data show that histone-activated platelets possess a procoagulant phenotype that drives plasma thrombin generation and suggest that TLR2 and TLR4 mediate the activation process.
Multi-material optical fiber fabrication and applications (2011)

I review our progress in the emerging area of multi-material fibers. Applications range from mid-infrared linear and nonlinear chalcogenide glass fibers and fiber tapers, to the scalable and scale-invariant fabrication of micro- and nano-scale structures.
Solid phase peptide synthesis: recent advances and applications. (1994)

Techniques for the synthesis of peptides by solid phase procedures have advanced considerably over recent years and now enable the rapid and efficient preparation of complex and difficult sequences. These developments have led to many novel and unique applications of synthetic peptides which will find increasing and important utility in biotechnology.
Indirect monitoring and analysis of truncal stress over extended time periods (1986)

Low back pain is a common ailment encountered in clinical practice, yet there has hitherto been no completely satisfactory method for the measurement of truncal stress, which is a major factor in low back pain. Truncal stress has been difficult to record during the course of a working day because subjects were constrained by trailing cables attached to the monitoring equipment. We have used a pressure sensitive transmitter (radio pill) to record intra-abdominal pressure, which has been shown previously to be an indirect measure of truncal stress. The system makes possible multichannel recordings on magnetic tape throughout the working day by using a portable, battery powered recorder strapped to the subject's waist. A novel ferrite rod contributes materially to minimizing artefacts due to signal loss. The recorded data are replayed, at 60 times real time, into a microcomputer programmed to analyse this data.
Sample size recalculation using conditional power (2001)

The sample size required to achieve a given power at a prespecified absolute difference in mean response may depend on one or more nuisance parameters, which are usually unknown. Proposed methods for using an internal pilot to recalculate the sample size using estimates of these parameters have been well studied. Most of these methods ignore the fact that data on the parameter of interest from within this internal pilot will contribute towards the value of the final test statistic. We propose a method which involves recalculating the target sample size by computing the number of further observations required to maintain the probability of rejecting the null hypothesis at the end of the study under the prespecified absolute difference in mean response conditional on the data observed so far. We do this within the framework of a two-group error-spending sequential test, modified so as to prevent inflation of the type I error rate.
Presence and physical state of HPV DNA in prostate and urinary‐tract tissues (1992)

Neoplastic and non-neoplastic tissues from the urinary tract and the prostate were analyzed for the presence of human papillomavirus (HPV) DNA. The analysis was performed by PCR using primers specific for HPV 6/11 and 16. HPV DNA was present in bladder, ureter, kidney and prostate, with percentages ranging between 46% and 87%. Benign and oncogenic HPV types were detected with similar frequencies both in non-neoplastic and in neoplastic biopsies, and HPV 16 was not preferentially associated with malignant lesions. In all instances, small amounts of HPV DNA were present in the tissues, suggesting the absence of productive infection. Analysis of the physical state of HPV DNA performed by 2-dimensional gel electrophoresis and Southern blot hybridization revealed that HPV 16 DNA harbored in the urinary tract can be integrated also in non-neoplastic tissues. The results indicate that HPV 16 does not seem to be associated with urinary-tract and prostate oncogenesis, but that these tissues may represent an important reservoir for the transmission of HPV types normally infecting the genital tract.
A differential error reference adaptive echo canceller for multilevel PAM line codes (2002)

The objective of any local echo canceller connected to any end of a digital subscriber line (DSL) is to compensate the outgoing transmit signal energy in the receiving path (commonly called near-echo) that the hybrid circuit leaks. The observed signals that usually play the role of error references for adaptive echo cancellers (EC) in data communications are basically composed by far-end data plus a residual echo. The EC goal is to eliminate that residual echo. However, depending on the convergence stage, the presence of data in the error reference may mask the effective error reference (the residual echo). We show a new adaptive EC that offers better convergence properties than those associated to the simplest EC algorithms (standard LMS and decision-directed) for multilevel PAM signals. It exploits the discrete nature of the far-end signal to self-cancel the masking effect by adding (or subtracting) a weighted old version of the error reference to the current one. We show that the new error cost function is now closer to the instantaneous optimal one: its corresponding MLE. This new error surface presents a more robust (or uniform) behavior during the convergence period.
REGULATION OF FATTY ACID SYNTHESIS (1997)

All plant cells produce fatty acids from acetyl-CoA by a common pathway localized in plastids. Although the biochemistry of this pathway is now well understood, much less is known about how plants control the very different amounts and types of lipids produced in different tissues. Thus, a central challenge for plant lipid research is to provide a molecular understanding of how plants regulate the major differences in lipid metabolism found, for example, in mesophyll, epidermal, or developing seed cells. Acetyl-CoA carboxylase (ACCase) is one control point that regulates rates of fatty acid synthesis. However, the biochemical modulators that act on ACCase and the factors that in turn control these modulators are poorly understood. In addition, little is known about how the expression of genes involved in fatty acid synthesis is controlled. This review evaluates current knowledge of regulation of plant fatty metabolism and attempts to identify the major unanswered questions.
FlashBack (2016)

Virtual reality head-mounted displays (VR HMDs) are attracting users with the promise of full sensory immersion in virtual environments. Creating the illusion of immersion for a near-eye display results in very heavy rendering workloads: low latency, high framerate, and high visual quality are all needed. Tethered VR setups in which the HMD is bound to a powerful gaming desktop limit mobility and exploration, and are difficult to deploy widely. Products such as Google Cardboard and Samsung Gear VR purport to offer any user a mobile VR experience, but their GPUs are too power-constrained to produce an acceptable framerate and latency, even for scenes of modest visual quality.
Identification of Ubiquitin Ligases Required for Skeletal Muscle Atrophy (2001)

Skeletal muscle adapts to decreases in activity and load by undergoing atrophy. To identify candidate molecular mediators of muscle atrophy, we performed transcript profiling. Although many genes were up-regulated in a single rat model of atrophy, only a small subset was universal in all atrophy models. Two of these genes encode ubiquitin ligases: Muscle RING Finger 1 (MuRF1), and a gene we designate Muscle Atrophy F-box (MAFbx), the latter being a member of the SCF family of E3 ubiquitin ligases. Overexpression of MAFbx in myotubes produced atrophy, whereas mice deficient in either MAFbx or MuRF1 were found to be resistant to atrophy. These proteins are potential drug targets for the treatment of muscle atrophy.
The Netflix Recommender System (2015)

This article discusses the various algorithms that make up the Netflix recommender system, and describes its business purpose. We also describe the role of search and related algorithms, which for us turns into a recommendations problem as well. We explain the motivations behind and review the approach that we use to improve the recommendation algorithms, combining A/B testing focused on improving member retention and medium term engagement, as well as offline experimentation using historical member engagement data. We discuss some of the issues in designing and interpreting A/B tests. Finally, we describe some current areas of focused innovation, which include making our recommender system global and language aware.
Evidence of Molecular Evolution Driven by Recombination Events Influencing Tropism in a Novel Human Adenovirus that Causes Epidemic Keratoconjunctivitis (2009)

In 2005, a human adenovirus strain (formerly known as HAdV-D22/H8 but renamed here HAdV-D53) was isolated from an outbreak of epidemic keratoconjunctititis (EKC), a disease that is usually caused by HAdV-D8, -D19, or -D37, not HAdV-D22. To date, a complete change of tropism compared to the prototype has never been observed, although apparent recombinant strains of other viruses from species Human adenovirus D (HAdV-D) have been described. The complete genome of HAdV-D53 was sequenced to elucidate recombination events that lead to the emergence of a viable and highly virulent virus with a modified tropism. Bioinformatic and phylogenetic analyses of this genome demonstrate that this adenovirus is a recombinant of HAdV-D8 (including the fiber gene encoding the primary cellular receptor binding site), HAdV-D22, (the epsilon determinant of the hexon gene), HAdV-D37 (including the penton base gene encoding the secondary cellular receptor binding site), and at least one unknown or unsequenced HAdV-D strain. Bootscanning analysis of the complete genomic sequence of this novel adenovirus, which we have re-named HAdV-D53, indicated at least five recombination events between the aforementioned adenoviruses. Intrahexon recombination sites perfectly framed the epsilon neutralization determinant that was almost identical to the HAdV-D22 prototype. Additional bootscan analysis of all HAdV-D hexon genes revealed recombinations in identical locations in several other adenoviruses. In addition, HAdV-D53 but not HAdV-D22 induced corneal inflammation in a mouse model. Serological analysis confirmed previous results and demonstrated that HAdV-D53 has a neutralization profile representative of the epsilon determinant of its hexon (HAdV-D22) and the fiber (HAdV-D8) proteins. Our recombinant hexon sequence is almost identical to the hexon sequences of the HAdV-D strain causing EKC outbreaks in Japan, suggesting that HAdV-D53 is pandemic as an emerging EKC agent. This documents the first genomic, bioinformatic, and biological descriptions of the molecular evolution events engendering an emerging pathogenic adenovirus.
Treatment of multiple sclerosis with interferon beta : an appraisal of cost-effectiveness and quality of life (2000)

The impact of multiple sclerosis on QoL is substantial. Future trials should base outcomes measurement on QoL and be better linked to natural history and cost data. IFbeta-1b produces important occasional short term QoL gains, but small gains in QALYs overall and large additional costs.
<title>High-resolution phase zone plates for water window wavelengths</title> (1998)

High-resolution x-ray microscopy has applications in the fields of biology, colloid physics, and solid state physics. For each of these applications it is essential that the micro zone plates used as objectives in the x-ray microscope combine high resolution with optimal diffraction efficiency, so as to minimize exposure time and the x-ray dose absorbed by the specimen. The outermost zone width constitutes an important property of the zone plate, since the first-order spatial resolution scales linearly with this parameter. The other fundamental property of a micro zone plate is its diffraction efficiency, which should be both high and uniform. The combination of small outermost zones and the zone height required for optimal diffraction efficiency leads to high aspect ratios of the nanostructures. We report here the technique to manufacture these micro zone plates using microscopic glavanoforms and electrodeposition. Copolymer galvanoforms for nickel micro zone plates were irradiated with high doses of x-ray radiation to increase the degree of cross-linking of the copolymer network in this way, exact pattern replication in the galvanoform was obtained for zone aspect ratios of up to 8:1. Using these galvanoforms, nickel micro zone plates were produced for the soft x-ray wavelength 2.4 nm, with smallest zone widths of 30 nm and 40 nm, achieving first-order diffraction efficiencies of up to 15 percent and 20 percent, respectively.
Emergence of viruses resistant to neutralization by V3-specific antibodies in experimental human immunodeficiency virus type 1 IIIB infection of chimpanzees (1990)

Emergence in two chimpanzees of human immunodeficiency virus type 1 (HIV-1) IIIB variants resistant to neutralization by the preexisting antibody is described. Viruses isolated from the HIV-1 IIIB gp120-vaccinated and -challenged animal were more resistant to neutralization by the chimpanzee's own serum than viruses isolated from the naive infected animal, indicating immune pressure as the selective mechanism. However, all reisolated viruses were 16- to 256-fold more neutralization resistant than the inoculum virus to antibodies binding to the third variable domain (V3) of the HIV-1 external envelope. Early chimpanzee serum samples that neutralized the inoculum strain but not the reisolated viruses were found to bind an HIV-1 IIIB common nonapeptide (IQRGPGRAF) derived from the gp120 isolate-specific V3 domain shown to induce isolate-specific neutralization in other animals. Amplification of the V3 coding sequence by polymerase chain reaction and subsequent sequence analysis of the neutralization-resistant variants obtained from in vivo-infected animals indicated that early resistance to neutralization by an HIV-1 IIIB monoclonal antibody (0.5 beta) was conferred by changes outside the direct binding site for the selective neutralizing antibody. The reisolated neutralization-resistant isolates consisted of the lower-replication-competent virus subpopulations of the HIV-1 IIIB stock, as confirmed by biological and sequence analyses. In vitro passage of the HIV-1 IIIB stock through chimpanzee and human peripheral blood mononuclear cell cultures void of HIV-specific antibody resulted in homogenic amplification of the more-replication-competent subpopulation preexisting in the original viral stock, suggesting a role for the immune system in suppressing the more-replication-competent viruses.