gebhart/patrepeval huggingface dataset:
Synthetic RORγt Agonists Enhance Protective Immunity (2016)

The T cell specific RORγ isoform RORγt has been shown to be the key lineage-defining transcription factor to initiate the differentiation program of TH17 and TC17 cells, cells that have demonstrated antitumor efficacy. RORγt controls gene networks that enhance immunity including increased IL17 production and decreased immune suppression. Both synthetic and putative endogenous agonists of RORγt have been shown to increase the basal activity of RORγt enhancing TH17 cell proliferation. Here, we show that activation of RORγt using synthetic agonists drives proliferation of TH17 cells while decreasing levels of the immune checkpoint protein PD-1, a mechanism that should enhance antitumor immunity while blunting tumor associated adaptive immune resistance. Interestingly, putative endogenous agonists drive proliferation of TH17 cells but do not repress PD-1. These findings suggest that synthetic agonists of RORγt should activate TC17/TH17 cells (with concomitant reduction in the Tregs population), repress PD-1, and produce IL17 in situ (a factor associated with good prognosis in cancer). Enhanced immunity and blockage of immune checkpoints has transformed cancer treatment; thus such a molecule would provide a unique approach for the treatment of cancer.
Enhanced image capture through fusion (2002)

The authors present an extension to the pyramid approach to image fusion. The modifications address problems that were encountered with past implementations of pyramid-based fusion. In particular, the modifications provide greater shift invariance and immunity to video noise, and provide at least a partial solution to the problem of combining components that have roughly equal salience but opposite contrasts. The fusion algorithm was found to perform well for a range of tasks without requiring adjustment of the algorithm parameters. Results were remarkably insensitive to changes in these parameters, suggesting that the procedure is both robust and generic. A composite imaging technique is outlined that may provide a powerful tool for image capture. By fusing a set of images obtained under restricted, narrowband, imaging conditions, it is often possible to construct an image that has enhanced information content when compared to a single image obtained directly with a broadband sensor.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Synthetic vaccines and HIV-1 hypervariability: a "mixotope" approach. (1992)

The hypervariability of the gp120 envelope protein principal neutralizing domain, the V3 loop, represents a major problem in the design of vaccines against HIV-1. We have designed a mixed V3 loop peptide, termed "mixotope," obtained in a unique synthesis, and containing around 7.5 x 10(5) different sequences of 22 to 25 residues, organized around the conserved GPGR tetrapeptide. Free or coupled to a carrier protein, the "mixotope" induced in rabbits broadly specific antibodies, which recognized different individual V3 loop sequences, and the native gp120 protein. The "mixotope" approach may allow researchers to focus vaccine strategy against hypervariable functional epitopes of various pathogens.
Autism-specific maternal autoantibodies recognize critical proteins in developing brain (2013)

Autism spectrum disorders (ASDs) are neurodevelopmental in origin, affecting an estimated 1 in 88 children in the United States. We previously described ASD-specific maternal autoantibodies that recognize fetal brain antigens. Herein, we demonstrate that lactate dehydrogenase A and B (LDH), cypin, stress-induced phosphoprotein 1 (STIP1), collapsin response mediator proteins 1 and 2 (CRMP1, CRMP2) and Y-box-binding protein to comprise the seven primary antigens of maternal autoantibody-related (MAR) autism. Exclusive reactivity to specific antigen combinations was noted in 23% of mothers of ASD children and only 1% of controls. ASD children from mothers with specific reactivity to LDH, STIP1 and CRMP1 and/or cypin (7% vs 0% in controls; P<0.0002; odds ratios of 24.2 (95% confidence interval: 1.45-405)) had elevated stereotypical behaviors compared with ASD children from mothers lacking these antibodies. We describe the first panel of clinically significant biomarkers with over 99% specificity for autism risk thereby advancing our understanding of the etiologic mechanisms and therapeutic possibilities for MAR autism.
FTIR microscopic imaging of collagen and proteoglycan in bovine cartilage (2000)

Articular cartilage, a connective tissue that provides resistance to compressive forces during joint movements, has not been examined in detail by conventional Fourier transform infrared (FTIR) spectroscopy, microspectroscopy (FTIRM), or imaging (FTIRI). The current study reports FTIRM and FTIRI analyses of normal bovine cartilage and identifies the specific molecular components of cartilage that contribute to its IR spectrum. FTIRM data acquired through the superficial, middle, and deep zones of thin sections of bovine articular cartilage showed a variation in intensities of the absorbance bands that arise from the primary nonaqueous components of cartilage, collagen, and proteoglycan (primarily aggrecan) and thus reflected the differences in quantity of these specific components. The spectra of mixtures of model compounds, which had varying proportions of type II collagen and aggrecan, were analyzed to identify spectral markers that could be used to quantitatively analyze these components in cartilage. Collagen and aggrecan were then imaged by FTIRI based on markers found in the model compounds. Polarization experiments were also performed to determine the spatial distribution of the collagen orientation in the different zones of cartilage. This study provides a framework in which complex pathological changes in this heterogeneous tissue can be assessed by IR microscopic imaging.
Peripheral and central mechanisms of visceral sensitization in man (2007)

Visceral hypersensitivity (perception of gastrointestinal sensory events at a lower-than-normal threshold) is considered to be an important pathophysiological mechanism in the development of functional gastrointestinal disorders (FGIDs), such as irritable bowel syndrome, non-cardiac chest pain and functional dyspepsia. These disorders are associated with significant health care and socioeconomic costs due to factors such as repeated visits to consultants, hospitalizations and work absenteeism. Despite the presence of extensive evidence linking visceral hypersensitivity and FGIDs, the mechanism(s) underlying visceral hypersensitivity has not been fully elucidated. Suggested hypotheses include sensitization of afferent neurones, both at the level of the enteric and the (afferent) autonomic nervous system (peripheral sensitization), sensitization of spinal cord dorsal horn neurones (central sensitization) and psychosocial factors/psychiatric comorbidity influencing the processing of afferent signals at the level of the brain. Importantly, these hypotheses may be complementary rather than mutually exclusive. However, the degree to which each of these mechanisms contributes to the overall perception of visceral pain, and therefore the generation of symptoms, still remains unclear. This article discusses the mechanisms that may underlie visceral hypersensitivity, with reference to FGIDs. Understanding these mechanisms is essential in order to improve the diagnosis and treatment of patients with these disorders.
Object Storage: The Future Building Block for Storage Systems A Position Paper (2006)

The concept of object storage was introduced in the early 1990's by the research community. Since then it has greatly matured and is now in its early stages of adoption by the industry. Yet, object storage is still not widely accepted. Viewing object store technology as the future building block particularly for large storage systems, our team in IBM Haifa Research Lab has invested substantial efforts in this area. In this position paper we survey the latest developments in the area of object store technology, focusing on standardization, research prototypes, and technology adoption and deployment. A major step has been the approval of the TIO OSD protocol (version I) as an OSD standard in late 2004. We also report on prototyping efforts that are carried out in IBM Haifa Research Lab in building an object store. Our latest prototype is compliant with a large subset of the TIO standard. To facilitate deployment of the new technology and protocol in the community at large, our team also implemented a TIO-compliant OSD (iSCSI) initiator for Linux. The initiator is interoperable with object disks of other vendors. The initiator is available as an open source driver for Linux.
Improved modeling techniques for turbomachinery flow fields (1995)

This program has the objective of developing an improved methodology for modeling turbomachinery flow fields, including the prediction of losses and efficiency. Specifically, the program addresses the treatment of the mixing stress tensor terms attributed to deterministic flow field mechanisms required in steady-state Computational Fluid Dynamic (CFD) models for turbomachinery flow fields. These mixing stress tensors arise due to spatial and temporal fluctuations (in an absolute frame of reference) caused by rotor-stator interaction due to various blade rows and by blade-to-blade variation of flow properties. This will be accomplished in a cooperative program by Penn State University and the Allison Engine Company. These tasks include the acquisition of previously unavailable experimental data in a high-speed turbomachinery environment, the use of advanced techniques to analyze the data, and the development of a methodology to treat the deterministic component of the mixing stress tenor.
Trait stacking in transgenic crops: Challenges and opportunities (2010)

In recent years, there has been a rapid increase in the planting of transgenic crops with stacked traits. Most of these products have been formed by conventional breeding, i.e. the crossing of transgenic plant (event) containing individual transgenes with other event(s) containing single or double transgenic traits. Many biotech companies are developing stacked trait products with increasing numbers of insect and herbicide tolerance genes for controlling a broad range of insect pests and weeds. There has also been an increase in development of technologies for molecular stacking of multiple traits in a single transgene locus. In this review we look at the status of stacked trait products, crop trait stacking technologies and the technical challenges we are facing. We also review recent progress in developing technology for assembling large transgene arrays in vitro (molecular stacks), their delivery to crop plants and issues they pose for transgene expression.
Proteoglycans in male reproductive tract (1994)

Proteoglycans in male reproductive tract have been mainly characterized in testicular extracellular matrix and somatic cells. Heparan sulfate, chondroitin sulfate and hybrid chondroitin/heparan sulfate proteoglycans coexist within the testes. Their biological roles are not currently established, however, the molecular characterization of some of them is indicative that they might be involved in various regulatory processes during spermatogenesis.
Elastic deformation and the laws of friction (1957)

Abstract This paper examines whether the hypothesis of elastic deformation of surface protuberances is consistent with Amontons’s law, that the friction is proportional to the applied load. For a single elastic contact, the area of contact A is known to be proportional to the ⅔ power of the load W. Since the frictional force is generally assumed to be proportional to A, it has been thought that in elastic deformation Amontons’s law would not be obeyed. However, conforming surfaces usually touch at many points, and it is shown that in these circumstances A and W become nearly proportional. Experiments are described which show that the general law is that the friction is proportional to the true area of contact; whether or not Amontons’s law is obeyed depends upon the surface topography. For highly elastic materials such as Perspex, Amontons’s law is obeyed when contact is made at many points, and other relations between A and W are observed when the contacts are few. Experiments with lubricated brass specimens show that the same conclusions apply to carefully prepared or well run-in metal surfaces running in conditions where the damage is small.
Nutlin-3, the small-molecule inhibitor of MDM2, promotes senescence and radiosensitises laryngeal carcinoma cells harbouring wild-type p53 (2010)

This is the first study showing Nutlin-3 as an effective radiosensitiser in LSCC cells that retain wild-type p53. The clinical application of Nutlin-3 might improve local recurrence rates or allow treatment de-escalation in these patients.
Hole-mediated chemisorption of atomic hydrogen in silicon (1985)

It has been shown that at 120 °C atomic hydrogen diffuses into p-type silicon where it ties to a Si dangling bond near an acceptor. However, a thin n-type surface layer blocks the entry of atomic hydrogen. This demonstrates that free holes in the surface layer are needed to permit the entry of atomic hydrogen.
The Extended Cleavage Specificity of Human Thrombin (2012)

Thrombin is one of the most extensively studied of all proteases. Its central role in the coagulation cascade as well as several other areas has been thoroughly documented. Despite this, its consensus cleavage site has never been determined in detail. Here we have determined its extended substrate recognition profile using phage-display technology. The consensus recognition sequence was identified as, P2-Pro, P1-Arg, P1'-Ser/Ala/Gly/Thr, P2'-not acidic and P3'-Arg. Our analysis also identifies an important role for a P3'-arginine in thrombin substrates lacking a P2-proline. In order to study kinetics of this cooperative or additive effect we developed a system for insertion of various pre-selected cleavable sequences in a linker region between two thioredoxin molecules. Using this system we show that mutations of P2-Pro and P3'-Arg lead to an approximate 20-fold and 14-fold reduction, respectively in the rate of cleavage. Mutating both Pro and Arg results in a drop in cleavage of 200-400 times, which highlights the importance of these two positions for maximal substrate cleavage. Interestingly, no natural substrates display the obtained consensus sequence but represent sequences that show only 1-30% of the optimal cleavage rate for thrombin. This clearly indicates that maximal cleavage, excluding the help of exosite interactions, is not always desired, which may instead cause problems with dysregulated coagulation. It is likely exosite cooperativity has a central role in determining the specificity and rate of cleavage of many of these in vivo substrates. Major effects on cleavage efficiency were also observed for residues as far away as 4 amino acids from the cleavage site. Insertion of an aspartic acid in position P4 resulted in a drop in cleavage by a factor of almost 20 times.
A mismatch bubble in double-stranded DNA suffices to direct precise transcription initiation by Escherichia coli RNA polymerase. (1994)

Formation of a transcription-competent "open" complex between Escherichia coli RNA polymerase and a promoter, where base pairing is disrupted over a region of 12 base pairs including the start site of transcription, is a complex process involving at least three steps: recognition of specific DNA sequences, a conformational change in RNA polymerase, and DNA melting. By using synthetic constructs devoid of promoter-specific sequences, we show here that a mismatch bubble of 12 base pairs suffices to direct transcription initiation in divergent directions from its edges, reflecting the absence of polarity determinants for RNA polymerase binding. Bubble transcription is obtained with both core polymerase and holoenzyme, but efficient formation of heparin-resistant initiation complexes requires the sigma (specificity) factor. Based on these results it is likely that the sigma factor blocks access of the heparin to a site on the holoenzyme.
Capillary Tube Resistive Thermal Cycling (1998)

A system that performs rapid thermal cycling of microliter and smaller liquid volumes inside glass capillary tubes that have an optically transparent thin film of indium-tin oxide (ITO) covering the exterior is described. The ITO film acts as both a heater and a temperature sensor, while cooling is accelerated with forced air. Unlike existing batch-mode thermal cycling systems, this system allows control over each sample's temperature profile. Temperature transition rates of 44 degrees Celsius per second during heating and 15 degrees Celsius per second during cooling have been achieved, allowing successful polymerase chain reaction (PCR) experiments to be performed in 20 min. Capillary external temperature can be regulated typically to within +/- 0.25 degrees Celsius, and peak temperatures more than 800 degrees Celsius have been demonstrated. Capillary internal (sample) temperatures at present are controllable typically to within 2 degrees Celsius. The resistive film can be used as a temperature sensor, and the optical transparency of the thin-film coating could permit fluorescent monitoring of the sample during thermal cycling, making this method well suited for real-time quantitative PCRs.
Differential Effects of Resveratrol and SRT1720 on Lifespan of AdultCaenorhabditis elegans (2010)

Resveratrol and SRT1720 have been shown to act as sirtuin activators that may ameliorate type 2 diabetes and metabolic diseases in mice. Moreover, resveratrol extends lifespan in model organisms like C. elegans, N. FURZERI, and possibly D. melanogaster. The aim of the study was to test whether pharmacological concentrations of resveratrol and SRT1720 are capable of extending lifespan in a nematodal model organism for aging processes, the roundworm Caenorhabditis elegans. Several hundreds of adult C. ELEGANS roundworms were maintained on agar plates and fed E. COLI strain OP50 bacteria. Resveratrol (5 micromolar, 500 nanomolar) or SRT1720 (1 micromolar, 100 nanomolar) was applied to the agar to test whether they may promote longevity by quantifying survival in the presence and absence of the respective compounds. At a dose of 5 micromolar, which is pharmacologically relevant and 20 times lower than previously published concentrations, resveratrol significantly extends C. elegans lifespan by 3.6% (mean lifespan) and 3.4% (maximum lifespan). By unexpected contrast, SRT1720, which was previously proposed to be several hundred times more active than resveratrol, did not extend lifespan at none of the concentrations tested. Thus, in the model organisms C. elegans, resveratrol is capable of promoting longevity at a concentration that pharmacologically relevant and 20 times lower than previously published doses. The sirtuin activator SRT1720 did not extend lifespan, suggesting that in C. elegans, some relevant effects of resveratrol cannot be mimicked by SRT1720.
Genetic analysis of epidermin biosynthetic genes and epidermin‐negative mutants of Staphylococcus epidermidis (1992)

Epidermin is produced by Staphylococcus epidermidis Tü3298 which harbors the 54-kb plasmid, pTü32. The plasmid contains not only the epidermin structural gene epiA, but also a flanking DNA region which is necessary for epidermin biosynthesis. The DNA sequence of this region revealed, in addition to epiA, five additional open reading frames, epiB, C, D, Q and P [Schnell, N., Engelke, G., Augustin J., Rosenstein, R., Ungermann, V., Götz, F. & Entian, K.-D. (1992) Eur. J. Biochem. 204, 57-68]. We isolated a number of stable mutants from strain Tü3298 which are unable to produce biologically active epidermin. Complementation studies using the newly constructed staphylococcal plasmid vectors pT181mcs and pCU1 led to their classification as epiA, epiB, epiC or epiD mutants. Furthermore, evidence is presented that epiB lacks its own promoter and is co-transcribed from the epiA promoter. There is evidence that epiC and D possess their own promoters. Although epiQ and epiP mutants were not isolated, it could be shown by heterologous gene expression in S. carnosus and S. xylosus that the corresponding DNA region is involved in epidermin biosynthesis. We can not exclude the possibility that, in addition to the four open reading frames, epiA, B, C, D, and the DNA region comprising epiQ and P, host-encoded functions are necessary for epidermin production. Thus, the genetic information for epidermin biosynthesis in S. carnosus and S. xylosus is located on an 8-kb DNA fragment of pTü32. A further characterization of the two epiA mutants revealed that in both mutants, the preepidermin nucleotide sequence was changed. In one mutant, the mutation led to a substitution of Ser3 by Asn; in the other of Gly10 by Glu.
<title>Subwavelength photoresist grating metrology using scatterometry</title> (1995)

A precise and accurate technique for the characterization of periodic line/space gratings is presented. The technique, known as scatterometry, derives its sensitivity and robustness from the wealth of information present in diffracted optical radiation. Scatterometry is capable of determining width, height, and overall shape of sub-half micron lines as well as the thickness of underlying thin films. The characterization process consists of three elements: a diffraction measurement apparatus, a model built on calibration data, and a statistical analysis routine that uses the model to correlate empirical data to the unknown parameters of the structure. The measurement technique was evaluated on twenty five wafers fabricated with deliberate deviation in focus, exposure dose, and underlying thin film thickness. Each wafer consisted of developed photoresist lines on an antireflecting layer, placed on layers of polycrystalline silicon on gate oxide on a silicon substrate. Scatterometry was used to simultaneously determine the width and height of the nominal 0.25 micrometers and 0.35 micrometers photoresist lines, as well as the thickness of underlying layers. Comparison of results obtained using reference methods (ellipsometry and scanning electron microscopy) are included.
Regulation of the Ysa Type III Secretion System ofYersinia enterocoliticaby YsaE/SycB and YsrS/YsrR (2004)

Yersinia enterocolitica biovar 1B contains two type III secretion systems (TTSSs), the plasmid-encoded Ysc-Yop system and the chromosomally encoded Ysa-Ysp system. Proteins secreted from the Ysa TTSS (Ysps) have only been detected in vitro when cells are cultured at 26 degrees C in a high-NaCl medium. However, the exact role of the Ysa TTSS is unclear. Thus, investigations into the regulation of this system may help elucidate the role of the Ysps during the life cycle of Y. enterocolitica. Here we present evidence that the AraC-like regulator YsaE acts together with the chaperone SycB to regulate transcription of the sycByspBCDA operon, a phenomenon similar to that seen in the closely related Salmonella SPI-1 and Shigella flexneri Mxi-Spa-Ipa TTSSs. Deletion of either sycB or ysaE results in a twofold reduction in the activity of a sycB-lacZ fusion compared to the wild type. In a reconstituted Escherichia coli system, transcription of sycB was activated sixfold only when both YsaE and SycB were present, demonstrating that they are necessary for activation. ysrR and ysrS are located near the ysa genes and encode a putative two-component regulatory system. Mutations in either gene indicated that both YsrR and YsrS were required for secretion of Ysps. In addition, transcription from sycB-lacZ and ysaE-lacZ fusions was decreased 6.5- and 25-fold, respectively, in the ysrS mutant compared to the wild type. Furthermore, in the absence of NaCl, the activity of ysaE-lacZ was reduced 25-fold in the wild-type and DeltaysrS strains, indicating that YsrS is probably required for the salt-dependent expression of the ysa locus. These results suggest that the putative two-component system YsrRS may be a key element in the regulatory cascade for the Ysa TTSS.