gebhart/patrepeval huggingface dataset:
Crystal Structures of Branched-Chain Amino Acid Aminotransferase Complexed with Glutamate and Glutarate:  True Reaction Intermediate and Double Substrate Recognition of the Enzyme, (2003)

Branched-chain amino acid aminotransferase (BCAT), which has pyridoxal 5'-phosphate as a cofactor, is a key enzyme in the biosynthetic pathway of hydrophobic amino acids (leucine, isoleucine, and valine). The enzyme reversibly catalyzes the transfer of the amino group of a hydrophobic amino acid to 2-oxoglutarate to form a 2-oxo acid and glutamate. Therefore, the active site of BCAT should have a mechanism to enable recognition of an acidic amino acid as well as a hydrophobic amino acid (double substrate recognition). The three-dimensional structures of Escherichia coli BCAT (eBCAT) in complex with the acidic substrate (glutamate) and the acidic substrate analogue (glutarate) have been determined by X-ray diffraction at 1.82 and 2.15 A resolution, respectively. The enzyme is a homo hexamer, with the polypeptide chain of the subunit folded into small and large domains, and an interdomain loop. The eBCAT in complex with the natural substrate, glutamate, was assigned as a ketimine as the most probable form based upon absorption spectra of the crystal complex and the shape of the residual electron density corresponding to the cofactor-glutamate bond structure. Upon binding of an acidic substrate, the interdomain loop approaches the substrate to shield it from the solvent region, as observed in the complex with a hydrophobic substrate. Both the acidic and the hydrophobic side chains of the substrates are bound to almost the same position in the pocket of the enzyme and are identical in structure. The inner side of the pocket is mostly hydrophobic to accommodate the hydrophobic side chain but has four sites to coordinate with the gamma-carboxylate of glutamate. The mechanism for the double substrate recognition observed in eBCAT is in contrast to those in aromatic amino acid and histidinol-phosphate aminotransferases. In an aromatic amino acid aminotransferase, the acidic side chain is located at the same position as that for the aromatic side chain because of large-scale rearrangements of the hydrogen bond network. In the histidinol-phosphate aminotransferase, the acidic and basic side chains are located at different sites and interact with different residues of the disordered loop.
EyeQ: practical network performance isolation at the edge (2013)

The datacenter network is shared among untrusted tenants in a public cloud, and hundreds of services in a private cloud. Today we lack fine-grained control over network bandwidth partitioning across tenants. In this paper we present EyeQ, a simple and practical system that provides tenants with bandwidth guarantees as if their endpoints were connected to a dedicated switch. To realize this goal, EyeQ leverages the high bisection bandwidth in a datacenter fabric and enforces admission control on traffic, regardless of the tenant transport protocol. We show that this pushes bandwidth contention to the network's edge, enabling EyeQ to support end-to-end minimum bandwidth guarantees to tenant end-points in a simple and scalable manner at the servers. EyeQ requires no changes to applications and is deployable with support from the network available today. We evaluate EyeQ with an efficient software implementation at 10Gb/s speeds using unmodified applications and adversarial traffic patterns. Our evaluation demonstrates EyeQ's promise of predictable network performance isolation. For instance, even with an adversarial tenant with bursty UDP traffic, EyeQ is able to maintain the 99.9th percentile latency for a collocated memcached application close to that of a dedicated deployment.
Phase II trial of single-agent sorafenib in patients with advanced non-small cell lung carcinoma (2006)

7002 Background: Sorafenib, an oral multi-kinase inhibitor, targets the Raf/MEK/ERK pathway at the level of Raf kinase and receptor tyrosine kinases, and has shown efficacy against several tumor types in phase I/II trials. Non-small-cell lung cancer (NSCLC) is associated with mutations in k-ras, upstream of Raf/MEK/ERK. Methods: This multi-center, uncontrolled, phase II trial evaluated efficacy (every 8 weeks using RECIST) and safety of sorafenib (400 mg bid, continuous) in patients with relapsed or refractory advanced NSCLC. Plasma for proteomic biomarker analysis (ELISA [n=44]; mass-spectrometry [n=43]) was taken at screening, Day 21 of Cycle 1, and Day 1 of Cycle 3. Results: Fifty-two of 54 patients enrolled received sorafenib. Most (49/52) patients who received sorafenib had stage IV NSCLC. Thirty patients (59%) out of 51 evaluable for efficacy had SD. Although there were no confirmed PRs, tumor shrinkage was observed in 15 (29%) patients (four had ≥30% shrinkage). Patients with SD had a median progression-free survival (PFS) of 23.7 weeks, while all evaluable patients (n=51) had a median PFS of 11.9 weeks and median overall survival of 29.3 weeks. The most frequent drug-related adverse events observed in 52 patients were diarrhea (21 [40%] patients), hand-foot skin reaction (HFS; 19 [37%]), fatigue (14 [27%]), and nausea (13 [25%]). Frequent drug-related adverse events ≥ grade 3 included HFS (n=5 [10%]) and hypertension (n=2 [4%]). Three patients discontinued due to adverse events (HFS, elevated lipase, and myocardial infarction). There were nine deaths within 30 days of discontinuation of sorafenib (n=5 PD; n=2 cardiopulmonary arrest; n=1 hemoptysis; and n=1 unknown cause). The levels of five proteins measured by ELISA, either at screening or change over treatment duration, correlated significantly with time to progression (TTP) or maximum tumor shrinkage. Levels of five additional proteins, identified by mass-spectrometry, also correlated with TTP. Conclusions: Identified biomarkers may help assess efficacy of sorafenib in NSCLC patients. Sorafenib 400 mg bid is generally well tolerated and shows promising efficacy in patients with advanced, progressive NSCLC, with approximately 60% of pts achieving disease stabilization. [Table: see text]
Preparation of tumor-specific boron compounds. 1. In vitro studies using boron-labeled antibodies and elemental boron as neutron targets (1972)

In vitro studies using boron-labeled antibodies and elemental boron as neutron target in therapy for tumors and cancer
Automation in genotyping of single nucleotide polymorphisms (2001)

Automation for genotyping of single nucleotide polymorphisms (SNPs) can be split into the automation of the sample preparation and the automation of the analysis technology. SNP genotyping methods are reviewed and solutions for their automation discussed. A panacea for SNP genotyping does not exist. Different scientific questions require adapted solutions. The choice of a technology for SNP genotyping depends on whether few different SNPs are to be genotyped in many individuals, or many different SNPs are to be genotyped in few individuals. The requirements of throughput and the ease of establishing an SNP genotyping operation are important, as well as the degree of integration. The potential and state-of-the-art of different solutions are outlined.
Shape adaptive padding for MPEG-4 (2000)

In MPEG-4, the boundary blocks of reference video objects are padded by replicating the boundary samples towards the exterior. This scheme does not make use of the trend of pixel value variation often present near object boundaries in padding the exterior pixels of the reference video object. Rather, it results in a break of this trend at the video object boundary, resulting in higher prediction errors for those pixel locations that are within the shape of the current block, but are outside that of the predicted block. In this paper, we propose a novel shape distortion adaptive hybrid padding technique to minimise prediction errors and improve compression efficiency. We show that this technique results in boundary block coding gains of up to 9% as compared to that of the MPEG-4 scheme.
[Relationship between IL-1 beta and TNF-alpha in subretinal fluids of rhegmatogenous retinal detachment with PVR]. (1998)

The concentrations of IL-1 beta and TNF-alpha in subretinal fluids from 49 patients with rhegmatogenous retinal detachment with proliferative vitreoretinopathy(PVR) were measured by Enzyme-linked immunosorbent assay (ELISA). The results showed that all subretinal fluids contained IL-1 beta, their concentrations were positive correlation with severity of PVR (r = 0.677) and no correlation with age, sex, holes, ranges and times of retinal detachment, TNF-alpha was detected in 18/49 subretinal fluids including 2 patients with PVR-1 beta and 16 patients with PVR-C and the above cases. It suggested that IL-1 beta and TNF-a are involved in the pathogenesis of PVR.
Neuromodulation targets intrinsic cardiac neurons to attenuate neuronally mediated atrial arrhythmias (2011)

Our objective was to determine whether atrial fibrillation (AF) results from excessive activation of intrinsic cardiac neurons (ICNs) and, if so, whether select subpopulations of neurons therein represent therapeutic targets for suppression of this arrhythmogenic potential. Trains of five electrical stimuli (0.3-1.2 mA, 1 ms) were delivered during the atrial refractory period to mediastinal nerves (MSN) on the superior vena cava to evoke AF. Neuroanatomical studies were performed by injecting the neuronal tracer DiI into MSN sites that induced AF. Functional studies involved recording of neuronal activity in situ from the right atrial ganglionated plexus (RAGP) in response to MSN stimulation (MSNS) prior to and following neuromodulation involving either preemptive spinal cord stimulation (SCS; T(1)-T(3), 50 Hz, 200-ms duration) or ganglionic blockade (hexamethonium, 5 mg/kg). The tetramethylindocarbocyanine perchlorate (DiI) neuronal tracer labeled a subset (13.2%) of RAGP neurons, which also colocalized with cholinergic or adrenergic markers. A subset of DiI-labeled RAGP neurons were noncholinergic/nonadrenergic. MSNS evoked an ∼4-fold increase in RAGP neuronal activity from baseline, which SCS reduced by 43%. Hexamethonium blocked MSNS-evoked increases in neuronal activity. MSNS evoked AF in 78% of right-sided MSN sites, which SCS reduced to 33% and hexamethonium reduced to 7%. MSNS-induced bradycardia was maintained with SCS but was mitigated by hexamethonium. We conclude that MSNS activates subpopulations of intrinsic cardiac neurons, thereby resulting in the formation of atrial arrhythmias leading to atrial fibrillation. Stabilization of ICN local circuit neurons by SCS or the local circuit and autonomic efferent neurons with hexamethonium reduces the arrhythmogenic potential.
Antibiotic Resistance Among Gram-Negative Bacilli in US Intensive Care Units (2003)

This study documents the increasing incidence of ciprofloxacin resistance among gram-negative bacilli that has occurred coincident with increased use of fluoroquinolones. More judicious use of fluoroquinolones will be necessary to limit this downward trend.
CD8 T Cell Responses to Infectious Pathogens (2003)

CD8 T cells respond to viral infections but also participate in defense against bacterial and protozoal infections. In the last few years, as new methods to accurately quantify and characterize pathogen-specific CD8 T cells have become available, our understanding of in vivo T cell responses has increased dramatically. Pathogen-specific T cells, once thought to be quite rare following infection, are now known to be present at very high frequencies, particularly in peripheral, nonlymphoid tissues. With the ability to visualize in vivo CD8 T cell responses has come the recognition that T cell expansion is programmed and, to a great extent, independent of antigen concentrations. Comparison of CD8 T cell responses to different pathogens also highlights the intricate relationship between microbially induced innate inflammatory responses and the kinetics, magnitude, and character of long-term T cell responses. This review describes recent progress in some of the major murine models of CD8 T cell-mediated immunity to viral, bacterial, and protozoal infection.
Nanoscale semiconducting silicon as a nutritional food additive (2007)

Very high surface area silicon powders can be realized by high energy milling or electrochemical etching techniques. Such nanoscale silicon structures, whilst biodegradable in the human gastrointestinal tract, are shown to be remarkably stable in most foodstuffs and beverages. The potential for using silicon to improve the shelf life and bioavailability of specific nutrients in functional foods is highlighted. Published drug delivery data implies that the nanoentrapment of hydrophobic nutrients will significantly improve their dissolution kinetics, through a combined effect of nanostructuring and solid state modification. Nutrients loaded to date include vitamins, fish oils, lycopene and coenzyme Q10. In addition, there is growing published evidence that optimized release of orthosilicic acid, the biodegradation product of semiconducting silicon in the gut, offers beneficial effects with regard bone health. The utility of nanoscale silicon in the nutritional field shows early promise and is worthy of much further study.
Intratumor depletion of CD4+ cells unmasks tumor immunogenicity leading to the rejection of late-stage tumors (2005)

Tumor environment can be critical for preventing the immunological destruction of antigenic tumors. We have observed a selective accumulation of CD4(+)CD25(+) T cells inside tumors. In a murine fibrosarcoma L(d)-expressing Ag104, these cells made up the majority of tumor-infiltrating lymphocytes at the late stage of tumor progression, and their depletion during the effector phase, rather than priming phase, successfully enhanced antitumor immunity. We show here that CD4(+)CD25(+) T cells suppressed the proliferation and interferon-gamma production of CD8(+) T cells in vivo at the local tumor site. Blockade of the effects of IL-10 and TGF-beta partially reversed the suppression imposed by the CD4(+) cells. Furthermore, local depletion of CD4(+) cells inside the tumor resulted in a change of cytokine milieu and led to the eradication of well-established highly aggressive tumors and the development of long-term antitumor memory. Therefore, CD4(+)CD25(+) T cells maintained an environment in the tumor that concealed the immunogenicity of tumor cells to permit progressive growth of antigenic tumors. Our study illustrates that the suppression of antitumor immunity by regulatory T cells occurs predominantly at the tumor site, and that local reversal of suppression, even at a late stage of tumor development, can be an effective treatment for well-established cancers.
A Definitive Role of RhoC in Metastasis of Orthotopic Lung Cancer in Mice (2004)

RhoC plays a crucial role in metastasis of lung cancer. RhoC does not affect tumor growth but enhances the metastatic nature of lung cancer by not only stimulating cell motility but also up-regulating certain MMPs. Attenuation of RhoC activity may be a potential target in the development of a novel strategy for treating metastasis of lung cancer.
Emergence of a Scientific and Commercial Research and Development Infrastructure for Human Gene Therapy (2005)

A research and clinical subfield known as "human gene therapy" has grown rapidly since 1990, when the first human trials were approved in the United States. Using quantitative data, this paper describes and analyzes the research and commercial infrastructure, including academic centers, publications, intellectual property, and biotechnology firms, that has developed around the goal of discovering clinical applications for the modification and transport of DNA to somatic cells. Despite setbacks and few documented successes, the subfield of human gene therapy continues to serve as an influential clinical paradigm for the treatment of inherited and noninherited diseases.
A set of ordered cosmids and a detailed genetic and physical map for the 8 Mb Streptomyces coelicolor A3(2) chromosome (1996)

A Supercos-1 library carrying chromosomal DNA of a plasmid-free derivative of Streptomyces coelicolor A3(2) was organized into an ordered encyclopaedia of overlapping clones by hybridization. The minimum set of overlapping clones representing the entire chromosome (with three short gaps) consists of 319 cosmids. The average insert size is 37.5 kb and the set of clones therefore divides the chromosome into 637 alternating unique and overlapping segments which have an average length of approx. 12.5 kb. More than 170 genes, gene clusters and other genetic markers were mapped to their specific segment by hybridization to the encyclopaedia. Genes could be cloned by direct transformation and complementation of S. coelicolor mutants with cosmids isolated from Escherichia coli, selecting for insertion into the chromosome by homologous recombination. As in other streptomycetes, the ends of the chromosome have long terminal inverted repeats.
Improving Lambda Red Genome Engineering in Escherichia coli via Rational Removal of Endogenous Nucleases (2012)

Lambda Red recombineering is a powerful technique for making targeted genetic changes in bacteria. However, many applications are limited by the frequency of recombination. Previous studies have suggested that endogenous nucleases may hinder recombination by degrading the exogenous DNA used for recombineering. In this work, we identify ExoVII as a nuclease which degrades the ends of single-stranded DNA (ssDNA) oligonucleotides and double-stranded DNA (dsDNA) cassettes. Removing this nuclease improves both recombination frequency and the inheritance of mutations at the 3' ends of ssDNA and dsDNA. Extending this approach, we show that removing a set of five exonucleases (RecJ, ExoI, ExoVII, ExoX, and Lambda Exo) substantially improves the performance of co-selection multiplex automatable genome engineering (CoS-MAGE). In a given round of CoS-MAGE with ten ssDNA oligonucleotides, the five nuclease knockout strain has on average 46% more alleles converted per clone, 200% more clones with five or more allele conversions, and 35% fewer clones without any allele conversions. Finally, we use these nuclease knockout strains to investigate and clarify the effects of oligonucleotide phosphorothioation on recombination frequency. The results described in this work provide further mechanistic insight into recombineering, and substantially improve recombineering performance.
Differential chemokine response of human monocytes to yeast and hyphal forms of Candida albicans and its relation to the beta-1,6 glucan of the fungal cell wall. (2000)

Hyphae formation from yeast cells is a virulence trait enabling the human opportunistic pathogen Candida albicans to invade host tissues. Hyphal cells proved to be much less efficient than yeast cells in stimulating production of macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, interleukin-8 (IL-8), and particularly, monocyte chemotactic protein-1 (MCP-1) by human monocyte. This different stimulation did not depend on the monocyte inability to ingest the hyphae nor did it imply hyphal resistance to the extracellular killing by the monocytes. Purified hyphal and yeast cell walls reproduced the differences shown by the intact cells, and chemical-enzymatic dissection of cell wall components suggested that cell wall beta-1,6 rather than beta-1,3 glucan was the main chemokine inducer. Coherently, immunofluorescence studies with an anti beta-1,6 glucan serum showed that the surface expression of this polysaccharide was much lower on hyphae than on yeast cells. By minimizing chemokine induction, the formation of hyphal filaments might facilitate C. albicans escaping from host immunity.
Fabrication and charging characteristics of MOS capacitor structure with metal nanocrystals embedded in gate oxide (2007)

Metal–oxide–semiconductor capacitor structure with metal nanocrystals embedded in the gate oxide for the application of nonvolatile memory (NVM) is fabricated. Optimal process parameters are investigated and Au nanocrystals are adopted in this paper. High-frequency capacitance versus voltage (C–V) and conductance versus voltage (G–V) measurements demonstrate the memory effect of the structure which is shown to originate from the confined states of metal nanocrystals. Capacitance versus time (C–t) measurement under a constant gate bias is executed to evaluate the retention performance and an exponential decaying trend is observed and discussed. It is found that with respect to semiconductor counterparts, Au nanocrystals can provide enhanced retention performance, which confirms the high capacity of Au nanocrystals for NVM applications.
Phosphonium-Containing ABA Triblock Copolymers: Controlled Free Radical Polymerization of Phosphonium Ionic Liquids (2011)

Phosphonium ion-containing acrylate triblock (ABA) copolymers were synthesized using nitroxide mediated radical polymerization. The polymerization of styrenic phosphonium-containing ionic liquid monomers using a difunctional alkoxyamine initiator, DEPN2, afforded an ABA triblock copolymer with an n-butyl acrylate soft center block (DP ∼ 400) and symmetric phosphonium-containing external reinforcing blocks (DP < 30). Two phosphonium monomers with different alkyl substituent lengths enabled an investigation of the effects of ionic aggregation of phosphonium cations on the physical properties of ABA block copolymer ionomers. Subsequently, the thermomechanical properties and morphologies of these materials were compared to a noncharged triblock copolymer analogue with neutral polystyrene external blocks. Shortening the alkyl substituents on the phosphonium cation enhanced the hydrophilicity of tributyl-4-vinylbenzyl phosphonium chloride (BPCl) relative to trioctyl-4-vinylbenzyl phosphonium chloride (OPCl). In both cases, phosphonium cations promoted microphase-separation and thermoplastic elastomer performance for the OPCl- and BPCl-containing triblock copolymers compared to a less well-defined, microphase segregated morphology for the styrene analogue. Dynamic mechanical analysis (DMA) of phosphonium-containing triblock copolymers exhibited well-defined rubbery plateau regions, whereas the plateau was shortened for the nonionic analogue. The solid state morphologies of the block copolymers were studied using small-angle X-ray scattering (SAXS) and transmission electron microscopy (TEM), and both techniques revealed phase separation at the nanoscale. DMA studies indicated that phosphonium aggregation governed flow activation energies.
Cell-Based Therapy for Myocardial Ischemia and Infarction: Pathophysiological Mechanisms (2007)

Cell-based cardiac repair has emerged as an attractive approach to preventing or reversing heart failure resulting from myocyte dysfunction-e.g., due to infarction-and to enhancing the development of collaterals in patients with symptoms of myocardial ischemia. These two problems involve both overlapping and differing mechanisms, and these differences must be considered in cell-based therapies. In terms of myocardial dysfunction due to infarction, only committed cardiomyocytes have been shown to form new myocardium that is electrically coupled with the host heart. Despite this, multiple cell populations appear to improve function of the infarcted heart, including many that are clearly nonmyogenic. In terms of myocardial ischemia, although cell-based strategies improve ischemia in animal models, clinical trials to date have not shown robustly beneficial results. We review the evidence for potential mechanisms underlying the benefits of cell transplantation in the heart and discuss the clinical contexts in which they may be relevant.