gebhart/patrepeval huggingface dataset:
Sputter deposition of YBa2Cu3O7−x films on Si at 500 °C with conducting metallic oxide as a buffer layer (1990)

Superconducting YBa2Cu3O7−x thin films were deposited on Si substrates at 500 °C by rf magnetron sputtering from a stoichiometric oxide target. Metallic oxide RuO2, sputtered by reactive dc magnetron, was used as a buffer layer to nucleate the superconducting film and minimize the reactions between Si and superconductor. The as-deposited thin films, without further post high-temperature annealing, were completely superconductive at 79 K. Very smooth surface morphology was demonstrated by scanning electron microscopy. X-ray diffraction data indicated that the films had a randomly oriented polycrystalline structure. Auger electron spectroscopy did not reveal interdiffusion of elements in the three layers.
Active Combustion Control Using a Fluidic Oscillator for Asymmetric Fuel Flow Modulation (2009)

Fluidic oscillators are of special interest for fuel-based active control schemes featuring high frequency fuel flow modulation, as they are much more durable then conventional valves due to the absence of fast moving parts. In this work the performance of a fluidic oscillator in an active combustion control scheme is demonstrated. The oscillation frequency was controlled by varying the inlet mass flow of the oscillator. High speed camera recordings and hot wire measurements were performed to investigate the fluidics' oscillation characteristics. The oscillator was then incorporated into a bluff body burner, where it modulated parts of the fuel flow blended with nitrogen. Pressure and heat release fluctuations in the combustor were recorded and images of the flame were taken. At stable combustion the spectra of the heat release signals showed a clear peak corresponding to the fluidics' oscillation frequency, thus validating the ability of the oscillator to influence the combustion process. When operating ...
CDR3 Spectratyping Analysis of the TCR Repertoire in Myasthenia Gravis (2006)

Because myasthenia gravis (MG) is an autoimmune disease mediated by Abs specific for the acetylcholine receptor, helper T cells play a role in Ab production. In this study, we have performed large-scale cross-sectional and longitudinal TCR studies by CDR3 spectratyping using PBL and thymus tissues from MG patients. We found that there was no preferential usage of any particular TCR beta-chains that was identical among MG patients. However, the longitudinal study clearly demonstrated that one or more TCR Vbeta expansions persisted frequently in MG patients. Importantly, persistent TCR expansions correlated with clinical severity and high anti-acetylcholine receptor Ab titer. Finally, examinations of T cells expressing CXCR5, i.e., follicular B-helper T cells, revealed that spectratype expansions in MG patients were detected mainly in the CD4+ CXCR5+ T cell populations, whereas CD8+ T cells were the major source of clonal expansion in healthy subjects. These findings suggest that persistent clonal expansions of T cells in MG patients are associated with the development and maintenance of MG. Close examination of pathogenic T cells in MG provides useful information to elucidate the pathogenesis and to estimate the disease status.
A lupus anti-DNA autoantibody mediates autocatalytic, targeted delivery of nanoparticles to tumors (2016)

Strategies to target nanoparticles to tumors that rely on surface modification with ligands that bind molecules overexpressed on cancer cells or the tumor neovasculature suffer from a major limitation: with delivery of toxic agents the amount of molecules available for targeting decreases with time; consequently, the efficiency of nanoparticle delivery is reduced. To overcome this limitation, here we propose an autocatalytic tumor-targeting mechanism based on targeting extracellular DNA (exDNA). exDNA is enriched in the tumor microenviroment and increases with treatment with cytotoxic agents, such as doxorubicin (DOX), due to release of DNA by dying tumor cells. We tested this approach using poly(lactic-co-glycolic acid) (PLGA) nanoparticles surface-conjugated with fragments of 3E10 (3E10EN), a lupus anti-DNA autoantibody. We demonstrated that 3E10EN-conjugated nanoparticles bound to DNA and preferentially localized to tumors in vivo. The efficiency of tumor localization of 3E10EN-conjugated, DOX-loaded nanoparticles increased with time and subsequent treatments, demonstrating an autocatalytic effect. 3E10EN-conjugated DOX-loaded nanoparticles exhibited a significant anti-tumor effect that was superior to all controls. This work demonstrates the promise of autocatalytic drug delivery mechanisms and establishes proof of concept for a new anti-DNA autoantibody-based approach for enhancing delivery of nanoparticles to tumors.
Abstract C246: nab®-paclitaxel targets tumor stroma and results, combined with gemcitabine, in high efficacy against pancreatic cancer models (2009)

Abstract nab®-paclitaxel (Abraxane ™, Abraxis Bioscience, Los Angeles, CA) is an albumin-bound nano particle formulation of paclitaxel that may target SPARC (secreted protein acid-rich in cysteine). In a phase I/II study in patients with advanced pancreatic cancer, the combination of nab®-paclitaxel and gemcitabine resulted in impressive clinical activity with an objective response rate of 40%, 10.3 months median survival and 78 % of patients having a decrement of CA199 &amp;gt; 50 % (Von Hoff et al, ASCO 2009). To gain insight into the mechanisms underlying the high efficacy of this combination, we treated 11 freshly generated pancreatic cancer xenografts from the Johns Hopkins PancXenoBank collection. nab®-paclitaxel, in combination with gemcitabine, doubled the response rate of either agent alone and resulted in a 57% response rate, mimicking the results obtained in the clinical trial. Tumors treated with nab®-paclitaxel showed a marked decrement in the otherwise abundant fibrotic stroma characteristic of pancreatic cancer and present in control and gemcitabine only treated animals. The elimination of the stroma resulted in marked cellular tumors and increased tumor vascularization and cell-vessel proximity. Consequently, the intratumoral concentration of gemcitabine increased by 3.7 fold in mice treated with nabR-paclitaxel and gemcitabine versus those receiving gemcitabine alone. We conclude that nab®-paclitaxel effectively eliminates pancreatic cancer stroma resulting in increased delivery of gemcitabine and high antitumor effects. Targeting tumor stroma appears a promising strategy in pancreatic cancer. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C246.
Parenteral Fish Oil as Monotherapy Prevents Essential Fatty Acid Deficiency in Parenteral Nutrition–dependent Patients (2010)

: When dosed appropriately, fish oil-based lipid emulsions contain sufficient amounts of essential fatty acids to prevent EFAD and sustain growth in patients who are completely dependent on PN.
Dendritic Cells Transduced with an Adenovirus Vector Encoding Epstein-Barr Virus Latent Membrane Protein 2B: a New Modality for Vaccination (1999)

Epstein-Barr virus (EBV) is a herpesvirus commonly associated with several malignancies, particularly in immunocompromised hosts. As a strategy for stimulating immunity against EBV for the treatment of EBV-associated tumors, we have genetically engineered dendritic cells (DC) to express EBV antigens, such as latent membrane protein 2B (LMP2B), using recombinant adenovirus vectors. CD8(+) T lymphocytes from HLA-A2.1(+), EBV-seropositive healthy donors were cultured with autologous DC infected with recombinant adenovirus vector AdEGFP, encoding an enhanced green fluorescent protein (EGFP), or AdLMP2B at a multiplicity of infection of 250. After 48 h, >95% of the DC were positive for EGFP expression as assessed by fluorescence-activated cell sorting analysis, indicating efficient gene transfer. AdLMP2-transduced DC were used to stimulate CD8(+) T cells. Responder CD8(+) T cells were tested for gamma interferon (IFN-gamma) release by enzyme-linked spot (ELISPOT) assay and cytotoxic activity. Prior to in vitro stimulation, the frequencies of T-cells directed against two HLA-A2-presented LMP2 peptides (LMP2 329-337 and LMP2 426-434) were very low as assessed by IFN-gamma spot formation (T-cell frequency, <0.003%). IFN-gamma ELISPOT assays performed at day 14 showed a significant (2-log) increase of the day 0 frequency of T cells reactive against the LMP2 329-337 peptide, from 0.003 to 0.3 (P < 0.001). Moreover, specific cytolytic activity was observed against the autologous EBV B-lymphoblastoid cell lines after 21 days of stimulation of T-cell responders with AdLMP2-transduced DC (P < 0.01). In summary, autologous mature DC genetically modified with an adenovirus encoding EBV antigens stimulate the generation of EBV-specific CD8(+) effector T cells in vitro, supporting the potential application of EBV-based adenovirus vector vaccination for the immunotherapy of the EBV-associated malignancies.
Digital Light-Directed Synthesis. A Microarray Platform That Permits Rapid Reaction Optimization on a Combinatorial Basis (2000)

Solution reactions using photogenerated reagents (Gao, X.; Yu, P.; LeProust, E.; Sonigo, L.; Pellois, J. P.; Zhang, H. J. Am. Chem. Soc. 1998, 120, 12698) are a potentially powerful means for combinatorial parallel synthesis of addressable molecular microarrays. In this report, we demonstrate that this chemistry permits combinatorial screening of reaction conditions on a microarray platform. Using this method of optimization and our reaction apparatus, efficient photogenerated acids and reaction conditions suitable for removal of the acid labile protection group on 5'-O of nucleotides are identified in a short period of time. The chemistry platform demonstrated opens new avenues for rapid, simultaneous investigation of multiple reactions using different reagents and reaction parameters directly on a solid support (e.g., a glass plate). The combinatorial screening method described may be extended to include general organic reactions employing photogenerated and conventional reagents as well as a microarray reaction device. This should be especially valuable for efficient synthesis of addressable organic compound libraries.
Characterization of a tumor necrosis factor alpha (TNF-alpha) inhibitor: evidence of immunological cross-reactivity with the TNF receptor. (1990)

Previous studies have shown that urine of febrile patients contains a tumor necrosis factor alpha inhibiting activity (TNF-alpha Inh) when tested in a cytotoxicity assay using the tumor necrosis factor alpha (TNF-alpha)-susceptible cell line L929. In the present study, we investigated the relationship between the TNF-alpha Inh and a potential soluble form of the receptor, as the former has been shown to block TNF-alpha activities by binding to the ligand. We demonstrate that human TNF-alpha is affected to a greater extent than is murine TNF-alpha. This species specificity of the inhibitor correlates with the binding studies of TNF receptor interactions already reported. We raised a polyclonal antibody to TNF-alpha Inh that neutralizes its activity and does not recognize TNF-alpha. Solubilized cross-linked 125I-labeled TNF-alpha receptor complex could be immunoprecipitated by using either anti-TNF-alpha or anti-TNF-alpha Inh antibody, suggesting immunological cross-reactivity between the receptor and the inhibitor. By using fluorescein isothiocyanate-coupled TNF-alpha, it was possible to visualize by fluorescence-activated cell sorter analysis the TNF-alpha receptor on phytohemagglutinin/interleukin 2-activated T cells. A similar increase of immunofluorescence intensity of the activated T cells was observed by using anti-TNF-alpha Inh antibody revealed with a fluorescein isothiocyanate-coupled goat anti-rabbit IgG1 conjugate, suggesting that the TNF-alpha Inh is also expressed as a membrane protein. Taken together, our results suggest that the TNF-alpha Inh originally described might be a soluble form of the TNF receptor itself.
Hydroxycarbamide alters erythroid gene expression in children with sickle cell anaemia (2012)

Sickle cell anaemia (SCA) is a severe debilitating haematological disorder associated with a high degree of morbidity and mortality. The level of fetal haemoglobin (HbF) is well-recognized as a critical laboratory parameter: lower HbF is associated with a higher risk of vaso-occlusive complications, organ damage, and early death. Hydroxycarbamide treatment can induce HbF, improve laboratory parameters, and ameliorate clinical complications of SCA but its mechanisms of action remain incompletely defined and the HbF response is highly variable. To identify pathways of hydroxycarbamide activity, we performed microarray expression analyses of early reticulocyte RNA obtained from children with SCA enrolled in the HydroxyUrea Study of Long-term Effects (NCT00305175) and examined the effects of hydroxycarbamide exposure in vivo. Hydroxycarbamide affected a large number of erythroid genes, with significant decreases in the expression of genes involved in translation, ribosome assembly and chromosome organization, presumably reflecting the daily cytotoxic pulses of hydroxycarbamide. Hydroxycarbamide also affected expression of numerous genes associated with HbF including BCL11A, a key regulator of baseline HbF levels. Together, these data indicate that hydroxycarbamide treatment for SCA leads to substantial changes in erythroid gene expression, including BCL11A and other potential signalling pathways associated with HbF induction.
Attitudes Concerning Extended Teacher Education Programs: A Rural/Urban Comparison. (1989)

Stimulated by changes proposed by the Holmes and Carnegie reports, this study was conducted to assessthe attitudes of rural and urban teacher educators and graduate students toward extended teacher education programs. Data were collected from faculty and graduate students affiliated with 44 teacher preparation institutions in the south-central region of the United States. Lessthan one-fourth of the entire sample expressed consistent support for extending the programs. Lessthan a third of the sample favored the expansion of the liberal arts component of teacher education programs. Within the framework of extended programs, over half of the sample favored increasing professional coursework and more than seventy percent favored increased field experiences. Less than 10%thought that their own teacher education had been inadequate, again indicating support for existing four-year programs. Rural/urban comparisons showed that faculty and students in urban areas were generally more supportive of the types of changes recommended in the Holmes and Carnegie reports. Implications for rural education, rural teacher education, and possible outcomes in a time of projected teacher shortages are explored.
Quantitative mechanics of endothelial phagocytosis of silicon microparticles (2009)

Endothelia, once thought of as a barrier to the delivery of therapeutics, is now a major target for tissue-specific drug delivery. Tissue- and disease-specific molecular presentations on endothelial cells provide targets for anchoring or internalizing delivery vectors. Porous silicon delivery vectors are phagocytosed by vascular endothelial cells. The rapidity and efficiency of silicon microparticle uptake lead us to delineate the kinetics of internalization. To discriminate between surface-attached and -internalized microparticles, we developed a double fluorescent/FRET flow cytometric approach. The approach relies on quenching of antibody-conjugated fluorescein isothiocyanate covalently attached to the microparticle surface by attachment of a secondary antibody labeled with an acceptor fluorophore, phycoerythrin. The resulting half-time for microparticle internalization was 15.7 min, with confirmation provided by live confocal imaging as well as transmission electron microscopy.
The second ‘CHiME’ speech separation and recognition challenge: Datasets, tasks and baselines (2013)

Distant-microphone automatic speech recognition (ASR) re-mains a challenging goal in everyday environments involving multiple background sources and reverberation. This paper reports on the results of the 2nd ‘CHiME ’ Challenge, an ini-tiative designed to analyse and evaluate the performance of ASR systems in a real-world domestic environment. We dis-cuss the rationale for the challenge and provide a summary of the datasets, tasks and baseline systems. The paper overviews the systems that were entered for the two challenge tracks: small-vocabulary with moving talker and medium-vocabulary with stationary talker. We present a summary of the chal-lenge findings including novel results produced by challenge system combination. Possible directions for future challenges are discussed. Index Terms — Noise-robust ASR, ‘CHiME ’ Challenge 1.
The maximum weight perfect matching problem for complete weighted graphs is in PC (2002)

There are efficient sequential algorithms that use linear programming (LP) for computing maximum weight matchings. Finding a deterministic parallel algorithm for computing maximum weight matchings in complete graphs has been an open problem for some time. Since LP is known to be P-complete, then, by the parallel computation thesis, it is unlikely that there exists an NC algorithm that uses LP to solve the maximum weight matching problem. The authors present an LP-based parallel algorithm for maximum weight matching in a complete weighted graph. The algorithm is designed for the EREW PRAM model of parallel computation, and runs in O(n/sup 3//p+n/sup 2/logn) time for p<or=n, where p is the number of processors and n is the number of vertices in the graph. This algorithm provides an optimal speedup with respect to the O(n/sup 3/) sequential LP-based solution of Gabow (1974) or Lawler (1976), for p<or=n/log n. This is the first deterministic optimal speedup parallel algorithm designed for the maximum weight matching problem on complete graphs.<<ETX>>
Mitogenic CD28 Signals Require the Exchange Factor Vav1 to Enhance TCR Signaling at the SLP-76-Vav-Itk Signalosome (2007)

Almost all physiological T cell responses require costimulation-engagement of the clonotypic TCR with MHC/Ag and CD28 by its ligands CD80/86. Whether CD28 provides signals that are qualitatively unique or quantitatively amplify TCR signaling is poorly understood. In this study, we use superagonistic CD28 Abs, which induce T cell proliferation without TCR coligation, to determine how CD28 contributes to mitogenic responses. We show that mitogenic CD28 signals require but do not activate the proximal TCR components TCRzeta and Zap-70 kinase. In cell lines lacking proximal TCR signaling, an early defect in the CD28 pathway is in phosphorylation of the adaptor molecule SLP-76, which we show is essential for recruitment of the exchange factor Vav leading to Ca(2+) flux and IL-2 production. Point mutations in CD28 that result in diminished Vav phosphorylation also result in defective Ca(2+) flux, IL-2 production, and Tec-kinase phosphorylation. Using Vav1-deficient mice, we further demonstrate the importance of Vav1 for efficient proliferation, IL-2 production, and Ca(2+) flux. Our results indicate that CD28 signals feed into the TCR signaling pathway at the level of the SLP-76 signalosome.
Antisense therapy of cancer. (1995)

Binding sites for the NF-kappa B transcription factor complex, composed of two subunits, p50 (NFKB1) and p65 (rel A), are present in many cell adhesion molecules, cytokines, and growth-factor receptors. Antisense techniques were used to establish the role of NF-kappa B in cell growth. Surprisingly, antisense phosphorothioate oligomers to the rel A subunit of NF-kappa B caused a pronounced block of cellular adhesion. Since adhesion plays an important role in diseases including cancer and inflammation, this chance observation was extended to various in vitro and in vivo models. Our results establish the in vivo efficacy of phosphorothioate oligomers.
The design and proof of concept for a CD8+ T cell‐based vaccine inducing cross‐subtype protection against influenza A virus (2012)

In this study, we examined the reactivity of human peripheral blood mononuclear cells to a panel of influenza A virus (IAV) CD8(+) T-cell epitopes that are recognised by the major human leukocyte antigen (HLA) groups represented in the human population. We examined the level of recognition in a sample of the human population and the potential coverage that could be achieved if these were incorporated into a T-cell epitope-based vaccine. We then designed a candidate influenza vaccine that incorporated three of the examined HLA-A2-restricted influenza epitopes into Pam2Cys-based lipopeptides. These lipopeptides do not require the addition of an adjuvant and can be delivered directly to the respiratory mucosa enabling the generation of local memory cell populations that are crucial for clearance of influenza. Intranasal administration of a mixture of three lipopeptides to HLA-A2 transgenic HHD mice elicited multiple CD8(+) T-cell specificities in the spleen and lung that closely mimicked the response generated following natural infection with influenza. These CD8(+) T cells were associated with viral reduction following H3N1 influenza virus challenge for as long as 3 months after lipopeptide administration. In addition, lipopeptides containing IAV-targeting epitopes conferred substantial benefit against death following infection with a virulent H1N1 strain. Because CD8(+) T cell epitopes are often derived from highly conserved regions of influenza viruses, such vaccines need not be reformulated annually and unlike current antibody-inducing vaccines could provide cross-protective immunity against newly emerging pandemic viruses.
Rapid quantitation of methylation differences at specific sites using methylation-sensitive single nucleotide primer extension (Ms-SNuPE) (1997)

We have developed a rapid quantitative method (Ms-SNuPE) for assessing methylation differences at specific CpG sites based on bisulfite treatment of DNA followed by single nucleotide primer extension. Genomic DNA was first reacted with sodium bisulfite to convert unmethylated cytosine to uracil while leaving 5-methylcytosine unchanged. Amplification of the desired target sequence was then performed using PCR primers specific for bisulfite-converted DNA and the resulting product isolated and used as a template for methylation analysis at the CpG site(s) of interest. This methylation-sensitive technique has several advantages over existing methods used for detection of methylation changes because small amounts of DNA can be analyzed including microdissected pathology sections and it avoids utilization of restriction enzymes for determining the methylation status at CpG sites.