gebhart/patrepeval huggingface dataset:
Analysis of the T cell response to tumor and viral peptide antigens by an IFNγ‐ELISPOT assay (1997)

We have established a sensitive ELISPOT assay measuring interferon γ (IFN γ) release on a single-cell basis to detect influenza peptide-specific CD8+ T cells in uncultured peripheral blood mononuclear cells (PBMC). Using this method, we studied the T cell response to HLA-A1 and HLA-A2.1 binding peptide epitopes derived from the MAGE-1 and MAGE-3 proteins, from the melanoma-associated antigens tyrosinase, Melan-A/MART-1 and gp100, and from influenza proteins in stage IV melanoma patients and healthy controls. In 18 of 24 HLA-A2-positive donors (75%), but only in 9 of 25 HLA-A2-positive melanoma patients (36%) T cells reactive with the influenza matrix peptide were demonstrated (p = 0.007). T cells responding to one or several of the melanoma-associated peptides were detected in 5 of 25 HLA-A2-positive patients with metastatic melanoma. Four of these 5 patients had been treated with interleukin-2- and IFNα-containing therapy. Two of the 24 healthy donors had T cells reactive with the MART-1 27-35 peptide. No reactivity with the HLA-A1-binding peptides from MAGE-1 or MAGE-3 was detected in any of the HLA-A1-positive healthy controls or melanoma patients. These results show that the IFNγ-ELISPOT assay is suitable to determine quantitatively T cells reactive with melanoma-associated and influenza peptide epitopes in uncultured PBMC. The failure to detect T cells responding to influenza in many melanoma patients with progressive disease may indicate an impairment of their T cell function. Int. J. Cancer 71: 932-936, 1997. © 1997 Wiley-Liss Inc.
Substrate sequence effects on "hammerhead" RNA catalytic efficiency. (1990)

The "hammerhead" RNA self-cleaving domain can be assembled from two RNA molecules: a large (approximately 34 nucleotide) ribozyme RNA containing most of the catalytically essential nucleotides and a small (approximately 13 nucleotide) substrate RNA containing the cleavage site. Four such hammerheads that contained identical catalytic core sequences but differed in the base composition of the helices that are involved in substrate binding had been reported to vary in cleavage rates by more than 70-fold under similar reaction conditions. Steady-state kinetic analyses reveal that kcat values are nearly the same for these hammerheads but Km values vary nearly 60-fold. The substrates for reactions having high Km values form aggregates that are virtually nonreactive. These observations demonstrate that the secondary structure of substrate RNA can be a major determinant of hammerhead catalytic efficiency.
Exploring the past and the future of protein evolution with ancestral sequence reconstruction: the ‘retro’ approach to protein engineering (2016)

A central goal in molecular evolution is to understand the ways in which genes and proteins evolve in response to changing environments. In the absence of intact DNA from fossils, ancestral sequence reconstruction (ASR) can be used to infer the evolutionary precursors of extant proteins. To date, ancestral proteins belonging to eubacteria, archaea, yeast and vertebrates have been inferred that have been hypothesized to date from between several million to over 3 billion years ago. ASR has yielded insights into the early history of life on Earth and the evolution of proteins and macromolecular complexes. Recently, however, ASR has developed from a tool for testing hypotheses about protein evolution to a useful means for designing novel proteins. The strength of this approach lies in the ability to infer ancestral sequences encoding proteins that have desirable properties compared with contemporary forms, particularly thermostability and broad substrate range, making them good starting points for laboratory evolution. Developments in technologies for DNA sequencing and synthesis and computational phylogenetic analysis have led to an escalation in the number of ancient proteins resurrected in the last decade and greatly facilitated the use of ASR in the burgeoning field of synthetic biology. However, the primary challenge of ASR remains in accurately inferring ancestral states, despite the uncertainty arising from evolutionary models, incomplete sequences and limited phylogenetic trees. This review will focus, firstly, on the use of ASR to uncover links between sequence and phenotype and, secondly, on the practical application of ASR in protein engineering.
JavaScript: The Complete Reference (2004)

From the Publisher:
Develop powerful,full-featured Web pages with JavaScript using this comprehensive resource. Including thorough coverage of object models,XML,server-side JavaScript,and embedded objectsplus details on special browser considerations,this guide is an excellent reference no matter what your level of experience. 

The most in-depth guide to JavaScript available Create dynamic and flexible Web pages with JavaScript using this comprehensive resource. Whether you're a new or more experienced developer,you'll find quality coverage of every topic you're looking forfrom fundamentals such as language syntax to advanced topics including interaction with browser plug-ins and the emerging W3C DOM standard. You'll learn to create cross-browser scripts for common tasks including form validation,visual effects,navigation systems and much more. In addition to the comprehensive tutorials that make up each chapter,the appendices contain helpful material that's quickly accessibleincluding object references,a browser compatibility chart,and other key JavaScript syntax charts. For a thorough and authoritative book on the latest version of JavaScript that's geared toward developers at every levelthis is the ideal resource for you. 

Get an overview of JavaScript and Web programming Find out about core features and functionalityincluding variables,functions,and objects Acquire solid language fundamentals,including the effective use of JavaScript's object-oriented features Understand the differences between the standard Document Object Model (DOM) and Browser Object Models (BOM) Manipulate images and layout with JavaScript Addsophisticated navigation systems using DHTML Parse XML with JavaScript and control windows and frames Deal with browser incompatibilities and learn tips for debugging
In vivoelectrical conductivity of hepatic tumours (2003)

Knowledge of electrical tissue conductivity is necessary to determine deposition of electromagnetic energy and can further be used to diagnostically differentiate between normal and neoplastic tissue. We measured 17 rats with a total of 24 tumours of the K12/TRb rat colon cancer cell line. In each animal we measured in vivo hepatic tumour and normal tissue conductivity at seven frequencies from 10 Hz to 1 MHz, at different tumour stages between 6 and 12 weeks after induction. Conductivity of normal liver tissue was 1.26 +/- 0.15 mS cm(-1) at 10 Hz, and 4.61 +/- 0.42 mS cm(-1) at 1 MHz. Conductivity of tumour was 2.69 +/- 0.91 mS cm(-1) at 10 Hz, and 5.23 +/- 0.82 mS cm(-1) at 1 MHz. Conductivity was significantly different between normal and tumour tissue (p < 0.05). We determined the percentage of necrosis and fibrosis at the measurement site. We fitted the conductivity data to the Cole-Cole model. For the tumour data we determined Spearman's correlation coefficients between the Cole-Cole parameters and age, necrosis, fibrosis and tumour volume and found significant correlation between necrosis and the Cole-Cole parameters (p < 0.05). We conclude that necrosis within the tumour and the associated membrane breakdown is likely responsible for the observed change in conductivity.
Analysis of Macrophage Scavenger Receptor (SR-A) Expression in Human Aortic Atherosclerotic Lesions (1999)

The class A scavenger receptors (SR-As) are trimeric, integral membrane glycoproteins that exhibit unusually broad ligand-binding properties. A number of studies have suggested that these receptors may play an important role in host defense and in many macrophage-associated pathological processes, including atherosclerosis and Alzheimer's disease. The study of the expression and function of these receptors in human disease has been hampered by the lack of suitable antibodies recognizing human SR-A. This has generated questions regarding the nature of receptors responsible for scavenger receptor activity detected in a variety of cell types, including monocytes, macrophages, smooth muscle cells, and endothelial cells. To address these questions, we have produced high-titer antisera recognizing human SR-A by using mice deficient for SR-A (SR-A -/-). We show that SR-A -/- mice produce a significantly higher-titer immune response than do wild-type (SR-A +/+) littermates, with antisera of the former having a broad species reactivity and recognizing SR-A from humans, mice, and rabbits. The antisera recognize both type I and II SR-A in a wide range of immunological techniques. Using these antisera we show that the expression of SR-A protein is induced during monocyte to macrophage differentiation and that SR-A mediates 80% of the uptake of acetylated low density lipoprotein by human monocyte-derived macrophages. We also establish that human SR-A is expressed by tissue macrophages in liver and lung and by macrophage-derived foam cells within aortic atherosclerotic lesions, with little detectable expression by smooth muscle cells or aortic endothelium.
Immunohistochemical localization of relaxin in human prostate. (1989)

We identified relaxin in human male prostate by use of an anti-human relaxin analogue polyclonal antibody and the avidin-biotin-immunoperoxidase method. The antibody was obtained by immunizing a rabbit with a synthetic human relaxin analogue which has 95% sequence homology with native human relaxin. Human prostate tissues incubated with the anti-human relaxin analogue exhibited positive immunostaining up to an antibody dilution of 1:3200. Inhibition of immunostaining with this antibody by excess relaxin analogue demonstrated specificity of the antibody. The exact role of relaxin in human male reproductive physiology remains to be fully elucidated.
Continuous iterated density estimation evolutionary algorithms within the IDEA framework (2000)

In this paper, we formalize the notion of performing optimization by iterated density estimation evolutionary algorithms as the IDEA framework. These algorithms build probabilistic models and estimate probability densities based upon a selection of available points. We show how these probabilistic models can be built and used for dierent probability density functions within the IDEA framework. We put the emphasis on techniques for vectors of continuous random variables and thereby introduce new continuous evolutionary optimization algorithms.
Aspirin promotes TFF2 gene activation in human gastric cancer cell lines (2001)

Trefoil factor family (TFF) peptides promote cell migration, heal the mucosa and may suppress tumor growth. In reporter gene assays we show that aspirin (1-12 mM) evokes a six-fold up-regulation of TFF2, but not TFF1 and TFF3 transcription in human gastrointestinal cell lines. 6 h after application up-regulation of endogenous TFF2 mRNA was observed. TFF2 transcription was enhanced by indomethacin and arachidonic acid but repressed by staurosporine, suggesting mediation via protein kinase C. We mapped an aspirin responding element -546 to -758 bp upstream of TFF2. Up-regulation of TFF2 by aspirin may partially explain the chemopreventive potential of low dose aspirin in gastrointestinal carcinogenesis.
A new kind of carbohydrate array, its use for profiling antiglycan antibodies, and the discovery of a novel human cellulose-binding antibody (2003)

In this study, we use a novel glycan array to analyze the glycan-binding antibody repertoire in a pool of affinity-purified IgG collected from a healthy human population. The glycan array used is based on mono- and oligosaccharides covalently linked to the surface via a long linker at their reducing ends. They are thus presented to the medium with a well-defined orientation and are accessible for specific binding by glycan-binding proteins, such as antibodies and lectins. A novel anticellulose antibody was detected that binds specifically to beta4-linked saccharides with a preference for glucopyranose over galactopyranose residues. We also found previously known antiglycan antibodies against mono- and oligosaccharides that are constituents of commonly occurring bacterial polysaccharides. We propose that this array can facilitate high-throughput screening of glycan-binding proteins and the search for biomarkers for personalized medicine.
用多分量地震测量描述裂缝性储层：庆祝 石油物探 创刊30周年 (1992)

科罗拉多矿业学院在落基山脉的三个油田开展了多分量地震测量,其目的是为了对这些油田储集层的天然裂缝引起的各向异性进行三维成像。在锡洛(Silo)油田,一块强横波各向异性(达7％)区域对应于白垩系尼奥布拉雷(Niobrara)上白垩统储层中的张性裂缝带。该强横波各向异性区域与覆盖在下伏盐层溶化边缘上的上白垩统地层披盖相吻合。最新的水平井信息和产量数据都证实了上白垩统地层中的裂缝沿着平行于下伏盐层边缘的北西-南东走向而增加。 在南卡斯珀克雷科(Casper Creek)油田进行的多分量地震测量,查明了以往由井控无法确定的断层和裂缝带。通过断层和裂缝的双向定位,划分出宾夕法尼亚统特斯里普(Tensleep)砂岩储层。对该重油储层蒸汽注入过程的线性流动形式和热异常的观测,也证实了断层和裂缝带的存在。 在塞达希尔(Cedar Hill)煤成甲烷气田,煤层中天然张开裂缝的存在与否决定了产量的急剧变化。最近开展的多分量三维地震测量,指出了煤层中裂缝的地层控制与差异压实作用有关。这项正在进行中的研究项目表明,储层中裂缝网的地球物理测定作为裂缝性储层经济开采的一项主要研究领域是非常重要的。
Media creates positive publicity for traditional therapists (2002)

The media has exerted a powerful influence on women, encouraging them to question the wisdom of taking drugs as prescribed by their doctors. We as herbalists have so much to offer the 600,000 women in Australia who are currently on HRT and need some support while coming off it. We need to let these women know where we are and what we can do for them. (non-author abstract)
Contactless Conductivity Detection for Capillary Electrophoresis (1998)

A contactless capacitively coupled conductivity detector for capillary electrophoresis is introduced. The detector consists of two electrodes which are placed cylindrically around the outer polyimide coating of the fused-silica capillary with a detection gap of 2 mm. The electrodes form a cylindrical capacitor, and the electric conductivity of the solution in the gap between the electrodes is measured. A high audio or low ultrasonic frequency for coupling of the ac voltage is used in order to minimize the influence of reactance of the liquid. For an improved version of the detector, two syringe cannulas are used as the electrodes and the capillary is simply assembled into the tubing. This allows an easy placement of the detector on various positions along the capillary. The limit of detection of inorganic cations and anions is 200 ppb, as determined for sodium and chloride, respectively.
Inter-Instrument Comparison of Bioimpedance Spectroscopic Analysers (2009)

Three commercially available bioimpedance spectroscopy analysers were compared for technical performance and for their design purpose of prediction of body composition. All three analysers were electronically stable, remaining in calibration over a year, and provided highly reproducible (coefficients of variation < 0.5%) and accurate (within 0.5% of component values) measurements of impedances of a test circuit. Whole body impedances in humans were highly correlated between all three instruments although significant biases between instruments were observed, particularly for the measurement of intracellular resistance. However, when the measured impedances, and using instrument-specific resistivity coefficients, were used to predict fat-free mass of the subjects, the difference between instruments was approximately 1.7 kg fat-free mass, a value comparable with that observed for the error associated with reference methods such as multi-compartment models of body composition. It is concluded that, with appropriate regard to standardisation of measurement protocol, all three analysers are suitable for their design purpose of estimating body composition in humans.
RAG-1 and RAG-2, Adjacent Genes That Synergistically Activate V(D)J Recombination (1990)

The vast repertoire of immunoglobulins and T cell receptors is generated, in part, by V(D)J recombination, a series of genomic rearrangements that occur specifically in developing lymphocytes. The recombination activating gene, RAG-1, which is a gene expressed exclusively in maturing lymphoid cells, was previously isolated. RAG-1 inefficiently induced V(D)J recombinase activity when transfected into fibroblasts, but cotransfection with an adjacent gene, RAG-2, has resulted in at least a 1000-fold increase in the frequency of recombination. The 2.1-kilobase RAG-2 complementary DNA encodes a putative protein of 527 amino acids whose sequence is unrelated to that of RAG-1. Like RAG-1, RAG-2 is conserved between species that carry out V(D)J recombination, and its expression pattern correlates precisely with that of V(D)J recombinase activity. In addition to being located just 8 kilobases apart, these convergently transcribed genes are unusual in that most, if not all, of their coding and 3' untranslated sequences are contained in single exons. RAG-1 and RAG-2 might activate the expression of the V(D)J recombinase but, more likely, they directly participate in the recombination reaction.
Structural Basis for Sequence-Specific Recognition of DNA by TAL Effectors (2012)

TAL (transcription activator-like) effectors, secreted by phytopathogenic bacteria, recognize host DNA sequences through a central domain of tandem repeats. Each repeat comprises 33 to 35 conserved amino acids and targets a specific base pair by using two hypervariable residues [known as repeat variable diresidues (RVDs)] at positions 12 and 13. Here, we report the crystal structures of an 11.5-repeat TAL effector in both DNA-free and DNA-bound states. Each TAL repeat comprises two helices connected by a short RVD-containing loop. The 11.5 repeats form a right-handed, superhelical structure that tracks along the sense strand of DNA duplex, with RVDs contacting the major groove. The 12th residue stabilizes the RVD loop, whereas the 13th residue makes a base-specific contact. Understanding DNA recognition by TAL effectors may facilitate rational design of DNA-binding proteins with biotechnological applications.
Propeptin, a New Inhibitor of Prolyl Endopeptidase Produced by Microbispora. I. Fermentation, Isolation and Biological Properties. (1997)

Propeptin, an inhibitor of the prolyl endopeptidase isolated from the mycelium of Microbispora sp. SNA-115, is an atypical cyclic peptide antibiotic. It was purified by column chromatographies on silica gel and Sephadex LH-20 and high performance liquid chromatography using an ODS column. Propeptin has the molecular formula of C113H142N26O27 and consists of nineteen amino acids. Propeptin inhibited prolyl endopeptidase of the genus Flavobacterium competitively when Z-Gly-Pro-pNA was used as a substrate. The inhibitor constant (Ki) was 0.70 microM.
Analysis of Arabidopsis mutants deficient in flavonoid biosynthesis (1995)

Eleven loci that play a role in the synthesis of flavonoids in Arabidopsis are described. Mutations at these loci, collectively named transparent testa (tt), disrupt the synthesis of brown pigments in the seed coat (testa). Several of these loci (tt3, tt4, tt5 and ttg) are also required for the accumulation of purple anthocyanins in leaves and stems and one locus (ttg) plays additional roles in trichome and root hair development. Specific functions were previously assigned to tt1-7 and ttg. Here, the results of additional genetic, biochemical and molecular analyses of these mutants are described. Genetic map positions were determined for tt8, tt9 and tt10. Thin-layer chromatography identified tissue- and locus-specific differences in the flavonols and anthocyanidins synthesized by mutant and wild-type plants. It was found that UV light reveals distinct differences in the floral tissues of tt3, tt4, tt5, tt6 and ttg, even though these tissues are indistinguishable under visible light. Evidence was also uncovered that tt8 and ttg specifically affect dihydroflavonol reductase gene expression. A summary of these and previously published results are incorporated into an overview of the genetics of flavonoid biosynthesis in Arabidopsis.
Participation of Presenilin 2 in Apoptosis: Enhanced Basal Activity Conferred by an Alzheimer Mutation (1996)

Overexpression of the familial Alzheimer's disease gene Presenilin 2 (PS2) in nerve growth factor-differentiated PC12 cells increased apoptosis induced by trophic factor withdrawal or beta-amyloid. Transfection of antisense PS2 conferred protection against apoptosis induced by trophic withdrawal in nerve growth factor-differentiated or amyloid precursor protein-expressing PC12 cells. The apoptotic cell death induced by PS2 protein was sensitive to pertussis toxin, suggesting that heterotrimeric GTP-binding proteins are involved. A PS2 mutation associated with familial Alzheimer's disease was found to generate a molecule with enhanced basal apoptotic activity. This gain of function might accelerate the process of neurodegeneration that occurs in Alzheimer's disease, leading to the earlier age of onset characteristic of familial Alzheimer's disease.
An early-biomarker algorithm predicts lethal graft-versus-host disease and survival (2017)

<b>BACKGROUND.</b> No laboratory test can predict the risk of nonrelapse mortality (NRM) or severe graft-versus-host disease (GVHD) after hematopoietic cellular transplantation (HCT) prior to the onset of GVHD symptoms. <b>METHODS.</b> Patient blood samples on day 7 after HCT were obtained from a multicenter set of 1,287 patients, and 620 samples were assigned to a training set. We measured the concentrations of 4 GVHD biomarkers (ST2, REG3α, TNFR1, and IL-2Rα) and used them to model 6-month NRM using rigorous cross-validation strategies to identify the best algorithm that defined 2 distinct risk groups. We then applied the final algorithm in an independent test set (<i>n</i> = 309) and validation set (<i>n</i> = 358). <b>RESULTS.</b> A 2-biomarker model using ST2 and REG3α concentrations identified patients with a cumulative incidence of 6-month NRM of 28% in the high-risk group and 7% in the low-risk group (<i>P</i> < 0.001). The algorithm performed equally well in the test set (33% vs. 7%, <i>P</i> < 0.001) and the multicenter validation set (26% vs. 10%, <i>P</i> < 0.001). Sixteen percent, 17%, and 20% of patients were at high risk in the training, test, and validation sets, respectively. GVHD-related mortality was greater in high-risk patients (18% vs. 4%, <i>P</i> < 0.001), as was severe gastrointestinal GVHD (17% vs. 8%, <i>P</i> < 0.001). The same algorithm can be successfully adapted to define 3 distinct risk groups at GVHD onset. <b>CONCLUSION.</b> A biomarker algorithm based on a blood sample taken 7 days after HCT can consistently identify a group of patients at high risk for lethal GVHD and NRM. <b>FUNDING.</b> The National Cancer Institute, American Cancer Society, and the Doris Duke Charitable Foundation.
Controlled Trial and Dose-Finding Study of Ivermectin for Treatment of Onchocerciasis (1987)

Ivermectin, given as a single oral dose, has shown considerable promise as a new treatment for onchocerciasis. We assessed the safety and efficacy of ivermectin and tried to determine the optimal dose. Two hundred Liberians received 100, 150, or 200 micrograms of ivermectin/kg or placebo and were followed up for 12 months. Therapy was associated with only minimal systemic and ocular side effects. A 200-micrograms/kg dose was associated with greater systemic reaction than was a 100-micrograms/kg dose. Each treatment group had significant reduction in skin microfilaria counts by day 3 and a decrease of approximately 95% at three months. At three months the proportion of persons with no microfilariae in a specimen of skin was significantly less in the 100-micrograms/kg group than in the 150-micrograms/kg or 200-micrograms/kg groups. At 12 months, the level of microfilariae in skin was still reduced approximately 80%. Significant reduction in ocular involvement was seen in all groups. These results confirm that single-dose ivermectin is effective and well-tolerated and suggest that 150 micrograms of ivermectin/kg may be the optimal dose for initial therapy.