gebhart/patrepeval huggingface dataset:
Integrin-linked Kinase (ILK) Binding to Paxillin LD1 Motif Regulates ILK Localization to Focal Adhesions (2001)

Paxillin is a focal adhesion adapter protein involved in integrin signaling. Paxillin LD motifs bind several focal adhesion proteins including the focal adhesion kinase, vinculin, the Arf-GTPase-activating protein paxillin-kinase linker, and the newly identified actin-binding protein actopaxin. Microsequencing of peptides derived from a 50-kDa paxillin LD1 motif-binding protein revealed 100% identity with integrin-linked kinase (ILK)-1, a serine/threonine kinase that has been implicated in integrin, growth factor, and Wnt signaling pathways. Cloning of ILK from rat smooth muscle cells generated a cDNA that exhibited 99.6% identity at the amino acid level with human ILK-1. A monoclonal antibody raised against a region of the carboxyl terminus of ILK, which is identical in rat and human ILK-1 protein, recognized a 50-kDa protein in all cultured cells and tissues examined. Binding experiments showed that ILK binds directly to the paxillin LD1 motif in vitro. Co-immunoprecipitation from fibroblasts confirmed that the association between paxillin and ILK occurs in vivo in both adherent cells and cells in suspension. Immunofluorescence microscopy of fibroblasts demonstrated that endogenous ILK as well as transfected green fluorescent protein-ILK co-localizes with paxillin in focal adhesions. Analysis of the deduced amino acid sequence of ILK identified a paxillin-binding subdomain in the carboxyl terminus of ILK. In contrast to wild-type ILK, paxillin-binding subdomain mutants of ILK were unable to bind to the paxillin LD1 motif in vitro and failed to localize to focal adhesions. Thus, paxillin binding is necessary for efficient focal adhesion targeting of ILK and may therefore impact the role of ILK in integrin-mediated signal transduction events.
Insulin activates the kinase activity of the Raf-1 proto-oncogene by increasing its serine phosphorylation. (1990)

Insulin was found to stimulate the serine/threonine kinase activity of the proto-oncogene product Raf-1. This stimulation was observed in HeLa, NIH 3T3, and Chinese hamster ovary cells, all overexpressing the human insulin receptor. In the HeLa cells, 100 pM insulin gave a significant increase in Raf-1 kinase activity, and 100 nM insulin caused a maximal 2-5-fold increase in activity. The increase in activity was detected after 2 min of insulin treatment and peaked after 5 min. In addition to stimulating Raf-1 kinase activity, insulin caused a shift in the electrophoretic mobility of the Raf-1 protein and an increase in the amount of serine phosphorylation of Raf-1. Moreover, a serine/threonine-specific phosphatase, phosphatase 1, but not two tyrosine-specific phosphatases, was found to deactivate the insulin-activated Raf-1 kinase activity. These findings indicate that insulin activates the serine/threonine kinase activity of the Raf-1 proto-oncogene by increasing its content of phosphoserine.
Network Anomaly Detection: Methods, Systems and Tools (2013)

Network anomaly detection is an important and dynamic research area. Many network intrusion detection methods and systems (NIDS) have been proposed in the literature. In this paper, we provide a structured and comprehensive overview of various facets of network anomaly detection so that a researcher can become quickly familiar with every aspect of network anomaly detection. We present attacks normally encountered by network intrusion detection systems. We categorize existing network anomaly detection methods and systems based on the underlying computational techniques used. Within this framework, we briefly describe and compare a large number of network anomaly detection methods and systems. In addition, we also discuss tools that can be used by network defenders and datasets that researchers in network anomaly detection can use. We also highlight research directions in network anomaly detection.
Increasing Serum Half-life and Extending Cholesterol Lowering in Vivo by Engineering Antibody with pH-sensitive Binding to PCSK9 (2012)

Target-mediated clearance and high antigen load can hamper the efficacy and dosage of many antibodies. We show for the first time that the mouse, cynomolgus, and human cross-reactive, antagonistic anti-proprotein convertase substilisin kexin type 9 (PCSK9) antibodies J10 and the affinity-matured and humanized J16 exhibit target-mediated clearance, resulting in dose-dependent pharmacokinetic profiles. These antibodies prevent the degradation of low density lipoprotein receptor, thus lowering serum levels of LDL-cholesterol and potently reducing serum cholesterol in mice, and selectively reduce LDL-cholesterol in cynomolgus monkeys. In order to increase the pharmacokinetic and efficacy of this promising therapeutic for hypercholesterolemia, we engineered pH-sensitive binding to mouse, cynomolgus, and human PCSK9 into J16, resulting in J17. This antibody shows prolonged half-life and increased duration of cholesterol lowering in two species in vivo by binding to endogenous PCSK9 in mice and cynomolgus monkeys, respectively. The proposed mechanism of this pH-sensitive antibody is that it binds with high affinity to PCSK9 in the plasma at pH 7.4, whereas the antibody-antigen complex dissociates at the endosomal pH of 5.5-6.0 in order to escape from target-mediated degradation. Additionally, this enables the antibody to bind to another PCSK9 and therefore increase the antigen-binding cycles. Furthermore, we show that this effect is dependent on the neonatal Fc receptor, which rescues the dissociated antibody in the endosome from degradation. Engineered pH-sensitive antibodies may enable less frequent or lower dosing of antibodies hampered by target-mediated clearance and high antigen load.
Homogeneity of Asthma Genome Scan Results (2001)

Three different samples of families with asthmatic patients, the German data set and the CSGA data set subdivided into Caucasian and African American groups, were analyzed using the maximum lod score statistic. Although different scores were obtained in each sample, the Wald's likelihood homogeneity test did not reveal any significant genetic heterogeneity. This may be due to the very large variance of the model-free linkage statistics.
Pathogenesis and immune mechanisms of chronic inflammatory bowel diseases. (1997)

The inflammatory bowel diseases (IBDs) are characterized by intestinal inflammation of unknown etiology. Two distinct disorders, Crohn's disease and ulcerative colitis, have been identified. Three theories of IBD etiology are currently under consideration: 1) reaction to a persistent intestinal infection, 2) existence of a defective mucosal barrier to luminal antigens, and 3) a dysregulated host immune response to ubiquitous antigens. In each of these theories, either pathogenic or resident luminal bacteria constantly stimulate the mucosal and systemic immune systems to perpetuate the inflammatory cascade. Chronicity of inflammation results from an interaction of the persistent stimulus of microbial antigens with genetically determined host susceptibility factors that determine the individual's immune response or mucosal barrier function. The pathogenesis of IBD involves a series of steps, beginning with the breach of the intestinal mucosal barrier by infectious agents or toxins. The defective barrier exposes lamina propria immune cells to the continual presence of resident luminal bacteria, bacterial products, or dietary antigens, which perpetuates the inflammatory cascade. Many immunoregulatory abnormalities are noted in IBD, including the ratio of proinflammatory to immunosuppressive cytokines, selective activation of T(H) lymphocyte subsets, and abnormalities in epithelial antigen presentation. When activated during the initial inflammatory process, macrophages and T lymphocytes secrete a host of cytokines, which recruit other inflammatory cell types, thereby continuing the process. Tissue injury is the net result of the soluble products of the activated inflammatory cells. Knowledge of the pathogenesis in IBD suggests that the ultimate goals of therapy should be to block the proinflammatory mediators toward the proximal, rather than the distal, end of the cascade, to decrease the constant antigenic drive of luminal bacteria, and to correct the dysregulated immune response.
Bolivia - Participatory Rural Investment Project - environmental impact analysis (1997)

This report is an environmental assessment reviewing the environmental screening procedures of the Bolivia's Participatory Rural Investment Project (FDC), which builds and improves municipal infrastructure; and strengthens municipal administration and management with community participation. This impact analysis details how the screening procedures are being applied, evaluates the project's environmental impacts, and suggests mitigation measures. Measures include segregation and disposal of waste materials at dump sites; construction of retaining walls; resort to reforestation to control erosion; replacement of the natural vegetal cover and adjacent forest; construction of longitudinal drainage crossing primary and secondary roads as well as hillsides; control of wastewater, runoff, and garbage from the worksite to avoid damage to river beds and aquatic life; prevention of oil and fuel leaks from machinery and vehicles; synchronized usage of machinery and vehicles in order to reduce air emissions; relocation of displaced human settlements; management of liquid flows to water bodies; and control of solid wastes, liquid flows, and gaseous emissions during the project's operation.
Transfer of thin Au films to polydimethylsiloxane (PDMS) with reliable bonding using (3-mercaptopropyl)trimethoxysilane (MPTMS) as a molecular adhesive (2013)

This paper describes the transfer of thin gold films deposited on rigid silicon substrates to polydimethylsiloxane (PDMS) with reliable and strong bonding. Modification of the Au surfaces with (3-mercaptopropyl)trimethoxysilane (MPTMS) as a molecular adhesive was carried out to promote adhesion between Au and PDMS. The degree of bonding with respect to the concentration of MPTMS, treatment time and methods of deposition was investigated by a simple adhesion test using two different adhesive tapes. The effect of hydrolysis of MPTMS is discussed based on the bonding mechanism of MPTMS to the PDMS prepolymer. Also, the adsorption of MPTMS on Au deposited by different methods is discussed. The results indicate that liquid deposition of MPTMS provides the strongest adhesion between Au and PDMS among the different deposition methods and the different linker molecules. Based on these studies, the Au patterns with linewidth of less 2 µm were successfully transferred to PDMS with reliable and strong bonding in a full 3 inch wafer scale, using a dry peel-off process.
Prediction of response of mutated alpha-galactosidase A to a pharmacological chaperone (2008)

Mapping the missense mutations to the structure of alpha-Gal A identified several factors that may influence response. Mutations in regions that are not in alpha-helix or beta-sheets, neither involved in disulfide bonds nor with an identified functional or structural role were more likely to respond. Predictability is, however, not precise and testing of each mutation for response to pharmacological chaperone therapy is necessary for Fabry disease and related lysosomal storage disorders.
Synthesis and SAR Studies of Novel Triazolopyrimidine Derivatives as Potent, Orally Active Angiotensin II Receptor Antagonists (1994)

The synthesis and pharmacological activity of new nonpeptide angiotensin II (AII) receptor antagonists are presented. These [1,2,4]-triazolo[1,5-c]pyrimidine and 1,2,4-triazolo[4,3-c]pyrimidine derivatives represent a new class of bicyclic antagonists that produced a potent, oral antihypertensive activity in the renal artery-ligated rat model. In vitro, they displayed a high affinity for rat adrenal AII receptors and were found to be specific for the AT1 receptor subtype. A SAR study has shown the importance of the 8-[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl for oral activity and the critical role of alkyl substituents at 5- and 7-positions. No significant differences were found between the [1,5-c] and [4,3-c]series. UP 269-6 (5-methyl-7-n-propyl-8-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl ]- [1,2,4]-triazolo[1,5-c]pyrimidin-2(3H)-one, derivative 29) was selected as the lead compound. It was shown to be a highly potent antihypertensive derivative (decrease in mean arterial pressure of 39.6 +/- 7.2 mmHg at 1 mg/kg po in renal artery-ligated rat) with a long duration of action which displayed a high affinity for adrenal AII receptors with a marked selectivity for the AT1 receptor subtype (Ki AT1 = 24 nM; Ki AT2 = 79,200 nM). This compound is currently undergoing extensive pharmacological and clinical development.
Oligonucleotide Sequences Required for Natural Killer Cell Activation (1992)

Based on the previous finding that certain 30-mer single-stranded oligodeoxyribonucleotides (oligonucleotides) having particular 6-mer palindromic sequences could induce interferon-alpha and -gamma, and enhance natural killer activity, the present study was carried out to clarify the entire relationship between the activity and the sequence of 30-mer oligonucleotides. The results indicated that the activity depended critically on the presence of particular palindromic sequences including the 5'-CG-3' motif(s). The size and the number of palindromes as well as the extra-palindromic sequences also influenced the activity. An oligonucleotide with a 10-mer palindrome and extra-palindromic oligoguanylate sequences showed the strongest activity among the oligonucleotides tested.
Formation of carbon nanocapsules with SiC nanoparticles prepared by polymer pyrolysis (1998)

Carbon nanocapsules with SiC nanoparticles were produced by thermal decomposition of polyvinyl alcohol with SiC clusters at 500 °C in Ar gas atmosphere. High-resolution electron microscopy also showed the formation of carbon hollow structures such as nanoparticles, polyhedra, and clusters. The present work indicates that the pyrolysis of polymer materials with clusters is a useful fabrication method for the mass-production of carbon nanocapsules at low temperatures compared to the ordinary arc discharge method.
Catalytic Reduction of Aromatic Nitro Compounds by Coinage Metal Nanoparticles (2001)

ADVERTISEMENT RETURN TO ISSUEPREVNoteCatalytic Reduction of Aromatic Nitro Compounds by Coinage Metal NanoparticlesNarayan Pradhan, Anjali Pal, and Tarasankar PalView Author Information Department of Civil Engineering, Department of Chemistry, Indian Institute of Technology, Kharagpur 721 302, India Cite this: Langmuir 2001, 17, 5, 1800–1802Publication Date (Web):February 2, 2001Publication History Received20 June 2000Revised30 November 2000Published online2 February 2001Published inissue 1 March 2001https://pubs.acs.org/doi/10.1021/la000862dhttps://doi.org/10.1021/la000862dbrief-reportACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views5349Altmetric-Citations520LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Metal nanoparticles,Metals,Nanoparticles,Redox reactions,Silver Get e-Alerts
A note on the power of Fisher's least significant difference procedure (2006)

Fisher's least significant difference (LSD) procedure is a two-step testing procedure for pairwise comparisons of several treatment groups. In the first step of the procedure, a global test is performed for the null hypothesis that the expected means of all treatment groups under study are equal. If this global null hypothesis can be rejected at the pre-specified level of significance, then in the second step of the procedure, one is permitted in principle to perform all pairwise comparisons at the same level of significance (although in practice, not all of them may be of primary interest). Fisher's LSD procedure is known to preserve the experimentwise type I error rate at the nominal level of significance, if (and only if) the number of treatment groups is three. The procedure may therefore be applied to phase III clinical trials comparing two doses of an active treatment against placebo in the confirmatory sense (while in this case, no confirmatory comparison has to be performed between the two active treatment groups). The power properties of this approach are examined in the present paper. It is shown that the power of the first step global test--and therefore the power of the overall procedure--may be relevantly lower than the power of the pairwise comparison between the more-favourable active dose group and placebo. Achieving a certain overall power for this comparison with Fisher's LSD procedure--irrespective of the effect size at the less-favourable dose group--may require slightly larger treatment groups than sizing the study with respect to the simple Bonferroni alpha adjustment. Therefore if Fisher's LSD procedure is used to avoid an alpha adjustment for phase III clinical trials, the potential loss of power due to the first-step global test should be considered at the planning stage.
Answer Finding Guided by Question Semantic Constraints (2002)

As part of the task of automated question answering from a large collection of text documents, the reduction of the search space to a smaller set of document passages that are actually searched for answers constitutes a difficult but rewarding research issue. We propose a set of precision-enhancing filters for passage retrieval based on semantic constraints detected in the submitted questions. The approach improves the performance of the underlying question answering system in terms of both answer accuracy and time performance.
Thermal Decomposition of NaNO3 and KNO3 * (1981)

Mixtures of sodium nitrate and potassium nitrate have potential applications as high temperature heat transfer fluids and thermal storage media in solar thermal electric power plants. High temperature salt stability is an important characteristic for these applications; therefore the decomposition of the nitrates was studied to elucidate the mechanisms by which nitrates decompose. To this end, the decomposition of sodium nitrate and potassium nitrate was studied isothermally in vacuum at temperatures ranging from 620–750 K using simultaneous thermogravimetric analysis and mass spectrometry. Decomposition in vacuum was observed as low as 620 K. Nitrogen, nitric oxide, and oxygen were observed to be products of nitrate decomposition.
Capsicum (2003)

Capsicum has been used since ancient times not only as a traditional medicine but also as a natural colorant. The medicinal properties of capsicum make it popular in both ayurvedic and homeopathic treatments. In Capsicum: The Genus Capsicum, experts provide information on all aspects of this plant, including its ethnobotany, chemistry, pharmacology, toxicology, cultivation, tissue culture and commercial uses. Capsaicin, the pungent, principle component of capsicum, was used in the recent discovery of a hot receptor, or pain sensor, in the human heart. This and a variety of other therapeutic properties have earned capsicum much industrial importance. This book details the therapeutic applications of capsaicin together with its action on different biological systems.
Human pluripotent stem cells (2010)

Item consists of a digitized copy of an audio recording of a Craig Laronge University of Wisconsin Lecture delivered at the Vancouver Institute by James Thomson on January 23, 2010. Original audio recording available in the University Archives (UBC AT 3614).
IL-17 is essential for host defense against cutaneous Staphylococcus aureus infection in mice (2010)

Staphylococcus aureus is the most common cause of skin and soft tissue infections, and rapidly emerging antibiotic-resistant strains are creating a serious public health concern. If immune-based therapies are to be an alternative to antibiotics, greater understanding is needed of the protective immune response against S. aureus infection in the skin. Although neutrophil recruitment is required for immunity against S. aureus, a role for T cells has been suggested. Here, we used a mouse model of S. aureus cutaneous infection to investigate the contribution of T cells to host defense. We found that mice deficient in gammadelta but not alphabeta T cells had substantially larger skin lesions with higher bacterial counts and impaired neutrophil recruitment compared with WT mice. This neutrophil recruitment was dependent upon epidermal Vgamma5+ gammadelta T cell production of IL-17, but not IL-21 and IL-22. Furthermore, IL-17 induction required IL-1, TLR2, and IL-23 and was critical for host defense, since IL-17R-deficient mice had a phenotype similar to that of gammadelta T cell-deficient mice. Importantly, gammadelta T cell-deficient mice inoculated with S. aureus and treated with a single dose of recombinant IL-17 had lesion sizes and bacterial counts resembling those of WT mice, demonstrating that IL-17 could restore the impaired immunity in these mice. Our study defines what we believe to be a novel role for IL-17-producing epidermal gammadelta T cells in innate immunity against S. aureus cutaneous infection.
The first-in-class alkylating deacetylase inhibitor molecule tinostamustine shows antitumor effects and is synergistic with radiotherapy in preclinical models of glioblastoma (2018)

Our data suggest that tinostamustine deserves further investigation in patients with glioblastoma.
Supporting collaboration in notecards (1986)

This paper describes a project underway to investigate computer support for collaboration. In particular, we focus on experience with and extensions to NoteCards, a hypertext-based idea structuring system. The forms of collaboration discussed include draft-passing, simultaneous sharing and online presentations. The requirement that mutual intelligibility be maintained between collaborators leads to the need for support of annotative and procedural as well as substantive activities.