gebhart/patrepeval huggingface dataset:
EphB ligand, ephrinB2, suppresses the VEGF‐ and angiopoietin‐1‐induced Ras/mitogen‐activated protein kinase pathway in venous endothelial cells (2002)

Interaction between ephrinB2 and EphB4 in endothelial cells at the arterial-venous capillary interface is critical for proper embryonic capillary morphogenesis. However, the intracellular downstream signaling of ephrinB2-EphB in vascular endothelial cells is unknown. This study examined the effect of ephrinB2-induced activation of EphB kinases on vascular endothelial growth factor (VEGF)- and angiopoietin-1 (Ang1)-induced Ras/mitogen-activated protein kinase (MAPK) signaling cascades in human umbilical vein endothelial cells (HUVECs). Reverse transcriptase-polymer chain reaction results showed that HUVECs expressed three kinds of EphB kinases known to bind to ephrinB2: EphB2, EphB3, and EphB4. EphrinB2 not only increased the phosphorylation of EphB2 and EphB4 in a time-dependent manner but also increased recruitment of p120-Ras-GTPase-activating protein (p120-RasGAP) to EphB2 and EphB4. Accordingly, ephrinB2 inhibited VEGF- and Ang1-induced Ras-MAPK activities, whereas ephrinB2 did not alter VEGF-induced Flk phosphorylation or Ang1-induced Tie2 phosphorylation. Furthermore, ephrinB2 suppressed VEGF- and Ang1-induced proliferation and/or migration, which are mediated mainly through Ras/MAPK signaling cascades. From these results, we propose that ephrinB2-EphB, signaling through Ras/MAPK cascade, may be critical for proper morphogenesis of capillary endothelium through the arrest of endothelial cell proliferation and migration at the arterial-venous interface.
Multilocus Sequence Typing ofStreptococcus pyogenesand the Relationships betweenemmType and Clone (2001)

Multilocus sequence typing (MLST) is a tool that can be used to study the molecular epidemiology and population genetic structure of microorganisms. A MLST scheme was developed for Streptococcus pyogenes and the nucleotide sequences of internal fragments of seven selected housekeeping loci were obtained for 212 isolates. A total of 100 unique combinations of housekeeping alleles (allelic profiles) were identified. The MLST scheme was highly concordant with several other typing methods. The emm type, corresponding to a locus that is subject to host immune selection, was determined for each isolate; of the >150 distinct emm types identified to date, 78 are represented in this report. For a given emm type, the majority of isolates shared five or more of the seven housekeeping alleles. Stable associations between emm type and MLST were documented by comparing isolates obtained decades apart and/or from different continents. For the 33 emm types for which more than one isolate was examined, only five emm types were present on widely divergent backgrounds, differing at four or more of the housekeeping loci. The findings indicate that the majority of emm types examined define clones or clonal complexes. In addition, an MLST database is made accessible to investigators who seek to characterize other isolates of this species via the internet (http://www.mlst.net).
A simple and general parameterization quantifying performance in fading channels (2003)

We quantify the performance of wireless transmissions over random fading channels at high signal-to-noise ratio (SNR). The performance criteria we consider are average probability of:error and outage probability. We show that as functions of the average SNR, they can both be characterized by two parameters: the diversity and coding gains. They both exhibit identical diversity orders, but their coding gains in decibels differ by a constant. The diversity and coding gains are found to depend on the behavior of-the random SNR's probability density function only at the origin, or equivalently, on the decaying order of the corresponding moment generating function (i.e., how fast the moment generating function goes to zero as its argument goes to infinity). Diversity and coding gains for diversity combining systems are expressed in terms of the diversity branches' individual diversity and coding gains, where the branches can come from any diversity technique such as space, time, frequency, or, multipath. The proposed analysis offers a simple and unifying approach to evaluating the performance of uncoded and (possibly space-time) coded transmissions over fading channels, and the method applies to almost all digital modulation schemes, including M-ary phaseshift keying, quadrature amplitude modulation, and frequency-shift keying with coherent or noncoherent detection.
Streptavidin-Polyvinylamine Conjugates Labeled with a Europium Chelate: Applications in Immunoassay, Immunohistochemistry, and Microarrays (2000)

The new detection reagent may find important applications in biotechnology.
Molecular Dissection of Human Interleukin-31-mediated Signal Transduction through Site-directed Mutagenesis (2009)

Interleukin (IL)-31 is a recently described cytokine, preferentially produced by T helper 2 lymphocytes and associated with skin diseases, such as atopic dermatitis. IL-31 is a member of the four alpha-helix bundle cytokine family and is related to the IL-6 subgroup. Its heterodimeric membrane receptor is composed of the gp130-like receptor (GPL) subunit associated to the oncostatin M receptor subunit. We identified critical amino acids implicated in the ligand receptor interaction by computational analysis combined with site-directed mutagenesis. Six IL-31 residues selected for their putative involvement in cytokine receptor contact sites were alanine-substituted, and the corresponding proteins were expressed in mammalian and bacterial systems. Biochemical, membrane binding, cell signaling, and cell proliferation analyses showed that mutation E44A, E106A, or H110A abolished IL-31 binding to GPL and the subsequent signaling events. A second ligand receptor-binding site involved Lys(134), with alanine substitution leading to a protein that still binds GPL, but is unable to recruit the second receptor subunit and the subsequent signaling pathways. The results indicate that IL-31 recognizes its receptor complex through two different binding sites, and we propose a three-dimensional model for IL-31.
Pilot symbol assisted BPSK on Rayleigh fading channels with diversity: performance analysis and parameter optimization (1998)

The loss due to imperfect channel estimation is derived for pilot symbol assisted binary phase-shift keying (BPSK) on fading channels with diversity. The presented approach, which holds for both narrow-band and spread spectrum communication, further provides an analytical optimization of pilot symbol spacing. The loss due to channel estimation is demonstrated to be low if the maximum Doppler frequency is significantly less than the bit rate.
Proteomic Analysis of Conditioned Media from the PC3, LNCaP, and 22Rv1 Prostate Cancer Cell Lines: Discovery and Validation of Candidate Prostate Cancer Biomarkers (2008)

Early detection of prostate cancer is problematic due to the lack of a marker that has high diagnostic sensitivity and specificity. The prostate specific antigen (PSA) test, in combination with digital rectal examination, is the gold standard for prostate cancer diagnosis. However, this modality suffers from low specificity. Therefore, specific markers for clinically relevant prostate cancer are needed. Our objective was to proteomically characterize the conditioned media from three human prostate cancer cell lines of differing origin [PC3 (bone metastasis), LNCaP (lymph node metastasis), and 22Rv1 (localized to prostate)] to identify secreted proteins that could serve as novel prostate cancer biomarkers. Each cell line was cultured in triplicate, followed by a bottom-up analysis of the peptides by two-dimensional chromatography and tandem mass spectrometry. Approximately, 12% (329) of the proteins identified were classified as extracellular and 18% (504) as membrane-bound among which were known prostate cancer biomarkers such as PSA and KLK2. To select the most promising candidates for further investigation, tissue specificity, biological function, disease association based on literature searches, and comparison of protein overlap with the proteome of seminal plasma and serum were examined. On the basis of this, four novel candidates, follistatin, chemokine (C-X-C motif) ligand 16, pentraxin 3 and spondin 2, were validated in the serum of patients with and without prostate cancer. The proteins presented in this study represent a comprehensive sampling of the secreted and shed proteins expressed by prostate cancer cells, which may be useful as diagnostic, prognostic or predictive serological markers for prostate cancer.
Foamy Virus Protein—Nucleic Acid Interactions during Particle Morphogenesis (2016)

Compared with orthoretroviruses, our understanding of the molecular and cellular replication mechanism of foamy viruses (FVs), a subfamily of retroviruses, is less advanced. The FV replication cycle differs in several key aspects from orthoretroviruses, which leaves established retroviral models debatable for FVs. Here, we review the general aspect of the FV protein-nucleic acid interactions during virus morphogenesis. We provide a summary of the current knowledge of the FV genome structure and essential sequence motifs required for RNA encapsidation as well as Gag and Pol binding in combination with details about the Gag and Pol biosynthesis. This leads us to address open questions in FV RNA engagement, binding and packaging. Based on recent findings, we propose to shift the point of view from individual glycine-arginine-rich motifs having functions in RNA interactions towards envisioning the FV Gag C-terminus as a general RNA binding protein module. We encourage further investigating a potential new retroviral RNA packaging mechanism, which seems more complex in terms of the components that need to be gathered to form an infectious particle. Additional molecular insights into retroviral protein-nucleic acid interactions help us to develop safer, more specific and more efficient vectors in an era of booming genome engineering and gene therapy approaches.
Interferon Expression in Crohn's Disease Patients: Increased Interferon-γ and -α mRNA in the Intestinal Lamina Propria Mononuclear Cells (1994)

The in vivo interferon (IFN) activation in Crohn's disease was evaluated by measuring the relative amounts of IFN-alpha and -gamma mRNA in freshly isolated human lamina propria mononuclear cells (LPMC) from patients with Crohn's disease and controls. Both IFN-gamma and IFN-alpha mRNA, as estimated by dot blot analysis, were increased in Crohn's disease (LPMC), although the relative amounts of IFN mRNA appeared to differ among patients. Appreciable amounts of IFN-gamma mRNA were found in Crohn's disease peripheral blood mononuclear cells (PBMC) extracts, whereas the same cells were negative for IFN-alpha mRNA. Only minute amounts of IFN-gamma RNA were found sporadically in control LPMC while no IFN-alpha was detected. Control PBMC were shown to be virtually negative for both IFN-alpha and IFN-gamma mRNA. These data suggest that IFN induction in the normal human gut is a well-controlled function and that in Crohn's disease tissues, both IFN-gamma and IFN-alpha production are dysregulated. The increased IFN activity may represent a major feature in the induction and perpetuation of the chronic inflammatory process in Crohn's disease.
Gene Silencing by Small Regulatory RNAs in Mammalian Cells (2007)

Since some years, activation of RNA interference (RNAi) has been developed into a widely used and powerful biological tool to functionally annotate genomes. Several variants of small regulatory RNAs can trigger this evolutionary highly conserved cellular pathway leading to specific hybridisation to and subsequent degradation or translational repression of target mRNAs. These regulatory RNAs include synthetic double-stranded small interfering RNAs (siRNAs), pol III transcribed small hairpin RNAs (shRNAs), or endogenous or artificial micro RNAs (miRNAs) which are expressed from pol II promoters as primary pri-miRNA transcripts subsequently processed into mature miRNAs in a regulated multi-step process. Depending on the mode of activation RNA-processing and efficacy as well as kinetics of RNAi may differ from transient effects to long-lasting gene silencing. However, one of the major challenges for in vitro and in vivo application of RNAi still remains the efficient delivery of suitable RNAi-triggers to target cells. This review highlights the mechanism of RNAi and its activation, the use of plasmid-based and retro-/ lentiviral vector-based systems to mediate long-term RNAi, kinetic aspects of RNAi and their impact on selection of cell populations with modified gene expression.
Diagnosis of Perioperative Myocardial Infarction with Measurement of Cardiac Troponin I (1994)

The measurement of cardiac troponin I is a sensitive and specific method for the diagnosis of perioperative myocardial infarction. It avoids the high incidence of false diagnoses associated with the use of MB creatine kinase as a diagnostic marker.
Glioma Specific Extracellular Missense Mutations in the First Cysteine Rich Region of Epidermal Growth Factor Receptor (EGFR) Initiate Ligand Independent Activation (2011)

The epidermal growth factor receptor (EGFR) is overexpressed or mutated in glioma. Recently, a series of missense mutations in the extracellular domain (ECD) of EGFR were reported in glioma patients. Some of these mutations clustered within a cysteine-rich region of the EGFR targeted by the therapeutic antibody mAb806. This region is only exposed when EGFR activates and appears to locally misfold during activation. We expressed two of these mutations (R324L and E330K) in NR6 mouse fibroblasts, as they do not express any EGFR-related receptors. Both mutants were autophosphorylated in the absence of ligand and enhanced cell survival and anchorage-independent and xenograft growth. The ECD truncation that produces the de2-7EGFR (or EGFRvIII), the most common EGFR mutation in glioma, generates a free cysteine in this same region. Using a technique optimized for detecting disulfide-bonded dimers, we definitively demonstrated that the de2-7EGFR is robustly dimerized and that ablation of the free cysteine prevents dimerization and activation. Modeling of the R324L mutation suggests it may cause transient breaking of disulfide bonds, leading to similar disulfide-bonded dimers as seen for the de2-7EGFR. These ECD mutations confirm that the cysteine-rich region of EGFR around the mAb806 epitope has a significant role in receptor activation.
The design space of input devices (1990)

A bewildering variety of devices for communication from humans to computers now exists on the market. In order to make sense of this variety, and to aid in the design of new input devices, we propose a framework for describing and analyzing input devices. Following Mackinlay's semantic analysis of the design space for graphical presentations, our goal is to provide tools for the generation and test of input device designs. The descriptive tools we have created allow us to describe the semantics of a device and measure its expressiveness. Using these tools, we have built a taxonomy of input devices that goes beyond earlier taxonomies of Buxton & Baecker and Foley, Wallace, & Chan. In this paper, we build on these descriptive tools, and proceed to the use of human performance theories and data for evaluation of the effectiveness of points in this design space. We focus on two figures of merit, footprint and bandwidth, to illustrate this evaluation. The result is the systematic integration of methods for both generating and testing the design space of input devices.
Differential Inhibition of Membrane Type 3 (MT3)-Matrix Metalloproteinase (MMP) and MT1-MMP by Tissue Inhibitor of Metalloproteinase (TIMP)-2 and TIMP-3 Regulates Pro-MMP-2 Activation (2004)

The membrane type (MT)-matrix metalloproteinases (MMPs) constitute a subgroup of membrane-anchored MMPs that are major mediators of pericellular proteolysis and physiological activators of pro-MMP-2. The MT-MMPs also exhibit differential inhibition by members of the tissue inhibitor of metalloproteinase (TIMP) family. Here we investigated the processing, catalytic activity, and TIMP inhibition of MT3-MMP (MMP-16). Inhibitor profile and mutant enzyme studies indicated that MT3-MMP is regulated on the cell surface by autocatalytic processing and ectodomain shedding. Inhibition kinetic studies showed that TIMP-3 is a high affinity inhibitor of MT3-MMP when compared with MT1-MMP (K(i) = 0.008 nm for MT3-MMP versus K(i) = 0.16 nm for MT1-MMP). In contrast, TIMP-2 is a better inhibitor of MT1-MMP. MT3-MMP requires TIMP-2 to accomplish full pro-MMP-2 activation and this process is enhanced in marimastatpretreated cells, consistent with regulation of active enzyme turnover by synthetic MMP inhibitors. TIMP-3 also enhances the activation of pro-MMP-2 by MT3-MMP but not by MT1-MMP. TIMP-4, in contrast, cannot support pro-MMP-2 activation with either enzyme. Affinity chromatography experiments demonstrated that pro-MMP-2 can assemble trimolecular complexes with a catalytic domain of MT3-MMP and TIMP-2 or TIMP-3 suggesting that pro-MMP-2 activation by MT3-MMP involves ternary complex formation on the cell surface. These results demonstrate that TIMP-3 is a major regulator of MT3-MMP activity and further underscores the unique interactions of TIMPs with MT-MMPs in the control of pericellular proteolysis.
Diversification, expression, and γδ T cell recognition of evolutionarily distant members of the MIC family of major histocompatibility complex class I-related molecules (1998)

Distant relatives of major histocompatibility complex (MHC) class I molecules, human MICA and MICB, function as stress-induced antigens that are broadly recognized by intestinal epithelial gamma delta T cells. They may thus play a central role in the immune surveillance of damaged, infected, or otherwise stressed intestinal epithelial cells. However, the generality of this system in evolution and the mode of recognition of MICA and MICB are undefined. Analysis of cDNA sequences from various primate species defined translation products that are homologous to MICA and MICB. All of the MIC polypeptides have common characteristics, although they are extraordinarily diverse. The most notable alterations are several deletions and frequent amino acid substitutions in the putative alpha-helical regions of the alpha1 alpha2 domains. However, the primate MIC molecules were expressed on the surfaces of normal and transfected cells. Moreover, despite their sharing of relatively few identical amino acids in potentially accessible regions of their alpha1 alpha2 domains, they were recognized by diverse human intestinal epithelial gamma delta T cells that are restricted by MICA and MICB. Thus, MIC molecules represent a family of MHC proteins that are structurally diverse yet appear to be functionally conserved. The promiscuous mode of gamma delta T cell recognition of these antigens may be explained by their sharing of a single conserved interaction site.
Extracellular matrix signaling through growth factor receptors during wound healing (2004)

Recently, extracellular matrix components have been shown to contain domains that can interact with and activate receptors with intrinsic tyrosine kinase activity. These receptor tyrosine kinases are strong mediators of the cell responses of proliferation, migration, differentiation, and dedifferentiation. However, an interesting question is raised as to why cells would present growth factor receptor ligands in such a manner, as the majority of growth factors are small, soluble, or only transiently tethered ligands. With the exception of the discoidin domain receptors that bind collagen, the other described domains interact with a receptor that binds ubiquitous soluble peptide growth factors, the epidermal growth factor receptor. Unlike traditional growth factors, these individual "matrikine" domains within tenascin-C, laminin, collagen, and decorin possess relatively low binding affinity (high nanomolar or micromolar) and are often presented in multiple valency. The presentation of ligands within the extracellular matrix in this fashion might allow for unique biochemical and physiological outcomes. This new class of "matrikine" ligand may be critical for wound healing, as the majority of known extracellular matrix components possessing matrikines play a strong role, or are presented uniquely, during skin repair. Tenascin-C expression, for instance, is uniquely regulated spatially and has been proposed to present pro-migratory tracks during skin repair through its epidermal growth factor-like repeats. The epidermal growth factor-like repeats of laminin-5 act as cryptic ligands revealed upon matrix metalloproteinase-2 degradation of the surrounding extracellular matrix. The deletion of the discoidin domain receptors 1 and 2 for collagen have negative consequences on the role of fibroblasts and epithelial cells for matrix metalloproteinase production, migration, proliferation, and extracellular matrix turnover. Finally, decorin can bind to, inhibit, and down-regulate epidermal growth factor receptor levels and signaling, suggesting a tonic role of the epidermal growth factor binding domain of decorin in the resolution of wound healing. We provide a model framework for further studies into this emerging class of signals.
Aspects of Data Modeling and Query Processing for Complex Multidimensional Data (2000)

This thesis is about data modeling and query processing for complex multidimensional data. Multidimensional data has become the subject of much attention in both academia and industry in recent years, fueled by the popularity of data warehousing and On-Line Analytical Processing (OLAP) applications. One application area where complex multidimensional data is common is within medical informatics, an area that may benefit significantly from the functionality offered by data warehousing and OLAP. However, the special nature of clinical applications poses different and new requirements to data warehousing technologies, over those posed by conventional data warehouse applications. This thesis presents a number of exciting new research challenges posed by clinical applications, to be met by the database research community. These include the need for complex-data modeling features, advanced temporal support, advanced classification structures, continuously valued data, dimensionally reduced ...
Diffusion in Polymer Gel Implants (1974)

Crosslinked polyacrylamide and polyvinylpyrrolidone gels have been used to subcutaneously implant (125)I-labeled immunoglobulin, (125)I-labeled luteinizing hormone, (125)I-labeled bovine serum albumin, (125)I-labeled insulin, [(3)H]prostaglandin F(2alpha), and Na(125)I into hamsters. From the rates of absorption of the solutes, their diffusion coefficients were determined. The diffusion coefficients showed a logarithmic dependence on implant polymer concentration and solute molecular weight. Release of the solutes from gel preparations incubated 10 mM phosphate buffer (pH 7.2) at 37 degrees revealed a similar relationship between solute diffusion coefficient, molecular weight, and the concentration of polymer. A general equation was derived that gives the expected diffusion coefficient of a substance in a polymer gel from its molecular weight, diffusion coefficient in solvent, and polymer concentration of the gel.