gebhart/patrepeval huggingface dataset:
α2,6-Sialic Acid on Platelet Endothelial Cell Adhesion Molecule (PECAM) Regulates Its Homophilic Interactions and Downstream Antiapoptotic Signaling (2010)

Antiangiogenesis therapies are now part of the standard repertoire of cancer therapies, but the mechanisms for the proliferation and survival of endothelial cells are not fully understood. Although endothelial cells are covered with a glycocalyx, little is known about how endothelial glycosylation regulates endothelial functions. Here, we show that alpha2,6-sialic acid is necessary for the cell-surface residency of platelet endothelial cell adhesion molecule (PECAM), a member of the immunoglobulin superfamily that plays multiple roles in cell adhesion, mechanical stress sensing, antiapoptosis, and angiogenesis. As a possible underlying mechanism, we found that the homophilic interactions of PECAM in endothelial cells were dependent on alpha2,6-sialic acid. We also found that the absence of alpha2,6-sialic acid down-regulated the tyrosine phosphorylation of PECAM and recruitment of Src homology 2 domain-containing protein-tyrosine phosphatase 2 and rendered the cells more prone to mitochondrion-dependent apoptosis, as evaluated using PECAM- deficient endothelial cells. The present findings open up a new possibility that modulation of glycosylation could be one of the promising strategies for regulating angiogenesis.
The Borrelia burgdorferi flagellum-associated 41-kilodalton antigen (flagellin): molecular cloning, expression, and amplification of the gene (1990)

Monoclonal antibodies directed against the major Borrelia burgdorferi flagellar protein, the 41-kilodalton (kDa) protein flagellin, were used to monitor cloning and expression of the flagellin gene from a Borrelia burgdorferi genomic library. The structure of the gene was analyzed, and recombinant nonfusion flagellin was produced in Escherichia coli. A DNA sequence analysis of the 41-kDa flagellin gene revealed the presence of an open reading frame that encoded a protein having 336 amino acid residues and a calculated molecular mass of 35.8 kDa, indicating that there was posttranslational modification of the natural 41-kDa flagellin protein. Upstream from the AUG start codon sequence we identified motifs corresponding to consensus procaryotic promoter elements which could be utilized by the cloned flagellin gene when it was expressed in E. coli MC1061. The deduced flagellin protein sequence exhibited high levels of homology to sequences of flagellin proteins from Bacillus subtilis and Salmonella typhimurium. The levels of sequence similarity for the amino- and carboxy-terminal portions were about 65 and 56%, respectively. DNA sequence information on the flagellin gene was used to design oligonucleotides for gene amplification by the polymerase chain reaction method, and by using this method 0.01 pg of Borrelia burgdorferi DNA could be detected. Our results provide a basis for further biochemical analysis of the 41-kDa flagellin protein, investigation of the role of this protein in host-pathogen interactions, and development of a standardized reagent for diagnostic systems for Borrelia burgdorferi infections.
Tensor-product parity code for magnetic recording (2006)

In magnetic recording, a standard code architecture consists of an outer Reed-Solomon code in concatenation with an inner parity code. The inner parity code is used to detect and correct common error events. Generally, a parity code with short block length performs better, as multiple error events within one block and, consequently, miscorrection are less likely. In this paper, we study an inner code that offers the same system performance as a parity code with very short block length, even as short as the symbol length (in bits) of the outer Reed-Solomon code, but with higher code rate. This code is a tensor-product code, with a Bose-Chauduri-Hocquenghem (BCH) code and a short parity code as constituent codes. The decoder for this code is not much more complex than the optimal decoder of the baseline parity-coded channel; in fact, the only additional steps are Viterbi detection matched to the channel and decoding of the BCH code.
Fully parallel, high-speed incoherent optical method for performing discrete Fourier transforms (1978)

An incoherent optical data-processing method is described, which has the potential for performing discrete Fourier transforms of short length at rates far exceeding those afforded by both special-purpose digital hardware and representative coherent optical processors.
The Promise of Integrins as Effective Targets for Anticancer Agents (2002)

This review will briefly describe integrin function, address why integrins are attractive targets for chemotherapeutic drug design, and discuss some ongoing studies aimed at inhibiting integrin activity. Integrins are cell surface heterodimeric receptors. They modulate many cellular processes including: growth, death (apoptosis), adhesion, migration, and invasion by activating several signaling pathways. Many potential chemotherapeutic agents target integrins directly (eg, polypeptides, monoclonal antibodies, adenovirus vectors). These agents may be clinically useful in controlling the metastatic spread of cancer.
Design of Selective Eglin Inhibitors of HCV NS3 Proteinase (1998)

Hepatitis C virus (HCV) infection is a major health problem that leads to cirrhosis and hepatocellular carcinoma in a substantial number of infected individuals, estimated to be 100-200 million worldwide. Unfortunately, immunotherapy or other effective treatments for HCV infection are not yet available, and interferon administration has limited efficacy. Different approaches to HCV therapy are being explored, and these include inhibition of the viral proteinase, helicase, and RNA-dependent RNA polymerase and development of a vaccine. Here we present the design of selective inhibitors with nanomolar potencies of HCV NS3 proteinase based on eglin c. These eglin c mutants were generated by reshaping the inhibitor active site-binding loop, and the results emphasize the role played by residues P5-P4' in enzyme recognition. In addition, alanine scanning experiments provide evidence that the N terminus of eglin c also contributes to NS3 binding. These eglin inhibitors offer a unique tool for accurately assessing the requirements for effective inhibition of the enzymatic activity of NS3 and at the same time can be considered lead compounds for the identification of other NS3 inhibitors in targeted design efforts.
Nanoparticles, Lung Injury, and the Role of Oxidant Stress (2013)

The emergence of engineered nanoscale materials has provided significant advancements in electronic, biomedical, and material science applications. Both engineered nanoparticles and nanoparticles derived from combustion or incidental processes exhibit a range of physical and chemical properties that induce inflammation and oxidative stress in biological systems. Oxidative stress reflects the imbalance between the generation of reactive oxygen species and the biochemical mechanisms to detoxify and repair the damage resulting from reactive intermediates. This review examines current research on incidental and engineered nanoparticles in terms of their health effects on lungs and the mechanisms by which oxidative stress via physicochemical characteristics influences toxicity or biocompatibility. Although oxidative stress has generally been thought of as an adverse biological outcome, this review also briefly discusses some of the potential emerging technologies to use nanoparticle-induced oxidative stress to treat disease in a site-specific fashion.
Current Status and Perspectives in the Development of Camptothecins (2002)

Camptothecins are cytotoxic agents with a wide spectrum of antitumor activity. The unique mechanism of action, the impressive preclinical efficacy and the clinical success of irinotecan and topotecan have stimulated intensive efforts to identify novel analogues. The development of novel camptothecins was recently rationalized on the basis of the detailed knowledge of mechanism of drug-target interaction and was aimed to overcome the major limitations of these drugs (i.e. lactone ring instability and reversibility of topoisomerase I-DNA cleavage complexes). The development of novel series of analogues (7-substituted camptothecins, silatecans and homocamptothecins) resulted in identification of promising compounds, which are currently in clinical development. Considering the lack of precise correlations between preclinical activity and clinical efficacy of camptothecins, the potential advantages of novel analogs in clinical therapy remains to be documented. However, a rational basis for drug selection and development is now provided by the recognition of major limitations of these agents and by a detailed knowledge of multiple interactions between drug, cellular target and serum albumin. Inhibition of the nuclear enzyme DNA topoisomerase I has proven to be a promising strategy in the design of antitumor agents, in spite of a limited cellular basis of selectivity in cytotoxic action of camptothecins (i.e., overexpression of the target enzyme in tumor cells, and increased sensitivity of proliferating cells). The interest in topoisomerase I as a therapeutic target promoted various efforts to identify other chemotypes effective as topoisomerase inhibitors and chemical/modelling efforts to rationally design specific analogs among known inhibitors. Additional approaches, including drug delivery/formulation, optimization of dose/schedule and route of administration, are expected to improve the therapy with camptothecins and other inhibitors.
GENETIC CONTROL OF THE ANTIBODY RESPONSE (1965)

Immunization of CBA and C57 mice with a branched, multichain synthetic polypeptide, poly (tyr,glu)-poly DL-ala--poly lys, ((T,G)-A--L), in Freund's complete adjuvant results in a tenfold or more difference in the antigen-binding capacity of sera from the two strains, although they respond equally to bovine serum albumin. Immunization of CBA x C57 F(1), F(1) x CBA, and F(1) x C57 mice reveals definite genetic control of the response to (T,G)-A--L, which appears to be due to a single major genetic factor, with perhaps one or more modifying factors. Immunization of CBA and C57 mice with (H,G)-A--L, a synthetic polypeptide in which histidine replaces tyrosine, gives the opposite result, CBA's respond and C57's do not. From this, it appears that the genetic control of the response to (T,G)-A--L is specific for the antigenic determinant. The implications of these results are discussed.
Epidemiology of Clostridium difficile Infection (2013)

There has been dramatic change in the epidemiology of Clostridium difficile infection (CDI) since the turn of the 21st century noted by a marked increase in incidence and severity, occurring at a disproportionately higher frequency in older patients. Historically considered a nosocomial infection associated with antibiotic exposure, CDI has now also emerged in the community in populations previously considered low risk. Emerging risk factors and disease recurrence represent continued challenges in the management of CDI. The increased incidence and severity associated with CDI has coincided with the emergence and rapid spread of a previously rare strain, ribotype 027. Recent data from the United States and Europe suggest that the incidence of CDI may have reached a crescendo in the recent years and is perhaps beginning to plateau. The acute care direct costs of CDI were estimated to be US$4.8 billion in 2008. However, nearly all the published studies have focused on CDI diagnosed and treated in the acute care hospital setting and fail to measure the burden outside the hospital, including recently discharged patients, outpatients, and those in long-term care facilities. Enhanced surveillance methods are needed to monitor the incidence, to identify populations at risk, and to characterize the molecular epidemiology of strains causing CDI.
DEMONSTRATION OF CYTOKERATIN IN ENDOTHELIAL CELLS OF THE SYNOVIAL MICROVASCULATURE IN SITU AND IN VITRO (1993)

We have used a panel of anti-cytokeratin antibodies and immunofluorescence microscopy to examine synovial tissue from a variety of large and small joints in patients with various rheumatic conditions, including RA, OA, AS, pigmented villonodular synovitis (PVNS) and tenosynovitis (TS). In every case we regularly found blood vessels with endothelia which express cytokeratin. Positive staining was obtained with a guinea pig anti-keratin antibody, with monoclonal antibody 8.13 and with a monoclonal antibody specific for keratin 18. Staining of endothelial cells was confirmed by double labelling with antibodies to cytokeratin and factor VIII/von Willebrand factor. We also detected a polypeptide corresponding to cytokeratin 18 (MW 45,000) by Western blotting of synovial tissue. In addition we have isolated pure populations of synovial endothelial cells in culture and demonstrate an extensive cytokeratin intermediate filament network which co-localizes with vimentin filaments. An understanding of the role of the cytokeratin 18 network in synovial endothelium may be important for our understanding of endothelial changes in synovial disease.
Synthesis of Nanocrystal−Polymer Transparent Hybrids via Polyurethane Matrix Grafted onto Functionalized CdS Nanocrystals (2006)

We reported the first synthesis of CdS nanocrystal-polymer transparent hybrids by using polyurethane (PU) grafted onto quantum dots (QDs) CdS nanocrystals. In a typical run, the appropriate amounts of cadmium chloride (CdCl2) and sodium sulfide (Na2S) in the presence of 2-mercaptoethanol (ME) as the organic ligand are well dispersed in H2O/DMF solution without any aggregation. From a combination of transmission electron microscopy (TEM) and a computing method of Brus's model according to UV-vis absorption spectra, the particle size of as-prepared hydroxyl-coated CdS nanocrystals is about 5 nm. Then, PU-CdS transparent nanocomposites hybrids were synthesized by a two-step reaction. The effect of the different ratios of ME/Cd2+ and H2O/DMF on the resulting particle size of CdS nanocrystals was investigated by UV-vis absorption measurements. FT-IR and TGA characterizations indicate the formation of robust bonding between CdS nanocrystals and the organic ligand. The fluorescence measurement shows that CdS-PU hybrids exhibit good optical properties.
PLANTCELLULAR ANDMOLECULARRESPONSES TOHIGHSALINITY (2000)

Plant responses to salinity stress are reviewed with emphasis on molecular mechanisms of signal transduction and on the physiological consequences of altered gene expression that affect biochemical reactions downstream of stress sensing. We make extensive use of comparisons with model organisms, halophytic plants, and yeast, which provide a paradigm for many responses to salinity exhibited by stress-sensitive plants. Among biochemical responses, we emphasize osmolyte biosynthesis and function, water flux control, and membrane transport of ions for maintenance and re-establishment of homeostasis. The advances in understanding the effectiveness of stress responses, and distinctions between pathology and adaptive advantage, are increasingly based on transgenic plant and mutant analyses, in particular the analysis of Arabidopsis mutants defective in elements of stress signal transduction pathways. We summarize evidence for plant stress signaling systems, some of which have components analogous to those that regulate osmotic stress responses of yeast. There is evidence also of signaling cascades that are not known to exist in the unicellular eukaryote, some that presumably function in intercellular coordination or regulation of effector genes in a cell-/tissue-specific context required for tolerance of plants. A complex set of stress-responsive transcription factors is emerging. The imminent availability of genomic DNA sequences and global and cell-specific transcript expression data, combined with determinant identification based on gain- and loss-of-function molecular genetics, will provide the infrastructure for functional physiological dissection of salt tolerance determinants in an organismal context. Furthermore, protein interaction analysis and evaluation of allelism, additivity, and epistasis allow determination of ordered relationships between stress signaling components. Finally, genetic activation and suppression screens will lead inevitably to an understanding of the interrelationships of the multiple signaling systems that control stress-adaptive responses in plants.
Mobile robot localization using landmarks (2002)

We describe an efficient algorithm for localizing a mobile robot in an environment with landmarks. We assume that the robot has a camera and maybe other sensors that enable it to both identify landmarks and measure the angles subtended by these landmarks. We show how to estimate the robot's position using a new technique that involves a complex number representation of the landmarks. Our algorithm runs in time linear in the number of landmarks. We present results of our simulations and propose how to use our method for robot navigation.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Acceptor Specificity of the Pasteurella Hyaluronan and Chondroitin Synthases and Production of Chimeric Glycosaminoglycans (2006)

The hyaluronan (HA) synthase, PmHAS, and the chondroitin synthase, PmCS, from the Gram-negative bacterium Pasteurella multocida polymerize the glycosaminoglycan (GAG) sugar chains HA or chondroitin, respectively. The recombinant Escherichia coli-derived enzymes were shown previously to elongate exogenously supplied oligosaccharides of their cognate GAG (e.g. HA elongated by PmHAS). Here we show that oligosaccharides and polysaccharides of certain noncognate GAGs (including sulfated and iduronic acid-containing forms) are elongated by PmHAS (e.g. chondroitin elongated by PmHAS) or PmCS. Various acceptors were tested in assays where the synthase extended the molecule with either a single monosaccharide or a long chain (approximately 10(2-4) sugars). Certain GAGs were very poor acceptors in comparison to the cognate molecules, but elongated products were detected nonetheless. Overall, these findings suggest that for the interaction between the acceptor and the enzyme (a) the orientation of the hydroxyl at the C-4 position of the hexosamine is not critical, (b) the conformation of C-5 of the hexuronic acid (glucuronic versus iduronic) is not crucial, and (c) additional negative sulfate groups are well tolerated in certain cases, such as on C-6 of the hexosamine, but others, including C-4 sulfates, were not or were poorly tolerated. In vivo, the bacterial enzymes only process unsulfated polymers; thus it is not expected that the PmCS and PmHAS catalysts would exhibit such relative relaxed sugar specificity by acting on a variety of animal-derived sulfated or epimerized GAGs. However, this feature allows the chemoenzymatic synthesis of a variety of chimeric GAG polymers, including mimics of proteoglycan complexes.
Current-mode CMOS multiple-valued logic circuits (1994)

Current-mode CMOS circuits are receiving increasing attention. Current-mode CMOS multiple-valued logic circuits are interesting and may have applications in digital signal processing and computing. In this paper we review several of the current-mode CMOS multiple-valued logic (MVL) circuits that we have studied over the past decade. These circuits include a simple current threshold comparator, current-mode MVL encoders and decoders, current-mode quaternary threshold logic full adders (QFAs), current-mode MVL latches, current-mode latched QFA circuits, and current-mode analog-to-quaternary converter circuits. Each of these circuits is presented and its performance described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Identification of motifs in cholera toxin A1 polypeptide that are required for its interaction with human ADP-ribosylation factor 6 in a bacterial two-hybrid system (2000)

The latent ADP-ribosyltransferase activity of cholera toxin (CT) that is activated after proteolytic nicking and reduction is associated with the CT A1 subunit (CTA1) polypeptide. This activity is stimulated in vitro by interaction with eukaryotic proteins termed ADP-ribosylation factors (ARFs). We analyzed this interaction in a modified bacterial two-hybrid system in which the T18 and T25 fragments of the catalytic domain of Bordetella pertussis adenylate cyclase were fused to CTA1 and human ARF6 polypeptides, respectively. Direct interaction between the CTA1 and ARF6 domains in these hybrid proteins reconstituted the adenylate cyclase activity and permitted cAMP-dependent signal transduction in an Escherichia coli reporter system. We constructed improved vectors and reporter strains for this system, and we isolated variants of CTA1 that showed greatly decreased ability to interact with ARF6. Amino acid substitutions in these CTA1 variants were widely separated in the primary sequence but were contiguous in the three-dimensional structure of CT. These residues, which begin to define the ARF interaction motif of CTA1, are partially buried in the crystal structure of CT holotoxin, suggesting that a change in the conformation of CTA1 enables it to bind to ARF. Variant CTA polypeptides containing these substitutions assembled into holotoxin as well as wild-type CTA, but the variant holotoxins showed greatly reduced enterotoxicity. These findings suggest functional interaction between CTA1 and ARF is required for maximal toxicity of CT in vivo.
Recruitment of substrate-specificity properties from one enzyme into a related one by protein engineering. (1987)

The Bacillus licheniformis and Bacillus amyloliquefaciens subtilisins differ by 31% in protein sequence and by factors of greater than 60 in catalytic efficiency, kcat/Km, toward various substrates. Despite large differences in sequence and substrate specificity for these serine proteases, only two amino acid substitutions (residues 156 and 217) occur within 4 A (contact distance) of modeled substrates, and a third substitution (residue 169) is within 7 A. The three B. licheniformis substitutions (Ser-156/Ala-169/Leu-217) were introduced into the wild-type B. amyloliquefaciens subtilisin (Glu-156/Gly-169/Tyr-217) by site-directed mutagenesis. The substrate specificity of the triple mutant approaches that of B. licheniformis enzyme when assayed with seven different substrates that vary in charge, size, and hydrophobicity. Thus, specificity properties of distantly related and functionally divergent enzymes can be exchanged by limited amino acid replacements, in this case representing less than 4% of the sequence differences.
Mining longitudinal web queries: Trends and patterns (2003)

Abstract This project analyzed 541,920 user queries submitted to and executed in an academic Website during a four‐year period (May 1997 to May 2001) using a relational database. The purpose of the study is three‐fold: (1) to understand Web users' query behavior; (2) to identify problems encountered by these Web users; (3) to develop appropriate techniques for optimization of query analysis and mining. The linguistic analyses focus on query structures, lexicon, and word associations using statistical measures such as Zipf distribution and mutual information. A data model with finest granularity is used for data storage and iterative analyses. Patterns and trends of querying behavior are identified and compared with previous studies.
Rhythms in Human Performance: 1 ½-Hour Oscillations in Cognitive Style (1979)

Performance on verbal and spatial matching tasks was assessed every 15 minutes for 8 hours. Significant 60- to 100-minute oscillations were observed for each task. These oscillations were 180 degrees out of phase, supporting the hypothesis that in humans the basic rest activity cycle involves alternating activation of processing systems residing in the two cerebral hemispheres.