gebhart/patrepeval huggingface dataset:
CD28 and Inducible Costimulatory Protein Src Homology 2 Binding Domains Show Distinct Regulation of Phosphatidylinositol 3-Kinase, Bcl-xL, and IL-2 Expression in Primary Human CD4 T Lymphocytes (2003)

Ligation of either CD28 or inducible costimulatory protein (ICOS) produces a second signal required for optimal T cell activation and proliferation. One prominent difference between ICOS- and CD28-costimulated T cells is the quantity of IL-2 produced. To understand why CD28 but not ICOS elicits major increases in IL-2 expression, we compared the abilities of these molecules to activate the signal transduction cascades implicated in the regulation of IL-2. Major differences were found in the regulation of phosphatidylinositol 3-kinase activity (PI3K) and c-jun N-terminal kinase. ICOS costimulation led to greatly augmented levels of PI3K activity compared with CD28 costimulation, whereas only CD28 costimulation activated c-jun N-terminal kinase. To examine how these differences in signal transduction affected IL-2 production, we transduced primary human CD4 T cells with a lentiviral vector that expressed the murine CD28 extracellular domain with a variety of human CD28 and ICOS cytoplasmic domain swap constructs. These domains were able to operate as discrete signaling units, suggesting that they can function independently. Our results show that even though the ICOS Src homology (SH) 2 binding domain strongly activated PI3K, it was unable to substitute for the CD28 SH2 binding domain to induce high levels of IL-2 and Bcl-x(L). Moreover, the CD28 SH2 binding domain alone was sufficient to mediate optimal levels of Bcl-x(L) induction, whereas the entire CD28 cytoplasmic tail was required for high levels of IL-2 expression. Thus, differences within their respective SH2 binding domains explain, at least in part, the distinct regulation of IL-2 and Bcl-x(L) expression following ICOS- or CD28-mediated costimulation.
Efficacy of transarterial chemoembolization on lesion reduction in colorectal liver metastases. (2012)

Following failure of systemic chemotherapy, transarterial chemoembolization (TACE) is an available method to control unresectable liver metastases from colorectal carcinoma (CRC). The aim of present study was to evaluate the efficacy of chemoembolization for inoperable metastatic liver lesions from CRC. Forty-five CRC patients with liver metastases resistant to systemic chemotherapy were enrolled in our study. For each patient, three session of TACE were conducted with 45 days interval. A combination of mitomycin, doxorubicin, and lipiodol were used for TACE. A tri-phasic computed tomography scan and biochemical laboratory tests were performed for all patients at baseline and 30 days after each TACE. Image analysis included measurement of lesion diameters as well as contrast enhancement. Eleven patients deceased before completing three session and the final analyses were performed on the remaining 34 patients. Evaluation of a total 93 lesions in all patients after chemoembolization sessions revealed a 25.88% reduction in anteroposterior (AP) diameter, 33.92% transverse (T) diameter, and 42.22% in product of APxT diameter of lesions (P<0.001 for all instances). CT scan showed a total disappearance of 33% of lesions and evident reduction in contrast enhancement in 16% of them. There were no changes in contrast enhancement in 51% of lesions. Evaluation of single largest lesion in each patient revealed 57.32% reduction in AP diameter, 59.66% in T diameter, and 62.17% in product of APxT diameters (P<0.001 for all diameters). TACE offers a viable option for CRC patients with unresectable liver metastases by significantly reducing lesion size and contrast enhancement.
Acridinium esters as high-specific-activity labels in immunoassay. (1983)

A chemiluminescent acridinium ester has been synthesized that reacts spontaneously with proteins to yield stable, immunoreactive derivatives of high specific activity. The compound has been used to prepare chemiluminescent monoclonal antibodies to human alpha 1-fetoprotein having average incorporation ratios as great as 2.8 mol of label per mole of antibody, which corresponds to a detection limit of approximately 8 X 10(-19) mol. These antibodies have been used in the preliminary development of a two-site immunochemiluminometric assay for human alpha 1-fetoprotein, which requires only a 30-min incubation and a quantification time of 5 s per sample.
Ribozyme-Mediated Repair of Sickle β-Globin mRNAs in Erythrocyte Precursors (1998)

Sickle cell anemia is the most common heritable hematological disease, yet no curative treatment exists for this disorder. Moreover, the intricacies of globin gene expression have made the development of treatments for hemoglobinopathies based on gene therapy difficult. An alternative genetic approach to sickle cell therapy is based on RNA repair. A trans-splicing group I ribozyme was used to alter mutant beta-globin transcripts in erythrocyte precursors derived from peripheral blood from individuals with sickle cell disease. Sickle beta-globin transcripts were converted into messenger RNAs encoding the anti-sickling protein gamma-globin. These results suggest that RNA repair may become a useful approach in the treatment of genetic disorders.
Acute Lung Injury: A Clinical and Molecular Review (2016)

ARDS is primarily a clinicoradiologic diagnosis; however, lung biopsy plays an important diagnostic role in certain cases. A significant amount of progress has been made in the elucidation of ARDS pathophysiology and in predicting patient response, however, currently there is no viable predictive molecular biomarkers for predicting the severity of ARDS, or molecular-based ARDS therapies. The proinflammatory cytokines TNF-α (tumor necrosis factor α), interleukin (IL)-1β, IL-6, IL-8, and IL-18 are among the most promising as biomarkers for predicting morbidity and mortality.
Pathogenesis of alphavirus infection as demonstrated by infection of ECV 304 transformed human umbilical vein capillary endothelial cells with Semliki Forest virus (1993)

Routes of alphaviral entry have been studied with the transformed human endothelial vein cell line ECV 304. This cell line can be cultured on tissue culture inserts which permits apical (lumenal) and basolateral (ablumenal) cell surfaces to be infected and observed separately. Semliki Forest Virus (SFV), a prototype alphavirus, was able to infect and replicate from both the apical and basolateral sides. Transcytosis is not the route by which SFV passes the endothelial cell barrier as demonstrated by polarised infection of junctionally tight ECV monolayers in which translation was inhibited. A "grow-through" replication may play a role in SFV pathogenesis. Infected ECV cells produced interfering substances that inhibited viral infection. Higher multiplicities of infection resulted in infection and complete destruction of the monolayer.
Bayesian Approach for Indoor Pedestrian Localisation (2006)

The principal concept of navigation is to start from a known (initial) position and to ensure a continued and reliable localisation of the user during his/her movement. The initial position of the trajectory is usually obtained via GPS or defined by the user. Consider a pedestrian navigation system which contains a GPS receiver and a set of inertial sensors, connected with a map database. In the urban environment and indoors the localisation depends entirely on the measurements from the inertial sensors. The trajectory is defined in a local coordinate system and with an arbitrary orientation. The problem to solve is to determine the userâs location using the map database and inertial measurements of the navigation system. The idea behind our approach is to find the location and orientation of the trajectory and thus the userâs location. The proposed solution associates the userâs trajectory with the map database applying statistical methods in combination with map-matching. Similar geometric forms must be identified in both the trajectory and the link-node model. The trajectory, defined by a set of consecutive points, is transformed to a set of lines thanks to a dedicated motion model. In this research we propose a solution based on statistical methods where the history of the route and actual measurements are treated at the same time. The determination of the absolute position is entirely represented by its probability density function (PDF) in the frame of Bayesian inference. Following this approach the posterior estimation of the userâs location can be calculated using prior information and actual measurements. Because of the non-linear nature of the estimation problem, non-linear filtering techniques like particle filters (Sequential Monte Carlo methods) are applied.
Loss of P16INK4 expression is frequent in high grade gliomas. (1995)

P16INK4 is a cell cycle regulator that specifically binds to and inactivates cyclin-dependent kinase 4 (CDK4). Its encoding gene (p16/CDKN2) maps to chromosome 9p21, a region that undergoes frequent loss of heterozygosity in a variety of human tumors. We have analyzed the p16/CDKN2 gene and its expression in a series of primary glioma samples. Although homozygous deletion or mutation of the p16/CDKN2 gene was uncommon in this series and P16INK4 protein was detectable in all grade II tumors, it was present in only 50% of grade III and grade IV samples. Conversely, in some grade IV tumors that level of P16INK4 protein was elevated; in these cases, its target, CDK4, was amplified and overexpressed. These results suggest: (a) the involvement of P16INK4 in glioma progression; (b) that mechanisms other than mutation or deletion can down-regulate expression of the p16/CDKN2 gene; and (c) that the balance between CDK4 and its cognate inhibitor, P16INK4, may confer a cell growth advantage and facilitate tumor progression.
LIZARD COMMUNITY AND THE GENETIC VARIABILITY FOR TWO LACERTID SPECIES IN DAMIETTA, NORTH EGYPT (2008)

The structure of the lizard community in Damietta was analyzed in the present study. Five locations were selected as a study area, each represents different habitat of Damietta Governorate. Seven lizard species were recorded which are related to four families and five genera. They were Chamaeleo africanus, Hemidactylus turcicus, Chalcides ocellatus, Mabuya quinquetaeniata, Mabuya vittata, Acanthodactylus boskianus and Acanthodactylus scutellatus. The lacertid lizards Acanthodactylus boskianus and Acanthodactylus scutellatus were the most common species in the community. Therefore, the study was extended to reveal the genetic variability for the population of these two species in Damietta. Four arbitrary chosen enzymes were analyzed electrophoretically. These enzymes were Glucose-6-phosphate dehydrogenase (G6PDH), esterase (EST), lactate dehydrogenase (LDH) and acid phosphatase (ACP). Eleven presumed gene loci have been recorded. A. scutellatus showed higher genetic variability with a polymorphism of 90% of its population compared to 82% for the samples of A. boskianus.
3D analysis of SEM images of corrosion casting using adaptive stereo matching (2007)

The corrosion casting method represents one of the most widely used technique to study the 3D microvascularization of many tissues, both in their normal and pathological conditions. For a long time this technique was used only to perform a qualitative evaluation of the images obtained by scanning electron microscopy (SEM). A quantitative evaluation of vascular parameters (e.g., interbranching and intervascular distances, angle measurements, lengths and diameters) was lacking, mainly because of the difficulties found in the measurement performed on 2D SEM images. Then, some authors reported a quantitative method based on the analyses of stereo-pair images that allowed precise morphometric measurements. To visualize the specimens in 3D, it was necessary to use red-green glasses. In this article we describe a new approach by which we can automatically obtain a 3D reconstruction of vascular cast specimen's surface directly from stereo-images. Moreover, we developed a software that performed micrometric measurements on the 3D construct generated from the stereo-pictures. In conclusion, implementing together these two softwares and applying them to corrosion casting samples made it possible to render in 3D the surface of corrosion cast as well as make quantitative measurements on the corrosion casts.
3D-QSAR-Assisted Design, Synthesis, and Evaluation of Novobiocin Analogues (2012)

Hsp90 is an attractive therapeutic target for the treatment of cancer. Extensive structural modifications to novobiocin, the first Hsp90 C-terminal inhibitor discovered, have produced a library of novobiocin analogues and revealed some structure-activity relationships. Based upon the most potent novobiocin analogues generated from prior studies, a three-dimensional quantitative structure-activity (3D-QSAR) model was built. In addition, a new set of novobiocin analogues containing various structural features supported by the 3D-QSAR model were synthesized and evaluated against two breast cancer cell lines. Several new inhibitors produced anti-proliferative activity at mid nano-molar concentrations, which results through Hsp90 inhibition.
Comparison and analysis of Pd- and Pt-GaAs Schottky diodes for hydrogen detection (1994)

Hydrogen-sensing behaviors of Pd- and Pt-GaAs Schottky diodes, fabricated on the same GaAs substrate, have been systematically compared and analyzed as a function of hydrogen partial pressure and temperature by I-V and ΔI-t methods under steady-state and transient conditions. The effects of hydrogen adsorption on the device parameters such as the barrier height and the ideality factor are investigated. The significant differences in their hydrogen sensing characteristics have been examined in terms of sensitivity limit, linearity of response, response rate, and response time. Adsorption activation energy of hydrogen and the heat of adsorption per hydrogen molecule on the surface of Pd and Pt are investigated and compared in both devices in a low-temperature range (27–100 °C). For the temperature range investigated, Pd-GaAs shows better performance for H2 detection than Pt-GaAs under the same testing conditions. The physical and chemical mechanisms responsible for hydrogen detection are discussed. Analysis of the steady-state reaction kinetics using I-V method confirmed that the atomistic hydrogen adsorption process is responsible for the barrier height change in the diodes.
Risk-benefit considerations in the treatment of relapsing-remitting multiple sclerosis (2013)

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system and mainly affects young adults. Its natural history has changed in recent years with the advent of disease-modifying drugs, which have been available since the early 1990s. The increasing number of first-line and second-line treatment options, together with the variable course of the disease and patient lifestyles and expectations, makes the therapeutic decision a real challenge. The aim of this review is to give a comprehensive overview of the main present and some future drugs for relapsing-remitting MS, including risk-benefit considerations, to enable readers to draw their own conclusions regarding the risk-benefit assessment of personalized treatment strategies, taking into account not only treatment-related but also disease-related risks. We performed a Medline literature search to identify studies on the treatment of MS with risk stratification and risk-benefit considerations. We focused our attention on studies of disease-modifying, immunomodulating, and immunosuppressive drugs, including monoclonal antibodies. Here we offer personal considerations, stemming from long-term experience in the treatment of MS and thorough discussions with other neurologists closely involved in the care of patients with the disease. MS specialists need to know not only the specific risks and benefits of single drugs, but also about drug interactions, either in simultaneous or serial combination therapy, and patient comorbidities, preferences, and fears. This has to be put into perspective, considering also the risks of untreated disease in patients with different clinical and radiological characteristics. There is no single best treatment strategy, but therapy has to be tailored to the patient. This is a time-consuming task, rich in complexity, and influenced by the attitude towards risk on the parts of both the patient and the clinical team. The broader the MS drug market becomes, the harder it will be for the clinician to help the patient decide which therapeutic strategy to opt for.
Development of a glycoconjugate vaccine to prevent invasive Salmonella Typhimurium infections in sub-Saharan Africa (2017)

Invasive infections associated with non-typhoidal Salmonella (NTS) serovars Enteritidis (SE), Typhimurium (STm) and monophasic variant 1,4,[5],12:i:- are a major health problem in infants and young children in sub-Saharan Africa, and currently, there are no approved human NTS vaccines. NTS O-polysaccharides and flagellin proteins are protective antigens in animal models of invasive NTS infection. Conjugates of SE core and O-polysaccharide (COPS) chemically linked to SE flagellin have enhanced the anti-COPS immune response and protected mice against fatal challenge with a Malian SE blood isolate. We report herein the development of a STm glycoconjugate vaccine comprised of STm COPS conjugated to the homologous serovar phase 1 flagellin protein (FliC) with assessment of the role of COPS O-acetyls for functional immunity. Sun-type COPS conjugates linked through the polysaccharide reducing end to FliC were more immunogenic and protective in mice challenged with a Malian STm blood isolate than multipoint lattice conjugates (>95% vaccine efficacy [VE] versus 30-43% VE). Immunization with de-O-acetylated STm-COPS conjugated to CRM197 provided significant but reduced protection against STm challenge compared to mice immunized with native STm-COPS:CRM197 (63-74% VE versus 100% VE). Although OPS O-acetyls were highly immunogenic, post-vaccination sera that contained various O-acetyl epitope-specific antibody profiles displayed similar in vitro bactericidal activity when equivalent titers of anti-COPS IgG were assayed. In-silico molecular modeling further indicated that STm OPS forms a single dominant conformation, irrespective of O-acetylation, in which O-acetyls extend outward and are highly solvent exposed. These preclinical results establish important quality attributes for an STm vaccine that could be co-formulated with an SE-COPS:FliC glycoconjugate as a bivalent NTS vaccine for use in sub-Saharan Africa.
SCOP: a Structural Classification of Proteins database (2000)

The Structural Classification of Proteins (SCOP) database provides a detailed and comprehensive description of the relationships of known protein structures. The classification is on hierarchical levels: the first two levels, family and superfamily, describe near and distant evolutionary relationships; the third, fold, describes geometrical relationships. The distinction between evolutionary relationships and those that arise from the physics and chemistry of proteins is a feature that is unique to this database so far. The sequences of proteins in SCOP provide the basis of the ASTRAL sequence libraries that can be used as a source of data to calibrate sequence search algorithms and for the generation of statistics on, or selections of, protein structures. Links can be made from SCOP to PDB-ISL: a library containing sequences homologous to proteins of known structure. Sequences of proteins of unknown structure can be matched to distantly related proteins of known structure by using pairwise sequence comparison methods to find homologues in PDB-ISL. The database and its associated files are freely accessible from a number of WWW sites mirrored from URL http://scop.mrc-lmb.cam.ac.uk/scop/
Deep CTR Prediction in Display Advertising (2016)

Click through rate (CTR) prediction of image ads is the core task of online display advertising systems, and logistic regression (LR) has been frequently applied as the prediction model. However, LR model lacks the ability of extracting complex and intrinsic nonlinear features from handcrafted high-dimensional image features, which limits its effectiveness. To solve this issue, in this paper, we introduce a novel deep neural network (DNN) based model that directly predicts the CTR of an image ad based on raw image pixels and other basic features in one step. The DNN model employs convolution layers to automatically extract representative visual features from images, and nonlinear CTR features are then learned from visual features and other contextual features by using fully-connected layers. Empirical evaluations on a real world dataset with over 50 million records demonstrate the effectiveness and efficiency of this method.
A Concise, Stereocontrolled Synthesis of (−)-Saframycin A by the Directed Condensation of α-Amino Aldehyde Precursors (1999)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTA Concise, Stereocontrolled Synthesis of (−)-Saframycin A by the Directed Condensation of α-Amino Aldehyde PrecursorsAndrew G. Myers and Daniel W. KungView Author Information Department of Chemistry and Chemical Biology Harvard University, Cambridge, Massachusetts 02138 Cite this: J. Am. Chem. Soc. 1999, 121, 46, 10828–10829Publication Date (Web):November 5, 1999Publication History Received24 August 1999Published online5 November 1999Published inissue 1 November 1999https://pubs.acs.org/doi/10.1021/ja993079khttps://doi.org/10.1021/ja993079krapid-communicationACS PublicationsCopyright © 1999 American Chemical SocietyRequest reuse permissionsArticle Views1489Altmetric-Citations78LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Aldehydes,Anions,Condensation,Cyclization,Nitrogen compounds Get e-Alerts
Peptide nucleic acid.DNA strand displacement loops as artificial transcription promoters. (1994)

Homopyrimidine peptide nucleic acids (PNAs) form loop structures when binding to complementary double-stranded DNA by strand displacement, and we now show that RNA polymerase recognizes these and initiates RNA transcription from PNA/double-stranded DNA strand displacement complexes at an efficiency comparable to that of the strong Escherichia coli lacUV5 promoter. Thus PNA targets can be considered as artificial promoters controlled positively by the corresponding PNA as a transcription factor. Our results have implications for the mechanism of action of RNA polymerase and suggest the use of PNA as specific gene activating reagents and drugs.