gebhart/patrepeval huggingface dataset:
Structure‐function relationship in the globular type III antifreeze protein: Identification of a cluster of surface residues required for binding to ice (1994)

Antifreeze proteins (AFPs) depress the freezing point of aqueous solutions by binding to and inhibiting the growth of ice. Whereas the ice-binding surface of some fish AFPs is suggested by their linear, repetitive, hydrogen bonding motifs, the 66-amino-acid-long Type III AFP has a compact, globular fold without any obvious periodicity. In the structure, 9 beta-strands are paired to form 2 triple-stranded antiparallel sheets and 1 double-stranded antiparallel sheet, with the 2 triple sheets arranged as an orthogonal beta-sandwich (Sönnichsen FD, Sykes BD, Chao H, Davies PL, 1993, Science 259:1154-1157). Based on its structure and an alignment of Type III AFP isoform sequences, a cluster of conserved, polar, surface-accessible amino acids (N14, T18, Q44, and N46) was noted on and around the triple-stranded sheet near the C-terminus. At 3 of these sites, mutations that switched amide and hydroxyl groups caused a large decrease in antifreeze activity, but amide to carboxylic acid changes produced AFPs that were fully active at pH 3 and pH 6. This is consistent with the observation that Type III AFP is optimally active from pH 2 to pH 11. At a concentration of 1 mg/mL, Q44T, N14S, and T18N had 50%, 25%, and 10% of the activity of wild-type antifreeze, respectively. The effects of the mutations were cumulative, such that the double mutant N14S/Q44T had 10% of the wild-type activity and the triple mutant N14S/T18N/Q44T had no activity. All mutants with reduced activity were shown to be correctly folded by NMR spectroscopy. Moreover, a complete characterization of the triple mutant by 2-dimensional NMR spectroscopy indicated that the individual and combined mutations did not significantly alter the structure of these proteins. These results suggest that the C-terminal beta-sheet of Type III AFP is primarily responsible for antifreeze activity, and they identify N14, T18, and Q44 as key residues for the AFP-ice interaction.
Cell Cycle and Cancer: Critical Events at the G1 Restriction Point (1996)

In eukaryotic cells, each phase of the cell division cycle is controlled by the sequential activation of various cyclin-dependent kinases (Cdks). These kinases are known to phosphorylate various substrates whose activity is critical for cell cycle progression. As key regulators of the cell cycle, Cdks must be strictly controlled by both extracellular and intracellular signals for adequate responses to occur. There are several distinct molecular mechanisms for controlling the activity of the different Cdks: regulated synthesis and destruction of the activating subunit (cyclin), regulated synthesis and destruction of the inhibitory subunit (Cki), and posttranslational modification of the kinase subunit by highly specific kinases and phosphatases. During the G1 phase of the cell cycle, cells sense, integrate positive and negative signals, and transmit them to the cell cycle machinery. Because of this pivotal role, a vast majority of oncogenic events selectively target elements controlling the G1. In this review we discuss the elements controlling the G1 phase in relationship to the genesis of cancer.
Therapeutic drug monitoring (TDM) of the recent antipsychotic ziprasidone in dried blood spots (DBS) and plasma (2011)

Introduction: Ziprasidone (5-[2-[4-(1,2-benzisothiazol-3-yl)-1-piperazin-yl]ethyl]-6-chloro-1,3-dihydro-2H-indol-2-one) is the most recent atypical antipsychotic introduced onto the market. It probably has the highest selectivity of any antipsychotic agent toward &#13;\n5-HT2A receptors relative to D2 and 5-HT2C receptors. The main clinical advantage of ziprasidone with respect to other atypical antipsychotics seems to be its low incidence of metabolic side effects. However, the drug can cause severe undesired effects, mainly QTc prolongation and orthostatic hypotension. For this reason, an accurate TDM of patients is advised during ziprasidone therapy. Aim of this study is the development of an original analytical method for the determination of ziprasidone in dried blood spots (DBS) and plasma of psychotic patients, based on HPLC with spectrofluorimetric and spectrophotometric detection. DBS testing has the advantage of being a minimally invasive procedure; moreover, DBS can be easily stored and transported without the need for refrigeration.&#13;\nMethods: The analysis is carried out on a C8 reversed phase column, using a phosphate buffer / acetonitrile mixture as the mobile phase. Ziprasidone is natively fluorescent under the chromatographic conditions used, therefore fluorimetric detection is suitable for its dosage, granting satisfactory sensitivity and selectivity to the assay. &#13;\nThe sample pre-treatment of DBS is based on a very fast and feasible solvent extraction procedure, while plasma sample cleaning is achieved by solid phase extraction.&#13;\nResults: The results obtained until now are satisfactory in terms of precision and extraction yield on both matrices.&#13;\nConclusions: Method validation is currently in progress. From preliminary assays, the method seems to be suitable for the TDM of ziprasidone in DBS and plasma.
Harrison's Principles of Internal Medicine, CD-ROM (2001)

Part I: Introduction to Clinical Medicine. Part II: Cardinal Manifestations and Presentation of Disease. Part III: Genetics and Disease. Part IV: Clinical Pharmacology. Part V: Nutrition. Part VI: Oncology and Hematology. Part VII: Infectious Diseases. Part VIII: Disorders of the Cardiovascular System. Part IX: Disorders of the Respiratory System. Part X: Disorders of the Kidney and Urinary Tract. Part XI: Disorders of the Gastrointestinal System. Part XII: Disorders of the Immune System, connective Tissue, and Joints. Part XIII: Endocrinology and Metabolism. Part XIV: Neurologic Disorders. Part XV: Environmental and Occupational Hazards. Appendix A: Laboratory Values of Clinical Importance. Appendix B: Instructions for Collection and Transport of Specimen Culture.
Influence of calcium on phosphatidylglycerol. Two separate lamellar structures (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInfluence of calcium on phosphatidylglycerol. Two separate lamellar structuresKarl Harlos and Hansjoerg EiblCite this: Biochemistry 1980, 19, 5, 895–899Publication Date (Print):March 4, 1980Publication History Published online1 May 2002Published inissue 4 March 1980https://pubs.acs.org/doi/10.1021/bi00546a011https://doi.org/10.1021/bi00546a011research-articleACS PublicationsRequest reuse permissionsArticle Views114Altmetric-Citations65LEARN 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 Get e-Alerts
LncRNA DQ786243 expression as a biomarker for assessing prognosis in patients with gastric cancer. (2018)

Our data suggest, for the first time, that the evaluation of the DQ786243 expression in GC tissues is a useful tool for predicting prognosis of GC.
Human liver cell transplantation (1989)

Abstract Isolated cryopreserved human liver cells, attached to collagen-coated microcarriers, were injected intraperitoneally into mutant rat recipients genetically deficient in either bilirubin uridine diphosphoglucuronosyltransferase activity (Gunn rats) or albumin synthesis (Nagase analbuminemic rats). One group of the recipient Gunn and analbuminemic rats were made genetically immunodeficient by interbreeding with athymic rats with inherited T-cell deficiency. Injected microcarriers and cells formed aggregates on the surface of the pancreas. There was no morphologic evidence of rejection in athymic recipients, whereas immunocompetent recipients demonstrated rejection within 5 days of transplantation. Athymic-Gunn rat recipients demonstrated excretion of bilirubin glucuronides in bile for 30 days and reduction in their serum bilirubin levels. In recipient athymic-analbuminemic rats, plasma albumin levels increased from pretransplantation levels of 0.025–0.05 mg/ml to 3.9–4.8 mg/ml 8 days posttransplantation and remained nearly at that level throughout the 30 days of the study. A method of harvesting, attaching to microcarriers, cryopreserving, and in vivo testing of human hepatocytes with prolonged survival and function in athymic-Gunn and athymic-analbuminemic hybrid rats is reported. These rats are excellent animal models for testing xenograft function.
Performance Evaluation of 2-Element Arrays of Circular Patch Antennas in Indoor Clustered MIMO Channels (2006)

In this paper we present a computationally efficient method to evaluate the performance of circular patch arrays (CPAs) in clustered MIMO channel models. The proposed method is based on bounds to the eigenvalues of the spatial correlation matrix that are shown to depend only on the channel angle spread. From these bounds, we derive a closed-form expression of the MIMO ergodic capacity as a function of the angle spread, which is used to estimate the performance of CPAs in different propagation environments. This method yields dramatic reduction in computational complexity due to the reduced number of channel parameters required for performance evaluation of CPAs. Simulation results show that through this method it is possible to predict the performance of CPAs, with negligible capacity loss (below 2%), for the most practical channel scenarios
Use of Pore Casts and Scanning Electron Microscope to Study Pore Geometry (1970)

ABSTRACT Various types of pore casts, replicas of void space, useful for the study of pore geometry can be prepared from rocks impregnated with plastic. Conventional light microscopes are suitable for examination of most pore casts, however the scanning electron microscope is definitely superior and is essential for good photographic illustrations. Study of pore casts provides information on the distribution and shape of pores and interconnecting passageways that influence permeability and control the flow of fluids.
‘Photonic Hook’ based optomechanical nanoparticle manipulator (2018)

Specialized electromagnetic fields can be used for nanoparticle manipulation along a specific path, allowing enhanced transport and control over the particle's motion. In this paper, we investigate the optical forces produced by a curved photonic jet, otherwise known as the "photonic hook", created using an asymmetric cuboid. In our case, this cuboid is formed by appending a triangular prism to one side of a cube. A gold nanoparticle immersed in the cuboid's transmitted field moves in a curved trajectory. This result could be used for moving nanoparticles around obstacles; hence we also consider the changes in the photonic hook's forces when relatively large glass and gold obstacles are introduced at the region where the curved photonic jet is created. We show, that despite the obstacles, perturbing the field distribution, a particle can move around glass obstacles of a certain thickness. For larger glass slabs, the particle will be trapped stably near it. Moreover, we noticed that a partial obstruction of the photonic jet's field using the gold obstacle results in a complete disruption of the particle's trajectory.
Muscle-invasive urothelial bladder cancer: an update on systemic therapy (2015)

Urothelial carcinoma is a common malignancy that carries a poor prognosis when the disease includes muscle invasion. Metastatic urothelial carcinoma is almost uniformly fatal. The evidence behind treatment options in the neoadjuvant, adjuvant and metastatic settings are discussed in this manuscript, with a focused review of standard and investigational cytotoxic, targeted, and immunotherapy approaches. We have focused especially on neoadjuvant cisplatin-based therapy (supported by level one evidence) and on novel immunotherapy agents such as checkpoint inhibitors, which have shown great promise in early clinical studies.
The role of imprinted genes in humans (2012)

Genomic imprinting, a process of epigenetic modification which allows the gene to be expressed in a parent-of-origin specific manner, has an essential role in normal growth and development. Imprinting is found predominantly in placental mammals, and has potentially evolved as a mechanism to balance parental resource allocation to the offspring. Therefore, genetic and epigenetic disruptions which alter the specific dosage of imprinted genes can lead to various developmental abnormalities often associated with fetal growth and neurological behaviour. Over the past 20 years since the first imprinted gene was discovered, many different mechanisms have been implicated in this special regulatory mode of gene expression. This review includes a brief summary of the current understanding of the key molecular events taking place during imprint establishment and maintenance in early embryos, and their relationship to epigenetic disruptions seen in imprinting disorders. Genetic and epigenetic causes of eight recognised imprinting disorders including Silver-Russell syndrome (SRS) and Beckwith-Wiedemann syndrome (BWS), and also their association with Assisted reproductive technology (ART) will be discussed. Finally, the role of imprinted genes in fetal growth will be explored by investigating their relationship to a common growth disorder, intrauterine growth restriction (IUGR) and also their potential role in regulating normal growth variation.
Liver-Directed Gene Transfer Vectors (1998)

The ultimate goal of liver-directed gene therapy for genetic diseases is the stable expression of a therapeutic transgene in a significant proportion of hepatocytes. This article considers the various liver-directed gene transfer procedures studied so far. Performances and limitations of currently available vector systems are discussed with respect to their clinical relevance. Although some improvements have been reported, naked DNA and nonviral gene transfer vectors induce transient expression in only a limited number of cells. Clinical applications of retrovirus-mediated gene transfer are hampered by the need to induce hepatocyte division. First-generation adenovirus vectors are highly efficient; however, they induce an immune response leading to the rapid rejection of transduced cells. Promising new vector systems have emerged, including gutless adenovirus vectors, adeno-associated vectors, and lentivirus vectors. However, these systems are still poorly documented and their relevance to liver-directed gene therapy must be confirmed.
A search engine for natural language applications (2005)

Many modern natural language-processing applications utilize search engines to locate large numbers of Web documents or to compute statistics over the Web corpus. Yet Web search engines are designed and optimized for simple human queries---they are not well suited to support such applications. As a result, these applications are forced to issue millions of successive queries resulting in unnecessary search engine load and in slow applications with limited scalability.In response, this paper introduces the Bindings Engine (BE), which supports queries containing typed variables and string-processing functions. For example, in response to the query "powerful ‹noun›" BE will return all the nouns in its index that immediately follow the word "powerful", sorted by frequency. In response to the query "Cities such as ProperNoun(Head(‹NounPhrase›))", BE will return a list of proper nouns likely to be city names.BE's novel neighborhood index enables it to do so with O(k) random disk seeks and O(k) serial disk reads, where k is the number of non-variable terms in its query. As a result, BE can yield several orders of magnitude speedup for large-scale language-processing applications. The main cost is a modest increase in space to store the index. We report on experiments validating these claims, and analyze how BE's space-time tradeoff scales with the size of its index and the number of variable types. Finally, we describe how a BE-based application extracts thousands of facts from the Web at interactive speeds in response to simple user queries.
Immunogenic targeting of recombinant peptide vaccines to human antigen-presenting cells by chimeric anti-HLA-DR and anti-surface immunoglobulin D antibody Fab fragments in vitro (1995)

To increase the inherently weak immunogenicity of synthetic peptide vaccines, we used recombinant DNA techniques to generate chimeras between immunogenic determinants of human immunodeficiency virus type 1 (HIV-1) gp120 and antibody Fab fragments reactive with surface structures displayed specifically on human antigen-presenting cells (APCs), including surface immunoglobulin D (sIgD) and class II major histocompatibility complex (MHC) molecules. Hybridomas producing anti-human MHC class II (HLA-DR) or surface immunoglobulin D monoclonal antibodies (MAbs) that recognize nonpolymorphic determinants were used to clone chimeric Fab gene fragments by employing an established procedure to generate antigen-binding Fab libraries in phagemid vector pComb3. Molecular and immunochemical analysis indicated that the expected chimeric Fab fragments expressing the HIV-1 epitopes were correctly cloned and expressed in Escherichia coli and retained the binding specificity of the native (hybridoma-derived) MAb. The chimeric Fab fragments targeted the linked HIV-1-derived antigenic determinants to the surface of human APCs in vitro, as evidenced by fluorescence-activated cell sorter analysis. Furthermore, such recombinant immunotargeted HIV-1 peptide antigens demonstrated improved immunogenicity over equivalent nonimmunotargeted control antigens, as shown by their ability to stimulate interleukin-2 production by CD4+ T-helper cells from human donors exposed to HIV-1 antigens. These data suggest that immunotargeting of recombinant peptide antigens via the attached Fab fragments facilitates uptake by human APCs with subsequent access to the MHC class II processing pathway, thereby validating the immunotargeting concept for such recombinant subunit vaccines in an in vitro human system.
Human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) demonstrates structural and functional similarities to the α 4 β 7-integrin binding domains of murine MAdCAM-1, but extreme divergence of mucin-like sequences (1996)

The mucosal vascular addressin, mucosal addressin cell adhesion molecule-1 (MAdCAM-1), is an Ig family adhesion receptor preferentially expressed by venular endothelial cells at sites of lymphocyte extravasation in murine mucosal lymphoid tissues and lamina propria. MAdCAM-1 specifically binds both human and mouse lymphocytes that express the homing receptor for Peyer's patches, the integrin alpha 4 beta 7. Functional expression cloning was used to isolate a cDNA from a macaque mesenteric lymph node library that encodes the homologue to murine MAdCAM-1. The macaque cDNA was subsequently used to clone the human homologue as well. Expression of human MAdCAM-1 RNA is restricted to mucosal tissues, gut-associated lymphoid tissues and spleen. Human MAdCAM-1 selectively binds both murine and human lymphocyte cell lines expressing alpha 4 beta 7. Human and macaque MAdCAM-1 have two Ig-like domains that are similar to the two amino-terminal integrin binding domains of murine MAdCAM-1. The conservation of sequences within the region homologous to the mucin/IgA domain of murine MAdCAM-1 is, however, much less apparent. These receptors exhibit considerable variation from murine MAdCAM-1 with respect to the length of the mucin-like sequence and the lack of a membrane proximal Ig (IgA-like) domain. The isolation of these different species of MAdCAM-1 demonstrates greater seleoffctive pressure for maintenance of amino acids involved in alpha 4 beta 7 binding than those sequences presumably involved in the presentation of carbohydrates for selectin binding.
Neutralization of the human immunodeficiency virus type 1 primary isolate JR-FL by human monoclonal antibodies correlates with antibody binding to the oligomeric form of the envelope glycoprotein complex (1997)

To test whether antibodies that are neutralizing or nonneutralizing for human immunodeficiency virus type 1 (HIV-1) primary isolates can be distinguished by their affinities for the oligomeric envelope glycoproteins, we selected HIV-1(JR-FL) as a model primary virus and a panel of 13 human monoclonal antibodies (MAbs) and evaluated three parameters: (i) half-maximal binding to recombinant monomeric envelope, gp120(JR-FL); (ii) half-maximal binding to oligomeric envelope of HIV-1(JR-FL) expressed on the surface of transfected 293 cells; and (iii) neutralization of HIV-1(JR-FL) in a peripheral blood mononuclear cell-based neutralization assay. Two conclusions can be drawn from these experiments. First, we confirm that antibody interactions with monomeric gp120 do not predict primary virus neutralization. Second, we show that neutralization correlates qualitatively with the relative affinity of an antibody for the oligomeric envelope glycoproteins, at least for HIV-1(JR-FL).
Gynecologic tumors in tamoxifen‐treated women with breast cancer (1994)

Tamoxifen is a safe and reliable treatment of breast cancer, but data suggest an association with endometrial cancer. We propose close monitoring of patients taking tamoxifen and prompt evaluation of any uterine bleeding or pelvic complaint.
Gene transfer from Escherichia coli to Campylobacter species: development of shuttle vectors for genetic analysis of Campylobacter jejuni (1987)

A shuttle cloning vector (pIL550) has been constructed which can be mobilized from Escherichia coli to Campylobacter jejuni, Campylobacter coli, and Campylobacter fetus by complementation with the transfer functions of an IncP plasmid in trans, with a frequency of 10(-4) transconjugants per donor. We also present evidence for a DNA modification system in C. jejuni.
Divergence between cytotoxic effector function and tumor necrosis factor alpha production for inflammatory CD4+ T cells from mice with Sendai virus pneumonia (1993)

Sendai virus pneumonia in beta 2-microglobulin-deficient [beta 2-m(-/-)] mice lacking CD8+ T cells is characterized by the development of CD4+ cytotoxic T lymphocytes that can be recovered directly from the respiratory tract. These CD4+ cytotoxic T lymphocytes are not found in beta 2-m (+/+) mice, though inflammatory CD4+ T cells from both beta 2-m (-/-) and beta 2-m (+/+) mice produce substantial amounts of tumor necrosis factor alpha. Blocking experiments with a monoclonal antibody that also inhibits tumor necrosis factor beta show that the secreted forms of these two cytokines are not responsible for virus-specific killing of class II major histocompatibility complex-compatible targets. Comparison of electron micrographs indicates that the CD4+ effectors from the beta 2-m (-/-) mice are potent inducers of apoptosis, while this is not the case for the beta 2-m (+/+) CD4+ set. These experiments further define the functional status of virus-specific CD4+ T cells responding in vivo in the presence or absence of CD8+ effectors.