gebhart/patrepeval huggingface dataset:
IL-15 Is Highly Expressed in Inflammatory Bowel Disease and Regulates Local T Cell-Dependent Cytokine Production (2000)

IL-15 shares biological activities but no significant sequence homology with IL-2. It induces T cell recruitment to sites of inflammation, T cell proliferation, and cytokine production and rescue from apoptosis. The aim of this study was to investigate expression of IL-15 and its effects on proinflammatory cytokine production in inflammatory bowel disease (IBD). Immunohistochemistry demonstrated local IL-15 production by macrophages in inflamed mucosa from IBD patients. Isolated lamina propria mononuclear cells from these patients but not from controls produced IL-15 when stimulated with LPS or IFN-gamma. Moreover, lamina propria T cells (LP-T) from IBD patients were more responsive to IL-15 as compared with controls, and IL-15 alone without a primary T cell stimulus induced IFN-gamma and TNF production by isolated IBD LP-T cells, especially by LP-T cells from patients with Crohn's disease. LP-T cells from IBD patients could induce CD40-CD40 ligand (CD40L) interaction-dependent TNF and IL-12 production by monocytes in a coculture system. This capacity of LP-T cells was strongly enhanced by preincubation in IL-15 and was the result of higher CD40L expression after culture in IL-15. These data indicate that IL-15 is overexpressed in the inflamed mucosa in IBD and that IL-15 enhances local T cell activation, proliferation, and proinflammatory cytokine production by both T cells and macrophages, the latter via a CD40-CD40L interaction-dependent mechanism. Treatment directed against IL-15 may have therapeutic potential in IBD.
Peginterferon plus Adefovir versus Either Drug Alone for Hepatitis Delta (2011)

Treatment with peginterferon alfa-2a for 48 weeks, with or without adefovir, resulted in sustained HDV RNA clearance in about one quarter of patients with HDV infection. (Current Controlled Trials number, ISRCTN83587695.).
Synthesis and Applications of Molecular Sieve Layers and Membranes (1996)

Strategies for the preparation of zeolite molecular sieve membranes and layers on different substrates are reviewed. Membranes (and continuous thin films) have been synthesized with ZSM-5 (MFI) type molecular sieves and other zeolites, either as free-standing specimens, grown on various supports according to several schemes, or embedded in polymer matrices. The membranes have been studied for molecule-selective separations and for catalytic reactions. Layers of presynthesized molecular sieves have been deposited by means of sol−gel matrixes and other bonding agents, molecular attachment layers, and via sputtering or laser ablation techniques. The resulting nanoporous layers have been applied in highly selective sensors, for the alignment of NLO chromophores and for molecular separations. Finally, oriented molecular sieve layers have been grown on self-assembled organic mono- and multilayers presenting phosphonate groups at the interface. Mixed phosphonate/alkyl films show profound effects on the surface crystallization of metallophosphate molecular sieves. MFI type zeolites have also been grown through the vapor phase on alkylammonium-modified gold substrates.
INTRACELLULAR PATHOGENS AND THE ACTIN CYTOSKELETON (1998)

Many pathogens actively exploit the actin cytoskeleton during infection. This exploitation may take place during entry into mammalian cells after engagement of a receptor and/or as series of signaling events culminating in the engulfment of the microorganism. Although actin rearrangements are a common feature of most internalization events (e.g. entry of Listeria, Salmonella, Shigella, Yersinia, Neisseria, and Bartonella), bacterial and other cellular factors involved in entry are specific to each bacterium. Another step during which pathogens harness the actin cytoskeleton takes place in the cytosol, within which some bacteria (Listeria, Shigella, Rickettsia) or viruses (vaccinia virus) are able to move. Movement is coupled to a polarized actin polymerization process, with the formation of characteristic actin tails. Increasing attention has focused on this phenomenon due to its striking similarity to cellular events occurring at the leading edge of locomoting cells. Thus pathogens are convenient systems in which to study actin cytoskeleton rearrangements in response to stimuli at the plasma membrane or inside cells.
Studies of as-Triazine Derivatives. XV. Intramolecular Reverse-Election Demand Diels-Alder Reaction of 1,2,4-Triazine Derivatives (1990)

5,6-Diphenyl-1,2,4-triazine-3-carboxylic acid esters which have acetylenic function in the alcoholic moiety of the ester group were converted to the pyridine derivatives condensed with lactone ring by means of intramolecular reverse electron-demand Diels-Alder reaction.This type ring-transformation was applicable to the corresponding 3.5-diphenyl-1.2.4triarine-6-carboxylic acid esters.According to the similar manner, b e n z o f u r o [ 2 , 3 -b l p y r i d i n e s .benzofuro[2,3-clpyridines. and b e n z o f u r o [ 2 , 3 -d l p y r i m i d i n e s were synthesized in satisfactory
Magnetic nanoparticles for interstitial thermotherapy – feasibility, tolerance and achieved temperatures (2006)

Further improvement of the temperature distribution is required by refining the implantation techniques or simply by increasing the amount of nanofluid or elevation of the magnetic field strength. From the actual nanoparticle distribution and derived temperatures we can extrapolate, that already a moderate increase of the H-field by only 2 kA/m would significantly improve the 42 degrees C coverage towards 100% (98%). This illustrates the great potential of the nanofluid-based heating technology.
Molecular modeling software and methods for medicinal chemistry (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMolecular modeling software and methods for medicinal chemistryN. Claude Cohen, Jeffrey M. Blaney, Christine Humblet, Peter Gund, and David C. BarryCite this: J. Med. Chem. 1990, 33, 3, 883–894Publication Date (Print):March 1, 1990Publication History Published online1 May 2002Published inissue 1 March 1990https://pubs.acs.org/doi/10.1021/jm00165a001https://doi.org/10.1021/jm00165a001research-articleACS PublicationsRequest reuse permissionsArticle Views1049Altmetric-Citations123LEARN 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
Structure and function of lysosomal phospholipase A2 and lecithin:cholesterol acyltransferase (2015)

Lysosomal phospholipase A2 (LPLA2) and lecithin:cholesterol acyltransferase (LCAT) belong to a structurally uncharacterized family of key lipid-metabolizing enzymes responsible for lung surfactant catabolism and for reverse cholesterol transport, respectively. Whereas LPLA2 is predicted to underlie the development of drug-induced phospholipidosis, somatic mutations in LCAT cause fish eye disease and familial LCAT deficiency. Here we describe several high-resolution crystal structures of human LPLA2 and a low-resolution structure of LCAT that confirms its close structural relationship to LPLA2. Insertions in the α/β hydrolase core of LPLA2 form domains that are responsible for membrane interaction and binding the acyl chains and head groups of phospholipid substrates. The LCAT structure suggests the molecular basis underlying human disease for most of the known LCAT missense mutations, and paves the way for rational development of new therapeutics to treat LCAT deficiency, atherosclerosis and acute coronary syndrome.
Replacing Antibodies: Engineering New Binding Proteins (2013)

Nature's reliance on proteins to carry out nearly all biological processes has led to the evolution of biomolecules that exhibit a seemingly endless range of functions. Much research has been devoted toward advancing this process in the laboratory in order to create new proteins with improved or unique capabilities. The protein-engineering field has rapidly evolved from pioneering studies in engineering protein stability and activity to an application-driven powerhouse on the forefront of emerging technologies in biomedical engineering and biotechnology. A classic protein-engineering technique in the medical field has focused on manipulating antibodies and antibody fragments for various applications. New classes of alternative scaffolds have recently challenged this paradigm, and these structures have been successfully engineered for applications including targeted cancer therapy, regulated drug delivery, in vivo imaging, and a host of others. This review aims to capture recent advances in the engineering of nonimmunoglobulin scaffolds as well as some of the applications for these molecular recognition elements in the biomedical field.
Protection of Mg Alloys against Galvanic and Other Forms of Corrosion (2005)

This DOI is not currently attached to any metadata records. DOIs can’t actually ever be deleted (they’re persistent), but sometimes our members create DOIs in error. We do have a process to approximate deletion which we follow only in rare cases where the DOI has been genuinely created in error, and most crucially, if the DOI has never been published anywhere online or in print and never otherwise distributed to or communicated with anyone (authors, readers, reviewers, etc.
Blue Gene: A vision for protein science using a petaflop supercomputer (2001)

In December 1999, IBM announced the start of a five-year effort to build a massively parallel computer, to be applied to the study of biomolecular phenomena such as protein folding. The project has two main goals: to advance our understanding of the mechanisms behind protein folding via large-scale simulation, and to explore novel ideas in massively parallel machine architecture and software. This project should enable biomolecular simulations that are orders of magnitude larger than current technology permits. Major areas of investigation include: how to most effectively utilize this novel platform to meet our scientific goals, how to make such massively parallel machines more usable, and how to achieve performance targets, with reasonable cost, through novel machine architectures. This paper provides an overview of the Blue Gene project at IBM Research. It includes some of the plans that have been made, the intended goals, and the anticipated challenges regarding the scientific work, the software applic ation, and the hardware design.
Toothpicks, Serendipity and the Emergence of the Escherichia coli DnaK (Hsp70) and GroEL (Hsp60) Chaperone Machines (2006)

THE purpose of this essay is to retrace some of the early steps that I and a few (then) young geneticists took in the late 1960s and early 1970s to define the Escherichia coli functions used by phage to properly execute their developmental cycle. Eventually, this led to the discovery and functional understanding of the so-called DnaK (Hsp70) and GroEL (Hsp60) molecular chaperone machines, universally conserved among the biological kingdoms (Lindquist and Craig 1988; Georgopoulos and Welch 1993). Now we know that these and other molecular chaperone machines are involved in a multitude of biological processes, including protection of nascent polypeptide chains from premature aggregation, disaggregation of protein aggregates, polypeptide transport across biological membranes, and proteolysis (Bukau and Horwich 1998; Hartl and Hayer-Hartl 2002; Craig et al. 2006). Because protein denaturation and aggregation are enhanced by various environmental stresses, e.g., an increase in temperature, it is not surprising that the DnaK (Hsp70) and GroEL (Hsp60) molecular chaperone machines were also discovered independently as “heat-shock” or “stress” proteins. Because of their very short growth cycles, phage have evolved a variety of strategies to subvert and customize host functions for their own use. Phage likely have a greater need than their hosts for quick and abundant chaperone power to carry out their developmental cycle in a timely fashion. If they fail to complete their cycle before the host lyses, infectious phage progeny will not be released into the medium, risking their extinction. This differential need for chaperone power likely explains why many of the bacterial mutations found to block phage development were eventually shown to be in genes encoding the GroEL and DnaK chaperone machines.
Adaptive image coding using spectral classification (1998)

We present a new classification scheme, dubbed spectral classification, which uses the spectral characteristics of the image blocks to classify them into one of a finite number of classes. A vector quantizer with an appropriate distortion measure is designed to perform the classification operation. The application of the proposed spectral classification scheme is then demonstrated in the context of adaptive image coding. It is shown that the spectral classifier outperforms gain-based classifiers while requiring a lower computational complexity.
Endosomal Escape: A Bottleneck in Intracellular Delivery (2014)

With advances in therapeutic science, apart from drugs, newer bioactive moieties like oligonucleotides, proteins, peptides, enzymes and antibodies are constantly being introduced for the betterment of therapeutic efficacy. These moieties have intracellular components of the cells like cytoplasm and nucleus as one of their pharmacological sites for exhibiting therapeutic activity. Despite their promising efficacy, their intracellular bioavailability has been critically hampered leading to failure in the treatment of numerous diseases and disorders. The endosomal uptake pathway is known to be a rate-limiting barrier for such systems. Bioactive molecules get trapped in the endosomal vesicles and degraded in the lysosomal compartment, necessitating the need for effective strategies that facilitate the endosomal escape and enhance the cytosolic bioavailability of bioactives. Microbes like viruses and bacteria have developed their innate mechanistic tactics to translocate their genome and toxins by efficiently penetrating the host cell membrane. Understanding this mechanism and exploring it further for intracellular delivery has opened new avenues to surmount the endosomal barrier. These strategies include membrane fusion, pore formation and proton sponge effects. On the other hand, progress in designing a novel smart polymeric carrier system that triggers endosomal escape by undergoing modulations in the intracellular milieu has further led to an improvement in intracellular delivery. These comprise pH, enzyme and temperature-induced modulators, synthetic cationic lipids and photo-induced physical disruption. Each of the aforementioned strategies has its own unique mechanism to escape the endosome. This review recapitulates the numerous strategies designed to surmount the bottleneck of endosomal escape and thereby achieve successful intracellular uptake of bioactives.
Identification of novel peptide antagonists for GPIIb/IIIa from a conformationally constrained phage peptide library (1992)

Methods have recently been developed to present vast libraries of random peptides on the surface of filamentous phage. To introduce a degree of conformational constraint into random peptides, a library of hexapeptides flanked by cysteine residues (capable of forming cyclic disulfides) was constructed. This library was screened using the platelet glycoprotein, IIb/IIIa, which mediates the aggregation of platelets through binding of fibrinogen. A variety of peptides containing the sequence Arg-Gly-Asp or Lys-Gly-Asp were discovered and synthesized. The cyclic, disulfide-bonded forms of the peptides bound IIb/IIIa with dissociation constants in the nanomolar range, while reduced forms or an analogue in which Ser replaced the Cys residues bound considerably less tightly. These results demonstrate the feasibility for introducing conformational constraints into random peptide libraries and also demonstrates the potential for using phage peptide libraries to discover pharmacologically active lead compounds.
Methylation of the androgen receptor minimal promoter silences transcription in human prostate cancer. (2000)

Advanced hormone-independent prostate cancer is characterized by a significant loss of androgen receptor (AR) expression in 20-30% of the tumors. The transcriptional block underlying this phenomenon is not known, but we have proposed that methylation of CpG sites in the AR promoter may reversibly inactivate transcription of the AR (D. F. Jarrard et al, Cancer Res., 58: 5310-5314, 1998). In this study, detailed methylation analysis using bisulfite sequencing was performed on a series of AR expression-positive and -negative prostate cancer cells. We found that methylation of several consensus sequences in the AR promoter (from -131 to -121 and +44 to +54) are tightly linked to the loss of AR expression in metastatic hormone-independent prostate cancer cell lines. These consensus sites of methylation correlate with the minimal promoter region critical for AR transcription. In human tissues, no methylation was demonstrated in normal or primary prostate cancers that express the AR. Four of 15 tumors obtained from men who had died from hormone-independent prostate cancer demonstrated a significant loss of AR expression immunohistochemically and two (50%) of these AR-negative tumors contained AR methylation. We conclude that the AR promoter contains specific CpG methylation hot spots that are markers for gene silencing. Furthermore, AR methylation may represent a phenotype important in the development of hormone independence in a subset of advanced prostate cancer in which AR expression is lost. The finding of AR methylation also represents the first report of aberrant methylation on an X-linked gene associated with a somatic male cancer.
Crystal-orientation effects on the piezoelectric field and electronic properties of strained wurtzite semiconductors (1999)

Crystal orientation effects on the piezoelectric field and electronic properties of strained GaN bulk semiconductors are investigated. Analytical expressions for the band gap, wave function, and momentum matrix element of strained wurtzite GaN using a recently derived block-diagonalized Hamiltonian are shown. We find that the energy separation between the top two valence bands increases with the angle \ensuremath{\theta} between the growth ${(z}^{\ensuremath{'}})$ direction and the c axis. This results in a significant reduction of the effective mass of the top valence band along the transverse ${(k}_{x}^{\ensuremath{'}})$ direction with increasing angle for both compressively and tensilely strained GaN crystals. Similar results are observed in the valence-band dispersion relations for the quantum-well (QW) structure. The dispersion curves for the QW structure also show a lifting of the Kramers degeneracy due to the piezoelectric field, which causes an asymmetry in the potential. We find that the optical matrix element of the TE polarization between the conduction (C) and heavy hole (HH) bands of the compressively strained GaN for a growth direction with $\ensuremath{\theta}&gt;~30\ifmmode^\circ\else\textdegree\fi{}$ is about twice as large as that of the (0001) orientation $(\ensuremath{\theta}=0\ifmmode^\circ\else\textdegree\fi{}).$ The piezoelectric polarizations of the compressive and tensile strains are plotted as a function of the growth direction. The crystal orientation at which a maximum polarization occurs is shown as a function of strain. In particular, the GaN crystal along the $(101\ifmmode\bar\else\textasciimacron\fi{}0)$ growth direction $(\ensuremath{\theta}=90\ifmmode^\circ\else\textdegree\fi{})$ shows zero normal piezoelectric polarization ${(P}_{z}^{\ensuremath{'}})$ for the compressive and tensile strains. These results show that crystal orientation dependence of the piezoelectric field and strain significantly affect the electronic transport properties as well as optical interband absorption properties.
Redundant role of the Syk protein tyrosine kinase in mouse NK cell differentiation. (1999)

Syk and ZAP-70 subserve nonredundant functions in B and T lymphopoiesis. In the absence of Syk, B cell development is blocked, while T cell development is arrested in the absence of ZAP-70. The receptors and the signaling molecules required for differentiation of NK cells are poorly characterized. Here we investigate the role of the Syk protein tyrosine kinase in NK cell differentiation. Hemopoietic chimeras were generated by reconstituting alymphoid (B-, T-, NK-) recombinase-activating gene-2 x common cytokine receptor gamma-chain double-mutant mice with Syk-/- fetal liver cells. The phenotypically mature Syk-/- NK cells that developed in this context were fully competent in natural cytotoxicity and in calibrating functional inhibitory receptors for MHC molecules. Syk-deficient NK cells demonstrated reduced levels of Ab-dependent cellular cytotoxicity. Nevertheless, Syk-/- NK cells could signal through NK1. 1 and 2B4 activating receptors and expressed ZAP-70 protein. We conclude that the Syk protein tyrosine kinase is not essential for murine NK cell development, and that compensatory signaling pathways (including those mediated through ZAP-70) may sustain most NK cell functions in the absence of Syk.
Association of RANTES G-403A gene polymorphism with increased risk of coronary arteriosclerosis (2004)

RANTES A-403 was associated with CAD independently from conventional risk factors and CRP or fibrinogen as inflammatory biomarkers. The association was enhanced in smokers and ACS, conditions where platelet activation and inflammation predominate. RANTES A-403 may increase genetic susceptibility to CAD.
An algorithm for protein engineering: simulations of recursive ensemble mutagenesis. (1992)

An algorithm for protein engineering, termed recursive ensemble mutagenesis, has been developed to produce diverse populations of phenotypically related mutants whose members differ in amino acid sequence. This method uses a feedback mechanism to control successive rounds of combinatorial cassette mutagenesis. Starting from partially randomized "wild-type" DNA sequences, a highly parallel search of sequence space for peptides fitting an experimenter's criteria is performed. Each iteration uses information gained from the previous rounds to search the space more efficiently. Simulations of the technique indicate that, under a variety of conditions, the algorithm can rapidly produce a diverse population of proteins fitting specific criteria. In the experimental analog, genetic selection or screening applied during recursive ensemble mutagenesis should force the evolution of an ensemble of mutants to a targeted cluster of related phenotypes.