gebhart/patrepeval huggingface dataset:
Engineered tobacco etch virus (TEV) protease active in the secretory pathway of mammalian cells (2015)

Tobacco etch virus protease (TEVp) is a unique endopeptidase with stringent substrate specificity. TEVp has been widely used as a purified protein for in vitro applications, but also as a biological tool directly expressing it in living cells. To adapt the protease to diverse applications, several TEVp mutants with different stability and enzymatic properties have been reported. Herein we describe the development of a novel engineered TEVp mutant designed to be active in the secretory pathway. While wild type TEVp targeted to the secretory pathway of mammalian cells is synthetized as an N-glycosylated and catalytically inactive enzyme, a TEVp mutant with selected mutations at two verified N-glycosylation sites and at an exposed cysteine was highly efficient. This mutant was very active in the endoplasmic reticulum (ER) of living cells and can be used as a biotechnological tool to cleave proteins within the secretory pathway. As an immediate practical application we report the expression of a complete functional monoclonal antibody expressed from a single polypeptide, which was cleaved by our TEVp mutant into the two antibody chains and secreted as an assembled and functional molecule. In addition, we show active TEVp mutants lacking auto-cleavage activity.
Artificial neural networks for early breast carcinoma detection (2002)

This paper shows a model designed for an efficient detection of patients with breast carcinoma (BC), using an artificial neural network (NN). A multilayer NN is used as a convenient modeling tool for the identification of a chosen set of risk factors and symptoms which characterizes the patients suffering from BC. We used a properly selected representative learning set of patterns referring to 60 patients for the BC identification process (the NN learning task). The other set of patterns referring to 140 patients was used as a test set for verification of the proposed model. The instructed NN successfully identified 198 test patterns, which means that identification accuracy was greater than 98%. Previously set hypothesis, which claimed that hyperspace of weight matrix enables an efficient separation of healthy group of patients from group suffering from BC, proved to be correct. Expert knowledge was used for proper selection of corresponding sets of risk factors and symptoms on one side and for selection of a representative set of learning patterns on the other side.
CD47 in the Immune Response: Role of Thrombospondin and SIRP-&#945; Reverse Signaling (2008)

The past decades have been marked by spectacular progress towards understanding how dendritic cells (DCs) interact with T cells to elicit protective immune responses to fight infectious diseases and cancer. DCs that are lying at the interface between innate and adaptive immunity, are educated in peripheral tissues prior to their journey to the secondary lymphoid organs (SLO) whereby they dictate different classes of T cell responses. Uncontrolled or unwanted inflammatory responses are the price to pay to eliminate pathogens. However, if not self-limited, they may induce collateral damages that result in chronic inflammation often associated with autoimmune disorders. CD47 and its two ligands, i.e. thrombospondin 1 (TSP-1) and SIRP-alpha, were identified as a previously unappreciated inhibitory axis of DC and T cell functions. TSP-1 is predominantly a negative regulator of DC and T cell function while basal SIRP-alpha ligation on APC by CD47 enforces tolerance. Yet, CD47/SIRP-alpha interaction positively controls DC and innate cell transendothelial migration. Due to the promiscuity of the protein interactions for CD47 and its ligands, it is quite interesting to note that deletion of the CD47 gene in mice largely agrees with the in vitro data with human cells. In fact, the well-conserved tissue distribution of CD47 and SIRP-alpha across species may facilitate the transition from bench to bedside. We thus propose CD47/TSP-1/SIRP-alpha axis as an important sensor to maintain homeostasis and regulate innate and adaptive immune responses.
Molecular Genetics of Epidermolysis Bullosa (1992)

Blisters following minor trauma characterize epidermolysis bullosa, a group of hereditary diseases of the skin. In the simplex type, epidermal basal cells are fragile, and mutations of genes encoding keratin intermediate filament proteins underlie that fragility. In the dystrophic types, the causative mutation appears to be in the gene encoding type VII collagen, which is the major component of anchoring fibrils. These recent findings afford solid evidence that at least one function of the cytoskeletal intermediate filament network is the provision of mechanical stability and that anchoring fibrils indeed do anchor the epidermis to the underlying dermis.
Reduced spatio-temporal transcoding using an intra refresh technique (2003)

This paper addresses the problem of transcoding compressed video bitstreams to reduced spatio-temporal resolutions. We propose a new technique to compensate drift error based on the principle of intra-block refresh. We also investigate other important issues related to the transcoding, such as the re-estimation of motion vectors and DCT coefficients. The rate control related to intra-refresh is also addressed. Our experimental results show that the intrarefresh method offers a good trade-off between quality and complexity in comparison to the reference method.
An Apolipoprotein E-Derived Peptide Mediates Uptake of Sterically Stabilized Liposomes into Brain Capillary Endothelial Cells (2005)

A promising strategy to solve the problems of insufficient membrane penetration of drugs and low target specificity is the localization of targeting and uptake-facilitating ligands on the surface of drug-carrier systems. This study investigated the role of a peptide derived from the LDL receptor (LDLr)-binding domain of apolipoprotein E (apoE) in initiating endocytosis in brain capillary endothelial cells. The highly cationic tandem dimer of apoE residues (141-150) was coupled covalently onto poly(ethylene glycol)-derivatized liposomes. Membrane binding and cellular uptake was monitored qualitatively by confocal-laser-scanning microscopy as well as quantitatively using a fluorescence assay. The peptide mediated an efficient, energy-dependent translocation of liposomes across the membrane of brain capillary endothelial cells. Liposomes without surface-located peptides displayed neither membrane accumulation nor cellular uptake. Low peptide affinity to LDLr and internalization of the complex into fibroblasts with up- and down-regulated receptor expression levels, as well as complex translocation into cells incubated with an antibody against the LDLr, pointed to a dominating role of an LDLr-independent transport route. Enzymatic digestion of heparan sulfate proteoglycan (HSPG) with heparinase I and addition of heparin and poly-l-lysin as competitors of HSPG and HSPG ligands, respectively, resulted in a significant loss in liposome internalization. The results suggested that HSPG played a major role in the apoE-peptide-mediated uptake of liposomes into endothelial cells of brain microvessels.
Limonene hydroperoxide analogues show specific patch test reactions (2014)

The results are in accordance with the experimental studies, as limonene-1-hydroperoxide gave more positive patch test reactions in the tested patients than limonene-2-hydroperoxide. Furthermore, the results support the specificity of the allergenic activity of the limonene hydroperoxide analogues and the importance of oxidized limonene as a cause of contact allergy.
LLVM: A compilation framework for lifelong program analysis & transformation (2004)

We describe LLVM (low level virtual machine), a compiler framework designed to support transparent, lifelong program analysis and transformation for arbitrary programs, by providing high-level information to compiler transformations at compile-time, link-time, run-time, and in idle time between runs. LLVM defines a common, low-level code representation in static single assignment (SSA) form, with several novel features: a simple, language-independent type-system that exposes the primitives commonly used to implement high-level language features; an instruction for typed address arithmetic; and a simple mechanism that can be used to implement the exception handling features of high-level languages (and setjmp/longjmp in C) uniformly and efficiently. The LLVM compiler framework and code representation together provide a combination of key capabilities that are important for practical, lifelong analysis and transformation of programs. To our knowledge, no existing compilation approach provides all these capabilities. We describe the design of the LLVM representation and compiler framework, and evaluate the design in three ways: (a) the size and effectiveness of the representation, including the type information it provides; (b) compiler performance for several interprocedural problems; and (c) illustrative examples of the benefits LLVM provides for several challenging compiler problems.
Characteristics of the surface-induced orientation for symmetric diblock PS/PMMA copolymers (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCharacteristics of the surface-induced orientation for symmetric diblock PS/PMMA copolymersThomas P. Russell, G. Coulon, V. R. Deline, and D. C. MillerCite this: Macromolecules 1989, 22, 12, 4600–4606Publication Date (Print):December 1, 1989Publication History Published online1 May 2002Published inissue 1 December 1989https://pubs.acs.org/doi/10.1021/ma00202a036https://doi.org/10.1021/ma00202a036research-articleACS PublicationsRequest reuse permissionsArticle Views2533Altmetric-Citations291LEARN 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
The RNA- and DNA-targeting CRISPR–Cas immune systems of Pyrococcus furiosus (2013)

Using the hyperthermophile Pyrococcus furiosus, we have delineated several key steps in CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) invader defence pathways. P. furiosus has seven transcriptionally active CRISPR loci that together encode a total of 200 crRNAs (CRISPR RNAs). The 27 Cas proteins in this organism represent three distinct pathways and are primarily encoded in two large gene clusters. The Cas6 protein dices CRISPR locus transcripts to generate individual invader-targeting crRNAs. The mature crRNAs include a signature sequence element (the 5' tag) derived from the CRISPR locus repeat sequence that is important for function. crRNAs are tailored into distinct species and integrated into three distinct crRNA-Cas protein complexes that are all candidate effector complexes. The complex formed by the Cmr [Cas module RAMP (repeat-associated mysterious proteins)] (subtype III-B) proteins cleaves complementary target RNAs and can be programmed to cleave novel target RNAs in a prokaryotic RNAi-like manner. Evidence suggests that the other two CRISPR-Cas systems in P. furiosus, Csa (Cas subtype Apern) (subtype I-A) and Cst (Cas subtype Tneap) (subtype I-B), target invaders at the DNA level. Studies of the CRISPR-Cas systems from P. furiosus are yielding fundamental knowledge of mechanisms of crRNA biogenesis and silencing for three of the diverse CRISPR-Cas pathways, and reveal that organisms such as P. furiosus possess an arsenal of multiple RNA-guided mechanisms to resist diverse invaders. Our knowledge of the fascinating CRISPR-Cas pathways is leading in turn to our ability to co-opt these systems for exciting new biomedical and biotechnological applications.
Defect reduction of GaAs/Si epitaxy by aspect ratio trapping (2008)

We report on the metallorganic chemical vapor deposition growth of GaAs on patterned Si (001) substrates, which utilizes the aspect ratio trapping method. It was found that when growing GaAs above the SiO2 trenched region, coalescence-induced threading dislocations and stacking faults originated on top of the GaAs/SiO2 interfaces. These defects were found to be indirectly related to the initial defect-trapping process during trenched GaAs growth. Causes of coalescence defect formation and its reduction were experimentally investigated by employing a two-step growth optimization scheme. Improvement of material quality has been characterized by cross-sectional and plan-view transmission electron microscopy and x-ray diffraction.
Development of Isomerization and Cycloisomerization with Use of a Ruthenium Hydride with N-Heterocyclic Carbene and Its Application to the Synthesis of Heterocycles (2006)

A pure ruthenium hydride complex with N-heterocyclic carbene (NHC) ligand was efficiently generated from the reaction of a second-generation Grubbs ruthenium catalyst with vinyloxytrimethylsilane and unambiguously characterized. This ruthenium hydride complex showed high catalytic activity for the selective isomerization of terminal olefin and for the cycloisomerization of 1,6-dienes. These reactions of N-allyl-o-vinylaniline lead to novel synthetic methods for heterocycles such as indoles and 3-methylene-2,3-dihydroindoles, which are useful synthons for bioactive natural products. These procedures address an important issue in diversity-oriented synthesis.
Relationship between traumatic events in childhood and chronic pain (1999)

Child traumatic events are significantly related to chronic pain. Since the problem of child abuse is broader than physical and sexual abuse, health and rehabilitation agencies must shift from individualized treatment to interdisciplinary treatment of the family and patient.
Stereochemical Requirements for the Mineralocorticoid Receptor Antagonist Activity of Dihydropyridines (2010)

A number of known 1,4-dihydropyridine CCBs were identified as having comparable potency to the steroidal MR antagonist eplerenone. Chiral resolution of mebudipine revealed that MR and CCB activity reside in opposite enantiomers. Small molecule X-ray crystal structures showed that the C4 stereochemistry of optimized selective MR analogues, e.g. 5, is consistent with MR-active mebudipine. Molecular modeling supports a binding pose consistent with that previously proposed for DHP diesters.
6×56-Gb/s mode-division multiplexed transmission over 33-km few-mode fiber enabled by 6×6 MIMO equalization (2011)

Mode-division multiplexing over 33-km few-mode fiber is investigated. It is shown that 6×6 MIMO processing can be used to almost completely compensate for crosstalk and intersymbol interference due to mode coupling in a system that transmits uncorrelated 28-GBaud QPSK signals on the six spatial and polarization modes supported by a novel few-mode fiber.
Hydrogen Production Using Sorption-Enhanced Reaction (2001)

This study examined the sorption-enhanced production of H2 via the steam−methane reforming process using a mixture of Ni-based commercial reforming catalyst and Ca-based sorbent obtained from commercial dolomite. The rates of the reforming, water−gas shift, and CO2 removal reactions are sufficiently fast that combined reaction equilibrium was closely approached, allowing for >95 mol % H2 (dry basis) to be produced in a single step. A dolomite pretreatment procedure was developed to remove sulfur, which was necessary to avoid poisoning of the reforming catalyst. The multicycle durability of the catalyst−sorbent mixture was studied as a function of regeneration temperature and gas composition using a laboratory-scale fixed-bed reactor. Twenty-five-cycle tests showed only moderate activity loss under most of the regeneration conditions studied. The primary loss in activity was associated with the inexpensive sorbent instead of the more expensive catalyst.
Distinction of virgin and memory T lymphocytes. Stable acquisition of the Pgp-1 glycoprotein concomitant with antigenic stimulation. (1987)

The Pgp-1 glycoprotein was identified on a minor (27%) subset of peripheral Lyt-2+ or L3T4+ T cells. In contrast, mature medullary-type thymocytes (Lyt-2+ L3T4-, Lyt-2- L3T4+) were nearly devoid of cells expressing detectable surface Pgp-1. The appearance of peripheral Pgp-1- T cells was found to be thymus dependent, as demonstrated by the diminished proportion of Pgp-1- T cells after thymectomy and their virtual absence in athymic nude mice. The subsequent acquisition of surface Pgp-1 was found to be a stable differentiation event occurring concomitantly with primary antigenic stimulation; selected Pgp-1- mature T cells from thymus or periphery acquired constitutive expression of Pgp-1 after stimulation in vitro with alloantigen or mitogens. These observations were extended by studies in vivo showing that immunization with various antigens augmented the percentage of Pgp-1+ spleen cells within the Lyt-2+ subset. Furthermore, the frequencies of antigen-specific CTLp, after immunization by any of three different antigens tested, were greatly enriched in the Pgp-1+ compared with the Pgp-1- subpopulations. Peritoneal exudate Lyt-2+ cells, after a localized allograft rejection, demonstrated a particularly prominent Pgp-1+ subpopulation (78%) that contained virtually all the allospecific cytolytic activity. A model consistent with all of these data proposes that mature thymocytes lacking surface Pgp-1 upon emigration to the periphery acquire its expression at the time of primary antigenic stimulation. Hence, expression of Pgp-1 among peripheral T cells is an important differentiation marker for identifying antigen-stimulated memory T cells.
Long-term safety and tolerability of asenapine: A double-blind, uncontrolled, long-term extension trial in adults with an acute manic or mixed episode associated with bipolar I disorder (2016)

ASN was generally safe and well tolerated in adults with an acute manic or mixed episode associated with bipolar I disorder.
Extended Analysis of the In Vitro Tropism of Porcine Endogenous Retrovirus (2000)

We previously reported that mitogenic activation of porcine peripheral blood mononuclear cells resulted in production of porcine endogenous retrovirus(es) (PERV[s]) capable of productively infecting human cells (C. Wilson et al., J. Virol. 72:3082-3087, 1998). We now extend that analysis to show that additional passage of isolated virus, named here PERV-NIH, through a human cell line yielded a viral population with a higher titer of infectious virus on human cells than the initial isolate. We show that in a single additional passage on a human cell line, the increase in infectivity for human cells is accounted for by selection against variants carrying pig-tropic envelope sequences (PERV-C) as well as by enrichment for replication-competent genomes. Sequence analysis of the envelope cDNA present in virions demonstrated that the envelope sequence of PERV-NIH is related to but distinct from previously reported PERV envelopes. The in vitro host range of PERV was studied in human primary cells and cell lines, as well as in cell lines from nonhuman primate and other species. This analysis reveals three patterns of susceptibility to infection among these host cells: (i) cells are resistant to infection in our assay; (ii) cells are infected by virus, as viral RNA is detected in the supernatant by reverse transcription-PCR, but the cells are not permissive to productive replication and spread; and (iii) cells are permissive to low-level productive replication. Certain cell lines were permissive for efficient productive infection and spread. These results may prove useful in designing appropriate animal models to assess the in vivo infectivity properties of PERV.
Genes coding for integration host factor are conserved in gram-negative bacteria (1991)

A genetic system for the selection of clones coding for integration host factor and HU homologs is described. We demonstrate that the himA and hip genes of Serratia marcescens and Aeromonas proteolytica can substitute for the Escherichia coli genes in a variety of biological assays. We find that the sequence and genetic organization of the himA and hip genes of S. marcescens are highly conserved.
Simplified amino acid alphabets for protein fold recognition and implications for folding (2000)

Protein design experiments have shown that the use of specific subsets of amino acids can produce foldable proteins. This prompts the question of whether there is a minimal amino acid alphabet which could be used to fold all proteins. In this work we make an analogy between sequence patterns which produce foldable sequences and those which make it possible to detect structural homologs by aligning sequences, and use it to suggest the possible size of such a reduced alphabet. We estimate that reduced alphabets containing 10-12 letters can be used to design foldable sequences for a large number of protein families. This estimate is based on the observation that there is little loss of the information necessary to pick out structural homologs in a clustered protein sequence database when a suitable reduction of the amino acid alphabet from 20 to 10 letters is made, but that this information is rapidly degraded when further reductions in the alphabet are made.
Advancement flap plasty for the closure of anal and recto-vaginal fistulas in Crohn's disease. (2001)

The management of anal fistulas in patients with IBD continues to be extremely challenging and, indeed, somewhat frustrating. Despite a global closure rate of about 75%, all patients should be informed about the risk of infection, early failure, eventual temporary disfunctioning stoma and the possibility of late recurrence (about 15%). Closure of a RVF in Crohn's disease should not be considered an easy undertaking, especially in patients with several Crohn localisations. The technique can be adapted to the local situation. Construction of a temporary stoma is not mandatory. However, stoma construction seems to be beneficial when extensive perianal or recto-vaginal dissection including eventual tissue interposition is required. Advancement flaps are an attractive surgical alternative for the management of all anal transsphincteric fistulas, also in Crohn's disease, because sphincter architecture and function are well preserved. Improved medical treatment and the changed approach from conservative to reparative surgery may well have resulted in a decreased need or at least in a delay of the need for a proctectomy. Although the surgical principles of advancement flap techniques are sound, these techniques have not been used for many decades. Skills needed, problematic approach, suboptimal quality of local tissues have contributed to its selective use and to the absence of prospective randomised studies.