gebhart/patrepeval huggingface dataset:
The role of interferons in the management of carcinoid tumours (1991)

Malignant carcinoid tumours with the carcinoid syndrome has over the years presented a therapeutic challenge. The patients might not only die from tumour progression but also from symptoms relating to hormone overproduction and the specific cardiac disease, e.g. right heart fibrosis and failure. Surgery has been the treatment of choice in local disease, but when liver metastases have developed other treatment procedures must be considered. Conventional chemotherapy has been of little beneficial value, with response rates of only 10-30%, whereas a new somatostatin analogue, octreotid, is effective in controlling clinical symptoms but not tumour progression. Interferon treatment was introduced in 1982 by our group, and we are now presenting treatment results of 130 patients with histologically verified malignant carcinoid tumours and liver metastases. One hundred and eleven patients were treated with a median dose of 6 mega units (MU) of interferon alpha, five times weekly (dose range 3-9 MU), whereas 29 patients received conventional chemotherapy. Forty-seven out of 111 patients (42%) treated with interferon alpha demonstrated a significant biochemical response and 15% demonstrated more than 50% reduction in tumour size. In another 43 (39%) patients stabilization of the carcinoid disease have been noted, whereas 21 (19%) showed progressive disease. The median duration of response was 34 months. Subjective responses with improvement of diarrhoea, flush and/or bronchoconstriction were noticed in 76 patients (68%). The 19 patients treated with chemotherapy demonstrated only 10% biochemical response, lasting for only 3-5 months. The survival analysis demonstrates a median survival of only 8 months in the group of patients treated with chemotherapy, compared to 80+ months (P less than 0.001) in the groups treated with interferon alpha. Interferon adverse reactions of fatigue, weight loss and anaemia were manageable. Neutralizing interferon antibodies were documented in 5-15% of the patients. Interferon alphas are active in patients with malignant carcinoid tumours. Clinical symptoms are significantly reduced following reduction of circulating hormones. Interferon might also have an impact on survival in this group of patients. The side-effects are moderate and managed by dose adjustments.
Cutaneous lupus erythematosus: Understanding of clinical features, genetic basis, and pathobiology of disease guides therapeutic strategies (2006)

Cutaneous features of the protean disease lupus erythematous (LE) constitute 4 of 11 diagnostic criteria for systemic lupus erythematosus (SLE) and are exhibited by approximately 3/4 of patients during the course of their disease. Because the pathogenesis of LE is multifactorial and polygenic, many of the details of the pathogenesis remain unclear. We review here the clinical features of cutaneous lupus and recent genetic data that elucidate potential candidate genes for both cutaneous lupus erythematosus (CLE) and SLE. We discuss advances in elucidating the autoimmune pathogenesis of CLE and SLE. Furthermore, promising experimental therapies based on these advances are reviewed in the context of B cell directed therapies, T cell directed therapies, disruption of B and T cell interactions, cytokine directed therapies and finally, end-effector targeted therapies.
Determining semantic similarity among entity classes from different ontologies (2003)

Semantic similarity measures play an important role in information retrieval and information integration. Traditional approaches to modeling semantic similarity compute the semantic distance between definitions within a single ontology. This single ontology is either a domain-independent ontology or the result of the integration of existing ontologies. We present an approach to computing semantic similarity that relaxes the requirement of a single ontology and accounts for differences in the levels of explicitness and formalization of the different ontology specifications. A similarity function determines similar entity classes by using a matching process over synonym sets, semantic neighborhoods, and distinguishing features that are classified into parts, functions, and attributes. Experimental results with different ontologies indicate that the model gives good results when ontologies have complete and detailed representations of entity classes. While the combination of word matching and semantic neighborhood matching is adequate for detecting equivalent entity classes, feature matching allows us to discriminate among similar, but not necessarily equivalent entity classes.
The reaction of heparin with proteins and complex bases (1943)

Research Article| July 01 1943 The reaction of heparin with proteins and complex bases L. B. Jaques L. B. Jaques 1The Department of Physiology, University of Toronto Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1943) 37 (2): 189–195. https://doi.org/10.1042/bj0370189 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation L. B. Jaques; The reaction of heparin with proteins and complex bases. Biochem J 1 July 1943; 37 (2): 189–195. doi: https://doi.org/10.1042/bj0370189 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1943 CAMBRIDGE UNIVERSITY PRESS1943 Article PDF first page preview Close Modal You do not currently have access to this content.
Three-dimensional structure of baculovirus-expressed Norwalk virus capsids (1994)

The three-dimensional structure of the baculovirus-expressed Norwalk virus capsid has been determined to a resolution of 2.2 nm using electron cryomicroscopy and computer image processing techniques. The empty capsid, 38.0 nm in diameter, exhibits T = 3 icosahedral symmetry and is composed of 90 dimers of the capsid protein. The striking features of the capsid structure are arch-like capsomeres, at the local and strict 2-fold axes, formed by dimers of the capsid protein and large hollows at the icosahedral 5- and 3-fold axes. Despite its distinctive architecture, the Norwalk virus capsid has several similarities with the structures of T = 3 single-stranded RNA (ssRNA) viruses. The structure of the protein subunit appears to be modular with three distinct domains: the distal globular domain (P2) that appears bilobed, a central stem domain (P1), and a lower shell domain (S). The distal domains of the 2-fold related subunits interact with each other to form the top of the arch. The lower domains of the adjacent subunits associate tightly to form a continuous shell between the radii of 11.0 and 15.0 nm. No significant mass density is observed below the radius of 11.0 mm. It is suspected that the hinge peptide in the adjoining region between the central domain and the shell domain may facilitate the subunits adapting to various quasi-equivalent environments. Architectural similarities between the Norwalk virus capsid and the other ssRNA viruses have suggested a possible domain organization along the primary sequence of the Norwalk virus capsid protein. It is suggested that the N-terminal 250 residues constitute the lower shell domain (S) with an eight-strand beta-barrel structure and that the C-terminal residues beyond 250 constitute the protruding (P1+P2) domains. A lack of an N-terminal basic region and the ability of the Norwalk virus capsid protein to form empty T = 3 shells suggest that the assembly pathway and the RNA packing mechanisms may be different from those proposed for tomato bushy stunt virus and southern bean mosaic virus but similar to that in tymoviruses and comoviruses.
Use of DNA immobilized on plastic and agarose supports to detect DNA by sandwich hybridization. (1985)

Cloned Salmonella DNA, which has been immobilized irreversibly on plastic and agarose solid supports, can form hybrids in both single-layer and "sandwich" hybridization protocols. In single-layer hybridization, 3 micrograms of immobilized DNA bound at least 30 fmol of a specific 800-base DNA sequence (equivalent to 8.5 ng, or the amount of that sequence present in 4 X 10(10) organisms). In a 4-h sandwich hybridization protocol, as little as 14 amol (equivalent to 8 pg, or the amount of that sequence present in 1 X 10(7) organisms) of a 1600-base sequence of DNA could be detected. The methods described should be applicable to use with any set of probes--not just from Salmonella--that fulfill the criteria specified. The ability to perform DNA hybridizations on solid-phase matrices such as those used for immunoassay should bring DNA hybridization into the realm of routine clinical laboratory procedures.
Oncogenic role of miR‐17‐92 cluster in anaplastic thyroid cancer cells (2008)

Micro RNAs (miRNAs) are non-coding small RNAs and constitute a novel class of negative gene regulators that are found in both plants and animals. Several miRNAs play crucial roles in cancer cell growth. To identify miRNAs specifically deregulated in anaplastic thyroid cancer (ATC) cells, we performed a comprehensive analysis of miRNA expressions in ARO cells and primary thyrocytes using miRNA microarrays. MiRNAs in a miR-17-92 cluster were overexpressed in ARO cells. We confirmed the overexpression of those miRNAs by Northern blot analysis in ARO and FRO cells. In 3 of 6 clinical ATC samples, miR-17-3p and miR-17-5p were robustly overexpressed in cancer lesions compared to adjacent normal tissue. To investigate the functional role of these miRNAs in ATC cells, ARO and FRO cells were transfected with miRNA inhibitors, antisense oligonucleotides containing locked nucleic acids. Suppression of miR-17-3p caused complete growth arrest, presumably due to caspase activation resulting in apoptosis. MiR-17-5p or miR-19a inhibitor also induced strong growth reduction, but only miR-17-5p inhibitor led to cellular senescence. On the other hand, miR-18a inhibitor only moderately attenuated the cell growth. Thus, we have clarified functional differences among the members of the cluster in ATC cells. In conclusion, these findings suggest that the miR-17-92 cluster plays an important role in certain types of ATCs and could be a novel target for ATC treatment.
Electron-transfer kinetics of zinc-substituted cytochrome c and its Ru(NH3)5(histidine-33) derivative (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElectron-transfer kinetics of zinc-substituted cytochrome c and its Ru(NH3)5(histidine-33) derivativeHorst. Elias, Mei H. Chou, and Jay R. WinklerCite this: J. Am. Chem. Soc. 1988, 110, 2, 429–434Publication Date (Print):January 1, 1988Publication History Published online1 May 2002Published inissue 1 January 1988https://pubs.acs.org/doi/10.1021/ja00210a019https://doi.org/10.1021/ja00210a019research-articleACS PublicationsRequest reuse permissionsArticle Views285Altmetric-Citations59LEARN 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 Get e-Alerts
Description of an Advantageous Optical Label-Free Biosensing Interferometric Read-Out Method to Measure Biological Species (2014)

In this article we report a new, simple, and reliable optical read-out detection method able to assess Rotavirus present in human sera as well as in the viral pollution sources. It is based on the interference of two interferometers used as biophotonic transducers. The method significantly improves the optical label-free biosensing response measuring both, the concentration of the AgR and its corresponding size. Two different immunoassays were carried out: Bovine Serum Albumin (BSA), and the recognition by its antibody (anti-BSA); and Rotavirus (AgR) and the recognition by its antibody (anti-AgR). In the cases studied, and using as model interferometer a simple Fabry-Perot transducer, we demonstrate a biosensing enhancement of two orders of magnitude in the Limit of Detection (LoD). In fact, this read-out optical method may have significant implications to enhance other optical label-free photonic transducers reported in the scientific literature.
Identification of the antigens predominantly reacted with serum from patients with hepatocellular carcinoma (2003)

Disease specific humoral immune response against TBP-1, p27(BBP), and rpL30 was induced in patients with HCC, and the antibodies against these antigens also may be used as tumor markers.
CAR-MODIFIED T CELLS CAPABLE OF DISTINGUISHING NORMAL CELLS FROM MALIGNANT CELLS (2014)

T cells can be redirected to target tumor-associated antigen (TAA) by genetic modification to express a chimeric antigen receptor (CAR), which fuses the specificity derived from an antibody to T-cell activation domains to result in lysis of TAA-expressing cells. Due to the potential for on-target, off-tissue toxicity, CAR+ T-cell therapy is currently limited to unique or lineage-restricted TAAs. Glioblastoma, a grade IV brain malignancy, overexpresses epidermal growth factor receptor (EGFR) in 40-50% of patients. EGFR also has widespread normal tissue expression. To target EGFR on glioblastoma while reducing the potential for normal tissue toxicity, EGFR-specific CAR generated from cetuximab, Cetux-CAR, was transiently expressed in T cells by RNA-modification. RNA-modified CAR+ T cells demonstrated similar cytotoxicity against EGFR+ cells, including normal renal cells, as DNA-modified CAR+ T cells. However, RNA-modified T cells lost CAR expression over time, concomitant with loss of functional specificity to EGFR. Transient expression of CAR limits potential for off-tissue toxicity at the expense of anti-tumor activity, and does not protect normal tissue from immediate toxicity. Recognizing that EGFR is overexpressed at a higher density on glioblastoma relative to normal tissue, we generated an EGFR-specific CAR from nimotuzumab, an EGFR-specific antibody with reduced binding to low density EGFR. While Cetux-CAR+ T cells produced cytokine and mediated lysis independent of EGFR density, function of Nimo-CAR+ T cells directly correlated with the EGFR density of targets, with reduced activity in response to low density EGFR, but equivalent activity in response to high density EGFR relative to Cetux-CAR+ T cells. Cetux-CAR+ T cells and Nimo-CAR+ T cells demonstrated equivalent control of intracranial glioma xenograft with intermediate EGFR density, but only Cetux-CAR+ T cells controlled xenografts with low EGFR density. In sum, transient expression of CAR has the potential to reduce long-term toxicity to normal tissue, but at the expense of anti-tumor activity. Rational design of CAR based on an antibody with reduced binding to low density EGFR generated EGFR-specific CAR able to tune T-cell function to antigen density resulting in discrimination of high EGFR density on malignant cells from low EGFR density on normal tissue.
Nanoparticle shape, thermodynamics and kinetics (2016)

Nanoparticles can be beautiful, as in stained glass windows, or they can be ugly as in wear and corrosion debris from implants. We estimate that there will be about 70,000 papers in 2015 with nanoparticles as a keyword, but only one in thirteen uses the nanoparticle shape as an additional keyword and research focus, and only one in two hundred has thermodynamics. Methods for synthesizing nanoparticles have exploded over the last decade, but our understanding of how and why they take their forms has not progressed as fast. This topical review attempts to take a critical snapshot of the current understanding, focusing more on methods to predict than a purely synthetic or descriptive approach. We look at models and themes which are largely independent of the exact synthetic method whether it is deposition, gas-phase condensation, solution based or hydrothermal synthesis. Elements are old dating back to the beginning of the 20th century-some of the pioneering models developed then are still relevant today. Others are newer, a merging of older concepts such as kinetic-Wulff constructions with methods to understand minimum energy shapes for particles with twins. Overall we find that while there are still many unknowns, the broad framework of understanding and predicting the structure of nanoparticles via diverse Wulff constructions, either thermodynamic, local minima or kinetic has been exceedingly successful. However, the field is still developing and there remain many unknowns and new avenues for research, a few of these being suggested towards the end of the review.
Effect of Hydrogen on p-Type Epitaxial Silicon Sheet-Resistance Measurements (1999)

The hydrogen ambient used during growth of epitaxial silicon layers can leave substantial amounts of adsorbed hydrogen on the surface, leading to a low initial surface potential. As the hydrogen is lost and the surface oxidizes, the surface potential increases, decreasing the conducting thickness of the epitaxial layer and increasing the measured sheet resistance. The surface potential and sheet resistance change rapidly for about one day and approach steady state after several days. ©1998 The Electrochemical Society
Highly Parallel Surface Reconstruction (2008)

We present a parallel surface reconstruction algorithm that runs entirely on the GPU. Like existing implicit surface reconstruction methods, our algorithm first builds an octree for the given set of oriented points, then computes an implicit function over the space of the octree, and finally extracts an isosurface as a water-tight triangle mesh. A key component of our algorithm is a novel technique for octree construction on the GPU. This technique builds octrees in real-time and uses level-order traversals to exploit the fine-grained parallelism of the GPU. Moreover, the technique produces octrees that provide fast access to the neighborhood information of each octree node, which is critical for fast GPU surface reconstruction. With an octree so constructed, our GPU algorithm performs Poisson surface reconstruction, which produces high quality surfaces through a global optimization. Given a set of 500K points, our algorithm runs at the rate of about five frames per second, which is over two orders of magnitude faster than previous CPU algorithms. To demonstrate the potential of our algorithm, we propose a userguided surface reconstruction technique which reduces the topological ambiguity and improves reconstruction results for imperfect scan data. We also show how to use our algorithm to perform onthe-fly conversion from dynamic point clouds to surfaces.
Proteins Specified by Herpes Simplex Virus XI. Identification and Relative Molar Rates of Synthesis of Structural and Nonstructural Herpes Virus Polypeptides in the Infected Cell (1973)

Analyses of polypeptides made in HEp-2 cells infected with herpes simplex virus type 1 by high-resolution polyacrylamide gel electrophoresis revealed the synthesis of at least 49 infected cell polypeptides (ICP) ranging in molecular weight from 15,000 to 280,000. Evidence for virus specificity based on increased rates of synthesis postinfection, immunological specificity, and viral control of mobility and rate of synthesis was available for 47 of the ICP. These 47 polypeptides can account for 75% of the virus genetic information assuming a DNA molecular weight of 10(8) and asymmetric transcription. On the basis of their mobility relative to virion proteins, the ICP were classified as structural (S, 23 polypeptides), nonstructural (NS, 16 polypeptides), and unassigned (U, 10 polypeptides). Analysis of the synthesis of the ICP revealed the following. (i) Rapid posttranslational cleavages of HSV proteins were not detected; in parallel experiments rapid posttranslational cleavages were readily demonstrated in poliovirus-infected cells and these were blocked by protease inhibitors. (ii) Slow posttranslational changes in the mobility of at least two polypeptides were observed. (iii) Analysis of the rates of synthesis of ICP examined at four intervals postinfection revealed regulation of the pattern and amount of ICP synthesized. ICP formed six classes (A to F) differing in their kinetics of synthesis. S and NS ICP were distributed nonrandomly among these classes. Thus, of the sum of S protein amino acid sequences apportioned among these kinetic classes, 47%, constituting class A and comprising "late" structural proteins, were characterized by progressively increasing rates of synthesis until at least 12 h postinfection; whereas "early" structural proteins constituting class C, amounting to 31% of the total amino acid sequences, were synthesized with initially increasing rates until 4 h postinfection and with declining rates thereafter. NS polypeptides and remaining S polypeptides were distributed among the other kinetic classes-B, D, E, and F. Control of protein abundance was evident in that the polypeptides were not made in equimolar amounts. However, S and NS polypeptides could not be differentiated on the basis of their molar rates of synthesis. The bulk of the detected polypeptides did not differ by more than eightfold in their molar rates of synthesis.
B7.2 provides co‐stimulatory functions in vivo in response to staphylococcal enterotoxin B (1995)

Excessive T cell activation induced by bacterial superantigens plays an important role in the pathology associated with Gram-positive bacteremia. To gain insight into the early phases of T cell activation by bacterial enterotoxins in vivo, we investigated the ability of antibodies to well-defined co-stimulatory molecules to inhibit T cell activation and the subsequent toxic shock syndrome induced in BALB/c mice following the injection of staphylococcal enterotoxin B (SEB). We demonstrate here that a single dose of anti-B7.2 antibodies, but not anti-B7.1 antibodies, significantly inhibits T cell activation, as judged by lower systemic IL-2 release, blastogenesis and IL-2 receptor expression, and reduces the lethal effect of SEB in D-galactosamine-sensitized mice. These results demonstrate that co-stimulation through the B7.2 molecule plays an important role in the activation of T cells in response to SEB in vivo and suggest alternative therapies for septic shock caused by bacterial enterotoxins based on blocking antibodies to co-stimulatory molecules.