gebhart/patrepeval huggingface dataset:
Anthracycline cardiomyopathy monitored by morphologic changes. (1978)

Seventy-six endomyocardial biopsies obtained from 60 patients receiving adriamycin (ADM) and other anthracycline analogs were studied. The biopsies were studied by light and electron microscopy. Two main types of myocyte degeneration were consistently present, the lesions were focal, and inflammatory infiltrate was absent. The severity of pathologic changes was graded on a scale from 0 (normal) to 3 (marked abnormality). Twelve patients receiving previous mediastinal irradiation (600-5700 rads) showed a mean pathology grade (2.0 +/- 0.89) that was significantly higher than in those patients receiving a comparable dose of ADM but who were not irradiated (1.18 +/- 0.23) (P less than 0.01). This study indicated that radiation, even if remote, enhances ADM-induced cardiotoxicity and evokes a "recall" phenomenon of latent acute irradiation changes. Our data suggest that a specific, progressive, subclinical injury to the heart occurs with anthracycline therapy that cannot be detected reliably by conventional tests. Anthracycline-induced cardiotoxicity in rabbits, monkeys, and dogs shows the same basic cellular lesions as in man. The analogs, adria-DNA and rubidazone, also show lesions similar to those produced by ADM in the human heart. The endomyocardial biopsy is a reliable method for monitoring cardiac damage due to anthracyclines in man.
Wnt pathway reprogramming during human embryonal carcinoma differentiation and potential for therapeutic targeting (2009)

During induced differentiation of human EC cells, the Wnt signalling pathway is reprogrammed and canonical Wnt signalling induced. Specific species regulating non-canonical Wnt signalling conferred growth inhibition when targeted for repression in these EC cells. Notably, FZD7 repression significantly inhibited growth of human EC cells and is a promising therapeutic target for TGCTs.
Antigen‐driven tissue‐specific suppression following oral tolerance: Orally administered myelin basic protein suppresses proteolipid protein‐induced experimental autoimmune encephalomyelitis in the SJL mouse (1994)

Immunomodulatory treatment paradigms have been applied to animal models of T cell-mediated autoimmune diseases in an attempt to develop an immunospecific and non-toxic form of therapy which can be applied to humans. These treatment paradigms are often directed to T cells with a restricted T cell receptor repertoire or that react with dominant peptide determinants. Experimental data, however, suggests that even if the initial T cell response is restricted to a specific self-protein in the target organ, spreading autoimmunity may develop with broadening of T cell autoreactivity to additional epitopes of the same autoantigen or to different autoantigens in the target organ. Thus, multiple autoantigens may become targets of the autoimmune response. This makes immunotherapeutic strategies based on suppressing responses to restricted proteins or clones of cells problematic. We have previously shown that suppression of experimental autoimmune encephalomyelitis (EAE) in the Lewis rat by oral myelin basic protein (MBP) is mediated by the release of transforming growth factor-beta after triggering by the oral tolerogen. Here, we report that in the SJL model of EAE oral administration of an autoantigen from the target tissue suppresses disease independent of whether it is or is not the inciting antigen. Thus, orally administered MBP or MBP peptides suppress proteolipid protein (PLP)-induced EAE, whereas intravenously administered MBP does not. Both oral and intravenous PLP, however, suppressed PLP disease. These findings have important implications for the use of oral tolerance as a therapeutic approach for the treatment of T cell-mediated inflammatory autoimmune diseases in man in which the inciting autoantigen is unknown or in which there is autoreactivity to multiple autoantigens in the target tissue.
Ordered activation of the Ig lambda locus in Abelson B cell lines. (1988)

Derivatives of the mu-producing Abelson line P8 have been analyzed for L chain gene rearrangements. Two of seven clones studied assembled their V lambda genes while growing in culture. V lambda gene rearrangements occurred only in those Abelson subclones that either were rearranging or had rearranged their recombining sequence (RS) element on both Ig kappa alleles. Our data suggest that (a) RS rearrangements are preferentially initiated in kappa- pre-B cells; and (b) the deletion or inactivation of sequences lying between J kappa and RS is a requirement for the activation of the Ig lambda locus.
Endothelial-leukocyte adhesive interactions in inflammatory diseases. (1993)

There is evidence that vascular endothelium directs the accumulation of leukocytes in inflammation through various means, particularly by the expression of specific cell surface molecules which are adhesive for ligands on circulating leukocytes. Examples of such molecules are E-selectin and intercellular adhesion molecule 1 (ICAM-1). In an experimental model of various forms of inflammation, E-selectin and ICAM-I were induced in association with adhesion and emigration of circulating polymorphonuclear and mononuclear leukocytes. Further work in humans showed endothelium to express E-selectin in inflammation. In addition, the presence of a leukocyte ligand for E-selectin, sialyl-Lewis X, has been seen on cells accumulating in inflammation. Furthermore, sialyl-Lewis X was also unexpectedly seen on endothelium. The role of sialyl-Lewis X on endothelium is as yet uncertain, although it may function as an adhesion receptor for leukocytes. Other endothelial adhesion receptors, such as vascular cell adhesion molecule 1 (VCAM-1), are described. Atherosclerosis shows many features in common with inflammation. These are discussed, and the demonstrated and potential relevance of endothelial adhesive phenomena in routine inflammation to those in atherosclerosis are reviewed. For example, a VCAM-1 homologue has been described on the endothelium over evolving atherosclerotic lesions in rabbits.
Photonic wavelength-division and time-division hybrid switching networks for large line-capacity broadband switching systems (2003)

It is shown that the multiplexity of hybrid switching networks, which is given by the product of wavelength-division multiplexity and time-division multiplexity, is sufficient to allow fabrication of large-line-capacity broadband switching systems. It is suggested that the achievement of eight wavelength-division multiplexity and eight time-division multiplexity for 150-Mb/s signals is a reasonable short-range, objective considering current semiconductor optical device technology. It is shown that a proposed 4096-line four-state junctor network for a 150-Mb/s channel has inherent advantages, providing more compact hardware and fewer optical fiber connections than conventional electronic/photonic broadband switching networks.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Ubiquitin and SUMO signalling in DNA repair (2010)

The repair of lesions and gaps in DNA follows different pathways, each mediated by specific proteins and complexes. Post-translational modifications in many of these proteins govern their activities and interactions, ultimately determining whether a particular pathway is followed. Prominent among these modifications are the addition of phosphate or ubiquitin (and ubiquitin-like) moieties that confer new binding surfaces and conformational states on the modified proteins. The present review summarizes some of consequences of ubiquitin and ubiquitin-like modifications and interactions that regulate nucleotide excision repair, translesion synthesis, double-strand break repair and interstrand cross-link repair, with the discussion of relevant examples in each pathway.
Addressable Microfluidic Polymer Chip for DNA‐Directed Immobilization of Oligonucleotide‐Tagged Compounds (2009)

A microfluidic polymer chip for the self-assembly of DNA conjugates through DNA-directed immobilization is developed. The chip is fabricated from two parts, one of which contains a microfluidic channel produced from poly(dimethylsiloxane) (PDMS) by replica-casting technique using a mold prepared by photolithographic techniques. The microfluidic part is sealed by covalent bonding with a chemically activated glass slide containing a DNA oligonucleotide microarray. The dimension of the PDMS-glass microfluidic chip is equivalent to standard microscope slides (76 x 26 mm(2)). The DNA microarray surface inside the microfluidic channels is configured through conventional spotting, and the resulting DNA patches can be conveniently addressed with compounds containing complementary DNA tags. To demonstrate the utility of the addressable surface within the microfluidic channel, DNA-directed immobilization (DDI) of DNA-modified gold nanoparticles (AuNPs) and DNA-conjugates of the enzymes glucose oxidase (GOx) and horseradish peroxidase (HRP) are carried out. DDI of AuNPs is used to demonstrate site selectivity and reversibility of the surface-modification process. In the case of the DNA-enzyme conjugates, the patterned assembly of the two enzymes allows the establishment and investigation of the coupled reaction of GOx and HRP, with particular emphasis on surface coverage and lateral flow rates. The results demonstrate that this addressable chip is well suited for the generation of fluidically coupled multi-enzyme microreactors.
Toward Detection and Localization of Instruments in Minimally Invasive Surgery (2012)

Methods for detecting and localizing surgical instruments in laparoscopic images are an important element of advanced robotic and computer-assisted interventions. Robotic joint encoders and sensors integrated or mounted on the instrument can provide information about the tool's position, but this often has inaccuracy when transferred to the surgeon's point of view. Vision sensors are currently a promising approach for determining the position of instruments in the coordinate frame of the surgical camera. In this study, we propose a vision algorithm for localizing the instrument's pose in 3-D leaving only rotation in the axis of the tool's shaft as an ambiguity. We propose a probabilistic supervised classification method to detect pixels in laparoscopic images that belong to surgical tools. We then use the classifier output to initialize an energy minimization algorithm for estimating the pose of a prior 3-D model of the instrument within a level set framework. We show that the proposed method is robust against noise using simulated data and we perform quantitative validation of the algorithm compared to ground truth obtained using an optical tracker. Finally, we demonstrate the practical application of the technique on in vivo data from minimally invasive surgery with traditional laparoscopic and robotic instruments.
Increased Immunogenicity of an Anchor-Modified Tumor-Associated Antigen Is Due to the Enhanced Stability of the Peptide/MHC Complex: Implications for Vaccine Design (2005)

The use of "anchor-fixed" altered peptide ligands is of considerable interest in the development of therapeutic vaccines for cancer and infectious diseases, but the mechanism by which successful altered peptide ligands elicit enhanced immunity is unclear. In this study, we have determined the crystallographic structure of a major tumor rejection Ag, gp100(209-217), in complex with the HLA-A*0201 (HLA-A2) molecule, as well as the structure of a modified version of the peptide which substitutes methionine for threonine at position 2 (T2M; gp100(209-2M)). The T2M-modified peptide, which is more immunogenic in vitro and in vivo, binds HLA-A2 with a approximately 9-fold greater affinity and has a approximately 7-fold slower dissociation rate at physiological temperature. Within the limit of the crystallographic data, the T2M substitution does not alter the structure of the peptide/HLA-A2 complex. Consistent with this finding, in peripheral blood from 95 human subjects, we were unable to identify higher frequencies of T cells specific for either the native or modified peptide. These data strongly support the conclusion that the greater immunogenicity of the gp100(209-2M) peptide is due to the enhanced stability of the peptide/MHC complex, validating the anchor-fixing approach for generating therapeutic vaccine candidates. Thermodynamic data suggest that the enhanced stability of the T2M-modified peptide/HLA-A2 complex is attributable to the increased hydrophobicity of the modified peptide, but the gain due to hydrophobicity is offset considerably by the loss of a hydrogen bond made by the native peptide to the HLA-A2 molecule. Our findings have broad implications for the optimization of current vaccine-design strategies.
Gene Therapy for Central Nervous System Injury: The Use of Cationic Liposomes: An Invited Review (1997)

This paper briefly reviews general principles of gene therapy with emphasis on the therapeutic potential of cationic liposome-mediated neurotrophin gene transfer to treat central nervous system (CNS) injury. Current developments in studies of gene therapy for CNS injury are both impressive and promising. Ex vivo gene transfer into the CNS is relatively mature in animal studies following more than a decade of experimental studies. In vivo gene transfer into the CNS has gained more attention recently. Although progress has been made using viral vectors, rapid advances in transfection technologies employing cationic liposomes, together with the relatively low toxicity of these nonviral vector systems, suggest that liposomes may have significant potential for clinical applications. Although many investigators have recognized that gene therapy may be useful for treatment of certain genetic defect diseases or cancer, gene therapy for CNS injury is relatively novel. In contrast to genetic defect disorders, temporary induction of transgenes may have therapeutic applications for CNS injuries such as stroke and trauma. Employing gene transfer techniques to achieve therapeutically useful levels of expression of neurotrophins in the CNS could provide a new strategy for treatment of the traumatically injured CNS.
Blautia faecis sp. nov., isolated from human faeces (2012)

A strictly anoxic, Gram-stain-positive, non-motile Blautia-like bacterium, designated strain M25(T), was isolated from a human faecal sample. Strain M25(T) was negative for both catalase and oxidase activity, utilized carbohydrates as fermentable substrates, produced lactate and acetate as the major end products of glucose fermentation in PYG medium, and had a DNA G+C content of 41.6 mol%. Comparative 16S rRNA gene sequencing showed that strain M25(T) was closely related to Ruminococcus obeum ATCC 29174(T) (96.40 % 16S rRNA gene sequence similarity) and Blautia glucerasea HFTH-1(T) (96.17 %) within the family Lachnospiraceae. Straight-chain saturated and monounsaturated cellular fatty acids were also detected, the majority being C(14 : 0), C(16 : 0) and C(16 : 0) dimethyl acetal acids. Based on the phenotypic, genotypic and phylogenetic characteristics presented in this study, strain M25(T) represents a novel species within the genus Blautia for which the name Blautia faecis sp. nov. is proposed. The type strain is M25(T) ( = KCTC 5980(T) = JCM 17205(T)).
Use of topical negative pressure therapy in postoperative dehisced or infected wounds (2004)

The management of acute postoperative infected and dehisced wounds varies across the UK. Options include saline-soaked gauze, alginate or hydrofibre dressings, and, more recently, topical negative pressure (TNP). Use of TNP has risen in popularity over the past five years or so, although its justification has primarily been driven by anecdotal evidence and case studies1 rather than by primary research.
A glypican-3-derived peptide vaccine against hepatocellular carcinoma (2012)

The results of a Phase I clinical trial in which a glypican-3 (GPC3)-derived peptide was tested in advanced hepatocellular carcinoma patients point to a strong correlation between immunological and clinical responses. This commentary reviews our fundamental studies and clinical trials on the GPC3-derived peptide vaccine.
Pro-drugs: An Overview and Definition (1975)

Historically the term pro-drug was first introduced by Albert (1,2) who used the word "pro-drug" or "pro-agent" to describe compounds which undergo biotransformation prior to exhibiting their pharmacological effects. Albert suggested that this concept could be used for many different purposes. For example, in his book "Selective Toxicity" (2) he mentions that "as a means of introducing selectivity into toxicity, the principle of latent activity has endless possibilities." Albert himself points out that the pro-drug approach is not new. Methenamine (I) and aspirin (II), both synthesized in the late nineteenth century, are examples of bioreversible derivatives of formaldehyde and salicylic acid respectively. Use of salicylic acid as an analgesic and anti-inflammatory agent was somewhat limited by its corrosiveness which was in part overcome with the use of II. Formaldehyde, although a useful topical antiseptic, could not be used orally as a urinary tract antiseptic until it was converted to I
ChemInform Abstract: THE STRUCTURE OF SOME REACTION PRODUCTS OF 2,3‐DIHYDROPHENALENE‐1,2,3‐TRIONE WITH UREA AND ITS HOMOLOGS (1978)

Abstract Das Phenalentrion (I) reagiert mit den Harnstoffen (II) zu den Spiro‐acenaphthenimidazolidindionen (III), deren Struktur durch 1 H‐NMR bestimmt wird.
Detection of human faces using decision trees (2002)

The paper proposes a novel algorithm for face detection using decision trees (DT) and shows its generality and feasibility using a database consisting of 2340 face images from the FERET database (corresponding to 817 subjects and including 190 sets of duplicates) over a semi-uniform background. The approach used for face detection involves three main stages, those of location, cropping, and post-processing. The first stage finds a rough approximation for the possible location of the face box, the second stage will refine it, and the last stage decider whether a face is present in the image and if the answer is positive would normalize the face image. The algorithm does not require multiple (scale) templates and the accuracy achieved is 96%. Accuracy is based on the visual observation that the face box includes both eyes, nose, and mouth, and that the top side of the box is below the hairline. Experiments were also performed to assess the accuracy of the algorithm in rejecting images where no face is present. Using a small database of 25 images of various but complex backgrounds the algorithm failed on two images for an overall accuracy rate of 92%.
Inhibition of Antigen-induced Eosinophilia and Airway Hyperresponsiveness by Antisense Oligonucleotides Directed against the Common β Chain of IL-3, IL-5, GM-CSF Receptors in a Rat Model of Allergic Asthma (2002)

Airway obstruction, hyperresponsiveness, and the accumulation and persistence within the airways of inflammatory cells characterize asthma. Interleukin (IL)-3, granulocyte macrophage colony- stimulating factor (GM-CSF), and IL-5 are among several cytokines that have been shown to be increased in asthma and to contribute to atopic inflammation. They mediate their effect via receptors that have a common beta subunit (beta(c)). We hypothesized that blocking of this common beta(c) would impair the airway response to antigen. We report that an antisense (AS) phosphorothioate oligodeoxynucleotide (ODN) found to specifically inhibit transcription of the beta(c) in rat bone marrow cells also caused inhibition of beta(c) mRNA expression and of immunoreactive cells within the lungs of Brown Norway (BN) rats when injected intratracheally (p < 0.01). Inhibition of beta(c) significantly reduced (p < 0.01) experimentally induced eosinophilia in vivo in ovalbumin (OVA)-sensitized BN rats after antigen challenge. Furthermore, when compared with mismatch-treated rats, beta(c) AS-ODN caused inhibition of antigen-induced airway hyperresponsiveness to leukotriene D4. Taken together, our findings demonstrate that the common beta(c) of IL-3, IL-5, and GM-CSF receptors is involved in the eosinophil influx and airway hyperresponsiveness that follow OVA challenge and underscore the potential utility of a topical antisense approach targeting beta(c) for the treatment of asthma.
Dictionary of microbiology and molecular biology. 2nd ed (1988)

Coronary artery stenting has definitely been proven to improve results of percutaneous revascularisation in a large number of patients. Stenting reduces restenosis in large vessels above 3 mm diameter. Stenting has not solved the problem of restenosis but in spite of the inevitable in-stent restenosis due to neointimal proliferation seems to yield better long-term results than conventional PTCA. Adjunctive pharmacological treatment with aspirin and clopidogrel in combination with improved stent deployment techniques has reduced the incidence of subacute stent thrombosis. GP IIb/IIIa inhibition is a promising mean for the reduction of procedure related ischaemic events and complications not only with stent implantation but also with conventional PTCA. Other new devices may further influence the treatment choices of stenting versus conventional PTCA in the future. Novel approaches such as brachytherapy and molecular genetic approaches to reduce in-stent restenosis are currently being investigated but to date no conclusions can be drawn as to their future place in clinical practice. From a mechanistic standpoint it seems obvious to give all our efforts to protect patients with coronary atherosclerosis from loss of myocardium either with coronary artery bypass grafting or percutaneous revascularisation. As both approaches are palliative in nature, it may be useful to attempt percutaneous revascularisation in patients amenable to this therapy and thus obviate or delay the need for definitive revascularisation by coronary artery bypass grafting. At the end of this discussion we would like to remind that medical therapy for coronary artery disease is of utmost importance as all revascularisation procedures do not influence the underlying disease. Besides symptomatic relief of angina, treatment of heart failure, and other beneficial strategies to improve endothelial function, medical therapy with lipid lowering compounds together with risk factor control offers the possibility to delay progression of coronary artery disease.
Energy Management Power Converters in Hybrid Electric and Fuel Cell Vehicles (2007)

Using a bidirectional dc-dc converter along with low-voltage energy storage for the high-voltage dc bus and traction motor drives has been a prominent option for hybrid electric and fuel cell vehicles. This paper will describe the significance of energy management power converters and their circuit topology options for efficiency, size, and cost considerations. Whether isolated or nonisolated, soft switching techniques have been widely used in high-power bidirectional dc-dc converters. Through some design examples, the component selection and circuit design optimization are discussed, and their efficiency evaluation results are also given. Major difficulties of developing a high-power bidirectional dc-dc converter are found in lack of high-power passive components and lack of multiphase dc-dc controllers. More development work needs to be done in these areas