gebhart/patrepeval huggingface dataset:
Anti-angiogenesis: A new potential strategy to inhibit restenosis (2001)

Microvessels are an integral component of the neointima developing in response to the acute vascular injury resulting from angioplasty. These vessels originate from the vasa vasorum of the adventitia, and as such appear similar to the microvessels present in atherosclerotic plaques. Several angiogenic factors have been found in atherosclerotic plaques and have been associated with increased microvascularity. In addition, most of these agents - either directly or indirectly - also induce smooth muscle cell (SMC) proliferation, an essential component of the developing neointima. We therefore propose: (1) these newly formed blood vessels are necessary for the development, maintenance, and expansion of the neointimal lesions present in restenosis; (2) the initiation, regulation and maintenance of these vessels is, at least in part, due to the coordinate sequential expression of hypoxia-inducible factor 1 (HIF-1), vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1), and/or other angiogenic factors such as the fibroblast growth factor (FGF) family of proteins; (3) targeted disruption of the signal transduction pathways modulated by these molecules may reduce vasa vasorum expansion and SMC proliferation. These effects, in turn, may inhibit neointimal expansion and thus the development of restenosis, especially following stenting.
Molecular Mechanisms of Cellular Demise Associated with Cryopreservation Failure (2002)

Current preservation strategies range from the storage of cells, tissues, and organs for hours at hypothermic temperatures (from 25°C to 4°C) to extended periods of time (i.e., years) at ultralow, subfreezing temperatures (-80°C or below). Biologic preservation serves many practical and useful purposes in today's society, ranging from the storage of biological material for research to preservation for use in medical transplantation procedures. Regardless of the end use, the goal of preservation is to extend the window of biological function. In the pursuit of the development of improved biopreservation methodologies, recent investigations have implicated the activation of genetically programmed cell death, apoptosis, and pathological cell death, necrosis, as limiting factors. Accordingly, we review the field of cryopreservation and apoptosis in an effort to provide a guide for future evaluations into the role of apoptosis in cryopreservation failure.
[Construction of animal models of keloid by tissue engineering]. (2005)

All the mice survived after surgery. The collagen patterns of all the keloids were remained after 24 weeks. A lot of fibroblasts and their secreted collagen were observed under light microscope. Enlarged rough endoplasmic reticula inside the fibroblasts were revealed by transmission electron microscopy. The fibroblasts in specimens remained the capability of synthesizing and secreting collagen. CONCLUSIONS There is a good affinity between PLA/PGA and fibroblasts. Complex of PLA/PGA and fibroblasts could be cultured into keloids in athymic mice.
Experience with a software-defined machine architecture (1992)

We have built a system in which the compiler back end and the linker work together to present an abstract machine at a considerably higher level than the actual machine. The intermediate language translated by the back end is the target language of all high-level compilers and is also the only assembly language generally available. This lets us do intermodule register allocation, which would be harder if some of the code in the program had come from a traditional assembler, out of sight of the optimizer. We do intermodule register allocation and pipeline instruction scheduling at link time, using information gathered by the compiler back end. The mechanism for analyzing and modifying the program at link time is also useful in a wide array of instrumentation tools.
Cytokines: interleukin and interferon therapy in dermatology (2002)

Journal Article Cytokines: interleukin and interferon therapy in dermatology Get access K. Asadullah, K. Asadullah Schering AG, Berlin, Germany, and K. Asadullah, Schering AG, D‐13342 Berlin, Germany. E‐mail: khusru.asadullah@schering.de Search for other works by this author on: Oxford Academic Google Scholar W. Sterry, W. Sterry Department of Dermatology and Allergy, University Hospital Charité, Berlin Humboldt University, Germany Search for other works by this author on: Oxford Academic Google Scholar U. Trefzer U. Trefzer Department of Dermatology and Allergy, University Hospital Charité, Berlin Humboldt University, Germany Search for other works by this author on: Oxford Academic Google Scholar Clinical and Experimental Dermatology, Volume 27, Issue 7, 1 October 2002, Pages 578–584, https://doi.org/10.1046/j.1365-2230.2002.01144.x Published: 01 October 2002 Article history Accepted: 17 June 2002 Published: 01 October 2002
An Improved Method for Determining Medium‐ and Long‐Chain FAMEs Using Gas Chromatography (2010)

The existing protocols for analyzing fatty acid methyl esters (FAMEs) using a one-step acetyl chloride (AC) catalyzed transesterification and extraction procedure cannot accurately determine the medium- and long-chain fatty acids simultaneously in clinical (enteral, parenteral) formulations. For example: (1) addition of AC at room temperature generates an exothermic reaction that often results in loss of sample and possible injury to the analyst; (2) certain polyunsaturated fatty acids (PUFAs) are less stable at elevated temperatures during the transesterification and contribute to the over-estimation of the C16:0 and C18:1 fatty acids; and (3) the flame-ionization detector (FID) response varies depending on the carbon chain length of the fatty acids, that consequently impacts the underestimation of medium-chain fatty acid (C6-C10) recoveries. To overcome these deficiencies and accurately determine FAMEs, we have developed an improved one-step transesterification method that employs the addition of AC in tubes kept on a dry ice bath, the transesterification at room temperature, and the data analysis using relative response factors. Using this modified protocol, we determined the fatty acid composition of lipid emulsions (Omegaven and Lipidem) on a Shimadzu GC2010 gas chromatography (GC) system using a capillary GC column (Zebron ZB-WAX plus, 30 m, 0.25 mm ID, 0.25 microm). Our data suggest that the improved method can be easily used to accurately determine fatty acids (C6-C24) in functional foods and lipid emulsions.
An optimal spare-capacity assignment model for survivable networks with hop limits (2002)

The paper presents a new algorithm for spare-capacity assignment in survivable networks which use cross-connect systems as transmission hubs. The algorithm minimises total cost of spare capacity for required levels of network restoration following a single link failure (e.g. fibre cut) and limits the restoration routes to any predetermined hop limit. The algorithm is composed of two parts: Part 1 relies on a linear programming (LP) formulation (min-max) from which a lower bound solution is found; Part 2 rounds up the solution of Part 1 and uses a series of related LP schemes (max-flow), aimed at tightening the rounded-up assignment to a practical optimal solution which also supplies optimal restoration routes and capacities. For moderate networks an integer programming formulation of Part 1 can be used to obtain an optimal solution. A network example is analysed to illustrate the algorithm developed and to demonstrate its superiority over other schemes published in this area. In addition, a valuable trade-off between spare capacity and hop limit is presented.
Mass preserving nonrigid registration of CT lung images using cubic B‐spline (2009)

The authors propose a nonrigid image registration approach to align two computed-tomography (CT)-derived lung datasets acquired during breath-holds at two inspiratory levels when the image distortion between the two volumes is large. The goal is to derive a three-dimensional warping function that can be used in association with computational fluid dynamics studies. In contrast to the sum of squared intensity difference (SSD), a new similarity criterion, the sum of squared tissue volume difference (SSTVD), is introduced to take into account changes in reconstructed Hounsfield units (scaled attenuation coefficient, HU) with inflation. This new criterion aims to minimize the local tissue volume difference within the lungs between matched regions, thus preserving the tissue mass of the lungs if the tissue density is assumed to be relatively constant. The local tissue volume difference is contributed by two factors: Change in the regional volume due to the deformation and change in the fractional tissue content in a region due to inflation. The change in the regional volume is calculated from the Jacobian value derived from the warping function and the change in the fractional tissue content is estimated from reconstructed HU based on quantitative CT measures. A composite of multilevel B-spline is adopted to deform images and a sufficient condition is imposed to ensure a one-to-one mapping even for a registration pair with large volume difference. Parameters of the transformation model are optimized by a limited-memory quasi-Newton minimization approach in a multiresolution framework. To evaluate the effectiveness of the new similarity measure, the authors performed registrations for six lung volume pairs. Over 100 annotated landmarks located at vessel bifurcations were generated using a semiautomatic system. The results show that the SSTVD method yields smaller average landmark errors than the SSD method across all six registration pairs.
Not a star, but not a planet either (1996)

For more than two decades astronomers have eagerly awaited the discovery of a genuine brown dwarf. Brown dwarfs constitute a whole new class of astronomical objects that are similar to stars in the way they form but are not sufficiently massive to sustain nuclear fusion in their cores. For this reason brown dwarfs are often referred to as "failed stars". Despite their inherent faintness, several very promising candidates have now been identified.
Human HDAC7 Harbors a Class IIa Histone Deacetylase-specific Zinc Binding Motif and Cryptic Deacetylase Activity (2008)

Histone deacetylases (HDACs) are protein deacetylases that play a role in repression of gene transcription and are emerging targets in cancer therapy. Here, we characterize the structure and enzymatic activity of the catalytic domain of human HDAC7 (cdHDAC7). Although HDAC7 normally exists as part of a multiprotein complex, we show that cdHDAC7 has a low level of deacetylase activity which can be inhibited by known HDAC inhibitors. The crystal structures of human cdHDAC7 and its complexes with two hydroxamate inhibitors are the first structures of the catalytic domain of class IIa HDACs and demonstrate significant differences with previously reported class I and class IIb-like HDAC structures. We show that cdHDAC7 has an additional class IIa HDAC-specific zinc binding motif adjacent to the active site which is likely to participate in substrate recognition and protein-protein interaction and may provide a site for modulation of activity. Furthermore, a different active site topology results in modified catalytic properties and in an enlarged active site pocket. Our studies provide mechanistic insights into class IIa HDACs and facilitate the design of specific modulators.
<title>Generic mapping mechanism between content description metadata and user environments</title> (2002)

The number of terminals that have access to multimedia content by means of a network is rapidly increasing. More and more, the characteristics of different terminals are increasing in variety. In addition, their users can have different preferences. Therefore, the adaptation of multimedia content to a specific terminal and/or its user has become an important research issue. Such an adaptation is mainly based on two aspects: the description of the multimedia content and the description of the user environment. Both can be considered as metadata, and can be formatted in an XML language (e.g., MPEG-7 and CC/PP). However, it is not yet clear how we can realize a generic mapping mechanism between two such vocabularies. We feel that such a mechanism is necessary to accomplish a mature content adaptation framework. This paper describes how such a mechanism can be achieved. We attach requirements and preferences of the user environment to specific aspects of the description of multimedia content. Based on this information, we try to maximize the value of the adapted content, while making it appropriate for the terminal. We also take into account the extensibility of the existing vocabularies we focus on, because this means our mechanism will also be extensible.
Stable isotope studies of nicotine kinetics and bioavailability (1991)

The stable isotope-labeled compound 3',3'-dideuteronicotine was used to investigate the disposition kinetics of nicotine in smokers, the systemic absorption of nicotine from cigarette smoke, and the bioavailability of nicotine ingested as oral capsules. Blood levels of labeled nicotine could be measured for 9 hours after a 30-minute intravenous infusion. Analysis of disposition kinetics in 10 healthy men revealed a multiexponential decline after the end of an infusion, with an elimination half-life averaging 203 minutes. This half-life was longer than that previously reported, indicating the presence of a shallow elimination phase. Plasma clearance averaged 14.6 ml/min/kg. The average intake of nicotine per cigarette was 2.29 mg. A cigarette smoke-monitoring system that directly measured particulate matter in smoke was evaluated in these subjects. Total particulate matter, number of puffs on the cigarette, total puff volume, and time of puffing correlated with the intake of nicotine from smoking. The oral bioavailability of nicotine averaged 44%. This bioavailability is higher than expected based on the systemic clearance of nicotine and suggests that there may be significant extrahepatic metabolism of nicotine.
The Upstream Region of the Rpe65 Gene Confers Retinal Pigment Epithelium-specific Expression in Vivo and in Vitro and Contains Critical Octamer and E-box Binding Sites (2000)

RPE65 is essential for all-trans- to 11-cis-retinoid isomerization, the hallmark reaction of the retinal pigment epithelium (RPE). Here, we identify regulatory elements in the Rpe65 gene and demonstrate their functional relevance to Rpe65 gene expression. We show that the 5' flanking region of the mouse Rpe65 gene, like the human gene, lacks a canonical TATA box and consensus GC and CAAT boxes. The mouse and human genes do share several cis-acting elements, including an octamer, a nuclear factor one (NFI) site, and two E-box sites, suggesting a conserved mode of regulation. A mouse Rpe65 promoter/beta-galactosidase transgene containing bases -655 to +52 (TR4) of the mouse 5' flanking region was sufficient to direct high RPE-specific expression in transgenic mice, whereas shorter fragments (-297 to +52 or -188 to +52) generated only background activity. Furthermore, transient transfection of analogous TR4/luciferase constructs also directed high reporter activity in the human RPE cell line D407 but weak activity in the non-RPE cell lines HeLa, HepG2, and HS27. Functional binding of potential transcription factors to the octamer sequence, AP-4, and NFI sites was demonstrated by directed mutagenesis, electrophoretic mobility shift assay, and cross-linking. Mutations of these sites abolished binding and corresponding transcriptional activity and indicated that octamer and E-box transcription factors synergistically regulate the RPE65 promoter function. Thus, we have identified the regulatory region in the Rpe65 gene that accounts for tissue-specific expression in the RPE and found that octamer and E-box transcription factors play a critical role in the transcriptional regulation of the Rpe65 gene.
Kaposi sarcoma is a therapeutic target for vitamin D3receptor agonist (2000)

Kaposi sarcoma (KS) is responsive to a number of different steroid hormones, such as glucocorticoids and retinoids. An active metabolite of vitamin D, 1α,25 dihydroxyvitamin D3, was used to study the effect of this steroid hormone in KS. Steroid hormones exert their effect through their cognate nuclear receptors, which for vitamin D metabolites is the vitamin D receptor (VDR). It was first shown that KS cell lines and primary tumor tissue express high levels of VDR, whereas endothelial cells had minimal expression and fibroblasts had no expression. Second, KS cell growth was inhibited by VDR agonist 1α,25 dihydroxyvitamin D3 with a 50% inhibitory concentration of 5 × 10 −8 mol/L, whereas endothelial cells and fibroblast cells showed no response. Studies on the mechanism of KS tumor growth inhibition by 1α,25 dihydroxyvitamin D3 showed that production of autocrine growth factors interleukin (IL)-6 and IL-8 was reduced in a dose-dependent manner, whereas no effect was observed on vascular endothelial growth factor and basic fibroblast growth factor. Transcription initiated at the IL-6 promoter was repressed by VDR agonist. The DNA sequences required to mediate this repression were localized to nucleotides −225/−110 in the 5′-flanking region. The antitumor activity of VDR agonists was also confirmed in KS tumor xenograft and after topical application in patients with KS. 1α,25 Dihydroxyvitamin D3 and its analogs may thus be candidates for clinical development in KS.
Relation of infant feeding to adult serum cholesterol concentration and death from ischaemic heart disease. (1992)

Age of weaning and method of infant feeding may influence adult serum low density lipoprotein cholesterol concentrations and mortality from ischaemic heart disease. Adult serum apolipoprotein B concentrations are related to growth in fetal life and infancy.
Methane production by ruminants:its contribution to global warming (2000)

The aim of this paper is to review the role of methane in the global warming scenario and to examine the contribution to atmospheric methane made by enteric fermentation, mainly by ruminants. Agricultural emissions of methane in the EU-15 have recently been estimated at 10.2 million tonnes per year and represent the greatest source. Of these, approximately two-thirds come from enteric fermentation and one-third from livestock manure. Fermentation of feeds in the rumen is the largest source of methane from enteric fermentation and this paper considers in detail the reasons for, and the consequences of, the fact that the molar percentage of the different volatile fatty acids produced during fermentation influences the production of methane in the rumen. Acetate and butyrate promote methane production while propionate formation can be considered as a competitive pathway for hydrogen use in the rumen. The many alternative approaches to reducing methane are considered, both in terms of reduction per animal and reduction per unit of animal product. It was concluded that the most promising areas for future research for reducing methanogenesis are the development of new products/delivery systems for anti-methanogenic compounds or alternative electron acceptors in the rumen and reduction in protozoal numbers in the rumen. It is also stressed that the reason ruminants are so important to mankind is that much of the world's biomass is rich in fibre. They can convert this into high quality protein sources (i.e. meat and milk) for human consumption and this will need to be balanced against the concomitant production of methane. methane / ruminants / global warning / reduction strategies Rsum -Production de mthane par les ruminants : sa contribution au rchauffement de la plante. Cet article examine le rle du mthane dans le processus de rchauffement de la plante et value la contribution au mthane atmosphrique des gaz d'origine digestive issus principalement des ruminants. Les missions annuelles de mthane d'origine agricole dans l'Europe des quinze ont t estimes rcemment 10,2 millions de tonnes et reprsentent la principale source des entres
Phage Lytic Enzyme Cpl-1 as a Novel Antimicrobial for Pneumococcal Bacteremia (2003)

Streptococcus pneumoniae is becoming increasingly antibiotic resistant worldwide, and thus new antimicrobials are badly needed. We report the use of Cpl-1, the lytic enzyme of a pneumococcal bacteriophage, as an intravenous therapy for pneumococcal bacteremia in a mouse model. A 2000- microg dose of Cpl-1 reduced pneumococcal titers from a median of log(10) 4.70 CFU/ml to undetectable levels (<log(10) 2.00 CFU/ml) within 15 min. This dose given 1 h after intravenous infection led to 100% survival at 48 h, compared to the 20% survival of buffer-treated controls. In advanced bacteremia, treatment with two doses at 5 and 10 h still resulted in significantly longer survival (P < 0.0001) and a hazard ratio of 0.29 (95% confidence interval, 0.04 to 0.35). The enzyme is immunogenic, but the treatment efficacy was not significantly diminished after previous intravenous exposure of mice and hyperimmune rabbit serum did not neutralize the activity. Cpl-1 is also very effective as a topical nasal treatment against colonization by S. pneumoniae. In vitro, the enzyme is active against many serotypes of S. pneumoniae, independent of their penicillin resistance, and it is very specific for this species. Bacteriophage enzymes are unusual but extremely effective antimicrobials and represent a new weapon against infections with resistant bacteria.
Next generation maleimides enable the controlled assembly of antibody–drug conjugatesvianative disulfide bond bridging (2014)

The advent of Adcetris™ and Kadcyla™, two recently FDA-approved antibody-drug conjugates (ADCs), in the clinic has had a major impact on the treatment of lymphoma and breast cancer patients, respectively, worldwide. Despite these successes many new ADCs fail at various stages of development, often due to shortcomings in the methods used for their assembly. To address this problem we have developed next generation maleimides (NGMs), which specifically re-bridge reduced interchain disulfide bonds and allow the efficient conjugation of small molecules to antibodies, without the need for engineering of the target antibody. The method is site-specific and generates near homogeneous products in good yields. Moreover, adjustment of the reaction conditions allows control of the conjugation in terms of stoichiometry (drug-loading) and site selectivity. Using this method we prepared a series of ADCs from trastuzumab and doxorubicin (DOX) with a controlled drug-to-antibody ratio (DAR) of 1, 2, 3 and 4. All of these constructs were fully active by ELISA and had more than 90% of re-bridged disulfide bonds by CE-SDS when compared to clinical grade antibody. Furthermore, digest experiments of the DAR 2 material revealed that almost all of the drug had been targeted to the Fab arms of the antibody. Thus, NGMs offer a flexible and simple platform for the controlled assembly of ADCs from an antibody.