gebhart/patrepeval huggingface dataset:
Genetic Deletion of Low Density Lipoprotein Receptor Impairs Sterol-induced Mouse Macrophage ABCA1 Expression (2007)

Low density lipoprotein receptor (LDLR) mutations cause familial hypercholesterolemia and early atherosclerosis. ABCA1 facilitates free cholesterol efflux from peripheral tissues. We investigated the effects of LDLR deletion (LDLR(-/-)) on ABCA1 expression. LDLR(-/-) macrophages had reduced basal levels of ABCA1, ABCG1, and cholesterol efflux. A high fat diet increased cholesterol in LDLR(-/-) macrophages but not wild type cells. A liver X receptor (LXR) agonist induced expression of ABCA1, ABCG1, and cholesterol efflux in both LDLR(-/-) and wild type macrophages, whereas expression of LXRalpha or LXRbeta was similar. Interestingly, oxidized LDL induced more ABCA1 in wild type macrophages than LDLR(-/-) cells. LDL induced ABCA1 expression in wild type cells but inhibited it in LDLR(-/-) macrophages in a concentration-dependent manner. However, lipoproteins regulated ABCG1 expression similarly in LDLR(-/-) and wild type macrophages. Cholesterol or oxysterols induced ABCA1 expression in wild type macrophages but had little or inhibitory effects on ABCA1 expression in LDLR(-/-) macrophages. Active sterol regulatory element-binding protein 1a (SREBP1a) inhibited ABCA1 promoter activity in an LXRE-dependent manner and decreased both macrophage ABCA1 expression and cholesterol efflux. Expression of ABCA1 in animal tissues was inversely correlated to active SREBP1. Oxysterols inactivated SREBP1 in wild type macrophages but not in LDLR(-/-) cells. Oxysterol synergized with nonsteroid LXR ligand induced ABCA1 expression in wild type macrophages but blocked induction in LDLR(-/-) cells. Taken together, our studies suggest that LDLR is critical in the regulation of cholesterol efflux and ABCA1 expression in macrophage. Lack of the LDLR impairs sterol-induced macrophage ABCA1 expression by a sterol regulatory element-binding protein 1-dependent mechanism that can result in reduced cholesterol efflux and lipid accumulation in macrophages under hypercholesterolemic conditions.
Understanding Capsid Assembly and Genome Packaging for Adeno-Associated Viruses (2017)

Adeno-associated viruses (AAVs) are promising therapeutic viral vectors. Their capsid is assembled from viral proteins VP1, VP2 and VP3, aided by an assembly-activating protein, followed by replication protein mediated packaging of their 4.7-kb genome with inverted terminal repeats as packaging signals. To aid improvement of AAV vectors, knowledge of viral determinants of successful capsid assembly and genome packaging is important. We review the current knowledge of these two processes and efforts to overcome limited DNA packaging capacity and limit the packaging of unwanted foreign DNA in vector development. Residues involved in essential capsid assembly and genome packaging interactions cannot be manipulated in vector engineering. This information thus aids strategies to improve vector production and to increase AAV packaging capacity toward improved efficacy of this vector system.
Molecular Cloning of a Mouse Melanocortin 5 Receptor Gene Widely Expressed in Peripheral Tissues (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMolecular Cloning of a Mouse Melanocortin 5 Receptor Gene Widely Expressed in Peripheral TissuesOlivier Labbe, Frank Desarnaud, Dominique Eggerickx, Gilbert Vassart, and Marc ParmentierCite this: Biochemistry 1994, 33, 15, 4543–4549Publication Date (Print):April 19, 1994Publication History Published online1 May 2002Published inissue 19 April 1994https://pubs.acs.org/doi/10.1021/bi00181a015https://doi.org/10.1021/bi00181a015research-articleACS PublicationsRequest reuse permissionsArticle Views278Altmetric-Citations171LEARN 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
Applications of Soft Computing in Civil Engineering: A Review (2013)

The field of engineering is a creative one. The problems encountered in this field are generally unstructured and imprecise influenced by intuitions and past experiences of a designer. The conventional methods of computing relying on analytical or empirical relations become time consuming and labor intensive when posed with real life problems. To study, model and analyze such problems, approximate computer based Soft Computing techniques inspired by the reasoning, intuition, consciousness and wisdom possessed by a human beings are employed. In contrast to conventional computing techniques which rely on exact solutions, soft computing aims at exploiting given tolerance of imprecision, the trivial and uncertain nature of the problem to yield an approximate solution to a problem in quick time. Soft Computing being a multi-disciplinary field uses a variety of statistical, probabilistic and optimization tools which complement each other to produce its three main branches viz., Neural Networks, Genetic Algorithms and Fuzzy Logic. The review paper presents the applications of two major Soft Computing techniques viz., Artificial Neural Networks and Genetic Algorithms in the field of Civil Engineering, which to some extent has replaced the time consuming conventional techniques of computing with intelligent and time saving computing tools.
Angular‐dependent coherent scatter measured with a diagnostic x‐ray image intensifier‐based imaging system (1996)

Low-angle scatter of x rays at diagnostic energies is primarily coherent. This coherence gives rise to interference effects resulting in x-ray diffraction patterns that are characteristic of the scattering material. A method is described of imaging these low-angle (0 degree-10 degrees) x-ray diffraction properties of tissue specimens using a diagnostic x-ray beam and image intensifier-based system. The coherent-scatter cross sections of several materials measured this way are presented. It is shown theoretically that the measurements made with this system can be expressed as the mono-energetic cross section "blurred" by the x-ray spectrum using a linear superposition integral. Experimental results using aluminum powder confirm this. Using a 70 kVp x-ray beam filtered with gadolinium to reduce the spectral width, materials such as water, Lucite, and hydroxyapatite all have significantly different diffraction patterns. The cross sections determined from this analysis from the basis of a unique method of characterizing and identifying tissue samples according to their atomic structure rather than x-ray attenuation properties.
Insight into Lipid Surface Recognition and Reversible Conformational Adaptations of an Exchangeable Apolipoprotein by Multidimensional Heteronuclear NMR Techniques (1997)

Apolipophorin III (apoLp-III) from the insect Manduca sexta is a 166-residue (Mr 18,340) member of the exchangeable apolipoprotein class that functions to stabilize lipid-enriched plasma lipoproteins. In the present study, we present the secondary structure and global fold of recombinant apoLp-III derived from three-dimensional heteronuclear NMR spectroscopy experiments. Five discrete alpha-helical segments (21-30 residues in length) with well defined boundaries were characterized by four NMR parameters: medium range nuclear Overhauser enhancement contacts between proton pairs, chemical shift index, coupling constants, and amide proton exchange rates. An antiparallel arrangement of helical segments has been obtained based on the long range interhelical nuclear Overhauser enhancement contacts. The NMR solution structure reveals a globular, up and down helix bundle organization similar to that of Locusta migratoria apoLp-III (Breiter, D. R., Kanost, M. R., Benning, M. M., Wesenberg, G., Law, J. H., Wells, M. A., Rayment, I., and Holden, H. M. (1991) Biochemistry 30, 603-608). However, a short helix (comprised of 5 amino acids) has been identified in the region between helix 3 and helix 4. This helix is postulated to play a role in lipid surface recognition and/or initiation of binding. Our results also indicate the existence of buried polar and charged residues in the helix bundle, providing a structural basis for the relatively low stability of apoLp-III in its lipid-free state. It is suggested that the intrinsic low stability of lipid-free apoLp-III may be important in terms of its ability to undergo a reversible, lipid binding-induced, conformational change. This study underscores the striking resemblance in molecular architecture between insect apoLp-III and the N-terminal domain of human apolipoprotein E. The potential for application of NMR techniques to studies of the exchangeable apolipoproteins, possibly in their biologically active, lipid-associated state, has broad implications in terms of our understanding of the molecular basis of their physiological functions.
JAK2 associates with the beta c chain of the receptor for granulocyte-macrophage colony-stimulating factor, and its activation requires the membrane-proximal region. (1994)

The high-affinity receptor for granulocyte-macrophage colony-stimulating factor (GM-CSF) consists of a unique alpha chain and a beta c subunit that is shared with the receptors for interleukin-3 (IL-3) and IL-5. Two regions of the beta c chain have been defined; these include a membrane-proximal region of the cytoplasmic domain that is required for mitogenesis and a membrane-distal region that is required for activation of Ras, Raf-1, mitogen-activated protein kinase, and S6 kinase. Recent studies have implicated the cytoplasmic protein tyrosine kinase JAK2 in signalling through a number of the cytokine receptors, including the IL-3 and erythropoietin receptors. In the studies described here, we demonstrate that GM-CSF stimulation of cells induces the tyrosine phosphorylation of JAK2 and activates its in vitro kinase activity. Mutational analysis of the beta c chain demonstrates that only the membrane-proximal 62 amino acids of the cytosolic domain are required for JAK2 activation. Thus, JAK2 activation is correlated with induction of mitogenesis but does not, alone, activate the Ras pathway. Carboxyl truncations of the alpha chain, which inactivate the receptor for mitogenesis, are unable to mediate GM-CSF-induced JAK2 activation. Using baculovirus-expressed proteins, we further demonstrate that JAK2 physically associates with the beta c chain but not with the alpha chain. Together, the results further support the hypothesis that the JAK family of kinase are critical to coupling cytokine binding to tyrosine phosphorylation and ultimately mitogenesis.
Effect of Cyclodextrins on Biological Membrane. II. Mechanism of Enhancement on the Intestinal Absorption of Non-absorbable Drug by Cyclodextrins. (1992)

The effects of two kinds of cyclodextrins (CyDs), alpha- and beta-CyD, on biological membranes were investigated by measuring changes in the absorption of a non-absorbable drug, sulfanilic acid (SA), from the rat small intestine, using in situ and in vitro experiments. After pretreatment with a mucolytic agent, N-acetyl-L-cysteine (N-Ac), only beta-CyD increased the absorption of SA significantly compared to the absorption without pretreatment. The mechanism of the enhancing effect of CyDs on the absorption of SA was discussed. Almost no morphological change in the small intestine was observed by pretreatment with N-Ac alone, N-Ac or alpha- or beta-CyD combinations. The liberation of membrane components differed among the CyDs, e.g., alpha-CyD selectively released phospholipid while beta-CyD released mainly cholesterol from the intestinal membrane. It is suggested that the interaction of membrane components with CyDs may be at least partly responsible for the enhanced absorption of SA. Moreover it was found from in vitro electrophysiological experiment, that the alteration in enhanced permeability caused by beta-CyD occurred primarily in the transcellular pathways, rather than in the paracellular pathways of the small intestine. These results suggest that the enhancement of intestinal absorption by beta-CyD, after removal of the mucin layer from the intestinal surface, is due to the interaction between the membrane components and CyD. This interaction would induce disorder in cell membrane lipid, resulting in the increased permeability of the transcellular route.
Prestressed Continuous Composite Bridges under Dynamic Load (1990)

The dynamic and fatigue responses of continuous composite bridges with prestressed concrete deck slabs are investigated. The dynamic analysis of such continuous slab‐on‐steel girder bridges is based on the orthotropic plate theory using reliable estimates of the orthotropic rigidities of the bridge. Experimental results from tests on four 1/4‐scale models of continuous composite bridges verify and substantiate the analytical results. Two of the bridge models are tested under repeated loading at the resonance frequency of the structures. The dynamic strain variations due to repeated loading are determined for various components, such as the prestressing steel, the steel girders, the concrete deck slab, and the shear stud connectors. It is shown that prestressing the concrete deck slab in the vicinity of the pier supports eliminates transverse cracking of the slab, enhances the natural frequencies, and increases the fatigue life as well as the ultimate load‐carrying capacity.
The “Cyclopropyl Fragment” is a Versatile Player that Frequently Appears in Preclinical/Clinical Drug Molecules (2016)

Recently, there has been an increasing use of the cyclopropyl ring in drug development to transition drug candidates from the preclinical to clinical stage. Important features of the cyclopropane ring are, the (1) coplanarity of the three carbon atoms, (2) relatively shorter (1.51 Å) C-C bonds, (3) enhanced π-character of C-C bonds, and (4) C-H bonds are shorter and stronger than those in alkanes. The present review will focus on the contributions that a cyclopropyl ring makes to the properties of drugs containing it. Consequently, the cyclopropyl ring addresses multiple roadblocks that can occur during drug discovery such as (a) enhancing potency, (b) reducing off-target effects,
Methylenetetrahydrofolate reductase deficiency in a patient with phenotypic findings of Angelman syndrome (1998)

Deficiency of methylenetetrahydrofolate reductase (MTHFR) is associated with a variable phenotype that includes mental retardation, gait abnormalities, and seizures. Many of the same clinical findings are also seen in patients with Angelman syndrome. We report on a patient with MTHFR deficiency who was initially diagnosed as having Angelman syndrome. This case illustrates that MTHFR deficiency can mimic the phenotype of Angelman syndrome and that MTHFR deficiency should be excluded in patients with manifestations of Angelman syndrome whose molecular studies of chromosome 15 are normal. Am. J. Med. Genet. 77:198–200, 1998. © 1998 Wiley-Liss, Inc.
Genetic footprinting: a genomic strategy for determining a gene's function given its sequence. (1995)

This report describes an efficient strategy for determining the functions of sequenced genes in microorganisms. A large population of cells is subjected to insertional mutagenesis. The mutagenized population is then divided into representative samples, each of which is subjected to a different selection. DNA is prepared from each sample population after the selection. The polymerase chain reaction is then used to determine retrospectively whether insertions into a particular sequence affected the outcome of any selection. The method is efficient because the insertional mutagenesis and each selection need only to be performed once to enable the functions of thousands of genes to be investigated, rather than once for each gene. We tested this "genetic footprinting" strategy using the model organism Saccharomyces cerevisiae.
Two distinct human DNA diesterases that hydrolyze 3′-blocking deoxyribose fragments from oxidized DNA (1991)

Mammalian cells were investigated for enzymes that help correct oxidative damages in DNA. We focused on 3'-repair diesterases, which process DNA ends at oxidative strand breaks by removing 3'-blocking fragments of deoxyribose that prevent DNA repair synthesis. Two enzymes were found in a variety of mouse, bovine and human tissues and cultured cells. The two activities were purified to differing degrees from HeLa cells. One enzyme had the properties of the known HeLa AP endonuclease (Mr approximately 38,000, with identical substrate specificity and reaction requirements, and cross-reactivity with anti-HeLa AP endonuclease antiserum) and is presumed identical to that protein. The second activity did not interact with anti-HeLa AP endonuclease antibodies and had relatively less AP endonuclease activity. This second enzyme may have been detected in other studies but never characterized. In addition to the 3'-repair diesterase and AP endonuclease, this partially purified preparation also harbored DNA 3'-phosphatase and 3'-deoxyribose diesterase activities. It is unknown whether all activities detected in the second preparation are due to a single protein, although activity against undamaged DNA was not detected. The in vivo roles of these two widely distributed 3'-repair diesterase/AP endonucleases have not been determined, but with the characterizations presented here such questions may now be focused.
Laboratory Measurement of Lipid and Lipoprotein Risk Factors (1990)

Accuracy in measurement of serum cholesterol and the other lipid risk factors is essential for reliable patient classification within the context of newly implemented national coronary heart disease intervention programs utilizing uniform cutpoints. This requires agreement or traceability of laboratory methods to national reference systems, which provided the accuracy base for the population studies from which the cutpoints are derived. Adhering to accepted guidelines for patient preparation, blood collection and processing will minimize preanalytical variability. Standardization of the lipid/lipoprotein assays is the next essential step. The assay technology for cholesterol measurement is reasonably mature, although still not perfected; recent activities have focused primarily on achieving traceability of field methods through improving access to the accuracy base, the National Reference System for Cholesterol and developing better (commutable) reference materials. A major hindrance to standardization has been matrix interactions; alterations in reference materials from their preparation which change the measurement characteristics, necessitating the use of fresh specimens in accuracy studies. Considering the importance of LDL cholesterol which is the primary decision parameter in the new clinical guidelines; methodology for routine laboratory quantification is substantially lacking, the usual routine approach still involving estimation. Efforts to develop a reference system for LDL are just beginning. Field methods for HDL cholesterol are reasonably reliable but with some inter-method differences. Agreement on and access to a Reference Method is needed. Accuracy in triglyceride measurement is less important compared to the other risk factors. Convenient methods allowing correction for the free glycerol blank and ready access to a Reference Method are needed.
Current and Future Trends in Multimedia Standards (2009)

The ISO MPEG committee, after successful completion of the MPEG-1 and the MPEG-2 standards, is currently working on the next-generation standard called MPEG-4. Originally, MPEG-4 was conceived as a standard for coding limited-complexity audiovisual scenes at very low bit rates. However, in July 1994, its scope was expanded to include the coding of generic audiovisual scenes at low bit rates, while supporting a range of advanced functionalities that are not supported by other standards. Furthermore, the MPEG-4 standard is being designed not only to provide solutions for audio coding, video coding, and systems multiplexing of coded audiovisual data but also to do it in a truly flexible and extensible manner. This part of the chapter provides an overview of the current status of the MPEG-4 standard. First, we briefly describe the ITU-T H.263 standard, which forms the starting basis for the video part of the MPEG-4 standard. We then present the background of MPEG-4 and the requirements it is expected to satisfy. In the following four sections, we discuss the status of the four important parts of the MPEG-4 standard: MPEG-4 Video, MPEG-4 Audio, MPEG-4 Syntax Description Language (MSDL), and MPEG-4 Synthetic and Natural Hybrid Coding (SNHC). Finally, we summarize the current status of MPEG-4 and discuss the direction it is expected to take in the future.
Opioid-sparing Effects of a Low-dose Infusion of Naloxone in Patient-administered Morphine Sulfate (1997)

Naloxone is effective in preventing PCA opioid-related side effects. Naloxone infusion at 0.25 microg x kg(-1) x h(-1) not only attenuates these side effects but appears to reduce postoperative (beyond 4-8 h) opioid requirements. This dosing regimen can be prepared with 400 microg naloxone in 1,000 ml crystalloid given in 24 h to a patient weighing 70 kg.
Dominant, Gain-of-Function Mutant Produced by Truncation of RPGR (2003)

Certain truncated forms of RPGR can behave as a dominant, gain-of-function mutant. These data suggest that human RPGR mutations are not necessarily null and some may also act as dominant alleles, leading to a more severe phenotype than a null mutant.
Training Region-Based Object Detectors with Online Hard Example Mining (2016)

The field of object detection has made significant advances riding on the wave of region-based ConvNets, but their training procedure still includes many heuristics and hyperparameters that are costly to tune. We present a simple yet surprisingly effective online hard example mining (OHEM) algorithm for training region-based ConvNet detectors. Our motivation is the same as it has always been - detection datasets contain an overwhelming number of easy examples and a small number of hard examples. Automatic selection of these hard examples can make training more effective and efficient. OHEM is a simple and intuitive algorithm that eliminates several heuristics and hyperparameters in common use. But more importantly, it yields consistent and significant boosts in detection performance on benchmarks like PASCAL VOC 2007 and 2012. Its effectiveness increases as datasets become larger and more difficult, as demonstrated by the results on the MS COCO dataset. Moreover, combined with complementary advances in the field, OHEM leads to state-of-the-art results of 78.9% and 76.3% mAP on PASCAL VOC 2007 and 2012 respectively.