gebhart/patrepeval huggingface dataset:
IDH mutations in liver cell plasticity and biliary cancer (2014)

Intrahepatic cholangiocarcinoma (ICC) is an aggressive cancer associated with the bile ducts within the liver. These tumors are characterized by frequent gain-of-function mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes-that are also common in subsets of neural, haematopoietic and bone tumors, but rare or absent in the other types of gastrointestinal malignancy. Mutant IDH acts through a novel mechanism of oncogenesis, producing high levels of the metabolite 2-hydroxyglutarate, which interferes with the function of α-ketoglutarate-dependent enzymes that regulate diverse cellular processes including histone demethylation and DNA modification. Recently, we used in vitro stem cell systems and genetically engineered mouse models (GEMMs) to demonstrate that mutant IDH promotes ICC formation by blocking hepatocyte differentiation and increasing pools of hepatic progenitors that are susceptible to additional oncogenic hits leading to ICC. We found that silencing of HNF4A-encoding a master transcriptional regulator of hepatocyte identity and quiescence-was critical to mutant IDH-mediated inhibition of liver differentiation. In line with these findings, human ICC with IDH mutations are characterized by a hepatic progenitor cell transcriptional signature suggesting that they are a distinct ICC subtype as compared to IDH wild type tumors. The role of mutant IDH in controlling hepatic differentiation state suggests the potential of newly developed inhibitors of the mutant enzyme as a form of differentiation therapy in a solid tumor.
Structure of the recombinant full-length hamster prion protein PrP(29–231): The N terminus is highly flexible (1997)

The prion diseases seem to be caused by a conformational change of the prion protein (PrP) from the benign cellular form PrPC to the infectious scrapie form PrPSc; thus, detailed information about PrP structure may provide essential insights into the mechanism by which these diseases develop. In this study, the secondary structure of the recombinant Syrian hamster PrP of residues 29-231 [PrP(29-231)] is investigated by multidimensional heteronuclear NMR. Chemical shift index analysis and nuclear Overhauser effect data show that PrP(29-231) contains three helices and possibly one short beta-strand. Most striking is the random-coil nature of chemical shifts for residues 30-124 in the full-length PrP. Although the secondary structure elements are similar to those found in mouse PrP fragment PrP(121-231), the secondary structure boundaries of PrP(29-231) are different from those in mouse PrP(121-231) but similar to those found in the structure of Syrian hamster PrP(90-231). Comparison of resonance assignments of PrP(29-231) and PrP(90-231) indicates that there may be transient interactions between the additional residues and the structured core. Backbone dynamics studies done by using the heteronuclear [1H]-15N nuclear Overhauser effect indicate that almost half of PrP(29-231), residues 29-124, is highly flexible. This plastic region could feature in the conversion of PrPC to PrPSc by template-assisted formation of beta-structure.
A Missense Mutation in the Sodium Channel Scn8a Is Responsible for Cerebellar Ataxia in the Mouse Mutantjolting (1996)

The voltage-gated sodium channel Scn8a is broadly distributed in brain and spinal cord. We have identified a missense mutation in Scn8a that is associated with cerebellar ataxia in the jolting mutant, a mild allele of the "motor endplate disease" locus. The jolting mutation results in substitution of Thr for an evolutionarily conserved Ala residue in the cytoplasmic S4-S5 linker of domain III. Introduction of the corresponding mutation into the rat brain IIA sodium channel shifted the voltage dependence of activation by 14 mV in the depolarizing direction, without affecting the kinetics of fast inactivation or recovery from inactivation. A shift in the threshold of the Scn8a channel could account for the reduced spontaneous activity of Purkinje cells, reduced inhibitory output from the cerebellum, and loss of motor control observed in jolting mice.
Arthritis and pain. Future targets to control osteoarthritis pain (2007)

Clinical presentation of osteoarthritis (OA) is dominated by pain during joint use and at rest. OA pain is caused by aberrant functioning of a pathologically altered nervous system with key mechanistic drivers from peripheral nerves and central pain pathways. This review focuses on symptomatic pain therapy exemplified by molecular targets that alter sensitization and hyperexcitability of the nervous system, for example, opioids and cannabinoids. We highlight opportunities for targeting inflammatory mediators and their key receptors (for example, prostanoids, kinins, cytokines and chemokines), ion channels (for example, NaV1.8, NaV1.7 and CaV2.2) and neurotrophins (for example, nerve growth factor), noting evidence that relates to their participation in OA etiology and treatment. Future neurological treatments of pain appear optimistic but will require the systematic evaluation of emerging opportunities.
Dynamic resource allocation for cloud-based media processing (2013)

As an economic and scalable solution of providing interactive and adaptive media content across different devices, cloud-based media processing has recently attracted lots of attention from both academic and industry. Within a media cloud, a large number of media processing tasks will be dynamically spawn to run in parallel and then share resource with each other in the cloud. In such a dynamic and shared environment, how to appropriately provision cloud resource to different tasks with regards to both system efficiency and quality of service remains a challenging issue. Existing resource allocation algorithms consider generic task and only focus on maximizing system efficiency, but failed to meet the QoS requirement of media tasks. In this paper, we investigate the relationship between the properities of media tasks and their resource comsumption and accordingly propose a dynamic resource allocation solution. Our solution leverages machine learning technique to predict resource requirement and survival functions to prevent QoS degradation.
Structural Basis of Defects in the Sacsin HEPN Domain Responsible for Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) (2011)

Sacsin is a 520-kDa protein mutated in the early-onset neurodevelopmental and neurodegenerative disease autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). The C terminus of the protein contains an HEPN (higher eukaryotes and prokaryotes nucleotide-binding) domain of unknown function. Here, we determined the high-resolution 1.9-Å crystal structure of the HEPN domain from human sacsin. The structure is composed of five parallel α-helices with a large loop of several short helical segments. Two HEPN protomers assemble as a dimer to form a large positively charged cavity at the dimer interface that binds GTP and other nucleotides. The crystal structure reveals that the ARSACS N4549D mutation disrupts dimerization and protein folding. This study provides novel insights into the oligomerization state of sacsin and functions that are lost in mutations that cause ARSACS.
pH-dependent lysis of liposomes by adenovirus (1986)

Purified adenovirus induced a dose-dependent release of the water-soluble markers calcein and carboxyfluorescein from liposomes. Marker release was strongly dependent on pH, and at temperatures below 5 degrees C, the rate of release showed an optimum at a pH of about 6. This pH dependence parallels disruption of endocytic vesicles by adenovirus and the permeabilization that adenovirus induces on the cell surface. There did not seem to be a striking dependence on the lipid composition of the liposomes. Electron microscopy using a negative stain shows liposomes bound to adenovirus. In some cases, the liposomes were still intact, but many liposomes, which were attached to the vertices of the virus, appeared lysed. These data support the notion that adenovirus, which enters the host cell by receptor-mediated endocytosis, gains access to the cytoplasm by a subsequent pH-dependent disruption of the membrane of the endocytic vesicle.
Tolerance, Danger, and the Extended Family (1994)

For many years immunologists have been well served by the viewpoint that the immune system's primary goal is to discriminate between self and non-self. I believe that it is time to change viewpoints and, in this essay, I discuss the possibility that the immune system does not care about self and non-self, that its primary driving force is the need to detect and protect against danger, and that it does not do the job alone, but receives positive and negative communications from an extended network of other bodily tissues.
Water Gelation by Small Organic Molecules (2004)

ADVERTISEMENT RETURN TO ISSUEArticleNEXTWater Gelation by Small Organic MoleculesLara A. Estroff and Andrew D. HamiltonView Author Information Department of Chemistry, Yale University, P.O. Box 208107, New Haven, Connecticut 06520-8107 Cite this: Chem. Rev. 2004, 104, 3, 1201–1218Publication Date (Web):February 21, 2004Publication History Received10 April 2003Published online21 February 2004Published inissue 1 March 2004https://pubs.acs.org/doi/10.1021/cr0302049https://doi.org/10.1021/cr0302049research-articleACS PublicationsCopyright © 2004 American Chemical SocietyRequest reuse permissionsArticle Views16892Altmetric-Citations1885LEARN 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 SUBJECTS:Aggregation,Fibers,Gelation,Hydrophobicity,Molecules Get e-Alerts
Structural requirements for inhibition of cytokine-induced endothelial activation by unsaturated fatty acids (1998)

Dietary long-chain fatty acids (FA) may influence pathological processes involving endothelial activation, including inflammation and atherosclerosis. We have previously shown that the n-3 FA docosahexaenoate (DHA) inhibits endothelial activation in the range of nutritionally achievable plasma concentrations. The present study assessed structural determinants for this effect. Saturated, monounsaturated, and n-6 and n-3 polyunsaturated FA were incubated with cultured endothelial cells for 24-72 h alone, and then in the presence of interleukin-1, tumor necrosis factor, or bacterial lipopolysaccharide for an additional 24 h before assessing the expression of the vascular cell adhesion molecule-1 (VCAM-1) or other products of endothelial activation. No FA tested per se elicited endothelial activation. While saturated FA did not inhibit cytokine-induced expression of adhesion molecules, a progressively increasing inhibitory activity was observed, for the same chain length, with an increase in double bonds. Comparison of FA with the same length and number of unsaturation and only differing for the double bond position or for the cis/trans configuration indicated no difference in inhibitory potency, indicating no effect of the double bond position or configuration. As judged by Northern analysis, these latter FA also inhibited VCAM-1 messenger RNA steady state levels to the same extent, indicating a pre-translational site of action attributable to the single double bond. Thus the double bond is the minimum necessary and sufficient requirement for FA inhibition of endothelial activation. These properties are likely relevant to the anti-atherogenic and anti-inflammatory properties ascribed to n-3 FA, which are able to accommodate the highest number of double bonds in a fatty acid of given chain length.
Tunable Radio-Frequency Filters Using Acoustic Wave Resonators and Variable Capacitors (2010)

In this paper, we describe possible configurations for tunable filters based on RF surface or bulk acoustic wave (SAW/BAW) technologies. The frequency tuning is made possible by variable capacitors (VCs) connected to SAW/BAW resonators in the ladder-type filter configuration. First, it is shown that the passband edges can be controlled by one VC connected to each resonator. Second, it is discussed that the width and location of a passband can be controlled flexibly by two VCs connected to each resonator both in parallel and in series. Finally, the SAW filters with the proposed configuration are fabricated on a Cu-grating/15°YX-LiNbO 3 substrate structure, and the tuning capability is demonstrated.
cDNA Cloning Identified a Calmodulin-Binding Protein in Bovine Seminal Plasma as Bovine C-Type Natriuretic Peptide (1994)

A basic protein of apparent molecular weight 15 kD, designated bSVSP15, was purified from bovine seminal vesicle secretion to homogeneity, employing affinity absorption to calmodulin-Sepharose and reverse-phase HPLC. Immunoblotting identified bSVSP15 in bovine seminal plasma and seminal vesicle secretion, but it was not present either in extracts of bovine ampulla, epididymis, and testis or in serum or follicular fluid. When added to cAMP phosphodiesterase, bSVSP15 inhibited the activation of enzymatic activity by calmodulin in a reversible manner. Immunoscreening of a lambda gt11 expression cDNA library from bovine seminal vesicle tissue yielded two positive clones, pSVS4 and pSVS5, which were characterized by sequencing. Both sequences are identical, except for the 3' region. Because the derived amino acid sequence comprises, with an identity of 81%, the amino-terminal 21 residues of bSVSP15, cDNA clones pSVS4 and pSVS5 represent bSVSP15-specific mRNAs. The mature protein bSVSP15 contains 101 residues and is preceded by 25 residues of a signal sequence, characteristic for secretory proteins. Northern analysis identified two bSVSP15-specific mRNAs of 900 bp and 1200 bp, respectively. Sequence comparison yielded high homologies to human C-type natriuretic peptide. We conclude from this result that bSVSP15 is identical with the hitherto unknown bovine C-type natriuretic peptide.
High risk for attention deficit hyperactivity disorder among children of parents with childhood onset of the disorder: a pilot study (1995)

These results support the validity of the adult diagnosis of ADHD and suggest that the adult form of this disorder may have stronger familial etiological risk factors than its pediatric form. If these results are confirmed, families selected through adult probands with ADHD might be especially useful for testing genetic hypotheses about the disorder.
Temporal gene expression during differentiation of human embryonic stem cells and embryoid bodies (2004)

The present study provides a molecular basis for the identity of human ES cells and demonstrates that during their in vitro differentiation they express embryonic specific genes in a stage specific manner.
Refactoring-Aware Configuration Management for Object-Oriented Programs (2007)

Current text based software configuration management (SCM) systems have trouble with refactorings. Refactorings result in global changes and lead to merge conflicts. A refactoring-aware SCM system reduces merge conflicts, preserves program history better and makes it easier to understand program evolution. This paper describes MolhadoRef a refactoring-aware SCM system and the merge algorithm at its core. MolhadoRef records change operations (refactorings and edits) used to produce one version, and replays them when merging versions. Since refactorings are change operations with well defined semantics, MolhadoRef treats them intelligently. A case-study shows that MolhadoRef solves automatically more merge conflicts than CVS while resulting in fewer merge errors.
Dissolution and Hydrolysis of Cellulose in Subcritical and Supercritical Water (2000)

Decomposition experiments of microcrystalline cellulose were conducted in subcritical and supercritical water (25 MPa, 320−400 °C, and 0.05−10.0 s). At 400 °C hydrolysis products were mainly obtained, while in 320−350 °C water, aqueous decomposition products of glucose were the main products. Kinetic studies of cellulose, cellobiose, and glucose at these conditions showed that below 350 °C the cellulose decomposition rate was slower than the glucose and cellobiose decomposition rates, while above 350 °C, the cellulose hydrolysis rate drastically increased and became higher than the glucose and cellobiose decomposition rates. Direct observation of the cellulose reaction in high-temperature water at high-pressure conditions by using a diamond anvil cell (DAC) showed that, below 280 °C, cellulose particles became gradually smaller with increasing reaction time but, at high temperatures (300−320 °C), cellulose particles disappeared with increasing transparency and much more rapidly than expected from the lower temperature results. These results suggest that cellulose hydrolysis at high temperature takes place with dissolution in water. This is probably because of the cleavage of intra- and intermolecular hydrogen linkages in the cellulose crystal. Thus, a homogeneous atmosphere is formed in supercritical water, and this results in the drastic increase of the cellulose decomposition rate above 350 °C.
Distinct Role for Microglia in Rotenone-Induced Degeneration of Dopaminergic Neurons (2002)

Increasing evidence has suggested an important role for environmental factors such as exposure to pesticides in the pathogenesis of Parkinson's disease. In experimental animals the exposure to a common herbicide, rotenone, induces features of parkinsonism; mechanistically, rotenone-induced destruction of dopaminergic neurons has been attributed to its inhibition of the activity of neuronal mitochondrial complex I. However, the role of microglia, the resident brain immune cells in rotenone-induced neurodegeneration, has not been reported. Using primary neuron-enriched and neuron/glia cultures from the rat mesencephalon, we discovered an extraordinary feature for rotenone-induced degeneration of cultured dopaminergic neurons. Although little neurotoxicity was detected in neuron-enriched cultures after treatment for 8 d with up to 20 nm rotenone, significant and selective dopaminergic neurodegeneration was observed in neuron/glia cultures 2 d after treatment with 20 nm rotenone or 8 d after treatment with 1 nm rotenone. The greatly enhanced neurodegenerative ability of rotenone was attributed to the presence of glia, especially microglia, because the addition of microglia to neuron-enriched cultures markedly increased their susceptibility to rotenone. Mechanistically, rotenone stimulated the release of superoxide from microglia that was attenuated by inhibitors of NADPH oxidase. Furthermore, inhibition of NADPH oxidase or scavenging of superoxide significantly reduced the rotenone-induced neurotoxicity. This is the first report demonstrating that microglia play a pivotal role in rotenone-induced degeneration of dopaminergic neurons. The results of this study should advance our understanding of the mechanism of action for pesticides in the pathogenesis of Parkinson's disease.
Osteogenic Differentiation of Human Wharton's Jelly Stem Cells on Nanofibrous Substrates In Vitro (2010)

Most tissue engineering studies use human bone marrow mesenchymal stem cells for differentiation into desirable lineages. We derived a novel stem cell from the human umbilical cord Wharton's jelly (hWJSC) that has numerous advantages over other stem cell types in that they can be harvested in abundance very efficiently and painlessly with no risk of patient morbidity, have prolonged stemness properties in vitro, are hypoimmunogenic, and can be differentiated into many tissue types in two-dimensional culture. We compared four different three-dimensional nanofibrous scaffolds (polycaprolactone [PCL], PCL/collagen [PCL/Coll], PCL/hydroxyapatite [PCL/HA], and PCL/Coll/HA) for the attachment, proliferation, differentiation, and mineralization of hWJSCs into an osteogenic lineage. The collagen-based scaffolds (PCL/Coll and PCL/Coll/HA) showed better cell attachment and proliferation than PCL and PCL/HA, with increases of 41.80% and 38.52%, respectively. hWJSCs cultured on PCL/Coll/HA in the osteogenic medium up to 21 days demonstrated increased alkaline phosphatase activity and greater expression of osteocalcin, mineralization, and osteogenic-related genes compared to controls. Given the advantages of hWJSCs over other stem cell types, we propose that hWJSCs may be efficiently differentiated into an osteogenic lineage on a three-dimensional PCL/Coll/HA nanofibrous scaffold for the treatment of bone defects.
Angiogenesis inhibitors in cancer therapy. (2003)

The formation of new blood vessels is essential for tumor growth and progression. Angiogenesis inhibitors have been demonstrated to block tumor growth and/or metastasis. Although initial clinical data have been disappointing, new strategies to increase the efficacy of these drugs have ensured their ongoing clinical development. This review highlights the broad spectrum of angiogenesis inhibitors under investigation in both preclinical and clinical studies. From 'natural' inhibitors to thalidomide analogs, the number of compounds in development is extensive. Elucidating the mechanisms of action will enable their use in conjunction with existing/other novel therapies, thereby maximizing the potential efficacy of angiogenesis inhibitors to fulfill their promise in patients with cancer.
A pro‐inflammatory signature mediates FGF2‐induced angiogenesis (2008)

Fibroblast growth factor-2 (FGF2) is a potent angiogenic growth factor. Here, gene expression profiling of FGF2-stimulated microvascular endothelial cells revealed, together with a prominent pro-angiogenic profile, a pro-inflammatory signature characterized by the upregulation of pro-inflammatory cytokine/chemokines and their receptors, endothelial cell adhesion molecules and members of the eicosanoid pathway. Real-time quantitative PCR demonstrated early induction of most of the FGF2-induced, inflammation-related genes. Accordingly, chick embryo chorioallantoic membrane (CAM) and murine Matrigel plug angiogenesis assays demonstrated a significant monocyte/macrophage infiltrate in the areas of FGF2-driven neovascularization. Similar results were obtained when the conditioned medium (CM) of FGF2-stimulated endothelial cells was delivered onto the CAM, suggesting that FGF2-upregulated chemoattractants mediate the inflammatory response. Importantly, FGF2-triggered new blood vessel formation was significantly reduced in phosphatidylinositol 3-kinase-gamma null mice exhibiting defective leucocyte migration or in clodronate liposome-treated, macrophage-depleted mice. Furthermore, the viral pan-chemokine antagonist M3 inhibited the angiogenic and inflammatory responses induced by the CM of FGF2-stimulated endothelial cells and impaired FGF2-driven neovascularization in the CAM assay. These findings point to inflammatory chemokines as early mediators of FGF2-driven angiogenesis and indicate a non-redundant role for inflammatory cells in the neovascularization process elicited by the growth factor.