gebhart/patrepeval huggingface dataset:
NPC2 facilitates bidirectional transfer of cholesterol between NPC1 and lipid bilayers, a step in cholesterol egress from lysosomes (2008)

Egress of lipoprotein-derived cholesterol from lysosomes requires two lysosomal proteins, polytopic membrane-bound Niemann-Pick C1 (NPC1) and soluble Niemann-Pick C2 (NPC2). The reason for this dual requirement is unknown. Previously, we showed that the soluble luminal N-terminal domain (NTD) of NPC1 (amino acids 25-264) binds cholesterol. This NTD is designated NPC1(NTD). We and others showed that soluble NPC2 also binds cholesterol. Here, we establish an in vitro assay to measure transfer of [(3)H]cholesterol between these two proteins and phosphatidylcholine liposomes. Whereas NPC2 rapidly donates or accepts cholesterol from liposomes, NPC1(NTD) acts much more slowly. Bidirectional transfer of cholesterol between NPC1(NTD) and liposomes is accelerated >100-fold by NPC2. A naturally occurring human mutant of NPC2 (Pro120Ser) fails to bind cholesterol and fails to stimulate cholesterol transfer from NPC1(NTD) to liposomes. NPC2 may be essential to deliver or remove cholesterol from NPC1, an interaction that links both proteins to the cholesterol egress process from lysosomes. These findings may explain how mutations in either protein can produce a similar clinical phenotype.
The hepatic extracellular matrix. I. Electron immunohistochemical studies in normal rat liver. (1984)

Monospecific antibodies directed against fibronectin, type I collagen, and two basement membrane components, laminin and type IV collagen, were localized in normal rat liver by light and electron microscopy immunohistochemistry. Type I collagen was found in the liver capsule, protal stroma, and in Disse's space where it was often in direct contact with the hepatocyte plasmalemma; along the sinusoidal wall, type I collagen was more abundant at points of branching or inflexion. Collagen type IV was found in all basement membranes: ductal, neural, and vascular. In addition, small, discrete, discontinuous, deposits of type IV collagen were found along the entire length of the sinusoid. Laminin codistributed with type IV collagen in all basement membranes but was not found in the sinusoidal wall. The structural glycoprotein, fibronectin, was found in the liver capsule and portal stroma but not in basement membranes. However, fibronectin was found in direct contact with the hepatocytes microvilli forming an almost continuous structure; it was the most prominent component of the extracellular matrix in Disse's space. These findings provide a new image of the Disse's space. Rather than being an empty space, as suggested by classic electron microscopy, it was found to contain an extracellular matrix with several unique features: type I collagen, in direct contact with hepatocytes and endothelial cells, formed the scaffold of the hepatic lobule. Type IV collagen was found "free," not associated with laminin and not forming part of a basement membrane. Hepatocytes and endothelial cells lacked a basement membrane but were separated by an extracellular matrix containing predominantly fibronectin, some type I collagen, and occasional spotty deposits of type IV collagen. Future studies of the physiology and pathology of the hepatic sinusoid will have to take into account this unique extracellular matrix.
Synthesis of Uridine Phosphoramidite Analogs: Reagents for Site-Specific Incorporation of Photoreactive Sites into RNA Sequences (1994)

The synthesis of three new photoactive RNA phosphoramidites, 5-bromouridine, 5-iodouridine, and O4-triazolouridine, is reported. The 5' OH of bromouridine and iodouridine were protected as dimethoxytrityl ether using dimethoxytrityl chloride and pyridine. Selective protection of 2' OH was achieved as the corresponding tert-butyldimethylsilyl ether. Protected ribonucleosides were converted to phosphoramidites using 2-cyanoethyl N,N-diisopropylchlorophosphoramidite. O4-Triazolouridine phosphoramidite monomer was prepared in one step from uridine phosphoramidite. These phosphoramidites were used to incorporate photoprobes at any chosen sites in the RNA sequences during chemical syntheses. The modified monomers were incorporated into RNA oligomers with coupling yields > 98%. After chemical synthesis, O4-triazolouridine was converted to 4-thiouridine by the addition of thiolacetic acid during standard deprotection methods. The extent of thiation and incorporation of modified nucleotides into RNA sequences were confirmed by nuclease digest, HPLC, and gel electrophoresis.
Discriminant adaptive nearest neighbor classification (1996)

Nearest neighbour classification expects the class conditional probabilities to be locally constant, and suffers from bias in high dimensions. We propose a locally adaptive form of nearest neighbour classification to try to ameliorate this curse of dimensionality. We use a local linear discriminant analysis to estimate an effective metric for computing neighbourhoods. We determine the local decision boundaries from centroid information, and then shrink neighbourhoods in directions orthogonal to these local decision boundaries, and elongate them parallel to the boundaries. Thereafter, any neighbourhood-based classifier can be employed, using the modified neighbourhoods. The posterior probabilities tend to be more homogeneous in the modified neighbourhoods. We also propose a method for global dimension reduction, that combines local dimension information. In a number of examples, the methods demonstrate the potential for substantial improvements over nearest neighbour classification.
Relevance feedback revisited (1992)

Researchers have found relevance feedback to be effective in interactive information retrieval, although few formal user experiments have been made. In order to run a user experiment on a large document collection, experiments were performed at NIST to complete some of the missing links found in using the probabilistic retrieval model. These experiments, using the Cranfield 1400 collection, showed the importance of query expansion in addition to query reweighting, and showed that adding as few as 20 well-selected terms could result in performance improvements of over 100%. Additionally it was shown that performing multiple iterations of feedback is highly effective.
The Genetics of the Human APOE Polymorphism (2011)

Abstract The genetic origin of the three common variants of the human apolipoprotein E (apoE) protein, known as E2, E3 and E4, was understood in 1981, and since the mid 1980s these are probably the most-studied protein variants in human races. They have been related to a number of age-related diseases, including Alzheimer disease, as well as to healthy aging and longevity. The gene variants underlying these protein isoforms, known as ε2, ε3, and ε4, are allelic forms of the APOE gene, resulting from different haplotypes at the APOE locus (19q13.31). In particular, they result from three of the four haplotypes expected by the combinations of the alleles of the two single-nucleotide polymorphisms rs429358 and rs7412. The fourth missing haplotype, known as ε3r, has been identified in only two Caucasian families from Italy and in one Yoruba family from Nigeria worldwide. Thus, this fourth APOE gene variant is rare, and it encodes a protein isoform, identified as E3r, showing identical physical characteristics to E3, that conversely, is the most common form of apoE in humans. In this review article, we report the identification of the haplotype ε3r in a third Caucasian family from Italy, and then attempt to re-examine the current knowledge regarding the APOE polymorphism, taking into account this fourth haplotype. We also focus on the commonly accepted hypothesis for the evolution of the common APOE gene variants, in which we include the ε3r haplotype, previously not considered.
Synthesis and characterization of a novel hyaluronic acid hydrogel (2006)

Hyaluronic acid (hyaluronan, HA) has many medical applications as a biomaterial. To enhance its biostability, a novel hydrogel of cross-linked hyaluronic acid was prepared using a double cross-linking process, which involves building cross-linkages between hydroxyl group pairs and carboxyl group pairs. The present study explored a number of cross-linking processes in order to obtain different degrees of cross-linking, which were evaluated by the measurement of water absorption capacity as an index of the gel network density. To gain a better understanding of the stability of the gel, the chemical structure and particularly the rheological behaviour of the cross-linked HA, which included the influences of factors, such as degree of cross-linking, HA concentration and gel particle size, were investigated. The in vitro biostability against hyaluronidase and free radical degradation was tested to show that the cross-linked hydrogel had improved resistance to in vitro hyaluronidase and free radical degradation.
CLINICAL EVALUATION OF EPIGARD, A NEW SYNTHETIC SUBSTITUTE FOR HOMOGRAFT AND HETEROGRAFT SKIN (1973)

A Symposium on The Illinois Trauma Program: A Systems Approach To The Care Of The Critically Injured: PDF Only
Articulated all-para polymers with 2,6-benzobisoxazole, 2,6-benzobisthiazole, and 2,6-benzobisimidazole units in the backbone (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTArticulated all-para polymers with 2,6-benzobisoxazole, 2,6-benzobisthiazole, and 2,6-benzobisimidazole units in the backboneRobert C. Evers, Fred E. Arnold, and Thaddeus E. HelminiakCite this: Macromolecules 1981, 14, 4, 925–930Publication Date (Print):July 1, 1981Publication History Published online1 May 2002Published inissue 1 July 1981https://pubs.acs.org/doi/10.1021/ma50005a007https://doi.org/10.1021/ma50005a007research-articleACS PublicationsRequest reuse permissionsArticle Views497Altmetric-Citations63LEARN 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
Erv41p and Erv46p (2001)

Proteins contained on purified COPII vesicles were analyzed by matrix-assisted laser desorption ionization mass spectrometry combined with database searching. We identified four known vesicle proteins (Erv14p, Bet1p, Emp24p, and Erv25p) and an additional nine species (Yip3p, Rer1p, Erp1p, Erp2p, Erv29p, Yif1p, Erv41p, Erv46p, and Emp47p) that had not been localized to ER vesicles. Using antibodies, we demonstrate that these proteins are selectively and efficiently packaged into COPII vesicles. Three of the newly identified vesicle proteins (Erv29p, Erv41p, and Erv46p) represent uncharacterized integral membrane proteins that are conserved across species. Erv41p and Erv46p were further characterized. These proteins colocalized to ER and Golgi membranes and exist in a detergent-soluble complex that was isolated by immunoprecipitation. Yeast strains lacking Erv41p and/or Erv46p are viable but display cold sensitivity. The expression levels of Erv41p and Erv46p are interdependent such that Erv46p was reduced in an erv41Delta strain, and Erv41p was not detected in an erv46Delta strain. When the erv41Delta or ev46Delta alleles were combined with other mutations in the early secretory pathway, altered growth phenotypes were observed in some of the double mutant strains. A cell-free assay that reproduces transport between the ER and Golgi indicates that deletion of the Erv41p-Erv46p complex influences the membrane fusion stage of transport.
Comparative effectiveness of pharmacological interventions for nonalcoholic steatohepatitis: A systematic review and network meta‐analysis (2015)

Based on direct and network meta-analysis, pentoxifylline and obeticholic acid improve fibrosis, and vitamin E, TZDs, and obeticholic acid improve ballooning degeneration in patients with NASH. Future comparative trials of combination therapies targeting distinct histological features are warranted.
Delayed cerebral oxidative glucose metabolism after traumatic brain injury in young rats (2009)

Traumatic brain injury (TBI) results in a cerebral metabolic crisis that contributes to poor neurologic outcome. The aim of this study was to characterize changes in oxidative glucose metabolism in early periods after injury in the brains of immature animals. At 5 h after controlled cortical impact TBI or sham surgery to the left cortex, 21-22 day old rats were injected intraperitoneally with [1,6-13C]glucose and brains removed 15, 30 and 60 min later and studied by ex vivo 13C-NMR spectroscopy. Oxidative metabolism, determined by incorporation of 13C into glutamate, glutamine and GABA over 15-60 min, was significantly delayed in both hemispheres of brain from TBI rats. The most striking delay was in labeling of the C4 position of glutamate from neuronal metabolism of glucose in the injured, ipsilateral hemisphere which peaked at 60 min, compared with the contralateral and sham-operated brains, where metabolism peaked at 30 and 15 min, respectively. Our findings indicate that (i) neuronal-specific oxidative metabolism of glucose at 5-6 h after TBI is delayed in both injured and contralateral sides compared with sham brain; (ii) labeling from metabolism of glucose via the pyruvate carboxylase pathway in astrocytes was also initially delayed in both sides of TBI brain compared with sham brain; (iii) despite this delayed incorporation, at 6 h after TBI, both sides of the brain showed apparent increased neuronal and glial metabolism, reflecting accumulation of labeled metabolites, suggesting impaired malate aspartate shuttle activity. The presence of delayed metabolism, followed by accumulation of labeled compounds is evidence of severe alterations in homeostasis that could impair mitochondrial metabolism in both ipsilateral and contralateral sides of brain after TBI. However, ongoing oxidative metabolism in mitochondria in injured brain suggests that there is a window of opportunity for therapeutic intervention up to at least 6 h after injury.
Combination of nateglinide with thiazolidinediones in Type 2 diabetes (2009)

Insulin sensitivity and insulin secretion are reciprocally related such that insulin resistance is adapted by increased insulin secretion to maintain normal glucose and lipid homeostasis. Treatment of Type 2 diabetes should aim to restore and sustain the normal relationship between insulin sensitivity and secretion. Nateglinide is a rapid-onset, short-acting insulin-secretion enhancer that restores early-phase insulin secretion, reduces postprandial glucose excursions and prevents long-term hyperinsulinemia. Given its mechanism of action, it is evident that nateglinide would be more effective when used in combination with an insulin sensitizer, such as the thiazolidinediones. Thiazolidinediones do not stimulate insulin release and, therefore, are potentially suitable candidates for combination therapy with an insulin-secretion enhancer, such as nateglinide. Combination therapy of thiazolidinediones with nateglinide is effective, carries low risk of hypoglycemia and is suitable for patients with moderate renal impairment, although weight gain and edema are common side effects. Further studies are needed to determine whether nateglinide in combination with thiazolidinediones will help clinicians better achieve their treatment goals in targeting Type 2 diabetes. Moreover, comparative studies between nateglinide and medications targeting postprandial glycemia, such as dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 analogues, are necessary. This article summarizes data concerning the mechanism of action, efficacy and safety of therapy with nateglinide and thiazolidinediones as monotherapy and in combination treatment, and aims at a better understanding of the substrate defects their synergy hopes to defy.
Rate-distortion optimized client side rate control for adaptive media streaming (2009)

Media streaming over unreliable networks such as the Internet is growing in popularity, but presents unique challenges when trying to get the user experience to be on par with classical mediums such as cable television. These networks have variable network conditions which not only vary between a set of points in the network, but also change over time. In this paper, we present a rate-distortion (R-D) optimized algorithm for adapting the bitrate of streaming media from a chunked encoding, where each chunk is available at multiple bitrates (or quality levels) or is scalable coded. The optimization takes into account the desired startup latency, the desired client buffer size, the current client buffer size, and the estimated network bandwidth. The problem is formulated as a distortion minimization problem subject to multiple rate constraints. For video content, the solution gives a gain of up to 3-4 dB in PSNR in difficult portions of the video when compared to commonly used adaptation techniques and can achieve an arbitrarily small desired startup latency.
Mutation of a putative ADP‐ribosylation motif in the Pasteurella multocida toxin does not affect mitogenic activity (1994)

Pasteurella multocida toxin (PMT) is a potent mitogen for Swiss 3T3 fibroblasts and cytotoxic to embryonic bovine lung cells. Site-directed mutagenesis was used to investigate the functional significance of a three amino acid motif in PMT that is present in five other bacterial protein toxins which exhibit ADP-ribosyl transferase activity. Crude lysates of mutant clones were fully cytotoxic for embryonic bovine lung cells. Purified mutant toxin was also as effective at stimulating inositol phosphate turnover and nucleic acid synthesis as wild type toxin. We conclude that this motif has no functional significance in Pasteurella multocida toxin.
Heterotophic Growth of Ankistrodesmus Sp. for Lipid Production Using Cassava Starch Hydrolysate as a Carbon Source (2013)

Research has been done on the culture of Ankistrodesmus sp. through heterotrophic conditions to obtain lipid content. Heterotrophic culture with the addition of several concentrations of cassava starch hydrolysate (CSH) as a source of organic carbon that increased lipid content. The highest cell density and cell growth rate (cell division) of Ankistrodesmussp achieved at 10 g.l-1 of CSH concentration on 2.46 x 106 cells.ml-1 which occurred at the 8th day and 0.50 cells.day-1 respectively. While the highest biomass and lipid content achieved at 5 g.l-1 of CSH concentration on 0.94 g.l-1 and 26% respectively.
Hepatic Stellate Cells and Liver Fibrosis (2013)

Hepatic stellate cells are resident perisinusoidal cells distributed throughout the liver, with a remarkable range of functions in normal and injured liver. Derived embryologically from septum transversum mesenchyme, their precursors include submesothelial cells that invade the liver parenchyma from the hepatic capsule. In normal adult liver, their most characteristic feature is the presence of cytoplasmic perinuclear droplets that are laden with retinyl (vitamin A) esters. Normal stellate cells display several patterns of intermediate filaments expression (e.g., desmin, vimentin, and/or glial fibrillary acidic protein) suggesting that there are subpopulations within this parental cell type. In the normal liver, stellate cells participate in retinoid storage, vasoregulation through endothelial cell interactions, extracellular matrix homeostasis, drug detoxification, immunotolerance, and possibly the preservation of hepatocyte mass through secretion of mitogens including hepatocyte growth factor. During liver injury, stellate cells activate into alpha smooth muscle actin-expressing contractile myofibroblasts, which contribute to vascular distortion and increased vascular resistance, thereby promoting portal hypertension. Other features of stellate cell activation include mitogen-mediated proliferation, increased fibrogenesis driven by connective tissue growth factor, and transforming growth factor beta 1, amplified inflammation and immunoregulation, and altered matrix degradation. Evolving areas of interest in stellate cell biology seek to understand mechanisms of their clearance during fibrosis resolution by either apoptosis, senescence, or reversion, and their contribution to hepatic stem cell amplification, regeneration, and hepatocellular cancer.
Inclusion bodies in recombinant E. coli producing human calcitonin tetramer, as visualized by immuno‐gold electron microscopy (1987)

Inclusion bodies are described in recombinant E. coli cells harboring plasmid for the expression of a synthetic gene coding for human calcitonin tetramer. The inclusion bodies are visualized by electron microscopy and the protein is identified by immuno-gold technique, using antibodies against synthetic human calcitonin. The diameter of the inclusion bodies is 1 micron on the average.
Available Power Gain, Noise Figure, and Noise Measure of Two-Ports and Their Graphical Representations (1966)

The expressions for available power gain and noise measure of linear two-ports are introduced in terms of the two-port parameters and the gain and the noise parameters, respectively. Their graphical representations on the source admittance plane with rectangular coordinates are also shown. Furthermore, it is shown that the behavior of available power gain, noise figure, and noise measure can be represented on the Smith-chart or the complex reflection coefficient plane of the source admittance. It is more convenient to investigate the gain and noise performance of amplifiers over a wide range of source admittance in this representation than with rectangular coordinates. As an example of the graphical representation the gain and noise performance of a microwave transistor is illustrated on the Smith-chart.
Finite reservoir replica exchange to enhance canonical sampling in rugged energy surfaces (2006)

A "finite reservoir" replica exchange method is presented to further enhance sampling upon the regular replica exchange method (REM) in a rugged energy surface. The present method can facilitate important sampling more efficiently by exchanging structures with configurations randomly selected from a finite-sized reservoir; this finite reservoir is pregenerated and updated by a mechanism of replica exchange with neighboring "temperature" simulations. In practice, this proposal revises exchange schedule in REM simulations in order to make productive exchange for conformational "tunneling" more frequent.