gebhart/patrepeval huggingface dataset:
Receiver-driven layered multicast (1996)

State of the art, real-time, rate-adaptive, multimedia applications adjust their transmission rate to match the available network capacity. Unfortunately, this source-based rate-adaptation performs poorly in a heterogeneous multicast environment because there is no single target rate --- the conflicting bandwidth requirements of all receivers cannot be simultaneously satisfied with one transmission rate. If the burden of rate-adaption is moved from the source to the receivers, heterogeneity is accommodated. One approach to receiver-driven adaptation is to combine a layered source coding algorithm with a layered transmission system. By selectively forwarding subsets of layers at constrained network links, each user receives the best quality signal that the network can deliver. We and others have proposed that selective-forwarding be carried out using multiple IP-Multicast groups where each receiver specifies its level of subscription by joining a subset of the groups. In this paper, we extend the multiple group framework with a rate-adaptation protocol called Receiver-driven Layered Multicast, or RLM. Under RLM, multicast receivers adapt to both the static heterogeneity of link bandwidths as well as dynamic variations in network capacity (i.e., congestion). We describe the RLM protocol and evaluate its performance with a preliminary simulation study that characterizes user-perceived quality by assessing loss rates over multiple time scales. For the configurations we simulated, RLM results in good throughput with transient short-term loss rates on the order of a few percent and long-term loss rates on the order of one percent. Finally, we discuss our implementation of a software-based Internet video codec and its integration with RLM.
Understanding Neural Interactions in Learning and Memory Using Functional Neuroimaging (1998)

Neuroimaging methods such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) provide a unique opportunity to explore activity across the entire human brain in many different behaviors. An important additional feature is the ability to examine interacting neural systems using methods that focus on the covariances of activity. Two of these methods, partial least squares and structural equation modeling, are presented with specific examples. Shifting prefrontal and limbic interactions were observed in a working memory task for faces. In an episodic memory retrieval study, the activity of right prefrontal cortex was related to either memory search or successful retrieval depending on its interactions with other brain regions. This latter observation implies that regional activity must be evaluated within the neural context in which it occurs. The general hypothesis that learning and memory are emergent properties of network interactions is discussed, emphasizing that a region can play a different role across many functions and that role is governed by its interactions with anatomically related regions.
The Mechanism of the Base-Catalyzed Addition of Thiols to Maleic Anhydride (1964)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Mechanism of the Base-Catalyzed Addition of Thiols to Maleic AnhydrideBasil. Dmuchovsky, Billy D. Vineyard, and Ferdinand B. ZientyCite this: J. Am. Chem. Soc. 1964, 86, 14, 2874–2877Publication Date (Print):July 1, 1964Publication History Published online1 May 2002Published inissue 1 July 1964https://pubs.acs.org/doi/10.1021/ja01068a022https://doi.org/10.1021/ja01068a022research-articleACS PublicationsRequest reuse permissionsArticle Views1029Altmetric-Citations34LEARN 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
Peroxisome Proliferator—Activated Receptor (PPAR)-αActivation Lowers Muscle Lipids and Improves Insulin Sensitivity in High Fat—Fed Rats (2001)

Peroxisome proliferator-activated receptor (PPAR)-alpha agonists lower circulating lipids, but the consequences for muscle lipid metabolism and insulin sensitivity are not clear. We investigated whether PPAR-alpha activation improves insulin sensitivity in insulin-resistant rats and compared the effects with PPAR-gamma activation. Three-week high fat-fed male Wistar rats were untreated or treated with the specific PPAR-alpha agonist WY14643 or the PPAR-gamma agonist pioglitazone (both 3 mg x kg(-1) x day(-1)) for the last 2 weeks of high-fat feeding. Like pioglitazone, WY14643 lowered basal plasma levels of glucose, triglycerides (-16% vs. untreated), and leptin (-52%), and also muscle triglyceride (-34%) and total long-chain acyl-CoAs (LCACoAs) (-41%) (P < 0.05). In contrast to pioglitazone, WY14643 substantially reduced visceral fat weight and total liver triglyceride content (P < 0.01) without increasing body weight gain. WY14643 and pioglitazone similarly enhanced whole-body insulin sensitivity (clamp glucose infusion rate increased 35 and 37% and glucose disposal 22 and 15%, respectively, vs. untreated). Both agents enhanced insulin-mediated muscle glucose metabolic index (Rg') and reduced muscle triglyceride and LCACoA accumulation (P < 0.05). Although pioglitazone had more potent effects than WY14643 on muscle insulin sensitization, this was associated with its greater effect to reduce muscle LCACoA accumulation. Overall insulin-mediated muscle Rg' was inversely correlated with the content of LCACoAs (r = -0.74, P = 0.001) and with plasma triglyceride levels (r = -0.77, P < 0.001). We conclude that even though WY14643 and pioglitazone, representing PPAR-alpha and PPAR-gamma activation, respectively, may alter muscle lipid supply by different mechanisms, both significantly improve muscle insulin action in the high fat-fed rat model of insulin resistance, and this effect is proportional to the degree to which they reduce muscle lipid accumulation.
Two-step enhanced cancer immunotherapy with engineered Salmonella typhimurium secreting heterologous flagellin (2017)

We report a method of cancer immunotherapy using an attenuated <i>Salmonella typhimurium</i> strain engineered to secrete <i>Vibrio vulnificus</i> flagellin B (FlaB) in tumor tissues. Engineered FlaB-secreting bacteria effectively suppressed tumor growth and metastasis in mouse models and prolonged survival. By using Toll-like receptor 5 (TLR5)-negative colon cancer cell lines, we provided evidence that the FlaB-mediated tumor suppression upon bacterial colonization is associated with TLR5-mediated host reactions in the tumor microenvironment. These therapeutic effects were completely abrogated in TLR4 and MyD88 knockout mice, and partly in TLR5 knockout mice, indicating that TLR4 signaling is a requisite for tumor suppression mediated by FlaB-secreting bacteria, whereas TLR5 signaling augmented tumor-suppressive host reactions. Tumor microenvironment colonization by engineered <i>Salmonella</i> appeared to induce the infiltration of abundant immune cells such as monocytes/macrophages and neutrophils via TLR4 signaling. Subsequent secretion of FlaB from colonizing <i>Salmonella</i> resulted in phenotypic and functional activation of intratumoral macrophages with M1 phenotypes and a reciprocal reduction in M2-like suppressive activities. Together, these findings provide evidence that nonvirulent tumor-targeting bacteria releasing multiple TLR ligands can be used as cancer immunotherapeutics.
Group 4 metallocene olefin hydrosilylation catalysts (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTGroup 4 metallocene olefin hydrosilylation catalystsMichael R. Kesti and Robert M. WaymouthCite this: Organometallics 1992, 11, 3, 1095–1103Publication Date (Print):March 1, 1992Publication History Published online1 May 2002Published inissue 1 March 1992https://pubs.acs.org/doi/10.1021/om00039a015https://doi.org/10.1021/om00039a015research-articleACS PublicationsRequest reuse permissionsArticle Views660Altmetric-Citations103LEARN 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
R-Lipoic Acid Inhibits Mammalian Pyruvate Dehydrogenase Kinase (2004)

The four pyruvate dehydrogenase kinase (PDK) and two pyruvate dehydrogenase phosphatase (PDP) isoenzymes that are present in mammalian tissues regulate activity of the pyruvate dehydrogenase complex (PDC) by phosphorylation/dephosphorylation of its pyruvate dehydrogenase (E1) component. The effect of lipoic acids on the activity of PDKs and PDPs was investigated in purified proteins system. R-lipoic acid, S-lipoic acid and R-dihydrolipoic acid did not significantly affect activities of PDPs and at the same time inhibited PDKs to different extents (PDK1>PDK4 approximately PDK2>PDK3 for R-LA). Since lipoic acids inhibited PDKs activity both when reconstituted in PDC and in the presence of E1 alone, dissociation of PDK from the lipoyl domains of dihydrolipoamide acetyltransferase in the presence of lipoic acids is not a likely explanation for inhibition. The activity of PDK1 towards phosphorylation sites 1, 2 and 3 of E1 was decreased to the same extent in the presence of R-lipoic acid, thus excluding protection of the E1 active site by lipoic acid from phosphorylation. R-lipoic acid inhibited autophosphorylation of PDK2 indicating that it exerted its effect on PDKs directly. Inhibition of PDK1 by R-lipoic acid was not altered by ADP but was decreased in the presence of pyruvate which itself inhibits PDKs. An inhibitory effect of lipoic acid on PDKs would result in less phosphorylation of E1 and hence increased PDC activity. This finding provides a possible mechanism for a glucose (and lactate) lowering effect of R-lipoic acid in diabetic subjects.
Dickkopf-1: a suitable target for the management of myeloma bone disease (2009)

Bone disease remains a major problem in the management of patients with multiple myeloma (MM) and is characterized by the presence of lytic lesions due to increased osteoclastic activity and reduced osteoblast function. Wingless-type and integrase 1 (Wnt)/beta-catenin signaling is a central pathway for bone development and homeostasis. Dickkopf-1 (Dkk-1) is a soluble inhibitor of Wnt, which disrupts osteoblast differentiation and action. Dkk-1 is produced by myeloma cells and overexpressed in myeloma microenvironment of patients with extensive bone disease. In addition to its direct inhibitory effect of Dkk-1 on osteoblasts, Dkk-1 disrupts the Wnt3a-regulated osteoprotegerin and receptor activator of NF-kappaB ligand (RANKL) expression in osteoblasts and thus it indirectly enhances osteoclast function in MM. Dkk-1 serum and bone marrow plasma levels are increased in MM patients and correlated with advanced International Staging System stage and presence of osteolytic lesions. Preclinical studies in mouse myeloma models showed that targeting Dkk-1 with neutralizing anti-Dkk-1 antibodies resulted in increased numbers of osteoblasts, reduced numbers of multinucleated osteoclasts and increased bone volume. The bone anabolic effect of anti-Dkk-1 may also be associated with reduced myeloma burden. These data show that Dkk-1 has a pivotal role in bone health and disease and is a novel target for the management of myeloma patients with lytic bone disease.
Farnesoid X-Activated Receptor Induces Apolipoprotein C-II Transcription: a Molecular Mechanism Linking Plasma Triglyceride Levels to Bile Acids (2001)

The farnesoid X-activated receptor (FXR; NR1H4), a member of the nuclear hormone receptor superfamily, induces gene expression in response to several bile acids, including chenodeoxycholic acid. Here we used suppression subtractive hybridization to identify apolipoprotein C-II (apoC-II) as an FXR target gene. Retroviral expression of FXR in HepG2 cells results in induction of the mRNA encoding apoC-II in response to several FXR ligands. EMSAs demonstrate that recombinant FXR and RXR bind to two FXR response elements that are contained within two important distal enhancer elements (hepatic control regions) that lie 11 kb and 22 kb upstream of the transcription start site of the apoC-II gene. A luciferase reporter gene containing the hepatic control region or two copies of the wild-type FXR response element was activated when FXR-containing cells were treated with FXR ligands. In addition, we report that hepatic expression of both apoC-II and phospholipid transfer protein mRNAs increases when mice are fed diets supplemented with cholic acid, an FXR ligand, and this induction is attenuated in FXR null mice. Finally, we observed decreased plasma triglyceride levels in mice fed cholic acid- containing diets. These results identify a mechanism whereby FXR and its ligands lower plasma triglyceride levels. These findings may have important implications in the clinical management of hyperlipidemias.
Induction of interleukin-6 by interferon alfa and its abrogation by a serine protease inhibitor in patients with chronic hepatitis C (1996)

We investigated short-term alterations in plasma interleukin-6 (IL-6), interleukin-1beta (IL-1beta), and tumor necrosis factor alpha (TNF-alpha) levels induced by interferon alfa (IFN-alpha) injection in 18 patients with chronic hepatitis C. A single intramuscular injection of human recombinant IFN-alpha 2a (6 million units [MU]) significantly increased the plasma IL-6 level 6 hours after the injection (P < .05). On the other hand, the IFN-alpha injection did not affect the plasma TNF-alpha and IL-lbeta levels. Polymerase chain reaction (PCR) analysis showed accumulation of IL-6 gene transcripts in peripheral blood mononuclear cells (PBMC) after IFN-alpha injection, indicating that IFN-alpha enhances IL-6 production at the messenger RNA level. The induction of IL-6 by IFN-alpha was completely suppressed by the intravenous administration of gabexate mesilate (GM), a serine protease inhibitor. The mechanism whereby GM suppresses the elevation in circulating IL-6 levels seems to be the inhibition of IL-6 production at the messenger RNA level. Elevations of both serum C-reactive protein (CRP) levels and body temperature after GM-suppressed IFN-alpha injection suggest that the administration of GM by suppressing IL-6 production, may attenuate the IL-6-related responses induced by IFN-alpha injection. In conclusion, we found that IL-6 was induced by IFN-alpha in vivo, and that this induction was completely abrogated by the administration of GM. Our results indicate that serine protease inhibitors may be useful for inhibiting IL-6-relating responses.
The Non-competitive Antagonists 2-Methyl-6-(phenylethynyl)pyridine and 7-Hydroxyiminocyclopropan[b]chromen-1a-carboxylic Acid Ethyl Ester Interact with Overlapping Binding Pockets in the Transmembrane Region of Group I Metabotropic Glutamate Receptors (2000)

We have investigated the mechanism of inhibition and site of action of the novel human metabotropic glutamate receptor 5 (hmGluR5) antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP), which is structurally unrelated to classical metabotropic glutamate receptor (mGluR) ligands. Schild analysis indicated that MPEP acts in a non-competitive manner. MPEP also inhibited to a large extent constitutive receptor activity in cells transiently overexpressing rat mGluR5, suggesting that MPEP acts as an inverse agonist. To investigate the molecular determinants that govern selective ligand binding, a mutagenesis study was performed using chimeras and single amino acid substitutions of hmGluR1 and hmGluR5. The mutants were tested for binding of the novel mGluR5 radioligand [(3)H]2-methyl-6-(3-methoxyphenyl)ethynyl pyridine (M-MPEP), a close analog of MPEP. Replacement of Ala-810 in transmembrane (TM) VII or Pro-655 and Ser-658 in TMIII with the homologous residues of hmGluR1 abolished radioligand binding. In contrast, the reciprocal hmGluR1 mutant bearing these three residues of hmGluR5 showed high affinity for [(3)H]M-MPEP. Radioligand binding to these mutants was also inhibited by 7-hydroxyiminocyclopropan[b]chromen-1a-carboxylic acid ethyl ester (CPCCOEt), a structurally unrelated non-competitive mGluR1 antagonist previously shown to interact with residues Thr-815 and Ala-818 in TMVII of hmGluR1. These results indicate that MPEP and CPCCOEt bind to overlapping binding pockets in the TM region of group I mGluRs but interact with different non-conserved residues.
Huffman Coding with Non-sorted Frequencies (2008)

A standard way of implementing Huffman's optimal code construction algorithm is by using a sorted sequence of frequencies. Using only partial order may speed up the code construction, which is important in some applications, at the cost of possibly increasing the size of the encoded file.
The cGMP-phosphodiesterase and its contribution to sensitivity regulation in retinal rods (1995)

We have used the truncated outer segment preparation to measure rod cGMP-phosphodiesterase activity, as well as its modulation by Ca2+, in darkness and in light. The basal enzyme activity in darkness was approximately 0-3 s-1, and was largely independent of Ca2+ concentration from 10 nM to 10 microM. The steady state activity elicited by a step of light (lambda = 520 nm) was strongly enhanced by Ca2+, increasing from approximately 0.005 s-1/(h nu micron-2 s-1) at 10 nM Ca2+ to approximately 0.16 s-1/h nu micron-2 s-1) at 10 microM Ca2+. Based on these measurements, as well as previous measurements on the effects of Ca2+ on rod guanylate cyclase and the cGMP-gated channel, we have calculated the step response-intensity relation for the rod cell in steady state. This relation agrees reasonably well with the relation directly measured from intact rods. We have also evaluated the relative contributions from the three Ca2+ effects to rod sensitivity. At low background light intensities, the Ca2+ modulation of the guanylate cyclase appears to be the most important for sensitivity regulation. At higher light intensities, especially above half-saturation of the response, the Ca2+ modulation of the light-stimulated phosphodiesterase shows a progressively important influence on the light response; it also extends the Weber-Fechner behavior of the cell to higher intensities. The contribution of the Ca2+ modulation of the cGMP-gated channel is slight throughout.
Kinetic and Mechanistic Characterization of the Polyhydroxybutyrate Synthase from Ralstonia eutropha (2000)

Purified Ralstonia eutropha polyhydroxybutyrate (PHB) synthase from recombinant cells can exist as monomer and dimer. The polymerization reaction catalyzed by this enzyme displays a lag phase, which causes difficulties for kinetic and mechanistic characterization of the enzymatic polymerization reaction. In this study, we developed a method to eliminate the lag phase of PHB synthase by physical means, i.e., adding multihydroxyl compounds to the enzyme solution. This method allows us to recognize the nature of the lag phase as a physical rather than a chemical process. With such lag-phase-free-enzyme, the kinetic properties of the enzyme were investigated. The results indicate that 3-hydroxybutyryl-CoA (3HBCoA) is the optimal substrate for the enzyme. A slower catalytic rate and lower binding ability account for a lower reactivity of 3-hydroxyvaleryl-CoA (3HVCoA) compared to that of 3HBCoA. The change of hydroxyl group from the beta to the gamma position causes dramatic decreases in the binding ability of 4-hydroxybutyryl-CoA (4HBCoA). By using a dilution strategy and size exclusion chromatographic technique, the active form of the enzyme was identified to be the dimeric form. The number of catalytic sites in the dimeric form of the enzyme was examined by comparing the molecular weight of polyhydroxybutyrate as a function of substrate-to-enzyme ratio. The results suggest that the dimeric enzyme has only one catalytic site. A revised model of polymerization reaction catalyzed by R. eutropha PHB synthase is described.
Clonal extinction of myelomonocytic leukemic cells by serum from mice injected with endotoxin (1980)

Culture of WEHI-3B myelomonocytic leukemic cells in semi-solid agar medium containing post-endotoxin serum led to the development of maturing granulocytes and macrophages in most leukemic colonies. Colony size was consistently increased but the colony content of colony-forming cells (stem-cell self-replication) was markedly reduced. Serial recloning of WEHI-3B colony cells in the continuous presence of post-endotoxin serum led to clonal extinction of the leukemic cells in five of seven experiments. These effects of post-endotoxin serum on WEHI-3B cells were not seen in clonal cultures of 10 other tumor lines. Serum with the capacity to induce differentiation in WEHI-3B cells could be induced by the injection of as little as 0.1 microgram endotoxin and by purified bacterial cell-wall preparations. Serum activity reached peak levels 3 - 6 h after endotoxin injection and returned to preinjection levels within 48 h.
Ethylene-regulated gene expression: molecular cloning of the genes encoding an endochitinase from Phaseolus vulgaris. (1986)

A full-length copy of bean leaf chitinase mRNA has been cloned. The 1146-base-pair insert of pCH18 encodes the 27-residue amino-terminal signal peptide of the precursor and 301 residues of the mature protein. Utilizing pCH18 as a hybridization probe, we have shown that the increase in translatable chitinase mRNA seen upon ethylene treatment of bean seedlings is due to a 75- to 100-fold increase in steady-state mRNA levels. Southern blot analysis of bean genomic DNA revealed that chitinase is encoded by a small, multigene family consisting of approximately four members. From our nucleotide sequence analysis of five additional chitinase cDNA clones, it appears that at least two of these genes are expressed. Three of the bean chitinase genes have been isolated from a Sau3A genomic library and partially characterized.