gebhart/patrepeval huggingface dataset:
Proportional fair scheduling algorithm in OFDMA-based wireless systems with QoS constraints (2010)

In this work we consider the problem of downlink resource allocation for proportional fairness of long term received rates of data users and quality of service for real time sessions in an OFDMA-based wireless system. The base station allocates available power and subchannels to individual users based on long term average received rates, quality of service (QoS) based rate constraints and channel conditions. We formulate and solve a joint bandwidth and power optimization problem, solving which provides a performance improvement with respect to existing resource allocation algorithms. We propose schemes for flat as well as frequency selective fading cases. Numerical evaluation results show that the proposed method provides better QoS to voice and video sessions while providing more and fair rates to data users in comparison with existing schemes.
Complement C1q-induced activation of β-catenin signalling causes hypertensive arterial remodelling (2015)

Hypertension induces structural remodelling of arteries, which leads to arteriosclerosis and end-organ damage. Hyperplasia of vascular smooth muscle cells (VSMCs) and infiltration of immune cells are the hallmark of hypertensive arterial remodelling. However, the precise molecular mechanisms of arterial remodelling remain elusive. We have recently reported that complement C1q activates β-catenin signalling independent of Wnts. Here, we show a critical role of complement C1-induced activation of β-catenin signalling in hypertensive arterial remodelling. Activation of β-catenin and proliferation of VSMCs were observed after blood-pressure elevation, which were prevented by genetic and chemical inhibition of β-catenin signalling. Macrophage depletion and C1qa gene deletion attenuated the hypertension-induced β-catenin signalling, proliferation of VSMCs and pathological arterial remodelling. Our findings unveil the link between complement C1 and arterial remodelling and suggest that C1-induced activation of β-catenin signalling becomes a novel therapeutic target to prevent arteriosclerosis in patients with hypertension.
Tumor Growth Inhibition by Interferon-α using PEGylated Protein or Adenovirus Gene Transfer with Constitutive or Regulated Expression (2002)

Inducible synthesis and secretion of therapeutic proteins following gene transfer could be a viable strategy to deliver biopharmaceuticals that currently require parenteral administration. Evaluating the protein pharmacokinetics and biological responses generated by different delivery modalities will provide a better understanding of the advantages and disadvantages of each strategy. The interferon-alpha (IFN-alpha) family of proteins, used clinically for infectious and malignant diseases, has a short half-life, and IFN-alpha therapy requires frequent administration of the drug by injection. Subcutaneous xenograft tumors were inhibited by weekly administration of polyethylene glycol modified (PEGylated) IFN-alpha protein or by a single administration of an adenovirus constitutively expressing IFN-alpha (IACB). Both treatment modalities inhibited tumor growth in a dose-dependent manner, suggesting that increasing exposure to IFN-alpha could result in effective tumor control. A single adenovirus that encodes the components necessary for tetracycline induction (IADR) expressed IFN-alpha in a ligand-dependent manner. Adding doxycycline to the drinking water of mice treated intravenously with the inducible adenovirus IADR inhibited tumor growth by 85% compared with mice that were not given doxycycline. The correlation between serum IFN-alpha concentration and the degree of tumor growth inhibition did not depend on the delivery technology used. It is likely that it will be feasible to control expression of IFN-alpha by oral administration of small molecule drugs after gene delivery to induce therapeutic concentrations of proteins.
125,660 specimens of natural history: Re-imagining the practice of collection through Alfred R. Wallace's Malay expedition (2014)

In the era of the Anthropocene, the assumed division between nature and culture is radically destabilized. By taking a nineteenth century colonial collection of natu r:al history as a point of departure, the international touring eXhibition 125,660 Specimens of Natural History: Re-imagining the Practice of Collection Through Alfred R. Wallace's Malay Expedition (to premier at Komunitas Salihara, Jakarta, 2015) develops transcuttural artistic and curatorial methodologies as means to rethink tradttional views on collecting geographies, and museological genres in light of contemporary political and environmental issues. In our presentation to the Collecting Geographies conference at the Stedelijk Museum, we will discuss the conceptual framework of the project, including our research on other scientists worl
DNA microscopy: Optics-free spatio-genetic imaging by a stand-alone chemical reaction (2018)

Abstract Analyzing the spatial organization of molecules in cells and tissues is a cornerstone of biological research and clinical practice. However, despite enormous progress in profiling the molecular constituents of cells, spatially mapping these constituents remains a disjointed and machinery-intensive process, relying on either light microscopy or direct physical registration and capture. Here, we demonstrate DNA microscopy, a new imaging modality for scalable, optics-free mapping of relative biomolecule positions. In DNA microscopy of transcripts, transcript molecules are tagged in situ with randomized nucleotides, labeling each molecule uniquely. A second in situ reaction then amplifies the tagged molecules, concatenates the resulting copies, and adds new randomized nucleotides to uniquely label each concatenation event. An algorithm decodes molecular proximities from these concatenated sequences, and infers physical images of the original transcripts at cellular resolution. Because its imaging power derives entirely from diffusive molecular dynamics, DNA microscopy constitutes a chemically encoded microscopy system.
T-cell response to structural and nonstructural hepatitis C virus antigens in persistent and self-limited hepatitis C virus infections (1994)

Twenty-nine patients with chronic hepatitis C and 15 asymptomatic hepatitis C virus antibody-positive subjects who clinically recovered from hepatitis C virus infection were studied for their peripheral blood lymphomononuclear cell proliferative response to hepatitis C virus structural and nonstructural antigens (core, envelope, nonstructural 4 and nonstructural 5) expressed in yeast as superoxide dismutase fusion proteins, in an initial attempt to define some of the features of the virus-specific immune response. Hepatitis C virus core was the most immunogenic antigen for human leukocyte antigen class II-restricted T cells in both groups of patients studied, and the proliferative response to it was the most vigorous and the most frequently expressed in comparison with the other antigens tested. The specificity of the results was supported by the lack of response to hepatitis C virus antigens by healthy uninfected controls and confirmed by recognition of recombinant core proteins of different origin (yeast and baculovirus) by polyclonal T-cell lines produced by T-cell stimulation with yeast-derived core. Each of the antigens tested was able to induce significant although variable levels of proliferative response, indicating that all can be immunogenic at the T-cell level. Significant proliferative responses to core, nonstructural 4 and nonstructural 5 antigens were more frequently detected in subjects who were able to eradicate infection than in patients with chronic hepatitis C, although the difference was statistically not significant. No difference was observed between the two groups of patients with respect to the response to the putative envelope antigens.
Treatment of Male Hypogonadism with Testosterone Enanthate* (1980)

To determine the relative efficacy of several dosage regimens of testosterone enanthate in the treatment of male hypogonadism, we treated men who had primary hypogonadism with the following dosage regimens: 100 mg once a week, 200 mg every 2 weeks, 300 mg every 3 weeks, and 400 mg every 4 weeks, each for 12--16 weeks. Twenty-three men completed 37 dosage regimens. The 100-, 200-, and 300-mg dosages all suppressed the initially elevated serum LH concentrations to normal, but the 400-mg dosage did not. The 100- and 200-mg regimens suppressed the initially elevated serum FSH concentrations to normal, and the 300-mg regimen almost did not so. All four regimens produced serum testosterone concentrations that fluctuated largely within the normal range, the average concentration between doses was highest with 100 mg and lowest with 400 mg. The regimens of 200 mg every 2 weeks and 300 mg every 3 weeks appeared to be the most effective of those tested in terms of suppression of the serum LH concentration to normal and infrequency of administration. The close parallel of the FSH response to that of LH suggests that testosterone is the major physiological inhibitor of FSH as well as of LH.
Enhanced tumorigenesis in p53 knockout mice exposed in utero to high-dose vitamin E (2006)

The limited antioxidative capacity of the embryo and fetus may increase their risk for cancer initiation and/or promotion by reactive oxygen species (ROS)-mediated oxidative DNA damage and/or signaling. To determine if cancer can originate in utero, a high dietary dose of the antioxidant vitamin E (VE) (10% dl-a-tocopherol-acetate) was given to cancer-prone p53 knockout mice throughout pregnancy. Although reducing fetal death (P < 0.05), in utero exposure to VE enhanced postnatal tumorigenesis in both +/ (P < 0.04) and / (P < 0.0008) p53-deficient offspring. VE did not alter maternal weights, offspring p53 genotypic distribution or tumor spectrum. Constitutive embryonic DNA oxidation in untreated / p53 embryos [gestational day (GD) 13] was higher than in +/ and +/+ p53 littermates (P < 0.05). VE reduced DNA oxidation in / p53 embryos (P < 0.05) without affecting +/ and +/+ p53 littermates. VE had contrasting, tissue-dependent effects on fetal (GD 19) DNA oxidation, with reductions in / and +/ p53deficient fetal brains (P < 0.01), increases in skin (P < 0.05) and no effect in liver and thymus. The 250-fold increase in dietary VE levels produced only 1.6-6.3-fold, tissue-dependent increases in tissue concentrations. The greatest increase, in fetal skin, correlated with increased DNA oxidation in that tissue in / and +/ p53-deficient fetuses and enhanced tumorigenesis in these genotypes. These results show that some cancers may originate in utero and the risk can be enhanced by embryonic and fetal exposure to high dietary levels of VE. The elevated DNA oxidation in some tissues of untreated / p53 offspring suggests that ROS may contribute to their higher baseline tumor incidence. The limited and tissue-dependent disposition of VE indicates substantial conceptal regulation. The similarly selective and contrasting effects of VE on DNA oxidation may contribute to its controversial protective efficacy and suggest that its effects on tumorigenesis are cell-specific, possibly in high doses involving a pro-oxidative mechanism.
Psoriatic skin lesions contain biologically active amounts of an interleukin 1-like compound. (1986)

The presence of neutrophil chemoattractant material in aqueous extracts of lesional psoriatic scale has been investigated by use of an agarose microdroplet chemokinesis method in combination with ultrafiltration and high-performance liquid chromatography (HPLC). Fractions were also assayed for murine thymocyte co-stimulating activity. Aqueous extracts of psoriatic scale contained significantly greater neutrophil chemokinetic activity than extracts of scale from normal skin. Successive ultrafiltration of extracts showed that the chemokinetic material was 10 to 30 kd. Heat lability and gel filtration HPLC characteristics suggested that the major chemokinetically active material in aqueous extracts of psoriatic scale is different from C5a des arg. Reversed-phase HPLC of 0.1% trifluoroacetic acid/acetonitrile extracts of psoriatic scale revealed two clearly resolved peaks of chemokinetic activity, the major peak consistently containing thymocyte co-stimulating activity. No significant neutrophil chemokinetic activity was seen in fractions after reversed-phase HPLC of scale from normal skin. These findings suggest that a major portion of the neutrophil chemoattractant activity in aqueous extracts of psoriatic scale is due to interleukin 1-like material, which may play a role in the pathogenesis of this disease.
Defective DNA cross-link removal in Chinese hamster cell mutants hypersensitive to bifunctional alkylating agents. (1985)

DNA repair-deficient mutants from five genetic complementation groups isolated previously from Chinese hamster cells were assayed for survival after exposure to the bifunctional alkylating agents mitomycin C or diepoxybutane. Groups 1, 3, and 5 exhibited 1.6- to 3-fold hypersensitivity compared to the wild-type cells, whereas Groups 2 and 4 exhibited extraordinary hypersensitivity (30- to 90-fold). Mutants from Groups 1 and 2 were exposed to 22 other bifunctional alkylating agents in a rapid assay that compared cytotoxicity of the mutants to the wild-type parental strain, AA8. With all but two of the compounds, the Group 2 mutant (UV4) was 15- to 60-fold more sensitive than AA8 or the Group 1 mutant (UV5). UV4 showed only 6-fold hypersensitivity to quinacrine mustard. Alkaline elution measurements showed that this compound produced few DNA interstrand cross-links but numerous strand breaks that were revealed by proteinase treatment. Therefore, the extreme hypersensitivity of mutants from Groups 2 and 4 appeared specific for compounds the main cytotoxic lesions of which were DNA cross-links. Mutant UV5 was only 1- to 4-fold hypersensitive to all the compounds. Repair kinetics of DNA interstrand cross-link production and removal was measured by alkaline elution for AA8 and mutants UV4 and UV5 after exposure to diepoxybutane. Although the initial number of cross-links was similar for the three cell lines, during 24-h incubation, the efficiency of removal of cross-links was lowest in UV4 and intermediate in UV5. These results suggest that the different levels of sensitivity of the five complementation groups to bifunctional alkylation damage are specifically related to different efficiencies of DNA cross-link removal. The phenotype of hypersensitivity to both UV radiation and cross-link damage exhibited by the mutants in Groups 2 and 4 appears to differ from those of the known human DNA repair syndromes.
Allosteric Modulation of Seven Transmembrane Spanning Receptors: Theory, Practice, and Opportunities for Central Nervous System Drug Discovery (2011)

ADVERTISEMENT RETURN TO ISSUEPREVPerspectiveNEXTAllosteric Modulation of Seven Transmembrane Spanning Receptors: Theory, Practice, and Opportunities for Central Nervous System Drug DiscoveryBruce J. Melancon†‡§, Corey R. Hopkins†∥‡§, Michael R. Wood†∥‡§, Kyle A. Emmitte†∥‡§, Colleen M. Niswender†‡§, Arthur Christopoulos⊥, P. Jeffrey Conn†‡§, and Craig W. Lindsley*†∥‡§View Author Information† ‡ § †Department of Pharmacology, ‡Vanderbilt Center for Neuroscience Drug Discovery, and §Vanderbilt Specialized Chemistry Center (MLPCN), Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States∥ Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37232, United States⊥ Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Melbourne, Australia*Phone: 615-322-8700. Fax: 615-345-6532. E-mail: [email protected]Cite this: J. Med. Chem. 2012, 55, 4, 1445–1464Publication Date (Web):December 9, 2011Publication History Received25 August 2011Published online6 January 2012Published inissue 23 February 2012https://pubs.acs.org/doi/10.1021/jm201139rhttps://doi.org/10.1021/jm201139rreview-articleACS PublicationsCopyright © 2011 American Chemical SocietyRequest reuse permissionsArticle Views7319Altmetric-Citations193LEARN 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:Agonists,Ligands,Modulators,Polyacrylamide,Receptors Get e-Alerts
Determination of imipenem and cilastatin in serum by high-pressure liquid chromatography (1984)

Imipenem and cilastatin concentrations in serum were determined by using reverse-phase high-pressure liquid chromatography. Serum samples were stabilized with 0.5 M morpholineethanesulfonic acid buffer (pH 6.0) and subjected to ultrafiltration before chromatography. The elution solvent consisted of water or potassium phosphate buffered to pH 2.5 and methanol. The imipenem and cilastatin peaks were detected at 300 and 220 nm, respectively. Recovery from serum was 99% for both imipenem and cilastatin, and the limits of detectability for the two compounds were 0.3 and 0.5 microgram/ml, respectively. The assay may be readily applied to pharmacokinetic analysis of imipenem and cilastatin biodisposition in patients.
Evolution of avalanche conducting states in electrorheological liquids (1999)

Charge transport in electrorheological fluids is studied experimentally under strongly nonequilibrium conditions. By injecting an electrical current into a suspension of conducting nanoparticles we are able to initiate a process of self-organization which leads, in certain cases, to formation of a stable pattern which consists of continuous conducting chains of particles. The evolution of the dissipative state in such a system is a complex process. It starts as an avalanche process characterized by nucleation, growth, and thermal destruction of such dissipative elements as continuous conducting chains of particles as well as electroconvective vortices. A power-law distribution of avalanche sizes and durations, observed at this stage of the evolution, indicates that the system is in a self-organized critical state. A sharp transition into an avalanche-free state with a stable pattern of conducting chains is observed when the power dissipated in the fluid reaches its maximum. We propose a simple evolution model which obeys the maximum power condition and also shows a power-law distribution of the avalanche sizes.
MHC class II deprivation impairs CD4 T cell motility and responsiveness to antigen-bearing dendritic cells in vivo (2007)

The role continuous contact with self-peptide/MHC molecules (self ligands) in the periphery plays in the function of mature T cells remains unclear. Here, we elucidate a role for MHC class II molecules in T cell trafficking and antigen responsiveness in vivo. We find that naïve CD4 T cells deprived of MHC class II molecules demonstrate a progressive and profound defect in motility (measured by real-time two-photon imaging) and that these cells have a decreased ability to interact with limiting numbers of cognate antigen-bearing dendritic cells, but they do not demonstrate a defect in their responsiveness to direct stimulation with anti-CD3 monoclonal antibody. Using GST fusion proteins, we show that MHC class II availability promotes basal activation of Rap1 and Rac1 but does not alter the basal activity of Ras. We propose that tonic T cell receptor signaling from self-ligand stimulation is required to maintain a basal state of activation of small guanosine triphosphatases critical for normal T cell motility and that T cell motility is critical for the antigen receptivity of naïve CD4 T cells. These studies suggest a role for continuous self-ligand stimulation in the periphery for the maintenance and function of mature naïve CD4 T cells.
Challenges for the Delivery of Long-Chain n-3 Fatty Acids in Functional Foods (2012)

Extensive research has shown that increased consumption of long-chain omega-3 polyunsaturated fatty acids (n-3 LCPUFAs), namely α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), may lower the risk of chronic diseases, such as heart disease, cancer, and arthritis. Given that Western diets are deficient in n-3 LCPUFAs, enrichment of food products is seen as an alternative for increasing the intake of these fatty acids. However, because of the high instability of these fatty acids to oxidative deterioration, enrichment of foods with n-3 LCPUFAs has been technically challenging. This review provides an overview of different technical approaches that have been taken to overcome oxidation-related problems. This review also looks at the challenges faced by health organizations, food manufacturers, and food scientists for the delivery of long-chain n-3 fatty acids in functional foods.
Multi-Site Testing With a Point-of-Care Nerve Conduction Device Can Be Used in an Algorithm to Diagnose Diabetic Sensorimotor Polyneuropathy (2008)

A novel point-of-care device has reasonable diagnostic accuracy and thus may represent a sufficiently accurate alternative for detecting the diffuse electrophysiological criteria necessary to make the diagnosis of diabetic sensorimotor polyneuropathy.
Sorafenib Blocks the RAF/MEK/ERK Pathway, Inhibits Tumor Angiogenesis, and Induces Tumor Cell Apoptosis in Hepatocellular Carcinoma Model PLC/PRF/5 (2006)

Angiogenesis and signaling through the RAF/mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK cascade have been reported to play important roles in the development of hepatocellular carcinomas (HCC). Sorafenib (BAY 43-9006, Nexavar) is a multikinase inhibitor with activity against Raf kinase and several receptor tyrosine kinases, including vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor (PDGFR), FLT3, Ret, and c-Kit. In this study, we investigated the in vitro effects of sorafenib on PLC/PRF/5 and HepG2 HCC cells and the in vivo antitumor efficacy and mechanism of action on PLC/PRF/5 human tumor xenografts in severe combined immunodeficient mice. Sorafenib inhibited the phosphorylation of MEK and ERK and down-regulated cyclin D1 levels in these two cell lines. Sorafenib also reduced the phosphorylation level of eIF4E and down-regulated the antiapoptotic protein Mcl-1 in a MEK/ERK-independent manner. Consistent with the effects on both MEK/ERK-dependent and MEK/ERK-independent signaling pathways, sorafenib inhibited proliferation and induced apoptosis in both HCC cell lines. In the PLC/PRF/5 xenograft model, sorafenib tosylate dosed at 10 mg/kg inhibited tumor growth by 49%. At 30 mg/kg, sorafenib tosylate produced complete tumor growth inhibition. A dose of 100 mg/kg produced partial tumor regressions in 50% of the mice. In mechanism of action studies, sorafenib inhibited the phosphorylation of both ERK and eIF4E, reduced the microvessel area (assessed by CD34 immunohistochemistry), and induced tumor cell apoptosis (assessed by terminal deoxynucleotidyl transferase-mediated nick end labeling) in PLC/PRF/5 tumor xenografts. These results suggest that the antitumor activity of sorafenib in HCC models may be attributed to inhibition of tumor angiogenesis (VEGFR and PDGFR) and direct effects on tumor cell proliferation/survival (Raf kinase signaling-dependent and signaling-independent mechanisms).