gebhart/patrepeval huggingface dataset:
Pharmacology and function of melatonin receptors (1988)

The hormone melatonin is secreted primarily from the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone, through an action in the brain, appears to be involved in the regulation of various neural and endocrine processes that are cued by the daily change in photoperiod. This article reviews the pharmacological characteristics and function of melatonin receptors in the central nervous system, and the role of melatonin in mediating physiological functions in mammals. Melatonin and melatonin agonists, at picomolar concentrations, inhibit the release of dopamine from retina through activation of a site that is pharmacologically different from a serotonin receptor. These inhibitory effects are antagonized by the novel melatonin receptor antagonist luzindole (N-0774), which suggests that melatonin activates a presynaptic melatonin receptor. In chicken and rabbit retina, the pharmacological characteristics of the presynaptic melatonin receptor and the site labeled by 2-[125I]iodomelatonin are identical. It is proposed that 2-[125I]iodomelatonin binding sites (e.g., chicken brain) that possess the pharmacological characteristics of the retinal melatonin receptor site (order of affinities: 2-iodomelatonin greater than 6-chloromelatonin greater than or equal to melatonin greater than or equal to 6,7-di-chloro-2-methylmelatonin greater than 6-hydroxymelatonin greater than or equal to 6-methoxymelatonin greater than N-acetyltryptamine greater than or equal to luzindole greater than N-acetyl-5-hydroxytryptamine greater than 5-methoxytryptamine much greater than 5-hydroxytryptamine) be classified as ML-1 (melatonin 1). The 2-[125I]iodomelatonin binding site of hamster brain membranes possesses different binding and pharmacological characteristics from the retinal melatonin receptor site and should be classified as ML-2. In summary, the recent advances in the pharmacological characterization of melatonin receptors in the central nervous system will further stimulate the search for potent and selective melatonin receptor agonists and antagonists, and should aid in our understanding of the mechanism of action of melatonin in mammalian brain.
The expression of metastasis suppressor MIM/MTSS1 is regulated by DNA methylation (2006)

MIM/MTSS1 was initially described as a gene missing in invasive bladder cancer cell lines. Functional analysis revealed that MIM is an actin binding protein involved in the regulation of actin cytoskeleton dynamics. MIM was shown to be sonic hedgehog (Shh) signaling dependent and synergizes with the effects of Gli transcription factors. Overexpression of MIM in cell lines leads to the inhibition of cell proliferation. In this study, we showed that the inhibition of cell growth by MIM is anchorage independent. We identified and cloned the promoter region of MIM and located the main promoter activity to 276 bp of 5' flanking sequence sited within a CpG island. Analysis of DNA methylation using bisulphite sequencing revealed that MIM promoter is methylated in its 5' region in cells and tissue samples with reduced endogenous MIM expression. Using luciferase reporter assay, we demonstrated that nonmethylated MIM promoter has a similar activity in cell lines with different endogenous MIM expression. Inhibition of DNA methylation by 5-Aza-2'-deoxycytidine led to upregulation of MIM expression in a low expressing cell line. In conclusion, we clearly demonstrate here that the expression of metastasis suppressor MIM is regulated by DNA methylation of a CpG island within its promoter region.
Stability of Nb-Doped Cubic Li7La3Zr2O12with Lithium Metal (2013)

The garnet-type Nb-doped cubic lithium ion-conducting solid Li6.75-xLa3Zr1.75Nb0.25O12–0.5x (LLZ-Nb) was prepared with 0.46 wt% Al2O3 using a sol-gel precursor. LLZ-Nb sintered at 1,150°C for 36 h exhibited a bulk conductivity of 6.13 × 10−4 S cm−1 and a grain boundary conductivity of 7.76 × 10−3 S cm−1 at 25°C. The cell resistance of Li/LLZ-Nb/Li was gradually increased with storage time over 5 months. The increase in cell resistance was attributed to both the grain boundary and interfacial resistance between LLZ-Nb and the lithium electrode. The Li/LLZ-Nb/Li cell showed a short-circuit for 280 s polarization at 0.5 mA cm−2 and no short-circuit for 41 h polarization at 0.1 mA cm−2. LLZ-Nb was stable in saturated LiOH and LiCl aqueous solution.
Diabetes Beyond Insulin: Review of New Drugs for Treatment of Diabetes Mellitus (2007)

Diabetes mellitus (DM) is a progressive disease characterized by insulin deficiency and insulin resistance or both. The fasting and post-prandial blood glucose is elevated, exposing the patient to acute and chronic complications (micro- and macro-vascular) leading to blindness, kidney failure, heart disease, stroke and amputations. Improving glycemic control has been demonstrated to lower the risk of these complications. Owing to the progressive nature of the disease, an evolving treatment strategy is necessary to maintain glycemic control. Varieties of new pharmacologic interventions are developed in past 5 years to treat people with diabetes. Several studies have been carried out covering different aspects of pharmacological interventions (newer and old drugs) along with the effects of weight loss, diet and exercise. Two categories of drugs have been used for the treatment of Diabetes Mellitus: the insulin and oral agents. Insulin analogues are molecules that differ from human insulin in amino acid sequence but bind to the insulin receptors and act similarly in function. This article provides an update of pharmacologic interventions for diabetes with practical overview of the new drug options, new insulin analogues, pharmacology, clinical efficacy, safety, dosing, cost, with specific examples of each and their background and side effects used to achieve tight glucose control. These agents have distinct characteristics that help in their selection for the treatment of type 1 and type 2 diabetes.
Activity of second‐line chemotherapy in docetaxel‐refractory hormone‐refractory prostate cancer patients (2007)

Ixabepilone and MP had modest activity as second-line chemotherapy for docetaxel-refractory HRPC. The median survival for the entire cohort treated in this study was 9.8 months.
Angiotensin II inhibits and alters kinetics of voltage-gated K+channels of rat arterial smooth muscle (2001)

The vasoconstrictor angiotensin II (ANG II) inhibits several types of K(+) channels. We examined the inhibitory mechanism of ANG II on voltage-gated K(+) (K(V)) currents (I(K(V))) recorded from isolated rat arterial smooth muscle using patch-clamp techniques. Application of 100 nM ANG II accelerated the activation of I(K(V)) but also caused inactivation. These effects were abolished by the AT(1) receptor antagonist losartan. The protein kinase A (PKA) inhibitor Rp-cyclic 3',5'-hydrogen phosphothioate adenosine (100 microM) and an analog of diacylglycerol, 1,2-dioctanyoyl-rac-glycerol (2 microM), caused a significant reduction of I(K(V)). Furthermore, the combination of 5 microM PKA inhibitor peptide 5-24 (PKA-IP) and 100 microM protein kinase C (PKC) inhibitor peptide 19-27 (PKC-IP) prevented the inhibition by ANG II, although neither alone was effective. The ANG II effect seen in the presence of PKA-IP remained during addition of the Ca(2+)-dependent PKC inhibitor Gö6976 (1 microM) but was abolished in the presence of 40 microM PKC-epsilon translocation inhibitor peptide. These results demonstrate that ANG II inhibits K(V) channels through both activation of PKC-epsilon and inhibition of PKA.
Improved Precoding Method for PAPR Reduction in OFDM with Bounded Distortion (2010)

Orthogonal Frequency Division Multiplexing (OFDM) is a very attractive technique for high-data-rate transmission in wireless and wired applications. The main drawback of the OFDM technique is its high peak to average power ratio(PAPR). Several approaches exists to reduce PAPR of OFDM symbols. Precoding is a new method which is having less complexity compared to the other power reduction techniques and also it can reduce PAPR considerably and results in no distortion. Error control coding(convolution coding is used here) can also be introduced along with the Precoding technique in order to improve the bit error rate performance. Clipping and filtering with bounded distortion is a simple method and provides a high PAPR reduction at the cost of signal distortion. we can restrict this distortion within a particular limit using bounded distortion algorithm(BD). In this paper the PAPR reduction is obtained by combining the precoding method and clipping technique with BD i.e. this modified method takes the advantages of two PAPR reduction technique. This paper presents various computer simulation results to verify the effectiveness of this modified precoding method.
Neonatal Administration of IL-12 Enhances the Protective Efficacy of Antiviral Vaccines (2000)

Neonates are highly susceptible to infectious agents and are known to display polarized expression of Th2-like cytokines and Abs. This neonatal immune bias has important implications for the development of vaccine strategies, particularly against viral infections. We now report that coadministration of IL-12 and an influenza subunit vaccine at birth enhances the protective efficacy of antiviral vaccination. Immunization and treatment with IL-12 within 24 h of birth resulted in elevated expression of IFN-gamma, IL-10, and IL-15 mRNA in the spleens of newborn mice compared with animals exposed to vaccine only. In addition, these animals showed dramatic increases in IFN-gamma-, IL-2-, and IL-4-secreting cells, and in IgG2a Ab levels upon adult challenge compared with mice primed with vaccine alone. Most importantly, animals vaccinated and simultaneously treated with IL-12 at birth displayed enhanced survival after lethal challenge with infectious influenza virus as adults compared with infected animals that had been primed with vaccine alone. This augmented protection required B cells and could be transferred to naive mice by immune serum. Collectively, these results provide evidence that administration of IL-12 to neonates induces a Th1-like response in newborns and elicits protective antiviral immune memory.
Gamma interferon augments Fc gamma receptor-mediated dengue virus infection of human monocytic cells (1988)

It has been reported that anti-dengue antibodies at subneutralizing concentrations augment dengue virus infection of monocytic cells. This is due to the increased uptake of dengue virus in the form of virus-antibody complexes by cells via Fc gamma receptors. We analyzed the effects of recombinant human gamma interferon (rIFN-gamma) on dengue virus infection of human monocytic cells. U937 cells, a human monocytic cell line, were infected with dengue virus in the form of virus-antibody complexes after rIFN-gamma treatment. Pretreatment of U937 cells with rIFN-gamma resulted in a significant increase in the number of dengue virus-infected cells and in the yield of infectious virus. rIFN-gamma did not augment dengue virus infection when cells were infected with virus in the absence of anti-dengue antibodies. Gamma interferon (IFN-gamma) produced by peripheral blood lymphocytes from dengue-immune donors after in vitro stimulation with dengue antigens also augmented dengue virus infection of U937 cells. IFN-gamma did not augment dengue virus infections when cells were infected with virus in the presence of F(ab')2 prepared from anti-dengue immunoglobulin G. Human immunoglobulin inhibited IFN-gamma-induced augmentation. IFN-gamma increased the number of Fc gamma receptors on U937 cells. The increase in the percentage of dengue antigen-positive cells correlated with the increase in the number of Fc gamma receptors after rIFN-gamma treatment. These results indicate that IFN-gamma-induced augmentation of dengue virus infection is Fc gamma receptor mediated. Based on these results we conclude that IFN-gamma increases the number of Fc gamma receptors and that this leads to an augmented uptake of dengue virus in the form of dengue virus-antibody complexes, which results in augmented dengue virus infection.
DiverseNet: When One Right Answer is not Enough (2018)

Many structured prediction tasks in machine vision have a collection of acceptable answers, instead of one definitive ground truth answer. Segmentation of images, for example, is subject to human labeling bias. Similarly, there are multiple possible pixel values that could plausibly complete occluded image regions. State-of-the art supervised learning methods are typically optimized to make a single test-time prediction for each query, failing to find other modes in the output space. Existing methods that allow for sampling often sacrifice speed or accuracy. We introduce a simple method for training a neural network, which enables diverse structured predictions to be made for each test-time query. For a single input, we learn to predict a range of possible answers. We compare favorably to methods that seek diversity through an ensemble of networks. Such stochastic multiple choice learning faces mode collapse, where one or more ensemble members fail to receive any training signal. Our best performing solution can be deployed for various tasks, and just involves small modifications to the existing single-mode architecture, loss function, and training regime. We demonstrate that our method results in quantitative improvements across three challenging tasks: 2D image completion, 3D volume estimation, and flow prediction.
The Occurrence of Metastable Tetragonal Zirconia as a Crystallite Size Effect (1965)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Occurrence of Metastable Tetragonal Zirconia as a Crystallite Size EffectRonald C. GarvieCite this: J. Phys. Chem. 1965, 69, 4, 1238–1243Publication Date (Print):April 1, 1965Publication History Published online1 May 2002Published inissue 1 April 1965https://pubs.acs.org/doi/10.1021/j100888a024https://doi.org/10.1021/j100888a024research-articleACS PublicationsRequest reuse permissionsArticle Views4685Altmetric-Citations1315LEARN 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 options Get e-Alerts
Non-insulin-dependent diabetes mellitus: a clinical strategy. (1984)

In non-insulin-dependent diabetes mellitus (NIDDM), there are defects in both islet beta cell function (insulin secretion) and in insulin action. It is proposed that these may be two manifestations of a common defect involving glucose metabolism. These may be a consequence of some aspect of the insulin-deficient state, e.g., insulin deficiency or hyperglycemia. This implies that the defects of NIDDM are both "feed-forward" (i.e., they lessen with improvement of the metabolic state) and "fail-backward" (i.e., emerging defects in islet beta cell function and insulin action aggravate each other). A subclassification of NIDDM is proposed, based on presumed pathophysiologic defects. This subclassification divides patients, on the basis of fasting (basal) plasma glucose and postprandial glucose response to meals, into four categories: mild, moderate, severe, and very severe. The therapeutic strategies for these four categories are slightly different. Diet and exercise are always a component of therapy. Sulfonylureas are used, as needed, in patients with mild or moderate NIDDM. Basal insulin therapy may be used in moderate NIDDM. Some form of around-the-clock insulin therapy is used for patients with severe NIDDM. Very severe NIDDM is treated by more intensive insulin therapy.
Radiation Dose Estimates From Cardiac Multislice Computed Tomography in Daily Practice (2006)

The increase in spatial and temporal resolution with 64-slice CTA is associated with an increased radiation dose for coronary CTA. Dose-saving algorithms are very effective in reducing radiation exposure and should be used whenever possible.
NSs Protein of Rift Valley Fever Virus Promotes Posttranslational Downregulation of the TFIIH Subunit p62 (2011)

Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus) is an important emerging pathogen of humans and ruminants. Its NSs protein has previously been identified as a major virulence factor that suppresses host defense through three distinct mechanisms: it directly inhibits beta interferon (IFN-β) promoter activity, it promotes the degradation of double-stranded RNA-dependent protein kinase (PKR), and it suppresses host transcription by disrupting the assembly of the basal transcription factor TFIIH through sequestration of its p44 subunit. Here, we report that in addition to PKR, NSs also promotes the degradation of the TFIIH subunit p62. Infection of cells with the RVFV MP-12 vaccine strain reduced p62 protein levels to below the detection limit early in the course of infection. This NSs-mediated downregulation of p62 was posttranslational, as it was unaffected by pharmacological inhibition of transcription or translation and MP-12 infection had no effect on p62 mRNA levels. Treatment of cells with proteasome inhibitors but not inhibition of lysosomal acidification or nuclear export resulted in a stabilization of p62 in the presence of NSs. Furthermore, p62 could be coprecipitated with NSs from lysates of infected cells. These data suggest that the RVFV NSs protein is able to interact with the TFIIH subunit p62 inside infected cells and promotes its degradation, which can occur directly in the nucleus.
Magneto-optical investigation of spin–orbit torques in metallic and insulating magnetic heterostructures (2015)

Manipulating magnetism by electric current is of great interest for both fundamental and technological reasons. Much effort has been dedicated to spin-orbit torques (SOTs) in metallic structures, while quantitative investigation of analogous phenomena in magnetic insulators remains challenging due to their low electrical conductivity. Here we address this challenge by exploiting the interaction of light with magnetic order, to directly measure SOTs in both metallic and insulating structures. The equivalency of optical and transport measurements is established by investigating a heavy-metal/ferromagnetic-metal device (Ta/CoFeB/MgO). Subsequently, SOTs are measured optically in the contrasting case of a magnetic-insulator/heavy-metal (YIG/Pt) heterostructure, where analogous transport measurements are not viable. We observe a large anti-damping torque in the YIG/Pt system, revealing its promise for spintronic device applications. Moreover, our results demonstrate that SOT physics is directly accessible by optical means in a range of materials, where transport measurements may not be possible.
Effects of Tamoxifen on Benign Breast Disease in Women at High Risk for Breast Cancer (2003)

Women in this study who received tamoxifen, especially younger women (i.e., <50 years), had a reduced incidence of clinically detected benign breast disease and underwent fewer breast biopsies.
Structural and electrophysiological changes in the epicardial border zone of canine myocardial infarcts during infarct healing. (1985)

Structural and electrophysiological properties of the epicardial muscle which survives on the surface of transmural infarcts of the canine heart (epicardial border zone) were studied at different times after occlusion of the left anterior coronary artery (LAD). Isolated preparations were superfused in vitro, transmembrane potentials recorded, and impulse propagation mapped. In preparations from subacute infarcts (1 and 5 days), resting potential, action potential amplitude, upstroke velocity, and duration were all significantly reduced. Well-defined directional differences in propagation occurred. Propagation was more rapid in the direction perpendicular to the left anterior coronary artery than in the direction perpendicular to the base of the heart, because of the uniform anisotropic structure of the surviving muscle fibers which were arranged in tightly packed bundles oriented perpendicular to the left anterior coronary artery. The only ultrastructural abnormalities found in these muscle fibers was an accumulation of large amounts of lipid droplets. As the infarcts healed, resting potential, action potential amplitude, and upstroke velocity returned to normal by 2 weeks, although action potential duration decreased further. Lipid droplets had disappeared, and connective tissue had invaded the epicardial border zone, separating the muscle bundles. By 2 months, action potentials were normal, but the muscle fibers were widely separated and disoriented by the connective tissue (parallel bundles no longer were found). In these regions with a nonuniform anisotropic structure, the well-defined directional differences in impulse propagation were lost. However, activation was very slow, perhaps because of diminished connections between cells. The persistence of slow conduction in healed infarcts may contribute to the occurrence of chronic arrhythmias.
Pluripotent Cell Lines Derived from Common Marmoset (Callithrix jacchus) Blastocysts1 (1996)

We report the derivation of eight pluripotent cell lines from common marmoset (Callithrix jacchus) blastocysts. These cell lines are positive for a series of markers (alkaline phosphatase, SSEA-3, SSEA-4, TRA-1-60, and TRA-1-81) that characterize undifferentiated human embryonal carcinoma cells and rhesus embryonic stem cells. All eight cell lines had a modal chromosome number of 46; seven cell lines were XX and one was XY. Two cell lines (Cj11 and Cj62) were cultured continuously for over a year and remained undifferentiated and euploid. In the absence of fibroblast feeder layers, these cell lines differentiated to multiple cell types, even in the presence of leukemia inhibiting factor. Differentiated cells secreted bioactive CG into the culture medium and expressed alpha-CG, beta-CG, and alpha-fetoprotein mRNA, indicating trophoblast and endoderm differentiation. Bioactive CG secretion in differentiating cells was increased substantially in the presence of GnRH agonist D-Trp6-Pro9-NHEt. When grown at high densities, these cells formed embryoid bodies with a close resemblance to early postimplantation embryos, including the formation of a yolk sac, amnion, and an embryonic disc with an early primitive streak. These results make these pluripotent cells strong candidates for marmoset embryonic stem cells.
Role of LKB1-CRTC1 on Glycosylated COX-2 and Response to COX-2 Inhibition in Lung Cancer (2014)

CRTC1 activation is a key event that drives the LKB1-null mRNA signature in lung cancer. We also identified a positive feedback LKB1/CRTC1 signaling loop for COX-2/PGE2 regulation. These data suggest a role for LKB1 status and glycosylated COX-2 as specific biomarkers that provide a framework for selecting patients for COX-2 inhibition studies.