Miracle-dz/UniFAR-FTUs huggingface dataset:
Evidence for the existence of distinct biophases for alpha- and beta-adrenoceptors in the vascular tissue.

In dog mesenteric artery and saphenous vein strips, the inhibition of neuronal uptake by cocaine increased the potency of exogenous adrenaline for alpha-effects and did not change its potency for beta-effects, whereas inhibition of catechol-O-methyltransferase (COMT) by U-0521 enhanced the beta-effects more than the alpha-ones. On the other hand, cocaine prolonged the duration of adrenaline-induced contraction more than it prolonged the adrenaline-induced relaxation, while U-0521 prolonged the duration of the relaxation much more than that of the contraction. Cocaine and U-0521 also caused differential influences on alpha- and beta-effects caused by endogenous adrenaline, i.e., on alpha- and beta-effects caused by electrical stimulation of strips previously preloaded with adrenaline. It was also observed that the time elapsing between the beginning of the electrical stimulation and the onset of the response (latency) is longer for beta- than for alpha-responses when both are evoked by electrical stimulation. Furthermore, in these strips, alpha-adrenoceptor blocking agents more easily antagonized the contractions caused by exogenous adrenaline than contractions caused by electrical stimulation, whereas propranolol antagonized beta-responses caused by exogenous adrenaline as easily as beta-responses caused by electrical stimulation. It is concluded that there is a biophase for alpha-adrenoceptors, which is under greater influence of neuronal uptake, and another for beta-adrenoceptors, which is under greater influence of COMT activity.
TnI-Ultra assay measurements in cancer patients: Comparison with the conventional assay and clinical implication

Abstract The serial monitoring of cardiac troponin represents an effective approach for the early identification, assessment, and monitoring of chemotherapy-induced cardiac injury. Over the last few years new generations of troponin assays, referred to as sensitive and high sensitivity assays, able to detect very low concentrations of troponin, have been progressively released on different platforms. Some studies have assessed the comparability of the cTnI measurements with the new assays versus the conventional ones, but none of these in the oncological population. We compared the cTnI results determined on Stratus CS and ADVIA Centaur CP System in 70 breast cancer patients, for a total of 327 samples collected during different cycles of treatment. Correlation (Spearman = 0.732) and agreement (91.4%) between the assays were good (244 concordant negatives and 55 concordant positives), with a frequency of 8.6% discordant results among the cTnI measurements. Despite the well-known lack in the harmonization and standardization of the currently commercially available cTnI methods, we found a good clinical concordance of cTnI determination on both systems.
Conventional and power spectrum analysis of the effects of zolpidem on sleep EEG in patients with chronic primary insomnia.

STUDY OBJECTIVE The purpose of this study was 1) to assess the effect of zolpidem or a placebo on sleep in two groups of insomniac patients with a diagnosis of moderate-to-severe chronic primary insomnia and 2) to determine the effect of zolpidem on sleep structure using spectral analysis. DESIGN A randomized, double-blind, placebo-controlled trial. SETTING Sleep laboratory of the Department of Pharmacology and Therapeutics at the Clinics Hospital. PARTICIPANTS 12 female outpatients with chronic primary insomnia. INTERVENTIONS Zolpidem was given at a daily dose of 10 mg for 15 nights. RESULTS The hypnotic drug reduced sleep latency and waking time after sleep onset, and increased total sleep time and sleep efficiency. Values corresponding to visually scored slow wave sleep (stage 3 and 4) showed no significant changes. All-night spectral analysis of the EEG revealed that power density in NREM sleep was significantly increased in the low frequency band (0.25-1.0 Hz) in the zolpidem group during the first 2-h interval. CONCLUSIONS In agreement with previous findings obtained in patients with chronic primary insomnia, zolpidem significantly improved sleep induction and maintenance. Moreover, zolpidem increased power density in the 0.25-1.0 Hz band during short-term and intermediate-term treatment. Nevertheless, other frequency bands in the delta range showed a relative decrease which was not statistically significant.
Nabiximols in the treatment of spasticity, pain and urinary symptoms due to multiple sclerosis

Introduction: Over the last two decades, experimental and clinical data suggest a therapeutic benefit of cannabis-based medicines for a variety of multiple sclerosis (MS) symptoms. Clinical trials, both with synthetic or plant-derived cannabinoids, have demonstrated clinical efficacy of cannabinoids for the treatment of spasticity, neuropathic pain and bladder dysfunction. Nabiximols, a 1:1 mix of delta-9-tetrahydrocanabinol and cannabidiol extract from cloned chemovars, was licensed in the UK in 2010 and has also been approved in other European countries and Canada. The European Federation of Neurological Societies recommends that cannabis should be used only as a second or third line treatment in central neuropathic pain. Areas covered: After a brief discussion of the endocannabinoid system, this review focuses on the use of cannabis to improve MS symptoms. More specifically, the authors have analyzed clinical studies on cannabis-based medicine extract (CBME), in particular nabiximols, in spasticity, as well as pain, and bladder dysfunction in MS. The authors have considered the large randomized controlled trials examining the psychological effects associated with cannabinoids use as well as long-term follow-up studies. Expert opinion: Despite a number of trials with very promising results, there are still concerns related to relative paucity of data on long-term safety. Also, the long-term efficacy information in terms of the control of symptoms of a disease in which the natural history is progression is sparse. Therefore, further studies are required to improve the current knowledge of nabiximols.
Activation of the PI3K/Akt signal transduction pathway and increased levels of insulin receptor in protein repair‐deficient mice

Protein l‐isoaspartate (d‐aspartate) O‐methyltransferase is an enzyme that catalyses the repair of isoaspartyl damage in proteins. Mice lacking this enzyme (Pcmt1–/– mice) have a progressive increase in brain size compared with wild‐type mice (Pcmt1+/+ mice), a phenotype that can be associated with alterations in the PI3K/Akt signal transduction pathway. Here we show that components of this pathway, including Akt, GSK3β and PDK‐1, are more highly phosphorylated in the brains of Pcmt1–/– mice, particularly in cells of the hippocampus, in comparison with Pcmt1+/+ mice. Examination of upstream elements of this pathway in the hippocampus revealed that Pcmt1–/– mice have increased activation of insulin‐like growth factor‐I (IGF‐I) receptor and/or insulin receptor. Western blot analysis revealed an approximate 200% increase in insulin receptor protein levels and an approximate 50% increase in IGF‐I receptor protein levels in the hippocampus of Pcmt1–/– mice. Higher levels of the insulin receptor protein were also found in other regions of the adult brain and in whole tissue extracts of brain, liver, heart and testes of both juvenile and adult Pcmt1–/– mice. There were no significant differences in plasma insulin levels for adult Pcmt1–/– mice during glucose tolerance tests. However, they did show higher peak levels of blood glucose, suggesting a mild impairment in glucose tolerance. We propose that Pcmt1–/– mice have altered regulation of the insulin pathway, possibly as a compensatory response to altered glucose uptake or metabolism or as an adaptive response to a general accumulation of isoaspartyl protein damage in the brain and other tissues.
Electron mobility in n-channel depletion-type MOS transistors

It is found that surface electron mobility can exceed electron mobility in bulk. Field-effect mobilities of n-channel depletion-type MOS transistors were measured, comparing transistorG_{m} - V_{g}and diodeC - V_{g}characteristics. Electron mobility in a highly doped n-type channel layer exceeds that in bulk at around the onset of surface accumulation. This can be explained by reduction in ionized impurity scattering under accumulation conditions. In accumulation conditions, excessive electrons screen the Coulombic field from ionized impurities. This is confirmed by theoretical calculation based on the Maxwell-Boltzmann distribution of electrons and electron-concentration-dependent electron mobility.
The quest for regional legitimation: Analyzing the Arab League’s legitimizing role in the Arab spring

ABSTRACT The topic of international legitimacy has returned to centre stage during the Arab Spring, in which the Arab League has apparently assumed a prominent legitimation role. Although some scholarship has studied how international organizations are decisive in legitimizing actors and their actions during conflicts, relatively scant attention has been focused at constructing a comprehensive analytical framework for this kind of assessment that could be also applied to regional organizations (ROs). This paper proposes that when actors are involved in battles over international legitimation, analysing their access to the socially identified brokers of three legitimation functions (appropriateness, consensus, and empathy) is key to assess their success. Particularly, we argue that relevant identity-based ROs may have a crucial legitimizing role by operating as brokers of regional consensus. For this purpose, two case studies – Bahrain and Libya – illustrate how the Arab League’s brokerage influenced the legitimation of the actors involved and their outcomes. The findings suggest novel implications about the decisive legitimizing impact of regionalism on conflict resolution.
Rates of return to education in Sri Lanka

This paper explores the rates of return to education in Sri Lanka across the sexes and different types of employment during 2009/10. The endogeneity bias suggests that education may be associated with other characteristics such as ability and family background – excluding such attributes could lead to biased estimates of the return to education. To deal with this form of bias, the paper uses an Instrumental Variables (IV) approach to measure education. Our results reveal that the OLS estimates are downward biased, in comparison to the IV estimates. Further, we add to the literature by exploring the return to education across levels of education – primary, secondary and tertiary – and how it varies across sexes and types of employment. Finally for the self-employed, we analyse the association between inputs (land, raw materials, labour and capital), education and output using a household-level production function – for those in agriculture and non-agricultural activities. The results suggest that education at higher levels have a positive association with non-agricultural output, but not with agricultural output.
Duloxetine and Subacute Pain after Knee Arthroplasty when Added to a Multimodal Analgesic Regimen: A Randomized, Placebo-controlled, Triple-blinded Trial

Background:Duloxetine is effective for chronic musculoskeletal and neuropathic pain, but there are insufficient data to recommend the use of antidepressants for postoperative pain. The authors hypothesized that administration of duloxetine for 15 days would reduce pain with ambulation at 2 weeks after total knee arthroplasty. Methods:In this triple-blinded, randomized, placebo-controlled trial, patients received either duloxetine or placebo for 15 days, starting from the day of surgery. Patients also received a comprehensive multimodal analgesic regimen including neuraxial anesthesia, epidural analgesia, an adductor canal block, meloxicam, and oxycodone/acetaminophen as needed. The primary outcome was the pain score (0 to 10 numeric rating scale) with ambulation on postoperative day 14. Results:One hundred six patients were randomized and analyzed. On day 14, duloxetine had no effect on pain with ambulation; mean pain was 3.8 (SD, 2.3) for placebo versus 3.5 (SD, 2.1) for duloxetine (difference in means [95% CI], 0.4 [−0.5 to 1.2]; P = 0.386). Symptoms potentially attributable to duloxetine discontinuation at study drug completion (nausea, anxiety) occurred among nine patients (duloxetine) and five patients (placebo); this was not statistically significant (P = 0.247). Statistically significant secondary outcomes included opioid consumption (difference in mean milligram oral morphine equivalents [95% CI], 8.7 [3.3 to 14.1], P = 0.002 by generalized estimating equation) over the postoperative period and nausea on day 1 (P = 0.040). There was no difference in other side effects or in anxiety and depression scores. Conclusions:When included as a part of a multimodal analgesic regimen for knee arthroplasty, duloxetine does not reduce subacute pain with ambulation.
High-throughput screening and biosensing with fluorescent C. elegans strains.

High-throughput screening (HTS) is a powerful approach for identifying chemical modulators of biological processes. However, many compounds identified in screens using cell culture models are often found to be toxic or pharmacologically inactive in vivo(1-2). Screening in whole animal models can help avoid these pitfalls and streamline the path to drug development. C. elegans is a multicellular model organism well suited for HTS. It is small (<1 mm) and can be economically cultured and dispensed in liquids. C. elegans is also one of the most experimentally tractable animal models permitting rapid and detailed identification of drug mode-of-action(3). We describe a protocol for culturing and dispensing fluorescent strains of C. elegans for high-throughput screening of chemical libraries or detection of environmental contaminants that alter the expression of a specific gene. Large numbers of developmentally synchronized worms are grown in liquid culture, harvested, washed, and suspended at a defined density. Worms are then added to black, flat-bottomed 384-well plates using a peristaltic liquid dispenser. Small molecules from a chemical library or test samples (e.g., water, food, or soil) can be added to wells with worms. In vivo, real-time fluorescence intensity is measured with a fluorescence microplate reader. This method can be adapted to any inducible gene in C. elegans for which a suitable reporter is available. Many inducible stress and developmental transcriptional pathways are well defined in C. elegans and GFP transgenic reporter strains already exist for many of them(4). When combined with the appropriate transgenic reporters, our method can be used to screen for pathway modulators or to develop robust biosensor assays for environmental contaminants. We demonstrate our C. elegans culture and dispensing protocol with an HTS assay we developed to monitor the C. elegans cap 'n' collar transcription factor SKN-1. SKN-1 and its mammalian homologue Nrf2 activate cytoprotective genes during oxidative and xenobiotic stress(5-10). Nrf2 protects mammals from numerous age-related disorders such as cancer, neurodegeneration, and chronic inflammation and has become a major chemotherapeutic target(11-13). Our assay is based on a GFP transgenic reporter for the SKN-1 target gene gst-4(14), which encodes a glutathione-s transferase(6). The gst-4 reporter is also a biosensor for xenobiotic and oxidative chemicals that activate SKN-1 and can be used to detect low levels of contaminants such as acrylamide and methyl-mercury(15-16).
Widespread Distribution of Visual Responsiveness in Frontal, Prefrontal, and Prelimbic Cortical Areas of the Cat: An Electrophysiologic Investigation

By using multiple‐unit recording techniques, we explored the visual responsiveness of regions of cortex in and around the area described by others as the cat's “frontal eye fields” (Schlag J, Schlag‐Rey M [1970] Brain Res 22:1–13; Guitton D, Mandl G [1978] Brain Res 149:295–312; Pigarev IN [1984] Neirofiziologiia 16:761–766). Our exploration included most of the cat's motor areas (subdivisions of areas 4 and 6) as well as prefrontal and prelimbic regions. Visual responses were routinely obtained from portions of each of the areas we explored, including prefrontal and prelimbic cortex. The qualitative characteristics of visual responses appeared to vary with cytoarchitectonic area. With few exceptions, receptive fields in these areas were large (most exceeding 2,500 deg2) and included the area centralis. Such large fields and inclusion of central vision at nearly all sites precluded retinotopic organization and prevented delineating distinct visual field representations. The most reliable and robust visual activity was observed on the ventral bank of the cruciate sulcus in area 6aα. The regions reported to correspond to the “frontal eye fields” did not exhibit any unique visual properties that distinguished them from surrounding areas. The widespread distribution of visually driven activity we observed is consistent with the known pattern of both cortical and subcortical inputs to this broad region of cortex. The observation of visually responsive activity across broad regions of cortex that is nominally motor is consistent with recent studies involving awake animals. J. Comp. Neurol. 405:99–127, 1999. © 1999 Wiley‐Liss, Inc.
The efficacy of hydroxychloroquine in altering pregnancy outcome in women with antiphospholipid antibodies

Summary The use of low-dose aspirin and heparinoids has improved the pregnancy outcome in obstetric antiphospholipid syndrome (APS). However, current treatment fails in 20–30 % of APS pregnancies, raising the need to explore other treatments to improve obstetrical outcome. Hydroxychloroquine (HCQ) is widely used in patients with autoimmune diseases, mainly systemic lupus erythematous (SLE), due to its anti-inflammatory, anti-aggregant and immune-regulatory properties. Evidence from in vitro and animal models suggests a potential protective effect of HCQ in obstetric APS. Pending the availability of prospective trials, we aimed to systematically review the available evidence and to assess the clinical judgment of a panel of experts regarding the use of HCQ in improving pregnancy outcome in women with anti-phospholipid antibodies (aPL). Clinical data on the ability of HCQ to improve pregnancy outcome in women with aPL are very limited in the available literature. Only one cohort study evaluating maternal and fetal outcome of pregnancy in patients with SLE who were exposed to HCQ was identified. Four of 14 (29 %) treated with HCQ patients had pregnancy failure, compared with six of 24 (25 %) of patients not treated with HCQ. However, the effect of HCQ was not adjusted for the use of other medications such as aspirin, heparins or steroids. Selected experts were contacted by e-mail and asked to review the summary of the evidence provided by the working group and to briefly answer each of the proposed questions. Overall, the panel of experts agreed that adding HCQ could be considered in selected cases or after failure of standard treatment with aspirin and a heparin agent. Specifically, the majority of experts considered adding HCQ in specific scenarios, such as women with previous thrombosis (either arterial and/or venous), and/or with previous ischaemic placenta-mediated complications. Prospective studies are necessary before the use of HCQ during pregnancy in women with aPL should be routinely recommended for clinical practice.
ANALISIS KUALITATIF PEMBINGKAIAN AKHBAR THE STAR DAN UTUSAN MALAYSIA MENGENAI KNTROVERSI MAJLIS “THANKSGIVING” DI DUMC (A QUALITATIVE FRAMING ANALYSIS ON THE REPORTS OF THE CONTROVERSIAL THANKSGIVING DINNER IN DUMC BY THE STAR AND UTUSAN MALAYSIA NEWSPAPERS)

Kajian ini meneliti dan membandingkan bagaimana dua akhbar arus perdana berlainan bahasa di Malaysia, The Star dan Utusan Malaysia melaporkan isu konflik agama yang mencetuskan kontroversi berkaitan akidah dan kepercayaan umat Islam dalam satu majlis Thanksgiving yang melibatkan pelbagai kaum di Damansara Utama Methodist Church (DUMC). Majlis ini dianjurkan oleh organisasi Komuniti Harapan pada 3 Ogos, 2011. Tindakan diambil oleh Bahagian Penguatkuasa Jabatan Agama Islam Selangor (JAIS) yang menjalankan operasi pada majlis Thanksgiving itu menarik perhatian besar pihak media khususnya akhbar The Star dan Utusan Malaysia. Isu ini dianggap sebagai sebuah kes yang kontroversi untuk dikaji dan dibandingkan bagaimana media utama tempatan dan berlainan bahasa menonjolkan seterusnya membingkaikan isu konflik ini. The Star dan Utusan Malaysia dianalisis dengan objektif untuk menentukan pembingkaian berita (news frame) yang digunakan oleh kedua-dua akhbar dalam melaporkan mengenai isu ini seperti yang diperkenalkan oleh sarjana Robert Entman pada 1993. Dapatan kajian mendapati kedua-dua akhbar membingkai isu ini dengan memberi penekanan kepada isu konflik politik yang berlaku dalam parti gabungan Pakatan Rakyat (PR) terutamanya parti Parti Islam Semalaysia (PAS) dalam menangani isu ini. Selain bingkai konflik politik, kedua-dua akhbar menunjukkan perbezaan dalam membingkai isu ini. Akhbar The Star lebih membingkai isu ini dari sudut etika moral manakala akhbar Utusan Malaysia lebih membingkai isu ini dari sudut perlembagaan.
5-Azacytidine for the treatment of myelodysplastic syndromes

Introduction: 5-Azacytidine is a pyrimidine nucleoside analog of cytidine that undergoes incorporation into DNA and blocks DNA methyltransferase leading to hypomethylation and potentially beneficial re-expression of abnormally silenced genes. It is the first agent approved for use in patients with myelodysplastic syndromes (MDSs) based on its improvement in overall survival as monotherapy. Evidence of efficacy in combination with other agents is also accumulating. Areas covered: Key information on mechanisms of action is presented. Development, synthesis, and pharmacokinetics are also outlined. Key safety, tolerability, and efficacy data from clinical trials of 5-azacytidine as monotherapy as well as in combination are also presented. Expert opinion: Our understanding of the molecular basis and pathogenesis of MDS continues to evolve rapidly. 5-Azacytidine has been shown to improve both overall survival and quality of life in patients with high-risk MDS. Currently, the oral route of administration is undergoing evaluation in clinical trials. Used as a monotherapy and also in novel combinations, 5-azacytidine has the potential to further improve the prognosis of some patients with MDS.