Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of Ascorbate as an Endogenous Substance That Irreversibly Inhibits Binding of Dihydropyridine Calcium Channel Blockers

Abstract: Endogenous material present in heat‐denatured extracts of rat brain that inhibited the binding of [3H]‐isopropyl‐4‐(2,1,3‐benzoxadiazol‐4‐yl)‐1,4‐dihydro‐5‐methoxycarbonyl‐2,6‐dimethyl‐3‐pyridinecarboxylate ([3H]‐PN200‐110) to calcium channels in brain membranes was purified. Spectrophotometric analysis of material purified by strong anion‐exchange and reverse‐phase chromatography showed an absorption maximum at 266 nm at pH 7.0 that shifted to 245 nm at pH 2.0. This pH‐dependent spectral shift was indistinguishable from that of ascorbic acid. Samples of the purified extract contained ascorbic acid; however, the inhibition of binding by purified material was always greater than the inhibition seen with equivalent concentrations of ascorbate, implying the presence of additional inhibitory factors. Attempts to detect and identify such inhibitory substances by chromatography showed that inhibitory activity was coincident with the presence of ascorbate, and the inhibitory activity of purified material was abolished after treatment with ascorbic acid oxidase. Iron enhanced the inhibition produced by ascorbate, and chemical analysis of purified preparations revealed the presence of iron. Studies comparing the potency of the purified material with that of a mixture of ascorbate plus iron showed that the content of ascorbate and iron in the purified brain extract is sufficient to explain the observed inhibition of binding of [3H]PN200‐110.
Safety evaluation and risk assessment of electronic cigarettes as tobacco cigarette substitutes: a systematic review

Electronic cigarettes are a recent development in tobacco harm reduction. They are marketed as less harmful alternatives to smoking. Awareness and use of these devices has grown exponentially in recent years, with millions of people currently using them. This systematic review appraises existing laboratory and clinical research on the potential risks from electronic cigarette use, compared with the well-established devastating effects of smoking tobacco cigarettes. Currently available evidence indicates that electronic cigarettes are by far a less harmful alternative to smoking and significant health benefits are expected in smokers who switch from tobacco to electronic cigarettes. Research will help make electronic cigarettes more effective as smoking substitutes and will better define and further reduce residual risks from use to as low as possible, by establishing appropriate quality control and standards.
The role of 5-HT2C receptors in affective disorders.

5-HT(2C) receptors are predominantly localised in the brain and their dysregulation may contribute to particular symptoms of anxiety and depression. The marked affinity of several clinically established psychotropic agents sites (e.g., tricyclic antidepressants, clozapine, fluoxetine) for 5-HT(2C) receptor has generated interest in the therapeutic potential of selective, high affinity 5-HT(2C) receptor ligands. Like the selective serotonin re-uptake inhibitor (SSRI) fluoxetine, high affinity selective agonists such as Ro 60-0175 and Ro 60-0332 have potent in vivo activity in animal models suggestive of therapeutic action against depression, obsessive-compulsive disorder (OCD) and panic disorders. In contrast, 5-HT(2C) receptor antagonists such as SB-200646A or SB-221284 show signs of anxiolytic-like activity in tests for conditioned and phobic-like anxiety in rodents whereas they are inactive in tests indicative of antidepressant, antiOCD and antipanic activity. These results are consistent with an important hypothesis proposing that 5-HT has a complex, dual action on the neural mechanism of anxiety by either facilitating or inhibiting different kinds of anxiety in different brain regions. They also suggest that 5-HT(2C) receptor subtypes play an important role in the therapeutic properties of SSRIs. Certain 5-HT(2C) receptor antagonists may possess negative efficacy at 5-HT(2C) receptors and, as inverse agonists, may control constitutive receptor activity possibly characterising some psychopathological states. Receptor variants exist in the human population and indicate possible associations between somatic mutations in the 5-HT(2C) receptor and psychopathology or response to drug treatment. Selective 5-HT(2C) receptor ligands may offer innovative and improved therapeutic opportunities for the biological treatment of specific aspects of psychiatric syndromes.
Relation between the Incidence of Invasive Cervical Cancer and the Screening Interval: Is a Five Year Interval Too Long?

Objective –To examine the incidence of invasive cervical cancer per 100 000 women years at risk and relative risk according to screening history among eligible women aged 25–69 in Southampton and South West Hampshire during the three years after completion of the first round of comprehensive screening. Results –There was a significantly higher incidence of invasive cervical cancer in women who had not been screened during the preceding 0.5–5.5 years than in those who had been screened (relative risk (RR) 2.6; 95% confidence interval (CI) 1.6 to 4.3). Among the latter group of women (with interval cancers) there was a significantly higher incidence in those with a long interval of 3.5–5.5 years since their most recent smear than in those with a short interval of 0.5–3.5 years (RR 2.2; 95% CI 1.3 to 3.8). Among women with non-interval cancers, there was a significantly higher incidence among those who had no cytology record than among those who had been screened but were overdue for a smear (RR 3.0; 95% CI 1.2 to 7.3). When screen detected cancers were excluded from the figures the relative risks for all the comparative groups described above were greater, though the 95% confidence limits were wider because the numbers were smaller. The most pronounced difference in incidence was between symptomatic cancers in women with a short screening interval (5.8 per 100 000 women years at risk) and in women with no cytology record (71.3 per 100 000 years at risk). Most cancers were interval cancers (76%) because of the high screening coverage: 89.2% of eligible women aged 25–69 had been screened during the preceding 0.5–5.5 years. The overall incidence per 100 000 women years at risk approached that of interval cancers, and was nearer to that observed in the short than the long interval because 74.7% of women had been screened within 3.5 years. Conclusion –The results confirm the effectiveness of screening but suggest that a five year screening interval may be too long, at least during the early rounds of screening.
The Sample of M&A: Descriptive Statistics

This book examines the issue of mergers and acquisitions (M&As) in the context of technological development, and in particular the impact of M&As on the innovation process. In so doing, the book integrates two bodies of literature, on M&As, and on innovation studies, a nexus which the editors contend represents an important step in the advancement of our understanding of both with clear implications for competitive advantage and growth of firms. Drawing on perspectives from both management and economics, the book offers a cohesive blend of theory, methodology, and a wealth of empirical material.
An overview of inference methods in probabilistic classifier chains for multilabel classification

This study presents a review of the recent advances in performing inference in probabilistic classifier chains for multilabel classification. The interest of performing such inference arises in an attempt of improving the performance of the approach based on greedy search (the well‐known CC method) and simultaneously reducing the computational cost of an exhaustive search (the well‐known PCC method). Unlike PCC and as CC, inference techniques do not explore all the possible solutions, but they increase the performance of CC, sometimes reaching the optimal solution in terms of subset 0/1 loss, as PCC does. The ε‐approximate algorithm, the method based on a beam search and Monte Carlo sampling are those techniques. An exhaustive set of experiments over a wide range of datasets are performed to analyze not only to which extent these techniques tend to produce optimal solutions, otherwise also to study their computational cost, both in terms of solutions explored and execution time. Only ε‐approximate algorithm with ε=. 0 theoretically guarantees reaching an optimal solution in terms of subset 0/1 loss. However, the other algorithms provide solutions close to an optimal solution, despite the fact they do not guarantee to reach an optimal solution. The ε‐approximate algorithm is the most promising to balance the performance in terms of subset 0/1 loss against the number of solutions explored and execution time. The value of ε determines a degree to which one prefers to guarantee to reach an optimal solution at the expense of increasing the computational cost. WIREs Data Mining Knowl Discov 2016, 6:215–230. doi: 10.1002/widm.1185
Joint Chroma Subsampling and Distortion-Minimization-Based Luma Modification for RGB Color Images With Application

In this paper, we propose a novel and effective hybrid method, which joins the conventional chroma subsampling and the distortion-minimization-based luma modification together, to improve the quality of the reconstructed RGB full-color image. Assume the input RGB full-color image has been transformed to a YUV image, prior to compression. For each <inline-formula> <tex-math notation="LaTeX">$2\times 2$ </tex-math></inline-formula> UV block, one 4:2:0 subsampling is applied to determine the one subsampled U and V components, <inline-formula> <tex-math notation="LaTeX">$U_{s}$ </tex-math></inline-formula> and <inline-formula> <tex-math notation="LaTeX">$V_{s}$ </tex-math></inline-formula>. Based on <inline-formula> <tex-math notation="LaTeX">$U_{s}$ </tex-math></inline-formula>, <inline-formula> <tex-math notation="LaTeX">$V_{s}$ </tex-math></inline-formula>, and the corresponding <inline-formula> <tex-math notation="LaTeX">$2\times 2$ </tex-math></inline-formula> original RGB block, a main theorem is provided to determine the ideally modified <inline-formula> <tex-math notation="LaTeX">$2\times 2$ </tex-math></inline-formula> luma block in constant time such that the color peak signal-to-noise ratio (CPSNR) quality distortion between the original <inline-formula> <tex-math notation="LaTeX">$2\times 2$ </tex-math></inline-formula> RGB block and the reconstructed <inline-formula> <tex-math notation="LaTeX">$2\times 2$ </tex-math></inline-formula> RGB block can be minimized in a globally optimal sense. Furthermore, the proposed hybrid method and the delivered theorem are adjusted to tackle the digital time delay integration images and the Bayer mosaic images whose Bayer CFA structure has been widely used in modern commercial digital cameras. Based on the IMAX, Kodak, and screen content test image sets, the experimental results demonstrate that in high efficiency video coding, the proposed hybrid method has substantial quality improvement, in terms of the CPSNR quality, visual effect, CPSNR-bitrate trade-off, and Bjøntegaard delta PSNR performance, of the reconstructed RGB images when compared with existing chroma subsampling schemes.
Effects of arthroscopic partial meniscectomy on quadriceps strength: a systematic review.

CONTEXT Arthroscopic partial meniscectomy (APM) after meniscal tear has been widely accepted and associated with quick return to activity. Unfortunately, meniscectomy is associated with risk for knee osteoarthritis, which may be attributed to postsurgical quadriceps weakness. This has important implications, as the quadriceps play a prominent role in knee stabilization and energy attenuation in the lower extremity. OBJECTIVE To determine the magnitude of interlimb quadriceps strength deficits in people with unilateral APM by systematically reviewing the current literature. EVIDENCE ACQUISITION The Web of Knowledge databases were searched on September 22, 2010, using terms meniscus OR meniscectomy AND quadriceps strength OR quadriceps weakness. Included articles were written in English, reporting means and SDs of isokinetic peak torque at 60° and 180°/s for both limbs. EVIDENCE SYNTHESIS Four articles were included in the final analysis. Effect sizes and 95% confidence intervals (CI) were calculated between limbs for periods less than 1 mo, 1-3 mo, 3-6 mo, and more than 6 mo. CONCLUSION Homogeneous effect sizes indicate quadriceps weakness in the involved limb. Effects were strong at less than 1 mo (d = -1.01 to -1.62), while weak to strong effects were found for 1-3 mo (d = -0.40 to -8.04) and 3-6 mo (d = -0.40 to -5.11). Weak effects were found at more than 6 mo (d = -0.30 to -0.37). Definitive effects with a CI not crossing zero were found in 65% of the data. Although APM patients return to function within weeks after surgery, prolonged quadriceps strength deficits may increase the risk of knee-joint degeneration. Furthermore, evidence of bilateral dysfunction after unilateral injury may suggest that neuromuscular deficits post-APM are greater than the interlimb differences found in this review. Further research should be conducted to determine the nature of strength deficits and the best methods for restoring strength after APM.
Highly Sensitive Methods for Quantitation of Human Immunodeficiency Virus Type 1 RNA from Plasma, Cells, and Tissues

ABSTRACT Precise and sensitive quantitation of viral RNA in specimens from human immunodeficiency virus (HIV) type 1 (HIV-1)-infected individuals has become an indispensable tool for the monitoring of the efficacy of highly active antiretroviral combination therapy. The present report describes reproducible and efficient protocols with enhanced sensitivity for quantitation of HIV-1 RNA from plasma, peripheral blood mononuclear cells, and tissues with Qiagen silica columns for RNA purification combined with the Roche Amplicor HIV-1 Monitor test for quantitative reverse transcription-PCR (RT-PCR). Extraction of RNA from 0.5 ml of plasma resulted in the detection of fewer than 20 HIV RNA copies/ml of plasma, equivalent to the centrifugation-based boosted RT-PCR assay. Silica extraction of cellular RNA resulted in the detection of fewer than 3 HIV-1 RNA copies/μg of total RNA. These techniques facilitate direct comparisons of viral loads between liquid and cellular specimens. Application of these sensitive methods may improve the assessment of the response to new antiretroviral regimens.
L‐type calcium channel expression depends on the differentiated state of vascular smooth muscle cells

Despite intensive interest in understanding the differentiation of vascular smooth muscle cells (VSMC), no information is available about differential regulation of ion channels in these cells. Since expression of the L‐type Ca2+ channel can be influenced by differentiation in other cell types, we tested the hypothesis that the L‐type (C class) channel is a specific differentiation marker of VSMC and that expression of these channels depends on the state of cell differentiation. We used rat aortic (A7r5) VSMC, which express functional L‐type Ca2+ channels, and induced dedifferentiation by cell culture in different media. Treatment with retinoic acid was used to redifferentiate the VSMC. We characterized the differentiated state of the cells by using immunohistochemistry and Western blot analysis for smooth muscle (SM) α‐actin and SM‐myosin heavy chain (MHC). The number of functional Ca2+ channels was significantly decreased in dedifferentiated VSMC and increased upon differentiation with retinoic acid. Ca2+ channel function was assessed by whole‐cell voltage clamp techniques. Using Western blot and dihydropyridine binding analysis, we found that the expression of the Ca2+ channel α1 subunit, and to a lesser extent the β2 subunit, was directly correlated with the expression of SM α‐actin and SM‐MHC. We conclude that expression of L‐type Ca2+ channel α1 subunits, and thus a functional Ca2+ channel, is highly coordinated with expression of the SM‐specific proteins required for specialized smooth muscle cell functions. Furthermore, our results demonstrate that the L‐type Ca2+ channel is a novel marker for differentiation of VSMC. The data suggest that regulation of ion channel expression during differentiation may have physiological importance for normal smooth muscle function and may influence VSMC behavior under pathophysiological conditions.
HIV-1 Gag Processing Intermediates Trans-dominantly Interfere with HIV-1 Infectivity*

Protease inhibitors (PI) act by blocking human immunodeficiency virus (HIV) polyprotein processing, but there is no direct quantitative correlation between the degree of impairment of Gag processing and virion infectivity at low PI concentrations. To analyze the consequences of partial processing, virus particles were produced in the presence of limiting PI concentrations or by co-transfection of wild-type proviral plasmids with constructs carrying mutations in one or more cleavage sites. Low PI concentrations caused subtle changes in polyprotein processing associated with a pronounced reduction of particle infectivity. Dissection of individual stages of viral entry indicated a block in accumulation of reverse transcriptase products, whereas virus entry, enzymatic reverse transcriptase activity, and replication steps following reverse transcription were not affected. Co-expression of low amounts of partially processed forms of Gag together with wild-type HIV generally exerted a trans-dominant effect, which was most prominent for a construct carrying mutations at both cleavage sites flanking the CA domain. Interestingly, co-expression of low amounts of Gag mutated at the CA-SP1 cleavage site also affected processing activity at this site in the wild-type virus. The results indicate that low amounts (<5%) of Gag processing intermediates can display a trans-dominant effect on HIV particle maturation, with the maturation cleavage between CA and SP1 being of particular importance. These effects are likely to be important for the strong activity of PI at concentrations achieved in vivo and also bear relevance for the mechanism of action of the antiviral drug bevirimat.
Ecosystem services: from concept to practice

Introduction Ecosystem services are hot, and they have been hot for a while. In 1998, Costanza et al . published their famous article about the societal value produced by ecosystems through ecosystem service delivery, an article which at the time this introduction was written had been cited more than 10 000 times. In 2005, the Millennium Ecosystem Assessment (MEA) framed the need to protect biodiversity and the world’s ecosystems in terms of ecosystem services (MEA, 2005). In 2009, “The economics of ecosystems and biodiversity” (TEEB) followed up by presenting an approach to help decision-makers recognize, demonstrate, and capture the values of ecosystem services and biodiversity. And by now, most (inter)national policies in the field of nature conservation refer to ecosystem services when explaining the need for nature conservation, biodiversity protection, and sustainable resource use. Despite the popularity of the concept of ecosystem services, policy-makers and practitioners are struggling to implement the concept in practice. An important reason for this science–policy divide is the lack of an interdisciplinary framework that guides policy-makers through the definition and measurement of ecosystem services to their valuation and the translation of these values into effective policy instruments and governance arrangements (see also Daily et al ., 2009).
Compact Dual wide bandstop filter

In this work Dual bandstop filter (DBBSF) using coupled line loaded by a optimum bandstop filter, which consists of stepped impedance resonator. The novel transmission line structure consists of a parallel coupled microstrip line loaded by a modified optimum bandstop filter. The load can be realized by using the uniform characteristic impedance i.e. the total filter can be controlled by using only two characteristic impedances. The wide bandwidth in the stopbands, stopband zero positions can be controlled by using both the coupled line and a shunt stepped impedance open stub (SIOS) unit. Three transmission zeroes in the pass band were created by a mutual coupling between the coupled lines configuration. Design guidelines are derived using loss less transmission line model. The high impedance line required for the series transmission line (TL) sections facilitates convenient meandering that makes the geometry compact. To validate theoretical predictions, a prototype filter operating at two bands 0.74 and 2.2 GHz has been fabricated.
The Myth of the Annual Budget

Rarely do those who live through profound social change appreciate its significance. Traditional modes of thinking interfere with perceptions of reality. Predictions are often confounded in the complexities and uncertainties of the onrush of events. Such is now the predicament of public administrators caught in the throes of the federal budget crisis. Events have moved so swiftly that it is difficult to gain a sense of perspective, much less predict future direction. Where critics once worried about defects in the budget process, today they are more concerned about the possibility that the budget process itself may collapse. Three major explanations have been advanced for the current crisis in federal budgeting. One holds that the budget mechanism requires constant maintenance to perform properly. The current crisis has been precipitated from long-term neglect of essential maintenance. Once the required adjustments are made, the budget process will work smoothly again. Another contends that the disruption of underlying conventions has so heightened political conflict that the budget process has been overstrained. If budget policies were modified to reduce political conflict and conventions were followed, then the current crisis would pass. The third explanation maintains that government has become too big. The budget process cannot handle the load placed on it. A reduction in the size of the federal budget would restore effective budgeting. Although these explanations approach the federal budget crisis from different directions, they seem agreed that the budget process is fundamentally sound and that what needs to be done is to restore the principles on which it rests. In fact, there is good reason to believe that the problems underlying the federal budget are of such an unprecedented nature that the principles themselves are inappropriate and should be changed. Their solutions ignore the changing context of budgeting that makes traditional principles inadequate, even outmoded. What is now required is a fundamental rethinking of the basic principles, particularly the concept of the annual budget itself. Without such a reassessment the budget process will continue to be dominated by inconsistencies and contradictions. The principles of annual choice are denied in the reality of complex flows of funds which overlap from year to year. ' Control is the watchword, "uncontrollability" the refrain. Most appropriations are passed after the start of the fiscal year,2 and at its end billions of dollars are reported in unobligated balances.3 Budget unity is contradicted by the large sums of money allocated and spent outside the budget. Each element of the budget process-resolutions, authorizations, appropriations, reconciliation-requires elaborate explanation to reconcile textbook precepts with actual practice. Budget figures, once fairly stable and reliable quantities, evaporate in successive and competing assumptions and estimates. As the budget crisis deepens, budgetary concepts come to resemble myths, while the urgent issues of budgetary adaptation to a changing context remain ignored.