Miracle-dz/UniFAR-FTUs huggingface dataset:
Protein Kinase C-Independent Inhibition of Organic Cation Transporter 1 Activity by the Bisindolylmaleimide Ro 31-8220

Ro 31–8220 is a potent protein kinase C (PKC) inhibitor belonging to the chemical class of bisindolylmaleimides (BIMs). Various PKC-independent effects of Ro 31–8220 have however been demonstrated, including inhibition of the ATP-binding cassette drug transporter breast cancer resistance protein. In the present study, we reported that the BIM also blocks activity of the solute carrier organic cation transporter (OCT) 1, involved in uptake of marketed drugs in the liver, in a PKC-independent manner. Ro 31–8220, in contrast to other pan-PKC inhibitors such as staurosporine and chelerythrine, was thus shown to cis-inhibit uptake of the reference OCT1 substrate tetraethylammonium in OCT1-transfected HEK293 cells in a concentration-dependent manner (IC50 = 0.18 μM) and without altering membrane expression of OCT1. This blockage of OCT1 was also observed in human hepatic HepaRG cells that constitutionally express OCT1. It likely occurred through a mixed mechanism of inhibition. Ro 31–8220 additionally trans-inhibited TEA uptake in OCT1-transfected HEK293 cells, which likely discards a transport of Ro 31–8220 by OCT1. Besides Ro 31–8220, 7 additional BIMs, including the PKC inhibitor LY 333531, inhibited OCT1 activity, whereas 4 other BIMs were without effect. In silico analysis of structure-activity relationships next revealed that various molecular descriptors, especially 3D-WHIM descriptors related to total size, correspond to key physico-chemical parameters for inhibition of OCT1 activity by BIMs. In addition to activity of OCT1, Ro 31–8220 inhibited those of other organic cation transporters such as multidrug and toxin extrusion protein (MATE) 1 and MATE2-K, whereas, by contrast, it stimulated that of OCT2. Taken together, these data extend the nature of cellular off-targets of the BIM Ro 31–8220 to OCT1 and other organic cation transporters, which has likely to be kept in mind when using Ro 31–8220 and other BIMs as PKC inhibitors in experimental or clinical studies.
Celecoxib and 2,5-Dimethyl-Celecoxib Prevent Cardiac Remodeling Inhibiting Akt-Mediated Signal Transduction in an Inherited Dilated Cardiomyopathy Mouse Model

Celecoxib, a cyclooxygenase-2 (COX-2)-selective nonsteroidal anti-inflammatory drug, has been shown to inhibit Akt and prevent cardiac remodeling in aortic banding-induced failing heart in mice. However, it may be difficult to use celecoxib for the treatment of heart failure because of thromboembolic adverse reactions. Since 2,5-dimethyl (DM)-celecoxib, a derivative unable to inhibit COX-2, has been also reported to inhibit Akt, we attempted to examine whether DM-celecoxib retains the ability to prevent cardiac remodeling and improve cardiac functions using a mouse model of inherited dilated cardiomyopathy (DCM). DM-celecoxib as well as celecoxib administered daily for 4 weeks inhibited Akt and subsequent phosphorylation of glycogen synthase kinase-3β and mammalian target of rapamycin. Furthermore, both celecoxib and DM-celecoxib inhibited the activities of nuclear factor of activated T cell and β-catenin and the expression of TCF7L2 (T-cell-specific transcriptional factor-7L2) and c-Myc, downstream mediators related to cardiac hypertrophy. Functional and morphological measurements showed that these compounds improved left ventricular systolic functions (ejection fraction: vehicle, 34.7 ± 3.9%; 100 mg/kg celecoxib, 50.3 ± 1.1%, p < 0.01; 100 mg/kg DM-celecoxib, 49.8 ± 0.8%, p < 0.01), which was also evidenced by the decrease in β-myosin heavy chain and B-type natriuretic peptide, and prevented hypertrophic cardiac remodeling (heart/body weight ratio: vehicle, 10.4 ± 0.7 mg/g; 100 mg/kg celecoxib, 8.0 ± 0.3 mg/g, p < 0.01; 100 mg/kg DM-celecoxib, 8.2 ± 0.1 mg/g, p < 0.05). As a consequence, both compounds improved the survival rate (vehicle, 45%; 100 mg/kg celecoxib, 75%, p < 0.05; 100 mg/kg DM-celecoxib, 70%, p < 0.05). These results suggested that not only celecoxib but also DM-celecoxib prevents cardiac remodeling and reduces mortality in DCM through a COX-2-independent mechanism involving Akt and its downstream mediators.
A Transdisciplinary Framework for SLA in a Multilingual World

THE PHENOMENON OF MULTILINGUALISM is as old as humanity, but multilingualism has been catapulted to a new world order in the 21st century. Social relations, knowledge structures, and webs of power are experienced bymany people as highly mobile and interconnected—for good and for bad—as a result of broad sociopolitical events and global markets. As a consequence, today’s multilingualism is enmeshed in globalization, technologization, and mobility. Communication and meaning-making are often felt as deterritorialized, that is, lived as something “which does not belong to one locality but which organizes translocal trajectories and wider spaces” (Blommaert, 2010, p. 46), while language use and learning are seen as emergent, dynamic, unpredictable, open ended, and intersubjectively negotiated. In this context, increasingly numerous and more diverse populations of adults and youth become multilingual and transcultural later in life, either by elective choice or by forced circumstances, or for a mixture of reasons. They must learn to negotiate complex demands and opportunities for varied, emergent competencies across their languages. Understanding such learning requires the integrative consideration of learners’ mental and neurobiological processing, remembering and categorizing patterns, and momentto-moment use of language in conjunction with a variety of socioemotional, sociocultural, sociopolitical, and ideological factors. The field of second language acquisition (SLA) seeks (a) to understand the processes by which school-aged children, adolescents, and adults learn and use, at any point in life, an additional language, including second, foreign,
An applied mathematics perspective on stochastic modelling for climate

Systematic strategies from applied mathematics for stochastic modelling in climate are reviewed here. One of the topics discussed is the stochastic modelling of mid-latitude low-frequency variability through a few teleconnection patterns, including the central role and physical mechanisms responsible for multiplicative noise. A new low-dimensional stochastic model is developed here, which mimics key features of atmospheric general circulation models, to test the fidelity of stochastic mode reduction procedures. The second topic discussed here is the systematic design of stochastic lattice models to capture irregular and highly intermittent features that are not resolved by a deterministic parametrization. A recent applied mathematics design principle for stochastic column modelling with intermittency is illustrated in an idealized setting for deep tropical convection; the practical effect of this stochastic model in both slowing down convectively coupled waves and increasing their fluctuations is presented here.
Effects of market liberalisation on smoking in Japan

OBJECTIVE To document the effect of the liberalisation of the Japanese tobacco market on Japanese smoking rates and on Japanese tobacco industry practices. DATA SOURCE Asahi Shimbun (major daily newspaper) from 1980 to 1996. STUDY SELECTION Review of media coverage on the effects of market liberalisation following the imposition of the USA's section 301 trade sanction. DATA SYNTHESIS The opening of Japan's tobacco market to foreign cigarette companies stalled a decline in smoking prevalence. Smoking rates among young women increased significantly, and also appear to be on the rise among adolescents. Aggressive marketing and promotional activities by US and Japanese tobacco companies in response to trade liberalisation appear responsible for these adverse trends. Steep increases in sales through vending machines were also possible contributors to the rising smoking prevalence among adolescents. On the positive side, market liberalisation indirectly promoted smoking control efforts in Japan, by causing an anti-smoking movement to coalesce. CONCLUSION Market liberalisation in Japan played a significant role in increasing smoking prevalence among young women and adolescents while helping to transform the issue of smoking in Japan from a matter of individual choice to a public health problem.
Taxonomy, biostratigraphy, and phylogeny of Oligocene Globigerinitidae (Dipsidripella, Globigerinita, and Tenuitella)

The taxonomy, biostratigraphy, and phylogeny of the Oligocene Globigerinitidae (comprising the genera Dipsidripella, Globigerinita and Tenuitella) is reviewed. This family is here included in the Superfamily Globigerinitoidea based on the distinctive wall texture. The group is united by possessing a ‘radially crystalline’ wall texture (the glutinata-type wall) which typically bears pyramidal pustules and in most species is microperforate (pores <1 µm in diameter). The genus Dipsidripella is included in the family here for the first time. In Dipsidripella the wall is often medioperforate (pores 1-2 µm in diameter; danvillensis-subtype). The following species are recognized as valid and occurring in the Oligocene: Dipsidripella danvillensis (Howe and Wallace), Dipsidripella liqianyui Huber and Pearson, Globigerinita glutinata (Egger), Globigerinita uvula (Ehrenberg), Tenuitella angustiumbilicata (Bolli), Tenuitella gemma (Jenkins), Tenuitella munda (Jenkins), and Tenuitella praegemma (Li).
Judgments of Azimuth and Elevation as a Function of Monoscopic and Binocular Depth Cues Using a Perspective Display

The purpose of this study was to investigate the use of three-dimensional display formats for judgments of spatial information using an exocentric frame of reference. Eight subjects judged the azimuth and elevation that separated two computer-generated objects using either a perspective or stereoscopic display. Errors, which consisted of the difference in absolute value between the estimated and actual azimuth or elevation, were analyzed as the response variable. The data indicated that the stereoscopic display resulted in more accurate estimates of elevation, especially for images aligned approximately orthogonally to the viewing vector. However, estimates of relative azimuth direction were not improved by use of the stereoscopic display. Furthermore, it was shown that the effect of compression resulting from a 45--deg computer graphics eye point elevation produced a response bias that was symmetrical around the horizontal plane of the reference cube, and that the depth cue of binocular disparity provided by the stereoscopic display reduced the magnitude of the compression errors. Implications of the results for the design of spatial displays are discussed.
The alphaslider: a compact and rapid selector

Research has suggested that rapid, serial, visual presentation of text (RSVP) may be an effective way to scan and search through lists of text strings in search of words, names, etc. The Alphaslider widget employs RSVP as a method for rapidly scanning and searching lists or menus in a graphical user interface environment. The Alphaslider only uses an area less than 7 cm x 2.5 cm. The tiny size of the Alphaslider allows it to be placed on a credit card, on a control panel for a VCR, or as a widget in a direct manipulation based database interface. An experiment was conducted with four Alphaslider designs which showed that novice Alphaslider users could locate one item in a list of 10,000 film titles in 24 seconds on average, an expert user in about 13 seconds.
Fast Kernel-Based Independent Component Analysis

Recent approaches to independent component analysis (ICA) have used kernel independence measures to obtain highly accurate solutions, particularly where classical methods experience difficulty (for instance, sources with near-zero kurtosis). FastKICA (fast HSIC-based kernel ICA) is a new optimization method for one such kernel independence measure, the Hilbert-Schmidt Independence Criterion (HSIC). The high computational efficiency of this approach is achieved by combining geometric optimization techniques, specifically an approximate Newton-like method on the orthogonal group, with accurate estimates of the gradient and Hessian based on an incomplete Cholesky decomposition. In contrast to other efficient kernel-based ICA algorithms, FastKICA is applicable to any twice differentiable kernel function. Experimental results for problems with large numbers of sources and observations indicate that FastKICA provides more accurate solutions at a given cost than gradient descent on HSIC. Comparing with other recently published ICA methods, FastKICA is competitive in terms of accuracy, relatively insensitive to local minima when initialized far from independence, and more robust towards outliers. An analysis of the local convergence properties of FastKICA is provided.
Parameter Extraction and Comparison of Self-Heating Models for Power MOSFETs Based on Transient Current Measurements

A self-heating parameter extraction method for a circuit simulation model is discussed based on the transient drain current measurement, by using an 18-V LDMOS as a test device. Important quantities for self-heating models, self-heating-free drain current, thermal resistance Rth, and thermal capacitance Cth are directly and simultaneously extracted from the transient current measurements. The method is efficient in improving the fitting quality in the short-time domain after switching and in guaranteeing the consistency among the extracted quantities. Based on the method, two kinds of thermal network are compared and discussed for the on-wafer measurement. It is demonstrated that the 1R1C model using the method carries fitting errors only in the narrow range of time and that the fitting errors can be removed only by adding one pair of thermal resistance and thermal capacitance which represent the thermal distribution below the device.
valuating the stock – recruitment relationship and management reference oints : Application to summer flounder ( Paralichthys dentatus ) in the U . S . id-Atlantic ark

The stock–recruitment relationship is one of the most uncertain processes of fish population dynamics, and is highly influential with respect to fisheries management advice. The stock recruitment relationship has a direct impact on reference points commonly used in contemporary fisheries management. Simulation analysis has shown that the steepness of the Beverton–Holt stock–recruitment relationship is difficult to estimate for most fish stocks, which has led to the use of proxy reference points. Proxy maximum sustainable yield reference points based on spawning biomass-per-recruit, which are commonly used when the stock–recruitment relationship is uncertain, are a linear function of steepness. Risk in terms of lost yield is generally lower when steepness is underestimated compared to when steepness is overestimated because the yield curve is flat when steepness is high (close to one: recruitment is
Basic mechanics of DNA methylation and the unique landscape of the DNA methylome in metal-induced carcinogenesis

Abstract DNA methylation plays an intricate role in the regulation of gene expression and events that compromise the integrity of the methylome may potentially contribute to disease development. DNA methylation is a reversible and regulatory modification that elicits a cascade of events leading to chromatin condensation and gene silencing. In general, normal cells are characterized by gene-specific hypomethylation and global hypermethylation, while cancer cells portray a reverse profile to this norm. The unique methylome displayed in cancer cells is induced after exposure to carcinogenic metals such as nickel, arsenic, cadmium, and chromium (VI). These metals alter the DNA methylation profile by provoking both hyper- and hypo-methylation events. The metal-stimulated deviations to the methylome are possible mechanisms for metal-induced carcinogenesis and may provide potential biomarkers for cancer detection. Development of therapies based on the cancer methylome requires further research including human studies that supply results with larger impact and higher human relevance.
Quality Investing

Buying high quality assets without paying premium prices is just as much value investing as buying average quality assets at discount prices. Strategies that exploit the quality dimension of value can be profitable on their own, and accounting for both dimensions of value yields dramatic performance improvements over traditional value strategies. Gross profitability is particularly powerful among popular quality notions, especially among large cap stocks and for long-only investors.
Determinants of Satisfaction With Community Reintegration in Older Adults With Chronic Stroke: Role of Balance Self-Efficacy

Background and Purpose Many people with stroke have a low level of satisfaction with community reintegration. Although previous studies focused on the effect of physical factors on community reintegration, the effect of psychological factors, such as balance self-efficacy, has been ignored. The purpose of this study was to determine the contribution of balance self-efficacy to satisfaction with community reintegration in older adults with chronic stroke. Subjects A sample of 63 community-dwelling older adults (50 years of age or older) with chronic stroke (onset of 1 year or more) participated in this study. Methods This study involved a secondary analysis of data collected from a stroke exercise clinical trial. Satisfaction with community reintegration was measured with the Reintegration to Normal Living (RNL) Index, and balance self-efficacy was measured with the Activities-specific Balance Confidence (ABC) Scale. Results Bivariate correlation analyses showed that the RNL Index scores were moderately correlated with the ABC Scale scores. In a multiple regression analysis, after adjusting for age, sex, depression, and other impairments after stroke, balance self-efficacy remained independently associated with the RNL Index scores, accounting for 6.5% of the variance in the RNL Index scores. Discussion and Conclusion Balance self-efficacy is an independent predictor of satisfaction with community reintegration in older adults with chronic stroke. Improving balance self-efficacy may be instrumental in enhancing community reintegration in this population.
Human Capital, Capital Structure, and Employee Pay: An Empirical Analysis

We test the predictions of Titman (1984) and Berk, Stanton, and Zechner (2010) by examining the effect of leverage on labor costs. Leverage has a significantly positive impact on cash, equity-based, and total compensation of chief executive officers (CEOs). Compensation of new CEOs hired from outside the firm is positively related to prior-year firm leverage. In addition, leverage has a positive and significant impact on average employee pay. The incremental total labor expenses associated with an increase in leverage are large enough to offset the incremental tax benefits of debt. The empirical evidence supports the theoretical prediction that labor costs limit the use of debt.
Young people at risk for psychosis: case finding and sample characteristics of the Oulu Brain and Mind Study

Aim: Set within the general population‐based Northern Finland Birth Cohort 1986, the Oulu Brain and Mind Study aims to explore the causes and pathogenesis of psychotic illness by following young people at risk for psychosis due to having a first‐degree relative with psychotic illness or due to having experienced psychotic‐like symptoms themselves. We report the study methods and explore the relationship between these definitions of high risk for psychosis and operational criteria for a prodromal psychosis syndrome based on interview.
Parasite Co-Infections and Their Impact on Survival of Indigenous Cattle

In natural populations, individuals may be infected with multiple distinct pathogens at a time. These pathogens may act independently or interact with each other and the host through various mechanisms, with resultant varying outcomes on host health and survival. To study effects of pathogens and their interactions on host survival, we followed 548 zebu cattle during their first year of life, determining their infection and clinical status every 5 weeks. Using a combination of clinical signs observed before death, laboratory diagnostic test results, gross-lesions on post-mortem examination, histo-pathology results and survival analysis statistical techniques, cause-specific aetiology for each death case were determined, and effect of co-infections in observed mortality patterns. East Coast fever (ECF) caused by protozoan parasite Theileria parva and haemonchosis were the most important diseases associated with calf mortality, together accounting for over half (52%) of all deaths due to infectious diseases. Co-infection with Trypanosoma species increased the hazard for ECF death by 6 times (1.4–25; 95% CI). In addition, the hazard for ECF death was increased in the presence of Strongyle eggs, and this was burden dependent. An increase by 1000 Strongyle eggs per gram of faeces count was associated with a 1.5 times (1.4–1.6; 95% CI) increase in the hazard for ECF mortality. Deaths due to haemonchosis were burden dependent, with a 70% increase in hazard for death for every increase in strongyle eggs per gram count of 1000. These findings have important implications for disease control strategies, suggesting a need to consider co-infections in epidemiological studies as opposed to single-pathogen focus, and benefits of an integrated approach to helminths and East Coast fever disease control.
Determination of Sensitive Electrophysiologic Parameters at Follow-up of Different Steroid Treatments of Carpal Tunnel Syndrome

Nonsurgical treatment for carpal tunnel syndrome (CTS) is frequently offered to those with mild to moderate symptoms. However, the most sensitive electrophysiological parameters at follow-up, and most effective type of different methods of steroid treatment for CTS, remain unknown. The aim of this study was to compare the efficacy of local corticosteroid injection, phonophoresis, and iontophoresis for the treatment of CTS, and to evaluate the most sensitive electrophysiologic parameters at the follow-up visit. Different conservative treatments were applied in this prospective study. Fifty-six hands of 31 patients were randomly treated with local steroid injection, iontophoresis, or phonophoresis with 2- and 4-month follow-up visits. Conventional and new neurophysiologic sensorimotor nerve conduction parameters for CTS diagnosis were performed on the initial visit and at 2 and 4 months after treatment. The local steroid injection group showed a significant improvement in the mean nerve conduction parameters after the second and fourth months when compared with basal values, whereas no significant changes except the difference between the median and ulnar distal latency to the fourth digit (D4M-D4U), difference between sensory median distal latency to second digit and ulnar distal latency to the fifth digit (D2M-D5U), and median motor distal latency were observed in the iontophoresis and phonophoresis groups. At the end of follow-up period, the most sensitive parameters were D4M-D4U and D2M-D5U; the D4M-D4U was improved 60% in the injection group, 33% in iontophoresis group, and 39% in phonophoresis group, and the improvement of the D2M-D5U was 70%, 28%, and 28%, respectively, in the injection, iontophoresis, and phonophoresis groups. These findings show that steroid injection is superior to iontophoresis and phonophoresis in the treatment of CTS, and that the most sensitive neurophysiologic parameters in follow-up are D4M-D4U and D2M-D5U, being the objective measures of the outcome of CTS treatment.