Miracle-dz/UniFAR-FTUs huggingface dataset:
In Vitro Evaluation of Reversible and Irreversible Cytochrome P450 Inhibition: Current Status on Methodologies and their Utility for Predicting Drug–Drug Interactions

It is widely accepted that today’s practice of polypharmacy inevitably increases the incidence of drug–drug interactions (DDIs). Serious DDI is a major liability for any new chemical entity (NCE) entering the pharmaceutical market. As such, pharmaceutical companies employ various strategies to avoid problematic compounds for clinical development. A key cause for DDIs is the inhibition of cytochrome P450 enzymes (CYPs) that are responsible for metabolic clearance of many drugs. Screening for inhibition potency of CYPs by NCEs has therefore become a routine practice during the drug discovery stage. However, in order to make proper use of DDI data, an understanding of the strengths and weaknesses of the various experimental systems in current use is required. An illustrated review of experimental practices is presented with discussion of likely future developments. The combination of high quality in vitro data generation and the application of in vivo CYP inhibition modelling approaches should allow more informed decisions to be made in the search for drug molecules with acceptable DDI characteristics.
Gamma-Band Activity in Human Posterior Parietal Cortex Encodes the Motor Goal during Delayed Prosaccades and Antisaccades

Although it is well established that parietal cortex is important in processing sensorimotor transformations, less is known about the neuronal dynamics of this process in humans. Using magnetoencephalography, we investigated the dynamics of parietal oscillatory activity during saccade planning in terms of sensory and motor goal processing. In the experiments, a peripheral stimulus was flashed in either the left or right hemifield, followed by a 1.5 s delay period, after which the subject executed a saccade toward (prosaccade) or away from (antisaccade) the stimulus. In response to stimulus presentation, we observed an initial increase in gamma-band power (40–120 Hz) in a region in the posterior parietal cortex contralateral to the direction of the stimulus. This lateralized power enhancement, which was sustained in a more narrow frequency band (85–105 Hz) during the delay period of prosaccades, mapped to the hemisphere contralateral to the direction of the saccade goal during the delay period of antisaccades. These results suggest that neuronal gamma-band synchronization in parietal cortex represents the planned direction of the saccade, not the memorized stimulus location. In the lower-frequency bands, we observed sustained contralateral alpha (7–13 Hz) power suppression after stimulus presentation in parieto-occipital regions. The dynamics of the alpha band was strongly related to the processing of the stimulus and showed only modest selectivity for the goal of the saccade. We conclude that parietal gamma-band synchronization reflects a mechanism to encode the motor goals in the visuomotor processing for saccades.
Personality Traits and Academic Performance of Medical Students in Al–Ahsa, Saudi Arabia

Introduction: Students differ in their learning styles and generally do well in the environment that fit their personality types. Considerable research is being done to ascertain the personality types of students to create a rewarding environment that enhances their learning ability. Correlating personality with academic performance has come a long way since one of the earliest review articles in the field. The present study was conducted to determine various personality traits and its correlation with their academic performance so that the teaching and learning methods can be modified to produce excellent academic achievements by the students after awareness of their pattern of personality. Material andMethods: A Cross-sectional study was conducted among 416 medical students of College of Medicine, King Faisal University, Saudi Arabia. A self-administered Big Five Inventory (BFI) questionnaire was distributed and responses were collected. Results: In the present study, 155 (37.1%) participants were Traditional Curriculum students while 263 (62.9%) were PBL curriculum students. The ‘Conscientious Personality’ trait showed highly significant (p=0.0001) association with high GPA (4.5-5). However, no significant association was observed between other personality types (Openness, Extraversion, Agreeable, and Neuroticism) and GPA.Statistically no significant association was observed between personality traits and other characteristics of participants i.e. Gender, Marital status and teaching methods. Conclusions: Present study showed mixed pattern of personality traits of medical students. Few personality traits like Conscientiousness’ has significant influence with academic performance of students. They showed favorable attitude towards ‘Problem Based Learning’ curriculum as compared to ‘Traditional Curriculum’.
Stereotypes, students' perceptions and inherent creativity: further Australian evidence

The objectives of this study are to: ascertain how first year university students perceive accounting in a time period following the high profile corporate collapses of the early 21st century; understand the factors that influence these perceptions; and determine if there is an association between students' perceptions of accounting and their inherent creativity. The findings of the study show that the majority of first year university students still hold a traditional stereotypical perception of accounting. School teachers and subjects were reported by the students as being the main influences on their perceptions. Students' perceptions of accounting are also linked to their inherent creativity. A limitation of the study is that the sample is drawn from students at two Australian universities. Therefore, the results may not generalise to other institutions. This study contributes to the existing body of knowledge on students' perceptions of accounting and the impact of various factors. There are implications for educators in designing appropriate curricula and the promotion of accounting by the accounting profession.
Less-is-more effects without the recognition heuristic

Inferences consistent with “recognition-based” decision-making may be drawn for various reasons other than recognition alone. We demonstrate that, for 2-alternative forced-choice decision tasks, less-is-more effects (reduced performance with additional learning) are not restricted to recognition-based inference but can also be seen in circumstances where inference is knowledge-based but item knowledge is limited. One reason why such effects may not be observed more widely is the dependence of the effect on specific values for the validity of recognition and knowledge cues. We show that both recognition and knowledge validity may vary as a function of the number of items recognized. The implications of these findings for the special nature of recognition information, and for the investigation of recognition-based inference, are discussed.
Comprehensive mapping of antigen specific T cell responses in hepatitis C virus infected patients with or without spontaneous viral clearance

Elucidating protective immunity against HCV is important for the development of a preventative vaccine. We hypothesize that spontaneous resolution of acute HCV infection offers clue to protective immune responses, and that DAA therapy affects the quality and quantity of HCV-specific T cell responses. To test these hypotheses, we performed T cell epitope mapping in 111 HCV-infected individuals including 61 chronically HCV-1b (CHC-1b) infected, 24 chronically HCV-2a (CHC-2a) infected and 26 spontaneously recovered (SPR) patients with 376 overlapping peptides covering the entire HCV polyprotein. Selected T cell epitopes were then used to evaluate T cell responses in another 22 chronically HCV-1b infected patients on DAA therapy. Results showed that SPR had better HCV-specific T cell responses than CHC, as manifested by higher response rate, greater magnitude and broader epitope coverage. In addition, SPR recognized novel epitopes in Core, E1, E2, NS4B, NS5A regions that were not present in the CHC. Furthermore, during the first 24 weeks of DAA therapy, there was no functional immune reconstitution of HCV-specific T cells. These results indicate that T cell responses may be a correlate of protection. Therefore, effective preventative vaccines should elicit a robust T cell response. Although various DAA regimens efficiently cleared viruses from the blood of HCV-infected patients, there was no contemporaneous early T cell immune reconstitution, suggesting that early treatment is needed for preserving the functions of HCV-specific T cells.
Las bases epistémicas de la concepción feminista de la ciudadanía

The criticism from feminist political theory toward the concept of citizenship can be understood from a broad conception of epistemology and gnoseology in general. From this perspective, the axis of the feminist criticism is directed to the conception of the individual as universal citizen, based on the contractualist theory, arguing that it is has been built from a restricted universalism that unveils a gender bias. Thus, the article suggests that the epistemic support of the feminist analysis to the notion of citizenship concerns a challenge to the category of a subject of universal rights, proposing this recognition as a key to obtain the emancipation of women in relations of domination, arguing, on this basis, that the division between the public space and the private sphere is a fiction. From there, emerges the questioning by the type of subjects that should underpin the model of citizenship, from which feminism has based an important part of its proposal to transform the conception of politics as a space that recognizes the gender gap and sustains equity.
Rab39a Interacts with Phosphatidylinositol 3-Kinase and Negatively Regulates Autophagy Induced by Lipopolysaccharide Stimulation in Macrophages

Rab39a has pleiotropic functions in phagosome maturation, inflammatory activation and neuritogenesis. Here, we characterized Rab39a function in membrane trafficking of phagocytosis and autophagy induction in macrophages. Rab39a localized to the periphery of LAMP2-positive vesicles and showed the similar kinetics on the phagosome to that of LAMP1. The depletion of Rab39a did not influence the localization of LAMP2 to the phagosome, but it augments the autophagosome formation and LC3 processing by lipopolysaccharide (LPS) stimulation. The augmentation of autophagosome formation in Rab39a-knockdown macrophages was suppressed by Atg5 depletion or an inhibitor for phosphatidylinostol 3-kinase (PI3K). Immunoprecipitation analysis revealed that Rab39a interacts with PI3K and that the amino acid residues from 34th to 41st in Rab39a were indispensable for this interaction. These results suggest that Rab39a negatively regulates the LPS-induced autophagy in macrophages.
Prevalence and control of diabetes in Chinese adults.

IMPORTANCE Noncommunicable chronic diseases have become the leading causes of mortality and disease burden worldwide. OBJECTIVE To investigate the prevalence of diabetes and glycemic control in the Chinese adult population. DESIGN, SETTING, AND PARTICIPANTS Using a complex, multistage, probability sampling design, we conducted a cross-sectional survey in a nationally representative sample of 98,658 Chinese adults in 2010. MAIN OUTCOMES AND MEASURES Plasma glucose and hemoglobin A1c levels were measured after at least a 10-hour overnight fast among all study participants, and a 2-hour oral glucose tolerance test was conducted among participants without a self-reported history of diagnosed diabetes. Diabetes and prediabetes were defined according to the 2010 American Diabetes Association criteria; whereas, a hemoglobin A1c level of <7.0% was considered adequate glycemic control. RESULTS The overall prevalence of diabetes was estimated to be 11.6% (95% CI, 11.3%-11.8%) in the Chinese adult population. The prevalence among men was 12.1% (95% CI, 11.7%-12.5%) and among women was 11.0% (95% CI, 10.7%-11.4%). The prevalence of previously diagnosed diabetes was estimated to be 3.5% (95% CI, 3.4%-3.6%) in the Chinese population: 3.6% (95% CI, 3.4%-3.8%) in men and 3.4% (95% CI, 3.2%-3.5%) in women. The prevalence of undiagnosed diabetes was 8.1% (95% CI, 7.9%-8.3%) in the Chinese population: 8.5% (95% CI, 8.2%-8.8%) in men and 7.7% (95% CI, 7.4%-8.0%) in women. In addition, the prevalence of prediabetes was estimated to be 50.1% (95% CI, 49.7%-50.6%) in Chinese adults: 52.1% (95% CI, 51.5%-52.7%) in men and 48.1% (95% CI, 47.6%-48.7%) in women. The prevalence of diabetes was higher in older age groups, in urban residents, and in persons living in economically developed regions. Among patients with diabetes, only 25.8% (95% CI, 24.9%-26.8%) received treatment for diabetes, and only 39.7% (95% CI, 37.6%-41.8%) of those treated had adequate glycemic control. CONCLUSIONS AND RELEVANCE The estimated prevalence of diabetes among a representative sample of Chinese adults was 11.6% and the prevalence of prediabetes was 50.1%. Projections based on sample weighting suggest this may represent up to 113.9 million Chinese adults with diabetes and 493.4 million with prediabetes. These findings indicate the importance of diabetes as a public health problem in China.
Indices of body composition, energy and macronutrient intakes in young men and women with different physical activity

It has been shown that body mass index (BMI) commonly used in assessing nutritional status provides equivocal results since subjects with normal BMI are often characterized by abnormal body fat and fat free mass. In consequence, it has been suggested that an indices more precise than BMI of body composition should be used for evaluation of nutritional status and risk of malnutrition and/or obesity. This study aimed at evaluation of the relationship between different indices of body composition and dietary macronutrient intakes in young non-active and active adults. A total of 264 students (136 females and 128 males) participated in the study. Physical activity of 131 subjects (69 males and 62 females) was more than 7 h/week and were classified as active. A total of 133 subjects (59 males and 74 females) with physical activity less than 3 h/week were classified as non-active. Weight, height and waist circumference were measured using standard procedures. Body fat (BF) and fat free mass (FFM) were determined using the bioelectrical impedance method and Tanita equipment. Daily energy and macronutrient intakes were evaluated from four 24-hours recalls concerning two week days and weekend and analyzed using the Dieta 5.0. computerized programme. Basal metabolic rate (BMR) was calculated from body fat and fat free mass, and energy intake (EI) to BMR ratio was calculated to identify the under- and over-reporters. There were no differences in BMI between males and females with different physical activity. Both, non-active females and males were characterized by a higher percent of BF compared to those who were non-active. A difference in FFM was observed between active and nonactive females. Waist circumference in active males was lower vs. their sedentary counterparts. There were no differences in energy consumption between active and non-active students. Neither daily energy intake nor diet composition were correlated with indices of body composition. Additionally, it was observed that in both active and non-active females and active males underreporting was more pronounced in subjects with normal body fat. The above data possibly suggest that numerous participants were characterized by a distorted body image.
Original article. Biting behavior of Malaysian mosquitoes, Aedes albopictus Skuse, Armigeres kesseli Ramalingam, Culex quinquefasciatus Say, and Culex vishnui Theobald obtained from urban residential areas in Kuala Lumpur

Abstract Background: There are several species of mosquitoes that readily attack people, and some are capable of transmitting microbial organisms that cause human diseases including dengue, malaria, and Japanese encephalitis. The mosquitoes of major concern in Malaysia belong to the genera Culex, Aedes, and Armigeres. Objective: To study the host-seeking behavior of four Malaysian mosquitoes commonly found in urban residential areas in Kuala Lumpur. Methods: The host-seeking behavior of Aedes albopictus, Armigeres kesseli, Culex quinquefasciatus, and Culex vishnui was conducted in four urban residential areas in Fletcher Road, Kampung Baru, Taman Melati, and University of Malaya student hostel. The mosquito biting frequency was determined by using a bare leg catch (BLC) technique throughout the day (24 hours). The study was triplicated for each site. Results: Biting activity of Ae. albopictus in urban residential areas in Kuala Lumpur was detected throughout the day, but the biting peaked between 0600-0900 and 1500-2000, and had low biting activity from late night until the next morning (2000-0500) with biting rate ≤1 mosquito/man/hour. Biting behavior of Ar. kesseli was distinctly crepuscular, which exhibited two peaks of activity at 0600-0700 and 1900-2000, while Culex quinquefasciatus and Cx. vishnui were nocturnal feeders with multiple biting peaks throughout the night. Conclusion: This study recommends optimal time for fogging to be conducted in Malaysia and neighboring countries according to the peak biting peak obtained.
Evolutionary diversification of the African achyranthoid clade (Amaranthaceae) in the context of sterile flower evolution and epizoochory

Background and Aims Many African genera of the Amaranthaceae exhibit unique inflorescences that include sterile flowers modified to hooks or spines. Considering that the abundance of large terrestrial herbivores increased on the African continent with the expansion of grassland and savannah ecosystems, modified sterile flowers could have been an innovation that boosted the diversification of an African achyranthoid clade of Amaranthaceae, with large animals serving dispersal. Methods We generated an extensively sampled phylogeny comprising 26 of the 31 achyranthoid genera as well as representatives of all other lineages of Amaranthaceae. Phylogenetic tree inference employed four genomic regions, using parsimony, likelihood and Bayesian inference methods. We estimated divergence times, evaluated trait-dependant changes and species diversification rates using state-dependent speciation and extinction models, and reconstructed ancestral character states for modified sterile flowers. Key Results The achyranthoids were found to be a major clade of the Amaranthaceae, comprising mostly African members. Phylogenetic relationships within this clade were well resolved and supported two main subclades. Several genera were found to be polyphyletic. Our results indicate that the achyranthoids started to diversify ~28 million years ago, and that modified sterile flowers evolved multiple times. An asymmetry in transition rates towards the gain of sterile flowers was observed, whereas no trait-dependent increase in species diversification rates was detected. Bayesian rate heterogeneity analyses indicated that the achyranthoids diversified without significant rate shifts. Conclusions The accumulation of modified sterile flowers within achyranthoids appears to result from the higher transition rates in favour of modified sterile flowers. Multiple gains suggest an adaptive value for this trait. However, epizoochory does not appear to fuel species diversification, possibly due to extensive gene flow through regularly migrating mammals, which limits the possibility of speciation by isolation.
The adenovirus E4orf4 protein targets PP2A to the ACF chromatin-remodeling factor and induces cell death through regulation of SNF2h-containing complexes

The adenovirus E4 open-reading-frame 4 (E4orf4) protein regulates the progression of viral infection and when expressed individually it induces non-classical apoptosis in transformed cells. Here we show that E4orf4 associates with the ATP-dependent chromatin-remodeling factor ACF that consists of a sucrose non fermenting-2h (SNF2h) ATPase and an Acf1 regulatory subunit. Furthermore, E4orf4 targets protein phosphatase 2A (PP2A) to this complex and to chromatin. Obstruction of SNF2h activity inhibits E4orf4-induced cell death, whereas knockdown of Acf1 results in enhanced E4orf4-induced toxicity in both mammalian and yeast cells, and Acf1 overexpression inhibits E4orf4′s ability to downregulate early adenovirus gene expression in the context of viral infection. Knockdown of the Acf1 homolog, WSTF, inhibits E4orf4-induced cell death. Based on these results we suggest that the E4orf4–PP2A complex inhibits ACF and facilitates enhanced chromatin-remodeling activities of other SNF2h-containing complexes, such as WSTF–SNF2h. The resulting switch in chromatin remodeling determines life versus death decisions and contributes to E4orf4 functions during adenovirus infection.
Cognitive Architectures for Multimedia Learning

This article provides a tutorial overview of cognitive architectures that can form a theoretical foundation for designing multimedia instruction. Cognitive architectures include a description of memory stores, memory codes, and cognitive operations. Architectures that are relevant to multimedia learning include Paivio's dual coding theory, Baddeley's working memory model, Engelkamp's multimodal theory, Sweller's cognitive load theory, Mayer's multimedia learning theory, and Nathan's ANIMATE theory. The discussion emphasizes the interplay between traditional research studies and instructional applications of this research for increasing recall, reducing interference, minimizing cognitive load, and enhancing understanding. Tentative conclusions are that (a) there is general agreement among the different architectures, which differ in focus; (b) learners' integration of multiple codes is underspecified in the models; (c) animated instruction is not required when mental simulations are sufficient; (d) actions must be meaningful to be successful; and (e) multimodal instruction is superior to targeting modality-specific individual differences.
The Budgetary Implications of Marijuana Prohibition

Executive Summary • Government prohibition of marijuana is the subject of ongoing debate. • One issue in this debate is the effect of marijuana prohibition on government budgets. Prohibition entails direct enforcement costs and prevents taxation of marijuana production and sale. • This report examines the budgetary implications of legalizing marijuana – taxing and regulating it like other goods – in all fifty states and at the federal level. • The report estimates that legalizing marijuana would save $7.7 billion per year in government expenditure on enforcement of prohibition. $5.3 billion of this savings would accrue to state and local governments, while $2.4 billion would accrue to the federal government. • The report also estimates that marijuana legalization would yield tax revenue of $2.4 billion annually if marijuana were taxed like all other goods and $6.2 billion annually if marijuana were taxed at rates comparable to those on alcohol and tobacco. • Whether marijuana legalization is a desirable policy depends on many factors other than the budgetary impacts discussed here. But these impacts should be included in a rational debate about marijuana policy.