Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetics and Interactions of a Novel Antagonist of Chemokine Receptor 5 (CCR5) with Ritonavir in Rats and Monkeys: Role of CYP3A and P-Glycoprotein

The mechanisms of pharmacokinetic interactions of a novel anti-human immunodeficiency virus (anti-HIV-1) antagonist of chemokine receptor 5 (CCR5) [2-(R)-[N-methyl-N-(1-(R)-3-(S)-((4-(3-benzyl-1-ethyl-(1H)-pyrazol-5-yl)piperidin-1-yl)methyl)-4-(S)-(3-fluorophenyl)cyclopent-1-yl)amino]-3-methylbutanoic acid (MRK-1)] with ritonavir were evaluated in rats and monkeys. MRK-1 was a good substrate for the human (MDR1) and mouse (Mdr1a) multidrug resistance protein transporters and was metabolized by CYP3A isozymes in rat, monkey, and human liver microsomes. Both the in vitro MDR1-mediated transport and oxidative metabolism of MRK-1 were inhibited by ritonavir. Although the systemic pharmacokinetics of MRK-1 in rats and monkeys were linear, the oral bioavailability increased with an increase in dose from 2 to 10 mg/kg. The area under the plasma concentration-time curve (AUC) of MRK-1 was increased 4- to 6-fold when a 2 or 10 mg/kg dose was orally coadministered with 10 mg/kg ritonavir. Further pharmacokinetic studies in rats indicated that P-glycoprotein (P-gp) inhibition by ritonavir increased the intestinal absorption of 2 mg/kg MRK-1 maximally by ∼30 to 40%, and a major component of the interaction likely resulted from its reduced systemic clearance via the inhibition of CYP3A isozymes. Oral coadministration of quinidine (10 and 30 mg/kg) increased both the extent and the first-order rate of absorption of MRK-1 (2 mg/kg) by ∼40 to 50% and ∼100 to 300%, respectively, in rats, thus further substantiating the role of P-gp in modulating the intestinal absorption of MRK-1 in this species. At the 10 mg/kg MRK-1 dose, however, the entire increase in its AUC upon coadministration with ritonavir or quinidine could be attributed to a reduced systemic clearance, and no effects on intestinal absorption were apparent. In contrast to rats, the effects of P-gp in determining the intestinal absorption of MRK-1 appeared less significant in rhesus monkeys at either dose.
Free amino Acid composition of leaf exudates and Phloem sap : a comparative study in oats and barley.

Comparisons were made between the free amino acid composition in leaf exudates and that in pure phloem sap, using twin samples taken from a single leaf of two oat (Avena sativa L.) and three barley (Hordeum vulgare L.) varieties. Leaf exudate was collected in a 5 mm EDTA-solution (pH 7.0) from cut leaf blades and phloem sap was obtained through excised aphid (Rhopalosiphum padi L.) stylets. Fluorescent derivatives of amino acids were obtained using 9-fluorenylmethyl chloroformate and were separated by means of high performance liquid chromatography. The total concentration of free amino acids varied considerably in the exudate samples. There was no correlation between the total amino acid content in the exudate samples and that of the corresponding phloem sap samples, but the amino acid composition of the corresponding samples was highly correlated (median R(2)-value 0.848). There was only limited between-plant variation in phloem sap amino acid composition. Nevertheless, in comparisons involving all samples, many of the amino acids showed significant correlations between their relative amounts in exudate and phloem sap. The results presented here indicate that the exudate technique holds great promise as an interesting alternative to the laborious and time-consuming stylet-cutting technique of obtaining samples for comparative studies of phloem sap.
Moments of Discomfort and Conflict: Holocaust Museums as Agents of Change

Museums serve as a place of memory, where heritage is conserved, collections cared for, and the best possible conditions are created for visitors to experience exhibits and the meanings and events they represent. These cultural institutions are increasingly defined by the ability to act as disseminators of culture and history as well as conveyors of controversial issues and have the ability to provide a vast range of informal and purposeful learning opportunities for adults. Programming that addresses a range of issues centering on social and environmental consciousness and human rights allows cultural institutions to draw upon resources and expertise to provide chances for individuals to change professional practice, gain new perspectives on societal norms, and challenge existing mental models. The events of the Holocaust and its representation in museums serve as an agent of change to improve the social and environmental situations for individuals and the organizations and communities in which they live and work. Using transformational learning theory as a conceptual frame, this article presents two cases for exploring museums’ role in supporting HRD and offers suggestions for partnerships between organizations and museums. Looking to museums and historic sites as sources of human resource development has far-reaching implications for cultural, organizational, and individual practices and is an innovative approach to initiating societal and institutional change.
LVAD Inflow Cannula Covered with a Titanium Mesh Induces Neointimal Tissue with Neovessels

Background Thrombus formation at the interfaces of inflow cannulas and left ventricular apexes is considered to be one of the predominant sources of thromboembolic complication. Use of a fine titanium mesh-covered inflow cannula is expected to prevent such thrombus formation by inducing neointimal tissue around the cannula. Methods Titanium pins (20 mm long, 3 mm diameter) covered with a fine titanium mesh (wire dia. 85 μm; volumetric porosity 40–70%) were developed to mimic the inflow cannulas of left ventricular assist devices (LVADs). Smooth-surface pins of the same size were also designed. The pins were implanted into the left ventricular apexes of rabbits. The rabbits were bled without anticoagulation for between 1 week and 1 year. The tissues around the pins were evaluated histologically. Results 28 rabbits (mesh group, 15; smooth group, 13) were evaluated. The mesh-covered pins inhibited thrombus formation to a remarkable degree throughout the entire observation period. The tissues around the mesh-covered titanium pins appeared to be in the process of conversion from thrombus formation to granulation, resulting in the replacement of fibrotic tissue containing myofibroblasts with endothelialized and angiogenic tissue. On the surface of the mesh-covered pins, endothelial cells were arranged without platelet adhesion. The tissue formed around the smooth-surface pins was partially organized into a thrombus without angiogenesis. Conclusions The titanium-mesh surface modification prevented thrombus formation with formation of neointimal tissue with endothelialization and angiogenesis. This surface modification could prevent wedge thrombus formation among patients supported by LVADs.
The Benefits of Guide Dog Ownership

There is an apparent discrepancy between the actual number of guide dog owners and the proportion of visually impaired people who might benefit from a guide dog. This research aimed to provide an understanding of the reasons why many visually impaired people have not applied for a guide dog, the range of benefits offered by guide dogs, and how these might vary amongst different populations and under different circumstances. While previous research described a number of psychological and social benefits of assistant animal ownership, consistent with the companion animal literature, it also pointed to the importance of personal and social context on the impact and effectiveness of assistance animals. The study described here involved a telephone survey of over 800 visually impaired people and found that independence, confidence, companionship, increased and changed social interaction, as well as increased mobility, are commonly cited benefits of guide dog ownership. These psychological and social dimensions.
Semi-structured approach for a specific decision-making capacity assessment

We have realized a case-control study with the aim of finding predictors for psychic capacity of exercise and to evidence the influence of cognitive deterioration upon this capacity. 172 subjects were enrolled and tested, clinically and using specific instruments, if they are capable of signing a provisional act. We have created a questionnaire for the assessment of psychic capacity of exercise, which comprises 22 items. Correlations and associations between variables were conducted. We found a relationship between cognitive profile and competence to enter into an agreement with somebody else. Additional functional capacities for capacity of exercise were evidenced. The logistic regression analysis was statistical significant for one predictor.
Steady-state and transient analysis of multichannel filtered-x affine projection algorithms

The paper provides an analysis of the steady-state and transient behavior of two filtered-x affine projection algorithms suitable for multichannel active noise control. The analysis relies on energy conservation arguments, it does not apply the independence theory nor does it impose any restriction to the signal distributions. The paper also shows that filtered-x affine projection algorithms always provide a biased estimate of the minimum-mean-square solution of the active noise control problem.
Preconception vs. Observation, or the Contributions of Rational Choice Theory and Area Studies to Contemporary Political Science

United States was stridently proclaiming its 'victory' over the materialism of the former USSR, its academic political science establishment was endorsing a form of economic determinism that is more rigid and less insightful than the Marxism it had seemingly just discredited. This is so-called rational choice or public choice theory, the attempt to apply the neo-classical (i.e., the University of Chicago Economics Department's) model of a market to politics. This exercise infects political science with the same flaws that an extreme version of laissez faire ide-
In situ formation of nanocrystals from a self-microemulsifying drug delivery system to enhance oral bioavailability of fenofibrate

Objectives In situ formation of nanocrystals and dissolution profiles of fenofibrate (FFB) from a self-microemulsifying drug delivery system (SMEDDS) were characterized. Methods SMEDDS formulated with Myritol® and surfactant mixture (Smix) of D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) and either Tween® 20 (A, C, E, G, M, S, N, T, O) or Tween® 80 (B, D, F, H, P, U, Q, V, R) at various oil/Smix ratios (Group I: A and B of 0.42, C and D of 0.25, E and F of 0.11; Group II: G and H of 1.38, M and P of 1.11, S and U of 0.9, N and Q of 0.73, T and V of 0.58, and O and R of 0.46) and water contents (1: 9.5%, 2: 5.0%, 3: 0.0%, G–V: 4.5%). Their dissolutions were conducted at different rotation speeds. Two optimal SMEDDSs containing Tween 80(B2) or a higher oil/Smix ratio(Q) and B2(solution) were selected for pharmacokinetic study. Results FFB particles formed within the nanosize range from Group I gradually increased with time but decreased with increasing stirring rates. However, the mean size of FFB formed by B series was as low as 200 nm, which was smaller than that of A series at three stirring rates. The release rate from both groups obviously increased with increasing stirring rate. However, incomplete release was observed for S and N in Tween 20 series, whereas a faster release rate and complete release were observed for Tween 80 series with an insignificant difference among them. Results of pharmacokinetic study demonstrated that the highest-ranked area under the curve and Cmax values were for Q(SMEDDS) and B2(solution), respectively. The relative bioavailability of Q(SMEDDS) with respect to Tricor® was enhanced by about 1.14–1.22-fold. Conclusion SMEDDS, consisting of Myritol 318 and TPGS combined with Tween 80 at 4:1, was able to enhance the oral bioavailability of FFB.
Contrasting Visions: Identity, Literacy, and Boundary Work in a Fan Community

This article focuses on learning and identity-related practices of young female fans of a popular British boy band called One Direction. Drawing on qualitative inquiry into a fanfiction community formed around the band, analysis highlights (a) the literate work fans engage in, including writing, reading, critiquing, and collaborating on multimodal texts, (b) identity work performed by the fans with respect to what it means to be a true fan, a teen, and an effective writer within this community, and (c) ways in which the literate and identity work weave together to inform participation and identification in the One Direction fanfiction community, creating both links and ruptures between young people's out-of-school and in-school spaces. Analyses center on the ways the fans themselves define their involvement, with a focus on subgroup identities. Interview data highlight the ways fans used linguistic, technological, and social resources to stake out certain identities and to negotiate status within the site. Although power-laden dynamics defined community participation, fans felt ownership over their literacy and identity production practices, often drawing a contrast to school practices. We then discuss the meanings youth make of their fan practices and their contrastive experiences in fan and school spaces, connecting study findings to current debates on the import of pop culture in formal schooling.
Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation.

BACKGROUND The incidence of stroke in patients with atrial fibrillation is greatly reduced by oral anticoagulation, with the full effect seen at international normalized ratio (INR) values of 2.0 or greater. The effect of the intensity of oral anticoagulation on the severity of atrial fibrillation-related stroke is not known but is central to the choice of the target INR. METHODS We studied incident ischemic strokes in a cohort of 13,559 patients with nonvalvular atrial fibrillation. Strokes were identified through hospitalization data bases and validated on the basis of medical records, which also provided information on the use of warfarin or aspirin, the INR at admission, and coexisting illnesses. The severity of stroke was graded according to a modified Rankin scale. Thirty-day mortality was ascertained from hospitalization and mortality files. RESULTS Of 596 ischemic strokes, 32 percent occurred during warfarin therapy, 27 percent during aspirin therapy, and 42 percent during neither type of therapy. Among patients who were taking warfarin, an INR of less than 2.0 at admission, as compared with an INR of 2.0 or greater, independently increased the odds of a severe stroke in a proportional-odds logistic-regression model (odds ratio, 1.9; 95 percent confidence interval, 1.1 to 3.4) across three severity categories and the risk of death within 30 days (hazard ratio, 3.4; 95 percent confidence interval, 1.1 to 10.1). An INR of 1.5 to 1.9 at admission was associated with a mortality rate similar to that for an INR of less than 1.5 (18 percent and 15 percent, respectively). The 30-day mortality rate among patients who were taking aspirin at the time of the stroke was similar to that among patients who were taking warfarin and who had an INR of less than 2.0. CONCLUSIONS Among patients with nonvalvular atrial fibrillation, anticoagulation that results in an INR of 2.0 or greater reduces not only the frequency of ischemic stroke but also its severity and the risk of death from stroke. Our findings provide further evidence against the use of lower INR target levels in patients with atrial fibrillation.
On the spatial impedance control of Gough-Stewart platforms

Looks at the control of mechanical impedance of the so-called Gough-Stewart class of parallel platforms. Two methods of compliance control are presented. One is based on global potential energy functions that have previously been applied to controlling serial manipulators and electrodynamically levitated platforms. The second uses the exponential map to associate finite displacements of the platform from equilibrium with screw displacements. Compliant wrenches are then proportional to the screw displacements. Control of spatial damping is addressed as well, justifying the classification as impedance control. Control algorithms and simulation results are given.
A Sliding Mode Control law for epipolar visual servoing of differential-drive robots

In this paper, a robust control technique (sliding mode control) is proposed to be used in order to perform visual servoing for differential-drive mobile robots using the classical teach-by-showing strategy. We propose a commuted sliding mode control law that exploits the epipolar geometry. The major contribution of the paper is the design of a control law that solves the problem of passing through a singularity induced by the epipoles maintaining bounded inputs. Moreover, the designed control is able to drive the robot to the target even when it just starts on the singularity. The proposed approach does not need a precise camera calibration due to the robustness of the control system under uncertainty in parameters. It also ensures entire correction of both orientation and lateral error even with noise in the image. The effectiveness of our approach is tested via simulations.
Changes, problems and challenges of accounting education in Libya

While accounting education has existed in Libya for over 45 years, knowledge about it is scarce among Western accounting academics. This paper reports the development of accounting education and curricula since Libya's independence in the 1950s and examines its current problems during a decade of United Nations (UN) sanctions. Following an introduction to the accounting profession in Libya, the paper provides an overview of the changes to accounting education since 1957 and analyses major issues currently faced by Libyan accounting educators, including: a shortage of qualified accounting academics; inappropriateness of imported syllabuses to the peculiarities of the economy; the unfit marriage of academic teaching and professional training in the accounting curricula; and inadequate accounting research. The paper concludes that social and economic characteristics must be fully taken into account in the case of Libya in importing accounting education systems from the West.
Toward a (Pragmatic) Science of Strategic Intervention: Design Propositions for Scenario Planning

An enduring problem confronting design science is the question of how to distil design principles and propositions in contexts where only limited evidence has accrued directly in connection with the design problem at hand. This article illustrates how researchers can address this challenge by recourse to well-established bodies of basic theory and research in the wider social and organizational sciences that suggest robust design options. Adopting this approach, we draw upon the insights of social identity theory, self/social categorization theory and the Five Factor Model of human personality from the field of personality and social psychology to distil a series of propositions to inform the design of scenario planning interventions, centred on team composition and the facilitation process. In so doing, our article exemplifies the benefits of adopting a pragmatic science approach to the design of processes that promote organizational change and development, thus adding to the growing design science movement.
Therapeutic efficacy of azaindole-1 in experimental pulmonary hypertension

An accumulating body of evidence incriminates Rho kinase (ROCK) in the pathogenesis of pulmonary hypertension (PH). The therapeutic efficacy of azaindole-1, a novel highly selective and orally active ROCK inhibitor, has not yet been investigated in PH. This study aimed to investigate the effects of azaindole-1 on 1) acute hypoxic pulmonary vasoconstriction (HPV), 2) proliferation of pulmonary arterial smooth muscle cells (PASMCs) and 3) animal models of PH. Azaindole-1 significantly inhibited HPV in isolated, ventilated and buffer-perfused murine lungs and proliferation of primary rat PASMCs in vitro. Azaindole-1 was administered orally from 21 to 35 days after monocrotaline (MCT) injection in rats and hypoxic exposure in mice. Azaindole-1 (10 and 30 mg per kg body weight per day in rats and mice, respectively) significantly improved haemodynamics and right ventricular hypertrophy. Moreover, the medial wall thickness and muscularisation of peripheral pulmonary arteries were ameliorated. Azaindole-1 treatment resulted in a decreased immunoreactivity for phospho-myosin phosphatase target subunit 1 and proliferating cell nuclear antigen in pulmonary vessels of MCT-injected rats, suggesting an impaired ROCK activity and reduced proliferating cells. Azaindole-1 provided therapeutic benefit in experimental PH, and this may be attributable to its potent vasorelaxant and antiproliferative effects. Azaindole-1 may offer a useful approach for treatment of PH.
Prevalence of obesity in Portugal

Obesity is a serious health problem in developed countries. Knowledge of reliable and nationwide representative data is a must for any public health action. The dimension of this problem in Portugal was first assessed in 1995–1998. A similar populational survey using objective anthropometric measures is now being conducted (field work started in January 2003). A total of 6411 subjects aged 18–64 years old have already been measured and their respective body mass indexes (BMIs) calculated. Results from 2003 to 2005 show 38.6% is overweight and 13.8% has obesity. The total of overweight and obesity is 52.4%. In 1995–1998 survey, overweight was 35.2% and obesity was 14.4%. The total was 49.6%. These results suggest an increase of the overweight/obesity (altogether) prevalence in the last 10 years. Actual results show that more than half of the adult sample has excessive weight and 2.4% of the sample has low BMI. Finally, 45.6% of the sample suffers increased health risks because of high waist circumference (≥80 cm for women; ≥94 cm for men). These results highlight the fact that, although obesity was identified as a public health problem one decade ago, action to reduce it does not seem to have been very effective to date.
Problem drinking: the role of readiness to change and other patient factors in the prediction of dropout from treatment

The study examines the predictive role of readiness to change, demographic, socioeconomic, personal history and drinking factors in dropout from treatment for problem drinking. For the purposes of the study, 'dropout' refers to non-completion of treatment regardless of the reasons for such termination. The study was conducted at an alcohol treatment centre in Cape Town, South Africa. The participants were 62 male ( n = 48) and female ( n = 14) patients who were admitted to the treatment centre during April to September 1997. Information was elicited from the participants by means of: 1 an interview schedule designed for the study 2 the Readiness to Change Questionnaire (Treatment Version) (RCQ-TV) developed by Heather et al . (1996). Information regarding participants' termination of treatment was also obtained. The data were analysed using discriminant function analysis to distinguish between dropout and treatment completion. The results of the discriminant function analysis suggested that six patient factors contributed significantly to the discrimination between dropouts and completers of treatment. Those patients who did not complete treatment were more likely than those who completed treatment to: 1 consume wine most frequently 2 drink daily 3 have been living alone at the time of admission to treatment 4 have been separated from a spouse at the time of admission 5 have been in the Preparation-action stage of change 6 have had previous treatment for problem drinking. These results are discussed in relation to other relevant research. Recommendations are made for the implementation of the findings in treatment, and implications for possible future research are suggested.