Miracle-dz/UniFAR-FTUs huggingface dataset:
Use of Mechanistic Modeling to Assess Interindividual Variability and Interspecies Differences in Active Uptake in Human and Rat Hepatocytes

Interindividual variability in activity of uptake transporters is evident in vivo, yet limited data exist in vitro, confounding in vitro-in vivo extrapolation. The uptake kinetics of seven organic anion-transporting polypeptide substrates was investigated over a concentration range in plated cryopreserved human hepatocytes. Active uptake clearance (CLactive, u), bidirectional passive diffusion (Pdiff), intracellular binding, and metabolism were estimated for bosentan, pitavastatin, pravastatin, repaglinide, rosuvastatin, telmisartan, and valsartan in HU4122 donor using a mechanistic two-compartment model in Matlab. Full uptake kinetics of rosuvastatin and repaglinide were also characterized in two additional donors, whereas for the remaining drugs CLactive, u was estimated at a single concentration. The unbound affinity constant (Km, u) and Pdiff values were consistent across donors, whereas Vmax was on average up to 2.8-fold greater in donor HU4122. Consistency in Km, u values allowed extrapolation of single concentration uptake activity data and assessment of interindividual variability in CLactive across donors. The maximal contribution of active transport to total uptake differed among donors, for example, 85 to 96% and 68 to 87% for rosuvastatin and repaglinide, respectively; however, in all cases the active process was the major contributor. In vitro-in vivo extrapolation indicated a general underprediction of hepatic intrinsic clearance, an average empirical scaling factor of 17.1 was estimated on the basis of seven drugs investigated in three hepatocyte donors, and donor-specific differences in empirical factors are discussed. Uptake Km, u and CLactive, u were on average 4.3- and 7.1-fold lower in human hepatocytes compared with our previously published rat data. A strategy for the use of rat uptake data to facilitate the experimental design in human hepatocytes is discussed.
Using Cartoons to Teach Internet Security

Abstract While good user education can hardly secure a system, we believe that poor user education can put it at serious risk. The current problem of online fraud is exasperated by the fact that most users make security decisions, such as whether to install a given piece of software or not, based on a very rudimentary understanding of risk. We describe the design principles behind SecurityCartoon.com, the first cartoon-based approach aimed at improving the understanding of risk among typical Internet users. We argue why an approach like ours is likely to produce better long-term effects than currently practiced educational efforts with the same general goals. This belief is based on the apparent difference between our approach and currently used alternatives. At the heart of these differences are the four guiding principles of our approach: (1) A research driven content selection, according to which we select educational messages based on user studies; (2) accessibility of the material, to reach and maintain a large readership; (3) user immersion in the material, based on repetitions on a theme; and (4) adaptability to a changing threat.
Implementation of a Classroom Management Program with Urban Elementary Schools in Low-Income Neighborhoods: Does Program Fidelity Affect Student Behavior and Academic Outcomes?

Students with persistent disruptive behavior problems lose valuable time in academic lessons, are a distraction for classmates, and cause stress for teachers. Recent meta-analyses indicate that 87% to 92% of published studies on school-based interventions targeting student problem behaviors report results from demonstration projects (involving highly trained staff under ideal circumstances) rather than routine practice programs. This study investigates the routine use of a schoolwide classroom management program and its relationship to elementary students’ social and academic outcomes. Three years after training in the classroom management program, 56 second-, third-, and fourth-grade teachers in an urban school district were assessed for fidelity to the program. Program fidelity was determined via direct observation in the classroom and validated by teacher self-ratings of fidelity and administrator ratings of teacher fidelity. Dependent variables included student engagement during academic lessons, out-of-school suspension rates, and report card grades. Results indicated that high program fidelity was significantly related to greater academic engagement and fewer suspensions, but not higher report card grades. This study adds to the scant literature on implementation fidelity of routine programs with high-risk populations.
Angiopoietin-1 promotes atherosclerosis by increasing the proportion of circulating Gr1+ monocytes

Aims Atherosclerosis is a chronic inflammatory disease occurring within the artery wall. A crucial step in atherogenesis is the infiltration and retention of monocytes into the subendothelial space of large arteries induced by chemokines and growth factors. Angiopoietin-1 (Ang-1) regulates angiogenesis and reduces vascular permeability and has also been reported to promote monocyte migration in vitro. We investigated the role of Ang-1 in atherosclerosis-prone apolipoprotein-E (Apo-E) knockout mouse. Methods and results Apo-E knockout (Apo-E-/-) mice fed a western or normal chow diet received a single iv injection of adenovirus encoding Ang-1 or control vector. Adenovirus-mediated systemic expression of Ang-1 induced a significant increase in early atherosclerotic lesion size and monocyte/macrophage accumulation compared with control animals receiving empty vector. Ang-1 significantly increased plasma MCP-1 and VEGF levels as measured by ELISA. FACS analysis showed that Ang-1 selectively increased inflammatory Gr1+ monocytes in the circulation, while the cell-surface expression of CD11b, which mediates monocyte emigration, was significantly reduced. Conclusions Ang-1 specifically increases circulating Gr1+ inflammatory monocytes and increases monocyte/macrophage retention in atherosclerotic plaques, thereby contributing to development of atherosclerosis.
A Natural-Scene Gradient Distribution Prior and its Application in Light-Microscopy Image Processing

Signal processing in light-microscopy and cell imaging is concerned with reconstructing latent ground truth from imperfect images. This typically requires assuming prior knowledge about the latent ground truth. While this assumption regularizes the problem to an extent where it can be solved, it also biases the result toward the expected. It thus often remains unclear what prior to use for a given practical problem. We argue here that the gradient distribution of natural-scene images may provide a versatile and well-founded prior for light-microscopy images that does not impose assumptions about the geometry of the ground-truth signal, but only about its gradient spectrum. We provide motivation for this choice from different points of view, and we illustrate the resulting regularizer for use on light-microscopy images. We provide a simple parametric model for the resulting prior, leading to efficiently solvable variational problems. We demonstrate the use of these models and solvers in a variety of common image-processing tasks, including contrast enhancement, noise-level estimation, denoising, blind deconvolution, and dehazing. We conclude by discussing the limitations and possible interpretations of the prior.
Harbingers of new politics? The characteristics and attitudes of candidates in the Scottish parliament elections, 1999

'New politics' is a promiscuous term that is used by political commentators and analysts in their accounts of contemporary politics (Fielding, 2000). Devolution has been associated with 'new politics' as much as any of the other changes initiated since the 1997 general election. In this article we explore some of the meanings of new politics and the associations the term has with Scottish devolution, and we consider the extent to which 'new' can be used to describe the politics of contemporary Scotland. To do so, we present the results of a survey of candidates in the Scottish Parliament elections in 1999 and also, for comparison, the results of a survey of candidates in the Scottish local government elections (which took place on the same day), and a CREST survey of the Scottish electorate undertaken at the time of the elections. We present data on the socio-economic background and political experience of candidates and examine their identities, attitudes and political opinions in order to assess the impact of ideas connected with 'new polities'.
The Construction of Professional Knowledge: A Comparative Study of Social Assistants and Mediators

This work is centred on the dynamics of identity and professional development of two socio-professional groups; namely, Social Assistants and Mediators. It takes as its point of departure the characterisation of these socio-professional groups and their professionalization. The professionalization of the social groups matches the dynamics of identity development and presupposes social recognition of their professional knowledge and competences that are built in situations of real work and professional socialization (Dubar, 1997; Wittorski, 2008). Schon's (1996) "epistemology of professional practice" is paramount in this context, as theoretical knowledge and learning developed in formal training settings are insufficient for their professional daily work. The study of a qualitative nature was carried out using case studies in four countries - two in Europe and two in Latin America – Portugal, France, Brazil and Argentina. It had as its principal objectives the identification and analysis of the dynamics of identity and their articulation with the construction of professional knowledge in two socio-professional groups, which have been the subject of an increasing social visibility. The research strategies that we favoured were phenomenological and ethno-methodological, which turned out to be the two fundamental techniques for collecting information; namely, documentary research and biographical interviews. This methodology allowed us access to the socio-historical processes and subjective experiences of the participants with respect to their dynamics of professionalisation and in this way we could understand better the continuities and/or gaps in the processes in relation to their construction of identity. In order to analyse the data collected we turned to the emerging characterisations, a structural analysis of discourses and continuous comparison, when searching for evidence in the construction of the interpretative text. As the principal results of the study, we would stress the singularity of each one of these socio-professional groups taking into account their origins, their socio-historical processes and the theoretical and ethical assumptions that have structured their identities. Taking, as a reference, the geographical and cultural variable, it was not possible to find any significant differences in or between any of the groups, which indicates a consistent specific and cross-disciplinary professional ethos. Also evident was the particularity and relevance of professional knowledge in the assertion and professional development of both the Social Assistants and the Mediators. DOI: 10.5901/jesr.2014. v4n2p191
Older people's perceptions of personal safety in deprived communities: understanding the social causes of fear of crime

This study explored the neighbourhood‐level personal safety concerns experienced by older people living in socioeconomically deprived communities in South Wales. While there is a wealth of criminological literature focusing on whether older people experience high levels of fear of crime, much of it conflicting in its conclusions, such studies tell us little about the social and physical cues for feelings of fear that are evoked in older people on a community level. To provide a richer understanding of these issues the study adopted a predominantly qualitative approach to identify community characteristics that shaped older people's views of personal safety. This was supplemented by quantitative data regarding their actual experiences of crime. The main finding was that personal safety concerns were overwhelmingly related to the social connotations of specific community locations, such as those associated with the presence and behaviour of perceived 'undesirable others', rather than specific locations themselves or their physical characteristics. This raises questions and challenges about the development of appropriate and effective crime and fear reduction strategies that enable older people to feel safer in their communities, and so facilitate their community engagement and social inclusion.
Altered signal transduction in vascular smooth muscle cells of spontaneously hypertensive rats.

The hypothesis that signal transduction mediated by platelet-derived growth factor (PDGF) and angiotensin II (Ang II) is altered in vascular smooth muscle (VSM) cells from the spontaneously hypertensive rat (SHR) was tested by measuring changes in the cytosolic free calcium concentration ([Ca2+]i). [Ca2+]i was measured in cultured aortic smooth muscle cells from SHRs and Wistar-Kyoto (WKY) normotensive rats using fura-2 as a calcium indicator and a microscopic digital image analysis system. Activation of cells with Ang II resulted in a prompt though transient rise in [Ca2+]i; the maximum increase was observed after 10-30-second intervals. On the other hand, activation of cells with PDGF BB produced an increase in [Ca2+]i with a 40-60-second lag period; the maximum increase was observed 2-4 minutes after the addition of PDGF. PDGF-stimulated increases in [Ca2+]i were markedly inhibited by the addition of the calcium channel antagonist verapamil (100 microM) as well as by removal of calcium from the extracellular bathing medium. However, Ang II-stimulated [Ca2+]i was not significantly affected by the addition of verapamil or by removal of extracellular calcium. These results would indicate that PDGF-mediated increases in [Ca2+]i in VSM cells are predominantly via Ca2+ influx, whereas Ang II-mediated increases are due to calcium release from intracellular pools. Basal and PDGF- and Ang II-stimulated increases in [Ca2+]i were significantly greater (p less than 0.05) in SHR VSM cells compared with WKY cells. (ABSTRACT TRUNCATED AT 250 WORDS)
Prevalence of Theileria and Babesia species in Tunisian sheep

In this study, the prevalence of Theileria and Babesia species in sheep was assessed with Giemsa-stained blood smear examination and polymerase chain reaction to identify the different piroplasms in 270 sheep from three Tunisian bioclimatic zones (north, centre, and south). The overall infection prevalence by Babesia spp. and Theileria spp. in Giemsa-stained blood smears was 2.9% (8/270) and 4.8% (13/270) respectively. The molecular results showed that sheep were more often infected by Theileria ovis than Babesia ovis with an overall prevalence of 16.3% (44/270) and 7.8% (21/270) respectively (p = 0.01). The molecular prevalence by Babesia ovis was significantly higher in females than in males (p < 0.05). According to localities B. ovis was found exclusively in sheep from the centre of Tunisia (Kairouan) whereas Theileria ovis was found in all regions. Infections with T. ovis and B. ovis were confirmed by sequencing. The sequence of T. ovis in this study (accession numbers KM924442) falls into the same clade as T. ovis deposited in GenBank. The T. ovis amplicons (KM924442) showed 99%–100% identities with GenBank sequences. Moreover, comparison of the partial sequences of 18S rRNA gene of B. ovis described in this study (KP670199) revealed 99.4% similarity with B. ovis recently reported in northern Tunisia from sheep and goats. Three nucleotides were different at positions 73 (A/T), 417 (A/T), and 420 (G/T). It also had 99% identity with B. ovis from Spain, Turkey and Iraq. The results suggest a high T. ovis prevalence in Tunisia with a decreasing north-south gradient. This could be correlated to the vector tick distribution.
Design and the radiation patterns of rectangular symmetric bimorph piezoelectric transducers in cosinusoidal flexural vibration

In this article, the design of rectangular symmetric bimorph piezoelectric ceramic transducers with loose and fixed edges and with parallel electric excitation is studied. Rectangular piezoelectric ceramic transducers in cosinusoidal flexural vibration with straight and parallel nodal lines of vibration are studied. The radiation of the transducer in a plane perpendicular to the surface of the transducer and parallel to the nodal lines of vibrations is examined. The radiation patterns of such transducers are evaluated using the classic theory. The radiation pattern of the transducer is evaluated in a plane, perpendicular to the direction of flexural vibration of the nodal lines. In another perpendicular plane, the radiation pattern of the transducer is calculated the same as for an oscillating piston. Diagrams to calculate these radiation patterns are supplied. For effective operation of such transducers, vibrations of the piezoelectric ceramic plate arrays with the vibrations of elastic plates, on which the arrays are mounted, must be matched. When calculating the radiation patterns of simple bimorph rectangular transducers, the expressions of the transducer’s flexural vibration mode must be evaluated. In case of multi-component rectangular transducers, the distribution of vibrations on the transducer’s surface can be evaluated as harmonic. To aid the design of a transducer with one piezoelectric ceramic plate, a diagram for calculating the width of the ceramic plate and the width of the elastic metal plate is presented.
Visual motion observer-based pose control with panoramic camera via passivity approach

This paper considers the vision-based estimation and control with a panoramic camera via passivity approach. First, a hyperbolic projection of a panoramic camera is presented. Next, using standard body-attached coordinate frames (the world frame, mirror frame, camera frame and object frame), we represent the body velocity of the relative rigid body motion (position and orientation). After that, we propose a visual motion observer to estimate the relative rigid body motion from the measured camera data. We show that the estimation error system with a panoramic camera has the passivity which allows us to prove stability in the sense of Lyapunov. After that, stability and L2-gain performance analysis for the closed-loop system are discussed. Finally, simulation and experimental results are shown in order to confirm the proposed method.
FINANCING OF TERRORISM: SOURCES, METHODS, AND CHANNELS

Terrorism has global reach in its activities and in its sources of funding. There are manifold sources operating through methods that may be legal or illegal and sometimes even nefarious, and through routes that are often circuitous. Indeed, so-called charitable organizations are often used as a front to mobilize funds or serve as a conduit for the money. It is clear that if acts of terrorism are to be eliminated, the flow of money on which they ride must be stemmed at the source. This is one area in which stringent financial procedures and controls could be helpful. Equally important is the control that central banks must exercise in the financial sector, and the banking system in particular, to ensure greater accountability and better record keeping. Realistically, however, as long there is someone who operates a hawala system from a back of a store, money will keep flowing. No less important is the cooperation between countries and the enforcement of international conventions. A recent article on the transfer of money in Dubai notes that the authorities counted 429 suspicious money transfer operations between August 2001 and May 2003. Of these, only 46 cases were thoroughly investigated because there was little support from other countries involved, including Britain, Switzerland and the United States. Finally, education systems that teach jihad (holy war) as the highest calling for the individual and breeds religious intolerance must be reformed.
What do Support Analysts Know About Their Customers? On the Study and Prediction of Support Ticket Escalations in Large Software Organizations

Understanding and keeping the customer happy is a central tenet of requirements engineering. Strategies to gather, analyze, and negotiate requirements are complemented by efforts to manage customer input after products have been deployed. For the latter, support tickets are key in allowing customers to submit their issues, bug reports, and feature requests. Whenever insufficient attention is given to support issues, however, their escalation to management is time-consuming and expensive, especially for large organizations managing hundreds of customers and thousands of support tickets. Our work provides a step towards simplifying the job of support analysts and managers, particularly in predicting the risk of escalating support tickets. In a field study at our large industrial partner, IBM, we used a design science methodology to characterize the support process and data available to IBM analysts in managing escalations. Through iterative cycles of design and evaluation, we translated our understanding of support analysts' expert knowledge of their customers into features of a support ticket model to be implemented into a Machine Learning model to predict support ticket escalations. We trained and evaluated our Machine Learning model on over 2.5 million support tickets and 10,000 escalations, obtaining a recall of 79.9% and an 80.8% reduction in the workload for support analysts looking to identify support tickets at risk of escalation. Further on-site evaluations, through a prototype tool we developed to implement our Machine Learning techniques in practice, showed more efficient weekly support-ticket-management meetings. The features we developed in the Support Ticket Model are designed to serve as a starting place for organizations interested in implementing our model to predict support ticket escalations, and for future researchers to build on to advance research in escalation prediction.
Application of prewhitening to AR spectral estimation of EEG

Conventional fast Fourier transform (FFT) and autoregressive (AR) spectral estimation techniques do not always perform well when applied to short segments of single trial EEG. On this class of EEG signal, the conventional FFT-based methods can suffer from significant leakage problems while conventional AR methods can suffer from problems related to model order selection and retention of spectral information in the residuals. An established alternative to the conventional AR estimation scheme called prewhitened AR spectral estimation, which theoretically addresses these drawbacks, was applied to EEG signals. Relative comparisons of the performance of a conventional FFT-based estimate, the conventional AR estimate, and the prewhitened AR estimate on three different examples of real, short-segment, single-trial EEGs are presented. These comparisons demonstrate that the prewhitened AR method overcomes the inherent drawbacks of the conventional methods. <<ETX>>