Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of a Limited Sampling Strategy to Estimate Area Under the Curve of Tacrolimus in Adult Renal Transplant Patients

Limited sampling strategies have been developed to predict full AUCs. The goal of this study was to develop a limited sampling strategy to estimate the AUC of tacrolimus in adult renal transplant patients and to evaluate its predictive performance in an independent patient population. A total of 27 tacrolimus pharmacokinetic profiles were studied. Blood samples were collected before the dose (0) and at 0.5, 1, 2, 4, 6, 8, and 12 hours postdose. The study was divided into 2 phases. In phase 1, the goal was to obtain a sampling strategy from 14 pharmacokinetic profiles. In phase 2, the bias and precision of the model were evaluated in another 13 pharmacokinetic profiles. The best correlation was achieved at 4 hours after dose (r2 = 0.790). Stepwise multiple regression analysis determined that the abbreviated AUC at 0, 1, and 4 hours could accurately predict total AUC (r2 = 0.965). The following formula was developed: AUC = 8.90 + 4.0C0h+ 1.77C1h + 5.47C4h. No significant differences were found between calculated and estimated AUC (165.6 ± 41.1 and 166.7 ± 43.2 ng·h/mL, respectively). The mean prediction error (MPE), the relative prediction error (PE), and the mean squared error (MSE) were 0.48 ng·h/mL, 0.16%, and 40.0 ng·h/mL, respectively. The limited sampling with use of the 3 levels at 0, 1, and 4 hours postdose provides accurate, reliable determination of tacrolimus AUC in renal transplant patients.
Head Start's Lasting Benefits

The benefits of Head Start are under increased scrutiny as Congress debates its reauthorization. How effective is Head Start, and how can it be improved? We provide a current overview and critical evaluation of Head Start research and discuss implications of this research with an eye toward informing debate. There has been a good deal of controversy over whether Head Start produces lasting benefits, dating back to its early years. Our review finds mixed, but generally positive, evidence regarding Head Start's long-term benefits. Although studies typically find that increases in IQ fade out over time, many other studies also find decreases in grade retention and special education placements. Sustained increases in school achievement are sometimes found, but in other cases flawed research methods produce results that mimic fade-out. In recent years, the federal government has funded large-scale evaluations of Head Start and Early Head Start. Results from the Early Head Start evaluation are particularly informative, as study participants were randomly assigned to either the Early Head Start group or a control group. Early Head Start demonstrated modest improvements in children's development and parent beliefs and behavior. The ongoing National Head Start Impact Study, which is also using random assignment, should yield additional insight into Head Start's effectiveness. We conclude with suggestions for future research.
Conservation physiology for applied management of marine fish: an overview with perspectives on the role and value of telemetry

Physiological studies focus on the responses of cells, tissues and individuals to stressors, usually in laboratory situations. Conservation and management, on the other hand, focus on populations. The field of conservation physiology addresses the question of how abiotic drivers of physiological responses at the level of the individual alter requirements for successful conservation and management of populations. To achieve this, impacts of physiological effects at the individual level need to be scaled to impacts on population dynamics, which requires consideration of ecology. Successfully realizing the potential of conservation physiology requires interdisciplinary studies incorporating physiology and ecology, and requires that a constructive dialogue develops between these traditionally disparate fields. To encourage this dialogue, we consider the increasingly explicit incorporation of physiology into ecological models applied to marine fish conservation and management. Conservation physiology is further challenged as the physiology of an individual revealed under laboratory conditions is unlikely to reflect realized responses to the complex variable stressors to which it is exposed in the wild. Telemetry technology offers the capability to record an animal's behaviour while simultaneously recording environmental variables to which it is exposed. We consider how the emerging insights from telemetry can strengthen the incorporation of physiology into ecology.
A Model of Representational Spaces in Human Cortex

Current models of the functional architecture of human cortex emphasize areas that capture coarse-scale features of cortical topography but provide no account for population responses that encode information in fine-scale patterns of activity. Here, we present a linear model of shared representational spaces in human cortex that captures fine-scale distinctions among population responses with response-tuning basis functions that are common across brains and models cortical patterns of neural responses with individual-specific topographic basis functions. We derive a common model space for the whole cortex using a new algorithm, searchlight hyperalignment, and complex, dynamic stimuli that provide a broad sampling of visual, auditory, and social percepts. The model aligns representations across brains in occipital, temporal, parietal, and prefrontal cortices, as shown by between-subject multivariate pattern classification and intersubject correlation of representational geometry, indicating that structural principles for shared neural representations apply across widely divergent domains of information. The model provides a rigorous account for individual variability of well-known coarse-scale topographies, such as retinotopy and category selectivity, and goes further to account for fine-scale patterns that are multiplexed with coarse-scale topographies and carry finer distinctions.
Latency Optimization for Resource Allocation in Mobile-Edge Computation Offloading

By offloading intensive computation tasks to the edge cloud located at the cellular base stations, mobile-edge computation offloading (MECO) has been regarded as a promising means to accomplish the ambitious millisecond-scale end-to-end latency requirement of fifth-generation networks. In this paper, we investigate the latency-minimization problem in a multi-user time-division multiple access MECO system with joint communication and computation resource allocation. Three different computation models are studied, i.e., local compression, edge cloud compression, and partial compression offloading. First, closed-form expressions of optimal resource allocation and minimum system delay for both local and edge cloud compression models are derived. Then, for the partial compression offloading model, we formulate a piecewise optimization problem and prove that the optimal data segmentation strategy has a piecewise structure. Based on this result, an optimal joint communication and computation resource allocation algorithm is developed. To gain more insights, we also analyze a specific scenario where communication resource is adequate while computation resource is limited. In this special case, the closed-form solution of the piecewise optimization problem can be derived. Our proposed algorithms are finally verified by numerical results, which show that the novel partial compression offloading model can significantly reduce the end-to-end latency.
A Data-Driven Integrative Model of Sepal Primordium Polarity in Arabidopsis[C][W]

This study presents a new modeling approach allowing diverse types of data to be integrated in a coherent molecular regulatory network model. This was used to analyze sepal primordium development and revealed three previously unreported pathways potentially involved in polarity. Flower patterning is determined by a complex molecular network but how this network functions remains to be elucidated. Here, we develop an integrative modeling approach that assembles heterogeneous data into a biologically coherent model to allow predictions to be made and inconsistencies among the data to be found. We use this approach to study the network underlying sepal development in the young flower of Arabidopsis thaliana. We constructed a digital atlas of gene expression and used it to build a dynamical molecular regulatory network model of sepal primordium development. This led to the construction of a coherent molecular network model for lateral organ polarity that fully recapitulates expression and interaction data. Our model predicts the existence of three novel pathways involving the HD-ZIP III genes and both cytokinin and ARGONAUTE family members. In addition, our model provides predictions on molecular interactions. In a broader context, this approach allows the extraction of biological knowledge from diverse types of data and can be used to study developmental processes in any multicellular organism.
An Inflammatory Nucleus Pulposus Tissue Culture Model to Test Molecular Regenerative Therapies: Validation with Epigallocatechin 3-Gallate

Organ cultures are practical tools to investigate regenerative strategies for the intervertebral disc. However, most existing organ culture systems induce severe tissue degradation with only limited representation of the in vivo processes. The objective of this study was to develop a space- and cost-efficient tissue culture model, which represents degenerative processes of the nucleus pulposus (NP). Intact bovine NPs were cultured in a previously developed system using Dyneema jackets. Degenerative changes in the NP tissue were induced either by the direct injection of chondroitinase ABC (1–20 U/mL) or by the diffusion of interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) (both 100 ng/mL) from the culture media. Extracellular matrix composition (collagens, proteoglycans, water, and DNA) and the expression of inflammatory and catabolic genes were analyzed. The anti-inflammatory and anti-catabolic compound epigallocatechin 3-gallate (EGCG, 10 µM) was employed to assess the relevance of the degenerative NP model. Although a single injection of chondroitinase ABC reduced the proteoglycan content in the NPs, it did not activate cellular responses. On the other hand, IL-1β and TNF-α significantly increased the mRNA expression of inflammatory mediators IL-6, IL-8, inducible nitric oxide synthase (iNOS), prostaglandin-endoperoxide synthase 2 (PTGS2) and matrix metalloproteinases (MMP1, MMP3, and MMP13). The cytokine-induced gene expression in the NPs was ameliorated with EGCG. This study provides a proof of concept that inflammatory NP cultures, with appropriate containment, can be useful for the discovery and evaluation of molecular therapeutic strategies against early degenerative disc disease.
Combined panel of serum human tissue kallikreins and CA-125 for the detection of epithelial ovarian cancer

Objective To determine the predictive accuracy of the combined panels of serum human tissue kallikreins (hKs) and CA-125 for the detection of epithelial ovarian cancer. Methods Serum specimens collected from 5 Indonesian centers and 1 Vietnamese center were analyzed for CA-125, hK6, and hK10 levels. A total of 375 specimens from patients presenting with ovarian tumors, which include 156 benign cysts, 172 epithelial ovarian cancers (stage I/II, n=72; stage III/IV, n=100), 36 germ cell tumors and 11 borderline tumors, were included in the study analysis. Receiver operating characteristic analysis were performed to determine the cutoffs for age, CA-125, hK6, and hK10. Sensitivity, specificity, negative, and positive predictive values were determined for various combinations of the biomarkers. Results The levels of hK6 and hK10 were significantly elevated in ovarian cancer cases compared to benign cysts. Combination of 3 markers, age/CA-125/hk6 or CA-125/hk6/hk10, showed improved specificity (100%) and positive predictive value (100%) for prediction of ovarian cancer, when compared to the performance of single markers having 80-92% specificity and 74-87% positive predictive value. Four-marker combination, age/CA-125/hK6/hK10 also showed 100% specificity and 100% positive predictive value, although it demonstrated low sensitivity (11.9%) and negative predictive value (52.8%). Conclusion The combination of human tissue kallikreins and CA-125 showed potential for improving prediction of epithelial ovarian cancer in patients presenting with ovarian tumors.
(+)-SJ733, a clinical candidate for malaria that acts through ATP4 to induce rapid host-mediated clearance of Plasmodium

Significance Useful antimalarial drugs must be rapidly acting, highly efficacious, and have low potential for developing resistance. (+)-SJ733 targets a Plasmodium cation-transporting ATPase, ATP4. (+)-SJ733 cleared parasites in vivo as quickly as artesunate by specifically inducing eryptosis/senescence in infected, treated erythrocytes. Although in vitro selection of pfatp4 mutants with (+)-SJ733 proceeded with moderate frequency, during in vivo selection of pbatp4 mutants, resistance emerged slowly and produced marginally resistant mutants with poor fitness. In addition, (+)-SJ733 met all other criteria for a clinical candidate, including high oral bioavailability, a high safety margin, and transmission blocking activity. These results demonstrate that targeting ATP4 has great potential to deliver useful drugs for malaria eradication. Drug discovery for malaria has been transformed in the last 5 years by the discovery of many new lead compounds identified by phenotypic screening. The process of developing these compounds as drug leads and studying the cellular responses they induce is revealing new targets that regulate key processes in the Plasmodium parasites that cause malaria. We disclose herein that the clinical candidate (+)-SJ733 acts upon one of these targets, ATP4. ATP4 is thought to be a cation-transporting ATPase responsible for maintaining low intracellular Na+ levels in the parasite. Treatment of parasitized erythrocytes with (+)-SJ733 in vitro caused a rapid perturbation of Na+ homeostasis in the parasite. This perturbation was followed by profound physical changes in the infected cells, including increased membrane rigidity and externalization of phosphatidylserine, consistent with eryptosis (erythrocyte suicide) or senescence. These changes are proposed to underpin the rapid (+)-SJ733-induced clearance of parasites seen in vivo. Plasmodium falciparum ATPase 4 (pfatp4) mutations that confer resistance to (+)-SJ733 carry a high fitness cost. The speed with which (+)-SJ733 kills parasites and the high fitness cost associated with resistance-conferring mutations appear to slow and suppress the selection of highly drug-resistant mutants in vivo. Together, our data suggest that inhibitors of PfATP4 have highly attractive features for fast-acting antimalarials to be used in the global eradication campaign.
Functional Diversity of Fibroblast Growth Factors in Bone Formation

The functional significance of fibroblast growth factor (FGF) signaling in bone formation has been demonstrated through genetic loss-of-function and gain-of-function approaches. FGFs, comprising 22 family members, are classified into three subfamilies: canonical, hormone-like, and intracellular. The former two subfamilies activate their signaling pathways through FGF receptors (FGFRs). Currently, intracellular FGFs appear to be primarily involved in the nervous system. Canonical FGFs such as FGF2 play significant roles in bone formation, and precise spatiotemporal control of FGFs and FGFRs at the transcriptional and posttranscriptional levels may allow for the functional diversity of FGFs during bone formation. Recently, several research groups, including ours, have shown that FGF23, a member of the hormone-like FGF subfamily, is primarily expressed in osteocytes/osteoblasts. This polypeptide decreases serum phosphate levels by inhibiting renal phosphate reabsorption and vitamin D3 activation, resulting in mineralization defects in the bone. Thus, FGFs are involved in the positive and negative regulation of bone formation. In this review, we focus on the reciprocal roles of FGFs in bone formation in relation to their local versus systemic effects.
Deep-submicrometer channel design in silicon-on-insulator (SOI) MOSFET's

Short-channel effects in deep-submicrometer SOI MOSFET's are explored over a wide range of device parameters using two-dimensional numerical simulations. To obtain reduced short-channel effects in SOI over bulk technologies, the silicon film thickness must be considerably smaller than the bulk junction depth because of an additional charge-sharing phenomenon through the SOI buried oxide. The optimal design space, considering nominal and short-channel threshold voltage, shows ample design options for both fully and partially depleted devices, however, manufacturing considerations in the 0.1 /spl mu/m regime may favor partially depleted devices. <<ETX>>
The Expectancy-Value Theory of Achievement Motivation and the Enumeration of Possible Selves: Evidence for Outcomes During Emerging Adulthood

The expectancy-value theory of achievement motivation (Eccles, Adler, Futterman, Goff, Kaczala, et al., 1983; Wigfield & Eccles, 2000) posits that an “individual’s choice, persistence, and performance can be explained by their beliefs about how well they will do on the activity and the extent to which they value the activity” (Wigfield & Eccles, 2000, p. 68). Related research has focused on the enumeration of possible selves and how one’s hoped-for and feared possible selves (Markus & Nurius, 1986) influence motivation and engagement in activities related to goal choices. Most studies of motivation and achievement have focused on children and adolescents with respect to academic achievement and risk behaviors. Little work has been done to examine how these theoretical concepts apply to emerging adults and more distal life goals. This study examines how one’s hoped-for and feared possible selves are related to values and expectations, and how these constructs influence the achievement of distal life goals. It is hypothesized that one’s hoped-for and feared possible selves at age 18 years are related to expectancies and values 2 years later. It is also hypothesized that expectancies and values are related to goal achievement 10 years post-high school. Finally, it is hypothesized that expectancies and values mediate the relations between one’s ideas about possible selves and their achievement. Data for this study (n=1,240) are drawn from a 17-year longitudinal project, Michigan Study of Adolescent and Adult Life Transitions (MSALT), University of Michigan. (The MSALT research was supported by grants from the National Science Foundation [DBS9215008] to Bonnie L. Barber and Jacqueline S. Eccles, [92-1459-92] from the William T. Grant Foundation to Eccles and Barber, and by a Spencer Foundation grant to Eccles and Barber).
The Sage encyclopedia of intercultural competence

In 1980, SAGE published Geert Hofstede's Culture's Consequences. It opens with a quote from Blaise Pascal: "There are truths on this side of the Pyrenees that are falsehoods on the other. " The book became a classic-one of the most cited sources in the Social Science Citation Index-and subsequently appeared in a second edition in 2001. This new SAGE Encyclopedia of Intercultural Competence picks up on themes explored in that book. Cultural competence refers to the set of attitudes, practices, and policies that enables a person or agency to work well with people from differing cultural groups. Other related terms include cultural sensitivity, transcultural skills, diversity competence, and multicultural expertise. What defines a culture? What barriers might block successful communication between individuals or agencies of differing cultures? How can those barriers be understood and navigated to enhance intercultural communication and understanding? These questions and more are explained within the pages of this new reference work. Key Features: *300 to 350 entries organized in A-to-Z fashion in two volumes *Signed entries that conclude with Cross-References and Suggestions for Further Readings *Thematic "Reader's Guide" in the front matter grouping related entries by broad topic areas *Chronology that provides a historical perspective of the development of cultural competence as a discrete field of study *Resources appendix and a comprehensive Index The SAGE Encyclopedia of Intercultural Competence is an authoritative and rigorous source on intercultural competence and related issues, making it a must-have reference for all academic libraries.
The Nature of Morality

In this book, Arnold Green discusses the standards that define moral appraisal. Standards assume roles of conduct (however contradictory the rules may be) which can be imposed during socialization only within the traditional family. Otherwise, the basis of order, which is not collective but individual, is undermined by the extreme degree of disaffection we now face. All the panaceas offered, and in some cases enforced, by one intellectual minority or another, will inevitably have a destructive impact upon our communication with one another. Contents: Perception and Ideology; Self and Family; Relativism and the Family Institution; Religion as Vital Force; Social Class and Prejudice.
Compliance therapy: a randomised controlled trial in schizophrenia

Abstract >Objective To evaluate the efficacy of “compliance therapy” for improving adherence to prescribed drug treatment among patients with schizophrenia. Design Randomised controlled trial. Setting Urban catchment area psychiatric service. Participants 94 consecutive admissions of patients with schizophrenia, 56 agreed to participate. Intervention Compliance therapy and non-specific counselling, each consisting of 5 sessions lasting 30-60 minutes. Main outcome measures Compliance with drug treatment at one year; attitudes to treatment, symptomatology, insight, and quality of life at one year; length of “survival” in the community, bed days, and rehospitalisation rates at two years. Results Compliance therapy did not confer a major advantage over non-specific therapy in improving compliance at one year (43% (12/28) v 54% (15/28), difference −11% (95% confidence interval −37% to 15%) or in any of the secondary outcome measures—symptomatology, attitudes to treatment, insight, global assessment of functioning, and quality of life. Conclusion Compliance therapy may not be of benefit to patients with schizophrenia. Attitudes to treatment at baseline predicted adherence one year later and may be a clinically useful tool.
Radial-Basis-Function-Based Neural Network for Harmonic Detection

The widespread application of power-electronic loads has led to increasing harmonic pollution in the supply system. In order to prevent harmonics from deteriorating the power quality, detecting harmonic components for harmonic mitigations becomes a critical issue. In this paper, an effective procedure based on the radial-basis-function neural network is proposed to detect the harmonic amplitudes of the measured signal. By comparing with several commonly used methods, it is shown that the proposed solution procedure yields more accurate results and requires less sampled data for harmonic assessment.