Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulators of Calcium Homeostasis Identified by Inference of Kinetic Model Parameters from Live Single Cells Perturbed by siRNA

Estimation of parameters in a calcium regulatory network from single-cell data illustrates how this approach can reveal protein function. Computing Regulatory Functions Complex regulatory networks can be constructed without a complete understanding of the functions of each of the components. Bandara et al. illustrate how differential equations modeling and parameter estimation from experiments with live single cells can reveal protein function. They applied their computational approach to the analysis of the effects of small interfering RNAs targeting components of the calcium homeostasis network, which involves various channels, calcium sensors, and transporters in the endoplasmic reticulum and plasma membrane. This approach properly identified known functions of network components and revealed previously unknown mechanisms involved in regulating calcium homeostasis. In addition, both presenilin-2, a protein associated with Alzheimer’s disease, and ORAI2, a channel previously only implicated in store-operated calcium entry, were implicated in mediating calcium leak from the endoplasmic reticulum. Assigning molecular functions and revealing dynamic connections between large numbers of partially characterized proteins in regulatory networks are challenges in systems biology. We showed that functions of signaling proteins can be discovered with a differential equations model of the underlying signaling process to extract specific molecular parameter values from single-cell, time-course measurements. By analyzing the effects of 250 small interfering RNAs on Ca2+ signals in single cells over time, we identified parameters that were specifically altered in the Ca2+ regulatory system. Analysis of the screen confirmed known functions of the Ca2+ sensors STIM1 (stromal interaction molecule 1) and calmodulin and of Ca2+ channels and pumps localized in the endoplasmic reticulum (ER) or plasma membrane. Furthermore, we showed that the Alzheimer’s disease–linked protein presenilin-2 and the channel protein ORAI2 prevented overload of ER Ca2+ and that feedback from Ca2+ to phosphatidylinositol 4-kinase and PLCδ (phospholipase Cδ) may regulate the abundance of the plasma membrane lipid PI(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to control Ca2+ extrusion. Thus, functions of signaling proteins and dynamic regulatory connections can be identified by extracting molecular parameter values from single-cell, time-course data.
Enteral potassium supplementation in a pediatric cardiac intensive care unit: Evaluation of a practice change

Background: Potassium supplementation is a common practice in critically ill children, especially those with heart disease. Intravenous potassium supplementation is the standard route of administration in most intensive care units. Although the enteral route is safer and thus may be a reasonable alternative, data on the efficacy of enteral potassium administration are lacking. Methods: A change of practice to encourage use of enteral potassium was instituted in the cardiac intensive care unit at Texas Children's Hospital, and a review of this practice change was undertaken. The primary outcome of interest was the comparable efficacy of enteral and intravenous potassium administration. Patient demographic data, including urine output, diuretic use, route of potassium administration, and adverse events were documented and analyzed. Results: Seventy-six patients met inclusion criteria and received 399 bolus doses of potassium (166 intravenous and 233 enteral). No patients became hyperkalemic after either route of administration. The increase in serum potassium was similar in both groups of patients. Side effects of the two routes of administration were not different. Conclusions: The efficacy of enteral potassium is comparable to intravenous potassium for potassium replacement in pediatric patients after congenital heart surgery.
Acute kidney injury—an overview of diagnostic methods and clinical management

Abstract Acute kidney injury (AKI) is a common condition in multiple clinical settings. Patients with AKI are at an increased risk of death, over both the short and long term, and of accelerated renal impairment. As the condition has become more recognized and definitions more unified, there has been a rapid increase in studies examining AKI across many different clinical settings. This review focuses on the classification, diagnostic methods and clinical management that are available, or promising, for patients with AKI. Furthermore, preventive measures with fluids, acetylcysteine, statins and remote ischemic preconditioning, as well as when dialysis should be initiated in AKI patients are discussed. The classification of AKI includes both changes in serum creatinine concentrations and urine output. Currently, no kidney injury biomarkers are included in the classification of AKI, but proposals have been made to include them as independent diagnostic markers. Treatment of AKI is aimed at addressing the underlying causes of AKI, and at limiting damage and preventing progression. The key principles are: to treat the underlying disease, to optimize fluid balance and optimize hemodynamics, to treat electrolyte disturbances, to discontinue or dose-adjust nephrotoxic drugs and to dose-adjust drugs with renal elimination.
Confronting complexity in late‐onset Alzheimer disease: application of two‐stage analysis approach addressing heterogeneity and epistasis

Common diseases with a genetic basis are likely to have a very complex etiology, in which the mapping between genotype and phenotype is far from straightforward. A new comprehensive statistical and computational strategy for identifying the missing link between genotype and phenotype has been proposed, which emphasizes the need to address heterogeneity in the first stage of any analysis and gene‐gene interactions in the second stage. We applied this two‐stage analysis strategy to late‐onset Alzheimer disease (LOAD) data, which included functional and positional candidate genes and markers in a region of interest on chromosome 10. Bayesian classification found statistically significant clusterings for independent family‐based and case‐control datasets, which used the same five markers in leucine‐rich repeat transmembrane neuronal 3 (LRRTM3) as the most influential in determining cluster assignment. In subsequent analyses to detect main effects and gene‐gene interactions, markers in three genes—urokinase‐type plasminogen activator (PLAU), angiotensin 1 converting enzyme (ACE) and cell division cycle 2 (CDC2)—were found to be associated with LOAD in particular subsets of the data based on their LRRTM3 multilocus genotype. All of these genes are viable candidates for LOAD based on their known biological function, even though PLAU, CDC2 and LRRTM3 were initially identified as positional candidates. Further studies are needed to replicate these statistical findings and to elucidate possible biological interaction mechanisms between LRRTM3 and these genes. Genet. Epidemiol. 2007. © 2007 Wiley‐Liss, Inc.
International Health Tourism

This article gives an overview of the current developments in the medical tourism industry. It describes the globalization of medical tourism and argues that the overall increase in the flow of patients and health professionals, and medical technology, capital funding and regulatory regimes across national borders has triggered new patterns of consumption and production of healthcare services. This is illustrated with brief summaries presenting the state of medical tourism in various countries across the globe.
Recent trends in spending patterns of Supplemental Nutrition Assistance Program participants and other low-income Americans

Using Consumer Expenditure Survey data for the period 2004–2010, this article examines spending on food by Supplemental Nutrition Assistance Program (SNAP) participants, whether this spending changed over time, whether participants spent more on food than did program nonparticipants, and whether spending on nonfood goods and services differed between participants and nonparticipants. The article found that spending on food at home increased since 2006 by a greater amount for SNAP participants than it did for eligible nonparticipants, with participants’ spending eventually surpassing nonparticipants’ spending by 2010. As the largest share of total spending, housing expenditures increased steadily for both participants and nonparticipants, with SNAP participants spending amounts similar to those spent by eligible nonparticipants.
Infant Weaning Practices of some TIV Women Resident in Makurdi, Nigeria

The weaning practices in infants aged 4 to 9 months of two hundred Tiv mothers in Makurdi, Nigeria were examined. The data was collected using a questionnaire from these randomly selected women from a known population and who regularly visited the public post-natal clinic in Makurdi. The study showed that all the mothers breast-fed their infants and most introduced supplementary feed at 3 to 4 months. Most also fed the traditional pap or ‘akamu’ usually prepared by adding boiling water to fermented maize-sorghum paste. However, only a few of these (34%) enriched such paps. Price was a major determinant influencing the choice of feed fed to the infants. Only a few of the mothers (19%) used commercial milk formula, about a quarter fed legumes (24.5%) and fruits and vegetables (30%). The study showed that the mother's educational level and occupation influenced both time and duration of breast feeding and introduction of milk formula. Three-quarter of the mothers used bottle feeding while a quarter used spoon and cup and the feeds were improperly stored. The significance of these findings is discussed
Direct real-time observation of actin filament branching mediated by Arp2/3 complex using total internal reflection fluorescence microscopy

Existing methods for studying actin filament dynamics have allowed analysis only of bulk samples or individual filaments after treatment with the drug phalloidin, which perturbs filament dynamics. Total internal reflection fluorescence microscopy with rhodamine-labeled actin allowed us to observe polymerization in real time, without phalloidin. Direct measurements of filament growth confirmed the rate constants measured by electron microscopy and established that rhodamine actin is a kinetically inactive tracer for imaging. In the presence of activated Arp2/3 complex, growing actin filaments form branches at random sites along their sides, rather than preferentially from their barbed ends.
Subthreshold doses of specific phosphodiesterase type 3 and 4 inhibitors enhance the pulmonary vasodilatory response to nebulized prostacyclin with improvement in gas exchange.

Aerosolized prostacyclin (PGI(2)) has been suggested for selective pulmonary vasodilation, but its effect rapidly levels off after termination of nebulization. Stabilization of the second-messenger cAMP by phosphodiesterase (PDE) inhibition may offer a new strategy for amplification of the vasodilative response to nebulized PGI(2). In perfused rabbit lungs, continuous infusion of the thromboxane mimetic U46619 was used to establish stable pulmonary hypertension [increase in pulmonary arterial pressure (pPA) from approximately 7 to approximately 32 mm Hg], which is accompanied by progressive edema formation and severe disturbances in gas exchange with a predominance of shunt flow (increase from <2 to approximately 58%, as assessed by the multiple inert gas elimination technique). In the absence of PGI(2), dose-effect curves for intravascular and aerosol administration of the specific PDE3 inhibitor motapizone, the PDE4 inhibitor rolipram, and the dual-selective PDE3/4 inhibitor tolafentrine on pulmonary hemodynamics were established (potency rank order: rolipram > tolafentrine approximately motapizone; highest efficacy on coapplication of rolipram and motapizone). Ten-minute aerosolization of PGI(2) was chosen to effect a moderate pPA decrease (approximately 4 mm Hg; rapidly returning to prenebulization values within 10-15 min) with only a slight reduction in shunt flow (approximately 49%). Prior application of subthreshold doses of i.v. or inhaled PDE3 or PDE4 inhibitors, which per se did not affect pulmonary hemodynamics, caused prolongation of the post-PGI(2) decrease in pPA. The most effective approach, rolipram plus motapizone, amplified the maximum pPA decrease in response to PGI(2) to approximately 9 to 10 mm Hg, prolonged the post-PGI(2) vasorelaxation to >60 min, reduced the extent of lung edema formation by 50%, and decreased the shunt flow to approximately 19% (i.v. rolipram/motapizone) and 28% (aerosolized rolipram/motapizone). We conclude that lung PDE3/4 inhibition, achieved by intravascular or transbronchial administration of subthreshold doses of specific PDE inhibitors, synergistically amplifies the pulmonary vasodilatory response to inhaled PGI(2), concomitant with an improvement in ventilation-perfusion matching and a reduction in lung edema formation. The combination of nebulized PGI(2) and PDE3/4 inhibition may thus offer a new concept for selective pulmonary vasodilation, with maintenance of gas exchange in respiratory failure and pulmonary hypertension.
Venous thromboembolism and ethnicity

Venous thromboembolism (VTE) has long been considered a disease that affects predominantly white populations, a misconception resulting from a paucity of epidemiological data from non‐Western countries, and the low incidence of hereditary thrombophilia in those of non‐Caucasian background. Over the last decade, interest has grown in this area with the emergence of evidence that VTE is as prevalent, if not more so, in the black population and is also common in Asian groups. Much is still to be learned, as our current knowledge of hereditary thrombophilia and acquired risk factors do not fully explain the risk of VTE in non‐Caucasian groups. This review summarises the current understanding of ethnic variation in VTE and highlights the need for further research in this area.
‘This isn’t for the likes of us’: Taste and capability in aspirations for higher education

Student aspiration for higher education is high on the policy agenda of OECD nations. Typically it is derived from a suturing together of an economic and social inclusion agenda, aimed at widening the participation in higher education of students from disadvantaged backgrounds. In Australia, the 'problem' of student aspiration is particularly acute, not simply because of decades of under-representation by marginalised groups but also because on current estimates, government targets for increasing their participation are unlikely to be achieved. Australian universities charged with doing the government's bidding on achieving targets have ramped up their aspiration-raising outreach activities, with some institutional success but an overall sector-wide shortfall. We argue that this is because current policy and practice 'dissociate aspirations from the objective situation [economic circumstances and social norms] in which they are constituted' (Bourdieu 1990: 16). Little wonder that many students from disadvantaged backgrounds are convinced that higher education 'isn't for the likes of us' (Bourdieu 1990: 17). Far from a deficit account of their aspirational tastes, their 'adaptive preferences' (Nussbaum 2011) reflect their 'awareness of impossibility and of prohibition' (Bourdieu 1990: 17) in the invitation and destination. That is, the objective realities of students' different circumstances produce differential relations between the desire for and possibility of higher education: what is desired by the advantaged tends to mediate what (for them) is possible; what is possible for the disadvantaged tends to mediate what (for them) is desired. Building on Bourdieu and informed by the aspirations of students from advantaged and disadvantaged Central Queensland schools, we find that all students are capable of conceiving of and planning for one's life in relation to 'the good' (Nussbaum 2003), including conceptions and plans that involve higher education. Indeed, our data confirm other research findings that large numbers of students from disadvantaged backgrounds do aspire to undertake higher education (Sen 2009). However, the data also suggest that the established 'tour' to these destinations is conditioned by a particular aspirational 'map' (de Certeau 1984) that requires certain 'navigational capacities' (Appadurai 2004). We conclude that as long as aspiration for higher education remains a matter of taste, widening participation agendas in their current form will fail to attract the numbers desired to meet government and institutional objectives. What is required is an alternative appreciation of aspiration as a matter of capability (Sen 1999) and then an appetite to reposition higher education from aspirational destination to aspirational node.
Secondary education Greek philologists as adult learners on ICT

The aim of this study is to investigate the knowledge, skills and attitudes acquired by a group of secondary education teachers, called philologists in Greek, of the Prefecture of Kavala in Northern Greece after their training (B-Level) in the course: "Training Teachers to the Use and Exploitation of ICTs in Educational Process", offered by the Greek Ministry of Education. Specifically, the training course objectives are to determine whether there are changes in their way of teaching, due to the adult learning process they have followed, and also to identify the factors philologists believe that affect the use of ICT in their teaching practice. Qualitative research was conducted using focused interviews as the main tool. Additionally, two diaries were used, the informants’ and the researchers’ diary. The sample was eight philologists who successfully attended this training course and they taught at Kavala’s secondary education schools. Content analysis was chosen for data processing. The findings showed that the trained philologists acquired new knowledge and skills and cultivated fresh attitudes on the pedagogical use of new technologies. However, factors that might hinder the use of ICT (such as conflict with traditional teaching strategies, poor equipment, etc.) combined with the lack of feedback, led some of them reduce or even abandon the use of ICT in the classroom, which underlines the necessity of a strong follow-up process.
Premature ejaculation--does country of origin tell us anything about etiology?

INTRODUCTION Premature ejaculation is a common sexual problem. The etiology of this condition is unclear. It has been suggested that some racial groups may be more at risk than others. We had a clinical impression that in our unit in London, UK, there was a preponderance of men from Islamic and Asian backgrounds. AIM We therefore undertook a retrospective analysis of our clinic population over an eighteen-month period. METHODS A total of 123 patients were identified with a clinical diagnosis of PE based on the DSM-IV and UK national guidelines. MAIN OUTCOME MEASURE Demographic and clinical data were collected retrospectively: parameters of patients seen in the previous 18 months were identified, including self-identified ethnicity and age. Patient-defined ethnicity was compared with the ethnicity of self-referring patients attending our general sexual health services (outpatients), and also with local population census data. RESULTS A total of 60% of patients were from Islamic or Asian backgrounds but 12% and 11% came from those racial groups in local population census data and our general clinic population respectively (P<0.001). CONCLUSIONS It thus appears that there is a preponderance of men from Islamic and Asian backgrounds presenting to our unit with premature ejaculation. The reasons for this are unclear. Possible mechanisms include psychosocial, familial, or genetic influences.
Women Administrators in Academic Libraries: Three Decades of Change

From the 1960s until the 1990s, gender equity was a topic of great interest in library workforce studies. In the almost forty years since affirmative action law was made applicable to institutions of higher education, efforts have been made to increase the number of women administrators in academic libraries, and it is now assumed that women have achieved parity. However, there is little hard evidence available about their representation in all types and levels of academic libraries. A follow-up study was done to two earlier studies of the status of women in academic libraries. Using the American Library Directory as a source, the gender of individuals holding the positions of director, associate or assistant director, or department head in ARL and Liberal Arts I libraries in 1972, 1982, 1994, and 2004 were studied. Although women have not yet achieved parity at all levels, the percentage of women administrators has increased significantly over the years. There is still a substantial gap at the director's level in the Liberal Arts I and a smaller one at ARL libraries, however, the results show that since the 1970s, women have succeeded in almost erasing the gender gap in academic library administration.
Analysis of regional total factor energy efficiency in China under environmental constraints: based on undesirable-minds and DEA window model

With China’s entrance into the new economy, the improvement of energy efficiency has become an important indicator to measure the quality of ecological civilization construction and economic development. According to the panel data of Chinese regions in 1996-2014, the nearest distance to the efficient frontier of Undesirable-MinDS Xeon model and DEA window model have been used to calculate the total factor energy efficiency of China’s regions. Study found that: Under environmental constraints, China’s total factor energy efficiency has increased after the first drop in the overall 1996-2014, and then increases again. And the difference between the regions is very large, showing a characteristic of “the east is the highest, the west is lower, and lowest is in the central”; finally, this paper puts forward relevant policy suggestions.
Per capita alcohol consumption and ischaemic heart disease mortality.

AIM To test the hypothesis that alcohol consumption is inversely related to ischaemic heart disease (IHD) mortality at the population level. Most individual-level studies find a reduced risk of IHD with a moderate level of alcohol consumption, but it is as yet unknown whether this association also exists at the aggregate level. MEASUREMENTS The study period was approximately 1950 to 1995; 14 EU countries and Norway were included. Time series analyses on different data were utilized, and age-standardized IHD mortality for men and women in the age groups 30-44, 45-59, 60-74 and 30-74 years was measured. The effects of alcohol (sales per capita) were controlled for a weighted lag of per capita sales of cigarettes. FINDINGS There was a random distribution of insignificant negative and positive alcohol effect estimates. A slight indication of a cardioprotective effect of alcohol among 30- to 44-year-old women in high consumption countries could be observed (significant for Italy). Mean alcohol effect estimates were nearly exactly zero (absent alcohol effect) among men and weakly positive among women. Because changes in cigarette consumption were often significantly and positively related to subsequent changes in IHD mortality, poor validity in the IHD time series cannot explain the unsystematic findings. Including a 6-year weighted lag of alcohol consumption changed the weak positive effect among women to an absent alcohol effect. A brief analysis of abstinence rates indicated no particular relationship to IHD mortality. CONCLUSION The alleged cardioprotective alcohol effect is absent at the population level, and great caution should be taken concerning alcohol policies for cardioprotective purposes.