Miracle-dz/UniFAR-FTUs huggingface dataset:
The α1 Isoform of Na,K-ATPase Regulates Cardiac Contractility and Functionally Interacts and Co-localizes with the Na/Ca Exchanger in Heart*

The primary objective of this study was to examine the functional role of the Na,K-ATPase α1 isoform in the regulation of cardiac contractility. Previous studies using knock-out mice showed that the hearts of animals lacking one copy of the α1 or α2 isoform gene exhibit opposite phenotypes. Hearts from α2+/– animals are hypercontractile, whereas those of the α1+/– animals are hypocontractile. The cardiac phenotype of the α1+/– animals was unexpected as other studies suggest that inhibition of either isoform increases contraction. To help resolve this difference, we have used genetically engineered knock-in mice expressing a ouabain-sensitive α1 isoform and a ouabain-resistant α2 isoform of the Na,K-ATPase, and we analyzed cardiac contractility following selective inhibition of the α1 isoform by ouabain. Administration of ouabain to these animals and to isolated heart preparations selectively inhibits only the activity of the α1 isoform without affecting the activity of the α2 isoform. Low concentrations of ouabain resulted in positive cardiac inotropy in both isolated hearts and intact animals expressing the modified α1 and α2 isoforms. Pretreatment with 10 μm KB-R7943, which inhibits the reverse mode of the Na/Ca exchanger, abolished the cardiotonic effects of ouabain in isolated wild type and knock-in hearts. Immunoprecipitation analysis demonstrated co-localization of the α1 isoform and the Na/Ca exchanger in cardiac sarcolemma. The α1 isoform co-immunoprecipitated with the Na/Ca exchanger and vice versa. These results demonstrate that the α1 isoform regulates cardiac contractility, and that both the α1 and α2 isoforms are functionally and physically coupled with the Na/Ca exchanger in heart.
Loss of serum response element-binding activity and hyperphosphorylation of serum response factor during cellular aging

Human diploid fibroblasts undergo a limited number of population doublings in vitro and are used widely as a model of cellular aging. Despite growing evidence that cellular aging occurs as a consequence of altered gene expression, little is known about the activity of transcription factors in aging cells. Here, we report a dramatic reduction in the ability of proteins extracted from the nuclei of near-senescent fibroblasts to bind the serum response element which is necessary for serum-induced transcription of the c-fos gene. In contrast, the activities of proteins binding to the RNA polymerase core element, TATA, as well as to the cyclic AMP response element were maintained during cellular aging. While no major differences in the expression of the serum response factor (SRF) that binds the serum response element were seen between early-passage and late-passage cells, hyperphosphorylation of SRF was observed in near-senescent cells. Furthermore, removal of phosphatase inhibitors during the isolation of endogenous nuclear proteins restored the ability of SRF isolated from old cells to bind the SRE. These data, therefore, indicate that hyperphosphorylation of SRF plays a role in altering the ability of this protein to bind to DNA and regulate gene expression in senescent cells.
Counseling in the Gentrified Neighborhood: What School Counselors Should Know

Gentrification occurs when the prevailing demographic and economic environment of an urban neighborhood changes in ways related to social class and physical renewal. Gentrification effects are both positive and negative; however, low-income residents may be disproportionately negatively affected. As neighborhoods transform, schools also change. The literature on gentrification and its impacts highlights areas where school counselors can begin to address these issues.
Subjective Well-Being and Social Comparison: A Comparative Study on Rural Thailand and Vietnam

This paper analyzes the determinants of the households’ welfare perception using a survey database on rural areas in Thailand and Vietnam which have similar economic and social conditions. Welfare perception corresponds to the households’ subjective assessment of their general situations. We focus on the social comparison and take into account geographical isolation, relative poverty, harsh living conditions, economic and environmental risks as well as the households’ degree of risk acceptance. Our study shows that households, in both countries, are sensitive to income and relative poverty, but only Thai households are concerned with wealth comparison. In particular, this comparison is asymmetric. Environmental risks as well as households’ attitude to risks differently affect the households’ well-being in both countries. However, we observe a similarity in the effect of the risks’ monetary consequences.
Mathematical models for sustainable wealth redistribution

Economic inequality has increased in most large free-market economies during the last century and it has been suggested that this phenomenon is an inherent feature of free-market activities. It seems self-evident, however, that a continual rise in economic inequality is unsustainable. In fact, severe economic inequality has historically been associated with negative effects such as poor economic growth, severe financial recessions or even violent revolutions. Wealth redistribution is present in every form of government, although the extent thereof varies, and existing theoretical justifications of redistributive actions usually rely heavily on utility theory. Most economic postulates related to inequality are empirically inspired and defended, but because of the vast variety of possible economic contexts in which they may prevail, many of these claims are disputed. One example is the so-called Robin Hood paradox, which asserts that the extent of wealth redistribution is less in more unequal societies, where it is needed most, than in more economically equal societies. Another is the Kuznets curve, which predicts that the extent of inequality in a developing economy will follow an inverted ‘u’ curve as a result of development over time. The implications of increasing relative inequality over time as an inherent feature of wealth growth are investigated in the presence of wealth redistribution. Very simple mathematical model abstractions are employed to shed light on the possible evolution over time of wealth distribution in the context of very basic assumptions, since such behaviour may perhaps then also be inferred in more complicated settings. Assuming increasing per capita wealth growth-rate functions is one way of capturing increasing relative inequality over time, the very simplest case being linearly increasing per capita wealth growth-rate functions, which are considered in this thesis. Two examples of redistribution dynamics are investigated. One example mimics diffusion-like effects of trickle-down redistribution, while the other represents a conservative, linear-tax transfer scheme. It is established analytically within the context of the aforementioned mathematical models that increases in economic inequality can always be limited by means of sufficient redistribution. It is also demonstrated that the Robin Hood paradox may follow from very simple assumptions. It is furthermore illustrated that fluctuating behaviour in the evolution over time of wealth inequality can even manifest itself in the absence of time-dependent processes, and hence that explanations of such trends which merely assume time-dependent underlying processes might be of dubious value. Examples of analytical formulations of theoretical justifications for redistributive actions, independent of utility theory, are finally also provided. iii Stellenbosch University https://scholar.sun.ac.za
Role of STAT3 in ischemic preconditioning.

We recently demonstrated that ischemic preconditioning (IPC) induced by cyclic episodes of short durations of ischemia and reperfusion potentiates a signal transduction cascade involving protein tyrosine kinases and MAP kinases. A rapid activation of janus kinase (JAK) and several signal transducers and activators of the transcription (STATs) including STAT3, STAT5A and STAT6 has been shown to occur during myocardial ischemia and reperfusion. This study sought to examine if JAK/STAT signaling pathway play any role in classical early phase of IPC. Isolated working rat hearts were perfused for 15 min with KHB buffer in the absence or presence of a JAK kinase inhibitor tyrphostin AG490 (5 microm) followed by IPC, 30 min global ischemia and 2 h of reperfusion. The results demonstrated extensive phosphorylation of JAK2 and STAT3 in the IPC hearts which was almost completely abolished by an inhibitor of JAK2, AG490. IPC displayed cardioprotection as evidenced by improved post-ischemic contractile recovery, decreased myocardial infarct size and reduced number of apoptotic cardiomyocytes. AG490 blocked IPC-mediated cardioprotection by altering the IPC-mediated survival signal into death signal. Thus, IPC-induced upregulation of antiapoptotic gene bcl-2 and downregulation of pro-apoptotic gene bax are decreased and increased, respectively, in the AG490 treated hearts. The results suggest that early phase of IPC potentiates JAK/STAT signaling by activating STAT3 which transmits a survival signal to the myocardium.
Towards Effective Teams for the Identification of Code Smells

Code smells are symptoms of poor design and implementation choices. Several techniques for the automated detection of code smells have been proposed, but their effectiveness is limited due to the inherent subjectivity of the task. Accepting false warnings generated by a tool may lead to unnecessary maintenance effort. Moreover, bypassing undetected smells may contribute to the software degradation. Thus, developers need to perform a subsequent manual identification of code smells to confirm their occurrences as well as address both false and missing warnings. However, performing ad hoc manual identification of smells does not assure more effective results. Indeed, different context factors may influence on the conclusion about the incidence of a code smell. Based on evidence collected from previous work, this paper presents and discusses a set of context factors that may influence the effectiveness of smell identification tasks. These factors are addressed to human aspects, such as the interaction among individuals and their professional roles. Based on such factors, we present an initial set of practical suggestions for composing more effective teams to the identification of code smells.
Continuous correction of differential path length factor in near-infrared spectroscopy

Abstract. In continuous-wave near-infrared spectroscopy (CW-NIRS), changes in the concentration of oxyhemoglobin and deoxyhemoglobin can be calculated by solving a set of linear equations from the modified Beer-Lambert Law. Cross-talk error in the calculated hemodynamics can arise from inaccurate knowledge of the wavelength-dependent differential path length factor (DPF). We apply the extended Kalman filter (EKF) with a dynamical systems model to calculate relative concentration changes in oxy- and deoxyhemoglobin while simultaneously estimating relative changes in DPF. Results from simulated and experimental CW-NIRS data are compared with results from a weighted least squares (WLSQ) method. The EKF method was found to effectively correct for artificially introduced errors in DPF and to reduce the cross-talk error in simulation. With experimental CW-NIRS data, the hemodynamic estimates from EKF differ significantly from the WLSQ (p<0.001). The cross-correlations among residuals at different wavelengths were found to be significantly reduced by the EKF method compared to WLSQ in three physiologically relevant spectral bands 0.04 to 0.15 Hz, 0.15 to 0.4 Hz and 0.4 to 2.0 Hz (p<0.001). This observed reduction in residual cross-correlation is consistent with reduced cross-talk error in the hemodynamic estimates from the proposed EKF method.
Androgen insensitivity syndrome: an immunohistochemical, ultrastructural, and morphometric study.

OBJECTIVE To evaluate the morphometric, immunohistochemical, and ultrastructural lesions of the testes in prepubertal and adult patients with androgen insensitivity syndrome. METHODS We examined the testicular biopsy using immunohistochemistry for vimentin, smooth muscle actin, and collagen IV antigens. Quantification of seminiferous tubules and testicular interstitium was performed in prepubertal and adult patients with androgen insensitivity syndrome and results were compared with normal testes from both infants and adults. RESULTS The adult testes presented nodular and diffuse lesions that consisted of Sertoli-cell-only seminiferous tubules. Two types of Sertoli cells could be distinguished, namely, immature vimentin-positive Sertoli cells and nearly mature Sertoli cells. In the nodules, the lamina propria was thin and contained a scant number of actin-positive peritubular cells. Leydig cells were hyperplastic. The prepubertal patients showed only diffuse lesions characterized by Sertoli cell hyperplasia, decreased germ cell numbers, and a discontinuous immunoreaction to collagen IV. CONCLUSIONS The testicular lesions in androgen insensitivity syndrome are probably caused by primary alterations that begin during gestation. These lesions become progressively more pronounced at puberty, when the nodular lesion pattern (adenomas) is completely developed.
Research to reality: a process evaluation of a mini-grants program to disseminate evidence-based nutrition programs to rural churches and worksites.

OBJECTIVES To describe a project that used mini-grants plus technical assistance to disseminate evidence-based programs, to understand how the project worked in different settings, and to generate recommendations for future programming and evaluation. DESIGN Process evaluation using program records, activity forms completed by grantees, interviews, and focus groups. SETTING Churches and worksites in rural, southwest Georgia. PARTICIPANTS Site coordinators (n = 10), organizational leaders (n = 7), and project committee members (n = 25) involved in program implementation at 7 funded organizations. INTERVENTION The Emory Cancer Prevention and Control Research Network solicited applications from churches and worksites to implement one of 2 evidence-based nutrition programs: Body & Soul for churches and Treatwell 5-a-Day for worksites. Successful applicants (n = 7) received funding and technical assistance from Emory and agreed to conduct all required elements of the evidence-based program. MAIN OUTCOME MEASURES We assessed adoption, reach, implementation, and maintenance of specific programs and their core elements, as well as contextual influences and the resources required to implement the mini-grants program. RESULTS Four of the 7 funded organizations conducted all programmatic core elements; all 7 sites conducted at least 6 of 8 core elements, including at least 1 food-related policy or environmental change as a result of the program. Program reach varied widely across sites and core elements. All site coordinators stated that they intend to continue at least some of the activities conducted under the project. Sites reported that contextual factors such as the program's fit with the organization's mission, leadership support, and leadership or staffing transitions influenced program implementation. Over 18 months, Emory staff spent 47.7 hours providing technical assistance to grantees. CONCLUSIONS A mini-grants and technical assistance model has the potential to be an effective mechanism for disseminating evidence-based programs to community organizations, and further study of this method is warranted.
Clinical relevance and functional consequences of the TNFRSF1A multiple sclerosis locus

Objective: We set out to characterize the clinical impact and functional consequences of rs1800693G, the multiple sclerosis (MS) susceptibility allele found in the TNFRSF1A locus. Methods: We analyzed prospectively collected data on patients with MS to assess the role of the TNFRSF1A locus on disease course and treatment response. Using archival serum samples and freshly isolated monocytes from patients with MS and healthy subjects, we evaluated the effects of rs1800693G and a second risk allele, R92Q, on immune function. Results: In 772 patients with MS, we see no evidence that rs1800693G strongly influences clinical or radiographic indices of disease course and treatment response; thus, rs1800693G appears to be primarily involved in the onset of MS. At the molecular level, this validated susceptibility allele generates an RNA isoform, TNFRSF1A Δ6, that lacks the transmembrane and cytoplasmic domains. While there was no measurable effect on serum levels of soluble TNFRSF1A, rs1800693G appears to alter the state of monocytes, which demonstrate a more robust transcriptional response of CXCL10 and other genes in response to tumor necrosis factor (TNF)–α. We also report that activation of the TNF-α pathway results in altered expression of 6 other MS susceptibility genes, including T-cell activation rho GTPase activating protein (TAGAP) and regulator of G-protein signaling 1 (RGS1), which are not previously known to be responsive to TNF-α. Conclusions: The MS rs1800693G susceptibility allele affects the magnitude of monocyte responses to TNF-α stimulation, and the TNF pathway may be one network in which the effect of multiple MS genes becomes integrated.
Frequency and Quality of Return to Study Following Traumatic Brain Injury

Objective:To examine the frequency and experience of return to secondary or tertiary study over a 10-year period following traumatic brain injury (TBI). Participants:A group of 295 students with moderate to severe TBI followed prospectively. Setting:Epworth HealthCare TBI outpatient rehabilitation program follow-up clinic 1 to 10 years postinjury. Main Outcome Measures:Frequency of return to study. Also, for a subset, changes in course enrollment, utilization of additional educational supports, and experience of return to study postinjury. Results:Of those studying preinjury, 295 attended the follow-up clinic appointments, with 167 (56%) having returned to study. Those who did not return to study had significantly longer posttraumatic amnesia duration. The cross-sectional follow-up revealed that 60.4% were studying at 1 year postinjury, 37.5% at 2 years postinjury, 50.0% at 3 years postinjury, 31.1% at 5 years postinjury, and 2.0% at 10 years postinjury. Many had migrated into employment. A subsample of 95 participants reported on their educational experience. Of those, 28.7% changed their course enrollment from full-time to part-time. While supports such as tuition and special consideration were greatly increased postinjury, students reported the proportion of subjects passed of 79.0%. However, they experienced cognitive difficulties and fatigue and felt less satisfied with their studies. Conclusions:Return to study was relatively successful; however, this was associated with the experience of fatigue and need for far greater effort, assistance and reduced study hours, and somewhat less overall satisfaction.
[Impact on the risk of obesity due to interactions between fat mass- and obesity-associated gene rs9939609 variants and behavioral factors, in the Chinese school-aged children].

OBJECTIVE To investigate how the interactions between fat mass- and obesity-associated (FTO) gene rs9939609 variants and daily-life related behavioral factors would influence the risk of obesity among the Chinese school-aged children. METHODS 3503 school-aged children were selected from the Beijing Child and Adolescent Metabolic Syndrome (BCAMS) Study, and divided into obese children (n = 1229) and non-obese children (n = 2274). Venipuncture blood test, genotyping and questionnaire were performed. RESULTS Five common factors including protein foods, tobacco & alcohol, vegetables & fruits, sedentary behavior and physical exercise in spare time were extracted with factor analysis methodology. Data from logistic regression analysis showed that taking the interaction of rs9939609 variant with protein foods as an example, the risk of interaction accounted for 19.16% when both factors existing simultaneously. Similarly, the interactions of this SNP with vegetables & fruits, sedentary behavior and physical exercise in spare time appeared to be 5.97%, 19.62% and 12.43% respectively; however there might not be interaction between tobacco, alcohol and the SNP in the Chinese children. CONCLUSION Protein foods, vegetables & fruits, sedentary behavior and physical exercise might modify the effects of FTO rs9939609 variant on the risk of obesity in Chinese school-aged children. However, large-scale, prospective studies with detailed information on related behavioral factors would be ideal models for identifying the interactions between genes and environment.
Faculty Perception of Openness and Attitude to Open Sharing at the Indian National Open University

In the past decade, the educational scenario world over has significantly been impacted by open access and open education movements. The philosophy of openness and sharing forms the cornerstone of the open education movement. The distance education approaches, together with open educational resources (OER) and massive open online courses (MOOCs), are being used to serve the increasing educational needs of diverse communities. However, adoption of openness as a core value and as part of the institutional strategy still remains a challenge for academic institutions in general, and distance education institutions in particular, in developing countries like India. In this research study, the authors report an analysis of the perception of the faculty of the Indira Gandhi National Open University of India (IGNOU) about openness and their attitude towards sharing of resources in academic institutions. Data was collected through a structured questionnaire administered to the teachers and academics of IGNOU (N=69). The results indicated that: the faculty members valued sharing of resources in academic institutions; learning resources should be made available free of cost; there is a strong need for training on intellectual property rights, copyright, and creation and use of OER; and there should be an institutional policy on OER for its effective use.
Osteogenic Programming of Human Mesenchymal Stem Cells with Highly Efficient Intracellular Delivery of RUNX2

Mesenchymal stem cells (MSCs) are being exploited in regenerative medicine due to their tri‐lineage differentiation and immunomodulation activity. Currently, there are two major challenges when directing the differentiation of MSCs for therapeutic applications. First, chemical and growth factor strategies to direct osteogenesis in vivo lack specificity for targeted delivery with desired effects. Second, MSC differentiation by gene therapy is difficult as transfection with existing approaches is clinically impractical (viral transfection) or have low efficacy (lipid‐mediated transfection). These challenges can be avoided by directly delivering nonvirally derived recombinant protein transcription factors with the glycosaminoglycan‐binding enhanced transduction (GET) delivery system (P21 and 8R peptides). We used the osteogenic master regulator, RUNX2 as a programming factor due to its stage‐specific role in osteochondral differentiation pathways. Herein, we engineered GET‐fusion proteins and compared sequential osteogenic changes in MSCs, induced by exposure to GET fusion proteins or conventional stimulation methods (dexamethasone and Bone morphogenetic protein 2). By assessing loss of stem cell‐surface markers, upregulation of osteogenic genes and matrix mineralization, we demonstrate that GET‐RUNX2 efficiently transduces MSCs and triggers osteogenesis by enhancing target gene expression directly. The high transduction efficiency of GET system holds great promise for stem cell therapies by allowing reproducible transcriptional control in stem cells, potentially bypassing problems observed with high‐concentration growth‐factor or pleiotropic steroid therapies. Stem Cells Translational Medicine 2017;6:2146–2159