Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of Kinase-inactive c-Src Delays Oxidative Stress-induced Disassembly and Accelerates Calcium-mediated Reassembly of Tight Junctions in the Caco-2 Cell Monolayer*

The activity of Src kinases appears to play a role in both assembly and disassembly of tight junction. However, the role of a specific isoform of Src kinase in regulation of tight junction is not known. In the present study the role of c-Src in regulation of epithelial tight junction was investigated in Caco-2 cell monolayers. Oxidative stress (xanthine oxidase + xanthine) induced an activation and membrane translocation of c-Src. The oxidative stress-induced decrease in transepithelial electrical resistance, increase in inulin permeability, and redistribution of occludin and ZO-1 from the intercellular junctions were prevented by PP2. The rates of oxidative stress-induced activation of c-Src, tyrosine phosphorylation of ZO-1 and β-catenin, decrease in resistance, increase in permeability to inulin, and redistribution of occludin and ZO-1 were significantly greater in cells transfected with wild type c-Src, whereas it was low in cells transfected with kinase-inactive c-SrcK297R mutant, when compared with those in empty vector-transfected cells. The rates of recovery of resistance, increase in barrier to inulin, and reorganization of occludin and ZO-1 into the intercellular junctions during the calcium-induced reassembly of tight junction were much greater in Caco-2 cells transfected with c-SrcK297R as compared with those in cells transfected with empty vector or wild type c-Src. These results show that the dominant-negative expression of kinase-inactive c-Srcdelays the oxidative stress-induced disruption of tight junction and accelerates calcium-induced assembly of tight junction in Caco-2 cells and demonstrate that oxidative stress-induced disruption of tight junction is mediated by the activation of c-Src.
Clinical approach to the diagnosis and treatment of cystic fibrosis and CFTR-related disorders

ABSTRACT Introduction: Cystic fibrosis (CF) is the most frequent life-shortening autosomal recessive disorder in Caucasians. Defects or absence of the CF-transmembrane conductance regulator impair ion transport in apical membranes of exocrine glands. Leading symptoms of typical CF are exocrine pancreatic insufficiency and progressive pulmonary destruction, causing premature death. Additionally, patients can suffer from chronic rhinosinusitis, hepatic and intestinal involvement, diabetes and predominantly male infertility. Areas covered: CFTR-related disorders affect only one or several different organ systems, often to a milder degree. The definition and usage of the term has seen some variations in the last years, aiming to improve differentiation of the broad clinical spectrum associated with CFTR defects. In this review we present disease characteristics, diagnostic criteria, and treatment options of CFTR-related disorders for a multidisciplinary readership. Expert commentary: CFTR-related disorders are often diagnosed late, leading to lack of specialized attendance and adequate therapy. In clinical care, monitoring of the nutritional status, lung function, airway pathogen colonization and laboratory parameters is necessary to optimize therapy and the course of the disease.
Active Learning in Large Graduate Classes: Reflections on an “Attaining Citizenship” Simulation

Abstract This article details a role-playing “citizenship simulation” used in a large graduate seminar offered by the Masters of International Relations (IR) faculty at Monash University in Melbourne, Australia. While recognizing the need for a more systematic analysis of the relationship between class size and active learning strategies, this article offers an anecdotal reflection on the challenges faced when employing active learning in an IR course with growing enrollment numbers. We describe and analyze a simulation used in the graduate course to evaluate the feasibility and desirability of structuring large IR classrooms to include participatory group activities such as simulations. We also hope the simulation provides instructors with an effective sample design for simulations in their own larger courses.
Utilization of moiré interferometry to study the strain distribution within multi-layer thermoplastic elastomers

The use of soft elastomeric cushion form bearings as an alternative material to ultra-high molecular weight polyethylene (UHMWPE) has been proposed in the literature as providing enhanced lubrication and lower friction. However, the abrupt change in stiffness between the bearing's soft contact layer and its rigid support substrate results in high shear stresses and leads to the debonding of the soft layer from the substrate. The use of functionally modulus-graded material has been proposed as a solution to this problem. This paper investigates the use of moiré interferometry to study the strain distribution within and across the interfaces of multi-layer elastomeric samples, which were fabricated as models for functionally modulus-graded materials. While this technique has been widely used to study the strain distribution in rigid materials and composites, this paper represents the first report of its application to low-modulus polymers at temperatures where they exhibit significant viscoelastic behavior. The results presented clearly demonstrate that the moiré interferometry technique can be successfully applied in the field of low-modulus elastomeric materials. The analysis of the moiré patterns suggests that the soft elastomeric material under the contact point was subjected to a compressive εx and was pushed sideways. The analysis also showed that the maximum shear strain occurred where the deformation was constrained, which could possibly lead to a local fatigue failure in the sample.
Gender and Network Awareness in/for successful leadership in academic Science and Engineering

This paper focuses on gender and network awareness and their importance for academic leadership positions in Science, Engineering and Technology (SET). Empirical material stems from a German study (2009 to 2012) which focussed on the potential for innovation among women in leadership positions and the barriers they experience. The basis is a qualitative study with case studies in different organisations, a technical university and different research institutes from one big governmental research organisation. Semi-structured interviews and focus group discussions with female and male professors are the empirical basis for results. Research questions focus on effects of gender awareness on women professors’ strategic responses, different responses of individuals to inequalities when they become more network aware, and the importance of both gender and network awareness to counter inequalities. Gender aware female professors are more successful in individual coping strategies (handling visibility, fighting for acceptance and against discrimination, solidarity and support of women). Gender aware organisational cultures are evident in mentoring programs and equal opportunity policies. Interviewed professors show an overall high networking awareness. They are convinced that successful leadership in a technical field requires inclusion in internal and external networks, especially for information, cooperation and projects. Women in SET need to be gender and network aware to overcome hindrances stemming from their limited participation in powerful informal men’s networks.
The 3' untranslated region of picornavirus RNA: features required for efficient genome replication

The role of the 3' untranslated region (3'UTR) in the replication of enteroviruses has been studied with a series of mutants derived from either poliovirus type 3 (PV3) or a PV3 replicon containing the reporter gene chloramphenicol acetyltransferase. Replication was observed when the PV3 3'UTR was replaced with that of either coxsackie B4 virus, human rhinovirus 14 (HRV14), bovine enterovirus, or hepatitis A virus, despite the lack of sequence and secondary structure homology of the 3'UTRs of these viruses. The levels of replication observed for recombinants containing the 3'UTRs of hepatitis A virus and bovine enterovirus were lower than those for PV3 and the other recombinants. Extensive site-directed mutagenesis of the single stem-loop structure formed by the HRV14 3'UTR indicated the importance of (i) the loop sequence, (ii) the stability of the stem, and (iii) the location of the stem immediately upstream of the poly(A) tail. The role of a 4-bp motif at the base of the HRV14 stem, highly conserved among rhinoviruses, was examined by site-directed mutagenesis of individual base pairs. This analysis did not pinpoint a particular base pair as crucial for function. The requirement for immediate adjacent positioning of the open reading frame and the 3'UTR was examined by insertion of a 1.1-kb heterologous sequence. A replicon containing this insert replicated to about 30% of the level observed for the wild type. However, the corresponding virus consistently deleted most of the inserted fragment, suggesting that its presence was incompatible with a full replication cycle.
Heart rate variability as a predictor of cardiac dysrhythmias during weaning from mechanical ventilation.

BACKGROUND Weaning from mechanical ventilation to spontaneous breathing is associated with changes in the hemodynamic and autonomic nervous systems that are reflected by heart rate variability. Although cardiac dysrhythmias are an important manifestation of hemodynamic alterations, the impact of heart rate variability on the occurrence of dysrhythmias during weaning has not been specifically studied. OBJECTIVES To describe differences in heart rate variability spectral power and occurrence of cardiac dysrhythmias at baseline and during the initial trial of weaning from mechanical ventilation and to evaluate the impact of heart rate variability during weaning on occurrence of dysrhythmias. METHOD Continuous 3-lead electrocardiographic recordings were collected from 35 patients receiving mechanical ventilation for 24 hours at baseline and during the initial weaning trial. Heart rate variability was evaluated by using spectral power analysis. RESULTS Low-frequency power increased (P = .04) and high-frequency and very-low-frequency power did not change during weaning. The mean number of supraventricular ectopic beats per hour during weaning was higher than the mean at baseline (P < .001); the mean of ventricular ectopic beats did not change. Low-frequency power was a predictor of ventricular and supraventricular ectopic beats during weaning (P < .001). High-frequency power was predictive of ventricular and supraventricular (P = .02) ectopic beats during weaning. Very-low-frequency power was predictive of ventricular ectopic beats (P < .001) only. CONCLUSION Heart rate variability power spectra during weaning were predictive of dysrhythmias.
Control of epitheliomesenchymal transformation. I. Events in the onset of neural crest cell migration are separable and inducible by protein kinase inhibitors.

Neural tubes isolated from quail embryos prior to epitheliomesenchymal transformation (EMT) and neural crest (NC) cell migration, when explanted onto fibronectin surfaces, replicated properties of normal NC morphogenesis such as (i) cell outgrowth, (ii) loss of A-CAM (N-cadherin) junctions and adoption of mesenchymal form, and (iii) development of HNK-1 immunoreactivity. The timetable of property (i) was essentially normal but the outgrowing cells were initially mainly epithelial, unlike NC outgrowth in vivo and in cultures of older neural tubes. Mesenchymal properties (ii) and (iii) were progressively and variably retarded relative to the in vivo timetable. Achievement of these properties by EMT was principally related to proximity to the neural tube and to preexisting mesenchymal cells, rather than being related temporally to the outgrowth timetable. This EMT, combined with a higher mitotic rate in the mesenchyme cells, resulted in the outgrowth passing from mainly epithelial at 16 hr to mainly mesenchymal at 48 hr in vitro. Immediate precocious EMT and outgrowth of A-CAM negative mesenchymal cells from pre-EMT neural tubes was stimulated by the protein kinase inhibitors staurosporine and bisindolymaleimide in a cycloheximide-independent manner. EMT could be induced not only on the dorsal (i.e., NC) side, but also on the ventral side of the neural tube, but the ventral cells were less sensitive than the dorsal cells, and with developmental age became still less sensitive while the dorsal cells became more sensitive. The results suggest that the complex events of EMT in the NC system are not obligatorily coregulated, can be triggered by epigenetic events involving differential protein phosphorylation, and may be controlled via intraneural signaling.
Assessing the co-curricular course experience of distance learners : a Wawasan Open University model

This study investigated the implementation of the compulsory co-curriculum course in Wawasan Open University (WOU). The course focuses on providing an avenue for academic socialisation among distance learners to facilitate student-community management skills via co-curricular and social services. The purpose of this research is to determine the effect to which participation in co-curricular events enhances the achievement of student-learning outcomes in distance learners. The study was accomplished by using the pragmatist paradigm that combined the quantitative and qualitative approaches. In utilising the mixed methodology, quantitative data was generated through the online questionnaire method which was distributed among 426 students enrolled in the course. The students were asked to identify and reflect on their involvement in the course and how they viewed their participation within four correlated categories of feedback: Category 1: General information on the course. Category 2: Support provided by the tutor. Category 3: Group Assessment and teamwork. Category 4: Personal experience and challenges. The analysis of the quantitative data exhibited student satisfaction with positive feedback of the course as it correlated statistically to the success of achieving the objectives and learning outcomes. The analysis of the qualitative data revealed components of value, support, and teamwork were achieved with positive reception of the course linked to themes that contributed to the achievement of student learning outcomes.
Estrogenic activity of the insecticide chlordecone in the reproductive tract of birds and mammals.

Effects of the insecticide chlordecone (Kepone) on female reproduction in birds and mammals were reviewed. In different avian species, chlordecone inhibited or reduced reproduction and decreased egg hatchability and survival of the newborn. In Japanese quail, chronic chlordecone ingestion decreased total egg production and clutch size and increased egg breakage. Eggs produced by treated quail were significantly weaker and thinner. Chlordecone also decreased follicular development, induced ovarian regression, and inhibited ovulation and egg laying. Histological studies showed that when chlordecone was fed to sexually immature quail, the oviducts exhibited accelerated growth, cytodifferentiation, cellular hypertrophy, secretory activity, and maturation. Ultrastructure of the oviduct surface showed increased growth of microvilli and profuse ciliation. Chlordecone also stimulated granular endoplasmic reticulum and Golgi development and induced full secretory activity in the cytoplasm of estrogen‐sensitive qua.
Community Health Workers in Primary Care Practice

New, comprehensive, approaches for chronic disease management are needed to ensure that patients, particularly those more likely to experience health disparities, have access to the clinical care, self-management resources, and support necessary for the prevention and control of diabetes. Community health workers (CHWs) have worked in community settings to reduce health care disparities and are currently being deployed in some clinical settings as a means of improving access to and quality of care. Guided by the chronic care model, Baylor Health Care System embedded CHWs within clinical teams in community clinics with the goal of reducing observed disparities in diabetes care and outcomes. This study examines findings from interviews with patients, CHWs, and primary care providers (PCPs) to understand how health care delivery systems can be redesigned to effectively incorporate CHWs and how embedding CHWs in primary care teams can produce informed, activated patients and prepared, proactive practice teams who can work together to achieve improved patient outcomes. Respondents indicated that the PCPs continued to provide clinical exams and manage patient care, but the roles of diabetes education, nutritional counseling, and patient activation were shifted to the CHWs. CHWs also provided patients with social support and connection to community resources. Integration of CHWs into clinical care teams improved patient knowledge and activation levels, the ability of PCPs to identify and proactively address specific patient needs, and patient outcomes.
Federalism, Separation of Powers, and the Role of State Attorneys General in Multistate Litigation

Over the past two decades, state attorneys general have developed and refined the practice of multistate litigation as a powerful law enforcement tool. Part I reviews the powers and duties of state attorneys general and describes the rise of the multistate litigation phenomenon. Part III then identifies a facet of multistate litigation that may be relevant to a separation of powers analysis but which critics have yet to consider: namely the enforcement of federal law by state attorneys general. While this facet of multistate litigation is the one most vulnerable to criticism on constitutional grounds, Part III argues that several considerations minimize the concerns raised by a separation of powers challenge to enforcement of federal law by state attorneys general. I. State Attorneys General and Multistate Litigation . This type of cooperative law enforcement activity among state attorneys general became known as multistate litigation. Whether filed pursuant to state or federal law, multistate litigation is the product of close cooperation among the attorneys general who are parties to the lawsuit. This is an inversion of the more commonly expressed federalism concern, which is illustrated by the content of the Supreme Court's docket.
Media framing of the Egyptian monetary policy in domestic news websitesinsights from “The Flotation of the Egyptian Pound in 2016”

On the 3rd of November 2016, the Central Bank of Egypt has announced the free flotation of the Egyptian pound. The Central Bank (CBE) had devalued the currency to 13 EGP per USD. The event of the devaluation of the Egyptian pound against US dollars started an extensive debate across media outlets. A content analysis of 605 articles in three news websites (national, private, and partisan) has been done since the announcement date of its implementation in November 2016 till July 2017 along with analyzing the press releases of the Central Bank (CBE), to describe how the Central Bank (CBE) of Egypt has been able to send out its messages through news websites. The topic was explored through the agenda-setting and media framing theories, in order to track frames of the free flotation of the Egyptian pound and to identify trends in covering monetary policy in local news websites, to compare coverage of the new monetary decision across these news websites and to examine variations across them. The research sample covered different types of news websites (national, private, partisan) to ensure balance in the sample selection. The research found out that “El Watan” the private news website provided the highest positive and optimistic views of the flotation followed by Al Ahram the national website and Al Wafd the partisan news websites. “El Watan” together with “Al Ahram” relied on official sources in developing their news stories, yet Al Wafd relied on non-official sources. The frames mentioned in the press releases of the Central Bank (CBE) of Egypt were reflected in the media coverage of the three news websites however they were not constant in terms of duration or longevity. The frames applied in the press releases of the Central Bank (CBE) of Egypt were found to be six frames, “The free flotation of the Egyptian pound is a must”, “Stimulating the Egyptian economy is a shared responsibility”, “The free flotation of the Egyptian pound has positive outcomes”, “There are side effects for the free flotation of the Egyptian pound”, “Assuring the sustainability of the social aid programs for the needy people” and the frame that lasts through all press releases was “Assuring long term economic stability for investors and people”.
Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen.

CONTEXT The growth inhibitory effect of tamoxifen, which is used for the treatment of hormone receptor-positive breast cancer, is mediated by its metabolites, 4-hydroxytamoxifen and endoxifen. The formation of active metabolites is catalyzed by the polymorphic cytochrome P450 2D6 (CYP2D6) enzyme. OBJECTIVE To determine whether CYP2D6 variation is associated with clinical outcomes in women receiving adjuvant tamoxifen. DESIGN, SETTING, AND PATIENTS Retrospective analysis of German and US cohorts of patients treated with adjuvant tamoxifen for early stage breast cancer. The 1325 patients had diagnoses between 1986 and 2005 of stage I through III breast cancer and were mainly postmenopausal (95.4%). Last follow-up was in December 2008; inclusion criteria were hormone receptor positivity, no metastatic disease at diagnosis, adjuvant tamoxifen therapy, and no chemotherapy. DNA from tumor tissue or blood was genotyped for CYP2D6 variants associated with reduced (*10, *41) or absent (*3, *4, *5) enzyme activity. Women were classified as having an extensive (n=609), heterozygous extensive/intermediate (n=637), or poor (n=79) CYP2D6 metabolism. MAIN OUTCOME MEASURES Time to recurrence, event-free survival, disease-free survival, and overall survival. RESULTS Median follow-up was 6.3 years. At 9 years of follow-up, the recurrence rates were 14.9% for extensive metabolizers, 20.9% for heterozygous extensive/intermediate metabolizers, and 29.0% for poor metabolizers, and all-cause mortality rates were 16.7%, 18.0%, and 22.8%, respectively. Compared with extensive metabolizers, there was a significantly increased risk of recurrence for heterozygous extensive/intermediate metabolizers (time to recurrence adjusted hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.04-1.90) and for poor metabolizers (time to recurrence HR, 1.90; 95% CI, 1.10-3.28). Compared with extensive metabolizers, those with decreased CYP2D6 activity (heterozygous extensive/intermediate and poor metabolism) had worse event-free survival (HR, 1.33; 95% CI, 1.06-1.68) and disease-free survival (HR, 1.29; 95% CI, 1.03-1.61), but there was no significant difference in overall survival (HR, 1.15; 95% CI, 0.88-1.51). CONCLUSION Among women with breast cancer treated with tamoxifen, there was an association between CYP2D6 variation and clinical outcomes, such that the presence of 2 functional CYP2D6 alleles was associated with better clinical outcomes and the presence of nonfunctional or reduced-function alleles with worse outcomes.