Miracle-dz/UniFAR-FTUs huggingface dataset:
Multiple combinations of alternatively spliced exons in rat tropomyosin-alpha gene mRNA: evidence for 20 new isoforms in adult tissues and cultured cells.

Previous studies of the tropomyosin-alpha gene using Northern blot and ribonuclease protection assay methods identified the expression of nine isoforms generated by alternative splicing of exons. Several of these isoforms were characterized as tissue-specific and/or developmentally specific. The present study used a highly sensitive RT-PCR-based strategy to assay the expression of these and many novel isoforms in a variety of adult rat tissues. All 9 isoforms were found to be expressed in all tissues evaluated. Furthermore, 20 new isoforms were identified with varying tissue specificity. Sequence analysis confirmed exon splicing patterns. This greater degree of isoform generation parallels recent findings for another tropomyosin gene, the TM-5 gene, for which the generation of new isoforms, in particular, ones using novel junctions for carboxy-terminal-coding exons, was also shown. Several of the new cDNA-based isoforms predict tropomyosin protein species that are 10 amino acids longer than previously characterized high-molecular-weight tropomyosin-alpha gene isoforms. The apparent lack of significant tissue specificity in the expression of tropomyosin isoforms suggests that many of these isoforms have more generic roles in cell function.
Comparison of methods of measuring HER-2 in metastatic breast cancer patients treated with high-dose chemotherapy.

PURPOSE HER-2 is overexpressed in 20% to 30% of human breast cancer and is associated with poor outcome. Studies suggest an association between HER-2 overexpression and resistance to alkylating agents. To further evaluate this relationship, we assessed the interaction of HER-2, measured by different methods, and outcome after dose intensification with alkylating agents in metastatic breast cancer. PATIENTS AND METHODS From 1988 to 1995 at Duke University, 425 patients with metastatic breast cancer were enrolled in a study of high-dose alkylating agents (HDC) with autologous cellular support after doxorubicin-based therapy (AFM). HER-2 was measured in serum for shed extracellular domain (ECD) and in tissue by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). RESULTS HER-2 ECD was positive in 29% (19 of 65) of patients pre-AFM and in 11.7% (34 of 290) pre-HDC. Higher pre-AFM and higher pre-HDC HER-2 ECD predicted worse overall survival (P =.045 and P =.0096, respectively). HER-2 overexpression by IHC and FISH showed no correlation with worse disease-free survival or overall survival. FISH and ECD were highly specific for IHC (97.3% and 97.7% respectively). However, ECD had a low sensitivity for IHC-only 22% of patients with HER-2 in the primary tumor shed ECD into the serum. CONCLUSION These data suggest that the method of measuring HER-2 is important in predicting clinical outcome. HER2 ECD may identify a poor prognosis subgroup of HER-2-positive tumors. Lack of association of HER2 by IHC/FISH with worse outcome suggests that therapy with AFM and/or HDC therapy may be able to overcome the effect of this prognostic factor or it may not be a prognostic factor in this setting.
Russia's armed forces on the information war front. Strategic documents. OSW STUDIES 57 2016-06-27

The question about the role of the armed forces in the information space is in fact a question about the role of the factor of force in the Kremlin’s domestic and foreign policy. In Russia, this factor has invariably been treated as a hallmark of the country’s position as a global power, an instrument of deterrence, and a way to exert political pressure and build spheres of influence. The country’s military information strategy is designed to serve those tasks, and envisages multiple battle fronts, including internal and external affairs, the info-psychological front, the cyberspace and other spheres. Its visible consequences include a militarisation of the language of politics and propaganda, the imposition on public opinion of the narrative of an information war against Russia, and a radical change of the Russian army’s image. Today Russia forcefully demands that other countries respect its spheres of influence in the neighbourhood (as seen from its aggression against Ukraine and its armed intervention in Syria). It claims to be the guarantor of peace processes, even as it demolishes the European and global security architecture, and presents itself as a centre of power, asserting the right to co-decide on matters of global security.
Effects of visual flow direction on signs and symptoms of cybersickness

Our objective was to assess the influence of visual flow direction on physiological changes and symptoms elicited by cybersickness. Twelve healthy subjects (6 male and 6 female) were exposed to a 15-min virtual ride on a rollercoaster on two different days in a counterbalanced manner, such half of participants were facing forward during the first ride while another half was facing backward. Forehead skin conductance, heart rate and HRV parameters (SDRR, RMSSD) were collected as objective measures; subjective symptoms were assessed with the Motion Sickness Assessment Questioner immediately after exposure. We found that while nausea ratings at which participants terminated the experiment did not differ between forward/backward rides, the mean ride tolerance time was significantly longer during reverse ride compared to forward ride (6.1±0.4 vs 5.0±0.5 min, respectively, p = 0.01, η2 = 0.45). Analysis of HRV parameters revealed significant reduction in both RMSSD (p = 0.02, t = 2.62, η2 = 0.43) and SDRR (p = 0.01, t = 2.90, η2 = 0.45) in the forward ride; no such changes were found in the backward ride. We also found that amplitude of phasic changes in forehead skin conductance increased significantly in both ride directions. This increase however was significantly lower (p<0.05) in backward ride when compared to the forward ride. When assessed immediately post-ride, subjects reported significantly lower (p = 0.04) subjective symptom intensity after the reverse ride compared to the forward ride. We conclude that the direction of visual flow has a significant effect on the symptoms reported by the subjects and on the physiological changes during cybersickness.
Teenage Parents: Their Ambitions and Attainments.

Presents the results of a study of the effects of family formation during late adolescence upon postsecondary education career development womens orientation towards homemaking dependency on parents and society economic characteristics fertility and attitudes. The research is based on the National Longitudinal Study of the High School Class of 1973 (NLS) the more than 22000 participants of which were the subjects of follow up surveys in 1973 1974 and 1976. Tables include data on race ethnicity region socioeconomic status and family background. Measurements of academic aptitude and scholastic performance taken before the participants had graduated reveal that those who soon became parents ranked lower in these areas and in socioeconomic status than did their classmates. Thus preexisting differences would have led to different outcomes even in the absence of parenthood. Analysis also reveals that many of the adverse consequences attributed to early parenthood also showed up among those who married early but remained childless. The men were found to lag behind other men in both educational aspiration and attainment and to be less satisfied with career progress. Married women who became mothers early displayed a shift in career and educational goals and achievements and those who entered the labor market received considerably lower wages than nonmothers. Single mothers rely heavily on families and society for financial support. The NLS excludes those who became parents during early adolescence and those who dropped out of school before graduation. The long term effects of teenage marriage and parenthood have yet to become apparent.
Approaching Research Broadly, Not Just Deeply: The Case of Real Activities Manipulation

Abstract This commentary discusses how self-identification of accounting researchers by specific subfields (e.g., financial, managerial, audit, tax, systems, and non-profit/governmental) and further, by research method (e.g., archival, experimental, and analytical), limits the scope and potential insights that we can glean from our research. Using the example of research in Real Activities Management (RAM), we illustrate how extending enquiry beyond the boundaries of a narrow research identity can broaden the types of research questions we ask and what we learn from conducting our research. We start with financial accounting research that has documented the existence of RAM and its relation to accrual-based earnings management and then summarize research on the consequences of RAM. We next explore studies outside of the traditional financial accounting setting that have examined similar issues and discuss how incorporating insights from these studies can broaden the enquiry and enhance the contribution of this stream of literature. We conclude by providing an example of where this broader approach has been successfully applied, resulting in new and interesting insights into managerial behavior.
Nigericin-induced Impairment of Autophagic Flux in Neuronal Cells Is Inhibited by Overexpression of Bak*

Background: Exact mechanisms underlying regulatory roles for the Bcl-2 family remain to be delineated. Results: Overexpressed Bak blocked ionophore-induced impairment of autophagic flux in neuronal cells. Conclusion: Bak plays critical roles in maintaining autophagic flux and vacuole homeostasis. Significance: Our findings contribute to better understanding of the Bcl-2 family's potential as a novel therapeutic strategy in autophagy-associated neurodegeneration. Bak is a prototypic pro-apoptotic Bcl-2 family protein expressed in a wide variety of tissues and cells. Recent studies have revealed that Bcl-2 family proteins regulate apoptosis as well as autophagy. To investigate whether and how Bak exerts a regulatory role on autophagy-related events, we treated independent cell lines, including MN9D neuronal cells, with nigericin, a K+/H+ ionophore. Treatment of MN9D cells with nigericin led to an increase of LC3-II and p62 levels with concomitant activation of caspase. Ultrastructural examination revealed accumulation of autophagic vacuoles and swollen vacuoles in nigericin-treated cells. We further found that the LC3-II accumulated as a consequence of impaired autophagic flux and the disrupted degradation of LC3-II in nigericin-treated cells. In this cell death paradigm, both transient and stable overexpression of various forms of Bak exerted a protective role, whereas it did not inhibit the extent of nigericin-mediated activation of caspase-3. Subsequent biochemical and electron microscopic studies revealed that overexpressed Bak maintained autophagic flux and reduced the area occupied by swollen vacuoles in nigericin-treated cells. Similar results were obtained in nigericin-treated non-neuronal cells and another proton ionophore-induced cell death paradigm. Taken together, our study indicates that a protective role for Bak during ionophore-induced cell death may be closely associated with its regulatory effect on maintenance of autophagic flux and vacuole homeostasis.
Eliciting societal preferences of reimbursement decision criteria for anti cancer drugs in South Korea

ABSTRACT Introduction: In order to look beyond the cost-effectiveness analysis, this study used a multi-criteria decision analysis (MCDA), which reflects societal values with regard to reimbursement decisions. This study aims to elicit societal preferences of the reimbursement decision criteria for anti cancer drugs from public and healthcare professionals. Methods: Eight criteria were defined based on a literature review and focus group sessions: disease severity, disease population size, pediatrics targets, unmet needs, innovation, clinical benefits, cost-effectiveness, and budget impacts. Using quota sampling and purposive sampling, 300 participants from the Korean public and 30 healthcare professionals were selected for the survey. Preferences were elicited using an analytic hierarchy process. Results: Both groups rated clinical benefits the highest, followed by cost-effectiveness and disease severity, but differed with regard to disease population size and unmet needs. Innovation was the least preferred criteria. Conclusions: Clinical benefits and other social values should be reflected appropriately with cost-effectiveness in healthcare coverage. MCDA can be used to assess decision priorities for complicated health policy decisions, including reimbursement decisions. It is a promising method for making logical and transparent drug reimbursement decisions that consider a broad range of factors, which are perceived as important by relevant stakeholders.
Examining Partnerships between K-12 District Schools and College of Education Leadership Preparation Programs: A Case Study

ii Acknowledgements.iii List of Tables.xi List of Figures.xii Chapter I: Background . 1 Alabama Reform of School Leadership Programs.6 Statement of Problem.8 Purpose of the Study.9 Research Questions.9 Conceptual Framework.9 Assumptions.10 Delimitations.10 Limitations.12 Definition of Terms.12 Chapter II: Review of the Literature.14 Historical Background.14 Education Reform Efforts.15 Conceptual Framework.17 K12 University Partnerships as Part of Reform.21 Importance of K-12 University Partnership.29 Benefits/Barriers of a K-12 University Partnership.31 School Leaders and their role in Partnership Development.40 Role of Preparation Programs.44 Advisory Councils.52 Chapter III: Methodology.55
Delta-Hedged Gains and Risk-Neutral Moments

We investigate the well-documented underperformance of delta-hedged option portfolios in relation to ex ante moments of the stock market's return distribution. Using a sample of Standard and Poor's 500 index options, we find that delta-hedged option gains decrease with ex ante volatility, in support of a negative volatility risk premium. Moreover, the delta-hedged gains are negatively associated with skewness and kurtosis of call options, but positively associated with the higher moments of put options. These results suggest that investors pay a premium for call options in anticipation of a positive jump, while they pay a premium for put options in anticipation of a negative jump.
Spatiotemporal Analysis of Relative Convergence of EEGs Reveals Differences Between Brain Dynamics of Depressive Women and Men

A new nonlinear technique for analysis of brain dynamics called spatiotemporal analysis of relative convergence (STARC) of electroencephalograms (EEGs) is introduced, based on the relative convergence of EEGs of different loci. This technique shows how many times EEGs of each loci pair converge together, which in turn is used as an indicator to determine the different neuronal regions involved in performing the same task. A higher STARC value indicates that more regions are recruited to perform the same task. The STARC methodology was used to reveal sex difference pathophysiology and brain dynamics, using EEG data from 11 male and 11 female adults with major depressive disorder (MDD). The results show significant differences in relative convergences of EEGs of intraleft temporal and frontoleft temporal lobes at δ band, between male and female patients.
Moyamoya Disease: Evaluation of Postoperative Revascularization Using Multiphase Selective Arterial Spin Labeling MRI

Purpose The purpose of this study was to evaluate cerebral blood flow through the bypass in operated patients with Moyamoya disease using multiphase selective arterial spin labeling (ASL) technique. Materials and Methods Fifteen surgically treated cerebral hemispheres from 11 patients with Moyamoya disease were included. Selective ASL examinations were performed during the early postoperative period (mean, 5.5 days) on 4 hemispheres and late postoperative period (mean, 332.7 days) on 15 hemispheres. The labeling slab was positioned at the bypassed external carotid artery and 5 slices in each of the 10 sequential phases were acquired using a 3-T scanner. Results Two of 4 early postoperative ASL examinations and all late postoperative ASL examinations demonstrated blood flow through the bypass. The remaining 2 early postoperative ASL examinations showed absence of blood flow; however, blood flow improved on follow-up examinations. Conclusion Multiphase selective ASL technique can provide information about the dynamics of postoperative blood flow through the bypass in Moyamoya disease.
A Unique β-1,2-Mannosyltransferase of Thermotoga maritima That Uses Di-myo-Inositol Phosphate as the Mannosyl Acceptor

ABSTRACT In addition to di-myo-inositol-1,3′-phosphate (DIP), a compatible solute widespread in hyperthermophiles, the organic solute pool of Thermotoga maritima comprises 2-(O-β-d-mannosyl)-di-myo-inositol-1,3′-phosphate (MDIP) and 2-(O-β-d-mannosyl-1,2-O-β-d-mannosyl)-di-myo-inositol-1,3′-phosphate (MMDIP), two newly identified β-1,2-mannosides. In cells grown under heat stress, MDIP was the major solute, accounting for 43% of the total pool; MMDIP and DIP accumulated to similar levels, each corresponding to 11.5% of the total pool. The synthesis of MDIP involved the transfer of the mannosyl group from GDP-mannose to DIP in a single-step reaction catalyzed by MDIP synthase. This enzyme used MDIP as an acceptor of a second mannose residue, yielding the di-mannosylated compound. Minor amounts of the tri-mannosylated form were also detected. With a genomic approach, putative genes for MDIP synthase were identified in the genome of T. maritima, and the assignment was confirmed by functional expression in Escherichia coli. Genes with significant sequence identity were found only in the genomes of Thermotoga spp. , Aquifex aeolicus, and Archaeoglobus profundus. MDIP synthase of T. maritima had maximal activity at 95°C and apparent Km values of 16 mM and 0.7 mM for DIP and GDP-mannose, respectively. The stereochemistry of MDIP was characterized by isotopic labeling and nuclear magnetic resonance (NMR): DIP selectively labeled with carbon 13 at position C1 of the l-inositol moiety was synthesized and used as a substrate for MDIP synthase. This β-1,2-mannosyltransferase is unrelated to known glycosyltransferases, and within the domain Bacteria, it is restricted to members of the two deepest lineages, i.e., the Thermotogales and the Aquificales. To our knowledge, this is the first β-1,2-mannosyltransferase characterized thus far.
The Law, the Map and the Citizen: Designing a legal service infrastructure where rules make sense again

Law is being digitalised. When this research started, the notion of digitalisation of law was new. The early attempts were websites that provided legal sources. The question occurred if this would be helpful to the citizen seeking answers for day-to-day problems. The research question evolved from there. Can internet technology help the citizen in navigating law or does the mixing of these worlds create a digital bureaucratic labyrinth? To examine those questions, a lot of exploration and scoping was done. What technology are we addressing and what type of ‘help’ do we mean? And which Law is implied? And if a citizen is not ‘helped’ by the computer, could this affect his or her relationship with government? To investigate the influence of digitalised Law on this relationship, I had to explore theories about legitimacy, bureaucracies, trust and violations of ‘le contrat social’ between citizens and government. Three experiments with digital mapping technology and legal source material were then carried out in a living lab setting. A simple answer to the research question is that technology can indeed help with providing better knowability for citizens, better legal effect planning for legislators and improved co-design of law by stakeholders, thereby increasing the legitimacy of Law. However, it became also clear that a bad design of technology can result in the opposite, which was symbolised by Little Britain in one of their sketches by the phrase: ‘Computer says NO’ (see youtube). It is also made clear by the research results that internet technology requires a learning curve; that professional assistance is therefore still required and that information technology chosen in these experiments can help with harmonisation or mutual alignment of plans of action. The technology tested in this research cannot help in the final legal decision making process. The book ends with a chapter about recommendations for the Dutch digitalisation of the ‘Omgevingswet’.
Rate-limiting roles of the tenase complex of factors VIII and IX in platelet procoagulant activity and formation of platelet-fibrin thrombi under flow

The importance of factor Xa generation in thrombus formation has not been studied extensively so far. Here, we used mice deficient in either factor VIII or factor IX to determine the role of platelet-stimulated tenase activity in the formation of platelet-fibrin thrombi on collagen. With tissue factor present, deficiency in factor VIII or IX markedly suppressed thrombus growth, fibrin formation and platelet procoagulant activity (phosphatidylserine exposure). In either case, residual fibrin formation was eliminated in the absence of tissue factor. Effects of factor deficiencies were antagonized by supplementation of the missing coagulation factor. In wild-type thrombi generated under flow, phosphatidylserine-exposing platelets bound (activated) factor IX and factor X, whereas factor VIII preferentially co-localized at sites of von Willebrand factor binding. Furthermore, proteolytic activity of the generated activated factor X and thrombin was confined to the sites of phosphatidylserine exposure. With blood from a hemophilia A or B patient, the formation of platelet-fibrin thrombi was greatly delayed and reduced, even in the presence of high concentrations of tissue factor. A direct activated factor X inhibitor, rivaroxaban, added to human blood, suppressed both thrombin and fibrin formation. Together, these data point to a potent enforcement loop in thrombus formation due to factor X activation, subsequent thrombin and fibrin generation, causing activated factor X-mediated stimulation of platelet phosphatidylserine exposure. This implies that the factor VIII/factor IX-dependent stimulation of platelet procoagulant activity is a limiting factor for fibrin formation under flow conditions, even at high tissue factor concentrations.