Miracle-dz/UniFAR-FTUs huggingface dataset:
Auto-Inhibition of Ets-1 Is Counteracted by DNA Binding Cooperativity with Core-Binding Factor α2

ABSTRACT Auto-inhibition is a common transcriptional control mechanism that is well characterized in the regulatory transcription factor Ets-1. Autoinhibition of Ets-1 DNA binding works through an inhibitory module that exists in two conformations. DNA binding requires a change in the inhibitory module from the packed to disrupted conformation. This structural switch provides a mechanism to tightly regulate Ets-1 DNA binding. We report that the Ets-1 partner protein core-binding factor α2 (CBFα2; also known as AML1 or PEBP2) stimulates Ets-1 DNA binding and counteracts auto-inhibition. Support for this conclusion came from three observations. First, the level of cooperative DNA binding (10-fold) was similar to the level of repression by auto-inhibition (10- to 20-fold). Next, a region necessary for cooperative DNA binding mapped to the inhibitory module. Third, an Ets-1 mutant with a constitutively disrupted inhibitory module did not bind DNA cooperatively with CBFα2. Furthermore, two additional lines of evidence indicated that CBFα2 affects the structural switch by direct interactions with Ets-1. First, the retention of cooperative DNA binding on nicked duplexes eliminated a potential role of through-DNA effects. Second, cooperative DNA binding was observed on composite sites with altered spacing or reversed orientation. We suggest that only protein interactions can accommodate this observed flexibility. These findings provide a mechanism by which CBF relieves the auto-inhibition of Ets-1 and illustrates one strategy for the synergistic activity of regulatory transcription factors.
The Sustained-Exposure Dexamethasone Formulation OTO-104 Offers Effective Protection against Noise-Induced Hearing Loss

The otoprotective effects of OTO-104 were investigated both prior to and following acute acoustic trauma. Guinea pigs received a single intratympanic injection of OTO-104 and were assessed in a model of acute acoustic trauma. Doses of at least 2.0% OTO-104 offered significant protection against hearing loss induced by noise exposure when administered 1 day prior to trauma and up to 3 days thereafter. Otoprotection remained effective even with higher degrees of trauma. In contrast, the administration of a dexamethasone sodium phosphate solution did not protect against noise-induced hearing loss. Activation of the classical nuclear glucocorticoid and mineralocorticoid receptor pathways was required for otoprotection by OTO-104. The sustained exposure properties of OTO-104 were also superior to a steroid solution.
Incomplete Contracts and the Commons: Valuing the Strategic Role of Exit Costs

The paper deals with the question of the governance of common-pool resources when exogenous enforcement is not available. We assert that the recent 'linked games approach' seems to neglect that in order to be effective and to deter agents free-riding and/or hold-up, a linked game has to register a perfect synchronic transfers between agents involved in the 'principal' game. However, in a repeated setting, perfect synchronic transfers may be implemented only at very high costs. As a consequence, hold-up strategies may always occur, beside free-riding behaviours. We suggest, thus, that in order to be effective, a linked game should increase the exit costs of the potential opportunistic agent, in terms of quasi-rents loss. It is thus stressed that in order to prevent ex-post hold-up, the linked game should increase the ex-post specificity of opportunistic agents. Under given conditions, when a linked game increases the specificity degree of the potential opportunist, even in the absence of third party enforcement, agents commitment to cooperate is a self-sustaining equilibrium.
Clinical and molecular genetics of the short QT syndrome

Purpose of review Sudden cardiac death in patients without structural heart disease remains a challenge in diagnostics and risk stratification. Genetically determined arrhythmias are a potential cause for a primary electrical disease. A recently discovered primary electrical disease is discussed. Recent findings The inherited short QT syndrome is a recently recognized genetic condition, which is associated with atrial fibrillation, syncope and/or sudden cardiac death. Attention has been focused on diagnostic ECG features, the identification of underlying mutations and mechanisms of arrhythmogenesis. Summary The short QT syndrome is clinically associated with atrial fibrillation, syncope and sudden cardiac death. A shortened QT interval (QTc <360 ms) and reduced ventricular refractory period together with an increased dispersion of repolarization constitute the potential substrate for reentry and life-threatening ventricular tachyarrhythmia. To date, gain-of-function mutations in KCNH2, KCNQ1, KCNJ2, encoding potassium channels and loss-of-function mutations in CACNA1C and CACNB2b, encoding L-type calcium channel subunits have been identified. The therapy of choice is the implantable cardioverter defibrillator in symptomatic patients. Quinidine has been shown to prolong the QT interval and to normalize the effective refractory periods of the atrium and ventricle in patients with short QT-1 syndrome.
Excellence in Public Relations and Communication Management

Contents: Preface. J.E. Grunig, Communication, Public Relations, and Effective Organizations: An Overview of the Book. Part I: The Basic Theory. J.E. Grunig, J. White, The Effect of Worldviews on Public Relations Theory and Practice. L.A. Grunig, J.E. Grunig, W.P. Ehling, What Is an Effective Organization? J. White, D.M. Dozier, Public Relations and Management Decision Making. F.C. Repper, How Communication Managers Can Apply the Theories of Excellence and Effectiveness. Part II: The Program Level: Effective Planning of Communication Programs. J.E. Grunig, F.C. Repper, Strategic Management, Publics, and Issues. D.M. Dozier, W.P. Ehling, Evaluation of Public Relations Programs: What the Literature Tells Us About Their Effects. D.M. Dozier, F.C. Repper, Research Firms and Public Relations Practices. Part III: The Departmental Level: Characteristics of Excellent Public Relations Departments. J.E. Grunig, What Is Excellence in Management? W.P. Ehling, D.M. Dozier, Public Relations Management and Operations Research. J.E. Grunig, L.A. Grunig, Models of Public Relations and Communication. D.M. Dozier, The Organizational Roles of Communications and Public Relations Practitioners. W.P. Ehling, J. White, J.E. Grunig, Public Relations and Marketing Practices. D.M. Dozier, L.A. Grunig, The Organization of the Public Relations Function. L.C. Hon, L.A. Grunig, D.M. Dozier, Women in Public Relations: Problems and Opportunities. W.P. Ehling, Public Relations Education and Professionalism. Part IV: The Organizational Level: The Conditions That Make Excellence in Public Relations Possible. L.A. Grunig, How Public Relations/Communication Departments Should Adapt to the Structure and Environment of an Organization.And What They Actually Do. L.A. Grunig, Power in the Public Relations Department. L.A. Grunig, Activism: How It Limits the Effectiveness of Organizations and How Excellent Public Relations Departments Respond. J.E. Grunig, Symmetrical Systems of Internal Communication. K. Sriramesh, J.E. Grunig, J. Buffington, Corporate Culture and Public Relations. K. Sriramesh, J. White, Societal Culture and Public Relations. Part V: The Economic Level: What Public Relations and Communication Contribute to the Bottom Line. W.P. Ehling, Estimating the Value of Public Relations and Communication to an Organization.
Spotted Fever Group Rickettsiae: A Brief Review and a Canadian Perspective

Spotted fever group rickettsioses (SFGR) are infections caused by established and emerging human pathogens worldwide. These rickettsial agents are transmitted to humans via arthropods and may result in mild to severe and potentially fatal diseases. Spotted fever group rickettsioses are characterized by similar clinical features, including fever, rash, headache and myalgias, with the development of an inoculation eschar in many, but not all cases. Endemic rickettsial infections do occur but are infrequent in Canada, in contrast to the United States, where these infections are far more prevalent. Travel‐associated rickettsioses, however, are being diagnosed with increasing frequency in Canadian travellers returning from international trips abroad, in particular in travellers returning from Africa. The diagnosis of rickettsial infections can be challenging owing to the non‐specific nature of the clinical symptoms and the requirement for specialized testing. Serology cannot distinguish between the approximately 20 spotted fever group rickettsial species currently known or suspected to be capable of causing human infection. Molecular testing is required to determine the rickettsial species responsible for infection, but requires greater effort on the part of the clinician to collect appropriate samples, including cutaneous skin swabs from under the eschar or skin punch biopsies of the eschar or rash. Infections with spotted fever group rickettsiae likely occur more commonly than currently recognized and should be considered in patients with appropriate symptoms and exposure histories.
Youth, Pornography, and the Internet

The Internet has changed the way we access the world. This is especially true for kids, who soak up new technologies like eager little sponges. They have access to an enormous array of material, including educational links, sports info, chat roomsa "and, unfortunately, pornography. But we must approach our need to protect children with care to avoid placing unnecessary restrictions on the many positive features of the Internet. Youth, Pornography, and the Internet examines approaches to protecting children and teens from Internet pornography, threats from sexual predators operating on-line, and other inappropriate material on the Internet. The National Research Councila (TM)s Computer Science and Telecommunications Board explores a number of fundamental questions: Who defines what is inappropriate material? Do we control Internet access by a 17-year-old in the same manner as for a 7-year-old? What is the role of technology and policy in solving such a problem in the context of family, community, and society? The book discusses social and educational strategies, technological tools, and policy options for how to teach children to make safe and appropriate decisions about what they see and experience on the Internet. It includes lessons learned from case studies of community efforts to intervene in kidsa (TM) exposure to Internet porn. Providing a foundation for informed debate, this very timely and relevant book will be a must-read for a variety of audiences.
Central Bank Transparency and Independence: Updates and New Measures

This paper reports updated measures of transparency and independence for more than 100 central banks. The indices show that there has been steady movement in the direction of greater transparency and independence over time. In addition, we show that outcomes such as the variability of inflation are significantly affected by both central bank transparency and independence. Disentangling the impact of the two dimensions of central bank arrangements remains difficult, however.
Political changes and trends in cardiovascular risk factors in the Czech Republic, 1985-92.

BACKGROUND: Mortality from cardiovascular diseases is substantially higher in central and eastern Europe than in the west. After the fall of communism, these countries have undergone radical changes in their political, social, and economic environments but little is known about the impact of these changes on health behaviours or risk factors. Data from the Czech Republic, a country whose mortality rates from cardiovascular diseases are among the highest, were analysed in this report. OBJECTIVES: To examine the trends in cardiovascular risk factors in Czech population over the last decade during which a major and sudden change of the political and social system occurred in 1989, and whether the trends differed in relation to age and educational group. DESIGN AND SETTING: Data from three cross sectional surveys conducted in 1985, 1988, and 1992 as a part of the MONICA project were analysed. The surveys examined random samples of men and women aged 25-64 in six Czech districts and measured the following risk factors: smoking, blood pressure, body mass index (BMI), and total and high density lipoprotein (HDL) cholesterol. RESULTS: The numbers of subjects (response rate) examined were 2573 (84%) in 1985, 2769 (87%) in 1988, and 2353 (73%) in 1992. Total cholesterol and body mass index increased between 1985 and 1988 and decreased between 1988 and 1992. The prevalence of smoking was declining slightly in men between 1985 and 1992 but remained stable in women. There were only small changes in blood pressure. The decline in cholesterol and BMI in 1988-92 may be related to changes in foods consumption after the price deregulation in 1991. An improvement in risk profile was more pronounced in younger age groups, and the declines in cholesterol and obesity were substantially larger in men and women with higher education. By contrast, there was an increase in smoking in women educated only to primary level. CONCLUSION: Substantial changes in cholesterol, obesity, and women's smoking occurred in the Czech population after the political changes in 1989. Although a causal association cannot be claimed, national trends in foods consumption are consistent with changes in blood lipids and obesity. Further monitoring of trends is required to confirm these trends.
A statistical model for QTL mapping in polysomic autotetraploids underlying double reduction

As a group of economically important species, linkage mapping of polysomic autotetraploids, including potato, sugarcane and rose, is difficult to conduct due to their unique meiotic property of double reduction that allows sister chromatids to enter into the same gamete. We describe and assess a statistical model for mapping quantitative trait loci (QTLs) in polysomic autotetraploids. The model incorporates double reduction, built in the mixture model-based framework and implemented with the expectation-maximization algorithm. It allows the simultaneous estimation of QTL positions, QTL effects and the degree of double reduction as well as the assessment of the estimation precision of these parameters. We performed computer simulation to examine the statistical properties of the method and validate its use through analyzing real data in tetraploid switchgrass.
Endoscopic Management of Peri-Pancreatic Fluid Collections

In the past decade, there has been a progressive paradigm shift in the management of peri-pancreatic fluid collections after acute pancreatitis. Refinements in the definitions of fluid collections from the updated Atlanta classification have enabled better communication amongst physicians in an effort to formulate optimal treatments. Endoscopic ultrasound (EUS)-guided drainage of pancreatic pseudocysts has emerged as the procedure of choice over surgical cystogastrostomy. The approach provides similar success rates with low complications and better quality of life compared with surgery. However, an endoscopic “step up” approach in the management of pancreatic walled-off necrosis has also been advocated. Both endoscopic and percutaneous drainage routes may be used depending on the anatomical location of the collections. New-generation large diameter EUS-specific stent systems have also recently been described. The device allows precise and effective drainage of the collections and permits endoscopic necrosectomy through the stents.
Privatization in the Countries of Eastern and Central Europe and of the Former Soviet Union

In transition economics, privatization seems to have two basic motivations: separation of politics from the economy, and better corporate governance. While different countries have emphasized such motivations to varying degrees, it is clear that none of the privatization methods chosen is indisputably the best. Also, it has proved impossible to plan privatization in the sense that the emerging distribution of property rights has been virtually always different from the one that the authorities seem to have had in mind.
ABC of complementary medicine: herbal medicine.

The ABC of complementary medicine is edited and written by Catherine Zollman and Andrew Vickers. Catherine Zollman is a general practitioner in Bristol, and Andrew Vickers will shortly take up a post at Memorial Sloan-Kettering Cancer Center, New York. At the time of writing, both worked for the Research Council for Complementary Medicine, London. The series will be published as a book in spring 2000. The picture of a herbal dispensary is reproduced with permission of Paul Biddle/Science Photo Library. The pictures of Chinese herbal medicine are reproduced with permission of Rex Features/Hafenrichter. The picture of different herbal formulations is reproduced with permission of Alain Dex, Publiphoto Diffusion/Science Photo Library. The pictures of St John’s wort and valerian are reproduced with permission of Glenis Moore/A-Z Botanical and A-Z Botanical. The picture of echinacea is reproduced with permission of NHPA/Stephen Krasemann. The picture of a Western herbalist is reproduced with permission of BMJ/Ulrike Preuss.
High throughput parallel montgomery modular exponentiation on FPGA

Modular exponentiation is the key operation in public key cryptosystems such as RSA (Rivest, Shamir Adelman). It is implemented by repeated modular multiplications which are time consuming for large operands. Accelerating RSA requires reducing the number of modular multiplications with speeding up the modular multiplication. In this paper, we present a high throughput architecture implementing a fast modular exponentiation based on the square-and-multiply method, called binary method which allows the parallel execution of squares and multiplications by using two fast Montgomery modular multipliers. The Montgomery multiplication is based on a high radix-216 to reduce the iterations number of this operation where the multiplication of two 1024-bits numbers is performed in only 65 iterations. The CS (Carry Save) representation is advantageously used to overcome the carry propagation then the iteration cycle is independent of the data path length. The implementation results showed that the architecture computes a 1024 bits modular exponentiation in only 0.66 ms.
Intangible Income, Intercompany Transactions, Income Shifting, and the Choice of Location

The links between intangible income, intercompany transactions, income shifting and the choice of location are investigated using data on U.S. parent corporations and their manufacturing subsidiaries. The objective is to better understand the income shifting process and its implications. In particular, do opportunities for income shifting distort "real" behavior such as the choice of location and the volume of intercompany transactions? Do prospective benefits from income shifting change behavior in both high-tax and low-tax locations? The results present a coherent, consistent picture. Income derived from R&D based intangibles accounts for about half of the income shifted from high-tax to low-tax countries. R&D intensive subsidiaries engage in a greater volume of intercompany transactions and, therefore, have more opportunities for income shifting. In addition, subsidiaries in locations with either very high or very low statutory tax rates, with a strong incentive to shift income in or out, also undertake a significantly larger volume of intercompany transactions. Finally, R&D intensive U.S. parent companies respond to the opportunities for income shifting by investing in countries with either very high or very low statutory tax rates. As a sidelight, we find that the allocation of debt among subsidiaries and the shifting of R&D based intangible income together account for virtually all of the observed difference in profitability between high and low tax countries.
Uncertain futures?: youth attachment to the labor market in the United States and New England

In the wake of the Great Recession, high levels of unemployment and low labor force participation rates among U. S. youth are of great concern, receiving considerable attention from policy makers and the popular press. These trends have led observers to question what the future path of employment will look like for younger workers. Of particular concern is the share of the youth population that is idle, or what is technically termed “not in employment, education, or training” (NEET). These individuals are particularly vulnerable to continued adverse labor market outcomes and their prolonged detachment may result in significant individual and social costs. This report analyzes data from multiple sources to trace trends in labor force attachment among youth over the past two decades and quantify the contributing forces that may be driving observed declines in labor force attachment. The data indicate that while all youth were affected by the Great Recession, teens experienced a decline in labor force attachment even prior to the most recent downturn. Between 2000 and 2006, the U. S. economy employed fewer teens within almost all industries and occupations. This trend continued during the Great Recession and subsequent recovery — suggesting continued uncertainty for youth in the labor market. Yet contrary to conventional wisdom, youth did not become increasingly idle prior to the Great Recession, largely due to rising school enrollment. The share of youth not employed and not in school is no higher than it was two decades ago in the years just after the 1990-1991 recession. To inform regional policymakers, trends for the New England region are discussed throughout the report, specifically when trends for the region differ from those observed nationally. The report concludes with a discussion of the role that public policy could play in addressing the labor market challenges that youth face today.
Costing in new enterprise environment

Purpose – Faced with new wealth creation paradigm, triggered by technology and relentless globalization of markets, increasing number of companies are becoming knowledge‐based enterprises. This paper aims to discuss the change in enterprise environment; evolution of performance and cost measures; and the challenges for managerial accounting researchers and practitioners in developing value‐based costing and performance measurement systems (PMS). Design/methodology/approach – A conceptual discussion and approach are taken.Findings – Internet and e‐commerce have changed forever the way companies conduct their businesses. Virtual enterprise and efficient supply chain management systems will shape the future of these enterprises. Organizations are trying to become agile enterprises with the help of strategic alliances of firms and integration using information technologies. Traditional performance and cost measures are no longer suitable for developing and managing enterprises in the so‐called new environment.