Insight into the molecular and functional determinants of HP1043, the essential master regulator of Helicobacter pylori.

Helicobacter pylori is one of the most widespread and successful human pathogens, colonizing half of the population stomach mucosa and causing gastric malignancies in 1% of carriers. Due to the increasing number of antimicrobial-resistant strains, in 2017 the WHO included H. pylori among pathogens that pose a major threat for humankind. In this study, we propose as a molecular target for novel antimicrobial strategies HP1043, an orphan response regulator essential for the viability of H. pylori as it orchestrates all the most important cellular processes. Amino acids most relevant for HP1043 dimerization and target DNA recognition were identified and used to guide an in-silico protein-DNA docking and generate a high-resolution structural model of the interacting HP1043 dimer and its target DNA. The model was experimentally validated and exploited to carry out a virtual screening of small molecule libraries, identifying 8 compounds potentially able to interfere with HP1043 function and likely block H. pylori infection. A second line of research aimed at the characterization of the regulatory function of HP1043 and the tight mechanisms of regulation of hp1043 gene expression. In particular, we proved a direct interaction between HP1043 and the housekeeping sigma80 factor of the RNA polymerase. A conditional mutant H. pylori strain overexpressing a synthetic copy of the hp1043 gene altered in nucleotide sequence yet encoding the wild-type protein was generated, achieving increased intracellular levels of HP1043. However, overexpression of HP1043 did not result in an upregulation of target genes transcription nor modulation of hp1043 transcript levels, pinpointing the existence of multiple overlayed mechanisms of regulation that affect both protein levels and functionality as well as maintain steady the amount of hp1043 transcript. Finally, we proposed that a mechanism of post-transcriptional regulation could depend on an antisense transcript to the hp1043 gene which was validated in two different strains.

Outcomes of global coagulation assays in patients with Philadelphia-negative myeloproliferative neoplasms with respect to genetic determinants of clonal progression

Classical myeloproliferative neoplasms (MPNs) are hematopoietic stem cell disorders that manifest with inflammation, promotion of atherosclerosis, hypercoagulability, fibrosis, and clonal evolution. The complex biological background lends itself to multi-omics studies. We have previously shown that reduced platelet fibrinogen receptor (PFR) expression may follow hyperactivation of plasma-dependent mechanisms, such as tissue factor (TF) release, unbalanced thrombin generation, involvement of protease-activated receptors (PARs). Acetylsalicylic acid (ASA) helped to restore the expression of PFRs. In this study, we enrolled 53 MPN patients, subjecting them to advanced genetic testing (panel of 30 genes in NGS), global coagulation testing (Rotational Thromboelastometry - ROTEM) and cytofluorometric determination of PFRs. ROTEM parameters appear to differ considerably depending on the type of pathology under investigation, cell count, and selected mutations. Essential thrombocythemia (ET) and CALR mutation appear to correlate with increased efficiency of both classical coagulation pathways, with significantly more contracted clot formation times (CFTs). In contrast, primary myelofibrosis (PMF) and polycythemia vera (PV) show greater imbalances in the hemostatic system. PV, probably due to its peculiar hematological features, shows a lengthening of the CFT and, at the same time, a selective contraction of parameters in INTEM with the increase of platelets and white blood cells. PMF - in contrast - seems to exploit the extrinsic pathway more to increase cell numbers. The presence of DNMT3A mutations is associated with reduced clotting time (CT) in EXTEM, while ASXL1 causes reduced maximal lysis (ML). EZH2 could be responsible for the elongation of CFT in INTEM assay. In addition, increased PFR expression is associated with history of hemorrhage and sustained CT time in FIBTEM under ASA prophylaxis. Our findings corroborate the existing models on the connection between fibrosis, genetic complexity, clonal progression, and hypercoagulability. Global coagulation assays and PFR expression are potentially useful tools for dynamic evaluation of treatments’ outcomes.

Fair Copyright for Canada: Lessons for Online Social Movements from the First Canadian Facebook Uprising

Despite their growing importance, the political effectiveness of social media remains understudied. Drawing on and updating resource mobilization theory and political process theory, this article considers how social media make “political engagement more probable,” and the determinants of success for online social movements. It does so by examining the mainstreaming of the Canadian “user rights” copyright movement, focusing on the Fair Copyright for Canada Facebook page, created in December 2007. This decentralized, grassroots, social media-focused action – the first successful campaign of its kind in Canada and one of the first in the world – changed the terms of the Canadian copyright debate and legitimized Canadian user rights. As this case demonstrates, social media have changed the type and amount of resources needed to create and sustain social movements, creating openings for new groups and interests. Their success, however, remains dependent on the political context within which they operate.

Political intervention in economic activity

This paper proposes a political economy explanation of bailouts to declining industries. A model of probabilistic voting is developed, in which two candidates compete for the vote of two groups of the society through tactical redistribution. We allow politicians to have core support groups they understand better, this implies politicians are more or less effective to deliver favors to some groups. This setting is suited to reproduce pork barrels or machine politics and patronage. We use this model to illustrate the case of an economy with both an efficient industry and a declining one, in which workers elect their government. We present the conditions under which the political process ends up with the lagged-behind industry being allowed to survive.

Tecnología digital y sistema educativo : el reto de la globalización.

Digitalismo, mundialización y sociedades del conocimiento y civilización científico-técnica son conceptos que inciden en la educación en el marco general de la globalización. Los efectos de la nueva economía están sometidos a análisis, actualmente, pero está claro que la innovación y la competitividad en un mundo globalizado, así como el uso de las nuevas tecnologías, está afectando a los procesos educativos. La tecnología digital plantea nuevos retos a la educación desde la perspectiva de la globalización. En relación con estas corrientes se ha generado una actitud de mayor compromiso por parte de los profesionales para no abandonar a los jóvenes en la cultura globalizada de la comunicación sin formarlos acerca de cuándo, cómo y por qué usar las tecnologías emergentes.

How the Entrepreneurial Top Management Team Setup Influences Firm Performance and the Ability to Raise Capital: A Literature Review

This paper reviews research findings on entrepreneurial top management teams within the last 20 years. It concentrates on team-based management factors and their influence on a new venture’s growth and ability to raise capital. This paper integrates recent findings and provides an overview of the current state of research. Moreover, it contributes to the overall topic by proposing five clusters of major team-specific influences, derives determinants of success and failure, and reveals recommendations for further research.

An organizational learning approach to expatriate cross-cultural adjustment, organizational commitment, and job satisfaction

The purpose of this study was to investigate the relationship between organizational learning and expatriation in overseas subsidiaries as well as in organizations as a whole. In doing so, two issues were addressed--(i) the use of expatriation as firms internationalize, and (ii) the significance of various factors to expatriate success as firms gain international experience. The sample of companies for this study was drawn from U.S. Fortune 500 multinational corporations (MNCs) in two sets of related industries--computers/electronics and petroleum/chemicals. Based on the learning that takes place within organizations as they increase their involvement overseas, a positive relationship was expected between international experience and expatriation when internationalization was low, and a negative relationship was expected when internationalization was high. Results indicate a significant positive relationship between country experience and the proportion of expatriates in that subsidiary when subsidiaries were relatively young, and a negative relationship, however not significant, for more mature subsidiaries. The relationship between overall firm degree of internationalization (DOI) and the proportion of expatriates in the firm as a whole was negative regardless of stage of internationalization, but this relationship was significant only for highly internationalized firms. It was further suspected that individual, environmental, and family-related characteristics would have a significant effect on the success of expatriates whose firms were low on internationalization, and that organizational characteristics would play a significant role in highly internationalized firms. Support for these hypotheses was received with respect to certain outcomes and some determinants of success. The preponderance of support was found for those addressing the effects of both environmental and family-related characteristics on the cross-cultural adjustment of expatriates in firms with little international experience. Considerable support was also found for those hypotheses addressing the impact of organizational characteristics on the job satisfaction levels of expatriates assigned to mature subsidiaries. The relevant literatures on organizational learning and expatriation are reviewed, and a model is developed underlying the logic of the hypotheses. Research methods are then described in full detail, results are reported, and implications for theory and for management are discussed. ^

Invasion success and development of benthic assemblages: effect of timing, duration of submersion and substrate type

Copyright © 2013 Elsevier Ltd. All rights reserved.

Predictors of student success: a study of Portuguese Higher Education graduates

Work Projected presented in the context of a Directed Research Internship at the Directorate-General of Statistics of the Portuguese Ministry of Education, and as part of the requirements for the Award of a Masters Degree in Economics from the NOVA - School of Business and Economics

The success of worksite nutrition and physical activity interventions with environmental modifications A systematic review

Background: As obesity increases among U.S. workers, employers are implementing programs to increase physical activity and improve diets. Although programs to address individual determinants of obesity have been evaluated, less is known about the effects of workplace programs that change environmental factors, because most reviews have not isolated environmental programs; the one that did was published in 2005. ^ Objective: To update the 2005 review to determine the effectiveness of workplace environmental interventions. ^ Methods: The Medline database was searched for published English language reports (2003-2011) of randomized controlled (RCTs) or quasi-experimental trials (NRCTs) that evaluated strategies to modify physical activity opportunities or food services, targeting employees at least 18 years, not including retirees and that provided data for at least one physical activity, dietary, or health risk indicator. Three coders independently extracted study characteristics and scored the quality of study methods. Program effectiveness was determined using the 2005 review's best evidence approach. ^ Results: Seven studies represented in nine reports met eligibility criteria; three focused on diet and the remainder targeted diet and physical activity interventions. All but one study received a high quality score for internal validity. The evidence for the effectiveness of workplace environmental interventions was at best, inconclusive for diet and physical activity and limited for health risk indicators. The outcome constructs were inconsistent across the studies. ^ Conclusions: Limitations in the methods of the 2005 review made it challenging to draw conclusions about findings for this review that include: variation in outcome measures, reliance on distal measures without proximal behavior change measures, no distinction between changes at the workplace versus outside the workplace, and inappropriate analyses of cluster designs that biased findings toward statistical significance. The best evidence approach relied on vote-counting, using statistical significance alone rather than effect size and confidence intervals. Future research should address these limitations and use more rigorous methods; systematic reviews should use methods of meta-analysis to summarize study findings. These recommendations will help employers to better understand how environmental modifications in the workplace can support their efforts to combat the effects of obesity among employees.^

The effects of required/sequenced preparatory courses on academic success and retention at a community college

This dissertation had two purposes: first, to analyze how required sequenced college preparatory courses in mathematics, reading, and writing affect students' academic success and, second, to add to a theoretical model for predicting student retention at a community college. Grade point average, number of degree credits earned, and re-enrollment rate were measured as determinants of academic success. The treatment group had a significantly higher grade point average than the control group. There was no significant difference in the number of degree credits earned or re-enrollment rate for the groups. A series of logistic regressions used the independent variables E-ASSET scores in math, reading, and writing; number of college prep areas required; credits earned; grade point average; students' status; academic restrictions/required course sequencing; sex; race; and socio-economic status to determine the predictor variables for retention. The academic variable that showed the greatest potential as a predictor for retention was grade point average. Overall, receiving financial aid was the greatest predictor for re-enrollment. For a financial aid recipient the odds of re-enrollment were 2.70 times more likely than if no financial aid was received.

The effects of required/sequenced preparatory courses on academic success and retention at a community college

This dissertation had two purposes: first, to analyze how required sequenced college preparatory courses in mathematics, reading, and writing affect students' academic success and, second, to add to a theoretical model for predicting student retention at a community college. Grade point average, number of degree credits earned, and reenrollment rate were measured as determinants of academic success. The treatment group had a significantly higher grade point average than the control group. There was no significant difference in the number of degree credits earned or re-enrollment rate for the groups. A series of logistic regressions used the independent variables E-ASSET scores in math, reading, and writing; number of college prep areas required; credits earned; grade point average; students' status; academic restrictions/required course sequencing; sex; race; and socio-economic status to determine the predictor variables for retention. The academic variable that showed the greatest potential as a predictor for retention was grade point average. Overall, receiving financial aid was the greatest predictor for reenrollment. For a financial aid recipient the odds of reenrollment were 2.70 times more likely than if no financial aid was received.

Long-term Success of Family Firms: Investigating Specific Aspects of Firm-level Entrepreneurship and Individual-level Antecedents

Long-term success of family firms is of utmost social and economic importance. Three of its determinants are in the center of this Dissertation: firmlevel entrepreneurial orientation (EO), managers' entrepreneurial behavior, and value-creating attitudes of non-family employees. Each determinant and respective research gaps are addressed by one paper of this cumulative dissertation. Referring to firm-level EO, scholars claim that EO is a main antecedent to firms' both short- and long-term success. However, family firms seem to be successful across generations despite rather low levels of EO. The first paper addresses this paradox by investigating EO patterns of long-lived family firms in three Swiss case studies. The main finding is that the key to success is not to be as entrepreneurially as possible all the time, but to continuously adapt the EO profile depending on internal and external factors. Moreover, the paper suggest new subcategories to different EO dimensions. With regard to entrepreneurial behavior of managers, there is a lack of knowledge how individual-level and organizational level factors affect its evolvement. The second paper addresses this gap by investigating a sample of 403 middle-level managers from both family and non-family firms. It introduces psychological ownership of managers as individual-level antecedent and investigates the interaction with organizational factors. As a central insight, management support is found to strengthen the psychological ownership-entrepreneurial behavior relationship. The third paper is based on the fact that employees' justice perceptions are established antecedents of value-creating employee attitudes such as affective commitment and job satisfaction. Even though family firms are susceptible to nonfamily employees´ perceptions of injustice, corresponding research is scarce. Moreover, the mechanism connecting justice perceptions and positive outcomes is still unclear. Addressing these gaps, the analysis of a sample of 310 non-family employees reveals that psychological ownership is a mediator in the relationships between distributive justice perceptions and both affective commitment and job satisfaction. Altogether, the three papers offer valuable contributions to family business literature with respect to EO, entrepreneurial behavior, and value-creating employee attitudes. Thus, they increase current understanding about important determinants of family firms' long-term success, while opening up numerous ways of future research.

Shared structural determinants for the calcium-independent liposome membrane permeabilization and sarcolemma depolarization in Bothropstoxin-I, a LYS49-PLA(2) from the venom of Bothrops jararacussu

The structural determinants of myotoxicity of bothropstoxin-I (BthTX-I), a Lys49 phospholipase A(2) from Bothrops jararacussu venom, were studied by measuring the resting membrane potential in the mouse phrenic nerve-diaphragm preparation. This method proved to be around 100-fold more sensitive than the creatine kinase release assay, and was used to evaluate a total of 31 site-directed BthTX-I alanine scanning mutants. Mutants that reduced the resting membrane potential were located in a surface patch defined by residues in the C-terminal loop (residues 115-129), positions 37-39 in the membrane interfacial recognition surface (Y46 and K54), and residue K93. These results expand the known structural determinants of the biological activity as evaluated by previous creatine kinase release experiments. Furthermore, a strong correlation is observed between the structural determinants of sarcolemma depolarization and calcium-independent disruption of liposome membranes, suggesting that a common mechanism of action underlies the permeabilization of the biological and model membranes. (C) 2009 Elsevier Ltd. All rights reserved.

Promoting Success in the Introduction of Health Information Systems

The significant number of publications describing unsuccessful cases in the introduction of health information systems makes it advisable to analyze the factors that may be contributing to such failures. However, the very notion of success is not equally assumed in all publications. Based in a literature review, the authors argue that the introduction of systems must be based in an eclectic combination of knowledge fields, adopting methodologies that strengthen the role of organizational culture and human resources in this project, as a whole. On the other hand, the authors argue that the introduction of systems should be oriented by a previously defined matrix of factors, against which the success can be measured.