Efficient HIV-1 inhibition by a 16 nt-long RNA aptamer designed by combining in vitro selection and in silico optimisation strategies

The human immunodeficiency virus type-1 (HIV-1) genome contains multiple, highly conserved structural RNA domains that play key roles in essential viral processes. Interference with the function of these RNA domains either by disrupting their structures or by blocking their interaction with viral or cellular factors may seriously compromise HIV-1 viability. RNA aptamers are amongst the most promising synthetic molecules able to interact with structural domains of viral genomes. However, aptamer shortening up to their minimal active domain is usually necessary for scaling up production, what requires very time-consuming, trial-and-error approaches. Here we report on the in vitro selection of 64 nt-long specific aptamers against the complete 5' -untranslated region of HIV-1 genome, which inhibit more than 75% of HIV-1 production in a human cell line. The analysis of the selected sequences and structures allowed for the identification of a highly conserved 16 nt-long stem-loop motif containing a common 8 nt-long apical loop. Based on this result, an in silico designed 16 nt-long RNA aptamer, termed RNApt16, was synthesized, with sequence 5'-CCCCGGCAAGGAGGGG-3-'. The HIV-1 inhibition efficiency of such an aptamer was close to 85%, thus constituting the shortest RNA molecule so far described that efficiently interferes with HIV-1 replication.

Large-volume metrology instrument selection and measurability analysis

A wide range of metrology processes are involved in the manufacture of large products. In addition to the traditional tool-setting and product-verification operations, increasingly flexible metrology-enabled automation is also being used. Faced with many possible measurement problems and a very large number of metrology instruments employing diverse technologies, the selection of the appropriate instrument for a given task can be highly complex. Also, as metrology has become a key manufacturing process, it should be considered in the early stages of design, and there is currently very little research to support this. This paper provides an overview of the important selection criteria for typical measurement processes and presents some novel selection strategies. Metrics that can be used to assess measurability are also discussed. A prototype instrument selection and measurability analysis application is also presented, with discussion of how this can be used as the basis for development of a more sophisticated measurement planning tool. © 2010 Authors.

An investigation into the adoption and implementation of electronic commerce in Saudi Arabian small and medium enterprises

Saudi Arabian Small and Medium Enterprises (SMEs) will face fierce competition from new entrants to local markets as a result of their accession to the Word Trade Organisation (WTO), and electronic commerce (e-commerce) technologies can reinforce SME's competitive edge. This study investigates the state of e-commerce adoption and analyses the factors that determine the extent to which SMEs in Saudi Arabia are inclined towards deploying e-commerce technologies. This could assist future firms in designing effective implementation projects. Seven SMEs' e-commerce adoption levels are studied as a case. The Technology-Organization-Environment (TOE) framework was used as the major source of inspiration in our analysis of e-commerce adoption amongst Saudi SMEs. In addition to advancing research on e-commerce in Saudi Arabia, this chapter also highlights several directions for future inquiry and implications for managers and policymakers.

The risk of adverse selection and its management in the process of venture capital investment (The experience of Hungarian investors)

Venture capitalists can be regarded as financers of young, high-risk enterprises, seeking investments with a high growth potential and offering professional support above and beyond their capital investment. The aim of this study is to analyse the occurrence of information asymmetry between venture capital investors and entrepreneurs, with special regard to the problem of adverse selection. In the course of my empirical research, I conducted in-depth interviews with 10 venture capital investors. The aim of the research was to elicit their opinions about the situation regarding information asymmetry, how they deal with problems arising from adverse selection, and what measures they take to manage these within the investment process. In the interviews we also touched upon how investors evaluate state intervention, and how much they believe company managers are influenced by state support.

International stock portfolio selection and performance measures recognizing higher moments of return distributions

Since the seminal works of Markowitz (1952), Sharpe (1964), and Lintner (1965), numerous studies on portfolio selection and performance measure have been based upon the mean-variance framework. However, several researchers (e.g., Arditti (1967, and 1971), Samuelson (1970), and Rubinstein (1973)) argue that the higher moments cannot be neglected unless there is reason to believe that: (i) the asset returns are normally distributed and the investor's utility function is quadratic, or (ii) the empirical evidence demonstrates that higher moments are irrelevant to the investor's decision. Based on the same argument, this dissertation investigates the impact of higher moments of return distributions on three issues concerning the 14 international stock markets.^ First, the portfolio selection with skewness is determined using: the Polynomial Goal Programming in which investor preferences for skewness can be incorporated. The empirical findings suggest that the return distributions of international stock markets are not normally distributed, and that the incorporation of skewness into an investor's portfolio decision causes a major change in the construction of his optimal portfolio. The evidence also indicates that an investor will trade expected return of the portfolio for skewness. Moreover, when short sales are allowed, investors are better off as they attain higher expected return and skewness simultaneously.^ Second, the performance of international stock markets are evaluated using two types of performance measures: (i) the two-moment performance measures of Sharpe (1966), and Treynor (1965), and (ii) the higher-moment performance measures of Prakash and Bear (1986), and Stephens and Proffitt (1991). The empirical evidence indicates that higher moments of return distributions are significant and relevant to the investor's decision. Thus, the higher moment performance measures should be more appropriate to evaluate the performances of international stock markets. The evidence also indicates that various measures provide a vastly different performance ranking of the markets, albeit in the same direction.^ Finally, the inter-temporal stability of the international stock markets is investigated using the Parhizgari and Prakash (1989) algorithm for the Sen and Puri (1968) test which accounts for non-normality of return distributions. The empirical finding indicates that there is strong evidence to support the stability in international stock market movements. However, when the Anderson test which assumes normality of return distributions is employed, the stability in the correlation structure is rejected. This suggests that the non-normality of the return distribution is an important factor that cannot be ignored in the investigation of inter-temporal stability of international stock markets. ^

Development and implementation of a tool to assess the micro/macro elements in an organization

This study examines the congruency of planning between organizational structure and process, through an evaluation and planning model known as the Micro/Macro Dynamic Planning Grid. The model compares day-to-day planning within an organization to planning imposed by organizational administration and accrediting agencies. A survey instrument was developed to assess the micro and macro sociological analysis elements utilized by an organization.^ The Micro/Macro Dynamic Planning Grid consists of four quadrants. Each quadrant contains characteristics that reflect the interaction between the micro and macro elements of planning, objectives and goals within an organization. The Over Macro/Over Micro, Quadrant 1, contains attributes that reflect a tremendous amount of action and ongoing adjustments, typical of an organization undergoing significant changes in either leadership, program and/or structure. Over Macro/Under Micro, Quadrant 2, reflects planning characteristics found in large, bureaucratic systems with little regard given to the workings of their component parts. Under Macro/Under Micro, Quadrant 3, reflects the uncooperative, uncoordinated organization, one that contains a multiplicity of viewpoints, language, objectives and goals. Under Macro/Under Micro, Quadrant 4 represents the worst case scenario for any organization. The attributes of this quadrant are very reactive, chaotic, non-productive and redundant.^ There were three phases to the study: development of the initial instrument, pilot testing the initial instrument and item revision, and administration and assessment of the refined instrument. The survey instrument was found to be valid and reliable for the purposes and audiences herein described.^ In order to expand the applicability of the instrument to other organizational settings, the survey was administered to three professional colleges within a university.^ The first three specific research questions collectively answered, in the affirmative, the basic research question: Can the Micro/Macro Dynamic Planning Grid be applied to an organization through an organizational development tool? The first specific question: Can an instrument be constructed that applies the Micro/Macro Dynamic Planning Grid? The second specific research question: Is the constructed instrument valid and reliable? The third specific research question: Does an instrument that applies the Micro/Macro Dynamic Planning Grid assess congruency of micro and macro planning, goals and objectives within an organization? The fourth specific research question: What are the differences in the responses based on roles and responsibilities within an organization? involved statistical analysis of the response data and comparisons obtained with the demographic data. (Abstract shortened by UMI.) ^

Design and implementation of a multisite data repository for pediatric epilepsy

This dissertation established a software-hardware integrated design for a multisite data repository in pediatric epilepsy. A total of 16 institutions formed a consortium for this web-based application. This innovative fully operational web application allows users to upload and retrieve information through a unique human-computer graphical interface that is remotely accessible to all users of the consortium. A solution based on a Linux platform with My-SQL and Personal Home Page scripts (PHP) has been selected. Research was conducted to evaluate mechanisms to electronically transfer diverse datasets from different hospitals and collect the clinical data in concert with their related functional magnetic resonance imaging (fMRI). What was unique in the approach considered is that all pertinent clinical information about patients is synthesized with input from clinical experts into 4 different forms, which were: Clinical, fMRI scoring, Image information, and Neuropsychological data entry forms. A first contribution of this dissertation was in proposing an integrated processing platform that was site and scanner independent in order to uniformly process the varied fMRI datasets and to generate comparative brain activation patterns. The data collection from the consortium complied with the IRB requirements and provides all the safeguards for security and confidentiality requirements. An 1-MR1-based software library was used to perform data processing and statistical analysis to obtain the brain activation maps. Lateralization Index (LI) of healthy control (HC) subjects in contrast to localization-related epilepsy (LRE) subjects were evaluated. Over 110 activation maps were generated, and their respective LIs were computed yielding the following groups: (a) strong right lateralization: (HC=0%, LRE=18%), (b) right lateralization: (HC=2%, LRE=10%), (c) bilateral: (HC=20%, LRE=15%), (d) left lateralization: (HC=42%, LRE=26%), e) strong left lateralization: (HC=36%, LRE=31%). Moreover, nonlinear-multidimensional decision functions were used to seek an optimal separation between typical and atypical brain activations on the basis of the demographics as well as the extent and intensity of these brain activations. The intent was not to seek the highest output measures given the inherent overlap of the data, but rather to assess which of the many dimensions were critical in the overall assessment of typical and atypical language activations with the freedom to select any number of dimensions and impose any degree of complexity in the nonlinearity of the decision space.

Recruitment, Selection and Retention of Managers In the Hotel and Restaurant Industry

The recruitment, selection, and retention of competent, reliable, and motivated managers has been the cornerstone of any successful organization. This is generally a complex assignment due to the subjectivity involved in determining what traits are needed to make a good manager. In order to determine the status of the hospitality industry with regard to managerial concerns, leaders in the hotel and restaurant industry were surveyed on these issues.

Hospitality Information Systems: Intuitive, Object-Oriented, and Wireless Technology

Automated information system design and implementation is one of the fastest changing aspects of the hospitality industry. During the past several years nothing has increased the professionalism or improved the productivity within the industry more than the application of computer technology. Intuitive software applications, deemed the first step toward making computers more people-literate, object-oriented programming, intended to more accurately model reality, and wireless communications are expected to play a significant role in future technological advancement.

Selection and passage of county land preservation voter referendum: The role of government

County jurisdictions in America are increasingly exercising self-government in the provision of public community services through the context of second order federalism. In states exercising this form of contemporary governance, county governments with "reformed" policy-making structures and professional management practices, have begun to rival or surpass municipalities in the delivery of local services with regional implications such as environmental protection (Benton 2002, 2003; Marando and Reeves, 1993). ^ The voter referendum, a form of direct democracy, is an important component of county land preservation and environmental protection governmental policies. The recent growth and success of land preservation voter referendums nationwide reflects an increase in citizen participation in government and their desire to protect vacant land and its natural environment from threats of over-development, urbanization and sprawl, loss of open space and farmland, deterioration of ecosystems, and inadequate park and recreational amenities. ^ The study's design employs a sequential, mixed method. First, a quantitative approach employs the Heckman two-step model. It is fitted with variables for the non-random sample of 227 voter referendum counties and all non-voter referendum counties in the U.S. from 1988 to 2009. Second, the qualitative data collected from the in-depth investigation of three South Florida county case studies with twelve public administrator interviews is transformed for integration with the quantitative findings. The purpose of the qualitative method is to complement, explain and enrich the statistical analysis of county demographic, socio-economic, terrain, regional, governance and government, political preference, environmentalism, and referendum-specific factors. ^ The research finds that government factors are significant in terms of the success of land preservation voter referendums; more specifically, the presence of self-government authority (home rule charter), a reformed structure (county administrator/manager or elected executive), and environmental interest groups. In addition, this study concludes that successful counties are often located coastal, exhibit population and housing growth, and have older and more educated citizens who vote democratic in presidential elections. The analysis of case study documents and public administrator interviews finds that pragmatic considerations of timing, local politics and networking of regional stakeholders are also important features of success. Further research is suggested utilizing additional public participation, local government and public administration factors.^

The relationship between faculty perceptions and implementation of elements of transactional distance theory and online web-based course completion rates

The purpose of this study was to explore the relationship between faculty perceptions, selected demographics, implementation of elements of transactional distance theory and online web-based course completion rates. This theory posits that the high transactional distance of online courses makes it difficult for students to complete these courses successfully; too often this is associated with low completion rates. Faculty members play an indispensable role in course design, whether online or face-to-face. They also influence course delivery format from design through implementation and ultimately to how students will experience the course. This study used transactional distance theory as the conceptual framework to examine the relationship between teaching and learning strategies used by faculty members to help students complete online courses. Faculty members' sex, number of years teaching online at the college, and their online course completion rates were considered. A researcher-developed survey was used to collect data from 348 faculty members who teach online at two prominent colleges in the southeastern part of United States. An exploratory factor analysis resulted in six factors related to transactional distance theory. The factors accounted for slightly over 65% of the variance of transactional distance scores as measured by the survey instrument. Results provided support for Moore's (1993) theory of transactional distance. Female faculty members scored higher in all the factors of transactional distance theory when compared to men. Faculty number of years teaching online at the college level correlated significantly with all the elements of transactional distance theory. Regression analysis was used to determine that two of the factors, instructor interface and instructor-learner interaction, accounted for 12% of the variance in student online course completion rates. In conclusion, of the six factors found, the two with the highest percentage scores were instructor interface and instructor-learner interaction. This finding, while in alignment with the literature concerning the dialogue element of transactional distance theory, brings a special interest to the importance of instructor interface as a factor. Surprisingly, based on the reviewed literature on transactional distance theory, faculty perceptions concerning learner-learner interaction was not an important factor and there was no learner-content interaction factor.

AIDS workplace *policy adoption and implementation in local government: An analysis of departmental variation

This is an empirical study whose purpose was to examine the process of innovation adoption as an adaptive response by a public organization and its subunits existing under varying degrees of environmental uncertainty. Meshing organization innovation research and contingency theory to form a theoretical framework, an exploratory case study design was undertaken in a large, metropolitan government located in an area with the fourth highest prevalence rate of HIV/AIDS in the country. A number of environmental and organizational factors were examined for their influence upon decision making in the adoption/non-adoption as well as implementation of any number of AIDS-related policies, practices, and programs.^ The major findings of the study are as follows. For the county government itself (macro level), no AIDS-specific workplace policies have been adopted. AIDS activities (AIDS education, AIDS Task Force, AIDS Coordinator, etc.), adopted county-wide early in the epidemic, have all been abandoned. Worker infection rates, in the aggregate and throughout the epidemic have been small. As a result, absent co-worker conflict (isolated and negligible), no increase in employee health care costs, no litigation regarding discrimination, and no major impact on workforce productivity, AIDS has basically become a non-issue at the strategic core of the organization. At the departmental level, policy adoption decisions varied widely. Here the predominant issue is occupational risk, i.e., both objective as well as perceived. As expected, more AIDS-related activities (policies, practices, and programs) were found in departments with workers known to have significant risk for exposure to the AIDS virus (fire rescue, medical examiner, police, etc.). AIDS specific policies, in the form of OSHA's Bloodborn Pathogen Standard, took place primarily because they were legislatively mandated. Union participation varied widely, although not necessarily based upon worker risk. In several departments, the union was a primary factor bringing about adoption decisions. Additional factors were identified and included organizational presence of AIDS expertise, availability of slack resources, and the existence of a policy champion. Other variables, such as subunit size, centralization of decision making, and formalization were not consistent factors explaining adoption decisions. ^

Foreign-born CEOs, country-specific skills, selection, and strategic consequences

In this dissertation, I first suggest an extension of the managerial rents model and more specifically the managerial skills typology that it offers. Building on research in international business, I propose adding country-specific skills (CSS) to this typology in addition to firm-specific, industry-specific, and generic skills. I define CSS as managers' abilities that are applicable and specific to a particular national institutional context. Such skills are distinct from the other three types identified and are likely to influence managers' performance and the performance of their firms. So if CSS are distinct skills, what are the implications for strategy and international business research? In an attempt to respond to this question, I conduct two empirical essays in which I examine the implications of this refinement of the typology of managerial skills for CEO selection and firms' mergers and acquisitions (M&A;) strategy. In the first empirical essay, I puzzle at the fact that although CSS constitute a barrier to high-level executive mobility across countries, there have been a growing number of foreign-born CEOs being appointed across the globe. Why are these individuals being selected for the post of CEO? Using information on the appointment of foreign-born and national CEOs from 2005 to 2010 among global 500 companies, I show that internationalization pressures help explain their selection and that two types of firms are likely to appoint foreign leaders: highly internationalized firms and firms that are likely to internationalize. In the second empirical essay, I examine the strategic implications of country-specific skills. Employing the same sample as the one used in the first empirical essay, I demonstrate that given that their mindset is likely to be less focused on firms' home market, foreign-born CEOs may be prone to institute more changes in firms' cross-border M&A; strategy than their domestic counterparts. I also theorize on the moderating influence of CEOs' insiderness.