Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential induction of prehepatic and hepatic metabolism of verapamil by rifampin

Cytochrome P450 (CYP) enzymes, which metabolize numerous drugs, are expressed both in liver and in extrahepatic tissues. CYP3A4 for example is present and inducible by rifampin in epithelial cells of the gastrointestinal tract. It has been shown that such prehepatic metabolism contributes substantially to total clearance of CYP3A4 substrates (e.g., cyclosporine) before and even more pronounced during enzyme induction. We examined the effect of enzyme induction on prehepatic and hepatic metabolism of the model compound R/S‐verapamil after simultaneous oral and intravenous administration using a stable isotope technology. This approach allows us to exclude intraindividual day‐to‐day variability and is therefore suitable to quantitatively assess prehepatic extraction of high‐clearance drugs. Moreover, because verapamil is administered as a race‐mate with the S‐enantiomer being preferentially metabolized, we investigated the influence of induction on stereoselectivity of prehepatic and hepatic metabolism. Eight male volunteers received 120 mg of racemic verapamil bid for 24 days. Rifampin (600 mg daily) was given from day 5 to day 16. Systemic clearance and bioavailability of the verapamil enantiomers were determined by coadministering deuterated verapamil intravenously on day 4, on day 16, and on day 24. Effects of verapamil on atrioventricular conduction after oral and intravenous (iv) administration were assessed by measuring the maximum PR‐interval prolongation Rifampin increased the systemic clearance of the active S‐verapamil 1.3‐fold (P < .001). In contrast, rifampin increased the apparent oral clearance of S‐ verapamil 32‐fold (P < .001) and decreased its bioavailability 25‐fold (P < .001), with partial recovery after rifampin withdrawal (P < .01). With rifampin, the effect of oral verapamil on atrioventricular conduction was nearly abolished (P < .01), whereas no significant changes were observed after intravenous administration. Induction caused a considerable reduction of stereoselectivity after both intravenous and oral administration (P < .001). Rifampin altered the pharmacokinetics and the pharmacological effects of verapamil to a much greater extent after oral administration compared with intravenous administration. These data clearly indicate that prehepatic metabolism of verapamil (presumably in the gut wall) is preferentially induced compared with hepatic metabolism and that stereoselectivity of verapamil metabolism is affected by induction.
What Determines Long-Run Macroeconomic Stability? Democratic Institutions

We examine the deep determinants of long-run macroeconomic stability in a cross-country framework. We find that conflict, openness, and democratic political institutions have a strong and statistically significant causal impact on macroeconomic stability. Surprisingly the most robust relationship of the three is for democratic institutions. A one standard deviation increase in democracy can reduce nominal instability nearly fourfold. This impact is robust to alternative measures of democracy, samples, covariates, and definitions of conflict. It is particularly noteworthy that a variety of nominal pathologies discussed in the recent macroeconomic literature, such as procyclical policy, original sin, and debt intolerance, have common origins in weak democratic institutions. We also find evidence that democratic institutions both strongly influence monetary policy and have a strong, independent positive effect on stability after controlling for various policy variables.
Slope heuristics and V-Fold model selection in heteroscedastic regression using strongly localized bases

We investigate the optimality for model selection of the so-called slope heuristics, $V$-fold cross-validation and $V$-fold penalization in a heteroscedastic with random design regression context. We consider a new class of linear models that we call strongly localized bases and that generalize histograms, piecewise polynomials and compactly supported wavelets. We derive sharp oracle inequalities that prove the asymptotic optimality of the slope heuristics---when the optimal penalty shape is known---and $V$ -fold penalization. Furthermore, $V$-fold cross-validation seems to be suboptimal for a fixed value of $V$ since it recovers asymptotically the oracle learned from a sample size equal to $1-V^{-1}$ of the original amount of data. Our results are based on genuine concentration inequalities for the true and empirical excess risks that are of independent interest. We show in our experiments the good behavior of the slope heuristics for the selection of linear wavelet models. Furthermore, $V$-fold cross-validation and $V$-fold penalization have comparable efficiency.
Predicting Entrepreneurial Performance: Can Legitimacy Help?

Entrepreneurial organizations are “opaque” regarding the information necessary to evaluate the likelihood of their survival (Rutherford, Buller, & Stebbins, 2009). Compared to publicly traded corporations, there is little information available to individuals when making judgments about private entrepreneurial organizations. To overcome this problem, entrepreneurs should strive to establish themselves as legitimate organizations in the eyes their stakeholders. Here, legitimacy serves as an evaluative tool, analogous to bond ratings. With AAA rated bonds, there is no guarantee the bonds will not decrease in value but the rating does show that there is a consensus that they are of highest quality. The same can be said of entrepreneurs that are perceived to be legitimate by their stakeholders. This study tests whether this legitimacy manifests itself as financial performance.
Capacity building needs of poultry farmers for quail production in Kwara State, Nigeria

This paper investigated the capacity building needs of poultry farmers for quail production in Kwara State, Nigeria. A questionnaire was used to elicit information from 80 randomly sampled poultry farmers from the Poultry Association of Nigeria, Kwara State Chapter. The findings revealed that the majority (70.0%) of the poultry farmers were male with a mean age of 44 years, married (75.0%) and formally educated (98.75%). The poultry farmers were mostly (78.75%) small-scale producers rearing less than or equal to 500 birds on their farms. Capacity building was highly needed for quail husbandry and management practices, feeding and nutrition, housing and equipment, processing and marketing of products, among others. Seven challenges were identified by the poultry farmers as severe challenges militating against the diversification of their poultry enterprise to include quail production. Chi-square analysis revealed a significant relationship between the poultry farmers’ capacity building needs for quail production and their age (X2 = 5.545), educational level (X2 = 11.859) and years of farming experience (X2 = 9.604). It was recommended that extension agencies should package a robust training programme for poultry farmers on the areas of capacity deficiencies indicated for quail production. Key words: capacity building needs, poultry farmers, quail production, Kwara State, Nigeria.
Revisiting the applicability of porter’s model to the portuguese manufacturing : a departure from traditional strategies

The purpose of this paper is to analyze the strategies utilized in the Portuguese manufacturing environ-ment, and to compare the results with those of a similar study conducted in 1993. Self-administered surveys were employed and a total sample of 229 firms were used for the analysis. The responses were factor analyzed to establish patterns of strategic behaviours. In comparison with 1993, today’s Portuguese manu-facturing firms are using more product development and innovation in order to offer many new customized products to different markets. In most cases, they are capitalizing on flexible manufacturing to achieve more depth and breadth in their product lines. Classification- JEL:
Mitochondrial abnormalities in patients with LHON-like optic neuropathies.

PURPOSE To investigate certain biochemical and molecular characteristics of mitochondria in patients with Leber hereditary optic neuropathy (LHON)-like optic neuropathies. METHODS Patients who had LHON-like optic neuropathies in both eyes were selected from neuro-ophthalmology clinics. Evaluation included clinical examination, neuroimaging, and assessment of several mitochondrial parameters in the blood, including sequencing the entire mitochondrial (mt)DNA coding region, measuring relative mtDNA content, studying mitochondrial respiratory function in some patients, and sequencing the OPA1 and OPA3 genes. RESULTS Thirty-five patients (21 men and 14 women; average age at onset 19.0 +/- 8.7 years) met inclusion and exclusion criteria for LHON-like optic neuropathies with median visual acuity approximately 20/200. Other hereditary retinopathies and optic neuropathies were unlikely because of inclusion and exclusion criteria, because ERGs were normal, and because no patient had pathogenic sequence changes in the OPA1 or OPA3 genes. Compared with control subjects, these patients had more potentially pathogenic nonsynonymous mtDNA changes, greater relative mtDNA content (P < 0.001), and less mitochondrial respiratory activity (P < 0.001). Only six patients (17%) had primary LHON mutations; however, even the 29 patients without primary LHON mutations had significant evidence of mitochondrial abnormalities. Mitochondrial haplogroup distribution was similar in patients and control subjects. CONCLUSIONS Primary LHON mutations are less common in patients with LHON-like optic neuropathy selected from a clinical setting than in patients with LHON from multigenerational families. The results suggest that mitochondrial dysfunction plays a role in this type of optic neuropathy whether or not primary LHON mutations are present. This information has implications for diagnostic testing and for future investigations into mechanisms of disease.
Who needs experts most?board industry expertise and strategic change—a contingency perspective

Research summary: We analyze the effects of board industry expertise on corporate strategic change and the moderating role of institutional quality. We suggest that country‐level contingency factors mitigate the effect of experienced boards on strategy formation by providing alternative sources of information and control in strategic matters. We develop institutional quality as institutional information provision and institutional control provision to test our hypotheses on a sample of firms from MSCI Europe and the S&P 500. Our findings confirm that industry expertise is a salient driver of strategic change across countries. The strength of the effect, however, depends on the institutional quality. We submit that weak institutions require greater board industry expertise as an alternative channel of information and control. Management summary: This study provides new empirical evidence that experience in the firms' industries enables directors to increase strategic change. Our findings show that this effect is even stronger in countries with weak regulatory environments. We hereby provide guidance for multiple stakeholders. First, shareholders seeking a more active adjustment of their firms' strategies may want to compose boards that leverage such experienced directors. Second, directors can use their industry experience to control and to challenge managers better to move beyond the status quo. Third, managers lacking access to information on potential strategic change can use such experienced directors for strategic advice and as a source of information. Overall, we add to the understanding of the corporate board's role in shaping strategy and the influence of weak regulations. Copyright © 2016 John Wiley & Sons, Ltd.
Optimized allergen extracts and recombinant allergens in diagnostic applications

Due to inherent enzyme activities and other factors, allergen extracts from fruits, vegetables and other plant foods often lack sufficient biological activity (1–4). This lability also leads to consistency problems with different lots of commercial extracts, or to large variations between extracts from different manufacturers. In certain cases, special extraction procedures are required to obtain extracts that are suitable for in vitro an in vivo diagnosis (4–6). Although this problem has been known for more than 20 years (7), this article will show that some problems still need to be solved. In general, allergen extracts from plant materials contain many glycoproteins with N-linked glycans that bind IgE in a subgroup of patients sensitized to pollen and food. Some authors think that these IgE responses are clinically irrelevant (8, 9), whereas others have shown that IgE responses specific for these so-called crossreactive carbohydrate determinants (CCD) are frequently present in patients with adverse reactions to certain foods, and can be the unique detectable IgE response to these foods in such patients (10–12). Whether or not anti-glycan IgE is able to trigger allergic symptoms still needs to be answered. However, specific IgE responses in allergic patients are undoubtedly linked to the pathomechanism of the disease and should be taken into consideration. Diagnostic tools to pick up anti-CCD antibodies have been developed (10, 11) and are useful to highlight whether IgE reactivity to an allergen extract is caused by protein allergens or by carbohydrate moieties. In this context, recombinant food allergens produced in bacteria that completely lack N-glycosylations may not only be useful to capture anti-protein IgE responses, but also to proceed from an extract-specific diagnosis to a component-resolved diagnosis (13). This has been achieved with inhalant allergens, including complex systems such as grass pollen (14), and initial studies have been published for foods such as peanut (15) and pear (13). Componentresolved diagnosis may also offer the opportunity to distinguish between IgE directed against ‘‘mild’’ and ‘‘severe’’ food allergens (9). In principle, the panel of recombinant or purified natural allergens used to replace the extract should be as complete as possible, and the recombinant compounds should closely resemble the IgE reactivity of their natural homologues. Here we report examples selected from the area of pollenrelated food allergy that address the potential of optimized allergen extracts and recombinant allergens in the determination of food-specific IgE antibodies.
The service recovery paradox: true but overrated?

Purpose – The paper's aim is to test the existence of the service recovery paradox.Design/methodology/approach – To date, much of the literature exploring the service recovery paradox has generated mixed results. The paper argues that a service recovery paradox is a rare event, which makes its measurement difficult, since the “treatment group” sample size is usually too small to produce significant results. For that reason, the existence of the service recovery paradox in a banking context with more than 11,000 customer interviews based on actual customer encounters is tested.Findings – Overall, the survey findings support the argument that a service recovery paradox is a rare event, and the hypothesized mean differences are, albeit significant, not very large, which diminishes their managerial relevance to some degree.Research limitations/implications – Because of the required extremely large sample size, no multi‐item measures were collected. Furthermore, privacy concerns restricted us from a longitudin.
Dissipationless clustering of neutrinos around a cosmic-string loop.

The dissipationless clustering of weakly interacting massive neutrinos about a nonadiabatic pointlike seed perturbation (e.g., a cosmic-string loop) is studied. The clustering is described by the Liouville equation in an expanding universe which can be transformed into an integral equation for the density perturbation in Fourier space (the Gilbert equation). The analysis yields an accurate determination of the density profile about a seed, and a value for the maximal effective Jeans length 8h/sub 50/ /sup -2/ Mpc, where h/sub 50/ is the expansion rate in units of 50 km s/sup -1/ Mpc/sup -1/.
Short Selling, Regulatory Flip/Flops and Uncertainty: Implications for Asset Pricing and Asset Allocation

After seventy years with no changes to short sale regulation, the United States Securities and Exchange Commission intervened three times with regulatory action from July 2007 through October 2008. The Commission first loosened restrictions on short sales by repealing the “Uptick Rule” in July 2007. Then, amidst declining markets of July of 2008 and heightened uncertainty, the SEC issued a temporary order to restrict naked short sales in a small set of financial stocks, letting the order expire shortly thereafter. Just a month later, in September 2008, the SEC again intervened with an order restricting naked shorting in all stocks, and temporarily banning short sales in a large set of financial stocks. While classical models make predictions about how stock prices react to short sale constraints, they offer little insight into how regulatory changes and regulatory uncertainty about short sales affect the wider market. In this paper we investigate the spillover effect of the SEC regulatory flip flops on the U.S. market as a whole by examining the impact of changes from the perspectives of asset pricing and asset allocation. We find that all three regulatory changes significantly impact risk premia, with impacts differing across priced factors. We discover, however, that the welfare cost on out of sample returns for a broad equity long only investor is less clear cut, ranging from no impact for the first two regulatory actions to a significant daily loss from the September 2008 ban depending on the portfolio strategy employed.
Corporate Governance in Taiwan: A Survey

Asian economies began focusing on corporate governance regulation reform following the Asian financial crisis of 1997-98. After 2002, Taiwan’s government promulgated a series of corporate governance reforms to enhance the quality of governance. In this paper, we first review the regional context of Asian corporate governance issues, namely ownership structure, internal and external mechanisms and several other specific topics. This is then extended to the Taiwanese corporate governance framework. This survey not only seeks to understand the implementation of corporate governance regulations and innovation in Taiwan; it also serves as a reference point for future studies into this and related issues.
Erythropoietin and Erythropoietin Receptor Expression after Experimental Spinal Cord Injury Encourages Therapy by Exogenous Erythropoietin

OBJECTIVE:Erythropoietin (EPO) is a pleiotropic cytokine originally identified for its role in erythropoiesis. Recent studies have demonstrated that EPO and its receptor (EPO-R) are expressed in the central nervous system, where EPO exerts neuroprotective functions. Because the expression of the EPO and EPO-R network is poorly investigated in the central nervous system, the aim of the present study was to investigate whether the resident EPO and EPO-R network is activated in the injured nervous system. METHODS:A well-standardized model of compressive spinal cord injury in rats was used. EPO and EPO-R expression was determined by immunohistochemical analysis at 8 hours and at 2, 8, and 14 days in the spinal cord of injured and noninjured rats. RESULTS:In noninjured spinal cord, weak immunohistochemical expression of EPO and EPO-R was observed in neuronal and glial cells as well as in endothelial and ependymal cells. In injured rats, a marked increase of expression of EPO and EPO-R was observed in neurons, vascular endothelium, and glial cells at 8 hours after injury, peaking at 8 days, after which it gradually decreased. Two weeks after injury, EPO immunoreactivity was scarcely detected in neurons, whereas glial cells and vascular endothelium expressed strong EPO-R immunoreactivity. CONCLUSION:These observations suggest that the local EPO and EPO-R system is markedly engaged in the early stages after nervous tissue injury. The reduction in EPO immunoexpression and the increase in EPO-R staining strongly support the possible usefulness of a therapeutic approach based on exogenous EPO administration.
The effects of nonprofit brand equity on individual giving intention: mediating by the self-concept of individual donor

Currently nonprofit organizations have to rely more on individual donors and less on the government for funding. Therefore, understanding the individual donor from the perspective of nonprofit has been of increasing interest to nonprofit marketers. In this research, the effects of nonprofit organizational brand equity and individual self-concept on individual giving intention were studied by using survey to selected 393 valid respondents in China. The empirical results indicated that, (1) the three dimensions brand personality, brand image, and brand awareness of the nonprofit organization has positive direct impact on individual giving intention; (2) brand personality and brand awareness of the nonprofit organization has positive direct impact on the self-concept of individual donor; (3) the self-concept of individual donor has positive direct impact on individual giving intention; and (4) the self-concept of individual donor mediates significantly the relationships between brand personality, brand awareness, and individual giving intention, while not significantly between brand image and individual giving intention. Copyright © 2009 John Wiley & Sons, Ltd.
Firm entry and post-entry performance in selected Norwegian industries

This working paper provides some descriptive statistics concerning patterns of firm entry in selected Norwegian industries over the time period 1997-2005. The direct history of the employees in newborn firms and of the recently employed employees in established firms is used in order to compare the recruitment sources of newborn and established firms. Finally, some simple econometric analysis is performed and used as a tool for describing the importance of different determinants of post-entry survival and success of newborn firms.
A STUDY ON THE IMPACT OF INFORMATION AND COMMUNICATION TECHNOLOGY ON URBAN LOGISTICS SYSTEM: A CASE IN METRO MANILA

This study examined the impact of Information and Communication technology (ICT) on urban logistics system in Metro Manila. This was done by conducting a survey to 114 companies with focus on ICT logistics users on their use of ICT by getting the types of ICT use, the application areas, the barriers and future applications from ICT use by the private sectors. One of the major findings of the research is the impact level on ICT use by private firms in Metro Manila which falls into moderate impact and majority of the tested variables showed that no significant differences on the level of impacts on ICT use between firm types and sizes. Government perception and awareness was also considered to know if there are existing policies and initiatives that focus on monitoring the use of ICT in logistics. Case study of innovative ICT transport/logistic user was done to develop insights into how the technology impacts operational relations in the logistics chain and how technology can leverage operations management in a synergistic manner.