Miracle-dz/UniFAR-FTUs huggingface dataset:
Exaggerated Natriuresis in Experimental Hypertension 1

Abstract The exaggerated natriuretic response to intravenous isotonic saline volume expansion in conscious spontaneous hypertensive rats (SHR), compared to normotensive Wistar-Kyoto rats (WKY), is associated with an exaggerated inhibition of renal nerve activity. Following bilateral renal denervation, the natriuresis was significantly attenuated in SHR but unaffected in WKY. Thus, the exaggerated natriuretic response to intravenous isotonic saline in SHR is dependent on their enhanced inhibition of renal nerve activity. Conscious Dahl salt-sensitive rats, on either low or high salt diet, did not exhibit an exaggerated natriuretic response to intravenous isotonic saline volume expansion which may be explained by their known impairment of cardiopulmonary baroreceptor reflex mediated suppression of efferent sympathetic nerve activity during intravenous volume expansion. Conscious hypertensive DOCA-NaCl rats exhibited an exaggerated natriuretic response to oral but not to intravenous isotonic saline volume expansion, suggesting differences in gastrointestinal absorption of isotonic saline. It is concluded that enhanced inhibition of efferent renal sympathetic nerve activity via cardiopulmonary baroreceptor reflex activation contributes to the exaggerated natriuretic response to intravenous isotonic saline volume expansion in certain models of experimental hypertension.
PD 098059 Is a Specific Inhibitor of the Activation of Mitogen-activated Protein Kinase Kinase in Vitro and in Vivo(*)

PD 098059 has been shown previously to inhibit the dephosphorylated form of mitogen-activated protein kinase kinase-1 (MAPKK1) and a mutant MAPKK1(S217E,S221E), which has low levels of constitutive activity (Dudley, D. T., Pang, L., Decker, S. J., Bridges, A. J., and Saltiel, A. R.(1995) Proc. Natl. Acad. Sci. U. S. A. 92, 7686-7689). Here we report that PD 098059 does not inhibit Raf-activated MAPKK1 but that it prevents the activation of MAPKK1 by Raf or MEK kinase in vitro at concentrations (IC = 2-7 μM) similar to those concentrations that inhibit dephosphorylated MAPKK1 or MAPKK1(S217E,S221E). PD 098059 inhibited the activation of MAPKK2 by Raf with a much higher IC value (50 μM) and did not inhibit the phosphorylation of other Raf or MEK kinase substrates, indicating that it exerts its effect by binding to the inactive form of MAPKK1. PD 098059 also acts as a specific inhibitor of the activation of MAPKK in Swiss 3T3 cells, suppressing by 80-90% its activation by a variety of agonists. The high degree of specificity of PD 098059 in vitro and in vivo is indicated by its failure to inhibit 18 protein Ser/Thr kinases (including two other MAPKK homologues) in vitro by its failure to inhibit the in vivo activation of MAPKK and MAP kinase homologues that participate in stress and interleukin-1-stimulated kinase cascades in KB and PC12 cells, and by lack of inhibition of the activation of p70 S6 kinase by insulin or epidermal growth factor in Swiss 3T3 cells. PD 098059 (50 μM) inhibited the activation of p42 and isoforms of MAP kinase-activated protein kinase-1 in Swiss 3T3 cells, but the extent of inhibition depended on how potently c-Raf and MAPKK were activated by any particular agonist and demonstrated the enormous amplification potential of this kinase cascade. PD 098059 not only failed to inhibit the activation of Raf by platelet-derived growth factor, serum, insulin, and phorbol esters in Swiss 3T3 cells but actually enhanced Raf activity. The rate of activation of Raf by platelet-derived growth factor was increased 3-fold, and the subsequent inactivation that occurred after 10 min was prevented. These results indicate that the activation of Raf is suppressed and that its inactivation is accelerated by a downstream component(s) of the MAP kinase pathway.
Genetic selection of volunteers and concomitant dose adjustment leads to comparable hydralazine/valproate exposure

Hydralazine is an inhibitor of DNA methyltransferases, whereas valproate interferes with histone deacetylation. In combination, they show a marked synergism in reducing tumour growth as well as development of metastasis and inducing cell differentiation. Hydralazine is metabolized by the highly polymorphic N‐acetyltransferase 2. The current pilot study was performed to analyse the pharmacokinetic parameters of a single dose of hydralazine in 24 h (one tablet with 83 mg for slow acetylators and one tablet with 182 mg for fast acetylators) and three fixed doses of valproate (one tablet of controlled liberation with 700 mg every 8 h) in healthy genetically selected volunteers. Selection was performed based on their NAT2 activity as deduced from their genotype.
Other New Targets

Despite improvements in surgical and diagnostic techniques, the outcome for women with advanced epithelial ovarian cancer remains poor. Recent developments in the understanding of cancer biology have led to an explosion in clinical trials using targeted agents. In women with epithelial ovarian cancer, antiangiogenic agents have led the field. There are, however, other novel targets and agents undergoing evaluation. This review focuses on some of these newer approaches to targeted therapy highlighting the importance of trial design and incorporation of biomarkers as we move forward into the era of personalized medicine.
Cross-sectional age differences and longitudinal age changes of personality in middle adulthood and old age.

The present study examines different aspects of personality continuity (or change) in middle adulthood and old age both cross-sectionally and longitudinally. The sample comprised 445 middle-aged (42-46 years) and 420 older (60-64 years) participants, reassessed after a 4-year interval. Personality was measured using the NEO-FFI personality inventory. After having established strict factorial invariance, factor covariances were found to be equal for both age groups and at both testing occasions, indicating perfect structural continuity of personality. A number of age differences in personality emerged at both measurement occasions. Longitudinally, in both age groups, an average decline in Neuroticism was observed. Longitudinal stability coefficients were around . 80 in middle-aged and old participants, implying high, but not perfect, differential continuity. With respect to continuity of divergence, statistically significant cross-sectional age differences were found for the variance of Openness at both measurement occasions. Eventually, concerning specific versus general continuity, a variety of medium effect-sized correlated changes in the Big Five personality domains across the 4-year period was established, implying that personality changes share a certain amount of commonality.
Jobs for the Heartland: Place-Based Policies in 21st-Century America

ABSTRACT:The economic convergence of U.S. regions has slowed greatly, and rates of long-term nonemployment have even been diverging. Simultaneously, the rate of nonemployment for working age men has nearly tripled over the last 50 years, generating a social problem that is disproportionately centered in the eastern parts of the American heartland. Should more permanent economic divisions across space lead U.S. economists to rethink their traditional skepticism about place-based policies? We document that increases in labor demand appear to have greater effects on employment in areas where not working has been historically high, suggesting that subsidizing employment in such places could reduce the rate of not working. Proemployment policies, such as a ramped-up Earned Income Tax Credit, that are targeted toward regions with more elastic employment responses, however financed, could plausibly reduce suffering and materially improve economic performance.
The effects of corporate rebranding on customer satisfaction and loyalty: Empirical evidence from the Ghanaian banking industry

Abstract The study examined whether or not the rebranding activities in the Ghanaian banking industry, had any influence on customers’ perception on service quality, their level of satisfaction and their level of loyalty. These relationships were ascertained by running a moderation and linear regression analyses. The study identified that, rebranding had no statistically significant effect on perceived service quality, customer satisfaction and customer loyalty, in the Ghanaian banking industry. Rebranding had no moderating effect on the relationship between service quality and customer satisfaction. It also had no moderating effect on the relationship between service quality and customer loyalty. And finally, rebranding did not have a moderating effect on the relationship between customer satisfaction and customer loyalty. It was concluded that, rebranding activities in the Ghanaian banking industry had no significant effect on customers’ attitude towards the brand. Banks and other financial institutions must therefore be circumspect when it comes to investment in rebranding activities and be more interested in making investments that will positively influence the attitude of their customers.
Directors network centrality and earnings quality

ABSTRACT This study examines whether firms with network central boards of directors behave differently from other firms in terms of financial reporting quality. We find that earnings quality among firms is low when board networks are channels of incorrect information transmission (including earnings management information) and for firms whose directors are awarded equity-based compensation have connections through boardroom networks, but earnings quality is better for firms with good performance in spite of their networks. These results are robust to controlling for firm information environment, growth, size, age, leverage, performance, volatility in firm operations, and corporate governance.
Bilateral trade effects of fiscal devaluation: Evidence from OECD countries

ABSTRACT This paper empirically examines the effects of a fiscal devaluation on bilateral trade. To this end, employers’ social contribution (ESC) and value-added tax (VAT), which stand as the factors that represent typical fiscal devaluation, are embodied within the framework of a gravity model. Fixed effects vector decomposition (FEVD) technique is applied to the empirical models specified within this framework, employing panel data from 22 OECD countries over the 1980–2014 periods. The findings show that the effectiveness of the fiscal devaluation policy seems to alter with respect to how ESC and VAT are measured. Considering the fiscal devaluation policy implemented unilaterally, the policy turns out to be effective in nine countries in the sample.
Does Peer Review Identify the Best Papers? A Simulation Study of Editors, Reviewers, and the Scientific Publication Process

ABSTRACT How does the structure of the peer review process, which can vary among journals, influence the quality of papers published in a journal? This article studies multiple systems of peer review using computational simulation. I find that, under any of the systems I study, a majority of accepted papers are evaluated by an average reader as not meeting the standards of the journal. Moreover, all systems allow random chance to play a strong role in the acceptance decision. Heterogeneous reviewer and reader standards for scientific quality drive both results. A peer review system with an active editor—that is, one who uses desk rejection before review and does not rely strictly on reviewer votes to make decisions—can mitigate some of these effects.
Quantitative Detection of Borrelia burgdorferi in 2-Millimeter Skin Samples of Erythema Migrans Lesions: Correlation of Results with Clinical and Laboratory Findings

ABSTRACT Variability of disease manifestations has been noted in patients with Lyme disease. A contributing factor to this variation may be the number of spirochetes present in infected patients. We evaluated clinical and laboratory findings for patients with erythema migrans with regard to the number of Borrelia burgdorferi organisms detected by quantitative PCR (qPCR) in 2-mm skin biopsy specimens. B. burgdorferi was detected in 80% (40 of 50) of the specimens tested; the mean number of spirochetes in these specimens ranged over 3 orders of magnitude (10 to 11,000 spirochetes per 2-mm biopsy specimen). Larger numbers of spirochetes were significantly associated with a shorter duration of the erythema migrans skin lesion (P = 0.020), smaller skin lesions (P = 0.020), and infection with a specific genotype of B. burgdorferi (P = 0.008) but not with the number or severity of symptoms. Skin culture positivity was significantly associated with skin lesions containing larger numbers of spirochetes (P = 0.019).
Anti-Migration as a Threat to Internationalization?

Do anti-migration sentiments threaten internationalization? One major argument of the pro-Brexit campaign in the UK was that Brexit would allow greater control over immigration. The most recent US presidential election also focused on the issue of immigration. Anti-migration sentiments could constitute a threat to internationalization considering that migrants can help lower costs associated with internationalization. Despite the vast literature on the migration-trade nexus and its important implications for policy, however, there are very few examples where governments and policymakers have highlighted the role of migration for trade and other aspects of internationalization. One explanation could be the lack of an accessible and comprehensive survey of the available theory and evidence on the nexus between migration and internationalization. This article intends to bridge this gap. We review and discuss over 100 published papers on the subject, from the pioneering country-level studies to the nascent firm-level studies that exploit employeremployee data. To our knowledge, this is the first paper to provide a wide-ranging review of both the different strands of theory related to the relationship between migration and internationalization, as well as early and new empirical results on this nexus. We find substantial support in the literature of an internationalization facilitating influence of migration. The evidence can be found in various settings, from individual small countries to groups of large countries, in both developed and less developed economies, and for regions and firms. Although the evidence suggests that migration can help to increase confidence and facilitate the flow of information between countries, which reduces the costs of—and improves the prospects for—internationalization, we also find substantial gaps and inconsistencies in the previous literature. More research is therefore needed. The theory is still incomplete and does not provide a coherent framework for explaining the interlinkages between migration and internationalization. Furthermore, a large part of the empirical literature has been based on aggregate data, which has stood in the way of robust evidence on the direction of causation and the main mechanisms at play. The nascent firm-level approach has the potential to bridge several of the existing knowledge gaps, but the research is still in its initial stages. Our aim is that this article will encourage future research, which will fill in the missing pieces. In addition, we hope the article can help policymakers formulate better policies for the promotion of internationalization.
Critical Roles of Glucocorticoid-Induced Leucine Zipper in Infectious Bursal Disease Virus (IBDV)-Induced Suppression of Type I Interferon Expression and Enhancement of IBDV Growth in Host Cells via Interaction with VP4

ABSTRACT Infectious bursal disease (IBD) is an acute, highly contagious, and immunosuppressive avian disease caused by IBD virus (IBDV). Although IBDV-induced immunosuppression has been well established, the underlying exact molecular mechanism for such induction is not very clear. We report here the identification of IBDV VP4 as an interferon suppressor by interaction with the glucocorticoid-induced leucine zipper (GILZ) in host cells. We found that VP4 suppressed the expression of type I interferon in HEK293T cells after tumor necrosis factor alpha (TNF-α) treatment or Sendai virus (SeV) infection and in DF-1 cells after poly(I·C) stimulation. In addition, the VP4-induced suppression of type I interferon could be completely abolished by knockdown of GILZ by small interfering RNA (siRNA). Furthermore, knockdown of GILZ significantly inhibited IBDV growth in host cells, and this inhibition could be markedly mitigated by anti-alpha/beta interferon antibodies in the cell cultures (P < 0.001). Thus, VP4-induced suppression of type I interferon is mediated by interaction with GILZ, a protein that appears to inhibit cell responses to viral infection.
Measures of Continuity of Care: A Register-based Correlation Study

In an empirical study using data from a health center in Sweden, correlation coefficients were computed among nine different measures of continuity of care, five of them visit-based and four individual-based. Generally, the correlations were high. This may be due, in part, to the similar behavior of the measures for people making few visits. The correlations were also quite high, however, when the sample was restricted to people with many visits. Several measures display a significant dependence on utilization level. The results suggest that, for general purposes, the measure COC should be preferred among the individual-based measures and fraction-of-care continuity among the visitbased measures. On grounds of flexibility and ease of interpretation, the authors recommend fraction-of-care measures.
Pharmacokinetic Analysis of 11C-PBR28 in the Rat Model of Herpes Encephalitis: Comparison with (R)-11C-PK11195

11C-PBR28 is a second-generation translocator protein (TSPO) tracer with characteristics supposedly superior to the most commonly used tracer for neuroinflammation, (R)-11C-PK11195. Despite its use in clinical research, no studies on the imaging properties and pharmacokinetic analysis of 11C-PBR28 in rodent models of neuroinflammation have been published yet. Therefore, this study aimed to evaluate 11C-PBR28 as a tool for detection and quantification of neuroinflammation in preclinical research and to compare its imaging properties with (R)-11C-PK11195. The herpes simplex encephalitis (HSE) model was used for induction of neuroinflammation in male Wistar rats. Six or 7 d after virus inoculation, a dynamic 11C-PBR28 or (R)-11C-PK11195 PET scan with arterial blood sampling was obtained. Pharmacokinetic modeling was performed on the PET data and analyzed using volumes of interest and a voxel-based approach. Volume-of-interest– and voxel-based analysis of 11C-PBR28 images showed overexpression of TSPO in brain regions known to be affected in the HSE rat model. 11C-PBR28 was metabolized faster than (R)-11C-PK11195, with a metabolic half-life in plasma of 5 and 21 min, respectively. Overall, 11C-PBR28 was more sensitive than (R)-11C-PK11195 in detecting neuroinflammation. The binding potential (BPND) of 11C-PBR28 was significantly higher (P < 0.05) in the medulla (176%), pons (146%), midbrain (101%), hippocampus (85%), thalamus (73%), cerebellum (54%), and hypothalamus (49%) in HSE rats than in control rats, whereas (R)-11C-PK11195 showed a higher BPND only in the medulla (32%). The BPND in control animals was not significantly different between tracers, suggesting that the nonspecific binding of both tracers is similar. 11C-PBR28 was more sensitive than (R)-11C-PK11195 in the detection of TSPO overexpression in the HSE rat model, because more brain regions with significantly increased tracer uptake could be found, irrespective of the data analysis method used. These results suggest that 11C-PBR28 should be able to detect more subtle changes in microglial activation in preclinical models of neuroinflammation.
Skin Conductance Levels in Panic Disorder and Depression

Skin conductance level (SCL) was measured in 63 subjects with panic disorder, 21 of whom had major depression. Some evidence was found for low SCL being associated with depression, as has been recorded in depression without panic. The standard deviation of SCL was high and it is suggested that the etiology of depression in panic is different from primary depression, at least for some patients. High SCL was not associated with severity of illness. Recordings made in the usual small, isolated, sound-attenuated environment were compared with those made in a larger room with an investigator present for 10 patients and 10 normal controls. Lower SCLs were found in the larger room.
Pharmaceutical policies in Canadian family medicine training. Survey of residency programs.

OBJECTIVE To determine whether family medicine residency training programs have formal policies regarding interactions between residents and the pharmaceutical industry, to identify existing practices, and to find out what issues in industry-physician interaction are addressed during the 2-year core curriculum training in Canada. DESIGN Mailed survey using a questionnaire. SETTING The 16 Canadian residency training programs in family medicine. PARTICIPANTS Program directors of all 16 Canadian family medicine residency training programs replied. MAIN OUTCOME MEASURES Number of programs with formal pharmaceutical policies; number of programs offering formal curriculum coverage of related topics in the field; program practices regarding industry sampling, detailing, sponsorship, and access. RESULTS Only four of the 16 programs have formal policies or guidelines. Topics generally covered in core curriculum included critical appraisal (13/16) and cost trends (11/16). Few programs address determinants of prescribing (5/16), marketing techniques (4/16), provincial drug access programs (6/16), or the Canadian Medical Association guidelines on physician-industry interaction (5/16). Industry presence and sponsorship in family medicine training is notable, and screening is limited. Great variation exists, and programs are interested in future initiatives. CONCLUSIONS Family medicine training in Canada is attempting to address pharmaceutical issues. Interest is strong, but these issues need to be given more emphasis.
Simultaneous and functional binding of SmpB and EF-Tu-TP to the alanyl acceptor arm of tmRNA.

Transfer-messenger RNA (tmRNA) mimics functions of aminoacyl-tRNA and mRNA, subsequently, when rescuing stalled ribosomes on a 3' truncated mRNA without stop codon in bacteria. In addition, this mechanism marks prematurely terminated proteins by a C-terminal peptide tag as a signal for degradation by specific cellular proteases. For Escherichia coli, previous studies on initial steps of this "trans-translation" mechanism revealed that tmRNA alanylation by Ala-tRNA synthetase and binding of Ala-tmRNA by EF-Tu-GTP for subsequent delivery to stalled ribosomes are inefficient when compared to analogous reactions with canonical tRNA(Ala). In other studies, protein SmpB and ribosomal protein S1 appeared to bind directly to tmRNA and to be indispensable for trans-translation. Here, we have searched for additional and synergistic effects of the latter two on tmRNA alanylation and its subsequent binding to EF-Tu-GTP. Kinetic analysis of functioning combined with band-shift experiments and structural probing demonstrate, that tmRNA may indeed form a multimeric complex with SmpB, S1 and EF-Tu-GTP, which leads to a considerably enhanced efficiency of the initial steps of trans-translation. Whereas S1 binds to the mRNA region of tmRNA, we have found that SmpB and EF-Tu both interact with its acceptor arm region. Interaction with SmpB and EF-Tu was also observed at the acceptor arm of Ala-tRNA(Ala), but there the alanylation efficiency was inhibited rather than stimulated by SmpB. Therefore, SmpB may function as an essential modulator of the tRNA-like acceptor arm of tmRNA during its successive steps in trans-translation.