Miracle-dz/UniFAR-FTUs huggingface dataset:
High Selectivity for Inhibition of Phosphodiesterase III and Positive Inotropic Effects of MCI‐154 in Guinea Pig Myocardium

MCI-154 (0.3–100 μM) exerted a concentration-dependent positive inotropic effect in isolated guinea pig papillary muscles (EC50 0.8 μM). The efficacy of MCI-154 (253% of predrug value) was 1.7-fold higher than that of saterinone but comparable to that of milrinone. Carbachol markedly reduced the increase in force of contraction (FOC) of MCI-154. In intact contracting papillary muscles, the positive inotropic effect was accompanied by an increase in cyclicAMP content to 0.78 ± 0.09 pmol/ mg wet weight (n = 10), corresponding to 150% of the basal value (0.51 ± 0.05 pmol/mg wet weight, n = 21) in the presence of submaximal cyclicAMP phosphodiesterase (PDE) isoenzyme III inhibiting concentrations of MCI-154 (30 μM). MCI-154 (1–1,000 μM) concentration-dependently inhibited the activity of PDE III from homogenates of guinea pig myocardium. The IC50 was 3.8 μM. PDE I, II, and IV were not significantly affected up to 100 μM (PDE I and IV) and up to 1,000 μM (PDE II). In comparison, milrinone and saterinone were PDE III/ IV-selective PDE inhibitors. Rolipram inhibited PDE IV only. IBMX and theophylline were nonselective PDE inhibitors. MCI-154 had only a marginal positive chronotropic effect. The frequency of spontaneously beating right auricles from guinea pig heart was increased by 8.7% at most (n = 5). MCI-154 increased Ca2+ sensitivity in chemically skinned porcine ventricular muscle fibers. FOC was maximally enhanced to 129.3% of control value by MCI-154 (100 μM). The positive inotropic effect of MCI-154 is probably due mainly to inhibition of PDE III. In contrast to the PDE III/IV-selective PDE inhibitors milrione and saterinone, MCI-154 inhibited PDE III only. The increase in Ca2+ sensitivity of the contractile proteins by MCI-154 may contribute to the positive inotropic effect.
Estimating the effects of EU enlargement, WTO accession and formation of FTA with EU or CIS on Russian economy

Abstract: We estimate effects of Russia’s trade policy options on the production, welfare and trade flows. The computable general equilibrium model is used. We show that Russia looses in the case of EU enlargement unless non-tariff barriers in the accession countries are changed to the level of the EU. In all other trade arrangements – WTO accession, formation if Russia-EU FTA, and formation of a FTA between Russia and other CIS countries Russia improves its welfare. This seems to be the first paper, which includes data on CIS countries other than Russia. We show that CIS countries experience substantial gains from formation of FTA with Russia. Another novelty of this paper is an attempt to estimate non-tariff barriers to trade, and to accommodate the effect of their changes in the model. Inclusion of non-tariff barriers often changes the results dramatically, suggesting that CGE literature should pay more attention to incorporating such barriers. Keywords: CGE, EU enlargement, Russia, WTO accession, CIS, Free Trade Area, non-tariff measures of protection (NTM)
D-type cyclin-dependent kinase activity in mammalian cells

D-type cyclin-dependent kinase activities have not so far been detected in mammalian cells. Lysis of rodent fibroblasts, mouse macrophages, or myeloid cells with Tween 20 followed by precipitation with antibodies to cyclins D1, D2, and D3 or to their major catalytic partner, cyclin-dependent kinase 4 (cdk4), yielded kinase activities in immune complexes which readily phosphorylated the retinoblastoma protein (pRb) but not histone H1 or casein. Virtually all cyclin D1-dependent kinase activity in proliferating macrophages and fibroblasts could be attributed to cdk4. When quiescent cells were stimulated by growth factors to enter the cell cycle, cyclin D1-dependent kinase activity was first detected in mid G1, reached a maximum near the G1/S transition, and remained elevated in proliferating cells. The rate of appearance of kinase activity during G1 phase lagged significantly behind cyclin induction and correlated with the more delayed accumulation of cdk4 and formation of cyclin D1-cdk4 complexes. Thus, cyclin D1-associated kinase activity was not detected during the G0-to-G1 transition, which occurs within the first few hours following growth factor stimulation. Rodent fibroblasts engineered to constitutively overexpress either cyclin D1 alone or cyclin D3 together with cdk4 exhibited greatly elevated cyclin D-dependent kinase activity, which remained absent in quiescent cells but rose to supraphysiologic levels as cells progressed through G1. Therefore, despite continued enforced overproduction of cyclins and cdk4, the assembly of cyclin D-cdk4 complexes and the appearance of their kinase activities remained dependent upon serum stimulation, indicating that upstream regulators must govern formation of the active enzymes.
Interpretation of Air Pollution Mortality: Number of Deaths or Years of Life Lost?

Abstract This paper examines the relation between the results of epidemiologic studies of air pollution mortality and impact indicators that can be informative for environmental policy decisions. Using models that are simple and transparent, yet contain the essential features, it is shown that (1) number of deaths is not meaningful for air pollution, whereas loss of life expectancy (LLE) is an appropriate impact indicator; (2) the usual short term (time series) studies yield a change in daily number of deaths attributable to acute effects of pollution, without any information on the associated LLE (although some information on this has recently become available by extending the observation window of time series); and (3) long-term studies yield a change in age-specific mortality, which makes it possible to calculate the total population averaged LLE (acute and chronic effects) but not the total number of premature deaths attributable to air pollution. The latter is unobservable because one cannot distinguish whether few individuals suffer a large or many suffer a small LLE. The paper calculates the LLE from exposure to PM10 , as implied by the long-term mortality studies of adults and infants; population LLE for infants turns out to be an order of magnitude smaller than for adults. The LLE implied by short-term studies is a small fraction of the total loss implied by long-term studies, even if one assumes a very high loss per death. Applied to environmental policy, taking a permanent 50–70% reduction of PM10 as a reasonable goal, one finds a corresponding increase of average life expectancy in urban areas of the European Union (EU) and the United States of approximately four months.
Effect of Race on Fine Particle Deposition for Oral and Nasal Breathing

Abstract Nasal efficiency for removing fine particles from inhaled air may be affected by variations in nasal structure associated with race. In 11 African American and 11 Caucasian adults (age 18–31 yr) we measured the fractional deposition (DF) of fine particles (1 and 2 μm mass median aerodynamic diameter) (MMAD) for oral and nasal breathing using individual breathing patterns previously measured by respiratory inductance plethysmography during a graded exercise protocol. DF for both nasal and mouth breathing was measured separately by laser photometry at the same tidal volume and breathing rate for resting and light exercise (20% of maximum work load) conditions. From these DF measures, nasal deposition efficiency (NDE) was calculated for each condition. For light exercise conditions, NDE for both 1- and 2-μm particles was less in African Americans versus Caucasians, 0.15 ± 0.07 (SD) versus 0.24 ± 0.11 for 1-μm particles (p = .03), and 0.29 ± 0.13 versus 0.44 ± 0.11 for 2-μm particles (p = .006). The racial differences in NDE were associated with racial differences in nasal resistance and nostril shape. These race-dependent nasal efficiencies are dosimetric factors that should be considered in modeling and assessing particulate dose from human exposure to air pollutants.
Kinase-independent function of E-type cyclins in liver cancer

Significance Amplification of the cyclin E genes and overexpression of cyclin E proteins is very frequent in several human tumor types. In particular, overexpression of E cyclins was implicated in the pathogenesis of liver cancers. According to the current cell division models, E cyclins drive tumor cell proliferation by activating its kinase partner, the cyclin-dependent kinase 2 (CDK2). In this study, we demonstrate that E cyclins are dispensable for adult mouse physiology, but essential for liver cancer progression. Surprisingly, we found that the function of E cyclins in liver tumorigenesis is kinase independent. Our study suggests that agents targeting E cyclins would be efficacious in liver cancer treatment, as they would halt proliferation of tumor cells while sparing normal tissues. E-type cyclins (cyclins E1 and E2) are components of the core cell cycle machinery and are overexpressed in many human tumor types. E cyclins are thought to drive tumor cell proliferation by activating the cyclin-dependent kinase 2 (CDK2). The cyclin E1 gene represents the site of recurrent integration of the hepatitis B virus in the pathogenesis of hepatocellular carcinoma, and this event is associated with strong up-regulation of cyclin E1 expression. Regardless of the underlying mechanism of tumorigenesis, the majority of liver cancers overexpress E-type cyclins. Here we used conditional cyclin E knockout mice and a liver cancer model to test the requirement for the function of E cyclins in liver tumorigenesis. We show that a ubiquitous, global shutdown of E cyclins did not visibly affect postnatal development or physiology of adult mice. However, an acute ablation of E cyclins halted liver cancer progression. We demonstrated that also human liver cancer cells critically depend on E cyclins for proliferation. In contrast, we found that the function of the cyclin E catalytic partner, CDK2, is dispensable in liver cancer cells. We observed that E cyclins drive proliferation of tumor cells in a CDK2- and kinase-independent mechanism. Our study suggests that compounds which degrade or inhibit cyclin E might represent a highly selective therapeutic strategy for patients with liver cancer, as these compounds would selectively cripple proliferation of tumor cells, while sparing normal tissues.
Product innovation, process innovation and export propensity: persistence, complementarities and feedback effects in Spanish firms

ABSTRACT Drawing on a longitudinal data of Spanish manufacturing firms, this study explores the persistence of technological innovation and exports, their potential complementary relations and feedback effects. Empirical results suggest the presence of both true and spurious state dependence in all three activities. True state dependence in technical innovation and exports implies intertemporal spillovers relevant to the evaluation of innovation and export policy measures. However, given that results also suggest spurious state dependence, firm-specific characteristics should be taken into account in promoting technological innovations and exports. In addition, we find a strong complementarity between product and process innovation both through a contemporaneous effect and via unobserved firm characteristics. However, concerning complementarity between innovation and exports, results suggests complementarity only through contemporaneous effects. Finally, we find no support for the causal link from past product and process innovations to current export activities.
Antileishmanial Activity of Lavandula angustifolia and Rosmarinus Officinalis Essential Oils and Nano-emulsions on Leishmania major (MRHO/IR/75/ER)

Background: The aim of present study was to evaluate antileishmanial effects of Lavandula angustifolia (L. angustifolia) and Rosmarinus officinalis (R. officinalis) medicinal plants essential oils and nano-emulsions on Leishmania major (L. major). Methods: The present study was performed in Leishmaniasis Reference Lab at Mazandaran University of Medical Sciences, Iran during 2016–2017. The IC50 values were calculated in both the promastigote and amastigote stages in J774 macrophage in comparison with meglumine antimoniate (MA) as positive control. In addition, cytotoxicity effects of essential oils and nano-emulsions prepared from both plants against macrophages were evaluated. Results: Both essential oil and nano-emulsion of Lavander and Rosemary showed anti-leishmania activity on promastigote with IC50=0.11 μl/mL, IC50=0.26 μl/mL, and IC50=0.08 μl/mL respectively. Moreover, during amastigote assay, Lavander and Rosemary essential oils and nano-emulsion were effective at least in concentration of 0.12 μl/mL and 0.06 μl/mL (P=0.0001) respectively, on mean infected macrophages (MIR) and amastigotes in macrophages (P=0.0001). Additionally, cytotoxicity assay against macrophage revealed no toxicity on the host cells at IC50 concentrations. Conclusion: The nano-emulsions of both plants were more effective than essential oil in both MIR and amastigote. However, in comparison with MA, the Lavander essential oil is more effective in reducing MIR. Rosemary nano-emulsion reduced MIR significantly more than MA in concentration of 0.25 μl/mL (P<0.001). Further investigations are recommended to evaluate the effect of these medicinal plants in murine models.
Management innovation and organisational performance: the mediating role of high performance organisation framework

This study investigates the relationship between management innovation and organisational performance with the high performance organisation (HPO) factors of continuous improvement and renewal, workforce quality and long-term orientation as mediators. From a survey among 186 managers of the insurance industry in Ghana and with the use of PLS-SEM, the results show that management innovation appears to have a direct influence on organisational performance but when management innovation is combined with the HPO factors, it generates a synergy to increase organisations to become HPOs in an emerging market context.
Clinical Impact of 2-Deoxy-2-[18F]fluoro-D-Glucose (FDG)–Positron Emission Tomography (PET) on Treatment Choice in Recurrent Cancer of the Cervix Uteri

ObjectiveThe superiority of positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose (FDG) over computed tomography and magnetic resonance imaging in detecting recurrent cervical cancer and determining the extent of the disease has been demonstrated in several clinical trials. However, there is a lack of data concerning the clinical impact of the extra findings. We report here a prospective clinical study aimed at investigating the clinical impact of FDG-PET findings on the treatment plans in recurrent cervical cancer. Materials and MethodsThirty-six patients with suspected recurrent cervical cancer underwent FDG-PET. Relapses were confirmed in 26 cases, and one case of primary lung cancer was found. The clinical impact of the FDG-PET results was assessed using a systematic scoring system with a 4-grade scale. Median follow-up time after FDG-PET was 33.1 months (range, 5–83 months) for all patients and 22.4 months (range, 5–83 months) for patients with positive PET results. ResultsMore sites of metastases were detected with FDG-PET in 56% of the patients compared to the findings by conventional imaging. The results of FDG-PET led to a change in treatment modality for 33% of the patients; and for 22%, a change in dose or deliverance of treatment was recorded. Treatment intention was changed in 30%, in all but one patient, from curative to palliative. In 48% of the patients, the initially planned treatment was reduced regarding dose or extent, or was withheld. ConclusionIn recurrent cervical cancer, FDG-PET provides clinically valuable information with a high impact on treatment decisions.
Interactions of School Bonding, Disturbed Family Relationships, and Risk Behaviors Among Adolescents.

BACKGROUND Substance use, gambling, and violence represent a great risk for adolescent health. Schools are often referred to as the "best" places for health promotion and prevention, where positive school bonding serves as a strong protective factor for the development of risk behaviors and poor school bonding is associated with various risk behaviors. The purpose of this study was to examine the risk effect of disturbed family relations, the protective effect of school bonding, and the extent to which school can compensate for the negative effect of an adverse family environment related to the risk behaviors of the adolescents. METHODS A self-reported questionnaire was administered to a random sample of students in grades 9-11 from 30 high schools. A total of 1519 respondents were included in the analysis. Covariance analysis was used to test the impact of sex, school year, school bonding, and family relationships on risk behaviors and the interaction effect of school bonding and family relationships. RESULTS Both dimensions of school bonding, attachment to school, and commitment to schooling, were found to be significant predictors of risk behavior, with a commitment to schooling being an even more significant predictor than disturbed family relations. Students with greater school bonding and unfavorable family circumstances reported fewer risk behaviors than students of equal family circumstances but weak school bonding. CONCLUSIONS These findings emphasize the role of the school as a social compensator for the adverse effects of a disturbed family environment.
Board Size and Dividend Policy: A Review

The current study aimed at reviewing the theoretical and empirical research regarding board size and dividend policy.The role of board has been emphasized in the previous studies in monitoring the managerial decisions.In terms of the methodology, the current study has reviewed and identified most of previous studies on the role of board size and dividends. The results are mixed regarding the effectiveness of board depending on its size.The results of the previous studies are mixed and alternative views are reported based on agency theory and resource dependency theories. Future studies may focus on the composition of boards in terms of their education, knowledge and experience along with the board size.
Comparison between traditional strength training and complex contrast training on repeated sprint ability and muscle architecture in elite soccer players.

BACKGROUND The purpose of this study was to compare traditional strength training (TST) and complex contrast training (CCT) on the repeated-shuttle-sprint ability (RSSA), the countermovement squat jump (CMJ) height, the one repetition maximum (1RM) at squat on the Smith machine, and on muscle architecture in young, male elite soccer players. METHODS Twenty-two soccer players (mean age 18.4±0.4 years; mean weight 70.2±9.1 kg; mean height 179.9±7.5 cm) who belonged to the under-20 age group were randomly assigned into two groups: CCT (N.=10) or TST (N.=12). During the study period, the soccer players trained with CCT through power exercises performed before high-velocity exercises and TST based on a set-repetition format through daily, undulatory periodization. RESULTS After statistical analysis (P<0.05), the results demonstrated that the speciﬁc CCT regimen provided a significant improvement in the RSSA percent decrement (moderate effect size), CMJ (large effect size) and 1RM ability (large effect size). However, the TST promoted significant changes in 1RM (large effect size) and a significant increase in the muscle thickness of the vastus intermedius (moderate effect size). CONCLUSIONS The CCT protocol could be used to improve the RSSA parameters, CMJ and 1RM, and the TST developed dynamic strength and muscle growth. Coaches can choose either CCT or TST protocols according to the needs of their soccer players.
Access to condoms for female sex workers in Andhra Pradesh.

BACKGROUND Condoms are an essential part of comprehensive HIV prevention and care programmes. We report the accessibility of male condoms for female sex workers (FSWs) and the associated characteristics that may play a major role in determining access to condoms for FSWs. METHODS Confidential interviews of 6509 street- and home-based FSWs in 13 districts of the Indian state of Andhra Pradesh provided data on the number of paying clients and various aspects of access to free condoms and purchase of condoms. Access to condoms was defined as having ever obtained condoms either through free distribution or through purchase. Multivariate analyses were done separately for street- and home-based FSWs to describe correlates of their access to condoms. The requirement of condoms was assessed based on the number of paying clients during the past 15 days. RESULTS Data on condom access were available for 6465 (99.3%) FSWs. A total of 2850 (44.1%; 95% CI: 36.2%-52.0%) reported accessing free condoms ever and 2336 (36.1%; 95% CI: 30.6%-41.6%) had purchased condoms ever (not mutually exclusive). The primary sources for condoms were non-governmental organization facilities (73.8%) and pharmacies (79.7%) for free and purchased condoms, respectively. A total of 3510 (54.3%; 95% CI: 48.5%-60.1%) FSWs reported no access to free or purchased condoms during the past 15 days, and this no access was significantly higher for those > 30 years of age, with no schooling, street-based FSWs, and with no participation in a FSW support group (p < 0.001 for each in univariate analysis). Participation in a FSW support group was the main predictor of access to free condoms for both types of FSWs during the past 15 days with multivariate analysis. Condom requirements during the past 15 days were met for 67.5% of FSWs who had accessed only free condoms and for 33.8% of those who had accessed only purchased condoms. CONCLUSIONS One-fourth of FSWs had never accessed condoms, and a little over half of those who had ever accessed reported no access during the past 15 days. Condom requirements were not met for three-fifths of the FSWs. HIV prevention programmes need to Increase access to free condoms for FSWs in Andhra Pradesh as access to condoms is a necessary prerequisite for condom use.