544 research outputs found

    Comparative Experience of the Effectiveness of Financing Small Enterprises

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    The article considers existing criteria of estimation of financing subjects of small business in Germany and Russia for raising its effectiveness for Russia. We analyzed main directions and mechanisms of state support in these countries. The conducted analysis demonstrated that effectiveness indices of the activity of small enterprises in FGR essentially exceed analogous indices of the activity of enterprises of EU countries. A contribution, brought by small enterprises in the development of economy of Germany is just inestimable. For functioning and financing the activity of small enterprises in FGR, there were accepted correspondent normative acts, for example, the Trade code, one of which main statements is the following: family enterprises are encouraged in Germany by giving them the free access at markets, and there are different limitations for big enterprises. The parity of competitive flows is observed by prohibiting small business purchase for big enterprises – in Germany small enterprises are distinctly divided in dependent and independent by strict statistical accounting of these companies. The author denoted base state structures, curating programs for supporting small enterprises in Germany comparing with infrastructures, engaged for supporting subjects of small and middle business, existing in Russia. Unfortunately, program arrangements for supporting subjects of small business in RF don't include special measures for supporting priority types of activity. The support is mainly directed on certain categories of citizens: unemployed, families with many children, youth and so on

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    Decadal regional air quality simulations over Europe in present climate: near surface ozone sensitivity to external meteorological forcing

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    Abstract. Regional climate-air quality decadal simulations over Europe were carried out with the RegCM3/CAMx modeling system for the time slice 1991–2000, in order to study the impact of different meteorological forcing on surface ozone. The RegCM3 regional climate model was firstly constrained by the ERA40 reanalysis dataset which is considered as an experiment with perfect meteorological boundary conditions and then it was constrained by the global circulation model ECHAM5. A number of meteorological parameters were examined including the 500 mb geopotential height, solar radiation, temperature, cloud liquid water path, planetary boundary layer height and surface wind. The different RegCM meteorological forcing resulted in changes of near surface ozone over Europe ranging between ± 4 ppb for winter and summer. The area showing the greatest sensitivity in O3 during winter is central and southern Europe while in summer central north continental Europe. The different meteorological forcing impacts on the atmospheric circulation, which in turn affects cloudiness and solar radiation, temperature, wind patterns and the meteorology depended biogenic emissions. For comparison reasons, the impact of chemical boundary conditions on surface ozone was additionally examined with a series of sensitivity studies, indicating that surface ozone changes are comparable to those caused by the different meteorological forcing. These findings suggest that, when it comes to regional climate-air quality simulations, the selection of external meteorological forcing can be as important as the selection of adequate chemical lateral boundary conditions

    Electromechanical Behavior of Al/Al2_{2}O3_{3} Multilayers on Flexible Substrates: Insights from In Situ Film Stress and Resistance Measurements

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    A series of Al and Al/Al2_{2}O3_{3} thin-film multilayer structures on flexible polymer substrates are fabricated with a unique deposition chamber combining magnetron sputtering (Al) and atomic layer deposition (ALD, Al2_{2}O3_{3}, nominal thickness 2.4–9.4 nm) without breaking vacuum and thoroughly characterized using transmission electron microscopy (TEM). The electromechanical behavior of the multilayers and Al reference films is investigated in tension with in situ X-ray diffraction (XRD) and four-point probe resistance measurements. All films exhibit excellent interfacial adhesion, with no delamination in the investigated strain range (12%). For the first time, an adhesion-promoting naturally forming amorphous interlayer is confirmed for thin films sputter deposited onto polymers under laboratory conditions. The evolution of Al film stresses and electrical resistance reveal changes in the deformation behavior as a function of oxide thickness. Strengthening of Al is observed with increasing oxide thickness. Significant embrittlement can be avoided for oxide layer thicknesses ≀2.4 nm

    Pharmacologic suppression of JAK1/2 by JAK1/2 inhibitor AZD1480 potently inhibits IL-6-induced experimental prostate cancer metastases formation.

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    Metastatic prostate cancer is lethal and lacks effective strategies for prevention or treatment, requiring novel therapeutic approaches. Interleukin-6 (IL-6) is a cytokine that has been linked with prostate cancer pathogenesis by multiple studies. However, the direct functional roles of IL-6 in prostate cancer growth and progression have been unclear. In the present study, we show that IL-6 is produced in distant metastases of clinical prostate cancers. IL-6-activated signaling pathways in prostate cancer cells induced a robust 7-fold increase in metastases formation in nude mice. We further show that IL-6 promoted migratory prostate cancer cell phenotype, including increased prostate cancer cell migration, microtubule reorganization, and heterotypic adhesion of prostate cancer cells to endothelial cells. IL-6-driven metastasis was predominantly mediated by Stat3 and to lesser extent by ERK1/2. Most importantly, pharmacologic inhibition of Jak1/2 by AZD1480 suppressed IL-6-induced signaling, migratory prostate cancer cell phenotypes, and metastatic dissemination of prostate cancer in vivo in nude mice. In conclusion, we demonstrate that the cytokine IL-6 directly promotes prostate cancer metastasis in vitro and in vivo via Jak-Stat3 signaling pathway, and that IL-6-driven metastasis can be effectively suppressed by pharmacologic targeting of Jak1/2 using Jak1/2 inhibitor AZD1480. Our results therefore provide a strong rationale for further development of Jak1/2 inhibitors as therapy for metastatic prostate cancer

    Subcellular localization of MC4R with ADCY3 at neuronal primary cilia underlies a common pathway for genetic predisposition to obesity.

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    Most monogenic cases of obesity in humans have been linked to mutations in genes encoding members of the leptin-melanocortin pathway. Specifically, mutations in MC4R, the melanocortin-4 receptor gene, account for 3-5% of all severe obesity cases in humans1-3. Recently, ADCY3 (adenylyl cyclase 3) gene mutations have been implicated in obesity4,5. ADCY3 localizes to the primary cilia of neurons 6 , organelles that function as hubs for select signaling pathways. Mutations that disrupt the functions of primary cilia cause ciliopathies, rare recessive pleiotropic diseases in which obesity is a cardinal manifestation 7 . We demonstrate that MC4R colocalizes with ADCY3 at the primary cilia of a subset of hypothalamic neurons, that obesity-associated MC4R mutations impair ciliary localization and that inhibition of adenylyl cyclase signaling at the primary cilia of these neurons increases body weight. These data suggest that impaired signaling from the primary cilia of MC4R neurons is a common pathway underlying genetic causes of obesity in humans

    Electromechanical Behavior of Al Al2O3 Multilayers on Flexible Substrates Insights from In Situ Film Stress and Resistance Measurements

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    A series of Al and Al Al2O3 thin film multilayer structures on flexible polymer substrates are fabricated with a unique deposition chamber combining magnetron sputtering Al and atomic layer deposition ALD, Al2O3 , nominal thickness 2.4 9.4 nm without breaking vacuum and thoroughly characterized using transmission electron microscopy TEM . The electromechanical behavior of the multilayers and Al reference films is investigated in tension with in situ X ray diffraction XRD and four point probe resistance measurements. All films exhibit excellent interfacial adhesion, with no delamination in the investigated strain range 12 . For the first time, an adhesion promoting naturally forming amorphous interlayer is confirmed for thin films sputter deposited onto polymers under laboratory conditions. The evolution of Al film stresses and electrical resistance reveal changes in the deformation behavior as a function of oxide thickness. Strengthening of Al is observed with increasing oxide thickness. Significant embrittlement can be avoided for oxide layer thicknesses amp; 8804;2.4 n

    Polymorphism of the CD36 Gene and Cardiovascular Risk Factors in Patients with Coronary Artery Disease Manifested at a Young Age

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    This study investigates potential associations between CD36 gene variants and the presence of risk factors in Caucasians with coronary artery disease (CAD) manifested at a young age. The study group consisted of 90 patients; the men were ≀ 50 years old and the women were ≀ 55 years old. Amplicons of exons 4 and 5 including fragments of introns were analyzed by DHPLC. Two polymorphisms were found: IVS3-6 T/C (rs3173798) and IVS4-10 G/A (rs3211892). The C allele of the IVS3-6 T/C polymorphism was associated with higher prevalence of obesity and diabetes, higher hsCRP, lower Lp(a) serum concentrations, and younger age at myocardial infarction. The A allele of the IVS4-10 G/A polymorphism was associated with older age of myocardial infarction and higher white blood cell count. The functional role of CD36 polymorphisms in CAD development needs further research

    Subdividing Y-chromosome haplogroup R1a1 reveals Norse Viking dispersal lineages in Britain

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    The inïŹ‚uence of Viking-Age migrants to the British Isles is obvious in archaeological and place-names evidence, but their demographic impact has been unclear. Autosomal genetic analyses support Norse Viking contributions to parts of Britain, but show no signal corresponding to the Danelaw, the region under Scandinavian administrative control from the ninth to eleventh centuries. Y-chromosome haplogroup R1a1 has been considered as a possible marker for Viking migrations because of its high frequency in peninsular Scandinavia (Norway and Sweden). Here we select ten Y-SNPs to discriminate informatively among hg R1a1 sub-haplogroups in Europe, analyse these in 619 hg R1a1 Y chromosomes including 163 from the British Isles, and also type 23 short-tandem repeats (Y-STRs) to assess internal diversity. We ïŹnd three speciïŹcally Western-European sub-haplogroups, two of which predominate in Norway and Sweden, and are also found in Britain; starlike features in the STR networks of these lineages indicate histories of expansion. We ask whether geographical distributions of hg R1a1 overall, and of the two sub-lineages in particular, correlate with regions of Scandinavian inïŹ‚uence within Britain. Neither shows any frequency difference between regions that have higher (≄10%) or lower autosomal contributions from Norway and Sweden, but both are signiïŹcantly overrepresented in the region corresponding to the Danelaw. These differences between autosomal and Y-chromosomal histories suggest either male-speciïŹc contribution, or the inïŹ‚uence of patrilocality. Comparison of modern DNA with recently available ancient DNA data supports the interpretation that two sub-lineages of hg R1a1 spread with the Vikings from peninsular Scandinavia

    Human H5N1 influenza infections in Cambodia 2005-2011: case series and cost-of-illness.

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    BACKGROUND: Southeast Asia has been identified as a potential epicentre of emerging diseases with pandemic capacity, including highly pathogenic influenza. Cambodia in particular has the potential for high rates of avoidable deaths from pandemic influenza due to large gaps in health system resources. This study seeks to better understand the course and cost-of-illness for cases of highly pathogenic avian influenza in Cambodia. METHODS: We studied the 18 laboratory-confirmed cases of avian influenza subtype H5N1 identified in Cambodia between January 2005 and August 2011. Medical records for all patients were reviewed to extract information on patient characteristics, travel to hospital, time to admission, diagnostic testing, treatment and disease outcomes. Further data related to costs was collected through interviews with key informants at district and provincial hospitals, the Ministry of Health and non-governmental organisations. An ingredient-based approach was used to estimate the total economic cost for each study patient. Costing was conducted from a societal perspective and included both financial and opportunity costs to the patient or carer. Sensitivity analysis was undertaken to evaluate potential change or variation in the cost-of-illness. RESULTS: Of the 18 patients studied, 11 (61%) were under the age of 18 years. The majority of patients (16, 89%) died, eight (44%) within 24 hours of hospital admission. There was an average delay of seven days between symptom onset and hospitalisation with patients travelling an average of 148 kilometres (8-476 km) to the admitting hospital. Five patients were treated with oseltamivir of whom two received the recommended dose. For the 16 patients who received all their treatment in Cambodia the average per patient cost of H5N1 influenza illness was US300ofwhich85.0300 of which 85.0% comprised direct medical provider costs, including diagnostic testing (41.2%), pharmaceuticals (28.4%), hospitalisation (10.4%), oxygen (4.4%) and outpatient consultations (0.6%). Patient or family costs were US45 per patient (15.0%) of total economic cost. CONCLUSION: Cases of avian influenza in Cambodia were characterised by delays in hospitalisation, deficiencies in some aspects of treatment and a high fatality rate. The costs associated with medical care, particularly diagnostic testing and pharmaceutical therapy, were major contributors to the relatively high cost-of-illness
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