Access to finance and venture capital for industrial SMEs

SMEs play a crucial role for European economies. The numbers show the high importance of SMEs for national economies. Accordingly, it is no surprise that the regulatory framework SMEs are imbedded in is the subject of an important political discussion. In the discussion it is frequently mentioned by representatives of SMEs as well as associations of SMEs, that the access to finance for SMEs is still inferior. Based on the importance of SMEs for national economies and the discussion on the accessibility of financial resources for SMEs, it is the main objective of this study to provide solid data on the access of SMEs to financial resources. To provide the data, the study is focusing on four main issues. First of all, the importance of SMEs for national economies will be shown. After that the financing of SMEs in selected countries will be analysed. Then the availability of venture capital for SMEs will be discussed. Finally the tax regimes and the influence of the tax system on the access to finance for SMEs will be analysed. Since there is still a large variety among the tax systems of the European Union member states, the study has focused on Austria, France, Germany, Poland and the United Kingdom. --SME,financial structure,venture capital,tax framework,accounting standards

Phylogeny of the nematode genus Pristionchus and implications for biodiversity, biogeography and the evolution of hermaphroditism

<p>Abstract</p> <p>Background</p> <p>The nematode <it>Pristionchus pacificus </it>has originally been developed as a satellite organism for comparison to <it>Caenorhabditis elegans</it>. A 10X coverage of the whole genome of <it>P. pacificus </it>is available, making <it>P. pacificus </it>the first non-<it>Caenorhabditis </it>nematode with a fully sequenced genome. The macroevolutionary comparison between <it>P. pacificus </it>and <it>C. elegans </it>has been complemented by microevolutionary studies of closely related strains and species within the genus <it>Pristionchus</it>. In addition, new understanding of the biology of <it>Pristionchus </it>from field studies, demonstrating a close association with various scarab beetles and the Colorado potato beetle, supports consideration of this nematode in studies of ecosystems. In the course of field studies on four continents more than 1,200 isolates were established from 15,000 beetle specimens representing 18 <it>Pristionchus </it>species. Two remarkable features of the <it>Pristionchus </it>– beetle association are the high species specificity of the interaction and the interception of the beetle's sex communication system for host recognition by the nematodes, as suggested by chemotaxis studies. Evolutionary interpretations of differences in developmental, behavioral and ecological patterns require a phylogenetic framework of the genus <it>Pristionchus</it>.</p> <p>Results</p> <p>Here, we provide a robust phylogeny of all 18 available <it>Pristionchus </it>species based on a set of 27 ribosomal protein genes encompassing a total of 10,971 bp. The phylogenetic tree provides evidence for North American and European clades, which are embedded in a deeper clade that includes Asian species. It also indicates putative invasion events. Of the 18 <it>Pristionchus </it>species, 13 are gonochoristic and five are hermaphroditic. The phylogeny indicates that all hermaphroditic species have arisen independently within the genus <it>Pristionchus</it>.</p> <p>Conclusion</p> <p>Combined ribosomal protein cDNA data can provide the basis for reconstruction of a robust phylogenetic framework for microevolutionary and biogeographic analyses. An additional major implication of our studies is the use of <it>Pristionchus </it>for nematode biodiversity assessments. While some species are represented by more than 100 isolates, others were found less than four times. Such patterns were observed on all continents and in all phylogenetic clades indicating that species asymmetry is a widespread phenomenon, which can now be further investigated by molecular tools.</p

Sex, bugs and Haldane's rule: the nematode genus Pristionchus in the United States

BACKGROUND: The nematode Pristionchus pacificus has been developed as a satellite organism in evolutionary developmental biology for comparison to Caenorhabditis elegans. Comparative studies have revealed major differences in the regulation of developmental processes between P. pacificus and C. elegans. To place evolutionary developmental biology and the observed developmental differences between species in a comprehensive evolutionary context, such studies have to be complemented with ecological aspects. Knowledge about the ecology of the organism in question might indicate specific environmental conditions that can result in developmental adaptations and could account for species differences in development. To this end, we have started to investigate the ecology of Pristionchus nematodes. In recent field studies in Western Europe we found six Pristionchus species that are closely associated with scarab beetles and the Colorado potato beetle. This Pristionchus – beetle association provides the unique opportunity to combine research in evolutionary developmental biology with ecology. However, it remains unknown how general these findings from Europe are on a global scale. RESULTS: Here, we describe the Pristionchus species associated with scarab and Colorado potato beetles in the Eastern United States and show striking transatlantic differences and unexpected evolutionary and ecological patterns. Twohundredeighty of 285 (98%) isolates from American scarab beetles belong to five Pristionchus species, all of which are different from the European species. We describe four of them as novel Pristionchus species. The five American Pristionchus species fall into a single phylogenetic clade and have a male-female (gonochoristic) mode of reproduction, whereas the majority of European isolates are hermaphroditic. Crosses between the two most closely related species, P. aerivorus and P. pseudaerivorus n. sp., follow Haldane's rule in that heterogametic F1 males are inviable. We observed P. aerivorus and P. pseudaerivorus n. sp. coexisting on the same scarab beetle and obtained two cases of F1 hybrids from wild beetles. Finally, the Colorado potato beetle is associated with the same nematode, P. uniformis in the United States and Europe. Given the introduction of the Colorado potato beetle to Europe in 1877, our results suggest that P. uniformis was introduced together with its beetle vector. CONCLUSION: Taken together, the Pristionchus – beetle association provides a powerful tool for studying biodiversity, biogeography, speciation and species invasion on a global scale

Molecular phylogeny of beetle associated diplogastrid nematodes suggests host switching rather than nematode-beetle coevolution

<p>Abstract</p> <p>Background</p> <p>Nematodes are putatively the most species-rich animal phylum. They have various life styles and occur in a variety of habitats, ranging from free-living nematodes in aquatic or terrestrial environments to parasites of animals and plants. The rhabditid nematode <it>Caenorhabditis elegans </it>is one of the most important model organisms in modern biology. <it>Pristionchus pacificus </it>of the family of the Diplogastridae has been developed as a satellite model for comparison to <it>C. elegans</it>. The Diplogastridae, a monophyletic clade within the rhabditid nematodes, are frequently associated with beetles. How this beetle-association evolved and whether beetle-nematode coevolution occurred is still elusive. As a prerequisite to answering this question a robust phylogeny of beetle-associated Diplogastridae is needed.</p> <p>Results</p> <p>Sequences for the nuclear small subunit ribosomal RNA and for 12 ribosomal protein encoding nucleotide sequences were collected for 14 diplogastrid taxa yielding a dataset of 5996 bp of concatenated aligned sequences. A molecular phylogeny of beetle-associated diplogastrid nematodes was established by various algorithms. Robust subclades could be demonstrated embedded in a phylogenetic tree topology with short internal branches, indicating rapid ancestral divergences. Comparison of the diplogastrid phylogeny to a comprehensive beetle phylogeny revealed no major congruence and thus no evidence for a long-term coevolution.</p> <p>Conclusion</p> <p>Reconstruction of the phylogenetic history of beetle-associated Diplogastridae yields four distinct subclades, whose deep phylogenetic divergence, as indicated by short internal branch lengths, shows evidence for evolution by successions of ancient rapid radiation events. The stem species of the Diplogastridae existed at the same time period when the major radiations of the beetles occurred. Comparison of nematode and beetle phylogenies provides, however, no evidence for long-term coevolution of diplogastrid nematodes and their beetle hosts. Instead, frequent host switching is observed. The molecular phylogeny of the Diplogastridae provides a framework for further examinations of the evolution of these associations, for the study of interactions within the ecosystems, and for investigations of diplogastrid genome evolution.</p

Environmental change impacts on the C- and N-cycle of European forests: a model comparison study [Discussion paper]

Forests are important components of the greenhouse gas balance of Europe. There is considerable uncertainty about how predicted changes to climate and nitrogen deposition will perturb the carbon and nitrogen cycles of European forests and thereby alter forest growth, carbon sequestration and N2O emission. The present study aimed to quantify the carbon and nitrogen balance, including the exchange of greenhouse gases, of European forests over the period 2010–2030, with a particular emphasis on the spatial variability of change. The analysis was carried out for two tree species: European beech and Scots pine. For this purpose, four different dynamic models were used: BASFOR, DailyDayCent, INTEGRATOR and Landscape-DNDC. These models span a range from semi-empirical to complex mechanistic. Comparison of these models allowed assessment of the extent to which model predictions depended on differences in model inputs and structure. We found a European average carbon sink of 0.160 ± 0.020 kgC m−2 yr−1 (pine) and 0.138 ± 0.062 kgC m−2 yr−1 (beech) and N2O source of 0.285 ± 0.125 kgN ha−1 yr−1 (pine) and 0.575 ± 0.105 kgN ha−1 yr−1 (beech). The European average greenhouse gas potential of the carbon source was 18 (pine) and 8 (beech) times that of the N2O source. Carbon sequestration was larger in the trees than in the soil. Carbon sequestration and forest growth were largest in central Europe and lowest in northern Sweden and Finland, N. Poland and S. Spain. No single driver was found to dominate change across Europe. Forests were found to be most sensitive to change in environmental drivers where the drivers were limiting growth, where changes were particularly large or where changes acted in concert. The models disagreed as to which environmental changes were most significant for the geographical variation in forest growth and as to which tree species showed the largest rate of carbon sequestration. Pine and beech forests were found to have differing sensitivities to environmental change, in particular the response to changes in nitrogen and precipitation, with beech forest more vulnerable to drought. There was considerable uncertainty about the geographical location of N2O emissions. Two of the models BASFOR and LandscapeDNDC had largest emissions in central Europe where nitrogen deposition and soil nitrogen were largest whereas the two other models identified different regions with large N2O emission. N2O emissions were found to be larger from beech than pine forests and were found to be particularly sensitive to forest growth

Synchronous and proportional deglacial changes in Atlantic meridional overturning and northeast Brazilian precipitation

Changes in heat transport associated with fluctuations in the strength of the Atlantic meridional overturning circulation (AMOC) are widely considered to affect the position of the Intertropical Convergence Zone (ITCZ), but the temporal immediacy of this teleconnection has to date not been resolved. Based on a high-resolution marine sediment sequence over the last deglaciation, we provide evidence for a synchronous and near-linear link between changes in the Atlantic interhemispheric sea surface temperature difference and continental precipitation over northeast Brazil. The tight coupling between AMOC strength, sea surface temperature difference, and precipitation changes over northeast Brazil unambiguously points to a rapid and proportional adjustment of the ITCZ location to past changes in the Atlantic meridional heat transport

Thyrotropin-releasing hormone (TRH) promotes wound re-epithelialisation in frog and human skin

There remains a critical need for new therapeutics that promote wound healing in patients suffering from chronic skin wounds. This is, in part, due to a shortage of simple, physiologically and clinically relevant test systems for investigating candidate agents. The skin of amphibians possesses a remarkable regenerative capacity, which remains insufficiently explored for clinical purposes. Combining comparative biology with a translational medicine approach, we report the development and application of a simple ex vivo frog (Xenopus tropicalis) skin organ culture system that permits exploration of the effects of amphibian skin-derived agents on re-epithelialisation in both frog and human skin. Using this amphibian model, we identify thyrotropin-releasing hormone (TRH) as a novel stimulant of epidermal regeneration. Moving to a complementary human ex vivo wounded skin assay, we demonstrate that the effects of TRH are conserved across the amphibian-mammalian divide: TRH stimulates wound closure and formation of neo-epidermis in organ-cultured human skin, accompanied by increased keratinocyte proliferation and wound healing-associated differentiation (cytokeratin 6 expression). Thus, TRH represents a novel, clinically relevant neuroendocrine wound repair promoter that deserves further exploration. These complementary frog and human skin ex vivo assays encourage a comparative biology approach in future wound healing research so as to facilitate the rapid identification and preclinical testing of novel, evolutionarily conserved, and clinically relevant wound healing promoters

Circulating Tumor Cells Predict Survival in Early Average-to-High Risk Breast Cancer Patients

Background: Circulating tumor cells (CTCs) have been shown to predict reduced survival outcomes in metastatic breast cancer. Methods: CTCs were analyzed in 2026 patients with early breast cancer before adjuvant chemotherapy and in 1492 patients after chemotherapy using the CellSearch System. After immuno-magnetic enrichment for cells expressing the epithelial-cell adhesion molecule, CTCs were defined as nucleated cells expressing cytokeratin and lacking CD45. The patients were followed for a median of 35 months (range = 0–54). Kaplan–Meier analyses and the log-rank test were used for survival analyses. All statistical tests were two-sided. Results: Before chemotherapy, CTCs were detected in 21.5% of patients (n = 435 of 2026), with 19.6% (n = 136 of 692) of node-negative and 22.4% (n = 299 of 1334) of node-positive patients showing CTCs (P < .001). No association was found with tumor size, grading, or hormone receptor status. After chemotherapy, 22.1% of patients (n = 330 of 1493) were CTC positive. The presence of CTCs was associated with poor disease-free survival (DFS; P < .0001), distant DFS (P < .001), breast cancer-specific survival (P = .008), and overall survival (OS; P = .0002). CTCs were confirmed as independent prognostic markers in multivariable analysis for DFS (hazard ratio [HR] = 2.11; 95% confidence interval [CI] = 1.49 to 2.99; P < .0001) and OS (HR = 2.18; 95% CI = 1.32 to 3.59; P = .002). The prognosis was worst in patients with at least five CTCs per 30mL blood (DFS: HR = 4.51, 95% CI = 2.59 to 7.86; OS: HR = 3.60, 95% CI = 1.56 to 8.45). The presence of persisting CTCs after chemotherapy showed a negative influence on DFS (HR = 1.12; 95% CI = 1.02 to 1.25; P = .02) and on OS (HR = 1.16; 95% CI = 0.99 to 1.37; P = .06) Conclusions: These results suggest the independent prognostic relevance of CTCs both before and after adjuvant chemotherapy in a large prospective trial of patients with primary breast cancer

M4 Safety and tolerability of BN82451B in huntington’s disease

Background BN82451B is a small, orally active molecule with good CNS penetration. Preclinical studies in tgHD R6/2 mice suggested improved motor function and prolonged survival. In addition antidyskinetic activity was observed in other models. The proposed mechanisms of action (MOA) are (1) antiexcytotoxic due to a sodium channel blocking potential, (2) antioxidant, (3) anti-inflammatory due to a cyclooxygenase (COX) inhibitory potential and (4) mitochondrial protective. Aims The primary objective of this phase 2a study (NCT02231580) is to investigate the safety and tolerability of BN82451B bid versus placebo for 28 days in male HD subjects. Secondary objectives include assessment of pharmacokinetics and of pharmacodynamics via the effects on quantitative motor (Q-Motor) measures. UHDRS subscales are implemented as exploratory measures. Methods Subjects: We intend to recruit 30 male HD subjects. 24 receive BN82451B and 6 placebo. The study is conducted in an inpatient setting at a single phase I unit in Germany. Design A sequential design was chosen to enable dose escalation starting with 40 mg bid with a potential maximum dose of 80 mg bid. Three subsequent cohorts of 10 patients each are randomised with different starting doses. Subjects in group one are treated with 40 mg bid for 14 days and may be increased to 60 mg bid the subsequent 14 days. In group 2, subjects may first receive 60 mg bid with possible increase to 80 mg bid. Group 3 subjects may receive 80 mg bid for 28 days. Dose increases in the consecutive groups are subject to approval by a Data Review Committee (DRC). The decision to increase the dose in individual patient will be based on the investigator’s judgement. Results Results of the study are expected for Q4/2016. Conclusions Recruitment in this trial is difficult as in-patient periods of nearly one month are logistically challenging. Safety data will be available soon and pharmacodynamics readouts such as Q-motor measures may help to guide decisions on the further path of development of BN82451B