Start-ups, Long- and Short-Term Survivors and their Effect on Regional Employment Growth

We investigate the effects that regional start-up activity has on employment in new and in incumbent businesses. The analysis is performed for West German regions over the 1987-2002 period. It shows that the effects of new businesses on employment in the incumbents are significantly positive and that this indirect effect on incumbent employment leads to more jobs than what is created by the newcomers. We find that the effect of new business formation on incumbents is exclusively driven by start-ups that survive a certain period of time. We draw conclusions for policy and for further research.Entrepreneurship, new business formation, regional development, direct and indirect effects

The impact of sulfur hexafluoride (SF₆) sinks on age of air climatologies and trends

Mean age of air (AoA) is a common diagnostic for the strength of the stratospheric overturning circulation in both climate models and observations. AoA climatologies and AoA trends over the recent decades of model simulations and proxies derived from observations of long-lived tracers do not agree. Satellite observations show much older air than climate models, and while most models compute a clear decrease in AoA over the last decades, a 30-year time series from measurements shows a statistically nonsignificant positive trend in the Northern Hemisphere extratropical middle stratosphere. Measurement-based AoA derivations are often founded on observations of the trace gas sulfur hexafluoride (SF$_{6}$), a fairly long-lived gas with a near-linear increase in emissions during recent decades. However, SF$_{6}$ has chemical sinks in the mesosphere that are not considered in most model studies. In this study, we explicitly compute the chemical SF$_{6}$ sinks based on chemical processes in the global chemistry climate model EMAC (ECHAM/MESSy Atmospheric Chemistry). We show that good agreement between stratospheric AoA in EMAC and MIPAS (Michelson Interferometer for Passive Atmospheric Sounding) is reached through the inclusion of chemical SF$_{6}$ sinks, as these sinks lead to a strong increase in the stratospheric AoA and, therefore, to a better agreement with MIPAS satellite observations. Remaining larger differences at high latitudes are addressed, and possible reasons for these differences are discussed. Subsequently, we demonstrate that the AoA trends are also strongly influenced by the chemical SF6 sinks. Under consideration of the SF$_{6}$ sinks, the AoA trends over the recent decades reverse sign from negative to positive. We conduct sensitivity simulations which reveal that this sign reversal does not result from trends in the stratospheric circulation strength nor from changes in the strength of the SF$_{6}$ sinks. We illustrate that even a constant SF$_{6}$ destruction rate causes a positive trend in the derived AoA, as the amount of depleted SF$_{6}$ scales with increasing SF$_{6}$ abundance itself. In our simulations, this effect overcompensates for the impact of the accelerating stratospheric circulation which naturally decreases AoA. Although various sources of uncertainties cannot be quantified in detail in this study, our results suggest that the inclusion of SF$_{6}$ depletion in models has the potential to reconcile the AoA trends of models and observations. We conclude the study with a first approach towards a correction to account for SF$_{6}$ loss and deduce that a linear correction might be applicable to values of AoA of up to 4 years

Kräuter für Nutz- und Heimtiere: Ratgeber für die Anwendung ausgewählter Heil- und Gewürzpflanzen

Dieser Ratgeber führt wissenschaftliche Erkenntnisse und traditionelles Hausmittelwissen zusammen, beleuchtet alles Wissenswerte zu über 50 Heilpflanzen und gibt konkrete Anwendungsbeispiele. Ziel ist es, altbewährte Pflanzenanwendungen wieder mehr in die moderne Tierhaltung einzubinden. Der anwenderorientierte Aufbau des Buches ermöglicht es dem Leser, Kenntnisse über die verschiedenen Zubereitungen und Anwendungen von Heilpflanzen zu erwerben und diese in der Praxis einzusetzen. Zubereitung, Aufbewahrung und Anwendung von Kräutern, sowie deren Wirkung und Einsatz bei einzelnen Tierarten werden ausführlich dargestellt. „Die Aufgabe heutiger Wissenschaft ist weniger die Suche nach neuen wirksamen Pflanzen, vielmehr die Überprüfung und Absicherung dieses althergebrachten Wissensschatzes im Lichte moderner Erkenntnisse. Das Autorenteam setzt sich aus jungen engagierten Wissenschaftlern und Tierärzten zusammen. Ihnen ist es ein großes Anliegen, dass die Erkenntnisse der Kräuterheilkunde möglichst vielen Tierhaltern – insbesondere ihren Tieren – von Nutzen sein werden. Es bleibt der Wunsch: die vielen praktischen Anleitungen mögen einen starken Impuls zur Wiederbelebung der Kräuterheilkunde bei Tieren geben.“ Dr. Gerhard Plakol

Environmental heterogeneity predicts global species richness patterns better than area

Aim It is widely accepted that biodiversity is influenced by both niche‐related and spatial processes from local to global scales. Their relative importance, however, is still disputed, and empirical tests are surprisingly scarce at the global scale. Here, we compare the importance of area (as a proxy for pure spatial processes) and environmental heterogeneity (as a proxy for niche‐related processes) for predicting native mammal species richness world‐wide and within biogeographical regions. Location Global. Time period We analyse a spatial snapshot of richness data collated by the International Union for Conservation of Nature. Major taxa studied All terrestrial mammal species, including possibly extinct species and species with uncertain presence. Methods We applied a spreading dye algorithm to analyse how native mammal species richness changes with area and environmental heterogeneity. As measures for environmental heterogeneity, we used elevation ranges and precipitation ranges, which are well‐known correlates of species richness. Results We found that environmental heterogeneity explained species richness relationships better than did area, suggesting that niche‐related processes are more prevalent than pure area effects at broad scales. Main conclusions Our results imply that niche‐related processes are essential to understand broad‐scale species–area relationships and that habitat diversity is more important than area alone for the protection of global biodiversity

DSCAM-AS1 Long Non-Coding RNA Exerts Oncogenic Functions in Endometrial Adenocarcinoma via Activation of a Tumor-Promoting Transcriptome Profile

Accumulating evidence suggests that lncRNA DSCAM-AS1 acts tumor-promoting in various cancer entities. In breast cancer, DSCAM-AS1 was shown to be the lncRNA being most responsive to induction by estrogen receptor α (ERα). In this study, we examined the function of DSCAM-AS1 in endometrial adenocarcinoma using in silico and different in vitro approaches. Initial analysis of open-source data revealed DSCAM-AS1 overexpression in endometrial cancer (EC) (p < 0.01) and a significant association with shorter overall survival of EC patients (HR = 1.78, p < 0.01). In EC, DSCAM-AS1 was associated with endometrial tumor promotor gene PRL and with expression of ERα and its target genes TFF1 and PGR. Silencing of this lncRNA by RNAi in two EC cell lines was more efficient in ERα-negative HEC-1B cells and reduced their growth and the expression of proliferation activators like NOTCH1, PTK2 and EGR1. DSCAM-AS1 knockdown triggered an anti-tumoral transcriptome response as revealed by Affymetrix microarray analysis, emerging from down-regulation of tumor-promoting genes and induction of tumor-suppressive networks. Finally, several genes regulated upon DSCAM-AS1 silencing in vitro were found to be inversely correlated with this lncRNA in EC tissues. This study clearly suggests an oncogenic function of DSCAM-AS1 in endometrial adenocarcinoma via activation of a tumor-promoting transcriptome profile

ROS1 genomic rearrangements are rare actionable drivers in microsatellite stable colorectal cancer

c-Ros oncogene 1, receptor tyrosine kinase (ROS1) genomic rearrangements have been reported previously in rare cases of colorectal cancer (CRC), yet little is known about the frequency, molecular characteristics, and therapeutic vulnerabilities of ROS1-driven CRC. We analyzed a clinical dataset of 40 589 patients with CRC for ROS1 genomic rearrangements and their associated genomic characteristics (Foundation Medicine, Inc [FMI]). We moreover report the disease course and treatment response of an index patient with ROS1-rearranged metastatic CRC. ROS1 genomic rearrangements were identified in 34 (0.08%) CRC samples. GOPC-ROS1 was the most common ROS1 fusion identified (11 samples), followed by TTC28-ROS1 (3 samples). Four novel 5' gene partners of ROS1 were identified (MCM9, SRPK1, EPHA6, P4HA1). Contrary to previous reports on fusion-positive CRC, ROS1-rearrangements were found exclusively in microsatellite stable (MSS) CRCs. KRAS mutations were significantly less abundant in ROS1-rearranged vs ROS1 wild type cases. The index patient presented with chemotherapy-refractory metastatic right-sided colon cancer harboring GOPC-ROS1. Molecularly targeted treatment with crizotinib induced a rapid and sustained partial response. After 15 months on crizotinib disseminated tumor progression occurred and KRAS Q61H emerged in tissue and liquid biopsies. ROS1 rearrangements define a small, yet therapeutically actionable molecular subgroup of MSS CRC. In summary, the high prevalence of GOPC-ROS1 and noncanonical ROS1 fusions pose diagnostic challenges. We advocate NGS-based comprehensive molecular profiling of MSS CRCs that are wild type for RAS and BRAF and patient enrollment in precision trials. Keywords: ROS1 rearrangement; acquired resistance; colorectal cancer; crizotinib; molecular subgroups; precision treatmen

ROS1 genomic rearrangements are rare actionable drivers in microsatellite stable colorectal cancer.

c-Ros oncogene 1, receptor tyrosine kinase (ROS1) genomic rearrangements have been reported previously in rare cases of colorectal cancer (CRC), yet little is known about the frequency, molecular characteristics, and therapeutic vulnerabilities of ROS1-driven CRC. We analyzed a clinical dataset of 40 589 patients with CRC for ROS1 genomic rearrangements and their associated genomic characteristics (Foundation Medicine, Inc [FMI]). We moreover report the disease course and treatment response of an index patient with ROS1-rearranged metastatic CRC. ROS1 genomic rearrangements were identified in 34 (0.08%) CRC samples. GOPC-ROS1 was the most common ROS1 fusion identified (11 samples), followed by TTC28-ROS1 (3 samples). Four novel 5' gene partners of ROS1 were identified (MCM9, SRPK1, EPHA6, P4HA1). Contrary to previous reports on fusion-positive CRC, ROS1-rearrangements were found exclusively in microsatellite stable (MSS) CRCs. KRAS mutations were significantly less abundant in ROS1-rearranged vs ROS1 wild type cases. The index patient presented with chemotherapy-refractory metastatic right-sided colon cancer harboring GOPC-ROS1. Molecularly targeted treatment with crizotinib induced a rapid and sustained partial response. After 15 months on crizotinib disseminated tumor progression occurred and KRAS Q61H emerged in tissue and liquid biopsies. ROS1 rearrangements define a small, yet therapeutically actionable molecular subgroup of MSS CRC. In summary, the high prevalence of GOPC-ROS1 and noncanonical ROS1 fusions pose diagnostic challenges. We advocate NGS-based comprehensive molecular profiling of MSS CRCs that are wild type for RAS and BRAF and patient enrollment in precision trials

The impact of sulfur hexafluoride (SF6) sinks on age of air climatologies and trends

Mean age of air (AoA) is a common diagnostic for the strength of the stratospheric overturning circulation in both climate models and observations. AoA climatologies and AoA trends over the recent decades of model simulations and proxies derived from observations of long-lived tracers do not agree. Satellite observations show much older air than climate models, and while most models compute a clear decrease in AoA over the last decades, a 30-year time series from measurements shows a statistically nonsignificant positive trend in the Northern Hemisphere extratropical middle stratosphere. Measurement-based AoA derivations are often founded on observations of the trace gas sulfur hexafluoride (SF6), a fairly long-lived gas with a near-linear increase in emissions during recent decades. However, SF6 has chemical sinks in the mesosphere that are not considered in most model studies. In this study, we explicitly compute the chemical SF6 sinks based on chemical processes in the global chemistry climate model EMAC (ECHAM/MESSy Atmospheric Chemistry). We show that good agreement between stratospheric AoA in EMAC and MIPAS (Michelson Interferometer for Passive Atmospheric Sounding) is reached through the inclusion of chemical SF6 sinks, as these sinks lead to a strong increase in the stratospheric AoA and, therefore, to a better agreement with MIPAS satellite observations. Remaining larger differences at high latitudes are addressed, and possible reasons for these differences are discussed. Subsequently, we demonstrate that the AoA trends are also strongly influenced by the chemical SF6 sinks. Under consideration of the SF6 sinks, the AoA trends over the recent decades reverse sign from negative to positive. We conduct sensitivity simulations which reveal that this sign reversal does not result from trends in the stratospheric circulation strength nor from changes in the strength of the SF6 sinks. We illustrate that even a constant SF6 destruction rate causes a positive trend in the derived AoA, as the amount of depleted SF6 scales with increasing SF6 abundance itself. In our simulations, this effect overcompensates for the impact of the accelerating stratospheric circulation which naturally decreases AoA. Although various sources of uncertainties cannot be quantified in detail in this study, our results suggest that the inclusion of SF6 depletion in models has the potential to reconcile the AoA trends of models and observations. We conclude the study with a first approach towards a correction to account for SF6 loss and deduce that a linear correction might be applicable to values of AoA of up to 4 years