Cross-divisional innovation in large, multi-divisional firms: Economic relevance and managerial actions

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Motivations for Adolescent COVID-19 Vaccination: A Comparative Study of Adolescent and Caregiver Perspectives in Germany

Given the crucial role of vaccination in halting the COVID-19 pandemic, it is imperative to understand the factors that motivate adolescents to get vaccinated. We surveyed adolescents and their accompanying guardians scheduled to receive a COVID-19 vaccination (Comirnaty) in an urban region in Germany in mid-2021 regarding their motivation for getting vaccinated and collected data on their sociodemographic characteristics, medical history, vaccination status, and any history of COVID-19 infection in the family. We also queried information strategies related to the SARS-CoV-2 pandemic. Motivations for getting vaccinated were similar among adolescents and their parents. The primary reasons for vaccination were protection against SARS-CoV-2-related illness and gaining access to leisure facilities. This was not influenced by gender, health status, migration background, or the presence of chronic or acute diseases. The percentage of parents who had received SARS-CoV-2 immunization and the proportion of parents with a high level of education were higher among study participants than in the general population. Adolescents were especially willing to be vaccinated if they came from a better educational environment and had a high vaccination rate in the family. Emphasizing the importance of vaccination among all segments of the population and removing barriers to vaccines may lead to an ameliorated acceptance of COVID-19 vaccines

A genome-wide association study with tissue transcriptomics identifies genetic drivers for classic bladder exstrophy

Classic bladder exstrophy represents the most severe end of all human congenital anomalies of the kidney and urinary tract and is associated with bladder cancer susceptibility. Previous genetic studies identified one locus to be involved in classic bladder exstrophy, but were limited to a restrict number of cohort. Here we show the largest classic bladder exstrophy genome-wide association analysis to date where we identify eight genome-wide significant loci, seven of which are novel. In these regions reside ten coding and four non-coding genes. Among the coding genes is EFNA1, strongly expressed in mouse embryonic genital tubercle, urethra, and primitive bladder. Re-sequence of EFNA1 in the investigated classic bladder exstrophy cohort of our study displays an enrichment of rare protein altering variants. We show that all coding genes are expressed and/or significantly regulated in both mouse and human embryonic developmental bladder stages. Furthermore, nine of the coding genes residing in the regions of genome-wide significance are differentially expressed in bladder cancers. Our data suggest genetic drivers for classic bladder exstrophy, as well as a possible role for these drivers to relevant bladder cancer susceptibility

Intravenously Administered Alphavirus Vector VA7 Eradicates Orthotopic Human Glioma Xenografts in Nude Mice

VA7 is a neurotropic alphavirus vector based on an attenuated strain of Semliki Forest virus. We have previously shown that VA7 exhibits oncolytic activity against human melanoma xenografts in immunodeficient mice. The purpose of this study was to determine if intravenously administered VA7 would be effective against human glioma.In vitro, U87, U251, and A172 human glioma cells were infected and killed by VA7-EGFP. In vivo, antiglioma activity of VA7 was tested in Balb/c nude mice using U87 cells stably expressing firefly luciferase in subcutaneous and orthotopic tumor models. Intravenously administered VA7-EGFP completely eradicated 100% of small and 50% of large subcutaneous U87Fluc tumors. A single intravenous injection of either VA7-EGFP or VA7 expressing Renilla luciferase (VA7-Rluc) into mice bearing orthotopic U87Fluc tumors caused a complete quenching of intracranial firefly bioluminescence and long-term survival in total 16 of 17 animals. In tumor-bearing mice injected with VA7-Rluc, transient intracranial and peripheral Renilla bioluminescence was observed. Virus was well tolerated and no damage to heart, liver, spleen, or brain was observed upon pathological assessment at three and ninety days post injection, despite detectable virus titers in these organs during the earlier time point.VA7 vector is apathogenic and can enter and destroy brain tumors in nude mice when administered systemically. This study warrants further elucidation of the mechanism of tumor destruction and attenuation of the VA7 virus

Rethinking Land in the Anthropocene: from Separation to Integration

Nur wenn sich unser Umgang mit Land grundlegend ändert, können die Klimaschutzziele erreicht, der dramatische Verlust der biologischen Vielfalt abgewendet und das globale Ernährungssystem nachhaltig gestaltet werden. Der WBGU schlägt fünf exemplarische Mehrgewinnstrategien vor, um Konkurrenzen zwischen Nutzungsansprüchen zu überwinden. Diese sollten durch fünf Governance-Strategien vorangetrieben werden, darunter insbesondere die Setzung geeigneter Rahmenbedingungen, eine Neuorientierung der EUPolitik und die Errichtung von Gemeinschaften gleichgesinnter Staaten.Only if there is a fundamental change in the way we manage land can we reach the targets of climate-change mitigation, avert the dramatic loss of biodiversity and make the global food system sustainable. The WBGU proposes five multiple-benefit strategies illustrating ways of overcoming competition between rival claims to the use of land. These should be promoted by five governance strategies, especially by setting suitable framework conditions, reorienting EU policy and establishing alliances of like-minded states

Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located nearNEDD4LandSLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (R(g)ranging from 0.11 to 0.76, P-values Author summary Although twin studies have shown that body mass index (BMI) is highly heritable, many common genetic variants involved in the development of BMI have not yet been identified, especially in children. We studied associations of more than 40 million genetic variants with childhood BMI in 61,111 children aged between 2 and 10 years. We identified 25 genetic variants that were associated with childhood BMI. Two of these have not been implicated for BMI previously, located close to the genesNEDD4LandSLC45A3. We also show that the genetic background of childhood BMI overlaps with that of birth weight, adult BMI, waist-to-hip-ratio, diastolic blood pressure, type 2 diabetes, and age at menarche. Our results suggest that the biological processes underlying childhood BMI largely overlap with those underlying adult BMI. However, the overlap is not complete. Additionally, the genetic backgrounds of childhood BMI and other cardio-metabolic phenotypes are overlapping. This may mean that the associations of childhood BMI and later cardio-metabolic outcomes are partially explained by shared genetics, but it could also be explained by the strong association of childhood BMI with adult BMI.Peer reviewe

A Tooling and Production Strategy for a Fully Integral, Hig Production Rate NLF Upper Wing Skin

Abstract: A Tooling and Production Strategy for a Fully Integral, High Production Rate NLF Upper Wing Skin. Producing large integral composite components at a high production rate is a major challenge because the required level of process maturity is extremely high. Further more only a highly streamlined and optimised production approach can provide the required competitiveness. For a typical single aisle aircraft wing skin a length of up to 20m and typical laminate thicknesses of up to 25mm can be expected. In addition only secondary bonding or fully integral design approaches can provide the surface smoothness required for Natural Laminar Flow capabilities. In the framework of the LUFOIV Project LaWiPro it was decided to go for a fully integral design approach with integrated stringers and integrated rib caps following the tradition of the first Airbus CFRP VTP. In order to optimise the production sequence priority was given to minimised set-up and processing times. The so called “Shoe Box” solution that is currently investigated is based on a manufacturing optimised wing skin design without undercuts and interleaved Stringer, Rib Cap and Wing Skin plies. The production sequence starts with the wrapping of Hollow Tooling Modules that are afterwards combined to a row. Several rows of wrapped Tooling Modules are than placed on the referencing tooling base plate and covered with additional wing skin plies. After the set-up phase the tool is closed and placed in an autoclave or convection oven. To reduce the cycle time the Hollow Tooling Modules are connected to the process environment and there is a controlled airflow through the Tooling Modules. In the end the geometrical precision of the aerodynamic surfaces and also the joining areas is investigated with a contact-free high precision GOM-ATOS measuring equipment. Even though the first trials are based on prepreg it is an option to combine the prepreg wing skin laminate (e.g. ATL, AFP) with infused stringers and rib caps (Combined Prepreg Infusion (CPI)) or to chose a complete Infusion based approach. To evaluate the competitiveness of the “Shoe Box” solution all activities are accompanied by a related cost assessment that indicates areas that need to be improved from a maturity point of view or where automation concepts could be successfully applied to further reduce production costs

High Rate Production of Laminar Wing Covers with Modular ‘‘Shoe Box’’ Tooling.

Lightweight design is one of the major drivers for primary airframe structures because efficiency of future aircrafts is the dominating sales argument. CFRP (Carbon Fiber Reinforced Plastic) based airframe components do have the potential to challenge sophisticated aluminum structures but the complexity of the production sequence, the number of production parameters that have to be optimized and last not least the natural tolerances of the highly developed raw materials are crucial challenges for the development phase