Material Issues in Layered Forming

A brief overview of key issues in layered thermal processing is given. Incremental sintering and layered fusion ofpowder and molten droplets are discussed. The criteria for remelting the solid substrate are derivedfrom a one dimensional heat transfer model. Temperature gradients which occur during solidification and subsequent cooling. are responsible for the build up of internal stresses which can be estimated through establishing an elastic beam model. The difficulties as well as opportunities regarding the generation of multi-layer multi-material structures are also described in this article.Mechanical Engineerin

The Heterogeneity of Disruptive Behavior Disorders – Implications for Neurobiological Research and Treatment

Disruptive behavior disorders (DBDs) are reflected by a great variety of symptoms ranging from impulsive-hot-tempered quarrels to purposeful and goal-directed acts of cruelty. A growing body of data indicates that there are neurobiological factors that increase the risk for developing DBDs. In this review, we give a broad overview of recent studies investigating physiological, neural, genetic factors, and specific neurotransmitter systems. We also discuss the impact of psychosocial risk and consider the effects of gene-environment interactions. Due to the heterogeneity of DBDs, it is concluded that specific subtypes of disruptive behavior should be considered both in terms their biological basis and in regard to specific treatment needs

Effectiveness of a 16-Week Multimodal Exercise Program on Individuals With Dementia: Study Protocol for a Multicenter Randomized Controlled Trial

Background: The increasing prevalence of dementia in the next decades is accompanied by various societal and economic problems. Previous studies have suggested that physical activity positively affects motor and cognitive skills in individuals with dementia (IWD). However, there is insufficient evidence probably related to several methodological limitations. Moreover, to date adequate physical activity interventions specifically developed for IWD are lacking. Objective: This study aims to investigate the effectiveness of a multimodal exercise program (MEP) on motor and cognitive skills in IWD in a high-quality multicenter trial. Methods: A multicenter randomized controlled trial with baseline and postassessments will be performed. It is planned to enroll 405 participants with dementia of mild to moderate stage, aged 65 years and older. The intervention group will participate in a 16-week ritualized MEP especially developed for IWD. The effectiveness of the MEP on the primary outcomes balance, mobility, and gait will be examined using a comprehensive test battery. Secondary outcomes are strength and function of lower limbs, activities of daily living, and cognition (overall cognition, language, processing speed, learning and memory, and visual spatial cognition). Results: Enrollment for the study started in May 2015. It is planned to complete postassessments by the beginning of 2017. Results are expected to be available in the first half of 2017. Conclusions: This study will contribute to enhancing evidence for the effects of physical activity on motor and cognitive skills in IWD. Compared to previous studies, this study is characterized by a dementia-specific intervention based on scientific knowledge, a combination of motor and cognitive tasks in the intervention, and high standards regarding methodology. Findings are highly relevant to influence the multiple motor and cognitive impairments of IWD who are often participating in limited physical activity

Targeting class I histone deacetylases by the novel small molecule inhibitor 4SC-202 blocks oncogenic hedgehog-GLI signaling and overcomes smoothened inhibitor resistance

Aberrant activation of Hedgehog (HH)/GLI signaling is causally involved in numerous human malignancies, including basal cell carcinoma (BCC) and medulloblastoma. HH pathway antagonists targeting smoothened (SMO), an essential effector of canonical HH/GLI signaling, show significant clinical success in BCC patients and have recently been approved for the treatment of advanced and metastatic BCC. However, rapid and frequent development of drug resistance to SMO inhibitors (SMOi) together with severe side effects caused by prolonged SMOi treatment call for alternative treatment strategies targeting HH/GLI signaling downstream of SMO. In this study, we report that 4SC-202, a novel clinically validated inhibitor of class I histone deacetylases (HDACs), efficiently blocks HH/GLI signaling. Notably, 4SC-202 treatment abrogates GLI activation and HH target gene expression in both SMOi-sensitive and -resistant cells. Mechanistically, we propose that the inhibition of HDACs 1/2/3 is crucial for targeting oncogenic HH/GLI signaling, and that class I HDAC inhibitors either in combination with SMOi or as second-line therapy may improve the treatment options for HH-associated malignancies with SMOi resistance

Gestational Diabetes: Physical Activity Before Pregnancy and Its Influence on the Cardiovascular System

Objectives:Gestational diabetes mellitus (GDM) is a common complication in pregnancy, affecting around 14% of all pregnancies each year. It will likely further increase, as obesity becomes more prevalent. The impact of GDM on cardiovascular changes in pregnant women and her child is still unclear. The aim of the study was to measure the effects of physical activity before pregnancy on the cardiovascular system in patients with GDM in pregnancy. Methods:Two hundred and six pregnant women were included in this observational study. All participants were recruited at the tertiary level teaching University Hospital "Klinikum rechts der Isar" between 28 and 32 weeks gestation. Questionnaires dealing with pre-pregnancy daily and physical activity (PA) were evaluated. The cardiovascular status of the mothers included measurements of the intima-media thickness (IMT) of the carotid arteries. PA level was performed with a standardized 6-min-walking-test. Results:Ninety-nine women with GDM with a mean age of 33.84 (+/- 4.7) years were examined. One hundred seven healthy pregnant women aged 32.6 (+/- 4.2) years served as controls. The mean weight in the study group was 73.0 (+/- 20.3) kg and 61.7 (+/- 9.5) kg in the control group. Based on the higher weight in the study group, the Body Mass Index (BMI) was also significantly higher than in the control group (26.3 +/- 7.1 vs. 21.6 +/- 3;p< 0.001). The frequency of PA was significantly higher in the control group (p< 0.001). The objective fitness level was worse in pregnant women with GDM compared to healthy controls (472 vs. 523 m,p< 0.001). PA before and during pregnancy was less performed in the study group (86 vs. 64.5%,p= 0.002;69 vs. 45.7%,p= 0.003). Women who were physically inactive before pregnancy had a 3-times higher risk to develop GDM compared to active women (OR = 2.67). The IMT was significantly thicker in the study group (0.48 +/- 0.042 mm vs. 0.45 +/- 0.042) mm;p= 0.006). Conclusion:Physical activity before pregnancy and a lower initial weight reduces the risk of developing GDM and cardiovascular risk factors in pregnancy. The development of prevention programs is certainly necessary

Diverse types of knowledge on a plate: a multi-perspective and multi-method approach for the transformation of urban food systems towards sustainable diets

Urbanization processes are accompanied by growing global challenges for food systems. Urban actors are increasingly striving to address these challenges through a focus on sustainable diets. However, transforming food systems towards more sustainable diets is challenging and it is unclear what the local scope of action might be. Co-production of knowledge between science and non-science is particularly useful for analysing context-specific solutions and promise to result in more robust socio-economic, political and technical solutions. Thus, this paper aims to integrate different types and sources of knowledge to understand urban food systems transformation towards a more sustainable diet in Vienna; and, second, to analyse and reflect on the difficulties and ways forward to integrate diverse actors’ perspectives, multiple methods and epistemologies. We created different future scenarios that illustrate the synergies and trade-offs of various bundles of measures and the interactions among single dimensions of sustainable diets. These scenarios show that there is plenty of scope for local action, but co-ordination across diverse groups, interests, and types of knowledge is necessary to overcome lock-ins

Intratumor Heterogeneity of the Estrogen Receptor and the Long-term Risk of Fatal Breast Cancer.

Background:Breast cancer patients with estrogen receptor (ER)-positive disease have a continuous long-term risk for fatal breast cancer, but the biological factors influencing this risk are unknown. We aimed to determine whether high intratumor heterogeneity of ER predicts an increased long-term risk (25 years) of fatal breast cancer. Methods:The STO-3 trial enrolled 1780 postmenopausal lymph node-negative breast cancer patients randomly assigned to receive adjuvant tamoxifen vs not. The fraction of cancer cells for each ER intensity level was scored by breast cancer pathologists, and intratumor heterogeneity of ER was calculated using Rao's quadratic entropy and categorized into high and low heterogeneity using a predefined cutoff at the second tertile (67%). Long-term breast cancer-specific survival analyses by intra-tumor heterogeneity of ER were performed using Kaplan-Meier and multivariable Cox proportional hazard modeling adjusting for patient and tumor characteristics. Results:A statistically significant difference in long-term survival by high vs low intratumor heterogeneity of ER was seen for all ER-positive patients (P &lt; .001) and for patients with luminal A subtype tumors (P = .01). In multivariable analyses, patients with high intratumor heterogeneity of ER had a twofold increased long-term risk as compared with patients with low intratumor heterogeneity (ER-positive: hazard ratio [HR] = 1.98, 95% confidence interval [CI] = 1.31 to 3.00; luminal A subtype tumors: HR = 2.43, 95% CI = 1.18 to 4.99). Conclusions:Patients with high intratumor heterogeneity of ER had an increased long-term risk of fatal breast cancer. Interestingly, a similar long-term risk increase was seen in patients with luminal A subtype tumors. Our findings suggest that intratumor heterogeneity of ER is an independent long-term prognosticator with potential to change clinical management, especially for patients with luminal A tumors

First Measurement of the 96^{96}Ru(p,γ\gamma)97^{97}Rh Cross Section for the p-Process with a Storage Ring

This work presents a direct measurement of the $^{96}$Ru($p, \gamma$)$^{97}$Rh cross section via a novel technique using a storage ring, which opens opportunities for reaction measurements on unstable nuclei. A proof-of-principle experiment was performed at the storage ring ESR at GSI in Darmstadt, where circulating $^{96}$Ru ions interacted repeatedly with a hydrogen target. The $^{96}$Ru($p, \gamma$)$^{97}$Rh cross section between 9 and 11 MeV has been determined using two independent normalization methods. As key ingredients in Hauser-Feshbach calculations, the $\gamma$-ray strength function as well as the level density model can be pinned down with the measured ($p, \gamma$) cross section. Furthermore, the proton optical potential can be optimized after the uncertainties from the $\gamma$-ray strength function and the level density have been removed. As a result, a constrained $^{96}$Ru($p, \gamma$)$^{97}$Rh reaction rate over a wide temperature range is recommended for $p$-process network calculations.Comment: 10 pages, 7 figs, Accepted for publication at PR

Measurements of proton-induced reactions on ruthenium-96 in the ESR at GSI

8th International Conference on Nuclear Physics at Storage Rings Stori11, October 9-14, 2011 Laboratori Nazionale di Frascati, Italy. Storage rings offer the possibility of measuring proton- and alpha-induced reactions in inverse kinematics. The combination of this approachwith a radioactive beamfacility allows, in principle, the determination of the respective cross sections for radioactive isotopes. Such data are highly desired for a better understanding of astrophysical nucleosynthesis processes like the p-process. A pioneering experiment has been performed at the Experimental Storage Ring (ESR) at GSI using a stable 96Ru beam at 9-11 AMeV and a hydrogen target. Monte-Carlo simulations of the experiment were made using the Geant4 code. In these simulations, the experimental setup is described in detail and all reaction channels can be investigated. Based on the Geant4 simulations, a prediction of the shape of different spectral components can be performed. A comparison of simulated predictions with the experimental results shows a good agreement and allows the extraction of the cross section