Coated fat-based confectionery products

This invention concerns a fat-based confectionery product which is coated with a film forming agent and characterised in that it is heat resistant and in that it retains its shape when submitted to heat. This invention also disclosed the use of this coated fat-based confectionery in food product, as well as a food product comprising this coated fat-based confectionery, especially chocolate or baked food. Patent CA 2537661 A

Propensity Scoring after Multiple Imputation in a Retrospective Study on Adjuvant Radiation Therapy in Lymph-Node Positive Vulvar Cancer

Propensity scoring (PS) is an established tool to account for measured confounding in non-randomized studies. These methods are sensitive to missing values, which are a common problem in observational data. The combination of multiple imputation of missing values and different propensity scoring techniques is addressed in this work. For a sample of lymph node-positive vulvar cancer patients, we re-analyze associations between the application of radiotherapy and disease-related and non-related survival. Inverse-probability-of-treatment-weighting (IPTW) and PS stratification are applied after multiple imputation by chained equation (MICE). Methodological issues are described in detail. Interpretation of the results and methodological limitations are discussed

Distinct hypothalamus-habenula circuits govern risk preference

Appropriate evaluation of risk is essential for survival in complex, uncertain environments. Confronted with choosing between a certain (safe) and an uncertain (risky) option, animals of various species show strong preferential traits which are stable across extended periods of time$^{1-8}$. How such risk preference is encoded in the neural circuitry of the brain remains poorly understood. A candidate brain region is the lateral habenula (LHb), which has been shown to be prominently involved in various value-guided behaviors$^{9-12}$. Here, using a balanced two-alternative choice task involving risk of loss, we find that neuronal activity in the LHb prior to action selection reflects risk preference and is governed by distinct inputs from hypothalamic subregions. Specifically, by employing multi-fiber photometry and targeted optogenetic perturbations, we identified glutamatergic LHb projections from both lateral and medial hypothalamus (LH/MH) that provide functionally distinct synaptic inputs to the LHb before action selection. Microendoscopic two-photon calcium imaging revealed risk-preference-selective LHb neurons that decreased their selectivity upon chemogenetic silencing of MH but not LH inputs. Finally, optogenetic stimulation of MH→LHb axons evoked both excitatory and inhibitory postsynaptic responses in LHb neurons (indicative of glutamate/GABA co-release for fine-tuned gain control$^{13}$), whereas LH→LHb projections were purely excitatory. Our results thus reveal functionally distinct hypothalamus-habenula circuits that govern risk preference in situations of economic decision-making

Optimization potentials of the transverse flux machine over the product life cycle

This study focuses on improving the performance and reliability of a transverse flux machine (TFM) for automotive applications over the whole product life cycle. TFMs offer high torque density but present challenges in electromagnetic design, cooling, and vibration control. To address these issues, different measures like additive manufacturing, sensor integration, and optimization techniques are explored and evaluated. By incorporating sensors for real-time data collection during operation and integrating structural improvements during development, TFMs can achieve higher efficiency and reliability. This study gives an overview over several topics which have been researched in 2 projects, each of which consists of 3 participating institutions. It explores the integration of vibration sensors/actuators and temperature sensors. Additionally, additive manufacturing techniques are utilized for manufacturing of soft magnetic components to reduce eddy current losses and optimize the cooling. The findings demonstrate the potential of these approaches to enhance TFMs for automotive use, and further research is recommended to assess their durability and applicability under real-world conditions

Sunitinib Inhibits Cell Proliferation and Alters Steroidogenesis by Down-Regulation of HSD3B2 in Adrenocortical Carcinoma Cells

The multi-tyrosine kinase inhibitor sunitinib is used in the treatment of several solid tumors. Animal experiments pointed to an adrenotoxic effect of sunitinib. Therefore, we evaluated the expression of key targets of sunitinib in human adrenocortical carcinoma (ACC) tumor samples and investigated its in vitro effects in ACC cell lines. We carried out immunohistochemistry for vascular endothelial growth factor (VEGF) and its receptor (VEGF-R2) in 157 ACC samples and nine normal adrenal glands. VEGF and VEGF-R2 protein were expressed in 72 and 99% of ACC samples, respectively. Using NCI-H295 and SW13 ACC cell lines, we investigated the effects of sunitinib on cell proliferation. Sunitinib reduced dose-dependently cell viability of both NCI-H295 and SW13 cells (SW13: 0.1 μM 96 ± 7%, 1 μM 90 ± 9%*, 5 μM 62 ± 6%*, controls 100 ± 9%; *p < 0.05). To determine sunitinib effects on steroidogenesis, we measured steroid hormones in cell culture supernatant by gas chromatography–mass spectrometry. We observed a pronounced decrease of cortisol secretion (1 μM 90.1 ± 1.5%*, 5 μM 57.2 ± 0.3%*, controls 100 ± 2.4%) and a concomitant increase in the DHEA/4-androstenedione and 17-hydroxypregnenolone/17-hydroxyprogesterone ratios, indicating specific inhibition of 3β-hydroxysteroid dehydrogenase (HSD3B2). In yeast microsomes transformed with HSD3B2, no direct inhibition of HSD3B2 by sunitinib was detected. Sunitinib induced down-regulation of HSD3B2 mRNA and protein in ACC cell lines (mRNA: 1 μM 44 ± 16%*; 5 μM 22 ± 2%*; 10 μM 19 ± 4%*; protein: 1 μM 82 ± 8%; 5 μM 63 ± 8%*; 10 μM 55 ± 9%*). CYP11B1 was down-regulated at mRNA but not at protein level and CYP11A1 remained unchanged. In conclusion, target molecules of sunitinib are expressed in the vast majority of ACC samples. Sunitinib exhibits anti-proliferative effects in vitro, and appears to specifically block adrenal steroidogenesis by down-regulation of HSD3B2, rendering it a promising option for treatment of ACC

Reference on copy number variations in pleomorphic xanthoastrocytoma: Implications for diagnostic approach

Pleomorphic xanthoastrocytoma (PXA) poses a diagnostic challenge. The present study relies on methylation-based predictions and focuses on copy number variations (CNV) in PXA. We identified 551 tumors from patients having received the histologic diagnosis or differential diagnosis pleomorphic xanthoastrocytoma (PXA) uploaded to the web page www.molecularneuropathology.org. Of these 551 tumors, 165 received the prediction “methylation class (anaplastic) pleomorphic xanthoastrocytoma” with a calibrated score &gt;=0.9 by the brain tumor classifier version v12.8 and, therefore, were defined the PXA reference set designated mcPXAref. In addition to these 165 mcPXAref, 767 other tumors received the prediction mcPXA with a calibrated score &gt;=0.9 but without a histological PXA diagnosis. The total number of individual tumors predicted by histology and/or by methylome based classification as PXA, mcPXA or both was 1318, and these were designated the study cohort. The selection of a control cohort was guided by methylation-based predictions recurrently observed for the other 386/551 tumors diagnosed as histologic PXA. 131/386 received predictions for another entity besides PXA with a score &gt;=0.9. Control tumors corresponding to the 11 most common other predictions were selected, adding up to 1100 reference cases. CNV profiles were calculated from all methylation datasets of the study and control cohorts. Special attention was given to the 7/10 signature, gene amplifications and homozygous deletion of CDKN2A/B. Comparison of CNV in the subsets of the study cohort and the control cohort were used to establish relations independent of histological diagnoses. Tumors in mcPXA were highly homogenous in regard to CNV alterations, irrespective of the histological diagnoses. The 7/10 signature commonly present in glioblastoma, IDH-wildtype, was present in 15-20% of mcPXA, whereas amplification of oncogenes (likewise common in glioblastoma) was very rare in mcPXA (&lt;1%). In contrast, the histology-based PXA group exhibited high variance in regard to methylation classes as well as to CNVs. Our data add to the notion, that histologically defined PXA likely only represent a subset of the biological disease

Water and Sodium Regulation in Heart Failure

Heart failure is the pathophysiological state characterized by ventricular dysfunction and associated clinical symptoms. Decreased cardiac output or peripheral vascular resistance lead to arterial underfilling. That is an important signal which triggers multiple neurohormonal systems to maintain adequate arterial pressure and peripheral perfusion of the vital organs. The kidney is the principal organ affected when cardiac output declines. Alterations of hemodynamics and neurohormonal systems in heart failure result in renal sodium and water retention. Activation of sympathetic nervous system, renin-angiotensin-aldosterone system and non-osmotic vasopressin release stimulate the renal tubular reabsorption of sodium and water. Dysregulation of aquaporin-2 and sodium transporters also play an important role in the pathogenesis of renal sodium and water retention

Fabrication, structure and properties of epoxy/metal nanocomposites

Gd2O3 nanoparticles surface-modified with IPDI were compounded with epoxy. IPDI provided an anchor into the porous Gd2O3 surface and a bridge into the matrix, thus creating strong bonds between matrix and Gd2O3. 1.7 vol.-% Gd2O3 increased the Young’s modulus of epoxy by 16–19%; the surface-modified Gd2O3 nanoparticles improved the critical strain energy release rate by 64.3% as compared to 26.4% produced by the unmodified nanoparticles. The X-ray shielding efficiency of neat epoxy was enhanced by 300–360%, independent of the interface modification. Interface debonding consumes energy and leads to crack pinning and matrix shear banding; most fracture energy is consumed by matrix shear banding as shown by the large number of ridges on the fracture surface