Die Identifikation von Differenzierungsgenen in der Entwicklung von hämatopoetischen Stammzellen zu dendritischen Zellen

Die dendritische Zelle gehört zu den antigenpräsentierenden Zellen und ist der Initiator und Modulator der Immunantwort. Gegenwärtig existieren unterschiedliche Konzepte in Hinblick auf die Therapie von bösartigen Tumoren mit dendritischen Zellen. Voraussetzung für die Erforschung der Grundlagen ist die Anzüchtung von dendritischen Zellen in vitro in ausreichender Menge durch Stimulation CD34+ hämatopoetischer Stammzellen mit GM-CSF und TNF-α. Die diesem Differenzierungsschritt zugrunde liegenden Genexpressions-muster sind allerdings vollständig unbekannt. Das Ziel der Arbeit lag daher in der Identifizierung von Differenzierungsgenen in der Entwicklung von hämatopoetischen Stammzellen zu dendritischen Zellen. Hierzu wurde eine Suppressive Subtraktive Hybridisierung mit zwei Zellpopulationen durchgeführt. Die eine CD34+ Population wurde mit GM-CSF und TNF-α stimuliert und die Zweite mit M-CSF. Es konnten 27 Gene mit unterschiedlichen biologischen Funktionen wie Regulation der Zelldifferenzierung, -proliferation, -wachstum, -überleben und der Immunantwort identifiziert werden

BariSurg trial: Sleeve gastrectomy versus Roux-en-Y gastric bypass in obese patients with BMI 35–60 kg/m2 – a multi-centre randomized patient and observer blind non-inferiority trial

Background: Roux-en-Ygastric bypass (RYGB) and sleeve gastrectomy (SG) rank among the most frequently applied bariatric procedures worldwide due to their positive risk/benefit correlation. A systematic review revealed a similar excess weight loss (EWL) 2 years postoperatively between SG and RYGB. However, there is a lack of randomized controlled multi-centre trials comparing SG and RYGB, not only concerning EWL, but also in terms of remission of obesity-related co-morbidities, gastroesophageal reflux disease (GERD) and quality of life (QoL) in the mid- and long-term. Methods: The BariSurg trial was designed as a multi-centre, randomized controlled patient and observer blind trial. The trial protocol was approved by the corresponding ethics committees of the centres. To demonstrate EWL non-inferiority of SG compared to RYGB, power calculation was performed according to a non-inferiority study design. Morbidity, mortality, remission of obesity-related co-morbidities, GERD course and QoL are major secondary endpoints. 248 patients between 18 and 70 years, with a body mass index (BMI) between 35–60 kg/m2 and indication for bariatric surgery according to the most recent German S3-guidelines will be randomized. The primary and secondary endpoints will be assessed prior to surgery and afterwards at discharge and at the time points 3–6, 12, 24, 36, 48 and 60 months postoperatively. Discussion: With its five year follow-up, the BariSurg-trial will provide further evidence based data concerning the impact of SG and RYGB on EWL, remission of obesity-related co-morbidities, the course of GERD and QoL. Trial registration: The trial protocol has been registered in the German Clinical Trials Register DRKS0000476

improvement of Mechanical properties of WC-Co composites with heterogeneous structure fabricated by selective laser melting process

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Dual-Phase Al0.5CoCrFeMnNi 고엔트로피합금의 상온 및 극저온 인장 거동 분석

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탄소 첨가가 CoCrFeNiMo 중엔트로피합금의 미세조직과 기계적 특성 에 미치는 영향

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Correlation between microstructural heterogeneity and mechanical properties of WC-Co composite additively manufactured by selective laser melting

A unique heterogeneous microstructure was generated in the tungsten carbide-cobalt (WC-Co) composite additively-manufactured by selective laser melting (SLM). In this work, the effect of microstructural heterogeneity on mechanical properties and crack propagation in SLM-processed WC-Co is investigated. The strength and strain calculation model is constructed to analyze mechanical properties in heterogeneous WC-Co. Especially, this heterogeneity contributes to further deformation by interrupting crack propagation. The SLM process can be a candidate for manufacturing process to tailor microstructural heterogeneity of WC-Co composite. (c) 2021 Elsevier B.V. All rights reserved.11Nsciescopu

Reliability modeling of safety-critical network communication in a digitalized nuclear power plant

The Engineered Safety Feature-Component Control System (ESF-CCS), which uses a network communication system for the transmission of safety-critical information from group controllers (GCs) to loop controllers (LCs), was recently developed. However, the ESF-CCS has not been applied to nuclear power plants (NPPs) because the network communication failure risk in the ESF-CCS has yet to be fully quantified. Therefore, this study was performed to identify the potential hazardous states for network communication between GCs and LCs and to develop quantification schemes for various network failure causes. To estimate the risk effects of network communication failures in the ESF-CCS, a fault-tree model of an ESF-CCS signal failure in the containment spray actuation signal condition was developed for the case study. Based on a specified range of periodic inspection periods for network modules and the baseline probability of software failure, a sensitivity study was conducted to analyze the risk effect of network failure between GCs and LCs on ESF-CCS signal failure. This study is expected to provide insight into the development of a fault-tree model for network failures in digital I&C systems and the quantification of the risk effects of network failures for safety-critical information transmission in NPPs

Precipitation-driven metastability engineering of carbon-doped CoCrFeNiMo medium-entropy alloys at cryogenic temperature

Here, novel medium-entropy alloys with chemical compositions of Co17.5Cr12.5Fe55Ni10Mo4C1 and Co17.5Cr12.5Fe55Ni10Mo3C2 (at%) exhibiting excellent tensile properties at both room and liquid nitrogen temperatures have been developed. Precipitation of carbides changes the chemical composition and phase stability of the matrix, resulting in the controlled deformation-induced martensitic transformation from face-centered cubic to body-centered cubic of the alloys. The carbide precipitation, lattice distortion, and martensitic transformation led the alloy to have ultra-high yield strength of similar to 1 GPa and ultimate tensile strength of similar to 2 GPa with extra work hardening at liquid nitrogen temperature. (C) 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.11Nsciescopu

Effect of the combination of mitiglinide and metformin on glycemic control in patients with type 2 diabetes mellitus

Aims/Introduction: Mitiglinide is the newest drug in the meglitinide family. It increases the early-phase insulin release through rapid association-dissociation kinetics in the pancreatic beta cells. The efficacy and safety of adding meglitinide to metformin monotherapy in patients with type 2 diabetes are unknown. Materials and Methods: We carried out a prospective, randomized, multicenter trial to assess the efficacy and safety of combined treatment with mitiglinide and metformin for patients with type 2 diabetes who showed inadequate glycemic control with metformin monotherapy. Subjects with glycated hemoglobin (HbA(1c)) > 7.0% after an 8-week metformin run-in phase were randomized to a 16-week trial phase with metformin plus mitiglinide (Met + Mit) or metformin plus placebo (Met + Pcb). Results: Compared with the Met + Pcb group, the Met + Mit group showed a greater reduction in HbA(1c) (-0.7 +/- 0.6% vs -0.4 +/- 0.7%, P = 0.002), fasting plasma glucose (-0.77 +/- 1.76 mmol/L vs -0.05 +/- 1.60 mmol/L, P = 0.015) and 2-h postprandial glucose (-3.76 +/- 3.57 mmol/L vs -0.84 +/- 3.07 mmol/L, P < 0.0001). The proportion of the patients who achieved the target HbA(1c) value of < 7% at the end of the study was also higher in the Met + Mit group than the Met + Pcb group (49.3% vs 28.8%, P = 0.016). There were no differences in the adverse event rates between groups. Conclusions: Combination therapy with metformin and mitiglinide is effective and safe for the treatment of patients with type 2 diabetes who have inadequate glycemic control with metformin monotherapy. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00023.x, 2010)Kaku K, 2009, ENDOCR J, V56, P739, DOI 10.1507/endocrj.K09E-023Bolen S, 2007, ANN INTERN MED, V147, P386Ogawa K, 2007, INT HEART J, V48, P337Kumashiro N, 2007, ENDOCR J, V54, P163Yoshihara T, 2006, ENDOCR J, V53, P67Assaloni R, 2005, DIABETOLOGIA, V48, P1919, DOI 10.1007/s00125-005-1849-5Stumvoll M, 2005, LANCET, V365, P1333Leiter LA, 2005, CLIN THER, V27, pS42, DOI 10.1016/j.clinthera.2005.11.020Nakagami T, 2004, DIABETOLOGIA, V47, P385, DOI 10.1007/s00125-004-1334-6Raskin P, 2003, DIABETES CARE, V26, P2063Del Prato S, 2003, DIABETOLOGIA, V46, pM2, DOI 10.1007/s00125-002-0930-6Musi N, 2002, DIABETES, V51, P2074Wright A, 2002, DIABETES CARE, V25, P330MARRE M, 2002, DIABETES OBES METAB, V4, P177Bonora E, 2001, DIABETOLOGIA, V44, P2107Sunaga Y, 2001, EUR J PHARMACOL, V431, P119Zhou GC, 2001, J CLIN INVEST, V108, P1167Reimann F, 2001, BRIT J PHARMACOL, V132, P1542de Souza CJ, 2001, DIABETES OBES METAB, V3, P85HU S, 2001, INT J EXP DIABETES R, V2, P63Horton ES, 2000, DIABETES CARE, V23, P1660Hu SL, 2000, J PHARMACOL EXP THER, V293, P444Laghmich A, 1999, PHARMACOL RES, V40, P475Louchami K, 1999, PHARMACOL RES, V40, P297Moses R, 1999, DIABETES CARE, V22, P119Laghmich A, 1998, EUR J PHARMACOL, V348, P265TURNER NC, 1998, PROG DRUG RES, V51, P33Bailey CJ, 1996, NEW ENGL J MED, V334, P574TURNER RC, 1995, DIABETES, V44, P1249MALAISSE WJ, 1995, GEN PHARMACOL, V26, P1313STUMVOLL M, 1995, NEW ENGL J MED, V333, P550OHNOTA H, 1994, J PHARMACOL EXP THER, V269, P489BAKKALINADI A, 1994, DIABETES RES, V27, P61DEFRONZO RA, 1992, DIABETES CARE, V15, P318CONSOLI A, 1989, DIABETES, V38, P550EFENDIC S, 1984, ENDOCR REV, V5, P395STEINER KE, 1982, DIABETES, V31, P964CERASI E, 1967, DIABETES, V16, P615