Perinatal Obesity Induces Hepatic Growth Restriction with Increased DNA Damage Response,Senescence, and Dysregulated Igf-1-Akt-Foxo1 Signaling in Male Offspring of Obese Mice

Maternal obesity predisposes for hepato-metabolic disorders early in life. However, the underlying mechanisms causing early onset dysfunction of the liver and metabolism remain elusive. Since obesity is associated with subacute chronic inflammation and accelerated aging, we test the hypothesis whether maternal obesity induces aging processes in the developing liver and determines thereby hepatic growth. To this end, maternal obesity was induced with high-fat diet (HFD) in C57BL/6N mice and male offspring were studied at the end of the lactation [postnatal day 21 (P21)]. Maternal obesity induced an obese body composition with metabolic inflammation and a marked hepatic growth restriction in the male offspring at P21. Proteomic and molecular analyses revealed three interrelated mechanisms that might account for the impaired hepatic growth pattern, indicating prematurely induced aging processes: (1) Increased DNA damage response (γH2AX), (2) significant upregulation of hepatocellular senescence markers (Cdnk1a, Cdkn2a); and (3) inhibition of hepatic insulin/insulin-like growth factor (IGF)-1-AKT-p38-FoxO1 signaling with an insufficient proliferative growth response. In conclusion, our murine data demonstrate that perinatal obesity induces an obese body composition in male offspring with hepatic growth restriction through a possible premature hepatic aging that is indicated by a pathologic sequence of inflammation, DNA damage, senescence, and signs of a possibly insufficient regenerative capacity.     

Process and technology challenges in swift-starting virtual teams

Virtual teams often face tight schedules and a need to start quickly and perform instantly. The goal of our study was to enhance understanding of the challenges faced by such teams. We used time–interaction–performance theory as the framework for following the processes and functions within virtual teams working on a systems development task. Our study provided a detailed examination of the group process, applied to virtual teams working under time pressure. The challenges faced by virtual teams in such settings showed that teams must work to enhance their effectiveness in multiple dimensions.     

Development of a Modelica Compiler Using JastAdd

This paper describes experiences from implementing key parts of a compiler for Modelica, an object-oriented language supporting declarative modeling and simulation of complex physical systems. Our implementation uses the attribute-grammar based tool JastAdd. In particular, we discuss the implementation of Modelica name analysis which is highly context-dependent, type analysis which is based on structural subtyping, and flattening which is a fundamental part of the Modelica compilation process.of so called modifications, Modelica.     

Optimal shape design as a material distribution problem

Shape optimization in a general setting requires the determination of the optimal spatial material distribution for given loads and boundary conditions. Every point in space is thus a material point or a void and the optimization problem is a discrete variable one. This paper describes various ways of removing this discrete nature of the problem by the introduction of a density function that is a continuous design variable. Domains of high density then define the shape of the mechanical element. For intermediate densities, material parameters given by an artificial material law can be used. Alternatively, the density can arise naturally through the introduction of periodically distributed, microscopic voids, so that effective material parameters for intermediate density values can be computed through homogenization. Several examples in two-dimensional elasticity illustrate that these methods allow a determination of the topology of a mechanical element, as required for a boundary variations shape optimization technique.     

Accountability in Brazilian Governmental Software Project: How Chat Technology Enables Social Translucence in Bug Report Activities

Fixing software bug is part of the daily work routine in software engineering which requires collaboration and thus has been explored as a core CSCW domain, since the early inception of the research field. In this paper, we explore the use of chat technology in software engineering by analyzing the coordination between client and vendor in a large government software project in Brazil (Gov-IT). We collected our empirical material through face-to-face and online interviews, site and chat forums observations. Looking closely at the bug fixing activities within Gov-IT, we find that the client and the vendor use chat technology to coordinate their cooperative work by enabling the participants to monitor the availability of developers and the urgency of detecting bugs synchronously. This way, the chat technology made it possible for the client to report bugs and developers to resolve bugs in a timely manner. Moreover, the chat technology enabled the participants to request and share artefacts synchronously, making it possible to analyze and understand the contextual nature surrounding bugs faster than using the bug tracking system. Finally, the chat technology enabled participants in enacting commitment and interdependence across vendor and client, creating cooperative situations of mutual dependence. Our results suggest that we, as CSCW designers, must rethink the design of bug tracking systems and find new ways to re-configure systems, so they support the coordinative practices involved in detecting, analyzing, and resolving critical and severe software bugs synchronously.     

Evaluation of a Novel Thiol–Norbornene-Functionalized Gelatin Hydrogel for Bioprinting of Mesenchymal Stem Cells

Introduction: Three-dimensional bioprinting can be considered as an advancement of the classical tissue engineering concept. For bioprinting, cells have to be dispersed in hydrogels. Recently, a novel semi-synthetic thiolene hydrogel system based on norbornene-functionalized gelatin (GelNB) and thiolated gelatin (GelS) was described that resulted in the photoclick hydrogel GelNB/GelS. In this study, we evaluated the printability and biocompatibility of this hydrogel system towards adipose-tissue-derived mesenchymal stem cells (ASCs). Methods: GelNB/GelS was synthesized with three different crosslinking densities (low, medium and high), resulting in different mechanical properties with moduli of elasticity between 206 Pa and 1383 Pa. These hydrogels were tested for their biocompatibility towards ASCs in terms of their viability, proliferation and differentiation. The extrusion-based bioprinting of ASCs in GelNB/GelS-high was performed to manufacture three-dimensional cubic constructs. Results: All three hydrogels supported the viability, proliferation and chondrogenic differentiation of ASCs to a similar extent. The adipogenic differentiation of ASCs was better supported by the softer hydrogel (GelNB/GelS-low), whereas the osteogenic differentiation was more pronounced in the harder hydrogel (GelNB/GelS-high), indicating that the differentiation fate of ASCs can be influenced via the adaption of the mechanical properties of the GelNB/GelS system. After the ex vivo chondrogenic differentiation and subcutaneous implantation of the bioprinted construct into immunocompromised mice, the production of negatively charged sulfated proteoglycans could be observed with only minimal inflammatory signs in the implanted material. Conclusions: Our results indicate that the GelNB/GelS hydrogels are very well suited for the bioprinting of ASCs and may represent attractive hydrogels for subsequent in vivo tissue engineering applications.     

Shot-noise limited,supercontinuum-based optical coherence tomography

We present the first demonstration of shot-noise limited supercontinuum-based spectral domain optical coherence tomography (SD-OCT) with an axial resolution of ...     

The Pro-Inflammatory Deletion Allele of the NF-κB1 Polymorphism Is Characterized by a Depletion of Subunit p50 in Sepsis

The functionally important NF-κB1 promoter polymorphism (−94ins/delATTG) significantly shapes inflammation and impacts the outcome of sepsis. However, exploratory studies elucidating the molecular link of this genotype-dependent pattern are lacking. Accordingly, we analyzed lipopolysaccharide-stimulated peripheral blood mononuclear cells from both healthy volunteers (n = 20) and septic patients (n = 10). All individuals were genotyped for the −94ins/delATTG NF-κB1 promoter polymorphism. We found a diminished nuclear activity of the NF-κB subunit p50 in ID/DD genotypes after 48 h of lipopolysaccharide stimulation compared to II genotypes (p = 0.025). This was associated with higher TNF-α (p = 0.005) and interleukin 6 concentrations (p = 0.014) and an increased production of mitochondrial radical oxygen species in ID/DD genotypes (p = 0.001). Although ID/DD genotypes showed enhanced activation of mitochondrial biogenesis, they still had a significantly diminished cellular ATP content (p = 0.046) and lower mtDNA copy numbers (p = 0.010) compared to II genotypes. Strikingly, these findings were mirrored in peripheral blood mononuclear cells taken from septic patients. Our results emphasize the crucial aspect of considering NF-κB subunits in sepsis. We showed here that the deletion allele of the NF-κB1 (−94ins/delATTG) polymorphism was associated with the lower nuclear activity of subunit p50, which, in turn, was associated with aggravated inflammation and mitochondrial dysfunction.     

Measurements and Model Estimations of Viscosities of the MnO-CaO-SiO2-MgO-Al2O3 Melts

Metallurgical and Materials Transactions B - The viscosities of the MnO (0 to 55 mass pct)-CaO-SiO2-MgO (5 mass pct)-Al2O3 (20 mass pct) melts were measured by rotating cylinder method in the...