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.     

MAX-phase coatings produced by thermal spraying

This paper presents a comparative study on the Ti₂AlC coatings produced by different thermal spray methods, as Ti₂AlC is one of the most studied materials from the MAX-phase family. Microstructural analysis of coatings produced by High Velocity Air Fuel (HVAF), Cold Spray and High Velocity Oxygen Fuel (HVOF) has been carried out by means of the scanning electron microscopy equipped with an energy dispersive spectrometer (EDS). The volume fraction of porosity was determined using the ASTM standard E562. The phase characterization of the as-received powder and as-sprayed coatings was conducted using the X-ray diffraction with CrKα radiation. Impact of the spray parameters on the porosity and the mechanical properties of the coatings are discussed. The results show that the spraying temperature and velocity play a crucial role in coatings characteristics.     

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.     

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.     

Accelerated climate ageing of building materials, components and structures in the laboratory

Building materials, components and structures have to fulfil many functional demands during the lifetime of a building. Therefore, it is important to require satisfactory durability of these materials, components and structures. In fact, one single material failure may jeopardize whole components as well as structures. Unfortunately, experience shows that building products too often do not satisfy the various requirements after a relatively short period of use, i.e. the expected service life is considerably shorter than foreseen. This results in increased and large costs due to increased maintenance, extensive replacements of the specific building products and any possible consequential building damages. In addition, health hazards with respect to both risk and consequence may also become an issue. To avoid this, the solution is to apply building products which have properly documented adequate and satisfactory long-term durability. That is, building products which have been subjected to long-term natural outdoor climate exposure or appropriate accelerated climate ageing in the laboratory. This study examines the main climate exposures and how these may be reproduced in the laboratory in various ways. Thus, crucial properties of building products and their durability towards climate strains may be investigated within a relatively short time frame compared with natural outdoor climate ageing. Examples of miscellaneous climate ageing laboratory apparatuses, ageing methods and building product properties to be tested before, during and after ageing are given. A calculation method for estimating acceleration factors is also discussed. Various ageing examples are shown and discussed. A special note is made towards accelerated climate ageing of new and advanced materials being developed. Hence, this study addresses durability and the versatile and powerful application of accelerated climate ageing which is an all too overlooked field within materials science and engineering.     

Physical Characterization of Anhydrous and Hydrous Forms of the Hydrochloride Salt of BVT.5182 A Novel 5-HT6 Receptor Antagonist

ABSTRACT

The physicochemical properties of 1-benzenesulfonyl-4-(piperazin-1-yl)-indole hydrochloride, a novel 5-HT₆ receptor antagonist for the treatment of obesity were characterized. Two solid state forms were identified at ambient conditions (23°C): an anhydrate form (1) and a hydrate form (2), with 1.5 moles of H₂O. The latter easily dehydrates and rehydrates without affecting the crystal morphology. Investigations of the propensity for interconversion between the two forms reveal that a) conversion of 2→1 takes place above 145°C and that b) conversion of 1→2 only occurs after crystallization from supersaturated aqueous solutions at a water activity ≥0.94 or in the presence of comparable amounts of crystals of 2 in water at ambient conditions. However, in an equimolar suspension of 1 and 2 at 37°C no phase transformation was observed. Thus, the difference in chemical potential between the two forms is small. Form 1 was shown to have overall favorable solid state properties and, hence, considered the preferred form for continued pharmaceutical development. The characterization was performed by means of light microscopy, scanning electron microscopy, powder X-ray diffraction, FTIR/NIR-spectroscopy, differential scanning calorimetry, hot stage microscopy, thermogravimetry, dynamic vapor sorption, Karl Fischer water content determination, phase stability studies of suspensions, solubility, and intrinsic dissolution rate measurements.     

Deposition welding of hot forging dies using nanoparticle reinforced weld metal

In the application field of forging, the form-giving tool components are subject to process-related severe environmental conditions, such as high mechanical loads acting simultaneously with high tribological and thermal charges. Due to high machine hour rates as well as increasing environmental requirements in terms of energy consumption, wear protection methods and suitable repair measures for forging tools become more and more important. Laser deposition welding represents an established process for the repair of complex shaped surfaces. A new approach is the addition of nano-sized ceramic particles to improve the mechanical properties. The main idea is to reduce the grain size of the cladded layers by adding nano-sized nuclei. A fine grained microstructure will improve strength as well as ductility and fatigue resistance. Furthermore small hard particles can improve the wear resistance without affecting the friction of the surface. After the cladding process the surface has to be finished usually by turning, milling and grinding operations. Within the presented paper the potential of nanoparticle-reinforced deposition welding with regard to increasing the wear resistance of forging dies will be examined. First, the process of nanoparticle-reinforced deposition welding will be presented. Afterwards it will be shown that yttrium oxide, titanium carbide and tungsten carbide nanoparticles in an AISI H10 matrix material will influence the friction coefficient between forging tool and material as well as the wear properties.     

Surface wrinkling: the phenomenon causing bees in bitumen

The so called “bee phenomenon” in bitumen has been investigated by means of AFM quantitative nanomechanical property mapping. Bees are a phenomenon that can be observed by topography measurements using AFM. The characteristic “bee” appearance comes from regions with alternating higher and lower bands in the surface topography of bitumen, which are surrounded by a flat area. The proposed mechanism for bee formation is phase separation and differential contraction during cooling from melt temperatures leading to wrinkling due to differences in the elastic modulus of the material phases. Using a laminate wrinkling model, the thickness of the bee laminate was calculated from the wavelengths and Young’s moduli of the bee laminate and the matrix. It was found to vary between 70 and 140 nm for the five bitumen samples that contained significant amounts of wax.