The RAGE/DIAPH1 Signaling Axis & Implications for the Pathogenesis of Diabetic Complications

Increasing evidence links the RAGE (receptor for advanced glycation end products)/DIAPH1 (Diaphanous 1) signaling axis to the pathogenesis of diabetic complications. RAGE is a multi-ligand receptor and through these ligand–receptor interactions, extensive maladaptive effects are exerted on cell types and tissues targeted for dysfunction in hyperglycemia observed in both type 1 and type 2 diabetes. Recent evidence indicates that RAGE ligands, acting as damage-associated molecular patterns molecules, or DAMPs, through RAGE may impact interferon signaling pathways, specifically through upregulation of IRF7 (interferon regulatory factor 7), thereby heralding and evoking pro-inflammatory effects on vulnerable tissues. Although successful targeting of RAGE in the clinical milieu has, to date, not been met with success, recent approaches to target RAGE intracellular signaling may hold promise to fill this critical gap. This review focuses on recent examples of highlights and updates to the pathobiology of RAGE and DIAPH1 in diabetic complications.     

Consideration of the BDNF gene in relation to two phenotypes: Hoarding and obesity.

The gene coding for the brain derived neurotrophic factor (BDNF) has emerged as an interesting candidate for multiple brain and brain disorder-related phenomena. The primary aim of the present investigation was to consider the relationship between the BDNF Val66Met variant and two phenotypes: compulsive hoarding as a symptom dimension of obsessive–compulsive disorder (OCD), and body mass index (BMI). We examined the BDNF gene in a large (N = 301) clinical sample of probands with OCD. Participants were classified as hoarding or nonhoarding using a strict, multimeasure grouping approach. Results revealed that the Val/Val genotype was linked with hoarding classification and more severe hoarding behaviors, as well as greater BMI levels. Hoarding status was also associated with greater BMI scores, with individuals in the hoarding group being far more likely to be classified as obese compared with the nonhoarding group. Our findings may provide a distinct avenue through which hoarding and BMI could be linked. These findings are suggestive of a complex gene, body weight, and psychopathology relationship wherein a primitive, survival “thrifty gene” strategy may be conserved and represented in a subgroup of humans manifesting severe hoarding symptoms. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Efficient shape optimization for certain and uncertain aerodynamic design

In this paper, we present novel developments in aerodynamic shape optimization based on shape calculus as well as the proper treatment of aleatoric uncertainties in the field of aerodynamic design.     

Some viscosity characteristics of faba bean protein isolates within a pH range relevant for foods

The rheological behaviour of concentrated aqueous dispersions of unmodified (FBPI I) and acetylated (FBPI I) faba bean (Vicia faba L. minor) protein isolates are investigated within a pH range of 4.0 up to 7.5. Besides the fact that equal concentrated dispersions of FBPI I show a much lower apparent viscosity η than those prepared with FBPI II, η and the flow behaviour index n depend also on the kind of preparation. Especially the direction of pH shifting and the mode of pH adjustment lead to marked differences of the rheological properties. In the case of FBPI II dispersions a maximum of η and n is shown at pH 5.5 to 6.5, seldom at pH 7.0, probably connected with a maximum of the hydrodynamic volume. Holding the aqueous dispersions for 24h causes mostly an increase of η and n.     

Pin&Play: the surface as network medium

Integrating appliances in the home through a wired network often proves to be impractical: routing cables is usually difficult, changing the network structure afterward even more so, and portable devices can only be connected at fixed connection points. Wireless networks are not the answer either: batteries have to be regularly replaced or changed, and what they add to the device's size and weight might be disproportionate for smaller appliances. In Pin&Play, we explore a design space in between typical wired and wireless networks, investigating the use of surfaces to network objects that are attached to it. This article gives an overview of the network model, and describes functioning prototypes that were built as a proof of concept.     

Efficient silicon heterojunction solar cells based on p‐ and n‐type substrates processed at temperatures < 220°C

We present the optimization and characterization of heterojunction solar cells consisting of an amorphous silicon emitter, a single crystalline absorber and an amorphous silicon rear side which causes the formation of a back surface field (a‐Si:H/c‐Si/a‐Si:H). The solar cells were processed at temperatures <220°C. An optimum of the gas phase doping concentration of the a‐Si:H layers was found. For high gas phase doping concentrations, recombination via defects located at or nearby the interface leads to a decrease in solar cell efficiency. We achieved efficiencies >17% on p‐type c‐Si absorbers and >17·5% on n‐type absorbers. In contrast to the approach of Sanyo, no additional intrinsic a‐Si:H layers between the substrate and the doped a‐Si:H layers were inserted. Copyright © 2006 John Wiley & Sons, Ltd.     

Ultra-low-energy ion-beam-synthesis of Ge nanocrystals in thin ALD Al2O3 layers for memory applications

Structural and electrical properties of ALD-grown 5 and 7 nm-thick Al₂O₃ layers before and after implantation of Ge ions (1 keV, 0.5–1 × 10¹⁶ cm^?2) and thermal annealing at temperatures in the 700–1050 °C range are reported. Transmission Electron Microscopy reveals the development of a 1 nm-thick SiO₂-rich layer at the Al₂O₃/Si substrate interface as well as the formation of Ge nanocrystals with a mean diameter of ～5 nm inside the implanted Al₂O₃ layers after annealing at 800 °C for 20 min. Electrical measurements performed on metal–insulator–semiconductor capacitors using Ge-implanted and annealed Al₂O₃ layers reveal charge storage at low-electric fields mainly due to location of the Ge nanocrystals at a tunnelling distance from the substrate and their spatial dispersion inside the Al₂O₃ layers.     

One‐Step Formulation of Protein Microparticles with Tailored Properties: Hard Templating at Soft Conditions

Formulation of therapeutic proteins into particulate forms is a main strategy for site‐specific and prolonged protein delivery as well as for protection against degradation. Precise control over protein particle size, dispersity, purity, as well as mild preparation conditions and minimal processing steps are highly desirable. It is, however, hard to fit all these criteria with conventional preparation techniques. Here a one‐step hard‐templating synthesis of microparticles composed of functional, non‐denatured protein is reported. The method is based on filling porous CaCO₃ microtemplates with the protein near to its isoelectric point (pI) followed by pH‐ or EDTA‐mediated dissolution of the tempplates. In principle, a wide variety of proteins can be converted into microparticles using this approach. The main requirement is an overlap of the protein insolubility and a template solubility for a certain parameter (here pH or EDTA). Here the formulation of insulin particles is studied in detail and it is shown that particles consisting of high molecular weight protein (catalase) can also be prepared. In this context, the synthesis of CaCO₃ templates with controlled size, the mechanism of the protein microparticle formation and mechanical properties of the microparticles are discussed. For the first time, the fabrication of mesoporous monodispersed CaCO₃ microtemplates with identical porocity but tuned diameter from 3 to 20 μm is demonstrated. The protein particle diameter can be adjusted by choosing the appropriate template size that is critical for successful pulmonary delivery of insulin. As a first step towards insulin delivery, the in vitro release of insulin at physiological conditions is studied.     

Multicomponent Physical Vapor Deposited Films with Homogeneous Molecular Material Distribution Featuring Improved Resist Sensitivity

Each film preparation technique affects the physical properties of the resulting coating and thus defines its applicability in modern device construction. In this context solvent based spin coated and solvent‐free physical vapor deposited molecular glass photoresist films are systematically investigated for their dissolution behavior, sensitivity, and overall lithographic performance. These investigations demonstrate that the solvent‐free physical vapor deposition leads to a marked increase in sensitivity. This could be explained by the individual molecule by molecule deposition step producing a more homogeneous distribution of the multicomponent resist system, especially the photoacid generator. In addition, this assumption is supported by former published simulations focusing on aggregate formation within thin films. This work demonstrates that the lithographic sensitivity of multicomponent resist system is an intrinsic parameter to investigate molecular material distribution and indicates that the applied film preparation technique is crucial for the corresponding performance and applicability.