Genetic and Epigenomic Modifiers of Diabetic Neuropathy

Diabetic neuropathy (DN), the most common chronic and progressive complication of diabetes mellitus (DM), strongly affects patients’ quality of life. DN could be present as peripheral, autonomous or, clinically also relevant, uremic neuropathy. The etiopathogenesis of DN is multifactorial, and genetic components play a role both in its occurrence and clinical course. A number of gene polymorphisms in candidate genes have been assessed as susceptibility factors for DN, and most of them are linked to mechanisms such as reactive oxygen species production, neurovascular impairments and modified protein glycosylation, as well as immunomodulation and inflammation. Different epigenomic mechanisms such as DNA methylation, histone modifications and non-coding RNA action have been studied in DN, which also underline the importance of “metabolic memory” in DN appearance and progression. In this review, we summarize most of the relevant data in the field of genetics and epigenomics of DN, hoping they will become significant for diagnosis, therapy and prevention of DN.     

Flow of granules through cylindrical hopper

The gravity flow characteristics of pharmaceutically important granules were studied in a cylindrical hopper with attachable orifice disk at the bottom. Results indicate that materials property and orifice diameter play key role in determining mass flow rate while keeping environmental condition (temperature) at fixed range. A new dimensionally analyzed equation was developed to predict gravity flow of pharmaceutically important granules. The developed correlation agreed well with the experimental data. Calcium gluconate and lactose were used for preparing granules. Generally, glidant/lubricant materials are added to pharmaceutical granules during tablet manufacturing process, in order to improve physical property of granular material. Hence, the effect of glidant/lubricant on mass flow of granules through hopper was also studied. Magnesium stearate (1.5%) was added as glidant before granulation.     

Fast attack detection using correlation and summarizing of security alerts in grid computing networks

Due to the extensive growth of grid computing networks, security is becoming a challenge. Usual solutions are not enough to prevent sophisticated attacks fabricated by multiple users especially when the number of nodes connected to the network is changing over the time. Attackers can use multiple nodes to launch DDoS attacks which generate a large amount of security alerts. On the one hand, this large number of security alerts degrades the overall performance of the network and creates instability in the operation of the security management solutions. On the other hand, they can help in camouflaging other real attacks. To address these issues, a?correlation mechanism is proposed which reduces the security alerts and continue detecting attacks in grid computing networks. To obtain the more accurate results, a?major portion of the experiments are performed by launching DDoS and Brute Force (BF) attacks in real grid environment, i.e., the Grid??5000 (G5K) network.     

Understanding the influence of demographic and psychological variables on retirement planning.

The authors examined the degree to which workers were engaging in financial, health, interpersonal/leisure, and work planning for retirement, exploring whether demographic and psychological variables inhibited or promoted planning in each of these domains. Planning in each domain was influenced by a unique set of variables. Goals emerged as a consistent and positive predictor of planning. Gender accounted for health and interpersonal/leisure planning, while work planning behavior was negatively predicted by income. Time perspective also helped to clarify the amount of retirement planning undertaken in the financial and interpersonal/leisure domains. Practical implications for designing retirement interventions are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Investigation of surface and near-surface effects on hydrogen desorption kinetics of MgH2

Desorption of hydrogen atoms from the (110) surface of rutile magnesium hydride (MgH₂) was investigated using density functional theory (DFT) and pseudopotential method. System was represented by (110) (2×2) slab MgH₂ supercell with 12 atomic layers along the z-axis. The H-desorption was modeled by the successive release of the four two-fold bonded H atoms from the (110) surface of MgH₂. Dependence of the H-desorption energy on number and configuration of remaining surface hydrogen atoms has been determined. The features of the H atoms diffusion from the bulk towards the surface have been investigated, too. The results suggest that decrease in number of surface H atoms generally lowers the H-desorption energy in each desorption step and that both the H–H and the Mg–H interatomic interactions strongly influence the H-desorption process. The hydrogen vacancy formation energy in the first three sub-surface layers also exhibits a pronounced dependence on concentration. These findings lead to the conclusion that tendency of the MgH₂ (110) surface to preserve a maximum possible surface H concentration in its most stable configuration is the limiting factor for the H-desorption kinetics. In principle, the obtained results allow us to determine preferred paths of surface and sub-surface H-diffusion for a wide range of H concentrations and the principle features of the MgH₂ dehydrogenation process, at least for the H-rich region. Being rather comprehensive, the approach is applicable for other metal hydrides, as well.     

Web-conference supervision for advanced psychotherapy training: A practical guide.

The advent of readily accessible, inexpensive Web-conferencing applications has opened the door for distance psychotherapy supervision, using video recordings of treated clients. Although relatively new, this method of supervision is advantageous given the ease of use and low cost of various Internet applications. This method allows periodic supervision from point to point around the world, with no travel costs and no long gaps between direct training contacts. Web-conferencing permits face-to-face training so that the learner and supervisor can read each other's emotional responses while reviewing case material. It allows group learning from direct supervision to complement local peer-to-peer learning methods. In this article, we describe the relevant literature on this type of learning method, the practical points in its utilization, its limitations, and its benefits. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Metallo-functionalized first-generation salicylaldimine poly(propylenimine) tetraamine dendrimers: Electrochemical study and atomic force microscopy imaging

The adsorption and the redox processes of two first-generation salicylaldiamine dendritic ligands and their copper, cobalt and nickel metallo-functionalized complexes have been studied at two types of carbon electrode surface. Glassy carbon (GC) was used in an electrochemistry study and highly oriented pyrolitic graphite (HOPG) in ex situ atomic force microscopy (AFM) imaging. All salicylaldimine ligands and their metallo-functionalized complexes adsorb on the surface of the HOPG electrode, resulting in the formation of nanoclusters and films, which vary between 0.9 and 6 nm in size, depending on the metallo-functionalized salicylaldimine dendrimer chemical composition and solution concentration. Differential pulse voltammetry of the surface-confined films has shown that the anodic reactions observed correspond to the oxidation of the hydroxyl groups present in the ligand structure of all compounds. However, by following the changes in peak currents, potentials and width at half height it has been shown that destabilization of the ligand internal structure occurred in the metallo-functionalized complexes depending on the metal involved. The electrochemical behaviour of the surface-confined films observed in buffer solution was related to the morphology, obtained by AFM, of the immobilised first-generation salicylaldiamine dendritic ligands and corresponding salicylaldimine metallo-functionalized complexes.     

Vectorization and parallelization of a production reactor assembly code

In order to efficiently use new features of supercomputers, production codes, usually written 10 – 20 years ago, must be tailored for modern computer architectures. We have chosen to optimize the CPM-2 code, a production reactor assembly code based on the collision probability transport method. Substantional speedups in the execution times were obtained with the parallel/vector version of the CPM-2 code. In addition, we have developed a new transfer probability method, which removes some of the modelling limitations of the collision probability method encoded in the CPM-2 code, and can fully utilize parallel/vector architecture of a multiprocessor IBM 3090.     

Up-cycling of PET (polyethylene terephthalate) to the biodegradable plastic PHA (polyhydroxyalkanoate)

The conversion of the petrochemical polymer polyethylene terephthalate (PET) to a biodegradable plastic polyhydroxyal-kanoate (PHA) is described here. PET was pyrolised at 450 degrees C resulting in the production of a solid, liquid, and gaseous fraction. The liquid and gaseous fractions were burnt for energy recovery, whereas the solid fraction terephthalic acid (TA) was used as the feedstock for bacterial production of PHA. Strains previously reported to grow on TA were unable to accumulate PHA. We therefore isolated bacteria from soil exposed to PET granules at a PET bottle processing plant From the 32 strains isolated, three strains capable of accumulation of medium chain length PHA (mclPHA) from TA as a sole source of carbon and energy were selected for further study. These isolates were identified using 16S rDNA techniques as P. putida (GO16), P. putida (GO19), and P. frederiksbergensis (GO23). P. putida GO16 and GO19 accumulate PHA composed predominantly of a 3-hydroxydecanoic acid monomer while P. frederiksbergensis GO23 accumulates 3-hydroxydecanoic acid as the predominant monomer with increased amounts of 3-hydroxydodecanoic acid and 3-hydroxydodecenoic acid compared to the other two strains. PHA was detected in all three strains when nitrogen depleted below detectable levels in the growth medium. Strains GO16 and GO19 accumulate PHA at a maximal rate of approximately 8.4 mg PHA/l/h for 12 h before the rate of PHA accumulation decreased dramatically. Strain GO23 accumulates PHA at a lower maximal rate of 4.4 mg PHA/l/h but there was no slow down in the rate of PHA accumulation over time. Each of the PHA polymers is a thermoplastic with the onset of thermal degradation occurring around 308 degrees C with the complete degradation occurring by 370 degrees C. The molecular weight ranged from 74 to 123 kDa. X-ray diffraction indicated crystallinity of the order of 18-31%. Thermal analysis shows a low glass transition (-53 degrees C) with a broad melting endotherm between 0 and 45 degrees C.     

DPP-4 Cleaves α/β-Peptide Bonds: Substrate Specificity and Half-Lives

The incorporation of β-amino acids into a peptide sequence has gained particular attention as β- and α/β-peptides have shown remarkable proteolytic stability, even after a single homologation at the scissile bond. Several peptidases have been shown to cleave such bonds with high specificity but at a much slower rate compared to α-peptide bonds. In this study, a series of analogs of dipeptidyl peptidase-4 (DPP-4) substrate inhibitors were synthesized in order to investigate whether β-amino acid homologation at the scissile bond could be a valid approach to improving peptide stability towards DPP-4 degradation. DPP-4 cleaved the α/β-peptide bond after the N-terminal penultimate Pro with a broad specificity and retained full activity regardless of the β³-amino acid side chain and peptide length. Significantly improved half-lives were observed for β³Ile-containing peptides. Replacing the penultimate Pro with a conformationally constrained Pro mimetic led to proteolytic resistance. DPP-4 cleavage of α/β-peptide bonds with a broad promiscuity represents a new insight into the stability of peptide analogs containing β-amino acids as such analogs were thought to be stable towards enzymatic degradation.