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.     

Influence of the common varistor dopants (CoO, Cr2O3 and Nb2O5) on the structural properties of SnO2 ceramics

The influence of dopants commonly used in SnO₂ varistor ceramics, such as CoO, Cr₂O₃ or Nb₂O₅, on the structural properties of SnO₂ was investigated. Several SnO₂-based ceramics containing only one of the dopants were prepared and characterized. Spectroscopic investigations [visible, near infrared (IR) and IR region] were performed to obtain information about dopants valence states inside the ceramics, as well as about their influence on electronic structure of the material. Structural properties were investigated by X-ray diffraction analysis and mechanisms of dopant incorporation were proposed. Obtained results were confirmed with results of the electrical measurements. Microstructural changes in doped ceramics were investigated by scanning electron microscopy (SEM) analysis that showed great differences in densities, grain size, and morphology of the SnO₂ ceramics depending on type of dopants and their distribution.     

Reaction kinetics of metal deposition via surface limited red-ox replacement of underpotentially deposited metal monolayers

The study of the kinetics of metal deposition via surface limited red-ox replacement of underpotentially deposited metal monolayers is presented. The model system was Pt submonolayer deposition on Au(1 1 1) via red-ox replacement of Pb and Cu UPD monolayers on Au(1 1 1). The kinetics of a single replacement reaction was studied using the formalism of the comprehensive analytical model developed to fit the open circuit potential transients from deposition experiments. The practical reaction kinetics parameters like reaction half life, reaction order and reaction rate constant are determined and discussed with their relevance to design and control of deposition experiments. The effects of transport limitation and the role of the anions/electrolyte on deposition kinetics are investigated and their significance to design of effective deposition process is discussed.     

Privacy preserving data mining: A noise addition framework using a novel clustering technique

During the whole process of data mining (from data collection to knowledge discovery) various sensitive data get exposed to several parties including data collectors, cleaners, preprocessors, miners and decision makers. The exposure of sensitive data can potentially lead to breach of individual privacy. Therefore, many privacy preserving techniques have been proposed recently. In this paper we present a framework that uses a few novel noise addition techniques for protecting individual privacy while maintaining a high data quality. We add noise to all attributes, both numerical and categorical. We present a novel technique for clustering categorical values and use it for noise addition purpose. A security analysis is also presented for measuring the security level of a data set.     

A New Method for Pore Pressure Prediction on Malfunctioning Cells Using Artificial Neural Networks

Embankment rockfill dams are the most common dam construction types used in the world today. One third of all embankment dam failures are caused by dam slope instability. The dam is stable when the slopes are stable. Slope safety of the dam is assessed through pore and total pressure data analysis registered on pressure measurement cells installed in the dam. During the service life of a dam, one or more cells may malfunction after years of operation. Cell replacement implies economically unjustified high costs and is usually technically impossible and high risk. In this paper, the problem of a malfunctioning cell with a small available dataset is analysed. A new method for pore pressure prediction on malfunctioning cells has been developed using several successive artificial neural networks (ANNs) to obtain high accuracy of the predicted values. The results show that these predicted values are more precise than values we could have obtained using only one artificial neural network for prediction.

     

Close-packed noncircular nanodevice pattern generation by self-limiting ion-mill process

We describe a self-limiting, low-energy argon-ion-milling process that enables noncircular device patterns, such as squares or hexagons, to be formed using precursor arrays of uniform circular openings in poly(methyl methacrylate) defined using electron beam lithography. The proposed patterning technique is of particular interest for bit-patterned magnetic recording medium fabrication, where square magnetic bits result in improved recording system performance. Bit-patterned magnetic medium is among the primary candidates for the next generation magnetic recording technologies and is expected to extend the areal bit density limits far beyond 1 Tbit/in(2). The proposed patterning technology can be applied either for direct medium prototyping or for manufacturing of nanoimprint lithography templates or ion beam lithography stencil masks that can be utilized in mass production.     

A Novel KCNA2 Variant in a Patient with Non-Progressive Congenital Ataxia and Epilepsy: Functional Characterization and Sensitivity to 4-Aminopyridine

Kv1.2 channels, encoded by the KCNA2 gene, are localized in the central and peripheral nervous system, where they regulate neuronal excitability. Recently, heterozygous mutations in KCNA2 have been associated with a spectrum of symptoms extending from epileptic encephalopathy, intellectual disability, and cerebellar ataxia. Patients are treated with a combination of antiepileptic drugs and 4-aminopyridine (4-AP) has been recently trialed in specific cases. We identified a novel variant in KCNA2, E236K, in a Serbian proband with non-progressive congenital ataxia and early onset epilepsy, treated with sodium valproate. To ascertain the pathogenicity of E236K mutation and to verify its sensitivity to 4-AP, we transfected HEK 293 cells with Kv1.2 WT or E236K cDNAs and recorded potassium currents through the whole-cell patch-clamp. In silico analysis supported the electrophysiological data. E236K channels showed voltage-dependent activation shifted towards negative potentials and slower kinetics of deactivation and activation compared with Kv1.2 WT. Heteromeric Kv1.2 WT+E236K channels, resembling the condition of the heterozygous patient, confirmed a mixed gain- and loss-of-function (GoF/LoF) biophysical phenotype. 4-AP inhibited both Kv1.2 and E236K channels with similar potency. Homology modeling studies of mutant channels suggested a reduced interaction between the residue K236 in the S2 segment and the gating charges at S4. Overall, the biophysical phenotype of E236K channels correlates with the mild end of the clinical spectrum reported in patients with GoF/LoF defects. The response to 4-AP corroborates existing evidence that KCNA2-disorders could benefit from variant-tailored therapeutic approaches, based on functional studies.     

Characterization of natural isolate Lactobacillus acidophilus BGRA43 useful for acidophilus milk production

The adherence of P. aeruginosa to collagen membrane, sponge, and to a new anti-infective COLL dressing and the susceptibility of the organisms attached to the biomaterials to amikacin were investigated in vitro. After 17 h of attachment, the bacteria demonstrated an increased resistance to amikacin compared with their free-floating counterparts. Amikacin, even at a concentration exceeding 150 times the minimal bactericidal concentration (MBC) for the strain tested, did not eradicate the attached bacteria from the surface of collagen membrane. However, when the drug at a high concentration (over 16 times the minimal inhibitory concentration, MIC) was present in the incubation medium before it had been inoculated with P. aeruginosa, a reduction of 2 log10 units in the organisms adherent to the surface of collagen membrane was observed. We conclude that slow release of the antibiotic from the COLL dressing could control the bacterial colonization on the surface. In fact, the released amikacin at the final concentration of 32 times the MBC reduced the number of adherent bacteria by 6 log10 units. In contrast, ciprofloxacin at the same final bactericidal concentration completely eradicated the bacteria from the surface of COLL dressing. However, as ciprofloxacin is not recommended for use as a topical antimicrobial agent, a further search is needed to find an agent with a similar anticolonization activity.     

Circularly polarised printed antenna with conical beam

A new circularly polarised printed antenna concept with conical beam is presented. The proposed concept describes a simple printed structure with an omnidirectional pattern and maximum gain of ~6 dBi at elevation angles between 30° and 60°, with features suitable for various commercial applications. The voltage standing wave ratio is <1.3 and the axial ratio is <2 dB in the 3% operational bandwidth around 4.6 GHz. The experimental results show good agreement with those obtained by simulation     

The wave-equation FD-TD method for the efficient eigenvalueanalysis and S-matrix computation of waveguide structures

A modified finite-difference-time-domain (FDTD) formulation based on the direct discretization of the vector wave-equation is applied to the efficient analysis of hybrid-mode waveguiding structures. For both 3-D and 2-D waveguide eigenvalue problems, the formulation requires only one grid, and just the solution of three coupled equations is necessary. Numerical examples concerning the resonant frequencies for an inhomogeneously filled waveguide resonator as well as the fundamental- and higher-order-mode propagation factors for insulated image guides, shielded coupled dielectric guides, and lateral open dielectric ridge guides demonstrate the efficiency of the method. The theory is verified by comparison with results obtained by other methods