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.     

Enhanced high-frequency performance in a GaAs, self-aligned, n-JFETusing a carbon buried p-implant

C ion implantation has been employed, for the first time, to form the buried p-layer in GaAs, self-aligned, ion implanted JFETs. Comparable DC performance was seen for JFETs with C or Mg implants; however, C-backside JFETs showed superior high-frequency performance. High dose C-backside devices had a f_t of 28.3 GHz and a f_max of 43.2 GHz for a 0.5 μm gate length that were 28% and 46% higher, respectively, than comparable Mg-implanted JFETs. This enhancement is a result of the lower C_gs in the C-backside device resulting from he inherently low activation of the implanted C below the channel while the C still effectively compensated the tail of the Si-channel implant. This approach relaxes the trade-off between optimizing the DC and the AC performance for the buried p-implant in GaAs JFETs and MESFET's     

Biobased thermosets from the free‐radical copolymerization of conjugated linseed oil

New polymeric thermosets were prepared through the bulk free‐radical copolymerization of 100% conjugated linseed oil, acrylonitrile, and divinylbenzene. Under the appropriate reaction conditions and with the appropriate curing sequence, 61–96 wt % of the oil was incorporated into the crosslinked thermosets. The resulting yellow, transparent thermosets varied from being soft and flexible to being hard and brittle. Dynamic mechanical analysis and thermogravimetric analysis showed that these thermosets had good mechanical properties and thermal stability. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 979–985, 2007     

Predictive functional control based on an adaptive fuzzy model of a hybrid semi-batch reactor

In this paper a new approach to the control of a nonlinear, time-varying process is proposed. It is based on a recursive version of the fuzzy identification method and predictive functional control. First, the recursive fuzzy identification method is derived, after which it is used in connection with fuzzy predictive functional control to construct an adaptive fuzzy predictive functional controller. The adaptive FPFC is then tested on a nonlinear, time-varying, semi-batch reactor process and compared with the standard FPFC, which uses non-adaptive fuzzy model. The simulation results are promising; they indicate that the control of time-varying, nonlinear processes with the FPFC can be improved with the use of an adaptive fuzzy model. An improvement in reference tracking and disturbance rejection can be observed, but the main advantage is the reduced number of switchings between hot and cold water. This is an important improvement in the case of real applications.     

Modelling of interstitials in the bcc phase

There are several widespread thermodynamic datasets which produce a spurious bcc interstitial solution at high temperature and high X content (X is an interstitally dissolved element). The reason for this is the standard model for bcc interstitial solutions (M(V a,X)₃), which requires careful selection of optimising parameters to minimise spurious appearances of the bcc phase. In this work the model M(V a,X)₁ is suggested as an alternative. This model is much easier to handle and its parameters can be directly compared with those of the fcc phase. The two models are compared for the Fe–C and Nb–N systems. In the Fe–C system almost identical results are achieved. In Nb–N there are some differences for high N content, but there is no experimental data to clearly support any model.     

The use of data-derived label hierarchies in multi-label classification

Instead of traditional (multi-class) learning approaches that assume label independency, multi-label learning approaches must deal with the existing label dependencies and relations. Many approaches try to model these dependencies in the process of learning and integrate them in the final predictive model, without making a clear difference between the learning process and the process of modeling the label dependencies. Also, the label relations incorporated in the learned model are not directly visible and can not be (re)used in conjunction with other learning approaches. In this paper, we investigate the use of label hierarchies in multi-label classification, constructed in a data-driven manner. We first consider flat label sets and construct label hierarchies from the label sets that appear in the annotations of the training data by using a hierarchical clustering approach. The obtained hierarchies are then used in conjunction with hierarchical multi-label classification (HMC) approaches (two local model approaches for HMC, based on SVMs and PCTs, and two global model approaches, based on PCTs for HMC and ensembles thereof). The experimental results reveal that the use of the data-derived label hierarchy can significantly improve the performance of single predictive models in multi-label classification as compared to the use of a flat label set, while this is not preserved for the ensemble models.     

Catalytic contribution of flap-substrate hydrogen bonds in "HIV-1 protease" explored by chemical synthesis

An analogue of "HIV-1 protease" was designed in which the ability to donate important water-mediated hydrogen bonds to substrate was precisely and directly deleted. Chemical ligation of unprotected peptide segments was used to synthesize this "backbone-engineered" enzyme. The functionally relevant amide -CONH- linkage between residues Gly49-Ile50 in each flap of the enzyme was replaced by an isosteric thioester -COS- bond. The backbone-engineered enzyme had normal substrate specificity and affinity (Km). However, the catalytic activity (kcat) was reduced approximately 3000-fold compared to the native amide bond-containing enzyme. Inhibition by the reduced peptide bond substrate analogue MVT-101 was unaffected compared with native enzyme. By contrast, the normally tight-binding hydroxyethylamine inhibitor JG-365 bound to the backbone-engineered enzyme with an approximately 2500-fold reduction in affinity. The reduced catalytic activity of the -Gly49-psi(COS)-Ile50-backbone-engineered enzyme analogue provides direct experimental evidence to support the suggestion that backbone hydrogen bonds from the enzyme flaps to the substrate are important for the catalytic function of the HIV-1 protease.     

A heterogeneous modular robotic design for fast response to a diversity of tasks

This paper describes a heterogeneous modular robot system design which attempts to give a quick solution to a diversity of tasks. The approach is based on the use of an inventory of three types of modules i.e., power and control module, joint module and specialized module. Each module type aims to balance versatility and functionality. Their design permits rapid and cost effective design and fabrication. They are interchangeable in different ways to form different robot or system configurations. Depending on the task, the operator decides what type of robot can provide the best performance within the mission. A spherical joint module is described and used to build different robots, hence, forward and inverse kinematics models are obtained. Finally, from the modules described in this work, several robot configurations such as robotic arms, leg-based robots and wheel-based robots are assembled to demonstrate the execution of manipulation and locomotion tasks.     

A case study on the object-oriented framework for modeling product families with the dominant variation of the topology in the one-of-a-kind production

Traditional configuration-based product family modeling techniques do not yield favorable solutions for modeling the product families with the dominant product topology variations. This paper presents the case study for the modeling of variations of the product configuration, parameters, and topologies in mass production of custom windows and doors in a one-of-a-kind production (OKP) company. The case study is based on the object-oriented product family modeling framework we developed for OKP which is characterized by the dominant product variation by topology. The problem of variation in topology in our framework is solved by the manual model transformation in the computer-aided design module which creates a new metamodel of products with the desired topology and which is the basis for a further, automatic model transformation. Usage of our framework has a positive effect on the level of the product customizations and shortening of the leading time which helps OKP companies in obtaining a better position at the market. Our software solution for the designing and manufacturing of custom windows and doors based on our framework is implemented in more than 300 mostly small- and medium-sized enterprises. It proves our concept which can be used for the realization of the information systems for computer-aided one-of-a-kind production in the companies with a different production plan.