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.     

Performance-Analyse und -Optimierung in der Softwareentwicklung

Nicht-funktionale Anforderungen an ein Softwaresystem beschreiben Aspekte, die nicht direkt die Funktionalit?t, wie sie der Benutzer sieht, betreffen.     

Agens Faber: Toward a Theory of Artefacts for MAS

Human intelligence has evolved along with the use of more and more sophisticated tools, allowing Homo Faber (from Homo Habilis to Homo Sapiens Sapiens) to cope with environment changes, as well as to adapt the environment to his needs. Analogously, in this seminal paper we introduce the notion of Agens Faber, conveying the idea that agent intelligence should not be considered as separated by the agent ability to perceive and affect the environment—and so, that agent intelligence is strictly related to the artefacts that enable, mediate and govern any agent (intelligent) activity.

Along this line, we first discuss the notion of artefact for MAS in general, then we try to devise out the admissible / required / desirable features of an artefact for MAS. We elaborate on the many sorts of possible relations between agents and artefacts, focusing in particular on the issue of the rational exploitation of artefacts, and also rough out a possible taxonomy of artefacts for MAS.     

Improved accuracy and convergence of discretized population balance for aggregation: The cell average technique

A new discretization method for aggregation equations is developed. It is compared to the fixed pivot technique proposed by Kumar and Ramkrishna (1996a. On the solution of population balance equations by discretization—I. A fixed pivot technique. Chemical Engineering Science 51, 1311-1332). The numerical results for aggregation problems by discretized population balances are consistently overpredicting and diverge before the gelling point in the case of a gelling kernel. The present work establishes a new technique which assigns the particles within the cells more precisely. This is achieved by taking first the average of the newborn particles within the cell and then assigning them to the neighboring nodes such that pre-chosen properties are exactly preserved. The new technique preserves all the advantages of the conventional discretized methods and provides a significant improvement in predicting the particle size distribution (PSD). In addition, it is found that the technique is a powerful tool for the computation of gelling problems. The effectiveness of the technique is illustrated by application to several aggregation problems for suitably selected aggregation kernels including physically relevant kernels.     

Qualitative analysis of motion properties of semistate models of large-scale systems

This paper studies the behavior of motions of large-scale (LS) semistate systems (SSS) governed byP _i (t)x _i =M _i (t,x _i )x _i +f _i (t)+h _i (t, x), i=1,2,...,s, =(x ₁ ^T x ₂ ^T x _s ^T )^T, where matricesP _i (t) are singular. Using Lyapunov's approach and the tools for LS system analysis, a variant of attractivity and ultimate boundedness of appropriate time-variable sets are investigated. The results are based on a specific choice of the aggregate functions. It is assumed that the reduction of equations to a normal form of lower order is inconvenient. The aggregation-decomposition approach used in this paper reduces the dimensionality of an aggregate matrix of the system to the number of its systems. Motion properties of LS systems are deduced from the properties of its isolated subsystems, the character of interconnections, and the conditions imposed on the system aggregate matrix. Sufficient algebraic conditions for the above-mentioned motion properties are developed.     

Bone Marrow-Mesenchymal Stromal Cell Secretome as Conditioned Medium Relieves Experimental Skeletal Muscle Damage Induced by Ex Vivo Eccentric Contraction

Bone marrow-mesenchymal stem/stromal cells (MSCs) may offer promise for skeletal muscle repair/regeneration. Growing evidence suggests that the mechanisms underpinning the beneficial effects of such cells in muscle tissue reside in their ability to secrete bioactive molecules (secretome) with multiple actions. Hence, we examined the effects of MSC secretome as conditioned medium (MSC-CM) on ex vivo murine extensor digitorum longus muscle injured by forced eccentric contraction (EC). By combining morphological (light and confocal laser scanning microscopies) and electrophysiological analyses we demonstrated the capability of MSC-CM to attenuate EC-induced tissue structural damages and sarcolemnic functional properties’ modifications. MSC-CM was effective in protecting myofibers from apoptosis, as suggested by a reduced expression of pro-apoptotic markers, cytochrome c and activated caspase-3, along with an increase in the expression of pro-survival AKT factor. Notably, MSC-CM also reduced the EC-induced tissue redistribution and extension of telocytes/CD34⁺ stromal cells, distinctive cells proposed to play a “nursing” role for the muscle resident myogenic satellite cells (SCs), regarded as the main players of regeneration. Moreover, it affected SC functionality likely contributing to replenishment of the SC reservoir. This study provides the necessary groundwork for further investigation of the effects of MSC secretome in the setting of skeletal muscle injury and regenerative medicine.     

meSAT: multiple encodings of CSP to SAT

One approach for solving Constraint Satisfaction Problems (CSP) (and related Constraint Optimization Problems (COP)) involving integer and Boolean variables is reduction to propositional satisfiability problem (SAT). A number of encodings (e.g., direct, log, support, order) for this purpose exist as well as specific encodings for some constraints that are often encountered (e.g., cardinality constraints, global constraints). However, there is no single encoding that performs well on all classes of problems and there is a need for a system that supports multiple encodings. We present a system that translates specifications of finite linear CSP problems into SAT instances using several well-known encodings, and their combinations. We also present a methodology for selecting a suitable encoding based on simple syntactic features of the input CSP instance. Thorough evaluation has been performed on large publicly available corpora and our encoding selection method improves upon the efficiency of existing encodings and state-of-the-art tools used in comparison.     

Evaluation of the removal of n-butanol vapor by the poly(lactic acid)-zeolite-TiO2 composite and formation of by-products

The use of polymeric films incorporated with zeolite-TiO₂ composites associated with UV radiation can be an alternative in the removal of volatile organic compounds (VOCs) through the adsorption and photodegradation processes. This study produced poly(lactic acid) (PLA) films incorporated with 13× zeolite, TiO₂, and 13×-TiO₂ zeolite composite to remove n-butanol and evaluate the by-products generated in the process. The results showed that 13× zeolite and TiO₂ added individually or as a composite to PLA, gave the polymer matrix a significant increase in the removal capacity of n-butanol. The best performance was presented by the zeolite-TiO₂, composite, confirming a synergistic effect. However, the formation of CO and CO₂ exceeded the expected values, with the verification that the polymeric matrix underwent photodegradation action by TiO₂. The polymeric film only containing zeolite is the most suitable for the removal of VOCs, as it did not present degradation of the PLA, generating a lower concentration of by-products.