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The growing need for profit maximization and cost minimization has made the optimization field very attractive to both researchers and practitioners. In fact, many authors were interested in this field and they have developed a large number of optimization algorithms to solve either academic or real-life problems. Among such algorithms, we cite a well-known metaheuristic called the genetic algorithm. This optimizer tool, as any algorithm, suffers from some drawbacks; like the problem of premature convergence. In this paper, we propose a new selection strategy hoping to avoid such a problem. The proposed selection operator is based on the principle of the k-means clustering method for the purpose of guiding the genetic algorithm to explore different regions of the search space. We have elaborated a genetic algorithm based on this new selection mechanism. We have then tested our algorithm on various data instances of the 0/1 multidimensional knapsack problem. The obtained results are encouraging when compared with those reached by other versions of genetic algorithms and those reached by an adapted version of the particle swarm optimization algorithm.

In this paper, a numerical investigation is carried out on mixed convection in a vertical vented rectangular enclosure filled with Al2O3-water nanofluid. The mixed convection effect is attained by heating the right wall by a constant hot temperature and cooling the cavity by an injected or sucked imposed flow. The effects of some pertinent parameters such as the Reynolds number, 100 ≤ Re ≤ 5000, the solid volume fraction of the nanoparticles, 0 ≤ τ ≤ 0.1, and the aspect ratio of the cavity, 1 ≤ A ≤ 4, on flow and temperature patterns as well as on the heat transfer rate within the enclosure are presented for the two ventilation modes. For a value of the aspect ratio A = 2, the obtained results demonstrate that the increase of volume fraction of nanoparticles contributes to an enhancement of the heat transfer and to an increase of the mean temperature within the cavity. Also, it was revealed that the fluid suction mode yields the best heat transfer performance. In the case when A is varied from 1 to 4, it was obtained that the heat transfer enhancement, using nanofluids, is more pronounced at shallow enclosures than at tall ones. [ABSTRACT FROM AUTHOR]

In this paper is reported an analytical and numerical study on double-diffusive natural convection in a non-Newtonian power-law fluid confined in a shallow horizontal rectangular enclosure submitted to uniform heat and mass fluxes along its short vertical sides, while the horizontal ones are insulated and impermeable. Here, the cases of aiding and opposing thermal and solutal buoyancy forces of equal intensities are considered. In the first part of the work the full governing equations are solved and the effects of the power-law behavior index, n, and the generalized thermal Rayleigh number, RaT, are examined and analyzed. In the second part, an analytical solution, based on the parallel flow approximation valid in the case of a shallow cavity, is proposed and an excellent agreement of results between the two approaches is observed, which validates them mutually. [ABSTRACT FROM AUTHOR]

The present paper reports numerical results of mixed convection and surface radiation within a horizontal ventilated cavity heated from below and provided with an adiabatic thin partition on the heated surface. Air, a radiatively transparent medium, is considered to be the cooling fluid. The effect of the governing parameters, which are the Reynolds number, 200 ≤ Re ≤ 5000, the relative height of the baffle, 0 ≤ Hb ≤ 0.75, and the emissivity of the walls, 0 ≤ ϵ ≤ 1, on the fluid flow and heat transfer characteristics is studied in detail. The maximum and mean temperatures, the ratio, QE/QL, of the heat quantities leaving the cavity through the exit, QE, and through the left vertical cold side, QL, are also presented versus the above controlling parameters. [ABSTRACT FROM AUTHOR]

Laminar double-diffusive convection in a two-dimensional porous square cavity differentially heated and salted is studied numerically. The left vertical wall of the cavity is heated with a temperature varying sinusoidally in time, while the opposite cold wall is maintained at a constant temperature. The same walls of the cavity are salted with constant and different concentrations (the concentration of the heated wall is higher than that of the cooled one). The remaining horizontal walls are considered adiabatic and impermeable. The parameters governing the problem are the amplitude of the variable temperature (0 ⩽ a ⩽ 1), its period (0.0001 ⩽ τ ⩽ 10), the buoyancy forces ratio (-5 ⩽ N ⩽ +5), the Lewis number (0.1 ⩽ Le ⩽ 10) and the thermal Darcy-Rayleigh number (RT = 400). Effects of these parameters on fluid flow, temperature and concentration distributions and mean heat and mass transfers within the cavity are analyzed. Results obtained show that both heat and mass transfers could be significantly enhanced or reduced, with respect to those generated in the case of constant heating conditions by proper choice of the parameters related to the periodic temperature. [ABSTRACT FROM AUTHOR]

Natural convection heat transfer in a shallow horizontal rectangular enclosure is considered. The enclosure contains non-Newtonian fluids and is exposed to cross-gradients of temperatures. The power-law model is used to characterize the non-Newtonian fluid behavior. Analytical solution is obtained in the central region of the cavity in terms of stream function and temperature fields, assuming a parallel flow in the central part of the enclosure. The analytical results are compared against the numerical solution, obtained by solving the full governing equations using a finite difference method. It is demonstrated that multiple steady state convective flows are possible. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is characterized by albuminuria, loss of renal function, renal fibrosis and infiltration of macrophages originating from peripheral monocytes inside kidneys. DN is also associated with intrarenal overactivation of the renin-angiotensin system (RAS), an enzymatic cascade which is expressed and controlled at the cell and/or tissue levels. All members of the RAS are present in the kidneys and most of them are also expressed in monocytes/macrophages. This review focuses on the control of monocyte recruitment and the modulation of macrophage polarization by the RAS in the context of DN. The local RAS favors the adhesion of monocytes on renal endothelial cells and increases the production of monocyte chemotactic protein-1 and of osteopontin in tubular cells, driving monocytes into the kidneys. There, proinflammatory cytokines and the RAS promote the differentiation of macrophages into the M1 proinflammatory phenotype, largely contributing to renal lesions of DN. Finally, resolution of the inflammatory process is associated with a phenotype switch of macrophages into the M2 anti-inflammatory subset, which protects against DN. The pharmacologic interruption of the RAS reduces albuminuria, improves the trajectory of the renal function, decreases macrophage infiltration in the kidneys and promotes the switch of the macrophage phenotype from M1 to M2.

Recent breakthrough studies suggest that metabolic signals such as AMP/NAD(+) and acetyl-CoA during fasting and feeding, respectively, translate the energetic cell status into specific transcriptional metabolic programs. Notably, NAD(+) and acetyl-CoA modulate chromatin packaging and gene expression as substrates of histone deacetylases or histone acetyltransferases, respectively. These energetic sensors regulate circadian rhythms and their related physiological processes. In addition, NAD(+) indirectly activates peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) during fasting, whereas acetyl-CoA inactivates PGC-1alpha upon feeding. In this review, we focus on recent evidence supporting the concept of an energetic code by which metabolic sensors control homeostasis during fasting and feeding and discuss its relevance to the pathophysiology of type 2 diabetes., (Copyright (c) 2009 Elsevier Ltd. All rights reserved.)

The transcription factor FoxO1 plays a central role in the metabolic adaptations to fasting. Furthermore, FoxO1 and its homologs encode enzymes buffering ROS (reactive oxygen species) or repairing damaged DNA, and are involved in stalling the ageing process across evolution. Our recent work conducted in primary cultures of rat hepatocytes suggests new mechanisms by which FoxO1 exerts some of these functions. They revealed an unexpected role for FoxO1 in amplifying metabolic, survival, mitogenic and stress signals, and the existence of multiple feed-back loops by which FoxO1 integrates and controls these pathways. Furthermore, these effects were found to be independent of FoxO1 direct binding to DNA.

Insulin inhibits forkhead O class (FoxO) transcription factors, which down-regulate the expression of genes involved in metabolism, cell cycle arrest, and apoptosis. After being phosphorylated by protein kinase B (PKB) on S253 in its DNA-binding domain, Foxo1 is phosphorylated on T24 and additional sites, which overall triggers its nuclear exclusion. During this process, Foxo1 is thought to retain some transcriptional activity and signaling potential. To evaluate this Foxo1 action, we used a Foxo1-ADA mutant that is constitutively nuclear due to mutation of T24 and S316 to A and harbors a mutation of S253 to D. Adenoviral-mediated expression of Foxo1-ADA in hepatocytes activates PKB and MAPK pathways more than expression of wild-type or of a transactivation domain-deleted mutant (Delta256). PKB activation cannot be accounted for by a Foxo1-mediated increase in upstream signaling components such as insulin receptor substrate 1 or 2 or by Foxo1-mediated down-regulation of Tribbles homolog 3. In contrast, Foxo1-ADA increases p38 activity, and p38 is required for effects of Foxo1 on PKB, at least in part. We propose that Foxo1 turns on a feed-forward loop, relayed by p38 and acting to amplify both PKB activation and Foxo1 inhibition. To conclude, key signaling pathways are activated in hepatocytes through nuclear Foxo1.

ANT1, TWINKLE and POLG genes affect mtDNA stability and are involved in autosomal dominant PEO, while mutations in POLG are responsible for numerous clinical presentations, including autosomal recessive PEO, sensory ataxic neuropathy, dysarthria and ophthalmoparesis (SANDO), spino-cerebellar ataxia and epilepsy (SCAE) or Alpers syndrome. In this study, we report on the mutational analysis of ANT1, TWINKLE and POLG genes in 15 unrelated patients, using a dHPLC-based protocol. This series of patients illustrates the large array of clinical presentations associated with mtDNA stability defects, ranging from isolated benign PEO to fatal Alpers syndrome. A total of seven different mutations were identified in six of 15 patients (40%). Six different recessive mutations were found in POLG, one in TWINKLE while no mutation was identified in ANT1. Among the POLG mutations, three are novel and include two missense and one frameshift changes. Seventeen neutral changes and polymorphisms were also identified, including four novel neutral polymorphisms. Overall, this study illustrates the variability of phenotypes associated with mtDNA stability defects, increases the mutational spectrum of POLG variants and provides an efficient and reliable detection protocol for ANT1, TWINKLE and POLG mutational screening.