The Age-Sensitive Efficacy of Calorie Restriction on Mitochondrial Biogenesis and mtDNA Damage in Rat Liver

Calorie restriction (CR) is the most efficacious treatment to delay the onset of age-related changes such as mitochondrial dysfunction. However, the sensitivity of mitochondrial markers to CR and the age-related boundaries of CR efficacy are not fully elucidated. We used liver samples from ad libitum-fed (AL) rats divided in: 18-month-old (AL-18), 28-month-old (AL-28), and 32-month-old (AL-32) groups, and from CR-treated (CR) 28-month-old (CR-28) and 32-month-old (CR-32) counterparts to assay the effect of CR on several mitochondrial markers. The age-related decreases in citrate synthase activity, in TFAM, MFN2, and DRP1 protein amounts and in the mtDNA content in the AL-28 group were prevented in CR-28 counterparts. Accordingly, CR reduced oxidative mtDNA damage assessed through the incidence of oxidized purines at specific mtDNA regions in CR-28 animals. These findings support the anti-aging effect of CR up to 28 months. Conversely, the protein amounts of LonP1, Cyt c, OGG1, and APE1 and the 4.8 Kb mtDNA deletion content were not affected in CR-28 rats. The absence of significant differences between the AL-32 values and the CR-32 counterparts suggests an age-related boundary of CR efficacy at this age. However, this only partially curtails the CR benefits in counteracting the generalized aging decline and the related mitochondrial involvement.     

Workers’ rest allowance and smoothing of the workload in assembly lines

Ergonomic aspects have a crucial role in manual assembly systems. They impact on the workers’ health, final product quality and productivity. For these reasons, there is the necessity to integrate them into the assembly line balancing phase as, whereas, only time and cost variables are considered. In this study, human energy expenditures are considered as ergonomic aspects and we integrate them, for the first time, into the assembly line balancing problem type 2 through the rest allowance evaluation. We consider as an objective function the minimization of the smoothness index. Firstly, a new optimal method based on mixed integer linear programming and a new linearization methodology are proposed. Then, a heuristic approach is introduced. To complete the study, a computational experimentation is presented to validate the mathematical model and to compare the methodologies proposed in terms of computational time, complexity and solution. Additionally, we provide a detailed analysis of the impact that rest allowance evaluation can have on productivity comparing the results obtained, taking into account the rest allowance integration before, during and after the assembly balancing process.     

Milk from cows fed a diet with a high forage:concentrate ratio improves inflammatory state,oxidative stress,and mitochondrial function in rats

Excessive energy intake may evoke complex biochemical processes characterized by inflammation, oxidative stress, and impairment of mitochondrial function that represent the main factors underlying noncommunicable diseases. Because cow milk is widely used for human nutrition and in food industry processing, the nutritional quality of milk is of special interest with respect to human health. In our study, we analyzed milk produced by dairy cows fed a diet characterized by a high forage:concentrate ratio (high forage milk, HFM). In view of the low n-6:n-3 ratio and high content of conjugated linoleic acid of HFM, we studied the effects of this milk on lipid metabolism, inflammation, mitochondrial function, and oxidative stress in a rat model. To this end, we supplemented for 4 wk the diet of male Wistar rats with HFM and with an isocaloric amount (82 kJ, 22 mL/d) of milk obtained from cows fed a diet with low forage:concentrate ratio, and analyzed the metabolic parameters of the animals. Our results indicate that HFM may positively affect lipid metabolism, leptin:adiponectin ratio, inflammation, mitochondrial function, and oxidative stress, providing the first evidence of the beneficial effects of HFM on rat metabolism.     

Macrophage Immunomodulation Through New Polymers that Recapitulate Functional Effects of Itaconate as a Power House of Innate Immunity

Itaconate (ITA) is an emerging powerhouse of innate immunity with therapeutic potential that is limited in its ability to be administered in a soluble form. A library of polyester materials that incorporate ITA into polymer backbones resulting in materials with inherent immunoregulatory behavior is developed. Harnessing hydrolytic degradation release from polyester backbones, ITA polymers result in the mechanism specific immunoregulatory properties on macrophage polarization in vitro. In a functional assay, the polymer-released ITA inhibits bacterial growth on acetate. Translation to an in vivo model of biomaterial associated inflammation, intraperitoneal injection of ITA polymers demonstrate a rapid resolution of inflammation in comparison to a control polymer silicone, demonstrating the value of sustained biomimetic presentation of ITA.     

Transformations for nonideal uniform circular arrays operating in correlated signal environments

The Davies transformation is a method to transform the steering vector of a uniform circular array (UCA) to one with Vandermonde form. As such, it allows techniques such as spatial smoothing for direction-of-arrival (DOA) estimation in a correlated signal environment, developed originally for uniform linear arrays, to be applied to UCAs. However, the Davies transformation can be highly sensitive to perturbations of the underlying array model. This paper presents a method for deriving a more robust transformation using optimization techniques. The effectiveness of the method is illustrated through a number of DOA estimation examples.     

A new approach to the optimization of robust antenna arrayprocessors

The authors present a method for solving a class of optimization problems with nonsmooth constraints. In particular, they apply the method to the design of narrowband minimum-power antenna array processors which are robust in the presence of errors such as array element placement, look direction misalignment, and frequency offset. They first show that the constrained minimum power problem has a unique global minimum provided that the constraint set is nonempty. Then it is shown how the design problem derived directly from considerations of the sensitivity of the antenna array processor to errors can be transformed into a quadratic programming problem with linear inequality constraints which can be solved efficiently by the standard active set strategy. They also present numerical results for two types of nonsmooth constraints developed to provided robustness. These results confirm the effectiveness of the method     

Purification and renaturation of recombinant human lymphotoxin (tumour necrosis factor beta) expressed in Escherichia coli as inclusion bodies

High level expression of recombinant human tumour necrosis factor β (rh TNF-β) in Escherichia coli results in the formation of two portions of protein, namely soluble active protein and insoluble protein which is inactive and aggregates in the form of inclusion bodies (IBs). In this study, a procedure for purification and renaturation of rh TNF-β from inclusion bodies has been designed and verified experimentally with a product purity of more than 90% and a recovery of about 30%. The procedure includes washing of IBs with specific wash buffer (Triton X-100/EDTA/lysozyme/PMSF), their solubilization with 8 mol dm^?3 alkaline urea, purification with ion-exchange columns, refolding with renaturation buffer and finally concentration and desalination with an ultrafiltration membrane. The characteristics of the renatured protein were identical with those of purified protein from the soluble fraction as demonstrated by (1) SDS-PAGE, (2) cytotoxic activity on mouse L929 cells, (3) N-terminal amino acid sequence, and (4) gel filtration chromatography.     

Digital Laguerre filter design with maximum passband-to-stopband energy ratio subject to peak and Group delay constraints

In this paper, we formulate a general design of transversal filter structures with maximum relative passband-to-stopband energy ratio subject to complex frequency response constraints in the passband and the stopband as well as additional constraints such as constraints. These constraints are important for applications where the suppression of noise at certain frequencies are important. Additional constraints are introduced allowing approximately linear phase and constant group delay in the passband. For a given set of basis functions, the design problem can be formulated as a semi-infinite quadratic optimization problem in the filter coefficients, which are the decision variables to be optimized. In this paper, we focus on the design of digital Laguerre filter and digital finite impulse response (FIR) filter structures. A modified bridging algorithm is developed for searching for the optimum pole of the Laguerre filters. Design examples are given to demonstrate the effectiveness of the proposed algorithm.     

A logic of argumentation for specification and verification of abstract argumentation frameworks

In this paper, we propose a logic of argumentation for the specification and verification (LA4SV) of requirements on Dung??s abstract argumentation frameworks. We distinguish three kinds of decision problems for argumentation verification, called extension verification, framework verification, and specification verification respectively. For example, given a political requirement like ??if the argument to increase taxes is accepted, then the argument to increase services must be accepted too,?? we can either verify an extension of acceptable arguments, or all extensions of an argumentation framework, or all extensions of all argumentation frameworks satisfying a framework specification. We introduce the logic of argumentation verification to specify such requirements, and we represent the three verification problems of argumentation as model checking and theorem proving properties of the logic. Moreover, we recast the logic of argumentation verification in a modal framework, in order to express multiple extensions, and properties like transitivity and reflexivity of the attack relation. Finally, we introduce a logic of meta-argumentation where abstract argumentation is used to reason about abstract argumentation itself. We define the logic of meta-argumentation using the fibring methodology in such a way to represent attack relations not only among arguments but also among attacks. We show how to use this logic to verify the requirements of argumentation frameworks where higher-order attacks are allowed [A preliminary version of the logic of argumentation compliance was called the logic of abstract argumentation?(2005).]     

Post-Translational Modifications of Retroviral HIV-1 Gag Precursors: An Overview of Their Biological Role

Protein post-translational modifications (PTMs) play key roles in eukaryotes since they finely regulate numerous mechanisms used to diversify the protein functions and to modulate their signaling networks. Besides, these chemical modifications also take part in the viral hijacking of the host, and also contribute to the cellular response to viral infections. All domains of the human immunodeficiency virus type 1 (HIV-1) Gag precursor of 55-kDa (Pr55^Gag), which is the central actor for viral RNA specific recruitment and genome packaging, are post-translationally modified. In this review, we summarize the current knowledge about HIV-1 Pr55^Gag PTMs such as myristoylation, phosphorylation, ubiquitination, sumoylation, methylation, and ISGylation in order to figure out how these modifications affect the precursor functions and viral replication. Indeed, in HIV-1, PTMs regulate the precursor trafficking between cell compartments and its anchoring at the plasma membrane, where viral assembly occurs. Interestingly, PTMs also allow Pr55^Gag to hijack the cell machinery to achieve viral budding as they drive recognition between viral proteins or cellular components such as the ESCRT machinery. Finally, we will describe and compare PTMs of several other retroviral Gag proteins to give a global overview of their role in the retroviral life cycle.