Effects of Aging and Hypercholesterolemia on Oxidative Stress and DNA Damage in Bone Marrow Mononuclear Cells in Apolipoprotein E-deficient Mice

Recent evidence from apolipoprotein E-deficient (apoE^−/−) mice shows that aging and atherosclerosis are closely associated with increased oxidative stress and DNA damage in some cells and tissues. However, bone marrow cells, which are physiologically involved in tissue repair have not yet been investigated. In the present study, we evaluated the influence of aging and hypercholesterolemia on oxidative stress, DNA damage and apoptosis in bone marrow cells from young and aged apoE^−/− mice compared with age-matched wild-type C57BL/6 (C57) mice, using the comet assay and flow cytometry. The production of both superoxide and hydrogen peroxide in bone marrow cells was higher in young apoE^−/− mice than in age-matched C57 mice, and reactive oxygen species were increased in aged C57 and apoE^−/− mice. Similar results were observed when we analyzed the DNA damage and apoptosis. Our data showed that both aging and hypercholesterolemia induce the increased production of oxidative stress and consequently DNA damage and apoptosis in bone marrow cells. This study is the first to demonstrate a functionality decrease of the bone marrow, which is a fundamental extra-arterial source of the cells involved in vascular injury repair.     

Viral Transduction Enhancing Effect of EF-C Peptide Nanofibrils Is Mediated by Cellular Protrusions

Self-assembling peptide nanofibrils (PNF) have gained increasing attention as versatile molecules in material science and biomedicine. One important application of PNF is to enhance retroviral gene transfer, a technology that has been central for gene therapy approaches. The best-investigated and commercially available PNF is derived from a 12-mer peptide termed EF-C. The mechanism of transduction enhancement depends on the polycationic surface of EF-C PNF, which bind to the negatively charged membranes of viruses and cells, thereby overcoming electrostatic repulsions and increasing virion attachment and fusion. To better understand how EF-C PNF interact with the cell surface, scanning electron and time-lapse confocal microscopy were performed. The fibrils are found to be actively engaged by cellular protrusions such as filopodia. Consequently, chemical suppression of protrusion formation abrogates fibril binding and virion delivery to the cell surface of immortalized and primary T cells. Vice versa, induction of plasma membrane blebs result in increased fibril binding. Thus, the mechanism of PNF-mediated viral transduction enhancement involves an active engagement of virus-loaded fibrils by cellular protrusions, which may explain its superior performance over soluble transduction enhancers.     

SMEs' Preference for Innovation Networks: A Choice Experimental Approach

The objective of this paper is to evaluate the importance of selected characteristics of innovation networks in affecting the decision of food SMEs when joining such networks. The paper develops and tests a series of hypotheses through a choice experiment exercise ran on a sample of 231 firms in six EU countries. The results showed that SMEs prefer networks that are composed of manufacturers and supply chain members, where information is shared confidentially among network partners, and when the network provides support to help the firm build its own networks of partners for innovation. In addition, SMEs' choice of the network is also affected by the interaction between specific network attributes and two firm characteristics, i.e. the firm's collaborative experience and innovation objectives. Based on the results, we conclude that the success of inter‐organizational networks depends on the fit between the network's design and the innovation and networking behaviour of the firms.     

Stereo music visualization through manifold harmonics

Music visualizations are nowadays included with virtually any media player. They usually rely on harmonic analysis of each sound channel, which automatically generate parameters for procedural image generation. However, only few music visualizations make use of 3d shapes. This paper proposes to use spectral mesh processing techniques, here manifold harmonics, to produce 3d stereo music visualization. The images are generated from 3d models by deforming an initial shape, mapping the sound frequencies to the mesh harmonics. A symmetry criterion is introduced to enhance the stereo effects on the deformed shape. A concise representation of the frequency mapping is proposed to allow for an animated gallery interface with genetic reproduction. Such galleries let the user quickly navigate between visual effects. Rendering such animated galleries in real time is a challenging task, since it requires computing and rendering the deformed shapes at a very high rate. This paper introduces a direct GPU implementation of manifold harmonics filters, which allows the displaying of the animated galleries.     

Estimation of vaccine efficacy in a repeated measures study under heterogeneity of exposure or susceptibility to infection

Vaccine efficacy (VE) is commonly estimated through proportional hazards modelling of the time to first infection or disease, even when the event of interest can recur. These methods can result in biased estimates when VE is heterogeneous across levels of exposure and susceptibility in subjects. These two factors are important sources of unmeasured heterogeneity, since they vary within and across areas, and often cannot be individually quantified. We propose an estimator of VE per exposure that accounts for heterogeneous susceptibility and exposure for a repeated measures study with binary recurrent outcomes. The estimator requires only information about the probability distribution of environmental exposures. Through simulation studies, we compare the properties of this estimator with proportional hazards estimation under the heterogeneity of exposure. The methods are applied to a reanalysis of a malaria vaccine trial in Brazil.     

A safety study of oral xanthohumol administration and its influence on fertility in Sprague Dawley rats

Xanthohumol (XN) is a prenylated chalcone, which has been shown to possess a broad range of potential cancer preventive and additional biological activities. In the present study, we have determined the subchronic 4-wk toxicity of XN and monitored its influence on fertility and development of offspring in two fertility studies. Four-week-old female Sprague Dawley (SD) rats were treated with 0.5% XN in the diet or with 1,000 mg XN/kg body weight (b.w.) per day by gavage for 28 days. No remarkable treatment-related changes in general appearance and b.w. occurred during the study. After autopsy, liver, kidney, lung, heart, stomach, and spleen were examined macroscopically and histopathologically. Relative liver weights of animals in both treatment groups were significantly reduced by 30--40% in comparison with the control group, indicating weak hepatotoxicity. Also, mammary glands of treated rats appeared less developed compared to the controls. Consequently, we investigated the influence of XN on rat reproduction. In two fertility studies, XN (100 mg/kg b.w. per day), given either for 4 wk prior to or during mating, gestation, and nursing, did not cause any adverse effects on female reproduction and the development of offspring. Noteworthy, treatment of male rats prior to mating significantly (p=0.027) increased the sex ratio of male to female offspring. Overall, lifelong treatment at a daily dose of 100 mg/kg b.w. in a two-generation study did not affect the development of SD rats.     

Failure Analysis of Additively Manufactured Polyester Test Specimens Exposed to Various Liquid Media

Journal of Failure Analysis and Prevention - Additive manufacturing platforms that rely on thermoplastic feedstock materials are now expected to fabricate components intended for deployment in a...     

A Survey on the Use of P2P Technology for Network Management

Network management has steadily evolved over recent years. Along with the growing need for advanced features in network management solutions, several distribution models were investigated, varying from centralized to fully distributed models. Despite the common agreement that some sort of distribution is really needed to execute management tasks, there seems to exist a permanent quest for the next distributed network management model. Among the distributed models, an interesting and emerging possibility is the use of P2P technology in network management, also known as P2P-Based Network Management (P2PBNM). Several investigations have shown that P2PBNM can be seen as an enabler for advanced network management features. However, due to the dispersion concerning the concepts and features related to these investigations, it is difficult to draw a comprehensive picture of the P2PBNM area. The purpose of this article is to look at literature on P2PBNM and to highlight initiatives regarding the use of P2P technology in network management. Furthermore, such initiatives are classified in respect to proposed review questions. Finally, future trends are discussed in order to predict what the future holds for P2PBNM.     

Synthetic Cancer‐Targeting Innate Immune Stimulators Give Insights into Avidity Effects

Multispecific and multivalent antibodies are seen as promising cancer therapeutics, and numerous antibody fragments and derivatives have been developed to exploit avidity effects that result in increased selectivity. Most of these multispecific and multivalent antibody strategies make use of recombinant expression of antigen‐binding modules. In contrast, chemical synthesis and chemoselective ligations can be used to generate a variety of molecules with different numbers and combinations of binding moieties in a modular and homogeneous fashion. In this study we synthesized a series of targeted immune system engagers (ISErs) by using solid‐phase peptide synthesis and chemoselective ligations. To explore avidity effects, we constructed molecules bearing different numbers and combinations of two “binder” peptides that target ephrin A2 and integrin α₃ receptors and an “effector” peptide that binds to formyl peptide receptors and stimulates an immune response. We investigated various strategies for generating multivalent and multispecific targeted innate immune stimulators and studied their activities in terms of binding to cancer cells and stimulation of immune cells. This study gives insights into the influence that multivalency and receptor density have on avidity effects and is useful for the design of potential anticancer therapeutics.