Efficient Excitation of Hybrid Modes in a THz Clinotron

Journal of Infrared, Millimeter, and Terahertz Waves - Various regimes of hybrid, bulk-surface, modes being excited in the clinotron oscillator with a sheet electron beam and nonuniform grating...     

Cell Sheet Comprised of Mesenchymal Stromal Cells Overexpressing Stem Cell Factor Promotes Epicardium Activation and Heart Function Improvement in a Rat Model of Myocardium Infarction

Cell therapy of the post-infarcted myocardium is still far from clinical use. Poor survival of transplanted cells, insufficient regeneration, and replacement of the damaged tissue limit the potential of currently available cell-based techniques. In this study, we generated a multilayered construct from adipose-derived mesenchymal stromal cells (MSCs) modified to secrete stem cell factor, SCF. In a rat model of myocardium infarction, we show that transplantation of SCF producing cell sheet induced activation of the epicardium and promoted the accumulation of c-kit positive cells in ischemic muscle. Morphometry showed the reduction of infarct size (16%) and a left ventricle expansion index (0.12) in the treatment group compared to controls (24–28%; 0.17–0.32). The ratio of viable myocardium was more than 1.5-fold higher, reaching 49% compared to the control (28%) or unmodified cell sheet group (30%). Finally, by day 30 after myocardium infarction, SCF-producing cell sheet transplantation increased left ventricle ejection fraction from 37% in the control sham-operated group to 53%. Our results suggest that, combining the genetic modification of MSCs and their assembly into a multilayered construct, we can provide prolonged pleiotropic effects to the damaged heart, induce endogenous regenerative processes, and improve cardiac function.     

Crack-like formation of failure-decided angle points on middle planes of the layers resistant to bending in multi-layer structure - a continuum model

A theoretical model is considered that describes, in a continuum approximation, formation of a segment of angle points on the middle planes of thin layers forming a multi-layer structure. These points are associated with the jumps of the slope of the middle planes on the segment. A 2-D case is dealt with. The structure is assumed to be a half-plane with its boundary parallel to the layers and acted upon by a symmetric distribution of the displacements normal to the boundary. The layers forming the structure are assumed capable of mutually gliding with respect to each other and of revealing their flexure rigidity under the above loading. The continuum approximation to describe the above multi-layer structure has been applied. Physically the above mathematical angle points may (depending on the layer material properties) emerge either as a result of transverse fracture of the layers or as a result of intensive local plastic deformation (formation of the plastic `hinges'). As a result, the bending moment drops drastically, so that it is assumed dropping down to zero. This condition is employed to determine the distribution of the above slope jumps. The segment length is determined by equating the bending moment at the remote (from the boundary) end of the segment to a critical (specified) value of the bending moment. Thus, the problem of determining the slope jumps on the segment is reduced to a Fredholm integral equation of the first kind with the kernel having an integrable singularity. This equation has been solved numerically. The results of the calculations are presented.     

An optimal control method for aggregate production planning in large-scale manufacturing systems with capacity expansion and deterioration

An optimal control approach to continuous-time aggregate production planning problems is presented. The proposed approach describes the production and capacity evolution (expansion, sell and deterioration) processes in the form of differential equations with regular production, subcontracting and capacity change rates controllable on one hierarchical level. In this way, the traditional disadvantages of the two-level problem consideration (one level for strategic capacity planning and the other for production smoothing) are avoided. Analytical properties for optimal production and capacity control regimes and conditions for their changeover are derived by the maximum principle. Based on these results, an insight into the optimal behaviour of the production system is gained and a fast numerical method is developed to identify and sequence the optimal regimes for arbitrary demand profiles. A computational example illustrates the effectiveness of the approach.     

Therapeutic Effects of hiPSC-Derived Glial and Neuronal Progenitor Cells-Conditioned Medium in Experimental Ischemic Stroke in Rats

Transplantation of various types of stem cells as a possible therapy for stroke has been tested for years, and the results are promising. Recent investigations have shown that the administration of the conditioned media obtained after stem cell cultivation can also be effective in the therapy of the central nervous system pathology (hypothesis of their paracrine action). The aim of this study was to evaluate the therapeutic effects of the conditioned medium of hiPSC-derived glial and neuronal progenitor cells in the rat middle cerebral artery occlusion model of the ischemic stroke. Secretory activity of the cultured neuronal and glial progenitor cells was evaluated by proteomic and immunosorbent-based approaches. Therapeutic effects were assessed by overall survival, neurologic deficit and infarct volume dynamics, as well as by the end-point values of the apoptosis- and inflammation-related gene expression levels, the extent of microglia/macrophage infiltration and the numbers of formed blood vessels in the affected area of the brain. As a result, 31% of the protein species discovered in glial progenitor cells-conditioned medium and 45% in neuronal progenitor cells-conditioned medium were cell type specific. The glial progenitor cell-conditioned media showed a higher content of neurotrophins (BDNF, GDNF, CNTF and NGF). We showed that intra-arterial administration of glial progenitor cells-conditioned medium promoted a faster decrease in neurological deficit compared to the control group, reduced microglia/macrophage infiltration, reduced expression of pro-apoptotic gene Bax and pro-inflammatory cytokine gene Tnf, increased expression of anti-inflammatory cytokine genes (Il4, Il10, Il13) and promoted the formation of blood vessels within the damaged area. None of these effects were exerted by the neuronal progenitor cell-conditioned media. The results indicate pronounced cytoprotective, anti-inflammatory and angiogenic properties of soluble factors secreted by glial progenitor cells.     

Pre-Senescence Induction in Hepatoma Cells Favors Hepatitis C Virus Replication and Can Be Used in Exploring Antiviral Potential of Histone Deacetylase Inhibitors

Recent evidence suggests that fibrotic liver injury in patients with chronic hepatitis C correlates with cellular senescence in damaged liver tissue. However, it is still unclear how senescence can affect replication of the hepatitis C virus (HCV). In this work, we report that an inhibitor of cyclin-dependent kinases 4/6, palbociclib, not only induced in hepatoma cells a pre-senescent cellular phenotype, including G1 arrest in the cell cycle, but also accelerated viral replicon multiplication. Importantly, suppression of HCV replication by direct acting antivirals (DAAs) was barely affected by pre-senescence induction, and vice versa, the antiviral activities of host-targeting agents (HTAs), such as inhibitors of human histone deacetylases (HDACi), produced a wide range of reactions—from a dramatic reduction to a noticeable increase. It is very likely that under conditions of the G1 arrest in the cell cycle, HDACi exhibit their actual antiviral potency, since their inherent anticancer activity that complicates the interpretation of test results is minimized.     

Exo-mechanism proximity-accelerated alkylations: investigations of linkers, electrophiles and surface mutations in engineered cyclophilin-cyclosporin systems

Investigations on the scope and utility of exo-mechanism proximity-accelerated reactions in engineered receptor-ligand systems are reported. We synthesized a series of electrophilic cyclosporin (CsA) derivatives by varying electrophiles and linker lengths, prepared a series of nucleophilic cysteine mutations on the surface of cyclophilin A (Cyp), and examined their reactivity and specificity in proximity-accelerated reactions. Acrylamide and epoxide electrophiles afforded useful reactivity and high specificity for alkylation of engineered receptors in Jurkat cell extracts. We found that remote cysteines (>17 A from the ligand) could be alkylated with useful rates under physiological conditions. The results from mutations of the receptor surface suggest that the dominant factors governing the rates of proximity-accelerated reactions are related to the local environment of the reactive group on the protein surface. This study defines several parameters affecting reactivity in exo-mechanism proximity-accelerated reactions and provides guidance for the design of experiments for biological investigations involving proximity-accelerated reactions.     

A corpus of Schlieren photography of speech production: potential methodology to study aerodynamics of labial,nasal and vocalic processes

Language Resources and Evaluation - This report presents a corpus of articulations recorded with Schlieren photography, a recording technique to visualize aeroflow dynamics for two purposes. First,...     

Enterprise Social Networks as Digital Infrastructures - Understanding the Utilitarian Value of Social Media at the Workplace

ABSTRACT

In this study, we first show that while both the perceived usefulness and perceived enjoyment of enterprise social networks impact employees’ intentions for continuous participation, the utilitarian value significantly outpaces its hedonic value. Second, we prove that the network’s utilitarian value is constituted by its digital infrastructure characteristics: versatility, adaptability, interconnectedness and invisibility-in-use. The study is set within a software engineering company and bases on quantitative survey research, applying partial least squares structural equation modeling.     

Design and analysis of a social botnet

Online Social Networks (OSNs) have attracted millions of active users and have become an integral part of today’s web ecosystem. Unfortunately, in the wrong hands, OSNs can be used to harvest private user data, distribute malware, control botnets, perform surveillance, spread misinformation, and even influence algorithmic trading. Usually, an adversary starts off by running an infiltration campaign using hijacked or adversary-owned OSN accounts, with an objective to connect with a large number of users in the targeted OSN. In this article, we evaluate how vulnerable OSNs are to a large-scale infiltration campaign run by socialbots: bots that control OSN accounts and mimic the actions of real users. We adopted the design of a traditional web-based botnet and built a prototype of a Socialbot Network (SbN): a group of coordinated programmable socialbots. We operated our prototype on Facebook for 8 weeks, and collected data about user behavior in response to a large-scale infiltration campaign. Our results show that (1) by exploiting known social behaviors of users, OSNs such as Facebook can be infiltrated with a success rate of up to 80%, (2) subject to user profile privacy settings, a successful infiltration can result in privacy breaches where even more private user data are exposed, (3) given the economics of today’s underground markets, running a large-scale infiltration campaign might be profitable but is still not particularly attractive as a sustainable and independent business, (4) the security of socially-aware systems that use or integrate OSN platforms can be at risk, given the infiltration capability of an adversary in OSNs, and (5) defending against malicious socialbots raises a set of challenges that relate to web automation, online-offline identity binding, and usable security.