DEPP functionally graded piezoceramics via micro-fabrication by co-extrusion

This paper introduces the Dual Electro/Piezo Property (DEPP) gradient technique via Micro-Fabrication through Co-eXtrusion (MFCX) which pairs a high displacement lead zirconate titanate (PZT) piezoceramic with a high permittivity barium titanate (BT) dielectric. By grading with this material combination spatially across an actuator, the electric field is concentrated in the more active region for improved efficiency, higher displacements, and complex motions. To aid in synthesis and analysis of any gradient profile, compositional maps are provided for key material properties (density, stiffness, permittivity, and piezoelectric coefficients). The DEPP technique was validated, independent of the MFCX process, by powder pressing a conventional bimodal gradient beam which demonstrated through experiments high displacement capabilities at lower driving potentials than comparable functionally graded piezoceramic actuators. For more complex gradients, the MFCX process was adapted to the DEPP gradient technique and illustrated by the fabrication of a linearly graded prototype whose monolithic nature and gradual material variation significantly reduces internal stresses, improves reliability, and extends service lifetime.     

NKG2C+ NK Cells for Immunotherapy of Glioblastoma Multiforme

In glioblastoma, non-classical human leucocyte antigen E (HLA-E) and HLA-G are frequently overexpressed. HLA-E loaded with peptides derived from HLA class I and from HLA-G contributes to inhibition of natural killer (NK) cells with expression of the inhibitory receptor CD94/NKG2A. We investigated whether NK cells expressing the activating CD94/NKG2C receptor counterpart were able to exert anti-glioma effects. NKG2C+ subsets were preferentially expanded by a feeder cell line engineered to express an artificial disulfide-stabilized trimeric HLA-E ligand (HLA-E*spG). NK cells expanded by a feeder cell line, which facilitates outgrowth of conventional NKG2A+, and fresh NK cells, were included for comparison. Expansion via the HLA-E*spG feeder cells selectively increased the fraction of NKG2C+ NK cells, which displayed a higher frequency of KIR2DL2/L3/S2 and CD16 when compared to expanded NKG2A+ NK cells. NKG2C+ NK cells exhibited increased cytotoxicity against K562 and KIR:HLA-matched and -mismatched primary glioblastoma multiforme (GBM) cells when compared to NKG2A+ NK cells and corresponding fresh NK cells. Cytotoxic responses of NKG2C+ NK cells were even more pronounced when utilizing target cells engineered with HLA-E*spG. These findings support the notion that NKG2C+ NK cells have potential therapeutic value for treating gliomas.     

Semi-empirical Density Estimations for Binary,Ternary and Multicomponent Alkali Nitrate–Nitrite Molten Salt Mixtures

For sensible thermal energy storage in Concentrating Solar Power (CSP) plants, a molten salt mixture of 60 wt% sodium nitrate (NaNO₃) and 40 wt% potassium nitrate (KNO₃), known as Solar Salt, is commonly utilized. The paper presents semi-empirical estimation results of the density of Solar Salt and alternative molten salt mixtures with low melting temperatures in a range from 70 °C to 140 °C. These mixtures are Hitec, HitecXL, LiNO₃–KNO₃–NaNO₃ and a multicomponent mixture. The paper shows that density values of mixtures can be closely predicted from single salt densities. The paper examines different estimation rules for mixtures. The quasilinear volumetric additivity rule (QVAR) is known for ternary reciprocal systems. For the first time, the presented work extends the QVAR to multicomponent mixtures. Temperature-dependent densities of selected salt mixtures of the system Ca,Li,K,Na//NO₂,NO₃ were estimated. Estimations are motivated by a fast and reliable method compared to time-consuming and error-prone measurements of several mixtures.     

Comments on 'Formal specification of user interfaces: a comparison and evaluation of four axiomatic approaches' by U.H. Chi

A recent paper (see ibid., vol.11, no.8, p.671-88, Aug. 1985) compared several axiomatic methods of formal specification, one of which was Z. As a result of a comparison made with Z and a similar, but executable, specification language called Me too, it was pointed out that one of the Z specifications given was not correct. In this response, the erroneous function is described and some conclusions are drawn about the process of formal specification.<>     

A Comparison of Mamdani and Sugeno Fuzzy Based Packet Scheduler for MANET with a Realistic Wireless Propagation Model

 The mobile nature of the nodes in a wireless mobile ad-hoc network (MANET) and the error prone link connectivity between nodes pose many challenges. These include frequent route changes, high packet loss, etc. Such problems increase the end-toend delay and decrease the throughput. This paper proposes two adaptive priority packet scheduling algorithms for MANET based on Mamdani and Sugeno fuzzy inference system. The fuzzy systems consist of three input variables: data rate, signal-to-noise ratio (SNR) and queue size. The fuzzy decision system has been optimised to improve its efficiency. Both fuzzy systems were verified using the Matlab fuzzy toolbox and the performance of both algorithms were evaluated using the riverbed modeler (formally known as OPNET modeler). The results were compared to an existing fuzzy scheduler under various network loads, for constant-bit-rate (CBR) and variable-bit-rate (VBR) traffic. The measuring metrics which form the basis for performance evaluation are end-to-end delay, throughput and packet delivery ratio. The proposed Mamdani and Sugeno scheduler perform better than the existing scheduler for CBR traffic. The end-to-end delay for Mamdani and Sugeno scheduler was reduced by an average of 52% and 54%, respectively. The performance of the throughput and packet delivery ratio for CBR traffic are very similar to the existing scheduler because of the characteristic of the traffic. The network was also at full capacity. The proposed schedulers also showed a better performance for VBR traffic. The end-to-end delay was reduced by an average of 38% and 52%, respectively. Both the throughput and packet delivery ratio (PDR) increased by an average of 53% and 47%, respectively. The Mamdani scheduler is more computationally complex than the Sugeno scheduler, even though they both showed similar network performance. Thus, the Sugeno scheduler is more suitable for real-time applications.     

Evidence for Oxidative Pathways in the Pathogenesis of PD: Are Antioxidants Candidate Drugs to Ameliorate Disease Progression?

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that arises due to a complex and variable interplay between elements including age, genetic, and environmental risk factors that manifest as the loss of dopaminergic neurons. Contemporary treatments for PD do not prevent or reverse the extent of neurodegeneration that is characteristic of this disorder and accordingly, there is a strong need to develop new approaches which address the underlying disease process and provide benefit to patients with this debilitating disorder. Mitochondrial dysfunction, oxidative damage, and inflammation have been implicated as pathophysiological mechanisms underlying the selective loss of dopaminergic neurons seen in PD. However, results of studies aiming to inhibit these pathways have shown variable success, and outcomes from large-scale clinical trials are not available or report varying success for the interventions studied. Overall, the available data suggest that further development and testing of novel therapies are required to identify new potential therapies for combating PD. Herein, this review reports on the most recent development of antioxidant and anti-inflammatory approaches that have shown positive benefit in cell and animal models of disease with a focus on supplementation with natural product therapies and selected synthetic drugs.     

Next-Generation Grade and Survival Expression Biomarkers of Human Gliomas Based on Algorithmically Reconstructed Molecular Pathways

In gliomas, expression of certain marker genes is strongly associated with survival and tumor type and often exceeds histological assessments. Using a human interactome model, we algorithmically reconstructed 7494 new-type molecular pathways that are centered each on an individual protein. Each single-gene expression and gene-centric pathway activation was tested as a survival and tumor grade biomarker in gliomas and their diagnostic subgroups (IDH mutant or wild type, IDH mutant with 1p/19q co-deletion, MGMT promoter methylated or unmethylated), including the three major molecular subtypes of glioblastoma (proneural, mesenchymal, classical). We used three datasets from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas, which in total include 527 glioblastoma and 1097 low grade glioma profiles. We identified 2724 such gene and 2418 pathway survival biomarkers out of total 17,717 genes and 7494 pathways analyzed. We then assessed tumor grade and molecular subtype biomarkers and with the threshold of AUC > 0.7 identified 1322/982 gene biomarkers and 472/537 pathway biomarkers. This suggests roughly two times greater efficacy of the reconstructed pathway approach compared to gene biomarkers. Thus, we conclude that activation levels of algorithmically reconstructed gene-centric pathways are a potent class of new-generation diagnostic and prognostic biomarkers for gliomas.     

Aging of Vascular System Is a Complex Process: The Cornerstone Mechanisms

Aging is one of the most intriguing processes of human ontogenesis. It is associated with the development of a wide variety of diseases affecting all organs and their systems. The victory over aging is the most desired goal of scientists; however, it is hardly achievable in the foreseeable future due to the complexity and ambiguity of the process itself. All body systems age, lose their performance, and structural disorders accumulate. The cardiovascular system is no exception. And it is cardiovascular diseases that occupy a leading position as a cause of death, especially among the elderly. The aging of the cardiovascular system is well described from a mechanical point of view. Moreover, it is known that at the cellular level, a huge number of mechanisms are involved in this process, from mitochondrial dysfunction to inflammation. It is on these mechanisms, as well as the potential for taking control of the aging of the cardiovascular system, that we focused on in this review.     

Sphingolipid Catabolism and Glycerophospholipid Levels Are Altered in Erythrocytes and Plasma from Multiple Sclerosis Patients

Multiple sclerosis (MS) is an autoimmune, inflammatory, degenerative disease of the central nervous system. Changes in lipid metabolism have been suggested to play important roles in MS pathophysiology and progression. In this work we analyzed the lipid composition and sphingolipid-catabolizing enzymes in erythrocytes and plasma from MS patients and healthy controls. We observed reduction of sphingomyelin (SM) and elevation of its products—ceramide (CER) and shingosine (SPH). These changes were supported by the detected up-regulation of the activity of acid sphingomyelinase (ASM) in MS plasma and alkaline ceramidase (ALCER) in erythrocytes from MS patients. In addition, Western blot analysis showed elevated expression of ASM, but not of ALCER. We also compared the ratios between saturated (SAT), unsaturated (UNSAT) and polyunsaturated fatty acids and suggest, based on the significant differences observed for this ratio, that the UNSAT/SAT values could serve as a marker distinguishing erythrocytes and plasma of MS from controls. In conclusion, the application of lipid analysis in the medical practice would contribute to definition of more precise diagnosis, analysis of disease progression, and evaluation of therapeutic strategies. Based on the molecular changes of blood lipids in neurodegenerative pathologies, including MS, clinical lipidomic analytical approaches could become a promising contemporary tool for personalized medicine.     

JavAdaptor—Flexible runtime updates of Java applications

Software is changed frequently during its life cycle. New requirements come, and bugs must be fixed. To update an application, it usually must be stopped, patched, and restarted. This causes time periods of unavailability, which is always a problem for highly available applications. Even for the development of complex applications, restarts to test new program parts can be time consuming and annoying. Thus, we aim at dynamic software updates to update programs at runtime. There is a large body of research on dynamic software updates, but so far, existing approaches have shortcomings either in terms of flexibility or performance. In addition, some of them depend on specific runtime environments and dictate the program's architecture. We present JavAdaptor , the first runtime update approach based on Java that (a) offers flexible dynamic software updates, (b) is platform independent, (c) introduces only minimal performance overhead, and (d) does not dictate the program architecture. JavAdaptor combines schema changing class replacements by class renaming and caller updates with Java HotSwap using containers and proxies. It runs on top of all major standard Java virtual machines. We evaluate our approach's applicability and performance in non‐trivial case studies and compare it with existing dynamic software update approaches. Copyright © 2012 John Wiley & Sons, Ltd.