Giant Electroresistance in Edge Metal-Insulator-Metal Tunnel Junctions Induced by Ferroelectric Fringe Fields

An enormous amount of research activities has been devoted to developing new types of non-volatile memory devices as the potential replacements of current flash memory devices. Theoretical device modeling was performed to demonstrate that a huge change of tunnel resistance in an Edge Metal-Insulator-Metal (EMIM) junction of metal crossbar structure can be induced by the modulation of electric fringe field, associated with the polarization reversal of an underlying ferroelectric layer. It is demonstrated that single three-terminal EMIM/Ferroelectric structure could form an active memory cell without any additional selection devices. This new structure can open up a way of fabricating all-thin-film-based, high-density, high-speed, and low-power non-volatile memory devices that are stackable to realize 3D memory architectureope

Fabrication of Coaxial Si1−xGex Heterostructure Nanowires by O2 Flow-Induced Bifurcate Reactions

We report on bifurcate reactions on the surface of well-aligned Si1−xGex nanowires that enable fabrication of two different coaxial heterostructure nanowires. The Si1−xGex nanowires were grown in a chemical vapor transport process using SiCl4 gas and Ge powder as a source. After the growth of nanowires, SiCl4 flow was terminated while O2 gas flow was introduced under vacuum. On the surface of nanowires was deposited Ge by the vapor from the Ge powder or oxidized into SiO2 by the O2 gas. The transition from deposition to oxidation occurred abruptly at 2 torr of O2 pressure without any intermediate region and enables selectively fabricated Ge/Si1−xGex or SiO2/Si1−xGex coaxial heterostructure nanowires. The rate of deposition and oxidation was dominated by interfacial reaction and diffusion of oxygen through the oxide layer, respectively

Prognostic value of simple frailty and malnutrition screening tools in patients with acute heart failure due to left ventricular systolic dysfunction

Background: Frailty and malnutrition are common in patients with heart failure (HF), and are associated with adverse outcomes. We studied the prognostic value of three malnutrition and three frailty indices in patients admitted acutely to hospital with HF. Methods: 265 consecutive patients [62% males, median age 80 (interquartile range (IQR): 72–86) years, median NTproBNP 3633 (IQR: 2025–6407) ng/l] admitted with HF between 2013 and 2014 were enrolled. Patients were screened for frailty using the Derby frailty index (DFI), acute frailty network (AFN) frailty criteria, and clinical frailty scale (CFS) and for malnutrition using the geriatric nutritional risk index (GNRI), controlling nutritional status (CONUT) score and prognostic nutritional index (PNI). Results: According to the CFS (> 4), DFI, and AFN, 53, 50, and 53% were frail, respectively. According to the GNRI (≤ 98), CONUT score (> 4), and PNI (≤ 38), 46, 46, and 42% patients were malnourished, respectively. During a median follow-up of 598 days (IQR 319–807 days), 113 patients died. One year mortality was 1% for those who were neither frail nor malnourished; 15% for those who were either malnourished or frail; and 65% for those who were both malnourished and frail. Amongst the malnutrition scores, PNI, and amongst the frailty scores, CFS increased model performance most compared with base model. A final model, including CFS and PNI, increased c-statistic for mortality prediction from 0.68 to 0.84. Conclusion: Worsening frailty and malnutrition indices are strongly related to worse outcome in patients hospitalised with HF

Neighbourhood Reduction in Global and Combinatorial Optimization: The Case of the p-Centre Problem

Neighbourhood reductions for a class of location problems known as the vertex (or discrete) and planar (or continuous) p-centre problems are presented. A brief review of these two forms of the p-centre problem is first provided followed by those respective reduction schemes that have shown to be promising. These reduction schemes have the power of transforming optimal or near optimal methods such as metaheuristics or relaxation-based procedures, which were considered relatively slow, into efficient and exciting ones that are now able to find optimal solutions or tight lower/upper bounds for larger instances. Research highlights of neighbourhood reduction for global and combinatorial optimisation problems in general and for related location problems in particular are also given

Icariin and its Derivative Icariside II Extend Healthspan via Insulin/IGF-1 Pathway in C. elegans

Compounds that delay aging might also postpone age-related diseases and extend healthspan in humans. Icariin is a flavonol extracted from several plant species of the Epimedium family. The icariin and its metabolic derivatives have been shown to exert wide protective effects in age-related diseases. However, whether icariin and its derivatives have the potency of delaying aging remains unclear. Here, we report that icariin and its derivative icariside II extend C. elegans lifespan. Using HPLC, we found high level of icariside II in the animals treated with icariin, suggesting icariside II is the bioactive form in vivo of icariin. Icariside II also increased the thermo and oxidative stress tolerance, slowed locomotion decline in late adulthood and delayed the onset of paralysis mediated by polyQ and Aβ1–42 proteotoxicity. The lifespan extension effect of icariside II is dependent on the insulin/IGF-1 signaling (IIS) since the daf-16(mu86) and daf-2(e1370) failed to show any lifespan extension upon icariside II treatment. Consistently, icariside II treatment upregulates the expression of DAF-16 targets in the wild-type. Moreover, our data suggests that the heat shock transcription factor HSF-1 has a role in icariside II-dependent lifespan extension further implicating the IIS pathway. In conclusion, we demonstrate a novel natural compound, icariside II as the bioactive form of icariin, extends the healthspan via IIS pathway in C. elegans

Structural Analysis of the UBA Domain of X-linked Inhibitor of Apoptosis Protein Reveals Different Surfaces for Ubiquitin-Binding and Self-Association

BACKGROUND: Inhibitor of apoptosis proteins (IAPs) belong to a pivotal antiapoptotic protein family that plays a crucial role in tumorigenesis, cancer progression, chemoresistance and poor patient-survival. X-linked inhibitor of apoptosis protein (XIAP) is a prominent member of IAPs attracting intense research because it has been demonstrated to be a physiological inhibitor of caspases and apoptosis. Recently, an evolutionarily conserved ubiquitin-associated (UBA) domain was identified in XIAP and a number of RING domain-bearing IAPs. This has placed the IAPs in the group of ubiquitin binding proteins. Here, we explore the three-dimensional structure of the XIAP UBA domain (XIAP-UBA) and how it interacts with mono-ubiquitin and diubiquitin conjugates. PRINCIPAL FINDINGS: The solution structure of the XIAP-UBA domain was determined by NMR spectroscopy. XIAP-UBA adopts a typical UBA domain fold of three tightly packed alpha-helices but with an additional N-terminal 3(10) helix. The XIAP-UBA binds mono-ubiquitin as well as Lys48-linked and linear-linked diubiquitins at low-micromolar affinities. NMR analysis of the XIAP-UBA-ubiquitin interaction reveals that it involves the classical hydrophobic patches surrounding Ile44 of ubiquitin and the conserved MGF/LV motif surfaces on XIAP-UBA. Furthermore, dimerization of XIAP-UBA was observed. Mapping of the self-association surface of XIAP-UBA reveals that the dimerization interface is formed by residues in the N-terminal 3(10) helix, helix alpha1 and helix alpha2, separate from the ubiquitin-binding surface. CONCLUSION: Our results provide the first structural information of XIAP-UBA and map its interaction with mono-ubiquitin, Lys48-linked and linear-linked diubiquitins. The notion that XIAP-UBA uses different surfaces for ubiquitin-binding and self-association provides a plausible model to explain the reported selectivity of XIAP in binding polyubiquitin chains with different linkages.published_or_final_versio

Diversity, Phylogeny and Expression Patterns of Pou and Six Homeodomain Transcription Factors in Hydrozoan Jellyfish Craspedacusta sowerbyi

Formation of all metazoan bodies is controlled by a group of selector genes including homeobox genes, highly conserved across the entire animal kingdom. The homeobox genes from Pou and Six classes are key members of the regulation cascades determining development of sensory organs, nervous system, gonads and muscles. Besides using common bilaterian models, more attention has recently been targeted at the identification and characterization of these genes within the basal metazoan phyla. Cnidaria as a diploblastic sister group to bilateria with simple and yet specialized organs are suitable models for studies on the sensory organ origin and the associated role of homeobox genes. In this work, Pou and Six homeobox genes, together with a broad range of other sensory-specific transcription factors, were identified in the transcriptome of hydrozoan jellyfish Craspedacusta sowerbyi. Phylogenetic analyses of Pou and Six proteins revealed cnidarian-specific sequence motifs and contributed to the classification of individual factors. The majority of the Craspedacusta sowerbyi Pou and Six homeobox genes are predominantly expressed in statocysts, manubrium and nerve ring, the tissues with sensory and nervous activities. The described diversity and expression patterns of Pou and Six factors in hydrozoan jellyfish highlight their evolutionarily conserved functions. This study extends the knowledge of the cnidarian genome complexity and shows that the transcriptome of hydrozoan jellyfish is generally rich in homeodomain transcription factors employed in the regulation of sensory and nervous functions

Composition and Function of Haemolymphatic Tissues in the European Common Shrew

BACKGROUND: Studies of wild animals responding to their native parasites are essential if we are to understand how the immune system functions in the natural environment. While immune defence may bring increased survival, this may come at a resource cost to other physiological traits, including reproduction. Here, we tested the hypothesis that wild common shrews (Sorex araneus), which produce large numbers of offspring during the one breeding season of their short life span, forgo investment in immunity and immune system maintenance, as increased longevity is unlikely to bring further opportunities for mating. In particular, we predicted that adult shrews, with shorter expected lifespans, would not respond as effectively as young animals to infection. METHODOLOGY/PRINCIPAL FINDINGS: We examined haemolymphatic tissues from wild-caught common shrews using light and transmission electron microscopy, applied in conjunction with immunohistology. We compared composition and function of these tissues in shrews of different ages, and the extent and type of inflammatory reactions observed in response to natural parasitic infections. All ages seemed able to mount systemic, specific immune responses, but adult shrews showed some signs of lymphatic tissue exhaustion: lymphatic follicles in adults (n = 21) were both smaller than those in sub-adults (n = 18; Wald = 11.1, p<0.05) and exhibited greater levels of depletion (Wald = 13.3, p<0.05). CONCLUSIONS/SIGNIFICANCE: Contrary to our expectations, shrews respond effectively to their natural parasites, and show little indication of immunosenescence as adults. The pancreas of Aselli, a unique lymphoid organ, may aid in providing efficient immune responses through the storage of large numbers of plasma cells. This may allow older animals to react effectively to previously encountered parasites, but infection by novel agents, and eventual depletion of plasma cell reserves, could both still be factors in the near-synchronous mortality of adult shrews observed shortly after breeding