Geometric conductive filament confinement by nanotips for resistive switching of HfO2-RRAM devices with high performance

Filament-type HfO2-based RRAM has been considered as one of the most promising candidates for future non-volatile memories. Further improvement of the stability, particularly at the "OFF" state, of such devices is mainly hindered by resistance variation induced by the uncontrolled oxygen vacancies distribution and filament growth in HfO2 films. We report highly stable endurance of TiN/Ti/HfO2/Si-tip RRAM devices using a CMOS compatible nanotip method. Simulations indicate that the nanotip bottom electrode provides a local confinement for the electrical field and ionic current density; thus a nano-confinement for the oxygen vacancy distribution and nano-filament location is created by this approach. Conductive atomic force microscopy measurements confirm that the filaments form only on the nanotip region. Resistance switching by using pulses shows highly stable endurance for both ON and OFF modes, thanks to the geometric confinement of the conductive path and filament only above the nanotip. This nano-engineering approach opens a new pathway to realize forming-free RRAM devices with improved stability and reliability

Cardiac Implantable Electronic Device-Related Infection Due to Granulicatella adiacens.

Cardiac implantable electronic device-related infection is clinically challenging. Curative treatment commonly includes system removal. A case caused by Granulicatella adiacens occurred in a 32-year-old woman. Clinical course, literature review, and biofilm investigations enabled successful antibiotic management without system removal

Swiss Adult Congenital HEart disease Registry (SACHER) - rationale, design and first results.

In 2013, a prospective registry for adults with congenital heart disease (CHD) was established in Switzerland, providing detailed data on disease characteristics and outcomes: Swiss Adult Congenital HEart disease Registry (SACHER). Its aim is to improve the knowledge base of outcomes in adults with CHD. The registry design and baseline patient characteristics are reported. All patients with structural congenital heart defects or hereditary aortopathies, followed-up at dedicated adult CHD clinics, are asked to participate in SACHER. Data of participants are pseudonymised and collected in an electronic, web-based, database (secuTrial®). Collected data include detailed diagnosis, type of repair procedures, previous complications and adverse outcomes during follow-up. From May 2014 to December 2016, 2836 patients (54% male, mean age 34 ± 14 years), with a wide variety of congenital heart lesions, have been enrolled into SACHER. Most prevalent were valve lesions (25%), followed by shunt lesions (22%), cyanotic and other complex congenital heart disease (16%), diseases affecting the right heart, i.e., tetralogy of Fallot or Ebstein anomaly (15%), and diseases of the left ventricular outflow tract (13%); 337 patients (12%) had concomitant congenital syndromes. The majority had undergone previous repair procedures (71%), 47% of those had one or more reinterventions. SACHER collects multicentre data on adults with CHD. Its structure enables prospective data analysis to assess detailed, lesion-specific outcomes with the aim to finally improve long-term outcomes

Hepatic stellate cells suppress NK cell-sustained breast cancer dormancy

The persistence of undetectable disseminated tumour cells (DTCs) after primary tumour resection poses a major challenge to effective cancer treatment; 1-3; . These enduring dormant DTCs are seeds of future metastases, and the mechanisms that switch them from dormancy to outgrowth require definition. Because cancer dormancy provides a unique therapeutic window for preventing metastatic disease, a comprehensive understanding of the distribution, composition and dynamics of reservoirs of dormant DTCs is imperative. Here we show that different tissue-specific microenvironments restrain or allow the progression of breast cancer in the liver-a frequent site of metastasis; 4; that is often associated with a poor prognosis; 5; . Using mouse models, we show that there is a selective increase in natural killer (NK) cells in the dormant milieu. Adjuvant interleukin-15-based immunotherapy ensures an abundant pool of NK cells that sustains dormancy through interferon-γ signalling, thereby preventing hepatic metastases and prolonging survival. Exit from dormancy follows a marked contraction of the NK cell compartment and the concurrent accumulation of activated hepatic stellate cells (aHSCs). Our proteomics studies on liver co-cultures implicate the aHSC-secreted chemokine CXCL12 in the induction of NK cell quiescence through its cognate receptor CXCR4. CXCL12 expression and aHSC abundance are closely correlated in patients with liver metastases. Our data identify the interplay between NK cells and aHSCs as a master switch of cancer dormancy, and suggest that therapies aimed at normalizing the NK cell pool might succeed in preventing metastatic outgrowth

CP-31398, a putative p53-stabilizing molecule tested in mammalian cells and in yeast for its effects on p53 transcriptional activity

BACKGROUND: CP-31398 is a small molecule that has been reported to stabilize the DNA-binding core domain of the human tumor suppressor protein p53 in vitro. The compound was also reported to function as a potential anti-cancer drug by rescuing the DNA-binding activity and, consequently, the transcription activation function of mutant p53 protein in mammalian tissue culture cells and in mice. RESULTS: We performed a series of gene expression experiments to test the activity of CP-31398 in yeast and in human cell cultures. With these cell-based assays, we were unable to detect any specific stimulation of mutant p53 activity by this compound. Concentrations of CP-31398 that were reported to be active in the published work were highly toxic to the human H1299 lung carcinoma and Saos-2 cell lines in our experiments. CONCLUSION: In our experiments, the small molecule CP-31398 was unable to reactivate mutant p53 protein. The results of our in vivo experiments are in agreement with the recently published biochemical analysis of CP-31398 showing that this molecule does not bind p53 as previously claimed, but intercalates into DNA

Comprehensive analysis of the base composition around the transcription start site in Metazoa

BACKGROUND: The transcription start site of a metazoan gene remains poorly understood, mostly because there is no clear signal present in all genes. Now that several sequenced metazoan genomes have been annotated, we have been able to compare the base composition around the transcription start site for all annotated genes across multiple genomes. RESULTS: The most prominent feature in the base compositions is a significant local variation in G+C content over a large region around the transcription start site. The change is present in all animal phyla but the extent of variation is different between distinct classes of vertebrates, and the shape of the variation is completely different between vertebrates and arthropods. Furthermore, the height of the variation correlates with CpG frequencies in vertebrates but not in invertebrates and it also correlates with gene expression, especially in mammals. We also detect GC and AT skews in all clades (where %G is not equal to %C or %A is not equal to %T respectively) but these occur in a more confined region around the transcription start site and in the coding region. CONCLUSIONS: The dramatic changes in nucleotide composition in humans are a consequence of CpG nucleotide frequencies and of gene expression, the changes in Fugu could point to primordial CpG islands, and the changes in the fly are of a totally different kind and unrelated to dinucleotide frequencies

Chronic Intranasal Treatment with an Anti-Aβ30-42 scFv Antibody Ameliorates Amyloid Pathology in a Transgenic Mouse Model of Alzheimer's Disease

Amyloid-beta peptide (Aβ)-directed active and passive immunization therapeutic strategies reduce brain levels of Aβ, decrease the severity of beta-amyloid plaque pathology and reverse cognitive deficits in mouse models of Alzheimer's disease (AD). As an alternative approach to passive immunization with full IgG molecules, single-chain variable fragment (scFv) antibodies can modulate or neutralize Aβ-related neurotoxicity and inhibit its aggregation in vitro. In this study, we characterized a scFv derived from a full IgG antibody raised against the C-terminus of Aβ, and studied its passage into the brains of APP transgenic mice, as well as its potential to reduce Aβ-related pathology. We found that the scFv entered the brain after intranasal application, and that it bound to beta-amyloid plaques in the cortex and hippocampus of APP transgenic mice. Moreover, the scFv inhibited Aβ fibril formation and Aβ-mediated neurotoxicity in vitro. In a preventative therapeutic approach chronic intranasal treatment with scFv reduced congophilic amyloid angiopathy (CAA) and beta-amyloid plaque numbers in the cortex of APPswe/PS1dE9 mice. This reduction of CAA and plaque pathology was associated with a redistribution of brain Aβ from the insoluble fraction to the soluble peptide pool. Due to their lack of the effector domain of full IgG, scFv may represent an alternative tool for the treatment of Aβ-related pathology without triggering Fc-mediated effector functions. Additionally, our observations support the possibility that Aβ-directed immunotherapy can reduce Aβ deposition in brain vessels in transgenic mice

Theory and simulation of quantum photovoltaic devices based on the non-equilibrium Green's function formalism

This article reviews the application of the non-equilibrium Green's function formalism to the simulation of novel photovoltaic devices utilizing quantum confinement effects in low dimensional absorber structures. It covers well-known aspects of the fundamental NEGF theory for a system of interacting electrons, photons and phonons with relevance for the simulation of optoelectronic devices and introduces at the same time new approaches to the theoretical description of the elementary processes of photovoltaic device operation, such as photogeneration via coherent excitonic absorption, phonon-mediated indirect optical transitions or non-radiative recombination via defect states. While the description of the theoretical framework is kept as general as possible, two specific prototypical quantum photovoltaic devices, a single quantum well photodiode and a silicon-oxide based superlattice absorber, are used to illustrated the kind of unique insight that numerical simulations based on the theory are able to provide.Comment: 20 pages, 10 figures; invited review pape