Focused-ion-beam milling based nanostencil mask fabrication for spin transfer torque studies

Focused-ion-beam milling is used to fabricate nanostencil masks suitable for the fabrication of magnetic nanostructures relevant for spin transfer torque studies. Nanostencil masks are used to define the device dimensions prior to the growth of the thin film stack. They consist of a wet etch resistant top layer and an insulator on top of a pre-patterned bottom electrode. The insulator supports a hard mask and gives rise to an undercut by its selective etching. The approach is demonstrated by fabricating current perpendicular to the plane Co/Cu/Co nanopillar junctions, which exhibit current-induced magnetization dynamics.Comment: 13 pages, 3 figures, submitted to AP

Strongyloides stercoralis in Swiss dogs – a retrospective study suggests an increasing occurrence of this potentially zoonotic parasite as a consequence of dog imports

Strongyloides stercoralis is a worldwide occurring nematode infecting canids and primates (including humans), responsible for a largely underestimated zoonotic disease. We here present 18 cases including overall 20 dogs affected by S. stercoralis, diagnosed in Switzerland between 2010 and 2020. The Baermann examination was positive for S. stercoralis larvae in 10, suspicious in 4, negative in one and not performed in 2 dogs. In 3 dogs the infection was identified only at necropsy by histology or by direct faecal or mucosal smears from intestinal tissue. Confirmation of suspected, necropsied and Baermann-negative dogs relied on genetic analyses. Twelve dogs had a history of import from Eastern Europe (n=4), the Mediterranean basin (n=5) or Germany (n=3). They were 7 weeks to 9,5 months old, and also the dogs supposedly born in Switzerland were younger than one year (except two, aged 15 months and 14 years). Thirteen dogs were males and 6 females (1 unknown). The most represented breeds were Chihuahuas (n=5), French Bulldogs (n=4) and Pomeranians (n=3). The most frequent clinical sign and reason for presentation was diarrhoea, occurring in 11/20 animals. Further gastrointestinal symptoms were vomiting, anorexia/hyporexia, adipsia, dehydration, tense abdomen and tenesmus. Respiratory symptoms were the second most frequent, with coughing in 7/20 animals, followed by tachypnoea/dyspnoea in 5 and (reverse) sneezing in 3 dogs. Treatment with 50 mg/kg BW fenbendazole p.o. over 5 days was successful in 4 cases in which a follow-up examination was performed 3–6 weeks later; prolonged treatment over 21 days was also effective. Ivermectin off-label protocols described in the literature, e.g. 0,8 mg/kg BW s.c. or 0,5 mg/kg BW i.m. repeated after 2 weeks, were successful based on control examinations performed 3–10 weeks later. Strongyloides stercoralis infections are clinically relevant, potentially zoonotic and need to be included in differential diagnoses in case of canine gastrointestinal and respiratory disorders, especially in young and imported dogs

Perpendicular exchange bias in antiferromagnetic-ferromagnetic nanostructures

This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics.Exchange bias effects have been induced along the perpendicular-to-film direction in nanostructures prepared by electron beamlithography, consisting of a ferromagnetic [Pt/Co] multilayer exchange coupled to an antiferromagnet (FeMn). As a general trend, the exchange bias field and the blocking temperature decrease, whereas the coercivity increases, as the size of the nanostructures is reduced

PITX1 is a regulator of TERT expression in prostate cancer with prognostic power

Simple Summary Most prostate cancer is of an indolent form and is curable. However, some prostate cancer belongs to rather aggressive subtypes leading to metastasis and death, and immediate therapy is mandatory. However, for these, the therapeutic options are highly invasive, such as radical prostatectomy, radiation or brachytherapy. Hence, a precise diagnosis of these tumor subtypes is needed, and the thus far applied diagnostic means are insufficient for this. Besides this, for their endless cell divisions, prostate cancer cells need the enzyme telomerase to elongate their telomeres (chromatin endings). In this study, we developed a gene regulatory model based on large data from transcription profiles from prostate cancer and chromatin-immuno-precipitation studies. We identified the developmental regulator PITX1 regulating telomerase. Besides observing experimental evidence of PITX1′s functional role in telomerase regulation, we also found PITX1 serving as a prognostic marker, as concluded from an analysis of more than 15,000 prostate cancer samples. Abstract The current risk stratification in prostate cancer (PCa) is frequently insufficient to adequately predict disease development and outcome. One hallmark of cancer is telomere maintenance. For telomere maintenance, PCa cells exclusively employ telomerase, making it essential for this cancer entity. However, TERT, the catalytic protein component of the reverse transcriptase telomerase, itself does not suit as a prognostic marker for prostate cancer as it is rather low expressed. We investigated if, instead of TERT , transcription factors regulating TERT may suit as prognostic markers. To identify transcription factors regulating TERT , we developed and applied a new gene regulatory modeling strategy to a comprehensive transcriptome dataset of 445 primary PCa. Six transcription factors were predicted as TERT regulators, and most prominently, the developmental morphogenic factor PITX1. PITX1 expression positively correlated with telomere staining intensity in PCa tumor samples. Functional assays and chromatin immune-precipitation showed that PITX1 activates TERT expression in PCa cells. Clinically, we observed that PITX1 is an excellent prognostic marker, as concluded from an analysis of more than 15,000 PCa samples. PITX1 expression in tumor samples associated with (i) increased Ki67 expression indicating increased tumor growth, (ii) a worse prognosis, and (iii) correlated with telomere length

The Role of DNA Methylation in Genome Defense in Cnidaria and Other Invertebrates

Considerable attention has recently been focused on the potential involvement of DNA methylation in regulating gene expression in cnidarians. Much of this work has been centered on corals, in the context of changes in methylation perhaps facilitating adaptation to higher seawater temperatures and other stressful conditions. Although first proposed more than 30 years ago, the possibility that DNA methylation systems function in protecting animal genomes against the harmful effects of transposon activity has largely been ignored since that time. Here, we show that transposons are specifically targeted by the DNA methylation system in cnidarians, and that the youngest transposons (i.e., those most likely to be active) are most highly methylated. Transposons in longer and highly active genes were preferentially methylated and, as transposons aged, methylation levels declined, reducing the potentially harmful side effects of CpG methylation. In Cnidaria and a range of other invertebrates, correlation between the overall extent of methylation and transposon content was strongly supported. Present transposon burden is the dominant factor in determining overall level of genomic methylation in a range of animals that diverged in or before the early Cambrian, suggesting that genome defense represents the ancestral role of CpG methylation

Novel HBsAg markers tightly correlate with occult HBV infection and strongly affect HBsAg detection.

Occult HBV infection (OBI) is a threat for the safety of blood-supply, and has been associated with the onset of HBV-related hepatocellular carcinoma and lymphomagenesis. Nevertheless, genetic markers in HBsAg (particularly in D-genotype, the most common in Europe) significantly associated with OBI in vivo are missing. Thus, the goal of this study is to define: (i) prevalence and clinical profile of OBI among blood-donors; (ii) HBsAg-mutations associated with OBI; (iii) their impact on HBsAg-detection. OBI was searched among 422,278 blood-donors screened by Nucleic-Acid-Testing. Following Taormina-OBI-definition, 26 (0.006%) OBI-patients were identified. Despite viremia <50IU/ml, HBsAg-sequences were obtained for 25/26 patients (24/25 genotype-D). OBI-associated mutations were identified by comparing OBI-HBsAg with that of 82 chronically-infected (genotype-D) patients as control. Twenty HBsAg-mutations significantly correlated for the first time with OBI. By structural analysis, they localized in the major HBV B-cell-epitope, and in HBsAg-capsid interaction region. 14/24 OBI-patients (58.8%) carried in median 3 such mutations (IQR:2.0-6.0) against 0 in chronically-infected patients. By co-variation analysis, correlations were observed for R122P+S167L (phi=0.68, P=0.01), T116N+S143L (phi=0.53, P=0.03), and Y100S+S143L (phi=0.67, p<0.001). Mutants (obtained by site-directed mutagenesis) carrying T116N, T116N+S143L, R122P, R122P+Q101R, or R122P+S167L strongly decreased HBsAg-reactivity (54.9±22.6S/CO, 31.2±12.0S/CO, 6.1±2.4S/CO, 3.0±1.0S/CO and 3.9±1.3S/CO, respectively) compared to wild-type (306.8±64.1S/CO). Even more, Y100S and Y100S+S143L supernatants show no detectable-HBsAg (experiments in quadruplicate). In conclusions, unique HBsAg-mutations in genotype-D, different than those described in genotypes B/C (rarely found in western countries), tightly correlate with OBI, and strongly affect HBsAg-detection. By altering HBV-antigenicity and/or viral-particle maturation, they may affect full-reliability of universal diagnostic-assays for HBsAg-detection

Anti-HBV treatment induces novel reverse transcriptase mutations with reflective effect on HBV S antigen

The identification of novel reverse-transcriptase (RT) drug-resistance mutations is critical in predicting the probability of success to anti-HBV treatment. Furthermore, due to HBV-RT/HBsAg gene-overlap, they can have an impact on HBsAg-detection and quantification

Low-frequency noise and tunnelling magnetoresistance in Fe(110)/MgO(111)/Fe(110) epitaxial magnetic tunnel junctions

We report on tunnelling magnetoresistance (TMR), current-voltage (IV) characteristics and low frequency noise in epitaxially grown Fe(110)/MgO(111)/Fe(110) magnetic tunnel junctions (MTJs) with dimensions from 2x2 to 20x20 um2. The evaluated MgO energy barrier (0.50+/-0.08 eV), the barrier width (13.1+/-0.5 angstrom) as well as the resistance times area product (7+/-1 Mohmsum2) show relatively small variation, confirming a high quality epitaxy and uniformity of all MTJs studied. The noise power, though exhibiting large variation, was observed to be roughly anticorrelated with the TMR. Surprisingly, for the largest junctions we observed a strong enhancement of the normalized low-frequency noise in the antiparallel magnetic configuration. This behaviour could be related to an interplay between the magnetic state and the local barrier defects structure of the epitaxial MTJsComment: 9 pages and 3 figure

Friction stir welding Ti-al alloys with ultrasonic impact

High performance and reduced weight and cost are gaining importance in the aviation industry. There are different approaches to meet these requirements. In this study, titanium and aluminum alloys were welded using friction stir welding. The samples were divided into two groups, one of which was welded using ultrasound. Studies have shown that the strength of samples is influenced by many factors that are usually not taken into account. For example, the complexity of the interface between dissimilar materials and its roughness. It was found that the application of ultrasound during welding often increases the complexity of the interface and decreases its roughness, which generally leads to strengthening. This effect can neutralize the increase in the volume fraction of intermetallic compounds during the intensification of the welding process. The final strength consists of the number of defects, the volume fraction of intermetallics and the complexity of the interface

C14ORF39/SIX6OS1 is a constituent of the synaptonemal complex and is essential for mouse fertility

Meiotic recombination generates crossovers between homologous chromosomes that are essential for genome haploidization. The synaptonemal complex is a ‘zipper’-like protein assembly that synapses homologue pairs together and provides the structural framework for processing recombination sites into crossovers. Humans show individual differences in the number of crossovers generated across the genome. Recently, an anonymous gene variant in C14ORF39/SIX6OS1 was identified that influences the recombination rate in humans. Here we show that C14ORF39/SIX6OS1 encodes a component of the central element of the synaptonemal complex. Yeast two-hybrid analysis reveals that SIX6OS1 interacts with the well-established protein synaptonemal complex central element 1 (SYCE1). Mice lacking SIX6OS1 are defective in chromosome synapsis at meiotic prophase I, which provokes an arrest at the pachytene-like stage and results in infertility. In accordance with its role as a modifier of the human recombination rate, SIX6OS1 is essential for the appropriate processing of intermediate recombination nodules before crossover formation.This work was supported by BFU_2014-59307-R, MEIONet and JCyLe (CSI052U16). LGH and NFM are supported by European Social Fund/JCyLe grants (EDU/1083/2013 and EDU/310/2015). ORD is a Sir Henry Dale Fellow jointly funded by the Wellcome Trust and Royal Society (Grant Number 104158/Z/14/Z). RB is funded by DFG (grant Be1168/8-1). AT and ID were supported by DFG grants TO421/8-2 and TO421/6-1, respectively.Peer reviewe