Supercurrent in Nb/InAs-Nanowire/Nb Josephson junctions

We report on the fabrication and measurements of planar mesoscopic Josephson junctions formed by InAs nanowires coupled to superconducting Nb terminals. The use of Si-doped InAs-nanowires with different bulk carrier concentrations allowed to tune the properties of the junctions. We have studied the junction characteristics as a function of temperature, gate voltage, and magnetic field. In junctions with high doping concentrations in the nanowire Josephson supercurrent values up to 100\,nA are found. Owing to the use of Nb as superconductor the Josephson coupling persists at temperatures up to 4K. In all junctions the critical current monotonously decreased with the magnetic field, which can be explained by a recently developed theoretical model for the proximity effect in ultra-small Josephson junctions. For the low-doped Josephson junctions a control of the critical current by varying the gate voltage has been demonstrated. We have studied conductance fluctuations in nanowires coupled to superconducting and normal metal terminals. The conductance fluctuation amplitude is found to be about 6 times larger in superconducting contacted nanowires. The enhancement of the conductance fluctuations is attributed to phase-coherent Andreev reflection as well as to the large number of phase-coherent channels due to the large superconducting gap of the Nb electrodes.Comment: 5 Figure, submitted to Journal of Applied Physic

ACOX2 deficiency: A disorder of bile acid synthesis with transaminase elevation, liver fibrosis, ataxia, and cognitive impairment

Acyl CoA Oxidase 2 (ACOX2) encodes branched-chain acyl-CoA oxidase, a peroxisomal enzyme believed to be involved in the metabolism of branched-chain fatty acids and bile acid intermediates. Deficiency of this enzyme has not been described previously. We report an 8-y-old male with intermittently elevated transaminase levels, liver fibrosis, mild ataxia, and cognitive impairment. Exome sequencing revealed a previously unidentified homozygous premature termination mutation (p.Y69*) in ACOX2 Immunohistochemistry confirmed the absence of ACOX2 expression in the patient's liver, and biochemical analysis showed marked elevation of intermediate bile acids upstream of ACOX2. These findings define a potentially treatable inborn error of bile acid biosynthesis caused by ACOX2 deficiency

Exome Sequencing Implicates Impaired GABA Signaling and Neuronal Ion Transport in Trigeminal Neuralgia

Trigeminal neuralgia (TN) is a common, debilitating neuropathic face pain syndrome often resistant to therapy. The familial clustering of TN cases suggests that genetic factors play a role in disease pathogenesis. However, no unbiased, large-scale genomic study of TN has been performed to date. Analysis of 290 whole exome-sequenced TN probands, including 20 multiplex kindreds and 70 parent-offspring trios, revealed enrichment of rare, damaging variants in GABA receptor-binding genes in cases. Mice engineered with a TN-associated de novo mutation (p.Cys188Trp) in the GABAA receptor Cl− channel γ-1 subunit (GABRG1) exhibited trigeminal mechanical allodynia and face pain behavior. Other TN probands harbored rare damaging variants in Na+ and Ca+ channels, including a significant variant burden in the α-1H subunit of the voltage-gated Ca2+ channel Cav3.2 (CACNA1H). These results provide exome-level insight into TN and implicate genetically encoded impairment of GABA signaling and neuronal ion transport in TN pathogenesis

Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas

RNA polymerase II mediates the transcription of all protein-coding genes in eukaryotic cells, a process that is fundamental to life. Genomic mutations altering this enzyme have not previously been linked to any pathology in humans, which is a testament to its indispensable role in cell biology. On the basis of a combination of next-generation genomic analyses of 775 meningiomas, we report that recurrent somatic p.Gln403Lys or p.Leu438_His439del mutations in POLR2A, which encodes the catalytic subunit of RNA polymerase II (ref. 1), hijack this essential enzyme and drive neoplasia. POLR2A mutant tumors show dysregulation of key meningeal identity genes including WNT6 and ZIC1/ZIC4. In addition to mutations in POLR2A, NF2, SMARCB1, TRAF7, KLF4, AKT1, PIK3CA, and SMO4 we also report somatic mutations in AKT3, PIK3R1, PRKAR1A, and SUFU in meningiomas. Our results identify a role for essential transcriptional machinery in driving tumorigenesis and define mutually exclusive meningioma subgroups with distinct clinical and pathological features

Exome sequencing implicates genetic disruption of prenatal neuro-gliogenesis in sporadic congenital hydrocephalus

Congenital hydrocephalus (CH), characterized by enlarged brain ventricles, is considered a disease of excessive cerebrospinal fluid (CSF) accumulation and thereby treated with neurosurgical CSF diversion with high morbidity and failure rates. The poor neurodevelopmental outcomes and persistence of ventriculomegaly in some post-surgical patients highlight our limited knowledge of disease mechanisms. Through whole-exome sequencing of 381 patients (232 trios) with sporadic, neurosurgically treated CH, we found that damaging de novo mutations account for >17% of cases, with five different genes exhibiting a significant de novo mutation burden. In all, rare, damaging mutations with large effect contributed to ~22% of sporadic CH cases. Multiple CH genes are key regulators of neural stem cell biology and converge in human transcriptional networks and cell types pertinent for fetal neuro-gliogenesis. These data implicate genetic disruption of early brain development, not impaired CSF dynamics, as the primary pathomechanism of a significant number of patients with sporadic CH

Notes on L-fuzzy ?-open sets

The aim of this paper is to present a common approach allowing to obtain families of L-fuzzy sets in an L-topological space of Goguen type generalizing the class of all open L-fuzzy sets. In particular, we study the notion of an L-fuzzy ?-open set where ? is a monotone operator on the family of all L-fuzzy subsets of an L-topological space X and discuss some properties of L-fuzzy ?-open sets

Performance of closed-form acoustic scene decomposition for forensic analysis

In-situ audio recordings for forensic analysis are generally made using purpose-installed microphones in order to capture speech and other relevant sounds in an environment. Often, post-processing efforts are focused on cleaning these recordings from interference. An acoustic scene is made up of audio objects and their not only contents, but also positions carry evidential importance. Therefore, in addition to cleaning target sources, detecting their locations may be required. This paper focuses on the performance of a closed-form acoustic scene decomposition technique, which blindly decomposes the sound field using signals obtained from a coincident microphone array. This decomposition both localises the audio objects and enhances them, thereby improving the intelligibility of speech signals. Detailed testing has been carried out in order to quantify the localisation, separation, speech intelligibility improvement and automatic speech recognition performances of the system. Multiple speech sources in both isotropic and directional fluctuating noise under typical application scenarios have been considered

Performance of closed-form acoustic scene decomposition for forensic analysis

In-situ audio recordings for forensic analysis are generally made using purpose-installed microphones in order to capture speech and other relevant sounds in an environment. Often, post-processing efforts are focused on cleaning these recordings from interference. An acoustic scene is made up of audio objects and their not only contents, but also positions carry evidential importance. Therefore, in addition to cleaning target sources, detecting their locations may be required. This paper focuses on the performance of a closed-form acoustic scene decomposition technique, which blindly decomposes the sound field using signals obtained from a coincident microphone array. This decomposition both localises the audio objects and enhances them, thereby improving the intelligibility of speech signals. Detailed testing has been carried out in order to quantify the localisation, separation, speech intelligibility improvement and automatic speech recognition performances of the system. Multiple speech sources in both isotropic and directional fluctuating noise under typical application scenarios have been considered