Non-equilibrium processing of Ni-Si alloys at high undercooling and high cooling rates

Melt encasement (fluxing) and drop-tube techniques have been used to solidify a Ni-25 at.% Si alloy under conditions of high undercooling and high cooling rates respectively. During undercooling experiments a eutectic structure was observed, comprising alternating lamellae of single phase γ(NiSi) and Ni-rich lamellae containing of a fine (200-400 nm) dispersion of β- NiSi and α-Ni. This is contrary to the equilibrium phase diagram from which direct solidification to β-NiSi would be expected for undercoolings in excess of 53 K. Conversely, during drop-tube experiments a fine (50 nm) lamellar structure comprising alternating lamellae of the metastable phase NiSi and β-NiSi is observed. This is also thought to be the result of primary eutectic solidification. Both observations would be consistent with the formation of the high temperature form of the β-phase (β/β) being suppressed from the melt

Microstructural Evolution and Phase Formation in Rapidly Solidified Ni-25.3 At. Pct Si Alloy

The drop-tube technique was used to solidify droplets of the Ni-25.3 at. pct Si alloy at high cooling rates. XRD, SEM, and TEM analysis revealed that the metastable phase, Ni25Si9, formed as the dominant phase in all ranges of the droplets, with γ-Ni31Si12 and β 1-Ni3Si also being present. Three different microstructures were observed: the regular and anomalous eutectic structures and near single-phase structure containing small inclusions of a second phase, termed here as heteroclite structure. Both eutectic structures comprise alternating lamellae of Ni25Si9 and β 1-Ni3Si, which, we conjecture, is a consequence of an unobserved eutectic reaction between the Ni25Si9 and β 1-Ni3Si phases. The matrix of the heteroclite structure is also identified as the metastable phase Ni25Si9, in which twined growth is observed in the TEM. As the cooling rate is increased (particle size decreased), the proportion of droplets displaying the entire heteroclite structure tends to increase, with its fraction increasing from 13.91 pct (300 to 500 µm) to 40.10 pct (75 to 106 µm). The thermodynamic properties of the Ni25Si9 phase were also studied by in-situ heating during XRD analysis and by DTA. This showed the decomposition of Ni25Si9 to β 1 and γ-Ni31Si12 for temperatures in excess of 790 K (517 °C)

Inositol-requiring 1/X-box-binding protein 1 is a regulatory hub that links endoplasmic reticulum homeostasis with innate immunity and metabolism

Inositol-requiring 1 (IRE1)/X-box-binding protein 1 (XBP1)-mediated signalling represents the most conserved branch of the unfolded protein response. A series of recent studies reveal novel and potentially ancient roles for this pathway in the coordination of metabolic and immune responses.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77427/1/189_ftp.pd

Characterization of a disease-associated mutation affecting a putative splicing regulatory element in intron 6b of the cystic fibrosis transmembrane conductance regulator (CFTR) gene

Cystic fibrosis (CF) is a common recessive disorder caused by >1600 mutations in the CF transmembrane conductance regulator (CFTR) gene. About 13% of CFTR mutations are classified as “splicing mutations,” but for almost 40% of these, their role in affecting the pre-mRNA splicing of the gene is not yet defined. In this work, we describe a new splicing mutation detected in three unrelated Italian CF patients. By DNA analyses and mRNA studies, we identified the c.1002–1110_1113delTAAG mutation localized in intron 6b of the CFTR gene. At the mRNA level, this mutation creates an aberrant inclusion of a sequence of 101 nucleotides between exons 6b and 7. This sequence corresponds to a portion of intron 6b and resembles a cryptic exon because it is characterized by an upstream ag and a downstream gt sequence, which are most probably recognized as 5′- and 3′-splice sites by the spliceosome. Through functional analysis of this splicing defect, we show that this mutation abolishes the interaction of the splicing regulatory protein heterogeneous nuclear ribonucleoprotein A2/B1 with an intronic splicing regulatory element and creates a new recognition motif for the SRp75 splicing factor, causing activation of the cryptic exon. Our results show that the c.1002–1110_1113delTAAG mutation creates a new intronic splicing regulatory element in intron 6b of the CFTR gene exclusively recognized by SRp75

Cytosolic thioredoxin reductase 1 is required for correct disulfide formation in the ER

Folding of proteins entering the secretory pathway in mammalian cells frequently requires the insertion of disulfide bonds. Disulfide insertion can result in covalent linkages found in the native structure as well as those that are not, so‐called non‐native disulfides. The pathways for disulfide formation are well characterized, but our understanding of how non‐native disulfides are reduced so that the correct or native disulfides can form is poor. Here, we use a novel assay to demonstrate that the reduction in non‐native disulfides requires NADPH as the ultimate electron donor, and a robust cytosolic thioredoxin system, driven by thioredoxin reductase 1 (TrxR1 or TXNRD1). Inhibition of this reductive pathway prevents the correct folding and secretion of proteins that are known to form non‐native disulfides during their folding. Hence, we have shown for the first time that mammalian cells have a pathway for transferring reducing equivalents from the cytosol to the ER, which is required to ensure correct disulfide formation in proteins entering the secretory pathway

Detection of pathological high-frequency oscillations in refractory epilepsy patients undergoing simultaneous stereo-electroencephalography and magnetoencephalography

BACKGROUND: Stereo-electroencephalography (SEEG) and magnetoencephalography (MEG) have generally been used independently as part of the pre-surgical evaluation of drug-resistant epilepsy (DRE) patients. However, the possibility of simultaneously employing these recording techniques to determine whether MEG has the potential of offering the same information as SEEG less invasively, or whether it could offer a greater spatial indication of the epileptogenic zone (EZ) to aid surgical planning, has not been previously evaluated. METHODS: Data from 24 paediatric and adult DRE patients, undergoing simultaneous SEEG and MEG as part of their pre-surgical evaluation, was analysed employing manual and automated high-frequency oscillations (HFOs) detection, and spectral and source localisation analyses. RESULTS: Twelve patients (50%) were included in the analysis (4 males; mean age=25.08 years) and showed interictal SEEG and MEG HFOs. HFOs detection was concordant between the two recording modalities, but SEEG displayed higher ability of differentiating between deep and superficial epileptogenic sources. Automated HFO detector in MEG recordings was validated against the manual MEG detection method. Spectral analysis revealed that SEEG and MEG detect distinct epileptic events. The EZ was well correlated with the simultaneously recorded data in 50% patients, while 25% patients displayed poor correlation or discordance. CONCLUSIONS: MEG recordings can detect HFOs, and simultaneous use of SEEG and MEG HFO identification facilitates EZ localisation during the presurgical planning stage for DRE patients. Further studies are necessary to validate these findings and support the translation of automated HFO detectors into routine clinical practice

Lamella structure formation in drop-tube processed Ni-25.3 at.% Si alloy

Rapid solidification experiments have been performed on an Ni-25.3 at.% Si alloy using drop tube techniques. The dominant phase formed is found to be Ni25Si9, with Ni31Si12 and β1-Ni3Si also being present. SEM and TEM analysis revealed a novel eutectic structure consisting of lamellar of metastable Ni25Si9 and β1-Ni3Si, the width of these being around 200 nm and 20 nm respectively. This result indicates that there is a possible eutectic reaction for the Ni25Si9 and β1-Ni3Si phases existing in the metastable phase diagram

Lumbar spinal stenosis: an update on the epidemiology, diagnosis and treatment

Lumbar spinal stenosis (LSS) is a common spinal disorder in the older population, and the clinical syndrome consisting of pain in the buttock or lower extremity, with or without low back pain and corresponding imaging findings of narrowing of spaces around neural and vascular elements in the lumbar spine. The diagnosis depends on history, symptoms, physical examination, radiographies. Varieties of non-operative and operative options are available for LSS patients. In this article, an update on the epidemiology, diagnosis and treatment of LSS was reviewed.published_or_final_versio

Mid-infrared frequency comb spanning an octave based on an Er fiber laser and difference-frequency generation

We describe a coherent mid-infrared continuum source with 700 cm-1 usable bandwidth, readily tuned within 600 - 2500 cm-1 (4 - 17 \mum) and thus covering much of the infrared "fingerprint" molecular vibration region. It is based on nonlinear frequency conversion in GaSe using a compact commercial 100-fs-pulsed Er fiber laser system providing two amplified near-infrared beams, one of them broadened by a nonlinear optical fiber. The resulting collimated mid-infrared continuum beam of 1 mW quasi-cw power represents a coherent infrared frequency comb with zero carrier-envelope phase, containing about 500,000 modes that are exact multiples of the pulse repetition rate of 40 MHz. The beam's diffraction-limited performance enables long-distance spectroscopic probing as well as maximal focusability for classical and ultraresolving near-field microscopies. Applications are foreseen also in studies of transient chemical phenomena even at ultrafast pump-probe scale, and in high-resolution gas spectroscopy for e.g. breath analysis.Comment: 8 pages, 2 figures revised version, added reference