Intermittent dislocation flow in viscoplastic deformation

The viscoplastic deformation (creep) of crystalline materials under constant stress involves the motion of a large number of interacting dislocations. Analytical methods and sophisticated `dislocation-dynamics' simulations have proved very effective in the study of dislocation patterning, and have led to macroscopic constitutive laws of plastic deformation. Yet, a statistical analysis of the dynamics of an assembly of interacting dislocations has not hitherto been performed. Here we report acoustic emission measurements on stressed ice single crystals, the results of which indicate that dislocations move in a scale-free intermittent fashion. This result is confirmed by numerical simulations of a model of interacting dislocations that successfully reproduces the main features of the experiment. We find that dislocations generate a slowly evolving configuration landscape which coexists with rapid collective rearrangements. These rearrangements involve a comparatively small fraction of the dislocations and lead to an intermittent behavior of the net plastic response. This basic dynamical picture appears to be a generic feature in the deformation of many other materials. Moreover, it should provide a framework for discussing fundamental aspects of plasticity, that goes beyond standard mean-field approaches that see plastic deformation as a smooth laminar flow

Crack-Like Processes Governing the Onset of Frictional Slip

We perform real-time measurements of the net contact area between two blocks of like material at the onset of frictional slip. We show that the process of interface detachment, which immediately precedes the inception of frictional sliding, is governed by three different types of detachment fronts. These crack-like detachment fronts differ by both their propagation velocities and by the amount of net contact surface reduction caused by their passage. The most rapid fronts propagate at intersonic velocities but generate a negligible reduction in contact area across the interface. Sub-Rayleigh fronts are crack-like modes which propagate at velocities up to the Rayleigh wave speed, VR, and give rise to an approximate 10% reduction in net contact area. The most efficient contact area reduction (~20%) is precipitated by the passage of slow detachment fronts. These fronts propagate at anomalously slow velocities, which are over an order of magnitude lower than VR yet orders of magnitude higher than other characteristic velocity scales such as either slip or loading velocities. Slow fronts are generated, in conjunction with intersonic fronts, by the sudden arrest of sub-Rayleigh fronts. No overall sliding of the interface occurs until either of the slower two fronts traverses the entire interface, and motion at the leading edge of the interface is initiated. Slip at the trailing edge of the interface accompanies the motion of both the slow and sub-Rayleigh fronts. We might expect these modes to be important in both fault nucleation and earthquake dynamics.Comment: 19 page, 5 figures, to appear in International Journal of Fractur

Can We Really Prevent Suicide?

Every year, suicide is among the top 20 leading causes of death globally for all ages. Unfortunately, suicide is difficult to prevent, in large part because the prevalence of risk factors is high among the general population. In this review, clinical and psychological risk factors are examined and methods for suicide prevention are discussed. Prevention strategies found to be effective in suicide prevention include means restriction, responsible media coverage, and general public education, as well identification methods such as screening, gatekeeper training, and primary care physician education. Although the treatment for preventing suicide is difficult, follow-up that includes pharmacotherapy, psychotherapy, or both may be useful. However, prevention methods cannot be restricted to the individual. Community, social, and policy interventions will also be essentia

The second data release of the INT Photometric Ha Survey of the Northern Galactic Plane (IPHAS DR2)

The INT/WFC Photometric Hα Survey of the Northern Galactic Plane (IPHAS) is a 1800 deg2 imaging survey covering Galactic latitudes |b| < 5° and longitudes ℓ = 30°–215° in the r, i, and Hα filters using the Wide Field Camera (WFC) on the 2.5-m Isaac Newton Telescope (INT) in La Palma. We present the first quality-controlled and globally calibrated source catalogue derived from the survey, providing single-epoch photometry for 219 million unique sources across 92 per cent of the footprint. The observations were carried out between 2003 and 2012 at a median seeing of 1.1 arcsec (sampled at 0.33 arcsec pixel−1) and to a mean 5σ depth of 21.2 (r), 20.0 (i), and 20.3 (Hα) in the Vega magnitude system. We explain the data reduction and quality control procedures, describe and test the global re-calibration, and detail the construction of the new catalogue. We show that the new calibration is accurate to 0.03 mag (root mean square) and recommend a series of quality criteria to select accurate data from the catalogue. Finally, we demonstrate the ability of the catalogue's unique (r − Hα, r − i) diagram to (i) characterize stellar populations and extinction regimes towards different Galactic sightlines and (ii) select and quantify Hα emission-line objects. IPHAS is the first survey to offer comprehensive CCD photometry of point sources across the Galactic plane at visible wavelengths, providing the much-needed counterpart to recent infrared surveys

Structure-based statistical analysis of transmembrane helices

Recent advances in determination of the high-resolution structure of membrane proteins now enable analysis of the main features of amino acids in transmembrane (TM) segments in comparison with amino acids in water-soluble helices. In this work, we conducted a large-scale analysis of the prevalent locations of amino acids by using a data set of 170 structures of integral membrane proteins obtained from the MPtopo database and 930 structures of water-soluble helical proteins obtained from the protein data bank. Large hydrophobic amino acids (Leu, Val, Ile, and Phe) plus Gly were clearly prevalent in TM helices whereas polar amino acids (Glu, Lys, Asp, Arg, and Gln) were less frequent in this type of helix. The distribution of amino acids along TM helices was also examined. As expected, hydrophobic and slightly polar amino acids are commonly found in the hydrophobic core of the membrane whereas aromatic (Trp and Tyr), Pro, and the hydrophilic amino acids (Asn, His, and Gln) occur more frequently in the interface regions. Charged amino acids are also statistically prevalent outside the hydrophobic core of the membrane, and whereas acidic amino acids are frequently found at both cytoplasmic and extra-cytoplasmic interfaces, basic amino acids cluster at the cytoplasmic interface. These results strongly support the experimentally demonstrated biased distribution of positively charged amino acids (that is, the so-called the positive-inside rule) with structural data

Directed evolution of a magnetic resonance imaging contrast agent for noninvasive imaging of dopamine

The development of molecular probes that allow in vivo imaging of neural signaling processes with high temporal and spatial resolution remains challenging. Here we applied directed evolution techniques to create magnetic resonance imaging (MRI) contrast agents sensitive to the neurotransmitter dopamine. The sensors were derived from the heme domain of the bacterial cytochrome P450-BM3 (BM3h). Ligand binding to a site near BM3h's paramagnetic heme iron led to a drop in MRI signal enhancement and a shift in optical absorbance. Using an absorbance-based screen, we evolved the specificity of BM3h away from its natural ligand and toward dopamine, producing sensors with dissociation constants for dopamine of 3.3–8.9 μM. These molecules were used to image depolarization-triggered neurotransmitter release from PC12 cells and in the brains of live animals. Our results demonstrate the feasibility of molecular-level functional MRI using neural activity–dependent sensors, and our protein engineering approach can be generalized to create probes for other targets.Charles A. Dana Foundation. Brain and Immuno-ImagingRaymond and Beverley Sackler FoundationNational Institutes of Health (U.S.) (grant R01-DA28299)National Institutes of Health (U.S.) (grant DP2-OD2441)National Institutes of Health (U.S.) (grant R01-GM068664)Jacobs Institute for Molecular Engineering for Medicine. Jacobs Institute for Molecular Engineering for MedicineNational Institutes of Health (U.S.) (grant R01-DE013023

Three new chondrosarcoma cell lines: one grade III conventional central chondrosarcoma and two dedifferentiated chondrosarcomas of bone

BackgroundChondrosarcoma is the second most common primary sarcoma of bone. High-grade conventional chondrosarcoma and dedifferentiated chondrosarcoma have a poor outcome. In pre-clinical research aiming at the identification of novel treatment targets, the need for representative cell lines and model systems is high, but availability is scarce.MethodsWe developed and characterized three cell lines, derived from conventional grade III chondrosarcoma (L835), and dedifferentiated chondrosarcoma (L2975 and L3252) of bone. Proliferation and migration were studied and we used COBRA-FISH and array-CGH for karyotyping and genotyping. Immunohistochemistry for p16 and p53 was performed as well as TP53 and IDH mutation analysis. Cells were injected into nude mice to establish their tumorigenic potential.ResultsWe show that the three cell lines have distinct migrative properties, L2975 had the highest migration rate and showed tumorigenic potential in mice. All cell lines showed chromosomal rearrangements with complex karyotypes and genotypic aberrations were conserved throughout late passaging of the cell lines. All cell lines showed loss of CDKN2A, while TP53 was wild type for exons 5–8. L835 has an IDH1 R132C mutation, L2975 an IDH2 R172W mutation and L3252 is IDH wild type.ConclusionsBased on the stable culturing properties of these cell lines and their genotypic profile resembling the original tumors, these cell lines should provide useful functional models to further characterize chondrosarcoma and to evaluate new treatment strategies

Effectiveness of continuous hypertonic saline infusion with an automated infusion pump for decompressive neuroplasty: a randomized clinical trial

BACKGROUND: Hypertonic saline (HS) injections for decompressive neuroplasty (DN) can cause pain. We assessed whether a continuous infusion of HS through an infusion pump would reduce injection-related pain compared with repeated bolus administrations. METHODS: Fifty patients scheduled for DN were randomized to either the bolus injection or the continuous infusion group. After appropriately placing the epidural catheter, 4 mL of 5% NaCl was injected as four boluses of 1 mL each at 15-minute intervals or infused over 1 hour using an infusion pump. The severity of pain induced by HS injection, as measured by the 11-point numerical rating scale (NRS), was the primary outcome. The severity of low back or lower extremity pain, as measured by the 11-point NRS and Oswestry Disability Index (ODI), 3 months following the procedure, was the secondary outcome. RESULTS: Data from 21 patients in the bolus group and 23 in the continuous infusion group were analyzed. No statistically significant difference in injection-related pain was identified between the two groups during the initial HS administration (P = 0.846). However, there was a statistically significant reduction in injection-related pain in the continuous infusion group compared to the bolus injection group from the second assessment onwards (P = 0.001, < 0.001, and < 0.001, respectively). No significant between-group differences in the NRS and ODI scores 3 months post-procedure were noted (P = 0.614 and 0.949, respectively). CONCLUSIONS: Our study suggests that administering HS through a continuous infusion is a useful modality for reducing HS injection-related pain during DN

Huntington's disease and its therapeutic target genes: a global functional profile based on the HD Research Crossroads database.

BACKGROUND: Huntington's disease (HD) is a fatal progressive neurodegenerative disorder caused by the expansion of the polyglutamine repeat region in the huntingtin gene. Although the disease is triggered by the mutation of a single gene, intensive research has linked numerous other genes to its pathogenesis. To obtain a systematic overview of these genes, which may serve as therapeutic targets, CHDI Foundation has recently established the HD Research Crossroads database. With currently over 800 cataloged genes, this web-based resource constitutes the most extensive curation of genes relevant to HD. It provides us with an unprecedented opportunity to survey molecular mechanisms involved in HD in a holistic manner. METHODS: To gain a synoptic view of therapeutic targets for HD, we have carried out a variety of bioinformatical and statistical analyses to scrutinize the functional association of genes curated in the HD Research Crossroads database. In particular, enrichment analyses were performed with respect to Gene Ontology categories, KEGG signaling pathways, and Pfam protein families. For selected processes, we also analyzed differential expression, using published microarray data. Additionally, we generated a candidate set of novel genetic modifiers of HD by combining information from the HD Research Crossroads database with previous genome-wide linkage studies. RESULTS: Our analyses led to a comprehensive identification of molecular mechanisms associated with HD. Remarkably, we not only recovered processes and pathways, which have frequently been linked to HD (such as cytotoxicity, apoptosis, and calcium signaling), but also found strong indications for other potentially disease-relevant mechanisms that have been less intensively studied in the context of HD (such as the cell cycle and RNA splicing, as well as Wnt and ErbB signaling). For follow-up studies, we provide a regularly updated compendium of molecular mechanism, that are associated with HD, at http://hdtt.sysbiolab.eu Additionally, we derived a candidate set of 24 novel genetic modifiers, including histone deacetylase 3 (HDAC3), metabotropic glutamate receptor 1 (GRM1), CDK5 regulatory subunit 2 (CDK5R2), and coactivator 1ß of the peroxisome proliferator-activated receptor gamma (PPARGC1B). CONCLUSIONS: The results of our study give us an intriguing picture of the molecular complexity of HD. Our analyses can be seen as a first step towards a comprehensive list of biological processes, molecular functions, and pathways involved in HD, and may provide a basis for the development of more holistic disease models and new therapeutics

Reliable and robust method for abdominal muscle mass quantification using CT/MRI: An explorative study in healthy subjects

BACKGROUND: Quantification of abdominal muscle mass by cross-sectional imaging has been increasingly used to diagnose sarcopenia; however, the technical method for quantification has not been standardized yet. We aimed to determine an optimal method to measure the abdominal muscle area. METHODS: Among 50 consecutive subjects who underwent abdominal CT and MRI for possible liver donation, total abdominal muscle area (TAMA) and total psoas muscle area (TPA) at the L3 inferior endplate level were measured by two blinded readers. Inter-scan agreement between CT and MRI and inter-reader agreement between the two readers were evaluated using intraclass correlation coefficient (ICC) and within-subject coefficient of variation (WSCV). To evaluate the effect of measurement level, one reader measured TAMA and TPA at six levels from the L2 to L4 vertebral bodies. RESULTS: TAMA was a more reliable biomarker than TPA in terms of inter-scan agreement (ICC: 0.928 vs. 0.788 for reader 1 and 0.853 vs. 0.821 for reader 2, respectively; WSCV: 8.3% vs. 23.4% for reader 1 and 10.4% vs. 22.3% for reader 2, respectively) and inter-reader agreement (ICC: 0.986 vs. 0.886 for CT and 0.865 vs. 0.669 for MRI, respectively; WSCV: 8.2% vs. 16.0% for CT and 11.6% vs. 29.7% for MRI, respectively). In terms of the measurement level, TAMA did not differ from the L2inf to L4inf levels, whereas TPA increased with a decrease in measurement level. CONCLUSIONS: TAMA is a better biomarker than TPA in terms of inter-scan and inter-reader agreement and robustness to the measurement level. CT was a more reliable imaging modality than MRI. Our results support the use of TAMA measured by CT as a standard biomarker for abdominal muscle area measurement