Modelling avalanches in martensites

Solids subject to continuous changes of temperature or mechanical load often exhibit discontinuous avalanche-like responses. For instance, avalanche dynamics have been observed during plastic deformation, fracture, domain switching in ferroic materials or martensitic transformations. The statistical analysis of avalanches reveals a very complex scenario with a distinctive lack of characteristic scales. Much effort has been devoted in the last decades to understand the origin and ubiquity of scale-free behaviour in solids and many other systems. This chapter reviews some efforts to understand the characteristics of avalanches in martensites through mathematical modelling.Comment: Chapter in the book "Avalanches in Functional Materials and Geophysics", edited by E. K. H. Salje, A. Saxena, and A. Planes. The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-319-45612-6_

Real-time imaging of hepatitis C virus infection using a fluorescent cell-based reporter system

Author Manuscript 2010 August 1Hepatitis C virus (HCV), which infects 2–3% of the world population, is a causative agent of chronic hepatitis and the leading indication for liver transplantation1. The ability to propagate HCV in cell culture (HCVcc) is a relatively recent breakthrough and a key tool in the quest for specific antiviral therapeutics. Monitoring HCV infection in culture generally involves bulk population assays, use of genetically modified viruses and/or terminal processing of potentially precious samples. Here we develop a cell-based fluorescent reporter system that allows sensitive distinction of individual HCV-infected cells in live or fixed samples. We demonstrate use of this technology for several previously intractable applications, including live-cell imaging of viral propagation and host response, as well as visualizing infection of primary hepatocyte cultures. Integration of this reporter with modern image-based analysis methods could open new doors for HCV research.New York (State). Dept. of Health (Empire State Stem Cell Fund Contract C023046)United States. Public Health Service (Grant R01 DK56966)National Institutes of Health (U.S.) (Roadmap for Medical Research Grant 1 R01 DK085713-01)Howard Hughes Medical Institute (Investigator

Development and Validity of the Rating-of-Fatigue Scale

Objective: The purpose of these experiments was to develop a rating-of-fatigue (ROF) scale capable of tracking the intensity of perceived fatigue in a variety of contexts. Methods: Four experiments were carried out. The first provided the evidential basis for the construction of the ROF scale. The second tested the face validity of the ROF, and the third tested the convergent and divergent validity of the ROF scale during ramped cycling to exhaustion and 30 min of resting recovery. The final experiment tested the convergent validity of the ROF scale with time of day and physical activity (accelerometer counts) across a whole week. Results: Modal selections of descriptions and diagrams at different levels of exertion and recovery were found during Experiment 1 upon which the ROF scale was constructed and finalised. In Experiment 2, a high level of face validity was indicated, in that ROF was reported to represent fatigue rather than exertion. Descriptor and diagrammatic elements of ROF reportedly added to the coherence and ease of use of the scale. In Experiment 3, high convergence between ROF and various physiological measures were found during exercise and recovery (heart rate, blood lactate concentration, oxygen uptake, carbon dioxide production, respiratory exchange ratio and ventilation rate were all P < 0.001). During ramped cycling to exhaustion ROF and RPE did correspond (P < 0.0001) but not during recovery, demonstrating discriminant validity. Experiment 4 found ROF to correspond with waking time during each day (Mon–Sun all P < 0.0001) and with physical activity (accelerometer count) (Mon–Sun all P < 0.001). Conclusions: The ROF scale has good face validity and high levels of convergent validity during ramped cycling to exhaustion, resting recovery and daily living activities. The ROF scale has both theoretical and applied potential in understanding changes in fatigue in a variety of contexts

Transcription Factor NF-κB Is Transported to the Nucleus via Cytoplasmic Dynein/Dynactin Motor Complex in Hippocampal Neurons

Mikenberg I, Widera D, Kaus A, Kaltschmidt B, Kaltschmidt C. Transcription Factor NF-kappa B Is Transported to the Nucleus via Cytoplasmic Dynein/Dynactin Motor Complex in Hippocampal Neurons. PLOS ONE. 2007;2(7):e589.Background. Long-term changes in synaptic plasticity require gene transcription, indicating that signals generated at the synapse must be transported to the nucleus. Synaptic activation of hippocampal neurons is known to trigger retrograde transport of transcription factor NF-kappa B. Transcription factors of the NF-kappa B family are widely expressed in the nervous system and regulate expression of several genes involved in neuroplasticity, cell survival, learning and memory. Principal Findings. In this study, we examine the role of the dynein/dynactin motor complex in the cellular mechanism targeting and transporting activated NF-kappa B to the nucleus in response to synaptic stimulation. We demonstrate that overexpression of dynamitin, which is known to dissociate dynein from microtubules, and treatment with microtubule-disrupting drugs inhibits nuclear accumulation of NF-kappa B p65 and reduces NF-kappa B-dependent transcription activity. In this line, we show that p65 is associated with components of the dynein/dynactin complex in vivo and in vitro and that the nuclear localization sequence (NLS) within NF-kappa B p65 is essential for this binding. Conclusion. This study shows the molecular mechanism for the retrograde transport of activated NF-kappa B from distant synaptic sites towards the nucleus

Effects of anthropogenic activities on the heavy metal levels in the clams and sediments in a tropical river

The present study aimed to assess the effects of anthropogenic activities on the heavy metal levels in the Langat River by transplantation of Corbicula javanica. In addition, potential ecological risk indexes (PERI) of heavy metals in the surface sediments of the river were also investigated. The correlation analysis revealed that eight metals (As, Co, Cr, Fe, Mn, Ni, Pb and Zn) in total soft tissue (TST) while five metals (As, Cd, Cr, Fe and Mn) in shell have positively and significantly correlation with respective metal concentration in sediment, indicating the clams is a good biomonitor of the metal levels. Based on clustering patterns, the discharge of dam impoundment, agricultural activities and urban domestic waste were identified as three major contributors of the metals in Pangsun, Semenyih and Dusun Tua, and Kajang, respectively. Various geochemical indexes for a single metal pollutant (geoaccumulation index (I geo), enrichment factors (EF), contamination factor (C f) and ecological risk (Er)) all agreed that Cd, Co, Cr, Cu, Fe, Mn, Ni and Zn are not likely to cause adverse effect to the river ecosystem, but As and Pb could pose a potential ecological risk to the river ecosystem. All indexes (degree of contamination (C d), combined pollution index (CPI) and PERI) showed that overall metal concentrations in the tropical river are still within safe limit. River metal pollution was investigated. Anthropogenic activities were contributors of the metal pollution. Geochemical indexes showed that metals are within the safe limit

Systematic and Evolutionary Insights Derived from mtDNA COI Barcode Diversity in the Decapoda (Crustacea: Malacostraca)

Background: Decapods are the most recognizable of all crustaceans and comprise a dominant group of benthic invertebrates of the continental shelf and slope, including many species of economic importance. Of the 17635 morphologically described Decapoda species, only 5.4% are represented by COI barcode region sequences. It therefore remains a challenge to compile regional databases that identify and analyse the extent and patterns of decapod diversity throughout the world. Methodology/Principal Findings: We contributed 101 decapod species from the North East Atlantic, the Gulf of Cadiz and the Mediterranean Sea, of which 81 species represent novel COI records. Within the newly-generated dataset, 3.6% of the species barcodes conflicted with the assigned morphological taxonomic identification, highlighting both the apparent taxonomic ambiguity among certain groups, and the need for an accelerated and independent taxonomic approach. Using the combined COI barcode projects from the Barcode of Life Database, we provide the most comprehensive COI data set so far examined for the Order (1572 sequences of 528 species, 213 genera, and 67 families). Patterns within families show a general predicted molecular hierarchy, but the scale of divergence at each taxonomic level appears to vary extensively between families. The range values of mean K2P distance observed were: within species 0.285% to 1.375%, within genus 6.376% to 20.924% and within family 11.392% to 25.617%. Nucleotide composition varied greatly across decapods, ranging from 30.8 % to 49.4 % GC content. Conclusions/Significance: Decapod biological diversity was quantified by identifying putative cryptic species allowing a rapid assessment of taxon diversity in groups that have until now received limited morphological and systematic examination. We highlight taxonomic groups or species with unusual nucleotide composition or evolutionary rates. Such data are relevant to strategies for conservation of existing decapod biodiversity, as well as elucidating the mechanisms and constraints shaping the patterns observed.FCT - SFRH/BD/25568/ 2006EC FP6 - GOCE-CT-2005-511234 HERMESFCT - PTDC/MAR/69892/2006 LusomarBo

Ultra-Rare Genetic Variation in the Epilepsies : A Whole-Exome Sequencing Study of 17,606 Individuals

Sequencing-based studies have identified novel risk genes associated with severe epilepsies and revealed an excess of rare deleterious variation in less-severe forms of epilepsy. To identify the shared and distinct ultra-rare genetic risk factors for different types of epilepsies, we performed a whole-exome sequencing (WES) analysis of 9,170 epilepsy-affected individuals and 8,436 controls of European ancestry. We focused on three phenotypic groups: severe developmental and epileptic encephalopathies (DEEs), genetic generalized epilepsy (GGE), and non-acquired focal epilepsy (NAFE). We observed that compared to controls, individuals with any type of epilepsy carried an excess of ultra-rare, deleterious variants in constrained genes and in genes previously associated with epilepsy; we saw the strongest enrichment in individuals with DEEs and the least strong in individuals with NAFE. Moreover, we found that inhibitory GABA(A) receptor genes were enriched for missense variants across all three classes of epilepsy, whereas no enrichment was seen in excitatory receptor genes. The larger gene groups for the GABAergic pathway or cation channels also showed a significant mutational burden in DEEs and GGE. Although no single gene surpassed exome-wide significance among individuals with GGE or NAFE, highly constrained genes and genes encoding ion channels were among the lead associations; such genes included CACNAIG, EEF1A2, and GABRG2 for GGE and LGI1, TRIM3, and GABRG2 for NAFE. Our study, the largest epilepsy WES study to date, confirms a convergence in the genetics of severe and less-severe epilepsies associated with ultra-rare coding variation, and it highlights a ubiquitous role for GABAergic inhibition in epilepsy etiology.Peer reviewe