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

Histone deacetylase adaptation in single ventricle heart disease and a young animal model of right ventricular hypertrophy.

BackgroundHistone deacetylase (HDAC) inhibitors are promising therapeutics for various forms of cardiac diseases. The purpose of this study was to assess cardiac HDAC catalytic activity and expression in children with single ventricle (SV) heart disease of right ventricular morphology, as well as in a rodent model of right ventricular hypertrophy (RVH).MethodsHomogenates of right ventricle (RV) explants from non-failing controls and children born with a SV were assayed for HDAC catalytic activity and HDAC isoform expression. Postnatal 1-day-old rat pups were placed in hypoxic conditions, and echocardiographic analysis, gene expression, HDAC catalytic activity, and isoform expression studies of the RV were performed.ResultsClass I, IIa, and IIb HDAC catalytic activity and protein expression were elevated in the hearts of children born with a SV. Hypoxic neonatal rats demonstrated RVH, abnormal gene expression, elevated class I and class IIb HDAC catalytic activity, and protein expression in the RV compared with those in the control.ConclusionsThese data suggest that myocardial HDAC adaptations occur in the SV heart and could represent a novel therapeutic target. Although further characterization of the hypoxic neonatal rat is needed, this animal model may be suitable for preclinical investigations of pediatric RV disease and could serve as a useful model for future mechanistic studies

Climate change and anthropogenic intervention impact on the hydrologic anomalies in a semi-arid area : lower Zab river basin, Iraq

Climate change impact, drought phenomena and anthropogenic stress are of increasing apprehension for water resource managers and strategists, particularly in arid regions. The current study proposes a generic methodology to evaluate the potential impact of such changes at a basin scale. The Lower Zab River Basin located in the north of Iraq has been selected for illustration purposes. The method has been developed through evaluating changes during normal hydrological years to separate the effects of climate change and estimate the hydrologic abnormalities utilising Indicators of Hydrologic Alteration. The meteorological parameters were perturbed by applying adequate delta perturbation climatic scenarios. Thereafter, a calibrated rainfall-runoff model was used for streamflow simulations. Findings proved that climate change has a more extensive impact on the hydrological characteristics of the streamflow than anthropogenic intervention (i.e. the construction of a large dam in the catchment). The isolated baseflow is more sensitive to the precipitation variations than to the variations of the potential evapotranspiration. The current hydrological anomalies are expected to continue. This comprehensive basin study demonstrates how climate change impact, anthropogenic intervention as well as hydro-climatic drought and hydrological anomalies can be evaluated with a new methodology

Joint angle variability and co-variation in a reaching with a rod task

The problem at the heart of motor control is how the myriad units of the neuromotor system are coordinated to perform goal-directed movements. Although for long these numerous degrees of freedom (DOFs) were considered redundant, recent views emphasize more that the DOFs should be considered abundant, allowing flexible performance. We studied how variability in arm joints was employed to stabilize the displaced end-effector in tool use to examine how the neuromotor system flexibly exploits DOFs in the upper extremity. Participants made pointing movements with the index finger and with the index finger extended by rods of 10, 20, and 30 cm. Using the uncontrolled manifold (UCM) method, the total joint angle variance was decomposed into two parts, the joint angle variance that did not affect the position of the end-effector (VUCM) and the variance that results in a deviation of the position of the end-effector from its mean (VORT). Analyses showed that some angles depended on length of the rod in use. For all rod lengths, VUCM was larger than VORT, and this did not differ over rod lengths, demonstrating that the arm was organized into a synergy. Finally, the variation in the joint angles in the arm as well as the degree of co-variation between these angles did not differ for the rod’s tip and the hand. We concluded that synergies are formed in the arm during reaching with an extended end-effector and those synergies stabilize different parts of the arm+rod system equally

Adaptation strategy to mitigate the impact of climate change on water resources in arid and semi-arid regions : a case study

Climate change and drought phenomena impacts have become a growing concern for water resources engineers and policy makers, mainly in arid and semi-arid areas. This study aims to contribute to the development of a decision support tool to prepare water resources managers and planners for climate change adaptation. The Hydrologiska Byråns Vattenbalansavdelning (The Water Balance Department of the Hydrological Bureau) hydrologic model was used to define the boundary conditions for the reservoir capacity yield model comprising daily reservoir inflow from a representative example watershed with the size of 14,924 km2 into a reservoir with the capacity of 6.80 Gm3. The reservoir capacity yield model was used to simulate variability in climate change-induced differences in reservoir capacity needs and performance (operational probability of failure, resilience, and vulnerability). Owing to the future precipitation reduction and potential evapotranspiration increase during the worst case scenario (−40% precipitation and +30% potential evapotranspiration), substantial reductions in streamflow of between −56% and −58% are anticipated for the dry and wet seasons, respectively. Furthermore, model simulations recommend that as a result of future climatic conditions, the reservoir operational probability of failure would generally increase due to declined reservoir inflow. The study developed preparedness plans to combat the consequences of climate change and drought

Pregnancy in multiple system atrophy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Multiple system atrophy is a late, adult-onset α-synucleinopathy with no data on the effect of pregnancy on the disease course. Early stage multiple system atrophy can be difficult to distinguish from Parkinson's disease.</p> <p>Case presentation</p> <p>We describe the case of an Irish woman with parkinsonism starting at age 31, initially diagnosed as having dopa-responsive, idiopathic Parkinson's disease, who successfully delivered a full-term child at age 35. Her pregnancy was complicated by severe orthostatic hypotension and motor fluctuations. Two years post-partum, she underwent bilateral subthalamic nuclei deep brain stimulation for intractable motor fluctuations and disabling dyskinesia. After this treatment course she experienced deterioration of motor symptoms and death eight years after disease onset. Post-mortem neuropathological examination revealed striatonigral degeneration and α-synuclein-positive glial cytoplasmic inclusions in brain stem nuclei, basal ganglia and white matter tracts, consistent with a neuropathological diagnosis of multiple system atrophy.</p> <p>Conclusions</p> <p>Multiple system atrophy can affect women of child-bearing age and pregnancy may be associated with marked disease progression.</p

Spontaneous upper limb monoplegia secondary to probable cerebral amyloid angiopathy

Cerebral amyloid angiopathy is a clinicopathological disorder characterised by vascular amyloid deposition initially in leptomeningeal and neocortical vessels, and later affecting cortical and subcortical regions. The presence of amyloid within the walls of these vessels leads to a propensity for primary intracerebral haemorrhage. We report the unusual case of a 77-year-old female who presented to our emergency department with sudden onset isolated hypoaesthesia and right upper limb monoplegia. A CT scan demonstrated a peripheral acute haematoma involving the left perirolandic cortices. Subsequent magnetic resonance imaging demonstrated previous superficial haemorrhagic events. One week following discharge the patient re-attended with multiple short-lived episodes of aphasia and jerking of the right upper limb. Further imaging demonstrated oedematous changes around the previous haemorrhagic insult. Cerebral amyloid angiopathy is an overlooked cause of intracerebral haemorrhage; the isolated nature of the neurological deficit in this case illustrates the many guises in which it can present

A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185 thousand CAD cases and controls, interrogating 6.7 million common (MAF>0.05) as well as 2.7 million low frequency (0.005<MAF<0.05) variants. In addition to confirmation of most known CAD loci, we identified 10 novel loci, eight additive and two recessive, that contain candidate genes that newly implicate biological processes in vessel walls. We observed intra-locus allelic heterogeneity but little evidence of low frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect siz

Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci.

Genetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all individuals born in Denmark since 1981 and diagnosed with schizophrenia as well as controls from the same birth cohort. Furthermore, we present the first genome-wide interaction survey of single nucleotide polymorphisms (SNPs) and maternal cytomegalovirus (CMV) infection. The GWA analysis included 888 cases and 882 controls, and the follow-up investigation of the top GWA results was performed in independent Danish (1396 cases and 1803 controls) and German-Dutch (1169 cases, 3714 controls) samples. The SNPs most strongly associated in the single-marker analysis of the combined Danish samples were rs4757144 in ARNTL (P=3.78 × 10(-6)) and rs8057927 in CDH13 (P=1.39 × 10(-5)). Both genes have previously been linked to schizophrenia or other psychiatric disorders. The strongest associated SNP in the combined analysis, including Danish and German-Dutch samples, was rs12922317 in RUNDC2A (P=9.04 × 10(-7)). A region-based analysis summarizing independent signals in segments of 100 kb identified a new region-based genome-wide significant locus overlapping the gene ZEB1 (P=7.0 × 10(-7)). This signal was replicated in the follow-up analysis (P=2.3 × 10(-2)). Significant interaction with maternal CMV infection was found for rs7902091 (P(SNP × CMV)=7.3 × 10(-7)) in CTNNA3, a gene not previously implicated in schizophrenia, stressing the importance of including environmental factors in genetic studies