ALBERT

Description: Activation of caspase-6 in the striatum of both presymptomatic and affected persons with Huntington's disease (HD) is an early event in the disease pathogenesis. However, little is known about the role of caspase-6 outside the central nervous system (CNS) and whether caspase activation might play a role in the peripheral phenotypes, such as muscle wasting observed in HD. We assessed skeletal muscle tissue from HD patients and well-characterized mouse models of HD. Cleavage of the caspase-6 specific substrate lamin A is significantly increased in skeletal muscle obtained from HD patients as well as in muscle tissues from two different HD mouse models. p53, a transcriptional activator of caspase-6, is upregulated in neuronal cells and tissues expressing mutant huntingtin. Activation of p53 leads to a dramatic increase in levels of caspase-6 mRNA, caspase-6 activity and cleavage of lamin A. Using mouse embryonic fibroblasts (MEFs) from YAC128 mice, we show that this increase in caspase-6 activity can be mitigated by pifithrin-α (pifα), an inhibitor of p53 transcriptional activity, but not through the inhibition of p53's mitochondrial pro-apoptotic function. Remarkably, the p53-mediated increase in caspase-6 expression and activation is exacerbated in cells and tissues of both neuronal and peripheral origin expressing mutant huntingtin (Htt). These findings suggest that the presence of the mutant Htt protein enhances p53 activity and lowers the apoptotic threshold, which activates caspase-6. Furthermore, these results suggest that this pathway is activated both within and outside the CNS in HD and may contribute to both loss of CNS neurons and muscle atrophy.

Description: Accurate information on thermal conductivity and thermal diffusivity of materials is of central importance in relation to geoscience and engineering problems involving the transfer of heat. Several methods, including the classical divided bar technique, are available for laboratory measurements of thermal conductivity, but much fewer for thermal diffusivity. We have generalized the divided bar technique to the transient case in which thermal conductivity, volumetric heat capacity and thereby also thermal diffusivity are measured simultaneously. As the density of samples is easily determined independently, specific heat capacity can also be determined. The finite element formulation provides a flexible forward solution for heat transfer across the bar, and thermal properties are estimated by inverse Monte Carlo modelling. This methodology enables a proper quantification of experimental uncertainties on measured thermal properties and information on their origin. The developed methodology was applied to various materials, including a standard ceramic material and different rock samples, and measuring results were compared with results applying traditional steady-state divided bar and an independent line-source method. All measurements show highly consistent results and with excellent reproducibility and high accuracy. For conductivity the obtained uncertainty is typically 1–3 per cent, and for diffusivity uncertainty may be reduced to about 3–5 per cent. The main uncertainty originates from the presence of thermal contact resistance associated with the internal interfaces in the bar. These are not resolved during inversion and it is imperative that they are minimized. The proposed procedure is simple and may quite easily be implemented to the many steady-state divided bar systems in operation. A thermally controlled bath, as applied here, may not be needed. Simpler systems, such as applying temperature-controlled water directly from a tap, may also be applied.

Description: The objective in this article is twofold. On one hand, a Model Output Statistics (MOS) framework for improved wind speed forecast accuracy is described and evaluated. On the other hand, the approach explored identifies unintuitive explanatory value from a diagnostic variable in an operational numerical weather prediction (NWP) model generating global weather forecasts four times daily, with numerous users worldwide. The analysis is based on two years of hourly wind speed time series measured at three locations; offshore, in coastal and flat terrain, and inland in complex topography, respectively. Based on the statistical model candidates inferred from the data, the lifted index NWP model diagnostic is consistently found among the NWP model predictors of the best performing statistical models across sites.

Description: [1]  We observe the nucleation phase of in-plane ruptures in the laboratory. We show that the nucleation is composed of two distinct phases, a quasi-static and an acceleration stage, followed by dynamic propagation. We propose an empirical model which describes the rupture length evolution: the quasi-static phase is described by an exponential growth while the acceleration phase is described by an inverse power law of time. The transition from quasistatic to accelerating rupture is related to the critical nucleation length, which scales inversely with normal stress in accordance with theoretical predictions, and to a critical surfacic power, which may be an intrinsic property of the interface. Finally, we discuss these results in the frame of previous studies and propose a scaling up to natural earthquake dimensions.

Description: Biochemistry DOI: 10.1021/acs.biochem.5b00292

Description: Empirically-based rate-and-state friction laws (RSFL) have been proposed to model the dependence of friction forces with slip and time. The relevance of the RSFL for earthquake mechanics is that few constitutive parameters define critical conditions for fault stability (i.e. critical stiffness and frictional fault behavior). However, the RSFL were determined from experiments conducted at sub-seismic slip rates ( V  〈 1 cm/s) and their extrapolation to earthquake deformation conditions ( V  〉 0.1 m/s) remains questionable on the basis of the experimental evidence of (1) large dynamic weakening and (2) activation of particular fault lubrication processes at seismic slip rates. Here we propose a modified RSFL (MFL) based on the review of a large published and unpublished dataset of rock-friction experiments performed with different testing machines. The MFL, valid at steady-state conditions from sub-seismic to seismic slip rates (0.1 µm/s 〈  V  〈 3 m/s), describes the initiation of a substantial velocity-weakening in the 1-20 cm/s range resulting in a critical stiffness increase that creates a peak of potential instability in that velocity regime. The MFL leads to a new definition of fault frictional stability with implications for slip event styles and relevance for models of seismic rupture nucleation, propagation and arrest.

Description: Adoption of no-till systems in Eastern Washington has been slow due to the difficulty of managing wheat (Triticum aestivum L.) straw residue and the unknown decomposition potential of cultivars. We hypothesize that by analyzing wheat straw with near-infrared spectroscopy (NIRS), calibration models can be developed to accurately predict fiber and chemical constituents of wheat, determining straw decomposition potential. Straw from a panel of 480 soft winter wheat cultivars adapted to the Pacific Northwest are analyzed for neutral detergent fiber (NDF), acid detergent fiber (ADF), acid detergent lignin (ADL), cellulose, hemicellulose, carbon (C), and nitrogen (N). Using modified partial least squares regression and cross validation techniques, specific environment and broad-based NIRS models are calibrated and predictive ability is validated. R2cal values from broad models are better than the specific models, and are 0.85 (NDF), 0.86 (ADF), 0.65 (ADL), 0.88 (cellulose), 0.42 (hemicellulose), 0.67 (C), and 0.73 (N). The corresponding SEP values are 1.68% (NDF), 1.54% (ADF), 0.62% (ADL), 1.14% (cellulose), 1.11% (hemicellulose), 1.23% (C), and 0.06% (N). A Finch × Eltan breeding population is used to further validate models and prediction accuracies for variety selection within a breeding program scenario. The broad NIRS models prove useful for estimating high and low ranges of NDF, ADF, and cellulose in wheat cultivars which translate into characteristics of slow and fast decomposition potential.