Molecular Mechanisms Underlying TDP-43 Pathology in Cellular and Animal Models of ALS and FTLD

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are neurodegenerative disorders that exist on a disease spectrum due to pathological, clinical and genetic overlap. In up to 97% of ALS cases and ~50% of FTLD cases, the primary pathological protein observed in affected tissues is TDP-43, which is hyperphosphorylated, ubiquitinated and cleaved. The TDP-43 is observed in aggregates that are abnormally located in the cytoplasm. The pathogenicity of TDP-43 cytoplasmic aggregates may be linked with both a loss of nuclear function and a gain of toxic functions. The cellular processes involved in ALS and FTLD disease pathogenesis include changes to RNA splicing, abnormal stress granules, mitochondrial dysfunction, impairments to axonal transport and autophagy, abnormal neuromuscular junctions, endoplasmic reticulum stress and the subsequent induction of the unfolded protein response. Here, we review and discuss the evidence for alterations to these processes that have been reported in cellular and animal models of TDP-43 proteinopathy.     

Fisher’s decision tree

Univariate decision trees are classifiers currently used in many data mining applications. This classifier discovers partitions in the input space via hyperplanes that are orthogonal to the axes of attributes, producing a model that can be understood by human experts. One disadvantage of univariate decision trees is that they produce complex and inaccurate models when decision boundaries are not orthogonal to axes. In this paper we introduce the Fisher’s Tree, it is a classifier that takes advantage of dimensionality reduction of Fisher’s linear discriminant and uses the decomposition strategy of decision trees, to come up with an oblique decision tree. Our proposal generates an artificial attribute that is used to split the data in a recursive way.The Fisher’s decision tree induces oblique trees whose accuracy, size, number of leaves and training time are competitive with respect to other decision trees reported in the literature. We use more than ten public available data sets to demonstrate the effectiveness of our method.     

Recent Lessons Learned in Structural Fire Engineering for Composite Steel Structures

The knowledge in the field of structural fire engineering has been greatly advanced through assessment of a number of real fires (WTC, Torre Windsor, Broadgate, etc.) and, especially, by the Cardington series of full scale structural fire tests. This knowledge has been used to validate and verify the use of computational finite element models that have expanded the range of structures that can be investigated under severe fire exposure. This paper presents a selection of key lessons learned by the authors through the assessment of structures in fire for real commercial building projects. The key areas of sensitivity that have been encountered are described and a discussion of each point presented. The paper is aimed at describing potential weaknesses that have been observed in the commercial work of the authors, often driven by the requirements for efficient ambient structural design. The paper concludes with some suggested advice for structural engineers aimed at increasing the general robustness of building structures. This is based on designing out as far as possible in the ambient design of a structure the potential weaknesses identified in past project work.     

The gene, ialA, associated with the invasion of human erythrocytes by Bartonella bacilliformis, designates a nudix hydrolase active on dinucleoside 5'-polyphosphates

ialA, one of two genes associated with the invasion of human red blood cells by Bartonella bacilliformis, the causative agent of several diseases, has been cloned and expressed in Escherichia coli. The protein, IalA, contains an amino acid array characteristic of a family of enzymes, the Nudix hydrolases, active on a variety of nucleoside diphosphate derivatives. IalA has been purified, identified, and characterized as an enzyme catalyzing the hydrolysis of members of a class of signaling nucleotides, the dinucleoside polyphosphates, with its highest activity on adenosine 5'-tetraphospho-5'-adenosine (Ap4A), but also hydrolyzing Ap5A, Ap6A, Gp4G, and Gp5G. In each case, a pyrophosphate linkage is cleaved yielding a nucleoside triphosphate and the remaining nucleotide moiety.     

Applications of Highly-Nonlinear Chalcogenide Glass Devices Tailored for High-Speed All-Optical Signal Processing

Ultrahigh nonlinear tapered fiber and planar rib Chalcogenide waveguides have been developed to enable highspeed all-optical signal processing in compact, low-loss optical devices through the use of four-wave mixing (FWM) and cross-phase modulation (XPM) via the ultra fast Kerr effect. Tapering a commercial As₂Se₃ fiber is shown to reduce its effective core area and enhance the Kerr nonlinearity thereby enabling XPM wavelength conversion of a 40 Gb/s signal in a shorter 16-cm length device that allows a broader wavelength tuning range due to its smaller net chromatic dispersion. Progress toward photonic chip-scale devices is shown by fabricating As₂S₃ planar rib waveguides exhibiting nonlinearity up to 2080 W^-1ldr km^-1 and losses as low as 0.05 dB/cm. The material's high refractive index, ensuring more robust confinement of the optical mode, permits a more compact serpentine-shaped rib waveguide of 22.5 cm length on a 7-cm- size chip, which is successfully applied to broadband wavelength conversion of 40-80 Gb/s signals by XPM. A shorter 5-cm length planar waveguide proves most effective for all-optical time-division demultiplexing of a 160 Gb/s signal by FWM and analysis shows its length is near optimum for maximizing FWM in consideration of its dispersion and loss.     

火灾中有保护和无保护边梁的组合钢结构框架

采用数字模型分析了钢混组合框架在火灾中的结构性能。两种情况下结构的性能是显著不同的。对只带防火保护的外梁与没有任何梁受保护两种情况的结构进行了比较,当边梁被保护时,底板趋向两个方向延伸,因为边梁对板周界应力的发展提供了足够的支撑;当边梁没有被保护时,板只朝一个方向延伸,其受力方式类似于悬链线。与拉伸膜相比悬链线梁为较弱的荷载载运机制。这种弱机制的结果是当边梁无保护时,柱位移向内预示出临近坍塌的可能性。混凝土楼板的应变模式取决于其承载机理,因此与边梁是否保护有关。当边梁有保护时尽管平均拉应变较高,但是最高拉应变都发生在边梁无保护时。反之,当边梁有保护时,在很低的温度,原梁就失稳。研究结论是边梁的结构布局在结构防火等方面具有一定的效果,有些有利,有些有害,然而,一般情况下,有保护边梁可以提供较高的防火等级。