Autophagy in Childhood Neurological Disorders

Autophagy is a tightly modulated lysosomal degradation pathway. Genetic disorders of autophagy during nervous system development may lead to developmental delay, neurodegeneration and other neurological signs in children. Here we aimed to summarize single gene disorders that perturb various steps of autophagy pathway and their roles in the causation of childhood neurological diseases. Numerous childhood-onset disorders are caused by mutations that impact the autophagy pathway. These can manifest with a range of features including ataxia, spastic paraplegia, and intellectual disability. Defective proteins causing such diseases can interfere with autophagy flux at different stages of the itinerary. Defective autophagy may be an important contributor to the pathological features of various childhood neurodegenerative disease and lead to the accumulation of aberrant protein and dysfunctional organelles. Insights into the relevant cell biological processes may help understand pathophysiological mechanisms and inspire autophagy-restoring therapeutic approaches.MR

Deletion within the Src homology domain 3 of Bruton's tyrosine kinase resulting in X-linked agammaglobulinemia (XLA).

The gene responsible for X-linked agammaglobulinemia (XLA) has been recently identified to code for a cytoplasmic tyrosine kinase (Bruton's agammaglobulinemia tyrosine kinase, BTK), required for normal B cell development. BTK, like many other cytoplasmic tyrosine kinases, contains Src homology domains (SH2 and SH3), and catalytic kinase domain. SH3 domains are important for the targeting of signaling molecules to specific subcellular locations. We have identified a family with XLA whose affected members have a point mutation (g-->a) at the 5' splice site of intron 8, resulting in the skipping of coding exon 8 and loss of 21 amino acids forming the COOH-terminal portion of the BTK SH3 domain. The study of three generations within this kinship, using restriction fragment length polymorphism and DNA analysis, allowed identification of the mutant X chromosome responsible for XLA and the carrier status in this family. BTK mRNA was present in normal amounts in Epstein-Barr virus-induced B lymphoblastoid cell lines established from affected family members. Although the SH3 deletion did not alter BTK protein stability and kinase activity of the truncated BTK protein was normal, the affected patients nevertheless have a severe B cell defect characteristic for XLA. The mutant protein was modeled using the normal BTK SH3 domain. The deletion results in loss of two COOH-terminal beta strands containing several residues critical for the formation of the putative SH3 ligand-binding pocket. We predict that, as a result, one or more crucial SH3 binding proteins fail to interact with BTK, interrupting the cytoplasmic signal transduction process required for B cell differentiation

On-the-fly computation method in field-programmable gate array for analog-to-digital converter linearity testing

© 2018 Published by ITB Journal Publisher. This paper presents a new approach to linearity testing of analog-to-digital converters (ADCs) through on-the-fly computation in field-programmable gate array (FPGA) hardware. The proposed method computes the linearity while it is processing without compromising the accuracy of the measurement, so very little overhead time is required to compute the final linearity. The results will be displayed immediately after a single ramp is supplied to the device under test. This is a cost-effective chip testing solution for semiconductor companies, achieved by reducing computing time and utilization of low-cost and low-specification automatic test equipment (ATE). The experimental results showed that the on-the-fly computation method significantly reduced the computation time (up to 44.4%) compared to the conventional process. Thus, for every 100M 12-bit ADC tested with 32 hits per code, the company can save up to 139,972 Php on electricity consumption

Simple and efficient methods for isolation and activity measurement of the recombinant hirudin variant 3 from Bacillus subtilis

A simple purification approach of the recombinant hirudin variant 3 from the Bacillus subtilis was established, by which the hirudin could be purified to the purity of 95% through one-step chromatography with the total recovery rate of 83.9%. A modified Markwardt thrombin titration method for measuring hirudin activity was also set up. Briefly, a series of concentrations of thrombin was prepared and titrated to hirudin sample, respectively and the anti-thrombin activity-range of hirudin was narrowed down by several thrombin solutions at high or low concentration and the optimum group of thrombin concentrations was determined for titration of the hirudin sample. In this modified method, the hirudin activity was determined more accurately, concisely and promptly than the classic Markwardt method.Key words: Hirudin, thrombin titration method, chromatography, purification

Ruin probabilities in classical risk models with gamma claims

In this paper, we provide three equivalent expressions for ruin probabilities in a Cramér–Lundberg model with gamma distributed claims. The results are solutions of integro-differential equations, derived by means of (inverse) Laplace transforms. All the three formulas have infinite series forms, two involving Mittag–Leffler functions and the third one involving moments of the claims distribution. This last result applies to any other claim size distributions that exhibits finite moments

Determining Principal Component Cardinality through the Principle of Minimum Description Length

PCA (Principal Component Analysis) and its variants areubiquitous techniques for matrix dimension reduction and reduced-dimensionlatent-factor extraction. One significant challenge in using PCA, is thechoice of the number of principal components. The information-theoreticMDL (Minimum Description Length) principle gives objective compression-based criteria for model selection, but it is difficult to analytically applyits modern definition - NML (Normalized Maximum Likelihood) - to theproblem of PCA. This work shows a general reduction of NML prob-lems to lower-dimension problems. Applying this reduction, it boundsthe NML of PCA, by terms of the NML of linear regression, which areknown.Comment: LOD 201

Low Friction Flows of Liquids at Nanopatterned Interfaces

With the recent important development of microfluidic systems, miniaturization of flow devices has become a real challenge. Microchannels, however, are characterized by a large surface to volume ratio, so that surface properties strongly affect flow resistance in submicrometric devices. We present here results showing that the concerted effect of wetting . properties and surface roughness may considerably reduce friction of the fluid past the boundaries. The slippage of the fluid at the channel boundaries is shown to be drastically increased by using surfaces that are patterned at the nanometer scale. This effect occurs in the regime where the surface pattern is partially dewetted, in the spirit of the 'superhydrophobic' effects that have been recently discovered at the macroscopic scales. Our results show for the first time that, in contrast to the common belief, surface friction may be reduced by surface roughness. They also open the possibility of a controlled realization of the 'nanobubbles' that have long been suspected to play a role in interfacial slippag

Exact ground states for the four-electron problem in a two-dimensional finite Hubbard square system

We present exact explicit analytical results describing the exact ground state of four electrons in a two dimensional square Hubbard cluster containing 16 sites taken with periodic boundary conditions. The presented procedure, which works for arbitrary even particle number and lattice sites, is based on explicitly given symmetry adapted base vectors constructed in r-space. The Hamiltonian acting on these states generates a closed system of 85 linear equations providing by its minimum eigenvalue the exact ground state of the system. The presented results, described with the aim to generate further creative developments, not only show how the ground state can be exactly obtained and what kind of contributions enter in its construction, but emphasize further characteristics of the spectrum. On this line i) possible explications are found regarding why weak coupling expansions often provide a good approximation for the Hubbard model at intermediate couplings, or ii) explicitly given low lying energy states of the kinetic energy, avoiding double occupancy, suggest new roots for pairing mechanism attracting decrease in the kinetic energy, as emphasized by kinetic energy driven superconductivity theories.Comment: 37 pages, 18 figure

Lattice Boltzmann simulations in microfluidics: probing the no-slip boundary condition in hydrophobic, rough, and surface nanobubble laden microchannels

In this contribution we review recent efforts on investigations of the effect of (apparent) boundary slip by utilizing lattice Boltzmann simulations. We demonstrate the applicability of the method to treat fundamental questions in microfluidics by investigating fluid flow in hydrophobic and rough microchannels as well as over surfaces covered by nano- or microscale gas bubbles.Comment: 11 pages, 6 figure

Controls on gut phosphatisation : the trilobites from the Weeks Formation Lagerstätte (Cambrian; Utah)

Despite being internal organs, digestive structures are frequently preserved in Cambrian Lagerstätten. However, the reasons for their fossilisation and their biological implications remain to be thoroughly explored. This is particularly true with arthropods--typically the most diverse fossilised organisms in Cambrian ecosystems--where digestive structures represent an as-yet underexploited alternative to appendage morphology for inferences on their biology. Here we describe the phosphatised digestive structures of three trilobite species from the Cambrian Weeks Formation Lagerstätte (Utah). Their exquisite, three-dimensional preservation reveals unique details on trilobite internal anatomy, such as the position of the mouth and the absence of a differentiated crop. In addition, the presence of paired pygidial organs of an unknown function is reported for the first time. This exceptional material enables exploration of the relationships between gut phosphatisation and the biology of organisms. Indeed, soft-tissue preservation is unusual in these fossils as it is restricted to the digestive structures, which indicates that the gut played a central role in its own phosphatisation. We hypothesize that the gut provided a microenvironment where special conditions could develop and harboured a source of phosphorus. The fact that gut phosphatization has almost exclusively been observed in arthropods could be explained by their uncommon ability to store ions (including phosphorous) in their digestive tissues. However, in some specimens from the Weeks Formation, the phosphatisation extends to the entire digestive system, suggesting that trilobites might have had some biological particularities not observed in modern arthropods. We speculate that one of them might have been an increased capacity for ion storage in the gut tissues, related to the moulting of their heavily-mineralised carapace