Theory of traveling filaments in bistable semiconductor structures

We present a generic nonlinear model for current filamentation in semiconductor structures with S-shaped current-voltage characteristics. The model accounts for Joule self-heating of a current density filament. It is shown that the self-heating leads to a bifurcation from static to traveling filament. Filaments start to travel when increase of the lattice temperature has negative impact on the cathode-anode transport. Since the impact ionization rate decreases with temperature, this occurs for a wide class of semiconductor systems whose bistability is due to the avalanche impact ionization. We develop an analytical theory of traveling filaments which reveals the mechanism of filament motion, find the condition for bifurcation to traveling filament, and determine the filament velocity.Comment: 13 pages, 5 figure

Drilling characteristics and properties analysis of fiber reinforced polymer composites: A comprehensive review

Fiber-reinforced polymer (FRP) composites play a vital role in the production of structural and semi-structural components for engineering applications. The drilling process is a commonly employed machining process for FRP composites to join the FRP structural elements. Usually, the FRP composites possess a heterogeneous nature because of their multi-layered structure, hybridization, and the presence of multi-phase materials. Hence, common problems like delaminations, fuzzing, buckling, cracking, matrix and fiber burning occur during the drilling operations. These problems cause dimensional inaccuracy, poor surface finish, and tool wear and reduce the mechanical strength of the composites. The optimum drilling parameters (drill geometry, speed, feed, and depth of cut) selection for the specific materials is good to achieve effective drilling performance and better surface quality of the holes. Yet, little study has been done on how all of these factors affect the size of the drilled hole. The majority of drilling studies on FRPCs in the past have focused on how to improve the hole quality by maximizing processing conditions, and there has been little discussion on the correlation between drilling conditions, physical properties, and production techniques. This is what motivated to review the characteristics and properties analysis of FRP composites. As a consequence of this research, it is anticipated that scientists and researchers would place a greater emphasis on the drilling characteristic of the workpieces made from FRPCs than on other attributes. This review clearly presents an overview of FRP composites drilling that had progressed from 2000 to 2021. The analysis of different drilling conditions and parameters like thrust force, drill geometry, temperature, speed, and feed also includes the post-drilling analysis through delaminations, thermal damage, and surface roughness. Furthermore, the recent developments in carbon, glass, and natural fiber reinforced polymer composites are studied with both conventional and nonconventional drilling techniques. Based on the above studies, some future challenges and conclusions are drawn from this review

The short bowel syndrome in children: peculiarities of etiopathogenesis, clinical signs and treatment (analysis of literature and own observations)

The short bowel syndrome in children: peculiarities of etiopathogenesis, clinical signs and treatment (analysis of literature and own observations

Breathing Current Domains in Globally Coupled Electrochemical Systems: A Comparison with a Semiconductor Model

Spatio-temporal bifurcations and complex dynamics in globally coupled intrinsically bistable electrochemical systems with an S-shaped current-voltage characteristic under galvanostatic control are studied theoretically on a one-dimensional domain. The results are compared with the dynamics and the bifurcation scenarios occurring in a closely related model which describes pattern formation in semiconductors. Under galvanostatic control both systems are unstable with respect to the formation of stationary large amplitude current domains. The current domains as well as the homogeneous steady state exhibit oscillatory instabilities for slow dynamics of the potential drop across the double layer, or across the semiconductor device, respectively. The interplay of the different instabilities leads to complex spatio-temporal behavior. We find breathing current domains and chaotic spatio-temporal dynamics in the electrochemical system. Comparing these findings with the results obtained earlier for the semiconductor system, we outline bifurcation scenarios leading to complex dynamics in globally coupled bistable systems with subcritical spatial bifurcations.Comment: 13 pages, 11 figures, 70 references, RevTex4 accepted by PRE http://pre.aps.or

Rescue of Photoreceptor Degeneration by Curcumin in Transgenic Rats with P23H Rhodopsin Mutation

The P23H mutation in the rhodopsin gene causes rhodopsin misfolding, altered trafficking and formation of insoluble aggregates leading to photoreceptor degeneration and autosomal dominant retinitis pigmentosa (RP). There are no effective therapies to treat this condition. Compounds that enhance dissociation of protein aggregates may be of value in developing new treatments for such diseases. Anti-protein aggregating activity of curcumin has been reported earlier. In this study we present that treatment of COS-7 cells expressing mutant rhodopsin with curcumin results in dissociation of mutant protein aggregates and decreases endoplasmic reticulum stress. Furthermore we demonstrate that administration of curcumin to P23H-rhodopsin transgenic rats improves retinal morphology, physiology, gene expression and localization of rhodopsin. Our findings indicate that supplementation of curcumin improves retinal structure and function in P23H-rhodopsin transgenic rats. This data also suggest that curcumin may serve as a potential therapeutic agent in treating RP due to the P23H rhodopsin mutation and perhaps other degenerative diseases caused by protein trafficking defects

Progressive Neurodegeneration or Endogenous Compensation in an Animal Model of Parkinson's Disease Produced by Decreasing Doses of Alpha-Synuclein

The pathological hallmarks of Parkinson's disease (PD) are degeneration of dopamine (DA) neurons of the substantia nigra (SN) and the presence of alpha-synuclein (α-syn)-rich Lewy bodies in DA cells that remain. To model these aspects of the disease, we previously showed that high titer (5.1×10exp12 gp/ml) AAV1/2 driven expression of A53T α-syn in the SN of rats caused nigrostriatal pathology including a loss of DA neurons, but also with toxicity in the GFP control group. In the current study, we evaluate the effects of two lower titers by dilution of the vector (1∶3 [1.7×10exp12] and 1∶10 [5.1×10exp11]) to define a concentration that produced pathology specific for α-syn. In GFP and empty vector groups there were no behavioural or post-mortem changes at 3 or 6 weeks post-administration at either vector dose. Dilution of the AAV1/2 A53T α-syn (1∶3) produced significant paw use asymmetry, reductions in striatal tyrosine hydroxylase (TH), and increases in DA turnover at 3 weeks in the absence of overt pathology. By 6 weeks greater evidence of pathology was observed and included, reductions in SN DA neurons, striatal DA, TH and DA-transporter, along with a sustained behavioural deficit. In contrast, the 1∶10 AAV1/2 A53T α-syn treated animals showed normalization between 3 and 6 weeks in paw use asymmetry, reductions in striatal TH, and increased DA turnover. Progression of dopaminergic deficits using the 1∶3 titer of AAV1/2 A53Tα-syn provides a platform for evaluating treatments directed at preventing and/or reversing synucleinopathy. Use of the 1∶10 titer of AAV1/2 A53T α-syn provides an opportunity to study mechanisms of endogenous compensation. Furthermore, these data highlight the need to characterize the titer of vector being utilized, when using AAV to express pathogenic proteins and model disease process, to avoid producing non-specific effects

Molecular Mechanism of the Constitutive Activation of the L250Q Human Melanocortin-4 Receptor Polymorphism †

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65471/1/j.1747-0285.2006.00362.x.pd

Model-Based Deconvolution of Cell Cycle Time-Series Data Reveals Gene Expression Details at High Resolution

In both prokaryotic and eukaryotic cells, gene expression is regulated across the cell cycle to ensure “just-in-time” assembly of select cellular structures and molecular machines. However, present in all time-series gene expression measurements is variability that arises from both systematic error in the cell synchrony process and variance in the timing of cell division at the level of the single cell. Thus, gene or protein expression data collected from a population of synchronized cells is an inaccurate measure of what occurs in the average single-cell across a cell cycle. Here, we present a general computational method to extract “single-cell”-like information from population-level time-series expression data. This method removes the effects of 1) variance in growth rate and 2) variance in the physiological and developmental state of the cell. Moreover, this method represents an advance in the deconvolution of molecular expression data in its flexibility, minimal assumptions, and the use of a cross-validation analysis to determine the appropriate level of regularization. Applying our deconvolution algorithm to cell cycle gene expression data from the dimorphic bacterium Caulobacter crescentus, we recovered critical features of cell cycle regulation in essential genes, including ctrA and ftsZ, that were obscured in population-based measurements. In doing so, we highlight the problem with using population data alone to decipher cellular regulatory mechanisms and demonstrate how our deconvolution algorithm can be applied to produce a more realistic picture of temporal regulation in a cell

α-Synuclein Suppression by Targeted Small Interfering RNA in the Primate Substantia Nigra

The protein α-synuclein is involved in the pathogenesis of Parkinson's disease and other neurodegenerative disorders. Its toxic potential appears to be enhanced by increased protein expression, providing a compelling rationale for therapeutic strategies aimed at reducing neuronal α-synuclein burden. Here, feasibility and safety of α-synuclein suppression were evaluated by treating monkeys with small interfering RNA (siRNA) directed against α-synuclein. The siRNA molecule was chemically modified to prevent degradation by exo- and endonucleases and directly infused into the left substantia nigra. Results compared levels of α-synuclein mRNA and protein in the infused (left) vs. untreated (right) hemisphere and revealed a significant 40–50% suppression of α-synuclein expression. These findings could not be attributable to non-specific effects of siRNA infusion since treatment of a separate set of animals with luciferase-targeting siRNA produced no changes in α-synuclein. Infusion with α-synuclein siRNA, while lowering α-synuclein expression, had no overt adverse consequences. In particular, it did not cause tissue inflammation and did not change (i) the number and phenotype of nigral dopaminergic neurons, and (ii) the concentrations of striatal dopamine and its metabolites. The data represent the first evidence of successful anti-α-synuclein intervention in the primate substantia nigra and support further development of RNA interference-based therapeutics

Cell Size and the Initiation of DNA Replication in Bacteria

In eukaryotes, DNA replication is coupled to the cell cycle through the actions of cyclin-dependent kinases and associated factors. In bacteria, the prevailing view, based primarily from work in Escherichia coli, is that growth-dependent accumulation of the highly conserved initiator, DnaA, triggers initiation. However, the timing of initiation is unchanged in Bacillus subtilis mutants that are ∼30% smaller than wild-type cells, indicating that achievement of a particular cell size is not obligatory for initiation. Prompted by this finding, we re-examined the link between cell size and initiation in both E. coli and B. subtilis. Although changes in DNA replication have been shown to alter both E. coli and B. subtilis cell size, the converse (the effect of cell size on DNA replication) has not been explored. Here, we report that the mechanisms responsible for coordinating DNA replication with cell size vary between these two model organisms. In contrast to B. subtilis, small E. coli mutants delayed replication initiation until they achieved the size at which wild-type cells initiate. Modest increases in DnaA alleviated the delay, supporting the view that growth-dependent accumulation of DnaA is the trigger for replication initiation in E. coli. Significantly, although small E. coli and B. subtilis cells both maintained wild-type concentration of DnaA, only the E. coli mutants failed to initiate on time. Thus, rather than the concentration, the total amount of DnaA appears to be more important for initiation timing in E. coli. The difference in behavior of the two bacteria appears to lie in the mechanisms that control the activity of DnaA