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

СУЧАСНІ ПІДХОДИ ДО ДІАГНОСТИКИ І ХІРУРГІЧНОГО ЛІКУВАННЯ ХВОРОБИ ГІРШПРУНГА У ДІТЕЙ РАННЬОГО ВІКУ

Мета – вивчити діагностичну значущість інструментальних, морфологічних і гістохімічних методів дослідження при вроджених вадах розвитку товстої кишки у дітей та їх роль у визначенні хірургічної тактики. Об’єкт і методи дослідження. Обстежено 847 пацієнтів з хронічними закрепами і іншими розладами ШКТ в період з 2007 до 2016 року. З них 119 (14,05%) дітей мали вроджені вади розвитку, серед яких хвороба Гіршпрунга склала 36,13%. Для контролю ефективності діагностики та лікування дітей з ХГ визначали клінічні, інструментальні, морфологічні і гістохімічні показники до і після лікування. Результати та їх обговорення. За результатами проведеного діагностичного пошуку було виявлено 36,13% пацієнтів з ХГ, 45,38% - з іншими дисгангліозами товстої кишки (інтестинальна дисплазія типу А і В, гіпогангліоз, незрілість гангліонарних клітин), 2,52% муковісцидозів і 15,97% дітей з іншою вродженою патологією. Визначено, що точність діагностики ВВР товстої кишки у дітей підвищується завдяки проведенню гістологічних і гістохімічних досліджень біопсійного клінічного матеріалу ураженої кишки. Іригографія і інтраопераційна візуальна оцінка ураженого кишкового сегменту є не точними діагностичними заходами і нерідко призводять до помилок у визначенні меж резекції кишки. Висновки. 1. Попередній діагноз ВВР товстої кишки, зокрема хвороби Гіршпрунга, встановлюється за результатами контрастної іригографії, яка не завжди є достовірною, особливо у новонароджених і немовлят. 2. Основним методом діагностики ХГ , крім анамнезу, клініки, іригографії, є гістологічне дослідження біопсійного матеріалу ураженого сегменту кишки. 3. Ефективність хірургічної допомоги дітям з ХГ підвищується завдяки своєчасній верифікації діагнозу на морфологічному і гістохімічному рівнях. Патоморфологами має бути верифікована і транзитна зона. 4. Комплексне застосування рентгенологічного, морфологічного і гістохімічного методів обстеження дозволяє своєчасно встановити діагноз ХГ у дітей майже зі 100% достовірністю і застосувати адекватну хірургічну тактику, включаючи визначення меж зони резекції

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

Limited effect of chronic valproic acid treatment in a mouse model of Machado-Joseph disease

Machado-Joseph disease (MJD) is an inherited neurodegenerative disease, caused by a CAG repeat expansion within the coding region of ATXN3 gene, and which currently lacks effective treatment. In this work we tested the therapeutic efficacy of chronic treatment with valproic acid (VPA) (200mg/kg), a compound with known neuroprotection activity, and previously shown to be effective in cell, fly and nematode models of MJD. We show that chronic VPA treatment in the CMVMJD135 mouse model had limited effects in the motor deficits of these mice, seen mostly at late stages in the motor swimming, beam walk, rotarod and spontaneous locomotor activity tests, and did not modify the ATXN3 inclusion load and astrogliosis in affected brain regions. However, VPA chronic treatment was able to increase GRP78 protein levels at 30 weeks of age, one of its known neuroprotective effects, confirming target engagement. In spite of limited results, the use of another dosage of VPA or of VPA in a combined therapy with molecules targeting other pathways, cannot be excluded as potential strategies for MJD therapeuticsPM received funding from Ataxia UK Grant (Project: Pharmacologic therapy for Machado-Joseph disease: from a C. elegans drug screen to a mouse model validation). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.info:eu-repo/semantics/publishedVersio

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

Protein misfolding and dysregulated protein homeostasis in autoinflammatory diseases and beyond.

Cells have a number of mechanisms to maintain protein homeostasis, including proteasome-mediated degradation of ubiquitinated proteins and autophagy, a regulated process of ‘self-eating’ where the contents of entire organelles can be recycled for other uses. The unfolded protein response prevents protein overload in the secretory pathway. In the past decade, it has become clear that these fundamental cellular processes also help contain inflammation though degrading pro-inflammatory protein complexes such as the NLRP3 inflammasome. Signaling pathways such as the UPR can also be co-opted by toll-like receptor and mitochondrial reactive oxygen species signaling to induce inflammatory responses. Mutations that alter key inflammatory proteins, such as NLRP3 or TNFR1, can overcome normal protein homeostasis mechanisms, resulting in autoinflammatory diseases. Conversely, Mendelian defects in the proteasome cause protein accumulation, which can trigger interferon-dependent autoinflammatory disease. In non-Mendelian inflammatory diseases, polymorphisms in genes affecting the UPR or autophagy pathways can contribute to disease, and in diseases not formerly considered inflammatory such as neurodegenerative conditions and type 2 diabetes, there is increasing evidence that cell intrinsic or environmental alterations in protein homeostasis may contribute to pathogenesis

Post translational changes to α-synuclein control iron and dopamine trafficking : a concept for neuron vulnerability in Parkinson's disease

Parkinson's disease is a multifactorial neurodegenerative disorder, the aetiology of which remains elusive. The primary clinical feature of progressively impaired motor control is caused by a loss of midbrain substantia nigra dopamine neurons that have a high α-synuclein (α-syn) and iron content. α-Syn is a neuronal protein that is highly modified post-translationally and central to the Lewy body neuropathology of the disease. This review provides an overview of findings on the role post translational modifications to α-syn have in membrane binding and intracellular vesicle trafficking. Furthermore, we propose a concept in which acetylation and phosphorylation of α-syn modulate endocytic import of iron and vesicle transport of dopamine during normal physiology. Disregulated phosphorylation and oxidation of α-syn mediate iron and dopamine dependent oxidative stress through impaired cellular location and increase propensity for α-syn aggregation. The proposition highlights a connection between α-syn, iron and dopamine, three pathological components associated with disease progression in sporadic Parkinson's disease

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

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

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