The Y-box binding protein 1 (YB-1) is a member of the family of DNA- and RNA binding proteins. It is involved in a wide variety of DNA/RNA-dependent events including cell proliferation and ...differentiation, stress response, and malignant cell transformation. Previously, YB-1 was detected in neurons of the neocortex and hippocampus, but its precise role in the brain remains undefined. Here we show that subchronic intranasal injections of recombinant YB-1, as well as its fragment YB-11-219, suppress impairment of spatial memory in olfactory bulbectomized (OBX) mice with Alzheimer's type degeneration and improve learning in transgenic 5XFAD mice used as a model of cerebral amyloidosis. YB-1-treated OBX and 5XFAD mice showed a decreased level of brain β-amyloid. In OBX animals, an improved morphological state of neurons was revealed in the neocortex and hippocampus; in 5XFAD mice, a delay in amyloid plaque progression was observed. Intranasally administered YB-1 penetrated into the brain and could enter neurons. In vitro co-incubation of YB-1 with monomeric β-amyloid (1-42) inhibited formation of β-amyloid fibrils, as confirmed by electron microscopy. This suggests that YB-1 interaction with β-amyloid prevents formation of filaments that are responsible for neurotoxicity and neuronal death. Our data are the first evidence for a potential therapeutic benefit of YB-1 for treatment of Alzheimer's disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
Spastic paraplegia type 30 (SPG30) caused by
KIF1A
mutations was first reported in 2011 and was initially considered a very rare autosomal recessive (AR) form. In the last years, ...thanks to the development of massive parallel sequencing, SPG30 proved to be a rather common autosomal dominant (AD) form of familial or sporadic spastic paraplegia (SPG),, with a wide range of phenotypes: pure and complicated. The aim of our study is to detect AD SPG30 cases and to examine their molecular and clinical characteristics for the first time in the Russian population.
Methods
Clinical, genealogical and molecular methods were used. Molecular methods included massive parallel sequencing (MPS) of custom panel ‘spastic paraplegias’ with 62 target genes complemented by familial Sanger sequencing. One case was detected by the whole -exome sequencing.
Results
AD SPG30 was detected in 10 unrelated families, making it the 3rd (8.4%) most common SPG form in the cohort of 118 families. No AR SPG30 cases were detected. In total, 9 heterozygous
KIF1A
mutations were detected, with 4 novel and 5 known mutations. All the mutations were located within
KIF1A
motor domain. Six cases had pure phenotypes, of which 5 were familial, where 2 familial cases demonstrated incomplete penetrance, early onset and slow relatively benign SPG course. All 4 complicated cases were caused by novel mutations without familial history. The phenotypes varied from severe in two patients (e.g. lack of walking, pronounced mental retardation) to relatively mild non-disabling symptoms in two others.
Conclusion
AD SPG30 is one of the most common forms of SPG in Russia, the disorder has pronounced clinical variability while pure familial cases represent a significant part.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Influence of dust void on neon DC discharge Shumova, V V; Polyakov, D N; Vasilyak, L M
Plasma sources science & technology,
02/2017, Letnik:
26, Številka:
3
Journal Article
Recenzirano
The diffusion/drift model of the positive column of glow discharge in neon with fine dust particles was used to study the role of a dust cloud with a void in the interaction between plasma and dust ...particles in the range of neon pressure and discharge current where dust particles may form structures with cavities. The results represent the nonlocal effect of void size on plasma composition, configuration of electric field and on distributions of plasma components in discharge with voids in dust structures. Simulations show that the electric field strength and the metastable atom concentration inside the void are higher than in the discharge without dust particles, while electron concentration may be either higher or lower.
Abstract
We consider the efficiency of an ion confinement inside a cloud of charged microparticles in a low-pressure DC discharge. To describe the ion confinement efficiency in such complex plasma, ...we propose the indicators calculated taking into account the processes responsible for the generation, the losses, and the accumulation of ions in a cloud of charged microparticles in a plasma using a fluid model. The efficiency of ion accumulation by a microparticle cloud shows the ratio of the average ion densities in discharge with microparticles and without them. The efficiency of ion accumulation by a microparticle shows the difference of average ion densities in a discharge with microparticles and without them, related to microparticle number density. The specific power costs of the existence of one ion in a microparticle cloud determines the linear power costs of the discharge in a cloud related to the linear number of ions in it. The power efficiency of ion accumulation by a microparticle cloud is defined as a ratio of specific power costs in a discharge without microparticles, to specific power costs of ion existence in a cloud. A strong dependence of indicators on the microparticle number density has been revealed. Inefficient conditions of ion confinement inside a cloud are found. Experimental data on dynamic instabilities of a discharge with microparticles was analyzed. It is found that efficiency of ion confinement is connected with dynamic processes in complex plasma. The limiting microparticle number density is shown to serve as the criterion of the occurrence of plasma instability. Exceeding the limiting microparticle number density results, generally, in the development of dynamic instability of complex plasma, and, in inefficient states, in quenching of the discharge.
The results of the measurement and simulation of electrical characteristics of neon dc discharge are presented. These results have been obtained in the discharge cooled to the temperature of liquid ...nitrogen (77 K). The experiments were carried out at a neon pressure of 18-187 Pa and a discharge current of 0.01-3.5 mA. Cooling in the subnormal discharge mode at a constant value of discharge current led to a change in the discharge mode. When cooled, the electric field in the positive column and at the boundary of the transition to the normal discharge increased, and the reduced electric field decreased in all the investigated ranges of discharge current, pressure and neon concentration. The simulation of the positive column, based on the diffusion-drift (fluid) model, has shown that the input in the ionization of processes involving excited atoms increases with decreasing discharge temperature.
In this work, we study the effectiveness of common hyperparameter optimization (HPO) methods for physics-informed neural networks (PINNs) with an application to the multidimensional Helmholtz ...problem. The network was built using the PyTorch framework without the use of specialized PINN-oriented libraries. We investigate the effect of hyperparameters on the NN model’s performance and conduct automatic hyperparameter optimization using different combinations of search algorithms and trial schedulers. We chose the open-source HPO framework, Ray Tune, which provides a unified interface for many HPO packages, as our HPO tool. We consider two search algorithms: random search and the Bayesian method based on the tree-structured Parzen estimator (TPE), in implementations by hyperopt and hpbandster, along with the asynchronous successive halving (ASHA) early-stopping algorithm. For our problem, enabling the early-stopping algorithm is shown to achieve faster HPO convergence speed than switching from random search to the Bayesian method.
An analysis of the formation of a void in the PK3 setup in dusty plasma with 3.4-μm-diameter melamine–formaldehyde particles—in an RF discharge in argon at a pressure of 12–50 Pa under microgravity ...conditions at the ISS is presented. The uniform state of the plasma can only be obtained at a voltage close to the discharge extinction voltage. The application of a low-frequency voltage of 20–50 Hz stabilizes the state of the dusty plasma and shifts the void formation threshold towards higher RF voltages. It is shown that the formation of a void is associated with non-local ionization of the plasma at the center of the discharge by fast electrons, which are heated in the near-electrode layers.
Dense dust structures have been observed in a glow DC discharge in neon at a temperature of 77 K. Dependencies of shape, axial and radial sizes of dust structures on discharge current, gas pressure ...and longitudinal electric field have been studied. At the intersection points of dependencies of radial and axial sizes of dust structures on discharge current, the Coulomb balls have been observed at pressures between 0.15 and 1.2 Torr. The correlation between the discharge parameters, at which Coulomb balls form, and their size, composition, phase and dynamic state of components has been revealed.
The dependence of the shape of the dust structures on discharge current and pressure in neon glow DC discharge at temperatures 77 K and 295 has been studied experimentally. It was found that when the ...discharge current was increased, the radial size of the dust cloud increased, and the axial size decreased. It was found that at 295 the dust clouds were formed by individual dust particles, while at 77 K they consisted of a mixture of dust particles and simplest threadlike clusters formed from dust particles. The decrease of gas pressure led to increase in distances between the dust particles and clusters, and reduced the dynamic stability of the dust particles and clusters. At 295 an increase of the discharge current resulted in the formation of voids in dust structures, while at 77 K the formation of the dust structures with voids was not observed even at maximum discharge currents. The formation of clusters at cryogenic cooling can be interpreted as 'condensation' and 'deposition' of dust particles.
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