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We compared the efficacy and safety of eltrombopag (ELTR) combined with immunosuppressive therapy (IST) and IST alone in treatment-naïve children with severe (SAA) and very severe (vSAA) aplastic anemia. Ninety-eight pediatric patients were randomized to receive horse antithymocyte globulin (hATG) and cyclosporin A (CsA) with (n = 49) or without (n = 49) ELTR. The primary endpoint was the overall response rate (ORR) at 4 months. After 4 months, nonresponders were crossed over to the alternative group. In all patients, the ORR in ELTR + IST and IST groups was similar (65% vs 53%; P = .218); however, the complete response (CR) rate was significantly higher in the ELTR + IST group (31% vs 12%; P = .027). In severity subgroups, the ORR was 89% vs 57% (P = .028) in favor of IST + ELTR in SAA, but it did not differ in patients with vSAA (52% vs 50%; P = .902). At 6 months after the crossover, 61% of initial ELTR(−) patients achieved a response compared with 17% of initial ELTR(+) patients (P = .016). No significant difference in ELTR + IST and IST groups was observed in the 3-year overall survival (OS) (89% vs 91%; P = .673) or the 3-year event-free survival (EFS) (53% vs 41%; P = .326). There was no unexpected toxicity related to ELTR. Adding ELTR to standard IST was well tolerated and increased the CR rate. The greatest benefit from ELTR combined with IST was observed in patients with SAA but not in those with vSAA. The second course of IST resulted in a high ORR in initial ELTR(−) patients who added ELTR and had limited efficacy among patients who received ELTR upfront. This trial was registered at Clinicaltrials.gov as #NCT03413306.

The radiation of a vacuum arc was measured in the spectral region $200~\text {nm} \le \lambda \le 1100$ nm. The arc was initiated in the center of the cathode by breaking the current in the auxiliary circuit and was fed by the rectangular current pulse with a duration of 10 ms. The interelectrode gap was fixed at $h = 4$ mm, and the butt $2r =30$ -mm CuCr30 electrodes were used. The arc was stabilized by an external uniform axial magnetic field (AMF). The radiation was coming out of the vacuum chamber through quartz ultraviolet (KU)-1 quartz window. The radiation detector was a silicon photodiode with a diameter of $d =1.2$ mm. It was located on an axis intersecting the axis of symmetry of the discharge in the center of the interelectrode gap. The distance from the diode to the axis of symmetry was $L =1340$ mm. After amplification, the signal from the diode was recorded on an oscilloscope. The measurements were made in a range of currents from 10 to 25 kA in order to cover the modes with the anodic activity. It was found that under the conditions of these experiments, the anode activity begins to manifest itself at the end of the pulse, starting with currents exceeding 15 kA. As the current increases, the activity begins closer to the beginning of the pulse. Considering the type of the spectral sensitivity of the diode, two series of measurements were made—measurements without a filter and through a yellow filter ZhS-10 that cuts off radiation with $\lambda \le400$ nm. The results obtained made it possible to analyze the dependence of the radiation power on the arc current. The results showed that at high current densities in the developed vacuum arc with anodic activity, a significant part of the power is transferred by radiation. At the end of a pulse with a current of $\approx 25$ kA, the radiation power is $P_{\mathrm {uv}}~\approx ~150$ kW, while in the discharge, $P_{a} ~\approx ~800$ kW is released. That is, at high current densities at the end of the pulse, the radiation power reaches almost 20% of the power released in the arc at this time. Estimates of lateral losses due to radiation are made.

A pilot post-mortem study identifies a strong correlation between the attenuation coefficient estimated from the OCT data and some morphological features of the sample, namely the number of nuclei in the field of view of the histological image and the fiber structural parameter introduced in the study to quantify the difference in the myelinated fibers arrangements. The morphological features were identified from the histopathological images of the sample taken from the same locations as the OCT images and stained with the immunohistochemical (IHC) staining specific to the myelin. It was shown that the linear regression of the IHC quantitative characteristics allows adequate prediction of the attenuation coefficient of the sample. This discovery opens the opportunity for the usage of the OCT as a neuronavigation tool.

Nanosized films with ferromagnetic layers are widely used in nanoelectronics, sensor systems and telecommunications. Their properties may strongly differ from those of bulk materials that is on account of interfaces, intermediate layers and diffusion. In the present work, spectral ellipsometry and magnetooptical methods are adapted for characterization of the optical parameters and magnetization processes in two- and three-layer Cr/NiFe, Al/NiFe and Сr(Al)/Ge/NiFe films onto a sitall substrate for various thicknesses of Cr and Al layers. At a layer thickness below 20 nm, the complex refractive coefficients depend pronouncedly on the thickness. In two-layer films, remagnetization changes weakly over a thickness of the top layer, but the coercive force in three-layer films increases by more than twice upon remagnetization, while increasing the top layer thickness from 4 to 20 nm.

Recrystallization is a major means for controlling the grain size of steel during hot deformation. Usually, small grain sizes deliver superior mechanical properties. To aid the grain size controlling effect of recrystallization, small precipitates of carbo-nitride particles can be utilized to hinder the movement of grain boundaries. Interestingly, these particles are not only effective during grain growth, but also during recrystallization. In the present work, a recently developed state-parameter based model is introduced that is capable of describing both, the individual processes of static recrystallization, dynamic and static recovery and precipitation as well as the mutual interaction of these mechanisms in the course of elevated temperature processing. The evolution of state parameters within the model is discussed and the simulation results are compared to experimental information. Within our approach, a vast amount of experimental data for microalloyed steel is reproduced on basis of a single set of input parameters

RNA-seq is now the technology of choice for genome-wide differential gene expression experiments, but it is not clear how many biological replicates are needed to ensure valid biological interpretation of the results or which statistical tools are best for analyzing the data. An RNA-seq experiment with 48 biological replicates in each of two conditions was performed to answer these questions and provide guidelines for experimental design. With three biological replicates, nine of the 11 tools evaluated found only 20%–40% of the significantly differentially expressed (SDE) genes identified with the full set of 42 clean replicates. This rises to >85% for the subset of SDE genes changing in expression by more than fourfold. To achieve >85% for all SDE genes regardless of fold change requires more than 20 biological replicates. The same nine tools successfully control their false discovery rate at ≲5% for all numbers of replicates, while the remaining two tools fail to control their FDR adequately, particularly for low numbers of replicates. For future RNA-seq experiments, these results suggest that at least six biological replicates should be used, rising to at least 12 when it is important to identify SDE genes for all fold changes. If fewer than 12 replicates are used, a superior combination of true positive and false positive performances makes edgeRand DESeq2the leading tools. For higher replicate numbers, minimizing false positives is more important and DESeqmarginally outperforms the other tools.

The low-frequency effective permittivity of island metal films has been investigated as a function of the frequency of the electric field. It has been found that the low-frequency effective permittivity has a complex dependence on the measuring electric field frequency. It has been shown that, at the electric field frequency f= 1 kHz, the permittivity has a positive sign (ε ≈ 108). With an increase in the electric field frequency, the permittivity decreases, and in the single-layer FeNi film with a thickness d= 8 Å at a frequency f≈ 10 kHz, it is equal to zero (ε ≈ 0). With a further increase in the electric field frequency, the permittivity becomes negative and, at a frequency f= 100 kHz, reaches the value ε ≈–108. It has been established that an increase in the effective permittivity of island metal films with a decrease in the electric field frequency is associated with the activation or tunneling processes in island films.

The structures and electroluminescence characteristics of new two types of single mode A3B5semiconductor tunable lasers in the 1.8-3.9 µm spectral range have been demonstrated. The first type of tunable diode laser based on quaternary solid solutions GaInAsSb and GaAlAsSb lattice matched to GaSb substrate covers 1.8-2.4 µm spectral range. Such tunable 1.8-2.4 µm lasers have single mode or quasi- single mode operation in the wide temperature range from 1.6 to 300K. The second type of tunable diode laser based on multiple component InPAsSb/InAsSb lattice matched or mismatched to InAs substrate covers 2.8-3.9 µm spectral range, which was not available for diode laser specroscopy until nowadays. Such tunable 2.8-3.9 µm lasers have CW single mode operation up to 100K and pulse operation up to 180K. These lasers can be the key devices for diode laser spectroscopy and sensitive detection of pollutants.

In the present work we develop a physically based model of strength evolution during hot deformation of Al-Mg-Si alloys. The goal is to predict a change of material strength taking into account the impact of microchemistry, i.e. the influence of solutes and precipitates on strengthening and softening mechanisms. The material strengthening is considered in the present work in terms of solid solution strengthening (the Labusch-Naborro model), work hardening (the advanced one-parameter Kocks model), as well as precipitation strengthening due to the stress contribution of non-deformable particles, i.e. dispersoids (the Orowan by-pass). The material softening is described by dynamic recovery through thermal activation of dislocation climb. For the precipitation kinetics the computational thermodynamics code MatCalc (Materials Calculator) was used. The model was validated by comparison with experimental data of compression tests of the 6xxx series aluminium alloys and a reasonable agreement of the simulated and measured flow stress curves was found.

Friction stir spot welding (FSSW) as a variant of the linear friction stir welding is implemented in automotive industry as a partial replacement of resistance spot welding for aluminium. FSSW as a solid state joining technology, primarily takes advantage of severe thermoplastic deformation, to achieve the joining between two parts, which can be from the same material or even dissimilar. In this paper, the coupled thermo-mechanical viscoplastic finite element formulation is presented based on the character of FSSW. The model was calibrated by comparing temperature history obtained from the simulation with experimental data and subsequently used to investigate the effective strain distribution in the weld zone as well as the material flow and the shape of the stir zone.

Abstract: New magnetic structures such as multilayer systems of magnetic nanoislands being alternating layers of nanoislands of various magnets have been proposed. The electric, magnetic, and magnetooptical properties of the systems have been studied. The magnetoresistance of ∼2% related to the anisotropic effect has been revealed. In multilayer structures of magnetic nanoislands, a unidirectional axis of predominant magnetization has been found, which changes its orientation depending on the structure parameters. The magnetic field required to reorient the axis in the opposite direction has been estimated to be 2 kOe < H A < 20 kOe. The periodic multilayer structures of magnetic nanoislands are very sensitive to hyperweak magnetic fields (to 10−6 Oe).

Process parameters in aluminium extrusion technology are key points that influence product properties. The precipitation hardening aluminium alloy 6082 is investigated according to different process conditions and the influence onto the final microstructure is simulated as well as experimentally verified. A physical microstructure model based on three dislocation types and three nucleation sites for recrystallization is implemented into the commercial Finite Element package FORGE 2008 to calculate both the microstructure evolution during the extrusion process as well as the recrystallized fraction after the process. The precipitation kinetics during homogenization was investigated using the thermodynamic calculation software MatCalc since the main nucleation mechanism for recrystallization is particle stimulated. The experimental validation was done by miniature extrusion tests and the microstructure was investigated metallographically and by EBSD measurements.

We compared the efficacy and safety of eltrombopag (ELTR) combined with immunosuppressive therapy (IST) and IST alone in treatment-naïve children with severe (SAA) and very severe (vSAA) aplastic anemia. Ninety-eight pediatric patients were randomized to receive horse antithymocyte globulin and cyclosporin A with (n=49) or without (n=49) ELTR. The primary endpoint was the overall response rate (ORR) at 4 months. After 4 months, nonresponders were crossed over to the alternative group. In all patients, the ORR in ELTR+IST and IST groups was similar (65% vs. 53%, p=0.218); however, the complete response (CR) rate was significantly higher in ELTR+IST group (31% vs. 12%, p=0.027). In severity subgroups, the ORR was 89% vs. 57% (p=0.028) in favor of IST+ELTR in SAA, but it did not differ in patients with vSAA (52% vs. 50%, p=0.902). At 6 months after the crossover, 61% of initial ELTR(-) patients achieved a response compared to 17% of initial ELTR(+) patients (p=0.016). No significant difference in ELTR+IST and IST groups was observed in the 3-year OS (89% vs. 91%, p=0.673) or the 3-year EFS (53% vs. 41%, p=0.326). There was no unexpected toxicity related to ELTR. Adding ELTR to standard IST was well tolerated and increased the CR rate. The greatest benefit from ELTR combined with IST was observed in patients with SAA, but not in those with vSAA. The second course of IST resulted in a high ORR in initial ELTR(-) patients who added ELTR and had limited efficacy among patients who received ELTR upfront. Clinicaltrials.gov#NCT03413306.

There are many applications for mid-infrared light sources which has stimulated intensive research into the physics and technology of narrow gap materials and devices. In this article we give an overview of the development of mid-infrared LEDs and diode lasers being studied in our laboratory. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

The neuroprotective effect of Thr-Gly-Glu-Asn-His-Arg hexapeptide (HLDF-6), a biologically active fragment of the differentiation factor of human leukemia cells (HLDF), was demonstrated on models of Alzheimer’s disease in vivo and in vitro. The syndromes of this pathology were induced in male rats by injection of beta-amyloid peptide (25–35) and ibotenic acid into the hippocampus. HLDF-6 prevented loss of long-term memory and decrease in the exploratory behavior of these animals and significantly decreased the number of pyknotic neurons in the CA1 area of the hippocampus. This peptide also exerts a protective effect in vitro on the primary cultures of the rat hippocampal and cerebellar neurons under conditions of the beta-amyloid toxicity. An increase in the dihydrotestosterone (DHT) content was demonstrated in the blood plasma of rats with the syndrome of Alzheimer’s disease and in the medium of the culture of hippocampal neurons in the presence of the Aβ(25–35) peptide. HLDF-6 inhibited this increase in both cases. A probable mechanism of the neuroprotective effect of HLDF-6 was suggested as being connected to its possible effect on both the biosynthesis and the metabolism of sex steroid hormones.

Abstract: Effects of homologous peptides HLDF-6 and PEDF-6 on behavior of animals with experimental Alzheimer’s disease induced by chronic intracerebroventricular administration of β-amyloid peptide Aβ(25–35) were studied in the zoosocial recognition test and Morris water maze. Peptides HLDF-6 and PEDF-6 possessed neuroprotective activity and counteracted the toxic effect of Aβ(25–35). Peptides HLDF-6 and PEDF-6 mainly improved long-term memory and working memory, respectively.

Abstract The present report describes in vivo investigations of genome activity and its role in the mechanisms forming long-term synaptic plasticity in defensive behavior command neuron LPl1 during the acquisition of nociceptive sensitization by common snails. Transcription processes were recorded using SYTO 16, a specific fluorescent indicator of DNA activity, along with in vivo computer image analysis. Studies in control snails showed that application of nociceptive stimuli to the head led to biphasic changes in the bioelectrical responses of neurons to tactile and chemical stimulation-depression of responses in the short-term stage (during the 1 h after training) and their facilitation during the long-term stage of sensitization (more than 24 h). There were marked increases in fluorescence over the nucleus of the command neuron stained with SYTO 16 at 15–20 min from the start of training, this lasting 4–5 h. Acquisition of sensitization in the presence of the RNA synthesis inhibitor actinomycin D (20 µM) to the neuron led to the complete elimination of changes in fluorescence and synaptic facilitation in the responses of LPl1 to sensory stimulation in the long-term stage of sensitization but had no effect during the short-term stage of sensitization. Actinomycin D given 30 min after the end of acquisition of sensitization (1 h after the start) had no effect on the dynamics of fluorescence or synaptic facilitation. Thus, the acquisition of nociceptive sensitization is accompanied by a rapid (within 15–20 min) activation of the DNA of neuron LPl1 and subsequent (about 1 h) display of long-term synaptic facilitation. Induction of both processes was suppressed by the RNA synthesis inhibitor over a relatively short time period-1 h from the moment at which training started.

The development of sensitization in edible snails during intracellular injection of oligonucleotides specifically inhibiting C/EBP transcription factors results in selective suppression of synaptic facilitation in responses of LP11 neurons evoked by chemical stimulation of the head. At the same time, facilitation of the responses to tactile stimulation of the head or foot developed as in control sensitized animals. The data are interpreted from the viewpoint of P. K. Anokhin hypothesis that integrative function of cerebral neurons involved in construction of biologic functional systems is based on peculiar pre- and postsynaptic chemical processes selectively projected onto the genome of neural cell.

The effects of antibodies to the serotonin-modulated protein SMP-69 on the activity of defensive behavior command neurons LPl1 and RPl1 in semi-intact preparations from common snails were studied. Antibody to SMP-69 increased membrane excitability and facilitated neuron responses to chemical sensory stimulation by application of dilute quinine solution to the animal's head, these effects being seen at 1–1.5 h. The synaptic effects of the antibodies were specific, as they had no influence on responses induced by tactile stimulation of the head. The neuronal effects of antibody SMP-69 were similar to changes in the activity of cells LPl1 and RPl1 induced by serotonin and cAMP, and to changes seen when snails acquired nociceptive sensitization. It seems likely that a protein homologous to mammalian SMP-69 is involved in the mechanisms controlling excitability and long-term specific plasticity of the synaptic inputs to neurons LPl1 and RPl1 from chemoreceptors on the snail's head.

The spontaneous emission of 3.3 μm light emitting diodes (LEDs) and lasers based on InAs alloys were studied as a function of hydrostatic pressure. An increase in light output with increasing pressure has been observed, with a general comparison of the performances of type I and type II structures given in terms of the radiative and non-radiative processes involved. The experimental results provide evidence that the so-called CHSH Auger process is insignificant in these devices. However, Auger recombination mechanisms are still shown to dominate the response of these type II LEDs in contrast to type I lasers where competing radiative processes appear more significant.

It is proved that if a normal semifinite weight ϕ on a von Neumann algebra $$\mathcal{M}$$ satisfies the inequality $$\phi (|a_1 + a_2 |) \leqslant \phi (|a_1 |) + \phi (|a_2 |)$$ for any selfadjoint operators $$a_1 ,a_2 $$ in $$\mathcal{M}$$ , then this weight is a trace. Several similar characterizations of traces among the normal semifinite weights are proved. In particular, Gardner's result on the characterization of traces by the inequality $$|\phi (a)|{\text{ }} \leqslant {\text{ }}\phi (|a|)$$ is refined and reinforced.

Effects of idiotypic and antiidiotypic antibodies against protein S100b on synaptic transmission and long-term potentiation of CA1 pyramidal neurons in rat hippocampus were studied. Idiotypic antibodies against protein S100b inhibited synaptic transmission from Schaffer collateral axons to pyramidal neurons, but had no effect on neuronal responses to antidromic stimulation. Antiidiotypic antibodies against protein S100b facilitated neuronal responses to orthodromic stimulation. Idiotypic antibodies against protein S100b suppressed changes in neuronal responses to orthodromic stimulation during long-term potentiation, while antiidiotypic antibodies facilitated these effects. Our findings suggest that the effects of idiotypic and antiidiotypic antibodies to protein S100b are associated with their regulatory influences on synaptic transmission. These mechanisms differ from mechanisms of synaptic plasticity involved in long-term potentiation.

The effects of antibodies to a total fraction of s100 proteins and protein s100b on the activity of defensive behavior command neurons LPl1 and RPl1 were studied in common snails, using non-sensitized animals and animals which had acquired nociceptive sensitization. In non-sensitized snails, application of antibodies against s100 or s100b (0.1 mg/ml) induced membrane depolarization, increased membrane permeability, and suppressed slow excitatory postsynaptic potentials in the responses of neurons to sensory stimulation. Acquisition of sensitization in snails in the presence of antibodies to s100 or s100b (0.1 mg/ml) led to significantly less marked facilitation of synaptic transmission and smaller increases in neuron membrane excitability than in cells of control sensitized animals. The difference in synaptic facilitation in the neurons of control sensitized snails and neurons in sensitized snails given antibody was comparable with the magnitude of synaptic depression due to antibody in non-sensitized animals. At a dose of 0.01 mg/ml, antibody had no effect on these measures of neuron activity. It is suggested that s100 proteins, particularly s100b, are involved in the mechanisms regulating excitability, the membrane potential, and synaptic transmission in command neurons in untrained snails, as well as in the mechanism of plasticity of the electrogenic membranes of nerve cells during the acquisition of nociceptive sensitization.

InAsSbInAsSbP double heterostructure diode lasers for the spectral range of 3.3 μm grown by liquid phase epitaxy have been investigated. Emission spectra, far–field patterns and wavelength tuning versus current have been studied in the wide current range from threshold value Ithup to 3Ithat the temperature of liquid nitrogen. Controlled by current, wavelength tuning in single–mode lasing has been obtained both towards the shorter wavelengths (up to 4.56 cm−1) and towards the longer wavelengths (up to 0.9 cm−1) at the temperature T 77 K. Comparison of the emission properties of the lasers, driven by different types of current (short pulse current, sawtooth pulse current and in quasi–continuous–wave (CW) regime) showed the same quantum–mechanical nature of current tuning. The theoretical model of this nonlinear optical phenomenon is proposed. The estimated times of current tuning defined mainly by the photon lifetime in the cavity are ca.10−9to 10−12s.

The use of a rare earth gettering technique for the growth of very pure InAs(Sb) epitaxial layers of high quantum efficiency and its application for the fabrication of powerful 4.6 4;μm LEDs operating at room temperature is reported. By introducing the rare earth element Gd or Yb into the liquid phase during LPE growth, it is found that the carrier concentration of InAs(Sb) layers can be effectively reduced to ∼6×1015 4;cm−3, and that the photoluminescence (PL) intensity of such layers can be considerably increased by between 10 and 100 times compared with untreated material. This behaviour is attributed to the gettering of residual impurities and the corresponding reduction of non-radiative recombination centres in the presence of the rare earth. This technique is used to purify the InAs0.89Sb0.11 ternary material in the active region of an InAs0.55Sb0.15P0.30/InAs0.89Sb0.11/InAs0.55Sb0.15P0.30 symmetrical double heterostructure LED. A pulsed optical output power in excess of 1 4;mW at room temperature is measured, making these emitters suitable for use in portable instruments for the environmental monitoring of carbon monoxide at 4.6 4;μm.

The role of brain-specific nonhistone Np-3.5 proteins of chromatin in the processes of the reproduction of a developed defense habit in response to food was studied in preliminarily trained edible snails. It was found that gamma globulins to Np-3.5 over the course of tens of minutes suppress behavioral and neuronal reactions elicited by a specific conditional stimulus, carrot juice, while not altering the reaction to a different conditional stimulus, apple juice. The gamma globulins to other nonhistone proteins of chromatin did not exert an influence on the reproduction of habits of food rejection. It is hypothesized that brain-specific nonhistone Np-3.5 proteins of chromatin are selectively involved in the molecular processes supporting the neurophysiological mechanisms of the extraction of information from long-term memory.