Four Ras guanine nucleotide-releasing proteins (RasGRP1 through 4) belong to the family of guanine nucleotide exchange factors (GEFs). RasGRPs catalyze the release of GDP from small GTPases Ras and ...Rap and facilitate their transition from an inactive GDP-bound to an active GTP-bound state. Thus, they regulate critical cellular responses via many downstream GTPase effectors. Similar to other RasGRPs, the catalytic module of RasGRP1 is composed of the Ras exchange motif (REM) and Cdc25 domain, and the EF hands and C1 domain contribute to its cellular localization and regulation. RasGRP1 can be activated by a diacylglycerol (DAG)-mediated membrane recruitment and protein kinase C (PKC)-mediated phosphorylation. RasGRP1 acts downstream of the T cell receptor (TCR), B cell receptors (BCR), and pre-TCR, and plays an important role in the thymocyte maturation and function of peripheral T cells, B cells, NK cells, mast cells, and neutrophils. The dysregulation of RasGRP1 is known to contribute to numerous disorders that range from autoimmune and inflammatory diseases and schizophrenia to neoplasia. Given its position at the crossroad of cell development, inflammation, and cancer, RASGRP1 has garnered interest from numerous disciplines. In this review, we outline the structure, function, and regulation of RasGRP1 and focus on the existing knowledge of the role of RasGRP1 in leukemia and other cancers.
The paper presents the results of modeling the electrophysical parameters of AlGaAs/InGaAs/GaAs pseudomorphic high electron mobility transistor (pHEMT) structures via self-consistent solution of the ...Schrödinger and Poisson equations. On the basis of numerical calculations, a method for analyzing nonlinear distortions of the transfer current–voltage characteristics of such transistors is proposed. The effect of the spacer layers and the doping level of the δ layer on the nonlinearity of the current–voltage characteristics is estimated.
Summary Background This study describes an outbreak of tuberculosis (TB) in a nursing home for men with mental disorders where residency is lengthy or permanent. This type of setting can provide a ...model of transmission as contact with the rest of society is extremely limited. Aim To determine if cases of TB, diagnosed around the same time and in the same place, are linked based on results using molecular and conventional methods. Methods The strains of Mycobacterium tuberculosis were analysed by drug resistance testing and mycobacterial interspersed repetitive units-variable number tandem repeats (MIRU-VNTRV). Microbiological results were related to clinical history and time of diagnosis. Findings Nine patients were diagnosed with TB, and strains were recovered from seven of these patients. Unexpectedly, the strains with the same genotype showed different patterns of resistance, and only two strains demonstrated identical patterns. MIRU-VNTR analysis demonstrated that one patient was infected with two different strains. Conclusion Variation between the strains indicates that the outbreak may have arisen from several sources of infection. The variation in resistance indicates that rapid emergence of antimicrobial resistance is possible. As such, several questions are raised concerning source of infection, development of disease, resistance and mixed infections.
The ratio of low-frequency (LF, ~0.1 Hz) waves of RR interval duration (RRI) and systolic blood pressure (SAP) reflects the cardiac baroreflex sensitivity (BRS). Gravitational unloading (GU) may ...alter BRS during head-up tilt test (HUT) and lower body negative pressure (LBNP) test. Both effects cause blood redistribution to the lower body, but HUT is accompanied by greater unloading of sinocarotid baroreceptors than LBNP and activation of the vestibulosympathetic reflex. However, GU effects on BRS in these tests have not been directly compared previously. In this study we tested the hypothesis that the effect of dry immersion (DI, on-ground model of GU) on BRS in the same subjects will be more pronounced during HUT than during LBNP, while causing a comparable decrease in stroke volume (SV). Nine healthy men participated in two test sessions (before and after 7-day DI) consisting of five 3-min HUT (65°C) and five 3-min LBNP (–35 mmHg) with data averaging in each test. Wavelet analysis was used to determine the amplitude of the RRI and SAP waves in the 0.05–0.13 Hz range. The amplitude of LF waves of SAP increased in both tests, after DI—more significantly in HUT. The amplitude of LF RRI waves decreased in two tests; the percentage decrease did not differ between tests and did not change under the influence of DI. The α-coefficient (the ratio of RRI and SAP LF wave amplitudes) decreased equally in two tests before DI. After DI, more pronounced α-coefficient reduction was observed in HUT test but not in LBNP test. Thus, the effect of DI on BRS is evident in HUT, but not in LBNP, which may be explained by the more pronounced influence of HUT on the mechanisms of neural control of heart rhythm.
The nonlinearity of the gate–drain current–voltage characteristics in classical Schottky transistors and two-dimensional electron gas field-effect transistors based on AlGaAs/InGaAs/GaAs and ...InGaAs/GaAs compounds is analyzed. The carrier velocity-overshoot effect in the transistor channel is analyzed for various doping profiles of the structures under study.
We studied the effects of long-term anti-orthostatic hypokinesia (head-down bed rest—BR, a model of gravitational unloading) on the dynamics of orthostasis-induced changes in the content of total ...(THb), deoxygenated (HHb), and oxygenated (OHb) hemoglobin in the calf at the level of the gastrocnemius muscle medial head using near-infrared spectroscopy. In seven young men, 2–4 days before and on the 19th day of BR, a passive head-up tilt test was performed (15 min in the supine position, then 15 min at 65°). After BR, there was an increase in heart rate and a decrease in stroke volume in the supine position, as well as more pronounced changes in these parameters during orthostasis. Blood pressure in the supine position and orthostasis did not change after BR. THb content increased gradually during orthostasis and reached a plateau by the end of the test; after BR, an increase in the half-rise time and a twofold increase in the plateau level were observed. Tissue HHb content by the end of the tilt test also increased after BR. The dynamics of OHb before BR was more complicated: this indicator grew, reached a maximum during a minute, and then gradually decreased to half of the maximum by the end of the test. After BR, the dynamics of OHb changed drastically: the signal increased gradually and reached a level that was twice the peak value of OHb content before BR. The results allow us to conclude that exposure to BR weakens the compensatory constriction of calf vessels during tilt test; consequently, it is followed by higher blood accumulation in calf vascular bed, which, in turn, leads to smaller SV during orthostasis.
This paper presents the results of studies of the capacitance-voltage characteristics (CVC) of GaAs/In
0.53
Ga
0.47
As HEMT before and after neutron irradiation with a fluence of (6.3 ± 1.3) × 10
14
...cm
–2
. Based on the experimentally obtained characteristics, the effective electron distribution profiles of the structure are calculated before and after the radiation impact. The effect of radiation defects on the δ-layers of the structure is analyzed.
Objectives.
To study post-operative cognitive dysfunction (POCD)-associated parameters of high-frequency β activity in patients who have undergone coronary bypass (CB) with on-pump circulation.
...Materials and methods.
A total of 60 patients were investigated 3–5 days before operation and on day 7–10 after CB using neuropsychological testing and recording of the resting EEG in 62 standard leads with the eyes closed. Study results were processed statistically in Statistica 10 and a data clustering method was developed; optimum solutions were sought using software implementation of a binary clipping and branching algorithm.
Results.
Patients with POCD were found to have greater pre- and post-operative levels of power of biopotentials in the high-frequency (20–30 Hz) β2 range as compared with patients without post-operative cognitive decline. A regression model demonstrated that the post-operative cognitive decline corresponded to high pre-operative β2 activity indicators in the right frontal areas of the cortex and lower levels in the left parietal areas after CB. Clustering of β2 power measures before and after CB showed that the best measures of cognitive status corresponded to stable assignation of patients to the clusters identifi ed.
Conclusions.
Specifi c correlates of POCD were identifi ed in CB patients characterized by pre-operative increases in β2 activity in the frontal areas of the right hemisphere and post-operative decreases in the left parietal areas of the cortex. The method of classifying patients in terms of levels of the pre- and post-operative β2 rhythm has good discriminating ability. Stable assignment of patients to clusters based on β2 activity was characterized by higher levels of cognitive status.
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