The statistical method is applied to calculate the new channel of radiative losses of alpha particles, deuterons, and tritons when exciting multielectron impurity ions in thermonuclear plasma. A new ...statistical model of Coulomb–Born atom excitation is elaborated accounting for the normalization of transition probabilities. The radiative losses of multielectron tungsten ions are calculated within the scope of two statistical plasma models—local plasma frequency (LPF) and Coulomb–Born models. The results of both models are in a good agreement with each other; the sum of the radiative losses of fast heavy ions are of the same order of magnitude as those of electrons, including bremsstrahlung and radiative and dielectronic recombination.
Humanized Mouse Model of HIV Infection Leontyev, D. S.; Glazkova, D. V.; Bezborodova, O. A. ...
Bulletin of experimental biology and medicine,
05/2023, Letnik:
175, Številka:
1
Journal Article
Recenzirano
The development of new drugs for the treatment of HIV infection requires testing of their efficacy in a relevant animal model, such as humanized mice, which, unfortunately, are not yet available in ...Russia. In the present study, we have developed conditions for the humanization of immunodeficient NSG mice with human hematopoietic stem cells. Humanized animals generated during the study showed a high degree of chimerism and harbored repopulation of the entire range of human lymphocytes required for HIV replication in the blood and organs. Inoculation of these mice with HIV-1 virus led to stable viremia, which was confirmed by the presence of viral RNA in blood plasma throughout the entire period of observation and proviral DNA in the organs of animals 4 weeks after HIV infection.
A statistical description is proposed for the shape of heavy impurity spectra observed in tokamaks and stellarators, corresponding to the quasicontinuous radiation distribution, and called the ...quasicontinuum. For the tungsten ions, in particular, it is located in the spectral range of ∼2 to 7 nm. The method is based on the statistical plasma model of atom, which allows expressing the quasicontinuum structure through the electron density distribution of multielectron ions. The Slater distribution is used as a model density distribution. The quasicontinuum is formed by the great number of closely spaced lines of heavy ions with different degrees of ionization, and its calculation is very complicated. A comparison of the results obtained within the statistical approach with the results of the level-by-level quantum mechanical calculations shows that such a model plausibly describes the envelopes of the individual line arrays in the ion spectra. In contrast to the level-by-level calculation codes, the statistical atom model is rather simple and it can be used by a large number of users. The quasicontinuum was simulated for the tungsten, gold, lead, and gadolinium ions, which are observed in plasmas of fusion facilities. The simulation results are in fairly good agreement with the experimental data. The studies of the tungsten quasicontinuum are of interest from the point of view of plasma diagnostics, as well as determination of the tungsten impurity density and its transport in fusion facilities.
Intravenous immunoglobulin (IVIg) has been used to treat a variety of autoimmune disorders including multiple sclerosis (MS); however its mechanism of action remains elusive. Recent work has shown ...that interleukin-11 (IL-11) mRNAs are upregulated by IVIg in MS patient T cells. Both IVIg and IL-11 have been shown to ameliorate experimental autoimmune encephalomyelitis (EAE), an animal model of MS. The objective of this study was to determine whether the protective effects of IVIg in EAE occur through an IL-11 and IL-11 receptor (IL-11R)-dependent mechanism.
We measured IL-11 in the circulation of mice and IL-11 mRNA expression in various organs after IVIg treatment. We then followed with EAE studies to test the efficacy of IVIg in wild-type (WT) mice and in mice deficient for the IL-11 receptor (IL-11Rα-/-). Furthermore, we evaluated myelin-specific Th1 and Th17 responses and assessed spinal cord inflammation and demyelination in WT and IL-11Rα-/- mice, with and without IVIg treatment. We also examined the direct effects of mouse recombinant IL-11 on the production of IL-17 by lymph node mononuclear cells.
IVIg treatment induced a dramatic surge (>1000-fold increase) in the levels of IL-11 in the circulation and a prominent increase of IL-11 mRNA expression in the liver. Furthermore, we found that IL-11Rα-/- mice, unlike WT mice, although initially protected, were resistant to full protection by IVIg during EAE and developed disease with a similar incidence and severity as control-treated IL-11Rα-/- mice, despite initially showing protection. We observed that Th17 cytokine production by myelin-reactive T cells in the draining lymph nodes was unaffected by IVIg in IL-11Rα-/- mice, yet was downregulated in WT mice. Finally, IL-11 was shown to directly inhibit IL-17 production of lymph node cells in culture.
These results implicate IL-11 as an important immune effector of IVIg in the prevention of Th17-mediated autoimmune inflammation during EAE.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BACKGROUND:Previous studies support dasatinib as a potent inhibitor of HIV-1 replication. However, a functional distinction between 2 kinase targets of the drug, ABL1 and ARG, has not been assessed.
...SETTING:We used primary CD4 T‐cells, CD8-depleted peripheral blood mononuclear cells (PBMCs) from a treatment naïve HIV-1 patient, and a humanized mouse model of HIV-1 infection. We assessed the roles of ABL1 and ARG during HIV-1 infection and use of dasatinib as a potential antiviral against HIV-1 in humanized mice.
METHODS:Primary CD4 T‐cells were administered siRNA targeting ABL1 or ARG, then infected with HIV-1 containing luciferase reporter viruses. Quantitative polymerase chain reaction of viral integration of 4 HIV-1 strains was also assessed. CD8-depleted PBMCs were treated for 3 weeks with dasatinib. NSG mice were engrafted with CD34 pluripotent stem cells from human fetal cord blood, and infected with Ba-L virus after 19 weeks. Mice were treated daily with dasatinib starting 5 weeks after infection.
RESULTS:siRNA knockdown of ABL1 or ARG had no effect on viral reverse transcripts, but increased 2-LTR circles 2- to 4-fold and reduced viral integration 2- to 12-fold. siRNA knockdown of ARG increased SAMHD1 activation, whereas knockdown of either kinase reduced RNA polymerase II activation. Treating CD8-depleted PBMCs from a treatment-naïve patient with 50 nM of dasatinib for 3 weeks reduced p24 levels by 99.8%. Ba-L (R5)-infected mice injected daily with dasatinib showed a 95.1% reduction in plasma viral load after 2 weeks of treatment.
CONCLUSIONS:We demonstrate a novel nuclear role for ABL1 and ARG in ex vivo infection experiments, and proof-of-principle use of dasatinib in a humanized mouse model of HIV-1 infection.
The dielectronic recombination rate of multielectron ions was calculated by means of the statistical approach. It is based on an idea of collective excitations of atomic electrons with the local ...plasma frequencies. These frequencies are expressed via the Thomas-Fermi model electron density distribution. The statistical approach provides fast computation of DR rates that are compared with the modern quantum mechanical calculations. The results are important for current studies of thermonuclear plasmas with the tungsten impurities.
Background This study evaluated preoperative predictors of in-hospital death for the surgical treatment of patients with acute type A aortic dissection (Type A) and created an easy-to-use scorecard ...to predict in-hospital death. Methods We reviewed retrospectively all consecutive patients who underwent operations for acute Type A between 1996 and 2011 at 2 tertiary care institutions. A logistic regression model was created to identify independent preoperative predictors of in-hospital death. The results were used to create a scorecard predicting operative risk. Results Emergency operations were performed in 534 consecutive patients for acute Type A. Mean age was 61 ± 14 years and 36.3% were women. Critical preoperative state was present in 31% of patients and malperfusion of one or more end organs in 36%. Unadjusted in-hospital mortality was 18.7% and not significantly different between institutions. Independent predictors of in-hospital death were age 50 to 70 years (odds ratio OR, 3.8; p = 0.001), age older than 70 years (OR, 2.8; p = 0.03), critical preoperative state (OR, 3.2; p < 0.001), visceral malperfusion (OR, 3.0; p = 0.003), and coronary artery disease (OR, 2.2; p = 0.006). Age younger than 50 years (OR, 0.3; p = 0.01) was protective for early survival. Using this information, we created an easily usable mortality risk score based on these variables. The patients were stratified into four risk categories predicting in-hospital death: less than 10%, 10% to 25%, 25% to 50%, and more than 50%. Conclusions This represents one of the largest series of patients with Type A in which a risk model was created. Using our approach, we have shown that age, critical preoperative state, and malperfusion syndrome were strong independent risk factors for early death and could be used for the preoperative risk assessment.
This paper presents the results of X-ray diffraction studies on a single crystal of lead zirconate titanate PbZr
0.993
Ti
0.007
O
3
in the region of existence of an intermediate ferroelectric phase. ...In addition to the known superstructure reflections of the M type
q
M
=
and the first-order satellite reflections
q
M
+ {δ, δ, δ}, unknown second-order satellites have been observed near
q
M
and near the Bragg reflections. Structural model of regular system of antiphase domains is used for diffraction calculation. The model is shown to describe the first- and second-orders satellite reflections in the vicinity of
q
M
, but it cannot explain the appearance of satellites around the main Bragg peaks. A possible origin of the system of the superstructures observed in the intermediate phase is discussed.
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