Оценка надежности высоконадежных систем с учетом ЗИП

Предложены приближенные верхние и нижние оценки коэффициента готовности высоконадежной восстанавливаемой системы со структурной избыточностью. Полученные расчетные соотношения могут использоваться для оценки надежности высоконадежных систем с учетом различных стратегий пополнения ЗИП

Differences in Antioxidant and Lipid Handling Protein Expression Influence How Cells Expressing Distinct Mutant TP53 Subtypes Maintain Iron Homeostasis

The tumor suppressor TP53 is the most commonly mutated gene in human cancers, and iron is necessary for cancer cell growth and proliferation, but there is a significant gap in knowledge for how the two cooperate to affect cellular physiology. Elucidating this role is complicated, however, because each TP53 mutation subtype exhibits unique phenotypic responses to changes in iron availability. The goal of this work was to determine how cells expressing distinct TP53 mutation subtypes respond to iron restriction. Utilizing a reverse genetics approach, we generated eight isogenic cell lines that either lacked TP53 expression, expressed wild-type TP53, or expressed one of the six most common TP53 “hotspot” mutations. We then employed isobaric peptide labeling and mass spectrometry to quantitively measure changes in global protein expression, both in response to induction of mutant TP53 expression, and in response to iron chelation. Our findings indicate that mutant TP53-dependent sensitivities to iron restriction are not driven by differences in responsiveness to iron chelation, but more so by mutant TP53-dependent differences in cellular antioxidant and lipid handling protein expression. These findings reinforce the importance of distinguishing between TP53 mutation subtypes when investigating approaches to target mutant TP53. We also identify unique TP53-dependent perturbances in protein expression patterns that could be exploited to improve iron-targeted chemotherapeutic strategies

A Comparative Study of the Metabolic and Skeletal Response of C57BL/6J and C57BL/6N Mice in a Diet-Induced Model of Type 2 Diabetes

Type 2 diabetes mellitus (T2DM) represents a complex clinical scenario of altered energy metabolism and increased fracture incidence. The C57BL/6 mouse model of diet-induced obesity has been used to study the mechanisms by which altered glucose homeostasis affects bone mass and quality, but genetic variations in substrains of C57BL/6 may have confounded data interpretation. This study investigated the long-term metabolic and skeletal consequences of two commonly used C57BL/6 substrains to a high fat (HF) diet. Male C57BL/6J, C57BL/6N, and the negative control strain, C3H/HeJ, mice were fed a control or HF diet for 24 wks. C57BL/6N mice on a HF diet demonstrated an increase in plasma insulin and blood glucose as early as 4 wk, whereas these responses were delayed in the C57BL/6J mice. The C57BL/6N mice exhibited more severe hepatic steatosis and inflammation. Only the C57BL/6N mice lost significant trabecular bone in response to the high fat diet. The C3H/HeJ mice were protected from bone loss. The data show that C57BL/6J and C57BL/6N mice differ in their metabolic and skeletal response when fed a HF diet. These substrain differences should be considered when designing experiments and are likely to have implications on data interpretation and reproducibility

Structural study of bimetallic CoxRh1−xCo_xRh_{1-x} nanoparticles: Size and composition effects

The structure of ultrafine bimetallic CoxRh1?x nanoparticles synthesized in mild conditions by codecomposition of organometallic precursors in the presence of a polymer or a ligand has been studied using high-resolution electron microscopy and wide-angle x-ray scattering techniques. While pure rhodium particles exhibit the main structural features of a face centered cubic (fcc), alloying with cobalt induces a progressive loss of periodicities, leading in high-cobalt-content particles to a polytetrahedral structure close to the one already encountered in pure-cobalt particles. When increasing the synthesis temperature, the polytetrahedral structure remains remarkably stable, while particles with higher rhodium content clearly evolve towards perfect fcc. Increasing the size of the particles up to 5–6nm stabilizes the structural phases encountered in the phase diagram of the bulk alloy. Different element-sensitive techniques, x-ray absorption spectroscopy (XANES and EXAFS) and energy-filtering transmission electron microscopy, have also been implemented in order to get chemical information. Evidence is given for a cobalt surface segregation in these bimetallic particles, highly favorable for magnetic-moment enhancement

qRT-PCR Analyses of Genes Involved in Osteoclastogenesis and Osteoblast Activity.

<p>Bone marrow (A) was analyzed for relative mRNA abundance of the osteoclastgensis gene nuclear factor of activated T-cells (<i>Nfatc1</i>), while the flushed femur (B-D) was used to assess genes involved in osteoblast activity and function: alkaline phosphatase (<i>Alp</i>), type 1 collagen (<i>Col1a1</i>), and osteocalcin (<i>Ocn</i>) in sham-operated (Sham) and ovariectomized (OVX) mice fed control diet, or control diet supplemented with either 25% (w/w) dried plum, apple, apricot, grape, or mango. Bars represent the mean ± SE, <i>n</i>  =  6 mice in each group. Bars that share the same superscript letter are not significantly different from each other (<i>p<</i>0.05).</p

Percent Change in Vertebral Trabecular Bone Normalized to OVX-Control at Baseline.

<p>Percent change in vertebral BV/TV in ovariectomized (OVX) mice fed control diet, or control diet supplemented with either 25% (w/w) dried plum, apple, apricot, grape, or mango relative to baseline OVX controls. The percent change was calculated by determining the difference between the OVX group mean BV/TV at baseline and BV/TV of individual animals at the final time point, and then expressing that value relative to baseline. Bars represent the mean ± SE, <i>n</i>  =  6 mice in each group. Bars that share the same superscript letter are not significantly different from each other (<i>p<</i>0.05).</p

Histological Images of the Tibia and µCT Analyses of Trabecular Bone Volume in the Vertebra and Tibia.

<p>Representative images of the proximal tibia are shown with H&E stain following the 8 week treatment period (A). Comparisons of trabecular bone morphometric parameters in sham-operated (Sham) and osteopenic ovariectomized (OVX) mice fed control diet, or control diet supplemented with either 25% (w/w) dried plum, apple, apricot, grape, or mango. Trabecular bone microarchitectural of (B) bone volume/total volume (BV/TV) in the vertebral body (□) and proximal tibia (▪). Bars represent the mean ± SE, <i>n</i>  =  6 mice in each group. Bars that share the same superscript letter are not significantly different from each other (<i>p<</i>0.05).</p