Targeting of reactive isolevuglandins in mitochondrial dysfunction and inflammation.

Inflammation is a major cause of morbidity and mortality in Western societies. Despite use of multiple drugs, both chronic and acute inflammation still represent major health burdens. Inflammation produces highly reactive dicarbonyl lipid peroxidation products such as isolevuglandins which covalently modify and cross-link proteins via lysine residues. Mitochondrial dysfunction has been associated with inflammation; however, its molecular mechanisms and pathophysiological role are still obscure. We hypothesized that inflammation-induced isolevuglandins contribute to mitochondrial dysfunction and mortality. To test this hypothesis, we have (a) investigated the mitochondrial dysfunction in response to synthetic 15-E2-isolevuglandin (IsoLG) and its adducts; (b) developed a new mitochondria-targeted scavenger of isolevuglandins by conjugating 2-hydroxybenzylamine to the lipophilic cation triphenylphosphonium, (4-(4-aminomethyl)-3-hydroxyphenoxy)butyl)-triphenylphosphonium (mito2HOBA); (c) tested if mito2HOBA protects from mitochondrial dysfunction and mortality using a lipopolysaccharide model of inflammation. Acute exposure to either IsoLG or IsoLG adducts with lysine, ethanolamine or phosphatidylethanolamine inhibits mitochondrial respiration and attenuates Complex I activity. Complex II function was much more resistant to IsoLG. We confirmed that mito2HOBA markedly accumulates in isolated mitochondria and it is highly reactive with IsoLGs. To test the role of mitochondrial IsoLGs, we studied the therapeutic potential of mito2HOBA in lipopolysaccharide mouse model of sepsis. Mito2HOBA supplementation in drinking water (0.1 g/L) to lipopolysaccharide treated mice increased survival by 3-fold, improved complex I-mediated respiration, and histopathological analyses supported mito2HOBA-mediated protection of renal cortex from cell injury. These data support the role of mitochondrial IsoLG in mitochondrial dysfunction and inflammation. We conclude that reducing mitochondrial IsoLGs may be a promising therapeutic target in inflammation and conditions associated with mitochondrial oxidative stress and dysfunction

Atomically thin boron nitride: a tunnelling barrier for graphene devices

We investigate the electronic properties of heterostructures based on ultrathin hexagonal boron nitride (h-BN) crystalline layers sandwiched between two layers of graphene as well as other conducting materials (graphite, gold). The tunnel conductance depends exponentially on the number of h-BN atomic layers, down to a monolayer thickness. Exponential behaviour of I-V characteristics for graphene/BN/graphene and graphite/BN/graphite devices is determined mainly by the changes in the density of states with bias voltage in the electrodes. Conductive atomic force microscopy scans across h-BN terraces of different thickness reveal a high level of uniformity in the tunnel current. Our results demonstrate that atomically thin h-BN acts as a defect-free dielectric with a high breakdown field; it offers great potential for applications in tunnel devices and in field-effect transistors with a high carrier density in the conducting channel.Comment: 7 pages, 5 figure

Psychosocial aspects of the usage of modern technologies in diabetes mellitus

This article represents a review of trials on the relationship between the use of modern technologies in the treatment of diabetes, such as continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM), and the psychological characteristics of patients. The review includes Russian studies and foreign publications. The analysis showed that the psychological aspects of using CSII are considered more often than CGM. Most Russian authors agree that the use of technology is associated with an increased psychological well-being of patients. Foreign researchers generally agree with the same point of view but also report a weaker correlation. One of the most significant conclusions of this analysis is that the use of modern technologies itself does not guarantee an improved quality of life (QOL) and psychological well-being, but technologies such as CSII and CGM provide patients with opportunities to achieve greater effectiveness in treating diabetes, improving clinical and metabolic parameters and therefore improving QOL. However, the use of these devices, as well as many other technological tools, is associated with certain psychological problems, both in terms of their acquisition and influence on patients’ subjective well-being. Early diagnosis and prevention of such problems should be one of the tasks in preparing patients for the use of modern technologies. A positive effect on both clinical and metabolic indicators as well as on the mental sphere and social life of patients can be achieved only by combining complete training (optimally—according to specialised programmes) with medical support

How close can one approach the Dirac point in graphene experimentally?

The above question is frequently asked by theorists who are interested in graphene as a model system, especially in context of relativistic quantum physics. We offer an experimental answer by describing electron transport in suspended devices with carrier mobilities of several 10^6 cm^2V^-1s^-1 and with the onset of Landau quantization occurring in fields below 5 mT. The observed charge inhomogeneity is as low as \approx10^8 cm^-2, allowing a neutral state with a few charge carriers per entire micron-scale device. Above liquid helium temperatures, the electronic properties of such devices are intrinsic, being governed by thermal excitations only. This yields that the Dirac point can be approached within 1 meV, a limit currently set by the remaining charge inhomogeneity. No sign of an insulating state is observed down to 1 K, which establishes the upper limit on a possible bandgap

An economic value of the glycated hemoglobin test in diabetes mellitus type 2 diagnosis

BACKGROUND: Diagnostic of diabetes mellitus type 2 (DM2T) in time is very actual for treatment and prevention of potential complications of illness. Fasting blood glucose test (FBG) is a widely used method of primary DM2T diagnose. Glycated hemoglobin (HbA1c) test is an alternative and used more rarely due to expensive. AIM: Modelling of comparative expenditures for DM2T control in cases of primary diagnostic by HbA1c test or FBG test usage in 20-years horizon. METHODS: Retrospective analysis of aggregated epidemiological Russian NATION study data in 810 patients with prediabetes and DM2T with both analysis performed, with sensitivity and specificity of each is detected. The simulation model of DM2T outcomes has been used for Health Technology assessment (direct and indirect costs of Diabetes control during 20 years). Three algorithms of the DM2T treatment were investigated for understanding of expenditures in case on diagnostic on-time and case of late verification with metformin, gliflozines, gliptins, Glucagon-like peptide-1 receptor agonists, basal insulin analogs and their combinations. RESULTS: FBG test has more negative results for DM2T diagnostics in compare with HbA1c analysis (77,4% and 36,5% accordingly). Amount of false negative results in FBG test in 3 times more often occurred in comparison with HbA1c. HbA1c test in 3 times more precisely than FBG test for carbon metabolism abnormalities detection. Diagnostic in time with HbA1c test in compare with late process of illness detection by FBG can cut common expenditures on 26,3-27,7% depending on treatment option due to macrovasular complications decreasing. Disability rate is expected decrease on 21% to 20-th year in case of diagnostic with HbA1c performing instead FBG test. CONCLUSION: HbA1c test has diagnostic advantages in compare with FBG test for primary investigation (dispanserization). Direct and indirect expenditures in average for one patient with DM2T on 20-years horizon including cost of drugs, analysis, complications, disabilities are less in case of diagnostic in time with HbA1c test in comparison with late diagnostics in case of FBG test execution

Micrometer-scale ballistic transport in encapsulated graphene at room temperature

Devices made from graphene encapsulated in hexagonal boron-nitride exhibit pronounced negative bend resistance and an anomalous Hall effect, which are a direct consequence of room-temperature ballistic transport on a micrometer scale for a wide range of carrier concentrations. The encapsulation makes graphene practically insusceptible to the ambient atmosphere and, simultaneously, allows the use of boron nitride as an ultrathin top gate dielectric

«DIARISK» — the first national prediabetes and diabetes mellitus type 2 risk calculator

BACKGRAUND: The need to create a national questionnaire for screening the population for disorders of carbohydrate metabolism.AIMS: Develop a highly specific and sensitive questionnaire-calculator of the risk of prediabetes (PreD) and diabetes mellitus type 2 (DM2T) based on depersonalized data of individuals who have these diagnoses confirmed in the national epidemiological study NATION.METHODS: The express method of prediabetes (PreD) and diabetes mellitus type 2 (DM2T) risks has been created, validated and proposed for clinical usage for the first time in the Russian Federation, it was based of NATION epidemiologic study database (more than 26 000 participants). The following mathematical instruments have been used: mathematic modelling, main components methodology, binary variables, correlation analysis and single-factor analysis of variance.RESULTS: Highest coefficients of logistic regression for PreD (p<0.05) were identified for age — ≥52 years old for women and ≥59 years old for men (1,48); body mass index ≥31 (0.75); waist circumference ≥100 сm for women and ≥112 cm for men (0.90). In the same time coefficients for DM2T were for for age — ≥52 years old for women and ≥59 years old for men (1,24); body mass index ≥31 (1,19), high blood fasting glucose analysis in the past (1,37); waist circumference / hip circumference ratio ≥0.85 for women and ≥0.92 for men (1,05), high blood pressure (0.69). Correlation coefficients were taken into account and score has been used for specialized questionnaire creation. Sensitivity and specificity for PreD were 83,8% and 59,3% accordingly, for DM2T — 85,4% and 73,6% accordingly. DM2T may be suspected when total score of questionnaire is 11 and higher, and PreD — when total score will be ≥7 and <11.CONCLUSIONS: The calculator based on questionnaire (DIARISK) allows to separate of potential patient for PreD and DM2T confirmation during first examination or dispanserization. A patent for innovation has been issued

On-chip picosecond pulse detection and generation using graphene photoconductive switches

We report on the use of graphene for room temperature on-chip detection and generation of pulsed terahertz (THz) frequency radiation, exploiting the fast carrier dynamics of light-generated hot carriers, and compare our results with conventional low-temperature-grown gallium arsenide (LT-GaAs) photoconductive (PC) switches. Coupling of picosecond-duration pulses from a biased graphene PC switch into Goubau line waveguides is also demonstrated. A Drude transport model based on the transient photoconductance of graphene is used to describe the mechanism for both detection and generation of THz radiation

Search for Top Squark Pair Production in the Dielectron Channel

This report describes the first search for top squark pair production in the channel stop_1 stopbar_1 -> b bbar chargino_1 chargino_1 -> ee+jets+MEt using 74.9 +- 8.9 pb^-1 of data collected using the D0 detector. A 95% confidence level upper limit on sigma*B is presented. The limit is above the theoretical expectation for sigma*B for this process, but does show the sensitivity of the current D0 data set to a particular topology for new physics.Comment: Five pages, including three figures, submitted to PRD Brief Report

Measurement of the Top Quark Pair Production Cross Section in pbar-p Collisions Using Multijet Final States

We have studied tbar-t production using multijet final states in pbar-p collisions at a center-of-mass energy of 1.8 TeV, with an integrated luminosity of 110.3 pb(-1). Each of the top quarks with these final states decays exclusively to a bottom quark and a W boson, with the W bosons decaying into quark-antiquark pairs. The analysis has been optimized using neural networks to achieve the smallest expected fractional uncertainty on the tbar-t production cross section, and yields a cross section of 7.1 +/- 2.8(stat.) +/- 1.5(syst.) pb, assuming a top quark mass of 172.1 GeV/c^(2). Combining this result with previous D0 measurements, where one or both of the W bosons decay leptonically, gives a tbar t production cross section of 5.9 +/- 1.2(stat) +/- 1.1(syst) pb.Comment: 30 pages, 32 figures; no substative change in revisio