Cellular and Exosomal Regulations of Sepsis-Induced Metabolic Alterations

Sepsis is a sustained systemic inflammatory condition involving multiple organ failures caused by dysregulated immune response to infections. Sepsis induces substantial changes in energy demands at the cellular level leading to metabolic reprogramming in immune cells and stromal cells. Although sepsis-associated organ dysfunction and mortality have been partly attributed to the initial acute hyperinflammation and immunosuppression precipitated by a dysfunction in innate and adaptive immune responses, the late mortality due to metabolic dysfunction and immune paralysis currently represent the major problem in clinics. It is becoming increasingly recognized that intertissue and/or intercellular metabolic crosstalk via endocrine factors modulates maintenance of homeostasis, and pathological events in sepsis and other inflammatory diseases. Exosomes have emerged as a novel means of intercellular communication in the regulation of cellular metabolism, owing to their capacity to transfer bioactive payloads such as proteins, lipids, and nucleic acids to their target cells. Recent evidence demonstrates transfer of intact metabolic intermediates from cancer-associated fibroblasts via exosomes to modify metabolic signaling in recipient cells and promote cancer progression. Here, we review the metabolic regulation of endothelial cells and immune cells in sepsis and highlight the role of exosomes as mediators of cellular metabolic signaling in sepsis.     

On prioritized weighted aggregation in multi-criteria decision making

This paper deals with multi-criteria decision making (MCDM) problems with multiple priorities, in which priority weights associated with the lower priority criteria are related to the satisfactions of the higher priority criteria. Firstly, we propose a prioritized weighted aggregation operator based on ordered weighted averaging (OWA) operator and triangular norms (t-norms). To preserve the tradeoffs among the criteria in the same priority level, we suggest that the degree of satisfaction regarding each priority level is viewed as a pseudo criterion. On the other hand, t-norms are used to model the priority relationships between the criteria in different priority levels. In particular, we show that strict Archimedean t-norms perform better in inducing priority weights. As Hamacher family of t-norms provide a wide class of strict Archimedean t-norms ranging from the product to weakest t-norm, Hamacher parameterized t-norms are used to induce the priority weight for each priority level. Secondly, considering decision maker (DM)’s requirement toward higher priority levels, a benchmark based approach is proposed to induce priority weight for each priority level. In particular, ?ukasiewicz implication is used to compute benchmark achievement for crisp requirements; target-oriented decision analysis is utilized to obtain the benchmark achievement for fuzzy requirements. Finally, some numerical examples are used to illustrate the proposed prioritized aggregation technique as well as to compare with previous research.     

Construction of novel subtilisin E with high specificity, activity and productivity through multiple amino acid substitutions

Through three cumulative amino acid substitutions, we constructed novel mutant subtilisins E of Bacillus subtilis, all with high specificity, activity and productivity. The substitution of conserved Gly127, constituting P1 substrate-binding pocket, with Ala and Val showed a marked preference for the small P1 substrate. Leu was then substituted for Ile31 next to the catalytic Asp32 to enhance the catalytic activity. Both double mutants (I31L/G127A and I31L/G127V) showed a 3-5- fold increase in catalytic efficiency due to a large kcat, without any change in the specificity of the mutants at position 127. Molecular modeling suggests that large P1 residues were unable to access the pocket because of steric hindrance. A third mutation was introduced by replacing Tyr(-1) with Ala in the propeptide essential for autoprocessing to active mature subtilisin in vivo. A prominent 7-20- fold increase in active enzyme production occurred in the triple mutants (Y-1A/I31L/G127A and Y-1A/I31L/G127V).      

Temperature dependence of absorption coefficient spectra for μc-Si films by resonant photothermal bending spectroscopy

Resonant photothermal bending spectroscopy (R-PBS) has been developed for estimating absorption coefficient spectra of thin film semiconductors. This technique has been applied to hydrogenated microcrystalline silicon (μc-Si:H) films at different measurement temperatures. It is found that absorption coefficient of μc-Si:H films at 0.7–1.1 eV is relevant for the localized states and decreases with increasing measurement temperature. The localized state exists at 0.7 eV in the band gap from the band edge. The origin of the absorption is also discussed.     

Clinical features of small hepatocellular carcinomas as assessed by histologic grades

This paper outlines three important issues in the clinical management of sexually transmitted diseases (STDs) in Papua New Guinea which have, until now, gone unrecognized or been neglected. Suggestions for possible solutions are made. The high prevalence of both chlamydial and trichomonal infections in women cannot be ignored. Both of these infections have been shown to increase the transmission of HIV. The current algorithm for the treatment of vaginal discharges does not include treatment for trichomonal infection in the first instance, yet trichomoniasis has been shown to be the most common STD in community studies both here and elsewhere. Trichomoniasis is usually asymptomatic in men, but still increases the risk of HIV transmission; furthermore, it causes illness in their female partners and thus needs to be treated. The current recommended regimens for the treatment of gonococcal and chlamydial infection are complex due to the number of drugs recommended for gonorrhoea to combat the problem of drug resistance, and the length of therapy for chlamydia. Compliance with such a regimen is likely to be poor, particularly in asymptomatic partners. We need to consider the relative advantages provided by a drug which could be given as a single oral dose for chlamydia, and perhaps for both infections. Azithromycin is one possibility, as it has been shown to be effective for chlamydial infection in numerous studies, and has been found satisfactory for gonorrhoea where local isolates were susceptible. Testing of a small number of isolates from Papua New Guinea has shown that azithromycin may be suitable for use here, but further susceptibility testing needs to be performed. Utilization of services for STDs, particularly by women, is extremely low. This is due to a combination of factors involving limited knowledge of symptomatology and its significance, the asymptomatic nature of many infections, the structure of the services, health worker behaviour, and social attitudes. To address these issues we must make modifications to STD service provision, as well as provide widespread information about the potentially serious consequences of contracting STDs, including both infertility and AIDS. Possible modifications to the services are discussed, and include making routine screening available for women through currently existing services such as family planning and antenatal clinics and considering the possibility of establishing Women's Health Clinics which would provide all primary reproductive health services in an integrated manner.     

Voluntary settlement and the spirit of independence: Evidence from Japan's "northern frontier."

The authors hypothesized that economically motivated voluntary settlement in the frontier fosters independent agency. While illuminating the historical origin of American individualism, this hypothesis can be most powerfully tested in a region that is embedded in a broader culture of interdependence and yet has undergone a recent history of such settlement. The authors therefore examined residents of Japan's northern island (Hokkaido). Hokkaido was extensively settled by ethnic Japanese beginning in the 1870s and for several decades thereafter. Many of the current residents of Hokkaido are the descendents of the original settlers from this period. As predicted, Japanese socialized and/or immersed in Hokkaido were nearly as likely as European Americans in North America to associate happiness with personal achievement (Study 1), to show a personal dissonance effect wherein self-justification is motivated by a threat to personal self-images (Study 2), and to commit a dispositional bias in causal attribution (Study 3). In contrast, these marker effects of independent agency were largely absent for non-Hokkaido residents in Japan. Implications for theories of cultural change and persistence are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Numerical analysis of unsteady behavior of cloud cavitation around a NACA0015 foil

Three-dimensional unsteady cavitating flow around a NACA0015 hydrofoil fixed between the sidewalls was simulated and the mechanism of U-shaped cloud cavity formation was clarified. A local homogeneous model was used for the modeling of the vapor–liquid two-phase medium. The compressible two-phase Navier–Stokes equations as the governing equations were solved. To describe the phase change between water and vapor, the mass transfer model based on the theory of evaporation/condensation on a plane interface was introduced. The cell-centered finite volume method was employed to discretize the governing equations. Assuming turbulent flow, the turbulent eddy viscosity coefficient was computed by using the Baldwin–Lomax model with the Degani–Schiff modification. As a result, even in the case of cavitating flow without sidewalls, the shed cloud cavities has slightly 3D structure, which was not so much large as extending across the whole spanwise direction. On the other hand, in the case of cavitating flow with sidewalls, the end of sheet cavities bows in the spanwise direction because of the development of boundary layer near both sidewalls. After that, due to the occurring of the reentrant jet towards the mid-span region, the sheet cavities breaks off from mid-span region near the leading edge of the hydrofoil, and became the vortical cloud cavities, which have the large-scale U-shaped structure.     

Clinical effect of immunochemotherapy for a patient with advanced gallbladder cancer: report of a case

BACKGROUND: The aim of this study was to evaluate pain and pulmonary function the first two days after abdominal and laparoscopic hysterectomy. METHODS: Women scheduled for abdominal hysterectomy were prospectively randomized to either laparoscopic (n=20) or abdominal (n=20) hysterectomy. Analgesics were self-administered by the patients by means of a programable infusion pump containing morphine. Postoperative pain was evaluated using a visual analog scale. Oxygen saturation was measured with an oxymeter. Pulmonary function was assessed using a peak flow meter measuring peak expiratory flow and a vitalograph measuring forced vital capacity and forced expiratory volume in one second. RESULTS: Pain scores were lower after laparoscopic hysterectomy at the first (p<0.05) and second postoperative day (p<0.01). Lung function was impaired on days 1 and 2 postoperatively, measured as peak expiratory flow, forced vital capacity and forced expiratory volume in one second, in both groups compared to the preoperative values. The patients undergoing laparoscopic hysterectomy had less impairment of lung function measured by peak expiratory flow (p<0.01), forced vital capacity (p<0.05) and forced expiratory volume in one second (p<0.05) the first postoperative day compared to the patients undergoing abdominal hysterectomy. The second postoperative day differences between the groups remained for peak expiratory flow (p<0.05) and forced expiratory volume in one second (p<0.05). CONCLUSIONS: Laparoscopic hysterectomy results in less pain and less impairment of respiratory function compared to abdominal hysterectomy.     

Relation between filter using covariance information and Kalman filter

This paper presents sequential algorithms for the optimal impulse function, Kalman gain and the error variance in linear least squares filtering problems, when the autocovariance function of the signal is given in the form of a semi-degenerate kernel, and the additive observation noise in white Gaussian. A digital simulation result indicates that the algorithms presented in this paper are feasible, and that the values of Kalman gain and the error variance calculated by these algorithms approach to those obtained by the Kalman filter theory, for time sufficiently large.