Kinetics of Cd(ii) adsorption and desorption on ferrihydrite: experiments and modeling.

PubMed

Liang, Yuzhen; Tian, Lei; Lu, Yang; Peng, Lanfang; Wang, Pei; Lin, Jingyi; Cheng, Tao; Dang, Zhi; Shi, Zhenqing

2018-05-15

The kinetics of Cd(ii) adsorption/desorption on ferrihydrite is an important process affecting the fate, transport, and bioavailability of Cd(ii) in the environment, which was rarely systematically studied and understood at quantitative levels. In this work, a combination of stirred-flow kinetic experiments, batch adsorption equilibrium experiments, high-resolution transmission electron microscopy (HR-TEM), and mechanistic kinetic modeling were used to study the kinetic behaviors of Cd(ii) adsorption/desorption on ferrihydrite. HR-TEM images showed the open, loose, and sponge-like structure of ferrihydrite. The batch adsorption equilibrium experiments revealed that higher pH and initial metal concentration increased Cd(ii) adsorption on ferrihydrite. The stirred-flow kinetic results demonstrated the increased adsorption rate and capacity as a result of the increased pH, influent concentration, and ferrihydrite concentration. The mechanistic kinetic model successfully described the kinetic behaviors of Cd(ii) during the adsorption and desorption stages under various chemistry conditions. The model calculations showed that the adsorption rate coefficients varied as a function of solution chemistry, and the relative contributions of the weak and strong ferrihydrite sites for Cd(ii) binding varied with time at different pH and initial metal concentrations. Our model is able to quantitatively assess the contributions of each individual ferrihydrite binding site to the overall Cd(ii) adsorption/desorption kinetics. This study provided insights into the dynamic behavior of Cd(ii) and a predictive modeling tool for Cd(ii) adsorption/desorption kinetics when ferrihydrite is present, which may be helpful for the risk assessment and management of Cd contaminated sites.

Postnatally elevated levels of insulin-like growth factor (IGF)-II fail to rescue the dwarfism of IGF-I-deficient mice except kidney weight.

PubMed

Moerth, Corinna; Schneider, Marlon R; Renner-Mueller, Ingrid; Blutke, Andreas; Elmlinger, Martin W; Erben, Reinhold G; Camacho-Hübner, Cecilia; Hoeflich, Andreas; Wolf, Eckhard

2007-01-01

This study tested whether elevated levels of IGF-II in the postnatal period can rescue the dwarfism in IGF-I-deficient mice. Heterozygous Igf1 mutant mice [I(+/-) II(wt)] were crossed with heterozygous Igf1 mutant, phosphoenolpyruvate carboxykinase promoter IGF-II transgenic mice [I(+/-) II(tg)], and [I(+/+) II(wt)], [I(+/+) II(tg)], [I(-/-) II(wt)], and [I(-/-) II(tg)] offspring were investigated. IGF-II levels were 11- and 6-fold higher in male and female [I(-/-) II(tg)] vs. [I(-/-) II(wt)] animals. Western ligand blot analysis revealed markedly reduced activities of 30- and 32-kDa IGF binding proteins (IGFBPs) (most likely IGFBP-1 and IGFBP-2) and the 39- to 43-kDa IGFBP-3 double band in serum from IGF-I-deficient mice. These binding proteins were partially restored by overexpression of IGF-II. Analysis of weight data from the early postnatal period until d 60 showed that, in the absence of IGF-I, elevated levels of IGF-II have no effect on body weight gain. A detailed analysis of body proportions, bone parameters, and organ weights of 60-d-old mice also failed to show effects of IGF-II with one important exception: in Igf1 mutant and also Igf1 intact male mice, IGF-II overexpression significantly increased absolute (+32.4 and +28.6%; P < 0.01) and relative kidney weights (+29.0 and +22.4%; P < 0.001). These changes in kidney weight were associated with reduced phosphorylation of p38 MAPK. In summary, our genetic model shows that substantial amounts of IGF-II in the circulation do not rescue the postnatal growth deficit of IGF-I-deficient mice but increase absolute and relative kidney weights of normal and IGF-I-deficient male mice, suggesting a gender-specific role of IGF-II for kidney growth.

Biosorption studies on copper (II) and cadmium (II) using pretreated rice straw and rice husk.

PubMed

Li, W C; Law, F Y; Chan, Y H M

2017-04-01

This study investigated the adsorption and removal behaviour of copper (Cu) (II) and cadmium (Cd) (II) ions using rice husk and rice straw in aqueous solutions. Different parameters were used to investigate their adsorption performance in saline conditions and the optimal level of biosorption at different pH levels. The main parameters were pH (3, 6 and 9), initial concentration level of heavy metals (Cu (II) 5, 10, 20, 40 and 60 mg/L and Cd (II) 0.5, 1, 2, 4 and 8 mg/L, respectively), salinity (0, 50 and 100 mM NaCl) and contact time (ranging from 3 to 60 min). Langmuir and Freundlich isotherm models were applied to analyse the removal efficiency and sorption capacity of the pretreated rice husk and rice straw. The removal efficiency and adsorption capacity generally increased with the pH and reached a plateau in alkaline conditions. The percentage removal of Cu (II) by rice husk reached 97 % at pH 9 and 95 % by rice straw at pH 6. Biosorption performance increased in the absence of NaCl. Kinetic studies for both metals revealed that the biosorption of Cu (II) and Cd (II) onto rice straw and husk was pseudo-second order.

Input selection and performance optimization of ANN-based streamflow forecasts in the drought-prone Murray Darling Basin region using IIS and MODWT algorithm

NASA Astrophysics Data System (ADS)

Prasad, Ramendra; Deo, Ravinesh C.; Li, Yan; Maraseni, Tek

2017-11-01

Forecasting streamflow is vital for strategically planning, utilizing and redistributing water resources. In this paper, a wavelet-hybrid artificial neural network (ANN) model integrated with iterative input selection (IIS) algorithm (IIS-W-ANN) is evaluated for its statistical preciseness in forecasting monthly streamflow, and it is then benchmarked against M5 Tree model. To develop hybrid IIS-W-ANN model, a global predictor matrix is constructed for three local hydrological sites (Richmond, Gwydir, and Darling River) in Australia's agricultural (Murray-Darling) Basin. Model inputs comprised of statistically significant lagged combination of streamflow water level, are supplemented by meteorological data (i.e., precipitation, maximum and minimum temperature, mean solar radiation, vapor pressure and evaporation) as the potential model inputs. To establish robust forecasting models, iterative input selection (IIS) algorithm is applied to screen the best data from the predictor matrix and is integrated with the non-decimated maximum overlap discrete wavelet transform (MODWT) applied on the IIS-selected variables. This resolved the frequencies contained in predictor data while constructing a wavelet-hybrid (i.e., IIS-W-ANN and IIS-W-M5 Tree) model. Forecasting ability of IIS-W-ANN is evaluated via correlation coefficient (r), Willmott's Index (WI), Nash-Sutcliffe Efficiency (ENS), root-mean-square-error (RMSE), and mean absolute error (MAE), including the percentage RMSE and MAE. While ANN models are seen to outperform M5 Tree executed for all hydrological sites, the IIS variable selector was efficient in determining the appropriate predictors, as stipulated by the better performance of the IIS coupled (ANN and M5 Tree) models relative to the models without IIS. When IIS-coupled models are integrated with MODWT, the wavelet-hybrid IIS-W-ANN and IIS-W-M5 Tree are seen to attain significantly accurate performance relative to their standalone counterparts. Importantly, IIS-W-ANN model accuracy outweighs IIS-ANN, as evidenced by a larger r and WI (by 7.5% and 3.8%, respectively) and a lower RMSE (by 21.3%). In comparison to the IIS-W-M5 Tree model, IIS-W-ANN model yielded larger values of WI = 0.936-0.979 and ENS = 0.770-0.920. Correspondingly, the errors (RMSE and MAE) ranged from 0.162-0.487 m and 0.139-0.390 m, respectively, with relative errors, RRMSE = (15.65-21.00) % and MAPE = (14.79-20.78) %. Distinct geographic signature is evident where the most and least accurately forecasted streamflow data is attained for the Gwydir and Darling River, respectively. Conclusively, this study advocates the efficacy of iterative input selection, allowing the proper screening of model predictors, and subsequently, its integration with MODWT resulting in enhanced performance of the models applied in streamflow forecasting.

Preliminary Modelling of Radiation Levels at the Fermilab PIP-II Linac

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lari, L.; Cerutti, F.; Esposito, L. S.

PIP-II is the Fermilab's flagship project for providing powerful, high-intensity proton beams to the laboratory's experiments. The heart of PIP-II is an 800-MeV superconducting linac accelerator. It will be located in a new tunnel with new service buildings and connected to the present Booster through a new transfer line. To support the design of civil engineering and mechanical integration, this paper provides preliminary estimation of radiation level in the gallery at an operational beam loss limit of 0.1 W/m, by means of Monte Carlo calculations with FLUKA and MARS15 codes.

Motion analysis and trials of the deep sea hybrid underwater glider Petrel-II

NASA Astrophysics Data System (ADS)

Liu, Fang; Wang, Yan-hui; Wu, Zhi-liang; Wang, Shu-xin

2017-03-01

A hybrid underwater glider Petrel-II has been developed and field tested. It is equipped with an active buoyancy unit and a compact propeller unit. Its working modes have been expanded to buoyancy driven gliding and propeller driven level-flight, which can make the glider work in strong currents, as well as many other complicated ocean environments. Its maximal gliding speed reaches 1 knot and the propelling speed is up to 3 knots. In this paper, a 3D dynamic model of Petrel-II is derived using linear momentum and angular momentum equations. According to the dynamic model, the spiral motion in the underwater space is simulated for the gliding mode. Similarly the cycle motion on water surface and the depth-keeping motion underwater are simulated for the level-flight mode. These simulations are important to the performance analysis and parameter optimization for the Petrel-II underwater glider. The simulation results show a good agreement with field trials.

Angiotensin II alters the expression of duodenal iron transporters, hepatic hepcidin, and body iron distribution in mice.

PubMed

Tajima, Soichiro; Ikeda, Yasumasa; Enomoto, Hideaki; Imao, Mizuki; Horinouchi, Yuya; Izawa-Ishizawa, Yuki; Kihira, Yoshitaka; Miyamoto, Licht; Ishizawa, Keisuke; Tsuchiya, Koichiro; Tamaki, Toshiaki

2015-08-01

Angiotensin II (ANG II) has been shown to affect iron metabolism through alteration of iron transporters, leading to increased cellular and tissue iron contents. Serum ferritin, a marker of body iron storage, is elevated in various cardiovascular diseases, including hypertension. However, the associated changes in iron absorption and the mechanism underlying increased iron content in a hypertensive state remain unclear. The C57BL6/J mice were treated with ANG II to generate a model of hypertension. Mice were divided into three groups: (1) control, (2) ANG II-treated, and (3) ANG II-treated and ANG II receptor blocker (ARB)-administered (ANG II-ARB) groups. Mice treated with ANG II showed increased serum ferritin levels compared to vehicle-treated control mice. In ANG II-treated mice, duodenal divalent metal transporter-1 and ferroportin (FPN) expression levels were increased and hepatic hepcidin mRNA expression and serum hepcidin concentration were reduced. The mRNA expression of bone morphogenetic protein 6 and CCAAT/enhancer-binding protein alpha, which are regulators of hepcidin, was also down-regulated in the livers of ANG II-treated mice. In terms of tissue iron content, macrophage iron content and renal iron content were increased by ANG II treatment, and these increases were associated with reduced expression of transferrin receptor 1 and FPN and increased expression of ferritin. These changes induced by ANG II treatment were ameliorated by the administration of an ARB. Angiotensin II (ANG II) altered the expression of duodenal iron transporters and reduced hepcidin levels, contributing to the alteration of body iron distribution.

Community-based implementation and effectiveness in a randomized trial of a risk reduction intervention for HIV-serodiscordant couples: study protocol

PubMed Central

2014-01-01

Background The HIV/AIDS epidemic continues to disproportionately affect African American communities in the US, particularly those located in urban areas. Despite the fact that HIV is often transmitted from one sexual partner to another, most HIV prevention interventions have focused only on individuals, rather than couples. This five-year study investigates community-based implementation, effectiveness, and sustainability of ‘Eban II,’ an evidence-based risk reduction intervention for African-American heterosexual, serodiscordant couples. Methods/design This hybrid implementation/effectiveness implementation study is guided by organizational change theory as conceptualized in the Texas Christian University Program Change Model (PCM), a model of phased organizational change from exposure to adoption, implementation, and sustainability. The primary implementation aims are to assist 10 community-based organizations (CBOs) to implement and sustain Eban II; specifically, to partner with CBOs to expose providers to the intervention; facilitate its adoption, implementation and sustainment; and to evaluate processes and determinants of implementation, effectiveness, fidelity, and sustainment. The primary effectiveness aim is to evaluate the effect of Eban II on participant (n = 200 couples) outcomes, specifically incidents of protected sex and proportion of condom use. We will also determine the cost-effectiveness of implementation, as measured by implementation costs and potential cost savings. A mixed methods evaluation will examine implementation at the agency level; staff members from the CBOs will complete baseline measures of organizational context and climate, while key stakeholders will be interviewed periodically throughout implementation. Effectiveness of Eban II will be assessed using a randomized delayed enrollment (waitlist) control design to evaluate the impact of treatment on outcomes at posttest and three-month follow-up. Multi-level hierarchical modeling with a multi-level nested structure will be used to evaluate the effects of agency- and couples-level characteristics on couples-level outcomes (e.g., condom use). Discussion This study will produce important information regarding the value of the Eban II program and a theory-guided implementation process and tools designed for use in implementing Eban II and other evidence-based programs in demographically diverse, resource-constrained treatment settings. Trial registration NCT00644163 PMID:24950708

Community-based implementation and effectiveness in a randomized trial of a risk reduction intervention for HIV-serodiscordant couples: study protocol.

PubMed

Hamilton, Alison B; Mittman, Brian S; Williams, John K; Liu, Honghu H; Eccles, Alicia M; Hutchinson, Craig S; Wyatt, Gail E

2014-06-20

The HIV/AIDS epidemic continues to disproportionately affect African American communities in the US, particularly those located in urban areas. Despite the fact that HIV is often transmitted from one sexual partner to another, most HIV prevention interventions have focused only on individuals, rather than couples. This five-year study investigates community-based implementation, effectiveness, and sustainability of 'Eban II,' an evidence-based risk reduction intervention for African-American heterosexual, serodiscordant couples. This hybrid implementation/effectiveness implementation study is guided by organizational change theory as conceptualized in the Texas Christian University Program Change Model (PCM), a model of phased organizational change from exposure to adoption, implementation, and sustainability. The primary implementation aims are to assist 10 community-based organizations (CBOs) to implement and sustain Eban II; specifically, to partner with CBOs to expose providers to the intervention; facilitate its adoption, implementation and sustainment; and to evaluate processes and determinants of implementation, effectiveness, fidelity, and sustainment. The primary effectiveness aim is to evaluate the effect of Eban II on participant (n = 200 couples) outcomes, specifically incidents of protected sex and proportion of condom use. We will also determine the cost-effectiveness of implementation, as measured by implementation costs and potential cost savings. A mixed methods evaluation will examine implementation at the agency level; staff members from the CBOs will complete baseline measures of organizational context and climate, while key stakeholders will be interviewed periodically throughout implementation. Effectiveness of Eban II will be assessed using a randomized delayed enrollment (waitlist) control design to evaluate the impact of treatment on outcomes at posttest and three-month follow-up. Multi-level hierarchical modeling with a multi-level nested structure will be used to evaluate the effects of agency- and couples-level characteristics on couples-level outcomes (e.g., condom use). This study will produce important information regarding the value of the Eban II program and a theory-guided implementation process and tools designed for use in implementing Eban II and other evidence-based programs in demographically diverse, resource-constrained treatment settings. NCT00644163.

GAMES II Project: a general architecture for medical knowledge-based systems.

PubMed

Bruno, F; Kindler, H; Leaning, M; Moustakis, V; Scherrer, J R; Schreiber, G; Stefanelli, M

1994-10-01

GAMES II aims at developing a comprehensive and commercially viable methodology to avoid problems ordinarily occurring in KBS development. GAMES II methodology proposes to design a KBS starting from an epistemological model of medical reasoning (the Select and Test Model). The design is viewed as a process of adding symbol level information to the epistemological model. The architectural framework provided by GAMES II integrates the use of different formalisms and techniques providing a large set of tools. The user can select the most suitable one for representing a piece of knowledge after a careful analysis of its epistemological characteristics. Special attention is devoted to the tools dealing with knowledge acquisition (both manual and automatic). A panel of practicing physicians are assessing the medical value of such a framework and its related tools by using it in a practical application.

Continuity Between DSM-5 Section II and III Personality Disorders in a Dutch Clinical Sample.

PubMed

Orbons, Irene M J; Rossi, Gina; Verheul, Roel; Schoutrop, Mirjam J A; Derksen, Jan L L; Segal, Daniel L; van Alphen, Sebastiaan P J

2018-05-14

The goal of this study was to evaluate the continuity across the Section II personality disorders (PDs) and the proposed Section III model of PDs in the Diagnostic and Statistical Manual of Mental Disorders (5th ed. [DSM-5]; American Psychiatric Association, 2013a ). More specifically, we analyzed association between the DSM-5 Section III pathological trait facets and Section II PDs among 110 Dutch adults (M age = 35.8 years, range = 19-60 years) receiving mental health care. We administered the Structured Clinical Interview for DSM-IV Axis II Disorders to all participants. Participants also completed the self-report Personality Inventory for DSM-5 (PID-5) as a measure of pathological trait facets. The distributions underlying the dependent variable were modeled as criterion counts, using negative binomial regression. The results provided some support for the validity of the PID-5 and the DSM-5 Section III Alternative Model, although analyses did not show a perfect match. Both at the trait level and the domain level, analyses showed mixed evidence of significant relationships between the PID-5 trait facets and domains with the traditional DSM-IV PDs.

Study of Montmorillonite Clay for the Removal of Copper (II) by Adsorption: Full Factorial Design Approach and Cascade Forward Neural Network

PubMed Central

Turan, Nurdan Gamze; Ozgonenel, Okan

2013-01-01

An intensive study has been made of the removal efficiency of Cu(II) from industrial leachate by biosorption of montmorillonite. A 24 factorial design and cascade forward neural network (CFNN) were used to display the significant levels of the analyzed factors on the removal efficiency. The obtained model based on 24 factorial design was statistically tested using the well-known methods. The statistical analysis proves that the main effects of analyzed parameters were significant by an obtained linear model within a 95% confidence interval. The proposed CFNN model requires less experimental data and minimum calculations. Moreover, it is found to be cost-effective due to inherent advantages of its network structure. Optimization of the levels of the analyzed factors was achieved by minimizing adsorbent dosage and contact time, which were costly, and maximizing Cu(II) removal efficiency. The suggested optimum conditions are initial pH at 6, adsorbent dosage at 10 mg/L, and contact time at 10 min using raw montmorillonite with the Cu(II) removal of 80.7%. At the optimum values, removal efficiency was increased to 88.91% if the modified montmorillonite was used. PMID:24453833

A comparison between the observed and predicted Fe II spectrum in different plasmas

NASA Astrophysics Data System (ADS)

Johansson, S.

This paper gives a survey of the spectral distribution of emission lines of Fe II, predicted from a single atomic model. The observed differences between the recorded and the predicted spectrum are discussed in terms of deficiencies of the model and interactions within the emitting plasma. A number of illustrative examples of unexpected features with applications to astrophysics are given. Selective population, due to charge transfer and resonant photo excitation, is elucidated. The future need of more laboratory data for Fe II as regards energy levels and line classification is also discussed.

Enalapril protects against myocardial ischemia/reperfusion injury in a swine model of cardiac arrest and resuscitation

PubMed Central

Wang, Guoxing; Zhang, Qian; Yuan, Wei; Wu, Junyuan; Li, Chunsheng

2016-01-01

There is strong evidence to suggest that angiotensin-converting enzyme inhibitors (ACEIs) protect against local myocardial ischemia/reperfusion (I/R) injury. This study was designed to explore whether ACEIs exert cardioprotective effects in a swine model of cardiac arrest (CA) and resuscitation. Male pigs were randomly assigned to three groups: sham-operated group, saline treatment group and enalapril treatment group. Thirty minutes after drug infusion, the animals in the saline and enalapril groups were subjected to ventricular fibrillation (8 min) followed by cardiopulmonary resuscitation (up to 30 min). Cardiac function was monitored, and myocardial tissue and blood were collected for analysis. Enalapril pre-treatment did not improve cardiac function or the 6-h survival rate after CA and resuscitation; however, this intervention ameliorated myocardial ultrastructural damage, reduced the level of plasma cardiac troponin I and decreased myocardial apoptosis. Plasma angiotensin (Ang) II and Ang-(1–7) levels were enhanced in the model of CA and resuscitation. Enalapril reduced the plasma Ang II level at 4 and 6 h after the return of spontaneous circulation whereas enalapril did not affect the plasma Ang-(1–7) level. Enalapril pre-treatment decreased the myocardial mRNA and protein expression of angiotensin-converting enzyme (ACE). Enalapril treatment also reduced the myocardial ACE/ACE2 ratio, both at the mRNA and the protein level. Enalapril pre-treatment did not affect the upregulation of ACE2, Ang II type 1 receptor (AT1R) and MAS after CA and resuscitation. Taken together, these findings suggest that enalapril protects against ischemic injury through the attenuation of the ACE/Ang II/AT1R axis after CA and resuscitation in pigs. These results suggest the potential therapeutic value of ACEIs in patients with CA. PMID:27633002

Hierarchical competition models with the Allee effect II: the case of immigration.

PubMed

Assas, Laila; Dennis, Brian; Elaydi, Saber; Kwessi, Eddy; Livadiotis, George

2015-01-01

This is part II of an earlier paper that dealt with hierarchical models with the Allee effect but with no immigration. In this paper, we greatly simplify the proofs in part I and provide a proof of the global dynamics of the non-hyperbolic cases that were previously conjectured. Then, we show how immigration to one of the species or to both would, drastically, change the dynamics of the system. It is shown that if the level of immigration to one or to both species is above a specified level, then there will be no extinction region where both species go to extinction.

40 CFR 80.45 - Complex emissions model.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) VOCW% = Percentage change in winter VOC emissions from baseline levels (8) Phase II total VOC emissions... its domain Phase I = The years 1995-1999 Phase II = Year 2000 and beyond (b) Weightings and baselines... appropriate pollutant and Phase: Table 1—Normal and Higher Emitter Weightings for Exhaust Emissions Phase I...

Whole blood lead levels are associated with biomarkers of joint tissue metabolism in African American and white men and women: the Johnston County Osteoarthritis Project.

PubMed

Nelson, Amanda E; Chaudhary, Sanjay; Kraus, Virginia B; Fang, Fang; Chen, Jiu-Chiuan; Schwartz, Todd A; Shi, Xiaoyan A; Renner, Jordan B; Stabler, Thomas V; Helmick, Charles G; Caldwell, Kathleen; Poole, A Robin; Jordan, Joanne M

2011-11-01

To examine associations between biomarkers of joint tissue metabolism and whole blood lead (Pb), separately for men and women in an African American and Caucasian population, which may reflect an underlying pathology. Participants in the Johnston County Osteoarthritis Project Metals Exposure Sub-Study (329 men and 342 women) underwent assessment of whole blood Pb and biochemical biomarkers of joint tissue metabolism. Urinary cross-linked N telopeptide of type I collagen (uNTX-I) and C-telopeptide fragments of type II collagen (uCTX-II), serum cleavage neoepitope of type II collagen (C2C), serum type II procollagen synthesis C-propeptide (CPII), and serum hyaluronic acid (HA) were measured using commercially available kits; the ratio of [C2C:CPII] was calculated. Serum cartilage oligomeric matrix protein (COMP) was measured by an in-house assay. Multiple linear regression models were used to examine associations between continuous blood Pb and biomarker outcomes, adjusted for age, race, current smoking status, and body mass index. Results are reported as estimated change in biomarker level for a 5-unit change in Pb level. The median Pb level among men and women was 2.2 and 1.9μg/dL, respectively. Correlations were noted between Pb levels and the biomarkers uNTX-I, uCTX-II, and COMP in women, and between Pb and uCTX-II, COMP, CPII, and the ratio [C2C:CPII] in men. In adjusted models among women, a 5-unit increase in blood Pb level was associated with a 28% increase in uCTX-II and a 45% increase in uNTX-I levels (uCTX-II: 1.28 [95% CI: 1.04-1.58], uNTX-I: 1.45 [95% CI:1.21-1.74]). Among men, levels of Pb and COMP showed a borderline positive association (8% increase in COMP for a 5-unit change in Pb: 1.08 [95% CI: 1.00-1.18]); no other associations were significant after adjustment. Based upon known biomarker origins, the novel associations between blood Pb and biomarkers appear to be primarily reflective of relationships to bone and calcified cartilage turnover among women and cartilage metabolism among men, suggesting a potential gender-specific effect of Pb on joint tissue metabolism that may be relevant to osteoarthritis. Copyright © 2011 Elsevier Inc. All rights reserved.

Whole blood lead levels are associated with biomarkers of joint tissue metabolism in African American and White men and women: The Johnston County Osteoarthritis Project

PubMed Central

Nelson, Amanda E.; Chaudhary, Sanjay; Kraus, Virginia B.; Fang, Fang; Chen, Jiu-Chiuan; Schwartz, Todd A.; Shi, Xiaoyan A.; Renner, Jordan B.; Stabler, Thomas V.; Helmick, Charles G.; Caldwell, Kathleen; Poole, A. Robin; Jordan, Joanne M.

2011-01-01

Purpose To examine associations between biomarkers of joint tissue metabolism and whole blood lead (Pb), separately for men and women in an African American and Caucasian population, which may reflect an underlying pathology. Methods Participants in the Johnston County Osteoarthritis Project Metals Exposure Sub-study (329 men and 342 women) underwent assessment of whole blood Pb and biochemical biomarkers of joint tissue metabolism. Urinary cross-linked N telopeptide of type I collagen (uNTX-I) and C-telopeptide fragments of type II collagen (uCTX-II), and serum cleavage neoepitope of type II collagen (C2C), serum type II procollagen synthesis C-propeptide (CPII), and serum hyaluronic acid (HA) were measured using commercially available kits; the ratio of [C2C:CPII] was calculated. Serum cartilage oligomeric matrix protein (COMP) was measured by an in-house assay. Multiple linear regression models were used to examine associations between continuous blood Pb and biomarker outcomes, adjusted for age, race, current smoking status, and body mass index. Results are reported as estimated change in biomarker level for a 5-unit change in Pb level. Results The median Pb level among men and women was 2.2 and 1.9 µg/dL, respectively. Correlations were noted between Pb levels and the biomarkers uNTX-I, uCTX-II, and COMP in women, and between Pb and uCTX-II, COMP, CPII, and the ratio [C2C:CPII] in men. In adjusted models among women, a 5-unit increase in blood Pb level was associated with a 28% increase in uCTX-II and a 45% increase in uNTX-I levels (uCTX-II: 1.28 [95%CI: 1.04–1.58], uNTX-I: 1.45 [95%CI:1.21–1.74]). Among men, levels of Pb and COMP showed a borderline positive association (8% increase in COMP for a 5-unit change in Pb: 1.08 [95% CI: 1.00–1.18])); no other associations were significant after adjustment. Conclusions Based upon known biomarker origins, the novel associations between blood Pb and biomarkers appear to be primarily reflective of relationships to bone and calcified cartilage turnover among women and cartilage metabolism among men, suggesting a potential gender-specific effect of Pb on joint tissue metabolism that may be relevant to osteoarthritis. PMID:21839992

The impact of reduced gastric acid secretion on dissolution of salts of weak bases in the fasted upper gastrointestinal lumen: Data in biorelevant media and in human aspirates.

PubMed

Litou, Chara; Vertzoni, Maria; Xu, Wei; Kesisoglou, Filippos; Reppas, Christos

2017-06-01

To propose media for simulating the intragastric environment under reduced gastric acid secretion in the fasted state at three levels of simulation of the gastric environment and evaluate their usefulness in evaluating the intragastric dissolution of salts of weak bases. To evaluate the importance of bicarbonate buffer in biorelevant in vitro dissolution testing when using Level II biorelevant media simulating the environment in the fasted upper small intestine, regardless of gastric acid secretions. Media for simulating the hypochlorhydric and achlorhydric conditions in stomach were proposed using phosphates, maleates and bicarbonates buffers. The impact of bicarbonates in Level II biorelevant media simulating the environment in upper small intestine was evaluated so that pH and bulk buffer capacity were maintained. Dissolution data were collected using two model compounds, pioglitazone hydrochloride and semifumarate cocrystal of Compound B, and the mini-paddle dissolution apparatus in biorelevant media and in human aspirates. Simulated gastric fluids proposed in this study were in line with pH, buffer capacity, pepsin content, total bile salt/lecithin content and osmolality of the fasted stomach under partial and under complete inhibition of gastric acid secretion. Fluids simulating the conditions under partial inhibition of acid secretion were useful in simulating concentrations of both model compounds in gastric aspirates. Bicarbonates in Level III biorelevant gastric media and in Level II biorelevant media simulating the composition in the upper intestinal lumen did not improve simulation of concentrations in human aspirates. Level III biorelevant media for simulating the intragastric environment under hypochlorhydric conditions were proposed and their usefulness in the evaluation of concentrations of two model salts of weak bases in gastric aspirates was shown. Level II biorelevant media for simulating the environment in upper intestinal lumen led to underestimation of concentrations in aspirates, even when bicarbonate buffer was used. Copyright © 2017 Elsevier B.V. All rights reserved.

Modeling the World Health Organization Disability Assessment Schedule II using non-parametric item response models.

PubMed

Galindo-Garre, Francisca; Hidalgo, María Dolores; Guilera, Georgina; Pino, Oscar; Rojo, J Emilio; Gómez-Benito, Juana

2015-03-01

The World Health Organization Disability Assessment Schedule II (WHO-DAS II) is a multidimensional instrument developed for measuring disability. It comprises six domains (getting around, self-care, getting along with others, life activities and participation in society). The main purpose of this paper is the evaluation of the psychometric properties for each domain of the WHO-DAS II with parametric and non-parametric Item Response Theory (IRT) models. A secondary objective is to assess whether the WHO-DAS II items within each domain form a hierarchy of invariantly ordered severity indicators of disability. A sample of 352 patients with a schizophrenia spectrum disorder is used in this study. The 36 items WHO-DAS II was administered during the consultation. Partial Credit and Mokken scale models are used to study the psychometric properties of the questionnaire. The psychometric properties of the WHO-DAS II scale are satisfactory for all the domains. However, we identify a few items that do not discriminate satisfactorily between different levels of disability and cannot be invariantly ordered in the scale. In conclusion the WHO-DAS II can be used to assess overall disability in patients with schizophrenia, but some domains are too general to assess functionality in these patients because they contain items that are not applicable to this pathology. Copyright © 2014 John Wiley & Sons, Ltd.

Bartter/Gitelman syndromes as a model to study systemic oxidative stress in humans.

PubMed

Maiolino, Giuseppe; Azzolini, Matteo; Rossi, Gian Paolo; Davis, Paul A; Calò, Lorenzo A

2015-11-01

Reactive oxygen species (ROS) are intermediates in reduction-oxidation reactions that begin with the addition of one electron to molecular oxygen, generating the primary ROS superoxide, which in turn interacts with other molecules to produce secondary ROS, such as hydrogen peroxide, hydroxyl radical, and peroxynitrite. ROS are continuously produced during metabolic processes and are deemed to play an important role in cardiovascular diseases, namely, myocardial hypertrophy and fibrosis and atherosclerosis, via oxidative damage of lipids, proteins, and deoxyribonucleic acid. Angiotensin II (Ang II) is a potent vasoactive agent that also exerts mitogenic, proinflammatory, and profibrotic effects through several signaling pathways, in part involving ROS, particularly superoxide and hydrogen peroxide. Moreover, Ang II stimulates NADPH oxidases, leading to higher ROS generation and oxidative stress. Bartter/Gitelman syndrome patients, despite elevated plasma renin activity, Ang II, and aldosterone levels, exhibit reduced peripheral resistance, normal/low blood pressure, and blunted pressor effect of vasoconstrictors. In addition, notwithstanding the activation of the renin-angiotensin system and the increased plasma levels of Ang II, these patients display decreased production of ROS, reduced oxidative stress, and increased antioxidant defenses. In fact, Bartter/Gitelman syndrome patients are characterized by reduced levels of p22(phox) gene expression and undetectable plasma peroxynitrite levels, while showing increased plasma antioxidant power and expression of antioxidant enzymes, such as heme oxygenase-1. In conclusion, multifarious data suggest that Bartter and Gitelman syndrome patients are a model of low oxidative stress and high antioxidant defenses. The contribution offered by the study of these syndromes in elucidating the molecular mechanisms underlying this favorable status could offer chances for new therapeutic targets in disease characterized by high levels of reactive oxygen species. Copyright © 2015 Elsevier Inc. All rights reserved.

Laboratory demonstrations of superconducting gravity and inertial sensors for space and airborne gravity measurements

NASA Technical Reports Server (NTRS)

Paik, Ho J.; Canavan, Edgar R.; Kong, Qin; Moody, M. V.

1992-01-01

The paper describes the superconducting gravity gradiometers (SGGs) and superconducting accelerometers being developed at the University of Maryland, which take advantage of many exotic properties of superconductivity to obtain the required low noise, high stability, and large dynamic range. Results of laboratory demonstrations of some of these instruments are presented together with the design and operating principles. Particular attention is given to the three-axis Model II SGG and a six-axis superconducting accelerometer model (Model I SSA). Model II SGG, after a residual common-mode balance, exhibited a noise level of 0.05/sq rt Hz above 0.1 Hz and a 1/f-squared noise below 0.1 Hz. All six channels of Model I SSA operated simultaneously with linear and angular acceleration noise levels of 3 x 10 exp -10 g(E)/sq rt Hz and 5 x 10 exp -8 rad/sec per sec per sq rt Hz, respectively.

Opportunities for maternal transport for delivery of very low birth weight infants.

PubMed

Robles, D; Blumenfeld, Y J; Lee, H C; Gould, J B; Main, E; Profit, J; Melsop, K; Druzin, M

2017-01-01

To assess frequency of very low birth weight (VLBW) births at non-level III hospitals. Retrospective cohort study using linked California birth certificate and discharge data of 2008 to 2010 for deliveries of singleton or first-born infant of multiple gestations with birth weight 400 to 1500 g. Delivery rates by neonatal level of care were obtained. Risk of delivery at non-level III centers was estimated in univariable and multivariable models. Of the 1 508 143 births, 13 919 (9.2%) were VLBW; birth rate at non-level III centers was 14.9% (8.4% in level I and 6.5% in level II). Median rate of VLBW births was 0.3% (range 0 to 4.7%) annually at level I and 0.5% (range 0 to 1.6%) at level II hospitals. Antepartum stay for >24 h occurred in 14.0% and 26.9% of VLBW births in level I and level II hospitals, respectively. Further improvement is possible in reducing VLBW infant delivery at suboptimal sites, given the window of opportunity for many patients.

Chronic inhibition of Ca(2+)/calmodulin kinase II activity in the pilocarpine model of epilepsy.

PubMed

Churn, S B; Kochan, L D; DeLorenzo, R J

2000-09-01

The development of symptomatic epilepsy is a model of long-term plasticity changes in the central nervous system. The rat pilocarpine model of epilepsy was utilized to study persistent alterations in calcium/calmodulin-dependent kinase II (CaM kinase II) activity associated with epileptogenesis. CaM kinase II-dependent substrate phosphorylation and autophosphorylation were significantly inhibited for up to 6 weeks following epileptogenesis in both the cortex and hippocampus, but not in the cerebellum. The net decrease in CaM kinase II autophosphorylation and substrate phosphorylation was shown to be due to decreased kinase activity and not due to increased phosphatase activity. The inhibition in CaM kinase II activity and the development of epilepsy were blocked by pretreating seizure rats with MK-801 indicating that the long-lasting decrease in CaM kinase II activity was dependent on N-methyl-D-aspartate receptor activation. In addition, the inhibition of CaM kinase II activity was associated in time and regional localization with the development of spontaneous recurrent seizure activity. The decrease in enzyme activity was not attributed to a decrease in the alpha or beta kinase subunit protein expression level. Thus, the significant inhibition of the enzyme occurred without changes in kinase protein expression, suggesting a long-lasting, post-translational modification of the enzyme. This is the first published report of a persistent, post-translational alteration of CaM kinase II activity in a model of epilepsy characterized by spontaneous recurrent seizure activity.

Effects of changes in sodium balance on plasma and kidney angiotensin II levels in anesthetized and conscious Ren-2 transgenic rats.

PubMed

Husková, Zuzana; Kramer, Herbert J; Vanourková, Zdenka; Cervenka, Ludek

2006-03-01

Since there is as yet no general agreement regarding the role of plasma and kidney angiotensin II (ANG II) in the development of hypertension in Ren-2 transgenic rats (TGR), in the present study we evaluated plasma and kidney ANG II levels in anesthetized and conscious TGR and in normotensive Hannover-Sprague-Dawley rats (HanSD) fed a normal salt diet (NS). Given the importance of ANG II in the development of salt-sensitive hypertension, and the fact that hypertensinogenic actions of ANG II are mediated via ANG II type 1 (AT1) receptors, the effects of high salt (HS) intake and of sodium depletion on blood pressure (BP), ANG II levels and kidney AT1 receptor protein expression in TGR and HanSD were also examined. Rats were maintained on a NS diet (0.6% NaCl) or fed a HS diet (2% NaCl) for 4 days or were sodium depleted (40 mg/l furosemide for 1 day followed by 3 days of 0.01% NaCl diet). They were sacrificed either by an overdose of anesthetic (thiopental sodium) or by decapitation (without anesthetic) and plasma and kidney ANG II levels were determined by radioimmunoassay during the prehypertensive (32 days old), the early (52 days) and the maintenance (90 days) phases of hypertension. Total kidney AT1 receptor protein levels were assessed by Western blot analysis. In anesthetized animals fed the NS diet, plasma ANG II levels were lower in 32-day-old TGR than in HanSD, but at 52 and 90 days of age no significant differences were noted. ANG II concentrations in kidney tissue were similar in 32- and 90-day-old TGR and HanSD, but were higher in 52-day-old TGR than in HanSD. In contrast, in conscious animals immediately after decapitation, plasma and kidney ANG II levels were higher in TGR than in HanSD at all ages. HS diet did not change BP but suppressed ANG II levels in HanSD at all ages. In contrast, HS diet increased BP but did not decrease plasma and kidney ANG II levels in TGR at all ages. Sodium restriction did not alter BP and resulted in a marked increase in ANG II levels in HanSD, but caused a significant decrease in BP in TGR without altering plasma or tissue ANG II concentrations. There were no significant differences in renal AT1 receptor protein expression between HanSD and TGR at any age of any of the experimental groups. On the basis of our present results we conclude that TGR exhibit a disrupted interaction between sodium homeostasis and the regulation of the renin-angiotensin system (RAS) activity which results in the loss of BP regulation in this model.

Expression of Angiotensin II and Aldosterone in Radiation-induced Lung Injury.

PubMed

Cao, Shuo; Wu, Rong

2012-12-01

Radiation-induced lung injury (RILI) is the most common, dose-limiting complication in thoracic malignancy radiotherapy. Considering its negative impact on patients and restrictions to efficacy, the mechanism of RILI was studied. Wistar rats were locally irradiated with a single dose of 0, 16, and 20 Gy to the right half of the lung to establish a lung injury model. Two and six months after irradiation, the right half of the rat lung tissue was removed, and the concentrations of TGF-β1, angiotensin II, and aldosterone were determined via enzyme-linked immunosorbent assay. Statistical differences were observed in the expression levels of angiotensin II and aldosterone between the non-irradiation and irradiation groups. Moreover, the expression level of the angiotensin II-aldosterone system increased with increasing doses, and the difference was still observed as time progressed. Angiotensin II-aldosterone system has an important pathophysiological function in the progression of RILI.

Biomarker-Based Prediction Models for Response to Treatment in Systemic Sclerosis-Related Interstitial Lung Disease

DTIC Science & Technology

2017-10-01

in the baseline samples of the Scleroderma Lung Study II (SLS II). We are currently analyzing whether these serum proteins have predictive...In this project, we use the valuable samples collected in the Scleroderma Lung Study II (SLSII) clinical trial and the observational cohort, GENISOS...determine key serum protein levels and transcript signatures in whole blood and skin samples collected in the SLSII study . The identified candidate

Effect of Bizhongxiao decoction and its dismantled formulae on IL-1 and TNF levels in collagen-induced arthritis in rat synovial joints

PubMed Central

2012-01-01

Background Rheumatoid arthritis (RA), a chronic autoimmune disease, affects sufferers in many different ways. Treatment of this chronic condition is particularly challenging. Traditional Chinese Medicine (TCM) provides alternatives. Bizhongxiao decoction (BZX) is a TCM complex, which has been used clinically for many years to treat RA. The purpose of this study is to compare the effects of BZX decoction and its dismantled formulae on IL-1 and TNF-1 levels in rats with RA, and to elucidate its mechanism of action. Methods Ninety healthy normal female SD rats were randomly divided into six groups: normal (control), model, BZX decoction, and the three dismantled formulae (I: heat-clearing and detoxication, II: dissipating dampness, and III: blood circulation promotion). Apart from the normal (control) group, the rats in each group were injected subcutaneously with bovine type II collagen and complete Freund adjuvant to establish a collagen-induced arthritis model, so that inhibition of foot swelling in the rats by BZX decoction and its dismantled formulae could be observed. Immunohistochemistry was used to assess the levels of the inflammatory cytokines IL-1 and TNF in synovial joints at various time points. Results Twenty-one days after the model was established, the levels of TNF and IL-1 were significantly higher in the model group, BZX decoction group and dismantled formula groups I, II and III than in the normal controls (P < 0.05). The levels of these cytokines were significantly higher in the model group than the BZX decoction or the three dismantled formula groups (P <0.01). At longer times, the TNF and IL-1 levels in model group rose gradually; those in the BZX decoction and dismantled formula groups were gradually reduced. The cytokine levels in the BZX decoction group were lower than in the three dismantled formula groups and continued to decline. Conclusions BZX decoction and the three dismantled formulae examined down-regulated the inflammatory factors IL-1 and TNF in collagen-induced arthritis rat models, but BZX exerted the strongest effect. PMID:23163934

[Effect of electroacupuncture intervention on expression of extracellular matrix collagen and metabolic enzymes].

PubMed

Liao, Jun; Zhang, Le; Ke, Mei-gui; Xu, Teng

2013-12-01

To observe the effect of electroacupuncture (EA) at "Dazhui" (GV 14) on the contents of extracellular matrix (ECM), collagen type II (COL-II), collagen type V (COL-V), matrix metalloproteinase (MMP)-13, tissue inhibitor of metalloproteinase (TIMP)-1 in rats with cervicovertebral disc degeneration so as to explore its mechanism underlying relief of intervertebral disc degeneration. A total of 28 SD rats were randomly divided into sham group (n = 7), model group (n = 7), EA group (n = 7) and medication group (n = 7). The model of cervical intervertebral disc degeneration was established by trans-section of the deep neck splenius, the longest muscles of head, neck costocervicalis, head semi-spinatus muscle, supraspinous ligament and interspinal ligaments of cervical 2-7 segments, etc. to produce imbalance between the dynamic and static force. EA was applied to "Dazhui" (GV 14) for 30 min, once daily for 28 days, with a 2 days' interval between two courses. Animals of the medication group were treated by oral administration of meloxicam tablets (0.75 mg/kg) once daily for 28 days, with a 2 days' interval between two courses. Immunohistochemistry was used to measure the expression of ECM, COL- II, COL-V, MMP-13 and TIMP-1 in the cervicovertebral disc tissue. Compared with the sham group, the expression levels of ECM and COL-II proteins in the cervicovertebral disc tissue were significantly decreased in the model group (P < 0.01), while COL-V and MMP-13 expression levels in the model group were significantly increased (P < 0.01, P < 0.05). Compared with the model group, both ECM and COL-Il expression levels were considerably increased in the EA group and medication group (P < 0.01), while COL-V and MMP-13 expression levels were considerably down-regulated (P < 0.01, P < 0.05). No significant differences were found among the four groups in TIMP-1 expression levels (P > 0.05). EA of "Dazhui" (GV 14) can effectively regulate extracellular matrix system in rats with cervical intervertebral disc degeneration, which is possibly related to its effect in relieving cervical spondylosis.

User’s Manual for SEEK TALK Full Scale Engineering Development Life Cycle Cost (LCC) Model. Volume II. Model Equations and Model Operations.

DTIC Science & Technology

1981-04-01

LIFE CYCLE COST (LCC) LCC SENSITIVITY ANALYSIS LCC MODE , REPAIR LEVEL ANALYSIS (RLA) 20 ABSTRACT (Cnn tlnue on reverse side It necessary and Identify... level analysis capability. Next it provides values for Air Force input parameters and instructions for contractor inputs, general operating...Maintenance Manhour Requirements 39 5.1.4 Calculation of Repair Level Fractions 43 5.2 Cost Element Equations 47 5.2.1 Production Cost Element 47

Winds from T Tauri stars. I - Spherically symmetric models

NASA Technical Reports Server (NTRS)

Hartmann, Lee; Avrett, Eugene H.; Loeser, Rudolf; Calvet, Nuria

1990-01-01

Line fluxes and profiles are computed for a sequence of spherically symmetric T Tauri wind models. The calculations indicate that the H-alpha emission of T Tauri stars arises in an extended and probably turbulent circumstellar envelope at temperatures above about 8000 K. The models predict that Mg II resonance line emission should be strongly correlated with H-alpha fluxes; observed Mg II/H-alpha ratios are inconsistent with the models unless extinction corrections have been underestimated. The models predict that most of the Ca II resonance line and IR triplet emission arises in dense layers close to the star rather than in the wind. H-alpha emission levels suggest mass loss rates of about 10 to the -8th solar mass/yr for most T Tauri stars, in reasonable agreement with independent analysis of forbidden emission lines. These results should be useful for interpreting observed line profiles in terms of wind densities, temperatures, and velocity fields.

Lifetime measurements using two-step laser excitation for high-lying even-parity levels and improved theoretical oscillator strengths in Y II

NASA Astrophysics Data System (ADS)

Palmeri, P.; Quinet, P.; Lundberg, H.; Engström, L.; Nilsson, H.; Hartman, H.

2017-10-01

We report new time-resolved laser-induced fluorescence lifetime measurements for 22 highly excited even-parity levels in singly ionized yttrium (Y II). To populate these levels belonging to the configurations 4d6s, 5s6s 4d5d, 5p2, 4d7s and 4d6d, a two-step laser excitation technique was used. Our previous pseudo-relativistic Hartree-Fock model (Biémont et al. 2011) was improved by extending the configuration interaction up to n = 10 to reproduce the new experimental lifetimes. A set of semi-empirical oscillator strengths extended to transitions falling in the spectral range λλ194-3995 nm, depopulating these 22 even-parity levels in Y II, is presented and compared to the values found in the Kurucz's data base (Kurucz 2011).

Validation of PEP-II Resonantly Excited Turn-by-Turn BPM Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yan, Yiton T.; Cai, Yunhai; Colocho, William.

2007-06-28

For optics measurement and modeling of the PEP-II electron (HER) and position (LER) storage rings, we have been doing well with MIA [1] which requires analyzing turn-by-turn Beam Position Monitor (BPM) data that are resonantly excited at the horizontal, vertical, and longitudinal tunes. However, in anticipation that certain BPM buttons and even pins in the PEP-II IR region would be missing for the run starting in January 2007, we had been developing a data validation process to reduce the effect due to the reduced BPM data accuracy on PEP-II optics measurement and modeling. Besides the routine process for ranking BPMmore » noise level through data correlation among BPMs with a singular-value decomposition (SVD), we could also check BPM data symplecticity by comparing the invariant ratios. Results from PEP-II measurement will be presented.« less

Epileptogenesis causes an N-methyl-d-aspartate receptor/Ca2+-dependent decrease in Ca2+/calmodulin-dependent protein kinase II activity in a hippocampal neuronal culture model of spontaneous recurrent epileptiform discharges.

PubMed

Blair, Robert E; Sombati, Sompong; Churn, Severn B; Delorenzo, Robert J

2008-06-24

Alterations in the function of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) have been observed in both in vivo and in vitro models of epileptogenesis; however the molecular mechanism mediating the effects of epileptogenesis on CaM kinase II has not been elucidated. This study was initiated to evaluate the molecular pathways involved in causing the long-lasting decrease in CaM kinase II activity in the hippocampal neuronal culture model of low Mg2+-induced spontaneous recurrent epileptiform discharges (SREDs). We show here that the decrease in CaM kinase II activity associated with SREDs in hippocampal cultures involves a Ca2+/N-methyl-d-aspartate (NMDA) receptor-dependent mechanism. Low Mg2+-induced SREDs result in a significant decrease in Ca2+/calmodulin-dependent substrate phosphorylation of the synthetic peptide autocamtide-2. Reduction of extracellular Ca2+ levels (0.2 mM in treatment solution) or the addition of dl-2-amino-5-phosphonovaleric acid (APV) 25 microM blocked the low Mg2+-induced decrease in CaM kinase II-dependent substrate phosphorylation. Antagonists of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainic acid receptor or L-type voltage sensitive Ca2+ channel had no effect on the low Mg2+-induced decrease in CaM kinase II-dependent substrate phosphorylation. The results of this study demonstrate that the decrease in CaM kinase II activity associated with this model of epileptogenesis involves a selective Ca2+/NMDA receptor-dependent mechanism and may contribute to the production and maintenance of SREDs in this model.

Epileptogenesis causes an N-methyl-d-aspartate receptor/Ca2+-dependent decrease in Ca2+/calmodulin-dependent protein kinase II activity in a hippocampal neuronal culture model of spontaneous recurrent epileptiform discharges

PubMed Central

Blair, Robert E.; Sombati, Sompong; Churn, Severn B.; DeLorenzo, Robert J.

2008-01-01

Alterations in the function of Ca2+/calmodulin-dependent protein kinase II (CaM Kinase II) have been observed in both in vivo and in vitro models of epileptogenesis; however the molecular mechanism mediating the effects of epileptogenesis on CaM Kinase II have not been elucidated. This study was initiated to evaluate the molecular pathways involved in causing the long lasting decrease in CaM Kinase II activity in the hippocampal neuronal culture model of low Mg2+ induced spontaneous recurrent epileptiform discharges (SREDs). We show here that the decrease in CaM kinase II activity associated with SREDs in hippocampal cultures involves a Ca2+/N-methyl-d-aspartate (NMDA) receptor-dependent mechanism. Low Mg2+ induced SREDs results in a significant decrease in Ca2+/calmodulin-dependent substrate phosphorylation of the synthetic peptide autocamtide-2. Reduction of extracellular Ca2+ levels (0.2 mM in treatment solution) or the addition of DL-2-amino-5-phosphonovaleric acid (APV) 25 µM blocked the low Mg2+ induced decrease in CaM kinase II-dependent substrate phosphorylation. Antagonists of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainic acid receptor or L-type voltage sensitive Ca2+ channel had no effect on the low Mg2+ induced decrease in CaM kinase II-dependent substrate phosphorylation. The results of this study demonstrate that the decrease in CaM kinase II activity associated with this model of epileptogenesis involves a selective Ca2+/NMDA receptor-dependent mechanism and may contribute to the production and maintenance of SREDs in this model. PMID:18495112

Anomalous Nernst effect in type-II Weyl semimetals

NASA Astrophysics Data System (ADS)

Saha, Subhodip; Tewari, Sumanta

2018-01-01

Topological Weyl semimetals (WSM), a new state of quantum matter with gapless nodal bulk spectrum and open Fermi arc surface states, have recently sparked enormous interest in condensed matter physics. Based on the symmetry and fermiology, it has been proposed that WSMs can be broadly classified into two types, type-I and type-II Weyl semimetals. While the undoped, conventional, type-I WSMs have point like Fermi surface and vanishing density of states (DOS) at the Fermi energy, the type-II Weyl semimetals break Lorentz symmetry explicitly and have tilted conical spectra with electron and hole pockets producing finite DOS at the Fermi level. The tilted conical spectrum and finite DOS at Fermi level in type-II WSMs have recently been shown to produce interesting effects such as a chiral anomaly induced longitudinal magnetoresistance that is strongly anisotropic in direction and a novel anomalous Hall effect. In this work, we consider the anomalous Nernst effect in type-II WSMs in the absence of an external magnetic field using the framework of semi-classical Boltzmann theory. Based on both a linearized model of time-reversal breaking WSM with a higher energy cut-off and a more realistic lattice model, we show that the anomalous Nernst response in these systems is strongly anisotropic in space, and can serve as a reliable signature of type-II Weyl semimetals in a host of magnetic systems with spontaneously broken time reversal symmetry.

Oral treatment with Cu(II)(atsm) increases mutant SOD1 in vivo but protects motor neurons and improves the phenotype of a transgenic mouse model of amyotrophic lateral sclerosis.

PubMed

Roberts, Blaine R; Lim, Nastasia K H; McAllum, Erin J; Donnelly, Paul S; Hare, Dominic J; Doble, Philip A; Turner, Bradley J; Price, Katherine A; Lim, Sin Chun; Paterson, Brett M; Hickey, James L; Rhoads, Timothy W; Williams, Jared R; Kanninen, Katja M; Hung, Lin W; Liddell, Jeffrey R; Grubman, Alexandra; Monty, Jean-Francois; Llanos, Roxana M; Kramer, David R; Mercer, Julian F B; Bush, Ashley I; Masters, Colin L; Duce, James A; Li, Qiao-Xin; Beckman, Joseph S; Barnham, Kevin J; White, Anthony R; Crouch, Peter J

2014-06-04

Mutations in the metallo-protein Cu/Zn-superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS) in humans and an expression level-dependent phenotype in transgenic rodents. We show that oral treatment with the therapeutic agent diacetyl-bis(4-methylthiosemicarbazonato)copper(II) [Cu(II)(atsm)] increased the concentration of mutant SOD1 (SOD1G37R) in ALS model mice, but paradoxically improved locomotor function and survival of the mice. To determine why the mice with increased levels of mutant SOD1 had an improved phenotype, we analyzed tissues by mass spectrometry. These analyses revealed most SOD1 in the spinal cord tissue of the SOD1G37R mice was Cu deficient. Treating with Cu(II)(atsm) decreased the pool of Cu-deficient SOD1 and increased the pool of fully metallated (holo) SOD1. Tracking isotopically enriched (65)Cu(II)(atsm) confirmed the increase in holo-SOD1 involved transfer of Cu from Cu(II)(atsm) to SOD1, suggesting the improved locomotor function and survival of the Cu(II)(atsm)-treated SOD1G37R mice involved, at least in part, the ability of the compound to improve the Cu content of the mutant SOD1. This was supported by improved survival of SOD1G37R mice that expressed the human gene for the Cu uptake protein CTR1. Improving the metal content of mutant SOD1 in vivo with Cu(II)(atsm) did not decrease levels of misfolded SOD1. These outcomes indicate the metal content of SOD1 may be a greater determinant of the toxicity of the protein in mutant SOD1-associated forms of ALS than the mutations themselves. Improving the metal content of SOD1 therefore represents a valid therapeutic strategy for treating ALS caused by SOD1. Copyright © 2014 the authors 0270-6474/14/348021-11$15.00/0.

AT1 receptor blocker losartan protects against mechanical ventilation-induced diaphragmatic dysfunction

PubMed Central

Kwon, Oh Sung; Smuder, Ashley J.; Wiggs, Michael P.; Hall, Stephanie E.; Sollanek, Kurt J.; Morton, Aaron B.; Talbert, Erin E.; Toklu, Hale Z.; Tumer, Nihal

2015-01-01

Mechanical ventilation is a life-saving intervention for patients in respiratory failure. Unfortunately, prolonged ventilator support results in diaphragmatic atrophy and contractile dysfunction leading to diaphragm weakness, which is predicted to contribute to problems in weaning patients from the ventilator. While it is established that ventilator-induced oxidative stress is required for the development of ventilator-induced diaphragm weakness, the signaling pathway(s) that trigger oxidant production remain unknown. However, recent evidence reveals that increased plasma levels of angiotensin II (ANG II) result in oxidative stress and atrophy in limb skeletal muscles. Using a well-established animal model of mechanical ventilation, we tested the hypothesis that increased circulating levels of ANG II are required for both ventilator-induced diaphragmatic oxidative stress and diaphragm weakness. Cause and effect was determined by administering an angiotensin-converting enzyme inhibitor (enalapril) to prevent ventilator-induced increases in plasma ANG II levels, and the ANG II type 1 receptor antagonist (losartan) was provided to prevent the activation of ANG II type 1 receptors. Enalapril prevented the increase in plasma ANG II levels but did not protect against ventilator-induced diaphragmatic oxidative stress or diaphragm weakness. In contrast, losartan attenuated both ventilator-induced oxidative stress and diaphragm weakness. These findings indicate that circulating ANG II is not essential for the development of ventilator-induced diaphragm weakness but that activation of ANG II type 1 receptors appears to be a requirement for ventilator-induced diaphragm weakness. Importantly, these experiments provide the first evidence that the Food and Drug Administration-approved drug losartan may have clinical benefits to protect against ventilator-induced diaphragm weakness in humans. PMID:26359481

The effect of resveratrol on angiotensin II levels and the rate of transcription of its receptors in the rat cardiac hypertrophy model.

PubMed

Dorri Mashhadi, Fahimeh; Zavvar Reza, Javad; Jamhiri, Mohabbat; Hafizi, Zeinab; Zare Mehrjardi, Fatemeh; Safari, Fatemeh

2017-03-01

This study investigated the effect of resveratrol on serum and cardiac levels of angiotensin II and transcription of its main receptors following pressure overload induced-hypertrophy. Rats were divided into untreated (Hyp) and resveratrol treated hypertrophied groups (H + R). Intact animals served as the control (Ctl). Cardiac hypertrophy was induced by abdominal aortic banding. Blood pressure (BP) was recorded via left carotid artery cannula. Fibrosis was confirmed by Masson trichrome staining. Angiotensin II level was measured using an ELIZA test. Gene expression was assessed by a real time PCR (RT-PCR) technique. We observed that in the H + R group BP and heart weight/body weight were decreased significantly (p < 0.001, p < 0.05, respectively vs Hyp). The cardiac levels of angiotensin II and AT1a mRNA were increased in the Hyp group (p < 0.01 vs Ctl). In the H + R group the AT1a mRNA level was decreased significantly (p < 0.05 vs Hyp). It could be concluded that resveratrol protects the heart against hypertrophy progression in part by affecting cardiac AT1a transcription.

Solar Occultation Retrieval Algorithm Development

NASA Technical Reports Server (NTRS)

Lumpe, Jerry D.

2004-01-01

This effort addresses the comparison and validation of currently operational solar occultation retrieval algorithms, and the development of generalized algorithms for future application to multiple platforms. initial development of generalized forward model algorithms capable of simulating transmission data from of the POAM II/III and SAGE II/III instruments. Work in the 2" quarter will focus on: completion of forward model algorithms, including accurate spectral characteristics for all instruments, and comparison of simulated transmission data with actual level 1 instrument data for specific occultation events.

Predicting heavy metals' adsorption edges and adsorption isotherms on MnO2 with the parameters determined from Langmuir kinetics.

PubMed

Hu, Qinghai; Xiao, Zhongjin; Xiong, Xinmei; Zhou, Gongming; Guan, Xiaohong

2015-01-01

Although surface complexation models have been widely used to describe the adsorption of heavy metals, few studies have verified the feasibility of modeling the adsorption kinetics, edge, and isotherm data with one pH-independent parameter. A close inspection of the derivation process of Langmuir isotherm revealed that the equilibrium constant derived from the Langmuir kinetic model, KS-kinetic, is theoretically equivalent to the adsorption constant in Langmuir isotherm, KS-Langmuir. The modified Langmuir kinetic model (MLK model) and modified Langmuir isotherm model (MLI model) incorporating pH factor were developed. The MLK model was employed to simulate the adsorption kinetics of Cu(II), Co(II), Cd(II), Zn(II) and Ni(II) on MnO2 at pH3.2 or 3.3 to get the values of KS-kinetic. The adsorption edges of heavy metals could be modeled with the modified metal partitioning model (MMP model), and the values of KS-Langmuir were obtained. The values of KS-kinetic and KS-Langmuir are very close to each other, validating that the constants obtained by these two methods are basically the same. The MMP model with KS-kinetic constants could predict the adsorption edges of heavy metals on MnO2 very well at different adsorbent/adsorbate concentrations. Moreover, the adsorption isotherms of heavy metals on MnO2 at various pH levels could be predicted reasonably well by the MLI model with the KS-kinetic constants. Copyright © 2014. Published by Elsevier B.V.

IGF-II promotes neuroprotection and neuroplasticity recovery in a long-lasting model of oxidative damage induced by glucocorticoids.

PubMed

Martín-Montañez, E; Millon, C; Boraldi, F; Garcia-Guirado, F; Pedraza, C; Lara, E; Santin, L J; Pavia, J; Garcia-Fernandez, M

2017-10-01

Insulin-like growth factor-II (IGF-II) is a naturally occurring hormone that exerts neurotrophic and neuroprotective properties in a wide range of neurodegenerative diseases and ageing. Accumulating evidence suggests that the effects of IGF-II in the brain may be explained by its binding to the specific transmembrane receptor, IGFII/M6P receptor (IGF-IIR). However, relatively little is known regarding the role of IGF-II through IGF-IIR in neuroprotection. Here, using adult cortical neuronal cultures, we investigated whether IGF-II exhibits long-term antioxidant effects and neuroprotection at the synaptic level after oxidative damage induced by high and transient levels of corticosterone (CORT). Furthermore, the involvement of the IGF-IIR was also studied to elucidate its role in the neuroprotective actions of IGF-II. We found that neurons treated with IGF-II after CORT incubation showed reduced oxidative stress damage and recovered antioxidant status (normalized total antioxidant status, lipid hydroperoxides and NAD(P) H:quinone oxidoreductase activity). Similar results were obtained when mitochondria function was analysed (cytochrome c oxidase activity, mitochondrial membrane potential and subcellular mitochondrial distribution). Furthermore, neuronal impairment and degeneration were also assessed (synaptophysin and PSD-95 expression, presynaptic function and FluoroJade B® stain). IGF-II was also able to recover the long-lasting neuronal cell damage. Finally, the effects of IGF-II were not blocked by an IGF-IR antagonist, suggesting the involvement of IGF-IIR. Altogether these results suggest that, in or model, IGF-II through IGF-IIR is able to revert the oxidative damage induced by CORT. In accordance with the neuroprotective role of the IGF-II/IGF-IIR reported in our study, pharmacotherapy approaches targeting this pathway may be useful for the treatment of diseases associated with cognitive deficits (i.e., neurodegenerative disorders, depression, etc.). Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Assessment of type II diabetes mellitus using irregularly sampled measurements with missing data.

PubMed

Barazandegan, Melissa; Ekram, Fatemeh; Kwok, Ezra; Gopaluni, Bhushan; Tulsyan, Aditya

2015-04-01

Diabetes mellitus is one of the leading diseases in the developed world. In order to better regulate blood glucose in a diabetic patient, improved modelling of insulin-glucose dynamics is a key factor in the treatment of diabetes mellitus. In the current work, the insulin-glucose dynamics in type II diabetes mellitus can be modelled by using a stochastic nonlinear state-space model. Estimating the parameters of such a model is difficult as only a few blood glucose and insulin measurements per day are available in a non-clinical setting. Therefore, developing a predictive model of the blood glucose of a person with type II diabetes mellitus is important when the glucose and insulin concentrations are only available at irregular intervals. To overcome these difficulties, we resort to online sequential Monte Carlo (SMC) estimation of states and parameters of the state-space model for type II diabetic patients under various levels of randomly missing clinical data. Our results show that this method is efficient in monitoring and estimating the dynamics of the peripheral glucose, insulin and incretins concentration when 10, 25 and 50% of the simulated clinical data were randomly removed.

Experimental type II diabetes and related models of impaired glucose metabolism differentially regulate glucose transporters at the proximal tubule brush border membrane.

PubMed

Chichger, Havovi; Cleasby, Mark E; Srai, Surjit K; Unwin, Robert J; Debnam, Edward S; Marks, Joanne

2016-06-01

What is the central question of this study? Although SGLT2 inhibitors represent a promising treatment for patients suffering from diabetic nephropathy, the influence of metabolic disruption on the expression and function of glucose transporters is largely unknown. What is the main finding and its importance? In vivo models of metabolic disruption (Goto-Kakizaki type II diabetic rat and junk-food diet) demonstrate increased expression of SGLT1, SGLT2 and GLUT2 in the proximal tubule brush border. In the type II diabetic model, this is accompanied by increased SGLT- and GLUT-mediated glucose uptake. A fasted model of metabolic disruption (high-fat diet) demonstrated increased GLUT2 expression only. The differential alterations of glucose transporters in response to varying metabolic stress offer insight into the therapeutic value of inhibitors. SGLT2 inhibitors are now in clinical use to reduce hyperglycaemia in type II diabetes. However, renal glucose reabsorption across the brush border membrane (BBM) is not completely understood in diabetes. Increased consumption of a Western diet is strongly linked to type II diabetes. This study aimed to investigate the adaptations that occur in renal glucose transporters in response to experimental models of diet-induced insulin resistance. The study used Goto-Kakizaki type II diabetic rats and normal rats rendered insulin resistant using junk-food or high-fat diets. Levels of protein kinase C-βI (PKC-βI), GLUT2, SGLT1 and SGLT2 were determined by Western blotting of purified renal BBM. GLUT- and SGLT-mediated d-[(3) H]glucose uptake by BBM vesicles was measured in the presence and absence of the SGLT inhibitor phlorizin. GLUT- and SGLT-mediated glucose transport was elevated in type II diabetic rats, accompanied by increased expression of GLUT2, its upstream regulator PKC-βI and SGLT1 protein. Junk-food and high-fat diet feeding also caused higher membrane expression of GLUT2 and its upstream regulator PKC-βI. However, the junk-food diet also increased SGLT1 and SGLT2 levels at the proximal tubule BBM. Glucose reabsorption across the proximal tubule BBM, via GLUT2, SGLT1 and SGLT2, is not solely dependent on glycaemic status, but is also influenced by diet-induced changes in glucose metabolism. We conclude that different metabolic disturbances result in complex adaptations in renal glucose transporter protein levels and function. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

Liquid propulsion turbomachinery model testing

NASA Technical Reports Server (NTRS)

Mcdaniels, David M.; Snellgrove, Lauren M.

1992-01-01

For the past few years an extensive experimental program to understand the fluid dynamics of the Space Shuttle Main Engine hot gas manifold has been in progress. This program includes models of the Phase II and II+ manifolds for each of the air and water flow facilities, as well as two different turbine flow paths and two simulated power levels for each manifold. All models are full-scale (geometric). The water models are constructed partially of acrylic to allow flow visualization. The intent of this paper is to discuss the concept, including the test objectives, facilities, and models, and to summarize the data for an example configuration, including static pressure data, flow visualization, and the solution of a specific flow problem.

Alveolar type II cell transplantation restores pulmonary surfactant protein levels in lung fibrosis.

PubMed

Guillamat-Prats, Raquel; Gay-Jordi, Gemma; Xaubet, Antoni; Peinado, Victor I; Serrano-Mollar, Anna

2014-07-01

Alveolar Type II cell transplantation has been proposed as a cell therapy for the treatment of idiopathic pulmonary fibrosis. Its long-term benefits include repair of lung fibrosis, but its success partly depends on the restoration of lung homeostasis. Our aim was to evaluate surfactant protein restoration after alveolar Type II cell transplantation in an experimental model of bleomycin-induced lung fibrosis in rats. Lung fibrosis was induced by intratracheal instillation of bleomycin. Alveolar Type II cells were obtained from healthy animals and transplanted 14 days after bleomycin was administered. Furthermore, one group transplanted with alveolar macrophages and another group treated with surfactant were established to evaluate the specificity of the alveolar Type II cell transplantation. The animals were euthanized at 21 days after bleomycin instillation. Lung fibrosis was confirmed by a histologic study and an evaluation of the hydroxyproline content. Changes in surfactant proteins were evaluated by mRNA expression, Western blot and immunofluorescence studies. The group with alveolar Type II cell transplantation was the only one to show a reduction in the degree of lung fibrosis and a complete recovery to normal levels of surfactant proteins. One of the mechanisms involved in the beneficial effect of alveolar Type II cell transplantation is restoration of lung surfactant protein levels, which is required for proper respiratory function. Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Interplay between autophagy and apoptosis in lead(II)-induced cytotoxicity of primary rat proximal tubular cells.

PubMed

Chu, Bing-Xin; Fan, Rui-Feng; Lin, Shu-Qian; Yang, Du-Bao; Wang, Zhen-Yong; Wang, Lin

2018-05-01

Autophagy and apoptosis are two different biological processes that determine cell fates. We previously reported that autophagy inhibition and apoptosis induction are involved in lead(II)-induced cytotoxicity in primary rat proximal tubular (rPT) cells, but the interplay between them remains to be elucidated. Firstly, data showed that lead(II)-induced elevation of LC3-II protein levels can be significantly modulated by 3-methyladenine or rapamycin; moreover, protein levels of Autophagy-related protein 5 (Atg5) and Beclin-1 were markedly up-regulated by lead(II) treatment, demonstrating that lead(II) could promote the autophagosomes formation in rPT cells. Next, we applied three pharmacological agents and genetic method targeting the early stage of autophagy to validate that enhancement of autophagosomes formation can inhibit lead(II)-induced apoptotic cell death in rPT cells. Simultaneously, lead(II) inhibited the autophagic degradation of rPT cells, while the addition of autophagic degradation inhibitor bafilomycin A1 aggravated lead(II)-induced apoptotic death in rPT cells. Collectively, this study provided us a good model to know about the dynamic process of lead(II)-induced autophagy in rPT cells, and the interplay between autophagy and apoptosis highlights a new sight into the mechanism of lead(II)-induced nephrotoxicity. Copyright © 2018. Published by Elsevier Inc.

The effect of long-term conventional physical therapy and independent predictive factors analysis in children with cerebral palsy.

PubMed

Chen, Yi-Nien; Liao, Su-Fen; Su, Li-Fei; Huang, Hsin-Ya; Lin, Chung-Che; Wei, Ta-Sen

2013-10-01

This study evaluated the effect of long-term conventional physical therapy (PT) on cerebral palsy (CP) children and to identify the predictors of therapy's response. We performed a retrospective review of CP children treated with PT, and their motor function was assessed every 3 months between 2008 and 2011. Fifty-six children with a mean age of 4.2 ± 2.8 years, gross motor function classification system (GMFCS) levels were level I (n = 14), level II (n = 20), level III (n = 5), level IV (n = 8), and level V (n = 9). In the generalized estimating equations model, there was a significant improvement in the Gross Motor Function Measure (GMFM-66) score (p < 0.001); the improvement was different in five GMFCS levels (p < 0.001) and GMFCS level II had faster progression. The younger CP children had better PT efficacy, and the GMFM-66 score continued improving until 8.4 years old in the older group. The long-term conventional PT is effective even in older CP children, and PT was most efficient in younger children and GMFCS level II.

The chromospheric structure of the cool giant star g Herculis

NASA Technical Reports Server (NTRS)

Luttermoser, Donald G.; Johnson, Hollis R.; Eaton, Joel

1994-01-01

Non-Local Thermodynamic Equilibrium (LTE) calculations of semiempirical chromospheric models are presented for 30 g Her (M6 III). This star is one of the coolest (T(sub eff) = 3250 K) SRb (semiregular) variable stars and has a mass perhaps as great as 4 solar mass. Chromospheric features we have observed in its spectrum include Mg II h and k; C II) UV0.01, which is sensitive to electron density; Mg I lambda 2852; Ca II H, K, and IRT; Ca I lambda 4227 and lambda 6573; Al II) UV 1; and H alpha. We pay special attention to fitting the C II intersystem lines and the Mg II resonance lines but use all the other features as constraints to some extent. The equations of radiative transfer and statistical equilibrium are solved self-consistently for H I, H(-), H2, He I, C I, C II, Na I, Mg I, Mg II, Al I, Al II, Ca I, and Ca II with the equivalent two-level technique. To simplify these calculations, a one-dimensional hydrostatic, plane-parallel atmosphere is assumed. We investigate 10 separate 'classical' chromospheric models, differing most importantly in total mass column density above the temperature minimum. Synthetic spectra from these models fit some but not all of the observations. These comparisons are discussed in detail. However, we find that no single-component classical model in hydrostatic equilibrium is able to reproduce both the Mg II line profiles and the relative strengths of the CII) lines. In all these models, chromospheric emission features are formed relatively close to the star (approximately less than 0.05 R(sub *). The circumstellar environment has a thick, cool component overlying the Mg II emission region, which is relatively static and very turbulent. Finally, we find that thermalization in the Mg II h and k lines in the coolest giant stars is controlled by continuum absorption from Ca I 4p 4p3 P0 bound-free opacity and not collisional de-excitation as is the case for warmer K giants.

A non-local thermodynamical equilibrium line formation for neutral and singly ionized titanium in model atmospheres of reference A-K stars

NASA Astrophysics Data System (ADS)

Sitnova, T. M.; Mashonkina, L. I.; Ryabchikova, T. A.

2016-09-01

We construct a model atom for Ti I-II using more than 3600 measured and predicted energy levels of Ti I and 1800 energy levels of Ti II, and quantum mechanical photoionization cross-sections. Non-local thermodynamical equilibrium (NLTE) line formation for Ti I and Ti II is treated through a wide range of spectral types from A to K, including metal-poor stars with [Fe/H] down to -2.6 dex. NLTE leads to weakened Ti I lines and positive abundance corrections. The magnitude of NLTE corrections is smaller compared to the literature data for FGK atmospheres. NLTE leads to strengthened Ti II lines and negative NLTE abundance corrections. For the first time, we have performed NLTE calculations for Ti I-II in the 6500 ≤ Teff ≤ 13 000 K range. For four A-type stars, we derived in LTE an abundance discrepancy of up to 0.22 dex between Ti I and Ti II, which vanishes in NLTE. For four other A-B stars, with only Ti II lines observed, NLTE leads to a decrease of line-to-line scatter. An efficiency of inelastic Ti I + H I collisions was estimated from an analysis of Ti I and Ti II lines in 17 cool stars with -2.6 ≤ [Fe/H] ≤ 0.0. Consistent NLTE abundances from Ti I and Ti II were obtained by applying classical Drawinian rates for the stars with log g ≥ 4.1, and neglecting inelastic collisions with H I for the very metal-poor (VMP) giant HD 122563. For the VMP turn-off stars ([Fe/H] ≤ -2 and log g ≤ 4.1), we obtained the positive abundance difference Ti I-II already in LTE, which increases in NLTE. Accurate collisional data for Ti I and Ti II are necessary to help solve this problem.

Mössbauer, EPR, and Modeling Study of Iron Trafficking and Regulation in Δccc1 and CCC1-up Saccharomyces cerevisiae

PubMed Central

2015-01-01

Strains lacking and overexpressing the vacuolar iron (Fe) importer CCC1 were characterized using Mössbauer and EPR spectroscopies. Vacuolar Fe import is impeded in Δccc1 cells and enhanced in CCC1-up cells, causing vacuolar Fe in these strains to decline and accumulate, respectively, relative to WT cells. Cytosolic Fe levels should behave oppositely. The Fe content of Δccc1 cells grown under low-Fe conditions was similar to that in WT cells. Most Fe was mitochondrial with some nonheme high spin (NHHS) FeII present. Δccc1 cells grown with increasing Fe concentration in the medium contained less total Fe, less vacuolar HS FeIII, and more NHHS FeII than in comparable WT cells. As the Fe concentration in the growth medium increased, the concentration of HS FeIII in Δccc1 cells increased to just 60% of WT levels, while NHHS FeII increased to twice WT levels, suggesting that the NHHS FeII was cytosolic. Δccc1 cells suffered more oxidative damage than WT cells, suggesting that the accumulated NHHS FeII promoted Fenton chemistry. The Fe concentration in CCC1-up cells was higher than in WT cells; the extra Fe was present as NHHS FeII and FeIII and as FeIII oxyhydroxide nanoparticles. These cells contained less mitochondrial Fe and exhibited less ROS damage than Δccc1 cells. CCC1-up cells were adenine-deficient on minimal medium; supplementing with adenine caused a decline of NHHS FeII suggesting that some of the NHHS FeII that accumulated in these cells was associated with adenine deficiency rather than the overexpression of CCC1. A mathematical model was developed that simulated changes in Fe distributions. Simulations suggested that only a modest proportion of the observed NHHS FeII in both strains was the cytosolic form of Fe that is sensed by the Fe import regulatory system. The remainder is probably generated by the reduction of the vacuolar NHHS FeIII species. PMID:24785783

Mössbauer, EPR, and modeling study of iron trafficking and regulation in Δccc1 and CCC1-up Saccharomyces cerevisiae.

PubMed

Cockrell, Allison; McCormick, Sean P; Moore, Michael J; Chakrabarti, Mrinmoy; Lindahl, Paul A

2014-05-13

Strains lacking and overexpressing the vacuolar iron (Fe) importer CCC1 were characterized using Mössbauer and EPR spectroscopies. Vacuolar Fe import is impeded in Δccc1 cells and enhanced in CCC1-up cells, causing vacuolar Fe in these strains to decline and accumulate, respectively, relative to WT cells. Cytosolic Fe levels should behave oppositely. The Fe content of Δccc1 cells grown under low-Fe conditions was similar to that in WT cells. Most Fe was mitochondrial with some nonheme high spin (NHHS) Fe(II) present. Δccc1 cells grown with increasing Fe concentration in the medium contained less total Fe, less vacuolar HS Fe(III), and more NHHS Fe(II) than in comparable WT cells. As the Fe concentration in the growth medium increased, the concentration of HS Fe(III) in Δccc1 cells increased to just 60% of WT levels, while NHHS Fe(II) increased to twice WT levels, suggesting that the NHHS Fe(II) was cytosolic. Δccc1 cells suffered more oxidative damage than WT cells, suggesting that the accumulated NHHS Fe(II) promoted Fenton chemistry. The Fe concentration in CCC1-up cells was higher than in WT cells; the extra Fe was present as NHHS Fe(II) and Fe(III) and as Fe(III) oxyhydroxide nanoparticles. These cells contained less mitochondrial Fe and exhibited less ROS damage than Δccc1 cells. CCC1-up cells were adenine-deficient on minimal medium; supplementing with adenine caused a decline of NHHS Fe(II) suggesting that some of the NHHS Fe(II) that accumulated in these cells was associated with adenine deficiency rather than the overexpression of CCC1. A mathematical model was developed that simulated changes in Fe distributions. Simulations suggested that only a modest proportion of the observed NHHS Fe(II) in both strains was the cytosolic form of Fe that is sensed by the Fe import regulatory system. The remainder is probably generated by the reduction of the vacuolar NHHS Fe(III) species.

Copper(II) complex with 6-methylpyridine-2-carboxyclic acid: Experimental and computational study on the XRD, FT-IR and UV-Vis spectra, refractive index, band gap and NLO parameters

NASA Astrophysics Data System (ADS)

Altürk, Sümeyye; Avcı, Davut; Başoğlu, Adil; Tamer, Ömer; Atalay, Yusuf; Dege, Necmi

2018-02-01

Crystal structure of the synthesized copper(II) complex with 6-methylpyridine-2-carboxylic acid, [Cu(6-Mepic)2·H2O]·H2O, was determined by XRD, FT-IR and UV-Vis spectroscopic techniques. Furthermore, the geometry optimization, harmonic vibration frequencies for the Cu(II) complex were carried out by using Density Functional Theory calculations with HSEh1PBE/6-311G(d,p)/LanL2DZ level. Electronic absorption wavelengths were obtained by using TD-DFT/HSEh1PBE/6-311G(d,p)/LanL2DZ level with CPCM model and major contributions were determined via Swizard/Chemissian program. Additionally, the refractive index, linear optical (LO) and non-nonlinear optical (NLO) parameters of the Cu(II) complex were calculated at HSEh1PBE/6-311G(d,p) level. The experimental and computed small energy gap shows the charge transfer in the Cu(II) complex. Finally, the hyperconjugative interactions and intramolecular charge transfer (ICT) were studied by performing of natural bond orbital (NBO) analysis.

Copper(II) complex with 6-methylpyridine-2-carboxyclic acid: Experimental and computational study on the XRD, FT-IR and UV-Vis spectra, refractive index, band gap and NLO parameters.

PubMed

Altürk, Sümeyye; Avcı, Davut; Başoğlu, Adil; Tamer, Ömer; Atalay, Yusuf; Dege, Necmi

2018-02-05

Crystal structure of the synthesized copper(II) complex with 6-methylpyridine-2-carboxylic acid, [Cu(6-Mepic) 2 ·H 2 O]·H 2 O, was determined by XRD, FT-IR and UV-Vis spectroscopic techniques. Furthermore, the geometry optimization, harmonic vibration frequencies for the Cu(II) complex were carried out by using Density Functional Theory calculations with HSEh1PBE/6-311G(d,p)/LanL2DZ level. Electronic absorption wavelengths were obtained by using TD-DFT/HSEh1PBE/6-311G(d,p)/LanL2DZ level with CPCM model and major contributions were determined via Swizard/Chemissian program. Additionally, the refractive index, linear optical (LO) and non-nonlinear optical (NLO) parameters of the Cu(II) complex were calculated at HSEh1PBE/6-311G(d,p) level. The experimental and computed small energy gap shows the charge transfer in the Cu(II) complex. Finally, the hyperconjugative interactions and intramolecular charge transfer (ICT) were studied by performing of natural bond orbital (NBO) analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

A Confirmatory Factor Analysis of the California Verbal Learning Test-Second Edition (CVLT-II) in the Standardization Sample

ERIC Educational Resources Information Center

Donders, Jacobus

2008-01-01

The purpose of this study is to determine the latent structure of the California Verbal Learning Test-Second Edition (CVLT-II; Delis, Kramer, Kaplan, & Ober, 2000) at three different age levels, using the standardization sample. Maximum likelihood confirmatory factor analyses are performed to test four competing hypothetical models for fit and…

Genome-Wide RNA Polymerase II Profiles and RNA Accumulation Reveal Kinetics of Transcription and Associated Epigenetic Changes During Diurnal Cycles

PubMed Central

Gilardi, Federica; Liechti, Robin; Martin, Olivier; Harshman, Keith; Delorenzi, Mauro; Desvergne, Béatrice; Herr, Winship; Deplancke, Bart; Schibler, Ueli; Rougemont, Jacques; Guex, Nicolas; Hernandez, Nouria; Naef, Felix

2012-01-01

Interactions of cell-autonomous circadian oscillators with diurnal cycles govern the temporal compartmentalization of cell physiology in mammals. To understand the transcriptional and epigenetic basis of diurnal rhythms in mouse liver genome-wide, we generated temporal DNA occupancy profiles by RNA polymerase II (Pol II) as well as profiles of the histone modifications H3K4me3 and H3K36me3. We used these data to quantify the relationships of phases and amplitudes between different marks. We found that rhythmic Pol II recruitment at promoters rather than rhythmic transition from paused to productive elongation underlies diurnal gene transcription, a conclusion further supported by modeling. Moreover, Pol II occupancy preceded mRNA accumulation by 3 hours, consistent with mRNA half-lives. Both methylation marks showed that the epigenetic landscape is highly dynamic and globally remodeled during the 24-hour cycle. While promoters of transcribed genes had tri-methylated H3K4 even at their trough activity times, tri-methylation levels reached their peak, on average, 1 hour after Pol II. Meanwhile, rhythms in tri-methylation of H3K36 lagged transcription by 3 hours. Finally, modeling profiles of Pol II occupancy and mRNA accumulation identified three classes of genes: one showing rhythmicity both in transcriptional and mRNA accumulation, a second class with rhythmic transcription but flat mRNA levels, and a third with constant transcription but rhythmic mRNAs. The latter class emphasizes widespread temporally gated posttranscriptional regulation in the mouse liver. PMID:23209382

Electroacupuncture improves cerebral blood flow and attenuates moderate ischemic injury via Angiotensin II its receptors-mediated mechanism in rats.

PubMed

Li, Jing; He, Jiaojun; Du, Yuanhao; Cui, Jingjun; Ma, Ying; Zhang, Xuezhu

2014-11-11

To investigate the effects and potential mechanism of electroacupuncture intervention on expressions of Angiotensin II and its receptors-mediated signaling pathway in experimentally induced cerebral ischemia. Totally 126 male Wistar rats were randomly divided into control group, model group and EA group. The latter two were further divided into ten subgroups (n = 6) following Middle Cerebral Artery Occlusion (MCAO). Changes in regional cerebral blood flow (rCBF) and expressions of Angiotensin II and its receptors (AT1R, AT2R), as well as effector proteins in phosphatidyl inositol signal pathway were monitored before and at different times after MCAO. MCAO-induced decline of ipsilateral rCBF was partially suppressed by electroacupuncture, and contralateral blood flow was also superior to that of model group. Angiotensin II level was remarkably elevated immediately after MCAO, while electroacupuncture group exhibited significantly lower levels at 1 to 3 h and the value was significantly increased thereafter. The enhanced expression of AT1R was partially inhibited by electroacupuncture, while increased AT2R level was further induced. Electroacupuncture stimulation attenuated and postponed the upregulated-expressions of Gq and CaM these upregulations. ELISA results showed sharply increased expressions of DAG and IP3, which were remarkably neutralized by electroacupuncture. MCAO induced significant increases in expression of Angiotensin II and its receptor-mediated signal pathway. These enhanced expressions were significantly attenuated by electroacupuncture intervention, followed by reduced vasoconstriction and improved blood supply in ischemic region, and ultimately conferred beneficial effects on cerebral ischemia.

Simulation model for wind energy storage systems. Volume II. Operation manual. [SIMWEST code

DOE Office of Scientific and Technical Information (OSTI.GOV)

Warren, A.W.; Edsinger, R.W.; Burroughs, J.D.

1977-08-01

The effort developed a comprehensive computer program for the modeling of wind energy/storage systems utilizing any combination of five types of storage (pumped hydro, battery, thermal, flywheel and pneumatic). An acronym for the program is SIMWEST (Simulation Model for Wind Energy Storage). The level of detail of SIMWEST is consistent with a role of evaluating the economic feasibility as well as the general performance of wind energy systems. The software package consists of two basic programs and a library of system, environmental, and load components. Volume II, the SIMWEST operation manual, describes the usage of the SIMWEST program, the designmore » of the library components, and a number of simple example simulations intended to familiarize the user with the program's operation. Volume II also contains a listing of each SIMWEST library subroutine.« less

Kinetic model to explain the effect of ocean warming and acidification on the Fe(II) oxidation rate in oligotrophic and eutrophic natural waters

NASA Astrophysics Data System (ADS)

González-Dávila, M.; Samperio-Ramos, G.; Santana-Casiano, J. M.; Gonzallez, A. G.; Pérez-Almeida, N.

2016-12-01

The speciation of inorganic Fe(II) as a function of the pH and temperature have been modeled in order to elucidate the inorganic Fe(II) redox behavior over a wide range of scenarios of acidification and global warming of the upper ocean, as well as, changes due to natural ambient fluctuations of pH and temperature. In addition, a kinetic modeling approach has been carried out to elucidate the fractional contribution of most kinetically active Fe(II) species to the overall oxidation rate to improve our future and present knowledge with respect to redox iron chemistry in the marine systems. The kinetic model considers the interactions of Fe(II) with the major ions in seawater, including phosphate and silicate and the competition with copper with the ROS. The model has been applied to the experimental results in order to describe the effect of temperature and pH in the speciation of Fe(II) and to compute the fractional contribution of each Fe(II)-specie to the overall oxidation rate. The oxidation rates (kapp) of nanomolar levels of Fe(II) have been studied in seawater enriched with nutrients (SWEN) in air saturated conditions. The nutrient effect (nitrate, phosphate and silicate), on the oxidation of Fe(II), has been evaluated as a function of pH (7.2-8.2), temperature (5-35 ºC) and salinity (10-37.09). The oxidation of Fe(II) was faster in the presence of nutrient with the change in the Fe(II) oxidation rates (Δlogkapp) more intensive at higher temperatures over the entire pH range studied. From the model it can be observed that the inorganic speciation of Fe(II) is controlled largely by pH, either in SW or in SWEN. A greater presence of Fe-nutrient reactive species (FeH3SiO4+ and FePO4-) in SWEN at higher temperatures explained the changes in the oxidation process. The individual oxidation rates by oxygen, for the Fe(II) most kinetically active species (Fe2+, FeOH+, Fe(OH)2, FeCO3(OH)-, FeCO3, Fe(CO3)22-, FeH3SiO3+, FePO4-), were fitted as a function of the temperature.

Thermodynamic Analysis of Nickel(II) and Zinc(II) Adsorption to Biochar.

PubMed

Alam, Md Samrat; Gorman-Lewis, Drew; Chen, Ning; Flynn, Shannon L; Ok, Yong Sik; Konhauser, Kurt O; Alessi, Daniel S

2018-05-21

While numerous studies have investigated metal uptake from solution by biochar, few of these have developed a mechanistic understanding of the adsorption reactions that occur at the biochar surface. In this study, we explore a combined modeling and spectroscopic approach for the first time to describe the molecular level adsorption of Ni(II) and Zn(II) to five types of biochar. Following thorough characterization, potentiometric titrations were carried out to measure the proton (H + ) reactivity of each biochar, and the data was used to develop protonation models. Surface complexation modeling (SCM) supported by synchrotron-based extended X-ray absorption fine structure (EXAFS) was then used to gain insights into the molecular scale metal-biochar surface reactions. The SCM approach was combined with isothermal titration calorimetry (ITC) data to determine the thermodynamic driving forces of metal adsorption. Our results show that the reactivity of biochar toward Ni(II) and Zn(II) directly relates to the site densities of biochar. EXAFS along with FT-IR analyses, suggest that Ni(II) and Zn(II) adsorption occurred primarily through proton-active carboxyl (-COOH) and hydroxyl (-OH) functional groups on the biochar surface. SCM-ITC analyses revealed that the enthalpies of protonation are exothermic and Ni(II) and Zn(II) complexes with biochar surface are slightly exothermic to slightly endothermic. The results obtained from these combined approaches contribute to the better understanding of molecular scale metal adsorption onto the biochar surface, and will facilitate the further development of thermodynamics-based, predictive approaches to biochar removal of metals from contaminated water.

Intracellular Zn(II) Intoxication Leads to Dysregulation of the PerR Regulon Resulting in Heme Toxicity in Bacillus subtilis

PubMed Central

2016-01-01

Transition metal ions (Zn(II), Cu(II)/(I), Fe(III)/(II), Mn(II)) are essential for life and participate in a wide range of biological functions. Cellular Zn(II) levels must be high enough to ensure that it can perform its essential roles. Yet, since Zn(II) binds to ligands with high avidity, excess Zn(II) can lead to protein mismetallation. The major targets of mismetallation, and the underlying causes of Zn(II) intoxication, are not well understood. Here, we use a forward genetic selection to identify targets of Zn(II) toxicity. In wild-type cells, in which Zn(II) efflux prevents intoxication of the cytoplasm, extracellular Zn(II) inhibits the electron transport chain due to the inactivation of the major aerobic cytochrome oxidase. This toxicity can be ameliorated by depression of an alternate oxidase or by mutations that restrict access of Zn(II) to the cell surface. Conversely, efflux deficient cells are sensitive to low levels of Zn(II) that do not inhibit the respiratory chain. Under these conditions, intracellular Zn(II) accumulates and leads to heme toxicity. Heme accumulation results from dysregulation of the regulon controlled by PerR, a metal-dependent repressor of peroxide stress genes. When metallated with Fe(II) or Mn(II), PerR represses both heme biosynthesis (hemAXCDBL operon) and the abundant heme protein catalase (katA). Metallation of PerR with Zn(II) disrupts this coordination, resulting in depression of heme biosynthesis but continued repression of catalase. Our results support a model in which excess heme partitions to the membrane and undergoes redox cycling catalyzed by reduced menaquinone thereby resulting in oxidative stress. PMID:27935957

Uncertainties in Atomic Data and Their Propagation Through Spectral Models. I.

NASA Technical Reports Server (NTRS)

Bautista, M. A.; Fivet, V.; Quinet, P.; Dunn, J.; Gull, T. R.; Kallman, T. R.; Mendoza, C.

2013-01-01

We present a method for computing uncertainties in spectral models, i.e., level populations, line emissivities, and emission line ratios, based upon the propagation of uncertainties originating from atomic data.We provide analytic expressions, in the form of linear sets of algebraic equations, for the coupled uncertainties among all levels. These equations can be solved efficiently for any set of physical conditions and uncertainties in the atomic data. We illustrate our method applied to spectral models of Oiii and Fe ii and discuss the impact of the uncertainties on atomic systems under different physical conditions. As to intrinsic uncertainties in theoretical atomic data, we propose that these uncertainties can be estimated from the dispersion in the results from various independent calculations. This technique provides excellent results for the uncertainties in A-values of forbidden transitions in [Fe ii]. Key words: atomic data - atomic processes - line: formation - methods: data analysis - molecular data - molecular processes - techniques: spectroscopic

Computational model for operation of 2 mum co-doped Tm,Ho solid state lasers.

PubMed

Louchev, Oleg A; Urata, Yoshiharu; Saito, Norihito; Wada, Satoshi

2007-09-17

A computational model for operation of co-doped Tm,Ho solid-state lasers is developed coupling (i) 8-level rate equations with (ii) TEM00 laser beam distribution, and (iii) complex heat dissipation model. Simulations done for Q-switched approximately 0.1 J giant pulse generation by Tm,Ho:YLF laser show that approximately 43% of the 785 nm light diode side-pumped energy is directly transformed into the heat inside the crystal, whereas approximately 45% is the spontaneously emitted radiation from (3)F(4), (5)I(7) , (3)H(4) and (3)H(5) levels. In water-cooled operation this radiation is absorbed inside the thermal boundary layer where the heat transfer is dominated by heat conduction. In high-power operation the resulting temperature increase is shown to lead to (i) significant decrease in giant pulse energy and (ii) thermal lensing.

Heterogeneous models for an early discrimination between sepsis and non-infective SIRS in medical ward patients: a pilot study.

PubMed

Mearelli, Filippo; Fiotti, Nicola; Altamura, Nicola; Zanetti, Michela; Fernandes, Giovanni; Burekovic, Ismet; Occhipinti, Alessandro; Orso, Daniele; Giansante, Carlo; Casarsa, Chiara; Biolo, Gianni

2014-10-01

The objective of the study was to determine the accuracy of phospholipase A2 group II (PLA2-II), interferon-gamma-inducible protein 10 (IP-10), angiopoietin-2 (Ang-2), and procalcitonin (PCT) plasma levels in early ruling in/out of sepsis among systemic inflammatory response syndrome (SIRS) patients. Biomarker levels were determined in 80 SIRS patients during the first 4 h of admission to the medical ward. The final diagnosis of sepsis or non-infective SIRS was issued according to good clinical practice. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for sepsis diagnosis were assessed. The optimal biomarker combinations with clinical variables were investigated by logistic regression and decision tree (CART). PLA2-II, IP-10 and PCT, but not Ang-2, were significantly higher in septic (n = 60) than in non-infective SIRS (n = 20) patients (P ≤ 0.001, 0.027, and 0.002, respectively). PLA2-II PPV and NPV were 88 and 86%, respectively. The corresponding figures were 100 and 31% for IP-10, and 93 and 35% for PCT. Binary logistic regression model had 100% PPV and NPV, while manual and software-generated CART reached an overall accuracy of 95 and 98%, respectively, both with 100% NPV. PLA2-II and IP-10 associated with clinical variables in regression or decision tree heterogeneous models may be valuable biomarkers for sepsis diagnosis in SIRS patients admitted to medical ward (MW). Further studies are needed to introduce them into clinical practice.

A Multilevel Analysis of Phase II of the Louisiana School Effectiveness Study.

ERIC Educational Resources Information Center

Kennedy, Eugene; And Others

This paper presents findings of a study that used conventional modeling strategies (student- and school-level) and a new multilevel modeling strategy, Hierarchical Linear Modeling, to investigate school effects on student-achievement outcomes for data collected as part of Phase 2 of the Louisiana School Effectiveness Study. The purpose was to…

THE HANLE AND ZEEMAN POLARIZATION SIGNALS OF THE SOLAR Ca II 8542 Å LINE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Štěpán, Jiri; Bueno, Javier Trujillo

We highlight the main results of a three-dimensional (3D) multilevel radiative transfer investigation about the solar disk-center polarization of the Ca ii 8542 Å line. First, through the use of a 3D model of the solar atmosphere, we investigate the linear polarization that occurs due to the atomic level polarization produced by the absorption and scattering of anisotropic radiation, taking into account the symmetry-breaking effects caused by its thermal, dynamic, and magnetic structure. Second, we study the contribution of the Zeeman effect to the linear and circular polarization. Finally, we show examples of the Stokes profiles produced by the jointmore » action of the atomic level polarization and the Hanle and Zeeman effects. We find that the Zeeman effect tends to dominate the linear polarization signals only in the localized patches of opposite magnetic polarity, where the magnetic field is relatively strong and slightly inclined; outside such very localized patches, the linear polarization is often dominated by the contribution of atomic level polarization. We demonstrate that a correct modeling of this last contribution requires taking into account the symmetry-breaking effects caused by the thermal, dynamic, and magnetic structure of the solar atmosphere, and that in the 3D model used the Hanle effect in forward-scattering geometry (disk-center observation) mainly reduces the polarization corresponding to the zero-field case. We emphasize that, in general, a reliable modeling of the linear polarization in the Ca ii 8542 Å line requires taking into account the joint action of atomic level polarization and the Hanle and Zeeman effects.« less

Development of Airport Noise Mapping using Matlab Software (Case Study: Adi Soemarmo Airport - Boyolali, Indonesia)

NASA Astrophysics Data System (ADS)

Andarani, Pertiwi; Setiyo Huboyo, Haryono; Setyanti, Diny; Budiawan, Wiwik

2018-02-01

Noise is considered as one of the main environmental impact of Adi Soemarmo International Airport (ASIA), the second largest airport in Central Java Province, Indonesia. In order to manage the noise of airport, airport noise mapping is necessary. However, a model that requires simple input but still reliable was not available in ASIA. Therefore, the objective of this study are to develop model using Matlab software, to verify its reliability by measuring actual noise exposure, and to analyze the area of noise levels‥ The model was developed based on interpolation or extrapolation of identified Noise-Power-Distance (NPD) data. In accordance with Indonesian Government Ordinance No.40/2012, the noise metric used is WECPNL (Weighted Equivalent Continuous Perceived Noise Level). Based on this model simulation, there are residence area in the region of noise level II (1.912 km2) and III (1.16 km2) and 18 school buildings in the area of noise levels I, II, and III. These land-uses are actually prohibited unless noise insulation is equipped. The model using Matlab in the case of Adi Soemarmo International Airport is valid based on comparison of the field measurement (6 sampling points). However, it is important to validate the model again once the case study (the airport) is changed.

Theoretical basal Ca II fluxes for late-type stars: results from magnetic wave models with time-dependent ionization and multi-level radiation treatments

NASA Astrophysics Data System (ADS)

Fawzy, Diaa E.; Stȩpień, K.

2018-03-01

In the current study we present ab initio numerical computations of the generation and propagation of longitudinal waves in magnetic flux tubes embedded in the atmospheres of late-type stars. The interaction between convective turbulence and the magnetic structure is computed and the obtained longitudinal wave energy flux is used in a self-consistent manner to excite the small-scale magnetic flux tubes. In the current study we reduce the number of assumptions made in our previous studies by considering the full magnetic wave energy fluxes and spectra as well as time-dependent ionization (TDI) of hydrogen, employing multi-level Ca II atomic models, and taking into account departures from local thermodynamic equilibrium. Our models employ the recently confirmed value of the mixing-length parameter α=1.8. Regions with strong magnetic fields (magnetic filling factors of up to 50%) are also considered in the current study. The computed Ca II emission fluxes show a strong dependence on the magnetic filling factors, and the effect of time-dependent ionization (TDI) turns out to be very important in the atmospheres of late-type stars heated by acoustic and magnetic waves. The emitted Ca II fluxes with TDI included into the model are decreased by factors that range from 1.4 to 5.5 for G0V and M0V stars, respectively, compared to models that do not consider TDI. The results of our computations are compared with observations. Excellent agreement between the observed and predicted basal flux is obtained. The predicted trend of Ca II emission flux with magnetic filling factor and stellar surface temperature also agrees well with the observations but the calculated maximum fluxes for stars of different spectral types are about two times lower than observations. Though the longitudinal MHD waves considered here are important for chromosphere heating in high activity stars, additional heating mechanism(s) are apparently present.

75 FR 41440 - Takes of Marine Mammals Incidental to Specified Activities; Taking Marine Mammals Incidental to...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-16

... regasification process itself is an activity that does not rise to the level of taking, as the modeled source... a marine mammal or marine mammal stock in the wild [``Level A harassment'']; or (ii) has the... [``Level B harassment'']. Summary of Request NMFS received an application on December 14, 2009, from...

Characterization of xenobiotic metabolizing enzymes of a reconstructed human epidermal model from adult hair follicles.

PubMed

Bacqueville, Daniel; Jacques, Carine; Duprat, Laure; Jamin, Emilien L; Guiraud, Beatrice; Perdu, Elisabeth; Bessou-Touya, Sandrine; Zalko, Daniel; Duplan, Hélène

2017-08-15

In this study, a comprehensive characterization of xenobiotic metabolizing enzymes (XMEs) based on gene expression and enzyme functionality was made in a reconstructed skin epidermal model derived from the outer root sheath (ORS) of hair follicles (ORS-RHE). The ORS-RHE model XME gene profile was consistent with native human skin. Cytochromes P450 (CYPs) consistently reported to be detected in native human skin were also present at the gene level in the ORS-RHE model. The highest Phase I XME gene expression levels were observed for alcohol/aldehyde dehydrogenases and (carboxyl) esterases. The model was responsive to the CYP inducers, 3-methylcholanthrene (3-MC) and β-naphthoflavone (βNF) after topical and systemic applications, evident at the gene and enzyme activity level. Phase II XME levels were generally higher than those of Phase I XMEs, the highest levels were GSTs and transferases, including NAT1. The presence of functional CYPs, UGTs and SULTs was confirmed by incubating the models with 7-ethoxycoumarin, testosterone, benzo(a)pyrene and 3-MC, all of which were rapidly metabolized within 24h after topical application. The extent of metabolism was dependent on saturable and non-saturable metabolism by the XMEs and on the residence time within the model. In conclusion, the ORS-RHE model expresses a number of Phase I and II XMEs, some of which may be induced by AhR ligands. Functional XME activities were also demonstrated using systemic or topical application routes, supporting their use in cutaneous metabolism studies. Such a reproducible model will be of interest when evaluating the cutaneous metabolism and potential toxicity of innovative dermo-cosmetic ingredients. Copyright © 2017 Elsevier Inc. All rights reserved.

North Atlantic Coast Comprehensive Study Phase I: Statistical Analysis of Historical Extreme Water Levels with Sea Level Change

DTIC Science & Technology

2014-09-01

14-7 ii Abstract The U.S. North Atlantic coast is subject to coastal flooding as a result of both severe extratropical storms (e.g., Nor’easters...Products and Services, excluding any kind of high-resolution hydrodynamic modeling. Tropical and extratropical storms were treated as a single...joint probability analysis and high-fidelity modeling of tropical and extratropical storms

Nickel adsorption onto polyurethane ethylene and vinyl acetate sorbents.

PubMed

Iqbal, Munawar; Ali, Zahid; Qamar, M Afzal; Ali, Abid; Hussain, Fida; Abbas, Mazhar; Nisar, Jan

2017-07-01

The present study was conducted to appraise the efficiencies of polyurethane ethylene sorbent (PES) and vinyl acetate sorbent (VAS) for nickel (Ni) adsorption. Process variables, i.e. Ni(II) ions initial concentration, pH, contact time and adsorbent dosage were optimized by response surface methodology (RSM) approach. The Ni(II) adsorption was fitted to the kinetic models (pseudo-first-order and pseudo-second-order) and adsorption isotherms (Freundlich and Langmuir). At optimum conditions of process variables, 171.99 mg/g (64.7%) and 388.08 mg/g (92.7%) Ni(II) was adsorbed onto PES and VAS, respectively. The RSM analysis revealed that maximum Ni(II) adsorption can be achieved at 299 mg/L Ni(II) ions initial concentration, 4.5 pH, 934 min contact time and 1.3 g adsorbent dosage levels for PES, whereas the optimum values for VAS were found to be 402 mg/L Ni(II) ions initial concentration, 4.6 pH, 881 min contact time and 1.2 g adsorbent dosage, respectively. The -OH and -C = O- were involved in the Ni(II) adsorption onto PES and VAS adsorbents. At optimum levels, up to 53.67% and 80.0% Ni(II) was removed from chemical industry wastewater using PES and VAS, respectively, which suggest that PES and VAS could possibly be used for Ni(II) adsorption from industrial wastewater.

Multiple mentoring relationships facilitate learning during fieldwork.

PubMed

Nolinske, T

1995-01-01

Fieldwork provides a means by which students are socialized into their profession and their careers. During Level I and Level II fieldwork, students acquire and apply the knowledge, skills, and attitudes that will enable them to achieve entry-level competence The experiences that students have during Level II fieldwork influence their subsequent career choices. To support these experiences, students form a variety of helping relationships with faculty members, clinicians, peers, family, and friends. This article examines the role and responsibilities of the student as protégé and of the clinical educator as information peer, collegial peer, special peer, and mentor. In light of the challenges faced by most clinicians secondary to health care reform, an alternative to the one-to-one supervision model is presented. The multiple mentoring model of fieldwork supervision has several advantages: (a) fieldwork educators work with students according to their strengths and interests; (b) the model promotes collegiality and clinical reasoning skills because students use each other as resources and observe different fieldwork educators approaching similar situations; and (c) the model allows a fieldwork site to accept more students at one time, while minimizing stress on any one fieldwork educator. A framework defining the functions of the mentor-protégé relationship is provided, with an emphasis on the effect that clinical educators have in their roles as mentors, guides, role models, and teachers who provide opportunities for the student to develop entry-level competency in a chosen profession.

A model study of assisted adiabatic transfer of population in the presence of collisional dephasing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Masuda, Shumpei, E-mail: shumpei.masuda@aalto.fi; Rice, Stuart A., E-mail: s-rice@uchicago.edu

2015-06-28

Previous studies have demonstrated that when experimental conditions generate non-adiabatic dynamics that prevents highly efficient population transfer between states of an isolated system by stimulated Raman adiabatic passage (STIRAP), the addition of an auxiliary counter-diabatic field (CDF) can restore most or all of that efficiency. This paper examines whether that strategy is also successful in a non-isolated system in which the energies of the states fluctuate, e.g., when a solute is subject to collisions with solvent. We study population transfer in two model systems: (i) the three-state system used by Demirplak and Rice [J. Chem. Phys. 116, 8028 (2002)] andmore » (ii) a four-state system, derived from the simulation studies of Demirplak and Rice [J. Chem. Phys. 125, 194517 (2006)], that mimics HCl in liquid Ar. Simulation studies of the vibrational manifold of HCl in dense fluid Ar show that the collision induced vibrational energy level fluctuations have asymmetric distributions. Representations of these asymmetric energy level fluctuation distributions are used in both models (i) and (ii). We identify three sources of degradation of the efficiency of STIRAP generated selective population transfer in model (ii): too small pulse areas of the laser fields, unwanted interference arising from use of strong fields, and the vibrational detuning. For both models (i) and (ii), our examination of the efficiency of STIRAP + CDF population transfer under the influence of the asymmetric distribution of the vibrational energy fluctuations shows that there is a range of field strengths and pulse durations under which STIRAP + CDF control of population transfer has greater efficiency than does STIRAP generated population transfer.« less

Long-term ELBARA-II Assistance to SMOS Land Product and Algorithm Validation at the Valencia Anchor Station (MELBEX Experiment 2010-2013)

NASA Astrophysics Data System (ADS)

Lopez-Baeza, Ernesto; Wigneron, Jean-Pierre; Schwank, Mike; Miernecki, Maciej; Kerr, Yann; Casal, Tania; Delwart, Steven; Fernandez-Moran, Roberto; Mecklenburg, Susanne; Coll Pajaron, M. Amparo; Salgado Hernanz, Paula

The main activity of the Valencia Anchor Station (VAS) is currently now to support the validation of SMOS (Soil Moisture and Ocean Salinity) Level 2 and 3 land products (soil moisture, SM, and vegetation optical depth, TAU). With this aim, the European Space Agency (ESA) has provided the Climatology from Satellites Group of the University of Valencia with an ELBARA-II microwave radiometer under a loan agreement since September 2009. During this time, brightness temperatures (TB) have continuously been acquired, except during normal maintenance or minor repair interruptions. ELBARA-II is an L-band dual-polarization radiometer with two channels (1400-1418 MHz, 1409-1427 MHz). It is continuously measuring over a vineyard field (El Renegado, Caudete de las Fuentes, Valencia) from a 15 m platform with a constant protocol for calibration and angular scanning measurements with the aim to assisting the validation of SMOS land products and the calibration of the L-MEB (L-Band Emission of the Biosphere) -basis for the SMOS Level 2 Land Processor- over the VAS validation site. One of the advantages of using the VAS site is the possibility of studying two different environmental conditions along the year. While the vine cycle extends mainly between April and October, during the rest of the year the area remains under bare soil conditions, adequate for the calibration of the soil model. The measurement protocol currently running has shown to be robust during the whole operation time and will be extended in time as much as possible to continue providing a long-term data set of ELBARA-II TB measurements and retrieved SM and TAU. This data set is also showing to be useful in support of SMOS scientific activities: the VAS area and, specifically the ELBARA-II site, offer good conditions to control the long-term evolution of SMOS Level 2 and Level 3 land products and interpret eventual anomalies that may obscure sensor hidden biases. In addition, SM and TAU that are currently retrieved from the ELBARA-II TB data by inversion of the L-MEB model, can also be compared to the Level 2 and Level 3 SMOS products. L-band ELBARA-II measurements provide area-integrated estimations of SM and TAU that are much more representative of the soil and vegetation conditions at field scale than ground measurements (from capacitive probes for SM and destructive measurements for TAU). For instance, Miernecki et al., (2012) and Wigneron et al. (2012) showed that very good correlations could be obtained from TB data and SM retrievals obtained from both SMOS and ELBARA-II over the 2010-2011 time period. The analysis of the quality of these correlations over a long time period can be very useful to evaluate the SMOS measurements and retrieved products (Level 2 and 3). The present work that extends the analysis over almost 4 years now (2010-2013) emphasizes the need to (i) maintain the long-time record of ELBARA-II measurements (ii) enhance as much as possible the control over other parameters, especially, soil roughness (SR), vegetation water content (VWC) and surface temperature, to interpret the retrieved results obtained from both SMOS and ELBARA-II instruments.

Plasma insulin-like growth factors, insulin-like binding protein-3, and outcome in metastatic colorectal cancer: results from intergroup trial N9741.

PubMed

Fuchs, Charles S; Goldberg, Richard M; Sargent, Daniel J; Meyerhardt, Jeffrey A; Wolpin, Brian M; Green, Erin M; Pitot, Henry C; Pollak, Michael

2008-12-15

Insulin-like growth factor (IGF)-I and IGF-II stimulate neoplastic cell growth and inhibit apoptosis, whereas IGF-binding protein-3 (IGFBP-3) inhibits the bioavailability of IGF-I and has independent proapoptotic activity. We examined the influence of baseline plasma levels of IGF-I, IGF-II, IGFBP-3, and C-peptide on outcome among patients receiving first-line chemotherapy for metastatic colorectal cancer. The plasma levels of IGF-I, IGF-II, IGFBP-3, and C-peptide as well as data on prognostic factors and body size were measured at baseline among 527 patients participating in a randomized trial of first-line chemotherapy for metastatic colorectal cancer. Higher baseline plasma IGFBP-3 levels were associated with a significantly greater chemotherapy response rate (P = 0.03) after adjusting for other prognostic factors, whereas neither IGF-I nor IGF-II levels significantly predicted tumor response. Higher levels of IGF-I, IGF-II, and IGFBP-3 were all univariately associated with improved overall survival (P = 0.0001 for all). In a model that mutually adjusted for IGF-I and IGFBP-3, as well as other prognostic factors, increasing baseline-circulating IGFBP-3 was associated with a significantly longer time to tumor progression (P = 0.03), whereas circulating IGF-I was not associated with disease progression (P = 0.95). Levels of C-peptide were not associated with any measure of patient outcome. Among colorectal cancer patients receiving first-line chemotherapy, increasing levels of IGFBP-3, an endogenous antagonist to IGF-I, are associated with an improved objective treatment response and a prolonged time to cancer progression. The IGF pathway may represent an important target for future treatment strategies.

Development of a traffic noise prediction model for an urban environment.

PubMed

Sharma, Asheesh; Bodhe, G L; Schimak, G

2014-01-01

The objective of this study is to develop a traffic noise model under diverse traffic conditions in metropolitan cities. The model has been developed to calculate equivalent traffic noise based on four input variables i.e. equivalent traffic flow (Q e ), equivalent vehicle speed (S e ) and distance (d) and honking (h). The traffic data is collected and statistically analyzed in three different cases for 15-min during morning and evening rush hours. Case I represents congested traffic where equivalent vehicle speed is <30 km/h while case II represents free-flowing traffic where equivalent vehicle speed is >30 km/h and case III represents calm traffic where no honking is recorded. The noise model showed better results than earlier developed noise model for Indian traffic conditions. A comparative assessment between present and earlier developed noise model has also been presented in the study. The model is validated with measured noise levels and the correlation coefficients between measured and predicted noise levels were found to be 0.75, 0.83 and 0.86 for case I, II and III respectively. The noise model performs reasonably well under different traffic conditions and could be implemented for traffic noise prediction at other region as well.

DRAINMOD-FOREST: Integrated modeling of hydrology, soil carbon and nitrogen dynamics, and plant growth for drained forests

Treesearch

Shiying Tian; Mohamed A. Youssef; R. Wayne Skaggs; Devendra M. Amatya; G.M. Chescheir

2012-01-01

We present a hybrid and stand-level forest ecosystem model, DRAINMOD-FOREST, for simulating the hydrology, carbon (C) and nitrogen (N) dynamics, and tree growth for drained forest lands under common silvicultural practices. The model was developed by linking DRAINMOD, the hydrological model, and DRAINMOD-N II, the soil C and N dynamics model, to a forest growth model,...

Circadian and Brain State Modulation of Network Hyperexcitability in Alzheimer's Disease.

PubMed

Brown, Rosalind; Lam, Alice D; Gonzalez-Sulser, Alfredo; Ying, Andrew; Jones, Mary; Chou, Robert Chang-Chih; Tzioras, Makis; Jordan, Crispin Y; Jedrasiak-Cape, Izabela; Hemonnot, Anne-Laure; Abou Jaoude, Maurice; Cole, Andrew J; Cash, Sydney S; Saito, Takashi; Saido, Takaomi; Ribchester, Richard R; Hashemi, Kevan; Oren, Iris

2018-01-01

Network hyperexcitability is a feature of Alzheimer' disease (AD) as well as numerous transgenic mouse models of AD. While hyperexcitability in AD patients and AD animal models share certain features, the mechanistic overlap remains to be established. We aimed to identify features of network hyperexcitability in AD models that can be related to epileptiform activity signatures in AD patients. We studied network hyperexcitability in mice expressing amyloid precursor protein (APP) with mutations that cause familial AD, and compared a transgenic model that overexpresses human APP (hAPP) (J20), to a knock-in model expressing APP at physiological levels (APP NL/F ). We recorded continuous long-term electrocorticogram (ECoG) activity from mice, and studied modulation by circadian cycle, behavioral, and brain state. We report that while J20s exhibit frequent interictal spikes (IISs), APP NL/F mice do not. In J20 mice, IISs were most prevalent during daylight hours and the circadian modulation was associated with sleep. Further analysis of brain state revealed that IIS in J20s are associated with features of rapid eye movement (REM) sleep. We found no evidence of cholinergic changes that may contribute to IIS-circadian coupling in J20s. In contrast to J20s, intracranial recordings capturing IIS in AD patients demonstrated frequent IIS in non-REM (NREM) sleep. The salient differences in sleep-stage coupling of IIS in APP overexpressing mice and AD patients suggests that different mechanisms may underlie network hyperexcitability in mice and humans. We posit that sleep-stage coupling of IIS should be an important consideration in identifying mouse AD models that most closely recapitulate network hyperexcitability in human AD.

Circadian and Brain State Modulation of Network Hyperexcitability in Alzheimer’s Disease

PubMed Central

Ying, Andrew; Jones, Mary; Chou, Robert Chang-Chih; Jordan, Crispin Y.; Jedrasiak-Cape, Izabela; Abou Jaoude, Maurice; Hashemi, Kevan

2018-01-01

Abstract Network hyperexcitability is a feature of Alzheimer’ disease (AD) as well as numerous transgenic mouse models of AD. While hyperexcitability in AD patients and AD animal models share certain features, the mechanistic overlap remains to be established. We aimed to identify features of network hyperexcitability in AD models that can be related to epileptiform activity signatures in AD patients. We studied network hyperexcitability in mice expressing amyloid precursor protein (APP) with mutations that cause familial AD, and compared a transgenic model that overexpresses human APP (hAPP) (J20), to a knock-in model expressing APP at physiological levels (APPNL/F). We recorded continuous long-term electrocorticogram (ECoG) activity from mice, and studied modulation by circadian cycle, behavioral, and brain state. We report that while J20s exhibit frequent interictal spikes (IISs), APPNL/F mice do not. In J20 mice, IISs were most prevalent during daylight hours and the circadian modulation was associated with sleep. Further analysis of brain state revealed that IIS in J20s are associated with features of rapid eye movement (REM) sleep. We found no evidence of cholinergic changes that may contribute to IIS-circadian coupling in J20s. In contrast to J20s, intracranial recordings capturing IIS in AD patients demonstrated frequent IIS in non-REM (NREM) sleep. The salient differences in sleep-stage coupling of IIS in APP overexpressing mice and AD patients suggests that different mechanisms may underlie network hyperexcitability in mice and humans. We posit that sleep-stage coupling of IIS should be an important consideration in identifying mouse AD models that most closely recapitulate network hyperexcitability in human AD. PMID:29780880

Assay for hypoglycemic functional food of cocoyam (Xanthosoma sagittifolium (L.) Schott.) tuber

NASA Astrophysics Data System (ADS)

Handajani, N. S.; Harini, M.; Yuliningsih, R.; Afianatuzzahra, S.; Hasanah, U.; Widiyani, T.

2018-03-01

Diabetes Mellitus (DM) type II is a degenerative disease that is a major killer in many countries. It is characterized by an increase of the blood glucose level above normal. It is important to choose an appropriate food sources using glycemic index (GI) concept in order to prevent blood glucose increase. One of Indonesian traditional carbohydrate source is cocoyam (Xanthosoma sagittifolium (L.) Schott.) tuber. The tuber is assumed having a higher carbohydrate content with lower GI. The research aims to measure GI of cocoyam tuber (CT) and determine glucose and glycogen level in animal model after CT fed. Experimental research was carried out by using completely randomized design. We used twenty four male rats as animal models. They were grouped in to 4 different treatments. Group I was treated with standard feed, group II was treated with standard feed and glucose, group III was treated with steamed CT, and group IV was treated hypoglicemic agent standard, glibencamide. The research results that GI of steamed CT was low. It was 54. Blood glucose of diabetic rats after fed by CT decreased significantly (p<0.05), similar to diabetic rats after treated by glibencamide. Whereas glycogen level in diabetic rats after fed by CT was higher than in diabetic rats after fed by standard feed. Cocoyam tuber increased glycogen level in diabetic rats significantly (p<0,05). Glycogen level in diabetic rats fed by CT was as high as in healthy rats. Therefore CT is potential consumed for DM type II patients.

PolarWindsII_DAWN_DC8_1

Atmospheric Science Data Center

2018-04-18

... Layer Winds Surface Winds Upper Level Winds Wind Profiles LIDAR Calibration/Validation Order Data:  ... Model Barrier Flow Case Study DAWN Coherent Wind Profiling Flights DAWN Overview and Preliminary Flight Results ...

Effect of Dunaliella tertiolecta organic exudates on the Fe(II) oxidation kinetics in seawater.

PubMed

González, A G; Santana-Casiano, J M; González-Dávila, M; Pérez-Almeida, N; Suárez de Tangil, M

2014-07-15

The role played by the natural organic ligands excreted by the green algae Dunaliella tertiolecta on the Fe(II) oxidation rate constants was studied at different stages of growth. The concentration of dissolved organic carbon increased from 2.1 to 7.1 mg L(-1) over time of culture. The oxidation kinetics of Fe(II) was studied at nanomolar levels and under different physicochemical conditions of pH (7.2-8.2), temperature (5-35 °C), salinity (10-37), and dissolved organic carbon produced by cells (2.1-7.1 mg L(-1)). The experimental rate always decreased in the presence of organic exudates with respect to that in the control seawater. The Fe(II) oxidation rate constant was also studied in the context of Marcus theory, where ΔG° was 39.31-51.48 kJ mol(-1). A kinetic modeling approach was applied for computing the equilibrium and rate constants for Fe(II) and exudates present in solution, the Fe(II) speciation, and the contribution of each Fe(II) species to the overall oxidation rate constant. The best fit model took into account two acidity equilibrium constants for the Fe(II) complexing ligands with pKa,1=9.45 and pKa,2=4.9. The Fe(II) complexing constants were KFe(II)-LH=3×10(10) and KFe(II)-L=10(7), and the corresponding computed oxidation rates were 68±2 and 36±8 M(-1) min(-1), respectively.

Osthole prevents intestinal ischemia-reperfusion-induced lung injury in a rodent model.

PubMed

Mo, Li-Qun; Chen, Ye; Song, Li; Wu, Gang-Ming; Tang, Ni; Zhang, Ying-Ying; Wang, Xiao-Bin; Liu, Ke-Xuan; Zhou, Jun

2014-06-15

Intestinal ischemia-reperfusion (II/R) is associated with high morbidity and mortality. The aim of this study was to investigate the effects of osthole on lung injury and mortality induced by II/R. A rat model of II/R was induced by clamping the superior mesenteric artery for 90 min followed by reperfusion for 240 min. Osthole was administrated intraperitoneally at 30 min before intestinal ischemia (10 or 50 mg/kg). The survival rate and mean arterial pressure were observed. Blood samples were obtained for blood gas analyses. Lung injury was assessed by the histopathologic changes (hematoxylin and eosin staining), lung wet-to-dry weight ratio, and pulmonary permeability index. The levels of reactive oxygen species, malondialdehyde, interleukin 6, and tumor necrosis factor α, as well as the activities of superoxide dismutase and myeloperoxidase in lung were measured. The survival rate, ratio of arterial oxygen tension to fraction of inspired oxygen, and mean arterial pressure decreased significantly after II/R. Results also indicated that II/R-induced severe lung injury evidenced by increase in pathologic scores, lung wet-to-dry weight ratio, and pulmonary permeability index, which was accompanied by increases in the levels of pulmonary reactive oxygen species, malondialdehyde, interleukin 6, tumor necrosis factor α, and the pulmonary myeloperoxidase activity and a decrease in superoxide dismutase activity. Osthole could significantly ameliorate lung injury and improve the previously mentioned variables. These findings indicated that osthole could attenuate the lung injury induced by II/R in rats, at least in part, by inhibiting inflammatory response and oxidative stress. Copyright © 2014 Elsevier Inc. All rights reserved.

Articulated Instruction Objectives Guide for Typewriting (Module 1.0--Typewriting I) (Module 2.0--Typewriting II). Project Period, March 1981-February 1982 (Pilot Model). Edition I.

ERIC Educational Resources Information Center

Reid, Barbara; And Others

Developed during the course of a project designed to provide a continuous, competency-based line of vocational training in business and office education programs at the secondary and postsecondary levels, this package consists of an instructor's guide and learning modules for use in Typewriting I and Typewriting II. Various aspects of implementing…

Placental lactogen secretion during prolonged-pregnancy in the rat: the ovary plays a pivotal role in the control of placental function.

PubMed

Shiota, K; Furuyama, N; Takahashi, M

1991-10-01

The serum of rats at mid-pregnancy contains at least 2 distinct placental lactogen (PL)-like substances tentatively termed placental lactogen-alpha (PL-alpha) and placental lactogen-beta (PL-beta) (Endocrinol Japon 38: 533-540, 1991). We have investigated the secretory patterns of three placental lactogens (PL-alpha, PL-beta and placental lactogen-II) during normal pregnancy and in two prolonged-pregnancy models. Pregnancy was prolonged by the introduction of new corpora lutea by inducing ovulation on day 15 of pregnancy by successive treatments with PMSG (30 IU/rat, sc on day 12) and hCG (10 IU/rat, iv on day 14), and in the second model by progesterone implants on day 15 of pregnancy. During normal pregnancy, each of the 3 PLs exhibited only one secretory peak in the serum; PL-alpha and PL-beta on day 12 and placental lactogen II (PL-II) on day 20. Interestingly, in the rats with new sets of corpora lutea, serum PL-alpha and PL-beta levels began to increase again on day 18 and showed peaks on day 20 for PL-alpha and on day 22 for PL-beta. In this model, the initiation of PL-II secretion was not affected, but high levels were maintained until day 26, when parturition occurred. In rats receiving either PMSG or hCG, the secretory patterns of the PLs were similar to as those during normal pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Planning level assessment of greenhouse gas emissions for alternative transportation construction projects : carbon footprint estimator, phase II, volume I - GASCAP model.

DOT National Transportation Integrated Search

2014-03-01

The GASCAP model was developed to provide a software tool for analysis of the life-cycle GHG : emissions associated with the construction and maintenance of transportation projects. This phase : of development included techniques for estimating emiss...

Framework for a Quantitative Systemic Toxicity Model (FutureToxII)

EPA Science Inventory

EPA’s ToxCast program profiles the bioactivity of chemicals in a diverse set of ~700 high throughput screening (HTS) assays. In collaboration with L’Oreal, a quantitative model of systemic toxicity was developed using no effect levels (NEL) from ToxRefDB for 633 chemicals with HT...

Transcranial direct current stimulation (tDCS) reverts behavioral alterations and brainstem BDNF level increase induced by neuropathic pain model: Long-lasting effect.

PubMed

Filho, Paulo Ricardo Marques; Vercelino, Rafael; Cioato, Stefania Giotti; Medeiros, Liciane Fernandes; de Oliveira, Carla; Scarabelot, Vanessa Leal; Souza, Andressa; Rozisky, Joanna Ripoll; Quevedo, Alexandre da Silva; Adachi, Lauren Naomi Spezia; Sanches, Paulo Roberto S; Fregni, Felipe; Caumo, Wolnei; Torres, Iraci L S

2016-01-04

Neuropathic pain (NP) is a chronic pain modality that usually results of damage in the somatosensory system. NP often shows insufficient response to classic analgesics and remains a challenge to medical treatment. The transcranial direct current stimulation (tDCS) is a non-invasive technique, which induces neuroplastic changes in central nervous system of animals and humans. The brain derived neurotrophic factor plays an important role in synaptic plasticity process. Behavior changes such as decreased locomotor and exploratory activities and anxiety disorders are common comorbidities associated with NP. Evaluate the effect of tDCS treatment on locomotor and exploratory activities, and anxiety-like behavior, and peripheral and central BDNF levels in rats submitted to neuropathic pain model. Rats were randomly divided: Ss, SsS, SsT, NP, NpS, and NpT. The neuropathic pain model was induced by partial sciatic nerve compression at 14 days after surgery; the tDCS treatment was initiated. The animals of treated groups were subjected to a 20 minute session of tDCS, for eight days. The Open Field and Elevated Pluz Maze tests were applied 24 h (phase I) and 7 days (phase II) after the end of tDCS treatment. The serum, spinal cord, brainstem and cerebral cortex BDNF levels were determined 48 h (phase I) and 8 days (phase II) after tDCS treatment by ELISA. The chronic constriction injury (CCI) induces decrease in locomotor and exploratory activities, increases in the behavior-like anxiety, and increases in the brainstem BDNF levels, the last, in phase II (one-way ANOVA/SNK, P<0.05 for all). The tDCS treatment already reverted all these effects induced by CCI (one-way ANOVA/SNK, P<0.05 for all). Furthermore, the tDCS treatment decreased serum and cerebral cortex BDNF levels and it increased these levels in the spinal cord in phase II (one-way ANOVA/SNK, P<0.05). tDCS reverts behavioral alterations associated to neuropathic pain, indicating possible analgesic and anxiolytic tDCS effects. tDCS treatment induces changes in the BDNF levels in different regions of the central nervous system (CNS), and this effect can be attributed to different cellular signaling activations. Copyright © 2015 Elsevier Inc. All rights reserved.

Elevation of autophagy markers in Sjögren syndrome dry eye.

PubMed

Byun, Yong-Soo; Lee, Hyun Jung; Shin, Soojung; Chung, So-Hyang

2017-12-08

Autophagy is known to be implicated in the pathogenesis of Sjögren syndrome (SS), but evidences are limited. We aimed to examine the levels of autophagy markers in tear film and conjunctival epithelial cells from SS dry eye patients, and analyze their correlations with clinical features. Patients with SS dry eye exhibited lower Schirmer values, lower tear breakup time, and higher ocular staining scores. In tears, ATG5 and LC3B-II/I levels were significantly higher in SS dry eye. ATG5 and LC3B-II mRNA in the conjunctiva were also elevated in SS dry eye compared with non-SS dry eye. The immunostaining of conjunctival epithelium showed a punctate pattern of ATG5 and LC3B-II in SS dry eye. These staining patterns were also observed in the lacrimal gland of SS animal models. ATG5 levels in tears and the conjunctival epithelium strongly correlated with ocular staining scores, and one month of topical corticosteroid treatment reduced both ATG5 and LC3B-II/I levels in tear film and the conjunctival epithelium of patients with SS dry eye. Our results suggest that autophagy is enhanced or dysregulated in SS and autophagy markers may be serve as both diagnostic and therapeutic biomarkers in SS dry eye.

Tight-binding model of the photosystem II reaction center: application to two-dimensional electronic spectroscopy

NASA Astrophysics Data System (ADS)

Gelzinis, Andrius; Valkunas, Leonas; Fuller, Franklin D.; Ogilvie, Jennifer P.; Mukamel, Shaul; Abramavicius, Darius

2013-07-01

We propose an optimized tight-binding electron-hole model of the photosystem II (PSII) reaction center (RC). Our model incorporates two charge separation pathways and spatial correlations of both static disorder and fast fluctuations of energy levels. It captures the main experimental features observed in time-resolved two-dimensional (2D) optical spectra at 77 K: peak pattern, lineshapes and time traces. Analysis of 2D spectra kinetics reveals that specific regions of the 2D spectra of the PSII RC are sensitive to the charge transfer states. We find that the energy disorder of two peripheral chlorophylls is four times larger than the other RC pigments.

Insulin-like signaling (IIS) responses to temperature, genetic background, and growth variation in garter snakes with divergent life histories.

PubMed

Reding, Dawn M; Addis, Elizabeth A; Palacios, Maria G; Schwartz, Tonia S; Bronikowski, Anne M

2016-07-01

The insulin/insulin-like signaling pathway (IIS) has been shown to mediate life history trade-offs in mammalian model organisms, but the function of this pathway in wild and non-mammalian organisms is understudied. Populations of western terrestrial garter snakes (Thamnophis elegans) around Eagle Lake, California, have evolved variation in growth and maturation rates, mortality senescence rates, and annual reproductive output that partition into two ecotypes: "fast-living" and "slow-living". Thus, genes associated with the IIS network are good candidates for investigating the mechanisms underlying ecological divergence in this system. We reared neonates from each ecotype for 1.5years under two thermal treatments. We then used qPCR to compare mRNA expression levels in three tissue types (brain, liver, skeletal muscle) for four genes (igf1, igf2, igf1r, igf2r), and we used radioimmunoassay to measure plasma IGF-1 and IGF-2 protein levels. Our results show that, in contrast to most mammalian model systems, igf2 mRNA and protein levels exceed those of igf1 and suggest an important role for igf2 in postnatal growth in reptiles. Thermal rearing treatment and recent growth had greater impacts on IGF levels than genetic background (i.e., ecotype), and the two ecotypes responded similarly. This suggests that observed ecotypic differences in field measures of IGFs may more strongly reflect plastic responses in different environments than evolutionary divergence. Future analyses of additional components of the IIS pathway and sequence divergence between the ecotypes will further illuminate how environmental and genetic factors influence the endocrine system and its role in mediating life history trade-offs. Copyright © 2016 Elsevier Inc. All rights reserved.

Expression of Allene Oxide Synthase Determines Defense Gene Activation in Tomato1

PubMed Central

Sivasankar, Sobhana; Sheldrick, Bay; Rothstein, Steven J.

2000-01-01

Allene oxide synthase (AOS; hydroperoxide dehydratase; EC 4.2.1.92) catalyzes the first step in the biosynthesis of jasmonic acid from lipoxygenase-derived hydroperoxides of free fatty acids. Using the AOS cDNA from tomato (Lycopersicon esculentum), in which the role of jasmonic acid in wound-induced defense gene activation has been best described, we examined the kinetics of AOS induction in response to wounding and elicitors, in parallel with that of the wound-inducible PIN II (proteinase inhibitor II) gene. AOS was induced in leaves by wounding, systemin, 12-oxophytodienoic acid, and methyl jasmonate. The levels of AOS mRNA started declining by 4 h after induction, whereas the levels of PIN II mRNA continued to increase up to 20 h after induction. Salicylic acid inhibited AOS and PIN II expression, and the addition of 12-oxophytodienoic acid or methyl jasmonate did not prevent the inhibition of PIN II expression in the presence of salicylic acid. Ethylene induced the expression of AOS, but the presence of ethylene alone did not produce an optimal induction of PIN II. The addition of silver thiosulfate, an ethylene action inhibitor, prevented the wound-induced expression of both AOS and PIN II. Products of hydroperoxide lyase affected neither AOS nor PIN II, but induced expression of prosystemin. Based on these results, we propose an updated model for defense gene activation in tomato. PMID:10759530

Bauhinia variegata (Caesalpiniaceae) leaf extract: An effective treatment option in type I and type II diabetes.

PubMed

Kulkarni, Yogesh A; Garud, Mayuresh S

2016-10-01

Among various metabolic disorders, diabetes mellitus is one of the most common disorder. Present study was designed to evaluate the effectiveness of aqueous extract of Bauhinia variegata leaves (AE) in animal models of type I and type II diabetes. Type I diabetes was induced by streptozotocin at the dose of 55mg/kg (i.p.) in male Sprague Dawley rats while type II diabetes was induced by high fat diet and streptozotocin at the dose of 35mg/kg (i.p.). Diabetic animals were treated with AE at the dose of 250, 500 and 1000mg/kg. Glipizide (5mg/kg) was used as standard treatment drug. Treatment was given for 28days. Parameters evaluated were body weight, plasma glucose, cholesterol, triglyceride, aspartate aminotransferase, alanine transaminase, alkaline phosphatase, total proteins, albumin, creatinine and bun urea nitrogen. In type II diabetes, high density lipoprotein levels in plasma and plasma insulin level were also evaluated. Histopathological study of pancreases were carried out in type I study. AE showed significant decrease in plasma glucose significantly. AE was also found to decrease cholesterol, triglyceride, creatinine and blood urea nitrogen level in both types of diabetes. AE did not show any significant effect on plasma levels of aspartate aminotransferase, alanine transaminase, alkaline phosphatase. AE was found to increase the albumin and total protein levels. Histopathological study showed that AE decreases the necrotic changes in the pancreatic tissue. Aqueous extract of B. variegata leaves was found effective in treatment of both type I and type II diabetes. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Protein classification based on text document classification techniques.

PubMed

Cheng, Betty Yee Man; Carbonell, Jaime G; Klein-Seetharaman, Judith

2005-03-01

The need for accurate, automated protein classification methods continues to increase as advances in biotechnology uncover new proteins. G-protein coupled receptors (GPCRs) are a particularly difficult superfamily of proteins to classify due to extreme diversity among its members. Previous comparisons of BLAST, k-nearest neighbor (k-NN), hidden markov model (HMM) and support vector machine (SVM) using alignment-based features have suggested that classifiers at the complexity of SVM are needed to attain high accuracy. Here, analogous to document classification, we applied Decision Tree and Naive Bayes classifiers with chi-square feature selection on counts of n-grams (i.e. short peptide sequences of length n) to this classification task. Using the GPCR dataset and evaluation protocol from the previous study, the Naive Bayes classifier attained an accuracy of 93.0 and 92.4% in level I and level II subfamily classification respectively, while SVM has a reported accuracy of 88.4 and 86.3%. This is a 39.7 and 44.5% reduction in residual error for level I and level II subfamily classification, respectively. The Decision Tree, while inferior to SVM, outperforms HMM in both level I and level II subfamily classification. For those GPCR families whose profiles are stored in the Protein FAMilies database of alignments and HMMs (PFAM), our method performs comparably to a search against those profiles. Finally, our method can be generalized to other protein families by applying it to the superfamily of nuclear receptors with 94.5, 97.8 and 93.6% accuracy in family, level I and level II subfamily classification respectively. Copyright 2005 Wiley-Liss, Inc.

Neuroprotective effect of humic Acid on focal cerebral ischemia injury: an experimental study in rats.

PubMed

Ozkan, Adile; Sen, Halil Murat; Sehitoglu, Ibrahim; Alacam, Hasan; Guven, Mustafa; Aras, Adem Bozkurt; Akman, Tarik; Silan, Coşkun; Cosar, Murat; Karaman, Handan Isin Ozisik

2015-02-01

Stroke is still a major cause of death and permanent neurological disability. As humic acids are well-known antioxidant molecules, the purpose of this study was to investigate the potential neuroprotective effects of humic acid in a focal cerebral ischemia model. Twenty-four rats were divided equally into three groups. A middle cerebral artery occlusion model was performed in this study where control (group II) and humic acid (group III) were administered intraperitoneally following an ischemic experimental procedure. Group I was evaluated as sham. Malondialdehyde (MDA), superoxide dismutase (SOD), and nuclear respiratory factor-1 (NRF-1) levels were analyzed biochemically on the right side of the ischemic cerebral hemisphere, while ischemic histopathological studies were completed on the left side to investigate the antioxidant status. Biochemical results showed that SOD and NRF-1 levels were significantly increased in the humic acid group (III) compared with the control group (II) while MDA levels were significantly decreased. On histopathological examination, cerebral edema, vacuolization, degeneration, and destruction of neural elements were decreased in the humic acid group (III) compared with the control group (II). Cerebral ischemia was attenuated by humic acid administration. These observations indicate that humic acid may have potential as a therapeutic agent in cerebral ischemia by preventing oxidative stress.

Identification of potential serum markers for nasopharyngeal carcinoma from a xenografted mouse model using Cy-dye labeling combined with three-dimensional fractionation.

PubMed

Wu, Chih-Ching; Peng, Pei-Hua; Chang, Ya-Ting; Huang, Yu-Shan; Chang, Kai-Ping; Hao, Sheng-Po; Tsang, Ngan-Ming; Yeh, Chau-Ting; Chang, Yu-Sun; Yu, Jau-Song

2008-09-01

Nasopharyngeal carcinoma (NPC), one of the most common cancers in Southeast Asia, is commonly diagnosed late due to its deep location and vague symptoms. To identify biomarkers for improving NPC diagnosis, we established a proteomic platform for detecting aberrant serum proteins in nude mice bearing NPC xenografts. We first removed the three most abundant proteins from serum samples of tumor-bearing and control mice, and then labeled the samples with different fluorescent cyanine (Cy) dyes. The labeled serum proteins were then mixed equally and fractionated with ion-exchange chromatography followed by SDS-PAGE. Differentially expressed proteins were identified by in-gel tryptic digestion and MALDI-TOF MS. We identified peroxiredoxin 2 (Prx-II) and carbonic anhydrase 2 (CA-II) as being elevated in the xenograft mouse model compared to controls. Western blot analysis confirmed up-regulation of Prx-II and CA-II in plasma from five NPC patients, and ELISA showed that plasma Prx-II levels were significantly higher in NPC patients (n = 84) versus healthy controls (n = 90) (3.03 +/- 4.47 versus 1.90 +/- 2.74 microg/mL, p = 0.047). In conclusion, Cy dye labeling combined with three-dimensional fractionation is a feasible strategy for identifying differentially expressed serum proteins in an NPC xenograft model, and Prx-II may represent a potential NPC biomarker.

Effect of AMPK signal pathway on pathogenesis of abdominal aortic aneurysms

PubMed Central

Yang, Le; Shen, Lin; Gao, Peixian; Li, Gang; He, Yuxiang; Wang, Maohua; Zhou, Hua; Yuan, Hai; Jin, Xing; Wu, Xuejun

2017-01-01

Background and aims Determine the effect of AMPK activation and inhibition on the development of AAA (abdominal aortic aneurysm). Methods AAA was induced in ApoE−/− mice by Ang II (Angiotensin II)-infusion. AICAR (5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside) was used as AMPK activator and Compound C was used as AMPK inhibitor. We further investigate the effect of metformin, a widely used anti-diabetic drug which could activate AMPK signal pathway, on the pathogenesis of aneurysm. Results Phospho-AMPK level was significantly decreased in AAA tissue compared with control aortas. AICAR significantly reduced the incidence, severity and mortality of aneurysm in the Ang II-infusion model. AICAR also alleviated macrophage infiltration and neovascularity in Ang II infusion model at day 28. The expression of pro-inflammatory factors, angiogenic factors and the activity of MMPs were also alleviated by AICAR during AAA induction. On the other hand, Compound C treatment did not exert obvious protective effect. AMPK activation may inhibit the activation of nuclear factor-κB (NF-κB) and signal transducer and activator of transcription-3 (STAT-3) during AAA induction. Administration of metformin also activated AMPK signal pathway and retarded AAA progression in Ang II infusion model. Conclusions Activation of AMPK signaling pathway may inhibit the Ang II-induced AAA in mice. Metformin may be a promising approach to the treatment of AAA. PMID:29190959

Distance determination to Broad Line Absorbers in AGN

NASA Astrophysics Data System (ADS)

Bautista, Manuel; Arav, N.; Dunn, J.; Edmonds, D.; Korista, K. T.; Moe, M.; Benn, C.; Ignacio, G.

2009-01-01

We present various techniques for the determination of the physical conditions (density, temperature, total hydrogen column density, and ionization structure), chemical composition, and distances of Broad Line Absorbers (BAL) to the central engine in AGN. We start by discussing various density diagnostics from absorption lines from species such as C II, Si II, and Fe III. On the other hand, lines from metastable levels Fe II are often affected by Bowen fluorescence by scattered C IV photons. Lines from metastable levels of Ni II are usually excited by continuum fluorescence and mostly sensitive to the strength of the radiation field shortward of the Lyman continuum and as such they cam be used as direct distance indicators. Further, we show how the total hydrogen density of the absorber, its ionization parameter and distance can be determined through photoionization modeling of the absorber. Finally, we present our results for outflows of three different quasars: QSO 2359-1241 and SDSS J0318-0600.

Transition probabilities for the 3s2 3p(2P0)-3s3p2(4P) intersystem lines of Si II

NASA Technical Reports Server (NTRS)

Calamai, Anthony G.; Smith, Peter L.; Bergeson, S. D.

1993-01-01

Intensity ratios of lines of the spin-changing 'intersystem' multiplet of S II (4P yields 2P0) at 234 nm have been used to determine electron densities and temperatures in a variety of astrophysical environments. However, the accuracy of these diagnostic calculations have been limited by uncertainties associated with the available atomic data. We report the first laboratory measurement, using an ion-trapping technique, of the radiative lifetimes of the three metastable levels of the 3s3p2 4P term of Si II. Our results are 104 +/- 16, 406 +/- 33, and 811 +/- 77 micro-s for lifetimes of the J = 1/2, 5/2, and 3/2 levels, respectively. A-values were derived from our lifetimes by use of measured branching fractions. Our A-values, which differ from calculated values by 30 percent or more, should give better agreement between modeled and observed Si II line ratios.

Family Integrated Care (FICare) in Level II Neonatal Intensive Care Units: study protocol for a cluster randomized controlled trial.

PubMed

Benzies, Karen M; Shah, Vibhuti; Aziz, Khalid; Isaranuwatchai, Wanrudee; Palacio-Derflingher, Luz; Scotland, Jeanne; Larocque, Jill; Mrklas, Kelly; Suter, Esther; Naugler, Christopher; Stelfox, Henry T; Chari, Radha; Lodha, Abhay

2017-10-10

Every year, about 15 million of the world's infants are born preterm (before 37 weeks gestation). In Alberta, the preterm birth rate was 8.7% in 2015, the second highest among Canadian provinces. Approximately 20% of preterm infants are born before 32 weeks gestation (early preterm), and require care in a Level III neonatal intensive care unit (NICU); 80% are born moderate (32 weeks and zero days [32 0/7 ] to 33 6/7 weeks) and late preterm (34 0/7 to 36 6/7 weeks), and require care in a Level II NICU. Preterm birth and experiences in the NICU disrupt early parent-infant relationships and induce parental psychosocial distress. Family Integrated Care (FICare) shows promise as a model of care in Level III NICUs. The purpose of this study is to evaluate length of stay, infant and maternal clinical outcomes, and costs following adaptation and implementation of FICare in Level II NICUs. We will conduct a pragmatic, cluster randomized controlled trial (cRCT) in ten Alberta Level II NICUs allocated to one of two groups: FICare or standard care. The FICare Alberta model involves three theoretically-based, standardized components: information sharing, parenting education, and family support. Our sample size of 181 mother-infant dyads per group is based on the primary outcome of NICU length of stay, 80% participation, and 80% retention at follow-up. Secondary outcomes (e.g., infant clinical outcomes and maternal psychosocial distress) will be assessed shortly after admission to NICU, at discharge and 2 months corrected age. We will conduct economic analysis from two perspectives: the public healthcare payer and society. To understand the utility, acceptability, and impact of FICare, qualitative interviews will be conducted with a subset of mothers at the 2-month follow-up, and with hospital administrators and healthcare providers near the end of the study. Results of this pragmatic cRCT of FICare in Alberta Level II NICUs will inform policy decisions by providing evidence about the clinical effectiveness and costs of FICare. ClinicalTrials.gov, ID: NCT02879799 . Registered on 27 May 2016. Protocol version: 9 June 2016; version 2.

Insulin-Like Growth Factor II Targets the mTOR Pathway to Reverse Autism-Like Phenotypes in Mice.

PubMed

Steinmetz, Adam B; Stern, Sarah A; Kohtz, Amy S; Descalzi, Giannina; Alberini, Cristina M

2018-01-24

Autism spectrum disorder (ASD) is a developmental disability characterized by impairments in social interaction and repetitive behavior, and is also associated with cognitive deficits. There is no current treatment that can ameliorate most of the ASD symptomatology; thus, identifying novel therapies is urgently needed. We used male BTBR T + Itpr3 tf /J (BTBR) mice, a model that reproduces most of the core behavioral phenotypes of ASD, to test the effects of systemic administration of insulin-like growth factor II (IGF-II), a polypeptide that crosses the blood-brain barrier and acts as a cognitive enhancer. We show that systemic IGF-II treatments reverse the typical defects in social interaction, cognitive/executive functions, and repetitive behaviors reflective of ASD-like phenotypes. In BTBR mice, IGF-II, via IGF-II receptor, but not via IGF-I receptor, reverses the abnormal levels of the AMPK-mTOR-S6K pathway and of active translation at synapses. Thus, IGF-II may represent a novel potential therapy for ASD. SIGNIFICANCE STATEMENT Currently, there is no effective treatment for autism spectrum disorder (ASD), a developmental disability affecting a high number of children. Using a mouse model that expresses most of the key core as well as associated behavioral deficits of ASD, that are, social, cognitive, and repetitive behaviors, we report that a systemic administration of the polypeptide insulin-like growth factor II (IGF-II) reverses all these deficits. The effects of IGF-II occur via IGF-II receptors, and not IGF-I receptors, and target both basal and learning-dependent molecular abnormalities found in several ASD mice models, including those of identified genetic mutations. We suggest that IGF-II represents a potential novel therapeutic target for ASD. Copyright © 2018 the authors 0270-6474/18/371015-15$15.00/0.

Ramifications of the Children's Surgery Verification Program for Patients and Hospitals.

PubMed

Baxter, Katherine J; Gale, Bonnie F; Travers, Curtis D; Heiss, Kurt F; Raval, Mehul V

2018-05-01

The American College of Surgeons in 2015 instituted the Children's Surgery Verification program delineating requirements for hospitals providing pediatric surgical care. Our purpose was to examine possible effects of the Children's Surgery Verification program by evaluating neonates undergoing high-risk operations. Using the Kid's Inpatient Database 2009, we identified infants undergoing operations for 5 high-risk neonatal conditions. We considered all children's hospitals and children's units Level I centers and considered all others Level II/III. We estimated the number of neonates requiring relocation and the additional distance traveled. We used propensity score adjusted logistic regression to model mortality at Level I vs Level II/III hospitals. Overall, 7,938 neonates were identified across 21 states at 91 Level I and 459 Level II/III hospitals. Based on our classifications, 2,744 (34.6%) patients would need to relocate to Level I centers. The median additional distance traveled was 6.6 miles. The maximum distance traveled varied by state, from <55 miles (New Jersey and Rhode Island) to >200 miles (Montana, Oregon, Colorado, and California). The adjusted odds of mortality at Level II/III vs Level I centers was 1.67 (95% CI 1.44 to 1.93). We estimate 1 life would be saved for every 32 neonates moved. Although this conservative estimate demonstrates that more than one-third of complex surgical neonates in 2009 would have needed to relocate under the Children's Surgery Verification program, the additional distance traveled is relatively short for most but not all, and this program might improve mortality. Local level ramifications of this novel national program require additional investigation. Copyright © 2018 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Identification of age-dependent motor and neuropsychological behavioural abnormalities in a mouse model of Mucopolysaccharidosis Type II

PubMed Central

Gleitz, Hélène F. E.; O’Leary, Claire; Holley, Rebecca J.

2017-01-01

Severe mucopolysaccharidosis type II (MPS II) is a progressive lysosomal storage disease caused by mutations in the IDS gene, leading to a deficiency in the iduronate-2-sulfatase enzyme that is involved in heparan sulphate and dermatan sulphate catabolism. In constitutive form, MPS II is a multi-system disease characterised by progressive neurocognitive decline, severe skeletal abnormalities and hepatosplenomegaly. Although enzyme replacement therapy has been approved for treatment of peripheral organs, no therapy effectively treats the cognitive symptoms of the disease and novel therapies are in development to remediate this. Therapeutic efficacy and subsequent validation can be assessed using a variety of outcome measures that are translatable to clinical practice, such as behavioural measures. We sought to consolidate current knowledge of the cognitive, skeletal and motor abnormalities present in the MPS II mouse model by performing time course behavioural examinations of working memory, anxiety, activity levels, sociability and coordination and balance, up to 8 months of age. Cognitive decline associated with alterations in spatial working memory is detectable at 8 months of age in MPS II mice using spontaneous alternation, together with an altered response to novel environments and anxiolytic behaviour in the open-field. Coordination and balance on the accelerating rotarod were also significantly worse at 8 months, and may be associated with skeletal changes seen in MPS II mice. We demonstrate that the progressive nature of MPS II disease is also seen in the mouse model, and that cognitive and motor differences are detectable at 8 months of age using spontaneous alternation, the accelerating rotarod and the open-field tests. This study establishes neurological, motor and skeletal measures for use in pre-clinical studies to develop therapeutic approaches in MPS II. PMID:28207863

Multigenerational Exposure of the Estuarine Sheepshead Minnow (Cyprinodon variegatus) to 17β-estradiol. II. Population-Level Effects Through Two Life Cycles

EPA Science Inventory

The evaluation of multi-generation, population-level impacts is particularly important in the risk assessment of endocrine disrupting compounds (EDCs) because adverse effects may not be evident during the first generation of exposure. Population models were developed for the shee...

A novel Alaska pollack-derived peptide, which increases glucose uptake in skeletal muscle cells, lowers the blood glucose level in diabetic mice.

PubMed

Ayabe, Tatsuhiro; Mizushige, Takafumi; Ota, Wakana; Kawabata, Fuminori; Hayamizu, Kohsuke; Han, Li; Tsuji, Tomoko; Kanamoto, Ryuhei; Ohinata, Kousaku

2015-08-01

We found that the tryptic digest of Alaska pollack protein exhibits a glucose-lowering effect in KK-Ay mice, a type II diabetic model. We then searched for glucose-lowering peptides in the digest. Ala-Asn-Gly-Glu-Val-Ala-Gln-Trp-Arg (ANGEVAQWR) was identified from a peak of the HPLC fraction selected based on the glucose-lowering activity in an insulin resistance test using ddY mice. ANGEVAQWR (3 mg kg(-1)) decreased the blood glucose level after intraperitoneal administration. Among its fragment peptides, the C-terminal tripeptide, Gln-Trp-Arg (QWR, 1 mg kg(-1)), lowered the blood glucose level, suggesting that the C-terminal is critical for glucose-lowering activity. QWR also enhanced glucose uptake into C2C12, a mouse skeletal muscle cell line. QWR did not induce the phosphorylation of serine/threonine protein kinase B (Akt) and adenosine monophosphate-activated protein kinase (AMPK). We also demonstrated that QWR lowered the blood glucose level in NSY and KK-Ay, type II diabetic models.

Leishmania infantum HSP70-II null mutant as candidate vaccine against leishmaniasis: a preliminary evaluation.

PubMed

Carrión, Javier; Folgueira, Cristina; Soto, Manuel; Fresno, Manuel; Requena, Jose M

2011-07-27

Visceral leishmaniasis is the most severe form of leishmaniasis and no effective vaccine exists. The use of live attenuated vaccines is emerging as a promising vaccination strategy. In this study, we tested the ability of a Leishmania infantum deletion mutant, lacking both HSP70-II alleles (ΔHSP70-II), to provide protection against Leishmania infection in the L. major-BALB/c infection model. Administration of the mutant line by either intraperitoneal, intravenous or subcutaneous route invariably leads to the production of high levels of NO and the development in mice of type 1 immune responses, as determined by analysis of anti-Leishmania IgG subclasses. In addition, we have shown that ΔHSP70-II would be a safe live vaccine as immunodeficient SCID mice, and hamsters (Mesocricetus auratus), infected with mutant parasites did not develop any sign of pathology. The results suggest that the ΔHSP70-II mutant is a promising and safe vaccine, but further studies in more appropriate animal models (hamsters and dogs) are needed to appraise whether this attenuate mutant would be useful as vaccine against visceral leishmaniasis.

Chance-constrained multi-objective optimization of groundwater remediation design at DNAPLs-contaminated sites using a multi-algorithm genetically adaptive method

NASA Astrophysics Data System (ADS)

Ouyang, Qi; Lu, Wenxi; Hou, Zeyu; Zhang, Yu; Li, Shuai; Luo, Jiannan

2017-05-01

In this paper, a multi-algorithm genetically adaptive multi-objective (AMALGAM) method is proposed as a multi-objective optimization solver. It was implemented in the multi-objective optimization of a groundwater remediation design at sites contaminated by dense non-aqueous phase liquids. In this study, there were two objectives: minimization of the total remediation cost, and minimization of the remediation time. A non-dominated sorting genetic algorithm II (NSGA-II) was adopted to compare with the proposed method. For efficiency, the time-consuming surfactant-enhanced aquifer remediation simulation model was replaced by a surrogate model constructed by a multi-gene genetic programming (MGGP) technique. Similarly, two other surrogate modeling methods-support vector regression (SVR) and Kriging (KRG)-were employed to make comparisons with MGGP. In addition, the surrogate-modeling uncertainty was incorporated in the optimization model by chance-constrained programming (CCP). The results showed that, for the problem considered in this study, (1) the solutions obtained by AMALGAM incurred less remediation cost and required less time than those of NSGA-II, indicating that AMALGAM outperformed NSGA-II. It was additionally shown that (2) the MGGP surrogate model was more accurate than SVR and KRG; and (3) the remediation cost and time increased with the confidence level, which can enable decision makers to make a suitable choice by considering the given budget, remediation time, and reliability.

First results of GERDA Phase II and consistency with background models

NASA Astrophysics Data System (ADS)

Agostini, M.; Allardt, M.; Bakalyarov, A. M.; Balata, M.; Barabanov, I.; Baudis, L.; Bauer, C.; Bellotti, E.; Belogurov, S.; Belyaev, S. T.; Benato, G.; Bettini, A.; Bezrukov, L.; Bode1, T.; Borowicz, D.; Brudanin, V.; Brugnera, R.; Caldwell, A.; Cattadori, C.; Chernogorov, A.; D'Andrea, V.; Demidova, E. V.; Di Marco, N.; Domula, A.; Doroshkevich, E.; Egorov, V.; Falkenstein, R.; Frodyma, N.; Gangapshev, A.; Garfagnini, A.; Gooch, C.; Grabmayr, P.; Gurentsov, V.; Gusev, K.; Hakenmüller, J.; Hegai, A.; Heisel, M.; Hemmer, S.; Hofmann, W.; Hult, M.; Inzhechik, L. V.; Janicskó Csáthy, J.; Jochum, J.; Junker, M.; Kazalov, V.; Kihm, T.; Kirpichnikov, I. V.; Kirsch, A.; Kish, A.; Klimenko, A.; Kneißl, R.; Knöpfle, K. T.; Kochetov, O.; Kornoukhov, V. N.; Kuzminov, V. V.; Laubenstein, M.; Lazzaro, A.; Lebedev, V. I.; Lehnert, B.; Liao, H. Y.; Lindner, M.; Lippi, I.; Lubashevskiy, A.; Lubsandorzhiev, B.; Lutter, G.; Macolino, C.; Majorovits, B.; Maneschg, W.; Medinaceli, E.; Miloradovic, M.; Mingazheva, R.; Misiaszek, M.; Moseev, P.; Nemchenok, I.; Palioselitis, D.; Panas, K.; Pandola, L.; Pelczar, K.; Pullia, A.; Riboldi, S.; Rumyantseva, N.; Sada, C.; Salamida, F.; Salathe, M.; Schmitt, C.; Schneider, B.; Schönert, S.; Schreiner, J.; Schulz, O.; Schütz, A.-K.; Schwingenheuer, B.; Selivanenko, O.; Shevzik, E.; Shirchenko, M.; Simgen, H.; Smolnikov, A.; Stanco, L.; Vanhoefer, L.; Vasenko, A. A.; Veresnikova, A.; von Sturm, K.; Wagner, V.; Wegmann, A.; Wester, T.; Wiesinger, C.; Wojcik, M.; Yanovich, E.; Zhitnikov, I.; Zhukov, S. V.; Zinatulina, D.; Zuber, K.; Zuzel, G.

2017-01-01

The GERDA (GERmanium Detector Array) is an experiment for the search of neutrinoless double beta decay (0νββ) in 76Ge, located at Laboratori Nazionali del Gran Sasso of INFN (Italy). GERDA operates bare high purity germanium detectors submersed in liquid Argon (LAr). Phase II of data-taking started in Dec 2015 and is currently ongoing. In Phase II 35 kg of germanium detectors enriched in 76Ge including thirty newly produced Broad Energy Germanium (BEGe) detectors is operating to reach an exposure of 100 kg·yr within about 3 years data taking. The design goal of Phase II is to reduce the background by one order of magnitude to get the sensitivity for T1/20ν = O≤ft( {{{10}26}} \\right){{ yr}}. To achieve the necessary background reduction, the setup was complemented with LAr veto. Analysis of the background spectrum of Phase II demonstrates consistency with the background models. Furthermore 226Ra and 232Th contamination levels consistent with screening results. In the first Phase II data release we found no hint for a 0νββ decay signal and place a limit of this process T1/20ν > 5.3 \\cdot {1025} yr (90% C.L., sensitivity 4.0·1025 yr). First results of GERDA Phase II will be presented.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Yi xi; Zhang, Man; Cai, Yuehua

Activation of the silent mating type information regulation 2 homolog 1 (SIRT1) has been shown consistent antiinflammatory function. However, little information is available on the function of SIRT1 during Angiotensin II (AngII)-induced atherosclerosis. Here we report atheroprotective effects of sirt1 activation in a model of AngII-accelerated atherosclerosis, characterized by suppression pro-inflammatory transcription factors Nuclear transcription factor (NF)-κB and Signal Transducers and Activators of Transcription. (STAT) signaling pathway, and atherosclerotic lesion macrophage content. In this model, administration of the SIRT1 agonist SRT1720 substantially attenuated AngII-accelerated atherosclerosis with decreasing blood pressure and inhibited NF-κB and STAT3 activation, which was associated with suppressionmore » of inflammatory factor and atherogenic gene expression in the artery. In vitro studies demonstrated similar changes in AngII-treated VSMCs and macrophages: SIRT1 activation inhibited the expression levels of proinflammatory factor. These studies uncover crucial proinflammatory mechanisms of AngII and highlight actions of SIRT1 activation to inhibit AngII signaling, which is atheroprotective. - Highlights: • SRT1720 reduced atherosclerotic lesion size in aortic arches and atherosclerotic lesion macrophage content. • SRT1720 could inhibit the phosphorylation of STAT3 and p65 phosphorylation and translocation. • SRT1720 could inhibit the expression of proinflammatory factor.« less

Edaravone inhibits pressure overload-induced cardiac fibrosis and dysfunction by reducing expression of angiotensin II AT1 receptor

PubMed Central

Zhang, Wei-Wei; Bai, Feng; Wang, Jin; Zheng, Rong-Hua; Yang, Li-Wang; James, Erskine A; Zhao, Zhi-Qing

2017-01-01

Angiotensin II (Ang II) is known to be involved in the progression of ventricular dysfunction and heart failure by eliciting cardiac fibrosis. The purpose of this study was to demonstrate whether treatment with an antioxidant compound, edaravone, reduces cardiac fibrosis and improves ventricular function by inhibiting Ang II AT1 receptor. The study was conducted in a rat model of transverse aortic constriction (TAC). In control, rats were subjected to 8 weeks of TAC. In treated rats, edaravone (10 mg/kg/day) or Ang II AT1 receptor blocker, telmisartan (10 mg/kg/day) was administered by intraperitoneal injection or gastric gavage, respectively, during TAC. Relative to the animals with TAC, edaravone reduced myocardial malonaldehyde level and increased superoxide dismutase activity. Protein level of the AT1 receptor was reduced and the AT2 receptor was upregulated, as evidenced by the reduced ratio of AT1 over AT2 receptor (0.57±0.2 vs 3.16±0.39, p<0.05) and less locally expressed AT1 receptor in the myocardium. Furthermore, the protein level of angiotensin converting enzyme 2 was upregulated. In coincidence with these changes, edaravone significantly decreased the populations of macrophages and myofibroblasts in the myocardium, which were accompanied by reduced levels of transforming growth factor beta 1 and Smad2/3. Collagen I synthesis was inhibited and collagen-rich fibrosis was attenuated. Relative to the TAC group, cardiac systolic function was preserved, as shown by increased left ventricular systolic pressure (204±51 vs 110±19 mmHg, p<0.05) and ejection fraction (82%±3% vs 60%±5%, p<0.05). Treatment with telmisartan provided a comparable level of protection as compared with edaravone in all the parameters measured. Taken together, edaravone treatment ameliorates cardiac fibrosis and improves left ventricular function in the pressure overload rat model, potentially via suppressing the AT1 receptor-mediated signaling pathways. These data indicate that edaravone might be selected in combination with other existing drugs in preventing progression of cardiac dysfunction in heart failure. PMID:29081650

Edaravone inhibits pressure overload-induced cardiac fibrosis and dysfunction by reducing expression of angiotensin II AT1 receptor.

PubMed

Zhang, Wei-Wei; Bai, Feng; Wang, Jin; Zheng, Rong-Hua; Yang, Li-Wang; James, Erskine A; Zhao, Zhi-Qing

2017-01-01

Angiotensin II (Ang II) is known to be involved in the progression of ventricular dysfunction and heart failure by eliciting cardiac fibrosis. The purpose of this study was to demonstrate whether treatment with an antioxidant compound, edaravone, reduces cardiac fibrosis and improves ventricular function by inhibiting Ang II AT1 receptor. The study was conducted in a rat model of transverse aortic constriction (TAC). In control, rats were subjected to 8 weeks of TAC. In treated rats, edaravone (10 mg/kg/day) or Ang II AT1 receptor blocker, telmisartan (10 mg/kg/day) was administered by intraperitoneal injection or gastric gavage, respectively, during TAC. Relative to the animals with TAC, edaravone reduced myocardial malonaldehyde level and increased superoxide dismutase activity. Protein level of the AT1 receptor was reduced and the AT2 receptor was upregulated, as evidenced by the reduced ratio of AT1 over AT2 receptor (0.57±0.2 vs 3.16±0.39, p <0.05) and less locally expressed AT1 receptor in the myocardium. Furthermore, the protein level of angiotensin converting enzyme 2 was upregulated. In coincidence with these changes, edaravone significantly decreased the populations of macrophages and myofibroblasts in the myocardium, which were accompanied by reduced levels of transforming growth factor beta 1 and Smad2/3. Collagen I synthesis was inhibited and collagen-rich fibrosis was attenuated. Relative to the TAC group, cardiac systolic function was preserved, as shown by increased left ventricular systolic pressure (204±51 vs 110±19 mmHg, p <0.05) and ejection fraction (82%±3% vs 60%±5%, p <0.05). Treatment with telmisartan provided a comparable level of protection as compared with edaravone in all the parameters measured. Taken together, edaravone treatment ameliorates cardiac fibrosis and improves left ventricular function in the pressure overload rat model, potentially via suppressing the AT1 receptor-mediated signaling pathways. These data indicate that edaravone might be selected in combination with other existing drugs in preventing progression of cardiac dysfunction in heart failure.

Hypoglycemic effect of hawthorn in type II diabetes mellitus rat model.

PubMed

Aierken, Aili; Buchholz, Tina; Chen, Chen; Zhang, Xiaoying; Melzig, Matthias F

2017-10-01

Hawthorn is a popular herb in many different traditional medicine systems, including traditional Chinese medicine, where it has long been used for the treatment of hyperglycemia. However, most of its varied biological activities remain unexplored. This study investigated the hypoglycemic effect of hawthorn extracts in type II diabetic (T2DM) rat model. A total of 54 rats were randomly divided into six groups: normal control group; type II diabetic model group (T2DM; these rats were induced by high-fat diet and streptozotocin); high, middle and low concentrations of hawthorn treatment (HT H , HT M and HT L T2DM rats were given hawthorn extract at a dose of 50, 100 and 200 mg kg -1 body weight, respectively); and positive control group (orlistat 40 mg kg -1 body weight). Triglyceride and total cholesterol serum levels were lower in the hawthorn extract-treated groups than in the T2DM control group (P < 0.01). Furthermore, hawthorn extracts decreased blood glucose level and increased plasma insulin release from pancreas. Positive effects of hawthorn against streptozotocin-induced T2DM were demonstrated. This study suggests that hawthorn extract represents a useful agent for the prevention or treatment of T2DM. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Increased cartilage type II collagen degradation in patients with osteogenesis imperfecta used as a human model of bone type I collagen alterations.

PubMed

Rousseau, Jean-Charles; Chevrel, Guillaume; Schott, Anne-Marie; Garnero, Patrick

2010-04-01

We investigated whether cartilage degradation is altered in adult patients with mild osteogenesis imperfecta (OI) used as a human model of bone type I collagen-related osteoarthritis (OA). Sixty-four adult patients with OI (39% women, mean age+/-SD: 37+/-12 years) and 64 healthy age-matched controls (54% women, 39+/-7 years) were included. We also compared data in 87 patients with knee OA (73% women, 63+/-8 years, mean disease duration: 6 years) and 291 age-matched controls (80% women, 62+/-10 years). Urinary C-terminal cross-linked telopeptide of type II collagen (CTX-II), a marker of cartilage degradation, urinary helical peptide of type I collagen (Helix-I), a marker of bone resorption, and the urinary ratio between non-isomerised/isomerised (alpha/beta CTX-I) type I collagen C-telopeptide, a marker of type I collagen maturation, were measured. Patients with OI had CTX-II levels similar to those of subjects with knee OA (p=0.89; mean+/-SEM; 460+/-57 ng/mmol Cr for OI group and 547+/-32 ng/mmol Cr for OA group) and significantly higher than both young (144+/-7.8 ng/mmol Cr, p<0.0001) and old controls (247+/-7 ng/mmol Cr, p<0.0001). In patients with OI, increased Helix-I (p<0.0001) and alpha/beta CTX-I (p=0.0067) were independently associated with increased CTX-II and together explained 26% of its variance (p< 0.0001). In patients with knee OA, increased levels of alpha/beta CTX-I ratio were also associated with higher CTX-II levels. Adult patients with OI or knee OA are characterized by increased cartilage type II collagen degradation, which is associated with increased type I collagen degradation for OI and lower type I collagen maturation for both OI and OA. These data suggest that both quantitative and qualitative alterations of bone type I collagen metabolism are involved in increased cartilage degradation in patients with OI or knee OA. Copyright 2009 Elsevier Inc. All rights reserved.

Have levels of evidence improved the quality of orthopaedic research?

PubMed

Cunningham, Brian P; Harmsen, Samuel; Kweon, Chris; Patterson, Jason; Waldrop, Robert; McLaren, Alex; McLemore, Ryan

2013-11-01

Since 2003 many orthopaedic journals have adopted grading systems for levels of evidence (LOE). It is unclear if the quality of orthopaedic literature has changed since LOE was introduced. We asked three questions: (1) Have the overall number and proportion of Level I and II studies increased in the orthopaedic literature since the introduction of LOE? (2) Is a similar pattern seen in individual orthopaedic subspecialty journals? (3) What is the interobserver reliability of grading LOE? We assigned LOE to therapeutic studies published in 2000, 2005, and 2010 in eight major orthopaedic subspecialty journals. Number and proportion of Level I and II publications were determined. Data were evaluated using log-linear models. Twenty-six reviewers (13 residents and 13 attendings) graded LOE of 20 blinded therapeutic articles from the Journal of Bone and Joint Surgery for 2009. Interobserver agreement relative to the Journal of Bone and Joint Surgery was assessed using a weighted kappa. The total number of Level I and II publications in subspecialty journals increased from 150 in 2000 to 239 in 2010. The proportion of high-quality publications increased with time (p < 0.001). All subspecialty journals other than the Journal of Pediatric Orthopaedics and the Journal of Orthopaedic Trauma showed a similar behavior. Average weighted kappa was 0.791 for residents and 0.842 for faculty (p = 0.209). The number and proportion of Level I and II publications have increased. LOE can be graded reliably with high interobserver agreement. The number and proportion of high-level studies should continue to increase.

What Are the Costs of Trauma Center Readiness? Defining and Standardizing Readiness Costs for Trauma Centers Statewide.

PubMed

Ashley, Dennis W; Mullins, Robert F; Dente, Christopher J; Garlow, Laura; Medeiros, Regina S; Atkins, Elizabeth V; Solomon, Gina; Abston, Dena; Ferdinand, Colville H

2017-09-01

Trauma center readiness costs are incurred to maintain essential infrastructure and capacity to provide emergent services on a 24/7 basis. These costs are not captured by traditional hospital cost accounting, and no national consensus exists on appropriate definitions for each cost. Therefore, in 2010, stakeholders from all Level I and II trauma centers developed a survey tool standardizing and defining trauma center readiness costs. The survey tool underwent minor revisions to provide further clarity, and the survey was repeated in 2013. The purpose of this study was to provide a follow-up analysis of readiness costs for Georgia's Level I and Level II trauma centers. Using the American College of Surgeons Resources for Optimal Care of the Injured Patient guidelines, four readiness cost categories were identified: Administrative, Clinical Medical Staff, Operating Room, and Education/Outreach. Through conference calls, webinars and face-to-face meetings with financial officers, trauma medical directors, and program managers from all trauma centers, standardized definitions for reporting readiness costs within each category were developed. This resulted in a survey tool for centers to report their individual readiness costs for one year. The total readiness cost for all Level I trauma centers was $34,105,318 (avg $6,821,064) and all Level II trauma centers was $20,998,019 (avg $2,333,113). Methodology to standardize and define readiness costs for all trauma centers within the state was developed. Average costs for Level I and Level II trauma centers were identified. This model may be used to help other states define and standardize their trauma readiness costs.

Desertification in the south Junggar Basin, 2000-2009: Part II. Model development and trend analysis

NASA Astrophysics Data System (ADS)

Jiang, Miao; Lin, Yi

2018-07-01

The substantial objective of desertification monitoring is to derive its development trend, which facilitates pre-making policies to handle its potential influences. Aiming at this extreme goal, previous studies have proposed a large number of remote sensing (RS) based methods to retrieve multifold indicators, as reviewed in Part I. However, most of these indicators individually capable of characterizing a single aspect of land attributes, e.g., albedo quantifying land surface reflectivity, cannot show a full picture of desertification processes; few comprehensive RS-based models have either been published. To fill this gap, this Part II was dedicated to developing a RS information model for comprehensively characterizing the desertification and deriving its trend, based on the indicators retrieved in Part I in the same case of the south Junggar Basin, China in the last decade (2000-2009). The proposed model was designed to have three dominant component modules, i.e., the vegetation-relevant sub-model, the soil-relevant sub-model, and the water-relevant sub-model, which synthesize all of the retrieved indicators to integrally reflect the processes of desertification; based on the model-output indices, the desertification trends were derived using the least absolute deviation fitting algorithm. Tests indicated that the proposed model did work and the study area showed different development tendencies for different desertification levels. Overall, this Part II established a new comprehensive RS information model for desertification risk assessment and its trend deriving, and the whole study comprising Part I and Part II advanced a relatively standard framework for RS-based desertification monitoring.

A Novel Tumor-Activated Prodrug Strategy Targeting Ferrous Iron Is Effective in Multiple Preclinical Cancer Models

PubMed Central

2016-01-01

Here we describe a new approach for tumor targeting in which augmented concentrations of Fe(II) in cancer cells and/or the tumor microenvironment triggers drug release from an Fe(II)-reactive prodrug conjugate. The 1,2,4-trioxolane scaffold developed to enable this approach can in principle be applied to a broad range of cancer therapeutics and is illustrated here with Fe(II)-targeted forms of a microtubule toxin and a duocarmycin-class DNA-alkylating agent. We show that the intrinsic reactivity/toxicity of the duocarmycin analog is masked in the conjugated form and this greatly reduced toxicity in mice. This in turn permitted elevated dosing levels, leading to higher systemic exposure and a significantly improved response in tumor xenograft models. Overall our results suggest that Fe(II)-dependent drug delivery via trioxolane conjugates could have significant utility in expanding the therapeutic index of a range of clinical and preclinical stage cancer chemotherapeutics. PMID:27936709

Competitive Strategies of States: A Life-Cycle Perspective. EQW Working Papers.

ERIC Educational Resources Information Center

Flynn, Patricia M.

This paper demonstrates that production life-cycle models provide a conceptual framework to analyze systematically the interrelationships between industrial and technological change and human resources. Section II presents the life-cycle model, focusing on its implications for the types and level of employment and skill requirements in an area.…

Curcumin modulates the effect of histone modification on the expression of chemokines by type II alveolar epithelial cells in a rat COPD model.

PubMed

Gan, Lixing; Li, Chengye; Wang, Jian; Guo, Xuejun

2016-01-01

Studies have suggested that histone modification has a positive impact on various aspects associated with the progression of COPD. Histone deacetylase 2 (HDAC2) suppresses proinflammatory gene expression through deacetylation of core histones. To investigate the effect of histone modification on the expression of chemokines in type II alveolar epithelial cells (AEC II) in a rat COPD model and regulation of HDAC2 expression by curcumin in comparison with corticosteroid. The rat COPD model was established by cigarette smoke exposure and confirmed by histology and pathophysioloy. AEC II were isolated and cultured in vitro from the COPD models and control animals. The cells were treated with curcumin, corticosteroid, or trichostatin A, and messenger RNA (mRNA) expression of interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-2α (MIP-2α) was assessed by quantitative real-time polymerase chain reaction (RT-PCR). The expression of HDAC2 was measured by Western blot. Chromatin immunoprecipitation was used to detect H3/H4 acetylation and H3K9 methylation in the promoter region of three kinds of chemokine genes (IL-8, MCP-1, and MIP-2α). Compared to the control group, the mRNAs of MCP-1, IL-8, and MIP-2α were upregulated 4.48-fold, 3.14-fold, and 2.83-fold, respectively, in the AEC II from COPD model. The protein expression of HDAC2 in the AEC II from COPD model was significantly lower than from the control group ( P <0.05). The decreased expression of HDAC2 was negatively correlated with the increased expression of IL-8, MCP-1, and MIP-2α mRNAs (all P <0.05). The level of H3/H4 acetylation was higher but H3K9 methylation in the promoter region of chemokine genes was lower in the cells from COPD model than from the control group (all P <0.05). Curcumin downregulated the expression of MCP-1, IL-8, and MIP-2α, and the expression was further enhanced in the presence of corticosteroid. Moreover, curcumin restored HDAC2 expression, decreased the levels of H3/H4 acetylation, and increased H3K9 methylation in the promoter region of chemokine in the presence or absence of dexamethasone (all P <0.05). Curcumin may suppress chemokines and restore corticosteroid resistance in COPD through modulating HDAC2 expression and its effect on histone modification.

A newly developed solution enhances thirty-hour preservation in a canine lung transplantation model.

PubMed

Liu, C J; Ueda, M; Kosaka, S; Hirata, T; Yokomise, H; Inui, K; Hitomi, S; Wada, H

1996-09-01

Ischemia and reperfusion cause the production of oxygen free radicals. These damage grafts or disrupt normal vascular homeostatic mechanisms, with a parallel reduction in endothelial nitric oxide and adenosine 3',5'-cyclic monophosphate levels. We hypothesized that lung preservation failure may be related to these events. To improve lung preservation, we prepared a new ET-Kyoto solution, which contains N-acetylcysteine (a radical scavenger), nitroglycerin (to elevate the nitric oxide level), and dibutyryl adenosine 3',5'-cyclic monophosphate (to elevate the adenosine 3',5'-cyclic monophosphate level) and examined its efficacy in a canine single-lung transplantation model. Lungs were flushed with new ET-Kyoto solution (group I, n = 9), basal ET-Kyoto solution (group II, n = 6), basal ET-Kyoto solution plus ethanol and propylene glycol (solvents of nitroglycerin; group III, n = 6), or low-potassium dextran glucose solution (group IV, n = 6), and stored at 4 degrees C for 30 hours. After left single-lung transplantation, the right main bronchus and right pulmonary artery were ligated and the functions of the transplanted lung were assessed for 6 hours. Arterial oxygen tension was significantly higher in group I than in groups II, III, and IV (p < 0.05). Peak inspiratory pressure and wet-to-dry lung weight ratio were significantly lower in group I than in groups II and IV (p < 0.01). Histologic and ultrastructural studies showed better preservation in group I than in groups II, III, and IV. We conclude that the new ET-Kyoto solution provides enhanced 30-hour lung preservation.

T-2 Toxin Alters the Levels of Collagen II and Its Regulatory Enzymes MMPs/TIMP-1 in a Low-Selenium Rat Model of Kashin-Beck Disease.

PubMed

Zhou, Xiaorong; Yang, Haojie; Guan, Fang; Xue, Senhai; Song, Daiqin; Chen, Jinghong; Wang, Zhilun

2016-02-01

The objectives of this study are to assess T-2 toxin's involvement in low selenium (Se)-induced Kashin-Beck disease (KBD) in rats and unveil the mechanisms underlying this disease. Two hundred thirty rats were randomly divided into two groups after weaning and fed normal or low-Se diets (n = 115), respectively, for a month. After low-Se model confirmation, rats in each group were subdivided into five: two subgroups (n = 20) were fed their current diets (normal or low-Se diets, respectively) for 30 and 90 days, respectively; two other subgroups (n = 25) received their current diets + low T-2 toxin (100 ng/g BW/day) for 30 and 90 days, respectively; and 25 rats were fed their current diets + high T-2 toxin (200 ng/g BW/day) for 30 days. Articular cartilage samples were extracted for hematoxylin and eosin (H&E) staining and immunohistochemistry. Western blot and reverse transcription-polymerase chain reaction (RT-PCR) were used to assess protein and mRNA levels, respectively, of collagen II, matrix metalloproteinase (MMP-1), MMP -3, MMP-13, and tissue inhibitor of metalloproteinase-1 (TIMP-1). Low Se and T-2 toxin synergistically affected animal fitness. Interestingly, low Se + T-2 toxin groups showed KBD characteristics. MMP-1, -3, and -13 mRNA and protein levels generally increased in low-Se groups, while collagen II and TIMP-1 levels showed a downward trend, compared with normal diet fed animals for the same treatment (P < 0.05). T-2 toxin's effect was dose but not time dependent. Low Se and T-2 toxin synergistically alter the expression levels of collagen II as well as its regulatory enzymes MMP-1, MMP-3, MMP-13, and TIMP-1, inducing cartilage damage. Therefore, T-2 toxin may cause KBD in low-Se conditions.

Voluntarily Reported Immunization Registry Data: Reliability and Feasibility to Predict Immunization Rates, San Diego, California, 2013.

PubMed

Madewell, Zachary J; Wester, Robert B; Wang, Wendy W; Smith, Tyler C; Peddecord, K Michael; Morris, Jessica; DeGuzman, Heidi; Sawyer, Mark H; McDonald, Eric C

Accurate data on immunization coverage levels are essential to public health program planning. Reliability of coverage estimates derived from immunization information systems (IISs) in states where immunization reporting by medical providers is not mandated by the state may be compromised by low rates of participation. To overcome this problem, data on coverage rates are often acquired through random-digit-dial telephone surveys, which require substantial time and resources. This project tested both the reliability of voluntarily reported IIS data and the feasibility of using these data to estimate regional immunization rates. We matched telephone survey records for 553 patients aged 19-35 months obtained in 2013 to 430 records in the San Diego County IIS. We assessed concordance between survey data and IIS data using κ to measure the degree of nonrandom agreement. We used multivariable logistic regression models to investigate differences among demographic variables between the 2 data sets. These models were used to construct weights that enabled us to predict immunization rates in areas where reporting is not mandated. We found moderate agreement between the telephone survey and the IIS for the diphtheria, tetanus, and acellular pertussis (κ = 0.49), pneumococcal conjugate (κ = 0.49), and Haemophilus influenzae type b (κ = 0.46) vaccines; fair agreement for the varicella (κ = 0.39), polio (κ = 0.39), and measles, mumps, and rubella (κ = 0.35) vaccines; and slight agreement for the hepatitis B vaccine (κ = 0.17). Consistency in factors predicting immunization coverage levels in a telephone survey and IIS data confirmed the feasibility of using voluntarily reported IIS data to assess immunization rates in children aged 19-35 months.

Voluntarily Reported Immunization Registry Data: Reliability and Feasibility to Predict Immunization Rates, San Diego, California, 2013

PubMed Central

Wester, Robert B.; Wang, Wendy W.; Smith, Tyler C.; Peddecord, K. Michael; Morris, Jessica; DeGuzman, Heidi; Sawyer, Mark H.; McDonald, Eric C.

2017-01-01

Objectives: Accurate data on immunization coverage levels are essential to public health program planning. Reliability of coverage estimates derived from immunization information systems (IISs) in states where immunization reporting by medical providers is not mandated by the state may be compromised by low rates of participation. To overcome this problem, data on coverage rates are often acquired through random-digit-dial telephone surveys, which require substantial time and resources. This project tested both the reliability of voluntarily reported IIS data and the feasibility of using these data to estimate regional immunization rates. Methods: We matched telephone survey records for 553 patients aged 19-35 months obtained in 2013 to 430 records in the San Diego County IIS. We assessed concordance between survey data and IIS data using κ to measure the degree of nonrandom agreement. We used multivariable logistic regression models to investigate differences among demographic variables between the 2 data sets. These models were used to construct weights that enabled us to predict immunization rates in areas where reporting is not mandated. Results: We found moderate agreement between the telephone survey and the IIS for the diphtheria, tetanus, and acellular pertussis (κ = 0.49), pneumococcal conjugate (κ = 0.49), and Haemophilus influenzae type b (κ = 0.46) vaccines; fair agreement for the varicella (κ = 0.39), polio (κ = 0.39), and measles, mumps, and rubella (κ = 0.35) vaccines; and slight agreement for the hepatitis B vaccine (κ = 0.17). Conclusions: Consistency in factors predicting immunization coverage levels in a telephone survey and IIS data confirmed the feasibility of using voluntarily reported IIS data to assess immunization rates in children aged 19-35 months. PMID:28379785

Modeling the effect of non-penetrating ballistic impact as a means of detecting behind armor blunt trauma.

PubMed

Roberts, Jack C; O'Connor, James V; Ward, Emily E

2005-06-01

According to the National Institute of Justice (NIJ) Standard 0101.04, the maximum deformation a soft armor vest can undergo without penetration is 44 mm. However, this does not take into account the effect of the pressure wave or energy transferred to the organs within the torso due to behind armor blunt trauma (BABT). Therefore, a study was undertaken to develop a finite element model (FEM) to study these effects. A finite element model (FEM) of the human thorax; complete with musculoskeletal structure and internal organs (heart, liver, lungs and stomach), intercostal muscle and skin, has been developed in LS-DYNA. A Kevlar vest was modeled on the chest to simulate non-penetrating ballistic impact. Using a projectile modeled with a size and mass equivalent to a 9 mm (124 grain) bullet at 360 and 425 m/s, four impacts were simulated against NIJ Level II and Level IIIa Kevlar vests at the midsternum and right thorax. At the same velocity, the pressures decreased by a factor of 3 and the energy absorbed by the organs decreased by a factor of 6 for the NIJ Level II and Level IIIa vests, respectively. As the projectile velocity increased, the peak pressures increased by a factor of 3 while the energy absorbed by the organs increased by a factor of 4. The resulting pressure profiles and kinetic energy exhibited by the respective organs indicate this model may be useful in identifying mechanisms of injury as well as organs at an elevated injury risk as a result of BABT.

Synthesis, crystal structure, spectroscopic characterization and nonlinear optical properties of manganese (II) complex of picolinate: A combined experimental and computational study

NASA Astrophysics Data System (ADS)

Tamer, Ömer; Avcı, Davut; Atalay, Yusuf; Çoşut, Bünyemin; Zorlu, Yunus; Erkovan, Mustafa; Yerli, Yusuf

2016-02-01

A novel manganese (II) complex with picolinic acid (pyridine 2-carboxylic acid, Hpic), namely, [Mn(pic)2(H2O)2] was prepared and its crystal structure was fully characterized by using single crystal X-ray diffraction. Picolinate (pic) ligands were coordinated to the central manganese(II) ion as bidentate N,O-donors through the nitrogen atoms of pyridine rings and the oxygen atoms of carboxylate groups forming five-membered chelate rings. The spectroscopic characterization of Mn(II) complex was performed by the applications of FT-IR, Raman, UV-vis and EPR techniques. In order to support these studies, density functional theory (DFT) calculations were carried out by using B3LYP level. IR and Raman spectra were simulated at B3LYP level, and obtained results indicated that DFT calculations generally give compatible results to the experimental ones. The electronic structure of the Mn(II) complex was predicted using time dependent DFT (TD-DFT) method with polarizable continuum model (PCM). Molecular stability, hyperconjugative interactions, intramolecular charge transfer (ICT) and bond strength were investigated by applying natural bond orbital (NBO) analysis. Nonlinear optical properties of Mn(II) complex were investigated by the determining of molecular polarizability (α) and hyperpolarizability (β) parameters.

Effects of cadmium on absorption, excretion, and distribution of nickel in rats.

PubMed

Li, Zhan; Gu, Jun-Ying; Wang, Xian-Wen; Fan, Qiao-Hui; Geng, Yan-Xia; Jiao, Zong-Xian; Hou, Yi-Ping; Wu, Wang-Suo

2010-06-01

The effects of cadmium (Cd (II)) on absorption, excretion, and distribution of nickel (Ni (II)) were studied in rats using (63)Ni-NiCl(2) as radiotracer in the presence and absence of CdCl(2), through intraperitoneal injection (i.p.). The time-concentration curves in the blood were fitted with a two-compartment model. The peak time (t ((peak))) is 0.31 h in the absence of Cd (II), and it is 5.5 h in the presence of Cd (II). The levels of nickels were higher at 3 h and lower (close to zero) at 24 h in all organs of interest, except kidneys, in the absence of Cd (II). There still residue Ni (II) at 72 h post-injection in the presence of Cd (II). The Cd (II) did effect the total Ni (II) excretion 24 h post-injection. Our study showed that cadmium has a competitive effect on the absorption of nickel and an inhibitory effect on the elimination of it, so cadmium may induce the bioaccumulation of nickel in the body.

Reopen parameter regions in two-Higgs doublet models

NASA Astrophysics Data System (ADS)

Staub, Florian

2018-01-01

The stability of the electroweak potential is a very important constraint for models of new physics. At the moment, it is standard for Two-Higgs doublet models (THDM), singlet or triplet extensions of the standard model to perform these checks at tree-level. However, these models are often studied in the presence of very large couplings. Therefore, it can be expected that radiative corrections to the potential are important. We study these effects at the example of the THDM type-II and find that loop corrections can revive more than 50% of the phenomenological viable points which are ruled out by the tree-level vacuum stability checks. Similar effects are expected for other extension of the standard model.

Competency-Based Adult Education Classroom Management Guide for Adult Basic Education Curriculum (Level II, 5-8).

ERIC Educational Resources Information Center

Singer, Elizabeth

This Competency-Based Adult Basic Education (CBABE) Classroom Management Guide was developed to aid the Adult Basic Education (ABE) facilitator in implementing a model CBABE Level 5-8 curriculum. First, introductory material provides background on the CBABE project at Brevard Community College (Florida) and the rationale for the development of the…

A High School Intensive Summer Mandarin Course: Program Model and Learner Outcomes

ERIC Educational Resources Information Center

Xu, Xiaoqiu; Padilla, Amado M.; Silva, Duarte; Masuda, Norman

2012-01-01

This article describes a STARTALK intensive summer high school Mandarin language and culture program that was conducted for three summers. Participants across the three years included 40 Mandarin Level II and 53 Mandarin Level III high school students. Quantitative and qualitative data are presented to show the effectiveness of the program.…

[Islet transplantation in type II diabetes mellitus--model of the spontaneous diabetic Cohen rat].

PubMed

Wiegand, S; Bretzel, R G; Cohen, A M; Federlin, K

1989-01-01

The spontaneous diabetic Cohen-rat is one of the few animal models of the diabetes mellitus Type II (NIDDM). A spontaneous diabetic animal line and a diabetes-resistant line originated from a parental lineage by genetic selection with regard to the glucose tolerance on condition of feeding of a saccharose-rich and copper-poor diet. In each case 1000 islets of the diabetes-resistant line were transplanted in 28 animals of the diabetic line. Body weight, blood-sugar concentration, glucosuria, glucose tolerance, and the HbA1 were normalized after the transplantation. The serum levels of insulin and glucagon increased. These results emphasize etiopathogenetic importance of the islets of Langerhans in this animal model.

Adaptation and Latent Structure of the Swahili Version of Beck Depression Inventory-II in a Low Literacy Population in the Context of HIV.

PubMed

Abubakar, Amina; Kalu, Raphael Birya; Katana, Khamis; Kabunda, Beatrice; Hassan, Amin S; Newton, Charles R; Van de Vijver, Fons

2016-01-01

We set out to adapt the Beck Depression Inventory (BDI)-II in Kenya and examine its factorial structure. In the first phase we carried out in-depth interviews involving 29 adult members of the community to elicit their understanding of depression and identify aspects of the BDI-II that required adaptation. In the second phase, a modified version of BDI-II was administered to 221 adults randomly selected from the community to allow for the evaluation of its psychometric properties. In the third phase of the study we evaluated the discriminative validity of BDI-11 by comparing a randomly chosen community sample (n = 29) with caregivers of adolescents affected by HIV (n = 77). A considerable overlap between the BDI symptoms and those generated in the interviews was observed. Relevant idioms and symptoms such as 'thinking too much' and 'Kuchoka moyo (having a tired heart)' were identified. The administration of the BDI had to be modified to make it suitable for the low literacy levels of our participants. Fit indices for several models (one factorial, two-factor model and a three factor model) were all within acceptable range. Evidence indicated that while multidimensional models could be fitted, the strong correlations between the factors implied that a single factor model may be the best suited solution (alpha [0.89], and a significant correlation with locally identified items [r = 0.51]) confirmed the good psychometric properties of the adapted BDI-II. No evidence was found to support the hypothesis that somatization was more prevalent. Lastly, caregivers of HIV affected adolescents had significantly higher scores compared to adults randomly selected from the community F(1, 121) = 23.31, p < .001 indicating the discriminative validity of the adapted BDI = II. With an adapted administration procedure, the BDI-II provides an adequate measure of depressive symptoms which can be used alongside other measures for proper diagnosis in a low literacy population.

Tell Me a Story About Healthy Snacking and I Will Follow: Comparing the Effectiveness of Self-Generated Versus Message-Aided Implementation Intentions on Promoting Healthy Snacking Habits Among College Students.

PubMed

Oh, Hyun Jung; Larose, Robert

2015-01-01

In the context of healthy snacking, this study examines whether the quality of mental imagery determines the effectiveness of combining the implementation intention (II) intervention with mental imagery. This study further explores whether providing narrative healthy snacking scenarios prior to forming an II enhances people's mental imagery experience when they are not motivated to snack healthfully. A 2 × 2 factorial design was employed to test the main effect of providing healthy snacking scenarios prior to II formation, and whether such effect depends on people's motivation level. The results from the experiment (N =148) showed significant main as well as interaction effects of the manipulation (with vs. without reading healthy snacking scenarios prior to II formation) and motivation level on ease and vividness of mental imagery. The regression model with the experiment and follow-up survey data (n = 128) showed a significant relationship between ease of mental imagery and actual snacking behavior after controlling for habit strength. The findings suggest that adding a narrative message to the II intervention can be useful, especially when the intervention involves mental imagery and invites less motivated people.

Optimal Sampling to Provide User-Specific Climate Information.

NASA Astrophysics Data System (ADS)

Panturat, Suwanna

The types of weather-related world problems which are of socio-economic importance selected in this study as representative of three different levels of user groups include: (i) a regional problem concerned with air pollution plumes which lead to acid rain in the north eastern United States, (ii) a state-level problem in the form of winter wheat production in Oklahoma, and (iii) an individual-level problem involving reservoir management given errors in rainfall estimation at Lake Ellsworth, upstream from Lawton, Oklahoma. The study is aimed at designing optimal sampling networks which are based on customer value systems and also abstracting from data sets that information which is most cost-effective in reducing the climate-sensitive aspects of a given user problem. Three process models being used in this study to interpret climate variability in terms of the variables of importance to the user comprise: (i) the HEFFTER-SAMSON diffusion model as the climate transfer function for acid rain, (ii) the CERES-MAIZE plant process model for winter wheat production and (iii) the AGEHYD streamflow model selected as "a black box" for reservoir management. A state-of-the-art Non Linear Program (NLP) algorithm for minimizing an objective function is employed to determine the optimal number and location of various sensors. Statistical quantities considered in determining sensor locations including Bayes Risk, the chi-squared value, the probability of the Type I error (alpha) and the probability of the Type II error (beta) and the noncentrality parameter delta^2. Moreover, the number of years required to detect a climate change resulting in a given bushel per acre change in mean wheat production is determined; the number of seasons of observations required to reduce the standard deviation of the error variance of the ambient sulfur dioxide to less than a certain percent of the mean is found; and finally the policy of maintaining pre-storm flood pools at selected levels is examined given information from the optimal sampling network as defined by the study.

Adsorption of Pb(II), Cu(II), Cd(II), Zn(II), Ni(II), Fe(II), and As(V) on bacterially produced metal sulfides.

PubMed

Jong, Tony; Parry, David L

2004-07-01

The adsorption of Pb(II), Cu(II), Cd(II), Zn(II), Ni(II), Fe(II) and As(V) onto bacterially produced metal sulfide (BPMS) material was investigated using a batch equilibrium method. It was found that the sulfide material had adsorptive properties comparable with those of other adsorbents with respect to the specific uptake of a range of metals and, the levels to which dissolved metal concentrations in solution can be reduced. The percentage of adsorption increased with increasing pH and adsorbent dose, but decreased with increasing initial dissolved metal concentration. The pH of the solution was the most important parameter controlling adsorption of Cd(II), Cu(II), Fe(II), Ni(II), Pb(II), Zn(II), and As(V) by BPMS. The adsorption data were successfully modeled using the Langmuir adsorption isotherm. Desorption experiments showed that the reversibility of adsorption was low, suggesting high-affinity adsorption governed by chemisorption. The mechanism of adsorption for the divalent metals was thought to be the formation of strong, inner-sphere complexes involving surface hydroxyl groups. However, the mechanism for the adsorption of As(V) by BPMS appears to be distinct from that of surface hydroxyl exchange. These results have important implications to the management of metal sulfide sludge produced by bacterial sulfate reduction.

Sildenafil Protects against Myocardial Ischemia-Reperfusion Injury Following Cardiac Arrest in a Porcine Model: Possible Role of the Renin-Angiotensin System

PubMed Central

Wang, Guoxing; Zhang, Qian; Yuan, Wei; Wu, Junyuan; Li, Chunsheng

2015-01-01

Sildenafil, a phosphodiesterase-5 inhibitor sold as Viagra, is a cardioprotector against myocardial ischemia/reperfusion (I/R) injury. Our study explored whether sildenafil protects against I/R-induced damage in a porcine cardiac arrest and resuscitation (CAR) model via modulating the renin-angiotensin system. Male pigs were randomly divided to three groups: Sham group, Saline group, and sildenafil (0.5 mg/kg) group. Thirty min after drug infusion, ventricular fibrillation (8 min) and cardiopulmonary resuscitation (up to 30 min) was conducted in these animals. We found that sildenafil ameliorated the reduced cardiac function and improved the 24-h survival rate in this model. Sildenafil partly attenuated the increases of plasma angiotensin II (Ang II) and Ang (1–7) levels after CAR. Sildenafil also decreased apoptosis and Ang II expression in myocardium. The increases of expression of angiotensin-converting-enzyme (ACE), ACE2, Ang II type 1 receptor (AT1R), and the Ang (1–7) receptor Mas in myocardial tissue were enhanced after CAR. Sildenafil suppressed AT1R up-regulation, but had no effect on ACE, ACE2, and Mas expression. Sildenafilfurther boosted the upregulation of endothelial nitric oxide synthase (eNOS), cyclic guanosine monophosphate (cGMP) and inducible nitric oxide synthase(iNOS). Collectively, our results suggest that cardioprotection of sildenafil in CAR model is accompanied by an inhibition of Ang II-AT1R axis activation. PMID:26569234

Activation of renin-angiotensin-aldosterone system (RAAS) in the lung of smoking-induced pulmonary arterial hypertension (PAH) rats.

PubMed

Yuan, Yi-Ming; Luo, Li; Guo, Zhen; Yang, Ming; Ye, Ren-Song; Luo, Chuan

2015-06-01

To explore the role of the renin-angiotensin-aldosterone system (RAAS) in the pathogenesis of pulmonary arterial hypertension (PAH) induced by chronic exposure to cigarette smoke. 48 healthy male SD rats were randomly divided into four groups (12/group): control group (group A); inhibitor alone group (group B); cigarette induction group (group C); cigarette induction + inhibitor group (group D). After the establishment of smoking-induced PAH rat model, the right ventricular systolic pressure (RVSP) was detected using an inserted catheter; western blotting was used to detect the protein expression of angiotensin-converting enzyme-2 (ACE2) and angiotensin-converting enzyme (ACE); expression levels of angiotensin II (AngII) in lung tissue were measured by radioimmunoassay. After six months of cigarette exposure, the RVSP of chronic cigarette induction group was significantly higher than that of the control group; expression levels of AngII and ACE increased in lung tissues, but ACE2 expression levels reduced. Compared with cigarette exposure group, after losartan treatment, RVSP, ACE and AngII obviously decreased (P<0.05), and ACE2 expression levels significantly increased. Chronic cigarette exposure may result in PAH and affect the protein expression of ACE2 and ACE in lung tissue, suggesting that ACE2 and ACE play an important role in the pathogenesis of smoking-induced PAH. © The Author(s) 2015.

The association of SNP276G>T at adiponectin gene with insulin resistance and circulating adiponectin in response to two different hypocaloric diets.

PubMed

de Luis, Daniel Antonio; Izaola, Olatz; Primo, David; Aller, R; Ortola, A; Gómez, E; Lopez, J J

2018-03-01

Several adiponectin gene (ADIPOQ) single nucleotide polymorphisms (SNPS) have been related with adiponectin levels and risk for obesity. The aim of our study was to analyze the effect of rs1501299 ADIPOQ gene polymorphism and dietary intake on total adiponectin levels and insulin resistance after two hypocaloric diets in obese subjects. A Caucasian population of 284 obese patients was enrolled in a randomized clinical trial with two hypocaloric diets (I: moderate carbohydrates vs II: low fat). Before and after 12 weeks on each hypocaloric diet, an anthropometric evaluation, an assessment of nutritional intake and a biochemical analysis were realized. The statistical analysis was performed for the combined GT and TT as a group (mutant) and GG as second group (wild) (dominant model). The genotype distribution was 149 GG, 124 GT and 21 TT. With caloric restriction strategies, body weight, body mass index (BMI), fat mass, waist circumference, systolic blood pressure, total LDL cholesterol, LDL cholesterol and leptin levels decreased. Only in subjects with GG genotype, diet I and II decreased fasting insulin levels, HOMA-IR and adiponectin levels. The improvement was similar with both diets; insulin concentrations (Diet I: -4.7 ± 1.4 mUI/L vs. Diet II: -5.9 ± 1.9 mUI/L: p = .76), HOMA-IR (Diet I: -1.4 ± 0.6 units vs. Diet II: -2.0 ± 0.7 units: p = .56) and adiponectin levels (Diet I: -10.2 ± 3.4 ng/dl vs. Diet II: -14.0 ± 2.9 ng/dl: p = .33). The GG genotype of ADIPOQ gene variant (rs1501299) is associated with an increase in adiponectin levels and a decrease of insulin and HOMA-IR after weight loss. Copyright © 2018 Elsevier B.V. All rights reserved.

Fibrocytes in the fibrotic lung: altered phenotype detected by flow cytometry.

PubMed

Reese, Charles; Lee, Rebecca; Bonner, Michael; Perry, Beth; Heywood, Jonathan; Silver, Richard M; Tourkina, Elena; Visconti, Richard P; Hoffman, Stanley

2014-01-01

Fibrocytes are bone marrow hematopoietic-derived cells that also express a mesenchymal cell marker (commonly collagen I) and participate in fibrotic diseases of multiple organs. Given their origin, they or their precursors must be circulating cells before recruitment into target tissues. While most previous studies focused on circulating fibrocytes, here we focus on the fibrocyte phenotype in fibrotic tissue. The study's relevance to human disease is heightened by use of a model in which bleomycin is delivered systemically, recapitulating several features of human scleroderma including multi-organ fibrosis not observed when bleomycin is delivered directly into the lungs. Using flow cytometry, we find in the fibrotic lung a large population of CD45(high) fibrocytes (called Region I) rarely found in vehicle-treated control mice. A second population of CD45+ fibrocytes (called Region II) is observed in both control and fibrotic lung. The level of CD45 in circulating fibrocytes is far lower than in either Region I or II lung fibrocytes. The chemokine receptors CXCR4 and CCR5 are expressed at higher levels in Region I than in Region II and are present at very low levels in all other lung cells including CD45+/collagen I- leucocytes. The collagen chaperone HSP47 is present at similar high levels in both Regions I and II, but at a higher level in fibrotic lung than in control lung. There is also a major population of HSP47(high)/CD45- cells in fibrotic lung not present in control lung. CD44 is present at higher levels in Region I than in Region II and at much lower levels in all other cells including CD45+/collagen I- leucocytes. When lung fibrosis is inhibited by restoring caveolin-1 activity using a caveolin-1 scaffolding domain peptide (CSD), a strong correlation is observed between fibrocyte number and fibrosis score. In summary, the distinctive phenotype of fibrotic lung fibrocytes suggests that fibrocyte differentiation occurs primarily within the target organ.

Fibrocytes in the fibrotic lung: altered phenotype detected by flow cytometry

PubMed Central

Reese, Charles; Lee, Rebecca; Bonner, Michael; Perry, Beth; Heywood, Jonathan; Silver, Richard M.; Tourkina, Elena; Visconti, Richard P.; Hoffman, Stanley

2014-01-01

Fibrocytes are bone marrow hematopoietic-derived cells that also express a mesenchymal cell marker (commonly collagen I) and participate in fibrotic diseases of multiple organs. Given their origin, they or their precursors must be circulating cells before recruitment into target tissues. While most previous studies focused on circulating fibrocytes, here we focus on the fibrocyte phenotype in fibrotic tissue. The study's relevance to human disease is heightened by use of a model in which bleomycin is delivered systemically, recapitulating several features of human scleroderma including multi-organ fibrosis not observed when bleomycin is delivered directly into the lungs. Using flow cytometry, we find in the fibrotic lung a large population of CD45high fibrocytes (called Region I) rarely found in vehicle-treated control mice. A second population of CD45+ fibrocytes (called Region II) is observed in both control and fibrotic lung. The level of CD45 in circulating fibrocytes is far lower than in either Region I or II lung fibrocytes. The chemokine receptors CXCR4 and CCR5 are expressed at higher levels in Region I than in Region II and are present at very low levels in all other lung cells including CD45+/collagen I- leucocytes. The collagen chaperone HSP47 is present at similar high levels in both Regions I and II, but at a higher level in fibrotic lung than in control lung. There is also a major population of HSP47high/CD45- cells in fibrotic lung not present in control lung. CD44 is present at higher levels in Region I than in Region II and at much lower levels in all other cells including CD45+/collagen I- leucocytes. When lung fibrosis is inhibited by restoring caveolin-1 activity using a caveolin-1 scaffolding domain peptide (CSD), a strong correlation is observed between fibrocyte number and fibrosis score. In summary, the distinctive phenotype of fibrotic lung fibrocytes suggests that fibrocyte differentiation occurs primarily within the target organ. PMID:24999331

The response to oestrogen deprivation of the cartilage collagen degradation marker, CTX-II, is unique compared with other markers of collagen turnover

PubMed Central

Bay-Jensen, Anne-Christine; Tabassi, Nadine CB; Sondergaard, Lene V; Andersen, Thomas L; Dagnaes-Hansen, Frederik; Garnero, Patrick; Kassem, Moustapha; Delaissé, Jean-Marie

2009-01-01

Introduction The urinary level of the type II collagen degradation marker CTX-II is increased in postmenopausal women and in ovariectomised rats, suggesting that oestrogen deprivation induces cartilage breakdown. Here we investigate whether this response to oestrogen is also true for other type II collagen turnover markers known to be affected in osteoarthritis, and whether it relates to its presence in specific areas of cartilage tissue. Methods The type II collagen degradation markers CTX-II and Helix-II were measured in the body fluids of premenopausal and postmenopausal women and in those of ovariectomised rats receiving oestrogen or not. Levels of PIIANP, a marker of type II collagen synthesis, were also measured in rats. Rat knee cartilage was analysed for immunoreactivity of CTX-II and PIIANP and for type II collagen expression. Results As expected, urinary levels of CTX-II are significantly increased in postmenopausal women and also in oestrogen-deprived rats, although only transiently. However, in neither case were these elevations paralleled by a significant increase of Helix-II levels and PIIANP levels did not change at any time. CTX-II immunoreactivity and collagen expression were detected in different cartilage areas. The upper zone is the area where CTX-II immunoreactivity and collagen expression best reflected the differences in urinary levels of CTX-II measured in response to oestrogen. However, correlations between urinary levels of CTX-II and tissue immunostainings in individual rats were not statistically significant. Conclusions We found only a small effect of oestrogen deprivation on cartilage. It was detected by CTX-II, but not by other type II collagen turnover markers typically affected in osteoarthritis. PMID:20527083

AGN-driven helium reionization and the incidence of extended He III regions at redshift z > 3

NASA Astrophysics Data System (ADS)

Compostella, Michele; Cantalupo, Sebastiano; Porciani, Cristiano

2014-12-01

We use hydrodynamic simulations post-processed with the radiative-transfer code RADAMESH to assess recent claims that the low He II opacity observed in z > 3 quasar spectra may be incompatible with models of He II reionization driven by the observed population of active galactic nuclei (AGNs). In particular, building upon our previous work, we consider an early population of sources and start the radiative-transfer calculation at redshifts z ≥ 5. Our model faithfully reproduces the emissivity of optically selected AGNs as inferred from measurements of their luminosity function. We find that He II reionization is very extended in redshift (Δz ≥ 2) and highly spatially inhomogeneous. In fact, mock spectra extracted from the simulations show a large variability in the evolution of the He II effective optical depth within chunks of size Δz = 0.04. Regions with low opacity (τ_ {He {II}}^eff < 3) can be found at high redshift, in agreement with the most recent observations of UV-transmitting quasars. At the highest redshift currently probed by observations (z ˜ 3.4), our updated model predicts a much lower He II effective optical depth than previous simulations in the literature relieving most of the tension with the current data, that, however, still persists at about the (Gaussian) 1σ to 2σ level. Given the very small number of observed lines of sight, our analysis indicates that current data cannot rule out a purely AGN-driven scenario with high statistical significance.

Activation of calcineurin in human failing heart ventricle by endothelin-1, angiotensin II and urotensin II

PubMed Central

Li, Joan; Wang, Jianchun; Russell, Fraser D; Molenaar, Peter

2005-01-01

The calcineurin (CaN) enzyme–transcriptional pathway is critically involved in hypertrophy of heart muscle in some animal models. Currently there is no information concerning the regulation of CaN activation by endogenous agonists in human heart. Human right ventricular trabeculae from explanted human (14 male/2 female) failing hearts were set up in a tissue bath and electrically paced at 1 Hz and incubated with or without 100 nM endothelin-1 (ET-1), 10 μM, angiotensin-II (Ang II) or 20 nM human urotensin-II (hUII) for 30 min. Tissues from four patients were incubated with 200 nM tacrolimus (FK506) for 30 min and then incubated in the presence or absence of ET-1 for a further 30 min. ET-1 increased contractile force in all 13 patients (P<0.001). Ang II and hUII increased contractile force in three out of eight and four out of 10 patients but overall nonsignificantly (P>0.1). FK506 had no effect on contractile force (P=0.12). ET-1, Ang II and hUII increased calcineurin activity by 32, 71 and 15%, respectively, while FK506 reduced activity by 34%. ET-1 in the presence of FK506 did not restore calcineurin activity (P=0.1). There was no relationship between basal CaN activity and expression levels in the right ventricle. Increased levels of free phosphate were detected in ventricular homogenates that were incubated with PKCɛ compared to samples incubated without PKCɛ. Endogenous cardiostimulants which activate Gαq-coupled receptors increase the activity of calcineurin in human heart following acute (30 min) exposure. PKC may contribute to this effect by increasing levels of phosphorylated calcineurin substrate. PMID:15821752

Regular Article Macroautophagy is Defective in Mucolipin 1-Deficient Mouse Neurons

PubMed Central

Curcio-Morelli, Cyntia; Charles, Florie A.; Micsenyi, Matthew C.; Cao, Yi; Venugopal, Bhuvarahamurthy; Browning, Marsha F.; Dobrenis, Kostantin; Cotman, Susan L.; Walkley, Steven U.; Slaugenhaupt, Susan A.

2013-01-01

Mucolipidosis Type IV is a neurodegenerative lysosomal disease clinically characterized by psychomotor retardation, visual impairment, and achlorhydria. In this study we report the development of a neuronal cell model generated from cerebrum of Mcoln1-/- embryos. Prior functional characterization of MLIV cells has been limited to fibroblast cultures gleaned from patients. The current availability of the mucolipin-1 knockout mouse model Mcoln1-/- allows the study of mucolipin1-defective neurons, which is important since the disease is characterized by severe neurological impairment. Electron microscopy studies reveal significant membranous intracytoplasmic storage bodies, which correlate with the storage morphology observed in cerebral cortex of Mcoln1-/- P7 pups and E17 embryos. The Mcoln1-/- neuronal cultures show an increase in size of LysoTracker and Lamp1 positive-vesicles. Using this neuronal model system, we show that macroautophagy is defective in mucolipin-1 deficient neurons and that LC3-II levels are significantly elevated. Treatment with rapamycin plus protease inhibitors did not increase levels of LC3-II in Mcoln1-/- neuronal cultures, indicating that the lack of mucolipin-1 affects LC3-II clearance. P62/SQSTM1 and ubiquitin levels were also increased in Mcoln1-/- neuronal cultures, suggesting an accumulation of protein aggregates and a defect in macroautophagy which could help explain the neurodegeneration observed in MLIV. This study describes, for the first time, a defect in macroautophagy in mucolipin-1 deficient neurons, which corroborates recent findings in MLIV fibroblasts and provides new insight into the neuronal pathogenesis of this disease. PMID:20600908

Iron cycling under oscillatory redox conditions: from observations to processes

NASA Astrophysics Data System (ADS)

Meile, C. D.; Chen, C.; Barcellos, D.; Wilmoth, J.; Thompson, A.

2017-12-01

Fe oxyhydroxides play a critical role in soils through their role as structural entities, their high sorption capacity, their role as terminal electron acceptors in the respiration of organic matter, as well as their potential to affect the reactivity of that organic matter. In soils that undergo repeated fluctuations in O2 concentrations, soil iron undergoes transformations between reduced and oxidized forms. The rate of Fe(II) oxidation can govern the nature of Fe(III) oxyhydroxides formed, and hence can affect rates of OC mineralization under suboxic conditions. But it remains unclear if this same behavior occurs in soils, where Fe(II) is mainly present as surface complexes. We documented the impact of such redox oscillations on iron cycling through targeted experiments, in which the magnitude and frequency of redox oscillations were varied systematically on soils from the Luquillo Critical Zone Observatory, Puerto Rico. Our observations demonstrated that higher O2 concentrations led to a faster Fe(II) oxidation and resulted in less crystalline Fe(III)-oxyhydroxides than lower O2 concentrations. We further studied the dynamics of iron phases by amending soil slurries with isotopically-labeled 57Fe(II) and developed a numerical model to quantify the individual processes. Our model showed a higher rate of Fe(III) reduction and increased sorption capacity following the oxidation of Fe(II) at high O2 levels than at low O2 levels, and revealed rapid Fe atom exchange between solution and solid phase. Concurrent measurements of CO2 in our oscillation experiments further illustrated the importance O2 fluctuations on coupled Fe-C dynamics.

A Modular Approach to Teaching Mathematical Modeling in Biotechnology in the Undergraduate Curriculum

ERIC Educational Resources Information Center

Larripa, Kamila R.; Mazzag, Borbala

2016-01-01

Our paper describes a solution we found to a still existing need to develop mathematical modeling courses for undergraduate biology majors. Some challenges of such courses are: (i) relatively limited exposure of biology students to higher-level mathematical and computational concepts; (ii) availability of texts that can give a flavor of how…

Sample Size Determination for Rasch Model Tests

ERIC Educational Resources Information Center

Draxler, Clemens

2010-01-01

This paper is concerned with supplementing statistical tests for the Rasch model so that additionally to the probability of the error of the first kind (Type I probability) the probability of the error of the second kind (Type II probability) can be controlled at a predetermined level by basing the test on the appropriate number of observations.…

Keratins Are Altered in Intestinal Disease-Related Stress Responses.

PubMed

Helenius, Terhi O; Antman, Cecilia A; Asghar, Muhammad Nadeem; Nyström, Joel H; Toivola, Diana M

2016-09-10

Keratin (K) intermediate filaments can be divided into type I/type II proteins, which form obligate heteropolymers. Epithelial cells express type I-type II keratin pairs, and K7, K8 (type II) and K18, K19 and K20 (type I) are the primary keratins found in the single-layered intestinal epithelium. Keratins are upregulated during stress in liver, pancreas, lung, kidney and skin, however, little is known about their dynamics in the intestinal stress response. Here, keratin mRNA, protein and phosphorylation levels were studied in response to murine colonic stresses modeling human conditions, and in colorectal cancer HT29 cells. Dextran sulphate sodium (DSS)-colitis was used as a model for intestinal inflammatory stress, which elicited a strong upregulation and widened crypt distribution of K7 and K20. K8 levels were slightly downregulated in acute DSS, while stress-responsive K8 serine-74 phosphorylation (K8 pS74) was increased. By eliminating colonic microflora using antibiotics, K8 pS74 in proliferating cells was significantly increased, together with an upregulation of K8 and K19. In the aging mouse colon, most colonic keratins were upregulated. In vitro, K8, K19 and K8 pS74 levels were increased in response to lipopolysaccharide (LPS)-induced inflammation in HT29 cells. In conclusion, intestinal keratins are differentially and dynamically upregulated and post-translationally modified during stress and recovery.

Modeling Neutron stars as r-process sources in Ultra Faint Dwarf galaxies

NASA Astrophysics Data System (ADS)

Safarzadeh, Mohammadtaher; Scannapieco, Evan

2018-06-01

To explain the high observed abundances of r-process elements in local ultrafaint dwarf (UFD) galaxies, we perform cosmological zoom simulations that include r-process production from neutron star mergers (NSMs). We model star formation stochastically and simulate two different haloes with total masses ≈108 M⊙ at z = 6. We find that the final distribution of [Eu/H] versus [Fe/H] is relatively insensitive to the energy by which the r-process material is ejected into the interstellar medium, but strongly sensitive to the environment in which the NSM event occurs. In one halo, the NSM event takes place at the centre of the stellar distribution, leading to high levels of r-process enrichment such as seen in a local UFD, Reticulum II (Ret II). In a second halo, the NSM event takes place outside of the densest part of the galaxy, leading to a more extended r-process distribution. The subsequent star formation occurs in an interstellar medium with shallow levels of r-process enrichment that results in stars with low levels of [Eu/H] compared to Ret II stars even when the maximum possible r-process mass is assumed to be ejected. This suggests that the natal kicks of neutron stars may also play an important role in determining the r-process abundances in UFD galaxies, a topic that warrants further theoretical investigation.

Chance-constrained multi-objective optimization of groundwater remediation design at DNAPLs-contaminated sites using a multi-algorithm genetically adaptive method.

PubMed

Ouyang, Qi; Lu, Wenxi; Hou, Zeyu; Zhang, Yu; Li, Shuai; Luo, Jiannan

2017-05-01

In this paper, a multi-algorithm genetically adaptive multi-objective (AMALGAM) method is proposed as a multi-objective optimization solver. It was implemented in the multi-objective optimization of a groundwater remediation design at sites contaminated by dense non-aqueous phase liquids. In this study, there were two objectives: minimization of the total remediation cost, and minimization of the remediation time. A non-dominated sorting genetic algorithm II (NSGA-II) was adopted to compare with the proposed method. For efficiency, the time-consuming surfactant-enhanced aquifer remediation simulation model was replaced by a surrogate model constructed by a multi-gene genetic programming (MGGP) technique. Similarly, two other surrogate modeling methods-support vector regression (SVR) and Kriging (KRG)-were employed to make comparisons with MGGP. In addition, the surrogate-modeling uncertainty was incorporated in the optimization model by chance-constrained programming (CCP). The results showed that, for the problem considered in this study, (1) the solutions obtained by AMALGAM incurred less remediation cost and required less time than those of NSGA-II, indicating that AMALGAM outperformed NSGA-II. It was additionally shown that (2) the MGGP surrogate model was more accurate than SVR and KRG; and (3) the remediation cost and time increased with the confidence level, which can enable decision makers to make a suitable choice by considering the given budget, remediation time, and reliability. Copyright © 2017 Elsevier B.V. All rights reserved.

Biochemical and developmental characterization of carbonic anhydrase II from chicken erythrocytes.

PubMed

Nishita, Toshiho; Tomita, Yuichiro; Imanari, Takao; Ichihara, Nobutsune; Orito, Kensuke; Arishima, Kazuyoshi

2011-03-07

Carbonic anhydrase (CA) of the chicken has attracted attention for a long time because it has an important role in the eggshell formation. The developmental profile of CA-II isozyme levels in chicken erythrocytes has not been determined or reported. Furthermore, the relations with CA-II in erythrocyte and egg production are not discussed. In the present study, we isolated CA-II from erythrocytes of chickens and determined age-related changes of CA-II levels in erythrocytes. Chicken CA-II was purified by a combination of column chromatography. The levels of CA-II in the hemolysate of the chicken were determined using the ELISA system in blood samples from 279 female chickens, ages 1 to 93 weeks, 69 male chickens, ages 3 to 59 weeks and 52 weeks female Araucana-chickens. The mean concentration of CA-II in hemolysate from 1-week-old female was 50.8 ± 11.9 mg/g of Hb. The mean levels of CA-II in 25-week-old (188.1 ± 82.6 mg/g of Hb), 31-week-old (193.6 ± 69.7 mg/g of Hb) and 49-week-old (203.8 ± 123.5 mg/g of Hb) female-chickens showed the highest level of CA-II. The levels of CA-II in female WL-chickens significantly decreased at 63 week (139.0 ± 19.3 mg/g of Hb). The levels of CA-II in female WL-chicken did not change from week 63 until week 93.The mean level of CA-II in hemolysate of 3-week-old male WL-chickens was 78.3 ± 20.7 mg/g of Hb. The levels of CA-II in male WL-chickens did not show changes in the week 3 to week 59 timeframe. The mean level of CA-II in 53-week-old female Araucana-chickens was 23.4 ± 1.78 mg/g of Hb. These levels of CA-II were about 11% of those of 49-week-old female WL-chickens. Simple linear regression analysis showed significant associations between the level of CA-II and egg laying rate from 16 week-old at 63 week-old WL-chicken (p<0.01). Developmental changes and sexual differences of CA-II concentration in WL-chicken erythrocytes were observed. The concentration of CA-II in the erythrocyte of WL-chicken was much higher than that in Araucana-chicken (p<0.01). © 2011 Nishita et al; licensee BioMed Central Ltd.

Zn II(atsm) is protective in amyotrophic lateral sclerosis model mice via a copper delivery mechanism.

PubMed

McAllum, Erin J; Roberts, Blaine R; Hickey, James L; Dang, Theresa N; Grubman, Alexandra; Donnelly, Paul S; Liddell, Jeffrey R; White, Anthony R; Crouch, Peter J

2015-09-01

Mutations in the metalloprotein Cu,Zn-superoxide dismutase (SOD1) cause approximately 20% of familial cases of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease for which effective therapeutics do not yet exist. Transgenic rodent models based on over-expression of mutant SOD1 have been developed and these have provided opportunity to test new therapeutic strategies and to study the mechanisms of mutant SOD1 toxicity. Although the mechanisms of mutant SOD1 toxicity are yet to be fully elucidated, incorrect or incomplete metallation of SOD1 confers abnormal folding, aggregation and biochemical properties, and improving the metallation state of SOD1 provides a viable therapeutic option. The therapeutic effects of delivering copper (Cu) to mutant SOD1 have been demonstrated recently. The aim of the current study was to determine if delivery of zinc (Zn) to SOD1 was also therapeutic. To investigate this, SOD1G37R mice were treated with the metal complex diacetyl-bis(4-methylthiosemicarbazonato)zinc(II) [Zn(II)(atsm)]. Treatment resulted in an improvement in locomotor function and survival of the mice. However, biochemical analysis of spinal cord tissue collected from the mice revealed that the treatment did not increase overall Zn levels in the spinal cord nor the Zn content of SOD1. In contrast, overall levels of Cu in the spinal cord were elevated in the Zn(II)(atsm)-treated SOD1G37R mice and the Cu content of SOD1 was also elevated. Further experiments demonstrated transmetallation of Zn(II)(atsm) in the presence of Cu to form the Cu-analogue Cu(II)(atsm), indicating that the observed therapeutic effects for Zn(II)(atsm) in SOD1G37R mice may in fact be due to in vivo transmetallation and subsequent delivery of Cu. Copyright © 2015. Published by Elsevier Inc.

Herbal prescription Chang'an II repairs intestinal mucosal barrier in rats with post-inflammation irritable bowel syndrome

PubMed Central

Wang, Feng-yun; Su, Min; Zheng, Yong-qiu; Wang, Xiao-ge; Kang, Nan; Chen, Ting; Zhu, En-lin; Bian, Zhao-xiang; Tang, Xu-dong

2015-01-01

Aim: The herbal prescription Chang'an II is derived from a classical TCM formula Tong-Xie-Yao-Fang for the treatment of liver-qi stagnation and spleen deficiency syndrome of irritable bowel syndrome (IBS). In this study we investigated the effects of Chang'an II on the intestinal mucosal immune barrier in a rat post-inflammation IBS (PI-IBS) model. Methods: A rat model of PI-IBS was established using a multi-stimulation paradigm including early postnatal sibling deprivation, bondage and intrarectal administration of TNBS. Four weeks after TNBS administration, the rats were treated with Chang'an II (2.85, 5.71 and 11.42 g·kg−1·d−1, ig) for 14 d. Intestinal sensitivity was assessed based on the abdominal withdrawal reflex (AWR) scores and fecal water content. Open field test and two-bottle sucrose intake test were used to evaluate the behavioral changes. CD4+ and CD8+ cells were counted and IL-1β and IL-4 levels were measured in intestinal mucosa. Transmission electron microscopy was used to evaluate ultrastructural changes of the intestinal mucosal barrier. Results: PI-IBS model rats showed significantly increased AWR reactivity and fecal water content, and decreased locomotor activity and sucrose intake. Chang'an II treatment not only reduced AWR reactivity and fecal water content, but also suppressed the anxiety and depressive behaviors. Ultrastructural study revealed that the gut mucosal barrier function was severely damaged in PI-IBS model rats, whereas Chang'an II treatment relieved intestinal mucosal inflammation and repaired the gut mucosal barrier. Furthermore, PI-IBS model rats showed a significantly reduced CD4+/CD8+ cell ratio in lamina propria and submucosa, and increased IL-1β and reduced IL-4 expression in intestinal mucosa, whereas Chang'an II treatment reversed PI-IBS-induced changes in CD4+/CD8+ cell ratio and expression of IL-1β and IL-4. Conclusion: Chang'an II treatment protects the intestinal mucosa against PI-IBS through anti-inflammatory, immunomodulatory and anti-anxiety effects. PMID:25960135

Herbal prescription Chang'an II repairs intestinal mucosal barrier in rats with post-inflammation irritable bowel syndrome.

PubMed

Wang, Feng-yun; Su, Min; Zheng, Yong-qiu; Wang, Xiao-ge; Kang, Nan; Chen, Ting; Zhu, En-lin; Bian, Zhao-xiang; Tang, Xu-dong

2015-06-01

The herbal prescription Chang'an II is derived from a classical TCM formula Tong-Xie-Yao-Fang for the treatment of liver-qi stagnation and spleen deficiency syndrome of irritable bowel syndrome (IBS). In this study we investigated the effects of Chang'an II on the intestinal mucosal immune barrier in a rat post-inflammation IBS (PI-IBS) model. A rat model of PI-IBS was established using a multi-stimulation paradigm including early postnatal sibling deprivation, bondage and intrarectal administration of TNBS. Four weeks after TNBS administration, the rats were treated with Chang'an II (2.85, 5.71 and 11.42 g · kg(-1) · d(-1), ig) for 14 d. Intestinal sensitivity was assessed based on the abdominal withdrawal reflex (AWR) scores and fecal water content. Open field test and two-bottle sucrose intake test were used to evaluate the behavioral changes. CD4(+) and CD8(+) cells were counted and IL-1β and IL-4 levels were measured in intestinal mucosa. Transmission electron microscopy was used to evaluate ultrastructural changes of the intestinal mucosal barrier. PI-IBS model rats showed significantly increased AWR reactivity and fecal water content, and decreased locomotor activity and sucrose intake. Chang'an II treatment not only reduced AWR reactivity and fecal water content, but also suppressed the anxiety and depressive behaviors. Ultrastructural study revealed that the gut mucosal barrier function was severely damaged in PI-IBS model rats, whereas Chang'an II treatment relieved intestinal mucosal inflammation and repaired the gut mucosal barrier. Furthermore, PI-IBS model rats showed a significantly reduced CD4(+)/CD8(+) cell ratio in lamina propria and submucosa, and increased IL-1β and reduced IL-4 expression in intestinal mucosa, whereas Chang'an II treatment reversed PI-IBS-induced changes in CD4(+)/CD8(+) cell ratio and expression of IL-1β and IL-4. Chang'an II treatment protects the intestinal mucosa against PI-IBS through anti-inflammatory, immunomodulatory and anti-anxiety effects.

Non-linear Equation using Plasma Brain Natriuretic Peptide Levels to Predict Cardiovascular Outcomes in Patients with Heart Failure

NASA Astrophysics Data System (ADS)

Fukuda, Hiroki; Suwa, Hideaki; Nakano, Atsushi; Sakamoto, Mari; Imazu, Miki; Hasegawa, Takuya; Takahama, Hiroyuki; Amaki, Makoto; Kanzaki, Hideaki; Anzai, Toshihisa; Mochizuki, Naoki; Ishii, Akira; Asanuma, Hiroshi; Asakura, Masanori; Washio, Takashi; Kitakaze, Masafumi

2016-11-01

Brain natriuretic peptide (BNP) is the most effective predictor of outcomes in chronic heart failure (CHF). This study sought to determine the qualitative relationship between the BNP levels at discharge and on the day of cardiovascular events in CHF patients. We devised a mathematical probabilistic model between the BNP levels at discharge (y) and on the day (t) of cardiovascular events after discharge for 113 CHF patients (Protocol I). We then prospectively evaluated this model on another set of 60 CHF patients who were readmitted (Protocol II). P(t|y) was the probability of cardiovascular events occurring after >t, the probability on t was given as p(t|y) = -dP(t|y)/dt, and p(t|y) = pP(t|y) = αyβP(t|y), along with p = αyβ (α and β were constant); the solution was p(t|y) = αyβ exp(-αyβt). We fitted this equation to the data set of Protocol I using the maximum likelihood principle, and we obtained the model p(t|y) = 0.000485y0.24788 exp(-0.000485y0.24788t). The cardiovascular event-free rate was computed as P(t) = 1/60Σi=1,…,60 exp(-0.000485yi0.24788t), based on this model and the BNP levels yi in a data set of Protocol II. We confirmed no difference between this model-based result and the actual event-free rate. In conclusion, the BNP levels showed a non-linear relationship with the day of occurrence of cardiovascular events in CHF patients.

FOSSIL2 energy policy model documentation: FOSSIL2 documentation

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

1980-10-01

This report discusses the structure, derivations, assumptions, and mathematical formulation of the FOSSIL2 model. Each major facet of the model - supply/demand interactions, industry financing, and production - has been designed to parallel closely the actual cause/effect relationships determining the behavior of the United States energy system. The data base for the FOSSIL2 program is large, as is appropriate for a system dynamics simulation model. When possible, all data were obtained from sources well known to experts in the energy field. Cost and resource estimates are based on DOE data whenever possible. This report presents the FOSSIL2 model at severalmore » levels. Volumes II and III of this report list the equations that comprise the FOSSIL2 model, along with variable definitions and a cross-reference list of the model variables. Volume II provides the model equations with each of their variables defined, while Volume III lists the equations, and a one line definition for equations, in a shorter, more readable format.« less

Leishmania infantum HSP70-II null mutant as candidate vaccine against leishmaniasis: a preliminary evaluation

PubMed Central

2011-01-01

Background Visceral leishmaniasis is the most severe form of leishmaniasis and no effective vaccine exists. The use of live attenuated vaccines is emerging as a promising vaccination strategy. Results In this study, we tested the ability of a Leishmania infantum deletion mutant, lacking both HSP70-II alleles (ΔHSP70-II), to provide protection against Leishmania infection in the L. major-BALB/c infection model. Administration of the mutant line by either intraperitoneal, intravenous or subcutaneous route invariably leads to the production of high levels of NO and the development in mice of type 1 immune responses, as determined by analysis of anti-Leishmania IgG subclasses. In addition, we have shown that ΔHSP70-II would be a safe live vaccine as immunodeficient SCID mice, and hamsters (Mesocricetus auratus), infected with mutant parasites did not develop any sign of pathology. Conclusions The results suggest that the ΔHSP70-II mutant is a promising and safe vaccine, but further studies in more appropriate animal models (hamsters and dogs) are needed to appraise whether this attenuate mutant would be useful as vaccine against visceral leishmaniasis. PMID:21794145

Stochastic dynamics of small ensembles of non-processive molecular motors: The parallel cluster model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Erdmann, Thorsten; Albert, Philipp J.; Schwarz, Ulrich S.

2013-11-07

Non-processive molecular motors have to work together in ensembles in order to generate appreciable levels of force or movement. In skeletal muscle, for example, hundreds of myosin II molecules cooperate in thick filaments. In non-muscle cells, by contrast, small groups with few tens of non-muscle myosin II motors contribute to essential cellular processes such as transport, shape changes, or mechanosensing. Here we introduce a detailed and analytically tractable model for this important situation. Using a three-state crossbridge model for the myosin II motor cycle and exploiting the assumptions of fast power stroke kinetics and equal load sharing between motors inmore » equivalent states, we reduce the stochastic reaction network to a one-step master equation for the binding and unbinding dynamics (parallel cluster model) and derive the rules for ensemble movement. We find that for constant external load, ensemble dynamics is strongly shaped by the catch bond character of myosin II, which leads to an increase of the fraction of bound motors under load and thus to firm attachment even for small ensembles. This adaptation to load results in a concave force-velocity relation described by a Hill relation. For external load provided by a linear spring, myosin II ensembles dynamically adjust themselves towards an isometric state with constant average position and load. The dynamics of the ensembles is now determined mainly by the distribution of motors over the different kinds of bound states. For increasing stiffness of the external spring, there is a sharp transition beyond which myosin II can no longer perform the power stroke. Slow unbinding from the pre-power-stroke state protects the ensembles against detachment.« less

Investigations in the possibility of early detection of colorectal cancer by gas chromatography/triple-quadrupole mass spectrometry

PubMed Central

Kawana, Shuichi; Unno, Yumi; Sakai, Takero; Okamoto, Koji; Yamada, Yasuhide; Sudo, Kazuki; Yamaji, Taiki; Saito, Yutaka; Kanemitsu, Yukihide; Okita, Natsuko Tsuda; Saito, Hiroshi; Tsugane, Shoichiro; Azuma, Takeshi; Ojima, Noriyuki; Yoshida, Masaru

2017-01-01

In developed countries, the number of patients with colorectal cancer has been increasing, and colorectal cancer is one of the most common causes of cancer death. To improve the quality of life of colorectal cancer patients, it is necessary to establish novel screening methods that would allow early detection of colorectal cancer. We performed metabolome analysis of a plasma sample set from 282 stage 0/I/II colorectal cancer patients and 291 healthy volunteers using gas chromatography/triple-quadrupole mass spectrometry in an attempt to identify metabolite biomarkers of stage 0/I/II colorectal cancer. The colorectal cancer patients included patients with stage 0 (N=79), I (N=80), and II (N=123) in whom invasion and metastasis were absent. Our analytical system detected 64 metabolites in the plasma samples, and the levels of 29 metabolites differed significantly (Bonferroni-corrected p=0.000781) between the patients and healthy volunteers. Based on these results, a multiple logistic regression analysis of various metabolite biomarkers was carried out, and a stage 0/I/II colorectal cancer prediction model was established. The area under the curve, sensitivity, and specificity values of this model for detecting stage 0/I/II colorectal cancer were 0.996, 99.3%, and 93.8%, respectively. The model's sensitivity and specificity values for each disease stage were >90%, and surprisingly, its sensitivity for stage 0, specificity for stage 0, and sensitivity for stage II disease were all 100%. Our predictive model can aid early detection of colorectal cancer and has potential as a novel screening test for cases of colorectal cancer that do not involve lymph node or distant metastasis. PMID:28179577

Investigations in the possibility of early detection of colorectal cancer by gas chromatography/triple-quadrupole mass spectrometry.

PubMed

Nishiumi, Shin; Kobayashi, Takashi; Kawana, Shuichi; Unno, Yumi; Sakai, Takero; Okamoto, Koji; Yamada, Yasuhide; Sudo, Kazuki; Yamaji, Taiki; Saito, Yutaka; Kanemitsu, Yukihide; Okita, Natsuko Tsuda; Saito, Hiroshi; Tsugane, Shoichiro; Azuma, Takeshi; Ojima, Noriyuki; Yoshida, Masaru

2017-03-07

In developed countries, the number of patients with colorectal cancer has been increasing, and colorectal cancer is one of the most common causes of cancer death. To improve the quality of life of colorectal cancer patients, it is necessary to establish novel screening methods that would allow early detection of colorectal cancer. We performed metabolome analysis of a plasma sample set from 282 stage 0/I/II colorectal cancer patients and 291 healthy volunteers using gas chromatography/triple-quadrupole mass spectrometry in an attempt to identify metabolite biomarkers of stage 0/I/II colorectal cancer. The colorectal cancer patients included patients with stage 0 (N=79), I (N=80), and II (N=123) in whom invasion and metastasis were absent. Our analytical system detected 64 metabolites in the plasma samples, and the levels of 29 metabolites differed significantly (Bonferroni-corrected p=0.000781) between the patients and healthy volunteers. Based on these results, a multiple logistic regression analysis of various metabolite biomarkers was carried out, and a stage 0/I/II colorectal cancer prediction model was established. The area under the curve, sensitivity, and specificity values of this model for detecting stage 0/I/II colorectal cancer were 0.996, 99.3%, and 93.8%, respectively. The model's sensitivity and specificity values for each disease stage were >90%, and surprisingly, its sensitivity for stage 0, specificity for stage 0, and sensitivity for stage II disease were all 100%. Our predictive model can aid early detection of colorectal cancer and has potential as a novel screening test for cases of colorectal cancer that do not involve lymph node or distant metastasis.

An ecological model of the habitat mosaic in estuarine nursery areas: Part II – Projecting effects of sea level rise on fish production

EPA Science Inventory

Understanding the response of fish populations to habitat change mediated by sea level rise (SLR) is a key component of ecosystem-based management. Yet, no direct link has been established between habitat change due to SLR and fish population production. Here we take a coupled ...

Evaluating Children's Learning Disabilities with an Apple II Personal Computer or Tempting Poor Learners with an Apple.

ERIC Educational Resources Information Center

Sisson, Lee Hansen; And Others

This paper describes the use of commercially-available software for the Apple Computer to augment diagnostic evaluations of learning disabled children and to enhance "learning to learn" strategies at the application/transfer level of learning. A short rationale discusses levels of evaluation and learning, using a model that synthesizes the ideas…

Junior high school students' cognitive process in solving the developed algebraic problems based on information processing taxonomy model

NASA Astrophysics Data System (ADS)

Purwoko, Saad, Noor Shah; Tajudin, Nor'ain Mohd

2017-05-01

This study aims to: i) develop problem solving questions of Linear Equations System of Two Variables (LESTV) based on levels of IPT Model, ii) explain the level of students' skill of information processing in solving LESTV problems; iii) explain students' skill in information processing in solving LESTV problems; and iv) explain students' cognitive process in solving LESTV problems. This study involves three phases: i) development of LESTV problem questions based on Tessmer Model; ii) quantitative survey method on analyzing students' skill level of information processing; and iii) qualitative case study method on analyzing students' cognitive process. The population of the study was 545 eighth grade students represented by a sample of 170 students of five Junior High Schools in Hilir Barat Zone, Palembang (Indonesia) that were chosen using cluster sampling. Fifteen students among them were drawn as a sample for the interview session with saturated information obtained. The data were collected using the LESTV problem solving test and the interview protocol. The quantitative data were analyzed using descriptive statistics, while the qualitative data were analyzed using the content analysis. The finding of this study indicated that students' cognitive process was just at the step of indentifying external source and doing algorithm in short-term memory fluently. Only 15.29% students could retrieve type A information and 5.88% students could retrieve type B information from long-term memory. The implication was the development problems of LESTV had validated IPT Model in modelling students' assessment by different level of hierarchy.

Recent theoretical advances on superradiant phase transitions

NASA Astrophysics Data System (ADS)

Baksic, Alexandre; Nataf, Pierre; Ciuti, Cristiano

2013-03-01

The Dicke model describing a single-mode boson field coupled to two-level systems is an important paradigm in quantum optics. In particular, the physics of ``superradiant phase transitions'' in the ultrastrong coupling regime is the subject of a vigorous research activity in both cavity and circuit QED. Recently, we explored the rich physics of two interesting generalizations of the Dicke model: (i) A model describing the coupling of a boson mode to two independent chains A and B of two-level systems, where chain A is coupled to one quadrature of the boson field and chain B to the orthogonal quadrature. This original model leads to a quantum phase transition with a double symmetry breaking and a fourfold ground state degeneracy. (ii) A generalized Dicke model with three-level systems including the diamagnetic term. In contrast to the case of two-level atoms for which no-go theorems exist, in the case of three-level system we prove that the Thomas-Reich-Kuhn sum rule does not always prevent a superradiant phase transition.

Evaluation of Assimilative SST Forecasts in the Okinawa Trough and Gulf of Mexico

DTIC Science & Technology

2012-12-06

Ruth H. Preller, 7300 Socurily, Code -- 1231 Office of 1008.3 ADOR/Director NCST E. R. Franchi , 7000 Public Affairs (Unclassified/ Unlimited Only...E. R. Franchi , 7000 Pubii<: Aifaini iiJneia5s;ii$(iF. · - Unlimited Only), Code 7030•4 0 ·-5 -J·z_...operational global ocean model GOFS 2.6. The SST level 2 data assimilated in these studies is provided by NAVOCEANO and introduced into NCODA via its OCNQC

A Stochastic Model of Plausibility in Live Virtual Constructive Environments

DTIC Science & Technology

2017-09-14

objective in virtual environment research and design is the maintenance of adequate consistency levels in the face of limited system resources such as...provides some commentary with regard to system design considerations and future research directions. II. SYSTEM MODEL DVEs are often designed as a...exceed the system’s requirements. Research into predictive models of virtual environment consistency is needed to provide designers the tools to

Alteration of infant attention and activity by polychlorinated biphenyls: unravelling critical windows of susceptibility using physiologically based pharmacokinetic modeling.

PubMed

Verner, M-A; Plusquellec, P; Muckle, G; Ayotte, P; Dewailly, E; Jacobson, S W; Jacobson, J L; Charbonneau, M; Haddad, S

2010-09-01

Pre- and postnatal exposure to polychlorinated biphenyls (PCBs) can impair behavioural function in animal models at doses within the range at which humans are commonly exposed. Yet, epidemiologic studies conducted in the US and Europe are inconsistent with regard to the developmental effects of lactational exposure to these chemicals. This inconsistency may be due to limitations in the current methodological approaches for assessing postnatal exposure to PCBs. Our study used a physiologically based pharmacokinetic (PBPK) model to simulate blood PCB levels during specific pre- and postnatal periods and to evaluate the relation of those levels to infant behaviour. A previously validated PBPK model was used to simulate infant blood PCB-153 levels at delivery and on a month-by-month basis during the first year of life for Inuit infants enrolled in a longitudinal birth cohort. Infant behaviour was assessed using the Behaviour Rating Scales (BRS) of the Bayley Scales of Infant Development (BSID-II) at 11 months of age and video coding of inattention and activity measured during the administration of the mental development subscale of the BSID-II. The estimated pre- and postnatal PCB exposure measures predicted significant increases in inattention and activity at 11 months. Whereas inattention was related to prenatal exposure, activity level, measured by non-elicited activity, was best predicted by postnatal exposure, with the strongest association obtained for simulated PCB levels during the 4th month of life. These findings are consistent with previous reports indicating PCB-induced behavioural alteration in attention and activity level. Simulated infant toxicokinetic profiles for the first year of life revealed windows of susceptibility during which PCBs may impair infant attention and activity. Copyright © 2010 Elsevier Inc. All rights reserved.

RAAS and stress markers in acute ischemic stroke: preliminary findings.

PubMed

Back, C; Thiesen, K L; Skovgaard, K; Edvinsson, L; Jensen, L T; Larsen, V A; Iversen, H K

2015-02-01

Angiotensin II type 1 receptor blockade has neuroprotective effects in animal stroke models, but no effects in clinical stroke trials. We evaluated cerebral and peripheral changes in the renin angiotensin aldosterone system (RAAS) and stress responses in acute ischemic stroke patients. Blood from a jugular and cubital vein was collected within 48 h of stroke onset, after 24 and 48 h, and renin, angiotensin I, angiotensin II, aldosterone, norepinephrine, epinephrine, and cortisol were measured. Post-stroke cubital vein samples were collected after 8 (4.7-10) months. The acute systolic blood pressure was significantly increased, 148 (141-168) vs 140 (130-147) mmHg post-stroke. Angiotensin I, renin and aldosterone levels were significantly lower, angiotensin II was unchanged, and ACE activity was higher in the acute phase compared to post-stroke. No differences in RAAS were detected between jugular and cubital plasma levels. Jugular venous plasma levels of epinephrine and cortisol were elevated in the acute phase compared to cubital levels (P < 0.05). Increased epinephrine and cortisol levels in the jugular vein blood may reflect a higher peripheral turnover. The observed changes in RAAS in the acute stroke phase are consistent with responses to increased blood pressure. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

High-level waste borosilicate glass: A compendium of corrosion characteristics. Volume 2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cunnane, J.C.; Bates, J.K.; Bradley, C.R.

The objective of this document is to summarize scientific information pertinent to evaluating the extent to which high-level waste borosilicate glass corrosion and the associated radionuclide release processes are understood for the range of environmental conditions to which waste glass may be exposed in service. Alteration processes occurring within the bulk of the glass (e.g., devitrification and radiation-induced changes) are discussed insofar as they affect glass corrosion.This document is organized into three volumes. Volumes I and II represent a tiered set of information intended for somewhat different audiences. Volume I is intended to provide an overview of waste glass corrosion,more » and Volume 11 is intended to provide additional experimental details on experimental factors that influence waste glass corrosion. Volume III contains a bibliography of glass corrosion studies, including studies that are not cited in Volumes I and II. Volume I is intended for managers, decision makers, and modelers, the combined set of Volumes I, II, and III is intended for scientists and engineers working in the field of high-level waste.« less

A Longitudinal Analysis of Stepfamily Relationship Quality and Adolescent Physical Health.

PubMed

Jensen, Todd M; Harris, Kathleen Mullan

2017-10-01

Approximately one third of youth are estimated to live with a biological parent and stepparent before reaching adulthood. Additional research is warranted whereby stepfamily processes are identified that drive variation in youth adjustment, particularly physical health. We examined stepfather-child, mother-child, and stepcouple relationship quality as predictors of levels and changes in adolescent physical health over time. We used a nationally representative sample of 1,233 adolescents living in biological mother-stepfather families from waves I (1994-1995) and II (1996) of the National Longitudinal Study of Adolescent to Adult Health. We incorporated measures of stepfather-child, mother-child, and stepcouple relationship quality, as well as adolescent reports of 10 physical health symptoms at waves I and II. Structural equation modeling was used to examine associations between wave I stepfamily relationships and adolescent physical symptoms at waves I and II. We used a zero-inflated negative binomial model to establish the validity of wave II adolescent physical symptoms as a predictor of an index of diagnosed chronic illnesses by wave IV (ages 26-32 years). Stepfather-child and mother-child relationship quality were negatively correlated with concurrent levels of adolescent physical symptoms. Stepfather-child relationship quality was negatively associated with change in adolescent physical symptoms over time. Adolescents with higher levels of physical symptoms at wave II were more likely to report chronic illnesses by adulthood. Stepfather-child relationship quality is a robust predictor of adolescent physical health throughout adolescence and is linked to chronic illness diagnoses in young adulthood. Future research should explore further the mechanisms that underlie this association. Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Dual processing model of medical decision-making.

PubMed

Djulbegovic, Benjamin; Hozo, Iztok; Beckstead, Jason; Tsalatsanis, Athanasios; Pauker, Stephen G

2012-09-03

Dual processing theory of human cognition postulates that reasoning and decision-making can be described as a function of both an intuitive, experiential, affective system (system I) and/or an analytical, deliberative (system II) processing system. To date no formal descriptive model of medical decision-making based on dual processing theory has been developed. Here we postulate such a model and apply it to a common clinical situation: whether treatment should be administered to the patient who may or may not have a disease. We developed a mathematical model in which we linked a recently proposed descriptive psychological model of cognition with the threshold model of medical decision-making and show how this approach can be used to better understand decision-making at the bedside and explain the widespread variation in treatments observed in clinical practice. We show that physician's beliefs about whether to treat at higher (lower) probability levels compared to the prescriptive therapeutic thresholds obtained via system II processing is moderated by system I and the ratio of benefit and harms as evaluated by both system I and II. Under some conditions, the system I decision maker's threshold may dramatically drop below the expected utility threshold derived by system II. This can explain the overtreatment often seen in the contemporary practice. The opposite can also occur as in the situations where empirical evidence is considered unreliable, or when cognitive processes of decision-makers are biased through recent experience: the threshold will increase relative to the normative threshold value derived via system II using expected utility threshold. This inclination for the higher diagnostic certainty may, in turn, explain undertreatment that is also documented in the current medical practice. We have developed the first dual processing model of medical decision-making that has potential to enrich the current medical decision-making field, which is still to the large extent dominated by expected utility theory. The model also provides a platform for reconciling two groups of competing dual processing theories (parallel competitive with default-interventionalist theories).

Post-stratification sampling in small area estimation (SAE) model for unemployment rate estimation by Bayes approach

NASA Astrophysics Data System (ADS)

Hanike, Yusrianti; Sadik, Kusman; Kurnia, Anang

2016-02-01

This research implemented unemployment rate in Indonesia that based on Poisson distribution. It would be estimated by modified the post-stratification and Small Area Estimation (SAE) model. Post-stratification was one of technique sampling that stratified after collected survey data. It's used when the survey data didn't serve for estimating the interest area. Interest area here was the education of unemployment which separated in seven category. The data was obtained by Labour Employment National survey (Sakernas) that's collected by company survey in Indonesia, BPS, Statistic Indonesia. This company served the national survey that gave too small sample for level district. Model of SAE was one of alternative to solved it. According the problem above, we combined this post-stratification sampling and SAE model. This research gave two main model of post-stratification sampling. Model I defined the category of education was the dummy variable and model II defined the category of education was the area random effect. Two model has problem wasn't complied by Poisson assumption. Using Poisson-Gamma model, model I has over dispersion problem was 1.23 solved to 0.91 chi square/df and model II has under dispersion problem was 0.35 solved to 0.94 chi square/df. Empirical Bayes was applied to estimate the proportion of every category education of unemployment. Using Bayesian Information Criteria (BIC), Model I has smaller mean square error (MSE) than model II.

Antioxidant-based therapies for angiotensin II-associated cardiovascular diseases

PubMed Central

Rosenbaugh, Erin G.; Savalia, Krupa K.; Manickam, Devika S.

2013-01-01

Cardiovascular diseases, including hypertension and heart failure, are associated with activation of the renin-angiotensin system (RAS) and increased circulating and tissue levels of ANG II, a primary effector peptide of the RAS. Through its actions on various cell types and organ systems, ANG II contributes to the pathogenesis of cardiovascular diseases by inducing cardiac and vascular hypertrophy, vasoconstriction, sodium and water reabsorption in kidneys, sympathoexcitation, and activation of the immune system. Cardiovascular research over the past 15–20 years has clearly implicated an important role for elevated levels of reactive oxygen species (ROS) in mediating these pathophysiological actions of ANG II. As such, the use of antioxidants, to reduce the elevated levels of ROS, as potential therapies for various ANG II-associated cardiovascular diseases has been intensely investigated. Although some antioxidant-based therapies have shown therapeutic impact in animal models of cardiovascular disease and in human patients, others have failed. In this review, we discuss the benefits and limitations of recent strategies, including gene therapy, dietary sources, low-molecular-weight free radical scavengers, polyethylene glycol conjugation, and nanomedicine-based technologies, which are designed to deliver antioxidants for the improved treatment of cardiovascular diseases. Although much work has been completed, additional research focusing on developing specific antioxidant molecules or proteins and identifying the ideal in vivo delivery system for such antioxidants is necessary before the use of antioxidant-based therapies for cardiovascular diseases become a clinical reality. PMID:23552499

Evidence for a link between sphingolipid metabolism and expression of CD1d and MHC-class II: monocytes from Gaucher disease patients as a model.

PubMed

Balreira, Andrea; Lacerda, Lúcia; Miranda, Clara Sá; Arosa, Fernando A

2005-06-01

Gaucher disease (GD) is an autosomal recessive inherited defect of the lysosomal enzyme glucocerebrosidase (GluCerase) that leads to glucosylceramide (GluCer) accumulation. We previously demonstrated the existence of imbalances in certain lymphocyte populations in GD patients. We now show that GluCerase-deficient monocytes from GD patients or monocytes from healthy subjects treated with conduritol-B-epoxide (CBE), an irreversible inhibitor of GluCerase activity, display high levels of surface expression of the lipid-binding molecule CD1d. GluCerase-deficient monocytes from GD patients also showed increased surface expression of major histocompatibility complex (MHC)-class II, but not of other lysosomal trafficking molecules, such as CD63 and MHC-class I. However, CD1d and MHC-class II mRNA levels were not increased. GluCerase-deficient monocytes from GD patients undergoing enzyme replacement therapy also exhibited increased levels of CD1d and MHC-class II and imbalances in the percentage of CD4+, CD8+, and Valpha24+ T cells. Interestingly, follow-up studies revealed that enzyme replacement therapy induced a decrease in MHC-class II expression and partial correction of the CD4+ T cell imbalances. These results reveal a new link between sphingolipid accumulation in monocytes and the expression of certain MHC molecules that may result in imbalances of regulatory T cell subsets. These immunological anomalies may contribute to the clinical heterogeneity in GD patients.

Establishment of a simple and quantitative immunospot assay for detecting anti-type II collagen antibody using an infrared fluorescence imaging system (IFIS).

PubMed

Ota, Shusuke; Kanazawa, Satoshi; Kobayashi, Masaaki; Otsuka, Takanobu; Okamoto, Takashi

2005-04-01

Antibodies to type II collagen (col II) have been detected in patients with rheumatoid arthritis and in animal models of collagen induced arthritis. Here, we describe a novel method to detect anti-col II antibodies using an immunospot assay with an infrared fluorescence imaging system. This method showed very high sensitivity and specificity, and was simple, with low background levels. It also showed higher reproducibility and linearity, with a dynamic range of approximately 500-fold, than the conventional immunospot assay with enhanced chemiluminescence detection. Using this method we were able to demonstrate the antibody affinity maturation process in mice immunized with col II. In these immunized mice, although cross-reactive antibodies reacting with other collagen species were detected in earlier stages of immunization, the titers of cross-reactive antibodies rapidly diminished after the antigen boost, concomitantly with the elevation of the anti-col II antibody. The method and its possible applications are discussed.

Association Between Helicopter vs Ground Emergency Medical Services and Survival for Adults With Major Trauma

PubMed Central

Galvagno, Samuel M.; Haut, Elliott R.; Zafar, S. Nabeel; Millin, Michael G.; Efron, David T.; Koenig, George J.; Baker, Susan P.; Bowman, Stephen M.; Pronovost, Peter J.; Haider, Adil H.

2012-01-01

Context Helicopter emergency medical services and their possible effect on outcomes for traumatically injured patients remain a subject of debate. Because helicopter services are a limited and expensive resource, a methodologically rigorous investigation of its effectiveness compared with ground emergency medical services is warranted. Objective To assess the association between the use of helicopter vs ground services and survival among adults with serious traumatic injuries. Design, Setting, and Participants Retrospective cohort study involving 223 475 patients older than 15 years, having an injury severity score higher than 15, and sustaining blunt or penetrating trauma that required transport to US level I or II trauma centers and whose data were recorded in the 2007–2009 versions of the American College of Surgeons National Trauma Data Bank. Interventions Transport by helicopter or ground emergency services to level I or level II trauma centers. Main Outcome Measures Survival to hospital discharge and discharge disposition. Results A total of 61 909 patients were transported by helicopter and 161 566 patients were transported by ground. Overall, 7813 patients (12.6%) transported by helicopter died compared with 17 775 patients (11%) transported by ground services. Before propensity score matching, patients transported by helicopter to level I and level II trauma centers had higher Injury Severity Scores. In the propensity score–matched multivariable regression model, for patients transported to level I trauma centers, helicopter transport was associated with an improved odds of survival compared with ground transport (odds ratio [OR], 1.16; 95% CI, 1.14–1.17; P<.001; absolute risk reduction [ARR], 1.5%). For patients transported to level II trauma centers, helicopter transport was associated with an improved odds of survival (OR, 1.15; 95% CI, 1.13–1.17; P < .001; ARR, 1.4%). A greater proportion (18.2%) of those transported to level I trauma centers by helicopter were discharged to rehabilitation compared with 12.7% transported by ground services (P < .001), and 9.3% transported by helicopter were discharged to intermediate facilities compared with 6.5% by ground services (P < .001). Fewer patients transported by helicopter left level II trauma centers against medical advice (0.5% vs 1.0%, P < .001). Conclusion Among patients with major trauma admitted to level I or level II trauma centers, transport by helicopter compared with ground services was associated with improved survival to hospital discharge after controlling for multiple known confounders. PMID:22511688

TRPM7 regulates angiotensin II-induced sinoatrial node fibrosis in sick sinus syndrome rats by mediating Smad signaling.

PubMed

Zhong, Hongbin; Wang, Tingjun; Lian, Guili; Xu, Changsheng; Wang, Huajun; Xie, Liangdi

2018-03-06

Sinoatrial node fibrosis is involved in the pathogenesis of sinus sick syndrome (SSS). Transient receptor potential (TRP) subfamily M member 7 (TRPM7) is implicated in cardiac fibrosis. However, the mechanisms underlying the regulation of sinoatrial node (SAN) fibrosis in SSS by TRPM7 remain unknown. The aim of this study was to investigate the role of angiotensin II (Ang II)/TRPM7/Smad pathway in the SAN fibrosis in rats with SSS. The rat SSS model was established with sodium hydroxide pinpoint pressing permeation. Forty-eight rats were randomly divided into six groups: normal control (ctrl), sham operation (sham), postoperative 1-, 2-, 3-, and 4-week SSS, respectively. The tissue explant culture method was used to culture cardiac fibroblasts (CFs) from rat SAN tissues. TRPM7 siRNA or encoding plasmids were used to knock down or overexpress TRPM7. Collagen (Col) distribution in SAN and atria was assessed using PASM-Masson staining. Ang II, Col I, and Col III levels in serum and tissues or in CFs were determined by ELISA. TRPM7, smad2 and p-smad2 levels were evaluated by real-time PCR, and/or western blot and immunohistochemistry. SAN and atria in rats of the SSS groups had more fibers and higher levels of Ang II, Col I and III than the sham rats. Similar findings were obtained for TRPM7 and pSmad2 expression. In vitro, Ang II promoted CFs collagen synthesis in a dose-dependent manner, and potentiated TRPM7 and p-Smad2 expression. TRPM7 depletion inhibited Ang II-induced p-Smad2 expression and collagen synthesis in CFs, whereas increased TRPM7 expression did the opposite. SAN fibrosis is regulated by the Ang II/TRPM7/Smad pathway in SSS, indicating that TRPM7 is a potential target for SAN fibrosis therapy in SSS.

Study of helium emissions from active solar regions

NASA Technical Reports Server (NTRS)

Kulander, J. L.

1973-01-01

A theoretical study is made of the visible and UV line radiation of He I atoms and He II ions from a plane-parallel model flare layer. Codes were developed for the solution of the statistically steady state equation for a 30 level He I - II - III model, and the line and continuum transport equations. These codes are described and documented in the report along with sample solutions. Optical depths and some line intensities are presented for a 1000 km thick layer. Solutions of the steady state equations are presented for electron temperatures 10,000 to 50,000 K and electron densities 10 to the 10th power to 10 to the 14th power/cu cm.

CHIMERA II - A real-time multiprocessing environment for sensor-based robot control

NASA Technical Reports Server (NTRS)

Stewart, David B.; Schmitz, Donald E.; Khosla, Pradeep K.

1989-01-01

A multiprocessing environment for a wide variety of sensor-based robot system, providing the flexibility, performance, and UNIX-compatible interface needed for fast development of real-time code is addressed. The requirements imposed on the design of a programming environment for sensor-based robotic control is outlined. The details of the current hardware configuration are presented, along with the details of the CHIMERA II software. Emphasis is placed on the kernel, low-level interboard communication, user interface, extended file system, user-definable and dynamically selectable real-time schedulers, remote process synchronization, and generalized interprocess communication. A possible implementation of a hierarchical control model, the NASA/NBS standard reference model for telerobot control system is demonstrated.

Synthesis and CV Studies of Dithiol-terminated Metal Terpyridine Complexes

NASA Technical Reports Server (NTRS)

Asano, Sylvia; Fan, Wendy; Ng, Hou-Tee; Han, Jie; Meyyappan, M.

2003-01-01

Transition metal coordination complexes possess unique electronic structures that should be a good model for studying electronic transport behavior at a molecular level. The discrete, multiple redox states, low redox potential and the superb ability to establish contact with other molecular and electronic components by coordination chemistry have made this a subject of investigation for their possible application as active electronic components in molecular devices. We present the synthesis and electrochemical characterization of 4'-thioacetylphenyl-2'2:6',2"-terpyridine iron(II) complex and compare it with a model bis-terpyridine iron(II) complex by cyclic voltammetry. With the use of different working electrodes, the behavior of these complexes show different electron transfer rates.

Consequences of land-cover misclassification in models of impervious surface

USGS Publications Warehouse

McMahon, G.

2007-01-01

Model estimates of impervious area as a function of landcover area may be biased and imprecise because of errors in the land-cover classification. This investigation of the effects of land-cover misclassification on impervious surface models that use National Land Cover Data (NLCD) evaluates the consequences of adjusting land-cover within a watershed to reflect uncertainty assessment information. Model validation results indicate that using error-matrix information to adjust land-cover values used in impervious surface models does not substantially improve impervious surface predictions. Validation results indicate that the resolution of the landcover data (Level I and Level II) is more important in predicting impervious surface accurately than whether the land-cover data have been adjusted using information in the error matrix. Level I NLCD, adjusted for land-cover misclassification, is preferable to the other land-cover options for use in models of impervious surface. This result is tied to the lower classification error rates for the Level I NLCD. ?? 2007 American Society for Photogrammetry and Remote Sensing.

Calpain-10 Activity Underlies Angiotensin II-Induced Aldosterone Production in an Adrenal Glomerulosa Cell Model

PubMed Central

Seremwe, Mutsa; Schnellmann, Rick G.

2015-01-01

Aldosterone is a steroid hormone important in the regulation of blood pressure. Aberrant production of aldosterone results in the development and progression of diseases including hypertension and congestive heart failure; therefore, a complete understanding of aldosterone production is important for developing more effective treatments. Angiotensin II (AngII) regulates steroidogenesis, in part through its ability to increase intracellular calcium levels. Calcium can activate calpains, proteases classified as typical or atypical based on the presence or absence of penta-EF-hands, which are involved in various cellular responses. We hypothesized that calpain, in particular calpain-10, is activated by AngII in adrenal glomerulosa cells and underlies aldosterone production. Our studies showed that pan-calpain inhibitors reduced AngII-induced aldosterone production in 2 adrenal glomerulosa cell models, primary bovine zona glomerulosa and human adrenocortical carcinoma (HAC15) cells, as well as CYP11B2 expression in the HAC15 cells. Although AngII induced calpain activation in these cells, typical calpain inhibitors had no effect on AngII-elicited aldosterone production, suggesting a lack of involvement of classical calpains in this process. However, an inhibitor of the atypical calpain, calpain-10, decreased AngII-induced aldosterone production. Consistent with this result, small interfering RNA (siRNA)-mediated knockdown of calpain-10 inhibited aldosterone production and CYP11B2 expression, whereas adenovirus-mediated overexpression of calpain-10 resulted in increased AngII-induced aldosterone production. Our results indicate that AngII-induced activation of calpain-10 in glomerulosa cells underlies aldosterone production and identify calpain-10 or its downstream pathways as potential targets for the development of drug therapies for the treatment of hypertension. PMID:25836666

Impact of angiotensin II on skeletal muscle metabolism and function in mice: contribution of IGF-1, Sirtuin-1 and PGC-1α.

PubMed

Kackstein, Katharina; Teren, Andrej; Matsumoto, Yasuharu; Mangner, Norman; Möbius-Winkler, Sven; Linke, Axel; Schuler, Gerhard; Punkt, Karla; Adams, Volker

2013-05-01

Activation of the renin-angiotensin-aldosterone system and increased levels of angiotensin II (Ang-II) occurs in numerous cardiovascular diseases such as chronic heart failure (CHF). Another hallmark in CHF is a reduced exercise tolerance with impaired skeletal muscle function. The aim of this study was to investigate in an animal model the impact of Ang-II on skeletal muscle function and concomitant molecular alterations. Mice were infused with Ang-II for 4 weeks. Subsequently, skeletal muscle function of the soleus muscle was assessed. Expression of selected proteins was quantified by qRT-PCR and Western blot. Infusion of Ang-II resulted in a 33% reduction of contractile force, despite a lack of changes in muscle weight. At the molecular level an increased expression of NAD(P)H oxidase and a reduced expression of Sirt1, PGC-1α and IGF-1 were noticed. No change was evident for the ubiquitin E3-ligases MuRF1 and MafBx and α-sarcomeric actin expression. Cytophotometrical analysis of the soleus muscle revealed a metabolic shift toward a glycolytic profile. This study provides direct evidence of Ang-II-mediated, metabolic deterioration of skeletal muscle function despite preserved muscle mass. One may speculate that the Ang-II-mediated loss of muscle force is due to an activation of NAD(P)H oxidase expression and a subsequent ROS-induced down regulation of IGF-1, PGC-1α and Sirt1. Copyright © 2012 Elsevier GmbH. All rights reserved.

Investigating Students' Mental Models and Knowledge Construction of Microscopic Friction. II. Implications for Curriculum Design and Development

ERIC Educational Resources Information Center

Corpuz, Edgar D.; Rebello, N. Sanjay

2011-01-01

Our previous research showed that students' mental models of friction at the atomic level are significantly influenced by their macroscopic ideas. For most students, friction is due to the meshing of bumps and valleys and rubbing of atoms. The aforementioned results motivated us to further investigate how students can be helped to improve their…

Selective adsorption of Pb(II), Cd(II), and Ni(II) ions from aqueous solution using chitosan-MAA nanoparticles.

PubMed

Heidari, Aghdas; Younesi, Habibollah; Mehraban, Zahra; Heikkinen, Harri

2013-10-01

Chitosan-MAA nanoparticles (CS-MAA) with an average size of 10-70 nm were prepared by polymerizing chitosan with methacrylic acid in aqueous solution. The physicochemical properties of nanoparticles were investigated using Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), dynamic light scattering (DLS) and nuclear magnetic resonance (NMR). The adsorption of Pb(II), Cd(II) and Ni(II) from aqueous solution on CS-MAA was studied in a batch system. The effects of the solution pH, initial metal concentration, contact time, and dosage of the adsorbent on the adsorption process were examined. The experimental data were analyzed using the pseudo-second-order kinetic equations and the Langmuir, Freundlich and Redlish-Peterson isotherms. The maximum adsorption capacity was 11.30, 1.84, and 0.87 mg/g for Pb(II), Cd(II) and Ni(II) ions, respectively, obtained by the Langmuir isotherm. However, the adsorption isotherm was better explained by the Freundlich rather than by the Langmuir model, as the high correlation coefficients (R(2)>0.99) were obtained at a higher confidence level. Copyright © 2013 Elsevier B.V. All rights reserved.

Multi-objective parametric optimization of Inertance type pulse tube refrigerator using response surface methodology and non-dominated sorting genetic algorithm

NASA Astrophysics Data System (ADS)

Rout, Sachindra K.; Choudhury, Balaji K.; Sahoo, Ranjit K.; Sarangi, Sunil K.

2014-07-01

The modeling and optimization of a Pulse Tube Refrigerator is a complicated task, due to its complexity of geometry and nature. The aim of the present work is to optimize the dimensions of pulse tube and regenerator for an Inertance-Type Pulse Tube Refrigerator (ITPTR) by using Response Surface Methodology (RSM) and Non-Sorted Genetic Algorithm II (NSGA II). The Box-Behnken design of the response surface methodology is used in an experimental matrix, with four factors and two levels. The diameter and length of the pulse tube and regenerator are chosen as the design variables where the rest of the dimensions and operating conditions of the ITPTR are constant. The required output responses are the cold head temperature (Tcold) and compressor input power (Wcomp). Computational fluid dynamics (CFD) have been used to model and solve the ITPTR. The CFD results agreed well with those of the previously published paper. Also using the results from the 1-D simulation, RSM is conducted to analyse the effect of the independent variables on the responses. To check the accuracy of the model, the analysis of variance (ANOVA) method has been used. Based on the proposed mathematical RSM models a multi-objective optimization study, using the Non-sorted genetic algorithm II (NSGA-II) has been performed to optimize the responses.

Outcome assessments in children with cerebral palsy, part II: discriminatory ability of outcome tools.

PubMed

Bagley, Anita M; Gorton, George; Oeffinger, Donna; Barnes, Douglas; Calmes, Janine; Nicholson, Diane; Damiano, Diane; Abel, Mark; Kryscio, Richard; Rogers, Sarah; Tylkowski, Chester

2007-03-01

Discriminatory ability of several pediatric outcome tools was assessed relative to Gross Motor Function Classification System (GMFCS) level in patients with cerebral palsy. Five hundred and sixty-two patients (400 with diplegia, 162 with hemiplegia; 339 males, 223 females; age range 4-18y, mean 11y 1mo [SD 3y 7mo]), classified as GMFCS Levels I to III, participated in this prospective multicenter, cross-sectional study. All tools were completed by parents and participants when appropriate. Effect size indices (ESIs) for parametric variables and odds ratios for non-parametric data quantified the magnitude of differences across GMFCS levels. Binary logistic regression models determined discrimination, and receiver operating characteristic curves addressed sensitivity and specificity. Between Levels I and II, the most discriminatory tools were Gross Motor Function Measure (GMFM-66), velocity, and WeeFIM Mobility. Between Levels II and III, the most discriminatory tools were GMFM Dimension E, Pediatric Functional Independence Measure (WeeFIM) Self-Care and Mobility, cadence, and Gillette Functional Assessment Questionnaire Question 1. Large ESIs were noted for Parent and Child reports of Pediatric Outcomes Data Collection Instrument (PODCI) Sports & Physical Function, Parent report of PODCI Global Function, GMFM Dimension E, and GMFM-66 across all GMFCS level comparisons. The least discriminatory tools were the Quality of Life and cognition measures; however, these are important in comprehensive assessments of treatment effects.

Atractylodes macrocephala Koidz stimulates intestinal epithelial cell migration through a polyamine dependent mechanism.

PubMed

Song, Hou-Pan; Li, Ru-Liu; Zhou, Chi; Cai, Xiong; Huang, Hui-Yong

2015-01-15

Atractylodes macrocephala Koidz (AMK), a valuable traditional Chinese herbal medicine, has been widely used in clinical practice for treating patients with disorders of the digestive system. AMK has shown noteworthy promoting effect on improving gastrointestinal function and immunity, which might represent a promising candidate for the treatment of intestinal mucosa injury. The aim of this study was to investigate the efficacy of AMK on intestinal mucosal restitution and the underlying mechanisms via intestinal epithelial (IEC-6) cell migration model. A cell migration model of IEC-6 cells was induced by a single-edge razor blade along the diameter of the cell layers in six-well polystyrene plates. After wounding, the cells were grown in control cultures and in cultures containing spermidine (5μM, SPD, reference drug), alpha-difluoromethylornithine (2.5mM, DFMO, polyamine inhibitor), AMK (50, 100, and 200mg/L), DFMO plus SPD and DFMO plus AMK for 12h. The polyamines content was detected by high-performance liquid chromatography (HPLC) with pre-column derivatization. The Rho mRNAs expression levels were assessed by Q-RT-PCR. The Rho and non-muscle myosin II proteins expression levels were analyzed by Western blot. The formation and distribution of non-muscle myosin II stress fibers were monitored with immunostaining techniques using specific antibodies and observed by confocal microscopy. Cell migration assay was carried out using inverted microscope and the Image-Pro Plus software. All of these indexes were used to evaluate the effectiveness of AMK. (1) Treatment with AMK caused significant increases in cellular polyamines content and Rho mRNAs and proteins expression levels, as compared to control group. Furthermore, AMK exposure increased non-muscle myosin II protein expression levels and formation of non-muscle myosin II stress fibers, and resulted in an acceleration of cell migration in IEC-6 cells. (2) Depletion of cellular polyamines by DFMO resulted in a decrease of cellular polyamines levels, Rho mRNAs and proteins expression, non-muscle myosin II protein formation and distribution, thereby inhibiting IEC-6 cell migration. AMK not only reversed the inhibitory effects of DFMO on the polyamines content, Rho mRNAs and proteins expression, non-muscle myosin II protein formation and distribution, but also restored cell migration to control levels. The results obtained from this study revealed that AMK significantly stimulates the migration of IEC-6 cells through a polyamine dependent mechanism, which could accelerate the healing of intestinal injury. These findings suggest the potential value of AMK in curing intestinal diseases characterized by injury and ineffective repair of the intestinal mucosa in clinical practice. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Inflammation and nerve injury induce expression of pancreatitis-associated protein-II in primary sensory neurons.

PubMed

He, Shao-Qiu; Yao, Jun-Ru; Zhang, Fang-Xiong; Wang, Qiong; Bao, Lan; Zhang, Xu

2010-04-26

Pancreatitis-associated protein (PAP)-I and -II, lectin-related secretory proteins, are members of the regenerating gene (Reg) family. Although expression of PAP-I was found in the dorsal root ganglion (DRG) neurons following peripheral nerve injury and cystitis, whether PAP-II could be expressed in DRG neurons in chronic pain models remains unclear. The present study shows an inflammation- and nerve injury-triggered expression of PAP-II in rat DRG neurons. In situ hybridization showed that only a few DRG neurons normally contained PAP-I and -II mRNAs. After peripheral inflammation, PAP-I and -II mRNAs were present in over half of small DRG neurons. Such an elevated expression of PAP-I and -II reached the peak level on the second day. Immunostaining showed that the expression of PAP-II was mostly increased in the isolectin B4-positive subset of small DRG neurons after inflammation. Furthermore, the expression of PAP-II was also induced in DRG neurons after peripheral nerve injury. Interestingly, PAP-II expression was shifted from small neurons on day 2 to large DRG neurons that expressed neuropeptide Y during the later post-injury days. These results suggest that PAP-II may play potential roles in the modulation of spinal sensory pathways in pathological pain states.

Confirmation of model-based dose selection for a Japanese phase III study of rivaroxaban in non-valvular atrial fibrillation patients.

PubMed

Kaneko, Masato; Tanigawa, Takahiko; Hashizume, Kensei; Kajikawa, Mariko; Tajiri, Masahiro; Mueck, Wolfgang

2013-01-01

This study was designed to confirm the appropriateness of the dose setting for a Japanese phase III study of rivaroxaban in patients with non-valvular atrial fibrillation (NVAF), which had been based on model simulation employing phase II study data. The previously developed mixed-effects pharmacokinetic/pharmacodynamic (PK-PD) model, which consisted of an oral one-compartment model parameterized in terms of clearance, volume and a first-order absorption rate, was rebuilt and optimized using the data for 597 subjects from the Japanese phase III study, J-ROCKET AF. A mixed-effects modeling technique in NONMEM was used to quantify both unexplained inter-individual variability and inter-occasion variability, which are random effect parameters. The final PK and PK-PD models were evaluated to identify influential covariates. The empirical Bayes estimates of AUC and C(max) from the final PK model were consistent with the simulated results from the Japanese phase II study. There was no clear relationship between individual estimated exposures and safety-related events, and the estimated exposure levels were consistent with the global phase III data. Therefore, it was concluded that the dose selected for the phase III study with Japanese NVAF patients by means of model simulation employing phase II study data had been appropriate from the PK-PD perspective.

Performance of the score systems Acute Physiology and Chronic Health Evaluation II and III at an interdisciplinary intensive care unit, after customization

PubMed Central

Markgraf, Rainer; Deutschinoff, Gerd; Pientka, Ludger; Scholten, Theo; Lorenz, Cristoph

2001-01-01

Background: Mortality predictions calculated using scoring scales are often not accurate in populations other than those in which the scales were developed because of differences in case-mix. The present study investigates the effect of first-level customization, using a logistic regression technique, on discrimination and calibration of the Acute Physiology and Chronic Health Evaluation (APACHE) II and III scales. Method: Probabilities of hospital death for patients were estimated by applying APACHE II and III and comparing these with observed outcomes. Using the split sample technique, a customized model to predict outcome was developed by logistic regression. The overall goodness-of-fit of the original and the customized models was assessed. Results: Of 3383 consecutive intensive care unit (ICU) admissions over 3 years, 2795 patients could be analyzed, and were split randomly into development and validation samples. The discriminative powers of APACHE II and III were unchanged by customization (areas under the receiver operating characteristic [ROC] curve 0.82 and 0.85, respectively). Hosmer-Lemeshow goodness-of-fit tests showed good calibration for APACHE II, but insufficient calibration for APACHE III. Customization improved calibration for both models, with a good fit for APACHE III as well. However, fit was different for various subgroups. Conclusions: The overall goodness-of-fit of APACHE III mortality prediction was improved significantly by customization, but uniformity of fit in different subgroups was not achieved. Therefore, application of the customized model provides no advantage, because differences in case-mix still limit comparisons of quality of care. PMID:11178223

Ni(II) removal from aqueous solutions using cone biomass of Thuja orientalis.

PubMed

Malkoc, Emine

2006-09-21

The biomass of terrestrial-plant materials has high removal capacities for a number of heavy metal ions. The Ni(II) biosorption capacity of the cone biomass of Thuja orientalis was studied in the batch mode. The biosorption equilibrium level was determined as a function of contact time, pH, temperature, agitation speed at several initial metal ion and adsorbent concentrations. The removal of Ni(II) from aqueous solutions increased with adsorbent concentration, temperature and agitation speed of the solution were increased. The biosorption process was very fast; 90% of biosorption occurred within 3 min and equilibrium was reached at around 7 min. It is found that the biosorption of Ni(II) on the cone biomass was correlated well (R2 > 0.99) with the Langmuir equation as compared to Freundlich, BET Temkin and D-R isotherm equation under the concentration range studied. According to Langmuir isotherm, the monolayer saturation capacity (Q(o)) is 12.42 mg g(-1). The pseudo-first-order, pseudo-second-order and intraparticle diffusion kinetic models were applied to test the experimental data for initial Ni(II) and cone biomass concentrations. The pseudo-second-order kinetic model provided the best correlation of the used experimental data compared to the pseudo-first-order and intraparticle diffusion kinetic models. The activation energy of biosorption (E(a)) was determined as 36.85 kJ mol(-1) using the Arrhenius equation. This study indicated that the cone biomass of T. orientalis can be used as an effective and environmentally friendly adsorbent for the treatment of Ni(II) containing aqueous solutions.

A model of attention-guided visual perception and recognition.

PubMed

Rybak, I A; Gusakova, V I; Golovan, A V; Podladchikova, L N; Shevtsova, N A

1998-08-01

A model of visual perception and recognition is described. The model contains: (i) a low-level subsystem which performs both a fovea-like transformation and detection of primary features (edges), and (ii) a high-level subsystem which includes separated 'what' (sensory memory) and 'where' (motor memory) structures. Image recognition occurs during the execution of a 'behavioral recognition program' formed during the primary viewing of the image. The recognition program contains both programmed attention window movements (stored in the motor memory) and predicted image fragments (stored in the sensory memory) for each consecutive fixation. The model shows the ability to recognize complex images (e.g. faces) invariantly with respect to shift, rotation and scale.

TOPICAL REVIEW: The shallow-to-deep instability of hydrogen and muonium in II VI and III V semiconductors

NASA Astrophysics Data System (ADS)

Cox, S. F. J.

2003-11-01

The structure and electrical activity of monatomic hydrogen defect centres are inferred from the spectroscopy and charge-state transitions of muonium, the light pseudo-isotope of hydrogen. Introductions are given to all these topics. Special attention is paid to the shallow-donor behaviour recently established in a number of II VI compounds and one III nitride. This contrasts with trapped-atom states suggestive of an acceptor function in other members of the II VI family as well as with the deep-level amphoteric behaviour which has long been known in the elemental group-IV semiconductors and certain III V compounds. The systematics of this remarkable shallow-to-deep instability are examined in terms of simple chemical considerations, as well as current theoretical and computational models. The muonium data appear to confirm predictions that the switch from shallow to deep behaviour is governed primarily by the depth of the conduction-band minimum below the vacuum continuum. The threshold electron affinity is around 3.5 eV, which compares favourably with computational estimates of a so-called pinning level for hydrogen (+/-) charge-state transitions of between -3 and -4.5 eV. A purely ionic model gives some intuitive understanding of this behaviour as well as the invariance of the threshold. Another current description applies equally to covalent materials and relates the threshold to the origin of the electrochemical scale. At the present level of approximation, zero-point energy corrections to the transition levels are small, so that muonium data should provide a reliable guide to the behaviour of hydrogen. Muonium spectroscopy proves to be more sensitive to the (0/+) donor level than to the (+/-) pinning level but, as a tool which does not rely on favourable hydrogen solubility, it looks set to test further predictions of these models in a large number of other materials, notably oxides. Certain candidate thin-film insulators and high-permittivity gate dielectrics appear to be uncomfortably close to conditions in which hydrogen impurity may cause electronic conduction.

Antiurolithic effect of olive oil in a mouse model of ethylene glycol-induced urolithiasis.

PubMed

Alenzi, Mohammed; Rahiman, Shaik; Tantry, Bilal Ahmad

2017-05-01

At present, commercially available antiurolithic drugs have more adverse effects than potential therapeutic or preventive effects with chronic use. With this in mind, the present study was designed to assess the antiurolithic effect of olive oil in a mouse model of ethylene glycol (EG)-induced urolithiasis. Adult albino mice were divided into 6 groups. Group I was fed the vehicle only. Group II was supplemented with 0.75% EG alone in drinking water during the experimental period to initiate deposition of calcium oxalate in kidneys, which leads to urolithiasis in animals. Groups III (olive oil control group) through V were fed olive oil orally at various doses during the experimental period. Group VI received cystone (750 mg/kg). Groups IV-VI additionally received 0.75% EG in drinking water ad libitum. SPSS ver.17.0 was used for statistical analysis. The study results showed significantly higher levels of serum urea, uric acid, and creatinine (p<0.05) in group II than in groups III-VI and I. Administration of olive oil at different doses restored the elevated serum parameters in groups IV and V compared with group II. Urine and kidney calcium, oxalate, and phosphate levels in groups IV-VI were significantly lower (p<0.05) than in animals with EG-induced urolithiasis (group II). Group V mice showed a significant restoration effect on serum as well as urine and kidney parameters compared with group II. Supplementation with olive oil (1.7 mL/kg body weight) reduced and prevented the growth of urinary stones, possibly by inhibiting renal tubular membrane damage due to peroxidative stress induced by hyperoxaluria.

Omega-3 fatty acid supplementation decreases DNA damage in brain of rats subjected to a chemically induced chronic model of Tyrosinemia type II.

PubMed

Carvalho-Silva, Milena; Gomes, Lara M; Scaini, Giselli; Rebelo, Joyce; Damiani, Adriani P; Pereira, Maiara; Andrade, Vanessa M; Gava, Fernanda F; Valvassori, Samira S; Schuck, Patricia F; Ferreira, Gustavo C; Streck, Emilio L

2017-08-01

Tyrosinemia type II is an inborn error of metabolism caused by a mutation in a gene encoding the enzyme tyrosine aminotransferase leading to an accumulation of tyrosine in the body, and is associated with neurologic and development difficulties in numerous patients. Because the accumulation of tyrosine promotes oxidative stress and DNA damage, the main aim of this study was to investigate the possible antioxidant and neuroprotective effects of omega-3 treatment in a chemically-induced model of Tyrosinemia type II in hippocampus, striatum and cerebral cortex of rats. Our results showed chronic administration of L-tyrosine increased the frequency and the index of DNA damage, as well as the 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in the hippocampus, striatum and cerebral cortex. Moreover, omega-3 fatty acid treatment totally prevented increased DNA damage in the striatum and hippocampus, and partially prevented in the cerebral cortex, whereas the increase in 8-OHdG levels was totally prevented by omega-3 fatty acid treatment in hippocampus, striatum and cerebral cortex. In conclusion, the present study demonstrated that the main accumulating metabolite in Tyrosinemia type II induce DNA damage in hippocampus, striatum and cerebral cortex, possibly mediated by free radical production, and the supplementation with omega-3 fatty acids was able to prevent this damage, suggesting that could be involved in the prevention of oxidative damage to DNA in this disease. Thus, omega-3 fatty acids supplementation to Tyrosinemia type II patients may represent a new therapeutic approach and a possible adjuvant to the curren t treatment of this disease.

Red Storm usage model :Version 1.12.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jefferson, Karen L.; Sturtevant, Judith E.

Red Storm is an Advanced Simulation and Computing (ASC) funded massively parallel supercomputer located at Sandia National Laboratories (SNL). The Red Storm Usage Model (RSUM) documents the capabilities and the environment provided for the FY05 Tri-Lab Level II Limited Availability Red Storm User Environment Milestone and the FY05 SNL Level II Limited Availability Red Storm Platform Milestone. This document describes specific capabilities, tools, and procedures to support both local and remote users. The model is focused on the needs of the ASC user working in the secure computing environments at Los Alamos National Laboratory (LANL), Lawrence Livermore National Laboratory (LLNL),more » and SNL. Additionally, the Red Storm Usage Model maps the provided capabilities to the Tri-Lab ASC Computing Environment (ACE) requirements. The ACE requirements reflect the high performance computing requirements for the ASC community and have been updated in FY05 to reflect the community's needs. For each section of the RSUM, Appendix I maps the ACE requirements to the Limited Availability User Environment capabilities and includes a description of ACE requirements met and those requirements that are not met in that particular section. The Red Storm Usage Model, along with the ACE mappings, has been issued and vetted throughout the Tri-Lab community.« less

Population pharmacodynamic model of bicarbonate response to acetazolamide in mechanically ventilated chronic obstructive pulmonary disease patients

PubMed Central

2011-01-01

Introduction Acetazolamide is commonly given to chronic obstructive pulmonary disease (COPD) patients with metabolic alkalosis. Little is known of the pharmacodynamics of acetazolamide in the critically ill. We undertook the pharmacodynamic modeling of bicarbonate response to acetazolamide in COPD patients under mechanical ventilation. Methods This observational, retrospective study included 68 invasively ventilated COPD patients who received one or multiple doses of 250 or 500 mg of acetazolamide during the weaning period. Among the 68 investigated patients, 207 time-serum bicarbonate observations were available for analysis. Population pharmacodynamics was modeled using a nonlinear mixedeffect model. The main covariates of interest were baseline demographic data, Simplified Acute Physiology Score II (SAPS II) at ICU admission, cause of respiratory failure, co-prescription of drugs interfering with the acid-base equilibrium, and serum concentrations of protein, creatinin, potassium and chloride. The effect of acetazolamide on serum bicarbonate levels at different doses and in different clinical conditions was subsequently simulated in silico. Results The main covariates interacting with acetazolamide pharmacodynamics were SAPS II at ICU admission (P = 0.01), serum chloride (P < 0.001) and concomitant administration of corticosteroids (P = 0.02). Co-administration of furosemide significantly decreased bicarbonate elimination. Acetazolamide induced a decrease in serum bicarbonate with a dose-response relationship. The amount of acetazolamide inducing 50% of the putative maximum effect was 117 ± 21 mg. According to our model, an acetazolamide dosage > 500 mg twice daily is required to reduce serum bicarbonate concentrations > 5 mmol/L in the presence of high serum chloride levels or coadministration of systemic corticosteroids or furosemide. Conclusions This study identified several covariates that influenced acetazolamide pharmacodynamics and could allow a better individualization of acetazolamide dosing when treating COPD patients with metabolic alkalosis. PMID:21917139

Treatment of liver injuries at level I and level II centers in a multi-institutional metropolitan trauma system. The Midwest Trauma Society Liver Trauma Study Group.

PubMed

Helling, T S; Morse, G; McNabney, W K; Beggs, C W; Behrends, S H; Hutton-Rotert, K; Johnson, D J; Reardon, T M; Roling, J; Scheve, J; Shinkle, J; Webb, J M; Watkins, M

1997-06-01

The development of trauma systems and trauma centers has had a major impact on the fate of the critically injured patient. However, some have suggested that care may be compromised if too many trauma centers are designated for a given area. As of 1987, the state of Missouri had designated six adult trauma centers, two Level I and four Level II, for the metropolitan Kansas City, Mo, area, serving a population of approximately 1 million people. To determine whether care was comparable between the Level I and II centers, we conducted a concurrent evaluation of the fate of patients with a sentinel injury, hepatic trauma, over a 6-year period (1987-1992) who were treated at these six trauma centers. All patients during the 6-year study period who suffered liver trauma and who survived long enough to be evaluated by computerized tomography or celiotomy were entered into the study. Patients with central nervous system trauma were excluded from analysis. Information concerning mechanism of injury, RTS, Injury Severity Score (ISS), presence of shock, liver injury scoring, mode of treatment, mortality, and length of stay were recorded on abstract forms for analysis. Care was evaluated by mortality, time to the operating room (OR), and intensive care unit (ICU) and hospital length of stay. Over the 6-year period 300 patients with non-central nervous system liver trauma were seen. Level I centers cared for 195 patients and Level II centers cared for 105. There was no difference in mean ISS or ISS > 25 between Level I and II centers. Fifty-five (28%) patients arrived in shock at Level I centers and 24 (23%) at Level II centers. Forty-eight patients (16%) died. Thirty-two (16%) died at Level I centers, and 16 (15%) died at Level II centers. Twenty of 55 patients (36%) in shock died at Level I centers, and 11 of 24 (46%) died at Level II centers (p = 0.428). Forty-three patients (22%) had liver scaling scores of IV-VI at Level I centers, and 10 (10%) had similar scores at Level II centers (p < 0.01). With liver scores IV-VI, 22 of 43 (51%) died at Level I centers and 10 of 14 (71%) died at Level II centers (p = 0.184). There was no difference in mean time or in delays beyond 1 hour to the OR for those patients in shock between Level I and II centers. There was a longer ICU stay at Level II centers (5.0 +/- 8.3 vs. 2.8 +/- 8.4 days, p = 0.04). This difference was confined to penetrating injuries. There was no difference in hospital length of stay. In a metropolitan trauma system, when Level I and II centers were compared for their ability to care for victims of hepatic trauma, there was no discernible difference in care rendered with respect to severity of injury, mortality, delays to the OR, or hospital length of stay. It was observed that more severe liver injuries were seen at Level I centers, but this did not seem to significantly affect care at Level II centers. There was a longer ICU stay observed at Level II centers owing to penetrating injuries, possibly because there were fewer penetrating injuries treated at these facilities. Although the bulk of patients were seen at Level I centers, care throughout the system was equivalent.

Modelling CEC variations versus structural iron reduction levels in dioctahedral smectites. Existing approaches, new data and model refinements.

PubMed

Hadi, Jebril; Tournassat, Christophe; Ignatiadis, Ioannis; Greneche, Jean Marc; Charlet, Laurent

2013-10-01

A model was developed to describe how the 2:1 layer excess negative charge induced by the reduction of Fe(III) to Fe(II) by sodium dithionite buffered with citrate-bicarbonate is balanced and applied to nontronites. This model is based on new experimental data and extends structural interpretation introduced by a former model [36-38]. The 2:1 layer negative charge increase due to Fe(III) to Fe(II) reduction is balanced by an excess adsorption of cations in the clay interlayers and a specific sorption of H(+) from solution. Prevalence of one compensating mechanism over the other is related to the growing lattice distortion induced by structural Fe(III) reduction. At low reduction levels, cation adsorption dominates and some of the incorporated protons react with structural OH groups, leading to a dehydroxylation of the structure. Starting from a moderate reduction level, other structural changes occur, leading to a reorganisation of the octahedral and tetrahedral lattice: migration or release of cations, intense dehydroxylation and bonding of protons to undersaturated oxygen atoms. Experimental data highlight some particular properties of ferruginous smectites regarding chemical reduction. Contrary to previous assumptions, the negative layer charge of nontronites does not only increase towards a plateau value upon reduction. A peak is observed in the reduction domain. After this peak, the negative layer charge decreases upon extended reduction (>30%). The decrease is so dramatic that the layer charge of highly reduced nontronites can fall below that of its fully oxidised counterpart. Furthermore, the presence of a large amount of tetrahedral Fe seems to promote intense clay structural changes and Fe reducibility. Our newly acquired data clearly show that models currently available in the literature cannot be applied to the whole reduction range of clay structural Fe. Moreover, changes in the model normalising procedure clearly demonstrate that the investigated low tetrahedral bearing nontronites (SWa-1, GAN and NAu-1) all exhibit the same behaviour at low reduction levels. Consequently, we restricted our model to the case of moderate reduction (<30%) in low tetrahedral Fe-bearing nontronites. Our adapted model provides the relative amounts of Na(+) (p) and H(+) (ni) cations incorporated in the structure as a function of the amount of Fe reduction. Two equations enable the investigated systems to be described: p=m/(1+Kr·ω·mrel) and ni=Kr·ω·m·mrel/(1+Kr·ω·mrel); where m is the Fe(II) content, mrel, the reduction level (m/mtot), ω, the cation exchange capacity (CEC, and Kr, an empirical constant specific to the system. Copyright © 2013 Elsevier Inc. All rights reserved.

Development of a novel walkability index for London, United Kingdom: cross-sectional application to the Whitehall II Study.

PubMed

Stockton, Jemima C; Duke-Williams, Oliver; Stamatakis, Emmanuel; Mindell, Jennifer S; Brunner, Eric J; Shelton, Nicola J

2016-05-18

Physical activity is essential for health; walking is the easiest way to incorporate activity into everyday life. Previous studies report positive associations between neighbourhood walkability and walking but most focused on cities in North America and Australasia. Urban form with respect to street connectivity, residential density and land use mix-common components of walkability indices-differs in European cities. The objective of this study was to develop a walkability index for London and test the index using walking data from the Whitehall II Study. A neighbourhood walkability index for London was constructed, comprising factors associated with walking behaviours: residential dwelling density, street connectivity and land use mix. Three models were produced that differed in the land uses included. Neighbourhoods were operationalised at three levels of administrative geography: (i) 21,140 output areas, (ii) 633 wards and (iii) 33 local authorities. A neighbourhood walkability score was assigned to each London-dwelling Whitehall II Study participant (2003-04, N = 3020, mean ± SD age = 61.0 years ± 6.0) based on residential postcode. The effect of changing the model specification and the units of enumeration on spatial variation in walkability was examined. There was a radial decay in walkability from the centre to the periphery of London. There was high inter-model correlation in walkability scores for any given neighbourhood operationalisation (0.92-0.98), and moderate-high correlation between neighbourhood operationalisations for any given model (0.39-0.70). After adjustment for individual level factors and area deprivation, individuals in the most walkable neighbourhoods operationalised as wards were more likely to walk >6 h/week (OR = 1.4; 95 % CI: 1.1-1.9) than those in the least walkable. Walkability was associated with walking time in adults. This walkability index could help urban planners identify and design neighbourhoods in London with characteristics more supportive of walking, thereby promoting public health.

Application of Six Sigma Model to Evaluate the Analytical Quality of Four HbA1c Analyzers.

PubMed

Maesa, Jos Eacute M; Fern Aacute Ndez-Riejos, Patricia; S Aacute Nchez-Mora, Catalina; Toro-Crespo, Mar Iacute A De; Gonz Aacute Lez-Rodriguez, Concepci Oacute N

2017-01-01

The Six Sigma Model is a global quality management system applicable to the determination of glycated hemoglobin (HbA1c). In addition, this model can ensure the three characteristics influencing the patient risk: the correct performance of the analytical method with low inaccuracy and bias, the quality control strategy used by the laboratory, and the necessary quality of the analyte. The aim of this study is to use the Six Sigma Model for evaluating quality criteria in the determination of glycated hemoglobin HbA1c and its application to assess four different HbA1c analyzers. Four HbA1c analyzers were evaluated: HA-8180V®, D-100®, G8®, and Variant II Turbo®. For 20 consecutive days, two levels of quality control (high and low) provided by the manufacturers were measured in each of the instruments. Imprecision (CV), bias, and Sigma values (σ) were calculated with the data obtained and a method decision chart was developed considering a range of quality requirements (allowable total error, TEa). For a TEa = 3%, HA-8180V = 1.54 σ, D-100 = 1.63 σ, G8 = 2.20 σ, and Variant II Turbo = -0.08 σ. For a TEa = 4%, HA-8180V = 2.34 σ, D-100 = 2.32 σ, G8 = 3.74 σ, and Variant II Turbo = 0.16 σ. For a TEa = 10%, HA8180V = 7.12 σ, D-100 = 6.46 σ, G8 = 13.0 σ, and Variant II Turbo = 1.56 σ. Applying the Stockholm consensus and its subsequent Milan review to the results: the maximum level in quality requirements for HbA1c is an allowable total error (TEa) = 3%, G8 is located in region 2 σ (2.20), which is a poor result, and HA-8180V and D-100 are both in region 1 σ (1.54 and 1.63, respectively), which is an unacceptable analytical performance.

Comparative study on kinetic adsorption of Cu(II), Cd(II) and Ni(II) ions from aqueous solutions using activated sludge and dried sludge

NASA Astrophysics Data System (ADS)

Ong, Soon-An; Toorisaka, Eiichi; Hirata, Makoto; Hano, Tadashi

2013-03-01

The adsorption of Cu(II), Cd(II) and Ni(II) ions from aqueous solutions by activated sludge and dried sludge was investigated under laboratory conditions to assess its potential in removing metal ions. The adsorption behavior of metal ions onto activated sludge and dried sludge was analyzed with Weber-Morris intra-particle diffusion model, Lagergren first-order model and pseudo second-order model. The rate constant of intra-particle diffusion on activated sludge and dried sludge increased in the sequence of Cu(II) > Ni(II) > Cd(II). According to the regression coefficients, it was observed that the kinetic adsorption data can fit better by the pseudo second-order model compared to the first-order Lagergren model with R 2 > 0.997. The adsorption capacities of metal ions onto activated sludge and dried sludge followed the sequence Ni(II) ≈ Cu(II) > Cd(II) and Cu(II) > Ni(II) > Cd(II).

Mercaptoacetamide-based class II HDAC inhibitor lowers Aβ levels and improves learning and memory in a mouse model of Alzheimer's disease.

PubMed

Sung, You Me; Lee, Taehee; Yoon, Hyejin; DiBattista, Amanda Marie; Song, Jung Min; Sohn, Yoojin; Moffat, Emily Isabella; Turner, R Scott; Jung, Mira; Kim, Jungsu; Hoe, Hyang-Sook

2013-01-01

Histone deacetylase inhibitors (HDACIs) alter gene expression epigenetically by interfering with the normal functions of HDAC. Given their ability to decrease Aβ levels, HDACIs are a potential treatment for Alzheimer's disease (AD). However, it is unclear how HDACIs alter Aβ levels. We developed two novel HDAC inhibitors with improved pharmacological properties, such as a longer half-life and greater penetration of the blood-brain barrier: mercaptoacetamide-based class II HDACI (coded as W2) and hydroxamide-based class I and IIHDACI (coded as I2) and investigated how they affect Aβ levels and cognition. HDACI W2 decreased Aβ40 and Aβ42 in vitro. HDACI I2 also decreased Aβ40, but not Aβ42. We systematically examined the molecular mechanisms by which HDACIs W2 and I2 can decrease Aβ levels. HDACI W2 decreased gene expression of γ-secretase components and increased the Aβ degradation enzyme Mmp2. Similarly, HDACI I2 decreased expression of β- and γ-secretase components and increased mRNA levels of Aβ degradation enzymes. HDACI W2 also significantly decreased Aβ levels and rescued learning and memory deficits in aged hAPP 3xTg AD mice. Furthermore, we found that the novel HDACI W2 decreased tau phosphorylation at Thr181, an effect previously unknown for HDACIs. Collectively, these data suggest that class II HDACls may serve as a novel therapeutic strategy for AD. Copyright © 2012 Elsevier Inc. All rights reserved.

Keratins Are Altered in Intestinal Disease-Related Stress Responses

PubMed Central

Helenius, Terhi O.; Antman, Cecilia A.; Asghar, Muhammad Nadeem; Nyström, Joel H.; Toivola, Diana M.

2016-01-01

Keratin (K) intermediate filaments can be divided into type I/type II proteins, which form obligate heteropolymers. Epithelial cells express type I-type II keratin pairs, and K7, K8 (type II) and K18, K19 and K20 (type I) are the primary keratins found in the single-layered intestinal epithelium. Keratins are upregulated during stress in liver, pancreas, lung, kidney and skin, however, little is known about their dynamics in the intestinal stress response. Here, keratin mRNA, protein and phosphorylation levels were studied in response to murine colonic stresses modeling human conditions, and in colorectal cancer HT29 cells. Dextran sulphate sodium (DSS)-colitis was used as a model for intestinal inflammatory stress, which elicited a strong upregulation and widened crypt distribution of K7 and K20. K8 levels were slightly downregulated in acute DSS, while stress-responsive K8 serine-74 phosphorylation (K8 pS74) was increased. By eliminating colonic microflora using antibiotics, K8 pS74 in proliferating cells was significantly increased, together with an upregulation of K8 and K19. In the aging mouse colon, most colonic keratins were upregulated. In vitro, K8, K19 and K8 pS74 levels were increased in response to lipopolysaccharide (LPS)-induced inflammation in HT29 cells. In conclusion, intestinal keratins are differentially and dynamically upregulated and post-translationally modified during stress and recovery. PMID:27626448

Adaptation and Latent Structure of the Swahili Version of Beck Depression Inventory-II in a Low Literacy Population in the Context of HIV

PubMed Central

Abubakar, Amina; Kalu, Raphael Birya; Katana, Khamis; Kabunda, Beatrice; Hassan, Amin S.; Newton, Charles R.; Van de Vijver, Fons

2016-01-01

Objective We set out to adapt the Beck Depression Inventory (BDI)-II in Kenya and examine its factorial structure. Methods In the first phase we carried out in-depth interviews involving 29 adult members of the community to elicit their understanding of depression and identify aspects of the BDI-II that required adaptation. In the second phase, a modified version of BDI-II was administered to 221 adults randomly selected from the community to allow for the evaluation of its psychometric properties. In the third phase of the study we evaluated the discriminative validity of BDI-11 by comparing a randomly chosen community sample (n = 29) with caregivers of adolescents affected by HIV (n = 77). Results A considerable overlap between the BDI symptoms and those generated in the interviews was observed. Relevant idioms and symptoms such as ‘thinking too much’ and ‘Kuchoka moyo (having a tired heart)’ were identified. The administration of the BDI had to be modified to make it suitable for the low literacy levels of our participants. Fit indices for several models (one factorial, two-factor model and a three factor model) were all within acceptable range. Evidence indicated that while multidimensional models could be fitted, the strong correlations between the factors implied that a single factor model may be the best suited solution (alpha [0.89], and a significant correlation with locally identified items [r = 0.51]) confirmed the good psychometric properties of the adapted BDI-II. No evidence was found to support the hypothesis that somatization was more prevalent. Lastly, caregivers of HIV affected adolescents had significantly higher scores compared to adults randomly selected from the community F(1, 121) = 23.31, p < .001 indicating the discriminative validity of the adapted BDI = II. Conclusions With an adapted administration procedure, the BDI-II provides an adequate measure of depressive symptoms which can be used alongside other measures for proper diagnosis in a low literacy population. PMID:27258530

Tidal-Fluvial and Estuarine Processes in the Lower Columbia River: II. Water Level Models, Floodplain Wetland Inundation, and System Zones

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jay, David A.; Borde, Amy B.; Diefenderfer, Heida L.

Spatially varying water-level regimes are a factor controlling estuarine and tidal-fluvial wetland vegetation patterns. As described in Part I, water levels in the Lower Columbia River and estuary (LCRE) are influenced by tides, river flow, hydropower operations, and coastal processes. In Part II, regression models based on tidal theory are used to quantify the role of these processes in determining water levels in the mainstem river and floodplain wetlands, and to provide 21-year inundation hindcasts. Analyses are conducted at 19 LCRE mainstem channel stations and 23 tidally exposed floodplain wetland stations. Sum exceedance values (SEVs) are used to compare wetlandmore » hydrologic regimes at different locations on the river floodplain. A new predictive tool is introduced and validated, the potential SEV (pSEV), which can reduce the need for extensive new data collection in wetland restoration planning. Models of water levels and inundation frequency distinguish four zones encompassing eight reaches. The system zones are the wave- and current-dominated Entrance to river kilometer (rkm) 5; the Estuary (rkm-5 to 87), comprised of a lower reach with salinity, the energy minimum (where the turbidity maximum normally occurs), and an upper estuary reach without salinity; the Tidal River (rkm-87 to 229), with lower, middle, and upper reaches in which river flow becomes increasingly dominant over tides in determining water levels; and the steep and weakly tidal Cascade (rkm-229 to 234) immediately downstream from Bonneville Dam. The same zonation is seen in the water levels of floodplain stations, with considerable modification of tidal properties. The system zones and reaches defined here reflect geological features and their boundaries are congruent with five wetland vegetation zones« less

Gestational exposure to elevated testosterone levels induces hypertension via heightened vascular angiotensin II type 1 receptor signaling in rats.

PubMed

Chinnathambi, Vijayakumar; More, Amar S; Hankins, Gary D; Yallampalli, Chandra; Sathishkumar, Kunju

2014-07-01

Pre-eclampsia is a life-threatening pregnancy disorder whose pathogenesis remains unclear. Plasma testosterone levels are elevated in pregnant women with pre-eclampsia and polycystic ovary syndrome, who often develop gestational hypertension. We tested the hypothesis that increased gestational testosterone levels induce hypertension via heightened angiotensin II signaling. Pregnant Sprague-Dawley rats were injected with vehicle or testosterone propionate from Gestational Day 15 to 19 to induce a 2-fold increase in plasma testosterone levels, similar to levels observed in clinical conditions like pre-eclampsia. A subset of rats in these two groups was given losartan, an angiotensin II type 1 receptor antagonist by gavage during the course of testosterone exposure. Blood pressure levels were assessed through a carotid arterial catheter and endothelium-independent vascular reactivity through wire myography. Angiotensin II levels in plasma and angiotensin II type 1 receptor expression in mesenteric arteries were also examined. Blood pressure levels were significantly higher on Gestational Day 20 in testosterone-treated dams than in controls. Treatment with losartan during the course of testosterone exposure significantly attenuated testosterone-induced hypertension. Plasma angiotensin II levels were not significantly different between control and testosterone-treated rats; however, elevated testosterone levels significantly increased angiotensin II type 1 receptor protein levels in the mesenteric arteries. In testosterone-treated rats, mesenteric artery contractile responses to angiotensin II were significantly greater, whereas contractile responses to K(+) depolarization and phenylephrine were unaffected. The results demonstrate that elevated testosterone during gestation induces hypertension in pregnant rats via heightened angiotensin II type 1 receptor-mediated signaling, providing a molecular mechanism linking elevated maternal testosterone levels with gestational hypertension. © 2014 by the Society for the Study of Reproduction, Inc.

Gestational Exposure to Elevated Testosterone Levels Induces Hypertension via Heightened Vascular Angiotensin II Type 1 Receptor Signaling in Rats1

PubMed Central

Chinnathambi, Vijayakumar; More, Amar S.; Hankins, Gary D.; Yallampalli, Chandra; Sathishkumar, Kunju

2014-01-01

ABSTRACT Pre-eclampsia is a life-threatening pregnancy disorder whose pathogenesis remains unclear. Plasma testosterone levels are elevated in pregnant women with pre-eclampsia and polycystic ovary syndrome, who often develop gestational hypertension. We tested the hypothesis that increased gestational testosterone levels induce hypertension via heightened angiotensin II signaling. Pregnant Sprague-Dawley rats were injected with vehicle or testosterone propionate from Gestational Day 15 to 19 to induce a 2-fold increase in plasma testosterone levels, similar to levels observed in clinical conditions like pre-eclampsia. A subset of rats in these two groups was given losartan, an angiotensin II type 1 receptor antagonist by gavage during the course of testosterone exposure. Blood pressure levels were assessed through a carotid arterial catheter and endothelium-independent vascular reactivity through wire myography. Angiotensin II levels in plasma and angiotensin II type 1 receptor expression in mesenteric arteries were also examined. Blood pressure levels were significantly higher on Gestational Day 20 in testosterone-treated dams than in controls. Treatment with losartan during the course of testosterone exposure significantly attenuated testosterone-induced hypertension. Plasma angiotensin II levels were not significantly different between control and testosterone-treated rats; however, elevated testosterone levels significantly increased angiotensin II type 1 receptor protein levels in the mesenteric arteries. In testosterone-treated rats, mesenteric artery contractile responses to angiotensin II were significantly greater, whereas contractile responses to K+ depolarization and phenylephrine were unaffected. The results demonstrate that elevated testosterone during gestation induces hypertension in pregnant rats via heightened angiotensin II type 1 receptor-mediated signaling, providing a molecular mechanism linking elevated maternal testosterone levels with gestational hypertension. PMID:24855104

Near-Infrared Spectra of Type Ia Supernovae

NASA Technical Reports Server (NTRS)

Marion, G. H.; Hoeflich, P.; Vacca, W. D.; Wheeler, J. C.

2003-01-01

We report near-infrared (NIR) spectroscopic observations of 12 'branch-normal' Type Ia supernovae (SNe Ia) that cover the wavelength region from 0.8 to 2.5 microns. Our sample more than doubles the number of SNe Ia with published NIR spectra within 3 weeks of maximum light. The epochs of observation range from 13 days before maximum light to 18 days after maximum light. A detailed model for a Type Ia supernovae is used to identify spectral features. The Doppler shifts of lines are measured to obtain the velocity and thus the radial distribution of elements. The NIR is an extremely useful tool to probe the chemical structure in the layers of SNe Ia ejecta. This wavelength region is optimal for examining certain products of the SNe Ia explosion that may be blended or obscured in other spectral regions. We identify spectral features from Mg II, Ca II, Si II, Fe II, Co II, Ni II, and possibly Mn II. We find no indications for hydrogen, helium, or carbon in the spectra. The spectral features reveal important clues about the physical characteristics of SNe Ia. We use the features to derive upper limits for the amount of unburned matter, to identify the transition regions from explosive carbon to oxygen burning and from partial to complete silicon burning, and to estimate the level of mixing during and after the explosion. Elements synthesized in the outer layers during the explosion appear to remain in distinct layers. That provides strong evidence for the presence of a detonation phase during the explosion as it occurs in delayed detonation or merger models. Mg II velocities are found to exceed 11,000 - 15,000 km/s, depending on the individual SNe Ia. That result suggests that burning during the explosion reaches the outermost layers of the progenitor and limits the amount of unburned material to less than 10% of the mass of the progenitor. Small residuals of unburned material are predicted by delayed detonation models but are inconsistent with pure deflagration or merger models. Differences in the spectra of the individual SNe Ia demonstrate the variety of these events.

MANUFACTURING PROCESS FUNCTIONS--I. AN ALTERNATIVE MODEL AND ITS COMPARISON WITH EXISTING FUNCTIONS (AND)II. SELECTION OF TRAINEES AND CONTROL OF THEIR PROGRESS.

ERIC Educational Resources Information Center

GLOVER, J.H.

THE CHIEF OBJECTIVE OF THIS STUDY OF SPEED-SKILL ACQUISITION WAS TO FIND A MATHEMATICAL MODEL CAPABLE OF SIMPLE GRAPHIC INTERPRETATION FOR INDUSTRIAL TRAINING AND PRODUCTION SCHEDULING AT THE SHOP FLOOR LEVEL. STUDIES OF MIDDLE SKILL DEVELOPMENT IN MACHINE AND VEHICLE ASSEMBLY, AIRCRAFT PRODUCTION, SPOOLMAKING AND THE MACHINING OF PARTS CONFIRMED…

Comprehensive Analysis Modeling of Small-Scale UAS Rotors

NASA Technical Reports Server (NTRS)

Russell, Carl R.; Sekula, Martin K.

2017-01-01

Multicopter unmanned aircraft systems (UAS), or drones, have continued their explosive growth in recent years. With this growth comes demand for increased performance as the limits of existing technologies are reached. In order to better design multicopter UAS aircraft, better performance prediction tools are needed. This paper presents the results of a study aimed at using the rotorcraft comprehensive analysis code CAMRAD II to model a multicopter UAS rotor in hover. Parametric studies were performed to determine the level of fidelity needed in the analysis code inputs to achieve results that match test data. Overall, the results show that CAMRAD II is well suited to model small-scale UAS rotors in hover. This paper presents the results of the parametric studies as well as recommendations for the application of comprehensive analysis codes to multicopter UAS rotors.

Azilsartan ameliorates apoptosis of dopaminergic neurons and rescues characteristic parkinsonian behaviors in a rat model of Parkinson's disease.

PubMed

Gao, Qing; Ou, Zhou; Jiang, Teng; Tian, You-Yong; Zhou, Jun-Shan; Wu, Liang; Shi, Jian-Quan; Zhang, Ying-Dong

2017-04-11

Loss of dopaminergic neurons within the substantia nigra (SN) is a pathological hallmark of Parkinson's disease (PD), which leads to the onset of motor symptoms. Previously, our in vitro studies revealed that Angiotensin II (Ang II) induced apoptosis of dopaminergic neurons through its type 1 receptor (AT1R), but these findings needed to be confirmed via animal experiments. Here, using a rotenone-induced rat model of PD, we observed an overactivation of Ang II/AT1R axis in the SN, since Ang II level and AT1R expression were markedly increased. Furthermore, we provided in vivo evidence that Ang II directly elicited apoptosis of dopaminergic neurons via activation of AT1R in the SN of rats. More importantly, we showed for the first time that oral administration of azilsartan, a newly developed AT1R blocker approved by the U.S. Food and Drug Administration for hypertension treatment, rescued the apoptosis of dopaminergic neurons and relieved the characteristic parkinsonian symptoms in PD rats. These results support the application of AT1R blockers in PD therapy, and strengthen the notion that many therapeutic agents may possess pleiotropic action in addition to their main applications.

Azilsartan ameliorates apoptosis of dopaminergic neurons and rescues characteristic parkinsonian behaviors in a rat model of Parkinson’s disease

PubMed Central

Gao, Qing; Ou, Zhou; Jiang, Teng; Tian, You-Yong; Zhou, Jun-Shan; Wu, Liang; Shi, Jian-Quan; Zhang, Ying-Dong

2017-01-01

Loss of dopaminergic neurons within the substantia nigra (SN) is a pathological hallmark of Parkinsons disease (PD), which leads to the onset of motor symptoms. Previously, our in vitro studies revealed that Angiotensin II (Ang II) induced apoptosis of dopaminergic neurons through its type 1 receptor (AT1R), but these findings needed to be confirmed via animal experiments. Here, using a rotenone-induced rat model of PD, we observed an overactivation of Ang II/AT1R axis in the SN, since Ang II level and AT1R expression were markedly increased. Furthermore, we provided in vivo evidence that Ang II directly elicited apoptosis of dopaminergic neurons via activation of AT1R in the SN of rats. More importantly, we showed for the first time that oral administration of azilsartan, a newly developed AT1R blocker approved by the U.S. Food and Drug Administration for hypertension treatment, rescued the apoptosis of dopaminergic neurons and relieved the characteristic parkinsonian symptoms in PD rats. These results support the application of AT1R blockers in PD therapy, and strengthen the notion that many therapeutic agents may possess pleiotropic action in addition to their main applications. PMID:28445961

The self as a mediator between personality and adjustment.

PubMed

Graziano, W G; Jensen-Campbell, L A; Finch, J F

1997-08-01

The self can be conceptualized as a mediating agent that translates personality into situated goal-directed activities and adaptation. This research used a level-of-analysis approach to link personality dimensions (Level I) to self-systems (Level II) and to teacher ratings of adjustment in African American, Mexican American, and European American students (N = 317). The authors hypothesized that links among aspects of self-esteem and teacher ratings of adjustment would be domain specific, and those links to dimensions of the 5-factor model would reflects the domain specificity. Structural equation modeling corroborated hypotheses about domain specificity in links between adjustment and 5-factor dimensions. Results were discussed in terms of levels of analysis for personality structure, personality development, and age-related adaptations to social contexts.

Recombinant adeno-associated virus vector carrying the thrombomodulin lectin-like domain for the treatment of abdominal aortic aneurysm.

PubMed

Lai, Chao-Han; Wang, Kuan-Chieh; Kuo, Cheng-Hsiang; Lee, Fang-Tzu; Cheng, Tsung-Lin; Chang, Bi-Ing; Yang, Yu-Jen; Shi, Guey-Yueh; Wu, Hua-Lin

2017-07-01

Thrombomodulin (TM), through its lectin-like domain (TMD1), sequesters proinflammatory high-mobility group box 1 (HMGB1) to prevent it from engaging the receptor for advanced glycation end product (RAGE) that sustains inflammation and tissue damage. Our previous study demonstrated that short-term treatment with recombinant TM containing all the extracellular domains (i.e., rTMD123) inhibits HMGB1-RAGE signaling and confers protection against CaCl 2 -induced AAA formation. In this study, we attempted to further optimize TM domains, as a potential therapeutic agent for AAA, using the recombinant adeno-associated virus (AAV) vector. The therapeutic effects of recombinant TMD1 (rTMD1) and recombinant AAV vectors carrying the lectin-like domain of TM (rAAV-TMD1) were evaluated in the CaCl 2 -induced AAA model and angiotensin II-infused AAA model, respectively. In the CaCl 2 -induced model, treatment with rTMD1 suppressed the tissue levels of HMGB1 and RAGE, macrophage accumulation, elastin destruction and AAA formation, and the effects were comparable to a mole-equivalent dosage of rTMD123. In the angiotensin II-infused model, a single intravenous injection of rAAV-TMD1 (10 11 genome copies), which resulted in a persistently high serum level of TMD1 for at least 12 weeks, effectively attenuated AAA formation with suppression of HMGB1 and RAGE levels and inhibition of proinflammatory cytokine production, macrophage accumulation, matrix metalloproteinase activities and oxidative stress in the aortic wall. These findings corroborate the therapeutic potential of the TM lectin-like domain in AAA. The attenuation of angiotensin II-infused AAA by one-time delivery of rAAV-TMD1 provides a proof-of-concept validation of its application as potential gene therapy for aneurysm development. Copyright © 2017 Elsevier B.V. All rights reserved.

Benchmarking Atomic Data for Astrophysics: Be-like Ions between B II and Ne VII

NASA Astrophysics Data System (ADS)

Wang, Kai; Chen, Zhan Bin; Zhang, Chun Yu; Si, Ran; Jönsson, Per; Hartman, Henrik; Gu, Ming Feng; Chen, Chong Yang; Yan, Jun

2018-02-01

Large-scale self-consistent multiconfiguration Dirac–Hartree–Fock and relativistic configuration interaction calculations are reported for the n≤slant 6 levels in Be-like ions from B II to Ne VII. Effects from electron correlation are taken into account by means of large expansions in terms of a basis of configuration state functions, and a complete and accurate data set of excitation energies; lifetimes; wavelengths; electric dipole, magnetic dipole, electric quadrupole, and magnetic quadrupole line strengths; transition rates; and oscillator strengths for these levels is provided for each ion. Comparisons are made with available experimental and theoretical results. The uncertainty of excitation energies is assessed to be 0.01% on average, which makes it possible to find and rule out misidentifications and aid new line identifications involving high-lying levels in astrophysical spectra. The complete data set is also useful for modeling and diagnosing astrophysical plasmas.

Design Definition Study Report. Full Crew Interaction Simulator-Laboratory Model (FCIS-LM) (Device X17B7). Volume II. Requirements.

DTIC Science & Technology

1978-06-01

stimulate at-least three levels of crew function. At the most complex level, visual cues are used to discriminate the presence or activities of...limited to motion on- set cues washed out at subliminal levels.. Because of the cues they provide the driver, gunner, and commander, and the dis...motion, i.e.,which physiological receptors are affected, how they function,and how they may be stimulated by a simulator motion system. I Motion is

Enhanced Photodynamic Therapy by Reduced Levels of Intracellular Glutathione Obtained By Employing a Nano-MOF with CuII as the Active Center.

PubMed

Zhang, Wei; Lu, Jun; Gao, Xiaonan; Li, Ping; Zhang, Wen; Ma, Yu; Wang, Hui; Tang, Bo

2018-02-16

In photodynamic therapy (PDT), the level of reactive oxygen species (ROS) produced in the cell directly determines the therapeutic effect. Improvement in ROS concentration can be realized by reducing the glutathione (GSH) level or increasing the amount of photosensitizer. However, excessive amounts photosensitizer may cause side effects. Therefore, the development of photosensitizers that reduce GSH levels through synergistically improving ROS concentration in order to strengthen the efficacy of PDT for tumor is important. We report a nano-metal-organic framework (Cu II -metalated nano-MOF {CuL-[AlOH] 2 } n (MOF-2, H 6 L=mesotetrakis(4-carboxylphenyl)porphyrin)) based on Cu II as the active center for PDT. This MOF-2 is readily taken up by breast cancer cells, and high levels of ROS are generated under light irradiation. Meanwhile, intracellular GSH is considerably decreased owing to absorption on MOF-2; this synergistically increases ROS concentration and accelerates apoptosis, thereby enhancing the effect of PDT. Notably, based on the direct adsorption of GSH, MOF-2 showed a comparable effect with the commercial antitumor drug camptothecin in a mouse breast cancer model. This work provides strong evidence for MOF-2 as a promising new PDT candidate and anticancer drug. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Condyle and mandibular bone change after unilateral condylar neck fracture in growing rats.

PubMed

Hu, Y; Yang, H-f; Li, S; Chen, J-z; Luo, Y-w; Yang, C

2012-08-01

Unilateral fracture of the condylar neck in immature subjects might lead to mandible asymmetry and condyle remodelling. A rat model was used to investigate mandibular deviation and condylar remodelling associated with condyle fracture. 72 4-week-old male rats were randomly divided into three groups: an experimental group (unilateral transverse condylar fracture induced surgically), a sham operation group (surgical exposure but no fracture), and a non-operative control group (no operation). The rats were killed at intervals up to 9weeks after surgery, and outcomes were assessed using various measures of mandible deviation, histological and X-ray observation, and immunohistochemical measures of expression levels of connective tissue growth factor (CTGF) and type II collagen (Col II). The fracture led to the degeneration of mandibular size, associated with atrophy of fractured condylar process. Progressive remodelling of cartilage and increasing expression levels of CTGF and Col II were found. The authors conclude that condylar fracture can lead to asymmetries in mandible and condyle remodelling and expression of CTGF and Col II in condylar cartilage on both the ipsilateral and the contralateral sides. Copyright © 2012 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

A VLA radio-continuum survey of a sample of confirmed and marginal barium stars

NASA Technical Reports Server (NTRS)

Drake, Stephen A.; Simon, Theodore; Linsky, Jeffrey L.

1987-01-01

Results are reported from a 6-cm VLA survey of five confirmed Ba II stars and eight mild Ba II stars, undertaken to search for evidence of gyrosynchrotron emission or thermal emission from the primary star's wind that is enhanced or photoionized by a white dwarf companion. Of these 13 stars, only Beta UMi was detected as a possible radio source at a flux level of 0.11 mJy (3sigma). The 6-cm radio luminosities (L6) of the other stars are as small as log L6 less than or equal to 14.0 and are an order of magnitude or more lower than the average levels found in RS CVn systems, but are consistent with the L6 upper limits previously found for stars of spectral type similar to the Ba II stars and normal elemental abundances. The upper limit to the radio luminosity for the possible mild Ba II star 56 Peg, when combined with its previously known X-ray luminosity, may provide useful constraints on the various models that have been proposed for this interesting object, once its orbital period is known.

Mitochondrial proteomic profiling reveals increased carbonic anhydrase II in aging and neurodegeneration.

PubMed

Pollard, Amelia; Shephard, Freya; Freed, James; Liddell, Susan; Chakrabarti, Lisa

2016-10-10

Carbonic anhydrase inhibitors are used to treat glaucoma and cancers. Carbonic anhydrases perform a crucial role in the conversion of carbon dioxide and water into bicarbonate and protons. However, there is little information about carbonic anhydrase isoforms during the process of ageing. Mitochondrial dysfunction is implicit in ageing brain and muscle. We have interrogated isolated mitochondrial fractions from young adult and middle aged mouse brain and skeletal muscle. We find an increase of tissue specific carbonic anhydrases in mitochondria from middle-aged brain and skeletal muscle. Mitochondrial carbonic anhydrase II was measured in the Purkinje cell degeneration ( pcd 5J ) mouse model. In pcd 5J we find mitochondrial carbonic anhydrase II is also elevated in brain from young adults undergoing a process of neurodegeneration. We show C.elegans exposed to carbonic anhydrase II have a dose related shorter lifespan suggesting that high CAII levels are in themselves life limiting. We show for the first time that the mitochondrial content of brain and skeletal tissue are exposed to significantly higher levels of active carbonic anhydrases as early as in middle-age. Carbonic anhydrases associated with mitochondria could be targeted to specifically modulate age related impairments and disease.

Identification of new fluorescence processes in the UV spectra of cool stars from new energy levels of Fe II and Cr II

NASA Technical Reports Server (NTRS)

Johansson, Sveneric; Carpenter, Kenneth G.

1988-01-01

Two fluorescence processes operating in atmospheres of cool stars, symbiotic stars, and the Sun are presented. Two emission lines, at 1347.03 and 1360.17 A, are identified as fluorescence lines of Cr II and Fe II. The lines are due to transitions from highly excited levels, which are populated radiatively by the hydrogen Lyman alpha line due to accidental wavelength coincidences. Three energy levels, one in Cr II and two in Fe II, are reported.

Ground-level falls: 9-year cumulative experience in a regionalized trauma system

PubMed Central

Cade, Angela; King, Brad; Berne, John; Fernandez, Luis; Norwood, Scott

2012-01-01

Ground-level falls (GLFs) are the leading cause of nonfatal hospitalized injuries in the US. We hypothesized that risk-adjusted mortality would not vary between levels of trauma center verification if regional triage functioned appropriately. Data were collected from our regional trauma registry for the years 2001 through 2009. A multilevel mixed-effects logistic regression model was developed to compare risk-adjusted mortality rates by trauma center level and by year. GLF patients numbered 8202 over 9 years with 2.1% mortality. Mean age was 74.5 years and mean probability of death was 0.021 (95% confidence interval [CI], 0.020–0.021). The level I center–treated patients had the highest probability of death (0.033) compared to levels II and III/IV patients (0.023 and 0.018, respectively; P < 0.001), with the highest mortality (6.0%, 3.1%, and 1.1% for levels I, II, and III/IV; P < 0.001). The adjusted odds ratio of mortality was lowest at the level I center (0.71; 95% CI, 0.56–0.91), while no difference existed between level II (1.17; 95% CI, 0.90–1.51) and level III/IV centers (1.22; 95% CI, 0.90–1.66). The 95% CIs for risk-adjusted mortality by year overlapped the 1.0 reference line for each year from 2002 to 2009. In conclusion, regional risk-adjusted mortality for GLF has varied little since 2002. More study is warranted to understand the lower risk-adjusted GLF mortality at the level I center for this growing patient population. PMID:22275774

Amyloidosis in transgenic mice expressing murine amyloidogenic apolipoprotein A-II (Apoa2c).

PubMed

Ge, Fengxia; Yao, Junjie; Fu, Xiaoying; Guo, Zhanjun; Yan, Jingmin; Zhang, Beiru; Zhang, Huanyu; Tomozawa, Hiroshi; Miyazaki, Junichi; Sawashita, Jinko; Mori, Masayuki; Higuchi, Keiichi

2007-07-01

In mice, apolipoprotein A-II (apoA-II) self-associates to form amyloid fibrils (AApoAII) in an age-associated manner. We postulated that the two most important factors in apoA-II amyloidosis are the Apoa2(c) allele, which codes for the amyloidogenic protein APOA2C (Gln5, Ala38) and transmission of amyloid fibrils. To characterize further the contribution of the Apoa2(c) allele to amyloidogenesis and improve detection of amyloidogenic materials, we established transgenic mice that overexpress APOA2C protein under the cytomegalovirus (CMV) immediate early gene (CMV-IE) enhancer/chicken beta promoter. Compared to transgene negative (Tg(-/-)) mice that express apoA-II protein mainly in the liver, mice homozygous (Tg(+/+)) and heterozygous (Tg(+/-)) for the transgene express a high level of apoA-II protein in many tissues. They also have higher plasma concentrations of apoA-II, higher ratios of ApoA-II/apolipoprotein A-I (ApoA-I) and higher concentrations of high-density lipoprotein (HDL) cholesterol. Following injection of AApoAII fibrils into Tg(+/+) mice, amyloid deposition was observed in the testis, liver, kidney, heart, lungs, spleen, tongue, stomach and intestine but not in the brain. In Tg(+/+) mice, but not in Tg(-/-) mice, amyloid deposition was induced by injection of less than 10(-8) mug AApoAII fibrils. Furthermore, deposition in Tg(+/+) mice occurred more rapidly and to a greater extent than in Tg(-/-) mice. These studies indicate that increased levels of APOA2C protein lead to earlier and greater amyloid deposition and enhanced sensitivity to the transmission of amyloid fibrils in transgenic mice. This transgenic mouse model should prove valuable for studies of amyloidosis.

Inhibition of endoplasmic reticulum stress by intermedin1-53 attenuates angiotensin II-induced abdominal aortic aneurysm in ApoE KO Mice.

PubMed

Ni, Xian-Qiang; Lu, Wei-Wei; Zhang, Jin-Sheng; Zhu, Qing; Ren, Jin-Ling; Yu, Yan-Rong; Liu, Xiu-Ying; Wang, Xiu-Jie; Han, Mei; Jing, Qing; Du, Jie; Tang, Chao-Shu; Qi, Yong-Fen

2018-06-26

Endoplasmic reticulum stress (ERS) is involved in the development of abdominal aortic aneurysm (AAA). Since bioactive peptide intermedin (IMD)1-53 protects against AAA formation, here we investigated whether IMD1-53 attenuates AAA by inhibiting ERS. AAA model was induced by angiotensin II (AngII) in ApoE KO mouse background. AngII-treated mouse aortas showed increased ERS gene transcription of caspase12, eukaryotic translation initiation factor 2a (eIf2a) and activating transcription factor 4(ATF4).The protein level of ERS marker glucose regulated protein 94(GRP94), ATF4 and C/EBP homologous protein 10(CHOP) was also up-regulated by AngII. Increased ERS levels were accompanied by severe VSMC apoptosis in human AAA aorta. In vivo administration of IMD1-53 greatly reduced AngII-induced AAA and abrogated the activation of ERS. To determine whether IMD inhibited AAA by ameliorating ERS, we used 2 non-selective ERS inhibitors phenyl butyrate (4-PBA) and taurine (TAU). Similar to IMD, PBA, and TAU significantly reduced the incidence of AAA and AAA-related pathological disorders. In vitro, AngII infusion up-regulated CHOP, caspase12 expression and led to VSMC apoptosis. IMD siRNA aggravated the CHOP, caspase12-mediated VSMC apoptosis, which was abolished by ATF4 silencing. IMD infusion promoted the phosphorylation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) in aortas in ApoE KO mice, and the AMPK inhibitor compound C abolished the protective effect of IMD on VSMC ERS and apoptosis induced by AngII. In conclusion, IMD may protect against AAA formation by inhibiting ERS via activating AMPK phosphorylation.

Combination of Acute Physiology and Chronic Health Evaluation II score, early lactate area, and N-terminal prohormone of brain natriuretic peptide levels as a predictor of mortality in geriatric patients with septic shock.

PubMed

Wang, Hao; Li, Zhong; Yin, Mei; Chen, Xiao-Mei; Ding, Shi-Fang; Li, Chen; Zhai, Qian; Li, Yuan; Liu, Han; Wu, Da-Wei

2015-04-01

Given the high mortality rates in elderly patients with septic shock, the early recognition of patients at greatest risk of death is crucial for the implementation of early intervention strategies. Serum lactate and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels are often elevated in elderly patients with septic shock and are therefore important biomarkers of metabolic and cardiac dysfunction. We hypothesized that a risk stratification system that incorporates the Acute Physiology and Chronic Health Evaluation (APACHE) II score and lactate and NT-proBNP biomarkers would better predict mortality in geriatric patients with septic shock than the APACHE II score alone. A single-center prospective study was conducted from January 2012 to December 2013 in a 30-bed intensive care unit of a triservice hospital. The lactate area score was defined as the sum of the area under the curve of serial lactate levels measured during the 24 hours following admission divided by 24. The NT-proBNP score was assigned based on NT-proBNP levels measured at admission. The combined score was calculated by adding the lactate area and NT-proBNP scores to the APACHE II score. Multivariate logistic regression analyses and receiver operating characteristic curves were used to evaluate which variables and scoring systems served as the best predictors of mortality in elderly septic patients. A total of 115 patients with septic shock were included in the study. The overall 28-day mortality rate was 67.0%. When compared to survivors, nonsurvivors had significantly higher lactate area scores, NT-proBNP scores, APACHE II scores, and combined scores. In the multivariate regression model, the combined score, lactate area score, and mechanical ventilation were independent risk factors associated with death. Receiver operating characteristic curves indicated that the combined score had significantly greater predictive power when compared to the APACHE II score or the NT-proBNP score (P < .05). A combined score that incorporates the APACHE II score with early lactate area and NT-proBNP levels is a useful method for risk stratification in geriatric patients with septic shock. Copyright © 2014 Elsevier Inc. All rights reserved.

Modeling joint restoration strategies for interdependent infrastructure systems.

PubMed

Zhang, Chao; Kong, Jingjing; Simonovic, Slobodan P

2018-01-01

Life in the modern world depends on multiple critical services provided by infrastructure systems which are interdependent at multiple levels. To effectively respond to infrastructure failures, this paper proposes a model for developing optimal joint restoration strategy for interdependent infrastructure systems following a disruptive event. First, models for (i) describing structure of interdependent infrastructure system and (ii) their interaction process, are presented. Both models are considering the failure types, infrastructure operating rules and interdependencies among systems. Second, an optimization model for determining an optimal joint restoration strategy at infrastructure component level by minimizing the economic loss from the infrastructure failures, is proposed. The utility of the model is illustrated using a case study of electric-water systems. Results show that a small number of failed infrastructure components can trigger high level failures in interdependent systems; the optimal joint restoration strategy varies with failure occurrence time. The proposed models can help decision makers to understand the mechanisms of infrastructure interactions and search for optimal joint restoration strategy, which can significantly enhance safety of infrastructure systems.

Thoracic Injury Risk Curves for Rib Deflections of the SID-IIs Build Level D.

PubMed

Irwin, Annette L; Crawford, Greg; Gorman, David; Wang, Sikui; Mertz, Harold J

2016-11-01

Injury risk curves for SID-IIs thorax and abdomen rib deflections proposed for future NCAP side impact evaluations were developed from tests conducted with the SID-IIs FRG. Since the floating rib guide is known to reduce the magnitude of the peak rib deflections, injury risk curves developed from SID-IIs FRG data are not appropriate for use with SID-IIs build level D. PMHS injury data from three series of sled tests and one series of whole-body drop tests are paired with thoracic rib deflections from equivalent tests with SID-IIs build level D. Where possible, the rib deflections of SID-IIs build level D were scaled to adjust for differences in impact velocity between the PMHS and SID-IIs tests. Injury risk curves developed by the Mertz-Weber modified median rank method are presented and compared to risk curves developed by other parametric and non-parametric methods.

Improved prediction models for PCC pavement performance-related specifications, volume II : PaveSpec 3.0 user's guide.

DOT National Transportation Integrated Search

2001-12-01

The current performance-related specifications (PRS) methodology has been under development by the Federal : Highway~Administration (FI-IWA) for several years and has now reached a level at which it can be implemented by : State highway agencies. PRS...

Intellectual Development and Interaction Effectiveness with DISCOVER.

ERIC Educational Resources Information Center

Roselle, Bruce E.; Hummel, Thomas J.

1988-01-01

Used Knefelkamp's and Slepitza's (1976) model of career-related intellectual development to investigate how students at different levels of development think as they interact with a computer-assisted career guidance system, DISCOVER II, which comprises modules on understanding interests, values, and abilities; searching for occupations based on…

Chronic production of angiotensin IV in the brain leads to hypertension that is reversible with an angiotensin II AT1 receptor antagonist.

PubMed

Lochard, Nadheige; Thibault, Gaétan; Silversides, David W; Touyz, Rhian M; Reudelhuber, Timothy L

2004-06-11

Angiotensin IV (Ang IV) is a metabolite of the potent vasoconstrictor angiotensin II (Ang II). Because specific binding sites for this peptide have been reported in numerous tissues including the brain, it has been suggested that a specific Ang IV receptor (AT4) might exist. Bolus injection of Ang IV in brain ventricles has been implicated in learning, memory, and localized vasodilatation. However, the functions of Ang IV in a physiological context are still unknown. In this study, we generated a transgenic (TG) mouse model that chronically releases Ang IV peptide specifically in the brain. TG mice were found to be hypertensive by the tail-cuff method as compared with control littermates. Treatment with the angiotensin-converting enzyme inhibitor captopril had no effect on blood pressure, but surprisingly treatment with the Ang II AT1 receptor antagonist candesartan normalized the blood pressure despite the fact that the levels of Ang IV in the brains of TG mice were only 4-fold elevated over the normal endogenous level of Ang peptides. Calcium mobilization assays performed on cultured CHO cells chronically transfected with the AT1 receptor confirm that low-dose Ang IV can mobilize calcium via the AT1 receptor only in the presence of Ang II, consistent with an allosteric mechanism. These results suggest that chronic elevation of Ang IV in the brain can induce hypertension that can be treated with angiotensin II AT1 receptor antagonists.

Antioxidant vitamins C, E and coenzyme Q10 vs Dexamethasone: comparisons of their effects in pulmonary contusion model

PubMed Central

2012-01-01

Background The goal of our study is to evaluate the effects of antioxidant vitamins (vitamin C and E), Coenzyme Q10 (CoQ10) and dexamethasone (Dxm) in experimental rat models with pulmonary contusion (PC). Methods Rats were randomly divided into six groups. Except for the control, all subgroups had a moderate pulmonary contusion. Animals in the group I and group II received intraperitoneal saline, group III received 10mg.kg-1 CoQ10 group IV received 100mg.kg-1 vitamin C, group V received 150mg.kg-1 vitamin E, and group VI received 10mg.kg-1 Dxm. Blood gas analysis, serum nitric oxide (NO) and malondialdehyde (MDA) levels as well as superoxide dismutase (SOD) activity assays, bronchoalveolar lavage (BAL) fluid and histopathological examination were performed. Results Administration of CoQ10 resulted in a significant increase in PaO2 values compared with the group I (p = 0.004). Levels of plasma MDA in group II were significantly higher than those in the group I (p = 0.01). Early administration of vitamin C, CoQ10, and Dxm significantly decreased the levels of MDA (p = 0.01). Lung contusion due to blunt trauma significantly decreased SOD activities in rat lung tissue compared with group I (p = 0.01). SOD levels were significantly elevated in animals treated with CoQ10, Vitamin E, or Dxm compared with group II (p = 0.01). Conclusions In our study, CoQ10, vitamin C, vitamin E and Dxm had a protective effect on the biochemical and histopathological outcome of PC after experimental blunt thorax trauma. PMID:23013526

Copper transport mediated by nanocarrier systems in a blood-brain barrier in vitro model.

PubMed

Fehse, Susanne; Nowag, Sabrina; Quadir, Mohiuddin; Kim, Kwang Sik; Haag, Rainer; Multhaup, Gerd

2014-05-12

Copper (Cu) is a cofactor of various metalloenzymes and has a role in neurodegenerative diseases with disturbed Cu homeostasis, for example, in Alzheimer's disease (AD) and Menkes disease. To address Cu imbalances, we synthesized two different dendritic nanoparticles (NP) for the transport of Cu(II) ions across the blood-brain barrier (BBB). The synthesized NPs show low toxicity and high water solubility and can stabilize high amounts of Cu(II). The Cu(II)-laden NPs crossed cellular membranes and increased the cellular Cu level. A human brain microvascular endothelial cell (HBMEC) model was established to investigate the permeability of the NPs through the BBB. By comparing the permeability × surface area product (PSe) of reference substances with those of NPs, we observed that NPs crossed the BBB model two times more effectively than (14)C-sucrose and sodium fluorescein (NaFl) and up to 60× better than Evans Blue labeled albumin (EBA). Our results clearly indicate that NPs cross the BBB model effectively. Furthermore, Cu was shielded by the NPs, which decreased the Cu toxicity. The novel design of the core-shell NP enabled the complexation of Cu(II) in the outer shell and therefore facilitated the pH-dependent release of Cu in contrast to core-multishell NPs, where the Cu(II) ions are encapsulated in the core. This allows a release of Cu into the cytoplasm. In addition, by using a cellular detection system based on a metal response element with green fluorescent protein (MRE-GFP), we demonstrated that Cu could also be released intracellularly from NPs and is accessible for biological processes. Our results indicate that NPs are potential candidates to rebalance metal-ion homeostasis in disease conditions affecting brain and neuronal systems.

Hydroxysafflor yellow A cardioprotection in ischemia-reperfusion (I/R) injury mainly via Akt/hexokinase II independent of ERK/GSK-3β pathway.

PubMed

Min, Jia; Wei, Cui

2017-03-01

Hydroxysafflor yellow A (HSYA) is the main active component of Carthamus tinctorius L which has been used for hundreds of years in Chinese folk medicine in the treatment cardiovascular disease. This study was designed to investigate whether HSYA exerts cardioprotection in ischemia-reperfusion (I/R) injury heart and the mechanisms involved. The protective effect and mechanisms in myocardial ischemia reperfusion injury of HSYA was evaluated by hypoxia-recover (H/R) injury cell model which induced by hypoxia and recovered with oxygen in H9c2 cells. PI3K/Akt and ERK as the reperfusion injury salvage kinase (RISK) pathway and Hexokinase II (HKII) were both examined. In H/R cell model, HSYA significantly reduced dehydrogenase (LDH), Caspase 3 level, alleviated oxidative stress injury and apoptosis, meanwhile restored mitochondrial energy metabolism. Pretreatment with PI3K inhibitor (LY294002) or hexokinase II inhibitor (3-BrPA), the protective effect of HSYA was significantly attenuated. On the contrary, pretreatment with ERK inhibitor (PD98059), the protective effect of HSYA on myocardial cells was decreased slightly, not as significant as PI3K inhibitor or hexokinase II inhibitor. ERK play a protective role in myocardial protection by phosphorylation of GSK3-β, but the effect of HSYA on phosphorylation of GSK3-β is weakly, however the effect of HSYA on Akt and hexokinase II were significantly up-regulated. Meanwhile, the phosphorylation of GSK3-β by HSYA was significantly reduced after gave the ERK inhibitor and had no significant difference between the model group. The cardioprotection effect of HSYA appears to be mainly mediated via the PI3K/Akt/hexokinase II. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Continuous assimilation of simulated Geosat altimetric sea level into an eddy-resolving numerical ocean model. I - Sea level differences. II - Referenced sea level differences

NASA Technical Reports Server (NTRS)

White, Warren B.; Tai, Chang-Kou; Holland, William R.

1990-01-01

The optimal interpolation method of Lorenc (1981) was used to conduct continuous assimilation of altimetric sea level differences from the simulated Geosat exact repeat mission (ERM) into a three-layer quasi-geostrophic eddy-resolving numerical ocean box model that simulates the statistics of mesoscale eddy activity in the western North Pacific. Assimilation was conducted continuously as the Geosat tracks appeared in simulated real time/space, with each track repeating every 17 days, but occurring at different times and locations within the 17-day period, as would have occurred in a realistic nowcast situation. This interpolation method was also used to conduct the assimilation of referenced altimetric sea level differences into the same model, performing the referencing of altimetric sea sevel differences by using the simulated sea level. The results of this dynamical interpolation procedure are compared with those of a statistical (i.e., optimum) interpolation procedure.

Airport-Noise Levels and Annoyance Model (ALAMO) user's guide

NASA Technical Reports Server (NTRS)

Deloach, R.; Donaldson, J. L.; Johnson, M. J.

1986-01-01

A guide for the use of the Airport-Noise Level and Annoyance MOdel (ALAMO) at the Langley Research Center computer complex is provided. This document is divided into 5 primary sections, the introduction, the purpose of the model, and an in-depth description of the following subsystems: baseline, noise reduction simulation and track analysis. For each subsystem, the user is provided with a description of architecture, an explanation of subsystem use, sample results, and a case runner's check list. It is assumed that the user is familiar with the operations at the Langley Research Center (LaRC) computer complex, the Network Operating System (NOS 1.4) and CYBER Control Language. Incorporated within the ALAMO model is a census database system called SITE II.

Validation of updated neutronic calculation models proposed for Atucha-II PHWR. Part I: Benchmark comparisons of WIMS-D5 and DRAGON cell and control rod parameters with MCNP5

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mollerach, R.; Leszczynski, F.; Fink, J.

2006-07-01

In 2005 the Argentine Government took the decision to complete the construction of the Atucha-II nuclear power plant, which has been progressing slowly during the last ten years. Atucha-II is a 745 MWe nuclear station moderated and cooled with heavy water, of German (Siemens) design located in Argentina. It has a pressure-vessel design with 451 vertical coolant channels, and the fuel assemblies (FA) are clusters of 37 natural UO{sub 2} rods with an active length of 530 cm. For the reactor physics area, a revision and update calculation methods and models (cell, supercell and reactor) was recently carried out coveringmore » cell, supercell (control rod) and core calculations. As a validation of the new models some benchmark comparisons were done with Monte Carlo calculations with MCNP5. This paper presents comparisons of cell and supercell benchmark problems based on a slightly idealized model of the Atucha-I core obtained with the WIMS-D5 and DRAGON codes with MCNP5 results. The Atucha-I core was selected because it is smaller, similar from a neutronic point of view, and more symmetric than Atucha-II Cell parameters compared include cell k-infinity, relative power levels of the different rings of fuel rods, and some two-group macroscopic cross sections. Supercell comparisons include supercell k-infinity changes due to the control rods (tubes) of steel and hafnium. (authors)« less

Synthesis, thermogravimetric, spectroscopic and theoretical characterization of copper(II) complex with 4-chloro-2-nitrobenzenosulfonamide

NASA Astrophysics Data System (ADS)

Camí, G.; Chacón Villalba, E.; Di Santi, Y.; Colinas, P.; Estiu, G.; Soria, D. B.

2011-05-01

4-Chloro-2-nitrobenzenesulfonamide (ClNbsa) was purified and characterized. A new copper(II) complex, [Cu(ClNbsa) 2(NH 3) 2], has been prepared using the sulfonamide as ligand. The thermal behavior of both, the ligand and the Cu(II) complex, was investigated by thermogravimetric analyses (TG) and differential thermal analysis (DT), and the electronic characteristics analyzed by UV-VIS, FTIR, Raman and 1H NMR spectroscopies. The experimental IR, Raman and UV-VIS spectra have been assigned on the basis of DFT calculations at the B3LYP level of theory using the standard (6-31 + G ∗∗) basis set. The geometries have been fully optimized in vacuum and in modeled dimethylsulfoxide (DMSO) solvent, using for the latter a continuum solvation model that reproduced the experimental conditions of the UV-VIS spectroscopy. The theoretical results converged to stable conformations for the free sulfonamide and for the complex, suggesting for the latter a distorted square planar geometry in both environments.

Abundance analysis of neodymium in the solar atmosphere

NASA Astrophysics Data System (ADS)

Abdelkawy, Ali G. A.; Shaltout, Abdelrazek M. K.; Beheary, M. M.; Bakry, A.

2017-10-01

Based on non-local thermodynamical equilibrium (NLTE) calculations, the solar neodymium (Nd) content was found based on a model atom of singly ionized neodymium (Nd II) containing 153 energy levels and 42 line transitions plus the ground state of Nd III. Here, we re-derive the solar Nd abundance using the model of the solar photosphere of Holweger & Müller.We succeed in selecting a good sample line list, relying on 20 Nd II solar lines together with the most accurate transition probabilities measured experimentally and available observational data. With damping parameters obtained from the literature, we find a mean NLTE solar photospheric Nd abundance of log ɛNd(1D) = 1.43 ± 0.16, which is in excellent agreement with the meteoritic value (log ɛNd = 1.45 ± 0.02). For a set of selected Nd II lines, the NLTE abundance correction is found to be +0.01 dex compared with the standard LTE effect. The influence of collisional interactions with electrons and neutral hydrogen atoms is investigated in detail.

Numerical study of the Columbia high-beta device: Torus-II

DOE Office of Scientific and Technical Information (OSTI.GOV)

Izzo, R.

1981-01-01

The ionization, heating and subsequent long-time-scale behavior of the helium plasma in the Columbia fusion device, Torus-II, is studied. The purpose of this work is to perform numerical simulations while maintaining a high level of interaction with experimentalists. The device is operated as a toroidal z-pinch to prepare the gas for heating. This ionization of helium is studied using a zero-dimensional, two-fluid code. It is essentially an energy balance calculation that follows the development of the various charge states of the helium and any impurities (primarily silicon and oxygen) that are present. The code is an atomic physics model ofmore » Torus-II. In addition to ionization, we include three-body and radiative recombination processes.« less

Non-thermal leptogenesis with distinct CP violation and minimal dark matter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Hang; Gu, Pei-Hong, E-mail: einsteinzh@sjtu.edu.cn, E-mail: peihong.gu@sjtu.edu.cn

We demonstrate a unified scenario for neutrino mass, baryon asymmetry, dark matter and inflation. In addition to a fermion triplet for the so-called minimal dark matter, we extend the standard model by three heavy fields including a scalar singlet, a fermion triplet and a fermion singlet/Higgs triplet. The heavy scalar singlet, which is expected to drive an inflation, and the dark matter fermion triplet are odd under an unbroken Z {sub 2} discrete symmetry, while the other fields are all even. The heavy fermion triplet offers a tree-level type-III seesaw and then mediates a three-body decay of the inflaton intomore » the standard model lepton and Higgs doublets with the dark matter fermion triplet. The heavy fermion singlet/Higgs triplet not only results in a type-I/II seesaw at tree level but also contributes to the inflaton decay at one-loop level. In this scenario, the type-I/II seesaw contains all of the physical CP phases in the lepton sector and hence the CP violation for the non-thermal leptogenesis by the inflaton decay exactly comes from the imaginary part of the neutrino mass matrix.« less

Theater-Level Gaming and Analysis Workshop for Force Planning. Volume II. Summary, Discussion of Issues and Requirements for Research. September 27- 29, 1977, Held at Xerox International Center for Training and Management Development, Leesburg, Virginia

DTIC Science & Technology

1981-05-01

be allocated to targets on the battlefield and in the rear area. The speaker describes the VECTOR I/NUCLEAR model, a combination of the UNICORN target...outlined. UNICORN is compatible with VECTOR 1 in level of detail. It is an expected value damage model and uses linear programming to optimize the...and a growing appreciation for the power of simulation in addressing large, complex problems, it was only a few short years before these games had

Ghrelin Attenuates Retinal Neuronal Autophagy and Apoptosis in an Experimental Rat Glaucoma Model.

PubMed

Zhu, Ke; Zhang, Meng-Lu; Liu, Shu-Ting; Li, Xue-Yan; Zhong, Shu-Min; Li, Fang; Xu, Ge-Zhi; Wang, Zhongfeng; Miao, Yanying

2017-12-01

Ghrelin, a natural ligand for the growth hormone secretagogue receptor type 1a (GHSR-1a), may protect retinal neurons against glaucomatous injury. We therefore characterized the underlying mechanism of the ghrelin/GHSR-1a-mediated neuroprotection with a rat chronic intraocular hypertension (COH) model. The rat COH model was produced by blocking episcleral veins. A combination of immunohistochemistry, Western blot, TUNEL assay, and retrograde labeling of retinal ganglion cells (RGCs) was used. Elevation of intraocular pressure induced a significant increase in ghrelin and GHSR-1a expression in retinal cells, including RGCs and Müller cells. Western blot confirmed that the protein levels of ghrelin exhibited a transient upregulation at week 2 after surgery (G2w), while the GHSR-1a protein levels were maintained at high levels from G2w to G4w. In COH retinas, the ratio of LC3-II/LC-I and beclin1, two autophagy-related proteins, were increased from G1w to G4w, and the cleavage product of caspase3, an apoptotic executioner, was detected from G2w to G4w. Intraperitoneal injection of ghrelin significantly increased the number of surviving RGCs; inhibited the changes of LC3-II/LC-I, beclin1, and the cleavage products of caspase3; and reduced the number of TUNEL-positive cells in COH retinas. Ghrelin treatment also reversed the decreased levels of p-Akt and p-mTOR, upregulated GHSR-1a protein levels, and attenuated glial fibrillary acidic protein levels in COH retinas. All these results suggest that ghrelin may provide neuroprotective effect in COH retinas through activating ghrelin/GHSR-1a system, which was mediated by inhibiting retinal autophagy, ganglion cell apoptosis, and Müller cell gliosis.

Effect of Interbody Fusion on the Remaining Discs of the Lumbar Spine in Subjects with Disc Degeneration.

PubMed

Ryu, Robert; Techy, Fernando; Varadarajan, Ravikumar; Amirouche, Farid

2016-02-01

To study effects (stress loads) of lumbar fusion on the remaining segments (adjacent or not) of the lumbar spine in the setting of degenerated adjacent discs. A lumbar spine finite element model was built and validated. The full model of the lumbar spine was a parametric finite element model of segments L 1-5 . Numerous hypothetical combinations of one-level lumbar spine fusion and one-level disc degeneration were created. These models were subjected to 10 Nm flexion and extension moments and the stresses on the endplates and consequently on the intervertebral lumbar discs measured. These values were compared to the stresses on healthy lumbar spine discs under the same load and fusion scenarios. Increased stress at endplates was observed only in the settings of L4-5 fusion and L3-4 disc degeneration (8% stress elevation at L2,3 in flexion or extension, and 25% elevation at L3,4 in flexion only). All other combinations showed less endplate stress than did the control model. For fusion at L3-4 and degeneration at L4-5 , the stresses in the endplates at the adjacent level inferior to the fused disc decreased for both loading disc height reductions. Stresses in flexion decreased after fusion by 29.5% and 25.8% for degeneration I and II, respectively. Results for extension were similar. For fusion at L2-3 and degeneration at L4-5 , stresses in the endplates decreased more markedly at the degenerated (30%), than at the fused level (14%) in the presence of 25% disc height reduction and 10 Nm flexion, whereas in extension stresses decreased more at the fused (24.3%) than the degenerated level (5.86%). For fusion at L3-4 and degeneration at L2-3 , there were no increases in endplate stress in any scenario. For fusion at L4-5 and degeneration at L3-4 , progression of degeneration from I to II had a significant effect only in flexion. A dramatic increase in stress was noted in the endplates of the degenerated disc (L3-4 ) in flexion for degeneration II. Stresses are greater in flexion at the endplates of L3-4 and in flexion and extension at L2-3 in the presence of L3-4 disc disease and L4-5 fusion than in the control group. In all other combinations of fusion and disc disease, endplate stress was less for all levels tested than in the control model. © 2016 Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.

What stresses remote area nurses? Current knowledge and future action.

PubMed

Lenthall, Sue; Wakerman, John; Opie, Tess; Dollard, Maureen; Dunn, Sandra; Knight, Sabina; Macleod, Martha; Watson, Colin

2009-08-01

Review and synthesise the literature identifying the stresses experienced by remote area nurses (RANs). Identify interventions implemented to address identified stresses. Explore the use of the job demands-resources (JD-R) model. A comprehensive literature review was conducted using the meta-databases Ovid and Informit. Remote Australian primary health care centres. The reported demands experienced by RANs can be grouped into four themes: (i) the remote context; (ii) workload and extended scope of practice; (iii) poor management; and (iv) violence in the workplace and community. In this high-demand, low-resource context, the JD-R model of occupational stress is particularly pertinent to examining occupational stress among RANs. The demands on RANs, such as the isolated geographical context, are immutable. However, there are key areas where resources can be enhanced to better meet the high level of need. These are: (i) adequate and appropriate education, training and orientation; (ii) appropriate funding of remote health services; and (iii) improved management practices and systems. There is a lack of empirical evidence relating to stresses experienced by RANs. The literature identifies some of the stresses experienced by RANs as unique to the remote context, while some are related to high demands coupled with a deficit of appropriate resources. Use of models, such as the JD-R model of occupational stress, might assist in identifying key areas where resources can be enhanced to better meet the high level of need and reduce RANs' levels of stress.

Inhibitor-based validation of a homology model of the active-site of tripeptidyl peptidase II.

PubMed

De Winter, Hans; Breslin, Henry; Miskowski, Tamara; Kavash, Robert; Somers, Marijke

2005-04-01

A homology model of the active site region of tripeptidyl peptidase II (TPP II) was constructed based on the crystal structures of four subtilisin-like templates. The resulting model was subsequently validated by judging expectations of the model versus observed activities for a broad set of prepared TPP II inhibitors. The structure-activity relationships observed for the prepared TPP II inhibitors correlated nicely with the structural details of the TPP II active site model, supporting the validity of this model and its usefulness for structure-based drug design and pharmacophore searching experiments.

Clothing adjustments for concealed soft body armor during moderate physical exertion.

PubMed

Ryan, Greg A; Bishop, Stacy H; Herron, Robert L; Katica, Charles P; Elbon, Bre'anna L; Bosak, Andrew M; Bishop, Phillip

2015-01-01

Previous research has studied the impact of Level II concealed soft body armor (SBA) on the augmentation of heat storage in a hot environment simulating a typical summer day in the southeastern United States (wet bulb globe temperature [WBGT] = 30°C) and noted a significant difference between macro- and micro-WBGTs. The purpose of this study was to characterize the microclimate (micro-WBGT) under a concealed Level II SBA during 60 min of moderately intense work at two separate macro-WBGTs (26°C and 30°C), and to establish WBGT corrections to allow prediction of heat strain in an individual wearing a concealed Level II SBA. A single trial was performed with nine volunteers (27 ± 4 years) outfitted with a simulated standard law enforcement uniform and a traditional concealed Level II SBA, in a moderately warm environment (WBGT = 26°C). Each participant performed cycles of 12 min of walking (1.25 L · min(-1)) and 3 min of arm curls (14.3 kg, 0.6 L · min(-1)) with a 5 min rest after every other cycle, for a total of 60 minutes. This trial was compared to an identical previously completed 60-min work bout at 30°C. A two-way repeated measures ANOVA with Post hoc Bonferroni and paired samples t-test analysis was conducted. A greater difference between macro- micro-WBGTs existed at 26°C compared to the 30°C macro-WBGT. Under these conditions, a moderate work in Level II SBA requires a WBGT correction of 8.9°C and 6.2°C at macro-WBGTs of 26°C and 30°C, respectively. A modified simple linear regression prediction model was established for mean Micro-WBGT for each macro-WBGTs after the plateau point at the 30 min mark. The derivation regressions at 26°C (R(2) = 0.99), and 30°C (R(2) = 0.99) indicate that micro-WBGT could be predicted for each 15 minutes time at both macro-WBGTs tested for individuals doing moderate intensity (300 Kcals · hr(-1)) work wearing concealed Level II SBA.

A 2D ion chamber array audit of wedged and asymmetric fields in an inhomogeneous lung phantom.

PubMed

Lye, Jessica; Kenny, John; Lehmann, Joerg; Dunn, Leon; Kron, Tomas; Alves, Andrew; Cole, Andrew; Williams, Ivan

2014-10-01

The Australian Clinical Dosimetry Service (ACDS) has implemented a new method of a nonreference condition Level II type dosimetric audit of radiotherapy services to increase measurement accuracy and patient safety within Australia. The aim of this work is to describe the methodology, tolerances, and outcomes from the new audit. The ACDS Level II audit measures the dose delivered in 2D planes using an ionization chamber based array positioned at multiple depths. Measurements are made in rectilinear homogeneous and inhomogeneous phantoms composed of slabs of solid water and lung. Computer generated computed tomography data sets of the rectilinear phantoms are supplied to the facility prior to audit for planning of a range of cases including reference fields, asymmetric fields, and wedged fields. The audit assesses 3D planning with 6 MV photons with a static (zero degree) gantry. Scoring is performed using local dose differences between the planned and measured dose within 80% of the field width. The overall audit result is determined by the maximum dose difference over all scoring points, cases, and planes. Pass (Optimal Level) is defined as maximum dose difference ≤3.3%, Pass (Action Level) is ≤5.0%, and Fail (Out of Tolerance) is >5.0%. At close of 2013, the ACDS had performed 24 Level II audits. 63% of the audits passed, 33% failed, and the remaining audit was not assessable. Of the 15 audits that passed, 3 were at Pass (Action Level). The high fail rate is largely due to a systemic issue with modeling asymmetric 60° wedges which caused a delivered overdose of 5%-8%. The ACDS has implemented a nonreference condition Level II type audit, based on ion chamber 2D array measurements in an inhomogeneous slab phantom. The powerful diagnostic ability of this audit has allowed the ACDS to rigorously test the treatment planning systems implemented in Australian radiotherapy facilities. Recommendations from audits have led to facilities modifying clinical practice and changing planning protocols.

A small molecule inhibitor of mutant IDH2 rescues cardiomyopathy in a D-2-hydroxyglutaric aciduria type II mouse model.

PubMed

Wang, Fang; Travins, Jeremy; Lin, Zhizhong; Si, Yaguang; Chen, Yue; Powe, Josh; Murray, Stuart; Zhu, Dongwei; Artin, Erin; Gross, Stefan; Santiago, Stephanie; Steadman, Mya; Kernytsky, Andrew; Straley, Kimberly; Lu, Chenming; Pop, Ana; Struys, Eduard A; Jansen, Erwin E W; Salomons, Gajja S; David, Muriel D; Quivoron, Cyril; Penard-Lacronique, Virginie; Regan, Karen S; Liu, Wei; Dang, Lenny; Yang, Hua; Silverman, Lee; Agresta, Samuel; Dorsch, Marion; Biller, Scott; Yen, Katharine; Cang, Yong; Su, Shin-San Michael; Jin, Shengfang

2016-11-01

D-2-hydroxyglutaric aciduria (D2HGA) type II is a rare neurometabolic disorder caused by germline gain-of-function mutations in isocitrate dehydrogenase 2 (IDH2), resulting in accumulation of D-2-hydroxyglutarate (D2HG). Patients exhibit a wide spectrum of symptoms including cardiomyopathy, epilepsy, developmental delay and limited life span. Currently, there are no effective therapeutic interventions. We generated a D2HGA type II mouse model by introducing the Idh2R140Q mutation at the native chromosomal locus. Idh2R140Q mice displayed significantly elevated 2HG levels and recapitulated multiple defects seen in patients. AGI-026, a potent, selective inhibitor of the human IDH2R140Q-mutant enzyme, suppressed 2HG production, rescued cardiomyopathy, and provided a survival benefit in Idh2R140Q mice; treatment withdrawal resulted in deterioration of cardiac function. We observed differential expression of multiple genes and metabolites that are associated with cardiomyopathy, which were largely reversed by AGI-026. These findings demonstrate the potential therapeutic benefit of an IDH2R140Q inhibitor in patients with D2HGA type II.

An interactive human carbonic anhydrase-II (hCA-II) receptor--pharmacophore molecular model & anti-convulsant activity of the designed and synthesized 5-amino-1,3,4-thiadiazole-2-thiol conjugated imine derivatives.

PubMed

Yusuf, Mohammad; Khan, Riaz A; Khan, Maria; Ahmed, Bahar

2013-05-01

New imines, derived from aromatic aldehyde, chalcones and 5-amino-1,3,4-thiadiazole-2-thiol exhibited promising anti-convulsant activity which is explained through chemo-biological interactions at receptor site producing the inhibition of human Carbonic Anhydrase-II enzyme (hCA-II) through the proposed pharmacophore model at molecular levels as basis for pharmacological activity. The compounds 5-{1-(4-Chlorophenyl)-3-[4-(methoxy-phenyl)-prop-2-en-1-ylidene]amino}-1,3,4-thiadiazole-2-thiol (2b), 5-{[1-(4-chloro-phenyl)]-3-[4-(dimethyl-amino-phenyl)-prop-2-en-1-ylidene]amino}-1,3,4-thiadiazole-2-thiol (2c) and 5-{[1-(4-chloro-phenyl)]-3-[(4-amino-phenyl)-prop-2-en-1-ylidene]amino}-1,3,4-thiadiazole-2-thiol (2f) showed 100% activity in comparison with standard Acetazolamide, a known anti-convulsant drug. The compounds 2c, 2f also passed the Rotarod and Ethanol Potentiation tests which further confirmed them to be safe in motor coordination activity and safe from generating neurological toxicity. © 2013 John Wiley & Sons A/S.

Integrating fine-scale soil data into species distribution models: preparing Soil Survey Geographic (SSURGO) data from multiple counties

Treesearch

Matthew P. Peters; Louis R. Iverson; Anantha M. Prasad; Steve N. Matthews

2013-01-01

Fine-scale soil (SSURGO) data were processed at the county level for 37 states within the eastern United States, initially for use as predictor variables in a species distribution model called DISTRIB II. Values from county polygon files converted into a continuous 30-m raster grid were aggregated to 4-km cells and integrated with other environmental and site condition...

Anthropometric specifications, development, and evaluation of EvaRID--a 50th percentile female rear impact finite element dummy model.

PubMed

Carlsson, Anna; Chang, Fred; Lemmen, Paul; Kullgren, Anders; Schmitt, Kai-Uwe; Linder, Astrid; Svensson, Mats Y

2014-01-01

Whiplash-associated disorders (WADs), or whiplash injuries, due to low-severity vehicle crashes are of great concern in motorized countries and it is well established that the risk of such injuries is higher for females than for males, even in similar crash conditions. Recent protective systems have been shown to be more beneficial for males than for females. Hence, there is a need for improved tools to address female WAD prevention when developing and evaluating the performance of whiplash protection systems. The objective of this study is to develop and evaluate a finite element model of a 50th percentile female rear impact crash test dummy. The anthropometry of the 50th percentile female was specified based on literature data. The model, called EvaRID (female rear impact dummy), was based on the same design concept as the existing 50th percentile male rear impact dummy, the BioRID II. A scaling approach was developed and the first version, EvaRID V1.0, was implemented. Its dynamic response was compared to female volunteer data from rear impact sled tests. The EvaRID V1.0 model and the volunteer tests compared well until ∼250 ms of the head and T1 forward accelerations and rearward linear displacements and of the head rearward angular displacement. Markedly less T1 rearward angular displacement was found for the EvaRID model compared to the female volunteers. Similar results were received for the BioRID II model when comparing simulated responses with experimental data under volunteer loading conditions. The results indicate that the biofidelity of the EvaRID V1.0 and BioRID II FE models have limitations, predominantly in the T1 rearward angular displacement, at low velocity changes (7 km/h). The BioRID II model was validated against dummy test results in a loading range close to consumer test conditions (EuroNCAP) and lower severity levels of volunteer testing were not considered. The EvaRID dummy model demonstrated the potential of becoming a valuable tool when evaluating and developing seats and whiplash protection systems. However, updates of the joint stiffness will be required to provide better correlation at lower load levels. Moreover, the seated posture, curvature of the spine, and head position of 50th percentile female occupants needs to be established and implemented in future models.

A sense of life: computational and experimental investigations with models of biochemical and evolutionary processes.

PubMed

Mishra, Bud; Daruwala, Raoul-Sam; Zhou, Yi; Ugel, Nadia; Policriti, Alberto; Antoniotti, Marco; Paxia, Salvatore; Rejali, Marc; Rudra, Archisman; Cherepinsky, Vera; Silver, Naomi; Casey, William; Piazza, Carla; Simeoni, Marta; Barbano, Paolo; Spivak, Marina; Feng, Jiawu; Gill, Ofer; Venkatesh, Mysore; Cheng, Fang; Sun, Bing; Ioniata, Iuliana; Anantharaman, Thomas; Hubbard, E Jane Albert; Pnueli, Amir; Harel, David; Chandru, Vijay; Hariharan, Ramesh; Wigler, Michael; Park, Frank; Lin, Shih-Chieh; Lazebnik, Yuri; Winkler, Franz; Cantor, Charles R; Carbone, Alessandra; Gromov, Mikhael

2003-01-01

We collaborate in a research program aimed at creating a rigorous framework, experimental infrastructure, and computational environment for understanding, experimenting with, manipulating, and modifying a diverse set of fundamental biological processes at multiple scales and spatio-temporal modes. The novelty of our research is based on an approach that (i) requires coevolution of experimental science and theoretical techniques and (ii) exploits a certain universality in biology guided by a parsimonious model of evolutionary mechanisms operating at the genomic level and manifesting at the proteomic, transcriptomic, phylogenic, and other higher levels. Our current program in "systems biology" endeavors to marry large-scale biological experiments with the tools to ponder and reason about large, complex, and subtle natural systems. To achieve this ambitious goal, ideas and concepts are combined from many different fields: biological experimentation, applied mathematical modeling, computational reasoning schemes, and large-scale numerical and symbolic simulations. From a biological viewpoint, the basic issues are many: (i) understanding common and shared structural motifs among biological processes; (ii) modeling biological noise due to interactions among a small number of key molecules or loss of synchrony; (iii) explaining the robustness of these systems in spite of such noise; and (iv) cataloging multistatic behavior and adaptation exhibited by many biological processes.

An integrative review of in-class activities that enable active learning in college science classroom settings

NASA Astrophysics Data System (ADS)

Arthurs, Leilani A.; Kreager, Bailey Zo

2017-10-01

Engaging students in active learning is linked to positive learning outcomes. This study aims to synthesise the peer-reviewed literature about 'active learning' in college science classroom settings. Using the methodology of an integrative literature review, 337 articles archived in the Educational Resources Information Center (ERIC) are examined. Four categories of in-class activities emerge: (i) individual non-polling activities, (ii) in-class polling activities, (iii) whole-class discussion or activities, and (iv) in-class group activities. Examining the collection of identified in-class activities through the lens of a theoretical framework informed by constructivism and social interdependence theory, we synthesise the reviewed literature to propose the active learning strategies (ALSs) model and the instructional decisions to enable active learning (IDEAL) theory. The ALS model characterises in-class activities in terms of the degrees to which they are designed to promote (i) peer interaction and (ii) social interdependence. The IDEAL theory includes the ALS model and provides a framework for conceptualising different levels of the general concept 'active learning' and how these levels connect to instructional decision-making about using in-class activities. The proposed ALS model and IDEAL theory can be utilised to inform instructional decision-making and future research about active learning in college science courses.

The selective cathepsin K inhibitor MIV-711 attenuates joint pathology in experimental animal models of osteoarthritis.

PubMed

Lindström, Erik; Rizoska, Biljana; Tunblad, Karin; Edenius, Charlotte; Bendele, Alison M; Maul, Don; Larson, Michael; Shah, Neha; Yoder Otto, Valerie; Jerome, Chris; Grabowska, Urszula

2018-03-09

MIV-711 is a highly potent and selective cathepsin K inhibitor. The current article summarizes the therapeutic effects of MIV-711 on joint pathology in rabbits subjected to anterior cruciate ligament transection (ACLT), and the prophylactic effects on joint pathology in dogs subjected to partial medial meniscectomy, two surgical models of osteoarthritis (OA). Starting 1 week after surgery, rabbits were dosed daily via oral gavage with either MIV-711 or vehicle (n = 7/group) for 7 weeks. The four treatment groups were: (1) sham + vehicle; (2) ACLT + vehicle; (3) ACLT + MIV-711, 30 µmol/kg and (4) ACLT + MIV-711, 100 µmol/kg. Subchondral bone and articular cartilage structures were assessed by µCT, histomorphometry, and scoring. Dogs subjected to partial medial meniscectomy received either MIV-711 (30 µmol/kg) or vehicle (n = 15/group) via oral gavage once daily, starting 1 day before meniscectomy, for 28 days. Cartilage degradation was assessed at the macroscopic and microscopic levels. The exposures of MIV-711 were assessed in both studies and biomarkers reflecting bone resorption (HP-1 in rabbits, CTX-I in dogs) and cartilage degradation (CTX-II) were measured. In ACLT rabbits, MIV-711 decreased HP-1 levels by up to 72% (p < 0.001) and CTX-II levels by up to 74% (p < 0.001) compared to ACLT vehicle controls. ACLT surgery significantly reduced the total thickness of the subchondral bone plate and reduced trabecular bone volume in the femur and tibia. These effects were reversed by MIV-711. ACLT resulted in cartilage thickening, which was attenuated by MIV-711. MIV-711 did not affect osteophyte formation or Mankin scores. In dogs, MIV-711 reduced CTX-I and CTX-II levels by 86% (p < 0.001) and 80% (p < 0.001), respectively. Synovial CTX-II levels were reduced by 55-57% (p < 0.001) compared to baseline. MIV-711-treated animals had 25-37% lower macroscopic scores in the femur condyles and 13-33% lower macroscopic scores in the tibial plateaus. MIV-711 prevents subchondral bone loss and partially attenuates cartilage pathology in two animal models of OA. These beneficial effects of MIV-711 on joint pathology are observed in conjunction with decreases in bone and cartilage biomarkers that have been shown to be clinically attainable in human. The data support the further development of MIV-711 for the treatment of OA.

Identification and expression analysis of leptin-regulated immediate early response and late target genes.

PubMed

Waelput, W; Verhee, A; Broekaert, D; Eyckerman, S; Vandekerckhove, J; Beattie, J H; Tavernier, J

2000-05-15

Using PC12 cells as an in vitro model system, we have identified a series of transcripts induced through activation of the leptin receptor. On the basis of kinetic studies, two distinct gene sets could be discerned: signal transducer and activator of transciption-3 (STAT-3), suppressor of cytokine signalling-3 (SOCS-3), MT-II (metallothionein-II), the serine/threonine kinase fibroblast-growth-factor-inducible kinase (Fnk) and modulator recognition factor (MRF-1), which are immediate early response genes, and pancreatitis-associated protein I (PAP I), squalene epoxidase, uridine diphosphate glucuronosyltransferase and annexin VIII, which are late induced target genes. At late time points a strong co-stimulation with beta-nerve growth factor or with the adenylate cyclase activator forskolin was observed. To assess the validity of the PC12-cell model system, we examined the effect of leptin administration on the gene transcription of STAT-3, MT-II, Fnk and PAP I in vivo. Leptin treatment of leptin-deficient ob/ob mice increased the STAT-3, SOCS-3, MT-II and Fnk mRNA, and MT-I protein levels in liver, whereas, in jejunum, expression of PAP I mRNA was down-regulated. Furthermore, administration of leptin to starved wild-type mice enhanced the expression of MT-II and Fnk mRNA in liver, but decreased MT-II and PAP I mRNA expression in jejunum. These findings may help to explain the obese phenotype observed in some colonies of MT-I- and MT-II-null mice and/or the observation that leptin protects against tumour-necrosis-factor toxicity in vivo.

Exoskeletal meal assistance system (EMAS II) for progressive muscle dystrophy patient.

PubMed

Hasegawa, Yasuhisa; Oura, Saori

2011-01-01

This paper introduces a 4-DOFs exoskeletal meal assistance system (EMAS II) for progressive muscle dystrophy patient. It is generally better for the patient to use his/her hands by himself in daily life because active works maintain level of residual functions, health and initiative of him/her. The EMAS II that has a new joystick-type user interface device and three-DOFs on a shoulder part is enhanced for an easier operation and more comfortable support on eating, as the succeeding model of the previous system that has two-DOFs on a shoulder. In order to control the 4-DOFs system by the simple user interface device, the EMAS II simulates upper limb motion patterns of a healthy person. The motion patterns are modeled by extracting correlations between the height of a user's wrist joint and that of the user's elbow joint at the table. Moreover, the EMAS II automatically brings user's hand up to his/her mouth or back to a table when he/she pushes a preset switch on the interface device. Therefore a user has only to control a position of his/her wrist to pick or scoop foods and then flip the switch to start automatic mode, while a height of the elbow joint is automatically controlled by the EMAS II itself. The results of experiments, where a healthy subject regarded as a muscle dystrophy patient eats a meal with EMAS II, show that the subject finished her meal in a natural way in 18 minutes 40 seconds which was within a recommended time of 30 minutes. © 2011 IEEE

External Validation of European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) for Risk Prioritization in an Iranian Population

PubMed Central

Atashi, Alireza; Amini, Shahram; Tashnizi, Mohammad Abbasi; Moeinipour, Ali Asghar; Aazami, Mathias Hossain; Tohidnezhad, Fariba; Ghasemi, Erfan; Eslami, Saeid

2018-01-01

Introduction The European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) is a prediction model which maps 18 predictors to a 30-day post-operative risk of death concentrating on accurate stratification of candidate patients for cardiac surgery. Objective The objective of this study was to determine the performance of the EuroSCORE II risk-analysis predictions among patients who underwent heart surgeries in one area of Iran. Methods A retrospective cohort study was conducted to collect the required variables for all consecutive patients who underwent heart surgeries at Emam Reza hospital, Northeast Iran between 2014 and 2015. Univariate and multivariate analysis were performed to identify covariates which significantly contribute to higher EuroSCORE II in our population. External validation was performed by comparing the real and expected mortality using area under the receiver operating characteristic curve (AUC) for discrimination assessment. Also, Brier Score and Hosmer-Lemeshow goodness-of-fit test were used to show the overall performance and calibration level, respectively. Results Two thousand five hundred eight one (59.6% males) were included. The observed mortality rate was 3.3%, but EuroSCORE II had a prediction of 4.7%. Although the overall performance was acceptable (Brier score=0.047), the model showed poor discriminatory power by AUC=0.667 (sensitivity=61.90, and specificity=66.24) and calibration (Hosmer-Lemeshow test, P<0.01). Conclusion Our study showed that the EuroSCORE II discrimination power is less than optimal for outcome prediction and less accurate for resource allocation programs. It highlights the need for recalibration of this risk stratification tool aiming to improve post cardiac surgery outcome predictions in Iran. PMID:29617500

Population Pharmacokinetic/Pharmacodynamic Analysis of Alirocumab in Healthy Volunteers or Hypercholesterolemic Subjects Using an Indirect Response Model to Predict Low-Density Lipoprotein Cholesterol Lowering: Support for a Biologics License Application Submission: Part II.

PubMed

Nicolas, Xavier; Djebli, Nassim; Rauch, Clémence; Brunet, Aurélie; Hurbin, Fabrice; Martinez, Jean-Marie; Fabre, David

2018-05-03

Alirocumab, a human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly lowers low-density lipoprotein cholesterol levels. This analysis aimed to develop and qualify a population pharmacokinetic/pharmacodynamic model for alirocumab based on pooled data obtained from 13 phase I/II/III clinical trials. From a dataset of 2799 individuals (14,346 low-density lipoprotein-cholesterol values), individual pharmacokinetic parameters from the population pharmacokinetic model presented in Part I of this series were used to estimate alirocumab concentrations. As a second step, we then developed the current population pharmacokinetic/pharmacodynamic model using an indirect response model with a Hill coefficient, parameterized with increasing low-density lipoprotein cholesterol elimination, to relate alirocumab concentrations to low-density lipoprotein cholesterol values. The population pharmacokinetic/pharmacodynamic model allowed the characterization of the pharmacokinetic/pharmacodynamic properties of alirocumab in the target population and estimation of individual low-density lipoprotein cholesterol levels and derived pharmacodynamic parameters (the maximum decrease in low-density lipoprotein cholesterol values from baseline and the difference between baseline low-density lipoprotein cholesterol and the pre-dose value before the next alirocumab dose). Significant parameter-covariate relationships were retained in the model, with a total of ten covariates (sex, age, weight, free baseline PCSK9, total time-varying PCSK9, concomitant statin administration, total baseline PCSK9, co-administration of high-dose statins, disease status) included in the final population pharmacokinetic/pharmacodynamic model to explain between-subject variability. Nevertheless, the high number of covariates included in the model did not have a clinically meaningful impact on model-derived pharmacodynamic parameters. This model successfully allowed the characterization of the population pharmacokinetic/pharmacodynamic properties of alirocumab in its target population and the estimation of individual low-density lipoprotein cholesterol levels.

Computational Analysis of Intra-Ventricular Flow Pattern Under Partial and Full Support of BJUT-II VAD.

PubMed

Zhang, Qi; Gao, Bin; Chang, Yu

2017-02-27

BACKGROUND Partial support, as a novel support mode, has been widely applied in clinical practice and widely studied. However, the precise mechanism of partial support of LVAD in the intra-ventricular flow pattern is unclear. MATERIAL AND METHODS In this study, a patient-specific left ventricular geometric model was reconstructed based on CT data. The intra-ventricular flow pattern under 3 simulated conditions - "heart failure", "partial support", and "full support" - were simulated by using fluid-structure interaction (FSI). The blood flow pattern, wall shear stress (WSS), time-average wall shear stress (TAWSS), oscillatory shear index (OSI), and relative residence time (RRT) were calculated to evaluate the hemodynamic effects. RESULTS The results demonstrate that the intra-ventricular flow pattern is significantly changed by the support level of BJUT-II VAD. The intra-ventricular vortex was enhanced under partial support and was eliminated under full support, and the high OSI and RRT regions changed from the septum wall to the cardiac apex. CONCLUSIONS In brief, the support level of the BJUT-II VAD has significant effects on the intra-ventricular flow pattern. The partial support mode of BJUT-II VAD can enhance the intra-ventricular vortex, while the distribution of high OSI and RRT moved from the septum wall to the cardiac apex. Hence, the partial support mode of BJUT-II VAD can provide more benefit for intra-ventricular flow pattern.

Reducing fatalities and severe injuries on Florida's high-speed multi-lane arterial corridors : part II, analysis of the crash level data, final report, April 2009

DOT National Transportation Integrated Search

2009-04-28

This report presents the analysis conducted to identify the factors that contribute to severe and fatal crash occurrence on multilane corridors. The authors preliminary investigation using simultaneous ordered probit model provided enough evidence...

They fight because we let them! Applying a situational crime prevention model to barroom violence.

PubMed

Graham, Kathryn

2009-03-01

This paper draws on situational crime prevention and social interactionist theories to develop a theoretical model for preventing aggression and injury in licensed drinking establishments. The model includes six components: (i) the presence of willing participants; (ii) the role of guardians, handlers and place managers; (iii) environmental deterrents of aggression; (iv) environmental precipitators of aggression; (v) theories regarding the effects of alcohol that contribute to increased risk of aggression; and (vi) social interaction theory relevant to the process of aggressive incidents in drinking establishments. The model provides a basis for developing a range of strategies to reduce barroom aggression that includes but is not restricted to addressing the role of alcohol. The paper discusses how these strategies can be developed and implemented through interventions, programs, policies or regulations at the level of the drinking establishment, the community level or the state/national level.

Dual processing model of medical decision-making

PubMed Central

2012-01-01

Background Dual processing theory of human cognition postulates that reasoning and decision-making can be described as a function of both an intuitive, experiential, affective system (system I) and/or an analytical, deliberative (system II) processing system. To date no formal descriptive model of medical decision-making based on dual processing theory has been developed. Here we postulate such a model and apply it to a common clinical situation: whether treatment should be administered to the patient who may or may not have a disease. Methods We developed a mathematical model in which we linked a recently proposed descriptive psychological model of cognition with the threshold model of medical decision-making and show how this approach can be used to better understand decision-making at the bedside and explain the widespread variation in treatments observed in clinical practice. Results We show that physician’s beliefs about whether to treat at higher (lower) probability levels compared to the prescriptive therapeutic thresholds obtained via system II processing is moderated by system I and the ratio of benefit and harms as evaluated by both system I and II. Under some conditions, the system I decision maker’s threshold may dramatically drop below the expected utility threshold derived by system II. This can explain the overtreatment often seen in the contemporary practice. The opposite can also occur as in the situations where empirical evidence is considered unreliable, or when cognitive processes of decision-makers are biased through recent experience: the threshold will increase relative to the normative threshold value derived via system II using expected utility threshold. This inclination for the higher diagnostic certainty may, in turn, explain undertreatment that is also documented in the current medical practice. Conclusions We have developed the first dual processing model of medical decision-making that has potential to enrich the current medical decision-making field, which is still to the large extent dominated by expected utility theory. The model also provides a platform for reconciling two groups of competing dual processing theories (parallel competitive with default-interventionalist theories). PMID:22943520

THE FORMATION OF IRIS DIAGNOSTICS. VII. THE FORMATION OF THE O i 135.56 NM LINE IN THE SOLAR ATMOSPHERE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Hsiao-Hsuan; Carlsson, Mats, E-mail: h.h.lin@astro.uio.no, E-mail: mats.carlsson@astro.uio.no

The O i 135.56 nm line is covered by NASA's Interface Region Imaging Spectrograph (IRIS) small explorer mission which studies how the solar atmosphere is energized. We study here the formation and diagnostic potential of this line by means of non-local thermodynamic equilibrium modeling employing both 1D semi-empirical and 3D radiation magnetohydrodynamic models. We study the basic formation mechanisms and derive a quintessential model atom that incorporates essential atomic physics for the formation of the O i 135.56 nm line. This atomic model has 16 levels and describes recombination cascades through highly excited levels by effective recombination rates. The ionizationmore » balance O i/O ii is set by the hydrogen ionization balance through charge exchange reactions. The emission in the O i 135.56 nm line is dominated by a recombination cascade and the line is optically thin. The Doppler shift of the maximum emission correlates strongly with the vertical velocity in its line forming region, which is typically located at 1.0–1.5 Mm height. The total intensity of the line emission is correlated with the square of the electron density. Since the O i 135.56 nm line is optically thin, the width of the emission line is a very good diagnostic of non-thermal velocities. We conclude that the O i 135.56 nm line is an excellent probe of the middle chromosphere, and compliments other powerful chromospheric diagnostics of IRIS such as the Mg ii h and k lines and the C ii lines around 133.5 nm.« less

Free radical scavenging activity and neuroprotective potentials of D138, one Cu(II)/Zn(II) Schiff-base complex derived from N,N'-bis(2-hydroxynaphthylmethylidene)-1,3-propanediamine.

PubMed

Wang, Che; Cai, Zheng-Xu; You, Zhong-Lu; Guo, Hui-Shu; Shang, De-Jing; Wang, Xiao-Ling; Zhang, Liang; Ma, Li-Jie; Tan, Jun; Le, Wei-Dong; Li, Song

2014-09-01

There is increasing evidence that free radicals play an important role in neuronal damages induced by diabetes mellitus or cerebral ischemia insults. Antioxidants with free radical scavenging activities have been shown to be beneficial and neuroprotective for these pathological conditions. Here, we report free radical scavenging activity and neuroprotective potential of D138, one copper(II)/zinc(II) Schiff-base complex derived from N,N'-2(2-hydroxynaphthylmethylidene)-1,3-propanediamine. The data from three in vitro assays, 2,2-diphenyl-1-picrylhydrazyl assay, nitro blue tetrazolium assay and hydroxyl radical scavenging assay, indicated that D138 presented a potent free radical scavenging activity. The neuroprotective and antioxidative effects of D138 were further evaluated in vivo using bilateral common carotid artery occlusion (BCCAO) mouse model and streptozotocin (STZ) diabetic mouse model. Our results indicated that treatment of D138 significantly ameliorated the hippocampal neuronal damage and the oxidative stress levels in these animal models. Moreover, D138 also reversed the behavioral deficiencies induced by BCCAO or STZ, as assessed by Y-maze test and fear conditioning test. In conclusion, all these findings support that D138 exerts free radical scavenging and neuroprotective activities and has the potentials to be a potent therapeutic candidate for brain oxidative damage induced by cerebral ischemia or diabetes mellitus.

CONSTRAINING THE SOLAR CORONAL MAGNETIC FIELD STRENGTH USING SPLIT-BAND TYPE II RADIO BURST OBSERVATIONS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kishore, P.; Ramesh, R.; Hariharan, K.

2016-11-20

We report on low-frequency radio (85–35 MHz) spectral observations of four different type II radio bursts, which exhibited fundamental-harmonic emission and split-band structure. Each of the bursts was found to be closely associated with a whitelight coronal mass ejection (CME) close to the Sun. We estimated the coronal magnetic field strength from the split-band characteristics of the bursts, by assuming a model for the coronal electron density distribution. The choice of the model was constrained, based on the following criteria: (1) when the radio burst is observed simultaneously in the upper and lower bands of the fundamental component, the locationmore » of the plasma level corresponding to the frequency of the burst in the lower band should be consistent with the deprojected location of the leading edge (LE) of the associated CME; (2) the drift speed of the type II bursts derived from such a model should agree closely with the deprojected speed of the LE of the corresponding CMEs. With the above conditions, we find that: (1) the estimated field strengths are unique to each type II burst, and (2) the radial variation of the field strength in the different events indicate a pattern. It is steepest for the case where the heliocentric distance range over which the associated burst is observed is closest to the Sun, and vice versa.« less

Numerical Modeling of Complex Targets for High-Energy- Density Experiments with Ion Beams and other Drivers

DOE PAGES

Koniges, Alice; Liu, Wangyi; Lidia, Steven; ...

2016-04-01

We explore the simulation challenges and requirements for experiments planned on facilities such as the NDCX-II ion accelerator at LBNL, currently undergoing commissioning. Hydrodynamic modeling of NDCX-II experiments include certain lower temperature effects, e.g., surface tension and target fragmentation, that are not generally present in extreme high-energy laser facility experiments, where targets are completely vaporized in an extremely short period of time. Target designs proposed for NDCX-II range from metal foils of order one micron thick (thin targets) to metallic foam targets several tens of microns thick (thick targets). These high-energy-density experiments allow for the study of fracture as wellmore » as the process of bubble and droplet formation. We incorporate these physics effects into a code called ALE-AMR that uses a combination of Arbitrary Lagrangian Eulerian hydrodynamics and Adaptive Mesh Refinement. Inclusion of certain effects becomes tricky as we must deal with non-orthogonal meshes of various levels of refinement in three dimensions. A surface tension model used for droplet dynamics is implemented in ALE-AMR using curvature calculated from volume fractions. Thick foam target experiments provide information on how ion beam induced shock waves couple into kinetic energy of fluid flow. Although NDCX-II is not fully commissioned, experiments are being conducted that explore material defect production and dynamics.« less

Physical properties of solar chromospheric plages. III - Models based on Ca II and Mg II observations

NASA Technical Reports Server (NTRS)

Kelch, W. L.; Linsky, J. L.

1978-01-01

Solar plages are modeled using observations of both the Ca II K and the Mg II h and k lines. A partial-redistribution approach is employed for calculating the line profiles on the basis of a grid of five model chromospheres. The computed integrated emission intensities for the five atmospheric models are compared with observations of six regions on the sun as well as with models of active-chromosphere stars. It is concluded that the basic plage model grid proposed by Shine and Linsky (1974) is still valid when the Mg II lines are included in the analysis and the Ca II and Mg II lines are analyzed using partial-redistribution diagnostics.

Effect of Cu(II), Cd(II) and Zn(II) on Pb(II) biosorption by algae Gelidium-derived materials.

PubMed

Vilar, Vítor J P; Botelho, Cidália M S; Boaventura, Rui A R

2008-06-15

Biosorption of Pb(II), Cu(II), Cd(II) and Zn(II) from binary metal solutions onto the algae Gelidium sesquipedale, an algal industrial waste and a waste-based composite material was investigated at pH 5.3, in a batch system. Binary Pb(II)/Cu(II), Pb(II)/Cd(II) and Pb(II)/Zn(II) solutions have been tested. For the same equilibrium concentrations of both metal ions (1 mmol l(-1)), approximately 66, 85 and 86% of the total uptake capacity of the biosorbents is taken by lead ions in the systems Pb(II)/Cu(II), Pb(II)/Cd(II) and Pb(II)/Zn(II), respectively. Two-metal results were fitted to a discrete and a continuous model, showing the inhibition of the primary metal biosorption by the co-cation. The model parameters suggest that Cd(II) and Zn(II) have the same decreasing effect on the Pb(II) uptake capacity. The uptake of Pb(II) was highly sensitive to the presence of Cu(II). From the discrete model it was possible to obtain the Langmuir affinity constant for Pb(II) biosorption. The presence of the co-cations decreases the apparent affinity of Pb(II). The experimental results were successfully fitted by the continuous model, at different pH values, for each biosorbent. The following sequence for the equilibrium affinity constants was found: Pb>Cu>Cd approximately Zn.

C-reactive protein: A differential biomarker for major depressive disorder and bipolar II disorder.

PubMed

Chang, Hui Hua; Wang, Tzu-Yun; Lee, I Hui; Lee, Sheng-Yu; Chen, Kao Chin; Huang, San-Yuan; Yang, Yen Kuang; Lu, Ru-Band; Chen, Po See

2017-02-01

Objectives We aimed to examine whether the C-reactive protein (CRP) level could be used to differentiate between major depressive disorder (MDD) and bipolar II disorder (BD II). Methods Ninety-six healthy controls, 88 BD II and 72 MDD drug-naïve patients in their major depressive episodes were enrolled. The fasting plasma level of high-sensitivity CRP was assessed at baseline and after treatment. Results The BD II patients presented significantly higher 17-item Hamilton Depression Rating Scale (HDRS) scores and CRP levels at baseline when adjustment for age, gender, and body mass index (P <  0.001 and P <  0.001, respectively). After treatment the CRP levels remained significantly different (P <  0.001), although the HDRS score was not significantly different between the BD II and MDD patients. A receiver-operating characteristic analysis showed that a baseline CRP level of 621.6 ng/mL could discriminate between BD II and MDD, with an area under the curve of 0.816 and a sensitivity and specificity of 0.699 and 0.882, respectively. Furthermore, the baseline CRP level greater than 621.6 ng/ml had 28.2 higher odds of a diagnosis of BD II (P <  0.001, 95% confidence interval: 10.96-72.35). Conclusions The level of CRP plays a role of biomarker to differentiate between MDD and BD II depression in both their depressed and euthymic state.

Extreme electronic modulation of the cofacial porphyrin structural motif.

PubMed

Fletcher, James T; Therien, Michael J

2002-04-24

The synthesis, electrochemistry, and optical spectroscopy of an extensive series of cofacial bis[(porphinato)zinc(II)] compounds are reported. These species were synthesized using sequential palladium-catalyzed cross-coupling and cobalt-mediated [2+2+2] cycloaddition reactions. This modular methodology enables facile control of the nature of macrocycle-to-macrocycle connectivity and allows unprecedented modulation of the redox properties of face-to-face porphyrin species. We report the synthesis of 5,6-bis[(5',5''-10',20'-bis[4-(3-methoxy-3-methylbutoxy)phenyl]porphinato)zinc(II)]indane (1), 5,6-bis[(2'-5',10',15',20'-tetraphenylporphinato)zinc(II)]indane (2), 5-([2'-5',10',15',20'-tetraphenylporphinato]zinc(II))-6-[(5"-10'',20''-bis[4-(3-methoxy-3-methylbutoxy)phenyl]porphinato)zinc(II)]indane (3), 5-([2'-5',10',15',20'-tetrakis(trifluoromethyl)porphinato]zinc(II))-6-[(5' '-10' ',20' '-bis[4-(3-methoxy-3-methylbutoxy)phenyl]porphinato)zinc(II)]indane (4), 5-(2'-5',10',15',20'-[tetrakis(trifluoromethyl)porphinato]zinc(II))-6-[(2''-5'',10'',15'',20''-tetraphenylporphinato)zinc(II)]indane (5), 5,6-bis([2'-5',15'-diphenyl-10',20'-(trifluoromethyl)porphinato]zinc(II))indane (6), and 5,6-bis([2'-5',10',15',20'-tetrakis(trifluoromethyl)porphinato]zinc(II))indane (7); 4-7 define the first examples of cofacial bis[(porphinato)metal] compounds in which sigma-electron-withdrawing perfluoroalkyl groups serve as macrocycle substituents, while 2, 6, and 7 constitute the first such structures that possess a beta-to-beta linkage topology. Cyclic voltammetric studies show that the electrochemically determined HOMO and LUMO energy levels of these cofacial bis(porphinato) complexes can be lowered by 780 and 945 mV, respectively, relative to the archetypal members of this class of compounds; importantly, these orbital energy levels can be modulated over well-defined increments throughout these wide potentiometric domains. Analyses of these cofacial bis[(porphinato)metal] potentiometric data, in terms of the absolute and relative frontier orbital energies of their constituent [porphinato]zinc(II) building blocks, as well as the nature of macrocycle-to-macrocycle connectivity, provide predictive electronic structural models that rationalize the redox behavior of these species.

From Neural and Social Cooperation to the Global Emergence of Cognition

PubMed Central

Grigolini, Paolo; Piccinini, Nicola; Svenkeson, Adam; Pramukkul, Pensri; Lambert, David; West, Bruce J.

2015-01-01

The recent article (Turalska et al., 2012) discusses the emergence of intelligence via criticality as a consequence of locality breakdown. Herein, we use criticality for the foundation of a novel generation of game theory making the local interaction between players yield long-range effects. We first establish that criticality is not confined to the Ising-like structure of the sociological model of (Turalska et al., 2012), called the decision making model (DMM), through the study of the emergence of altruism using the altruism-selfishness model (ASM). Both models generate criticality, one by imitation of opinion (DMM) and the other by imitation of behavior (ASM). The dynamics of a sociological network 𝒮 influences the behavioral network ℱ through two game theoretic paradigms: (i) the value of altruism; (ii) the benefit of rapid consensus. In (i), the network 𝒮 debates the moral issue of altruism by means of the DMM, while at the level ℱ the individuals operate according to the ASM. The individuals of the level 𝒮, through a weak influence on the individuals of the level ℱ, exert a societal control on ℱ, fitting the principle of complexity management and complexity matching. In (ii), the benefit to society is the rapid attainment of consensus in the 𝒮 level. The agents of the level ℱ operate according to the prisoner’s dilemma prescription, with the defectors acting as DMM contrarians at the level 𝒮. The contrarians, acting as the inhibitory links of neural networks, exert on society the same beneficial effect of maintaining the criticality-induced resilience that they generate in neural networks. The conflict between personal and social benefit makes the networks evolve toward criticality. Finally, we show that the theory of this article is compatible with recent discoveries in the burgeoning field of social neuroscience. PMID:26137455

Interleukin-6 is a key factor for immunoglobulin-like transcript-4-mediated immune injury in sepsis.

PubMed

Zhang, De Wen; He, Jian

2018-01-01

ILT4 + monocytes seem to be associated with poor prognosis of sepsis in humans, but the exact mechanisms are unknown. This study aimed to examine the biological behaviors and effects of immunoglobulin-like transcript-4 (ILT4) levels on monocytes during sepsis and on the prognosis of sepsis. ILT4 +/+ (WT) and ILT4-knockout (ILT4 -/- ) male BALB/c mice were used for sepsis modeling using cecal ligation puncture (CLP). Flow cytometry was used to measure the levels of ILT4 and major histocompatibility complex class II (MHC-II) on peripheral blood monocytes 24 h after CLP. ELISA was used to measure the serum levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, and IL-12 at 0, 6, 12, and 24 h after CLP. Survival and prognosis were monitored over the course of 168 h. ILT4 was highly expressed in peripheral blood monocytes of septic mice 24 h after CLP (1292.00 ± 143.70 vs. 193.50 ± 52.54, p  < 0.05). MHC-II levels on peripheral blood monocytes in ILT4 -/- mice were significantly higher than those in WT mice (49.38 ± 5.66% vs. 24.25 ± 6.76%, p  < 0.05). Serum IL-6 was significantly elevated 24 h after CLP (470.75 ± 88.03 vs. 54.25 ± 20.04, p  < 0.05). The serum IL-6 levels were significantly lower in ILT4 -/- mice compared with those in WT mice after CLP (241.25 ± 45.10 vs. 470.75 ± 88.03, p  < 0.05), but TNF-α, IL-1β, and IL-12 were not changed. The survival of ILT4 -/- mice was significantly better after CLP compared with that of WT mice. High levels of ILT4 on monocytes were observed in peripheral blood during sepsis and found to be associated with high serum IL-6 levels and low MHC-II levels on monocytes, possibly associated with higher mortality. ILT-4-IL-6-MHC-II could be a potential signaling pathway involved in sepsis.

Childbearing and Economic Work: The Health Balance of Women in Accra, Ghana.

PubMed

Waterhouse, Philippa; Hill, Allan G; Hinde, Andrew

2016-02-01

This study aims to investigate (1) whether the health of working women with young children differs from that of working women without young children, and (2) which social factors mediate the relationship between economic and maternal role performance and health among mothers with young children. The analyses uses panel data from 697 women present in both waves of the Women's Health Study for Accra (WHSA-I and WHSA-II); a community based study of women aged 18 years and older in the Accra Metropolitan Area of Ghana conducted in 2003 and 2008-2009. Change in physical and mental health between the survey waves is compared between women with a biological child alive at WHSA-II and born since WHSA-I and women without a living biological child at WHSA-II born in the interval. To account for attrition between the two survey waves selection models were used with unconditional change score models being used as the outcome model. We found in our sample of working women that those who had a child born between WHSA-I and WHSA-II who was still alive at WHSA-II did not experience a change in mental or physical health different from other women. Among working women with young children, educational status, relationship to the household head and household demography were associated with change in mental health at the 5 % level, whilst migration status and household demography was associated with change in physical health scores. The results suggest there are no health penalties of combining work and childbearing among women with young children in Accra, Ghana.

Fluorescence Lifetime Imaging of Physiological Free Cu(II) Levels in Live Cells with a Cu(II)-Selective Carbonic Anhydrase-Based Biosensor

PubMed Central

McCranor, Bryan J.; Szmacinski, Henryk; Zeng, Hui Hui; Stoddard, A.K.; Hurst, Tamiika; Fierke, Carol A.; Lakowicz, J.R.

2014-01-01

Copper is a required trace element that plays key roles in a number of human enzymes, such that copper deficiency or genetic defects in copper transport lead to serious or fatal disease. Rae, et al., had famously predicted that free copper ion levels in the cell cytoplasm were extremely low, typically too low to be observable. We recently developed a variant of human apocarbonic anhydrase II for sensing metal ions that exhibits 25-fold better selectivity for Cu(II) over Zn(II) than the wild type protein, enabling us to accurately measure Cu(II) in the presence of ordinary cellular (picomolar) concentrations of free zinc. We inserted a fluorescent labeled Cu(II)-specific variant of human apocarbonic anhydrase into PC-12 cells and found that the levels are indeed extremely low (in the femtomolar range). We imaged the free Cu(II) levels in living cells by means of frequency-domain fluorescence lifetime microscopy. Implications of this finding are discussed. PMID:24671220

Annexin II-binding immunoglobulins in patients with lupus nephritis and their correlation with disease manifestations.

PubMed

Cheung, Kwok Fan; Yung, Susan; Chau, Mel K M; Yap, Desmond Y H; Chan, Kwok Wah; Lee, Cheuk Kwong; Tang, Colin S O; Chan, Tak Mao

2017-04-25

Annexin II on mesangial cell surface mediates the binding of anti-dsDNA antibodies and consequent downstream inflammatory and fibrotic processes. We investigated the clinical relevance of circulating annexin II-binding immunoglobulins (Igs) in patients with severe proliferative lupus nephritis, and renal annexin II expression in relation to progression of nephritis in New Zealand Black and White F1 mice (NZBWF1/J) mice. Annexin II-binding Igs in serum were measured by ELISA. Ultrastructural localization of annexin II was determined by electron microscopy. Seropositivity rates for annexin II-binding IgG and IgM in patients with active lupus nephritis were significantly higher compared with controls (8.9%, 1.3% and 0.9% for annexin II-binding IgG and 11.1%, 4.0% and 1.9% for annexin II-binding IgM for patients with active lupus nephritis, patients with non-lupus renal disease and healthy subjects respectively). In lupus patients, annexin II-binding IgM level was higher at disease flare compared with remission. Annexin II-binding IgG and IgM levels were associated with that of anti-dsDNA and disease activity. Annexin II-binding IgG and IgM levels correlated with histological activity index in lupus nephritis biopsy samples. In NZBWF1/J mice, serum annexin II-binding IgG and IgM levels and glomerular annexin II and p11 expression increased with progression of active nephritis. Annexin II expression was present on mesangial cell surface and in the mesangial matrix, and co-localized with electron-dense deposits along the glomerular basement membrane. Our results show that circulating annexin II-binding IgG and IgM levels are associated with clinical and histological disease activity in proliferative lupus nephritis. The co-localization of annexin II and p11 expression with immune deposition in the kidney suggests pathogenic relevance. © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Interpreting the g loadings of intelligence test composite scores in light of Spearman's law of diminishing returns.

PubMed

Reynolds, Matthew R

2013-03-01

The linear loadings of intelligence test composite scores on a general factor (g) have been investigated recently in factor analytic studies. Spearman's law of diminishing returns (SLODR), however, implies that the g loadings of test scores likely decrease in magnitude as g increases, or they are nonlinear. The purpose of this study was to (a) investigate whether the g loadings of composite scores from the Differential Ability Scales (2nd ed.) (DAS-II, C. D. Elliott, 2007a, Differential Ability Scales (2nd ed.). San Antonio, TX: Pearson) were nonlinear and (b) if they were nonlinear, to compare them with linear g loadings to demonstrate how SLODR alters the interpretation of these loadings. Linear and nonlinear confirmatory factor analysis (CFA) models were used to model Nonverbal Reasoning, Verbal Ability, Visual Spatial Ability, Working Memory, and Processing Speed composite scores in four age groups (5-6, 7-8, 9-13, and 14-17) from the DAS-II norming sample. The nonlinear CFA models provided better fit to the data than did the linear models. In support of SLODR, estimates obtained from the nonlinear CFAs indicated that g loadings decreased as g level increased. The nonlinear portion for the nonverbal reasoning loading, however, was not statistically significant across the age groups. Knowledge of general ability level informs composite score interpretation because g is less likely to produce differences, or is measured less, in those scores at higher g levels. One implication is that it may be more important to examine the pattern of specific abilities at higher general ability levels. PsycINFO Database Record (c) 2013 APA, all rights reserved.

ERBB-Receptors and Drug Response in Breast Cancer

DTIC Science & Technology

1997-09-01

in topoisomerase II a (topo II a ) levels seen may be understood by global changes in DNA repair enzymes, brought about by signaling through the EGFR...ErbB-mediated signaling and topoisomerase II a levels specifically as they relate to drug sensitivity/resistance. This information will allow the use...topoisomerase II a levels and increased sensitivity to doxorubicin. In order to determine which, if any, of the specific receptors involved are

Effects of Mg II and Ca II ionization on ab-initio solar chromosphere models

NASA Technical Reports Server (NTRS)

Rammacher, W.; Cuntz, M.

1991-01-01

Acoustically heated solar chromosphere models are computed considering radiation damping by (non-LTE) emission from H(-) and by Mg II and Ca II emission lines. The radiative transfer equations for the Mg II k and Ca II K emission lines are solved using the core-saturation method with complete redistribution. The Mg II k and Ca II K cooling rates are compared with the VAL model C. Several substantial improvements over the work of Ulmschneider et al. (1987) are included. It is found that the rapid temperature rises caused by the ionization of Mg II are not formed in the middle chromosphere, but occur at larger atmospheric heights. These models represent the temperature structure of the 'real' solar chromosphere much better. This result is a major precondition for the study of ab-initio models for solar flux tubes based on MHD wave propagation and also for ab-initio models for the solar transition layer.

Evidence from mathematical modeling that carbonic anhydrase II and IV enhance CO2 fluxes across Xenopus oocyte plasma membranes

PubMed Central

Musa-Aziz, Raif; Boron, Walter F.

2014-01-01

Exposing an oocyte to CO2/HCO3− causes intracellular pH (pHi) to decline and extracellular-surface pH (pHS) to rise to a peak and decay. The two companion papers showed that oocytes injected with cytosolic carbonic anhydrase II (CA II) or expressing surface CA IV exhibit increased maximal rate of pHi change (dpHi/dt)max, increased maximal pHS changes (ΔpHS), and decreased time constants for pHi decline and pHS decay. Here we investigate these results using refinements of an earlier mathematical model of CO2 influx into a spherical cell. Refinements include 1) reduced cytosolic water content, 2) reduced cytosolic diffusion constants, 3) refined CA II activity, 4) layer of intracellular vesicles, 5) reduced membrane CO2 permeability, 6) microvilli, 7) refined CA IV activity, 8) a vitelline membrane, and 9) a new simulation protocol for delivering and removing the bulk extracellular CO2/HCO3− solution. We show how these features affect the simulated pHi and pHS transients and use the refined model with the experimental data for 1.5% CO2/10 mM HCO3− (pHo = 7.5) to find parameter values that approximate ΔpHS, the time to peak pHS, the time delay to the start of the pHi change, (dpHi/dt)max, and the change in steady-state pHi. We validate the revised model against data collected as we vary levels of CO2/HCO3− or of extracellular HEPES buffer. The model confirms the hypothesis that CA II and CA IV enhance transmembrane CO2 fluxes by maximizing CO2 gradients across the plasma membrane, and it predicts that the pH effects of simultaneously implementing intracellular and extracellular-surface CA are supra-additive. PMID:24965589

PPARδ binding to heme oxygenase 1 promoter prevents angiotensin II-induced adipocyte dysfunction in Goldblatt hypertensive rats.

PubMed

Sodhi, K; Puri, N; Kim, D H; Hinds, T D; Stechschulte, L A; Favero, G; Rodella, L; Shapiro, J I; Jude, D; Abraham, N G

2014-03-01

Renin-angiotensin system (RAS) regulates adipogenic response with adipocyte hypertrophy by increasing oxidative stress. Recent studies have shown the role of peroxisome proliferator-activated receptor-δ (PPARδ) agonist in attenuation of angiotensin II-induced oxidative stress. The aim of this study was to explore a potential mechanistic link between PPARδ and the cytoprotective enzyme heme oxygenase-1 (HO-1) and to elucidate the contribution of HO-1 to the adipocyte regulatory effects of PPARδ agonism in an animal model of enhanced RAS, the Goldblatt 2 kidney 1 clip (2K1C) model. We first established a direct stimulatory effect of the PPARδ agonist (GW 501516) on the HO-1 gene by demonstrating increased luciferase activity in COS-7 cells transfected with a luciferase-HO-1 promoter construct. Sprague-Dawley rats were divided into four groups: sham-operated animals, 2K1C rats and 2K1C rats treated with GW 501516, in the absence or presence of the HO activity inhibitor, stannous mesoporphyrin (SnMP). 2K1C animals had increased visceral adiposity, adipocyte hypertrophy, increased inflammatory cytokines, increased circulatory and adipose tisssue levels of renin and Ang II along with increased adipose tissue gp91 phox expression (P<0.05) when compared with sham-operated animals. Treatment with GW 501516 increased adipose tissue HO-1 and adiponectin levels (P<0.01) along with enhancement of Wnt10b and β-catenin expression. HO-1 induction was accompanied by the decreased expression of Wnt5b, mesoderm specific transcript (mest) and C/EBPα levels and an increased number of small adipocytes (P<0.05). These effects of GW501516 were reversed in 2K1C animals exposed to SnMP (P<0.05). Taken together, our study demonstrates, for the first time, that increased levels of Ang II contribute towards adipose tissue dysregulation, which is abated by PPARδ-mediated upregulation of the heme-HO system. These findings highlight the pivotal role and symbiotic relationship of HO-1, adiponectin and PPARδ in the regulation of metabolic homeostasis in adipose tissues.

Intake of melatonin is associated with amelioration of physiological changes, both metabolic and morphological pathologies associated with obesity: an animal model.

PubMed

Hussein, Mahmoud R; Ahmed, Omyma G; Hassan, Asmaa F; Ahmed, Marwa A

2007-02-01

Obesity and its associated metabolic pathologies are the most common and detrimental diseases, affecting over 50% of the adult population. Our knowledge about the protective effects of melatonin against high-fat diet (HFD)-induced obesity is still marginal. In this investigation, we hypothesized that melatonin can minimize the metabolic pathologies and morphological changes associated with obesity in animals receiving an HFD. To examine these effects, and to test our hypothesis, an animal model formed of male Boscat white rabbits was established. The animals were divided into three groups: (i) a control group fed regular diet; (ii) an obesity group fed an HFD for 12 weeks; and (iii) a treated group fed HFD for 12 weeks and then treated with melatonin for 4 weeks. The animals were killed and their serum and tissues were evaluated for: (i) lipid profile (cholesterol, triglycerides and low-density lipoprotein) and glucose; (ii) antioxidant enzyme (serum glutathione peroxidase, GSH-PX); and (iii) fatty changes (liver, kidney and blood vessels). Compared with the control group, intake of HFD (obesity group) was associated with: (i) a statistically significant increase in blood pressure, heart rate, sympathetic nerve activity, body weight, food consumption, serum lipids, blood glucose levels and atherogenic index; (ii) decreased level of GSH-PX and high-density lipoprotein (HDL); and (iii) fatty changes in the liver and kidney as well as atheromatous changes in the blood vessels. Compared with the obesity group, intake of melatonin (treated group) was associated with: (i) a statistically significant decrease in blood pressure, heart rate, sympathetic nerve activity, body weight, food consumption, serum lipids, blood glucose levels and atherogenic index; (ii) increased level of GSH-PX and HDL; and (iii) disappearance of fatty changes in the liver and kidney as well as atheromatous changes in the blood vessels. The administration of melatonin reduced the metabolic pathologies associated with the intake of HFD, suggesting a protective role. Although the underlying mechanisms are unclear, they may include its antioxidant and receptor-mediated effects. The clinical ramifications of these effects await further investigations.

A trauma network with centralized and local health care structures: Evaluating the effectiveness of the first certified Trauma Network of the German Society of Trauma Surgery

PubMed Central

Koller, Michael; Zeman, Florian; Kerschbaum, Maximilian; Hilber, Franz; Diepold, Eva; Loss, Julika; Herbst, Tanja; Nerlich, Michael

2018-01-01

Background Trauma is a global burden of disease and one of the main causes of death worldwide. Therefore, many countries around the world have implemented a wide range of different initiatives to minimize mortality rates after trauma. One of these initiatives is the bundling of treatment expertise in trauma centers and the establishment of trauma networks. Germany has a decentralized system of trauma care medical centers. Severely injured patients ought to receive adequate treatment in both level I and level II centers. This study investigated the effectiveness of a decentralized network and the question whether level I and level II centers have comparable patient outcome. Materials and methods In 2009, the first trauma network DGU® in Germany was certified in the rural area of Eastern Bavaria. All patients admitted to the 25 participating hospitals were prospectively included in this network in the framework of a study sponsored by the German Federal Ministry of Education and Research between March 2012 and February 2014. 2 hospitals were level I centers (maximal care centers), 8 hospitals were level II centers, and 15 hospitals were level III centers. The criterion for study inclusion was an injury severity score (ISS) ≥ 16 for patients´ primarily admitted to a level I or a level II center. Exclusion criteria were transferal to another hospital within 48 h, an unknown revised injury severity classification II score (RISC II), or primary admittance to a level III center (n = 52). 875 patients were included in the study. Univariate analyses were used regarding the preclinical and clinical parameters, the primary endpoint mortality rate, and the secondary endpoints length of stay, organ failure, and neurological outcome (GOS). The primary endpoint was additionally evaluated by means of multivariable analysis. Results Indices for injury severity (GCS, AISHead, ISS, and NISS) as well as the predicted probability of death (RISC II) were higher in level I centers than in level II centers. No significant differences were found between the mortality rate of the unadjusted analysis [level I: 21.6% (CI: 16.5, 27.9), level II: 18.1% (CI: 14.4, 22.5), p = 0.28] and that of the adjusted analysis [level I SMR: 0.94 (CI: 0.72, 1.21), level II SMR: 1.18 (CI 0.95, 1.48) SMR: expected vs. calculated mortality rate according to RISC II]. Multivariable analysis showed a survival advantage of patients admitted to a level I center with a probability of death of 13% (RISC II). The number need to treat was 10 patients. Discussion This study showed that a rural trauma network with centralized and local structures may achieve equivalent results with regard to mortality rates to those obtained in level I and level II centers. These results were furthered by a certain preclinical centralization (24/7 air rescue) of patients. The study also showed a survival advantage of patients admitted to a level I center with a probability of death of 13%. Preclinical and initial clinical evaluation with regard to probable mortality rates should be further improved to identify patients who would benefit from admittance to a level I center. PMID:29538456

A trauma network with centralized and local health care structures: Evaluating the effectiveness of the first certified Trauma Network of the German Society of Trauma Surgery.

PubMed

Ernstberger, Antonio; Koller, Michael; Zeman, Florian; Kerschbaum, Maximilian; Hilber, Franz; Diepold, Eva; Loss, Julika; Herbst, Tanja; Nerlich, Michael

2018-01-01

Trauma is a global burden of disease and one of the main causes of death worldwide. Therefore, many countries around the world have implemented a wide range of different initiatives to minimize mortality rates after trauma. One of these initiatives is the bundling of treatment expertise in trauma centers and the establishment of trauma networks. Germany has a decentralized system of trauma care medical centers. Severely injured patients ought to receive adequate treatment in both level I and level II centers. This study investigated the effectiveness of a decentralized network and the question whether level I and level II centers have comparable patient outcome. In 2009, the first trauma network DGU® in Germany was certified in the rural area of Eastern Bavaria. All patients admitted to the 25 participating hospitals were prospectively included in this network in the framework of a study sponsored by the German Federal Ministry of Education and Research between March 2012 and February 2014. 2 hospitals were level I centers (maximal care centers), 8 hospitals were level II centers, and 15 hospitals were level III centers. The criterion for study inclusion was an injury severity score (ISS) ≥ 16 for patients´ primarily admitted to a level I or a level II center. Exclusion criteria were transferal to another hospital within 48 h, an unknown revised injury severity classification II score (RISC II), or primary admittance to a level III center (n = 52). 875 patients were included in the study. Univariate analyses were used regarding the preclinical and clinical parameters, the primary endpoint mortality rate, and the secondary endpoints length of stay, organ failure, and neurological outcome (GOS). The primary endpoint was additionally evaluated by means of multivariable analysis. Indices for injury severity (GCS, AISHead, ISS, and NISS) as well as the predicted probability of death (RISC II) were higher in level I centers than in level II centers. No significant differences were found between the mortality rate of the unadjusted analysis [level I: 21.6% (CI: 16.5, 27.9), level II: 18.1% (CI: 14.4, 22.5), p = 0.28] and that of the adjusted analysis [level I SMR: 0.94 (CI: 0.72, 1.21), level II SMR: 1.18 (CI 0.95, 1.48) SMR: expected vs. calculated mortality rate according to RISC II]. Multivariable analysis showed a survival advantage of patients admitted to a level I center with a probability of death of 13% (RISC II). The number need to treat was 10 patients. This study showed that a rural trauma network with centralized and local structures may achieve equivalent results with regard to mortality rates to those obtained in level I and level II centers. These results were furthered by a certain preclinical centralization (24/7 air rescue) of patients. The study also showed a survival advantage of patients admitted to a level I center with a probability of death of 13%. Preclinical and initial clinical evaluation with regard to probable mortality rates should be further improved to identify patients who would benefit from admittance to a level I center.

Selection of a high-affinity and in vivo bioactive ssDNA aptamer against angiotensin II peptide.

PubMed

Heiat, Mohammad; Ranjbar, Reza; Latifi, Ali Mohammad; Rasaee, Mohammad Javad

2016-08-01

Unique features of aptamers have attracted interests for a broad range of applications. Aptamers are able to specifically bind to targets and inhibit their functions. This study, aimed to isolate the high affinity ssDNA aptamers against bio-regulator peptide angiotensin II (Ang II) and investigate their bioactivity in cellular and animal models. To isolate ssDNA aptamers, 12 rounds of affinity chromatography SELEX (Systematic Evolution of Ligands by EXponential enrichment) procedure were carried out. The SPR (surface plasmon resonance) and ELONA (enzyme linked oligonucleotide assay) analysis were used to determine the affinity and specificity of aptamers. The ability of selected aptamers to inhibit the proliferative effect of Ang II on human aortic vascular smooth muscle cells (HA-VSMCs) and their performance on Wistar rat urinary system and serum electrolyte levels were investigated. Two full-length aptamers (FLC112 and FLC125) with high affinity of respectively 7.52±2.44E-10 and 5.87±1.3E-9M were isolated against Ang II. The core regions of these aptamers (CRC112 and CRC125) also showed affinity of 5.33±1.15E-9 and 4.11±1.09E-9M. In vitro analysis revealed that FLC112 and FLC125 can inhibit the proliferative effect of Ang II on HA-VSMCs (P<0.05). They also significantly reduced the serum sodium level and increased the urine volume (P<0.05). The core regions of aptamers did not show high inhibitory potential against Ang II. It can be a spotlight that ssDNA aptamers have high potential for blocking Ang II. In conclusion, it appears that the researches focusing on high affinity and bioactive aptamers may lead to excellent results in blocking Ang II activity. Copyright © 2016 Elsevier Inc. All rights reserved.

SEISRISK II; a computer program for seismic hazard estimation

USGS Publications Warehouse

Bender, Bernice; Perkins, D.M.

1982-01-01

The computer program SEISRISK II calculates probabilistic ground motion values for use in seismic hazard mapping. SEISRISK II employs a model that allows earthquakes to occur as points within source zones and as finite-length ruptures along faults. It assumes that earthquake occurrences have a Poisson distribution, that occurrence rates remain constant during the time period considered, that ground motion resulting from an earthquake is a known function of magnitude and distance, that seismically homogeneous source zones are defined, that fault locations are known, that fault rupture lengths depend on magnitude, and that earthquake rates as a function of magnitude are specified for each source. SEISRISK II calculates for each site on a grid of sites the level of ground motion that has a specified probability of being exceeded during a given time period. The program was designed to process a large (essentially unlimited) number of sites and sources efficiently and has been used to produce regional and national maps of seismic hazard.}t is a substantial revision of an earlier program SEISRISK I, which has never been documented. SEISRISK II runs considerably [aster and gives more accurate results than the earlier program and in addition includes rupture length and acceleration variability which were not contained in the original version. We describe the model and how it is implemented in the computer program and provide a flowchart and listing of the code.

Near-Field Acoustic Power Level Analysis of F31/A31 Open Rotor Model at Simulated Cruise Conditions, Technical Report II

NASA Technical Reports Server (NTRS)

Sree, Dave

2015-01-01

Near-field acoustic power level analysis of F31A31 open rotor model has been performed to determine its noise characteristics at simulated cruise flight conditions. The non-proprietary parts of the test data obtained from experiments in the 8x6 supersonic wind tunnel were provided by NASA-Glenn Research Center. The tone and broadband components of total noise have been separated from raw test data by using a new data analysis tool. Results in terms of sound pressure levels, acoustic power levels, and their variations with rotor speed, freestream Mach number, and input shaft power, with different blade-pitch setting angles at simulated cruise flight conditions, are presented and discussed. Empirical equations relating models acoustic power level and input shaft power have been developed. The near-field acoustic efficiency of the model at simulated cruise conditions is also determined. It is hoped that the results presented in this work will serve as a database for comparison and improvement of other open rotor blade designs and also for validating open rotor noise prediction codes.

Comparing Families of Dynamic Causal Models

PubMed Central

Penny, Will D.; Stephan, Klaas E.; Daunizeau, Jean; Rosa, Maria J.; Friston, Karl J.; Schofield, Thomas M.; Leff, Alex P.

2010-01-01

Mathematical models of scientific data can be formally compared using Bayesian model evidence. Previous applications in the biological sciences have mainly focussed on model selection in which one first selects the model with the highest evidence and then makes inferences based on the parameters of that model. This “best model” approach is very useful but can become brittle if there are a large number of models to compare, and if different subjects use different models. To overcome this shortcoming we propose the combination of two further approaches: (i) family level inference and (ii) Bayesian model averaging within families. Family level inference removes uncertainty about aspects of model structure other than the characteristic of interest. For example: What are the inputs to the system? Is processing serial or parallel? Is it linear or nonlinear? Is it mediated by a single, crucial connection? We apply Bayesian model averaging within families to provide inferences about parameters that are independent of further assumptions about model structure. We illustrate the methods using Dynamic Causal Models of brain imaging data. PMID:20300649

The phenotypic equilibrium of cancer cells: From average-level stability to path-wise convergence.

PubMed

Niu, Yuanling; Wang, Yue; Zhou, Da

2015-12-07

The phenotypic equilibrium, i.e. heterogeneous population of cancer cells tending to a fixed equilibrium of phenotypic proportions, has received much attention in cancer biology very recently. In the previous literature, some theoretical models were used to predict the experimental phenomena of the phenotypic equilibrium, which were often explained by different concepts of stabilities of the models. Here we present a stochastic multi-phenotype branching model by integrating conventional cellular hierarchy with phenotypic plasticity mechanisms of cancer cells. Based on our model, it is shown that: (i) our model can serve as a framework to unify the previous models for the phenotypic equilibrium, and then harmonizes the different kinds of average-level stabilities proposed in these models; and (ii) path-wise convergence of our model provides a deeper understanding to the phenotypic equilibrium from stochastic point of view. That is, the emergence of the phenotypic equilibrium is rooted in the stochastic nature of (almost) every sample path, the average-level stability just follows from it by averaging stochastic samples. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prenatal Testosterone Exposure Decreases Aldosterone Production but Maintains Normal Plasma Volume and Increases Blood Pressure in Adult Female Rats.

PubMed

More, Amar S; Mishra, Jay S; Hankins, Gary D; Kumar, Sathish

2016-08-01

Plasma testosterone levels are elevated in pregnant women with preeclampsia and polycystic ovaries; their offspring are at increased risk for hypertension during adult life. We tested the hypothesis that prenatal testosterone exposure induces dysregulation of the renin-angiotensin-aldosterone system, which is known to play an important role in water and electrolyte balance and blood pressure regulation. Female rats (6 mo old) prenatally exposed to testosterone were examined for adrenal expression of steroidogenic genes, telemetric blood pressure, blood volume and Na(+) and K(+) levels, plasma aldosterone, angiotensin II and vasopressin levels, and vascular responses to angiotensin II and arg(8)-vasopressin. The levels of Cyp11b2 (aldosterone synthase), but not the other adrenal steroidogenic genes, were decreased in testosterone females. Accordingly, plasma aldosterone levels were lower in testosterone females. Plasma volume and serum and urine Na(+) and K(+) levels were not significantly different between control and testosterone females; however, prenatal testosterone exposure significantly increased plasma vasopressin and angiotensin II levels and arterial pressure in adult females. In testosterone females, mesenteric artery contractile responses to angiotensin II were significantly greater, while contractile responses to vasopressin were unaffected. Angiotensin II type-1 receptor expression was increased, while angiotensin II type-2 receptor was decreased in testosterone arteries. These results suggest that prenatal testosterone exposure downregulates adrenal Cyp11b2 expression, leading to decreased plasma aldosterone levels. Elevated angiotensin II and vasopressin levels along with enhanced vascular responsiveness to angiotensin II may serve as an underlying mechanism to maintain plasma volume and Na(+) and K(+) levels and mediate hypertension in adult testosterone females. © 2016 by the Society for the Study of Reproduction, Inc.

Oral Assessment Kit, Levels II & III. Draft.

ERIC Educational Resources Information Center

Agrelo-Gonzalez, Maria; And Others

The assessment packet includes a series of oral tests to help develop speaking as an integral part of second language instruction at levels II and III. It contains: 8 mini-tests for use at level II; 9 mini-tests for use at level III; a rating scale and score sheet masters for evaluating performance on these tests; and a collection of suggested…

PHISICS/RELAP5-3D RESULTS FOR EXERCISES II-1 AND II-2 OF THE OECD/NEA MHTGR-350 BENCHMARK

DOE Office of Scientific and Technical Information (OSTI.GOV)

Strydom, Gerhard

2016-03-01

The Idaho National Laboratory (INL) Advanced Reactor Technologies (ART) High-Temperature Gas-Cooled Reactor (HTGR) Methods group currently leads the Modular High-Temperature Gas-Cooled Reactor (MHTGR) 350 benchmark. The benchmark consists of a set of lattice-depletion, steady-state, and transient problems that can be used by HTGR simulation groups to assess the performance of their code suites. The paper summarizes the results obtained for the first two transient exercises defined for Phase II of the benchmark. The Parallel and Highly Innovative Simulation for INL Code System (PHISICS), coupled with the INL system code RELAP5-3D, was used to generate the results for the Depressurized Conductionmore » Cooldown (DCC) (exercise II-1a) and Pressurized Conduction Cooldown (PCC) (exercise II-2) transients. These exercises require the time-dependent simulation of coupled neutronics and thermal-hydraulics phenomena, and utilize the steady-state solution previously obtained for exercise I-3 of Phase I. This paper also includes a comparison of the benchmark results obtained with a traditional system code “ring” model against a more detailed “block” model that include kinetics feedback on an individual block level and thermal feedbacks on a triangular sub-mesh. The higher spatial fidelity that can be obtained by the block model is illustrated with comparisons of the maximum fuel temperatures, especially in the case of natural convection conditions that dominate the DCC and PCC events. Differences up to 125 K (or 10%) were observed between the ring and block model predictions of the DCC transient, mostly due to the block model’s capability of tracking individual block decay powers and more detailed helium flow distributions. In general, the block model only required DCC and PCC calculation times twice as long as the ring models, and it therefore seems that the additional development and calculation time required for the block model could be worth the gain that can be obtained in the spatial resolution« less

Performance of the IOTA ADNEX model in preoperative discrimination of adnexal masses in a gynecological oncology center.

PubMed

Araujo, K G; Jales, R M; Pereira, P N; Yoshida, A; de Angelo Andrade, L; Sarian, L O; Derchain, S

2017-06-01

To evaluate the performance of the International Ovarian Tumor Analysis (IOTA) ADNEX model in the preoperative discrimination between benign ovarian (including tubal and para-ovarian) tumors, borderline ovarian tumors (BOT), Stage I ovarian cancer (OC), Stage II-IV OC and ovarian metastasis in a gynecological oncology center in Brazil. This was a diagnostic accuracy study including 131 women with an adnexal mass invited to participate between February 2014 and November 2015. Before surgery, pelvic ultrasound examination was performed and serum levels of tumor marker CA 125 were measured in all women. Adnexal masses were classified according to the IOTA ADNEX model. Histopathological diagnosis was the gold standard. Receiver-operating characteristics (ROC) curve analysis was used to determine the diagnostic accuracy of the model to classify tumors into different histological types. Of 131 women, 63 (48.1%) had a benign ovarian tumor, 16 (12.2%) had a BOT, 17 (13.0%) had Stage I OC, 24 (18.3%) had Stage II-IV OC and 11 (8.4%) had ovarian metastasis. The area under the ROC curve (AUC) was 0.92 (95% CI, 0.88-0.97) for the basic discrimination between benign vs malignant tumors using the IOTA ADNEX model. Performance was high for the discrimination between benign vs Stage II-IV OC, BOT vs Stage II-IV OC and Stage I OC vs Stage II-IV OC, with AUCs of 0.99, 0.97 and 0.94, respectively. Performance was poor for the differentiation between BOT vs Stage I OC and between Stage I OC vs ovarian metastasis with AUCs of 0.64. The majority of adnexal masses in our study were classified correctly using the IOTA ADNEX model. On the basis of our findings, we would expect the model to aid in the management of women with an adnexal mass presenting to a gynecological oncology center. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Kinetic Model Facilitates Analysis of Fibrin Generation and Its Modulation by Clotting Factors: Implications for Hemostasis-Enhancing Therapies

DTIC Science & Technology

2014-01-01

facilitates analysis of fibrin generation and its modulation by clotting factors : implications for hemostasis-enhancing therapies† Alexander Y...investigate the ability of fibrinogen and a recently proposed prothrombin complex concentrate composition, PCC-AT (a combination of the clotting factors II...kinetics. Moreover, the model qualitatively predicted the impact of tissue factor and tPA/tenecteplase level variations on the fibrin output. In the

The effects of two different hypocaloric diets on glucagon-like peptide 1 in obese adults, relation with insulin response after weight loss.

PubMed

de Luis, Daniel A; Sagrado, Manuel Gonzalez; Conde, Rosa; Aller, Rocio; Izaola, Olatz

2009-01-01

Few studies have investigated the effect of type of diets on GLP-1 concentrations. The aim of this study was to compare the effect of two diets on circulating GLP-1 levels and the relation with insulin response after weight loss. A population of 118 obese patients were analyzed. Patients were randomly allocated to two groups: (a) Diet I (low carbohydrate) and (b) Diet II (low fat). Biochemical and anthropometric parameters were measured before and after 3 months of hypocaloric diet. Fifty-two patients (12 male/40 female) were treated with Diet I and 66 patients (21 male/45 female) with Diet II. In Group I, basal GLP-1 levels did not change after dietary treatment (9.4+/-3.3 vs. 9.9+/-3.1 ng/ml; ns). In Group II, GLP-1 levels decreased significantly (8.4%) (9.2+/-3.3 vs 8.7+/-3.1 ng/ml; P<.05). In the multivariate analysis with a dependent variable (levels of GLP-1), only insulin levels remained as an independent predictor in the model (F=5.9; P<.05), with an increase of 0.6 ng/ml (95% CI 0.1-1.1) GLP-1 concentrations with each increase of 1 mUI/ml of insulin. A hypocaloric diet with a low fat percentage decreased GLP-1 levels with a direct correlation with insulin levels. Nevertheless, patients with a hypocaloric diet with a low carbohydrate percentage treatment did not change GLP-1 levels. Diet macronutrient manipulation on GLP-1 response could be useful in an obesity nutrition therapy.

GLYDE-II: The GLYcan data exchange format

PubMed Central

Ranzinger, Rene; Kochut, Krys J.; Miller, John A.; Eavenson, Matthew; Lütteke, Thomas; York, William S.

2017-01-01

Summary The GLYcan Data Exchange (GLYDE) standard has been developed for the representation of the chemical structures of monosaccharides, glycans and glycoconjugates using a connection table formalism formatted in XML. This format allows structures, including those that do not exist in any database, to be unambiguously represented and shared by diverse computational tools. GLYDE implements a partonomy model based on human language along with rules that provide consistent structural representations, including a robust namespace for specifying monosaccharides. This approach facilitates the reuse of data processing software at the level of granularity that is most appropriate for extraction of the desired information. GLYDE-II has already been used as a key element of several glycoinformatics tools. The philosophical and technical underpinnings of GLYDE-II and recent implementation of its enhanced features are described. PMID:28955652

A multi-level simulation platform of natural gas internal reforming solid oxide fuel cell-gas turbine hybrid generation system - Part II. Balancing units model library and system simulation

NASA Astrophysics Data System (ADS)

Bao, Cheng; Cai, Ningsheng; Croiset, Eric

2011-10-01

Following our integrated hierarchical modeling framework of natural gas internal reforming solid oxide fuel cell (IRSOFC), this paper firstly introduces the model libraries of main balancing units, including some state-of-the-art achievements and our specific work. Based on gPROMS programming code, flexible configuration and modular design are fully realized by specifying graphically all unit models in each level. Via comparison with the steady-state experimental data of Siemens-Westinghouse demonstration system, the in-house multi-level SOFC-gas turbine (GT) simulation platform is validated to be more accurate than the advanced power system analysis tool (APSAT). Moreover, some units of the demonstration system are designed reversely for analysis of a typically part-load transient process. The framework of distributed and dynamic modeling in most of units is significant for the development of control strategies in the future.

Concepts and tools for predictive modeling of microbial dynamics.

PubMed

Bernaerts, Kristel; Dens, Els; Vereecken, Karen; Geeraerd, Annemie H; Standaert, Arnout R; Devlieghere, Frank; Debevere, Johan; Van Impe, Jan F

2004-09-01

Description of microbial cell (population) behavior as influenced by dynamically changing environmental conditions intrinsically needs dynamic mathematical models. In the past, major effort has been put into the modeling of microbial growth and inactivation within a constant environment (static models). In the early 1990s, differential equation models (dynamic models) were introduced in the field of predictive microbiology. Here, we present a general dynamic model-building concept describing microbial evolution under dynamic conditions. Starting from an elementary model building block, the model structure can be gradually complexified to incorporate increasing numbers of influencing factors. Based on two case studies, the fundamentals of both macroscopic (population) and microscopic (individual) modeling approaches are revisited. These illustrations deal with the modeling of (i) microbial lag under variable temperature conditions and (ii) interspecies microbial interactions mediated by lactic acid production (product inhibition). Current and future research trends should address the need for (i) more specific measurements at the cell and/or population level, (ii) measurements under dynamic conditions, and (iii) more comprehensive (mechanistically inspired) model structures. In the context of quantitative microbial risk assessment, complexity of the mathematical model must be kept under control. An important challenge for the future is determination of a satisfactory trade-off between predictive power and manageability of predictive microbiology models.

Predictors of activity limitation in people with gout: a prospective study.

PubMed

Stewart, Sarah; Rome, Keith; Eason, Alastair; House, Meaghan E; Horne, Anne; Doyle, Anthony J; Knight, Julie; Taylor, William J; Dalbeth, Nicola

2018-04-21

The objective of the study was to determine clinical factors associated with activity limitation and predictors of a change in activity limitation after 1 year in people with gout. Two hundred ninety-five participants with gout (disease duration < 10 years) attended a baseline assessment which included medical and disease-specific history, pain visual analog score and plain radiographs scored for erosion and narrowing. Activity limitation was assessed using the Health Assessment Questionnaire-II (HAQ-II). After 1 year, participants were invited to complete a further HAQ-II; follow-up questionnaires were available for 182 participants. Fully saturated and stepwise regression analyses were used to determine associations between baseline characteristics and HAQ-II at baseline and 1 year, and to determine predictors of worsening HAQ-II in those with normal baseline scores. Median (range) baseline HAQ-II was 0.20 (0-2.50) and 0.20 (0-2.80) after 1 year of follow-up. Pain score was the strongest independent predictor of baseline HAQ-II, followed by radiographic narrowing score, type 2 diabetes, swollen joint count, BMI, age and urate (model R 2  = 0.51, P < 0.001). Baseline HAQ-II was the strongest predictor of change in HAQ-II at 1 year, followed by tender joint count (model R 2  = 0.19, P < 0.001). Of those with HAQ-II scores of 0 at baseline (n = 59, 32% of those with follow-up data), most did not progress (n = 52, 88%); however, baseline pain score, type 2 diabetes and flare frequency were significant predictors of worsening HAQ-II in this group (R 2  = 0.34, P < 0.001). People with gout experience a wide range of activity limitation, and levels of activity limitation are, on average, stable over a 1-year period. Baseline pain scores are strongly associated with activity limitation and predict development of activity limitation in those with normal HAQ-II scores at baseline.

Empirical prediction of peak pressure levels in anthropogenic impulsive noise. Part I: Airgun arrays signals.

PubMed

Galindo-Romero, Marta; Lippert, Tristan; Gavrilov, Alexander

2015-12-01

This paper presents an empirical linear equation to predict peak pressure level of anthropogenic impulsive signals based on its correlation with the sound exposure level. The regression coefficients are shown to be weakly dependent on the environmental characteristics but governed by the source type and parameters. The equation can be applied to values of the sound exposure level predicted with a numerical model, which provides a significant improvement in the prediction of the peak pressure level. Part I presents the analysis for airgun arrays signals, and Part II considers the application of the empirical equation to offshore impact piling noise.

Angiotensin II Causes Neuronal Damage in Stretch-Injured Neurons: Protective Effects of Losartan, an Angiotensin T1 Receptor Blocker.

PubMed

Abdul-Muneer, P M; Bhowmick, Saurav; Briski, Nicholas

2017-11-08

Angiotensin II (Ang II) is a mediator of oxidative stress via activation/induction of reactive oxygen and nitrogen species-generating enzymes, NADPH oxidase (NOX) and inducible nitric oxide synthase (iNOS). We investigated the hypothesis that overproduction of Ang II during traumatic brain injury (TBI) induces the activation of the oxidative stress, which triggers neuroinflammation and cell apoptosis in a cell culture model of neuronal stretch injury. We first established that stretch injury causes a rapid increase in the level of Ang II, which causes the release of pro-inflammatory cytokines, IL-1β and TNF-α, via the induction of oxidative stress. Since angiotensin-converting enzyme (ACE) mediates the production of Ang II via the conversion of Ang I into Ang II, we analyzed the expression of ACE by western blotting. Further, we analyzed caspase-3-mediated apoptosis by TUNEL staining and annexin V western blotting. Angiotensin type I (AT 1 ) receptor antagonist losartan attenuated Ang II-induced oxidative stress and associated neuroinflammation and cell death in cultured neurons. Remarkably, we noticed that the expression of Ang II type 1 receptor (AngT 1 R) upregulated in neuronal stretch injury; losartan mitigates this upregulation. Findings from this study significantly extend our understanding of the pathophysiology of TBI and may have significant implications for developing therapeutic strategies for TBI-associated brain dysfunctions.

NAAG Peptidase Inhibitors Act via mGluR3: Animal Models of Memory, Alzheimer's, and Ethanol Intoxication.

PubMed

Olszewski, Rafal T; Janczura, Karolina J; Bzdega, Tomasz; Der, Elise K; Venzor, Faustino; O'Rourke, Brennen; Hark, Timothy J; Craddock, Kirsten E; Balasubramanian, Shankar; Moussa, Charbel; Neale, Joseph H

2017-09-01

Glutamate carboxypeptidase II (GCPII) inactivates the peptide neurotransmitter N-acetylaspartylglutamate (NAAG) following synaptic release. Inhibitors of GCPII increase extracellular NAAG levels and are efficacious in animal models of clinical disorders via NAAG activation of a group II metabotropic glutamate receptor. mGluR2 and mGluR3 knock-out (ko) mice were used to test the hypothesis that mGluR3 mediates the activity of GCPII inhibitors ZJ43 and 2-PMPA in animal models of memory and memory loss. Short- (1.5 h) and long- (24 h) term novel object recognition tests were used to assess memory. Treatment with ZJ43 or 2-PMPA prior to acquisition trials increased long-term memory in mGluR2, but not mGluR3, ko mice. Nine month-old triple transgenic Alzheimer's disease model mice exhibited impaired short-term novel object recognition memory that was rescued by treatment with a NAAG peptidase inhibitor. NAAG peptidase inhibitors and the group II mGluR agonist, LY354740, reversed the short-term memory deficit induced by acute ethanol administration in wild type mice. 2-PMPA also moderated the effect of ethanol on short-term memory in mGluR2 ko mice but failed to do so in mGluR3 ko mice. LY354740 and ZJ43 blocked ethanol-induced motor activation. Both GCPII inhibitors and LY354740 also significantly moderated the loss of motor coordination induced by 2.1 g/kg ethanol treatment. These data support the conclusion that inhibitors of glutamate carboxypeptidase II are efficacious in object recognition models of normal memory and memory deficits via an mGluR3 mediated process, actions that could have widespread clinical applications.

Renal Angiotensin-Converting Enzyme Is Essential for the Hypertension Induced by Nitric Oxide Synthesis Inhibition

PubMed Central

Giani, Jorge F.; Janjulia, Tea; Kamat, Nikhil; Seth, Dale M.; Blackwell, Wendell-Lamar B.; Shah, Kandarp H.; Shen, Xiao Z.; Fuchs, Sebastien; Delpire, Eric; Toblli, Jorge E.; Bernstein, Kenneth E.; McDonough, Alicia A.

2014-01-01

The kidney is an important source of angiotensin-converting enzyme (ACE) in many species, including humans. However, the specific effects of local ACE on renal function and, by extension, BP control are not completely understood. We previously showed that mice lacking renal ACE, are resistant to the hypertension induced by angiotensin II infusion. Here, we examined the responses of these mice to the low-systemic angiotensin II hypertensive model of nitric oxide synthesis inhibition with L-NAME. In contrast to wild-type mice, mice without renal ACE did not develop hypertension, had lower renal angiotensin II levels, and enhanced natriuresis in response to L-NAME. During L-NAME treatment, the absence of renal ACE was associated with blunted GFR responses; greater reductions in abundance of proximal tubule Na+/H+ exchanger 3, Na+/Pi co-transporter 2, phosphorylated Na+/K+/Cl− cotransporter, and phosphorylated Na+/Cl− cotransporter; and greater reductions in abundance and processing of the γ isoform of the epithelial Na+ channel. In summary, the presence of ACE in renal tissue facilitates angiotensin II accumulation, GFR reductions, and changes in the expression levels and post-translational modification of sodium transporters that are obligatory for sodium retention and hypertension in response to nitric oxide synthesis inhibition. PMID:25012170

Mediator MED23 regulates basal transcription in vivo via an interaction with P-TEFb.

PubMed

Wang, Wei; Yao, Xiao; Huang, Yan; Hu, Xiangming; Liu, Runzhong; Hou, Dongming; Chen, Ruichuan; Wang, Gang

2013-01-01

The Mediator is a multi-subunit complex that transduces regulatory information from transcription regulators to the RNA polymerase II apparatus. Growing evidence suggests that Mediator plays roles in multiple stages of eukaryotic transcription, including elongation. However, the detailed mechanism by which Mediator regulates elongation remains elusive. In this study, we demonstrate that Mediator MED23 subunit controls a basal level of transcription by recruiting elongation factor P-TEFb, via an interaction with its CDK9 subunit. The mRNA level of Egr1, a MED23-controlled model gene, is reduced 4-5 fold in Med23 (-/-) ES cells under an unstimulated condition, but Med23-deficiency does not alter the occupancies of RNAP II, GTFs, Mediator complex, or activator ELK1 at the Egr1 promoter. Instead, Med23 depletion results in a significant decrease in P-TEFb and RNAP II (Ser2P) binding at the coding region, but no changes for several other elongation regulators, such as DSIF and NELF. ChIP-seq revealed that Med23-deficiency partially reduced the P-TEFb occupancy at a set of MED23-regulated gene promoters. Further, we demonstrate that MED23 interacts with CDK9 in vivo and in vitro. Collectively, these results provide the mechanistic insight into how Mediator promotes RNAP II into transcription elongation.

Polymer blend particles with defined compositions for targeting antigen to both class I and II antigen presentation pathways

PubMed Central

Tran, Kenny K.; Zhan, Xi; Shen, Hong

2013-01-01

Defense against many persistent and difficult-to-treat diseases requires a combination of humoral, CD4+ and CD8+ T cell responses, which necessitates targeting antigens to both class I and II antigen presentation pathways. In this study, we developed polymer blend particles by mixing two functionally unique polymers, poly(lactide-co-glycolide) (PLGA) and a pH-responsive polymer, poly(dimethylaminoethyl methacrylate-co-propylacrylic acid-co-butyl methacrylate) (DMAEMA-co-PAA-co-BMA). We showed polymer blend particles enabled the delivery of antigens into both class I and II antigen presentation pathways in vitro. Increasing the ratio of the pH-responsive polymer in blend particles increased the degree of class I antigen presentation, while maintaining high levels of class II antigen presentation. In a mouse model, we demonstrated that a significantly higher and sustained level of CD4+ and CD8+ T cell responses, and comparable antibody responses, were elicited with polymer blend particles than PLGA particles and a conventional vaccine, Alum. The polymer blend particles offer a potential vaccine delivery platform to generate a combination of humoral and cell-mediated immune responses that insure robust and long-lasting immunity against many infectious diseases and cancers. PMID:24124123

Comparability of AMH levels among commercially available immunoassays

PubMed Central

Su, H. Irene; Sammel, Mary D.; Homer, Michael V.; Bui, Kim; Haunschild, Carolyn; Stanczyk, Frank Z.

2015-01-01

Objective To compare AMH levels among three commercially available AMH immunoassays (AMH Gen II, Beckman Coulter; Ultrasensitive AMH, AnshLab; picoAMH, AnshLab) Design Cross-sectional Setting Academic reproductive endocrinology program Patients 90 newly diagnosed breast cancer patients prior to cancer treatment Interventions None Outcome 1) proportion of detectable AMH levels by immunoassay, 2) comparability among assays Results At a mean age of 38.1, the median (interquartile range) for AMH levels for the cohort were 0.92 [1.35] ng/mL for the Gen II assay, 1.68 [2.30] ng/mL for the Ultrasensitive and 1.5 [2.41] ng/mL for the picoAMH assays. Significantly higher proportions of detectable AMH levels were observed with the picoAMH kit (97%) compared to both Gen II (84%) and Ultrasensitive (92%) assays. Although AMH results were highly correlated among assays (r=0.92–0.99), Gen II AMH levels were consistently lower than both Ultrasensitive and picoAMH levels. Moreover, as AMH levels increased, the magnitude of difference grew larger between Gen II and each of the other two assays. Conclusions Measurement of AMH levels with the picoAMH kit maximized detection at very low levels, particularly in contrast to the Gen II kit. Conversion of AMH levels from different immunoassays using regression equations is potentially highly inaccurate. PMID:24726216

Computer Assisted Vocational Math. Written for TRS-80, Model I, Level II, 16K.

ERIC Educational Resources Information Center

Daly, Judith; And Others

This computer-assisted curriculum is intended to be used to enhance a vocational mathematics/applied mathematics course. A total of 32 packets were produced to increase the basic mathematics skills of students in the following vocational programs: automotive trades, beauty culture, building trades, climate control, electrical trades,…

Establishing a Spinal Injury Criterion for Military Seats

DTIC Science & Technology

1997-01-01

Table represents 54 Trials (18 [phase I] + 36 [phase II]); "Combined Effects" of Delta V, Gpk & ATD Size illM-l A General Linear Model (GLM) analysis...5thpercentilemale AID would not have compliedwith the tolerance criterion under the higher impulse severity levels (i.e., 20 and 30 Gpk ). Similarly, the

Dynamic Evaluation of CMAQ Part II: Evaluation of relative response factor metrics for ozone attainment demonstrations

EPA Science Inventory

The U.S. Environmental Protection Agency provides guidelines on the use of air quality models for projecting whether an emission reduction strategy will lead to future pollutant levels that are at or below the National Ambient Air Quality Standards (NAAQS). The EPA's guidance doc...

Antibody-functionalized polymer nanoparticle leading to memory recovery in Alzheimer's disease-like transgenic mouse model.

PubMed

Carradori, Dario; Balducci, Claudia; Re, Francesca; Brambilla, Davide; Le Droumaguet, Benjamin; Flores, Orfeu; Gaudin, Alice; Mura, Simona; Forloni, Gianluigi; Ordoñez-Gutierrez, Lara; Wandosell, Francisco; Masserini, Massimo; Couvreur, Patrick; Nicolas, Julien; Andrieux, Karine

2018-02-01

Alzheimer's disease (AD) is a neurodegenerative disorder related, in part, to the accumulation of amyloid-β peptide (Aβ) and especially the Aβ peptide 1-42 (Aβ 1-42 ). The aim of this study was to design nanocarriers able to: (i) interact with the Aβ 1-42 in the blood and promote its elimination through the "sink effect" and (ii) correct the memory defect observed in AD-like transgenic mice. To do so, biodegradable, PEGylated nanoparticles were surface-functionalized with an antibody directed against Aβ 1-42 . Treatment of AD-like transgenic mice with anti-Aβ 1-42 -functionalized nanoparticles led to: (i) complete correction of the memory defect; (ii) significant reduction of the Aβ soluble peptide and its oligomer level in the brain and (iii) significant increase of the Aβ levels in plasma. This study represents the first example of Aβ 1-42 monoclonal antibody-decorated nanoparticle-based therapy against AD leading to complete correction of the memory defect in an experimental model of AD. Copyright © 2017 Elsevier Inc. All rights reserved.

Anomalous Nernst and thermal Hall effects in tilted Weyl semimetals

NASA Astrophysics Data System (ADS)

Ferreiros, Yago; Zyuzin, A. A.; Bardarson, Jens H.

2017-09-01

We study the anomalous Nernst and thermal Hall effects in a linearized low-energy model of a tilted Weyl semimetal, with two Weyl nodes separated in momentum space. For inversion symmetric tilt, we give analytic expressions in two opposite limits: For a small tilt, corresponding to a type-I Weyl semimetal, the Nernst conductivity is finite and independent of the Fermi level; for a large tilt, corresponding to a type-II Weyl semimetal, it acquires a contribution depending logarithmically on the Fermi energy. This result is in a sharp contrast to the nontilted case, where the Nernst response is known to be zero in the linear model. The thermal Hall conductivity similarly acquires Fermi surface contributions, which add to the Fermi level-independent, zero-tilt result, and is suppressed as one over the tilt parameter at half filling in the type-II phase. In the case of inversion-breaking tilt, with the tilting vector of equal modulus in the two Weyl cones, all Fermi surface contributions to both anomalous responses cancel out, resulting in zero Nernst conductivity. We discuss two possible experimental setups, representing open and closed thermoelectric circuits.

Geometry-dependent distributed polarizability models for the water molecule

DOE Office of Scientific and Technical Information (OSTI.GOV)

Loboda, Oleksandr; Ingrosso, Francesca; Ruiz-López, Manuel F.

2016-01-21

Geometry-dependent distributed polarizability models have been constructed by fits to ab initio calculations at the coupled cluster level of theory with up to noniterative triple excitations in an augmented triple-zeta quality basis set for the water molecule in the field of a point charge. The investigated models include (i) charge-flow polarizabilities between chemically bonded atoms, (ii) isotropic or anisotropic dipolar polarizabilities on oxygen atom or on all atoms, and (iii) combinations of models (i) and (ii). For each model, the polarizability parameters have been optimized to reproduce the induction energy of a water molecule polarized by a point charge successivelymore » occupying a grid of points surrounding the molecule. The quality of the models is ascertained by examining their ability to reproduce these induction energies as well as the molecular dipolar and quadrupolar polarizabilities. The geometry dependence of the distributed polarizability models has been explored by changing bond lengths and HOH angle to generate 125 molecular structures (reduced to 75 symmetry-unique ones). For each considered model, the distributed polarizability components have been fitted as a function of the geometry by a Taylor expansion in monomer coordinate displacements up to the sum of powers equal to 4.« less

TOWARD DETECTING THE 2175 A DUST FEATURE ASSOCIATED WITH STRONG HIGH-REDSHIFT Mg II ABSORPTION LINES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang Peng; Zhou Hongyan; Wang Junxian

2011-05-10

We report detections of 39 2175 A dust extinction bump candidates associated with strong Mg II absorption lines at z{approx} 1-1.8 on quasar spectra in Sloan Digital Sky Survey (SDSS) DR3. These strong Mg II absorption line systems are detected among 2951 strong Mg II absorbers with a rest equivalent width W{sub r} {lambda}2796> 1.0 A at 1.0 < z < 1.86, which is part of a full sample of 7421 strong Mg II absorbers compiled by Prochter et al. The redshift range of the absorbers is chosen to allow the 2175 A extinction features to be completely covered withinmore » the SDSS spectrograph operation wavelength range. An upper limit of the background quasar emission redshift at z = 2.1 is set to prevent the Ly{alpha} forest lines from contaminating the sensitive spectral region for the 2175 A bump measurements. The FM90 parameterization is applied to model the optical/UV extinction curve in the rest frame of Mg II absorbers of the 2175 A bump candidates. The simulation technique developed by Jiang et al. is used to derive the statistical significance of the candidate 2175 A bumps. A total of 12 absorbers are detected with 2175 A bumps at a 5{sigma} level of statistical significance, 10 are detected at a 4{sigma} level, and 17 are detected at a 3{sigma} level. Most of the candidate bumps in this work are similar to the relatively weak 2175 A bumps observed in the Large Magellanic Cloud LMC2 supershell rather than the strong ones observed in the Milky Way. This sample has greatly increased the total number of 2175 A extinction bumps measured on SDSS quasar spectra. Follow-up observations may rule out some of the possible false detections and reveal the physical and chemical natures of 2175 A quasar absorbers.« less

Toward Detecting the 2175 Å Dust Feature Associated with Strong High-redshift Mg II Absorption Lines

NASA Astrophysics Data System (ADS)

Jiang, Peng; Ge, Jian; Zhou, Hongyan; Wang, Junxian; Wang, Tinggui

2011-05-01

We report detections of 39 2175 Å dust extinction bump candidates associated with strong Mg II absorption lines at z~ 1-1.8 on quasar spectra in Sloan Digital Sky Survey (SDSS) DR3. These strong Mg II absorption line systems are detected among 2951 strong Mg II absorbers with a rest equivalent width Wr λ2796> 1.0 Å at 1.0 < z < 1.86, which is part of a full sample of 7421 strong Mg II absorbers compiled by Prochter et al. The redshift range of the absorbers is chosen to allow the 2175 Å extinction features to be completely covered within the SDSS spectrograph operation wavelength range. An upper limit of the background quasar emission redshift at z = 2.1 is set to prevent the Lyα forest lines from contaminating the sensitive spectral region for the 2175 Å bump measurements. The FM90 parameterization is applied to model the optical/UV extinction curve in the rest frame of Mg II absorbers of the 2175 Å bump candidates. The simulation technique developed by Jiang et al. is used to derive the statistical significance of the candidate 2175 Å bumps. A total of 12 absorbers are detected with 2175 Å bumps at a 5σ level of statistical significance, 10 are detected at a 4σ level, and 17 are detected at a 3σ level. Most of the candidate bumps in this work are similar to the relatively weak 2175 Å bumps observed in the Large Magellanic Cloud LMC2 supershell rather than the strong ones observed in the Milky Way. This sample has greatly increased the total number of 2175 Å extinction bumps measured on SDSS quasar spectra. Follow-up observations may rule out some of the possible false detections and reveal the physical and chemical natures of 2175 Å quasar absorbers.

Biosorption of Fe(II) and Mn(II) Ions from Aqueous Solution by Rice Husk Ash

PubMed Central

Zhao, Jiaying; Jiang, Zhao; Shan, Dexin; Lu, Yan

2014-01-01

Rice husk ash (RHA), an agricultural waste, was used as biosorbent for the removal of Iron(II) and Manganese(II) ions from aqueous solutions. The structural and morphological characteristics of RHA and its elemental compositions before and after adsorption of Fe(II) and Mn(II) were determined by scanning electron microscopic (SEM) and X-ray fluorescence (XRF) analyses. Batch experiments were carried out to determine the influence of initial pH, contact time, adsorbent dosage, and initial concentration on the removal of Fe(II) and Mn(II) ions. Langmuir, Freundlich, and Dubinin-Radushkevich (D-R) models were applied to describe the biosorption isotherm of the metal ions by RHA. The correlation coefficient (R 2) of Langmuir and Freundlich isotherm models equals 0.995 and 0.901 for Fe(II), 0.9862 and 0.8924 for Mn(II), respectively, so the Langmuir model fitted the equilibrium data better than the Freundlich isotherm model. The mean free energy values evaluated from the D-R model indicated that the biosorption of Fe(II) and Mn(II) onto RHA was physical in nature. Experimental data also showed that the biosorption processes of both metal ions complied with the pseudo-second-order kinetics. PMID:24982918

Lifestyle changes during adolescence and risk of breast cancer: an ecologic study of the effect of World War II in Norway.

PubMed

Tretli, S; Gaard, M

1996-09-01

There are biologic reasons to believe that the period between the larche and the first full-term pregnancy is a particularly sensitive period in a woman's life regarding the development of breast cancer. In this ecologic study, data provided by the Norwegian Cancer Registry were analyzed to compare risk of breast cancer among women who experienced this sensitive period before, during, or after World War II. An ordinary age-cohort model and a model where the cohort was described by exposure by calendar period and sensitivity to this exposure at different ages, were fitted to the data. The incidence of breast cancer was lower than expected among women who experienced puberty during the war. The estimated configuration of the exposure variable showed an increase in exposure up to the start of WWII to twice the level in 1916, dropped by 13 percent during the war, and increased again after the war. The level in 1975 was approximately 2.7 times higher than the level in 1916. The results indicate that one or more lifestyle factors that changed among adolescent women during the war, influenced their risk of breast cancer. Dietary intake of energy, fat, meat, milk, fish, fresh vegetables, and potatoes, in addition to physical activity level and height, are important factors to consider in relation to breast cancer risk.

Deep Segmentation from 2D Forward Modeling and 3D Tomography of the Maranhão-Barreirinhas-Ceará Margin, NW Brazil

NASA Astrophysics Data System (ADS)

Afonso Dias, Nuno; Afilhado, Alexandra; Schnürle, Philippe; Gallais, Flora; Soares, José; Fuck, Reinhardt; Cupertino, José; Viana, Adriano; Moulin, Maryline; Aslanian, Daniel; Matias, Luís; Evain, Mikael; Loureiro, Afonso

2017-04-01

The deep crustal structure of the North-East equatorial Brazilian margin, was investigated during the MAGIC (Margins of brAzil, Ghana and Ivory Coast) joint project, conducted in 2012. The main goal set to understand the fundamental processes leading to the thinning and finally breakup of the continental crust, in a context of a Pull-apart system with two strike-slip borders. The offshore Barreirinhas Basin, was probed by a set of 5 intersecting deep seismic wide-angle profiles, with the deployment of short-period OBS's from IFREMER and land stations from the Brazilian pool. The experiment was devoted to obtain the 2D structure along the directions of flow lines, parallel to margin segmentation and margin segmentation, from tomography and forward modeling. The OBS's deployed recorded also lateral shooting along some profiles, allowing a 3D tomography inversion complementing the results of 2D modeling. Due to the large variation of the water column thickness, heterogeneous crustal structure and Moho depth, several approaches were tested to generate initial input models, to set the grid parameterization and inversion parameters. The assessment of the 3D model was performed by standard synthetic tests and comparison with the obtained 2D forward models. The results evidence a NW-SE segmentation of the margin, following the opening direction of this pull-apart basin, and N-S segmentation that marks the passage between Basins II-III. The signature of the segmentation is evident in the tomograms, where the shallowing of the basement from Basin II towards the oceanic domain is well marked by a NW-SE velocity gradient. Both 2D forward modeling and 3D tomographic inversion indicate a N-S segmentation in the proto-oceanic and oceanic domains, at least at the shallow mantle level. In the southern area the mantle is much faster than on the north. In all profiles crossing Basin II, a deep layer with velocities of 7-4-7.6 km/s generates both refracted as well as reflected phases from its boundaries, in agreement with the 3D model, which indicate a much more gradual transition of crustal velocities to mantle-velocities, than in the remaining segments. The intersection of Basins II, III and proto-oceanic crust is well marked by the absence of seismic energy propagation at deep crust to mantle levels, with no lateral arrival being recorded. Publication supported by FCT- project UID/GEO/50019/2013 - Instituto Dom Luiz.

Profile of von Willebrand factor antigen and von Willebrand factor propeptide in an overall TIA and ischaemic stroke population and amongst subtypes.

PubMed

Tobin, W O; Kinsella, J A; Kavanagh, G F; O'Donnell, J S; McGrath, R T; Tierney, S; Egan, B; Feeley, T M; Coughlan, T; Collins, D R; O'Neill, D; Murphy, Sjx; Lim, S J; Murphy, R P; McCabe, Djh

2017-04-15

Von Willebrand factor propeptide (VWF:Ag II) is proposed to be a more sensitive marker of acute endothelial activation than von Willebrand factor antigen (VWF:Ag). Simultaneous data on VWF:Ag and VWF:Ag II profiles are very limited following TIA and ischaemic stroke. In this prospective, observational, case-control study, plasma VWF:Ag and VWF:Ag II levels were quantified in 164 patients≤4weeks of TIA or ischaemic stroke (baseline), and then ≥14days (14d) and ≥90days (90d) later, and compared with those from 27 healthy controls. TIA and stroke subtyping was performed according to the TOAST classification. The relationship between VWF:Ag and VWF:Ag II levels and platelet activation status was assessed. 'Unadjusted' VWF:Ag and VWF:Ag II levels were higher in patients at baseline, 14d and 90d than in controls (p≤0.03). VWF:Ag levels remained higher in patients than controls at baseline (p≤0.03), but not at 14d or 90d after controlling for differences in age or hypertension, and were higher in patients at baseline and 90d after controlling for smoking status (p≤0.04). 'Adjusted' VWF:Ag II levels were not higher in patients than controls after controlling for age, hypertension or smoking (p≥0.1). Patients with symptomatic carotid stenosis (N=46) had higher VWF:Ag and VWF:Ag II levels than controls at all time-points (p≤0.002). There was no significant correlation between platelet activation status and VWF:Ag or VWF:Ag II levels. VWF:Ag and VWF:Ag II levels are increased in an overall TIA and ischaemic stroke population, especially in patients with recently symptomatic carotid stenosis. VWF:Ag II was not superior to VWF:Ag at detecting acute endothelial activation in this cohort and might reflect timing of blood sampling in our study. Copyright © 2017 Elsevier B.V. All rights reserved.

Despite similar reduction of blood pressure and renal ANG II and ET-1 levels aliskiren but not losartan normalizes albuminuria in hypertensive Ren-2 rats.

PubMed

Vanourková, Z; Kramer, H J; Husková, Z; Cervenka, L; Vanecková, I

2010-01-01

The relationship between angiotensin II (ANG II) and endothelin-1 (ET-1) is known to be complex; both peptides can initiate and potentiate the gene expression of each other. This pilot study investigated the effects of the AT(1) receptor blocker losartan or the direct renin inhibitor aliskiren on mean arterial pressure (MAP) and albuminuria and the renal ANG II and ET-1 levels. 3-month-old male Ren-2 transgenic rats (TGR) were treated either with losartan (5 mg kg(-1) day(-1)) or aliskiren (10 mg kg(-1) day(-1)) for 10 weeks. At the end of the experiment, rats were decapitated and cortical and papillary parts of kidneys were separated. Plasma and tissue ANG II levels were measured by RIA and tissue ET-1 concentrations by ELISA. In all four groups of animals ET-1 levels were lowest in renal cortex and more than 100-fold higher in the papilla. Cortical and papillary ET-1 concentrations in untreated TGR significantly exceeded those of control HanSD rats and were significantly depressed by both drugs. In both strains, papillary ANG II concentrations were moderately but significantly higher than cortical ANG II, TGR exhibited higher ANG II levels both in cortex and papilla as compared to control HanSD rats. Aliskiren and losartan at the doses used depressed similarly the levels of ANG II in cortex and papilla and reduced ET-1 significantly in the renal cortex and papilla below control levels in HanSD rats. Albuminuria, which was more than twice as high in TGR as in HanSD rats, was normalized with aliskiren and reduced by 28% with losartan, although MAP was reduced to a similar degree by both drugs. Despite similar reductions of MAP and renal ET-1 and ANG II levels aliskiren appears to be more effective than losartan, at the doses used, in reducing albuminuria in heterozygous hypertensive Ren-2 rats.

Natriuretic peptide receptor-C activation attenuates angiotensin II-induced enhanced oxidative stress and hyperproliferation of aortic vascular smooth muscle cells.

PubMed

Madiraju, Padma; Hossain, Ekhtear; Anand-Srivastava, Madhu B

2018-02-07

We showed previously that natriuretic peptide receptor-C (NPR-C) agonist, C-ANP 4-23 , attenuated the enhanced expression of Giα proteins in vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) through the inhibition of enhanced oxidative stress. Since the enhanced levels of endogenous angiotensin II (Ang II) contribute to the overexpression of Giα proteins and augmented oxidative stress in VSMC from SHR, the present study was undertaken to investigate if C-ANP 4-23 could also attenuate angiotensin II (Ang II)-induced oxidative stress and associated signaling. Ang II treatment of aortic VSMC augmented the levels of superoxide anion (O 2 - ), NADPH oxidase activity, and the expression of NADPH oxidase subunits and C-ANP 4-23 treatment attenuated all these to control levels. In addition, Ang II-induced enhanced levels of thiobarbituric acid-reactive substances (TBARS) and protein carbonyl content were also attenuated toward control levels by C-ANP 4-23 treatment. On the other hand, Ang II inhibited the levels of nitric oxide (NO) and augmented the levels of peroxynitrite (OONO - ) in VSMC which were restored to control levels by C-ANP 4-23 treatment. Furthermore, C-ANP 4-23 treatment attenuated Ang II-induced enhanced expression of Giα proteins, phosphorylation of p38, JNK, and ERK 1,2 as well as hyperproliferation of VSMC as determined by DNA synthesis, and metabolic activity. These results indicate that C-ANP 4-23 , via the activation of NPR-C, attenuates Ang II-induced enhanced nitroxidative stress, overexpression of Giα proteins, increased activation of the p38/JNK/ERK 1,2 signaling pathways, and hyperproliferation of VSMC. It may be suggested that C-ANP 4-23 could be used as a therapeutic agent in the treatment of vascular remodeling associated with hypertension and atherosclerosis.

Using Pop-II models to predict effects of wolf predation and hunter harvests on elk, mule deer, and moose on the northern range

USGS Publications Warehouse

Mack, John A.; Singer, Francis J.

1993-01-01

The effects of establishing a gray wolf (Canis lupus) population in Yellowstone National Park were predicted for three ungulate species—elk (Cervus elaphus), mule deer (Odocoileus hemionus), and moose (Alces alces)—using previously developed POP-II population models. We developed models for 78 and 100 wolves. For each wolf population, we ran scenarios using wolf predation rates of 9, 12, and 15 ungulates/wolf/year. With 78 wolves and the antlerless elk harvest reduced 27%, our modeled elk population estimated were 5-18% smaller than the model estimate without wolves. With 100 wolves and the antlerless elk harvest reduced 27%, our elk population estimated were 11-30% smaller than the population estimates without wolves. Wolf predation effects were greater on the modeled mule deer population than on elk. With 78 wolves and no antlerless deer harvest, we predicted the mule deer population could be 13-44% larger than without wolves. With 100 wolves and no antlerless deer harvest, the mule deer population was 0-36% larger than without wolves. After wolf recovery, our POP-II models suggested moose harvests would have to be reduced at least 50% to maintain moose numbers at the levels predicted when wolves were not present. Mule deer and moose population data are limited, and these wolf predation effects may be overestimated if population sizes or male-female ratios were underestimated in our population models. We recommend additional mule deer and moose population data be obtained.

Robust Linear Models for Cis-eQTL Analysis.

PubMed

Rantalainen, Mattias; Lindgren, Cecilia M; Holmes, Christopher C

2015-01-01

Expression Quantitative Trait Loci (eQTL) analysis enables characterisation of functional genetic variation influencing expression levels of individual genes. In outbread populations, including humans, eQTLs are commonly analysed using the conventional linear model, adjusting for relevant covariates, assuming an allelic dosage model and a Gaussian error term. However, gene expression data generally have noise that induces heavy-tailed errors relative to the Gaussian distribution and often include atypical observations, or outliers. Such departures from modelling assumptions can lead to an increased rate of type II errors (false negatives), and to some extent also type I errors (false positives). Careful model checking can reduce the risk of type-I errors but often not type II errors, since it is generally too time-consuming to carefully check all models with a non-significant effect in large-scale and genome-wide studies. Here we propose the application of a robust linear model for eQTL analysis to reduce adverse effects of deviations from the assumption of Gaussian residuals. We present results from a simulation study as well as results from the analysis of real eQTL data sets. Our findings suggest that in many situations robust models have the potential to provide more reliable eQTL results compared to conventional linear models, particularly in respect to reducing type II errors due to non-Gaussian noise. Post-genomic data, such as that generated in genome-wide eQTL studies, are often noisy and frequently contain atypical observations. Robust statistical models have the potential to provide more reliable results and increased statistical power under non-Gaussian conditions. The results presented here suggest that robust models should be considered routinely alongside other commonly used methodologies for eQTL analysis.

Prescribing smoked cannabis for chronic noncancer pain: preliminary recommendations.

PubMed

Kahan, Meldon; Srivastava, Anita; Spithoff, Sheryl; Bromley, Lisa

2014-12-01

To offer preliminary guidance on prescribing smoked cannabis for chronic pain before the release of formal guidelines. We reviewed the literature on the analgesic effectiveness of smoked cannabis and the harms of medical and recreational cannabis use. We developed recommendations on indications, contraindications, precautions, and dosing of smoked cannabis, and categorized the recommendations based on levels of evidence. Evidence is mostly level II (well conducted observational studies) and III (expert opinion). Smoked cannabis might be indicated for patients with severe neuropathic pain conditions who have not responded to adequate trials of pharmaceutical cannabinoids and standard analgesics (level II evidence). Smoked cannabis is contraindicated in patients who are 25 years of age or younger (level II evidence); who have a current, past, or strong family history of psychosis (level II evidence); who have a current or past cannabis use disorder (level III evidence); who have a current substance use disorder (level III evidence); who have cardiovascular or respiratory disease (level III evidence); or who are pregnant or planning to become pregnant (level II evidence). It should be used with caution in patients who smoke tobacco (level II evidence), who are at increased risk of cardiovascular disease (level III evidence), who have anxiety or mood disorders (level II evidence), or who are taking higher doses of opioids or benzodiazepines (level III evidence). Cannabis users should be advised not to drive for at least 3 to 4 hours after smoking, for at least 6 hours after oral ingestion, and for at least 8 hours if they experience a subjective "high" (level II evidence). The maximum recommended dose is 1 inhalation 4 times per day (approximately 400 mg per day) of dried cannabis containing 9% delta-9-tetrahydrocannabinol (level III evidence). Physicians should avoid referring patients to "cannabinoid" clinics (level III evidence). Future guidelines should be based on systematic review of the literature on the safety and effectiveness of smoked cannabis. Further research is needed on the effectiveness and long-term safety of smoked cannabis compared with pharmaceutical cannabinoids, opioids, and other standard analgesics. Copyright© the College of Family Physicians of Canada.

Prescribing smoked cannabis for chronic noncancer pain

PubMed Central

Kahan, Meldon; Srivastava, Anita; Spithoff, Sheryl; Bromley, Lisa

2014-01-01

Objective To offer preliminary guidance on prescribing smoked cannabis for chronic pain before the release of formal guidelines. Quality of evidence We reviewed the literature on the analgesic effectiveness of smoked cannabis and the harms of medical and recreational cannabis use. We developed recommendations on indications, contraindications, precautions, and dosing of smoked cannabis, and categorized the recommendations based on levels of evidence. Evidence is mostly level II (well conducted observational studies) and III (expert opinion). Main message Smoked cannabis might be indicated for patients with severe neuropathic pain conditions who have not responded to adequate trials of pharmaceutical cannabinoids and standard analgesics (level II evidence). Smoked cannabis is contraindicated in patients who are 25 years of age or younger (level II evidence); who have a current, past, or strong family history of psychosis (level II evidence); who have a current or past cannabis use disorder (level III evidence); who have a current substance use disorder (level III evidence); who have cardiovascular or respiratory disease (level III evidence); or who are pregnant or planning to become pregnant (level II evidence). It should be used with caution in patients who smoke tobacco (level II evidence), who are at increased risk of cardiovascular disease (level III evidence), who have anxiety or mood disorders (level II evidence), or who are taking higher doses of opioids or benzodiazepines (level III evidence). Cannabis users should be advised not to drive for at least 3 to 4 hours after smoking, for at least 6 hours after oral ingestion, and for at least 8 hours if they experience a subjective “high” (level II evidence). The maximum recommended dose is 1 inhalation 4 times per day (approximately 400 mg per day) of dried cannabis containing 9% delta-9-tetrahydrocannabinol (level III evidence). Physicians should avoid referring patients to “cannabinoid” clinics (level III evidence). Conclusion Future guidelines should be based on systematic review of the literature on the safety and effectiveness of smoked cannabis. Further research is needed on the effectiveness and long-term safety of smoked cannabis compared with pharmaceutical cannabinoids, opioids, and other standard analgesics. PMID:25500598

Novel method of vulnerability assessment of simple landfills area using the multimedia, multipathway and multireceptor risk assessment (3MRA) model, China.

PubMed

Yuan, Ying; He, Xiao-Song; Xi, Bei-Dou; Wei, Zi-Min; Tan, Wen-Bing; Gao, Ru-Tai

2016-11-01

Vulnerability assessment of simple landfills was conducted using the multimedia, multipathway and multireceptor risk assessment (3MRA) model for the first time in China. The minimum safe threshold of six contaminants (benzene, arsenic (As), cadmium (Cd), hexavalent chromium [Cr(VI)], divalent mercury [Hg(II)] and divalent nickel [Ni(II)]) in landfill and waste pile models were calculated by the 3MRA model. Furthermore, the vulnerability indexes of the six contaminants were predicted based on the model calculation. The results showed that the order of health risk vulnerability index was As > Hg(II) > Cr(VI) > benzene > Cd > Ni(II) in the landfill model, whereas the ecology risk vulnerability index was in the order of As > Hg(II) > Cr(VI) > Cd > benzene > Ni(II). In the waste pile model, the order of health risk vulnerability index was benzene > Hg(II) > Cr(VI) > As > Cd and Ni(II), whereas the ecology risk vulnerability index was in the order of Hg(II) > Cd > Cr(VI) > As > benzene > Ni(II). These results indicated that As, Hg(II) and Cr(VI) were the high risk contaminants for the case of a simple landfill in China; the concentration of these in soil and groundwater around the simple landfill should be strictly monitored, and proper mediation is also recommended for simple landfills with a high concentration of contaminants. © The Author(s) 2016.

Multiaxial behavior of foams - Experiments and modeling

NASA Astrophysics Data System (ADS)

Maheo, Laurent; Guérard, Sandra; Rio, Gérard; Donnard, Adrien; Viot, Philippe

2015-09-01

Cellular materials are strongly related to pressure level inside the material. It is therefore important to use experiments which can highlight (i) the pressure-volume behavior, (ii) the shear-shape behavior for different pressure level. Authors propose to use hydrostatic compressive, shear and combined pressure-shear tests to determine cellular materials behavior. Finite Element Modeling must take into account these behavior specificities. Authors chose to use a behavior law with a Hyperelastic, a Viscous and a Hysteretic contributions. Specific developments has been performed on the Hyperelastic one by separating the spherical and the deviatoric part to take into account volume change and shape change characteristics of cellular materials.

Modeling joint restoration strategies for interdependent infrastructure systems

PubMed Central

Simonovic, Slobodan P.

2018-01-01

Life in the modern world depends on multiple critical services provided by infrastructure systems which are interdependent at multiple levels. To effectively respond to infrastructure failures, this paper proposes a model for developing optimal joint restoration strategy for interdependent infrastructure systems following a disruptive event. First, models for (i) describing structure of interdependent infrastructure system and (ii) their interaction process, are presented. Both models are considering the failure types, infrastructure operating rules and interdependencies among systems. Second, an optimization model for determining an optimal joint restoration strategy at infrastructure component level by minimizing the economic loss from the infrastructure failures, is proposed. The utility of the model is illustrated using a case study of electric-water systems. Results show that a small number of failed infrastructure components can trigger high level failures in interdependent systems; the optimal joint restoration strategy varies with failure occurrence time. The proposed models can help decision makers to understand the mechanisms of infrastructure interactions and search for optimal joint restoration strategy, which can significantly enhance safety of infrastructure systems. PMID:29649300

Age, size, and position of H ii regions in the Galaxy. Expansion of ionized gas in turbulent molecular clouds

NASA Astrophysics Data System (ADS)

Tremblin, P.; Anderson, L. D.; Didelon, P.; Raga, A. C.; Minier, V.; Ntormousi, E.; Pettitt, A.; Pinto, C.; Samal, M. R.; Schneider, N.; Zavagno, A.

2014-08-01

Aims: This work aims to improve the current understanding of the interaction between H ii regions and turbulent molecular clouds. We propose a new method to determine the age of a large sample of OB associations by investigating the development of their associated H ii regions in the surrounding turbulent medium. Methods: Using analytical solutions, one-dimensional (1D), and three-dimensional (3D) simulations, we constrained the expansion of the ionized bubble depending on the turbulence level of the parent molecular cloud. A grid of 1D simulations was then computed in order to build isochrone curves for H ii regions in a pressure-size diagram. This grid of models allowed us to date a large sample of OB associations that we obtained from the H ii Region Discovery Survey (HRDS). Results: Analytical solutions and numerical simulations showed that the expansion of H ii regions is slowed down by the turbulence up to the point where the pressure of the ionized gas is in a quasi-equilibrium with the turbulent ram pressure. Based on this result, we built a grid of 1D models of the expansion of H ii regions in a profile based on Larson's laws. We take the 3D turbulence into account with an effective 1D temperature profile. The ages estimated by the isochrones of this grid agree well with literature values of well known regions such as Rosette, RCW 36, RCW 79, and M 16. We thus propose that this method can be used to find ages of young OB associations through the Galaxy and also in nearby extra-galactic sources.

Bacopa monniera (L.) wettst inhibits type II collagen-induced arthritis in rats.

PubMed

Viji, V; Kavitha, S K; Helen, A

2010-09-01

Bacopa monniera (L.) Wettst is an Ayurvedic herb with antirheumatic potential. This study investigated the therapeutic efficacy of Bacopa monniera in treating rheumatoid arthritis using a type II collagen-induced arthritis rat model. Arthritis was induced in male Wistar rats by immunization with bovine type II collagen in complete Freund's adjuvant. Bacopa monniera extract (BME) was administered after the development of arthritis from day 14 onwards. The total duration of experiment was 60 days. Paw swelling, arthritic index, inflammatory mediators such as cyclooxygenase, lipoxygenase, myeloperoxidase and serum anti-collagen IgG and IgM levels were analysed in control and experimental rats. Arthritic induction significantly increased paw edema and other classical signs of arthritis coupled to upregulation of inflammatory mediators such as cyclooxygenase, lipoxygenase, neutrophil infiltration and increased anti-collagen IgM and IgG levels in serum. BME significantly inhibited the footpad swelling and arthritic symptoms. BME was effective in inhibiting cyclooxygenase and lipoxygenase activities in arthritic rats. Decreased neutrophil infiltration was evident from decreased myeloperoxidase activity and histopathological data where an improvement in joint architecture was also observed. Serum anti-collagen IgM and IgG levels were consistently decreased. Thus the study demonstrates the potential antiarthritic effect of Bacopa monniera for treating arthritis which might confer its antirheumatic activity. Copyright 2010 John Wiley & Sons, Ltd.

Pecan nutshell as biosorbent to remove Cu(II), Mn(II) and Pb(II) from aqueous solutions.

PubMed

Vaghetti, Julio C P; Lima, Eder C; Royer, Betina; da Cunha, Bruna M; Cardoso, Natali F; Brasil, Jorge L; Dias, Silvio L P

2009-02-15

In the present study we reported for the first time the feasibility of pecan nutshell (PNS, Carya illinoensis) as an alternative biosorbent to remove Cu(II), Mn(II) and Pb(II) metallic ions from aqueous solutions. The ability of PNS to remove the metallic ions was investigated by using batch biosorption procedure. The effects such as, pH, biosorbent dosage on the adsorption capacities of PNS were studied. Four kinetic models were tested, being the adsorption kinetics better fitted to fractionary-order kinetic model. Besides that, the kinetic data were also fitted to intra-particle diffusion model, presenting three linear regions, indicating that the kinetics of adsorption should follow multiple sorption rates. The equilibrium data were fitted to Langmuir, Freundlich, Sips and Redlich-Peterson isotherm models. Taking into account a statistical error function, the data were best fitted to Sips isotherm model. The maximum biosorption capacities of PNS were 1.35, 1.78 and 0.946mmolg(-1) for Cu(II), Mn(II) and Pb(II), respectively.

Modeling the mechanism of glycosylation reactions between ethanol, 1,2-ethanediol and methoxymethanol.

PubMed

Azofra, Luis Miguel; Alkorta, Ibon; Toro-Labbé, Alejandro; Elguero, José

2013-09-07

The mechanism of the S(N)2 model glycosylation reaction between ethanol, 1,2-ethanediol and methoxymethanol has been studied theoretically at the B3LYP/6-311+G(d,p) computational level. Three different types of reactions have been explored: (i) the exchange of hydroxyl groups between these model systems; (ii) the basic catalysis reactions by combination of the substrates as glycosyl donors (neutral species) and acceptors (enolate species); and (iii) the effect on the reaction profile of an explicit H2O molecule in the reactions considered in (ii). The reaction force, the electronic chemical potential and the reaction electronic flux have been characterized for the reaction path in each case. Energy calculations show that methoxymethanol is the worst glycosyl donor model among the ones studied here, while 1,2-ethanediol is the best, having the lowest activation barrier of 74.7 kJ mol(-1) for the reaction between this one and the ethanolate as the glycosyl acceptor model. In general, the presence of direct interactions between the atoms involved in the penta-coordinated TS increases the activation energies of the processes.

Mercerized mesoporous date pit activated carbon—A novel adsorbent to sequester potentially toxic divalent heavy metals from water

PubMed Central

Aldawsari, Abdullah; Hameed, B. H.; Alqadami, Ayoub Abdullah; Siddiqui, Masoom Raza; Alothman, Zeid Abdullah; Ahmed, A. Yacine Badjah Hadj

2017-01-01

A substantive approach converting waste date pits to mercerized mesoporous date pit activated carbon (DPAC) and utilizing it in the removal of Cd(II), Cu(II), Pb(II), and Zn(II) was reported. In general, rapid heavy metals adsorption kinetics for Co range: 25–100 mg/L was observed, accomplishing 77–97% adsorption within 15 min, finally, attaining equilibrium in 360 min. Linear and non-linear isotherm studies revealed Langmuir model applicability for Cd(II) and Pb(II) adsorption, while Freundlich model was fitted to Zn(II) and Cu(II) adsorption. Maximum monolayer adsorption capacities (qm) for Cd(II), Pb(II), Cu(II), and Zn(II) obtained by non-linear isotherm model at 298 K were 212.1, 133.5, 194.4, and 111 mg/g, respectively. Kinetics modeling parameters showed the applicability of pseudo-second-order model. The activation energy (Ea) magnitude revealed physical nature of adsorption. Maximum elution of Cu(II) (81.6%), Zn(II) (70.1%), Pb(II) (96%), and Cd(II) (78.2%) were observed with 0.1 M HCl. Thermogravimetric analysis of DPAC showed a total weight loss (in two-stages) of 28.3%. Infra-red spectral analysis showed the presence of carboxyl and hydroxyl groups over DPAC surface. The peaks at 820, 825, 845 and 885 cm-1 attributed to Zn–O, Pb–O, Cd–O, and Cu–O appeared on heavy metals saturated DPAC, confirmed their binding on DPAC during the adsorption. PMID:28910368

Mercerized mesoporous date pit activated carbon-A novel adsorbent to sequester potentially toxic divalent heavy metals from water.

PubMed

Aldawsari, Abdullah; Khan, Moonis Ali; Hameed, B H; Alqadami, Ayoub Abdullah; Siddiqui, Masoom Raza; Alothman, Zeid Abdullah; Ahmed, A Yacine Badjah Hadj

2017-01-01

A substantive approach converting waste date pits to mercerized mesoporous date pit activated carbon (DPAC) and utilizing it in the removal of Cd(II), Cu(II), Pb(II), and Zn(II) was reported. In general, rapid heavy metals adsorption kinetics for Co range: 25-100 mg/L was observed, accomplishing 77-97% adsorption within 15 min, finally, attaining equilibrium in 360 min. Linear and non-linear isotherm studies revealed Langmuir model applicability for Cd(II) and Pb(II) adsorption, while Freundlich model was fitted to Zn(II) and Cu(II) adsorption. Maximum monolayer adsorption capacities (qm) for Cd(II), Pb(II), Cu(II), and Zn(II) obtained by non-linear isotherm model at 298 K were 212.1, 133.5, 194.4, and 111 mg/g, respectively. Kinetics modeling parameters showed the applicability of pseudo-second-order model. The activation energy (Ea) magnitude revealed physical nature of adsorption. Maximum elution of Cu(II) (81.6%), Zn(II) (70.1%), Pb(II) (96%), and Cd(II) (78.2%) were observed with 0.1 M HCl. Thermogravimetric analysis of DPAC showed a total weight loss (in two-stages) of 28.3%. Infra-red spectral analysis showed the presence of carboxyl and hydroxyl groups over DPAC surface. The peaks at 820, 825, 845 and 885 cm-1 attributed to Zn-O, Pb-O, Cd-O, and Cu-O appeared on heavy metals saturated DPAC, confirmed their binding on DPAC during the adsorption.

Molecular mechanisms and signaling pathways of angiotensin II-induced muscle wasting: potential therapeutic targets for cardiac cachexia

PubMed Central

Yoshida, Tadashi; Tabony, A. Michael; Galvez, Sarah; Mitch, William E.; Higashi, Yusuke; Sukhanov, Sergiy; Delafontaine, Patrice

2013-01-01

Cachexia is a serious complication of many chronic diseases, such as congestive heart failure (CHF) and chronic kidney disease (CKD). Many factors are involved in the development of cachexia, and there is increasing evidence that angiotensin II (Ang II), the main effector molecule of the renin-angiotensin system (RAS), plays an important role in this process. Patients with advanced CHF or CKD often have increased Ang II levels and cachexia, and angiotensin-converting enzyme (ACE) inhibitor treatment improves weight loss. In rodent models, an increase in systemic Ang II leads to weight loss through increased protein breakdown, reduced protein synthesis in skeletal muscle and decreased appetite. Ang II activates the ubiquitin-proteasome system via generation of reactive oxygen species and via inhibition of the insulin-like growth factor-1 signaling pathway. Furthermore, Ang II inhibits 5′ AMP-activated protein kinase (AMPK) activity and disrupts normal energy balance. Ang II also increases cytokines and circulating hormones such as tumor necrosis factor-α, interleukin-6, serum amyloid-A, glucocorticoids and myostatin, which regulate muscle protein synthesis and degradation. Ang II acts on hypothalamic neurons to regulate orexigenic/anorexigenic neuropeptides, such as neuropeptide-Y, orexin and corticotropin-releasing hormone, leading to reduced appetite. Also, Ang II may regulate skeletal muscle regenerative processes. Several clinical studies have indicated that blockade of Ang II signaling via ACE inhibitors or Ang II type 1 receptor blockers prevents weight loss and improves muscle strength. Thus the RAS is a promising target for the treatment of muscle atrophy in patients with CHF and CKD. PMID:23769949

Overexpression of heterogeneous nuclear ribonucleoprotein F stimulates renal Ace-2 gene expression and prevents TGF-β1-induced kidney injury in a mouse model of diabetes.

PubMed

Lo, Chao-Sheng; Shi, Yixuan; Chang, Shiao-Ying; Abdo, Shaaban; Chenier, Isabelle; Filep, Janos G; Ingelfinger, Julie R; Zhang, Shao-Ling; Chan, John S D

2015-10-01

We investigated whether heterogeneous nuclear ribonucleoprotein F (hnRNP F) stimulates renal ACE-2 expression and prevents TGF-β1 signalling, TGF-β1 inhibition of Ace-2 gene expression and induction of tubulo-fibrosis in an Akita mouse model of type 1 diabetes. Adult male Akita transgenic (Tg) mice overexpressing specifically hnRNP F in their renal proximal tubular cells (RPTCs) were studied. Non-Akita littermates and Akita mice served as controls. Immortalised rat RPTCs stably transfected with plasmid containing either rat Hnrnpf cDNA or rat Ace-2 gene promoter were also studied. Overexpression of hnRNP F attenuated systemic hypertension, glomerular filtration rate, albumin/creatinine ratio, urinary angiotensinogen (AGT) and angiotensin (Ang) II levels, renal fibrosis and profibrotic gene (Agt, Tgf-β1, TGF-β receptor II [Tgf-βrII]) expression, stimulated anti-profibrotic gene (Ace-2 and Ang 1-7 receptor [MasR]) expression, and normalised urinary Ang 1-7 level in Akita Hnrnpf-Tg mice as compared with Akita mice. In vitro, hnRNP F overexpression stimulated Ace-2 gene promoter activity, mRNA and protein expression, and attenuated Agt, Tgf-β1 and Tgf-βrII gene expression. Furthermore, hnRNP F overexpression prevented TGF-β1 signalling and TGF-β1 inhibition of Ace-2 gene expression. These data demonstrate that hnRNP F stimulates Ace-2 gene transcription, prevents TGF-β1 inhibition of Ace-2 gene transcription and induction of kidney injury in diabetes. HnRNP F may be a potential target for treating hypertension and renal fibrosis in diabetes.

Exaggerated effects of particulate matter air pollution in genetic type II diabetes mellitus.

PubMed

Liu, Cuiqing; Bai, Yuntao; Xu, Xiaohua; Sun, Lixian; Wang, Aixia; Wang, Tse-Yao; Maurya, Santosh K; Periasamy, Muthu; Morishita, Masako; Harkema, Jack; Ying, Zhekang; Sun, Qinghua; Rajagopalan, Sanjay

2014-05-30

Prior experimental and epidemiologic data support a link between exposure to fine ambient particulate matter (<2.5 μm in aerodynamic diameter, PM2.5) and development of insulin resistance/Type II diabetes mellitus. This study was designed to investigate whether inhalational exposure of concentrated PM2.5 in a genetically susceptible animal model would result in abnormalities in energy metabolism and exacerbation of peripheral glycemic control. KKay mice, which are susceptible to Type II DM, were assigned to either concentrated ambient PM2.5 or filtered air (FA) for 5-8 weeks via a whole body exposure system. Glucose tolerance, insulin sensitivity, oxygen consumption and heat production were evaluated. At euthanasia, blood, spleen and visceral adipose tissue were collected to measure inflammatory cells using flow cytometry. Standard immnunohistochemical methods, western blotting and quantitative PCR were used to assess targets of interest. PM2.5 exposure influenced energy metabolism including O2 consumption, CO2 production, respiratory exchange ratio and thermogenesis. These changes were accompanied by worsened insulin resistance, visceral adiposity and inflammation in spleen and visceral adipose depots. Plasma adiponectin were decreased in response to PM2.5 exposure while leptin levels increased. PM2.5 exposure resulted in a significant increase in expression of inflammatory genes and decreased UCP1 expression in brown adipose tissue and activated p38 and ERK pathways in the liver of the KKay mice. Concentrated ambient PM2.5 exposure impairs energy metabolism, concomitant with abnormalities in glucose homeostasis, increased inflammation in insulin responsive organs, brown adipose inflammation and results in imbalance in circulating leptin/adiponectin levels in a genetically susceptible diabetic model. These results provide additional insights into the mechanisms surrounding air pollution mediated susceptibility to Type II DM.

Relationship between NOX4 level and angiotensin II signaling in Gitelman’s syndrome. Implications with hypertension

PubMed Central

Calò, Lorenzo A; Savoia, Carmine; Davis, Paul A; Pagnin, Elisa; Ravarotto, Verdiana; Maiolino, Giuseppe

2015-01-01

Recent evidence showed that endogenous nicotinamide adenine dinucleotide phosphate-oxidase 4 (NOX4) may exert a protective role on the cardiovascular system inducing vasodilation, reduction of blood pressure, and anti-proliferative actions. However, the functional significance of NOX4 in the cardiovascular system in humans remains elusive. Mononuclear cell levels of NOX4 were assessed by immunoblotting in 14 Gitelman’s patients (GS), a unique human model of endogenous Ang II signaling antagonism and activation of anti-atherosclerotic and anti-remodeling defenses, and compared to 11 untreated essential hypertensive patients as well as to 11 healthy normotensive subjects. The association between NOX4 and its effector heme oxygenase (HO-1) (sandwich immunoassay) was also evaluated. NOX4 protein levels were decreased in hypertensive patients as compared to both GS and healthy subjects (1.06±0.31 AU vs. 1.76±0.54, P=0.002 and vs. 1.61±0.54, P=0.018, respectively). NOX4 protein level did not differ between GS and healthy subjects. HO-1 levels were increased in GS patients as compared to both hypertensive patients and healthy subjects (8.65±3.08 ng/ml vs 3.70±1.19, P<0.0001, and vs 5.49±1.04, P=0.008, respectively. NOX4 levels correlate with HO-1 levels only in GS (r2=0.63; P=0.001), (r2=0.088; P=ns, in hypertensive patients and r2=0.082; P=ns, in healthy subjects). Our findings show that NOX4 and its effector HO-1 are reduced in hypertensive patients compared to GS patients, a human model opposite to hypertension. Although the functional significance of NOX4 needs further clarification, our preliminary data in a unique human model of anti-atherosclerotic and anti-remodeling defenses activation, highlight the potentially protective role of NOX4 in the human cardiovascular system. PMID:26221292

A new multi-layer approach for progressive damage simulation in composite laminates based on isogeometric analysis and Kirchhoff-Love shells. Part II: impact modeling

NASA Astrophysics Data System (ADS)

Pigazzini, M. S.; Bazilevs, Y.; Ellison, A.; Kim, H.

2017-11-01

In this two-part paper we introduce a new formulation for modeling progressive damage in laminated composite structures. We adopt a multi-layer modeling approach, based on isogeometric analysis, where each ply or lamina is represented by a spline surface, and modeled as a Kirchhoff-Love thin shell. Continuum damage mechanics is used to model intralaminar damage, and a new zero-thickness cohesive-interface formulation is introduced to model delamination as well as permitting laminate-level transverse shear compliance. In Part I of this series we focus on the presentation of the modeling framework, validation of the framework using standard Mode I and Mode II delamination tests, and assessment of its suitability for modeling thick laminates. In Part II of this series we focus on the application of the proposed framework to modeling and simulation of damage in composite laminates resulting from impact. The proposed approach has significant accuracy and efficiency advantages over existing methods for modeling impact damage. These stem from the use of IGA-based Kirchhoff-Love shells to represent the individual plies of the composite laminate, while the compliant cohesive interfaces enable transverse shear deformation of the laminate. Kirchhoff-Love shells give a faithful representation of the ply deformation behavior, and, unlike solids or traditional shear-deformable shells, do not suffer from transverse-shear locking in the limit of vanishing thickness. This, in combination with higher-order accurate and smooth representation of the shell midsurface displacement field, allows us to adopt relatively coarse in-plane discretizations without sacrificing solution accuracy. Furthermore, the thin-shell formulation employed does not use rotational degrees of freedom, which gives additional efficiency benefits relative to more standard shell formulations.

Neuroprotective Effects and Mechanisms of Curcumin-Cu(II) and -Zn(II) Complexes Systems and Their Pharmacological Implications.

PubMed

Yan, Fa-Shun; Sun, Jian-Long; Xie, Wen-Hai; Shen, Liang; Ji, Hong-Fang

2017-12-28

Alzheimer's disease (AD) is the main form of dementia and has a steadily increasing prevalence. As both oxidative stress and metal homeostasis are involved in the pathogenesis of AD, it would be interesting to develop a dual function agent, targeting the two factors. Curcumin, a natural compound isolated from the rhizome of Curcuma longa , is an antioxidant and can also chelate metal ions. Whether the complexes of curcumin with metal ions possess neuroprotective effects has not been evaluated. Therefore, the present study was designed to investigate the protective effects of the complexes of curcumin with Cu(II) or Zn(II) on hydrogen peroxide (H₂O₂)-induced injury and the underlying molecular mechanisms. The use of rat pheochromocytoma (PC12) cells, a widely used neuronal cell model system, was adopted. It was revealed that curcumin-Cu(II) complexes systems possessed enhanced O₂ ·- -scavenging activities compared to unchelated curcumin. In comparison with unchelated curcumin, the protective effects of curcumin-Cu(II) complexes systems were stronger than curcumin-Zn(II) system. Curcumin-Cu(II) or -Zn(II) complexes systems significantly enhanced the superoxide dismutase, catalase, and glutathione peroxidase activities and attenuated the increase of malondialdehyde levels and caspase-3 and caspase-9 activities, in a dose-dependent manner. The curcumin-Cu(II) complex system with a 2:1 ratio exhibited the most significant effect. Further mechanistic study demonstrated that curcumin-Cu(II) or -Zn(II) complexes systems inhibited cell apoptosis via downregulating the nuclear factor κB (NF-κB) pathway and upregulating Bcl-2/Bax pathway. In summary, the present study found that curcumin-Cu(II) or -Zn(II) complexes systems, especially the former, possess significant neuroprotective effects, which indicates the potential advantage of curcumin as a promising agent against AD and deserves further study.

Nanomagnet Logic: Architectures, design, and benchmarking

NASA Astrophysics Data System (ADS)

Kurtz, Steven J.

Nanomagnet Logic (NML) is an emerging technology being studied as a possible replacement or supplementary device for Complimentary Metal-Oxide-Semiconductor (CMOS) Field-Effect Transistors (FET) by the year 2020. NML devices offer numerous potential advantages including: low energy operation, steady state non-volatility, radiation hardness and a clear path to fabrication and integration with CMOS. However, maintaining both low-energy operation and non-volatility while scaling from the device to the architectural level is non-trivial as (i) nearest neighbor interactions within NML circuits complicate the modeling of ensemble nanomagnet behavior and (ii) the energy intensive clock structures required for re-evaluation and NML's relatively high latency challenge its ability to offer system-level performance wins against other emerging nanotechnologies. Thus, further research efforts are required to model more complex circuits while also identifying circuit design techniques that balance low-energy operation with steady state non-volatility. In addition, further work is needed to design and model low-power on-chip clocks while simultaneously identifying application spaces where NML systems (including clock overhead) offer sufficient energy savings to merit their inclusion in future processors. This dissertation presents research advancing the understanding and modeling of NML at all levels including devices, circuits, and line clock structures while also benchmarking NML against both scaled CMOS and tunneling FETs (TFET) devices. This is accomplished through the development of design tools and methodologies for (i) quantifying both energy and stability in NML circuits and (ii) evaluating line-clocked NML system performance. The application of these newly developed tools improves the understanding of ideal design criteria (i.e., magnet size, clock wire geometry, etc.) for NML architectures. Finally, the system-level performance evaluation tool offers the ability to project what advancements are required for NML to realize performance improvements over scaled-CMOS hardware equivalents at the functional unit and/or application-level.

Surface reaction of SnII on goethite (α-FeOOH): surface complexation, redox reaction, reductive dissolution, and phase transformation.

PubMed

Dulnee, Siriwan; Scheinost, Andreas C

2014-08-19

To elucidate the potential risk of (126)Sn migration from nuclear waste repositories, we investigated the surface reactions of Sn(II) on goethite as a function of pH and Sn(II) loading under anoxic condition with O2 level < 2 ppmv. Tin redox state and surface structure were investigated by Sn K edge X-ray absorption spectroscopy (XAS), goethite phase transformations were investigated by high-resolution transmission electron microscopy and selected area electron diffraction. The results demonstrate the rapid and complete oxidation of Sn(II) by goethite and formation of Sn(IV) (1)E and (2)C surface complexes. The contribution of (2)C complexes increases with Sn loading. The Sn(II) oxidation leads to a quantitative release of Fe(II) from goethite at low pH, and to the precipitation of magnetite at higher pH. To predict Sn sorption, we applied surface complexation modeling using the charge distribution multisite complexation approach and the XAS-derived surface complexes. Log K values of 15.5 ± 1.4 for the (1)E complex and 19.2 ± 0.6 for the (2)C complex consistently predict Sn sorption across pH 2-12 and for two different Sn loadings and confirm the strong retention of Sn(II) even under anoxic conditions.

Parameter study for child injury mitigation in near-side impacts through FE simulations.

PubMed

Andersson, Marianne; Pipkorn, Bengt; Lövsund, Per

2012-01-01

The objective of this study is to investigate the effects of crash-related car parameters on head and chest injury measures for 3- and 12-year-old children in near-side impacts. The evaluation was made using a model of a complete passenger car that was impacted laterally by a barrier. The car model was validated in 2 crash conditions: the Insurance Institute for Highway Safety (IIHS) and the US New Car Assessment Program (NCAP) side impact tests. The Small Side Impact Dummy (SID-IIs) and the human body model 3 (HBM3) (Total HUman Model for Safety [THUMS] 3-year-old) finite element models were used for the parametric investigation (HBM3 on a booster). The car parameters were as follows: vehicle mass, side impact structure stiffness, a head air bag, a thorax-pelvis air bag, and a seat belt with pretensioner. The studied dependent variables were as follows: resultant head linear acceleration, resultant head rotational acceleration, chest viscous criterion, rib deflection, and relative velocity at head impact. The chest measurements were only considered for the SID-IIs. The head air bag had the greatest effect on the head measurements for both of the occupant models. On average, it reduced the peak head linear acceleration by 54 g for the HBM3 and 78 g for the SID-IIs. The seat belt had the second greatest effect on the head measurements; the peak head linear accelerations were reduced on average by 39 g (HBM3) and 44 g (SID-IIs). The high stiffness side structure increased the SID-IIs' head acceleration, whereas it had marginal effect on the HBM3. The vehicle mass had a marginal effect on SID-IIs' head accelerations, whereas the lower vehicle mass caused 18 g higher head acceleration for HBM3 and the greatest rotational acceleration. The thorax-pelvis air bag, vehicle mass, and seat belt pretensioner affected the chest measurements the most. The presence of a thorax-pelvis air bag, high vehicle mass, and a seat belt pretensioner all reduced the chest viscous criterion (VC) and peak rib deflection in the SID-IIs. The head and thorax-pelvis air bags have the potential to reduce injury measurements for both the SID-IIs and the HBM3, provided that the air bag properties are designed to consider these occupant sizes also. The seat belt pretensioner is also effective, provided that the lateral translation of the torso is managed by other features. The importance of lateral movement management is greater the smaller the occupant is. Light vehicles require interior restraint systems of higher performance than heavy vehicles do to achieve the same level of injury measures for a given side structure. Copyright © 2012 Taylor & Francis Group, LLC

A prediction model of drug-induced ototoxicity developed by an optimal support vector machine (SVM) method.

PubMed

Zhou, Shu; Li, Guo-Bo; Huang, Lu-Yi; Xie, Huan-Zhang; Zhao, Ying-Lan; Chen, Yu-Zong; Li, Lin-Li; Yang, Sheng-Yong

2014-08-01

Drug-induced ototoxicity, as a toxic side effect, is an important issue needed to be considered in drug discovery. Nevertheless, current experimental methods used to evaluate drug-induced ototoxicity are often time-consuming and expensive, indicating that they are not suitable for a large-scale evaluation of drug-induced ototoxicity in the early stage of drug discovery. We thus, in this investigation, established an effective computational prediction model of drug-induced ototoxicity using an optimal support vector machine (SVM) method, GA-CG-SVM. Three GA-CG-SVM models were developed based on three training sets containing agents bearing different risk levels of drug-induced ototoxicity. For comparison, models based on naïve Bayesian (NB) and recursive partitioning (RP) methods were also used on the same training sets. Among all the prediction models, the GA-CG-SVM model II showed the best performance, which offered prediction accuracies of 85.33% and 83.05% for two independent test sets, respectively. Overall, the good performance of the GA-CG-SVM model II indicates that it could be used for the prediction of drug-induced ototoxicity in the early stage of drug discovery. Copyright © 2014 Elsevier Ltd. All rights reserved.

Mitochondrial Dysfunction in Schizophrenia: Determination of Mitochondrial Respiratory Activity in a Two-Hit Mouse Model.

PubMed

Monpays, Cécile; Deslauriers, Jessica; Sarret, Philippe; Grignon, Sylvain

2016-08-01

Schizophrenia is a chronic mental illness in which mitochondrial dysfunction has been suggested. Our laboratory recently developed a juvenile murine two-hit model (THM) of schizophrenia based on the combination of gestational inflammation, followed by juvenile restraint stress. We previously reported that relevant behaviors and neurochemical disturbances, including oxidative stress, were reversed by the antioxidant lipoic acid (LA), thereby pointing to the central role played by oxidative abnormalities and prompting us to investigate mitochondrial function. Mitochondrial activity was determined with the MitoXpress® commercial kit in two schizophrenia-relevant regions (prefrontal cortex (PFC) and striatum). Measurements were performed in state 3, with substrates for complex I- and complex II-induced respiratory activity (IRA). We observed an increase in complex I IRA in the PFC and striatum in both sexes but an increase in complex II activity only in males. LA treatment prevented this increase only in complex II IRA in males. Expression levels of the different respiratory chain complexes, as well as fission/fusion proteins and protein carbonylation, were unchanged. In conclusion, our juvenile schizophrenia THM shows an increase in mitochondrial activity reversed by LA, specifically in complex II IRA in males. Further investigations are required to determine the mechanisms of these modifications.

Intramammary inoculation of Panax ginseng plays an immunoprotective role in Staphylococcus aureus infection in a murine model.

PubMed

Silvestrini, P; Beccaria, C; Pereyra, E A L; Renna, M S; Ortega, H H; Calvinho, L F; Dallard, B E; Baravalle, C

2017-12-01

The immunoprotective effect of Panax ginseng (Pg) extract was investigated in a mouse mastitis model. Lactating female mice were intramammarily inoculated with Pg or placebo, and then were challenged with S. aureus, while other group was inoculated with S. aureus alone. The number of bacteria recovered from mammary glands was significantly lower in Pg-treated S. aureus-infected mice (group I) compared with placebo-treated S. aureus-infected mice (group II) and S. aureus-infected mice (group III). The mRNA expression of TLR2, TLR4, IL-1α and TNF-α was influenced by treatment; being the transcript levels for all genes higher in group I compared with group II and III. Activation of NF-κB and the number of monocytes-macrophages in mammary gland tissue was significantly increased in group I compared with group II and III. Pg extract was able to trigger an adequate immune response to confront an infection demonstrating its protective effect and potential for preventing bovine intramammary infections. Copyright © 2017 Elsevier Ltd. All rights reserved.

Long-Acting Phospholipid Gel of Exenatide for Long-Term Therapy of Type II Diabetes.

PubMed

Hu, Mei; Zhang, Yu; Xiang, Nanxi; Zhong, Ying; Gong, Tao; Zhang, Zhi-Rong; Fu, Yao

2016-06-01

This study aimed to develop a sustained-release formulation of exenatide (EXT) for the long-term therapeutic efficacy in the treatment of type II diabetes. In this study, we present an injectable phospholipid gel by mixing biocompatible phospholipid S100, medium chain triglyceride (MCT) with 85% (w/w) ethanol. A systemic pre-formulation study has been carried out to improve the stability of EXT during formulation fabrication. With the optimized formulation, the pharmacokinetic profiles in rats were studied and two diabetic animal models were employed to evaluate the therapeutic effect of EXT phospholipid gel via a single subcutaneous injection versus repeated injections of normal saline and EXT solution. With optimized formulation, sustained release of exenatide in vivo for over three consecutive weeks was observed after one single subcutaneous injection. Moreover, the pharmacodynamic study in two diabetic models justified that the gel formulation displayed a comparable hypoglycemic effect and controlled blood glucose level compared with exenatide solution treated group. EXT-loaded phospholipid gel represents a promising controlled release system for long-term therapy of type II diabetes.

Overcoming deep roots, fast rates, and short internodes to resolve the ancient rapid radiation of eupolypod II ferns.

PubMed

Rothfels, Carl J; Larsson, Anders; Kuo, Li-Yaung; Korall, Petra; Chiou, Wen-Liang; Pryer, Kathleen M

2012-05-01

Backbone relationships within the large eupolypod II clade, which includes nearly a third of extant fern species, have resisted elucidation by both molecular and morphological data. Earlier studies suggest that much of the phylogenetic intractability of this group is due to three factors: (i) a long root that reduces apparent levels of support in the ingroup; (ii) long ingroup branches subtended by a series of very short backbone internodes (the "ancient rapid radiation" model); and (iii) significantly heterogeneous lineage-specific rates of substitution. To resolve the eupolypod II phylogeny, with a particular emphasis on the backbone internodes, we assembled a data set of five plastid loci (atpA, atpB, matK, rbcL, and trnG-R) from a sample of 81 accessions selected to capture the deepest divergences in the clade. We then evaluated our phylogenetic hypothesis against potential confounding factors, including those induced by rooting, ancient rapid radiation, rate heterogeneity, and the Bayesian star-tree paradox artifact. While the strong support we inferred for the backbone relationships proved robust to these potential problems, their investigation revealed unexpected model-mediated impacts of outgroup composition, divergent effects of methods for countering the star-tree paradox artifact, and gave no support to concerns about the applicability of the unrooted model to data sets with heterogeneous lineage-specific rates of substitution. This study is among few to investigate these factors with empirical data, and the first to compare the performance of the two primary methods for overcoming the Bayesian star-tree paradox artifact. Among the significant phylogenetic results is the near-complete support along the eupolypod II backbone, the demonstrated paraphyly of Woodsiaceae as currently circumscribed, and the well-supported placement of the enigmatic genera Homalosorus, Diplaziopsis, and Woodsia.

Optimization of Stripping Voltammetric Sensor by a Back Propagation Artificial Neural Network for the Accurate Determination of Pb(II) in the Presence of Cd(II).

PubMed

Zhao, Guo; Wang, Hui; Liu, Gang; Wang, Zhiqiang

2016-09-21

An easy, but effective, method has been proposed to detect and quantify the Pb(II) in the presence of Cd(II) based on a Bi/glassy carbon electrode (Bi/GCE) with the combination of a back propagation artificial neural network (BP-ANN) and square wave anodic stripping voltammetry (SWASV) without further electrode modification. The effects of Cd(II) in different concentrations on stripping responses of Pb(II) was studied. The results indicate that the presence of Cd(II) will reduce the prediction precision of a direct calibration model. Therefore, a two-input and one-output BP-ANN was built for the optimization of a stripping voltammetric sensor, which considering the combined effects of Cd(II) and Pb(II) on the SWASV detection of Pb(II) and establishing the nonlinear relationship between the stripping peak currents of Pb(II) and Cd(II) and the concentration of Pb(II). The key parameters of the BP-ANN and the factors affecting the SWASV detection of Pb(II) were optimized. The prediction performance of direct calibration model and BP-ANN model were tested with regard to the mean absolute error (MAE), root mean square error (RMSE), average relative error (ARE), and correlation coefficient. The results proved that the BP-ANN model exhibited higher prediction accuracy than the direct calibration model. Finally, a real samples analysis was performed to determine trace Pb(II) in some soil specimens with satisfactory results.

Peak Lead Levels and Diagnostics in Lead Service Lines Dominated by PbO2 - abstract

EPA Science Inventory

Multiple studies have presented “profiles” of water lead levels from tap to main through lead service lines (LSLs), in systems where the LSLs were coated with common Pb(II) corrosion solids. These Pb(II) solids were either actual Pb(II) minerals or Pb(II) sorbed onto other pipe ...

Comparability of antimüllerian hormone levels among commercially available immunoassays.

PubMed

Su, H Irene; Sammel, Mary D; Homer, Michael V; Bui, Kim; Haunschild, Carolyn; Stanczyk, Frank Z

2014-06-01

To compare antimüllerian hormone (AMH) levels among three commercially available AMH immunoassays: AMH Gen II (Beckman Coulter), Ultrasensitive AMH (Ansh Labs), and picoAMH (Ansh Labs). Cross-sectional. Academic reproductive endocrinology program. 90 newly diagnosed breast cancer patients before cancer treatment. None. Proportion of detectable AMH levels by immunoassay, and comparability among assays. At a mean age of 38.1 years, the median (interquartile range) AMH level for the cohort was 0.92 [1.35] ng/mL for the Gen II assay, 1.68 [2.30] ng/mL for the Ultrasensitive assay, and 1.52 [2.41] ng/mL for the picoAMH assay. Significantly higher proportions of detectable AMH levels were observed with the picoAMH kit (97%) compared with both the Gen II (84%) and Ultrasensitive (92%) assays. Although the AMH results were highly correlated among the assays (r = 0.92-0.99), the Gen II AMH levels were consistently lower than both Ultrasensitive and picoAMH levels. Moreover, as AMH levels increased, the magnitude of difference grew larger between Gen II and each of the other two assays. Measurement of AMH levels with the picoAMH kit maximized detection at very low levels, particularly in contrast with the Gen II kit. Conversion of AMH levels from different immunoassays using regression equations is potentially highly inaccurate. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Screening level risk assessment model for chemical fate and effects in the environment.

PubMed

Arnot, Jon A; Mackay, Don; Webster, Eva; Southwood, Jeanette M

2006-04-01

A screening level risk assessment model is developed and described to assess and prioritize chemicals by estimating environmental fate and transport, bioaccumulation, and exposure to humans and wildlife for a unit emission rate. The most sensitive risk endpoint is identified and a critical emission rate is then calculated as a result of that endpoint being reached. Finally, this estimated critical emission rate is compared with the estimated actual emission rate as a risk assessment factor. This "back-tracking" process avoids the use of highly uncertain emission rate data as model input. The application of the model is demonstrated in detail for three diverse chemicals and in less detail for a group of 70 chemicals drawn from the Canadian Domestic Substances List. The simple Level II and the more complex Level III fate calculations are used to "bin" substances into categories of similar probable risk. The essential role of the model is to synthesize information on chemical and environmental properties within a consistent mass balance framework to yield an overall estimate of screening level risk with respect to the defined endpoint. The approach may be useful to identify and prioritize those chemicals of commerce that are of greatest potential concern and require more comprehensive modeling and monitoring evaluations in actual regional environments and food webs.

Rodent heart failure models do not reflect the human circulating microRNA signature in heart failure.

PubMed

Vegter, Eline L; Ovchinnikova, Ekaterina S; Silljé, Herman H W; Meems, Laura M G; van der Pol, Atze; van der Velde, A Rogier; Berezikov, Eugene; Voors, Adriaan A; de Boer, Rudolf A; van der Meer, Peter

2017-01-01

We recently identified a set of plasma microRNAs (miRNAs) that are downregulated in patients with heart failure in comparison with control subjects. To better understand their meaning and function, we sought to validate these circulating miRNAs in 3 different well-established rat and mouse heart failure models, and correlated the miRNAs to parameters of cardiac function. The previously identified let-7i-5p, miR-16-5p, miR-18a-5p, miR-26b-5p, miR-27a-3p, miR-30e-5p, miR-199a-3p, miR-223-3p, miR-423-3p, miR-423-5p and miR-652-3p were measured by means of quantitative real time polymerase chain reaction (qRT-PCR) in plasma samples of 8 homozygous TGR(mREN2)27 (Ren2) transgenic rats and 8 (control) Sprague-Dawley rats, 6 mice with angiotensin II-induced heart failure (AngII) and 6 control mice, and 8 mice with ischemic heart failure and 6 controls. Circulating miRNA levels were compared between the heart failure animals and healthy controls. Ren2 rats, AngII mice and mice with ischemic heart failure showed clear signs of heart failure, exemplified by increased left ventricular and lung weights, elevated end-diastolic left ventricular pressures, increased expression of cardiac stress markers and reduced left ventricular ejection fraction. All miRNAs were detectable in plasma from rats and mice. No significant differences were observed between the circulating miRNAs in heart failure animals when compared to the healthy controls (all P>0.05) and no robust associations with cardiac function could be found. The previous observation that miRNAs circulate in lower levels in human patients with heart failure could not be validated in well-established rat and mouse heart failure models. These results question the translation of data on human circulating miRNA levels to experimental models, and vice versa the validity of experimental miRNA data for human heart failure.

Insulin-like growth factor (IGF)-I, IGF-II and IGF-binding protein (IGFBP)-3 levels in Arab subjects with coronary heart disease.

PubMed

Akanji, A O; Suresh, C G; Al-Radwan, R; Fatania, H R

2007-01-01

Insulin-like growth factors (IGF-I, IGF-II) and their binding protein (IGFBP-3) may be risk markers for coronary heart disease (CHD). This study aimed to assess the levels and determinants of the serum levels of IGF-I, IGF-II and IGFBP-3 in Arab patients with established CHD. Two groups of subjects were matched for age, gender, BMI and waist-hip ratio (WHR): (i) CHD (n = 105), median age 51.0 (range 40.0-60.0) years; (ii) controls (n = 97) aged 49.0 (range 37.0-60.0) years. We measured fasting serum levels of glucose and lipoproteins (total cholesterol, triglycerides, LDL, HDL, apo B), insulin, HOMA-IR, IGF-I, IGF-II and IGFBP-3 and compared the results between groups. The effects of body mass and the metabolic syndrome (MS) on IGF levels were also examined, and linear correlations were sought between the various parameters. The levels of IGF-I, IGF-II and IGFBP-3 were significantly lower (all p<0.01) for the CHD group than for the control group. These differences were not influenced by BMI or with the presence of MS. In CHD, there were no significant correlations between levels of IGF-I and IGF-II and age, BMI, WHR, lipoprotein concentrations and insulin sensitivity, although IGFBP-3 had weakly significant relationships with some of the lipoproteins. Levels of IGF-I, IGF-II and IGFBP3 are reduced in male Arab patients with CHD, and did not appear influenced by traditional CHD risk factors such as age, BMI, insulin sensitivity and presence of MS. Perturbations in the IGF/IGFBP-3 axis may be potential additional targets for pharmacological manipulation in CHD.

Inclusive search for standard model Higgs boson production in the WW decay channel using the CDF II detector.

PubMed

Aaltonen, T; Adelman, J; Alvarez González, B; Amerio, S; Amidei, D; Anastassov, A; Annovi, A; Antos, J; Apollinari, G; Appel, J; Apresyan, A; Arisawa, T; Artikov, A; Asaadi, J; Ashmanskas, W; Attal, A; Aurisano, A; Azfar, F; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Barria, P; Bartos, P; Bauer, G; Beauchemin, P-H; Bedeschi, F; Beecher, D; Behari, S; Bellettini, G; Bellinger, J; Benjamin, D; Beretvas, A; Bhatti, A; Binkley, M; Bisello, D; Bizjak, I; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Bridgeman, A; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Burkett, K; Busetto, G; Bussey, P; Buzatu, A; Byrum, K L; Cabrera, S; Calancha, C; Camarda, S; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carls, B; Carlsmith, D; Carosi, R; Carrillo, S; Carron, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavaliere, V; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, K; Chokheli, D; Chou, J P; Chung, K; Chung, W H; Chung, Y S; Chwalek, T; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Compostella, G; Convery, M E; Conway, J; Corbo, M; Cordelli, M; Cox, C A; Cox, D J; Crescioli, F; Cuenca Almenar, C; Cuevas, J; Culbertson, R; Cully, J C; Dagenhart, D; d'Ascenzo, N; Datta, M; Davies, T; de Barbaro, P; De Cecco, S; Deisher, A; De Lorenzo, G; Dell'Orso, M; Deluca, C; Demortier, L; Deng, J; Deninno, M; d'Errico, M; Di Canto, A; Di Ruzza, B; Dittmann, J R; D'Onofrio, M; Donati, S; Dong, P; Dorigo, T; Dube, S; Ebina, K; Elagin, A; Erbacher, R; Errede, D; Errede, S; Ershaidat, N; Eusebi, R; Fang, H C; Farrington, S; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Ferrazza, C; Field, R; Flanagan, G; Forrest, R; Frank, M J; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garberson, F; Garcia, J E; Garfinkel, A F; Garosi, P; Gerberich, H; Gerdes, D; Gessler, A; Giagu, S; Giakoumopoulou, V; Giannetti, P; Gibson, K; Gimmell, J L; Ginsburg, C M; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Grinstein, S; Grosso-Pilcher, C; Group, R C; Grundler, U; Guimaraes da Costa, J; Gunay-Unalan, Z; Haber, C; Hahn, S R; Halkiadakis, E; Han, B-Y; Han, J Y; Happacher, F; Hara, K; Hare, D; Hare, M; Harr, R F; Hartz, M; Hatakeyama, K; Hays, C; Heck, M; Heinrich, J; Herndon, M; Heuser, J; Hewamanage, S; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Hou, S; Houlden, M; Hsu, S-C; Hughes, R E; Hurwitz, M; Husemann, U; Hussein, M; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ivanov, A; James, E; Jang, D; Jayatilaka, B; Jeon, E J; Jha, M K; Jindariani, S; Johnson, W; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Kar, D; Karchin, P E; Kato, Y; Kephart, R; Ketchum, W; Keung, J; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, H W; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kreps, M; Kroll, J; Krop, D; Krumnack, N; Kruse, M; Krutelyov, V; Kuhr, T; Kulkarni, N P; Kurata, M; Kwang, S; Laasanen, A T; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; LeCompte, T; Lee, E; Lee, H S; Lee, J S; Lee, S W; Leone, S; Lewis, J D; Lin, C-J; Linacre, J; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, C; Liu, T; Lockyer, N S; Loginov, A; Lovas, L; Lucchesi, D; Lueck, J; Lujan, P; Lukens, P; Lungu, G; Lys, J; Lysak, R; MacQueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maksimovic, P; Malde, S; Malik, S; Manca, G; Manousakis-Katsikakis, A; Margaroli, F; Marino, C; Marino, C P; Martin, A; Martin, V; Martínez, M; Martínez-Ballarín, R; Mastrandrea, P; Mathis, M; Mattson, M E; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzione, A; Mesropian, C; Miao, T; Mietlicki, D; Miladinovic, N; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyake, H; Moed, S; Moggi, N; Mondragon, M N; Moon, C S; Moore, R; Morello, M J; Morlock, J; Movilla Fernandez, P; Mülmenstädt, J; Mukherjee, A; Muller, Th; Murat, P; Mussini, M; Nachtman, J; Nagai, Y; Naganoma, J; Nakamura, K; Nakano, I; Napier, A; Nett, J; Neu, C; Neubauer, M S; Neubauer, S; Nielsen, J; Nodulman, L; Norman, M; Norniella, O; Nurse, E; Oakes, L; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Orava, R; Osterberg, K; Pagan Griso, S; Pagliarone, C; Palencia, E; Papadimitriou, V; Papaikonomou, A; Paramanov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Peiffer, T; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Pianori, E; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Potamianos, K; Poukhov, O; Prokoshin, F; Pronko, A; Ptohos, F; Pueschel, E; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ramakrishnan, V; Ranjan, N; Redondo, I; Renton, P; Renz, M; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rodriguez, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Roy, P; Ruiz, A; Russ, J; Rusu, V; Rutherford, B; Saarikko, H; Safonov, A; Sakumoto, W K; Santi, L; Sartori, L; Sato, K; Saveliev, V; Savoy-Navarro, A; Schlabach, P; Schmidt, A; Schmidt, E E; Schmidt, M A; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sforza, F; Sfyrla, A; Shalhout, S Z; Shears, T; Shepard, P F; Shimojima, M; Shiraishi, S; Shochet, M; Shon, Y; Shreyber, I; Simonenko, A; Sinervo, P; Sisakyan, A; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soha, A; Somalwar, S; Sorin, V; Squillacioti, P; Stanitzki, M; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Strycker, G L; Suh, J S; Sukhanov, A; Suslov, I; Taffard, A; Takashima, R; Takeuchi, Y; Tanaka, R; Tang, J; Tecchio, M; Teng, P K; Thom, J; Thome, J; Thompson, G A; Thomson, E; Tipton, P; Ttito-Guzmán, P; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Totaro, P; Trovato, M; Tsai, S-Y; Tu, Y; Turini, N; Ukegawa, F; Uozumi, S; van Remortel, N; Varganov, A; Vataga, E; Vázquez, F; Velev, G; Vellidis, C; Vidal, M; Vila, I; Vilar, R; Vogel, M; Volobouev, I; Volpi, G; Wagner, P; Wagner, R G; Wagner, R L; Wagner, W; Wagner-Kuhr, J; Wakisaka, T; Wallny, R; Wang, S M; Warburton, A; Waters, D; Weinberger, M; Weinelt, J; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Wilbur, S; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wolfe, H; Wright, T; Wu, X; Würthwein, F; Yagil, A; Yamamoto, K; Yamaoka, J; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yi, K; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanetti, A; Zeng, Y; Zhang, X; Zheng, Y; Zucchelli, S

2010-02-12

We present a search for standard model (SM) Higgs boson production using pp collision data at square root(s) = 1.96 TeV, collected with the CDF II detector and corresponding to an integrated luminosity of 4.8 fb(-1). We search for Higgs bosons produced in all processes with a significant production rate and decaying to two W bosons. We find no evidence for SM Higgs boson production and place upper limits at the 95% confidence level on the SM production cross section (sigma(H)) for values of the Higgs boson mass (sigma(H)) in the range from 110 to 200 GeV. These limits are the most stringent for m(H) > 130 GeV and are 1.29 above the predicted value of sigma(H) for c = 165 GeV.

Dynamical structure of center-of-pressure trajectories with and without functional taping in children with cerebral palsy level I and II of GMFCS.

PubMed

Pavão, Silvia Leticia; Ledebt, Annick; Savelsbergh, Geert J P; Rocha, Nelci Adriana C F

2017-08-01

Postural control during quiet standing was examined in typical children (TD) and children with cerebral palsy (CP) level I and II of GMFCS. The immediate effect on postural control of functional taping on the thighs was analyzed. We evaluated 43 TD, 17 CP children level I, and 10 CP children level II. Participants were evaluated in two conditions (with and without taping). The trajectories of the center of pressure (COP) were analyzed by means of conventional posturography (sway amplitude, sway-path-length) and dynamic posturography (degree of twisting-and-turning, sway regularity). Both CP groups showed larger sway amplitude than the TD while only the CP level II showed more regular COP trajectories with less twisting-and-turning. Functional taping didn't affect sway amplitude or sway-path-length. TD children exhibited more twisting-and-turning with functional taping, whereas no effects on postural sway dynamics were observed in CP children. Functional taping doesn't result in immediate changes in quiet stance in CP children, whereas in TD it resulted in faster sway corrections. Children level II invest more attention in postural control than level I, and TD. While quiet standing was more automatized in children level I than in level II, both CP groups showed a less stable balance than TD. Copyright © 2017 Elsevier B.V. All rights reserved.

How do type II topoisomerases use ATP hydrolysis to simplify DNA topology beyond equilibrium? Investigating the relaxation reaction of non-supercoiling type II topoisomerases

PubMed Central

Stuchinskaya, Tanya; Mitchenall, Lesley A.; Schoeffler, Allyn J.; Corbett, Kevin D.; Berger, James M.; Bates, Andrew D.; Maxwell, Anthony

2015-01-01

DNA topoisomerases control the topology of DNA (e.g. the level of supercoiling) in all cells. Type IIA topoisomerases are ATP-dependent enzymes that have been shown to simplify the topology of their DNA substrates to a level beyond that expected at equilibrium (i.e. more relaxed than the product of relaxation by ATP-independent enzymes, such as type I topoisomerases, or a lower than equilibrium level of catenation). The mechanism of this effect is currently unknown, although several models have been suggested. We have analysed the DNA relaxation reactions of type II topoisomerases to further explore this phenomenon. We find that all type IIA topoisomerases tested exhibit the effect to a similar degree and that it is not dependent on the C-terminal domains of the enzymes. As recently reported, the type IIB topoisomerase, topo VI (which is only distantly related to the type IIA enzymes), does not exhibit topology simplification. We find that topology simplification is not significantly dependent on circle size in the range ~2–9 kbp, and is not altered by reducing the free energy available from ATP hydrolysis by varying the ATP:ADP ratio. A direct test of one model (DNA tracking, i.e. sliding of a protein clamp along DNA to trap supercoils) suggests that this is unlikely to be the explanation for the effect. We conclude that geometric selection of DNA segments by the enzymes is likely to be a primary source of the effect but that it is possible that other factors contribute. We also speculate whether topology simplification might simply be an evolutionary relic, with no adaptive significance. PMID:19094994

How do type II topoisomerases use ATP hydrolysis to simplify DNA topology beyond equilibrium? Investigating the relaxation reaction of nonsupercoiling type II topoisomerases.

PubMed

Stuchinskaya, Tanya; Mitchenall, Lesley A; Schoeffler, Allyn J; Corbett, Kevin D; Berger, James M; Bates, Andrew D; Maxwell, Anthony

2009-02-06

DNA topoisomerases control the topology of DNA (e.g., the level of supercoiling) in all cells. Type IIA topoisomerases are ATP-dependent enzymes that have been shown to simplify the topology of their DNA substrates to a level beyond that expected at equilibrium (i.e., more relaxed than the product of relaxation by ATP-independent enzymes, such as type I topoisomerases, or a lower-than-equilibrium level of catenation). The mechanism of this effect is currently unknown, although several models have been suggested. We have analyzed the DNA relaxation reactions of type II topoisomerases to further explore this phenomenon. We find that all type IIA topoisomerases tested exhibit the effect to a similar degree and that it is not dependent on the supercoil-sensing C-terminal domains of the enzymes. As recently reported, the type IIB topoisomerase, topoisomerase VI (which is only distantly related to type IIA enzymes), does not exhibit topology simplification. We find that topology simplification is not significantly dependent on circle size in the range approximately 2-9 kbp and is not altered by reducing the free energy available from ATP hydrolysis by varying the ADP:ATP ratio. A direct test of one model (DNA tracking; i.e., sliding of a protein clamp along DNA to trap supercoils) suggests that this is unlikely to be the explanation for the effect. We conclude that geometric selection of DNA segments by the enzymes is likely to be a primary source of the effect, but that it is possible that other kinetic factors contribute. We also speculate whether topology simplification might simply be an evolutionary relic, with no adaptive significance.

Is pre-transplant sensitization against angiotensin II type 1 receptor still a risk factor of graft and patient outcome in kidney transplantation in the anti-HLA Luminex era? A retrospective study.

PubMed

Deltombe, Clement; Gillaizeau, Florence; Anglicheau, Daniel; Morelon, Emmanuel; Trébern-Launay, Katy; Le Borgne, Florent; Rimbert, Marie; Guérif, Pierrick; Malard-Castagnet, Stéphanie; Foucher, Yohann; Giral, Magali

2017-11-01

We aimed to assess the correlation of anti-angiotensin II type 1 receptor antibodies (anti-AT1R-Abs) before transplantation on a multicentric cohort of kidney transplant recipients (2008-2012), under tacrolimus and mycophenolate mofetil (MMF), screened by Luminex technology for anti-HLA immunization. Anti-AT1R antibody levels were measured by ELISA in pretransplantation sera of 940 kidney recipients from three French centers of the DIVAT cohort. Multivariable Cox models estimated the association between pretransplant anti-angiotensin II type 1 receptor antibodies and time to acute rejection episodes (ARE) or time to graft failure. Within our cohort, 387 patients (41.2%) had pretransplant AT1R-Abs higher than 10 U/ml and only 8% (72/970) greater than 17 U/ml. The cumulative probability of clinically relevant (cr)-ARE was 22.5% at 1 year post-transplantation [95% CI (19.9-25.4%)]. The cumulative probability of graft failure and patient death were 10.6% [95% CI (8.4-13.3%)] and 5.7% [95% CI (4.0-8.1%)] at 3 years post-transplantation, respectively. Multivariate Cox models indicated that pretransplant anti-AT1R antibody levels higher than 10 U/ml were not significantly independently associated with higher risks of acute rejection episodes [HR = 1.04, 95% CI (0.80-1.35)] nor with risk of graft failure [HR = 0.86, 95% CI (0.56-1.33)]. Our study did not confirm an association between pretransplant anti-AT1R antibody levels and kidney transplant outcomes. © 2017 Steunstichting ESOT.

Hospital-level Variation in Utilization of Surgery for Clinical Stage I-II Pancreatic Adenocarcinoma.

PubMed

Swords, Douglas S; Mulvihill, Sean J; Skarda, David E; Finlayson, Samuel R G; Stoddard, Gregory J; Ott, Mark J; Firpo, Matthew A; Scaife, Courtney L

2017-07-11

To (1) evaluate rates of surgery for clinical stage I-II pancreatic ductal adenocarcinoma (PDAC), (2) identify predictors of not undergoing surgery, (3) quantify the degree to which patient- and hospital-level factors explain differences in hospital surgery rates, and (4) evaluate the association between adjusted hospital-specific surgery rates and overall survival (OS) of patients treated at different hospitals. Curative-intent surgery for potentially resectable PDAC is underutilized in the United States. Retrospective cohort study of patients ≤85 years with clinical stage I-II PDAC in the 2004 to 2014 National Cancer Database. Mixed effects multivariable models were used to characterize hospital-level variation across quintiles of hospital surgery rates. Multivariable Cox proportional hazards models were used to estimate the effect of adjusted hospital surgery rates on OS. Of 58,553 patients without contraindications or refusal of surgery, 63.8% underwent surgery, and the rate decreased from 2299/3528 (65.2%) in 2004 to 4412/7092 (62.2%) in 2014 (P < 0.001). Adjusted hospital rates of surgery varied 6-fold (11.4%-70.9%). Patients treated at hospitals with higher rates of surgery had better unadjusted OS (median OS 10.2, 13.3, 14.2, 16.5, and 18.4 months in quintiles 1-5, respectively, P < 0.001, log-rank). Treatment at hospitals in lower surgery rate quintiles 1-3 was independently associated with mortality [Hazard ratio (HR) 1.10 (1.01, 1.21), HR 1.08 (1.02, 1.15), and HR 1.09 (1.04, 1.14) for quintiles 1-3, respectively, compared with quintile 5] after adjusting for patient factors, hospital type, and hospital volume. Quality improvement efforts are needed to help hospitals with low rates of surgery ensure that their patients have access to appropriate surgery.

Spreading out Muscle Mass within a Hill-Type Model: A Computer Simulation Study

PubMed Central

Günther, Michael; Röhrle, Oliver; Haeufle, Daniel F. B.; Schmitt, Syn

2012-01-01

It is state of the art that muscle contraction dynamics is adequately described by a hyperbolic relation between muscle force and contraction velocity (Hill relation), thereby neglecting muscle internal mass inertia (first-order dynamics). Accordingly, the vast majority of modelling approaches also neglect muscle internal inertia. Assuming that such first-order contraction dynamics yet interacts with muscle internal mass distribution, this study investigates two questions: (i) what is the time scale on which the muscle responds to a force step? (ii) How does this response scale with muscle design parameters? Thereto, we simulated accelerated contractions of alternating sequences of Hill-type contractile elements and point masses. We found that in a typical small muscle the force levels off after about 0.2 ms, contraction velocity after about 0.5 ms. In an upscaled version representing bigger mammals' muscles, the force levels off after about 20 ms, and the theoretically expected maximum contraction velocity is not reached. We conclude (i) that it may be indispensable to introduce second-order contributions into muscle models to understand high-frequency muscle responses, particularly in bigger muscles. Additionally, (ii) constructing more elaborate measuring devices seems to be worthwhile to distinguish viscoelastic and inertia properties in rapid contractile responses of muscles. PMID:23227110

Topology simplification: Important biological phenomenon or evolutionary relic?. Comment on "Disentangling DNA molecules" by Alexander Vologodskii

NASA Astrophysics Data System (ADS)

Bates, Andrew D.; Maxwell, Anthony

2016-09-01

The review, Disentangling DNA molecules[1], gives an excellent technical description of the phenomenon of topology simplification (TS) by type IIA DNA topoisomerases (topos). In the 20 years since its discovery [2], this effect has attracted a good deal of attention, probably because of its apparently magical nature, and because it seemed to offer a solution to the conundrum that all type II topos rely on ATP hydrolysis, but only bacterial DNA gyrases were known to transduce the free energy of hydrolysis into torsion (supercoiling) in the DNA. It made good sense to think that the other enzymes are using the energy to reduce the level of supercoiling, knotting, and particularly decatenation (unlinking), below equilibrium, since the key activity of the non-supercoiling topos is the removal of links between daughter chromosomes [3]. As Vologodskii discusses [1], there have been a number of theoretical models developed to explain how the local effect of a type II topo can influence the global level of knotting and catenation in large DNA molecules, and he explains how features of two of the most successful models (bent G segment and hooked juxtapositions) may be combined to explain the magnitude of the effect and overcome a kinetic problem with the hooked juxtaposition model.

Mitochondrial reactive oxygen species and complex II levels are associated with the outcome of hepatocellular carcinoma

PubMed Central

WU, JIANHUA; ZHAO, FEI; ZHAO, YUFEI; GUO, ZHANJUN

2015-01-01

In the present study, two oxidative stress parameters, reactive oxygen species (ROS) and mitochondrial respiratory complex II, were evaluated in the mitochondria of hepatocellular carcinoma (HCC) cells to determine the association between these parameters and the carcinogenesis and clinical outcome of HCC. High levels of ROS and low levels of complex II were found to be associated with reduced post-operative survival in HCC patients using the log-rank test. Furthermore, multivariate analysis confirmed that the levels of ROS [relative risk (RR)=2.867; 95% confidence interval (CI), 1.062–7.737; P=0.038] and complex II (RR=5.422; 95% CI, 1.273–23.088; P=0.022) were independent predictors for the survival of patients with HCC. Therefore, the analysis of ROS and complex II levels may provide a useful research and therapeutic tool for the prediction of HCC prognosis and treatment. PMID:26622849

Solid Phase Extraction of Inorganic Mercury Using 5-Phenylazo-8-hydroxyquinoline and Determination by Cold Vapor Atomic Fluorescence Spectroscopy in Natural Water Samples

PubMed Central

Daye, Mirna; Halwani, Jalal; Hamzeh, Mariam

2013-01-01

8-Hydroxyquinoline (8-HQ) was chosen as a powerful ligand for Hg solid phase extraction. Among several chelating resins based on 8-HQ, 5-phenylazo-8-hydroxyquinoline (5Ph8HQ) is used for mercury extraction in which the adsorption dynamics were fully studied. It has been shown that Hg(II) is totally absorbed by 5Ph8HQ within the first 30 minutes of contact time with t 1/2 5 minutes, following Langmuir adsorption model. At pH 4, the affinity of mercury is unchallenged by other metals except, for Cu(II), which have shown higher Kd value. With these latter characteristics, 5Ph8HQ was examined for the preconcentration of trace levels of Hg(II). The developed method showed quantitative recoveries of Hg(II) with LOD = 0.21 pg mL−1 and RSD = 3–6% using cold vapor atomic fluorescence spectroscopy (CV-AFS) with a preconcentration factor greater than 250. PMID:24459417

Evidence for Fluorescent Fe II Emission from Extended Low Ionization Outflows in Obscured Quasars

NASA Astrophysics Data System (ADS)

Wang, Tinggui; Ferland, Gary J.; Yang, Chenwei; Wang, Huiyuan; Zhang, Shaohua

2016-06-01

Recent studies have shown that outflows in at least some broad absorption line (BAL) quasars are extended well beyond the putative dusty torus. Such outflows should be detectable in obscured quasars. We present four WISE selected infrared red quasars with very strong and peculiar ultraviolet Fe II emission lines: strong UV Fe II UV arising from transitions to ground/low excitation levels, and very weak Fe II at wavelengths longer than 2800 Å. The spectra of these quasars display strong resonant emission lines, such as C IV, Al III and Mg II but sometimes, a lack of non-resonant lines such as C III], S III and He II. We interpret the Fe II lines as resonantly scattered light from the extended outflows that are viewed nearly edge-on, so that the accretion disk and broad line region are obscured by the dusty torus, while the extended outflows are not. We show that dust free gas exposed to strong radiation longward of 912 Å produces Fe II emission very similar to that observed. The gas is too cool to collisionally excite Fe II lines, accounting for the lack of optical emission. The spectral energy distribution from the UV to the mid-infrared can be modeled as emission from a clumpy dusty torus, with UV emission being reflected/scattered light either by the dusty torus or the outflow. Within this scenario, we estimate a minimum covering factor of the outflows from a few to 20% for the Fe II scattering region, suggesting that Fe II BAL quasars are at a special stage of quasar evolution.

Emergent cell and tissue dynamics from subcellular modeling of active biomechanical processes

NASA Astrophysics Data System (ADS)

Sandersius, S. A.; Weijer, C. J.; Newman, T. J.

2011-08-01

Cells and the tissues they form are not passive material bodies. Cells change their behavior in response to external biochemical and biomechanical cues. Behavioral changes, such as morphological deformation, proliferation and migration, are striking in many multicellular processes such as morphogenesis, wound healing and cancer progression. Cell-based modeling of these phenomena requires algorithms that can capture active cell behavior and their emergent tissue-level phenotypes. In this paper, we report on extensions of the subcellular element model to model active biomechanical subcellular processes. These processes lead to emergent cell and tissue level phenotypes at larger scales, including (i) adaptive shape deformations in cells responding to slow stretching, (ii) viscous flow of embryonic tissues, and (iii) streaming patterns of chemotactic cells in epithelial-like sheets. In each case, we connect our simulation results to recent experiments.

Performance of the LHCb RICH detectors during the LHC Run II

NASA Astrophysics Data System (ADS)

Papanestis, A.; D'Ambrosio, C.; LHCb RICH Collaboration

2017-12-01

The LHCb RICH system provides hadron identification over a wide momentum range (2-100 GeV/c). This detector system is key to LHCb's precision flavour physics programme, which has unique sensitivity to physics beyond the standard model. This paper reports on the performance of the LHCb RICH in Run II, following significant changes in the detector and operating conditions. The changes include the refurbishment of significant number of photon detectors, assembled using new vacuum technologies, and the removal of the aerogel radiator. The start of Run II of the LHC saw the beam energy increase to 6.5 TeV per beam and a new trigger strategy for LHCb with full online detector calibration. The RICH information has also been made available for all trigger streams in the High Level Trigger for the first time.

Development of Conceptual Learning and Development Assessment Series II: Cutting Tool. Technical Report No. 431. Reprinted December 1977.

ERIC Educational Resources Information Center

Klausmeier, Herbert J.; And Others

The Conceptual Learning and Development (CLD) Model suggests four successive levels of concept learning: (1) concrete--recognizing an object which has been encountered previously; (2) identity--recognizing a known object when it appears in a different spatial, time, or sensory perspective; (3) classificatory--generalizing that two items are alike…

KINETICS OF LOW SOURCE REACTOR STARTUPS. PART II

DOE Office of Scientific and Technical Information (OSTI.GOV)

hurwitz, H. Jr.; MacMillan, D.B.; Smith, J.H.

1962-06-01

A computational technique is described for computation of the probability distribution of power level for a low source reactor startup. The technique uses a mathematical model, for the time-dependent probability distribution of neutron and precursor concentration, having finite neutron lifetime, one group of delayed neutron precursors, and no spatial dependence. Results obtained by the technique are given. (auth)

40 CFR 86.1825-08 - Durability demonstration procedures for refueling emissions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... specified in § 86.1805, or (ii) At least 75 percent of the full useful life mileage. In which case, the... Durability demonstration procedures for refueling emissions. This section applies to 2008 and later model... emission levels and deterioration in actual use over the full useful life of candidate in-use vehicles of...

The CMS electron and photon trigger for the LHC Run 2

NASA Astrophysics Data System (ADS)

Dezoort, Gage; Xia, Fan

2017-01-01

The CMS experiment implements a sophisticated two-level triggering system composed of Level-1, instrumented by custom-design hardware boards, and a software High-Level-Trigger. A new Level-1 trigger architecture with improved performance is now being used to maintain the thresholds that were used in LHC Run I for the more challenging luminosity conditions experienced during Run II. The upgrades to the calorimetry trigger will be described along with performance data. The algorithms for the selection of final states with electrons and photons, both for precision measurements and for searches of new physics beyond the Standard Model, will be described in detail.

Simulation of the Greenland Ice Sheet over two glacial-interglacial cycles: investigating a sub-ice-shelf melt parameterization and relative sea level forcing in an ice-sheet-ice-shelf model

NASA Astrophysics Data System (ADS)

Bradley, Sarah L.; Reerink, Thomas J.; van de Wal, Roderik S. W.; Helsen, Michiel M.

2018-05-01

Observational evidence, including offshore moraines and sediment cores, confirm that at the Last Glacial Maximum (LGM) the Greenland ice sheet (GrIS) expanded to a significantly larger spatial extent than seen at present, grounding into Baffin Bay and out onto the continental shelf break. Given this larger spatial extent and its close proximity to the neighbouring Laurentide Ice Sheet (LIS) and Innuitian Ice Sheet (IIS), it is likely these ice sheets will have had a strong non-local influence on the spatial and temporal behaviour of the GrIS. Most previous paleo ice-sheet modelling simulations recreated an ice sheet that either did not extend out onto the continental shelf or utilized a simplified marine ice parameterization which did not fully include the effect of ice shelves or neglected the sensitivity of the GrIS to this non-local bedrock signal from the surrounding ice sheets. In this paper, we investigated the evolution of the GrIS over the two most recent glacial-interglacial cycles (240 ka BP to the present day) using the ice-sheet-ice-shelf model IMAU-ICE. We investigated the solid earth influence of the LIS and IIS via an offline relative sea level (RSL) forcing generated by a glacial isostatic adjustment (GIA) model. The RSL forcing governed the spatial and temporal pattern of sub-ice-shelf melting via changes in the water depth below the ice shelves. In the ensemble of simulations, at the glacial maximums, the GrIS coalesced with the IIS to the north and expanded to the continental shelf break to the southwest but remained too restricted to the northeast. In terms of the global mean sea level contribution, at the Last Interglacial (LIG) and LGM the ice sheet added 1.46 and -2.59 m, respectively. This LGM contribution by the GrIS is considerably higher (˜ 1.26 m) than most previous studies whereas the contribution to the LIG highstand is lower (˜ 0.7 m). The spatial and temporal behaviour of the northern margin was highly variable in all simulations, controlled by the sub-ice-shelf melting which was dictated by the RSL forcing and the glacial history of the IIS and LIS. In contrast, the southwestern part of the ice sheet was insensitive to these forcings, with a uniform response in all simulations controlled by the surface air temperature, derived from ice cores.

Berberine improves cognitive impairment by promoting autophagic clearance and inhibiting production of β-amyloid in APP/tau/PS1 mouse model of Alzheimer's disease.

PubMed

Huang, Min; Jiang, Xin; Liang, Yubin; Liu, Qiong; Chen, Siyan; Guo, Yi

2017-05-01

This study investigates the neuroprotective properties of berberine (a natural isoquinoline alkaloid isolated from the Rhizoma coptidis) and finds that berberine could promote β-amyloid (Aβ) clearance and inhibit Aβ production in the triple-transgenic mouse model of Alzheimer's disease (3×Tg-AD). During the study, berberine was first administrated to treat 3×Tg-AD mice and primary neurons. Morris water maze assay, western blotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining and histological analysis, transmission electron microscopic analysis were then used to evaluate the effects of the berberine administration. The result showed that berberine significantly improved 3×Tg-AD mice's spatial learning capacity and memory retention, promoted autophagy activity identified by the enhancement of brain LC3-II, beclin-1, hVps34, and Cathepsin-D levels as well as the reduction of brain P62 and Bcl-2 levels in AD mice, facilitated reduction of Aβ and APP levels, reduced Aβ plaque deposition in the hippocampus of AD mice, and inhibited b-site APP cleavage enzyme 1 (BACE1) expression. Similar results were also found in 3×Tg-AD primary hippocampal neurons: berbernine treatment decreased the levels of extracellular and intracellular Aβ1-42, increased the protein levels of LC3-II, beclin-1, hVps34, and Cathepsin-D, and decreased the levels of P62, Bcl-2, APP and BACE1 levels. In summary, berberine shows neuroprotective effects on 3×Tg-AD mice and may be a promising multitarget drug in the preventionand protection against AD. Copyright © 2017. Published by Elsevier Inc.

Source term model evaluations for the low-level waste facility performance assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yim, M.S.; Su, S.I.

1995-12-31

The estimation of release of radionuclides from various waste forms to the bottom boundary of the waste disposal facility (source term) is one of the most important aspects of LLW facility performance assessment. In this work, several currently used source term models are comparatively evaluated for the release of carbon-14 based on a test case problem. The models compared include PRESTO-EPA-CPG, IMPACTS, DUST and NEFTRAN-II. Major differences in assumptions and approaches between the models are described and key parameters are identified through sensitivity analysis. The source term results from different models are compared and other concerns or suggestions are discussed.

Safety evaluation for a cell-based immune support system in an ex vivo rat model of gram-negative sepsis.

PubMed

Sauer, Martin; Altrichter, Jens; Kreutzer, Hans-Jürgen; Schmidt, Heidrun; Nöldge-Schomburg, Gabriele; Schmidt, Reinhard; Mitzner, Steffen R

2009-10-01

Granulocyte dysfunction is a central component of immunodeficiency in septic patients. Granulocyte transfusions appear to be pathophysiologically useful; however, they cause unwanted side-effects in the lungs and other organs. This study evaluates the safety of an extracorporeal immune support system with granulocytic cells in a rat model of Gram-negative sepsis. Three groups of male CD rats received either saline (control group, I), a dose of Escherichia coli O7:K1 lethal to 90% of the animals (LD90) (septic group, II), or an LD90 dose of E. coli that was incubated with the human promyelocytic leukemia cell line (HL-60) (differentiated into the granulocytic direction) for 20 min prior to infusion (second septic group, III). The animals were observed for seven days. Pre-treatment with HL-60 cells resulted in no adverse effects in the group III animals. Significantly lower bacterial counts and endotoxin levels in the plasma were detected after 24 h as compared to group II (P < 0.05). Group III animals had better weight gain and more stable hemodynamics than group II animals (P < 0.01). Seven day survival was 0/8 in group II, 6/8 in group III, and 8/9 in group I (log-rank test: II-III: P < 0.001). The data suggest that extracorporeal use of granulocytes allows the therapeutic use of these cells while avoiding unwanted effects resulting from direct contact to internal organs.

A mathematical analysis of rebound in a target-mediated drug disposition model: II. With feedback.

PubMed

Aston, Philip J; Derks, Gianne; Agoram, Balaji M; van der Graaf, Piet H

2017-07-01

We consider the possibility of free receptor (antigen/cytokine) levels rebounding to higher than the baseline level after the application of an antibody drug using a target-mediated drug disposition model. It is assumed that the receptor synthesis rate experiences homeostatic feedback from the receptor levels. It is shown for a very fast feedback response, that the occurrence of rebound is determined by the ratio of the elimination rates, in a very similar way as for no feedback. However, for a slow feedback response, there will always be rebound. This result is illustrated with an example involving the drug efalizumab for patients with psoriasis. It is shown that slow feedback can be a plausible explanation for the observed rebound in this example.

A 2D ion chamber array audit of wedged and asymmetric fields in an inhomogeneous lung phantom

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lye, Jessica; Dunn, Leon, E-mail: leon.dunn@arpansa.gov.au; Alves, Andrew

Purpose: The Australian Clinical Dosimetry Service (ACDS) has implemented a new method of a nonreference condition Level II type dosimetric audit of radiotherapy services to increase measurement accuracy and patient safety within Australia. The aim of this work is to describe the methodology, tolerances, and outcomes from the new audit. Methods: The ACDS Level II audit measures the dose delivered in 2D planes using an ionization chamber based array positioned at multiple depths. Measurements are made in rectilinear homogeneous and inhomogeneous phantoms composed of slabs of solid water and lung. Computer generated computed tomography data sets of the rectilinear phantomsmore » are supplied to the facility prior to audit for planning of a range of cases including reference fields, asymmetric fields, and wedged fields. The audit assesses 3D planning with 6 MV photons with a static (zero degree) gantry. Scoring is performed using local dose differences between the planned and measured dose within 80% of the field width. The overall audit result is determined by the maximum dose difference over all scoring points, cases, and planes. Pass (Optimal Level) is defined as maximum dose difference ≤3.3%, Pass (Action Level) is ≤5.0%, and Fail (Out of Tolerance) is >5.0%. Results: At close of 2013, the ACDS had performed 24 Level II audits. 63% of the audits passed, 33% failed, and the remaining audit was not assessable. Of the 15 audits that passed, 3 were at Pass (Action Level). The high fail rate is largely due to a systemic issue with modeling asymmetric 60° wedges which caused a delivered overdose of 5%–8%. Conclusions: The ACDS has implemented a nonreference condition Level II type audit, based on ion chamber 2D array measurements in an inhomogeneous slab phantom. The powerful diagnostic ability of this audit has allowed the ACDS to rigorously test the treatment planning systems implemented in Australian radiotherapy facilities. Recommendations from audits have led to facilities modifying clinical practice and changing planning protocols.« less

Detection of copper, lead, cadmium and iron in wine using electronic tongue sensor system.

PubMed

Simões da Costa, A M; Delgadillo, I; Rudnitskaya, A

2014-11-01

An array of 10 potentiometric chemical sensors has been applied to the detection of total Fe, Cu, Pb and Cd content in digested wine. As digestion of organic matter of wine is necessary prior to the trace metal detection using potentiometric sensors, sample preparation procedures have been optimized. Different variants of wet and microwave digestion and dry ashing, 14 conditions in total, have been tested. Decomposition of organic matter was assessed using Fourier transform mid-infrared spectroscopy and total phenolic content. Dry ashing was found to be the most effective method of wine digestion. Measurements with sensors in individual solutions of Fe(III), Cu(II), Pb(II) and Cd(II) prepared on different backgrounds have shown that their detection limits were below typical concentration levels of these metals in wines and, in the case of Cu, Pb and Cd below maximum allowed concentrations. Detection of Fe in digested wine samples was possible using discrete iron-sensitive sensors with chalcogenide glass membranes with RMSEP of 0.05 mmol L(-1) in the concentration range from 0.0786 to 0.472 mmol L(-1). Low concentration levels of Cu, Pb and Cd in wine and cross-sensitivity of respective sensors resulted in the non-linearity of their responses, requiring back-propagation neural network for the calibration. Calibration models have been calculated using measurements in the model mixed solutions containing all three metals and a set of digested wine sample. RMSEP values for Cu, Pb and Cd were 3.9, 39 and 1.2 μmol L(-1) in model solutions and 2, 150 and 1 μmol L(-1) in digested wine samples. Copyright © 2014 Elsevier B.V. All rights reserved.

The Association of Serum Levels of Brain-Derived Neurotrophic Factor with the Occurrence of and Recovery from Delirium in Older Medical Inpatients.

PubMed

Williams, John; Finn, Karen; Melvin, Vincent; Meagher, David; McCarthy, Geraldine; Adamis, Dimitrios

2017-01-01

Limited studies of the association between BDNF levels and delirium have given inconclusive results. This prospective, longitudinal study examined the relationship between BDNF levels and the occurrence of and recovery from delirium. Participants were assessed twice weekly using MoCA, DRS-R98, and APACHE II scales. BDNF levels were estimated using an ELISA method. Delirium was defined with DRS-R98 (score > 16) and recovery from delirium as ≥2 consecutive assessments without delirium prior to discharge. We identified no difference in BDNF levels between those with and without delirium. Excluding those who never developed delirium ( n = 140), we examined the association of BDNF levels and other variables with delirium recovery. Of 58 who experienced delirium, 39 remained delirious while 19 recovered. Using Generalized Estimating Equations models we found that BDNF levels (Wald χ 2 = 7.155; df: 1, p = 0.007) and MoCA (Wald χ 2 = 4.933; df: 1, p = 0.026) were associated with recovery. No significant association was found for APACHE II, dementia, age, or gender. BDNF levels do not appear to be directly linked to the occurrence of delirium but recovery was less likely in those with continuously lower levels. No previous study has investigated the role of BDNF in delirium recovery and these findings warrant replication in other populations.

The Great Recession worsened blood pressure and blood glucose levels in American adults.

PubMed

Seeman, Teresa; Thomas, Duncan; Merkin, Sharon Stein; Moore, Kari; Watson, Karol; Karlamangla, Arun

2018-03-27

Longitudinal, individual-specific data from the Multi-Ethnic Study of Atherosclerosis (MESA) provide support for the hypothesis that the 2008 to 2010 Great Recession (GR) negatively impacted the health of US adults. Results further advance understanding of the relationship by ( i ) illuminating hypothesized greater negative impacts in population subgroups exposed to more severe impacts of the GR and ( ii ) explicitly controlling for confounding by individual differences in age-related changes in health over time. Analyses overcome limitations of prior work by ( i ) employing individual-level data that avoid concerns about ecological fallacy associated with prior reliance on group-level data, ( ii ) using four waves of data before the GR to estimate and control for underlying individual-level age-related trends, ( iii ) focusing on objective, temporally appropriate health outcomes rather than mortality, and ( iv ) leveraging a diverse cohort to investigate subgroup differences in the GR's impact. Innovative individual fixed-effects modeling controlling for individual-level age-related trajectories yielded substantively important insights: ( i ) significant elevations post-GR for blood pressure and fasting glucose, especially among those on medication pre-GR, and ( ii ) reductions in prevalence and intensity of medication use post-GR. Important differences in the effects of the GR are seen across subgroups, with larger effects among younger adults (who are likely still in the labor force) and older homeowners (whose declining home wealth likely reduced financial security, with less scope for recouping losses during their lifetime); least affected were older adults without a college degree (whose greater reliance on Medicare and Social Security likely provided more protection from the recession).

Explicit Finite Element Modeling of Multilayer Composite Fabric for Gas Turbine Engine Containment Systems, Phase II. Part 3; Material Model Development and Simulation of Experiments

NASA Technical Reports Server (NTRS)

Simmons, J.; Erlich, D.; Shockey, D.

2009-01-01

A team consisting of Arizona State University, Honeywell Engines, Systems & Services, the National Aeronautics and Space Administration Glenn Research Center, and SRI International collaborated to develop computational models and verification testing for designing and evaluating turbine engine fan blade fabric containment structures. This research was conducted under the Federal Aviation Administration Airworthiness Assurance Center of Excellence and was sponsored by the Aircraft Catastrophic Failure Prevention Program. The research was directed toward improving the modeling of a turbine engine fabric containment structure for an engine blade-out containment demonstration test required for certification of aircraft engines. The research conducted in Phase II began a new level of capability to design and develop fan blade containment systems for turbine engines. Significant progress was made in three areas: (1) further development of the ballistic fabric model to increase confidence and robustness in the material models for the Kevlar(TradeName) and Zylon(TradeName) material models developed in Phase I, (2) the capability was improved for finite element modeling of multiple layers of fabric using multiple layers of shell elements, and (3) large-scale simulations were performed. This report concentrates on the material model development and simulations of the impact tests.

Markedly accelerated catabolism of apolipoprotein A-II (ApoA-II) and high density lipoproteins containing ApoA-II in classic lecithin: cholesterol acyltransferase deficiency and fish-eye disease.

PubMed Central

Rader, D J; Ikewaki, K; Duverger, N; Schmidt, H; Pritchard, H; Frohlich, J; Clerc, M; Dumon, M F; Fairwell, T; Zech, L

1994-01-01

Classic (complete) lecithin:cholesterol acyltransferase (LCAT) deficiency and Fish-eye disease (partial LCAT deficiency) are genetic syndromes associated with markedly decreased plasma levels of high density lipoprotein (HDL) cholesterol but not with an increased risk of atherosclerotic cardiovascular disease. We investigated the metabolism of the HDL apolipoproteins (apo) apoA-I and apoA-II in a total of five patients with LCAT deficiency, one with classic LCAT deficiency and four with Fish-eye disease. Plasma levels of apoA-II were decreased to a proportionately greater extent (23% of normal) than apoA-I (30% of normal). In addition, plasma concentrations of HDL particles containing both apoA-I and apoA-II (LpA-I:A-II) were much lower (18% of normal) than those of particles containing only apoA-I (LpA-I) (51% of normal). The metabolic basis for the low levels of apoA-II and LpA-I:A-II was investigated in all five patients using both exogenous radiotracer and endogenous stable isotope labeling techniques. The mean plasma residence time of apoA-I was decreased at 2.08 +/- 0.27 d (controls 4.74 +/- 0.65 days); however, the residence time of apoA-II was even shorter at 1.66 +/- 0.24 d (controls 5.25 +/- 0.61 d). In addition, the catabolism of apoA-I in LpA-I:A-II was substantially faster than that of apoA-I in LpA-I. In summary, genetic syndromes of either complete or partial LCAT deficiency result in low levels of HDL through preferential hypercatabolism of apoA-II and HDL particles containing apoA-II. Because LpA-I has been proposed to be more protective than LpA-I:A-II against atherosclerosis, this selective effect on the metabolism of LpA-I:A-II may provide a potential explanation why patients with classic LCAT deficiency and Fish-eye disease are not at increased risk for premature atherosclerosis despite markedly decreased levels of HDL cholesterol and apoA-I. PMID:8282802

The Effect of Chromium Picolinate Supplementation on the Pancreas and Macroangiopathy in Type II Diabetes Mellitus Rats

PubMed Central

Huang, Shan; Peng, Wenfang; Jiang, Xiaohong; Shao, Kan; Xia, Lili; Tang, Yubin; Qiu, Jiayin

2014-01-01

Purpose. The aim was to explore the effect of the chromium picolinate (CrPic) administration on the pancreas and macroangiopathy of type II diabetes mellitus rats. Methods. The type II diabetes mellitus (T2DM) rat model was induced by low-dose streptozotocin (STZ). The rats were randomly divided into 5 groups (ten rats in each group). After supplementing CrPic for 15 weeks, the histopathological examination was performed by hematoxylin-eosin (HE) staining. Serum insulin and NO level were determined by radioimmunoassay and colorimetry, respectively. Serum glycosylated hemoglobin (HbA1C), adiponectin (APN), advanced glycation end products (AGES), and apelin were measured by ELISA. Real-time reverse transcription polymerase chain reaction (RT-PCR) was applied for detecting the mRNA expression of APN and apelin. Results. After CrPic treatment, compared with the T2DM control group (group 2), pancreas sections stained with HE showed the completed pancreatic cells structure and no inflammatory infiltration in groups 4 and 5. In addition, the levels of serum NO and insulin were significantly increased and the serum levels of HbA1C, AGES, APN, and apelin were significantly decreased in groups 4 and 5 compared with group 2. The mRNA expression of APN and apelin in groups 4 and 5 was also recovered to the normal level. Conclusion. CrPic can recover the function of Β-cells and alleviate macroangiopathy in STZ-induced T2DM rats. PMID:25054160

The effect of chromium picolinate supplementation on the pancreas and macroangiopathy in type II diabetes mellitus rats.

PubMed

Huang, Shan; Peng, Wenfang; Jiang, Xiaohong; Shao, Kan; Xia, Lili; Tang, Yubin; Qiu, Jiayin

2014-01-01

The aim was to explore the effect of the chromium picolinate (CrPic) administration on the pancreas and macroangiopathy of type II diabetes mellitus rats. The type II diabetes mellitus (T2DM) rat model was induced by low-dose streptozotocin (STZ). The rats were randomly divided into 5 groups (ten rats in each group). After supplementing CrPic for 15 weeks, the histopathological examination was performed by hematoxylin-eosin (HE) staining. Serum insulin and NO level were determined by radioimmunoassay and colorimetry, respectively. Serum glycosylated hemoglobin (HbA1C), adiponectin (APN), advanced glycation end products (AGES), and apelin were measured by ELISA. Real-time reverse transcription polymerase chain reaction (RT-PCR) was applied for detecting the mRNA expression of APN and apelin. After CrPic treatment, compared with the T2DM control group (group 2), pancreas sections stained with HE showed the completed pancreatic cells structure and no inflammatory infiltration in groups 4 and 5. In addition, the levels of serum NO and insulin were significantly increased and the serum levels of HbA1C, AGES, APN, and apelin were significantly decreased in groups 4 and 5 compared with group 2. The mRNA expression of APN and apelin in groups 4 and 5 was also recovered to the normal level. CrPic can recover the function of Β-cells and alleviate macroangiopathy in STZ-induced T2DM rats.

Effects of intravesical dexpanthenol use on lipid peroxidation and bladder histology in a chemical cystitis animal model.

PubMed

Bayrak, Omer; Seckiner, Ilker; Solakhan, Mehmet; Karakok, Metin; Erturhan, Sakip M; Yagci, Faruk

2012-05-01

To demonstrate the effects of intravesical dexpanthenol use on bladder histology and lipid peroxidation in a chemical cystitis animal model. Thirty-five New Zealand rabbits were divided into 3 groups. Cystitis was conducted with transurethral intravesical hydrochloric acid instillation on the subjects in groups I and II. Then, Group I subjects were transurethrally administered intravesical dexpanthenol therapy twice a week, Group II subjects were given only intravesical isotonic NaCl instillation, and Group III subjects were administered intravesical isotonic NaCl instillation without conducting chemical cystitis to create the same stress. Treatment schemes of all groups were arranged in the same manner. After 6-week therapy, the rabbits were sacrificed and histopathologic investigations were carried out to demonstrate changes in the urinary bladder. Serum and tissue malondialdehyde (MDA) values were examined to investigate the effect of dexpanthenol on lipid peroxidation. We observed that the basal membrane and mucosal integrity were maintained, inflammatory cells were suppressed, and MDA levels decreased in group I, which received dexpanthenol therapy. However, it was also observed that mucosal integrity was spoiled, numerous inflammatory cells were accumulated, and MDA levels were significantly increased in group II, which was administered isotonic NaCl. In light of our findings, intravesical dexpanthenol therapy could be a new therapeutic approach in the treatment of interstitial cystitis because of its low cost and acceptable side effects. Copyright © 2012 Elsevier Inc. All rights reserved.

Recent Advances in Understanding of Kinetic Interplay Between Phase II Metabolism and Efflux Transport.

PubMed

Wang, Shuai; Xing, Huijie; Zhao, Mengjing; Lu, Danyi; Li, Zhijie; Dong, Dong; Wu, Baojian

2016-01-01

Mechanistic understanding of the metabolism-transport interplay assumes great importance in pharmaceutical fields because the knowledge can help to interpret drug/xenobiotic metabolism and disposition studies as well as the drug-drug interactions in vivo. About 10 years ago, it started to recognize that cellular phase II metabolism is strongly influenced by the excretion (efflux transport) of generated metabolites, a kinetic phenomenon termed "phase II metabolism-transport interplay". This interplay is believed to have significant effects on the pharmacokinetics (bioavailability) of drugs/chemicals undergoing phase II metabolism. In this article, we review the studies investigating the phase II metabolism-transport interplay using cell models, perfused rat intestine, and intact rats. The potential confounding factors in exploring such interplay is also summarized. Moreover, the mechanism underlying the phase II metabolism-transport interplay is discussed. Various studies with engineered cells and rodents have demonstrated that there is an interaction (interplay) between phase II enzymes and efflux transporters. This type of interplay mainly refers to the dependence of phase II (conjugative) metabolism on the activities of efflux transporters. In general, inhibiting efflux transporters or decreasing their expression causes the reductions in metabolite excretion, apparent excretion clearance (CLapp) and total metabolism (fmet), as well as an increase in the intracellular level of metabolite (Ci). The deconjugation mediated by hydrolase (acting as a "bridge") is essential for the interplay to play out based on pharmacokinetic modeling/simulations, cell and animal studies. The hydrolases bridge the two processes (i.e., metabolite formation and excretion) and enable the interplay thereof (a bridging effect). Without the bridge, metabolite formation is independent on its downstream process excretion, thus impact of metabolite excretion on its formation is impossible. Deconjugation (mediated by hydrolases) plays an essential role in the conjugation-transport interplay. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Photodamage of a Mn(III/IV)-oxo mixed-valence compound and photosystem II: evidence that a high-valent manganese species is responsible for UV-induced photodamage of the oxygen-evolving complex in photosystem II.

PubMed

Wei, Zi; Cady, Clyde W; Brudvig, Gary W; Hou, Harvey J M

2011-01-01

The Mn cluster in photosystem II (PS II) is believed to play an important role in the UV photoinhibition of green plants, but the mechanism is still not clear at a molecular level. In this work, the photochemical stability of [Mn(III)(O)(2)Mn(IV)(H(2)O)(2)(Terpy)(2)](NO(3))(3) (Terpy=2,2':6',2''-terpyridine), designated as Mn-oxo mixed-valence dimer, a well characterized functional model of the oxygen-evolving complex in PS II, was examined in aqueous solution by exposing the complex to excess light irradiation at six different wavelengths in the range of 250 to 700 nm. The photodamage of the Mn-oxo mixed-valence dimer was confirmed by the decrease of its oxygen-evolution activity measured in the presence of the chemical oxidant oxone. Ultraviolet light irradiation induced a new absorption peak at around 400-440 nm of the Mn-oxo mixed-valence dimer. Visible light did not have the same effect on the Mn-oxo mixed-valence dimer. We speculate that the spectral change may be caused by conversion of the Mn(III)O(2)Mn(IV) dimer into a new structure--Mn(IV)O(2)Mn(IV). In the processes, the appearance of a 514 nm fluorescence peak was observed in the solution and may be linked to the hydration or protonation of Terpy ligand in the Mn-oxo dimer. In comparing the response of the PS II functional model compound and the PS II complex to excess light radiation, our results support the idea that UV photoinhibition is triggered at the Mn(4)Ca center of the oxygen-evolution complex in PS II by forming a modified structure, possibly a Mn(IV) species, and that the reaction of Mn ions is likely the initial step. Published by Elsevier B.V.

Modeling of Iron K Lines: Radiative and Auger Decay Data for Fe II-Fe IX

NASA Technical Reports Server (NTRS)

Palmeri, P.; Mendoza, C.; Kallman, T. R.; Bautista, M. A.; Melendez, M.

2003-01-01

A detailed analysis of the radiative and Auger de-excitation channels of K-shell vacancy states in Fe II-Fe IX has been carried out. Level energies, wavelengths, A-values, Auger rates and fluorescence yields have been calculated for the lowest fine-structure levels populated by photoionization of the ground state of the parent ion. Different branching ratios, namely K alpha 2/K alpha 1, K beta/K alpha, KLM/KLL, KMM/KLL, and the total K-shell fluorescence yields, omega(sub k), obtained in the present work have been compared with other theoretical data and solid-state measurements, finding good general agreement with the latter. The Kalpha 2/K alpha l ratio is found to be sensitive to the excitation mechanism. From these comparisons it has been possible to estimate an accuracy of approx.10% for the present transition probabilities.

Experimental evolution in silico: a custom-designed mathematical model for virulence evolution of Bacillus thuringiensis.

PubMed

Strauß, Jakob Friedrich; Crain, Philip; Schulenburg, Hinrich; Telschow, Arndt

2016-08-01

Most mathematical models on the evolution of virulence are based on epidemiological models that assume parasite transmission follows the mass action principle. In experimental evolution, however, mass action is often violated due to controlled infection protocols. This "theory-experiment mismatch" raises the question whether there is a need for new mathematical models to accommodate the particular characteristics of experimental evolution. Here, we explore the experimental evolution model system of Bacillus thuringiensis as a parasite and Caenorhabditis elegans as a host. Recent experimental studies with strict control of parasite transmission revealed that one-sided adaptation of B. thuringiensis with non-evolving hosts selects for intermediate or no virulence, sometimes coupled with parasite extinction. In contrast, host-parasite coevolution selects for high virulence and for hosts with strong resistance against B. thuringiensis. In order to explain the empirical results, we propose a new mathematical model that mimics the basic experimental set-up. The key assumptions are: (i) controlled parasite transmission (no mass action), (ii) discrete host generations, and (iii) context-dependent cost of toxin production. Our model analysis revealed the same basic trends as found in the experiments. Especially, we could show that resistant hosts select for highly virulent bacterial strains. Moreover, we found (i) that the evolved level of virulence is independent of the initial level of virulence, and (ii) that the average amount of bacteria ingested significantly affects the evolution of virulence with fewer bacteria ingested selecting for highly virulent strains. These predictions can be tested in future experiments. This study highlights the usefulness of custom-designed mathematical models in the analysis and interpretation of empirical results from experimental evolution. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.

The Strings of Eta Carina: The HST/STIS Spectra and [Ca II

NASA Technical Reports Server (NTRS)

Melendez, M. B.; Gull, T. R.; Bautista, M. A.; Badnell, N. R.

2006-01-01

Long linear, filamentary ejecta, are found to move at very high velocity external to the Homunculus, the circumstellar hourglass-shaped ejecta surrounding Eta Carinae. The origin of the strings is a puzzle. As an example, the Weigelt Blobs have N at 10X solar and C, O at 0.01X solar abundance, along with He/H significantly enhanced. This abundance pattern is evidence for extreme CNO-processing. Similarly, the Strontium Filament has Ti/Ni at 100X solar, presumably due to the lack of oxygen to form Ti-oxide precipitates onto dust grains. We have obtained 2-D spectra with the HST/STIS of the Strontium Filament and a portion of a string. These deep spectral exposures, at moderate dispersion, span much of the near red spectral region from 5000 to 9000A. We have identified twelve emission lines in these spectra with proper velocities and spatial structure of this string and obtained line ratios for [Ca II] (7293/7325A) and [Fe Ill (7157/8619A) which are useful for determining physical conditions in this nebulosity. In an attempt to use the [Ca II] ratio to determine the physical parameters, and ultimately the abundances in the strings, we have constructed a statistical equilibrium model for Ca II , including radiative and collisional rates. These results incorporate our newly calculated atomic data for levels n = 3,4,5 and 6 configurations of Ca II. The aim is to compute the [Ca II] line ratios and use them as a diagnostic of the physical parameters. Using the [Fe II] ratio we find that for Te=10,000 K, the electron density is Ne approx.10(exp 6)/cu cm. We plan to use the [Ca II] ratio to confirm this result. Then, we will extend the use of this multilevel model Ca II atom to study the physical conditions of the Strontium filament where eight lines of Ca II, both allowed and forbidden, had been identified. With the physical conditions determined, we will be able to derive reliable estimates for the gas phase abundances in the strings.

Intensity limits of the PSI Injector II cyclotron

NASA Astrophysics Data System (ADS)

Kolano, A.; Adelmann, A.; Barlow, R.; Baumgarten, C.

2018-03-01

We investigate limits on the current of the PSI Injector II high intensity separate-sector isochronous cyclotron, in its present configuration and after a proposed upgrade. Accelerator Driven Subcritical Reactors, neutron and neutrino experiments, and medical isotope production all benefit from increases in current, even at the ∼ 10% level: the PSI cyclotrons provide relevant experience. As space charge dominates at low beam energy, the injector is critical. Understanding space charge effects and halo formation through detailed numerical modelling gives clues on how to maximise the extracted current. Simulation of a space-charge dominated low energy high intensity (9.5 mA DC) machine, with a complex collimator set up in the central region shaping the bunch, is not trivial. We use the OPAL code, a tool for charged-particle optics calculations in large accelerator structures and beam lines, including 3D space charge. We have a precise model of the present (production) Injector II, operating at 2.2 mA current. A simple model of the proposed future (upgraded) configuration of the cyclotron is also investigated. We estimate intensity limits based on the developed models, supported by fitted scaling laws and measurements. We have been able to perform more detailed analysis of the bunch parameters and halo development than any previous study. Optimisation techniques enable better matching of the simulation set-up with Injector II parameters and measurements. We show that in the production configuration the beam current scales to the power of three with the beam size. However, at higher intensities, 4th power scaling is a better fit, setting the limit of approximately 3 mA. Currents of over 5 mA, higher than have been achieved to date, can be produced if the collimation scheme is adjusted.

RANDI 3.1 User’s Guide

DTIC Science & Technology

1994-08-20

ACKNOWLEDGMENTS The authors thank Ronald A. Wagstaff , Naval Rcsearch Laboratory, anid Walt McBride, Planning Systems Incorporated, for helpful discussions in...RANDI II) model developed at SACLANTCEN by M. Hamson and R. Wagstaff (1). RANDI 11 is aý, ambient noise model that predicts noise levels and...Program Element Number 0602435N, Program Manager Edward Chaika I i I U U I I I wID I 7 REFERENCES [1.1 Hamson, R. M., and Wagstaff , R. A., "An ambient

High-Fidelity Modeling of Computer Network Worms

DTIC Science & Technology

2004-06-22

plots the propagation of the TCP-based worm. This execution is among the largest TCP worm models simulated to date at packet-level. TCP vs . UDP Worm...the mapping of the virtual IP addresses to honeyd’s MAC address in the proxy’s ARP table. The proxy server listens for packets from both sides of...experimental setup, we used two ntium-4 ThinkPad , and an IBM Pentium-III ThinkPad ), running the proxy server and honeyd respectively. The Code Red II worm

Molecular mechanisms and signaling pathways of angiotensin II-induced muscle wasting: potential therapeutic targets for cardiac cachexia.

PubMed

Yoshida, Tadashi; Tabony, A Michael; Galvez, Sarah; Mitch, William E; Higashi, Yusuke; Sukhanov, Sergiy; Delafontaine, Patrice

2013-10-01

Cachexia is a serious complication of many chronic diseases, such as congestive heart failure (CHF) and chronic kidney disease (CKD). Many factors are involved in the development of cachexia, and there is increasing evidence that angiotensin II (Ang II), the main effector molecule of the renin-angiotensin system (RAS), plays an important role in this process. Patients with advanced CHF or CKD often have increased Ang II levels and cachexia, and angiotensin-converting enzyme (ACE) inhibitor treatment improves weight loss. In rodent models, an increase in systemic Ang II leads to weight loss through increased protein breakdown, reduced protein synthesis in skeletal muscle and decreased appetite. Ang II activates the ubiquitin-proteasome system via generation of reactive oxygen species and via inhibition of the insulin-like growth factor-1 signaling pathway. Furthermore, Ang II inhibits 5' AMP-activated protein kinase (AMPK) activity and disrupts normal energy balance. Ang II also increases cytokines and circulating hormones such as tumor necrosis factor-α, interleukin-6, serum amyloid-A, glucocorticoids and myostatin, which regulate muscle protein synthesis and degradation. Ang II acts on hypothalamic neurons to regulate orexigenic/anorexigenic neuropeptides, such as neuropeptide-Y, orexin and corticotropin-releasing hormone, leading to reduced appetite. Also, Ang II may regulate skeletal muscle regenerative processes. Several clinical studies have indicated that blockade of Ang II signaling via ACE inhibitors or Ang II type 1 receptor blockers prevents weight loss and improves muscle strength. Thus the RAS is a promising target for the treatment of muscle atrophy in patients with CHF and CKD. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting. Copyright © 2013 Elsevier Ltd. All rights reserved.

Imbalanced plasma ACE and ACE2 level in the uremic patients with cardiovascular diseases and its change during a single hemodialysis session.

PubMed

Yang, Chung-Wei; Lu, Li-Che; Chang, Chia-Chu; Cho, Ching-Chang; Hsieh, Wen-Yeh; Tsai, Chin-Hung; Lin, Yi-Chang; Lin, Chih-Sheng

2017-11-01

The renin-angiotensin system (RAS) has significant influences on heart and renal disease progression. Angiotensin converting enzyme (ACE) and angiotensin converting enzyme II (ACE2) are major peptidases of RAS components and play counteracting functions through angiotensin II (Ang II)/ATIR and angiotensin-(1-7) (Ang-(1-7))/Mas axis, respectively. There were 360 uremic patients on regular hemodialysis (HD) treatment (inclusive of 119 HD patients with cardiovascular diseases (CVD) and 241 HD patients without CVD and 50 healthy subjects were enrolled in this study. Plasma ACE, ACE2, Ang II and Ang-(1-7) levels of the HD patients were determined. We compared pre-HD levels of plasma ACE, ACE2, Ang II and Ang-(1-7) in the HD patients with and without CVD to those of the controls. The HD patients, particularly those with CVD, showed a significant increase in the levels of ACE and Ang II, whereas ACE2 and Ang-(1-7) levels were lower than those in the healthy controls. Therefore, imbalanced ACE/ACE2 was observed in the HD patients with CVD. In the course of a single HD session, the plasma ACE, ACE/ACE2 and Ang II levels in the HD patients with CVD were increased from pre-HD to post-HD. On the contrary, ACE2 levels were decreased after the HD session. These changes were not detected in the HD patients without CVD. Pathogenically imbalanced circulating ACE/ACE2 was detected in the HD patients, particularly those with CVD. HD session could increase ACE/Ang II/AT1R axis and decrease ACE2/Ang-(1-7)/Mas axis activity in the circulation of HD patients with CVD.

Ovarian factors inhibit and fetal factors stimulate the secretion of rat placental lactogen.

PubMed

Robertson, M C; Owens, R E; McCoshen, J A; Friesen, H G

1984-01-01

Removal of fetuses at day 14 of gestation (Ftx14) in the pregnant rat leads to a marked suppression of serum levels of rat placental lactogen (rPL-II). One might attribute this to compromised placental growth in the absence of a fetus. However, if ovariectomy and fetectomy (Ftx14 Ovx14) are carried out at the same time, a great increase in serum rPL-II levels is seen. This occurs despite a significant decrease in placental weight. When Ftx14 was performed on day 14 and Ovx was delayed 1, 2, or 3 days, the expected large increase in serum rPL-II was progressively attenuated compared to that seen when Ftx and Ovx were carried out simultaneously. Daily administration of 17 beta-estradiol (4 micrograms/rat X day) to Ftx14 Ovx14 pregnant rats resulted in a significant suppression of rPL-II and elevation of rPRL levels, a reversal of what is seen for these hormones in untreated Ftx14 Ovx14 animals. To test whether 17 beta-estradiol was acting through rat PRL (rPRL), serum levels of rPRL were elevated in Ftx13 Ovx13 animals with pimozide (0.6 mg/kg), a dopamine receptor blocker. There was no effect of this treatment on rPL-II levels. In late pregnancy (day 17) serum rPL-II levels remained high after removal of half the fetuses (1/2 Ftx), compared to the rapid fall in pregnant rats in which all fetuses were removed (Ftx17). Serum levels were also elevated in 1/2 Ftx animals compared to those in which half of the fetuses and placentas were removed by hemi-hysterectomy, suggesting that the increase in rPL-II levels in 1/2 Ftx animals was due to a stimulatory effect of the remaining fetuses on all of the placentas. These results indicate that the presence of the fetus is necessary for the normally observed increase in rPL-II levels in late pregnancy. In conclusion, fetal stimulators and ovarian inhibitors influence rPL-II secretion.

The anti-cancer drug Sunitinib promotes autophagy and protects from neurotoxicity in an HIV-1 Tat model of neurodegeneration

PubMed Central

Fields, Jerel A.; Metcalf, Jeff; Overk, Cassia; Adame, Anthony; Spencer, Brian; Wrasidlo, Wolfgang; Florio, Jazmin; Rockenstein, Edward; He, Johnny J.; Masliah, Eliezer

2017-01-01

Despite the success of antiretroviral therapies to control systemic HIV-1 infection, the prevalence of HIV-associated neurocognitive disorders (HAND) has not decreased among aging patients with HIV. Autophagy pathway alterations, triggered by HIV-1 proteins including gp120, Tat, and Nef, might contribute to the neurodegenerative process in aging patients with HAND. Although no treatments are currently available to manage HAND, we have previously shown that Sunitinib, an anti-cancer drug that blocks receptor tyrosine-kinase and cyclin kinase pathways, might be of interest. Studies in cancer models suggest that sunitinib might also modulate autophagy, which is dysregulated in our models of Tat-induced neurotoxicity. We evaluated the efficacy of sunitinib to promote autophagy in the CNS and ameliorate neurodegeneration using LC3-GFP expressing neuronal cells challenged with low concentrations of Tat and using inducible Tat transgenic mice. In neuronal cultures challenged with low levels of Tat, sunitinib increased markers of autophagy such as LC3-II and reduced p62 accumulation in a dose-dependent manner. In vivo, sunitinib treatment restored LC3-II, p62, and Endophilin B1 (EndoB1) levels in doxycycline-induced Tat transgenic mice. Moreover, in these animals sunitinib reduced the hyperactivation of CDK5, tau hyper-phosphorylation and p35 cleavage to p25. Restoration of CDK5 and autophagy were associated with reduced neurodegeneration and behavioral alterations. Alterations in autophagy in the Tat tg mice were associated with reduced levels of a CDK5 substrate, EndoB1, and levels of total EndoB1 were normalized by sunitinib treatment. We conclude that sunitinib might ameliorate Tat-mediated autophagy alterations and may decrease neurodegeneration in aging patients with HAND. PMID:28105557

Restoration of Spermatogenesis Using a New Combined Herbal Formula of Epimedium koreanum Nakai and Angelica gigas Nakai in an Luteinizing Hormone-Releasing Hormone Agonist-Induced Rat Model of Male Infertility

PubMed Central

2017-01-01

Purpose We investigated the protective effect of a mixture of 2 herbal extracts, KH-465, which consisted of Epimedium koreanum Nakai and Angelica gigas Nakai, on spermatogenesis in a luteinizing hormone-releasing hormone (LHRH) agonist-induced rat model of male infertility. Materials and Methods Seventy-five 12-week-old male Sprague-Dawley rats were randomly divided into 5 groups, containing 15 rats each: a normal control group that received no treatment and 4 experimental groups (I, II, III, and IV) in which an LHRH agonist was administered for 4 weeks to induce spermatogenic failure. Group I received distilled water, and groups II, III, and IV received 200 mg/kg/day of KH-465, 400 mg/kg/day KH-465, and depo-testosterone for 4 weeks, respectively. Weight changes of the testis and epididymis, sperm count motility, and levels of testosterone (T), free T, follicle-stimulating hormone (FSH), luteinizing hormone (LH), superoxide dismutase (SOD), and 8-hydroxy-2′-deoxyguanosine (8-OHdG) were estimated. Results Body, testis, and epididymis weight showed no significant differences among the control and experimental groups. Treatment with KH-465 increased the sperm count and motility. Serum hormone levels of T, free T, and FSH were not significantly different in the experimental groups, while the LH level was higher than in the LHRH agonist-induced control group, but not to a significant extent. Levels of SOD were higher and 8-OHdG were lower in the groups that received KH-465 than in the LHRH agonist-induced control group. Conclusions Our results suggest that KH-465 increased sperm production via reducing oxidative stress and had a positive effect in a male infertility model. PMID:29076302

Electronic band structures and optical properties of type-II superlattice photodetectors with interfacial effect.

PubMed

Qiao, Peng-Fei; Mou, Shin; Chuang, Shun Lien

2012-01-30

The electronic band structures and optical properties of type-II superlattice (T2SL) photodetectors in the mid-infrared (IR) range are investigated. We formulate a rigorous band structure model using the 8-band k · p method to include the conduction and valence band mixing. After solving the 8 × 8 Hamiltonian and deriving explicitly the new momentum matrix elements in terms of envelope functions, optical transition rates are obtained through the Fermi's golden rule under various doping and injection conditions. Optical measurements on T2SL photodetectors are compared with our model and show good agreement. Our modeling results of quantum structures connect directly to the device-level design and simulation. The predicted doping effect is readily applicable to the optimization of photodetectors. We further include interfacial (IF) layers to study the significance of their effect. Optical properties of T2SLs are expected to have a large tunable range by controlling the thickness and material composition of the IF layers. Our model provides an efficient tool for the designs of novel photodetectors.

Well-to-Wheels Greenhouse Gas Emission Analysis of High-Octane Fuels with Ethanol Blending: Phase II Analysis with Refinery Investment Options

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, Jeongwoo; Wang, Michael; Elgowainy, Amgad

Higher-octane gasoline can enable increases in an internal combustion engine’s energy efficiency and a vehicle’s fuel economy by allowing an increase in the engine compression ratio and/or by enabling downspeeding and downsizing. Producing high-octane fuel (HOF) with the current level of ethanol blending (E10) could increase the energy and greenhouse gas (GHG) emissions intensity of the fuel product from refinery operations. Alternatively, increasing the ethanol blending level in final gasoline products could be a promising solution to HOF production because of the high octane rating and potentially low blended Reid vapor pressure (RVP) of ethanol at 25% and higher ofmore » the ethanol blending level by volume. In our previous HOF well-to-wheels (WTW) report (the so-called phase I report of the HOF WTW analysis), we conducted WTW analysis of HOF with different ethanol blending levels (i.e., E10, E25, and E40) and a range of vehicle efficiency gains with detailed petroleum refinery linear programming (LP) modeling by Jacobs Consultancy and showed that the overall WTW GHG emission changes associated with HOFVs were dominated by the positive impact associated with vehicle efficiency gains and ethanol blending levels, while the refining operations to produce gasoline blendstock for oxygenate blending (BOB) for various HOF blend levels had a much smaller impact on WTW GHG emissions (Han et al. 2015). The scope of the previous phase I study, however, was limited to evaluating PADDs 2 and 3 operation changes with various HOF market share scenarios and ethanol blending levels. Also, the study used three typical configuration models of refineries (cracking, light coking, and heavy coking) in each PADD, which may not be representative of the aggregate response of all refineries in each PADD to various ethanol blending levels and HOF market scenarios. Lastly, the phase I study assumed no new refinery expansion in the existing refineries, which limited E10 HOF production to the volume achievable by the cracking refinery configuration. To be able to satisfy large market demands of E10 HOF, that study arbitrarily relaxed the RVP requirements by replacing reformulated gasoline (RFG) RVP requirement of 7 psi in summer with conventional gasoline (CG) RVP requirement of 9 psi in summer. To examine the response by all refineries in major refinery regions, this phase II of the HOF WTW analysis employed regionally aggregated refinery models for the following six regions: PADDs 1, 2, 3, 4, and 5 excluding California (CA) and CA separately. Using aggregate refinery models, this phase II study examined the impacts of ethanol blending and HOF market shares on the refinery operations in these six regions. Also, this study included refinery expansion to produce a pre-determined HOF volume with 10% ethanol blending. In particular, this study examined several refinery expansion options using refinery configuration models to investigate a practical refinery response to the increase in E10 HOF market demand.« less

Losartan counteracts the effects of cardiomyocyte swelling on glucose uptake and insulin receptor substrate-1 levels.

PubMed

Gerena, Yamil; Lozada, Janice Griselle; Collazo, Bryan Jael; Méndez-Álvarez, Jarold; Méndez-Estrada, Jennifer; De Mello, Walmor C

2017-10-01

A growing body of evidence demonstrates an association between Angiotensin II (Ang II) receptor blockers (ARBs) and enhanced glucose metabolism during ischemic heart disease. Despite these encouraging results, the mechanisms responsible for these effects during ischemia remain poorly understood. In this study we investigated the influence of losartan, an AT1 receptor blocker, and secreted Ang II (sAng II) on glucose uptake and insulin receptor substrate (IRS-1) levels during cardiomyocyte swelling. H9c2 cells were differentiated to cardiac muscle and the levels of myogenin, Myosin Light Chain (MLC), and membrane AT1 receptors were measured using flow cytometry. Intracellular Ang II (iAng II) was overexpressed in differentiated cardiomyocytes and swelling was induced after incubation with hypotonic solution for 40min. Glucose uptake and IRS-1 levels were monitored by flow cytometry using 2-NBDG fluorescent glucose (10μM) or an anti-IRS-1 monoclonal antibody in the presence or absence of losartan (10 -7 M). Secreted Angiotensin II was quantified from the medium using a specific Ang II-EIA kit. To evaluate the relationship between sAng II and losartan effects on glucose uptake, transfected cells were pretreated with the drug for 24h and then exposed to hypotonic solution in the presence or absence of the secreted peptide. The results indicate that: (1) swelling of transfected cardiomyocytes decreased glucose uptake and induced the secretion of Ang II to the extracellular medium; (2) losartan antagonized the effects of swelling on glucose uptake and IRS-1 levels in transfected cardiomyocytes; (3) the effects of losartan on glucose uptake were observed during swelling only in the presence of sAng II in the culture medium. Our study demonstrates that both losartan and sAng II have essential roles in glucose metabolism during cardiomyocyte swelling. Copyright © 2017 Elsevier Inc. All rights reserved.

Selenium Deficiency Induces Autophagy in Immune Organs of Chickens.

PubMed

Khoso, Pervez Ahmed; Pan, Tingru; Wan, Na; Yang, Zijiang; Liu, Ci; Li, Shu

2017-05-01

The aim of the present study was to investigate the effects of selenium (Se) deficiency on autophagy-related genes and on ultrastructural changes in the spleen, bursa of Fabricius, and thymus of chickens. The Se deficiency group was fed a basal diet containing Se at 0.033 mg/kg and the control group was fed the same basal diet containing Se at 0.15 mg/kg. The messenger RNA (mRNA) levels of the autophagy genes microtubule-associated protein 1 light chain 3 (LC3)-I, LC3-II, Beclin 1, dynein, autophagy associated gene 5 (ATG5), and target of rapamycin complex 1 (TORC1) were assessed using real-time qPCR. The protein levels of LC3-II, Beclin 1, and dynein were investigated using western blot analysis. Furthermore, the ultrastructure was observed using an electron microscope. The results indicated that spleen mRNA levels of LC3-I, LC3-II, Beclin 1, dynein, ATG5, and TORC1 and the protein levels of LC3-II, Beclin 1, and dynein were increased in the Se deficiency group compared with the control group. In the bursa of Fabricius, the mRNA levels of LC3-I, LC3-II, Beclin 1, dynein, ATG5, and TORC1 and the protein levels of Beclin 1 and dynein were increased; furthermore, the protein level of LC3-II was decreased in the Se deficiency group compared to the control group. In the thymus, the mRNA levels of LC3-I, Beclin 1, and ATG5 increased; the levels of LC3-II, dynein, and TORC1 were decreased; the protein level of Beclin 1 increased; and the levels of LC3-II and dynein decreased in the Se deficiency group compared to those in the control group. Further cellular morphological changes, such as autophagy vacuoles, autolysosomes, and lysosomal degradation, were observed in the spleen, bursa of Fabricius, and thymus of the Se-deficiency group. In summary, Se deficiency caused changes in autophagy-related genes, which increased the autophagic process and also caused structural damages to the immune organs of chickens.

Structural empowerment, job stress and burnout of nurses in China.

PubMed

Guo, Jiajia; Chen, Juan; Fu, Jie; Ge, Xinling; Chen, Min; Liu, Yanhui

2016-08-01

To investigate the status of structural empowerment, job stress and burnout in China, and to explore the relationships among them. The questionnaires of CWEQ-II, job stressors and MBI were used to investigate 1002 nurses working at tertiary-level hospitals. The average score of CWEQ-II was 2.23±0.59. The score of EE of MBI was 29.75±13.94, PA was 27.40±11.21, both of them showed a high level of exhaustion, DP was 8.07±5.82 and showed a middle level of exhaustion. The findings showed that workload and time pressure were the most frequently encountered job stress among staff nurses, the score was 3.23±0.95; There was a significantly correlation among structural empowerment, job stressors and the level of burnout(p<0.05). Hierarchical regression analysis showed that structural empowerment had significant influence on the every factors of job stressors (p<0.05) and burnout, job stressors had significant influence on the every factors of burnout (p<0.05). Structural equation modeling analyses revealed a good fit to the data based on various fit indices (χ(2)/df=2.29, GFI=0.945, CFI=0.965, IFI=0.966, RMSEA=0.061). Staff nurses felt that structural empowerment in their workplace resulted in lower levels of job stress which in turn strongly influenced Burnout. These results provide initial support for an expanded model of structural empowerment, and offer a broader understanding of the empowerment process. Copyright © 2016 Elsevier Inc. All rights reserved.

Angiotensin II induces calcium/calcineurin signaling and podocyte injury by downregulating microRNA-30 family members.

PubMed

Zhao, Yue; Wu, Junnan; Zhang, Mingchao; Zhou, Minlin; Xu, Feng; Zhu, Xiaodong; Zhou, Xianguang; Lang, Yue; Yang, Fan; Yun, Shifeng; Shi, Shaolin; Liu, Zhihong

2017-08-01

Angiotensin II (AngII) is capable of inducing calcium/calcineurin signaling and podocyte injury; however, the precise underlying mechanism is not well understood. Because we have previously demonstrated that microRNA-30s (miR-30s) inhibit calcium/calcineurin signaling in podocytes, we hypothesize that AngII may induce podocyte injury by downregulating miR-30s and thereby activating calcium/calcineurin signaling. To test this hypothesis, we used an AngII-induced podocyte injury mouse model. The mice were treated with AngII via infusion for 28 days, which resulted in hypertension, albuminuria, and glomerular damage. AngII treatment also resulted in a significant reduction of miR-30s and upregulation of calcium/calcineurin signaling components, including TRPC6, PPP3CA, PPP3CB, PPP3R1, and NFATC3, which are the known targets of miR-30s in podocytes. The delivery of miR-30a-expressing lentivirus to the podocytes on day 14 of the infusion ameliorated the AngII-induced podocyte and glomerular injury and attenuated the upregulation of the calcium/calcineurin signaling components. Similarly, treatment with losartan, which is an AngII receptor blocker, also prevented AngII-induced podocyte injury and calcium/calcineurin signaling activation. Notably, losartan was found to sustain miR-30 levels during AngII treatment both in vivo and in vitro. In conclusion, the effect of AngII on podocytes is in part mediated by miR-30s through calcium/calcineurin signaling, a novel mechanism underlying AngII-induced podocyte injury. • AngII infusion resulted in downregulation of miR-30s in podocytes. • Exogenous miR-30a delivery mitigated the glomerular and podocyte injuries induced by AngII. • Both miR-30a and losartan prevented AngII-induced activation of calcium-calcineurin signaling.

Selective aldosterone blockade prevents angiotensin II/salt-induced vascular inflammation in the rat heart.

PubMed

Rocha, Ricardo; Martin-Berger, Cynthia L; Yang, Pochang; Scherrer, Rachel; Delyani, John; McMahon, Ellen

2002-12-01

We studied the role of aldosterone (aldo) in myocardial injury in a model of angiotensin (Ang) II-hypertension. Wistar rats were given 1% NaCl (salt) to drink and randomized into one of the following groups (n = 10; treatment, 21 d): 1) vehicle control (VEH); 2) Ang II infusion (25 ng/min, sc); 3) Ang II infusion plus the selective aldo blocker, eplerenone (epl, 100 mg/kg.d, orally); 4) Ang II infusion in adrenalectomized (ADX) rats; and 5) Ang II infusion in ADX rats with aldo treatment (20 micro g/kg.d, sc). ADX rats received also dexamethasone (12 micro g/kg.d, sc). Systolic blood pressure increased with time in all treatment groups except the VEH group (VEH, 136 +/- 6; Ang II/NaCl, 203 +/- 12; Ang II/NaCl/epl, 196 +/- 10; Ang II/NaCl/ADX, 181 +/- 7; Ang II/NaCl/ADX/aldo, 236 +/- 8 mm Hg). Despite similar levels of hypertension, epl and ADX attenuated the increase in heart weight/body weight induced by Ang II. Histological examination of the hearts evidenced myocardial and vascular injury in the Ang II/salt (7 of 10 hearts with damage, P < 0.05 vs. VEH) and Ang II/salt/ADX/aldo groups (10 of 10 hearts with damage, P < 0.05). Injury included arterial fibrinoid necrosis, perivascular inflammation (primarily macrophages), and focal infarctions. Vascular lesions were associated with expression of the inflammatory mediators cyclooxygenase 2 (COX-2) and osteopontin in the media of coronary arteries. Myocardial injury, COX-2, and osteopontin expression were markedly attenuated by epl treatment (1 of 10 hearts with damage, P < 0.05 vs. Ang II/salt) and adrenalectomy (2 of 10 hearts with damage, P < 0.05 vs. Ang II/salt). Our data indicate that aldo plays a major role in Ang II-induced vascular inflammation in the heart and implicate COX-2 and osteopontin as potential mediators of the damage.

The presence of Ti(II) centers in doped nanoscale TiO2 and TiO2-xNx

NASA Astrophysics Data System (ADS)

Mikulas, Tanya; Fang, Zongtang; Gole, James L.; White, Mark G.; Dixon, David A.

2012-06-01

Unusual trends are observed in the Ti (2s, 2p) XPS spectra of Fe(II) doped TiO2 and TiO2-xNx. The binding energy of Ti (2s, 2p) initially decreases with increasing Fe(II) concentration, as expected, but increases at higher Fe(II) doping levels. Density functional theory is used to analyze the results. The observed VB-XPS and core level XPS spectra are consistent with the facile charge transfer sequence Ti(IV) + Fe(II) → Ti(III) + Fe(III) followed by Ti(III) + Fe(II) → Ti(II) + Fe(III). The formed Ti(II) sites may be relevant to nanoparticle catalysis on TiO2 surfaces.

Assessment of performance and utility of mortality prediction models in a single Indian mixed tertiary intensive care unit.

PubMed

Sathe, Prachee M; Bapat, Sharda N

2014-01-01

To assess the performance and utility of two mortality prediction models viz. Acute Physiology and Chronic Health Evaluation II (APACHE II) and Simplified Acute Physiology Score II (SAPS II) in a single Indian mixed tertiary intensive care unit (ICU). Secondary objectives were bench-marking and setting a base line for research. In this observational cohort, data needed for calculation of both scores were prospectively collected for all consecutive admissions to 28-bedded ICU in the year 2011. After excluding readmissions, discharges within 24 h and age <18 years, the records of 1543 patients were analyzed using appropriate statistical methods. Both models overpredicted mortality in this cohort [standardized mortality ratio (SMR) 0.88 ± 0.05 and 0.95 ± 0.06 using APACHE II and SAPS II respectively]. Patterns of predicted mortality had strong association with true mortality (R (2) = 0.98 for APACHE II and R (2) = 0.99 for SAPS II). Both models performed poorly in formal Hosmer-Lemeshow goodness-of-fit testing (Chi-square = 12.8 (P = 0.03) for APACHE II, Chi-square = 26.6 (P = 0.001) for SAPS II) but showed good discrimination (area under receiver operating characteristic curve 0.86 ± 0.013 SE (P < 0.001) and 0.83 ± 0.013 SE (P < 0.001) for APACHE II and SAPS II, respectively). There were wide variations in SMRs calculated for subgroups based on International Classification of Disease, 10(th) edition (standard deviation ± 0.27 for APACHE II and 0.30 for SAPS II). Lack of fit of data to the models and wide variation in SMRs in subgroups put a limitation on utility of these models as tools for assessing quality of care and comparing performances of different units without customization. Considering comparable performance and simplicity of use, efforts should be made to adapt SAPS II.

Highly Reproducible Label Free Quantitative Proteomic Analysis of RNA Polymerase Complexes*

PubMed Central

Mosley, Amber L.; Sardiu, Mihaela E.; Pattenden, Samantha G.; Workman, Jerry L.; Florens, Laurence; Washburn, Michael P.

2011-01-01

The use of quantitative proteomics methods to study protein complexes has the potential to provide in-depth information on the abundance of different protein components as well as their modification state in various cellular conditions. To interrogate protein complex quantitation using shotgun proteomic methods, we have focused on the analysis of protein complexes using label-free multidimensional protein identification technology and studied the reproducibility of biological replicates. For these studies, we focused on three highly related and essential multi-protein enzymes, RNA polymerase I, II, and III from Saccharomyces cerevisiae. We found that label-free quantitation using spectral counting is highly reproducible at the protein and peptide level when analyzing RNA polymerase I, II, and III. In addition, we show that peptide sampling does not follow a random sampling model, and we show the need for advanced computational models to predict peptide detection probabilities. In order to address these issues, we used the APEX protocol to model the expected peptide detectability based on whole cell lysate acquired using the same multidimensional protein identification technology analysis used for the protein complexes. Neither method was able to predict the peptide sampling levels that we observed using replicate multidimensional protein identification technology analyses. In addition to the analysis of the RNA polymerase complexes, our analysis provides quantitative information about several RNAP associated proteins including the RNAPII elongation factor complexes DSIF and TFIIF. Our data shows that DSIF and TFIIF are the most highly enriched RNAP accessory factors in Rpb3-TAP purifications and demonstrate our ability to measure low level associated protein abundance across biological replicates. In addition, our quantitative data supports a model in which DSIF and TFIIF interact with RNAPII in a dynamic fashion in agreement with previously published reports. PMID:21048197

CAN FLUORIDATION AFFECT WATER LEAD (II) LEVELS AND LEAD (II) NEUROTOXICITY?

EPA Science Inventory

Recent reports have attempted to show that certain approaches to fluoridating potable water is linked to increased levels of lead(II) in the blood. We examine these claims in light of the established science and critically evaluate their significance. The completeness of hexafl...

Hyperhidrosis: Anatomy, Pathophysiology and Treatment with Emphasis on the Role of Botulinum Toxins

PubMed Central

Lakraj, Amanda-Amrita D.; Moghimi, Narges; Jabbari, Bahman

2013-01-01

Clinical features, anatomy and physiology of hyperhidrosis are presented with a review of the world literature on treatment. Level of drug efficacy is defined according to the guidelines of the American Academy of Neurology. Topical agents (glycopyrrolate and methylsulfate) are evidence level B (probably effective). Oral agents (oxybutynin and methantheline bromide) are also level B. In a total of 831 patients, 1 class I and 2 class II blinded studies showed level B efficacy of OnabotulinumtoxinA (A/Ona), while 1 class I and 1 class II study also demonstrated level B efficacy of AbobotulinumtoxinA (A/Abo) in axillary hyperhidrosis (AH), collectively depicting Level A evidence (established) for botulinumtoxinA (BoNT-A). In a comparator study, A/Ona and A/Inco toxins demonstrated comparable efficacy in AH. For IncobotulinumtoxinA (A/Inco) no placebo controlled studies exist; thus, efficacy is Level C (possibly effective) based solely on the aforementioned class II comparator study. For RimabotulinumtoxinB (B/Rima), one class III study has suggested Level U efficacy (insufficient data). In palmar hyperhidrosis (PH), there are 3 class II studies for A/Ona and 2 for A/Abo (individually and collectively level B for BoNT-A) and no blinded study for A/Inco (level U). For B/Rima the level of evidence is C (possibly effective) based on 1 class II study. Botulinum toxins (BoNT) provide a long lasting effect of 3–9 months after one injection session. Studies on BoNT-A iontophoresis are emerging (2 class II studies; level B); however, data on duration and frequency of application is inconsistent. PMID:23612753

Pepsinogens I and II: purification from gastric mucosa and radioimmunoassay in serum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Samloff, I.M.

1982-01-01

Pepsinogen I and pepsinogen II were purified from gastric mucosa and used to develop a radioimmunoassay for pepsinogen II and an improved radioimmunoassay for pepsinogen I. Each immunochemically homogeneous preparation contained only its characteristic components by radioelectophoretic analysis, and migrated as a singly band in polyacrylamide gel. The mean (+/- SD) level of serum pepsinogen II in 42 healthy control subjects was 10,8 +/- 3.8 ng/ml, significantly less (p less than 0.001) than the level of pepsinogen I, which was 62.9 +/- 22.2 ng/ml. The correlation between serum pepsinogen I and pepsinogen II was highly significant (r . 0.700, pmore » less than 0.001) in these subjects. In 20 patients with pernicious anemia the mean serum pepsinogen II level was 10.6 +/- 2.5 ng/ml, not different from normal, but significantly higher (p less than 0.001) than the level of pepsinogen I which was 5.9 +/- 4.7 ng/ml. IN 10 patients with total gastrectomy, serum pepsinogen I was 3.9 +/- 3.1 ng/ml and serum pepsinogen II was 3.2 +/- 3.1 ng/ml; both values were significantly lower (p less than 0.001) than the corresponding levels in pernicious anemia. The predominance of pepsinogen I in the serum of healthy control subjects suggests that either the gastric chief cell normally releases more pepsinogen I than pepsinogen II into the circulation or that pepsinogen I has longer metabolic clearance rate than pepsinogen II. The marked decrease in serum pepsinogen I in patients with pernicious anemia is best explained by a loss of gastric chief cells due to severe atropic gastritis of the fundic glands. The normal distribution of serum pepsinogen II levels in these patients may reflect an increased number of pyloric glands due to pyloric gland metaplasia of the proximal stomach.« less

Internal Variations in Empirical Oxygen Abundances for Giant H II Regions in the Galaxy NGC 2403

NASA Astrophysics Data System (ADS)

Mao, Ye-Wei; Lin, Lin; Kong, Xu

2018-02-01

This paper presents a spectroscopic investigation of 11 {{H}} {{II}} regions in the nearby galaxy NGC 2403. The {{H}} {{II}} regions are observed with a long-slit spectrograph mounted on the 2.16 m telescope at XingLong station of National Astronomical Observatories of China. For each of the {{H}} {{II}} regions, spectra are extracted at different nebular radii along the slit-coverage. Oxygen abundances are empirically estimated from the strong-line indices R23, N2O2, O3N2, and N2 for each spectrophotometric unit, with both observation- and model-based calibrations adopted into the derivation. Radial profiles of these diversely estimated abundances are drawn for each nebula. In the results, the oxygen abundances separately estimated with the prescriptions on the basis of observations and models, albeit from the same spectral index, systematically deviate from each other; at the same time, the spectral indices R23 and N2O2 are distributed with flat profiles, whereas N2 and O3N2 exhibit apparent gradients with the nebular radius. Because our study naturally samples various ionization levels, which inherently decline at larger radii within individual {{H}} {{II}} regions, the radial distributions indicate not only the robustness of R23 and N2O2 against ionization variations but also the sensitivity of N2 and O3N2 to the ionization parameter. The results in this paper provide observational corroboration of the theoretical prediction about the deviation in the empirical abundance diagnostics. Our future work is planned to investigate metal-poor {{H}} {{II}} regions with measurable T e, in an attempt to recalibrate the strong-line indices and consequently disclose the cause of the discrepancies between the empirical oxygen abundances.

Low dose native type II collagen prevents pain in a rat osteoarthritis model

PubMed Central

2013-01-01

Background Osteoarthritis is the most widespread joint-affecting disease. Patients with osteoarthritis experience pain and impaired mobility resulting in marked reduction of quality of life. A progressive cartilage loss is responsible of an evolving disease difficult to treat. The characteristic of chronicity determines the need of new active disease modifying drugs. Aim of the present research is to evaluate the role of low doses of native type II collagen in the rat model of osteoarthritis induced by sodium monoiodoacetate (MIA). Methods 1, 3 and 10 mg kg-1 porcine native type II collagen were daily per os administered for 13 days starting from the day of MIA intra-articular injection. Results On day 14, collagen-treated rats showed a significant prevention of pain threshold alterations induced by MIA. Evaluation were performed on paws using mechanical noxious (Paw pressure test) or non-noxious (Electronic Von Frey test) stimuli, and a decrease of articular pain was directly measured on the damaged joint (PAM test). The efficacy of collagen in reducing pain was as higher as the dose was lowered. Moreover, a reduced postural unbalance, measured as hind limb weight bearing alterations (Incapacitance test), and a general improvement of motor activity (Animex test) were observed. Finally, the decrease of plasma and urine levels of CTX-II (Cross Linked C-Telopeptide of Type II Collagen), a biomarker of cartilage degradation, suggests a collagen-dependent decrease of structural joint damage. Conclusions These results describe the preclinical efficacy of low dosages of native type II collagen as pain reliever by a mechanism that involves a protective effect on cartilage. PMID:23915264

Severity and prognosis of acute organophosphorus pesticide poisoning are indicated by C-reactive protein and copeptin levels and APACHE II score

PubMed Central

WU, XINKUAN; XIE, WEI; CHENG, YUELEI; GUAN, QINGLONG

2016-01-01

The aim of the present study was to investigate the plasma levels of C-reactive protein (CRP) and copeptin, in addition to the acute physiology and chronic health evaluation II (APACHE II) scores, in patients with acute organophosphorus pesticide poisoning (AOPP). A total of 100 patients with AOPP were included and divided into mild, moderate and severe groups according to AOPP diagnosis and classification standards. Blood samples were collected from all patients on days 1, 3 and 7 following AOPP. The concentrations of CRP and copeptin in the plasma were determined using enzyme-linked immunosorbent assay. All AOPP patients underwent APACHE II scoring and the diagnostic value of these scores was analyzed using receiver operating characteristic curves (ROCs). On days 1, 3 and 7 after AOPP, the levels of CRP and copeptin were increased in correlation with the increase in AOPP severity, and were significantly higher compared with the control groups. Furthermore, elevated CRP and copeptin plasma levels were detected in patients with severe AOPP on day 7, whereas these levels were reduced in patients with mild or moderate AOPP. APACHE II scores, blood lactate level, acetylcholine esterase level, twitch disappearance time, reactivating agent dose and inability to raise the head were the high-risk factors that affected the prognosis of AOPP. Patients with plasma CRP and copeptin levels higher than median values had worse prognoses. The areas under curve for ROCs were 0.89, 0.75 and 0.72 for CRP levels, copeptin levels and APACHE II scores, respectively. In addition, the plasma contents of CRP and copeptin are increased according to the severity of AOPP. Therefore, the results of the present study suggest that CRP and copeptin levels and APACHE II scores may be used for the determination of AOPP severity and the prediction of AOPP prognosis. PMID:26997996

Severity and prognosis of acute organophosphorus pesticide poisoning are indicated by C-reactive protein and copeptin levels and APACHE II score.

PubMed

Wu, Xinkuan; Xie, Wei; Cheng, Yuelei; Guan, Qinglong

2016-03-01

The aim of the present study was to investigate the plasma levels of C-reactive protein (CRP) and copeptin, in addition to the acute physiology and chronic health evaluation II (APACHE II) scores, in patients with acute organophosphorus pesticide poisoning (AOPP). A total of 100 patients with AOPP were included and divided into mild, moderate and severe groups according to AOPP diagnosis and classification standards. Blood samples were collected from all patients on days 1, 3 and 7 following AOPP. The concentrations of CRP and copeptin in the plasma were determined using enzyme-linked immunosorbent assay. All AOPP patients underwent APACHE II scoring and the diagnostic value of these scores was analyzed using receiver operating characteristic curves (ROCs). On days 1, 3 and 7 after AOPP, the levels of CRP and copeptin were increased in correlation with the increase in AOPP severity, and were significantly higher compared with the control groups. Furthermore, elevated CRP and copeptin plasma levels were detected in patients with severe AOPP on day 7, whereas these levels were reduced in patients with mild or moderate AOPP. APACHE II scores, blood lactate level, acetylcholine esterase level, twitch disappearance time, reactivating agent dose and inability to raise the head were the high-risk factors that affected the prognosis of AOPP. Patients with plasma CRP and copeptin levels higher than median values had worse prognoses. The areas under curve for ROCs were 0.89, 0.75 and 0.72 for CRP levels, copeptin levels and APACHE II scores, respectively. In addition, the plasma contents of CRP and copeptin are increased according to the severity of AOPP. Therefore, the results of the present study suggest that CRP and copeptin levels and APACHE II scores may be used for the determination of AOPP severity and the prediction of AOPP prognosis.

A Variational Assimilation Method for Satellite and Conventional Data: Model 2 (version 1)

NASA Technical Reports Server (NTRS)

Achtemeier, Gary L.

1991-01-01

The Model II variational data assimilation model is the second of the four variational models designed to blend diverse meteorological data into a dynamically constrained data set. Model II differs from Model I in that it includes the thermodynamic equation as the fifth dynamical constraint. Thus, Model II includes all five of the primative equations that govern atmospheric flow for a dry atmosphere.

Angiotensin II-aldosterone interaction in human coronary microarteries involves GPR30, EGFR, and endothelial NO synthase.

PubMed

Batenburg, Wendy W; Jansen, Pieter M; van den Bogaerdt, Antoon J; J Danser, Alexander H

2012-04-01

The aim of this study was to investigate the aldosterone-angiotensin (Ang) II interaction in human coronary microarteries (HCMAs). HCMAs, obtained from 75 heart-beating organ donors, were mounted in myographs and exposed to Ang II, either directly or following a 30-min pre-incubation with aldosterone, 17β-oestradiol, hydrocortisone, the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580, the extracellular regulated kinase 1/2 (ERK1/2) inhibitor PD98059, the GPR30 antagonist G15, or the epidermal growth factor receptor (EGFR) antagonist AG1478. Ang II constricted HCMAs in a concentration-dependent manner. All steroids, at nanomolar levels, potentiated Ang II and G15 prevented this effect. The potentiation disappeared or was reversed into Ang II antagonism at micromolar steroid levels. NO synthase (NOS) inhibition prevented the latter antagonism in the case of 17β-oestradiol, whereas both aldosterone and 17β-oestradiol at micro- (but not nano-) molar levels induced endothelial NOS phosphorylation in human umbilical vein endothelial cells. AG1478, but not SB203580 or PD98059, abolished the Ang II-induced contraction in the presence of aldosterone or 17β-oestradiol, and none of these drugs affected Ang II alone. Steroids including aldosterone affect Ang II-induced vasoconstriction in a biphasic manner. Potentiation occurs at nanomolar steroid levels and depends on GPR30 and EGFR transactivation. At micromolar steroid levels, this potentiation either disappears (aldosterone and hydrocortisone) or is reversed into an inhibition (17β-oestradiol), and this is due to the endothelial NOS activation that occurs at such concentrations.

Anti-inflammatory drugs interacting with Zn (II) metal ion based on thiocyanate and azide ligands: synthesis, spectroscopic studies, DFT calculations and antibacterial assays.

PubMed

Chiniforoshan, Hossein; Tabrizi, Leila; Hadizade, Morteza; Sabzalian, Mohammad R; Chermahini, Alireza Najafi; Rezapour, Mehdi

2014-07-15

Zinc (II) complexes with non-steroidal anti-inflammatory drugs (NSAIDs) naproxen (nap) and ibuprofen (ibu) were synthesized in the presence of nitrogen donor ligands (thiocyanate or azide). The complexes were characterized by elemental analysis, FT-IR, (1)H NMR and UV-Vis spectroscopes. The binding modes of the ligands in complexes were established by means of molecular modeling of the complexes, and calculation of their IR, NMR and absorption spectra at DFT (TDDFT)/B3LYP level were studied. The experimental and calculated data verified monodentate binding through the carboxylic oxygen atoms of anti-inflammatory drugs in the zinc complexes. The calculated (1)H, FT-IR and UV-Vis data are in better agreement with the experimental results, and confirm the predicted tetrahedral structures for the Zn (II) complexes. In addition to DFT calculations of complexes, natural bond orbital (NBO) was performed at B3LYP/6-31+G(d,p) level of theory. Biological studies showed the antibacterial activity of zinc complexes against Gram-positive and Gram-negative bacterial strains. Copyright © 2014 Elsevier B.V. All rights reserved.

The Chancellor's Model School Project (CMSP)

NASA Technical Reports Server (NTRS)

Lopez, Gil

1999-01-01

What does it take to create and implement a 7th to 8th grade middle school program where the great majority of students achieve at high academic levels regardless of their previous elementary school backgrounds? This was the major question that guided the research and development of a 7-year long project effort entitled the Chancellor's Model School Project (CMSP) from September 1991 to August 1998. The CMSP effort conducted largely in two New York City public schools was aimed at creating and testing a prototype 7th and 8th grade model program that was organized and test-implemented in two distinct project phases: Phase I of the CMSP effort was conducted from 1991 to 1995 as a 7th to 8th grade extension of an existing K-6 elementary school, and Phase II was conducted from 1995 to 1998 as a 7th to 8th grade middle school program that became an integral part of a newly established 7-12th grade high school. In Phase I, the CMSP demonstrated that with a highly structured curriculum coupled with strong academic support and increased learning time, students participating in the CMSP were able to develop a strong foundation for rigorous high school coursework within the space of 2 years (at the 7th and 8th grades). Mathematics and Reading test score data during Phase I of the project, clearly indicated that significant academic gains were obtained by almost all students -- at both the high and low ends of the spectrum -- regardless of their previous academic performance in the K-6 elementary school experience. The CMSP effort expanded in Phase II to include a fully operating 7-12 high school model. Achievement gains at the 7th and 8th grade levels in Phase II were tempered by the fact that incoming 7th grade students' academic background at the CMSP High School was significantly lower than students participating in Phase 1. Student performance in Phase II was also affected by the broadening of the CMSP effort from a 7-8th grade program to a fully functioning 7-12 high school which as a consequence lessened the focus and structure available to the 7-8th grade students and teachers -- as compared to Phase I. Nevertheless, the CMSP does represent a unique curriculum model for 7th and 8th grade students in urban middle schools. Experience in both Phase I and Phase II of the project allowed the CMSP to be developed and tested along the broad range of parameters and characteristics that embody an operating public school in an urban environment.

Daily and Nondaily Smoking Varies by Acculturation among English-Speaking, US Latino Men and Women.

PubMed

Pulvers, Kim; Cupertino, A Paula; Scheuermann, Taneisha S; Sanderson Cox, Lisa; Ho, Yen-Yi; Nollen, Nicole L; Cuellar, Ruby; Ahluwalia, Jasjit S

2018-01-01

Higher smoking prevalence and quantity (cigarettes per day) has been linked to acculturation in the United States among Latinas, but not Latino men. Our study examines variation between a different and increasingly important target behavior, smoking level (nondaily vs daily) and acculturation by sex. An online English-language survey was administered to 786 Latino smokers during July through August 2012. The Brief Acculturation Rating Scale for Mexican Americans-II (ARSMA-II) and other acculturation markers were used. Multinomial logistic regression models were implemented to assess the association between smoking levels (nondaily, light daily, and moderate/heavy daily) with acculturation markers. Greater ARMSA-II scores (relative risk ratio, RRR =.81, 95% CI: .72-.91) and being born inside the United States ( RRR =.42, 95% CI: .24-.74) were associated with lower relative risk of nondaily smoking. Greater Latino orientation ( RRR =1.29, 95% CI: 1.11-1.48) and preference for Spanish language ( RRR =1.06, 95% CI: 1.02-1.10) and media ( RRR =1.12, 95% CI: 1.05-1.20) were associated with higher relative risk of nondaily smoking. The relationship between acculturation and smoking level did not differ by sex. This study found that among both male and female, English-speaking Latino smokers, nondaily smoking was associated with lower acculturation, while daily smoking was linked with higher acculturation.

The health care system is making 'too much noise' to provide family-centred care in neonatal intensive care units: Perspectives of health care providers and hospital administrators.

PubMed

Benzies, Karen M; Shah, Vibhuti; Aziz, Khalid; Lodha, Abhay; Misfeldt, Renée

2018-05-11

To describe the perspectives of health care providers and hospital administrators on their experiences of providing care for infants in Level II neonatal intensive care units and their families. We conducted 36 qualitative interviews with neonatal health care providers and hospital administrators and analysed data using a descriptive interpretive approach. 10 Level II Neonatal Intensive Care Units in a single, integrated health care system in one Canadian province. Three major themes emerged: (1) providing family-centred care, (2) working amidst health care system challenges, and (3) recommending improvements to the health care system. The overarching theme was that the health care system was making 'too much noise' for health care providers and hospital administrators to provide family-centred care in ways that would benefit infants and their families. Recommended improvements included: refining staffing models, enhancing professional development, providing tools to deliver consistent care, recognising parental capacity to be involved in care, strengthening continuity of care, supporting families to be with their infant, and designing family-friendly environments. When implementing family-centred care initiatives, health care providers and hospital administrators need to consider the complexity of providing care in Level II Neonatal Intensive Care Units, and recognise that health care system changes may be necessary to optimise implementation. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Simulating neutron star mergers as r-process sources in ultrafaint dwarf galaxies

NASA Astrophysics Data System (ADS)

Safarzadeh, Mohammadtaher; Scannapieco, Evan

2017-10-01

To explain the high observed abundances of r-process elements in local ultrafaint dwarf (UFD) galaxies, we perform cosmological zoom simulations that include r-process production from neutron star mergers (NSMs). We model star formation stochastically and simulate two different haloes with total masses ≈108 M⊙ at z = 6. We find that the final distribution of [Eu/H] versus [Fe/H] is relatively insensitive to the energy by which the r-process material is ejected into the interstellar medium, but strongly sensitive to the environment in which the NSM event occurs. In one halo, the NSM event takes place at the centre of the stellar distribution, leading to high levels of r-process enrichment such as seen in a local UFD, Reticulum II (Ret II). In a second halo, the NSM event takes place outside of the densest part of the galaxy, leading to a more extended r-process distribution. The subsequent star formation occurs in an interstellar medium with shallow levels of r-process enrichment that results in stars with low levels of [Eu/H] compared to Ret II stars even when the maximum possible r-process mass is assumed to be ejected. This suggests that the natal kicks of neutron stars may also play an important role in determining the r-process abundances in UFD galaxies, a topic that warrants further theoretical investigation.

BOOK REVIEW: Heterogeneous Materials I and Heterogeneous Materials II

NASA Astrophysics Data System (ADS)

Knowles, K. M.

2004-02-01

In these two volumes the author provides a comprehensive survey of the various mathematically-based models used in the research literature to predict the mechanical, thermal and electrical properties of hetereogeneous materials, i.e., materials containing two or more phases such as fibre-reinforced polymers, cast iron and porous ceramic kiln furniture. Volume I covers linear properties such as linear dielectric constant, effective electrical conductivity and elastic moduli, while Volume II covers nonlinear properties, fracture and atomistic and multiscale modelling. Where appropriate, particular attention is paid to the use of fractal geometry and percolation theory in describing the structure and properties of these materials. The books are advanced level texts reflecting the research interests of the author which will be of significant interest to research scientists working at the forefront of the areas covered by the books. Others working more generally in the field\

Pattern-oriented modelling: a ‘multi-scope’ for predictive systems ecology

PubMed Central

Grimm, Volker; Railsback, Steven F.

2012-01-01

Modern ecology recognizes that modelling systems across scales and at multiple levels—especially to link population and ecosystem dynamics to individual adaptive behaviour—is essential for making the science predictive. ‘Pattern-oriented modelling’ (POM) is a strategy for doing just this. POM is the multi-criteria design, selection and calibration of models of complex systems. POM starts with identifying a set of patterns observed at multiple scales and levels that characterize a system with respect to the particular problem being modelled; a model from which the patterns emerge should contain the right mechanisms to address the problem. These patterns are then used to (i) determine what scales, entities, variables and processes the model needs, (ii) test and select submodels to represent key low-level processes such as adaptive behaviour, and (iii) find useful parameter values during calibration. Patterns are already often used in these ways, but a mini-review of applications of POM confirms that making the selection and use of patterns more explicit and rigorous can facilitate the development of models with the right level of complexity to understand ecological systems and predict their response to novel conditions. PMID:22144392

The Effect of Long-Term Training Program on Balance in Children with Cerebral Palsy: Results of a Pilot Study for Individually Based Functional Exercises

ERIC Educational Resources Information Center

Uzun, Selda

2013-01-01

This study examines the effects of long-term training program on balance and center of pressure (COP) for four male children (13 years of age) with cerebral palsy (CP). These children were classified into one hemiplegic (level II), one diplegic (level II) and two quadriplegic children (levels III and II) using the Gross Motor Function…

Limitations and implications of stream classification

USGS Publications Warehouse

Juracek, K.E.; Fitzpatrick, F.A.

2003-01-01

Stream classifications that are based on channel form, such as the Rosgen Level II classification, are useful tools for the physical description and grouping of streams and for providing a means of communication for stream studies involving scientists and (or) managers with different backgrounds. The Level II classification also is used as a tool to assess stream stability, infer geomorphic processes, predict future geomorphic response, and guide stream restoration or rehabilitation activities. The use of the Level II classification for these additional purposes is evaluated in this paper. Several examples are described to illustrate the limitations and management implications of the Level II classification. Limitations include: (1) time dependence, (2) uncertain applicability across physical environments, (3) difficulty in identification of a true equilibrium condition, (4) potential for incorrect determination of bankfull elevation, and (5) uncertain process significance of classification criteria. Implications of using stream classifications based on channel form, such as Rosgen's, include: (1) acceptance of the limitations, (2) acceptance of the risk of classifying streams incorrectly, and (3) classification results may be used inappropriately. It is concluded that use of the Level II classification for purposes beyond description and communication is not appropriate. Research needs are identified that, if addressed, may help improve the usefulness of the Level II classification.

The impact of modifying antenna size of photosystem II on canopy photosynthetic efficiency – development of a new canopy photosynthesis model scaling from metabolism to canopy level processes

USDA-ARS?s Scientific Manuscript database

Canopy photosynthesis describes photosynthesis of an entire crop field and positively correlates with biomass production. Much effort in crop breeding has focused on improving canopy architecture and hence light distribution inside the canopy. Here, we develop a new integrated canopy photosynthesis ...

Basic Skills for Reflective Inquiry in the Social Studies. Bridges to the Future.

ERIC Educational Resources Information Center

Rodabaugh, Mary Jane; And Others

The document consists of five social studies units for developing basic inquiry skills at the secondary level. Students read and analyze data through the construction of a table and a graph in Unit I, "Reading Graphs and Charts." Topics include a model of consumer demand, census information, and national budgeting. In Unit II, "Community Change,"…

Huntington II Simulation Program - RATS. Student Workbook, Teacher's Guide, and Resource Handbook.

ERIC Educational Resources Information Center

Frishman, Austin

Presented are instructions for the use of "RATS," a model simulating the dynamics of a rat population in either a city or an apartment house. The student controls the conditions of growth and sets the points at which the computer program prints reports. The rat population is controlled by variables including garbage levels selected for the site,…

1 CFR 21.11 - Standard organization of the Code of Federal Regulations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... PREPARATION, TRANSMITTAL, AND PROCESSING OF DOCUMENTS PREPARATION OF DOCUMENTS SUBJECT TO CODIFICATION General... (h) Paragraphs, which are designated as follows: level 1(a), (b), (c), etc. level 2(1), (2), (3), etc. level 3(i), (ii), (iii), etc. level 4(A), (B), (C), etc. level 5(1), (2), (3), etc. level 6(i), (ii...

Safflor yellow B suppresses angiotensin II-mediated human umbilical vein cell injury via regulation of Bcl-2/p22{sup phox} expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Chaoyun; He, Yanhao; Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Key Laboratory of Environment and Genes Related to Disease, Ministry of Education, Xi'an, Shaanxi 710061

Intracellular reactive oxygen species (ROS) are derived from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Angiotensin II (Ang II) can cause endothelial dysfunction by promoting intracellular ROS generation. Safflor yellow B (SYB) effectively inhibits ROS generation by upregulating Bcl-2 expression. In this study, we examined the effects of SYB on Ang II-induced injury to human umbilical vein endothelial cells (HUVECs), and elucidated the roles of NADPH oxidase and Bcl-2. We treated cultured HUVECs with Ang II, SYB, and Bcl-2 siRNA, and determined NADPH oxidase activity and ROS levels. Furthermore, cellular and mitochondrial physiological states were evaluated, and the expression levels ofmore » target proteins were analyzed. Ang II significantly enhanced intracellular ROS levels, caused mitochondrial membrane dysfunction, and decreased cell viability, leading to apoptosis. This was associated with increased expression of AT1R and p22{sup phox}, increased NADPH oxidase activity, and an increased ratio of Bax/Bcl-2, leading to decreases in antioxidant enzyme activities, which were further strengthened after blocking Bcl-2. Compared to Ang II treatment alone, co-treatment with SYB significantly reversed HUVEC injury. Taken together, these results demonstrate that SYB could significantly protect endothelial cells from Ang II-induced cell damage, and that it does so by upregulating Bcl-2 expression and inhibiting ROS generation. - Highlights: • Angiotensin II depresses mitochondria physiological function. • Angiotensin II activates NADPH oxidase via up-regulating expresion of p22{sup phox}. • Bcl-2 plays a pivotal role in improving mitochondria function and regulates ROS level. • Inhibitor of Bcl-2 promotes angiotensin II mediated HUVEC injury. • SYB attenuates angiotensin II mediated HUVEC injury via up regulating Bcl-2 expression.« less

The application of a decision tree to establish the parameters associated with hypertension.

PubMed

Tayefi, Maryam; Esmaeili, Habibollah; Saberi Karimian, Maryam; Amirabadi Zadeh, Alireza; Ebrahimi, Mahmoud; Safarian, Mohammad; Nematy, Mohsen; Parizadeh, Seyed Mohammad Reza; Ferns, Gordon A; Ghayour-Mobarhan, Majid

2017-02-01

Hypertension is an important risk factor for cardiovascular disease (CVD). The goal of this study was to establish the factors associated with hypertension by using a decision-tree algorithm as a supervised classification method of data mining. Data from a cross-sectional study were used in this study. A total of 9078 subjects who met the inclusion criteria were recruited. 70% of these subjects (6358 cases) were randomly allocated to the training dataset for the constructing of the decision-tree. The remaining 30% (2720 cases) were used as the testing dataset to evaluate the performance of decision-tree. Two models were evaluated in this study. In model I, age, gender, body mass index, marital status, level of education, occupation status, depression and anxiety status, physical activity level, smoking status, LDL, TG, TC, FBG, uric acid and hs-CRP were considered as input variables and in model II, age, gender, WBC, RBC, HGB, HCT MCV, MCH, PLT, RDW and PDW were considered as input variables. The validation of the model was assessed by constructing a receiver operating characteristic (ROC) curve. The prevalence rates of hypertension were 32% in our population. For the decision-tree model I, the accuracy, sensitivity, specificity and area under the ROC curve (AUC) value for identifying the related risk factors of hypertension were 73%, 63%, 77% and 0.72, respectively. The corresponding values for model II were 70%, 61%, 74% and 0.68, respectively. We have developed a decision tree model to identify the risk factors associated with hypertension that maybe used to develop programs for hypertension management. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Interactions of biomacromolecules with reverse hexagonal liquid crystals: drug delivery and crystallization applications.

PubMed

Libster, Dima; Aserin, Abraham; Garti, Nissim

2011-04-15

Recently, self-assembled lyotropic liquid crystals (LLCs) of lipids and water have attracted the attention of both scientific and applied research communities, due to their remarkable structural complexity and practical potential in diverse applications. The phase behavior of mixtures of glycerol monooleate (monoolein, GMO) was particularly well studied due to the potential utilization of these systems in drug delivery systems, food products, and encapsulation and crystallization of proteins. Among the studied lyotropic mesophases, reverse hexagonal LLC (H(II)) of monoolein/water were not widely subjected to practical applications since these were stable only at elevated temperatures. Lately, we obtained stable H(II) mesophases at room temperature by incorporating triacylglycerol (TAG) molecules into the GMO/water mixtures and explored the physical properties of these structures. The present feature article summarizes recent systematic efforts in our laboratory to utilize the H(II) mesophases for solubilization, and potential release and crystallization of biomacromolecules. Such a concept was demonstrated in the case of two therapeutic peptides-cyclosporin A (CSA) and desmopressin, as well as RALA peptide, which is a model skin penetration enhancer, and eventually a larger macromolecule-lysozyme (LSZ). In the course of the study we tried to elucidate relationships between the different levels of organization of LLCs (from the microstructural level, through mesoscale, to macroscopic level) and find feasible correlations between them. Since the structural properties of the mesophase systems are a key factor in drug release applications, we investigated the effects of these guest molecules on their conformations and the way these molecules partition within the domains of the mesophases. The examined H(II) mesophases exhibited great potential as transdermal delivery vehicles for bioactive peptides, enabling tuning the release properties according to their chemical composition and physical properties. Furthermore, we showed a promising opportunity for crystallization of CSA and LSZ in single crystal form as model biomacromolecules for crystallographic structure determination. The main outcomes of our research demonstrated that control of the physical properties of hexagonal LLC on different length scales is key for rational design of these systems as delivery vehicles and crystallization medium for biomacromolecules. Copyright © 2011 Elsevier Inc. All rights reserved.

The role of DSM-5 borderline personality symptomatology and traits in the link between childhood trauma and suicidal risk in psychiatric patients.

PubMed

Bach, Bo; Fjeldsted, Rita

2017-01-01

Childhood traumas appear to be linked to suicidal behavior. However, the factors that mediate between these two phenomena are not sufficiently understood. Recent findings suggest that borderline personality disorder (BPD) may explain some of the association. The present study investigated the potential mediating role of BPD symptomatology and traits between reported childhood trauma and suicidal risk in adult psychiatric outpatients ( N  = 124). BPD symptomatology was measured with DSM-5 Section II criterion-counts (SCID-II; Structured Clinical Interview for DSM-IV Axis II), whereas BPD traits were measured with specified DSM-5 Section III traits (PID-5; Personality Inventory for DSM-5). Childhood traumas were self-reported (CTQ; Childhood Trauma Questionnaire), whereas level of suicidal risk was measured with a structured interview (MINI Suicidality Module; Mini International Neuropsychiatric Interview). Mediation effects were tested by bias-corrected (10.000 boot-strapped samples) confidence intervals. BPD features account for a considerable part of the cross-sectional association between childhood trauma and level of suicidal risk, even when controlling for the influence of gender, age, and educational level. This finding remained stable when testing the model without the suicidality-related BPD criterion and PID-5 items. DSM-5 Section II BPD criterion-counts explained 67% of the total effect, whereas DSM-5 Section III BPD traits accounted for 82% of the total effect. The specific DSM-5 Section III trait facets of "Depressivity" (52%) and "Perceptual Dysregulation" (37%) accounted for most of this effect. The findings provide preliminary support for the proposed mediation model indicating that BPD features may help explain relations between childhood trauma and elevated suicidal risk in adult life, in particular for DSM-5 Section III personality traits of depressivity (e.g., pessimism, guilt, and shame) and perceptual dysregulation (e.g., dissociation). To reduce the suicidal risk among those with a history of childhood trauma, BPD features (including "Depressivity" and "Perceptual Dysregulation") might be an important target of assessment, risk management, and treatment. However, other factors are likely to be involved, and a longitudinal and more large-scale design is warranted for a conclusive test of mediation.

High-Resolution Modeling to Assess Tropical Cyclone Activity in Future Climate Regimes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lackmann, Gary

2013-06-10

Applied research is proposed with the following objectives: (i) to determine the most likely level of tropical cyclone intensity and frequency in future climate regimes, (ii) to provide a quantitative measure of uncertainty in these predictions, and (iii) to improve understanding of the linkage between tropical cyclones and the planetary-scale circulation. Current mesoscale weather forecasting models, such as the Weather Research and Forecasting (WRF) model, are capable of simulating the full intensity of tropical cyclones (TC) with realistic structures. However, in order to accurately represent both the primary and secondary circulations in these systems, model simulations must be configured withmore » sufficient resolution to explicitly represent convection (omitting the convective parameterization scheme). Most previous numerical studies of TC activity at seasonal and longer time scales have not utilized such explicit convection (EC) model runs. Here, we propose to employ the moving nest capability of WRF to optimally represent TC activity on a seasonal scale using a downscaling approach. The statistical results of a suite of these high-resolution TC simulations will yield a realistic representation of TC intensity on a seasonal basis, while at the same time allowing analysis of the feedback that TCs exert on the larger-scale climate system. Experiments will be driven with analyzed lateral boundary conditions for several recent Atlantic seasons, spanning a range of activity levels and TC track patterns. Results of the ensemble of WRF simulations will then be compared to analyzed TC data in order to determine the extent to which this modeling setup can reproduce recent levels of TC activity. Next, the boundary conditions (sea-surface temperature, tropopause height, and thermal/moisture profiles) from the recent seasons will be altered in a manner consistent with various future GCM/RCM scenarios, but that preserves the large-scale shear and incipient disturbance activity. This will allow (i) a direct comparison of future TC activity that could be expected for an active or inactive season in an altered climate regime, and (ii) a measure of the level of uncertainty and variability in TC activity resulting from different carbon emission scenarios.« less

IL-10-dependent down-regulation of MHC class II expression level on monocytes by peritoneal fluid from endometriosis patients.

PubMed

Lee, Kyu-Sup; Baek, Dae-Won; Kim, Ki-Hyung; Shin, Byoung-Sub; Lee, Dong-Hyung; Kim, Ja-Woong; Hong, Young-Seoub; Bae, Yoe-Sik; Kwak, Jong-Young

2005-11-01

Endometriosis is a gynecologic disorder characterized by the ectopic growth of misplaced endometrial cells. Moreover, immunological abnormalities of cell-mediated and humoral immunity may be associated with the pathogenesis of endometriosis. The effects of peritoneal fluid (PF) from endometriosis patients on the expression levels of MHC class II and costimulatory molecules on the cell surfaces of monocytes were investigated. Compared to the PF of controls, the addition of 10% PF (n=10) from patients with endometriosis to culture medium significantly reduced the percentage of MHC class II-positive cells in cultures of a THP-1, monocytic cell line at 48 h. The effect of endometriosis patient PF (EPF) was dose-dependent, and similar effect was observed in peripheral blood monocytes. An inverse correlation was found between MHC class II expression level and IL-10 concentration in EPF (r=-0.518; p=0.019) and in the supernatant of peripheral blood monocyte cultured in EPF (r=-0.459; p=0.042) (n=20). The expression levels of costimulatory molecules (CD80 and CD86), but not of CD54 and B7-H1, were down-regulated by EPF. The mRNA level of HLA-DR was unaffected by EPF but protein level was reduced by EPF. Neutralizing IL-10 antibody abrogated MHC class II down-regulation on monocytes, which had been induced by EPF. However, in a functional assay, monocytes treated with EPF failed to stimulate T cell in mixed leukocyte reaction, although T cell proliferation was increased with EPF-treated monocytes and Staphylococcus enterotoxin B. These results suggest that MHC class II expression level on monocytes is down-regulated by EPF, but the cell stimulatory ability of monocytes does not coincide with MHC class II expression level.

Articulated, Performance-Based Instruction Guide for Drafting II. Final Document. Revised.

ERIC Educational Resources Information Center

Henderson, William Edward, Jr.

Developed during a project designed to provide continuous, performance-based vocational training at the secondary and postsecondary levels, this instructional guide is intended to help teachers implement a laterally and vertically articulated secondary level drafting II program. Introductory materials include a description of Drafting II,…

Novel Mechanism for Disrupted Circadian Blood Pressure Rhythm in a Rat Model of Metabolic Syndrome—The Critical Role of Angiotensin II

PubMed Central

Sueta, Daisuke; Kataoka, Keiichiro; Koibuchi, Nobutaka; Toyama, Kensuke; Uekawa, Ken; Katayama, Tetsuji; MingJie, Ma; Nakagawa, Takashi; Waki, Hidefumi; Maeda, Masanobu; Yasuda, Osamu; Matsui, Kunihiko; Ogawa, Hisao; Kim‐Mitsuyama, Shokei

2013-01-01

Background This study was performed to determine the characteristics and mechanism of hypertension in SHR/NDmcr‐cp(+/+) rats (SHRcp), a new model of metabolic syndrome, with a focus on the autonomic nervous system, aldosterone, and angiotensin II. Methods and Results We measured arterial blood pressure (BP) in SHRcp by radiotelemetry combined with spectral analysis using a fast Fourier transformation algorithm and examined the effect of azilsartan, an AT1 receptor blocker. Compared with control Wistar‐Kyoto rats (WKY) and SHR, SHRcp exhibited a nondipper‐type hypertension and displayed increased urinary norepinephrine excretion and increased urinary and plasma aldosterone levels. Compared with WKY and SHR, SHRcp were characterized by an increase in the low‐frequency power (LF) of systolic BP and a decrease in spontaneous baroreflex gain (sBRG), indicating autonomic dysfunction. Thus, SHRcp are regarded as a useful model of human hypertension with metabolic syndrome. Oral administration of azilsartan once daily persistently lowered BP during the light period (inactive phase) and the dark period (active phase) in SHRcp more than in WKY and SHR. Thus, angiotensin II seems to be involved in the mechanism of disrupted diurnal BP rhythm in SHRcp. Azilsartan significantly reduced urinary norepinephrine and aldosterone excretion and significantly increased urinary sodium excretion in SHRcp. Furthermore, azilsartan significantly reduced LF of systolic BP and significantly increased sBRG in SHRcp. Conclusions These results strongly suggest that impairment of autonomic function and increased aldosterone in SHRcp mediate the effect of angiotensin II on circadian blood pressure rhythms. PMID:23629805

PICASSO: an end-to-end image simulation tool for space and airborne imaging systems II. Extension to the thermal infrared: equations and methods

NASA Astrophysics Data System (ADS)

Cota, Stephen A.; Lomheim, Terrence S.; Florio, Christopher J.; Harbold, Jeffrey M.; Muto, B. Michael; Schoolar, Richard B.; Wintz, Daniel T.; Keller, Robert A.

2011-10-01

In a previous paper in this series, we described how The Aerospace Corporation's Parameterized Image Chain Analysis & Simulation SOftware (PICASSO) tool may be used to model space and airborne imaging systems operating in the visible to near-infrared (VISNIR). PICASSO is a systems-level tool, representative of a class of such tools used throughout the remote sensing community. It is capable of modeling systems over a wide range of fidelity, anywhere from conceptual design level (where it can serve as an integral part of the systems engineering process) to as-built hardware (where it can serve as part of the verification process). In the present paper, we extend the discussion of PICASSO to the modeling of Thermal Infrared (TIR) remote sensing systems, presenting the equations and methods necessary to modeling in that regime.

Developing child autonomy in pediatric healthcare: towards an ethical model.

PubMed

Martakis, Kyriakos; Brand, Helmut; Schröder-Bäck, Peter

2018-06-01

The changes initiated by the new National Civil and Commercial Code in Argentina underline the pediatric task to empower children's and adolescents' developing autonomy. In this paper, we have framed a model describing autonomy in child healthcare. We carried out a literature review focusing on i) the concept of autonomy referring to the absolute value of the autonomous individual, and ii) the age-driven process of competent decisionmaking development. We summarized our findings developing a conceptual model that includes the child, the pediatrician and the parents. The pediatricianchild relationship is based on different forms of guidance and cooperation, resulting in varying levels of activity and passivity. Parental authority influences the extent of autonomy, based on the level of respect of the child's moral equality. Contextual, existential, conceptual, and socialethical conditions shall be considered when applying the model to facilitate dialogue between pediatricians, children, parents and other actors. Sociedad Argentina de Pediatría.

Branching Fractions and log(gf)s for Weak Lines of Co II connected to the Ground and Low Metastable Levels

NASA Astrophysics Data System (ADS)

Lawler, James Edward; Feigenson, Thomas; Sneden, Chris; Cowan, John J.

2018-01-01

New branching fraction (BF) measurements and log(gf)s of Highly Reliable Lines (HRLs) of Co II are reported. Our measurements test and confirm earlier work by Salih et al. [1985] and Mullman et al. [1998] and expand the earlier BF measurements to include more weak and very weak HRLs. HRLs are UV lines that connect to the population reservoir levels including the ground and low metastable levels of Co+. Such levels contain most of the cobalt in the photospheres of typical F, G, and K stars used in abundance studies. HRLs are essentially immune to departures from Local Thermodynamic Equilibrium (LTE) because they connect to the primary reservoir levels. Lightly-populated high-lying levels of the ion and essentially all levels of the neutral atom have some possibility of being pulled out of LTE through various reactions. Weak and very weak HRLs are needed to determine Co abundances in higher metallicity stars while dominant branches are useful in low metallicity stars of abundance surveys. A large set of HRLs with reliable log(gf)s is desired to avoid blending and saturation problems in photospheric studies. The relative abundance of Fe-peak elements changes as a function of metallicity [e.g. Henry et al. 2010, Sneden et al. 2016] but contributions to the trends from nuclear physics effects in early stars need to be cleanly separated from effect due to limitations of classic photospheric models based on One Dimensional (1D) and LTE approximations. The 1D/LTE approximations of classic photospheric models, which work in well in metal rich dwarf stars such as the Sun, are a source of some concern in Metal Poor (MP) giant stars due to much lower electron and atom pressures. Our new measurements on HRLS of Co II are applied to determine stellar abundances in MP stars.Henry, R. B. C., Cowan, J. J., & Sobeck, J, 2010, ApJ 709, 715Mullman, K. L., Cooper, J. C., & Lawler, J. E. 1998, ApJ, 495, 503Salih, S., Lawler, J. E., & Whaling, W. 1985, PhRvA, 31, 744Sneden et al. 2016, ApJ 817:53Supported by the Univ. of Wisconsin – Hilldale Foundation, NASA grant NNX16AE96G, and NSF grants AST-1516182 & AST1616040.

Module modified acute physiology and chronic health evaluation II: predicting the mortality of neuro-critical disease.

PubMed

Su, Yingying; Wang, Miao; Liu, Yifei; Ye, Hong; Gao, Daiquan; Chen, Weibi; Zhang, Yunzhou; Zhang, Yan

2014-12-01

This study aimed to conduct and assess a module modified acute physiology and chronic health evaluation (MM-APACHE) II model, based on disease categories modified-acute physiology and chronic health evaluation (DCM-APACHE) II model, in predicting mortality more accurately in neuro-intensive care units (N-ICUs). In total, 1686 patients entered into this prospective study. Acute physiology and chronic health evaluation (APACHE) II scores of all patients on admission and worst 24-, 48-, 72-hour scores were obtained. Neurological diagnosis on admission was classified into five categories: cerebral infarction, intracranial hemorrhage, neurological infection, spinal neuromuscular (SNM) disease, and other neurological diseases. The APACHE II scores of cerebral infarction, intracranial hemorrhage, and neurological infection patients were used for building the MM-APACHE II model. There were 1386 cases for cerebral infarction disease, intracranial hemorrhage disease, and neurological infection disease. The logistic linear regression showed that 72-hour APACHE II score (Wals  =  173.04, P < 0.001) and disease classification (Wals  =  12.51, P  =  0.02) were of importance in forecasting hospital mortality. Module modified acute physiology and chronic health evaluation II model, built on the variables of the 72-hour APACHE II score and disease category, had good discrimination (area under the receiver operating characteristic curve (AU-ROC  =  0.830)) and calibration (χ2  =  12.518, P  =  0.20), and was better than the Knaus APACHE II model (AU-ROC  =  0.778). The APACHE II severity of disease classification system cannot provide accurate prognosis for all kinds of the diseases. A MM-APACHE II model can accurately predict hospital mortality for cerebral infarction, intracranial hemorrhage, and neurologic infection patients in N-ICU.

INCREASED HYPOTHALAMIC ANGIOTENSIN-(1-7) LEVELS IN RATS WITH AORTIC COARCTATION-INDUCED HYPERTENSION

PubMed Central

Gironacci, Mariela M.; Brosnihan, K. Bridget; Ferrario, Carlos M.; Gorzalczany, Susana; Lopez Verrilli, María A.; Pascual, Mariano; Taira, Carlos; Peña, Clara

2007-01-01

Since angiotensin (Ang) (1-7) injected into the brain blocked Ang II pressor actions in rats made hypertensive by aortic coarctation (CH), we examined systemic and tissue angiotensin peptide levels, specifically concentrating on the hypothalamic Ang-(1-7) levels. Plasma, heart and kidney isolated from CH rats showed increased levels of Ang I, Ang II and Ang-(1-7) compared with the normotensive group, with Ang II being the predominant peptide in heart and kidney. In the hypothalamus, equimolar amounts of Ang II and Ang-(1-7) were found in the sham group, whereas only Ang-(1-7) levels increased in CH rats. We conclude that aortic coarctation activates systemic and tissue renin-angiotensin system. The increased central levels of Ang-(1-7) in the CH rats suggest a potential mitigating role of this peptide in central control of the hypertensive process. PMID:17646033

Design, development, and application of LANDIS-II, a spatial landscape simulation model with flexible temporal and spatial resolution

Treesearch

Robert M. Scheller; James B. Domingo; Brian R. Sturtevant; Jeremy S. Williams; Arnold Rudy; Eric J. Gustafson; David J. Mladenoff

2007-01-01

We introduce LANDIS-II, a landscape model designed to simulate forest succession and disturbances. LANDIS-II builds upon and preserves the functionality of previous LANDIS forest landscape simulation models. LANDIS-II is distinguished by the inclusion of variable time steps for different ecological processes; our use of a rigorous development and testing process used...

The host dark matter haloes of [O II] emitters at 0.5 < z < 1.5

NASA Astrophysics Data System (ADS)

Gonzalez-Perez, V.; Comparat, J.; Norberg, P.; Baugh, C. M.; Contreras, S.; Lacey, C.; McCullagh, N.; Orsi, A.; Helly, J.; Humphries, J.

2018-03-01

Emission line galaxies (ELGs) are used in several ongoing and upcoming surveys (SDSS-IV/eBOSS, DESI) as tracers of the dark matter distribution. Using a new galaxy formation model, we explore the characteristics of [O II] emitters, which dominate optical ELG selections at z ≃ 1. Model [O II] emitters at 0.5 < z < 1.5 are selected to mimic the DEEP2, VVDS, eBOSS and DESI surveys. The luminosity functions of model [O II] emitters are in reasonable agreement with observations. The selected [O II] emitters are hosted by haloes with Mhalo ≥ 1010.3h-1M⊙, with ˜90 per cent of them being central star-forming galaxies. The predicted mean halo occupation distributions of [O II] emitters have a shape typical of that inferred for star-forming galaxies, with the contribution from central galaxies, < N > _{[O II] cen}, being far from the canonical step function. The < N > _{[O II] cen}} can be described as the sum of an asymmetric Gaussian for discs and a step function for spheroids, which plateau below unity. The model [O II] emitters have a clustering bias close to unity, which is below the expectations for eBOSS and DESI ELGs. At z ˜ 1, a comparison with observed g-band-selected galaxy, which is expected to be dominated by [O II] emitters, indicates that our model produces too few [O II] emitters that are satellite galaxies. This suggests the need to revise our modelling of hot gas stripping in satellite galaxies.

Chelation of Cu(II), Zn(II), and Fe(II) by Tannin Constituents of Selected Edible Nuts

PubMed Central

Karamać, Magdalena

2009-01-01

The tannin fractions isolated from hazelnuts, walnuts and almonds were characterised by colorimetric assays and by an SE-HPLC technique. The complexation of Cu(II) and Zn(II) was determined by the reaction with tetramethylmurexide, whereas for Fe(II), ferrozine was employed. The walnut tannins exhibited a significantly weaker reaction with the vanillin/HCl reagent than hazelnut and almond tannins, but the protein precipitation capacity of the walnut fraction was high. The SE-HPLC chromatogram of the tannin fraction from hazelnuts revealed the presence of oligomers with higher molecular weights compared to that of almonds. Copper ions were most effectively chelated by the constituents of the tannin fractions of hazelnuts, walnuts and almonds. At a 0.2 mg/assay addition level, the walnut tannins complexed almost 100% Cu(II). The Fe(II) complexation capacities of the tannin fractions of walnuts and hazelnuts were weaker in comparison to that of the almond tannin fraction, which at a 2.5 mg/assay addition level, bound Fe(II) by ~90%. The capacity to chelate Zn(II) was quite varied for the different nut tannin fractions: almond tannins bound as much as 84% Zn(II), whereas the value for walnut tannins was only 8.7%; and for hazelnut tannins, no Zn(II) chelation took place at the levels tested. PMID:20054482

Chelation of Cu(II), Zn(II), and Fe(II) by tannin constituents of selected edible nuts.

PubMed

Karamać, Magdalena

2009-12-22

The tannin fractions isolated from hazelnuts, walnuts and almonds were characterised by colorimetric assays and by an SE-HPLC technique. The complexation of Cu(II) and Zn(II) was determined by the reaction with tetramethylmurexide, whereas for Fe(II), ferrozine was employed. The walnut tannins exhibited a significantly weaker reaction with the vanillin/HCl reagent than hazelnut and almond tannins, but the protein precipitation capacity of the walnut fraction was high. The SE-HPLC chromatogram of the tannin fraction from hazelnuts revealed the presence of oligomers with higher molecular weights compared to that of almonds. Copper ions were most effectively chelated by the constituents of the tannin fractions of hazelnuts, walnuts and almonds. At a 0.2 mg/assay addition level, the walnut tannins complexed almost 100% Cu(II). The Fe(II) complexation capacities of the tannin fractions of walnuts and hazelnuts were weaker in comparison to that of the almond tannin fraction, which at a 2.5 mg/assay addition level, bound Fe(II) by approximately 90%. The capacity to chelate Zn(II) was quite varied for the different nut tannin fractions: almond tannins bound as much as 84% Zn(II), whereas the value for walnut tannins was only 8.7%; and for hazelnut tannins, no Zn(II) chelation took place at the levels tested.

Excitation rate coefficients and line ratios for the optical and ultraviolet transitions in S II

NASA Technical Reports Server (NTRS)

Cai, Wei; Pradhan, Anil K.

1993-01-01

New calculations are reported for electron excitation collision strengths, rate coefficients, transition probabilities, and line ratios for the astrophysically important optical and UV lines in S II. The collision strengths are calculated in the close coupling approximation using the R-matrix method. The present calculations are more extensive than previous ones, including all transitions among the 12 lowest LS terms and the corresponding 28 fine-structure levels in the collisional-radiative model for S II. While the present rate coefficients for electron impact excitation are within 10-30 percent of the previous values for the low-lying optical transitions employed as density diagnostics of H II regions and nebulae, the excitation rates for the UV transitions 4S super 0 sub 3/2 - 4Psub 1/2,3/2,5/2 differ significantly from earlier calculations, by up to factor of 2. We describe temperature and density sensitive flux ratios for a number of UV lines. The present UV results are likely to be of interest in a more accurate interpretation of S II emission from the Io plasma torus in the magnetosphere of Jupiter, as well as other UV sources observed from the IUE, ASTRO 1, and the HST.

A two-stage patient enrichment adaptive design in phase II oncology trials.

PubMed

Song, James X

2014-01-01

Illustrated is the use of a patient enrichment adaptive design in a randomized phase II trial which allows the evaluation of treatment benefits by the biomarker expression level and makes interim adjustment according to the pre-specified rules. The design was applied to an actual phase II metastatic hepatocellular carcinoma (HCC) trial in which progression-free survival (PFS) in two biomarker-defined populations is evaluated at both interim and final analyses. As an extension, a short-term biomarker is used to predict the long-term PFS in a Bayesian model in order to improve the precision of hazard ratio (HR) estimate at the interim analysis. The characteristics of the extended design are examined in a number of scenarios via simulations. The recommended adaptive design is shown to be useful in a phase II setting. When a short-term maker which correlates with the long-term PFS is available, the design can be applied in smaller early phase trials in which PFS requires longer follow-up. In summary, the adaptive design offers flexibility in randomized phase II patient enrichment trials and should be considered in an overall personalized healthcare (PHC) strategy. Copyright © 2013 Elsevier Inc. All rights reserved.

Transcriptional and functional studies of a Cd(II)/Pb(II)-responsive transcriptional regulator(CmtR) from Acidithiobacillus ferrooxidans ATCC 23270.

PubMed

Zheng, Chunli; Li, Yanjun; Nie, Li; Qian, Lin; Cai, Lu; Liu, Jianshe

2012-08-01

The acidophilic Acidithiobacillus ferrooxidans can resist exceptionally high cadmium (Cd) concentrations. This property is important for its use in biomining processes, where Cd and other metal levels range usually between 15 and 100 mM. To learn about the mechanisms that allow A. ferrooxidans cells to survive in this environment, a bioinformatic search of its genome showed the presence of that a Cd(II)/Pb(II)-responsive transcriptional regulator (CmtR) was possibly related to Cd homeostasis. The expression of the CmtR was studied by real-time reverse transcriptase PCR using A. ferrooxidans cells adapted for growth in the presence of high concentrations of Cd. The putative A. ferrooxidans Cd resistance determinant was found to be upregulated when this bacterium was exposed to Cd in the range of 15-30 mM. The CmtR from A. ferrooxidans was cloned and expressed in Escherichia coli, the soluble protein was purified by one-step affinity chromatography to apparent homogeneity. UV-Vis spectroscopic measurements showed that the reconstruction CmtR was able to bind Cd(II) forming Cd(II)-CmtR complex in vitro. The sequence alignment and molecular modeling showed that the crucial residues for CmtR binding were likely to be Cys77, Cys112, and Cys121. The results reported here strongly suggest that the high resistance of the extremophilic A. ferrooxidans to Cd including the Cd(II)/Pb(II)-responsive transcriptional regulator.

p38 mitogen-activated protein kinase is involved in arginase-II-mediated eNOS-Uncoupling in Obesity

PubMed Central

2014-01-01

Background Endothelial nitric oxide synthase (eNOS)-uncoupling links obesity-associated insulin resistance and type-II diabetes to the increased incidence of cardiovascular disease. Studies have indicated that increased arginase is involved in eNOS-uncoupling through competing with the substrate L-arginine. Given that arginase-II (Arg-II) exerts some of its biological functions through crosstalk with signal transduction pathways, and that p38 mitogen-activated protein kinase (p38mapk) is involved in eNOS-uncoupling, we investigated here whether p38mapk is involved in Arg-II-mediated eNOS-uncoupling in a high fat diet (HFD)-induced obesity mouse model. Methods Obesity was induced in wild type (WT) and Arg-II-deficient (Arg-II-/-) mice on C57BL/6 J background by high-fat diet (HFD, 55% fat) for 14 weeks starting from age of 7 weeks. The entire aortas were isolated and subjected to 1) immunoblotting analysis of the protein level of eNOS, Arg-II and p38mapk activation; 2) arginase activity assay; 3) endothelium-dependent and independent vasomotor responses; 4) en face staining of superoxide anion and NO production with Dihydroethidium and 4,5-Diaminofluorescein Diacetate, respectively, to assess eNOS-uncoupling. To evaluate the role of p38mapk, isolated aortas were treated with p38mapk inhibitor SB203580 (10 μmol/L, 1 h) prior to the analysis. In addition, the role of p38mapk in Arg-II-induced eNOS-uncoupling was investigated in cultured human endothelial cells overexpressing Arg-II in the absence or presence of shRNA against p38mapk. Results HFD enhanced Arg-II expression/activity and p38mapk activity, which was associated with eNOS-uncoupling as revealed by decreased NO and enhanced L-NAME-inhibitable superoxide in aortas of WT obese mice. In accordance, WT obese mice revealed decreased endothelium-dependent relaxations to acetylcholine despite of higher eNOS protein level, whereas Arg-II-/- obese mice were protected from HFD-induced eNOS-uncoupling and endothelial dysfunction, which was associated with reduced p38mapk activation in aortas of the Arg-II-/- obese mice. Moreover, overexpression of Arg-II in human endothelial cells caused eNOS-uncoupling and augmented p38mapk activation. The Arg-II-induced eNOS-uncoupling was prevented by silencing p38mapk. Furthermore, pharmacological inhibition of p38mapk recouples eNOS in isolated aortas from WT obese mice. Conclusions Taking together, we demonstrate here for the first time that Arg-II causes eNOS-uncoupling through activation of p38 mapk in HFD-induced obesity. PMID:25034973

Pyroclastic flow hazard at Volcán Citlaltépetl

USGS Publications Warehouse

Sheridan, Michael F.; Hubbard, Bernard E.; Carrasco-Nunez, Gerardo; Siebe, Claus

2004-01-01

Volcán Citlaltépetl (Pico de Orizaba) with an elevation of 5,675 m is the highest volcano in North America. Its most recent catastrophic events involved the production of pyroclastic flows that erupted approximately 4,000, 8,500, and 13,000 years ago. The distribution of mapped deposits from these eruptions gives an approximate guide to the extent of products from potential future eruptions. Because the topography of this volcano is constantly changing computer simulations were made on the present topography using three computer algorithms: energy cone, FLOW2D, and FLOW3D. The Heim Coefficient (μ), used as a code parameter for frictional sliding in all our algorithms, is the ratio of the assumed drop in elevation (H) divided by the lateral extent of the mapped deposits (L). The viscosity parameter for the FLOW2D and FLOW3D codes was adjusted so that the paths of the flows mimicked those inferred from the mapped deposits. We modeled two categories of pyroclastic flows modeled for the level I and level II events. Level I pyroclastic flows correspond to small but more frequent block-and-ash flows that remain on the main cone. Level II flows correspond to more widespread flows from catastrophic eruptions with an approximate 4,000-year repose period. We developed hazard maps from simulations based on a National Imagery and Mapping Agency (NIMA) DTED-1 DEM with a 90 m grid and a vertical accuracy of ±30 m. Because realistic visualization is an important aid to understanding the risks related to volcanic hazards we present the DEM as modeled by FLOW3D. The model shows that the pyroclastic flows extend for much greater distances to the east of the volcano summit where the topographic relief is nearly 4,300 m. This study was used to plot hazard zones for pyroclastic flows in the official hazard map that was published recently.

Detecting the Lμ-Lτ gauge boson at Belle II

NASA Astrophysics Data System (ADS)

Araki, Takeshi; Hoshino, Shihori; Ota, Toshihiko; Sato, Joe; Shimomura, Takashi

2017-03-01

We discuss the feasibility of detecting the gauge boson of the U (1 )Lμ-Lτ symmetry, which possesses a mass in the range between MeV and GeV, at the Belle-II experiment. The kinetic mixing between the new gauge boson Z' and photon is forbidden at the tree level and is radiatively induced. The leptonic force mediated by such a light boson is motivated by the discrepancy in muon anomalous magnetic moment and also the gap in the energy spectrum of cosmic neutrino. Defining the process e+e-→γ Z'→γ ν ν ¯ (missing energy) to be the signal, we estimate the numbers of the signal and the background events and show the parameter region to which the Belle-II experiment will be sensitive. The signal process in the Lμ-Lτ model is enhanced with a light Z', which is a characteristic feature differing from the dark photon models with a constant kinetic mixing. We find that the Belle-II experiment with the design luminosity will be sensitive to the Z' with the mass MZ'≲1 GeV and the new gauge coupling gZ'≳8 ×10-4 , which covers a half of the unconstrained parameter region that explains the discrepancy in muon anomalous magnetic moment. The possibilities to improve the significance of the detection are also discussed.

Effects of Low-Molecular-Weight Fucoidan and High Stability Fucoxanthin on Glucose Homeostasis, Lipid Metabolism, and Liver Function in a Mouse Model of Type II Diabetes.

PubMed

Lin, Hong-Ting Victor; Tsou, Yu-Chi; Chen, Yu-Ting; Lu, Wen-Jung; Hwang, Pai-An

2017-04-07

The combined effects of low-molecular-weight fucoidan (LMF) and fucoxanthin (Fx) in terms of antihyperglycemic, antihyperlipidemic, and hepatoprotective activities were investigated in a mouse model of type II diabetes. The intake of LMF, Fx, and LMF + Fx lowered the blood sugar and fasting blood sugar levels, and increased serum adiponectin levels. The significant decrease in urinary sugar was only observed in LMF + Fx supplementation. LMF and Fx had ameliorating effects on the hepatic tissue of db/db mice by increasing hepatic glycogen and antioxidative enzymes, and LMF was more effective than Fx at improving hepatic glucose metabolism. As for glucose and lipid metabolism in the adipose tissue, the expression of insulin receptor substrate (IRS)-1, glucose transporter (GLUT), peroxisome proliferator-activated receptor gamma (PPARγ), and uncoupling protein (UCP)-1 mRNAs in the adipose tissue of diabetic mice was significantly upregulated by Fx and LMF + Fx, and levels of inflammatory adipocytokines, such as adiponectin, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), were significantly modulated only by LMF + Fx supplementation. The efficacy of LMF + Fx supplementation on the decrease in urinary sugar and on glucose and lipid metabolism in the white adipose tissue of db/db mice was better than that of Fx or LMF alone, indicating the occurrence of a synergistic effect of LMF and Fx.

Plasma simulations that meet the challenges of HST & JWST Active Nuclei & Starburst observations

NASA Astrophysics Data System (ADS)

Ferland, Gary

2017-08-01

Recent HST AGN monitoring programs, such as the STORM Campaign, have resulted in the definitive set of emission-line-continuum lag measurements. The goals are to measure the structure of the inner regions of an AGN, understand the physics driving the variability, and use this to place black hole mass determinations on an even firmer footing. Photoionization models make it possible to convert these observations into physical parameters such as cloud density or location. Here I propose to improve the treatment of emission from species like C IV, C III], Mg II, or Fe II in the spectral / plasma simulation code Cloudy. Like all plasma codes, Cloudy uses a modified two-level approximation to solve for the ionization of many-electron ions. I have participated in meetings on modeling Tokamak plasmas, which share many of the properties of the BLR of AGN and have the advantage of being a controlled laboratory environment. These discussions have led to the development of tests to show the density range over which the two-level approximation is valid. It fails at the densities where the strong UV lines form. I will use the atomic data available within the fusion modeling community, along with the methods they have developed, to improve Cloudy models so that they can better inform us of the message in the UV spectrum. The improvements will be part of future releases of Cloudy, which is openly available and updated on a regular basis.

What spectroscopy reveals concerning the Mn oxidation levels in the oxygen evolving complex of photosystem II: X-ray to near infra-red.

PubMed

Pace, Ron J; Jin, Lu; Stranger, Rob

2012-08-28

Photosystem II (PS II), found in oxygenic photosynthetic organisms, catalyses the most energetically demanding reaction in nature, the oxidation of water to molecular oxygen and protons. The water oxidase in PS II contains a Mn(4)Ca cluster (oxygen evolving complex, OEC), whose catalytic mechanism has been extensively investigated but is still unresolved. In particular the precise Mn oxidation levels through which the cluster cycles during functional turnover are still contentious. In this, the first of several planned parts, we examine a broad range of published data relating to this question, while considering the recent atomic resolution PS II crystal structure of Umena et al. (Nature, 2011, 473, 55). Results from X-ray, UV-Vis and NIR spectroscopies are considered, using an approach that is mainly empirical, by comparison with published data from known model systems, but with some reliance on computational or other theoretical considerations. The intention is to survey the extent to which these data yield a consistent picture of the Mn oxidation states in functional PS II - in particular, to test their consistency with two current proposals for the mean redox levels of the OEC during turnover; the so called 'high' and 'low' oxidation state paradigms. These systematically differ by two oxidation equivalents throughout the redox accumulating catalytic S state cycle (states S(0)···S(3)). In summary, we find that the data, in total, substantially favor the low oxidation proposal, particularly as a result of the new analyses we present. The low oxidation state scheme is able to resolve a number of previously 'anomalous' results in the observed UV-Visible S state turnover spectral differences and in the resonant inelastic X-ray spectroscopy (RIXS) of the Mn pre-edge region of the S(1) and S(2) states. Further, the low oxidation paradigm is able to provide a 'natural' explanation for the known sensitivity of the OEC Mn cluster to cryogenic near infra-red (NIR) induced turnover to alternative spin/redox states in S(2) and S(3).

Social disparities in dietary habits among women: Geographic Research on Wellbeing (GROW) Study.

PubMed

Wang, May; Heck, Katherine; Winkleby, Marilyn; Cubbin, Catherine

2016-06-01

Relationships among race/ethnicity, individual socio-economic status (SES), neighbourhood SES and acculturation are complex. We sought to answer whether: (i) race/ethnicity, individual SES and neighbourhood SES have independent effects on women's fruit and vegetable consumption (FVC); (ii) SES modifies the effects of race/ethnicity on FVC; and (iii) nativity modifies the effect of Latina ethnicity on FVC. Cross-sectional surveys from the population-based Geographic Research on Wellbeing (GROW) Study were linked with census-tract level data. FVC was indicated by (i) consuming fruits and vegetables less often than daily (LOWFV) and (ii) not having fruits and vegetables in the home very often. Other variables included age, marital status, race/ethnicity, country of birth, educational attainment, family income and longitudinal neighbourhood poverty (based on latent class growth models). Weighted logistic regression models accounting for the complex sample design were constructed. California, USA, 2012-2013. Women (n 2669). In adjusted models, race/ethnicity, education and income were independently associated with FVC, but not neighbourhood poverty. Women of colour, high-school graduates and women with incomes at 301-400 % of the federal poverty level were at higher odds of LOWFV compared with non-Hispanic Whites, college graduates and those with incomes >400 % of the federal poverty level. Little evidence for interactions between race/ethnicity and individual or neighbourhood SES was found; similar patterns were observed for immigrant and US-born Latinas. Addressing the dietary needs of lower-SES communities requires multilevel interventions that simultaneously provide culturally tailored nutrition education and address the physical and economic accessibility of culturally acceptable fruits and vegetables.

Functional response models to estimate feeding rates of wading birds

USGS Publications Warehouse

Collazo, J.A.; Gilliam, J.F.; Miranda-Castro, L.

2010-01-01

Forager (predator) abundance may mediate feeding rates in wading birds. Yet, when modeled, feeding rates are typically derived from the purely prey-dependent Holling Type II (HoII) functional response model. Estimates of feeding rates are necessary to evaluate wading bird foraging strategies and their role in food webs; thus, models that incorporate predator dependence warrant consideration. Here, data collected in a mangrove swamp in Puerto Rico in 1994 were reanalyzed, reporting feeding rates for mixed-species flocks after comparing fits of the HoII model, as used in the original work, to the Beddington-DeAngelis (BD) and Crowley-Martin (CM) predator-dependent models. Model CM received most support (AIC c wi = 0.44), but models BD and HoII were plausible alternatives (AIC c ??? 2). Results suggested that feeding rates were constrained by predator abundance. Reductions in rates were attributed to interference, which was consistent with the independently observed increase in aggression as flock size increased (P < 0.05). Substantial discrepancies between the CM and HoII models were possible depending on flock sizes used to model feeding rates. However, inferences derived from the HoII model, as used in the original work, were sound. While Holling's Type II and other purely prey-dependent models have fostered advances in wading bird foraging ecology, evaluating models that incorporate predator dependence could lead to a more adequate description of data and processes of interest. The mechanistic bases used to derive models used here lead to biologically interpretable results and advance understanding of wading bird foraging ecology.

Biochemical and inflammatory biomarkers in ischemic stroke: translational study between humans and two experimental rat models

PubMed Central

2014-01-01

Background our objective was to examine the plasma levels of three biological markers involved in cerebral ischemia (IL-6, glutamate and TNF-alpha) in stroke patients and compare them with two different rat models of focal ischemia (embolic stroke model- ES and permanent middle cerebral artery occlusion ligation model-pMCAO) to evaluate which model is most similar to humans. Secondary objectives: 1) to analyze the relationship of these biological markers with the severity, volume and outcome of the brain infarction in humans and the two stroke models; and 2) to study whether the three biomarkers are also increased in response to damage in organs other than the central nervous system, both in humans and in rats. Methods Multi-center, prospective, case-control study including acute stroke patients (n = 58) and controls (n = 19) with acute non-neurological diseases Main variables: plasma biomarker levels on admission and at 72 h; stroke severity (NIHSS scale) and clinical severity (APACHE II scale); stroke volume; functional status at 3 months (modified Rankin Scale [mRS] and Barthel index [BI]). Experimental groups: ES (n = 10), pMCAO (n = 6) and controls (tissue stress by leg compression) (n = 6). Main variables: plasma biomarker levels at 3 and 72 h; volume of ischemic lesion (H&E) and cell death (TUNEL). Results in stroke patients, IL-6 correlated significantly with clinical severity (APACHE II scale), stroke severity (NIHSS scale), infarct volume (cm3) and clinical outcome (mRS) (r = 0.326, 0.497, 0.290 and 0.444 respectively; P < 0.05). Glutamate correlated with stroke severity, but not with outcome, and TNF-alpha levels with infarct volume. In animals, The ES model showed larger infarct volumes (median 58.6% vs. 29%, P < 0.001) and higher inflammatory biomarkers levels than pMCAO, except for serum glutamate levels which were higher in pMCAO. The ES showed correlations between the biomarkers and cell death (r = 0.928 for IL-6; P < 0.001; r = 0.765 for TNF-alpha, P < 0.1; r = 0.783 for Glutamate, P < 0.1) and infarct volume (r = 0.943 for IL-6, P < 0.0001) more similar to humans than pMCAO. IL-6, glutamate and TNF-α levels were not higher in cerebral ischemia than in controls. Conclusions Both models, ES and pMCAO, show differences that should be considered when conducting translational studies. IL-6, Glutamate and TNF-α are not specific for cerebral ischemia either in humans or in rats. PMID:25086655

Synergistic Instance-Level Subspace Alignment for Fine-Grained Sketch-Based Image Retrieval.

PubMed

Li, Ke; Pang, Kaiyue; Song, Yi-Zhe; Hospedales, Timothy M; Xiang, Tao; Zhang, Honggang

2017-08-25

We study the problem of fine-grained sketch-based image retrieval. By performing instance-level (rather than category-level) retrieval, it embodies a timely and practical application, particularly with the ubiquitous availability of touchscreens. Three factors contribute to the challenging nature of the problem: (i) free-hand sketches are inherently abstract and iconic, making visual comparisons with photos difficult, (ii) sketches and photos are in two different visual domains, i.e. black and white lines vs. color pixels, and (iii) fine-grained distinctions are especially challenging when executed across domain and abstraction-level. To address these challenges, we propose to bridge the image-sketch gap both at the high-level via parts and attributes, as well as at the low-level, via introducing a new domain alignment method. More specifically, (i) we contribute a dataset with 304 photos and 912 sketches, where each sketch and image is annotated with its semantic parts and associated part-level attributes. With the help of this dataset, we investigate (ii) how strongly-supervised deformable part-based models can be learned that subsequently enable automatic detection of part-level attributes, and provide pose-aligned sketch-image comparisons. To reduce the sketch-image gap when comparing low-level features, we also (iii) propose a novel method for instance-level domain-alignment, that exploits both subspace and instance-level cues to better align the domains. Finally (iv) these are combined in a matching framework integrating aligned low-level features, mid-level geometric structure and high-level semantic attributes. Extensive experiments conducted on our new dataset demonstrate effectiveness of the proposed method.

[Effects of Tetrandrine Prenatal Intervention on Alveolar Epithelial Cells Type I Differentiation in Rat Model of Nitrofen-induced Congenital Diaphragmatic Hernia].

PubMed

Xiao, Bin; Xu, Chang; Liu, Min; Ji, Yi; Yang Li-xun; Li, Tai-ming; Jiang, Jun; He, Tao-zhen

2016-03-01

To investigate the effects of Tetrandrine (TET) prenatal intervention on the differentiation of alveolar epithelial cells type I (AEC I) in rat model of Nitrofen-induced congenital diaphragmatic hernia (CDH). Timed-pregnant Sprague-Dawley rats were divided into three groups, namely control, CDH and TET group on day 9.5 of gestation. The rats in TET group and CDH group were given 125 mg of Nitrofen by gavage one time, while the rats in control group were given the same dose of seed fat. After that, the rats in TET group was given 30 mg/kg of TET by gavage once a day for three days from day 18.5 of gestation, while the rats in CDH and control group were given the same dose of normal saline. On day 21.5 of gestation, all fetuses were delivered by cesarean, the lungs of fetuses were histologically evaluated by microscope and electron microscope. The expressions of type I cell-specific protein (RT140) and thyroid transcription factor 1 (TTF1) in alveolar fluid content were analyzed by RT-PCR and immunohistochemistry staining. To detect the number of AEC I and AEC II of each group by transmission electron microscopy and calculate the percentage of AEC I and AEC II (I/II%). The microscope and electron microscope study found the lungs of fetuses in CDH group showed marked hypoplasia, in contrast to the improvement of hypoplasia in TET fetuses. The pulmonary alveolar area had significant difference statistically (P < 0.01) in each group, which present as control > TET > CDH. I/II% had significant difference statistically (P < 0.01) in each group, which present as control > TET > CDH. The expression level of TTF1 was up-regulated in both CDH and TET groups, and it was higher in CDH group (P < 0.01). The expression level of RT140 were down-regulated in CDH and TET groups, which was lower in CDH group (P < 0.01). The development of AEC I was interfered in CDH rat model, TET prenatal treatment could improve the lung development of CDH.

Efficiency of a cleanup technology to remove mercury from natural waters by means of rice husk biowaste: ecotoxicological and chemical approach.

PubMed

Rocha, Luciana S; Lopes, I; Lopes, Cláudia B; Henriques, Bruno; Soares, Amadeu M V M; Duarte, Armando C; Pereira, Eduarda

2014-01-01

In the present work, the efficiency of rice husk to remove Hg(II) from river waters spiked with realistic environmental concentrations of this metal (μg L(-1) range) was evaluated. The residual levels of Hg(II) obtained after the remediation process were compared with the guideline values for effluents discharges and water for human consumption, and the ecotoxicological effects using organisms of different trophic levels were assessed. The rice husk sorbent proved to be useful in decreasing Hg(II) contamination in river waters, by reducing the levels of Hg(II) to values of ca. 8.0 and 34 μg L(-1), for an Hg(II) initial concentration of 50 and 500 μg L(-1), respectively. The remediation process with rice husk biowaste was extremely efficient in river waters spiked with lower levels of Hg(II), being able to eliminate the toxicity to the exposed organisms algae Pseudokirchneriella subcapitata and rotifer Brachionus calyciflorus and ensure the total survival of Daphnia magna species. For concentrations of Hg(II) tenfold higher (500 μg L(-1)), the remediation process was not adequate in the detoxification process, still, the rice husk material was able to reduce considerably the toxicity to the bacteria Vibrio fischeri, algae P. subcapitata and rotifer B. calyciflorus, whose responses where fully inhibited during its exposure to the non-remediated river water. The use of a battery of bioassays with organisms from different trophic levels and whose sensitivity revealed to be different and dependent on the levels of Hg(II) contamination proved to be much more accurate in predicting the ecotoxicological hazard assessment of the detoxification process by means of rice husk biowaste.

Consumer preference in ranking walking function utilizing the walking index for spinal cord injury II.

PubMed

Patrick, M; Ditunno, P; Ditunno, J F; Marino, R J; Scivoletto, G; Lam, T; Loffree, J; Tamburella, F; Leiby, B

2011-12-01

Blinded rank ordering. To determine consumer preference in walking function utilizing the walking Index for spinal cord injury II (WISCI II) in individuals with spinal cord injury (SCI)from the Canada, the Italy and the United States of America. In all, 42 consumers with incomplete SCI (25 cervical, 12 thoracic, 5 lumbar) from Canada (12/42), Italy (14/42) and the United States of America (16/42) ranked the 20 levels of the WISCI II scale by their individual preference for walking. Subjects were blinded to the original ranking of the WISCI II scale by clinical scientists. Photographs of each WISCI II level used in a previous pilot study were randomly shuffled and rank ordered. Percentile, conjoint/cluster and graphic analyses were performed. All three analyses illustrated consumer ranking followed a bimodal distribution. Ranking for two levels with physical assistance and two levels with a walker were bimodal with a difference of five to six ranks between consumer subgroups (quartile analysis). The larger cluster (N=20) showed preference for walking with assistance over the smaller cluster (N=12), whose preference was walking without assistance and more devices. In all, 64% (27/42) of consumers ranked WISCI II level with no devices or braces and 1 person assistance higher than multiple levels of the WISCI II requiring no assistance. These results were unexpected, as the hypothesis was that consumers would rank independent walking higher than walking with assistance. Consumer preference for walking function should be considered in addition to objective measures in designing SCI trials that use significant improvement in walking function as an outcome measure.

Experimental and analytical study of loss-of-flow transients in EBR-II occurring at decay power levels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, L.K.; Mohr, D.; Feldman, E.E.

A series of eight loss-of-flow (LOF) tests have been conducted in EBR-II to study the transition between forced and natural convective flows following a variety of loss-of-primary-pumping power conditions from decay heat levels. Comparisons of measurements and pretest/posttest predictions were made on a selected test. Good agreements between measurements and predictions was found prior to and just after the flow reaching its minimum, but the agreement is not as good after that point. The temperatures are consistent with the flow response and the assumed decay power. The measured results indicate that the flows of driver and the instrumented subassemblies aremore » too much in the analytical model in the natural convective region. Although a parametric study on secondary flow, turbulent-laminar flow transition, heat transfer ability of the intermediate heat exchange at low flow and flow mixing in the primary tank has been performed to determine their effects on the flow, the cause of the discrepancy at very low flow level is still unknown.« less

Psychosis related to neurological conditions: pro and cons of the dis- / mis-connectivity models of schizophrenia

PubMed Central

Foucher, Jack R.; Luck, David

2006-01-01

Schizophrenia is still a condition with obscure causes and psychopathology. This paper aims to discuss the “disconnectivity” hypothesis in relation to some neurological conditions which are known to alter brain connectivity, as well as mimicking some aspects of the disorder. After a short historical introduction to the concept, we will examine the evidence for connectivity problems in schizophrenia, separating the anatomical level from the functional level. Then, we will discuss three different issues concerning connectivity: i) local reduction in connectivity without neuronal loss (within the gray matter); ii) reduction in or alteration of long-range connectivity (within the white matter); and iii) abnormal targets for connections. For each of these aspects, we will look at the conditions able to reproduce anomalies capable of increasing susceptibility to schizophrenia. We conclude that psychosis is more likely to occur: i) when long-range connectivity is concerned; ii) when lesions result in lengthening and scattering of conduction times; and iii) when there are high dopamine levels, shedding light on or adding weight to the idea of an interaction between dopamine and connectivity. PMID:16640110

The Mg II h and k lines. II - Comparison with synthesized profiles and Ca II K. [solar spectra

NASA Technical Reports Server (NTRS)

Ayres, T. R.; Linsky, J. L.

1976-01-01

Measured high-dispersion center and limb profiles of the solar Mg II h and k resonance lines are compared with synthetic spectra computed with a partial-redistribution formalism and based on several upper-photosphere and lower-chromosphere temperature distributions. Profiles of the analogously formed Ca II K resonance line are also synthesized for the same atmospheric models. The spectrum-synthesis approach is outlined, and the collisional and fixed radiative rates appropriate to the adopted model atoms and solar atmosphere are discussed. It is found that the HSRA and VAL models predict systematically lower intensities in the h, k, and K inner wings than observed and that models with a somewhat higher minimum temperature (about 4450 K) can reproduce the measured inner wings and limb darkening. A 'Ca II' solar model with a minimum temperature of 4450 K is proposed as an alternative to the class of models based on continuum observations.

Carbonate-mediated Fe(II) oxidation in the air-cathode fuel cell: a kinetic model in terms of Fe(II) speciation.

PubMed

Song, Wei; Zhai, Lin-Feng; Cui, Yu-Zhi; Sun, Min; Jiang, Yuan

2013-06-06

Due to the high redox activity of Fe(II) and its abundance in natural waters, the electro-oxidation of Fe(II) can be found in many air-cathode fuel cell systems, such as acid mine drainage fuel cells and sediment microbial fuel cells. To deeply understand these iron-related systems, it is essential to elucidate the kinetics and mechanisms involved in the electro-oxidation of Fe(II). This work aims to develop a kinetic model that adequately describes the electro-oxidation process of Fe(II) in air-cathode fuel cells. The speciation of Fe(II) is incorporated into the model, and contributions of individual Fe(II) species to the overall Fe(II) oxidation rate are quantitatively evaluated. The results show that the kinetic model can accurately predict the electro-oxidation rate of Fe(II) in air-cathode fuel cells. FeCO3, Fe(OH)2, and Fe(CO3)2(2-) are the most important species determining the electro-oxidation kinetics of Fe(II). The Fe(II) oxidation rate is primarily controlled by the oxidation of FeCO3 species at low pH, whereas at high pH Fe(OH)2 and Fe(CO3)2(2-) are the dominant species. Solution pH, carbonate concentration, and solution salinity are able to influence the electro-oxidation kinetics of Fe(II) through changing both distribution and kinetic activity of Fe(II) species.

In-flight source noise of an advanced full-scale single-rotation propeller

NASA Technical Reports Server (NTRS)

Woodward, Richard P.; Loffler, Irvin J.

1991-01-01

Flight tests to define the far-field tone source at cruise conditions have been completed on the full-scale SR-7L advanced turboprop, which was installed on the left wing of a Gulfstream II aircraft. These measurements defined source levels for input into long-distance propagation models to predict en route noise. Infight data were taken for seven test cases. The sideline directivities measured showed expected maximum levels near 105 deg from the propeller upstream axis. However, azimuthal directivities based on the maximum observed sideline tone levels showed highest levels below the aircraft. The tone level reduction associated with reductions in propeller tip speed is shown to be more significant in the horizontal plane than below the aircraft.

Screening and production of a potent extracellular Arthrobacter creatinolyticus urease for determination of heavy metal ions.

PubMed

Ramesh, Rajendran; Aarthy, Mayilvahanan; Gowthaman, Marichetti Kuppuswami; Gabrovska, Katya; Godjevargova, Tzonka; Kamini, Numbi Ramudu

2014-04-01

This paper describes the isolation of a potent extracellular urease producing microorganism, identified by 16S rRNA as Arthrobacter creatinolyticus MTCC 5604 and its medium optimization by classical one-factor-at-a-time method and central composite rotatable design (CCRD), a tool of response surface methodology (RSM). An optimal activity of 9.0 U ml(-1) was obtained by classical method and statistical optimization of the medium resulted in an activity of 17.35 U ml(-1) at 48 h and 30 °C. This activity was 4.91 times greater than the initial activity (3.53 U ml(-1) ) from the basal medium and the enzyme showed maximum activity at pH 8.0 and 60 °C and was stable at pH 7.0-9.0 and temperatures up to 50 °C. Furthermore, the enzyme was assessed for its activity reduction by determining the inhibitory concentration (IC50 ) of heavy metal ions and the inhibition of urease was in the order of Cu(II) > Cd(II) > Zn(II) > Ni(II). Urease was highly sensitive to Cu(II) and its inhibition was 94% and 100% in model solutions containing a mixture of Cu(II) with heavy metal ions Cd(II) and Zn(II), respectively. The results of these studies suggested that the enzyme could be utilized as sensors to determine the levels of Cu(II) ions in industrial effluents, contaminated soil and ground water. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Recombinant Trivalent Fusion Protein F1-LcrV-HSP70(II) Augments Humoral and Cellular Immune Responses and Imparts Full Protection against Yersinia pestis.

PubMed

Verma, Shailendra K; Batra, Lalit; Tuteja, Urmil

2016-01-01

Plague is one of the most dangerous infections in humans caused by Yersinia pestis, a Gram-negative bacterium. Despite of an overwhelming research success, no ideal vaccine against plague is available yet. It is well established that F1/LcrV based vaccine requires a strong cellular immune response for complete protection against plague. In our earlier study, we demonstrated that HSP70(II) of Mycobacterium tuberculosis modulates the humoral and cellular immunity of F1/LcrV vaccine candidates individually as well as in combinations in a mouse model. Here, we made two recombinant constructs caf1-lcrV and caf1-lcrV-hsp70(II). The caf1 and lcrV genes of Y. pestis and hsp70 domain II of M. tuberculosis were amplified by polymerase chain reaction. Both the recombinant constructs caf1-lcrV and caf1-lcrV-hsp70(II) were cloned in pET28a vector and expressed in Escherichia coli. The recombinant fusion proteins F1-LcrV and F1-LcrV-HSP70(II) were purified using Ni-NTA columns and formulated with alum to evaluate the humoral and cell mediated immune responses in mice. The protective efficacies of F1-LcrV and F1-LcrV-HSP70(II) were determined following challenge of immunized mice with 100 LD50 of Y. pestis through intraperitoneal route. Significant differences were noticed in the titers of IgG and it's isotypes, i.e., IgG1, IgG2b, and IgG3 in anti- F1-LcrV-HSP70(II) sera in comparison to anti-F1-LcrV sera. Similarly, significant differences were also noticed in the expression levels of IL-2, IFN-γ and TNF-α in splenocytes of F1-LcrV-HSP(II) immunized mice in comparison to F1-LcrV. Both F1-LcrV and F1-LcrV-HSP70(II) provided 100% protection. Our research findings suggest that F1-LcrV fused with HSP70 domain II of M. tuberculosis significantly enhanced the humoral and cellular immune responses in mouse model.

Guidelines for the Development and Implementation of a Logistic Resource Annex to the Five Year Defense Program. Volume 2. A Logistic Resource Annex for the Navy DNFYP

DTIC Science & Technology

1978-10-01

Force , Navy and Marine Corps. Coverage is less comprehensive on the Army because of work on this topic by the General Research Corporation. Volume I...presents recommendations on an OSD-level LRA data system. Volumes II, III, and IV cQver the Navy, Air Force , and Marine Corps respectively. Each of these...Resource Model/ Force Level Analysis Interactive Language System NAVAIR Naval Air Systems Command NAVCOMPT Navy Comptroller NAVFAC Naval Facilities

Control mechanisms in the third-generation planning. Case study: Control to realize sustainable cities

NASA Astrophysics Data System (ADS)

Wicaksono, A. D.

2017-06-01

Since the last few years, Indonesia has experienced important events that bring significant changes to the social, political and economic life. The changes directly or indirectly impact the field of planning. With the challenging condition which grows fast and is more complex ahead, and the greater demands on the role of planning, it is required that planning should have higher quality. This paper seeks to answer some questions as follows: (i) How are changes in paradigm and also the development of planning model for the current transition era?, (ii) What is the best way to improve the quality of planning control on the last generation planning model to realize sustainable city?. Analysis steps that will be used to achieve the paper objectives are: (i) Review of planning and sustainable cities theory, (ii) Pattern recognition, (iii) Identifying control mechanisms and sustainable urban forms, (iv) conceptualization. Based on discussion about sustainable cities and control mechanism, some conclusions can be generated as follows: (i) The third generation planning model is based on the theory of expanded system, emphasizing on the constraint of capacity and the ability of planners within the context of larger environment, (ii) There are various theoretical studies that recommend prescriptive model or solution for sustainable urban form and structure. The concepts of Sustainable Cities can be grouped in Neotraditional Development, Urban Containment, Compact City and The Eco-City. The four models above have criteria, namely (i) high density; (ii) a high level of diversity; (iii) mixed land use; (iv) compactness; (5) sustainable transport; (6) passive solar design; (7) Greening Ecological Design. The three main activities in control mechanisms are: Monitoring and Recommendation; a comparative review of the facts (conditions that exist or are developing) with the purpose (expected conditions, set out in urban planning) and recommendations; Evaluation, a review on the intended purposes and can be followed up with revised purposes; Intervention/Actions toward existing conditions.

Development and characterization of an effective food allergy model in Brown Norway rats.

PubMed

Abril-Gil, Mar; Garcia-Just, Alba; Pérez-Cano, Francisco J; Franch, Àngels; Castell, Margarida

2015-01-01

Food allergy (FA) is an adverse health effect produced by the exposure to a given food. Currently, there is no optimal animal model of FA for the screening of immunotherapies or for testing the allergenicity of new foods. The aim of the present study was to develop an effective and rapid model of FA in Brown Norway rats. In order to establish biomarkers of FA in rat, we compared the immune response and the anaphylactic shock obtained in this model with those achieved with only intraperitoneal immunization. Rats received an intraperitoneal injection of ovalbumin (OVA) with alum and toxin from Bordetella pertussis, and 14 days later, OVA by oral route daily for three weeks (FA group). A group of rats receiving only the i.p. injection (IP group) were also tested. Serum anti-OVA IgE, IgG1, IgG2a, IgG2b and IgA antibodies were quantified throughout the study. After an oral challenge, body temperature, intestinal permeability, motor activity, and mast cell protease II (RMCP-II) levels were determined. At the end of the study, anti-OVA intestinal IgA, spleen cytokine production, lymphocyte composition of Peyer's patches and mesenteric lymph nodes, and gene expression in the small intestine were quantified. Serum OVA-specific IgG1, IgG2a and IgG2b concentrations rose with the i.p. immunization but were highly augmented after the oral OVA administration. Anti-OVA IgE increased twofold during the first week of oral OVA gavage. The anaphylaxis in both IP and FA groups decreased body temperature and motor activity, whereas intestinal permeability increased. Interestingly, the FA group showed a much higher RMCP II serum protein and intestinal mRNA expression. These results show both an effective and relatively rapid model of FA assessed by means of specific antibody titres and the high production of RMCP-II and its intestinal gene expression.

Development and Characterization of an Effective Food Allergy Model in Brown Norway Rats

PubMed Central

Abril-Gil, Mar; Garcia-Just, Alba; Pérez-Cano, Francisco J.; Franch, Àngels; Castell, Margarida

2015-01-01

Background Food allergy (FA) is an adverse health effect produced by the exposure to a given food. Currently, there is no optimal animal model of FA for the screening of immunotherapies or for testing the allergenicity of new foods. Objective The aim of the present study was to develop an effective and rapid model of FA in Brown Norway rats. In order to establish biomarkers of FA in rat, we compared the immune response and the anaphylactic shock obtained in this model with those achieved with only intraperitoneal immunization. Methods Rats received an intraperitoneal injection of ovalbumin (OVA) with alum and toxin from Bordetella pertussis, and 14 days later, OVA by oral route daily for three weeks (FA group). A group of rats receiving only the i.p. injection (IP group) were also tested. Serum anti-OVA IgE, IgG1, IgG2a, IgG2b and IgA antibodies were quantified throughout the study. After an oral challenge, body temperature, intestinal permeability, motor activity, and mast cell protease II (RMCP-II) levels were determined. At the end of the study, anti-OVA intestinal IgA, spleen cytokine production, lymphocyte composition of Peyer’s patches and mesenteric lymph nodes, and gene expression in the small intestine were quantified. Results Serum OVA-specific IgG1, IgG2a and IgG2b concentrations rose with the i.p. immunization but were highly augmented after the oral OVA administration. Anti-OVA IgE increased twofold during the first week of oral OVA gavage. The anaphylaxis in both IP and FA groups decreased body temperature and motor activity, whereas intestinal permeability increased. Interestingly, the FA group showed a much higher RMCP II serum protein and intestinal mRNA expression. Conclusions These results show both an effective and relatively rapid model of FA assessed by means of specific antibody titres and the high production of RMCP-II and its intestinal gene expression. PMID:25923134

A Liver-Centric Multiscale Modeling Framework for Xenobiotics.

PubMed

Sluka, James P; Fu, Xiao; Swat, Maciej; Belmonte, Julio M; Cosmanescu, Alin; Clendenon, Sherry G; Wambaugh, John F; Glazier, James A

2016-01-01

We describe a multi-scale, liver-centric in silico modeling framework for acetaminophen pharmacology and metabolism. We focus on a computational model to characterize whole body uptake and clearance, liver transport and phase I and phase II metabolism. We do this by incorporating sub-models that span three scales; Physiologically Based Pharmacokinetic (PBPK) modeling of acetaminophen uptake and distribution at the whole body level, cell and blood flow modeling at the tissue/organ level and metabolism at the sub-cellular level. We have used standard modeling modalities at each of the three scales. In particular, we have used the Systems Biology Markup Language (SBML) to create both the whole-body and sub-cellular scales. Our modeling approach allows us to run the individual sub-models separately and allows us to easily exchange models at a particular scale without the need to extensively rework the sub-models at other scales. In addition, the use of SBML greatly facilitates the inclusion of biological annotations directly in the model code. The model was calibrated using human in vivo data for acetaminophen and its sulfate and glucuronate metabolites. We then carried out extensive parameter sensitivity studies including the pairwise interaction of parameters. We also simulated population variation of exposure and sensitivity to acetaminophen. Our modeling framework can be extended to the prediction of liver toxicity following acetaminophen overdose, or used as a general purpose pharmacokinetic model for xenobiotics.

A Liver-Centric Multiscale Modeling Framework for Xenobiotics

PubMed Central

Swat, Maciej; Cosmanescu, Alin; Clendenon, Sherry G.; Wambaugh, John F.; Glazier, James A.

2016-01-01

We describe a multi-scale, liver-centric in silico modeling framework for acetaminophen pharmacology and metabolism. We focus on a computational model to characterize whole body uptake and clearance, liver transport and phase I and phase II metabolism. We do this by incorporating sub-models that span three scales; Physiologically Based Pharmacokinetic (PBPK) modeling of acetaminophen uptake and distribution at the whole body level, cell and blood flow modeling at the tissue/organ level and metabolism at the sub-cellular level. We have used standard modeling modalities at each of the three scales. In particular, we have used the Systems Biology Markup Language (SBML) to create both the whole-body and sub-cellular scales. Our modeling approach allows us to run the individual sub-models separately and allows us to easily exchange models at a particular scale without the need to extensively rework the sub-models at other scales. In addition, the use of SBML greatly facilitates the inclusion of biological annotations directly in the model code. The model was calibrated using human in vivo data for acetaminophen and its sulfate and glucuronate metabolites. We then carried out extensive parameter sensitivity studies including the pairwise interaction of parameters. We also simulated population variation of exposure and sensitivity to acetaminophen. Our modeling framework can be extended to the prediction of liver toxicity following acetaminophen overdose, or used as a general purpose pharmacokinetic model for xenobiotics. PMID:27636091

Insertion/Deletion Polymorphisms and Serum Angiotensin-converting Enzyme Levels in Iranian Patients with Sarcoidosis

PubMed Central

JAVADI, Alireza; SHAMAEI, Masoud; ZAREI, Masoud; REZAEIAN, Lida; KIANI, Arda; ABEDINI, Atefeh

2016-01-01

Background: Sarcoidosis is a multisystem inflammatory disease of unknown origin with characterization of small granulomas. Angiotensin-converting enzyme (ACE) is a pathophysiologic marker of sarcoidosis. We present the ACE insertion/deletion (I/D) polymorphism in correlation with serum ACE level in Iranian patients with sarcoidosis. Methods: From Jan 2014 to Jan 2015, 102 Iranian patients who histopathologically diagnosed for sarcoidosis and 192 healthy age and sex-matched controls were recruited. PCR was used for detection of I/D polymorphism in ACE gene. Results: Frequency of II/ID/DD genotype in sarcoidosis disease was 17%, 35.5%, and 47.1%, respectively. The frequency of D allele was 0.65. A significant association between I/D genotypes and mean of sACE level was seen (DD=85.2±22.9, P<0.001). More frequent genotype in sarcoidosis patients was DD (47%), ID genotype (45.9%) was found more in controls. Logistic regression analysis adjusting age and sex showed that ID to II (OR=0.35, 95%CI=0.17–0.73, P=0.005) and DD to II (OR=2.11, 95%CI=0.98–4.54, P=0.05) could be considered as a predictor factor for the disease activity. No significant model for men in sarcoidosis group was seen, while women with II/ID were associated with a reduced risk for the disease. Conclusion: Although more regional studies with appropriate statistical scale must be done to provide a better diagnosis and prognostic tool for this disease, this study demonstrates that ID and DD genotype could be predictive factors for sarcoidosis. PMID:28032065

[Over-expression of BDNF inhibits angiotensin II-induced apoptosis of cardiomyocytes in SD rats].

PubMed

Cao, Jingli; Wu, Yingfeng; Liu, Geming; Li, Zhenlong

2018-03-01

Objective To investigate the role and molecular mechanism of brain-derived neurotrophic factor (BDNF) against the process of cardiomyocyte hypertrophy and apoptosis. Methods Cardiomyocyte hypertrophy were estabolished by angiotensin II (Ang II) in neonatal cardiomyocytes in vitro and incomplete ligature of abdominal aorta of SD rats in vivo. BDNF over-expressing recombinant vector pcDNA5-BDNF was transfected into cardiomyocytes by liposomes. Immunofluorescence staining was used to detect the effect of BDNF transfection on the surface area of myocardial cells. The effect of BDNF transfection on the apoptosis of cardiomyocytes was assayed by flow cytometry. Real-time fluorescent quantitative PCR was performed to detect the effect of over-expression of BDNF on the expressions of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) mRNAs in cardiomyocytes. Western blot assay was used to observe the changes of BDNF, ANP and BNP, calmodulin kinase 2 (CaMK2) and phosphorylated calmodulin kinase 2 (p-CaMK2), calcineurin (CaN), p-CaN, nuclear factor of activated T cells 3 (NFATC3) and p-NFATC3 protein expressions in the myocardial tissues and cardiomyocytes. Results The expression of BDNF protein increased significantly in cardiac hypertrophy animal and cell models in a time-dependent manner. Compared with the untransfected control cardiomyocytes, the surface area of cardiomyocytes, the rate of apoptosis, the levels of ANP and BNP mRNA and protein expression, the levels of p-CaMK2 and CaN protein in the BDNF over-expressed cardiomyocytes were remarkably reduced, while the level of p-NFATC3 protein rose significantly. Conclusion BDNF inhibits the apoptosis of cardiomyocytes induced by Ang II, and it plays the role by inhibiting CaMK2 and CaN signaling pathways.

Homology modeling, binding site identification and docking study of human angiotensin II type I (Ang II-AT1) receptor.

PubMed

Vyas, Vivek K; Ghate, Manjunath; Patel, Kinjal; Qureshi, Gulamnizami; Shah, Surmil

2015-08-01

Ang II-AT1 receptors play an important role in mediating virtually all of the physiological actions of Ang II. Several drugs (SARTANs) are available, which can block the AT1 receptor effectively and lower the blood pressure in the patients with hypertension. Currently, there is no experimental Ang II-AT1 structure available; therefore, in this study we modeled Ang II-AT1 receptor structure using homology modeling followed by identification and characterization of binding sites and thereby assessing druggability of the receptor. Homology models were constructed using MODELLER and I-TASSER server, refined and validated using PROCHECK in which 96.9% of 318 residues were present in the favoured regions of the Ramachandran plots. Various Ang II-AT1 receptor antagonist drugs are available in the market as antihypertensive drug, so we have performed docking study with the binding site prediction algorithms to predict different binding pockets on the modeled proteins. The identification of 3D structures and binding sites for various known drugs will guide us for the structure-based drug design of novel compounds as Ang II-AT1 receptor antagonists for the treatment of hypertension. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Functional Macroautophagy Induction by Influenza A Virus without a Contribution to Major Histocompatibility Complex Class II-Restricted Presentation▿†

PubMed Central

Comber, Joseph D.; Robinson, Tara M.; Siciliano, Nicholas A.; Snook, Adam E.; Eisenlohr, Laurence C.

2011-01-01

Major histocompatibility complex (MHC) class II-presented peptides can be derived from both exogenous (extracellular) and endogenous (biosynthesized) sources of antigen. Although several endogenous antigen-processing pathways have been reported, little is known about their relative contributions to global CD4+ T cell responses against complex antigens. Using influenza virus for this purpose, we assessed the role of macroautophagy, a process in which cytosolic proteins are delivered to the lysosome by de novo vesicle formation and membrane fusion. Influenza infection triggered productive macroautophagy, and autophagy-dependent presentation was readily observed with model antigens that naturally traffic to the autophagosome. Furthermore, treatments that enhance or inhibit macroautophagy modulated the level of presentation from these model antigens. However, validated enzyme-linked immunospot (ELISpot) assays of influenza-specific CD4+ T cells from infected mice using a variety of antigen-presenting cells, including primary dendritic cells, revealed no detectable macroautophagy-dependent component. In contrast, the contribution of proteasome-dependent endogenous antigen processing to the global influenza CD4+ response was readily appreciated. The contribution of macroautophagy to the MHC class II-restricted response may vary depending upon the pathogen. PMID:21525345