Flexibility of KorA, a plasmid-encoded, global transcription regulator, in the presence and the absence of its operator

PubMed Central

Rajasekar, Karthik V.; Lovering, Andrew L.; Dancea, Felician; Scott, David J.; Harris, Sarah A.; Bingle, Lewis E.H.; Roessle, Manfred; Thomas, Christopher M.; Hyde, Eva I.; White, Scott A.

2016-01-01

Abstract The IncP (Incompatibility group P) plasmids are important carriers in the spread of antibiotic resistance across Gram-negative bacteria. Gene expression in the IncP-1 plasmids is stringently controlled by a network of four global repressors, KorA, KorB, TrbA and KorC interacting cooperatively. Intriguingly, KorA and KorB can act as co-repressors at varying distances between their operators, even when they are moved to be on opposite sides of the DNA. KorA is a homodimer with the 101-amino acid subunits, folding into an N-terminal DNA-binding domain and a C-terminal dimerization domain. In this study, we have determined the structures of the free KorA repressor and two complexes each bound to a 20-bp palindromic DNA duplex containing its consensus operator sequence. Using a combination of X-ray crystallography, nuclear magnetic resonance spectroscopy, SAXS and molecular dynamics calculations, we show that the linker between the two domains is very flexible and the protein remains highly mobile in the presence of DNA. This flexibility allows the DNA-binding domains of the dimer to straddle the operator DNA on binding and is likely to be important in cooperative binding to KorB. Unexpectedly, the C-terminal domain of KorA is structurally similar to the dimerization domain of the tumour suppressor p53. PMID:27016739

Prediabetes is associated with microalbuminuria, reduced kidney function and chronic kidney disease in the general population: The KORA (Cooperative Health Research in the Augsburg Region) F4-Study.

PubMed

Markus, M R P; Ittermann, T; Baumeister, S E; Huth, C; Thorand, B; Herder, C; Roden, M; Siewert-Markus, U; Rathmann, W; Koenig, W; Dörr, M; Völzke, H; Schipf, S; Meisinger, C

2018-03-01

We investigated the associations of serum fasting (FG) and 2-h postload (2HG) glucose from an oral glucose tolerance test (OGTT), glycated hemoglobin (HbA1c), fasting insulin and the homeostasis model assessment-insulin resistance index (HOMA-IR) with urinary albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). We performed cross-sectional analyses of 2713 subjects (1429 women; 52.7%) without known type 2 diabetes, aged 31-82 years, from the KORA (Cooperative Health Research in the Augsburg Region) F4-Study. FG, 2HG, HbA1c, fasting insulin, HOMA-IR and glucose tolerance categories were analyzed for association with ACR and eGFR in multivariable adjusted linear and median regression models, and with isolated microalbuminuria (i-MA), isolated reduced kidney function (i-RKF) and chronic kidney disease (CKD, defined as MA and/or RKF) in multivariable adjusted logistic regression models. Among the 2713 study participants, 28% revealed prediabetes (isolated impaired fasting glucose [i-IFG], isolated glucose tolerance [i-IGT] or both by American Diabetes Association definition), 4.2% had unknown type 2 diabetes, 6.5% had i-MA, 3.1% i-RKF and 10.9% CKD. In multivariable adjusted analysis, all continuous variables (FG, 2HG, HbA1c, fasting insulin and HOMA-IR) were associated with i-MA, i-RKF and CKD. The odds ratios (ORs) for i-MA and CKD were 1.54 (95% confidence interval: 1.02-2.33) and 1.58 (1.10-2.25) for individuals with i-IFG. Moreover, the OR for i-RKF was 2.57 (1.31-5.06) for individuals with IFG + IGT. Our findings suggest that prediabetes might have harmful effects on the kidney. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Association of generic health-related quality of life (EQ-5D dimensions) and inactivity with lung function in lung-healthy German adults: results from the KORA studies F4L and Age.

PubMed

Luzak, Agnes; Karrasch, Stefan; Wacker, Margarethe; Thorand, Barbara; Nowak, Dennis; Peters, Annette; Schulz, Holger

2018-03-01

Among patients with lung disease, decreased lung function is associated with lower health-related quality of life. However, whether this association is detectable within the physiological variability of respiratory function in lung-healthy populations is unknown. We analyzed the association of each EQ-5D-3L dimension (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and self-reported physical inactivity with spirometric indices in lung-healthy adults. Modulating effects between inactivity and EQ-5D dimensions were considered. 1132 non-smoking, apparently lung-healthy participants (48% male, aged 64 ± 12 years) from the population-based KORA F4L and Age surveys in Southern Germany were analyzed. Associations of each EQ-5D dimension and inactivity with spirometric indices serving as outcomes (forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC), FEV 1 /FVC, and mid-expiratory flow) were examined by linear regression, considering possible confounders. Interactions between EQ-5D dimensions (no problems/any problems) and inactivity (four categories of time spent engaging in exercise: inactive to most active) were assessed. Among all participants 42% reported no problems in any EQ-5D dimension, 24% were inactive and 32% exercised > 2 h/week. After adjustment, FEV 1 was - 99 ml (95% CI - 166; - 32) and FVC was - 109 ml (95% CI - 195; - 24) lower among subjects with mobility problems. Comparable estimates were observed for usual activities. Inactivity was negatively associated with FVC (β-coefficient: - 83 ml, 95% CI - 166; 0), but showed no interactions with EQ-5D. Problems with mobility or usual activities, and inactivity were associated with slightly lower spirometric parameters in lung-healthy adults, suggesting a relationship between perceived physical functioning and volumetric lung function.

Intrinsic disorder in the partitioning protein KorB persists after co-operative complex formation with operator DNA and KorA.

PubMed

Hyde, Eva I; Callow, Philip; Rajasekar, Karthik V; Timmins, Peter; Patel, Trushar R; Siligardi, Giuliano; Hussain, Rohanah; White, Scott A; Thomas, Christopher M; Scott, David J

2017-08-30

The ParB protein, KorB, from the RK2 plasmid is required for DNA partitioning and transcriptional repression. It acts co-operatively with other proteins, including the repressor KorA. Like many multifunctional proteins, KorB contains regions of intrinsically disordered structure, existing in a large ensemble of interconverting conformations. Using NMR spectroscopy, circular dichroism and small-angle neutron scattering, we studied KorB selectively within its binary complexes with KorA and DNA, and within the ternary KorA/KorB/DNA complex. The bound KorB protein remains disordered with a mobile C-terminal domain and no changes in the secondary structure, but increases in the radius of gyration on complex formation. Comparison of wild-type KorB with an N-terminal deletion mutant allows a model of the ensemble average distances between the domains when bound to DNA. We propose that the positive co-operativity between KorB, KorA and DNA results from conformational restriction of KorB on binding each partner, while maintaining disorder. © 2017 The Author(s).

Quality of Diabetes Care in Germany Improved from 2000 to 2007 to 2014, but Improvements Diminished since 2007. Evidence from the Population-Based KORA Studies

PubMed Central

Knoll, Gabriella; Schunk, Michaela; Meisinger, Christa; Huth, Cornelia; Holle, Rolf

2016-01-01

Objective Little is known about the development of the quality of diabetes care in Germany. The aim of this study is to analyze time trends in patient self-management, physician-delivered care, medication, risk factor control, complications and quality of life from 2000 to 2014. Methods Analyses are based on data from individuals with type 2 diabetes of the population-based KORA S4 (1999–2001, n = 150), F4 (2006–2008, n = 203), FF4 (2013/14, n = 212) cohort study. Information on patient self-management, physician-delivered care, medication, risk factor control and quality of life were assessed in standardized questionnaires and examinations. The 10-year coronary heart disease (CHD) risk was calculated using the UKPDS risk engine. Time trends were analyzed using multivariable linear and logistic regression models adjusted for age, sex, education, diabetes duration, and history of cardiovascular disease. Results From 2000 to 2014 the proportion of participants with type 2 diabetes receiving oral antidiabetic/cardio-protective medication and of those reaching treatment goals for glycemic control (HbA1c<7%, 60% to 71%, p = 0.09), blood pressure (<140/80 mmHg, 25% to 69%, p<0.001) and LDL cholesterol (<2.6 mmol/l, 13% to 27%, p<0.001) increased significantly. However, improvements were generally smaller from 2007 to 2014 than from 2000 to 2007. Modeled 10-year CHD risk decreased from 30% in 2000 to 24% in 2007 to 19% in 2014 (p<0.01). From 2007 to 2014, the prevalence of microvascular complications decreased and quality of life increased, but no improvements were observed for the majority of indicators of self-management. Conclusion Despite improvements, medication and risk factor control has remained suboptimal. The flattening of improvements and deteriorations in quality of (self-) care since 2007 indicate that more effort is needed to improve quality of care and patient self-management. Due to selection or lead time bias an overestimation of quality of care improvements cannot be ruled out. PMID:27749939

Update of the German Diabetes Risk Score and external validation in the German MONICA/KORA study.

PubMed

Mühlenbruch, Kristin; Ludwig, Tonia; Jeppesen, Charlotte; Joost, Hans-Georg; Rathmann, Wolfgang; Meisinger, Christine; Peters, Annette; Boeing, Heiner; Thorand, Barbara; Schulze, Matthias B

2014-06-01

Several published diabetes prediction models include information about family history of diabetes. The aim of this study was to extend the previously developed German Diabetes Risk Score (GDRS) with family history of diabetes and to validate the updated GDRS in the Multinational MONItoring of trends and determinants in CArdiovascular Diseases (MONICA)/German Cooperative Health Research in the Region of Augsburg (KORA) study. We used data from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study for extending the GDRS, including 21,846 participants. Within 5 years of follow-up 492 participants developed diabetes. The definition of family history included information about the father, the mother and/or sibling/s. Model extension was evaluated by discrimination and reclassification. We updated the calculation of the score and absolute risks. External validation was performed in the MONICA/KORA study comprising 11,940 participants with 315 incident cases after 5 years of follow-up. The basic ROC-AUC of 0.856 (95%-CI: 0.842-0.870) was improved by 0.007 (0.003-0.011) when parent and sibling history was included in the GDRS. The net reclassification improvement was 0.110 (0.072-0.149), respectively. For the updated score we demonstrated good calibration across all tenths of risk. In MONICA/KORA, the ROC-AUC was 0.837 (0.819-0.855); regarding calibration we saw slight overestimation of absolute risks. Inclusion of the number of diabetes-affected parents and sibling history improved the prediction of type 2 diabetes. Therefore, we updated the GDRS algorithm accordingly. Validation in another German cohort study showed good discrimination and acceptable calibration for the vast majority of individuals. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Sensitivity Analysis of Weather Variables on Offsite Consequence Analysis Tools in South Korea and the United States.

PubMed

Kim, Min-Uk; Moon, Kyong Whan; Sohn, Jong-Ryeul; Byeon, Sang-Hoon

2018-05-18

We studied sensitive weather variables for consequence analysis, in the case of chemical leaks on the user side of offsite consequence analysis (OCA) tools. We used OCA tools Korea Offsite Risk Assessment (KORA) and Areal Location of Hazardous Atmospheres (ALOHA) in South Korea and the United States, respectively. The chemicals used for this analysis were 28% ammonia (NH₃), 35% hydrogen chloride (HCl), 50% hydrofluoric acid (HF), and 69% nitric acid (HNO₃). The accident scenarios were based on leakage accidents in storage tanks. The weather variables were air temperature, wind speed, humidity, and atmospheric stability. Sensitivity analysis was performed using the Statistical Package for the Social Sciences (SPSS) program for dummy regression analysis. Sensitivity analysis showed that impact distance was not sensitive to humidity. Impact distance was most sensitive to atmospheric stability, and was also more sensitive to air temperature than wind speed, according to both the KORA and ALOHA tools. Moreover, the weather variables were more sensitive in rural conditions than in urban conditions, with the ALOHA tool being more influenced by weather variables than the KORA tool. Therefore, if using the ALOHA tool instead of the KORA tool in rural conditions, users should be careful not to cause any differences in impact distance due to input errors of weather variables, with the most sensitive one being atmospheric stability.

Diagnostic utility of a one-item question to screen for depressive disorders: results from the KORA F3 study.

PubMed

Blozik, Eva; Scherer, Martin; Lacruz, Maria E; Ladwig, Karl-Heinz

2013-12-23

Screening for depressive disorders in the general adult population is recommended, however, it is unclear which instruments combine user friendliness and diagnostic utility. We evaluated the test performance of a yes/no single item screener for depressive disorders ("Have you felt depressed or sad much of the time in the past year?") in comparison to the depressive disorder module of the Patient Health Questionnaire (PHQ-9). Data from 3184 participants of the population-based KORA F3 survey in Augsburg/ Germany were used to analyse sensitivity, specificity, ROC area, positive likelihood ratio (LR+), negative likelihood ratio (LR-), positive predictive value (PPV), and negative predictive value (NPV) of the single item screener in comparison with "depressive mood" and "major depressive disorder" defined according to PHQ-9 (both interviewer-administered versions). In comparison to PHQ-9 "depressive mood", sensitivity was low (46%) with an excellent specificity (94%), (PPV 76%; NPV 82%; LR + 8.04; LR- .572, ROC area .702). When using the more conservative definition for "major depressive disorder", sensitivity increased to 83% with a specificity of 88%. The PPV under the conservative definition was low (32%), but NPV was 99% (LR + 6.65; LR- .196; ROC area .852). Results varied across age groups and between males and females. The single item screener is able to moderately decrease post-test probability of major depressive disorders and to identify populations that should undergo additional, more detailed evaluation for depression. It may have limited utility in combination with additional screening tests or for selection of at-risk populations, but cannot be recommended for routine use as a screening tool in clinical practice.

Diagnostic utility of a one-item question to screen for depressive disorders: results from the KORA F3 study

PubMed Central

2013-01-01

Background Screening for depressive disorders in the general adult population is recommended, however, it is unclear which instruments combine user friendliness and diagnostic utility. We evaluated the test performance of a yes/no single item screener for depressive disorders (“Have you felt depressed or sad much of the time in the past year?”) in comparison to the depressive disorder module of the Patient Health Questionnaire (PHQ-9). Methods Data from 3184 participants of the population-based KORA F3 survey in Augsburg/ Germany were used to analyse sensitivity, specificity, ROC area, positive likelihood ratio (LR+), negative likelihood ratio (LR-), positive predictive value (PPV), and negative predictive value (NPV) of the single item screener in comparison with “depressive mood” and “major depressive disorder” defined according to PHQ-9 (both interviewer-administered versions). Results In comparison to PHQ-9 “depressive mood”, sensitivity was low (46%) with an excellent specificity (94%), (PPV 76%; NPV 82%; LR + 8.04; LR- .572, ROC area .702). When using the more conservative definition for “major depressive disorder”, sensitivity increased to 83% with a specificity of 88%. The PPV under the conservative definition was low (32%), but NPV was 99% (LR + 6.65; LR- .196; ROC area .852). Results varied across age groups and between males and females. Conclusions The single item screener is able to moderately decrease post-test probability of major depressive disorders and to identify populations that should undergo additional, more detailed evaluation for depression. It may have limited utility in combination with additional screening tests or for selection of at-risk populations, but cannot be recommended for routine use as a screening tool in clinical practice. PMID:24359193

Using the Lagrangian Method to Track Trajectories of Fog And Mist in the Monterey Bay

DTIC Science & Technology

2017-12-01

inversions (Koračin et al. 2014). During these extensive research experiments (Pilié et al. 1979) the role of the Eastern Pacific High was the...the inversion , which then lifts and eventually erodes the marine layer (Koračin et al. 2005). 22 Figure 13. Trajectories from a thermal low lead... inversion characteristics support fog and stratus conditions. Figure 20. Annotation of “L” for June 1, which classifies “Local” wind conditions

Official statistics and claims data records indicate non-response and recall bias within survey-based estimates of health care utilization in the older population

PubMed Central

2013-01-01

Background The validity of survey-based health care utilization estimates in the older population has been poorly researched. Owing to data protection legislation and a great number of different health care insurance providers, the assessment of recall and non-response bias is challenging to impossible in many countries. The objective of our study was to compare estimates from a population-based study in older German adults with external secondary data. Methods We used data from the German KORA-Age study, which included 4,127 people aged 65–94 years. Self-report questions covered the utilization of long-term care services, inpatient services, outpatient services, and pharmaceuticals. We calculated age- and sex-standardized mean utilization rates in each domain and compared them with the corresponding estimates derived from official statistics and independent statutory health insurance data. Results The KORA-Age study underestimated the use of long-term care services (−52%), in-hospital days (−21%) and physician visits (−70%). In contrast, the assessment of drug consumption by postal self-report questionnaires yielded similar estimates to the analysis of insurance claims data (−9%). Conclusion Survey estimates based on self-report tend to underestimate true health care utilization in the older population. Direct validation studies are needed to disentangle the impact of recall and non-response bias. PMID:23286781

Subclinical Disease Burden as Assessed by Whole-Body MRI in Subjects With Prediabetes, Subjects With Diabetes, and Normal Control Subjects From the General Population: The KORA-MRI Study.

PubMed

Bamberg, Fabian; Hetterich, Holger; Rospleszcz, Susanne; Lorbeer, Roberto; Auweter, Sigrid D; Schlett, Christopher L; Schafnitzel, Anina; Bayerl, Christian; Schindler, Andreas; Saam, Tobias; Müller-Peltzer, Katharina; Sommer, Wieland; Zitzelsberger, Tanja; Machann, Jürgen; Ingrisch, Michael; Selder, Sonja; Rathmann, Wolfgang; Heier, Margit; Linkohr, Birgit; Meisinger, Christa; Weber, Christian; Ertl-Wagner, Birgit; Massberg, Steffen; Reiser, Maximilian F; Peters, Annette

2017-01-01

Detailed pathophysiological manifestations of early disease in the context of prediabetes are poorly understood. This study aimed to evaluate the extent of early signs of metabolic and cardio-cerebrovascular complications affecting multiple organs in individuals with prediabetes. Subjects without a history of stroke, coronary artery disease, or peripheral artery disease were enrolled in a case-control study nested within the Cooperative Health Research in the Region of Augsburg (KORA) FF4 cohort and underwent comprehensive MRI assessment to characterize cerebral parameters (white matter lesions, microbleeds), cardiovascular parameters (carotid plaque, left ventricular function, and myocardial late gadolinium enhancement [LGE]), and metabolic parameters (hepatic proton-density fat fraction [PDFF] and subcutaneous and visceral abdominal fat). Among 400 subjects who underwent MRI, 103 subjects had prediabetes and 54 had established diabetes. Subjects with prediabetes had an increased risk for carotid plaque and adverse functional cardiac parameters, including reduced early diastolic filling rates as well as a higher prevalence of LGE compared with healthy control subjects. In addition, people with prediabetes had significantly elevated levels of PDFF and total and visceral fat. Thus, subjects with prediabetes show early signs of subclinical disease that include vascular, cardiac, and metabolic changes, as measured by whole-body MRI after adjusting for cardiometabolic risk factors. © 2017 by the American Diabetes Association.

Feasibility, internal consistency and covariates of TICS-m (telephone interview for cognitive status-modified) in a population-based sample: findings from the KORA-Age study.

PubMed

Lacruz, Me; Emeny, Rt; Bickel, H; Linkohr, B; Ladwig, Kh

2013-09-01

Test the feasibility of the modified telephone interview for cognitive status (TICS-m) as a screening tool to detect cognitive impairment in a population-based sample of older subjects. Data were collected from 3,578 participants, age 65-94 years, of the KORA-Age study. We used analysis of covariance to test for significant sex, age and educational differences in raw TICS-m scores. Internal consistency was analysed by assessing Cronbach's alpha. Correction for education years was undertaken, and participants were divided in three subgroups following validated cut-offs. Finally, a logistic regression was performed to determine the impact of sex on cognition subgroups. Internal consistency of the TICS-m was 0.78. Study participants needed approximately 5.4 min to complete the interview. Lower raw TICS-m scores were associated with male sex, older age and lower education (all p < 0.0001). After correction for education years, 2,851 (79%) had a non-impaired cognitive status (score >31). Male sex was independently associated with having a score equal to or below 27 and 31 (OR = 1.9, 95% CI 1.4-2.5 and OR = 1.5, 95% CI 1.2-1.7, respectively). The TICS-m is a feasible questionnaire for community-dwelling older adults with normal cognitive function or moderate cognitive impairment. Lower cognitive performance was associated with being a man, being older, and having fewer years of formal education. Copyright © 2012 John Wiley & Sons, Ltd.

Hypertension in Germany.

PubMed

Neuhauser, Hannelore; Diederichs, Claudia; Boeing, Heiner; Felix, Stephan B; Jünger, Claus; Lorbeer, Roberto; Meisinger, Christine; Peters, Annette; Völzke, Henry; Weikert, Cornelia; Wild, Philipp; Dörr, Marcus

2016-12-02

Hypertension is a key risk factor. However, population data based on blood pressure measurements in Germany are scarce. Standardized blood pressure (BP) measurements and medication data from seven population-based studies conducted in Germany between 1994 and 2012 (66 845 participants, 25-74 years) were analyzed: the EPICPotsdam study (1994-1998, EPIC), the KORA-S4 Study (1999-2001) in Augsburg, and the Gutenberg Health Study (2007-2012, GHS) in Mainz/Mainz-Bingen provided data for descriptive comparisons. Time trends were analyzed based on identical study regions for the German National Health Interview and Examination Survey 1998 (BGS98) and the German Health Examination Survey for Adults (2008-11, DEGS1) as well as the Study of Health in Pomerania (SHIP) in Northeast Germany (1997-2001) and the SHIP-TREND study (2008-2012). BP data were adjusted for study-specific measurement devices based on calibration studies. After adjustment for study-specific measurement devices, mean systolic and diastolic BP values were lower and treatment proportions higher in recent (2007-2012) compared to older (1994-2001) studies. Mean BP decrease was most pronounced (systolic ≥ 10 mmHg) in the elderly (55-74 years). The regional SHIP-TREND data for Northeast Germany showed a decrease in mean systolic BP in young men aged 25 to 34 years; on a national level according to the DEGS1 data, however, no such decrease was observed for this group. New data add evidence for lower BP in Germany. However, the prevention potential remains high. Future research based on population-based data should place a special focus on blood pressure data in young men.

Will peripherally restricted kappa-opioid receptor agonists (pKORAs) relieve pain with less opioid adverse effects and abuse potential?

PubMed

Albert-Vartanian, A; Boyd, M R; Hall, A L; Morgado, S J; Nguyen, E; Nguyen, V P H; Patel, S P; Russo, L J; Shao, A J; Raffa, R B

2016-08-01

Optimal utilization of opioid analgesics is significantly limited by the central nervous system adverse effects and misuse/abuse potential of currently available drugs. It has been postulated that opioid-associated adverse effects and abuse potential would be greatly reduced if opioids could be excluded from reaching the brain. We review the basic science and clinical evidence of one such approach - peripherally restricted kappa-opioid receptor (KOR) agonists (pKORAs). Published and unpublished literature, websites and other sources were searched for basic science and clinical information related to the potential benefits and development of peripherally restricted kappa-opioid receptor agonists. Each source was summarized, reviewed and assessed. The historical development of pKORAs can be traced from the design of increasingly KOR-selective agonists, elucidation of the pharmacologic attributes of such compounds and strategies to restrict passage across the blood-brain barrier. Novel compounds are under development and have progressed to clinical trials. The results from recent clinical trials suggest that peripherally restricted opioids can be successfully designed and that they can retain analgesic efficacy with a more favourable adverse effect profile. © 2016 John Wiley & Sons Ltd.

Perceived risk of diabetes seriously underestimates actual diabetes risk: The KORA FF4 study

PubMed Central

Stang, Andreas; Bongaerts, Brenda; Kuss, Oliver; Herder, Christian; Roden, Michael; Quante, Anne; Holle, Rolf; Huth, Cornelia; Peters, Annette; Meisinger, Christa

2017-01-01

Objective Early detection of diabetes and prediabetic states is beneficial for patients, but may be delayed by patients´ being overly optimistic about their own health. Therefore, we assessed how persons without known diabetes perceive their risk of having or developing diabetes, and we identified factors associated with perception of diabetes risk. Research design and methods 1,953 participants without previously known diabetes from the population-based, German KORA FF4 Study (59.1 years, 47.8% men) had an oral glucose tolerance test. They estimated their probability of having undiagnosed diabetes mellitus (UDM) on a six category scale, and assessed whether they were at risk of developing diabetes in the future. We cross-tabulated glycemic status with risk perception, and fitted robust Poisson regression models to identify determinants of diabetes risk perception. Results 74% (95% CI: 65–82) of persons with UDM believed that their probability of having undetected diabetes was low or very low. 72% (95% CI: 69–75) of persons with prediabetes believed that they were not at risk of developing diabetes. In people with prediabetes, seeing oneself at risk of diabetes was associated with self-rated poor general health (prevalence ratio (PR) = 3.1 (95% CI: 1.4–6.8), parental diabetes (PR = 2.6, 1.9–3.4), high educational level (PR = 1.9 (1.4–2.5)), lower age (PR = 0.7, 0.6–0.8, per 1 standard deviation increase), female sex (PR = 1.2, 0.9–1.5) and obesity (PR = 1.5, 1.2–2.0). Conclusions People with undiagnosed diabetes or prediabetes considerably underestimate their probability of having or developing diabetes. Contrary to associations with actual diabetes risk, perceived diabetes risk was lower in men, lower educated and older persons. PMID:28141837

Association of daily tar and nicotine intake with incident myocardial infarction: Results from the population-based MONICA/KORA Augsburg Cohort Study 1984 - 2002

PubMed Central

2011-01-01

Background Cigarette smoking has been shown to be one of the most important risk factors for cardiovascular diseases. However, little is known about cumulative effects of daily tar and nicotine intake on the risk of incident myocardial infarction (MI) so far. To bridge this gap, we conducted an analysis in a large prospective study from Southern Germany investigating associations of daily tar and nicotine intake with an incident MI event. Methods The study was based on 4,099 men and 4,197 women participating in two population-based MONICA Augsburg surveys between 1984 and 1990 and followed up within the KORA framework until 2002. During a mean follow-up of 13.3 years, a number of 307 men and 80 women developed an incident MI event. Relative risks were calculated as hazard ratios (HRs) estimated by Cox proportional hazards models adjusted for cardiovascular risk factors. Results In the present study, male regular smokers consumed on average more cigarettes per day than female regular smokers (20 versus 15) and had a higher tar and nicotine intake per day. In men, the MI risk compared to never-smokers increased with higher tar intake: HRs were 2.24 (95% CI 1.40-3.56) for 1-129 mg/day, 2.12 (95% CI 1.37-3.29) for 130-259 mg/day and 3.01 (95% CI 2.08-4.36) for ≥ 260 mg/day. In women, the corresponding associations were comparable but more pronounced for high tar intake (HR 4.67, 95% CI 1.76-12.40). Similar associations were observed for nicotine intake. Conclusions The present study based on a large population-based sample adds important evidence of cumulative effects of tar and nicotine intake on the risk of incident MI. Even low or medium tar and nicotine intake revealed substantial risk increases as compared to never-smokers. Therefore, reduction of tar and nicotine contents in cigarettes cannot be seen as a suitable public health policy in preventing myocardial infarction. PMID:21542909

Comparison of traditional diabetes risk scores and HbA1c to predict type 2 diabetes mellitus in a population based cohort study.

PubMed

Krabbe, Christine Emma Maria; Schipf, Sabine; Ittermann, Till; Dörr, Marcus; Nauck, Matthias; Chenot, Jean-François; Markus, Marcello Ricardo Paulista; Völzke, Henry

2017-11-01

Compare performances of diabetes risk scores and glycated hemoglobin (HbA1c) to estimate the risk of incident type 2 diabetes mellitus (T2DM) in Northeast Germany. We studied 2916 subjects (20 to 81years) from the Study of Health in Pomerania (SHIP) in a 5-year follow-up period. Diabetes risk scores included the Cooperative Health Research in the Region of Augsburg (KORA) base model, the Danish diabetes risk score and the Data from the Epidemiological Study on the Insulin Resistance syndrome (D.E.S.I.R) clinical risk score. We assessed the performance of each of the diabetes risk scores and the HbA1c for 5-year risk of T2DM by the area under the receiver-operating characteristic curve (AUC) and calibration plots. In SHIP, the incidence of T2DM was 5.4% (n=157) in the 5-year follow-up period. Diabetes risk scores and HbA1c achieved AUCs ranging from 0.76 for the D.E.S.I.R. clinical risk score to 0.82 for the KORA base model. For diabetes risk scores, the discriminative ability was lower for the age group 55 to 74years. For HbA1c, the discriminative ability also decreased for the group 55 to 74years while it was stable in the age group 30 to 64years old. All diabetes risk scores and the HbA1c showed a good prediction for the risk of T2DM in SHIP. Which model or biomarker should be used is driven by its context of use, e.g. the practicability, implementation of interventions and availability of measurement. Copyright © 2017 Elsevier Inc. All rights reserved.

FTO Is Associated with Aortic Valve Stenosis in a Gender Specific Manner of Heterozygote Advantage: A Population-Based Case-Control Study.

PubMed

Thron, Cindy; Akhyari, Payam; Godehardt, Erhard; Lichtenberg, Artur; Rüther, Ulrich; Seehaus, Stefanie

2015-01-01

Single nucleotide polymorphisms (SNPs) within the Fat mass and obesity associated (FTO) gene have been linked with increased body weight. However, the data on an association of FTO with cardiovascular diseases remains conflicting. Therefore, we ascertained whether FTO is associated with aortic valve stenosis (AVS), one of the most frequent cardiovascular diseases in the Western world. In this population-based case-control study the FTO SNP rs9939609 was analyzed in 300 German patients with AVS and 429 German controls of the KORA survey S4, representing a random population. Blood samples were collected prior to aortic valve replacement in AVS cases and FTO rs9939609 was genotyped via ARMS-PCR. Genotype frequencies differed significantly between AVS cases and KORA controls (p = 0.004). Separate gender-analyses uncovered an association of FTO with AVS exclusively in males; homozygote carriers for the risk-allele (A) had a higher risk to develop AVS (p = 0.017, odds ratio (OR) 1.727; 95% confidence interval (CI) 1.087-2.747, recessive model), whereas heterozygote carriers for the risk-allele showed a lower risk (p = 0.002, OR 0.565, 95% CI 0.384-0.828, overdominant model). After adjustment for multiple co-variables, the odds ratios of heterozygotes remained significant for an association with AVS (p = 0.008, OR 0.565, 95% CI 0.369-0.861). This study revealed an association of FTO rs9939609 with AVS. Furthermore, this association was restricted to men, with heterozygotes having a significantly lower chance to develop AVS. Lastly, the association between FTO and AVS was independent of BMI and other variables such as diabetes mellitus.

FTO Is Associated with Aortic Valve Stenosis in a Gender Specific Manner of Heterozygote Advantage: A Population-Based Case-Control Study

PubMed Central

Thron, Cindy; Akhyari, Payam; Godehardt, Erhard; Lichtenberg, Artur; Rüther, Ulrich; Seehaus, Stefanie

2015-01-01

Background Single nucleotide polymorphisms (SNPs) within the Fat mass and obesity associated (FTO) gene have been linked with increased body weight. However, the data on an association of FTO with cardiovascular diseases remains conflicting. Therefore, we ascertained whether FTO is associated with aortic valve stenosis (AVS), one of the most frequent cardiovascular diseases in the Western world. Methods and Findings In this population-based case-control study the FTO SNP rs9939609 was analyzed in 300 German patients with AVS and 429 German controls of the KORA survey S4, representing a random population. Blood samples were collected prior to aortic valve replacement in AVS cases and FTO rs9939609 was genotyped via ARMS-PCR. Genotype frequencies differed significantly between AVS cases and KORA controls (p = 0.004). Separate gender-analyses uncovered an association of FTO with AVS exclusively in males; homozygote carriers for the risk-allele (A) had a higher risk to develop AVS (p = 0.017, odds ratio (OR) 1.727; 95% confidence interval (CI) 1.087–2.747, recessive model), whereas heterozygote carriers for the risk-allele showed a lower risk (p = 0.002, OR 0.565, 95% CI 0.384–0.828, overdominant model). After adjustment for multiple co-variables, the odds ratios of heterozygotes remained significant for an association with AVS (p = 0.008, OR 0.565, 95% CI 0.369–0.861). Conclusions This study revealed an association of FTO rs9939609 with AVS. Furthermore, this association was restricted to men, with heterozygotes having a significantly lower chance to develop AVS. Lastly, the association between FTO and AVS was independent of BMI and other variables such as diabetes mellitus. PMID:26431034

Effects of metformin on metabolite profiles and LDL cholesterol in patients with type 2 diabetes.

PubMed

Xu, Tao; Brandmaier, Stefan; Messias, Ana C; Herder, Christian; Draisma, Harmen H M; Demirkan, Ayse; Yu, Zhonghao; Ried, Janina S; Haller, Toomas; Heier, Margit; Campillos, Monica; Fobo, Gisela; Stark, Renee; Holzapfel, Christina; Adam, Jonathan; Chi, Shen; Rotter, Markus; Panni, Tommaso; Quante, Anne S; He, Ying; Prehn, Cornelia; Roemisch-Margl, Werner; Kastenmüller, Gabi; Willemsen, Gonneke; Pool, René; Kasa, Katarina; van Dijk, Ko Willems; Hankemeier, Thomas; Meisinger, Christa; Thorand, Barbara; Ruepp, Andreas; Hrabé de Angelis, Martin; Li, Yixue; Wichmann, H-Erich; Stratmann, Bernd; Strauch, Konstantin; Metspalu, Andres; Gieger, Christian; Suhre, Karsten; Adamski, Jerzy; Illig, Thomas; Rathmann, Wolfgang; Roden, Michael; Peters, Annette; van Duijn, Cornelia M; Boomsma, Dorret I; Meitinger, Thomas; Wang-Sattler, Rui

2015-10-01

Metformin is used as a first-line oral treatment for type 2 diabetes (T2D). However, the underlying mechanism is not fully understood. Here, we aimed to comprehensively investigate the pleiotropic effects of metformin. We analyzed both metabolomic and genomic data of the population-based KORA cohort. To evaluate the effect of metformin treatment on metabolite concentrations, we quantified 131 metabolites in fasting serum samples and used multivariable linear regression models in three independent cross-sectional studies (n = 151 patients with T2D treated with metformin [mt-T2D]). Additionally, we used linear mixed-effect models to study the longitudinal KORA samples (n = 912) and performed mediation analyses to investigate the effects of metformin intake on blood lipid profiles. We combined genotyping data with the identified metformin-associated metabolites in KORA individuals (n = 1,809) and explored the underlying pathways. We found significantly lower (P < 5.0E-06) concentrations of three metabolites (acyl-alkyl phosphatidylcholines [PCs]) when comparing mt-T2D with four control groups who were not using glucose-lowering oral medication. These findings were controlled for conventional risk factors of T2D and replicated in two independent studies. Furthermore, we observed that the levels of these metabolites decreased significantly in patients after they started metformin treatment during 7 years' follow-up. The reduction of these metabolites was also associated with a lowered blood level of LDL cholesterol (LDL-C). Variations of these three metabolites were significantly associated with 17 genes (including FADS1 and FADS2) and controlled by AMPK, a metformin target. Our results indicate that metformin intake activates AMPK and consequently suppresses FADS, which leads to reduced levels of the three acyl-alkyl PCs and LDL-C. Our findings suggest potential beneficial effects of metformin in the prevention of cardiovascular disease. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

The Human Blood Metabolome-Transcriptome Interface

PubMed Central

Schramm, Katharina; Adamski, Jerzy; Gieger, Christian; Herder, Christian; Carstensen, Maren; Peters, Annette; Rathmann, Wolfgang; Roden, Michael; Strauch, Konstantin; Suhre, Karsten; Kastenmüller, Gabi; Prokisch, Holger; Theis, Fabian J.

2015-01-01

Biological systems consist of multiple organizational levels all densely interacting with each other to ensure function and flexibility of the system. Simultaneous analysis of cross-sectional multi-omics data from large population studies is a powerful tool to comprehensively characterize the underlying molecular mechanisms on a physiological scale. In this study, we systematically analyzed the relationship between fasting serum metabolomics and whole blood transcriptomics data from 712 individuals of the German KORA F4 cohort. Correlation-based analysis identified 1,109 significant associations between 522 transcripts and 114 metabolites summarized in an integrated network, the ‘human blood metabolome-transcriptome interface’ (BMTI). Bidirectional causality analysis using Mendelian randomization did not yield any statistically significant causal associations between transcripts and metabolites. A knowledge-based interpretation and integration with a genome-scale human metabolic reconstruction revealed systematic signatures of signaling, transport and metabolic processes, i.e. metabolic reactions mainly belonging to lipid, energy and amino acid metabolism. Moreover, the construction of a network based on functional categories illustrated the cross-talk between the biological layers at a pathway level. Using a transcription factor binding site enrichment analysis, this pathway cross-talk was further confirmed at a regulatory level. Finally, we demonstrated how the constructed networks can be used to gain novel insights into molecular mechanisms associated to intermediate clinical traits. Overall, our results demonstrate the utility of a multi-omics integrative approach to understand the molecular mechanisms underlying both normal physiology and disease. PMID:26086077

Association between DNA Methylation in Whole Blood and Measures of Glucose Metabolism: KORA F4 Study

PubMed Central

Wahl, Simone; Kunze, Sonja; Molnos, Sophie; Volkova, Nadezda; Schramm, Katharina; Carstensen-Kirberg, Maren; Waldenberger, Melanie; Gieger, Christian; Peters, Annette; Illig, Thomas; Prokisch, Holger; Roden, Michael; Grallert, Harald

2016-01-01

Epigenetic regulation has been postulated to affect glucose metabolism, insulin sensitivity and the risk of type 2 diabetes. Therefore, we performed an epigenome-wide association study for measures of glucose metabolism in whole blood samples of the population-based Cooperative Health Research in the Region of Augsburg F4 study using the Illumina HumanMethylation 450 BeadChip. We identified a total of 31 CpG sites where methylation level was associated with measures of glucose metabolism after adjustment for age, sex, smoking, and estimated white blood cell proportions and correction for multiple testing using the Benjamini-Hochberg (B-H) method (four for fasting glucose, seven for fasting insulin, 25 for homeostasis model assessment-insulin resistance [HOMA-IR]; B-H-adjusted p-values between 9.2x10-5 and 0.047). In addition, DNA methylation at cg06500161 (annotated to ABCG1) was associated with all the aforementioned phenotypes and 2-hour glucose (B-H-adjusted p-values between 9.2x10-5 and 3.0x10-3). Methylation status of additional three CpG sites showed an association with fasting insulin only after additional adjustment for body mass index (BMI) (B-H-adjusted p-values = 0.047). Overall, effect strengths were reduced by around 30% after additional adjustment for BMI, suggesting that this variable has an influence on the investigated phenotypes. Furthermore, we found significant associations between methylation status of 21 of the aforementioned CpG sites and 2-hour insulin in a subset of samples with seven significant associations persisting after additional adjustment for BMI. In a subset of 533 participants, methylation of the CpG site cg06500161 (ABCG1) was inversely associated with ABCG1 gene expression (B-H-adjusted p-value = 1.5x10-9). Additionally, we observed an enrichment of the top 1,000 CpG sites for diabetes-related canonical pathways using Ingenuity Pathway Analysis. In conclusion, our study indicates that DNA methylation and diabetes-related traits are associated and that these associations are partially BMI-dependent. Furthermore, the interaction of ABCG1 with glucose metabolism is modulated by epigenetic processes. PMID:27019061

A Deep Learning Algorithm for Prediction of Age-Related Eye Disease Study Severity Scale for Age-Related Macular Degeneration from Color Fundus Photography.

PubMed

Grassmann, Felix; Mengelkamp, Judith; Brandl, Caroline; Harsch, Sebastian; Zimmermann, Martina E; Linkohr, Birgit; Peters, Annette; Heid, Iris M; Palm, Christoph; Weber, Bernhard H F

2018-04-10

Age-related macular degeneration (AMD) is a common threat to vision. While classification of disease stages is critical to understanding disease risk and progression, several systems based on color fundus photographs are known. Most of these require in-depth and time-consuming analysis of fundus images. Herein, we present an automated computer-based classification algorithm. Algorithm development for AMD classification based on a large collection of color fundus images. Validation is performed on a cross-sectional, population-based study. We included 120 656 manually graded color fundus images from 3654 Age-Related Eye Disease Study (AREDS) participants. AREDS participants were >55 years of age, and non-AMD sight-threatening diseases were excluded at recruitment. In addition, performance of our algorithm was evaluated in 5555 fundus images from the population-based Kooperative Gesundheitsforschung in der Region Augsburg (KORA; Cooperative Health Research in the Region of Augsburg) study. We defined 13 classes (9 AREDS steps, 3 late AMD stages, and 1 for ungradable images) and trained several convolution deep learning architectures. An ensemble of network architectures improved prediction accuracy. An independent dataset was used to evaluate the performance of our algorithm in a population-based study. κ Statistics and accuracy to evaluate the concordance between predicted and expert human grader classification. A network ensemble of 6 different neural net architectures predicted the 13 classes in the AREDS test set with a quadratic weighted κ of 92% (95% confidence interval, 89%-92%) and an overall accuracy of 63.3%. In the independent KORA dataset, images wrongly classified as AMD were mainly the result of a macular reflex observed in young individuals. By restricting the KORA analysis to individuals >55 years of age and prior exclusion of other retinopathies, the weighted and unweighted κ increased to 50% and 63%, respectively. Importantly, the algorithm detected 84.2% of all fundus images with definite signs of early or late AMD. Overall, 94.3% of healthy fundus images were classified correctly. Our deep learning algoritm revealed a weighted κ outperforming human graders in the AREDS study and is suitable to classify AMD fundus images in other datasets using individuals >55 years of age. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Physical activity is inversely associated with multimorbidity in elderly men: results from the KORA-Age Augsburg Study.

PubMed

Autenrieth, Christine S; Kirchberger, Inge; Heier, Margit; Zimmermann, Anja-Kerstin; Peters, Annette; Döring, Angela; Thorand, Barbara

2013-07-01

Physical activity is suggested to play a key role in the prevention of several chronic diseases. However, data on the association between physical activity and multimorbidity are lacking. Using data from 1007 men and women aged 65-94 years who participated in the population-based KORA (Cooperative Health Research in the Region of Augsburg)-Age project conducted in Augsburg/Germany and two adjacent counties in 2008/09, 13 chronic conditions were identified, and physical activity scores were calculated based on the self-reported physical activity scale for the elderly (PASE). Multivariable sex-specific logistic regression was applied to determine the association of the continuous physical activity score with multimorbidity (≥ 2 out of 13 diseases). Physical activity (mean PASE score±SD) was higher in men (125.1 ± 59.2) than in women (112.2 ± 49.2). Among men, the odds ratio (OR) for multimorbidity was 0.73 (95% CI: 0.60-0.90) for a 1 standard deviation increase of the PASE score. No significant results could be observed for women (OR: 1.05; 95% CI: 0.83-1.33). We demonstrated an inverse association between physical activity and multimorbidity among men. Further prospective studies have to confirm the temporality of effects. Copyright © 2013 Elsevier Inc. All rights reserved.

Functional Characterization of Promoter Variants of the Adiponectin Gene Complemented by Epidemiological Data

PubMed Central

Laumen, Helmut; Saningong, Akuma D.; Heid, Iris M.; Hess, Jochen; Herder, Christian; Claussnitzer, Melina; Baumert, Jens; Lamina, Claudia; Rathmann, Wolfgang; Sedlmeier, Eva-Maria; Klopp, Norman; Thorand, Barbara; Wichmann, H.-Erich; Illig, Thomas; Hauner, Hans

2009-01-01

OBJECTIVE Adiponectin (APM1, ACDC) is an adipocyte-derived protein with downregulated expression in obesity and insulin-resistant states. Several potentially regulatory single nucleotide polymorphisms (SNPs) within the APM1 gene promoter region have been associated with circulating adiponectin levels. None of them have been functionally characterized in adiponectin-expressing cells. Hence, we investigated three SNPs (rs16861194, rs17300539, and rs266729) for their influence on adiponectin promoter activity and their association with circulating adiponectin levels. RESEARCH DESIGN AND METHODS Basal and rosiglitazone-induced promoter activity of different SNP combinations (haplotypes) was analyzed in 3T3-L1 adipocytes using luciferase reporter gene assays and DNA binding studies comparing all possible APM1 haplotypes. This functional approach was complemented with analysis of epidemiological population-based data of 1,692 participants of the MONICA/KORA S123 cohort and 696 participants from the KORA S4 cohort for SNP and haplotype association with circulating adiponectin levels. RESULTS Major to minor allele replacements of the three SNPs revealed significant effects on promoter activity in luciferase assays. Particularly, a minor variant in rs16861194 resulted in reduced basal and rosiglitazone-induced promoter activity and hypoadiponectinemia in the epidemiological datasets. The haplotype with the minor allele in all three SNPs showed a complete loss of promoter activity, and no subject carried this haplotype in either of the epidemiological samples (combined P value for statistically significant difference from a random sample was 0.006). CONCLUSIONS Our results clearly demonstrate that promoter variants associated with hypoadiponectinemia in humans substantially affect adiponectin promoter activity in adipocytes. Our combination of functional experiments with epidemiological data overcomes the drawback of each approach alone. PMID:19074982

The Pharmacogenetic Footprint of ACE Inhibition: A Population-Based Metabolomics Study.

PubMed

Altmaier, Elisabeth; Menni, Cristina; Heier, Margit; Meisinger, Christa; Thorand, Barbara; Quell, Jan; Kobl, Michael; Römisch-Margl, Werner; Valdes, Ana M; Mangino, Massimo; Waldenberger, Melanie; Strauch, Konstantin; Illig, Thomas; Adamski, Jerzy; Spector, Tim; Gieger, Christian; Suhre, Karsten; Kastenmüller, Gabi

2016-01-01

Angiotensin-I-converting enzyme (ACE) inhibitors are an important class of antihypertensives whose action on the human organism is still not fully understood. Although it is known that ACE especially cleaves COOH-terminal dipeptides from active polypeptides, the whole range of substrates and products is still unknown. When analyzing the action of ACE inhibitors, effects of genetic variation on metabolism need to be considered since genetic variance in the ACE gene locus was found to be associated with ACE-concentration in blood as well as with changes in the metabolic profiles of a general population. To investigate the interactions between genetic variance at the ACE-locus and the influence of ACE-therapy on the metabolic status we analyzed 517 metabolites in 1,361 participants from the KORA F4 study. We replicated our results in 1,964 individuals from TwinsUK. We observed differences in the concentration of five dipeptides and three ratios of di- and oligopeptides between ACE inhibitor users and non-users that were genotype dependent. Such changes in the concentration affected major homozygotes, and to a lesser extent heterozygotes, while minor homozygotes showed no or only small changes in the metabolite status. Two of these resulting dipeptides, namely aspartylphenylalanine and phenylalanylserine, showed significant associations with blood pressure which qualifies them-and perhaps also the other dipeptides-as readouts of ACE-activity. Since so far ACE activity measurement is substrate specific due to the usage of only one oligopeptide, taking several dipeptides as potential products of ACE into account may provide a broader picture of the ACE activity.

RANTES/CCL5 and risk for coronary events: results from the MONICA/KORA Augsburg case-cohort, Athero-Express and CARDIoGRAM studies.

PubMed

Herder, Christian; Peeters, Wouter; Illig, Thomas; Baumert, Jens; de Kleijn, Dominique P V; Moll, Frans L; Poschen, Ulrike; Klopp, Norman; Müller-Nurasyid, Martina; Roden, Michael; Preuss, Michael; Karakas, Mahir; Meisinger, Christa; Thorand, Barbara; Pasterkamp, Gerard; Koenig, Wolfgang; Assimes, Themistocles L; Deloukas, Panos; Erdmann, Jeanette; Holm, Hilma; Kathiresan, Sekar; König, Inke R; McPherson, Ruth; Reilly, Muredach P; Roberts, Robert; Samani, Nilesh J; Schunkert, Heribert; Stewart, Alexandre F R

2011-01-01

The chemokine RANTES (regulated on activation, normal T-cell expressed and secreted)/CCL5 is involved in the pathogenesis of cardiovascular disease in mice, whereas less is known in humans. We hypothesised that its relevance for atherosclerosis should be reflected by associations between CCL5 gene variants, RANTES serum concentrations and protein levels in atherosclerotic plaques and risk for coronary events. We conducted a case-cohort study within the population-based MONICA/KORA Augsburg studies. Baseline RANTES serum levels were measured in 363 individuals with incident coronary events and 1,908 non-cases (mean follow-up: 10.2±4.8 years). Cox proportional hazard models adjusting for age, sex, body mass index, metabolic factors and lifestyle factors revealed no significant association between RANTES and incident coronary events (HR [95% CI] for increasing RANTES tertiles 1.0, 1.03 [0.75-1.42] and 1.11 [0.81-1.54]). None of six CCL5 single nucleotide polymorphisms and no common haplotype showed significant associations with coronary events. Also in the CARDIoGRAM study (>22,000 cases, >60,000 controls), none of these CCL5 SNPs was significantly associated with coronary artery disease. In the prospective Athero-Express biobank study, RANTES plaque levels were measured in 606 atherosclerotic lesions from patients who underwent carotid endarterectomy. RANTES content in atherosclerotic plaques was positively associated with macrophage infiltration and inversely associated with plaque calcification. However, there was no significant association between RANTES content in plaques and risk for coronary events (mean follow-up 2.8±0.8 years). High RANTES plaque levels were associated with an unstable plaque phenotype. However, the absence of associations between (i) RANTES serum levels, (ii) CCL5 genotypes and (iii) RANTES content in carotid plaques and either coronary artery disease or incident coronary events in our cohorts suggests that RANTES may not be a novel coronary risk biomarker. However, the potential relevance of RANTES levels in platelet-poor plasma needs to be investigated in further studies.

Mind over hormones: sex differences in associations of well-being with IGF-I, IGFBP-3 and physical activity in the KORA-Age study.

PubMed

Emeny, R T; Bidlingmaier, M; Lacruz, M E; Linkohr, B; Peters, A; Reincke, M; Ladwig, K H

2014-11-01

A ssociations between well-being, serum levels of insulin-like growth factor 1 (IGF-I), and its primary binding protein IGFBP-3, were examined in an epidemiologic study. The influence of physical activity on the effect of hormones on well-being was considered. Cross-sectional data from participants of the KORA-Age study (n=985, age 64-93) was analyzed in sex-specific multivariable regressions of well-being (World Health Organization (WHO) -5) or ill-being (geriatric depression scale (GDS) -15). Models were adjusted for age, physical activity, sleep, BMI, smoking, and cognition. Adjusted WHO-5 means demonstrated the interaction between hormone quintiles with physical activity. Full models indicated that increased IGFBP-3 positively associated with well-being in women (β estimate=0.14, standard error (SE)=0.06) and less so in men (β=0.11, SE=0.07). IGF-I associated positively with depression (β=0.11, SE=0.06) and negatively with well-being (β=-0.11, SE=0.06) in women. Similar but not statistically discernable effects were observed in men. Adjusted mean WHO-5 scores illustrated the positive effect of physical activity and IGFBP-3 on well-being in women only. Opposite and independent associations of IGF-I and IGFBP-3 on well-being observed in women suggests neuroprotective effects of IGFBP-3 in age. Copyright © 2014 Elsevier Inc. All rights reserved.

Associations between Traffic Noise, Particulate Air Pollution, Hypertension, and Isolated Systolic Hypertension in Adults: The KORA Study

PubMed Central

Wolf, Kathrin; Petz, Markus; Heinrich, Joachim; Cyrys, Josef; Peters, Annette

2014-01-01

Background: Studies on the association between traffic noise and cardiovascular diseases have rarely considered air pollution as a covariate in the analyses. Isolated systolic hypertension has not yet been in the focus of epidemiological noise research. Methods: The association between traffic noise (road and rail) and the prevalence of hypertension was assessed in two study populations with a total of 4,166 participants 25–74 years of age. Traffic noise (weighted day–night average noise level; LDN) at the facade of the dwellings was derived from noise maps. Annual average PM2.5 mass concentrations at residential addresses were estimated by land-use regression. Hypertension was assessed by blood pressure readings, self-reported doctor-diagnosed hypertension, and antihypertensive drug intake. Results: In the Greater Augsburg, Germany, study population, traffic noise and air pollution were not associated with hypertension. In the City of Augsburg population (n = 1,893), where the exposure assessment was more detailed, the adjusted odds ratio (OR) for a 10-dB(A) increase in noise was 1.16 (95% CI: 1.00, 1.35), and 1.11 (95% CI: 0.94, 1.30) after additional adjustment for PM2.5. The adjusted OR for a 1-μg/m3 increase in PM2.5 was 1.15 (95% CI: 1.02, 1.30), and 1.11 (95% CI: 0.98, 1.27) after additional adjustment for noise. For isolated systolic hypertension, the fully adjusted OR for noise was 1.43 (95% CI: 1.10, 1.86) and for PM2.5 was 1.08 (95% CI: 0.87, 1.34). Conclusions: Traffic noise and PM2.5 were both associated with a higher prevalence of hypertension. Mutually adjusted associations with hypertension were positive but no longer statistically significant. Citation: Babisch W, Wolf K, Petz M, Heinrich J, Cyrys J, Peters A. 2014. Associations between traffic noise, particulate air pollution, hypertension, and isolated systolic hypertension in adults: the KORA Study. Environ Health Perspect 122:492–498; http://dx.doi.org/10.1289/ehp.1306981 PMID:24602804

Epigenetic Signatures at AQP3 and SOCS3 Engage in Low-Grade Inflammation across Different Tissues

PubMed Central

Marzi, Carola; Holdt, Lesca M; Fiorito, Giovanni; Tsai, Pei-Chien; Kretschmer, Anja; Wahl, Simone; Guarrera, Simonetta; Teupser, Daniel; Spector, Tim D.; Iacoviello, Licia; Sacerdote, Carlotta; Strauch, Konstantin; Lee, Serene; Thasler, Wolfgang E.; Peters, Annette; Thorand, Barbara; Wolf, Petra; Prokisch, Holger; Tumino, Rosario; Gieger, Christian; Krogh, Vittorio; Panico, Salvatore; Bell, Jordana T.; Matullo, Giuseppe

2016-01-01

Background Elevated levels of C-reactive protein (CRP, determined by a high-sensitivity assay) indicate low-grade inflammation which is implicated in many age-related disorders. Epigenetic studies on CRP might discover molecular mechanisms underlying CRP regulation. We aimed to identify DNA methylation sites related to CRP concentrations in cells and tissues regulating low-grade inflammation. Results Genome-wide DNA methylation was measured in peripheral blood in 1,741 participants of the KORA F4 study using Illumina HumanMethylation450 BeadChip arrays. Four CpG sites (located at BCL3, AQP3, SOCS3, and cg19821297 intergenic at chromosome 19p13.2, P ≤ 1.01E-07) were significantly hypomethylated at high CRP concentrations independent of various confounders including age, sex, BMI, smoking, and white blood cell composition. Findings were not sex-specific. CRP-related top genes were enriched in JAK/STAT pathways (Benjamini-Hochberg corrected P < 0.05). Results were followed-up in three studies using DNA from peripheral blood (EPICOR, n = 503) and adipose tissue (TwinsUK, n = 368) measured as described above and from liver tissue (LMU liver cohort, n = 286) measured by MALDI-TOF mass spectrometry using EpiTYPER. CpG sites at the AQP3 locus (significant p-values in peripheral blood = 1.72E-03 and liver tissue = 1.51E-03) and the SOCS3 locus (p-values in liver < 2.82E-05) were associated with CRP in the validation panels. Conclusions Epigenetic modifications seem to engage in low-grade inflammation, possibly via JAK/STAT mediated pathways. Results suggest a shared relevance across different tissues at the AQP3 locus and highlight a role of DNA methylation for CRP regulation at the SOCS3 locus. PMID:27824951

Extensive alterations of the whole-blood transcriptome are associated with body mass index: results of an mRNA profiling study involving two large population-based cohorts.

PubMed

Homuth, Georg; Wahl, Simone; Müller, Christian; Schurmann, Claudia; Mäder, Ulrike; Blankenberg, Stefan; Carstensen, Maren; Dörr, Marcus; Endlich, Karlhans; Englbrecht, Christian; Felix, Stephan B; Gieger, Christian; Grallert, Harald; Herder, Christian; Illig, Thomas; Kruppa, Jochen; Marzi, Carola S; Mayerle, Julia; Meitinger, Thomas; Metspalu, Andres; Nauck, Matthias; Peters, Annette; Rathmann, Wolfgang; Reinmaa, Eva; Rettig, Rainer; Roden, Michael; Schillert, Arne; Schramm, Katharina; Steil, Leif; Strauch, Konstantin; Teumer, Alexander; Völzke, Henry; Wallaschofski, Henri; Wild, Philipp S; Ziegler, Andreas; Völker, Uwe; Prokisch, Holger; Zeller, Tanja

2015-10-15

Obesity, defined as pathologically increased body mass index (BMI), is strongly related to an increased risk for numerous common cardiovascular and metabolic diseases. It is particularly associated with insulin resistance, hyperglycemia, and systemic oxidative stress and represents the most important risk factor for type 2 diabetes (T2D). However, the pathophysiological mechanisms underlying these associations are still not completely understood. Therefore, in order to identify potentially disease-relevant BMI-associated gene expression signatures, a transcriptome-wide association study (TWAS) on BMI was performed. Whole-blood mRNA levels determined by array-based transcriptional profiling were correlated with BMI in two large independent population-based cohort studies (KORA F4 and SHIP-TREND) comprising a total of 1977 individuals. Extensive alterations of the whole-blood transcriptome were associated with BMI: More than 3500 transcripts exhibited significant positive or negative BMI-correlation. Three major whole-blood gene expression signatures associated with increased BMI were identified. The three signatures suggested: i) a ratio shift from mature erythrocytes towards reticulocytes, ii) decreased expression of several genes essentially involved in the transmission and amplification of the insulin signal, and iii) reduced expression of several key genes involved in the defence against reactive oxygen species (ROS). Whereas the first signature confirms published results, the other two provide possible mechanistic explanations for well-known epidemiological findings under conditions of increased BMI, namely attenuated insulin signaling and increased oxidative stress. The putatively causative BMI-dependent down-regulation of the expression of numerous genes on the mRNA level represents a novel finding. BMI-associated negative transcriptional regulation of insulin signaling and oxidative stress management provide new insights into the pathogenesis of metabolic syndrome and T2D.

Impact of vertigo and dizziness on self-perceived participation and autonomy in older adults: results from the KORA-Age study.

PubMed

Mueller, Martin; Strobl, Ralf; Jahn, Klaus; Linkohr, Birgit; Ladwig, Karl Heinz; Mielck, Andreas; Grill, Eva

2014-10-01

The impact of vertigo and dizziness on healthy ageing, and especially on participation, is not fully understood. The objective of this study was to investigate the association of vertigo and dizziness with self-perceived participation and autonomy in older non-institutionalised individuals, adjusted for the presence of other health conditions. Specifically, we wanted to investigate the different effects of vertigo and dizziness on specific components of participation, i.e. restrictions in indoor and outdoor autonomy, family role, social life and relationships, and work and education. Data originate from the second wave of the German KORA-Age cohort study collected in 2012. Participation and autonomy was investigated with the Impact on Participation and Autonomy Questionnaire. We used robust regression to analyse the association of vertigo and dizziness with self-perceived participation and autonomy adjusted for covariates. A total of 822 participants (49.6% female) had a mean age of 78.1 years (SD 6.39). Participation and autonomy were significantly lower in participants with vertigo and dizziness across all domains. Adjusted for age, sex, and chronic conditions, vertigo and dizziness were significantly associated with participation restrictions in all domains except social life and relationships. The results of our study indicate that vertigo and dizziness contribute to restrictions in participation and autonomy in individuals of older age. Recognising vertigo and dizziness as independent contributors to loss of autonomy and decreased chances for independent living may create new options for patient care and population health, such as the designing of complex interventions to maintain participation and autonomy.

Genetic variability comparison of cultured Israeli carp (Cyprinus carpio) from Korea using microsatellites.

PubMed

Kim, Jung Eun; Goo, In Bon; Hwang, Ju-Ae; Kim, Hyeong Su; Choi, Hye-Sung; Lee, Jeong-Ho

2018-06-01

In aquaculture, cultured fish often undergo continuous cross-fertilization without any inflow of new broodstock. This lowers genetic diversity, leading to increased disease rates and decreased survival rates. To improve the mass production and easy culture of Israeli carp, it is essential to investigate the population structure and genetic diversity of these fish. However, such a survey has not yet been performed on Korean Israeli carp. In this study, we used seven microsatellite markers to analyze the genetic diversity and association of cultured Israeli carp from Korea and China. The average numbers of alleles per locus (N A ) for two Korean (KorA and KorB) and two Chinese (ChA and ChB) populations were as follows: KorA (10.42), KorB (14.43), ChA (20.57) and ChB (20.71). The expected heterozygosity (H e ) ranged from 0.672 to 0.897 and from 0.827 to 0.938 in the Korean sample and Chinese sample respectively. The genetic diversity of the Korean Israeli carp was about half that of the Chinese carp. The diversity of the Korean Israeli carp was very low, suggesting that the immunity of this population could be weak, and that diversity-recovery studies are urgently needed. Therefore, our results may therefore form the foundation for future research efforts towards genetic monitoring and selective breeding, continuous research needs to be conducted in order to recover the genetic diversity of the Korean Israeli carp.

Living alone, obesity, and smoking increase risk for suicide independently of depressive mood findings from the population-based MONICA/KORA Augsburg cohort study.

PubMed

Schneider, Barbara; Lukaschek, Karoline; Baumert, Jens; Meisinger, Christa; Erazo, Natalia; Ladwig, Karl-Heinz

2014-01-01

Suicide is strongly associated with mental disorders, particularly with depression. There is insufficient knowledge to what extent sociodemographic and behavioral characteristics contribute to suicide risk. A population-based cohort study on three independent cross-sectional MONICA/KORA Augsburg surveys with 12,888 subjects (6456 men, 6432 women) was followed up on average for 12.0 years. Information on sociodemographic characteristics, chronic disease conditions, smoking habits, alcohol consumption, depressive symptoms, personality type, and other psychodiagnostic parameters was assessed by standardized interviews. Cox proportional hazards regression analyses were used to compute hazard ratios (HRs) as estimates of relative risks for suicide mortality. Additionally, population-attributable risks were calculated. Within the follow-up period, a total of 1449 persons had died, 38 of them by suicide. Although several variables were associated with increased risk in the basic analyses, only obesity (HR=2.73), smoking (HR=2.23), and living alone (HR=2.19) remained significantly associated with suicide additionally to male sex (HR=3.57) and depressed mood (HR=2.01) in a multivariate analysis. The generalization of our findings to countries with different social, economic or cultural conditions may be questioned. Our findings extend the knowledge about sociodemographic and behavioral risk factors for suicide in the general population: Suicide prevention measures should not consider only subjects with mental disorders but also address other adverse conditions. © 2013 Published by Elsevier B.V.

The association of air pollution and depressed mood in 70,928 individuals from four European cohorts.

PubMed

Zijlema, W L; Wolf, K; Emeny, R; Ladwig, K H; Peters, A; Kongsgård, H; Hveem, K; Kvaløy, K; Yli-Tuomi, T; Partonen, T; Lanki, T; Eeftens, M; de Hoogh, K; Brunekreef, B; Stolk, R P; Rosmalen, J G M

2016-03-01

Exposure to ambient air pollution may be associated with impaired mental health, including depression. However, evidence originates mainly from animal studies and epidemiological studies in specific subgroups. We investigated the association between air pollution and depressed mood in four European general population cohorts. Data were obtained from LifeLines (the Netherlands), KORA (Germany), HUNT (Norway), and FINRISK (Finland). Residential exposure to particles (PM2.5, PM2.5absorbance, PM10) and nitrogen dioxide (NO2) was estimated using land use regression (LUR) models developed for the European Study of Cohorts for Air Pollution Effects (ESCAPE) and using European wide LUR models. Depressed mood was assessed with interviews and questionnaires. Logistic regression analyses were used to investigate the cohort specific associations between air pollution and depressed mood. A total of 70,928 participants were included in our analyses. Depressed mood ranged from 1.6% (KORA) to 11.3% (FINRISK). Cohort specific associations of the air pollutants and depressed mood showed heterogeneous results. For example, positive associations were found for NO2 in LifeLines (odds ratio [OR]=1.34; 95% CI: 1.17, 1.53 per 10 μg/m(3) increase in NO2), whereas negative associations were found in HUNT (OR=0.79; 95% CI: 0.66, 0.94 per 10 μg/m(3) increase in NO2). Our analyses of four European general population cohorts found no consistent evidence for an association between ambient air pollution and depressed mood. Copyright © 2015 Elsevier GmbH. All rights reserved.

Mid-life job insecurity associated with subjective well-being in old age: results from the population-based MONICA/KORA study.

PubMed

Barrech, Amira; Baumert, Jens; Emeny, Rebecca T; Gündel, Harald; Ladwig, Karl-Heinz

2016-03-01

This study aimed to examine prospectively the influence of exposure to job insecurity during working life on subjective well-being (SWB) after retirement, an association which has not been studied to date. Data were derived from the prospective population-based MONICA/KORA study conducted in southern Germany. Participants were recruited and data were collected during three independent surveys between 1984-1995 (T1) and followed up in 2009 (T2). The study sample consisted of 1801 employed participants (1146 male/ 655 female) aged 41-72 years at T1 and ≥ 65 years at T2, without missing data. Self-administered questionnaires and clinical examinations were used to assess job insecurity and risk factors at T1 and SWB at T2. Mean follow-up was 19.6 years. Logistic regression analyses were performed to determine the association of job insecurity with SWB after retirement. We accounted for an extensive set of sociodemographic, lifestyle-, health- and work-related risk factors. At T1, 39.5% of the participants reported job insecurity, which was associated with a 1.40-fold [95% confidence interval (95% CI) 1.08-1.82] risk of low SWB at T2 in models adjusted for sociodemographic and lifestyle- and health-related conditions at T1. Additional adjustment for a set of work-related risk factors at T1 had little effect on this association. Exposure to job insecurity at midlife was associated with low SWB in retirement, even after controlling for an extensive set of risk factors. This shows that the negative effects of unstable working conditions might persist well into retirement, long after cessation of employment.

Anxiety Associated Increased CpG Methylation in the Promoter of Asb1: A Translational Approach Evidenced by Epidemiological and Clinical Studies and a Murine Model.

PubMed

Emeny, Rebecca T; Baumert, Jens; Zannas, Anthony S; Kunze, Sonja; Wahl, Simone; Iurato, Stella; Arloth, Janine; Erhardt, Angelika; Balsevich, Georgia; Schmidt, Mathias V; Weber, Peter; Kretschmer, Anja; Pfeiffer, Liliane; Kruse, Johannes; Strauch, Konstantin; Roden, Michael; Herder, Christian; Koenig, Wolfgang; Gieger, Christian; Waldenberger, Melanie; Peters, Annette; Binder, Elisabeth B; Ladwig, Karl-Heinz

2018-01-01

Epigenetic regulation in anxiety is suggested, but evidence from large studies is needed. We conducted an epigenome-wide association study (EWAS) on anxiety in a population-based cohort and validated our finding in a clinical cohort as well as a murine model. In the KORA cohort, participants (n=1522, age 32-72 years) were administered the Generalized Anxiety Disorder (GAD-7) instrument, whole blood DNA methylation was measured (Illumina 450K BeadChip), and circulating levels of hs-CRP and IL-18 were assessed in the association between anxiety and methylation. DNA methylation was measured using the same instrument in a study of patients with anxiety disorders recruited at the Max Planck Institute of Psychiatry (MPIP, 131 non-medicated cases and 169 controls). To expand our mechanistic understanding, these findings were reverse translated in a mouse model of acute social defeat stress. In the KORA study, participants were classified according to mild, moderate, or severe levels of anxiety (29.4%/6.0%/1.5%, respectively). Severe anxiety was associated with 48.5% increased methylation at a single CpG site (cg12701571) located in the promoter of the gene encoding Asb1 (β-coefficient=0.56 standard error (SE)=0.10, p (Bonferroni)=0.005), a protein hypothetically involved in regulation of cytokine signaling. An interaction between IL-18 and severe anxiety with methylation of this CpG cite showed a tendency towards significance in the total population (p=0.083) and a significant interaction among women (p=0.014). Methylation of the same CpG was positively associated with Panic and Agoraphobia scale (PAS) scores (β=0.005, SE=0.002, p=0.021, n=131) among cases in the MPIP study. In a murine model of acute social defeat stress, Asb1 gene expression was significantly upregulated in a tissue-specific manner (p=0.006), which correlated with upregulation of the neuroimmunomodulating cytokine interleukin 1 beta. Our findings suggest epigenetic regulation of the stress-responsive Asb1 gene in anxiety-related phenotypes. Further studies are necessary to elucidate the causal direction of this association and the potential role of Asb1-mediated immune dysregulation in anxiety disorders.

Anxiety Associated Increased CpG Methylation in the Promoter of Asb1: A Translational Approach Evidenced by Epidemiological and Clinical Studies and a Murine Model

PubMed Central

Emeny, Rebecca T; Baumert, Jens; Zannas, Anthony S; Kunze, Sonja; Wahl, Simone; Iurato, Stella; Arloth, Janine; Erhardt, Angelika; Balsevich, Georgia; Schmidt, Mathias V; Weber, Peter; Kretschmer, Anja; Pfeiffer, Liliane; Kruse, Johannes; Strauch, Konstantin; Roden, Michael; Herder, Christian; Koenig, Wolfgang; Gieger, Christian; Waldenberger, Melanie; Peters, Annette; Binder, Elisabeth B; Ladwig, Karl-Heinz

2018-01-01

Epigenetic regulation in anxiety is suggested, but evidence from large studies is needed. We conducted an epigenome-wide association study (EWAS) on anxiety in a population-based cohort and validated our finding in a clinical cohort as well as a murine model. In the KORA cohort, participants (n=1522, age 32–72 years) were administered the Generalized Anxiety Disorder (GAD-7) instrument, whole blood DNA methylation was measured (Illumina 450K BeadChip), and circulating levels of hs-CRP and IL-18 were assessed in the association between anxiety and methylation. DNA methylation was measured using the same instrument in a study of patients with anxiety disorders recruited at the Max Planck Institute of Psychiatry (MPIP, 131 non-medicated cases and 169 controls). To expand our mechanistic understanding, these findings were reverse translated in a mouse model of acute social defeat stress. In the KORA study, participants were classified according to mild, moderate, or severe levels of anxiety (29.4%/6.0%/1.5%, respectively). Severe anxiety was associated with 48.5% increased methylation at a single CpG site (cg12701571) located in the promoter of the gene encoding Asb1 (β-coefficient=0.56 standard error (SE)=0.10, p (Bonferroni)=0.005), a protein hypothetically involved in regulation of cytokine signaling. An interaction between IL-18 and severe anxiety with methylation of this CpG cite showed a tendency towards significance in the total population (p=0.083) and a significant interaction among women (p=0.014). Methylation of the same CpG was positively associated with Panic and Agoraphobia scale (PAS) scores (β=0.005, SE=0.002, p=0.021, n=131) among cases in the MPIP study. In a murine model of acute social defeat stress, Asb1 gene expression was significantly upregulated in a tissue-specific manner (p=0.006), which correlated with upregulation of the neuroimmunomodulating cytokine interleukin 1 beta. Our findings suggest epigenetic regulation of the stress-responsive Asb1 gene in anxiety-related phenotypes. Further studies are necessary to elucidate the causal direction of this association and the potential role of Asb1-mediated immune dysregulation in anxiety disorders. PMID:28540928

The association between patient-reported self-management behavior, intermediate clinical outcomes, and mortality in patients with type 2 diabetes: results from the KORA-A study.

PubMed

Laxy, Michael; Mielck, Andreas; Hunger, Matthias; Schunk, Michaela; Meisinger, Christa; Rückert, Ina-Maria; Rathmann, Wolfgang; Holle, Rolf

2014-06-01

Little is known about the impact of diabetes self-management behavior (SMB) on long-term outcomes. We aimed to examine the association among patient-reported SMB, intermediate clinical outcomes, and mortality in patients with type 2 diabetes. Data were collected from 340 patients with type 2 diabetes of the KORA-A study (1997/1998) who were recruited from two previous population-based surveys (n = 161) and a myocardial infarction registry (n = 179) in southern Germany. Based on previous methodological work, a high level of SMB was defined as being compliant with at least four of six different self-care dimensions, comprising physical exercise, foot care, blood glucose self-monitoring, weight monitoring, having a diet plan, and keeping a diabetes diary. The vital status of the participants was observed until 2009. Multivariable linear, logistic, and Cox regression models were applied to assess the association with intermediate clinical outcomes at baseline and to predict mortality over the follow-up period, adjusted for sociodemographic, behavioral, and disease-related factors. In the cross-sectional perspective, a high level of SMB was weakly associated with a lower glycated hemoglobin A1c level (-0.44% [-4.8 mmol/mol] [95% CI -0.88 to 0.00]), but not with low-density lipoprotein cholesterol, systolic blood pressure, or the presence of microalbuminuria, peripheral arterial disease, or polyneuropathy. During a mean follow-up time of 11.6 years, 189 patients died. SMB was a preventive factor for all-cause (hazard ratio 0.61 [95% CI 0.40-0.91]) and cardiovascular mortality (0.65 [95% CI 0.41-1.03]). Although measuring SMB is difficult and the used operationalization might be limited, our results give some indication that a high level of SMB is associated with prolonged life expectancy in patients with type 2 diabetes and highlight the potential impact of the patients' active contribution on the long-term trajectory of the disease. We assume that the used proxy for SMB is associated with unmeasured, but important, dimensions of health behavior. © 2014 by the American Diabetes Association.

Job strain as a risk factor for the onset of type 2 diabetes mellitus: findings from the MONICA/KORA Augsburg cohort study.

PubMed

Huth, Cornelia; Thorand, Barbara; Baumert, Jens; Kruse, Johannes; Emeny, Rebecca Thwing; Schneider, Andrea; Meisinger, Christa; Ladwig, Karl-Heinz

2014-09-01

To examine whether job strain is associated with an increased risk of subsequent Type 2 diabetes mellitus (T2DM) development in a population-based study of men and women. Data were derived from the prospective MONICA/KORA Augsburg study. We investigated 5337 working participants aged 29 to 66 years without diabetes at one of the three baseline surveys. Job strain was measured by the Karasek job content questionnaire. High job strain was defined by the quadrant approach, where high job demands combined with low job control were classified as high job strain. Continuous job strain (quotient of job demands divided by job control) was additionally analyzed as sensitivity analysis. Hazard ratios (HRs) were estimated using multivariable Cox proportional hazards models with adjustment for age, sex, survey, socioeconomic and life-style variables, parental history of diabetes, and body mass index. During a median follow-up of 12.7 years, 291 incident cases of T2DM were observed. The participants with high job strain at baseline had a 45% higher fully adjusted risk to develop T2DM than did those with low job strain (HR = 1.45 [95% confidence interval = 1.00-2.10], p = .048). On the continuous scale, more severe job strain in the magnitude of 1 standard deviation corresponded to a 12% increased fully adjusted T2DM risk (HR = 1.12 [95% confidence interval = 1.00-1.25], p = .045). Men and women who experience high job strain are at higher risk for developing T2DM independently of traditional risk factors. Preventive strategies to combat the globally increasing T2DM epidemic should take into consideration the adverse effects of high strain in the work environment.

Lack of supportive leadership behavior predicts suboptimal self-rated health independent of job strain after 10 years of follow-up: findings from the population-based MONICA/KORA study.

PubMed

Schmidt, Burkhard; Herr, Raphael M; Jarczok, Marc N; Baumert, Jens; Lukaschek, Karoline; Emeny, Rebecca T; Ladwig, Karl-Heinz

2018-04-23

Emerging cross-sectional research has identified lack of supportive leadership behavior (SLB) as a risk factor for workforce health. However, prospective evidence is hitherto lacking. SLB denotes support in difficult situations, recognition and feedback on work tasks. This study aims to determine the effect of SLB on suboptimal self-rated health (SRH) after 10 years considering potential moderators such as ages, sex, occupation and job strain. The sample included 884 employed participants drawn from the population-based prospective MONICA/KORA Study. SLB, SRH, as well as job strain were assessed by questionnaire. Logistic regressions estimated odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the effect of SLB at baseline on suboptimal SRH at follow-up. Analyses were adjusted for age, gender, lifestyle (alcohol, smoking, physical activity), socioeconomic status as well as for SRH and job strain at baseline. Lack of SLB was associated with suboptimal SRH at baseline [OR 2.00, (95% CI 1.19-3.46)] and at follow-up [OR 2.33, (95% CI 1.40-3.89)]. Additional adjustment for job strain did not substantially alter this association [OR 2.06, (95% CI 1.20-3.52)]. However, interactions between SLB and job strain as well as gender became evident, indicating moderating influences on the association between SLB and SRH. Lack of supportive leadership was associated with suboptimal SRH at 10 years' follow-up in men, even if SRH at baseline and other risk factors were taken into account. This effect is likely to be moderated by job strain.

Burden of disability attributable to vertigo and dizziness in the aged: results from the KORA-Age study.

PubMed

Mueller, Martin; Strobl, Ralf; Jahn, Klaus; Linkohr, Birgit; Peters, Annette; Grill, Eva

2014-10-01

Complaints of vertigo and dizziness are common in primary care in the aged. They can be caused by distinct vestibular disorders, but can also be a symptom in other conditions like non-vestibular sensory loss, vascular encephalopathy or anxiety. The aim of this study was to investigate the specific contribution of vertigo and dizziness to the total burden of disability in aged persons when controlling for the presence of other health conditions. Data originate from the MONICA/KORA study, a population-based cohort. Survivors of the original cohorts who were 65 years and older were examined by telephone interview in 2009. Disability was assessed with the Health Assessment Questionnaire. Logistic regression was used to adjust for potential confounders and additive regression to estimate the contribution of vertigo and dizziness to disability prevalence. Adjusted for age, sex and other chronic conditions, vertigo and dizziness were associated with disability (odds ratio 1.66, 95% confidence intervals 1.40-1.98). In both men and women between 65 and 79 years, vertigo and dizziness were among the strongest contributors to the burden of disability with a prevalence of 10.5% (6.6 to 15.1) in men and 9.0% (5.7 to 13.0) in women. In men, this effect is stable across all age-groups, whereas it decreases with age in women. Vertigo and dizziness independently and relevantly contribute to population-attributable disability in the aged. They are not inevitable consequences of ageing but arise from distinct disease entities. Careful management of vertigo and dizziness might increase population health and reduce disability. © The Author 2013. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Impaired Sleep Predicts Cognitive Decline in Old People: Findings from the Prospective KORA Age Study.

PubMed

Johar, Hamimatunnisa; Kawan, Rasmila; Emeny, Rebecca Thwing; Ladwig, Karl-Heinz

2016-01-01

To investigate the association between sleep-related characteristics and cognitive change over 3 years of follow up in an aged population. Sleep characteristics and covariates were assessed at baseline in a standardized interview and clinical examination of the population-based KORA Age Study (n = 740, mean age = 75 years). Cognitive score (determined by telephone interview for cognitive status, TICS-m) was recorded at baseline and 3 years later. At baseline, 82.83% (n = 613) of participants had normal cognitive status, 13.51% (n = 100) were classified with mild cognitive impairment (MCI), and 3.64% (n = 27) with probable dementia. The effect of three distinct patterns of poor sleep (difficulties initiating [DIS] or maintaining sleep [DMS], daytime sleepiness [DS] or sleep duration) were considered on a change in cognitive score with adjustments for potential confounders in generalized linear regression models. Cognitive decline was more pronounced in individuals with DMS compared to those with no DMS (β = 1.33, 95% CI = 0.41-2.24, P < 0.001). However, the predictive power of DMS was only significant in individuals with normal cognition and not impaired subjects at baseline. Prolonged sleep duration increased the risk for cognitive decline in cognitively impaired elderly (β = 1.86, 95% CI = 0.15-3.57, P = 0.03). Other sleep characteristics (DIS and DS) were not significantly associated with cognitive decline. DMS and long sleep duration were associated with cognitive decline in normal and cognitively impaired elderly, respectively. The identification of impaired sleep quality may offer intervention strategies to deter cognitive decline in the elderly with normal cognitive function. © 2016 Associated Professional Sleep Societies, LLC.

Association between social isolation and inflammatory markers in depressed and non-depressed individuals: results from the MONICA/KORA study.

PubMed

Häfner, S; Emeny, R T; Lacruz, M E; Baumert, J; Herder, C; Koenig, W; Thorand, B; Ladwig, K H

2011-11-01

Depressed individuals not only suffer from chronic low grade inflammation, but also exhibit an inflammatory hyper-responsiveness to acute stress. We investigate whether chronic stress also induces an exaggerated inflammatory response in individuals with increased depression features. As model for chronic stress, social isolation was chosen. Interleukin (IL)-6 and hs-CRP levels were assessed in 1547 subjects (847 men and 700 women), derived from the population-based MONICA/KORA study. Standardized questionnaires were used to assess depressed mood (depression and exhaustion subscale) and social isolation (social network index). The relationship between the two inflammatory markers, social isolation and depressed mood was examined taking into account interactions social isolation × depressed mood using multivariable linear regression models, adjusted for age, BMI, smoking, alcohol, and physical activity. Analyses were performed in men and women separately. We observed a significant interaction between depressed mood and social isolation regarding IL-6 and hs-CRP, respectively in men (p-value=0.02 for IL-6 and <0.01 for hs-CRP), evidencing a substantial synergistic effect of social isolation, and depressed mood on inflammatory responses. Furthermore, depressed and socially isolated men had highly significantly elevated IL-6 levels (geometric mean: 3.76 vs. 1.92 pg/ml, p-value <0.01) and heightened hs-CRP levels (geometric mean: 2.01 vs. 1.39 mg/l, p=0.08) in comparison with non-depressed and socially integrated men. In women, no significant associations were seen. The interaction of depressed mood and social isolation elicits a substantial synergistic impact on inflammatory markers in men, but not in depressed women. Copyright © 2011 Elsevier Inc. All rights reserved.

Reference Values of Impulse Oscillometric Lung Function Indices in Adults of Advanced Age

PubMed Central

Schulz, Holger; Flexeder, Claudia; Behr, Jürgen; Heier, Margit; Holle, Rolf; Huber, Rudolf M.; Jörres, Rudolf A.; Nowak, Dennis; Peters, Annette; Wichmann, H.-Erich; Heinrich, Joachim; Karrasch, Stefan

2013-01-01

Background Impulse oscillometry (IOS) is a non-demanding lung function test. Its diagnostic use may be particularly useful in patients of advanced age with physical or mental limitations unable to perform spirometry. Only few reference equations are available for Caucasians, none of them covering the old age. Here, we provide reference equations up to advanced age and compare them with currently available equations. Methods IOS was performed in a population-based sample of 1990 subjects, aged 45–91 years, from KORA cohorts (Augsburg, Germany). From those, 397 never-smoking, lung healthy subjects with normal spirometry were identified and sex-specific quantile regression models with age, height and body weight as predictors for respiratory system impedance, resistance, reactance, and other parameters of IOS applied. Results Women (n = 243) showed higher resistance values than men (n = 154), while reactance at low frequencies (up to 20 Hz) was lower (p<0.05). A significant age dependency was observed for the difference between resistance values at 5 Hz and 20 Hz (R5–R20), the integrated area of low-frequency reactance (AX), and resonant frequency (Fres) in both sexes whereas reactance at 5 Hz (X5) was age dependent only in females. In the healthy subjects (n = 397), mean differences between observed values and predictions for resistance (5 Hz and 20 Hz) and reactance (5 Hz) ranged between −1% and 5% when using the present model. In contrast, differences based on the currently applied equations (Vogel & Smidt 1994) ranged between −34% and 76%. Regarding our equations the indices were beyond the limits of normal in 8.1% to 18.6% of the entire KORA cohort (n = 1990), and in 0.7% to 9.4% with the currently applied equations. Conclusions Our study provides up-to-date reference equations for IOS in Caucasians aged 45 to 85 years. We suggest the use of the present equations particularly in advanced age in order to detect airway dysfunction. PMID:23691036

Dictionary of Basic Military Terms

DTIC Science & Technology

1965-04-01

having nuclear charges. 101 ATOMNAYA SILOVAYA (ENERGEHCHESKAYA) KORA- BEL’NAYA (SUDOVAYA) USTANOVKA (atomic power plant for ship propulsion )- A special...atomic power plant for ship propulsion consists of an atomic "boiler," or reactor, a turbine (steam or gas), and electro- mechanical machinery. The...type, is mounted on a heay artillery tractor chassis. A high - speed trench-digging machine can dig trenches to a depth of 1.5 meters. The machine’s

Contact allergy in patients with rosacea: a clinic-based, prospective epidemiological study.

PubMed

Jappe, U; Schäfer, T; Schnuch, A; Uter, W

2008-11-01

Rosacea is a relatively common inflammatory skin disease of unknown prevalence. The proportion of contact allergy complicating rosacea and its therapy, respectively, is largely unknown. To estimate the prevalence of specific contact allergy in rosacea patients and to compare this with the prevalence observed in the general population and in general patch test patients. In this prospective monocentre study, 78 patients with rosacea were investigated for contact sensitizations via patch testing the standard series, constituents of topical formulations, preservatives, fragrances, topically applied drugs and, if available, patient's own products. Positive reactions occurred to nickel (II) sulphate (12 of 78, 15.4%), fragrance mix I (4 of 77, 5.2%), balsam of Peru (8 of 77, 10.4%; significantly elevated prevalence compared to that observed in the population-based KORA study), potassium dichromate (4 of 78, 5.1%) and Lyral (3 of 78, 3.8%). Regarding topical antibiotics, only 1 of 78 (1.3%) patients was positive to neomycin sulphate, and none to metronidazole; however, 6 of 75 (8%) patients were positive to gentamicin sulphate, and 4 of 76 (5.3%) patients were positive to framycetin sulphate. No allergic but irritant patch test reactions, instead, were provoked by various patients' own products as well as by the irritant sodium lauryl sulphate (SLS) even in low concentrations. Despite the limited power of the study, a strikingly high prevalence of contact allergy to gentamicin sulphate was observed, which is probably due to antibiotic treatment of rosacea-associated eye symptoms. The reactions to the irritant SLS probably mirror the extreme skin sensitivity in rosacea.

Poor structural social support is associated with an increased risk of Type 2 diabetes mellitus: findings from the MONICA/KORA Augsburg cohort study.

PubMed

Altevers, J; Lukaschek, K; Baumert, J; Kruse, J; Meisinger, C; Emeny, R T; Ladwig, K H

2016-01-01

Several psychosocial factors have been shown to increase the risk of Type 2 diabetes mellitus. This study investigated the association between structural social support and incidence of Type 2 diabetes mellitus in men and women. Data were derived from three population-based MONICA/KORA surveys conducted in 1984-1995 in the Augsburg region (southern Germany) and followed up by 2009. The study population comprised 8952 participants (4669 men/4283 women) aged 30-74 years without diabetes at baseline. Structural social support was assessed using the Social Network Index. Sex-specific hazard ratios were estimated from Cox proportional hazard models. Within follow-up, 904 incident Type 2 diabetes mellitus cases (558 men, 346 women) were observed. Crude incidence rates for Type 2 diabetes mellitus per 10 000 person-years were substantially higher in poor compared with good structural social support (men: 94 vs. 69, women: 58 vs. 43). After adjustment for age, survey, parental history of diabetes, smoking status, alcohol intake, physical activity, hypertension, dyslipidaemia, BMI, education, sleep complaints and depressed mood, risk of Type 2 diabetes mellitus for participants with poor compared with good structural social support was 1.31 [95% confidence interval (CI) = 1.11-1.55] in men and 1.10 (95% CI = 0.88-1.37) in women. Stratified analyses revealed a hazard ratio of 1.50 (95% CI = 1.23-1.83) in men with a low level of education and 0.87 (95% CI = 0.62-1.22) in men with a high level of education (P for interaction: 0.0082). Poor structural social support is associated with Type 2 diabetes mellitus in men. This association is independent of risk factors at baseline and is particularly pronounced in men with a low level of education. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

Undernutrition in the Kora Mudi tribal population, West Bengal, India: a comparison of body mass index and mid-upper-arm circumference.

PubMed

Bisai, Samiran; Bose, Kaushik

2009-03-01

Undernutrition among adult tribal women is a major health problem in India. To compare the utility of two different anthropometric indicators of chronic energy deficiency (CED) among tribal Kora Mudi women and to determine which of these two is a better indicator of undernutrition. A cross-sectional study of 123 individuals was conducted. The body mass index (BMI) and mid-upper-arm circumference (MUAC) were used to evaluate CED. The prevalence of CED based on BMI less than 18.5 was 55.3%, and the prevalence of CED based on MUAC less than 22.0 cm was 51.2%. Both of these prevalence rates are classified in the very high-prevalence category (> or = 40%) and indicate a critical situation according to World Health Organization recommendations. Mean BMI increased significantly with higher quartile of MUAC. There was a significant difference in the prevalence of CED between the MUAC quartiles. The risk ratio for CED for women in the lowest quartile of MUAC was 9.33 compared with those in the highest quartile. There was a significant positive association between MUAC and BMI. Regression analysis demonstrated that MUAC had a significant positive impact on BMI; the percentage of the variation in BMI explained by MUAC was 52%. Logistic regression analysis demonstrated that overall, 82.11% of cases of CED were correctly classified with the use of MUAC. The use of MUAC correctly diagnosed 82.35% of cases of CED and 81.82% of women with normal nutritional status. This population was facing severe nutritional stress. With limited resources and in the absence of skilled manpower, it may be more appropriate to use MUAC for human population surveys, particularly among tribal populations of developing countries.

Genome-Wide Association Study of L-Arginine and Dimethylarginines Reveals Novel Metabolic Pathway for Symmetric Dimethylarginine

PubMed Central

Lüneburg, Nicole; Lieb, Wolfgang; Zeller, Tanja; Chen, Ming-Huei; Maas, Renke; Carter, Angela M.; Xanthakis, Vanessa; Glazer, Nicole L; Schwedhelm, Edzard; Seshadri, Sudha; Ikram, M. Arfan; Longstreth, W.T.; Fornage, Myriam; König, Inke R.; Loley, Christina; Ojeda, Francisco M.; Schillert, Arne; Wang, Thomas J.; Sticht, Heinrich; Kittel, Anja; König, Jörg; Benjamin, Emelia J.; Sullivan, Lisa M.; Bernges, Isabel; Anderssohn, Maike; Ziegler, Andreas; Gieger, Christian; Illig, Thomas; Meisinger, Christa; Wichmann, H.-Erich; Wild, Philipp S.; Schunkert, Heribert; Psaty, Bruce M.; Wiggins, Kerri L.; Heckbert, Susan R.; Smith, Nicholas; Lackner, Karl; Lunetta, Kathryn L.; Blankenberg, Stefan; Erdmann, Jeanette; Munzel, Thomas; Grant, Peter J.; Vasan, Ramachandran S.; Böger, Rainer H.

2016-01-01

Background Dimethylarginines (DMA) interfere with nitric oxide (NO) formation by inhibiting NO synthase (asymmetric dimethylarginine, ADMA) and L-arginine uptake into the cell (ADMA and symmetric dimethylarginine, SDMA). In prospective clinical studies ADMA has been characterized as a cardiovascular risk marker whereas SDMA is a novel marker for renal function and associated with all-cause mortality after ischemic stroke. The aim of the current study was to characterise the environmental and genetic contributions to inter-individual variability of these biomarkers. Methods and Results This study comprised a genome-wide association analysis of 3 well-characterized population-based cohorts (FHS (n=2992), GHS (n=4354) and MONICA/KORA F3 (n=581)) and identified replicated loci (DDAH1, MED23, Arg1 and AGXT2) associated with the inter-individual variability in ADMA, L-arginine and SDMA. Experimental in-silico and in-vitro studies confirmed functional significance of the identified AGXT2 variants. Clinical outcome analysis in 384 patients of the Leeds stroke study demonstrated an association between increased plasma levels of SDMA, AGXT2 variants and various cardiometabolic risk factors. AGXT2 variants were not associated with post-stroke survival in the Leeds study, nor were they associated with incident stroke in the CHARGE consortium. Conclusion These GWAS support the importance of DDAH1 and MED23/Arg1 in regulating ADMA and L-arginine metabolism, respectively, and identify a novel regulatory renal pathway for SDMA by AGXT2. AGXT2 variants might explain part of the pathogenic link between SDMA, renal function, and outcome. An association between AGXT2 variants and stroke is unclear and warrants further investigation. PMID:25245031

Symptoms of Insomnia and Sleep Duration and Their Association with Incident Strokes: Findings from the Population-Based MONICA/KORA Augsburg Cohort Study.

PubMed

Helbig, A Katharina; Stöckl, Doris; Heier, Margit; Ladwig, Karl-Heinz; Meisinger, Christa

2015-01-01

To examine the relationship between symptoms of insomnia and sleep duration and incident total (non-fatal plus fatal) strokes, non-fatal strokes, and fatal strokes in a large cohort of men and women from the general population in Germany. In four population-based MONICA (monitoring trends and determinants in cardiovascular disease)/KORA (Cooperative Health Research in the Region of Augsburg) surveys conducted between 1984 and 2001, 17,604 men and women (aged 25 to 74 years) were asked about issues like sleep, health behavior, and medical history. In subsequent surveys and mortality follow-ups, incident stroke cases (cerebral hemorrhage, ischemic stroke, transient ischemic attack, unknown stroke type) were gathered prospectively until 2009. Sex-specific hazard ratios (HR) and their 95% confidence intervals (CI) were estimated using sequential Cox proportional hazards regression models. During a mean follow-up of 14 years, 917 strokes (710 non-fatal strokes and 207 fatal strokes) were observed. Trouble falling asleep and difficulty staying asleep were not significantly related to any incident stroke outcome in either sex in the multivariable models. Among men, the HR for the association between short (≤5 hours) and long (≥10 hours) daily sleep duration and total strokes were 1.44 (95% CI: 1.01-2.06) and 1.63 (95% CI: 1.16-2.29), after adjustment for basic confounding variables. As for non-fatal strokes and fatal strokes, in the analyses adjusted for age, survey, education, physical activity, alcohol consumption, smoking habits, body mass index, hypertension, diabetes, and dyslipidemia, the increased risks persisted, albeit somewhat attenuated, but no longer remained significant. Among women, in the multivariable analyses the quantity of sleep was also not related to any stroke outcome. In the present study, symptoms of insomnia and exceptional sleep duration were not significantly predictive of incident total strokes, non-fatal strokes, and fatal strokes in either sex.

Symptoms of Insomnia and Sleep Duration and Their Association with Incident Strokes: Findings from the Population-Based MONICA/KORA Augsburg Cohort Study

PubMed Central

Helbig, A. Katharina; Stöckl, Doris; Heier, Margit; Ladwig, Karl-Heinz; Meisinger, Christa

2015-01-01

Objective To examine the relationship between symptoms of insomnia and sleep duration and incident total (non-fatal plus fatal) strokes, non-fatal strokes, and fatal strokes in a large cohort of men and women from the general population in Germany. Methods In four population-based MONICA (monitoring trends and determinants in cardiovascular disease)/KORA (Cooperative Health Research in the Region of Augsburg) surveys conducted between 1984 and 2001, 17,604 men and women (aged 25 to 74 years) were asked about issues like sleep, health behavior, and medical history. In subsequent surveys and mortality follow-ups, incident stroke cases (cerebral hemorrhage, ischemic stroke, transient ischemic attack, unknown stroke type) were gathered prospectively until 2009. Sex-specific hazard ratios (HR) and their 95% confidence intervals (CI) were estimated using sequential Cox proportional hazards regression models. Results During a mean follow-up of 14 years, 917 strokes (710 non-fatal strokes and 207 fatal strokes) were observed. Trouble falling asleep and difficulty staying asleep were not significantly related to any incident stroke outcome in either sex in the multivariable models. Among men, the HR for the association between short (≤5 hours) and long (≥10 hours) daily sleep duration and total strokes were 1.44 (95% CI: 1.01–2.06) and 1.63 (95% CI: 1.16–2.29), after adjustment for basic confounding variables. As for non-fatal strokes and fatal strokes, in the analyses adjusted for age, survey, education, physical activity, alcohol consumption, smoking habits, body mass index, hypertension, diabetes, and dyslipidemia, the increased risks persisted, albeit somewhat attenuated, but no longer remained significant. Among women, in the multivariable analyses the quantity of sleep was also not related to any stroke outcome. Conclusion In the present study, symptoms of insomnia and exceptional sleep duration were not significantly predictive of incident total strokes, non-fatal strokes, and fatal strokes in either sex. PMID:26230576

Identification and MS-assisted interpretation of genetically influenced NMR signals in human plasma

PubMed Central

2013-01-01

Nuclear magnetic resonance spectroscopy (NMR) provides robust readouts of many metabolic parameters in one experiment. However, identification of clinically relevant markers in 1H NMR spectra is a major challenge. Association of NMR-derived quantities with genetic variants can uncover biologically relevant metabolic traits. Using NMR data of plasma samples from 1,757 individuals from the KORA study together with 655,658 genetic variants, we show that ratios between NMR intensities at two chemical shift positions can provide informative and robust biomarkers. We report seven loci of genetic association with NMR-derived traits (APOA1, CETP, CPS1, GCKR, FADS1, LIPC, PYROXD2) and characterize these traits biochemically using mass spectrometry. These ratios may now be used in clinical studies. PMID:23414815

Are daylight saving time transitions associated with changes in myocardial infarction incidence? Results from the German MONICA/KORA Myocardial Infarction Registry.

PubMed

Kirchberger, Inge; Wolf, Kathrin; Heier, Margit; Kuch, Bernhard; von Scheidt, Wolfgang; Peters, Annette; Meisinger, Christa

2015-08-14

Some studies suggest that transitions to and from daylight saving time (DST) have an influence on acute myocardial infarction (AMI) incidence. However, the available publications have a number of limitations e.g. regarding sample size, exclusion of fatal AMI cases, precise assessment of AMI onset, and consideration of possible confounders, and they were conducted in countries with different geographical location. The objective of this study was to examine the association of DST transitions with AMI incidence recorded in the population-based German MONICA/KORA Myocardial Infarction Registry. The study sample consisted of 25,499 coronary deaths and non-fatal AMI cases aged 25-74 years. We used Poisson regression with indicator variables for the 3 days or the week after the spring and the autumn transition and adjusted for potential confounders to model the association between DST transitions and AMI incidence. In addition, we built an excess model by calculating observed over expected events per day. Overall, no significant changes of AMI risk during the first 3 days or 1 week after the transition to and from DST were found. However, subgroup analyses on the spring transition revealed significantly increased risks for men in the first 3 days after transition (RR 1.155, 95 % CI 1.000-1.334) and for persons who took angiotensine converting enzyme (ACE) inhibitors prior to the AMI (3 days: RR 1.489, 95 % CI 1.151-1.927; 1 week: RR 1.297, 95 % CI 1.063-1.582). After the clock shift in autumn, patients with a prior infarction had an increased risk to have a re-infarction (3 days: RR 1.319, 95 % CI 1.029-1.691; 1 week: RR 1.270, 95 % CI 1.048-1.539). Specific subgroups such as men and persons with a history of AMI or prior treatment with ACE inhibitors, may have a higher risk for AMI during DST. Further studies which include data on chronotype and sleep duration are needed in order to confirm these results.

Genome-Wide Association Study with Targeted and Non-targeted NMR Metabolomics Identifies 15 Novel Loci of Urinary Human Metabolic Individuality

PubMed Central

Raffler, Johannes; Friedrich, Nele; Arnold, Matthias; Kacprowski, Tim; Rueedi, Rico; Altmaier, Elisabeth; Bergmann, Sven; Budde, Kathrin; Gieger, Christian; Homuth, Georg; Pietzner, Maik; Römisch-Margl, Werner; Strauch, Konstantin; Völzke, Henry; Waldenberger, Melanie; Wallaschofski, Henri; Nauck, Matthias; Völker, Uwe; Kastenmüller, Gabi; Suhre, Karsten

2015-01-01

Genome-wide association studies with metabolic traits (mGWAS) uncovered many genetic variants that influence human metabolism. These genetically influenced metabotypes (GIMs) contribute to our metabolic individuality, our capacity to respond to environmental challenges, and our susceptibility to specific diseases. While metabolic homeostasis in blood is a well investigated topic in large mGWAS with over 150 known loci, metabolic detoxification through urinary excretion has only been addressed by few small mGWAS with only 11 associated loci so far. Here we report the largest mGWAS to date, combining targeted and non-targeted 1H NMR analysis of urine samples from 3,861 participants of the SHIP-0 cohort and 1,691 subjects of the KORA F4 cohort. We identified and replicated 22 loci with significant associations with urinary traits, 15 of which are new (HIBCH, CPS1, AGXT, XYLB, TKT, ETNPPL, SLC6A19, DMGDH, SLC36A2, GLDC, SLC6A13, ACSM3, SLC5A11, PNMT, SLC13A3). Two-thirds of the urinary loci also have a metabolite association in blood. For all but one of the 6 loci where significant associations target the same metabolite in blood and urine, the genetic effects have the same direction in both fluids. In contrast, for the SLC5A11 locus, we found increased levels of myo-inositol in urine whereas mGWAS in blood reported decreased levels for the same genetic variant. This might indicate less effective re-absorption of myo-inositol in the kidneys of carriers. In summary, our study more than doubles the number of known loci that influence urinary phenotypes. It thus allows novel insights into the relationship between blood homeostasis and its regulation through excretion. The newly discovered loci also include variants previously linked to chronic kidney disease (CPS1, SLC6A13), pulmonary hypertension (CPS1), and ischemic stroke (XYLB). By establishing connections from gene to disease via metabolic traits our results provide novel hypotheses about molecular mechanisms involved in the etiology of diseases. PMID:26352407

[Endemic syphillis in Upper Volta. A peculiar aspect of the epidemiological profile].

PubMed

Bourdillon, F; Monjour, L; Druilhe, P; Fribourg-Blanc, A; Kyelem, J M; Chastang, C; Gentilini, M

1981-01-01

A seroimmunological survey was realised in Upper Volta using an indirect immunofluorescence technique. It showed that endemic syphilis also known as bejel is not exclusively encountered in Sahelian regions. So, in Kora village which is located in a savannah area prevalence was around 10.3%. The disease particularly affects males. Congenital syphilis is certainly exceptional for first cases of serological treponematosis were only detected after 5 years. Endemic syphilis distribution in microfocuses in the village area underlines that promiscuity acts as a contributing factor for contamination.

Recognition of strong earthquake-prone areas with a single learning class

NASA Astrophysics Data System (ADS)

Gvishiani, A. D.; Agayan, S. M.; Dzeboev, B. A.; Belov, I. O.

2017-05-01

This article presents a new Barrier recognition algorithm with learning, designed for recognition of earthquake-prone areas. In comparison to the Crust (Kora) algorithm, used by the classical EPA approach, the Barrier algorithm proceeds with learning just on one "pure" high-seismic class. The new algorithm operates in the space of absolute values of the geological-geophysical parameters of the objects. The algorithm is used for recognition of earthquake-prone areas with M ≥ 6.0 in the Caucasus region. Comparative analysis of the Crust and Barrier algorithms justifies their productive coherence.

Triple Burden of Obesity, Undernutrition, and Cardiovascular Disease Risk among Indian Tribes

PubMed Central

2016-01-01

Background Socio-cultural transitions among individuals from vulnerable groups introduce epidemiological transition, with a concomitant increase in the prevalence of undernutrition, obesity, and cardiovascular disease risks. An accepted conventional wisdom exists for Indian tribes that they are undernourished and away from lifestyle-related diseases. However, the extent of this triple burden affecting them is unknown. In this study, we assessed this triple burden among the 9 major tribes of India. Methods and Findings During January 2011 to December 2013, we conducted a cross-sectional study among 1066 men and 1090 women constituting a total of 2156 adults belonging to the 9 major tribal groups: Santals, Oraons, and Koras (West Bengal); Santals, Bhumijs, and Bathudis (Odisha); and Dhodias, Kuknas, and Chaudharis (Gujarat) to estimate the prevalence of the triple burden (undernutrition, overweight or obesity, and hypertension). A high prevalence of undernutrition and hypertension was observed among the Koras (51.9%and 10.6%, respectively), Bathudis (51.3% and 12.1%, respectively), and Oraons (49.6% and 16.5%, respectively). However, the prevalence of overweight and hypertension among the Bhumijs (17.7% and 14.7%, respectively), Dhodias (23.8% and 12.9%, respectively), Kuknas (15.8% and 11.3%, respectively), and Santals of West Bengal (12.2% and 11.8%, respectively) and Odisha (15% and 9.6%, respectively) was most alarming. The prevalence of overweight or obesity among the women was 10.9% and 1.5%, respectively, with 14.0% hypertensive women. The prevalence of overweight and obesity among the men was 14.8% and 1.7%, respectively, with 9.2% hypertensive men. Undernutrition was highly prevalent among men and women. However, data from the past 30 years on systolic blood pressure (SBP) and body mass index (BMI) revealed that the studied tribes were at a higher risk than the general Indian population. In addition, a vast gender disparity with relation to the disease and risk prevalence was observed. Conclusion The alarming trend of an increasing prevalence of overweight/obesity, undernutrition, and hypertension is observed among indigenous populations of India, emphasizing the incorporation of a specific health management policy. PMID:26808418

Association between variations in the TLR4 gene and incident type 2 diabetes is modified by the ratio of total cholesterol to HDL-cholesterol

PubMed Central

Kolz, Melanie; Baumert, Jens; Müller, Martina; Khuseyinova, Natalie; Klopp, Norman; Thorand, Barbara; Meisinger, Christine; Herder, Christian; Koenig, Wolfgang; Illig, Thomas

2008-01-01

Background Toll-like receptor 4 (TLR4), the signaling receptor for lipopolysaccharides, is an important member of the innate immunity system. Since several studies have suggested that type 2 diabetes might be associated with changes in the innate immune response, we sought to investigate the association between genetic variants in the TLR4 gene and incident type 2 diabetes. Methods A case-cohort study was conducted in initially healthy, middle-aged subjects from the MONICA/KORA Augsburg studies including 498 individuals with incident type 2 diabetes and 1,569 non-cases. Seven SNPs were systematically selected in the TLR4 gene and haplotypes were reconstructed. Results The effect of TLR4 SNPs on incident type 2 diabetes was modified by the ratio of total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C). In men, four out of seven TLR4 variants showed significant interaction with TC/HDL-C after correction for multiple testing (p < 0.01). The influence of the minor alleles of those variants on the incidence of type 2 diabetes was observed particularly for male patients with high values of TC/HDL-C. Consistent with these findings, haplotype-based analyses also revealed that the effect of two haplotypes on incident type 2 diabetes was modified by TC/HDL-C in men (p < 10-3). However, none of the investigated variants or haplotypes was associated with type 2 diabetes in main effect models without assessment of effect modifications. Conclusion We conclude that minor alleles of several TLR4 variants, although not directly associated with type 2 diabetes might increase the risk for type 2 diabetes in subjects with high TC/HDL-C. Additionally, our results confirm previous studies reporting sex-related dissimilarities in the development of type 2 diabetes. PMID:18298826

Body weight dissatisfaction by socioeconomic status among obese, preobese and normal weight women and men: results of the cross-sectional KORA Augsburg S4 population survey.

PubMed

von Lengerke, Thomas; Mielck, Andreas

2012-05-09

Body weight dissatisfaction is an important factor in preventing weight gain and promoting weight loss or maintenance. This study focuses on differences in the rates of body weight dissatisfaction among obese, preobese and normal weight women and men by socioeconomic status within a general adult population in Germany. Data were analyzed from 4186 adults aged 25 to 74 who participated in a cross-sectional, representative population-based health survey (KORA S4, 1999-2001, Augsburg region/Germany). Body mass was measured anthropometrically and indexed following international standards. Among the 2123 women participating in the survey, 40.3% had a normal weight, 34.9% were preobese, and 24.8% were obese (compared to 25.9%, 51.4% and 22.6% among men, respectively). Body weight dissatisfaction, educational level, household income and occupational status were assessed by computer-aided personal interviewing. An index for socioeconomic status was calculated and categorized into quintiles. Multiple logistic regressions were performed to test for differences in the odds of body weight dissatisfaction across socioeconomic strata in normal weight, preobese and obese groups. Body mass index, age, family status, place of residence and health behaviors were adjusted for. Overall, being dissatisfied with one's body weight was more prevalent in women (48.3%) than in men (33.2%). In the normal weight group, no significant differences in the odds of being dissatisfied were found across socioeconomic groups among women or men. Among preobese men, compared to the lowest socioeconomic stratum, increased odds of being dissatisfied with one's body weight were associated with the highest socioeconomic index group (OR = 2.3, 95% CI: 1.4-3.8), middle and high educational level (OR = 1.6, 95% CI: 1.1-2.3, and OR = 1.9, 95% CI: 1.3-3.7), high income (OR = 1.8, 95% CI: 1.2-2.7), and middle and high occupational status (both OR = 1.8, 95% CI: 1.2-2.6). Among preobese women, the odds of being dissatisfied were only significantly elevated in those with a middle educational level (OR = 1.6, 95% CI: 1.1-2.3). Among obese men, elevated odds were found in the highest socioeconomic index group (OR = 3.7, 95% CI: 1.8-7.5) and in those with a high educational level (OR = 2.3, 95% CI: 1.3-4.1), high income (OR = 2.6, 95% CI: 1.4-4.7), and middle and high occupational status (both OR = 2.2, 95% CI: 1.3-3.6). The odds of dissatisfaction among obese women were not associated with socioeconomic status as a whole, but were associated with a high educational level, albeit with a comparatively large confidence interval (OR = 3.6, 95% CI: 1.0-12.8). In Germany, body weight dissatisfaction is more prevalent among obese and preobese men in high socioeconomic status groups, a pattern not found in women. The exception to this is a greater prevalence of dissatisfaction among obese and preobese women with a high educational level (albeit inconsistently). Moreover, there is a social gradient in body weight dissatisfaction, especially in obese men, which may partly explain why obesity is more prevalent in men with low socioeconomic status. It also suggests that they are a target group for obesity care in which body weight satisfaction is an important topic.

The privacy-reciprocity connection in biobanking: comparing German with UK strategies.

PubMed

Hobbs, A; Starkbaum, J; Gottweis, U; Wichmann, H E; Gottweis, H

2012-01-01

In recent years, the adequacy of the 'gift' model of research participation has been increasingly questioned. This study used focus groups to explore how potential and actual participants of biobanks in the UK and Germany negotiate the relationship between concerns over privacy protection, reciprocity and benefit sharing. In Germany, 15 focus groups (n = 151) were conducted: 11 general public groups (n = 116) and 4 with former cohort study participants including the KORA and the Popgen cohort study (n = 35). In the UK, 9 focus groups (n = 61) were conducted: 4 general public groups (n = 33) and 5 with UK Biobank and European Huntington's Disease (Euro-HD) Registry biorepository participants (n = 28). Forms of reciprocity were found to partially mitigate potential and actual biobank participants' concerns over personal privacy risks and future unintended consequences of biobank in both Germany and the UK. Specifically, notions of individual reciprocity were at the forefront in the context of personal disadvantages to participation, while communal reciprocity was prominent when potential and actual participants were discussing the uncertainty of the long-term nature of biobanking. The research indicates that reciprocity can be viewed as a mode to deal with individuals' concerns about participating in a biobank, both by acting as a return 'favor' or 'gift,' and through establishing an ongoing relationship between participants, researchers and society. It is suggested that future biobanking projects will need to flexibly combine individual and communal forms of reciprocity if they are to recruit and maintain sufficient numbers of participants. Copyright © 2012 S. Karger AG, Basel.

Air Force Support of Army Ground Operations Lessons Learned during World War II, Korea, and Vietnam

DTIC Science & Technology

1989-03-06

Th ;e 8epre--cdin this paper .rv thoe. of ’:ceauhor IDep 2rtmt-nt of Diefense rayo t gr: s hsPcC % FOC, O P 0- C GOUND OP!-txA’TONS ’A NS tTAI.D 11...NOTE S T edder, Wi.th Preudice: The War Memoirs . - y Air Force. Lord Tedaer. rr- 40-43. 2.".~ : X :"~ , M~.c, ’ = A r Power in Three Wars WW 7:, Kora...that FEAF assume operational control over land based Marine air units and over carri.er bjdsed aviation operating over Korea effective as soon as X

Time trends in type 2 diabetes patients' disease management and outcomes: evidence from two KORA surveys in Germany.

PubMed

Schunk, M; Schweikert, B; Gapp, O; Reitmeir, P; Meisinger, C; Mielck, A; Holle, R

2009-02-01

To explore time trends in diabetes management and intermediate health outcomes of people with type 2 diabetes, data from two population-based survey studies were compared. The surveys were conducted in the Augsburg region of Southern Germany in 1997/98 and in 2004/05, and included physical examinations, interviews, self-administered questionnaires and laboratory tests. Data from 334 participants aged 40-84 were analysed, including a longitudinal sub-sample of 50 persons. Results show significant time trends towards improvements over the seven year period. Controlling for age, sex, education and duration of diabetes, people felt better informed about diabetes (Odds Ratio (OR) 1.87; 95% CI: 1.12, 3.14) and stated greater adherence to the treatment plan (OR 4.42; CI: 2.62, 7.45) as well as higher participation in diabetes education programmes (OR 2.20; CI: 1.44, 3.38). Mean haemoglobin A1c levels decreased by -0.97% from 7.3% to 6.3% (CI:-0.66%, -1.28%). Physical activity (> or =1 h/week) was more frequent (OR 2.75; CI: 1.65, 4.59), although Body Mass Index increased by 1.43 kg/m (2) (CI: 0.86, 2.00). The positive changes in disease management and metabolic outcomes for type 2 diabetic patients between 1997/98 and 2004/05 indicate a shift towards greater patient involvement in diabetes care and possibly more efficient medical management practices.

Subclinical changes in MRI-determined right ventricular volumes and function in subjects with prediabetes and diabetes.

PubMed

Patscheider, Hannah; Lorbeer, Roberto; Auweter, Sigrid; Schafnitzel, Anina; Bayerl, Christian; Curta, Adrian; Rathmann, Wolfgang; Heier, Margit; Meisinger, Christa; Peters, Annette; Bamberg, Fabian; Hetterich, Holger

2018-07-01

The aim of this study was to assess subclinical changes in right ventricular volumes and function in subjects with prediabetes and diabetes and controls without a history of cardiovascular disease. Data from 400 participants in the KORA FF4 study without self-reported cardiovascular disease who underwent 3-T whole-body MRI were obtained. The right ventricle was evaluated using the short axis and a four-chamber view. Diabetes was defined according to WHO criteria. Associations between glucose tolerance and right ventricular parameters were assessed using multivariable adjusted linear regression models. Data from 337 participants were available for analysis. Of these, 43 (13%) had diabetes, 87 (26%) had prediabetes, and 207 (61%) were normoglycaemic controls. There was a stepwise decrease in right ventricular volumes in men with prediabetes and diabetes in comparison with controls, including right ventricular end-diastolic volume (β = -20.4 and β = -25.6, respectively; p ≤ 0.005), right ventricular end-systolic volume (β = -12.3 and β = -12.7, respectively; p ≤ 0.037) and right ventricular stroke volume (β = -8.1 and β = -13.1, respectively, p ≤ 0.016). We did not observe any association between prediabetes or diabetes and right ventricular volumes in women or between prediabetes or diabetes and right ventricular ejection fraction in men and women. This study points towards early subclinical changes in right ventricular volumes in men with diabetes and prediabetes. • MRI was used to detect subclinical changes in right ventricular parameters. • Diabetes mellitus is associated with right ventricular dysfunction. • Impairment of right ventricular volumes seems to occur predominantly in men.

Long-term associations of modeled and self-reported measures of exposure to air pollution and noise at residence on prevalent hypertension and blood pressure.

PubMed

Pitchika, Anitha; Hampel, Regina; Wolf, Kathrin; Kraus, Ute; Cyrys, Josef; Babisch, Wolfgang; Peters, Annette; Schneider, Alexandra

2017-09-01

Air pollution, traffic noise and noise annoyance are suggested to be associated with hypertension and blood pressure (BP); however, the evidence remains inconsistent. Our study examined the long-term associations of modeled and self-reported measures of air pollution and traffic noise on prevalent hypertension and BP. We analyzed cross-sectional data from 2552 participants aged 31-72years from the KORA F4 (2006-2008) study conducted in the region of Augsburg, Germany. Land-use regression models were used to estimate residential long-term exposure to particulate matter <2.5μm (PM 2.5 ), soot content of PM 2.5 (PM 2.5 abs) and nitrogen dioxide (NO 2 ). Road traffic noise levels at the facade of the dwellings were estimated for the participants' residences. Participants filled-in a questionnaire on noise annoyance and heavy traffic passing their residence. Linear and logistic regression models adjusting for confounders were used to assess the association between exposure measures and hypertension and BP. An interquartile increase in annual mean PM 2.5 (1μg/m 3 ) was significantly associated with 15% higher prevalence of hypertension, without (95% CI: 2.5; 28.0%) and with (95% CI: 0.7; 30.8%) adjustment for traffic noise. Diastolic blood pressure (DBP) was associated with air pollutants and traffic noise with percent increases in mean of 0.7 (95% CI: 0.2; 1.2), 0.6 (95% CI: 0.1; 1.1) and 0.3 (95% CI: 0.0; 0.7) for an interquartile increase in PM 2.5 (1μg/m 3 ) and PM 2.5 abs (0.2∗10 -5 /m), and 5dB(A) increase in 24-hour road traffic noise, respectively. Associations of PM 2.5 abs and NO 2 with hypertension or DBP were stronger in men and diabetic individuals. No clear associations were seen with systolic BP or noise annoyance. In conclusion, self-reported measures of air pollution or noise did not perform better than the objective measures. Our findings provide further evidence for a link between air pollution, noise and cardiovascular disease and indicate a stronger association for men and diabetic individuals. Copyright © 2017 Elsevier B.V. All rights reserved.

Body weight dissatisfaction by socioeconomic status among obese, preobese and normal weight women and men: results of the cross-sectional KORA Augsburg S4 population survey

PubMed Central

2012-01-01

Background Body weight dissatisfaction is an important factor in preventing weight gain and promoting weight loss or maintenance. This study focuses on differences in the rates of body weight dissatisfaction among obese, preobese and normal weight women and men by socioeconomic status within a general adult population in Germany. Methods Data were analyzed from 4186 adults aged 25 to 74 who participated in a cross-sectional, representative population-based health survey (KORA S4, 1999–2001, Augsburg region/Germany). Body mass was measured anthropometrically and indexed following international standards. Among the 2123 women participating in the survey, 40.3% had a normal weight, 34.9% were preobese, and 24.8% were obese (compared to 25.9%, 51.4% and 22.6% among men, respectively). Body weight dissatisfaction, educational level, household income and occupational status were assessed by computer-aided personal interviewing. An index for socioeconomic status was calculated and categorized into quintiles. Multiple logistic regressions were performed to test for differences in the odds of body weight dissatisfaction across socioeconomic strata in normal weight, preobese and obese groups. Body mass index, age, family status, place of residence and health behaviors were adjusted for. Results Overall, being dissatisfied with one’s body weight was more prevalent in women (48.3%) than in men (33.2%). In the normal weight group, no significant differences in the odds of being dissatisfied were found across socioeconomic groups among women or men. Among preobese men, compared to the lowest socioeconomic stratum, increased odds of being dissatisfied with one’s body weight were associated with the highest socioeconomic index group (OR = 2.3, 95% CI: 1.4–3.8), middle and high educational level (OR = 1.6, 95% CI: 1.1–2.3, and OR = 1.9, 95% CI: 1.3–3.7), high income (OR = 1.8, 95% CI: 1.2–2.7), and middle and high occupational status (both OR = 1.8, 95% CI: 1.2–2.6). Among preobese women, the odds of being dissatisfied were only significantly elevated in those with a middle educational level (OR = 1.6, 95% CI: 1.1–2.3). Among obese men, elevated odds were found in the highest socioeconomic index group (OR = 3.7, 95% CI: 1.8–7.5) and in those with a high educational level (OR = 2.3, 95% CI: 1.3–4.1), high income (OR = 2.6, 95% CI: 1.4–4.7), and middle and high occupational status (both OR = 2.2, 95% CI: 1.3–3.6). The odds of dissatisfaction among obese women were not associated with socioeconomic status as a whole, but were associated with a high educational level, albeit with a comparatively large confidence interval (OR = 3.6, 95% CI: 1.0–12.8). Conclusions In Germany, body weight dissatisfaction is more prevalent among obese and preobese men in high socioeconomic status groups, a pattern not found in women. The exception to this is a greater prevalence of dissatisfaction among obese and preobese women with a high educational level (albeit inconsistently). Moreover, there is a social gradient in body weight dissatisfaction, especially in obese men, which may partly explain why obesity is more prevalent in men with low socioeconomic status. It also suggests that they are a target group for obesity care in which body weight satisfaction is an important topic. PMID:22571239

Alanine and glycine conjugates of (2S,4R)-4-[18F]fluoroglutamine for tumor imaging.

PubMed

Zha, Zhihao; Ploessl, Karl; Lieberman, Brian P; Wang, Limin; Kung, Hank F

2018-05-01

Glutamine is an essential source of energy, metabolic substrates, and building block for supporting tumor proliferation. Previously, (2S,4R)-4-[ 18 F]fluoroglutamine (4F-Gln) was reported as a glutamine-related metabolic imaging agent. To improve the in vivo kinetics of this radiotracer, two new dipeptides, [ 18 F]Gly-(2S,4R)4-fluoroglutamine (Gly-4F-Gln) and [ 18 F]Ala-(2S,4R)4-fluoroglutamine (Ala-4F-Gln) were investigated. Radiolabeling was performed via 2-steps 18 F-fluorination. Cell uptake studies of Gly-4F-Gln and Ala-4F-Gln were investigated in 9 L cell lines. In vitro and in vivo metabolism studies were carried out in Fisher 344 rats. Biodistribution and microPET imaging studies were performed in 9 L tumor-bearing rats. In vitro incubation of these [ 18 F]dipeptides in rat and human blood showed a rapid conversion to (2S,4R)-4-[ 18 F]fluoroglutamine (t 1/2  = 2.3 and 0.2 min for [ 18 F]Gly-4F-Gln and [ 18 F]Ala-4F-Gln, respectively for human blood). Biodistribution and PET imaging in Fisher 344 rats bearing 9 L tumor xenografts showed that these dipeptides rapidly localized in the tumors, comparable to that of (2S,4R)-4-[ 18 F]fluoroglutamine (4F-Gln). The results support that these dipeptides, [ 18 F]Gly-4F-Gln and [ 18 F]Ala-4F-Gln, are prodrugs, which hydrolyze in the blood after an iv injection. They appear to be selectively taken up and trapped by tumor tissue in vivo. The dipeptide, [ 18 F]Ala-4F-Gln, may be suitable as a PET tracer for imaging glutaminolysis in tumors. Copyright © 2018 Elsevier Inc. All rights reserved.

The Completely Sequenced Plasmid pEST4011 Contains a Novel IncP1 Backbone and a Catabolic Transposon Harboring tfd Genes for 2,4-Dichlorophenoxyacetic Acid Degradation

PubMed Central

Vedler, Eve; Vahter, Merle; Heinaru, Ain

2004-01-01

The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D)-degrading bacterium Achromobacter xylosoxidans subsp. denitrificans strain EST4002 contains plasmid pEST4011. This plasmid ensures its host a stable 2,4-D+ phenotype. We determined the complete 76,958-bp nucleotide sequence of pEST4011. This plasmid is a deletion and duplication derivative of pD2M4, the 95-kb highly unstable laboratory ancestor of pEST4011, and was self-generated during different laboratory manipulations performed to increase the stability of the 2,4-D+ phenotype of the original strain, strain D2M4(pD2M4). The 47,935-bp catabolic region of pEST4011 forms a transposon-like structure with identical copies of the hybrid insertion element IS1071::IS1471 at the two ends. The catabolic regions of pEST4011 and pJP4, the best-studied 2,4-D-degradative plasmid, both contain homologous, tfd-like genes for complete 2,4-D degradation, but they have little sequence similarity other than that. The backbone genes of pEST4011 are most similar to the corresponding genes of broad-host-range self-transmissible IncP1 plasmids. The backbones of the other three IncP1 catabolic plasmids that have been sequenced (the 2,4-D-degradative plasmid pJP4, the haloacetate-catabolic plasmid pUO1, and the atrazine-catabolic plasmid pADP-1) are nearly identical to the backbone of R751, the archetype plasmid of the IncP1 β subgroup. We show that despite the overall similarity in plasmid organization, the pEST4011 backbone is sufficiently different (51 to 86% amino acid sequence identity between individual backbone genes) from the backbones of members of the three IncP1 subgroups (the α, β, and γ subgroups) that it belongs to a new IncP1subgroup, the δ subgroup. This conclusion was also supported by a phylogenetic analysis of the trfA2, korA, and traG gene products of different IncP1 plasmids. PMID:15489427

Transcytosis of F4 fimbriae by villous and dome epithelia in F4-receptor positive pigs supports importance of receptor-dependent endocytosis in oral immunization strategies.

PubMed

Snoeck, Veerle; Van den Broeck, Wim; De Colvenaer, Veerle; Verdonck, Frank; Goddeeris, Bruno; Cox, Eric

2008-07-15

Very few antigens have been described that induce an intestinal immunity when given orally. Our laboratory demonstrated that oral administration of isolated F4 (K88) fimbriae of Escherichia coli to F4-receptor positive (F4R(+)) pigs induces protective mucosal immunity against challenge infection. However, presence of F4-receptors (F4R) on villous enterocytes is a prerequisite for inducing the immune response, as no F4-specific antibody-secreting cells (ASC) can be induced in F4R(-) pigs. In this study, the in vivo binding of isolated F4 fimbriae (F4) to the gut epithelium was examined in F4R(+) and F4R(-) pigs. It was further investigated whether binding of F4 to the F4R results in endocytosis in and translocation across the gut epithelium using microscopy. F4 did not adhere to the intestinal epithelium of F4R(-) pigs, whereas it strongly adhered to the villous epithelium and the follicle-associated epithelium (FAE) of the jejunum and ileum of F4R(+) pigs. Following binding to F4R, F4 was endocytosed by villous enterocytes, follicle-associated enterocytes and M cells. Transcytosis of F4 across the epithelium resulted in the appearance of F4 in the lamina propria and dome region of the jejunal and ileal PP. This is the first study showing transcytosis of fimbriae across the gut epithelium. This receptor-dependent transcytosis can explain the success of F4 fimbriae as oral immunogen for inducing protective immunity in F4R(+) pigs strengthening the importance of receptor-dependent endocytosis and translocation in oral vaccine strategies. Further identification of the receptor responsible for this transport is in progress.

Examining the Impact of a University-driven Exercise Programming Event on End-of-semester Stress in Students.

PubMed

Koschel, Tessa L; Young, John C; Navalta, James W

2017-01-01

Stress levels in university students peak during the final exam period. An inverse association exists between Physical Activity (PA) and poor mental health. UNLV has created Fitness4Finals (F4F), an event novel in its approach to academic stress reduction by incorporating both physical activity and mental relaxation. To our knowledge, a university-driven programming event aimed at reducing physiological and psychological stress among students approaching final exams had never been studied. Therefore, the aims of this research were to 1) examine the influence of F4F on physiological stress and perceived psychological stress (PPS) and 2) to examine the relationship between physiological stress and PPS. Fifteen full-time university students were recruited to participate in their choice of one of two groups: F4F or control (NonF4F). Pre-F4F and post-F4F measures of physiological stress, measured by salivary cortisol, and perceived psychological stress, measured by survey were collected. The F4F event was held the week prior to final examinations. Participants in the F4F group engaged in one F4F activity per day for the duration of the 3-day event. Results of the repeated measures MANOVA indicated nonsignificant interaction (p = .864) between F4F participation, physiological stress and PPS. PPS and cortisol were not correlated at the onset of the study (r = -0.18, p = 0.48) or at the last sampling period (r = 0.097, p = 0.73). Preemptive elevated levels of PA in the F4F group may have influenced results. Qualitative data indicates a unanimous perceived reduction in stress from F4F participation. While the physiological measures of stress in the present study were not significantly different, the perceived stress reduction reported by F4F participants is influential. Further investigation with improvements in timing and measurement tools is warranted.

Semiconductor grade, solar silicon purification project

NASA Technical Reports Server (NTRS)

Ingle, W. M.; Chaney, R.; Thompson, S.

1977-01-01

The potential for a three step SiF2 polymer transport purification process was examined. The process involves reacting low cost mg silicon with SiF4 to yield SiF2 gas which is condensed to form polymeric (SiF2)x. The polymer is then heated above 400 C to yield Si, SiF4 and higher Si sub n F sub 2n+2 homologues. This report presents and discusses continuing progress on (1) observations on (SiF2)x polymer formation and depolymerization on the small coil, (2) mass balance studies, (3) partial pressures of SiF2 and SiF4, (4) AlF3 mass spectral studies, and (5) material analysis studies.

Clathrin-mediated endocytosis and transcytosis of enterotoxigenic Escherichia coli F4 fimbriae in porcine intestinal epithelial cells.

PubMed

Rasschaert, Kristien; Devriendt, Bert; Favoreel, Herman; Goddeeris, Bruno M; Cox, Eric

2010-10-15

Enterotoxigenic Escherichia coli (ETEC) cause severe diarrhea in neonatal and recently weaned piglets. Previously, we demonstrated that oral immunization of F4 receptor positive piglets with purified F4 fimbriae induces a protective F4-specific intestinal immune response. However, in F4 receptor negative animals no F4-specific immune response can be elicited, indicating that the induction of an F4-specific mucosal immune response upon oral immunisation is receptor-dependent. Although F4 fimbriae undergo transcytosis across the intestinal epithelium in vivo, the endocytosis pathways used remain unknown. In the present study, we characterized the internalization of F4 fimbriae in the porcine intestinal epithelial cell line IPEC-J2. The results in the present study demonstrate that F4 fimbriae are internalized through a clathrin-dependent pathway. Furthermore, our results suggest that F4 fimbriae are transcytosed across differentiated IPEC-J2 cells. This receptor-dependent transcytosis of F4 fimbriae may explain the immunogenicity of these fimbriae upon oral administration in vivo. (c) 2010 Elsevier B.V. All rights reserved.

Comparison of Ion Chemistries in Octafluoro-2-butene (2-C4F8) and in Octfluorocyclobutane (c-C4F8)

NASA Astrophysics Data System (ADS)

Jiao, Charles; Dejoseph, Charles; Garscadden, Alan

2007-10-01

2-C4F8 is one of the promising candidates to replace c-C4F8 that has been widely used for dielectric etching but is not environmentally friendly. In this study we have investigated electron impact ionization and ion-molecule reactions of 2-C4F8 using Fourier transform mass spectrometry (FTMS), and compared the results with those of c-C4F8 we have studied previously. Electron impact ionization of 2-C4F8 produces 15 ionic species including C4F7,8^+, C3F3,5,6^+, C2F4^+ and CF1-3^+ as the major ions. The total ionization cross section of 2-C4F8 reaches a maximum of 1.8x10-15 cm^2 at 90 eV. The ionization is dominated by the channel forming the parent ion C4F8^+ from 12 to 18 eV, and by the channel forming C3F5^+ from 18 to 70 eV. After 70 eV, CF3^+ becomes the dominant product ion. Among the major ions generated from the electron impact ionization of 2-C4F8, only CF^+, CF2^+ and CF3^+ are found to react with 2-C4F8, via F^- abstraction or charge transfer mechanism. The charge transfer reaction of Ar^++2-C4F8 produces primarily C4F7^+.

Epigenetics meets metabolomics: an epigenome-wide association study with blood serum metabolic traits

PubMed Central

Petersen, Ann-Kristin; Zeilinger, Sonja; Kastenmüller, Gabi; Römisch-Margl, Werner; Brugger, Markus; Peters, Annette; Meisinger, Christine; Strauch, Konstantin; Hengstenberg, Christian; Pagel, Philipp; Huber, Fritz; Mohney, Robert P.; Grallert, Harald; Illig, Thomas; Adamski, Jerzy; Waldenberger, Melanie; Gieger, Christian; Suhre, Karsten

2014-01-01

Previously, we reported strong influences of genetic variants on metabolic phenotypes, some of them with clinical relevance. Here, we hypothesize that DNA methylation may have an important and potentially independent effect on human metabolism. To test this hypothesis, we conducted what is to the best of our knowledge the first epigenome-wide association study (EWAS) between DNA methylation and metabolic traits (metabotypes) in human blood. We assess 649 blood metabolic traits from 1814 participants of the Kooperative Gesundheitsforschung in der Region Augsburg (KORA) population study for association with methylation of 457 004 CpG sites, determined on the Infinium HumanMethylation450 BeadChip platform. Using the EWAS approach, we identified two types of methylome–metabotype associations. One type is driven by an underlying genetic effect; the other type is independent of genetic variation and potentially driven by common environmental and life-style-dependent factors. We report eight CpG loci at genome-wide significance that have a genetic variant as confounder (P = 3.9 × 10−20 to 2.0 × 10−108, r2 = 0.036 to 0.221). Seven loci display CpG site-specific associations to metabotypes, but do not exhibit any underlying genetic signals (P = 9.2 × 10−14 to 2.7 × 10−27, r2 = 0.008 to 0.107). We further identify several groups of CpG loci that associate with a same metabotype, such as 4-vinylphenol sulfate and 4-androsten-3-beta,17-beta-diol disulfate. In these cases, the association between CpG-methylation and metabotype is likely the result of a common external environmental factor, including smoking. Our study shows that analysis of EWAS with large numbers of metabolic traits in large population cohorts are, in principle, feasible. Taken together, our data suggest that DNA methylation plays an important role in regulating human metabolism. PMID:24014485

Preliminary Study on LiF4-ThF4-PuF4 Utilization as Fuel Salt of miniFUJI Molten Salt Reactor

NASA Astrophysics Data System (ADS)

Waris, Abdul; Aji, Indarta K.; Pramuditya, Syeilendra; Widayani; Irwanto, Dwi

2016-08-01

miniFUJI reactor is molten salt reactor (MSR) which is one type of the Generation IV nuclear energy systems. The original miniFUJI reactor design uses LiF-BeF2-ThF4-233UF4 as a fuel salt. In the present study, the use of LiF4-ThF4-PuF4 as fuel salt instead of LiF-BeF2-ThF4-UF4 will be discussed. The neutronics cell calculation has been performed by using PIJ (collision probability method code) routine of SRAC 2006 code, with the nuclear data library is JENDL-4.0. The results reveal that the reactor can attain the criticality condition with the plutonium concentration in the fuel salt is equal to 9.16% or more. The conversion ratio diminishes with the enlarging of plutonium concentration in the fuel. The neutron spectrum of miniFUJI MSR with plutonium fuel becomes harder compared to that of the 233U fuel.

High susceptibility prevalence for F4+ and F18+Escherichia coli in Flemish pigs.

PubMed

Nguyen, Ut V; Coddens, Annelies; Melkebeek, Vesna; Devriendt, Bert; Goetstouwers, Tiphanie; Poucke, Mario Van; Peelman, Luc; Cox, Eric

2017-04-01

F4 and/or F18 enterotoxigenic Escherichia coli (F4 + /F18 + ETEC) are responsible for diarrhea while F18 + verotoxigenic E. coli (F18 + VTEC) cause edema disease in pigs. Both infections can result in severe economic losses, which are mainly the result of the medication, growth retardation and mortality. The susceptibility of piglets to these pathogens is determined by the presence of F4 and F18 receptors (F4R and F18R). Understanding the composition of the susceptibility phenotypes of pigs is useful for animal health and breeding management. This study aimed to determine the prevalence of the F4 ETEC susceptibility phenotypes and F18 + E. coli susceptibility among Flemish pig breeds by using the in vitro villous adhesion assay. In this study, seven F4 ETEC susceptibility phenotypes were found, namely A (F4 ab R + , ac R + , ad R + ; 59.16%), B (F4 ab R + , ac R + , ad R - ; 6.28%), C (F4 ab R + , ac R - , ad R + ; 2.62%), D (F4 ab R - , ac R - , ad R + ; 6.28%), E (F4 ab R - , ac R - , ad R - ; 24.08%), F (F4 ab R + , ac R - , ad R - ; 1.05%) and G (F4 ab R - , ac R + , ad R - ; 0.52%). F4ab and F4ac E. coli showed a stronger degree of adhesion to the intestinal villi (53.40% and 52.88% strong adhesion, respectively), compared to F4ad E. coli (43.46% strong adhesion). Furthermore, the correlation between F4ac and F4ab adhesion was higher (r=0.78) than between F4ac and F4ad adhesion (r=0.41) and between F4ab and F4ad adhesion (r=0.57). For F18 + E. coli susceptibility, seven out of 82 pigs were F18R negative (8.54%), but only two of these seven pigs (2.44%) were also negative for F4R. As such, the chance to identify a pig that is positive for a F4 ETEC variant or F18 + E. coli is 97.56%. Therefore, significant economic losses will arise due to F4 + and/or F18 + E. coli infections in the Flemish pig population due to the high susceptibility prevalence. Copyright © 2016 Elsevier B.V. All rights reserved.

Molecular pathways associated with blood pressure and hexadecanedioate levels.

PubMed

Menni, Cristina; Metrustry, Sarah J; Ehret, Georg; Dominiczak, Anna F; Chowienczyk, Phil; Spector, Tim D; Padmanabhan, Sandosh; Valdes, Ana M

2017-01-01

The dicarboxylic acid hexadecanedioate is associated with increased blood pressure (BP) and mortality in humans and feeding it to rats raises BP. Here we aim to characterise the molecular pathways that influence levels of hexadecanedioate linked to BP regulation, using genetic and transcriptomic studies. The top associations for hexadecanedioate in a genome-wide association scan (GWAS) conducted on 6447 individuals from the TwinsUK and KORA cohorts were tested for association with BP and hypertension in the International Consortium for BP and in a GWAS of BP extremes. Transcriptomic analyses correlating hexadecanedioate with gene expression levels in adipose tissue in 740 TwinsUK participants were further performed. GWAS showed 242 SNPs mapping to two independent loci achieving genome-wide significance. In rs414056 in the SCLO1B1 gene (Beta(SE) = -0.088(0.006)P = 1.65 x 10-51, P < 1 x 10-51), the allele previously associated with increased risk of statin associated myopathy is associated with higher hexadecanedioate levels. However this SNP did not show association with BP or hypertension. The top SNP in the second locus rs6663731 mapped to the intronic region of CYP4Z2P on chromosome 1 (0.045(0.007), P = 5.49x10-11). Hexadecanedioate levels also correlate with adipose tissue gene-expression of the 3 out of 4 CYP4 probes (P<0.05) and of alcohol dehydrogenase probes (Beta(SE) = 0.12(0.02); P = 6.04x10-11). High circulating levels of hexadecanedioate determine a significant effect of alcohol intake on BP (SBP: 1.12(0.34), P = 0.001; DBP: 0.70(0.22), P = 0.002), while no effect is seen in the lower hexadecanedioate level group. In conclusion, levels in fat of ADH1A, ADH1B and CYP4 encoding enzymes in the omega oxidation pathway, are correlated with hexadecanedioate levels. Hexadecanedioate appears to regulate the effect of alcohol on BP.

Associations between short-term exposure to particulate matter and ultrafine particles and myocardial infarction in Augsburg, Germany.

PubMed

Wolf, Kathrin; Schneider, Alexandra; Breitner, Susanne; Meisinger, Christa; Heier, Margit; Cyrys, Josef; Kuch, Bernhard; von Scheidt, Wolfgang; Peters, Annette

2015-08-01

Short-term exposure to increased particulate matter (PM) concentration has been reported to trigger myocardial infarction (MI). However, the association with ultrafine particles remains unclear. We aimed to assess the effects of short-term air pollution and especially ultrafine particles on registry-based MI events and coronary deaths in the area of Augsburg, Germany. Between 1995 and 2009, the MONICA/KORA myocardial infarction registry recorded 15,417 cases of MI and coronary deaths. Concentrations of PM<10μm (PM10), PM<2.5μm (PM2.5), particle number concentration (PNC) as indicator for ultrafine particles, and meteorological parameters were measured in the study region. Quasi-Poisson regression adjusting for time trend, temperature, season, and weekday was used to estimate immediate, delayed and cumulative effects of air pollutants on the occurrence of MI. The daily numbers of total MI, nonfatal and fatal events as well as incident and recurrent events were analysed. We observed a 1.3% risk increase (95%-confidence interval: [-0.9%; 3.6%]) for all events and a 4.4% [-0.4%; 9.4%] risk increase for recurrent events per 24.3μg/m(3) increase in same day PM10 concentrations. Nonfatal events indicated a risk increase of 3.1% [-0.1%; 6.5%] with previous day PM10. No association was seen for PM2.5 which was only available from 1999 on. PNC showed a risk increase of 6.0% [0.6%; 11.7%] for recurrent events per 5529 particles/cm(3) increase in 5-day average PNC. Our results suggested an association between short-term PM10 concentration and numbers of MI, especially for nonfatal and recurrent events. For ultrafine particles, risk increases were notably high for recurrent events. Thus, persons who already suffered a MI seemed to be more susceptible to air pollution. Copyright © 2015 Elsevier GmbH. All rights reserved.

Associations between traffic noise, particulate air pollution, hypertension, and isolated systolic hypertension in adults: the KORA study.

PubMed

Babisch, Wolfgang; Wolf, Kathrin; Petz, Markus; Heinrich, Joachim; Cyrys, Josef; Peters, Annette

2014-05-01

Studies on the association between traffic noise and cardiovascular diseases have rarely considered air pollution as a covariate in the analyses. Isolated systolic hypertension has not yet been in the focus of epidemiological noise research. The association between traffic noise (road and rail) and the prevalence of hypertension was assessed in two study populations with a total of 4,166 participants 25-74 years of age. Traffic noise (weighted day-night average noise level; LDN) at the facade of the dwellings was derived from noise maps. Annual average PM2.5 mass concentrations at residential addresses were estimated by land-use regression. Hypertension was assessed by blood pressure readings, self-reported doctor-diagnosed hypertension, and antihypertensive drug intake. In the Greater Augsburg, Germany, study population, traffic noise and air pollution were not associated with hypertension. In the City of Augsburg population (n = 1,893), where the exposure assessment was more detailed, the adjusted odds ratio (OR) for a 10-dB(A) increase in noise was 1.16 (95% CI: 1.00, 1.35), and 1.11 (95% CI: 0.94, 1.30) after additional adjustment for PM2.5. The adjusted OR for a 1-μg/m3 increase in PM2.5 was 1.15 (95% CI: 1.02, 1.30), and 1.11 (95% CI: 0.98, 1.27) after additional adjustment for noise. For isolated systolic hypertension, the fully adjusted OR for noise was 1.43 (95% CI: 1.10, 1.86) and for PM2.5 was 1.08 (95% CI: 0.87, 1.34). Traffic noise and PM2.5 were both associated with a higher prevalence of hypertension. Mutually adjusted associations with hypertension were positive but no longer statistically significant.

Sex differences in the association of social network satisfaction and the risk for type 2 diabetes.

PubMed

Lukaschek, K; Baumert, J; Kruse, J; Meisinger, C; Ladwig, K H

2017-05-02

The role of an individual's social network satisfaction (SNS) in the association of social isolation or living alone and incident type 2 diabetes (T2D) is unclear. We assessed the association of SNS with incident T2D and analysed potential modifications of the SNS-T2D association by social isolation or living alone. The study population (N = 6839 aged 25-74 years without diabetes at baseline) derived from the prospective population-based MONICA/KORA study (1989-2009). Social network satisfaction was assessed by a single item. Cox regression was used to estimate hazard ratios (HR) for SNS separately in men and women. In men with low SNS, risk for incident T2D increased significantly (HR: 2.15, 95% CI: 1.33-3.48, p value 0.002). After additional adjustments for social isolation or living alone, the risk for incident T2D was still significant, albeit less pronounced (HRs 1.85 or 2.05, p values 0.001 or 0.004). The interaction analysis showed an increased T2D risk effect for low SNS compared to high SNS in women living in a partnership (HR: 2.11, 95% CI: 1.00-4.44, p value for interaction: 0.047) and for moderate SNS compared to high SNS in socially connected women (1.56, 1.01-2.39, 0.010). Further research is needed to address the complexities of the perception of social relationships and social interactions, or interdependence, especially when another major public health issue such as T2D is concerned.

Implications of prevalent and incident diabetes mellitus on left ventricular geometry and function in the ageing heart: the MONICA/KORA Augsburg cohort study.

PubMed

Markus, M R Paulista; Stritzke, J; Wellmann, J; Duderstadt, S; Siewert, U; Lieb, W; Luchner, A; Döring, A; Keil, U; Schunkert, H; Hense, H-W

2011-03-01

It is unclear to what extent diabetes modulates the ageing-related adaptations of cardiac geometry and function. We examined 1005 adults, aged 25-74 years, from a population-based survey at baseline in 1994/5 and at follow-up in 2004/5. We compared persistently non-diabetic individuals (ND; no diabetes at baseline and at follow-up, n=833) with incident (ID; non-diabetic at baseline and diabetic at follow-up, n=36) and with prevalent diabetics (PD; diabetes at baseline and follow-up examination, n=21). Left ventricular (LV) geometry and function were evaluated by echocardiography. Statistical analyses were performed with multivariate linear regression models. Over ten years the PD group displayed a significantly stronger relative increase of LV mass (+9.34% vs. +23.7%) that was mediated by a more pronounced increase of LV end-diastolic diameter (+0% vs. +6.95%) compared to the ND group. In parallel, LA diameter increased (+4.50% vs. +12.7%), whereas ejection fraction decreased (+3.02% vs. -4.92%) more significantly in the PD group. Moreover, at the follow-up examination the PD and ID groups showed a significantly worse diastolic function, indicated by a higher E/EM ratio compared with the ND group (11.6 and 11.8 vs. 9.79, respectively). Long-standing diabetes was associated with an acceleration of age-related changes of left ventricular geometry accumulating in an eccentric remodelling of the left ventricle. Likewise, echocardiographic measures of systolic and diastolic ventricular function deteriorated more rapidly in individuals with diabetes. Copyright © 2009 Elsevier B.V. All rights reserved.

Implications of persistent prehypertension for ageing-related changes in left ventricular geometry and function: the MONICA/KORA Augsburg study.

PubMed

Markus, Marcello Ricardo Paulista; Stritzke, Jan; Lieb, Wolfgang; Mayer, Björn; Luchner, Andreas; Döring, Angela; Keil, Ulrich; Hense, Hans-Werner; Schunkert, Heribert

2008-10-01

It is unclear whether persistent prehypertension causes structural or functional alterations of the heart. We examined echocardiographic data of 1005 adults from a population-based survey at baseline in 1994/1995 and at follow-up in 2004/2005. We compared individuals who had either persistently normal (<120 mmHg systolic and <80 mmHg diastolic, n = 142) or prehypertensive blood pressure (120-139 mmHg or 80-89 mmHg, n = 119) at both examinations using multivariate regression modeling. Over 10 years, left ventricular end-diastolic diameters were stable and did not differ between the two groups. However, the prehypertensive blood pressure group displayed more pronounced ageing-related increases of left ventricular wall thickness (+4.7 versus +11.9%, P < 0.001) and left ventricular mass (+8.6 versus +15.7%, P = 0.006). Prehypertension was associated with a raised incidence of left ventricular concentric remodeling (adjusted odds ratio 10.7, 95% confidence interval 2.82-40.4) and left ventricular hypertrophy (adjusted odds ratio 5.33, 1.58-17.9). The ratio of early and late diastolic peak transmitral flow velocities (E/A) decreased by 7.7% in the normal blood pressure versus 15.7% in the prehypertensive blood pressure group (P = 0.003) and at follow-up the ratio of early diastolic peak transmitral flow and early diastolic peak myocardial relaxation velocities (E/EM) was higher (9.1 versus 8.5, P = 0.031) and left atrial size was larger (36.5 versus 35.3 mm, P = 0.024) in the prehypertensive blood pressure group. Finally, the adjusted odds ratio for incident diastolic dysfunction was 2.52 (1.01-6.31) for the prehypertensive blood pressure group. Persistent prehypertension accelerates the development of hypertrophy and diastolic dysfunction of the heart.

[Frailty in Germany: status and perspectives : Results from a workshop of the German Society for Epidemiology].

PubMed

Fuchs, Judith; Scheidt-Nave, Christa; Gaertner, Beate; Dapp, Ulrike; von Renteln-Kruse, Wolfgang; Saum, Kai-Uwe; Thorand, Barbara; Strobl, Ralf; Grill, Eva

2016-12-01

A standardized, valid and comparable operationalization and assessment of frailty in population-based studies is essential in order to describe the prevalence and determinants of frailty in the population. After an introduction to the subject the main goal of a workshop at the 9th annual meeting of the German Society for Epidemiology (DGEpi) was to present approaches and results from four different studies in Germany. The following four population-based studies were used to describe frailty in Germany: the German health interview and examination survey for adults (DEGS1), the epidemiological study on the chances of prevention, early recognition and optimized treatment of chronic diseases in the older population (ESTHER), the cooperative health research in the region Augsburg (KORA Age) study and the longitudinal urban cohort ageing study (LUCAS) in Hamburg. The four studies consistently showed that frailty is widespread in older and oldest-old persons in Germany. It is obvious that frailty represents a relevant concept in Germany even if there is currently no uniform basis for operationalization. Concepts and instruments for the collation of frailty should be included in future population-based studies in order to make a better assessment of older people's health situation and to describe the unused potential for prevention in an aging society.

Thermodynamic assessment of the LiF-NaF-BeF2-ThF4-UF4 system

NASA Astrophysics Data System (ADS)

Capelli, E.; Beneš, O.; Konings, R. J. M.

2014-06-01

The present study describes the full thermodynamic assessment of the LiF-NaF-BeF2-ThF4-UF4 system which is one of the key systems considered for a molten salt reactor fuel. The work is an extension of the previously assessed LiF-NaF-ThF4-UF4 system with addition of BeF2 which is characterized by very low neutron capture cross section and a relatively low melting point. To extend the database the binary BeF2-ThF4 and BeF2-UF4 systems were optimized and the novel data were used for the thermodynamic assessment of BeF2 containing ternary systems for which experimental data exist in the literature. The obtained database is used to optimize the molten salt reactor fuel composition and to assess its properties with the emphasis on the melting behaviour.

Scientific and Engineering Studies, Compiled 1992. Signal Processing Studies

DTIC Science & Technology

1992-01-01

RV y were also computed in terms of sequence IFn1; they turned out to be, for M > 4, Xy( 3 ) = M3 [ F3 - 3F 2 F1 + 2FJ , Xy( 4 ) - M4 [F4 - 4F 3 F1...for the flat component (A.5-13) when bpP /A is large. For sake of brevity, the Fourier transform of the sharp component (A.5-9) is straightforward and is... F3 . (9) K n=1ik=n K nlK Notice that moments of IxkI above the fourth need not be known. 5 TR 10237 The difficulty of attempting to evaluate (8

Pou4f2-GFP knock-in mouse line: A model for studying retinal ganglion cell development.

PubMed

Zheng, Dongwang; Yang, Xiaoyan; Sheng, Donglai; Yu, Dongliang; Liang, Guoqing; Guo, Luming; Xu, Mei; Hu, Xu; He, Daqiang; Yang, Yang; Wang, Yuying

2016-10-01

Pou4f2 acts as a key node in the comprehensive and step-wise gene regulatory network (GRN) and regulates the development of retinal ganglion cells (RGCs). Accordingly, deletion of Pou4f2 results in RGC axon defects and apoptosis. To investigate the GRN involved in RGC regeneration, we generated a mouse line with a POU4F2-green fluorescent protein (GFP) fusion protein expressed in RGCs. Co-localization of POU4F2 and GFP in the retina and brain of Pou4f2-GFP/+ heterozygote mice was confirmed using immunofluorescence analysis. Compared with those in wild-type mice, the expression patterns of POU4F2 and POU4F1 and the co-expression patterns of ISL1 and POU4F2 were unaffected in Pou4f2-GFP/GFP homozygote mice. Moreover, the quantification of RGCs showed no significant difference between Pou4f2-GFP/GFP homozygote and wild-type mice. These results demonstrated that the development of RGCs in Pou4f2-GFP/GFP homozygote mice was the same as in wild-type mice. Thus, the present Pou4f2-GFP knock-in mouse line is a useful tool for further studies on the differentiation and regeneration of RGCs. © 2016 Wiley Periodicals, Inc.

Heme oxygenase-1 gene promoter microsatellite polymorphism is associated with progressive atherosclerosis and incident cardiovascular disease.

PubMed

Pechlaner, Raimund; Willeit, Peter; Summerer, Monika; Santer, Peter; Egger, Georg; Kronenberg, Florian; Demetz, Egon; Weiss, Günter; Tsimikas, Sotirios; Witztum, Joseph L; Willeit, Karin; Iglseder, Bernhard; Paulweber, Bernhard; Kedenko, Lyudmyla; Haun, Margot; Meisinger, Christa; Gieger, Christian; Müller-Nurasyid, Martina; Peters, Annette; Willeit, Johann; Kiechl, Stefan

2015-01-01

The enzyme heme oxygenase-1 (HO-1) exerts cytoprotective effects in response to various cellular stressors. A variable number tandem repeat polymorphism in the HO-1 gene promoter region has previously been linked to cardiovascular disease. We examined this association prospectively in the general population. Incidence of stroke, myocardial infarction, or vascular death was registered between 1995 and 2010 in 812 participants of the Bruneck Study aged 45 to 84 years (49.4% males). Carotid atherosclerosis progression was quantified by high-resolution ultrasound. HO-1 variable number tandem repeat length was determined by polymerase chain reaction. Subjects with ≥32 tandem repeats on both HO-1 alleles compared with the rest of the population (recessive trait) featured substantially increased cardiovascular disease risk (hazard ratio [95% confidence interval], 5.45 [2.39, 12.42]; P<0.0001), enhanced atherosclerosis progression (median difference in atherosclerosis score [interquartile range], 2.1 [0.8, 5.6] versus 0.0 [0.0, 2.2] mm; P=0.0012), and a trend toward higher levels of oxidized phospholipids on apolipoprotein B-100 (median oxidized phospholipids/apolipoprotein B level [interquartile range], 11364 [4160, 18330] versus 4844 [3174, 12284] relative light units; P=0.0554). Increased cardiovascular disease risk in those homozygous for ≥32 repeats was also detected in a pooled analysis of 7848 participants of the Bruneck, SAPHIR, and KORA prospective studies (hazard ratio [95% confidence interval], 3.26 [1.50, 7.33]; P=0.0043). This study found a strong association between the HO-1 variable number tandem repeat polymorphism and cardiovascular disease risk confined to subjects with a high number of repeats on both HO-1 alleles and provides evidence for accelerated atherogenesis and decreased antioxidant defense in this vascular high-risk group. © 2014 American Heart Association, Inc.

In vitro and in vivo studies of pharmacokinetics and antitumor efficacy of D07001-F4, an oral gemcitabine formulation.

PubMed

Hao, Wei-Hua; Wang, Jong-Jing; Hsueh, Shu-Ping; Hsu, Pei-Jing; Chang, Li-Chien; Hsu, Chang-Shan; Hsu, Kuang-Yang

2013-02-01

The chemotherapy agent gemcitabine is currently administered intravenously because the drug has poor oral bioavailability. In order to assess the pharmacokinetics and antitumor activity of D07001-F4, a new self-microemulsifying oral drug delivery system preparation of gemcitabine, this study was performed to compare the effect of D07001-F4 with administered gemcitabine in vitro and in vivo. D07001-F4 pharmacokinetics was examined by evaluation of in vitro deamination of D07001-F4 and gemcitabine hydrochloride by recombinant human cytidine deaminase (rhCDA) and in vivo evaluation of D07001-F4 pharmacokinetics in mice. Antitumor activity was evaluated by comparing the effect of D07001-F4 and gemcitabine hydrochloride in inhibiting growth in nine cancer cell lines and by examining the effect of D07001-F4 and gemcitabine in two xenograft tumor models in mice. In vitro deamination of D07001-F4 by rhCDA was 3.3-fold slower than deamination of gemcitabine hydrochloride. Growth inhibition by D07001-F4 of 7 of the 8 cancer cell lines was increased compared with that seen with gemcitabine hydrochloride, and D07001-F4 inhibited the growth of pancreatic and colon cancer xenografts. In vivo pharmacokinetics showed the oral bioavailability of D07001-F4 to be 34%. D07001-F4 was effective against several cancer types, was metabolized more slowly than gemcitabine hydrochloride, and exhibited enhanced oral bioavailability.

Gender Disparities in the Prevalence of Undernutrition and the Higher Risk among the Young Women of Indian Tribes.

PubMed

Kshatriya, Gautam K; Acharya, Subhendu K

2016-01-01

High undernutrition is a grave concern in India. Marginalized populations like Indian tribes have been under the serious stress of such nutritional extreme. Women, in particular, are the worst sufferers. Gender-related comprehensive studies regarding the prevalence and risks of undernutrition among the tribes have not been properly pursued in India; the vulnerability of the young females has least been examined. We conducted a cross-sectional study during January 2011 to December 2013 among 1066 males and 1090 females (n = 2156) in the 20-60 years age group belonging to the nine major tribes; Santals, Oraons and Koras (West Bengal): Santals, Bhumijs and Bathudis (Odisha): Dhodias, Kuknas and Chaudharis (Gujarat). The undernutrition burden was estimated and such risks were analyzed for the women in comparison to the men. The overall undernutrition among the females was found to be 47.4% (95% CI 44.4-50.4) against 32.1% (95% CI 29.3-34.9) among males, indicating about a half of the female population undernourished. The odds of risks for underweight status among females were observed to be high in comparison to males with an odds of 1.9 (95% CI, 1.6-2.2; p≤0.001) for the overall undernutrition category, 1.7 (95% CI, 1.3-2.3; p≤0.001) for the mild undernutrition category, 1.3 (95% CI, 1.1-1.6; p≤0.01) for combined moderate and mild undernutrition category and 3.3 (95% CI at 2.3-4.6; p≤0.001) for severe undernutrition category. The young females were observed with a high prevalence of undernutrition along with increased risk. The 30-year mean BMI trend of the Indian population in comparison to the males, females, and overall tribal population places the tribal females at the highest risk. Indian tribes are suffering from the higher prevalence of undernutrition by further highlighting a high gender bias. The health and empowerment of adolescent and young tribal girls needs additional focus. Overall, no remarkable control on undernutrition has been achieved among Indian tribes despite various efforts.

Gender Disparities in the Prevalence of Undernutrition and the Higher Risk among the Young Women of Indian Tribes

PubMed Central

2016-01-01

Background High undernutrition is a grave concern in India. Marginalized populations like Indian tribes have been under the serious stress of such nutritional extreme. Women, in particular, are the worst sufferers. Gender-related comprehensive studies regarding the prevalence and risks of undernutrition among the tribes have not been properly pursued in India; the vulnerability of the young females has least been examined. Methods and Findings We conducted a cross-sectional study during January 2011 to December 2013 among 1066 males and 1090 females (n = 2156) in the 20–60 years age group belonging to the nine major tribes; Santals, Oraons and Koras (West Bengal): Santals, Bhumijs and Bathudis (Odisha): Dhodias, Kuknas and Chaudharis (Gujarat). The undernutrition burden was estimated and such risks were analyzed for the women in comparison to the men. The overall undernutrition among the females was found to be 47.4% (95% CI 44.4–50.4) against 32.1% (95% CI 29.3–34.9) among males, indicating about a half of the female population undernourished. The odds of risks for underweight status among females were observed to be high in comparison to males with an odds of 1.9 (95% CI, 1.6–2.2; p≤0.001) for the overall undernutrition category, 1.7 (95% CI, 1.3–2.3; p≤0.001) for the mild undernutrition category, 1.3 (95% CI, 1.1–1.6; p≤0.01) for combined moderate and mild undernutrition category and 3.3 (95% CI at 2.3–4.6; p≤0.001) for severe undernutrition category. The young females were observed with a high prevalence of undernutrition along with increased risk. The 30-year mean BMI trend of the Indian population in comparison to the males, females, and overall tribal population places the tribal females at the highest risk. Conclusion Indian tribes are suffering from the higher prevalence of undernutrition by further highlighting a high gender bias. The health and empowerment of adolescent and young tribal girls needs additional focus. Overall, no remarkable control on undernutrition has been achieved among Indian tribes despite various efforts. PMID:27379521

F4-related mutation and expression analysis of the aminopeptidase N gene in pigs.

PubMed

Goetstouwers, T; Van Poucke, M; Nguyen, V U; Melkebeek, V; Coddens, A; Deforce, D; Cox, E; Peelman, L J

2014-05-01

Intestinal infections with F4 enterotoxigenic Escherichia coli (ETEC) are worldwide an important cause of diarrhea in neonatal and recently weaned pigs. Adherence of F4 ETEC to the small intestine by binding to specific receptors is mediated by F4 fimbriae. Porcine aminopeptidase N (ANPEP) was recently identified as a new F4 receptor. In this study, 7 coding mutations and 1 mutation in the 3' untranslated region (3' UTR)were identified in ANPEP by reverse transcriptase (RT-) PCR and sequencing using 3 F4 receptor-positive (F4R+) and 2 F4 receptor-negative (F4R-) pigs, which were F4 phenotyped based on the MUC4 TaqMan, oral immunization, and the in vitro villous adhesion assay. Three potential differential mutations (g.2615C > T, g.8214A > G, and g.16875C > G) identified by comparative analysis between the 3 F4R+ and 2 F4R- pigs were genotyped in 41 additional F4 phenotyped pigs. However, none of these 3 mutations could be associated with F4 ETEC susceptibility. In addition, the RT-PCR experiments did not reveal any differential expression or alternative splicing in the small intestine of F4R+ and F4R- pigs. In conclusion, we hypothesize that the difference in F4 binding to ANPEP is due to modifications in its carbohydrate moieties.

APRI and FIB-4 are good predictors of the stage of liver fibrosis in chronic hepatitis B: the Chronic Hepatitis Cohort Study (CHeCS).

PubMed

Teshale, E; Lu, M; Rupp, L B; Holmberg, S D; Moorman, A C; Spradling, P; Vijayadeva, V; Boscarino, J A; Schmidt, M A; Gordon, S C

2014-12-01

We aim to determine the predictive ability of APRI, FIB-4 and AST/ALT ratio for staging of liver fibrosis and to differentiate significant fibrosis (F2-F4) from none to minimal fibrosis (F0-F1) in chronic hepatitis B (CHB). Liver biopsy results were mapped to an F0-4 equivalent fibrosis stage. Mean APRI and FIB-4 scores were significantly higher for each successive fibrosis level from F1 to F4 (P < 0.05). Based on optimized cut-offs, the AUROCs in distinguishing F2-F4 from F0 to F1 were 0.81 (0.76-0.87) for APRI, 0.81 (0.75-0.86) for FIB-4 and 0.56 (0.49-0.64) for AST/ALT ratio. APRI and FIB-4 distinguished F2-F4 from F0 to F1 with good sensitivity and specificity and can be useful for treatment decisions and monitoring progression of fibrosis. © 2014 John Wiley & Sons Ltd.

Induction of Th1 polarized immune responses by thiolated Eudragit-coated F4 and F18 fimbriae of enterotoxigenic Escherichia coli.

PubMed

Lee, Won-Jung; Cha, Seungbin; Shin, Minkyoung; Islam, Mohammad Ariful; Cho, Chong-su; Yoo, Han Sang

2011-10-01

Diarrhea in newborn and weaned piglets is mainly induced by enterotoxigenic Escherichia coli (ETEC) with fimbriae F4 (K88) and F18 (F107). In this study, we evaluated F4 and F18 coated with thiolated Eudragit microspheres (TEMS) as a candidate for an oral vaccine. The average particle sizes of TEMS, F4-loaded TEMS, and F18-loaded TEMS were measured as 4.2±0.75 μm, 4.7±0.50 μm, and 4.5±0.37 μm, respectively. F4 is more efficiently encapsulated than F18 in the loading with TEMS. In the release test, F4 and F18 fimbriae were protected in acidic circumstances, whereas most were released at pH 7.4 of intestine circumstances. Production of TNF-α and NO from RAW 264.7 cells was increased in a time-dependent manner after exposure to all groups, whereas only F4- or F18-loaded TEMS-stimulated IL-6 secretion. The levels of IFN-γ from mouse splenocytes after exposure to F4 or F18 were increased while IL-4 was not detectable. These results suggest that F4- and F18-loaded TEMS may effectively induce immune response with the efficient release of antigens to appropriate target sites. Copyright © 2011 Elsevier B.V. All rights reserved.

Comparison of antimicrobial effects of titanium tetrafluoride, chlorhexidine, xylitol and sodium fluoride on streptococcus mutans: An in-vitro study.

PubMed

Eskandarian, Tahereh; Motamedifar, Mohammad; Arasteh, Peyman; Eghbali, Seyed Sajad; Adib, Ali; Abdoli, Zahra

2017-03-01

No studies have yet documented the bactericidal effects of TiF4, and its role in the treatment of dental caries, and no definite protocol has been introduced to regulate its use. The aim of this study was to determine the antimicrobial/bactericidal effects of TiF4 on Streptococcus Mutans ( S. Mutans ) and to compare it with chlorhexidine (Chx), sodium fluoride (NaF) and xylitol. This study was conducted at the Shiraz University of Medical Sciences microbiology laboratory during March 2015 to September 2015. In this in-vitro study, first a bacterial suspension was prepared and adjusted to a 0.5 McFarland standard (equivalent to 1×10 8 CFU/ml). The minimal inhibitory concentration (MIC) and minimal bactericidal concentrations (MBC) of TiF4, Chx, NaF and xylitol were assessed using broth microdilution assay and disk diffusion methods. In order to neutralize the acidic nature of TiF4, we used a sodium hydroxide preparation to obtain a pH of 7.2 and repeated all of the previous tests with the neutralized TiF4 solution. We reported the final results as percentages where appropriate. The MIC of TiF4, NaF and Chx for S. Mutans were 12.5%, 12.5% and 6.25%, respectively. At a concentration of 12.5% the inhibition zone diameters were 9 mm, 15mm and 14mm for TiF4, NaF and Chx, respectively. The MBC was 25%, 12.5% and 12.5% for TiF4, NaF and Chx, respectively. Xylitol failed to show any bactericidal or growth inhibitory effect in all of its concentrations. When we repeated the tests with an adjusted pH, identical results were obtained. TiF4 solutions have anti-growth and bactericidal effects on S. Mutans at a concentration of 12.5% which is comparable with chlorhexidine and NaF, indicating the possible use of this solution in dental practice as an anti-cariogenic agent, furthermore the antimicrobial activity is unaffected by pH of the environment.

Comparison of antimicrobial effects of titanium tetrafluoride, chlorhexidine, xylitol and sodium fluoride on streptococcus mutans: An in-vitro study

PubMed Central

Eskandarian, Tahereh; Motamedifar, Mohammad; Arasteh, Peyman; Eghbali, Seyed Sajad; Adib, Ali; Abdoli, Zahra

2017-01-01

Introduction No studies have yet documented the bactericidal effects of TiF4, and its role in the treatment of dental caries, and no definite protocol has been introduced to regulate its use. The aim of this study was to determine the antimicrobial/bactericidal effects of TiF4 on Streptococcus Mutans (S. Mutans) and to compare it with chlorhexidine (Chx), sodium fluoride (NaF) and xylitol. Methods This study was conducted at the Shiraz University of Medical Sciences microbiology laboratory during March 2015 to September 2015. In this in-vitro study, first a bacterial suspension was prepared and adjusted to a 0.5 McFarland standard (equivalent to 1×108 CFU/ml). The minimal inhibitory concentration (MIC) and minimal bactericidal concentrations (MBC) of TiF4, Chx, NaF and xylitol were assessed using broth microdilution assay and disk diffusion methods. In order to neutralize the acidic nature of TiF4, we used a sodium hydroxide preparation to obtain a pH of 7.2 and repeated all of the previous tests with the neutralized TiF4 solution. We reported the final results as percentages where appropriate. Results The MIC of TiF4, NaF and Chx for S. Mutans were 12.5%, 12.5% and 6.25%, respectively. At a concentration of 12.5% the inhibition zone diameters were 9 mm, 15mm and 14mm for TiF4, NaF and Chx, respectively. The MBC was 25%, 12.5% and 12.5% for TiF4, NaF and Chx, respectively. Xylitol failed to show any bactericidal or growth inhibitory effect in all of its concentrations. When we repeated the tests with an adjusted pH, identical results were obtained. Conclusion TiF4 solutions have anti-growth and bactericidal effects on S. Mutans at a concentration of 12.5% which is comparable with chlorhexidine and NaF, indicating the possible use of this solution in dental practice as an anti-cariogenic agent, furthermore the antimicrobial activity is unaffected by pH of the environment. PMID:28461883

Study of fluorescence quenching due to 2, 3, 5, 6-tetrafluoro-7, 7', 8, 8'-tetracyano quinodimethane and its solid state diffusion analysis using photoluminescence spectroscopy.

PubMed

Tyagi, Priyanka; Tuli, Suneet; Srivastava, Ritu

2015-02-07

In this work, we have studied the fluorescence quenching and solid state diffusion of 2, 3, 5, 6-tetrafluoro-7,  7',  8,  8'-tetracyano quinodimethane (F4-TCNQ) using photoluminescence (PL) spectroscopy. Quenching studies were performed with tris (8-hydroxyquinolinato) aluminum (Alq3) in solid state samples. Thickness of F4-TCNQ was varied in order to realize different concentrations and study the effect of concentration. PL intensity has reduced with the increase in F4-TCNQ thicknesses. Stern-Volmer and bimolecular quenching constants were evaluated to be 13.8 M(-1) and 8.7 × 10(8) M(-1) s(-1), respectively. The quenching mechanism was found to be of static type, which was inferred by the independent nature of excited state life time from the F4-TCNQ thickness. Further, solid state diffusion of F4-TCNQ was studied by placing a spacing layer of α-NPD between F4-TCNQ and Alq3, and its thickness was varied to probe the diffusion length. PL intensity was found to increase with the increase in this thickness. Quenching efficiency was evaluated as a function of distance between F4-TCNQ and Alq3. These studies were performed for the samples having 1, 2.5, and 5.5 nm thicknesses of F4-TCNQ to study the thickness dependence of diffusion length. Diffusion lengths were evaluated to be 12.5, 15, and 20 nm for 1, 2.5, and 5.5 nm thicknesses of F4-TCNQ. These diffusion lengths were found to be very close to that of determined by secondary ion mass spectroscopy technique.

Aviation Officer Requirements Study.

DTIC Science & Technology

1982-08-31

r4444-444,, 44*44 * 4ri OW 4.YP F3 1X Tt FF 1r 1 i.111 * 21’ 1 * 34 FVA r i. i r n -t~I I~’JJ YirF Tz i. * I 4 * F*r_ v" J * f,4 fvA IiGr ti Ic:~ r A...7 F3 0- .- * 4*. * 4,*.&-4 l󈧰*4* 4 ~ *’Ř󈧰 44 4 *44 ’ k 4)* ,_𔃾- 4*4 4 721C 4 PARAMETER CATEGORY MENU SCr(EEN This screen appears af ter screen...0, 4, F3 1*(,I!X vF4./ 13-30 DATA 0, 4, 09, r2, ./ A*AX VAM!/ 1340 DATA 0, P.2 .. 0, P. 0 /*A4L1 VAW " " 13S-0 DATA 2, 4,21,1,5, 2.9 /*ALX VAOP

Seasonal and Solar Activity Variations of f3 Layer and StF-4 F-Layer Quadruple Stratification) Near the Equatorial Region

NASA Astrophysics Data System (ADS)

Tardelli, A.; Fagundes, P. R.; Pezzopane, M.; Kavutarapu, V.

2016-12-01

The ionospheric F-layer shape and electron density peak variations depend on local time, latitude, longitude, season, solar cycle, geomagnetic activity, and electrodynamic conditions. In particular, the equatorial and low latitude F-layer may change its shape and peak height in a few minutes due to electric fields induced by propagation of medium-scale traveling ionospheric disturbances (MSTIDs) or thermospheric - ionospheric coupling. This F-layer electrodynamics feature characterizing the low latitudes is one of the most remarkable ionospheric physics research field. The study of multiple-stratification of the F-layer has the initial records in the mid of the 20th century. Since then, many studies were focused on F3 layer. The diurnal, seasonal and solar activity variations of the F3 layer characteristics have been investigated by several researchers. Recently, investigations on multiple-stratifications of F-layer received an important boost after the quadruple stratification (StF-4) was observed at Palmas (10.3°S, 48.3°W; dip latitude 5.5°S - near equatorial region), Brazil (Tardelli & Fagundes, JGR, 2015). This study present the latest findings related with the seasonal and solar activity characteristics of the F3 layer and StF-4 near the equatorial region during the period from 2002 to 2006. A significant connection between StF-4 and F3 layer has been noticed, since the StF-4 is always preceded and followed by an F3 layer appearance. However, the F3 layer and StF-4 present different seasonal and solar cycle variations. At a near equatorial station Palmas, the F3 layer shows the maximum and minimum occurrence during summer and winter seasons respectively. On the contrary, the StF-4 presents the maximum and minimum occurrence during winter and summer seasons respectively. While the F3 layer occurrence is not affected by solar cycle, the StF-4 appearance is instead more frequent during High Solar Activity (HSA).

Effect of NaF, SnF(2), and TiF(4) Toothpastes on Bovine Enamel and Dentin Erosion-Abrasion In Vitro.

PubMed

Comar, Lívia Picchi; Gomes, Marina Franciscon; Ito, Naiana; Salomão, Priscila Aranda; Grizzo, Larissa Tercília; Magalhães, Ana Carolina

2012-01-01

The aim of this study was to compare the effect of toothpastes containing TiF(4), NaF, and SnF(2) on tooth erosion-abrasion. Bovine enamel and dentin specimens were distributed into 10 groups (n = 12): experimental placebo toothpaste (no F); NaF (1450 ppm F); TiF(4) (1450 ppm F); SnF(2) (1450 ppm F); SnF(2) (1100 ppm F) + NaF (350 ppm F); TiF(4) (1100 ppm F) + NaF (350 ppm F); commercial toothpaste Pro-Health (SnF(2)-1100 ppm F + NaF-350 ppm F, Oral B); commercial toothpaste Crest (NaF-1.500 ppm F, Procter & Gamble); abrasion without toothpaste and only erosion. The erosion was performed 4 × 90 s/day (Sprite Zero). The toothpastes' slurries were applied and the specimens abraded using an electric toothbrush 2 × 15 s/day. Between the erosive and abrasive challenges, the specimens remained in artificial saliva. After 7 days, the tooth wear was evaluated using contact profilometry (μm). The experimental toothpastes with NaF, TiF(4), SnF(2), and Pro-Health showed a significant reduction in enamel wear (between 42% and 54%). Pro-Health also significantly reduced the dentin wear. The toothpastes with SnF(2)/NaF and TiF(4)/NaF showed the best results in the reduction of enamel wear (62-70%) as well as TiF(4), SnF(2), SnF(2)/NaF, and TiF(4)/NaF for dentin wear (64-79%) (P < 0.05). Therefore, the experimental toothpastes containing both conventional and metal fluoride seem to be promising in reducing tooth wear.

Efficacy, pharmacokinetics, tisssue distribution, and metabolism of the Myc-Max disruptor, 10058-F4 [Z,E]-5-[4-ethylbenzylidine]-2-thioxothiazolidin-4-one, in mice.

PubMed

Guo, Jianxia; Parise, Robert A; Joseph, Erin; Egorin, Merrill J; Lazo, John S; Prochownik, Edward V; Eiseman, Julie L

2009-03-01

c-Myc is commonly activated in many human tumors and is functionally important in cellular proliferation, differentiation, apoptosis and cell cycle progression. The activity of c-Myc requires noncovalent interaction with its client protein Max. In vitro studies indicate the thioxothiazolidinone, 10058-F4, inhibits c-Myc/Max dimerization. In this study, we report the efficacy, pharmacokinetics and metabolism of this novel protein-protein disruptor in mice. SCID mice bearing DU145 or PC-3 human prostate cancer xenografts were treated with either 20 or 30 mg/kg 10058-F4 on a qdx5 schedule for 2 weeks for efficacy studies. For pharmacokinetics and metabolism studies, mice bearing PC-3 or DU145 xenografts were treated with 20 mg/kg of 10058-F4 i.v. Plasma and tissues were collected 5-1440 min after dosing. The concentration of 10058-F4 in plasma and tissues was determined by HPLC, and metabolites were characterized by LC-MS/MS. Following a single iv dose, peak plasma 10058-F4 concentrations of approximately 300 muM were seen at 5 min and declined to below the detection limit at 360 min. Plasma concentration versus time data were best approximated by a two-compartment, open, linear model. The highest tissue concentrations of 10058-F4 were found in fat, lung, liver, and kidney. Peak tumor concentrations of 10058-F4 were at least tenfold lower than peak plasma concentrations. Eight metabolites of 10058-F4 were identified in plasma, liver, and kidney. The terminal half-life of 10058-F4 was approximately 1 h, and the volume of distribution was >200 ml/kg. No significant inhibition of tumor growth was seen after i.v. treatment of mice with either 20 or 30 mg/kg 10058-F4. The lack of significant antitumor activity of 10058-F4 in tumor-bearing mice may have resulted from its rapid metabolism and low concentration in tumors.

Adjuvant effect of Gantrez®AN nanoparticles during oral vaccination of piglets against F4+enterotoxigenic Escherichia coli.

PubMed

Vandamme, Katrien; Melkebeek, Vesna; Vesna, Melkebeek; Cox, Eric; Eric, Cox; Remon, Jean Paul; Paul, Remon Jean; Vervaet, Chris; Chris, Vervaet

2011-02-15

In this study, the adjuvanticity of methylvinylether-co-maleic anhydride (Gantrez(®)AN) nanoparticles (NP) was investigated in an oral immunisation experiment of pigs against F4+enterotoxigenic Escherichia coli (F4+ETEC). In addition, Wheat Germ Agglutinin (WGA)-coating of the nanoparticles was tested for enterocyte-targeting. Pigs were either vaccinated with F4 fimbriae, F4 encapsulated in Gantrez(®)AN NP, F4 encapsulated in Gantrez(®)AN NP coated with WGA or F4 fimbriae mixed with empty Gantrez(®)AN NP. Only vaccination with the combination of F4 mixed with empty Gantrez(®)AN NP improved protection against F4+ETEC infection. In addition, vaccination with this formulation also resulted in an F4-specific serum antibody response prior to F4+ETEC challenge. Encapsulation of F4 in Gantrez(®)AN NP only raised the serum antibody response after F4+ETEC challenge compared to soluble F4, but did not improve protection, whereas WGA-coating almost completely abolished the serum antibody response. These data indicate that nanoparticle effects after F4 encapsulation were of lesser importance for the adjuvant effect of Gantrez(®)AN NP, contrarily to the reactivity of the Gantrez(®)AN polymer used to prepare the nanoparticles. Copyright © 2010 Elsevier B.V. All rights reserved.

PPAR γ is highly expressed in F4/80hi adipose tissue macrophages and dampens adipose-tissue inflammation

PubMed Central

Bassaganya-Riera, Josep; Misyak, Sarah; Guri, Amir J.; Hontecillas, Raquel

2009-01-01

Macrophage infiltration into adipose tissue is a hallmark of obesity. We recently reported two phenotypically distinct subsets of adipose tissue macrophages (ATM) based on the surface expression of the glycoprotein F4/80 and responsiveness to treatment with a peroxisome proliferator-activated receptor (PPAR) γ agonist. Hence, we hypothesized that F4/80hi and F4/80lo ATM differentially express PPAR γ. This study phenotypically and functionally characterizes F4/80hi and F4/80lo ATM subsets during obesity. Changes in gene expression were also examined on sorted F4/80lo and F4/80hi ATM by quantitative real-time RT-PCR. We show that while F4/80lo macrophages predominate in adipose tissue of lean mice, obesity causes accumulation of both F4/80lo and F4/80hi ATM. Moreover, accumulation of F4/80hi ATM in adipose tissue is associated with impaired glucose tolerance. Phenotypically, F4/80hi ATM express greater amounts of CD11c, MHC II, CD49b, and CX3CR1 and produce more TNF-α, MCP-1, and IL-10 than F4/80lo ATM. Gene expression analyses of the sorted populations revealed that only the F4/80lo population produced IL-4, whereas the F4/80hi ATM expressed greater amounts of PPAR γ, δ, CD36 and toll-like receptor-4. In addition, the deficiency of PPAR γ in immune cells favors expression of M1 and impairs M2 macrophage marker expression in adipose tissue. Thus, PPAR γ is differentially expressed in F4/80hi versus F4/80low ATM subsets and its deficiency favors a predominance of M1 markers in WAT. PMID:19423085

PPAR gamma is highly expressed in F4/80(hi) adipose tissue macrophages and dampens adipose-tissue inflammation.

PubMed

Bassaganya-Riera, Josep; Misyak, Sarah; Guri, Amir J; Hontecillas, Raquel

2009-01-01

Macrophage infiltration into adipose tissue is a hallmark of obesity. We recently reported two phenotypically distinct subsets of adipose tissue macrophages (ATM) based on the surface expression of the glycoprotein F4/80 and responsiveness to treatment with a peroxisome proliferator-activated receptor (PPAR) gamma agonist. Hence, we hypothesized that F4/80(hi) and F4/80(lo) ATM differentially express PPAR gamma. This study phenotypically and functionally characterizes F4/80(hi) and F4/80(lo) ATM subsets during obesity. Changes in gene expression were also examined on sorted F4/80(lo) and F4/80(hi) ATM by quantitative real-time RT-PCR. We show that while F4/80(lo) macrophages predominate in adipose tissue of lean mice, obesity causes accumulation of both F4/80(lo) and F4/80(hi) ATM. Moreover, accumulation of F4/80(hi) ATM in adipose tissue is associated with impaired glucose tolerance. Phenotypically, F4/80(hi) ATM express greater amounts of CD11c, MHC II, CD49b, and CX3CR1 and produce more TNF-alpha, MCP-1, and IL-10 than F4/80(lo) ATM. Gene expression analyses of the sorted populations revealed that only the F4/80(lo) population produced IL-4, whereas the F4/80(hi) ATM expressed greater amounts of PPAR gamma, delta, CD36 and toll-like receptor-4. In addition, the deficiency of PPAR gamma in immune cells favors expression of M1 and impairs M2 macrophage marker expression in adipose tissue. Thus, PPAR gamma is differentially expressed in F4/80(hi) versus F4/80(low) ATM subsets and its deficiency favors a predominance of M1 markers in WAT.

The fecal presence of enterotoxin and F4 genes as an indicator of efficacy of treatment with colistin sulfate in pigs.

PubMed

Rhouma, Mohamed; Fairbrother, John Morris; Thériault, William; Beaudry, Francis; Bergeron, Nadia; Laurent-Lewandowski, Sylvette; Letellier, Ann

2017-01-05

Enterotoxigenic Escherichia coli (ETEC) strains producing multiple enterotoxins are important causes of post-weaning diarrhea (PWD) in pigs. The aim of the present study was to investigate the fecal presence of ETEC enterotoxin as well as F4 and F18 genes as an indicator of colistin sulfate (CS) efficacy for treatment of PWD in pigs. Forty-eight piglets were weaned at the age of 21 days, and were divided into four groups: challenged treated, challenged untreated, unchallenged treated, and unchallenged untreated. Challenge was performed using 10 9  CFU of an ETEC: F4 strain, and treatment was conducted using oral CS at the dose of 50,000 IU/kg. The fecal presence of genes encoding for STa, STb, LT, F4 and F18 was detected using PCR. The PCR amplification of ETEC virulence genes showed that nearly 100% of pigs excreted genes encoding for STa and STb toxins in the feces before the challenge. These genes, in the absence of the gene encoding F4, were considered as a marker for F4-negative ETEC. One day after ETEC: F4 oral challenge pigs in the two challenged groups excreted the genes encoding LT and F4 in the feces. These genes were considered as a marker for F4-positive ETEC. However, the gene encoding F18 was not detected in any fecal samples of the 4 groups throughout the experiment. After only 3 days of successive oral treatment with CS, a significant reduction in both the F4-positive and negative ETEC populations was observed in the challenged treated group compared to the challenged untreated group (p < 0.0001). Our study is among the first to report that under controlled farming conditions, oral CS treatment had a significant effect on both fecal F4-positive and F4-negative ETEC in pigs. However, CS clinical efficiency was correlated with non-detection of F4-positive ETEC in the feces. Furthermore the fecal presence of F4-negative ETEC was not associated with clinical symptoms of post-weaning diarrhea in pigs.

Accuracy of real-time shear wave elastography for assessing liver fibrosis in chronic hepatitis C: a pilot study.

PubMed

Ferraioli, Giovanna; Tinelli, Carmine; Dal Bello, Barbara; Zicchetti, Mabel; Filice, Gaetano; Filice, Carlo

2012-12-01

Real-time shear wave elastography (SWE) is a novel, noninvasive method to assess liver fibrosis by measuring liver stiffness. This single-center study was conducted to assess the accuracy of SWE in patients with chronic hepatitis C (CHC), in comparison with transient elastography (TE), by using liver biopsy (LB) as the reference standard. Consecutive patients with CHC scheduled for LB by referring physicians were studied. One hundred and twenty-one patients met inclusion criteria. On the same day, real-time SWE using the ultrasound (US) system, Aixplorer (SuperSonic Imagine S.A., Aix-en-Provence, France), TE using FibroScan (Echosens, Paris, France), and US-assisted LB were consecutively performed. Fibrosis was staged according to the METAVIR scoring system. Analyses of receiver operating characteristic (ROC) curve were performed to calculate optimal area under the ROC curve (AUROC) for F0-F1 versus F2-F4, F0- F2 versus F3-F4, and F0-F3 versus F4 for both real-time SWE and TE. Liver stiffness values increased in parallel with degree of liver fibrosis, both with SWE and TE. AUROCs were 0.92 (95% confidence interval [CI]: 0.85-0.96) for SWE and 0.84 (95% CI: 0.76-0.90) for TE (P = 0.002), 0.98 (95% CI: 0.94-1.00) for SWE and 0.96 (95% CI: 0.90-0.99) for TE (P = 0.14), and 0.98 (95% CI: 0.93-1.00) for SWE and 0.96 (95% CI: 0.91-0.99) for TE (P = 0.48), when comparing F0-F1 versus F2- F4, F0- F2 versus F3-F4, and F0 -F3 versus F4, respectively. The results of this study show that real-time SWE is more accurate than TE in assessing significant fibrosis (≥ F2). With respect to TE, SWE has the advantage of imaging liver stiffness in real time while guided by a B-mode image. Thus, the region of measurement can be guided with both anatomical and tissue stiffness information. Copyright © 2012 American Association for the Study of Liver Diseases.

Mutations in the mitochondrial thioredoxin reductase gene TXNRD2 cause dilated cardiomyopathy.

PubMed

Sibbing, Dirk; Pfeufer, Arne; Perisic, Tamara; Mannes, Alexander M; Fritz-Wolf, Karin; Unwin, Sarah; Sinner, Moritz F; Gieger, Christian; Gloeckner, Christian Johannes; Wichmann, Heinz-Erich; Kremmer, Elisabeth; Schäfer, Zasie; Walch, Axel; Hinterseer, Martin; Näbauer, Michael; Kääb, Stefan; Kastrati, Adnan; Schömig, Albert; Meitinger, Thomas; Bornkamm, Georg W; Conrad, Marcus; von Beckerath, Nicolas

2011-05-01

Cardiac energy requirement is met to a large extent by oxidative phosphorylation in mitochondria that are highly abundant in cardiac myocytes. Human mitochondrial thioredoxin reductase (TXNRD2) is a selenocysteine-containing enzyme essential for mitochondrial oxygen radical scavenging. Cardiac-specific deletion of Txnrd2 in mice results in dilated cardiomyopathy (DCM). The aim of this study was to investigate whether TXNRD2 mutations explain a fraction of monogenic DCM cases. Sequencing and subsequent genotyping of TXNRD2 in patients diagnosed with DCM (n = 227) and in DCM-free (n = 683) individuals from the general population sample KORA S4 was performed. The functional impact of observed mutations on Txnrd2 function was tested in mouse fibroblasts. We identified two novel amino acid residue-altering TXNRD2 mutations [175G > A (Ala59Thr) and 1124G > A (Gly375Arg)] in three heterozygous carriers among 227 patients that were not observed in the 683 DCM-free individuals. Both DCM-associated mutations result in amino acid substitutions of highly conserved residues in helices contributing to the flavin-adenine dinucleotide (FAD)-binding domain of TXNRD2. Functional analysis of both mutations in Txnrd2(-/-) mouse fibroblasts revealed that contrasting to wild-type (wt) Txnrd2, neither mutant did restore Txnrd2 function. Mutants even impaired the survival of Txnrd2 wt cells under oxidative stress by a dominant-negative mechanism. For the first time, we describe mutations in DCM patients in a gene involved in the regulation of cellular redox state. TXNRD2 mutations may explain a fraction of human DCM disease burden.

Synthesis, enantiomeric resolution, F-18 labeling and biodistribution of reboxetine analogs: promising radioligands for imaging the norepinephrine transporter with positron emission tomography.

PubMed

Lin, Kuo-Shyan; Ding, Yu-Shin; Kim, Sung-Won; Kil, Kun-Eek

2005-05-01

Racemic and enantiomerically pure ((S,S) and (R,R)) 2-[alpha-(2-(2-[(18)F]fluoroethoxy)phenoxy)benzyl]morpholine ([(18)F]FRB) and its tetradeuterated form [(18)F]FRB-D(4), analogs of the highly selective norepinephrine reuptake inhibitor reboxetine (2-[alpha-(2-ethoxyphenoxy)benzyl]morpholine, RB), have been synthesized for studies of norepinephrine transporter (NET) system with positron emission tomography (PET). The [(18)F]fluorinated precursor, (S,S)/(R,R)-N-tert-butyloxycarbonyl-2-[alpha-(2-hydroxyphenoxy)benzyl]morpholine ((S,S)/(R,R)-N-Boc-desethylRB), was prepared by the N-protection of (S,S)/(R,R)-2-[alpha-(2-hydroxyphenoxy)benzyl]morpholine ((S,S)/(R,R)-desethylRB) with a tert-butyloxycarbonyl (Boc) group followed by enantiomeric resolution with chiral HPLC to provide both (S,S) and (R,R) enantiomers with >99% enantiomeric purity. These compounds were then used for radiosynthesis to prepare enantiomerically pure [(18)F]FRB and [(18)F]FRB-D(4) via the following three-step procedure: (1) formation of 1-bromo-2-[(18)F]fluoroethane ([(18)F]BFE or [(18)F]BFE-D(4)) by nucleophilic displacement of 2-bromoethyl triflate (or D(4) analog) with no-carrier added [(18)F]F(-) in THF; (2) reaction of [(18)F]BFE (or [(18)F]BFE-D(4)) with N-Boc-desethylRB in DMF in the presence of excess base; and (3) deprotection with trifluoroacetic acid. The racemates, (S,S) and (R,R) enantiomers of [(18)F]FRB and [(18)F]FRB-D(4) were obtained in 11-27% (decay corrected to the end of bombardment, EOB) in 120-min synthesis time with a radiochemical purity of >98% and specific activities of 21-48 GBq/micromol (EOB). The results of the whole-body biodistribution studies with (S,S)-[(18)F]FRB-D(4) were similar to those with (S,S)-[(18)F]FRB but showed relatively faster blood clearance and no significant in vivo defluorination. Positron emission tomography studies in baboon brain also showed that (S,S)-[(18)F]FRB-D(4) may be a potentially useful ligand for imaging NET with PET.

Comparative 4f-4f absorption spectral study for the interactions of Nd(III) with some amino acids: Preliminary thermodynamics and kinetic studies of interaction of Nd(III):glycine with Ca(II)

NASA Astrophysics Data System (ADS)

Moaienla, T.; Bendangsenla, N.; David Singh, Th.; Sumitra, Ch.; Rajmuhon Singh, N.; Indira Devi, M.

2012-02-01

Spectral analysis of Nd(III) complexes with some amino acids viz.; glycine, L-alanine, L-phenylalanine and L-aspartic acid in the presence and absence of Ca 2+ was carried out in some organic solvents; CH 3OH, CH 3CN, DMF and dioxane using comparative absorption spectra of 4f-4f transitions. The study was carried out by evaluating various energy interaction parameters like Slator-Condon ( Fk), Lande factor ( ξ4f), nephelauxetic ratio ( β), bonding parameter ( b1/2), percent-covalency ( δ) by applying partial and multiple regression analysis. The values of oscillator strength ( Pobs) and Judd-Ofelt electric dipole intensity parameter Tλ ( λ = 2, 4, 6) for different 4f-4f transitions have been calculated. On analysis of the variation of the various energy interaction parameters as well as the changes in the oscillator strength ( Pobs) and Tλ values, reveal the mode of binding with the different ligands. Kinetic studies for the complexation of Nd(III):glycine:Ca(II) have also been discussed at different temperatures in DMF medium and from it the values of activation energy ( Ea) and thermodynamic parameters like Δ H°, Δ S° and Δ G° for the complexation are evaluated.

Immunogenicity and Safety of a Booster Dose of an Investigational Adjuvanted Polyprotein HIV-1 Vaccine in Healthy Adults and Effect of Administration of Chloroquine

PubMed Central

Bourguignon, Patricia; Willekens, Julie; Janssens, Michel; Clement, Frédéric; Didierlaurent, Arnaud M.; Fissette, Laurence; Roman, François; Boutriau, Dominique

2014-01-01

This phase II study evaluated the effect of chloroquine on the specific CD8+ T-cell responses to and the safety of a booster dose of investigational human immunodeficiency virus type 1 (HIV-1) F4/AS01B vaccine containing 10 μg of recombinant fusion protein (F4) adjuvanted with the AS01B adjuvant system. Healthy adults aged 21 to 41 years, primed 3 years before with two F4/AS01B doses containing 10 or 30 μg of F4 (ClinicalTrials.gov registration number NCT00434512), were randomized (1:1) to receive the F4/AS01B booster administered alone or 2 days after chloroquine (300 mg). F4-specific CD8+/CD4+ T-cell responses were characterized by intracellular cytokine staining and lymphoproliferation assays and anti-F4 antibodies by enzyme-linked immunosorbent assays (ELISAs). No effect of chloroquine on CD4+/CD8+ T-cell and antibody responses and no vaccine effect on CD8+ T-cell responses (cytokine secretion or proliferation) were detected following F4/AS01B booster administration. In vitro, chloroquine had a direct inhibitory effect on AS01B adjuvant properties; AS01-induced cytokine production decreased upon coincubation of cells with chloroquine. In the pooled group of participants primed with F4/AS01B containing 10 μg of F4, CD4+ T-cell and antibody responses induced by primary vaccination persisted for at least 3 years. The F4/AS01B booster induced strong F4-specific CD4+ T-cell responses, which persisted for at least 6 months with similar frequencies and polyfunctional phenotypes as following primary vaccination, and high anti-F4 antibody concentrations, reaching higher levels than those following primary vaccination. The F4/AS01B booster had a clinically acceptable safety and reactogenicity profile. An F4/AS01B booster dose, administered alone or after chloroquine, induced robust antibody and F4-specific CD4+ T-cell responses but no significant CD8+ T-cell responses (cytokine secretion or proliferation) in healthy adults. (This study has been registered at ClinicalTrials.gov under registration number NCT00972725). PMID:24391139

An in vitro study on the effect of TiF(4) treatment against erosion by hydrochloric acid on pellicle-covered enamel.

PubMed

Hove, L H; Young, A; Tveit, A B

2007-01-01

The aim of this in vitro study was to examine the effect of fluoride treatment on pellicle-covered enamel exposed to an acidic challenge simulating gastric reflux. Sixteen bovine and 16 human teeth were sectioned into four pieces, divided into four groups: (1) control, (2) 2-hour pellicle, (3) TiF(4), and (4) 2-hour pellicle + TiF(4), and subsequently subjected to 3 ml 0.01 M HCl stepwise for 4 + 4 + 4 min. The acid was analysed for calcium by atomic absorption spectroscopy. TiF(4) reduced Ca release from enamel by 76, 57 and 56% following the 4 + 4 + 4-min acid exposures, respectively, in bovine and 44, 54 and 54% in human enamel. These results suggest that treatment of enamel with a TiF(4) solution, with or without pellicle removal, may provide protection for the enamel against acid attack.

Role of water in the dynamic disproportionation of Zn-based TCNQ(F4) coordination polymers (TCNQ = tetracyanoquinodimethane).

PubMed

Nafady, Ayman; Le, Thanh Hai; Vo, Nguyen; Haworth, Naomi L; Bond, Alan M; Martin, Lisandra L

2014-02-17

Intriguingly, coordination polymers containing TCNQ(2–) and TCNQF4(2–) (TCNQ = 7,7,8,8-tetracyanoquinodimethane, TCNQF4 = 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane, both designated as TCNQ(F4)(2–)) may be generated from reaction of metal ions with TCNQ(F4)•–. An explanation is now provided in terms of a solvent-dependent dynamic disproportionation reaction. A systematic study of reactions associated with TCNQ(F4) and electrochemically generated TCNQ(F4)MeCN•– and TCNQ(F4)MeCN(2–) revealed that disproportionation of TCNQ(F4)MeCN•– radical anions in acetonitrile containing a low concentration of water is facilitated by the presence of ZnMeCN(2+). Thus, while the disproportionation reaction 2TCNQ(F4)MeCN•– TCNQ(F4)MeCN + TCNQ(F4)MeCN(2–) is thermodynamically very unfavorable in this medium (Keq ≈ 9 × 10(–10); TCNQF4), the preferential precipitation of ZnTCNQ(F4)(s) drives the reaction: ZnMeCN(2+) + 2 TCNQ(F4)MeCN•– ZnTCNQ(F4)(s) + TCNQ(F4)MeCN. The concomitant formation of soluble TCNQ(F4)MeCN and insoluble ZnTCNQ(F4)(s) and the loss of TCNQ(F4)MeCN•– were verified by UV–visible and infrared spectroscopy and steady-state voltammetry. Importantly, the reverse reaction of comproportionation rather than disproportionation becomes the favored process in the presence of ≥3% (v/v) water, due to the increased solubility of solid ZnTCNQ(F4)(s). Thus, in this “wet” environment, ZnMeCN(2+) and TCNQ(F4)MeCN•– are produced from a mixture of ZnTCNQ(F4)(s) and TCNQ(F4)MeCN and with the addition of water provides a medium for synthesis of [Zn(TCNQ(F4))2(H2O)2]. An important conclusion from this work is that the redox level of TCNQ(F4)-based materials, synthesized from a mixture of metal cations and TCNQ(F4)•–, is controlled by a solvent-dependent disproportionation/comproportionation reaction that may be tuned to favor formation of solids containing the monoanion radical, the dianion, or even a mixture of both.

Inhibition of c-Myc by 10058-F4 induces growth arrest and chemosensitivity in pancreatic ductal adenocarcinoma.

PubMed

Zhang, Meng; Fan, Hai-Yan; Li, Sheng-Chao

2015-07-01

Pancreatic ductal adenocarcinoma (PDAC) is a formidable medical challenge due to its malignancies and the absence of effective treatment. c-Myc, as an important transcription factor, plays crucial roles in cell cycle progression, apoptosis and cellular transformation. The c-Myc inhibitor, 10058-F4, has been reported act as a tumor suppressor in several different tumors. In current study, the tumor-suppressive roles of 10058-F4 was observed in human pancreatic cancer cells in vitro as demonstrated by decreased cell viability, cell cycle arrest at the G1/S transition and increased caspase3/7 activity. And tumor responses to gemcitabine were also significantly enhanced by 10058-F4 in PANC-1 and SW1990 cells. In a subcutaneous xenograft model, however, 10058-F4 showed no significant influence on pancreatic tumorigenesis. When combined with gemcitabine, tumorigenesis was drastically attenuated compared with gemcitabine group or 10058-F4 group; this synergistic effect was accompanied with decreased PCNA-positive cells and reduced TUNEL-positive cells in the combined treated group. Subsequent studies revealed that decreased glycolysis may be involved in the inhibitory effect of 10058-F4 on PDAC. Taken together, this study demonstrates the roles of 10058-F4 in PDAC and provides evidence that 10058-F4 in combination with gemcitabine showed significant clinical benefit over the usage of gemcitabine alone. Copyright © 2015. Published by Elsevier Masson SAS.

First step in developing a 3D biodegradable fibrin scaffold for an artificial ovary.

PubMed

Luyckx, Valérie; Dolmans, Marie-Madeleine; Vanacker, Julie; Scalercio, Sarah R; Donnez, Jacques; Amorim, Christiani A

2013-11-25

Although transplantation of cryopreserved ovarian tissue is a promising approach to restore fertility in cancer patients, it is not advisable for women at risk of ovarian involvement due to the threat of reintroducing malignant cells. The aim of this study was therefore to find an alternative for these patients by development of an artificial ovary. For construction of the artificial ovary matrix, we used a central composite design to investigate nine combinations of fibrinogen (mg/ml) and thrombin (IU/mL) (F/T): F1/T4, F12.5/T1, F12.5/T20, F25/T0.1, F25/T4, F25/T500, F50/T1, F50/T20 and F100/T4. From the first qualitative analyses (handling and matrix size), five combinations (F12.5/T1, F25/T4, F50/T20, F50/T1 and F100/T4) yielded positive results. They were further evaluated in order to assess fibrin matrix degradation and homogeneous cell encapsulation (density), survival and proliferation (Ki67), and atresia (TUNEL) before and after 7 days of in vitro culture. To determine the best compromise between maximizing the dynamic density (Y1) and minimizing the apoptosis rate (Y2), we used the desirability function approach. Two combinations (F12.5/T1 and F25/T4) showed greater distribution of cells before in vitro culture, reproducible degradation of the fibrin network and adequate support for isolated human ovarian stromal cells, with a high proportion of Ki67-positive cells. SEM analysis revealed a network of fibers with regular pores and healthy stromal cells after in vitro culture with both F/T combinations. This study reports two optimal F/T combinations that allow survival and proliferation of isolated human ovarian cells. Further studies are required to determine if such a scaffold will also be a suitable environment for isolated ovarian follicles.

Efficient delivery of cell impermeable phosphopeptides by a cyclic peptide amphiphile containing tryptophan and arginine.

PubMed

Nasrolahi Shirazi, Amir; Tiwari, Rakesh Kumar; Oh, Donghoon; Banerjee, Antara; Yadav, Arpita; Parang, Keykavous

2013-05-06

Phosphopeptides are valuable reagent probes for studying protein-protein and protein-ligand interactions. The cellular delivery of phosphopeptides is challenging because of the presence of the negatively charged phosphate group. The cellular uptake of a number of fluorescent-labeled phosphopeptides, including F'-GpYLPQTV, F'-NEpYTARQ, F'-AEEEIYGEFEAKKKK, F'-PEpYLGLD, F'-pYVNVQN-NH2, and F'-GpYEEI (F' = fluorescein), was evaluated in the presence or absence of a [WR]4, a cyclic peptide containing alternative arginine (R) and tryptophan (W) residues, in human leukemia cells (CCRF-CEM) after 2 h incubation using flow cytometry. [WR]4 improved significantly the cellular uptake of all phosphopeptides. PEpYLGLD is a sequence that mimics the pTyr1246 of ErbB2 that is responsible for binding to the Chk SH2 domain. The cellular uptake of F'-PEpYLGLD was enhanced dramatically by 27-fold in the presence of [WR]4 and was found to be time-dependent. Confocal microscopy of a mixture of F'-PEpYLGLD and [WR]4 in live cells exhibited intracellular localization and significantly higher cellular uptake compared to that of F'-PEpYLGLD alone. Transmission electron microscopy (TEM) and isothermal calorimetry (ITC) were used to study the interaction of PEpYLGLD and [WR]4. TEM results showed that the mixture of PEpYLGLD and [WR]4 formed noncircular nanosized structures with width and height of 125 and 60 nm, respectively. ITC binding studies confirmed the interaction between [WR]4 and PEpYLGLD. The binding isotherm curves, derived from sequential binding models, showed an exothermic interaction driven by entropy. These studies suggest that amphiphilic peptide [WR]4 can be used as a cellular delivery tool of cell-impermeable negatively charged phosphopeptides.

Aryl-1H-imidazole[4,5f][1,10]phenanthroline Cu(II) complexes: Electrochemical and DNA interaction studies.

PubMed

Rajebhosale, Bharati S; Dongre, Shivali N; Deshpande, Sameer S; Kate, Anup N; Kumbhar, Anupa A

2017-10-01

The reaction of aryl imidazo[4,5f] [1,10]phenanthrolines with Cu(NO 3 ) 2 lead to the formation of Cu(II) complexes of the type [Cu(L)(NO 3 ) 2 ] where L=PIP, 2-(phenyl) [4,5f] imidazo phenanthroline; HPIP=2-(2-hydroxyphenyl)imidazo [4,5f] phenanthroline and NIP=2-(naphthyl) [4,5f] imidazo phenanthroline. The interaction of these complexes with calf thymus DNA has been studied using viscosity measurements, UV-visible and fluorescence spectroscopy. Chemical nuclease activity of these complexes has also been investigated. All complexes cleave DNA via oxidative pathway involving singlet oxygen. Molecular docking studies revealed that these complexes bind to DNA through minor groove. Copyright © 2017 Elsevier Inc. All rights reserved.

The erosion and abrasion-inhibiting effect of TiF(4) and NaF varnishes and solutions on enamel in vitro.

PubMed

Levy, Flávia Mauad; Magalhães, Ana Carolina; Gomes, Marina Franciscon; Comar, Livia Picchi; Rios, Daniela; Buzalaf, Marília Afonso Rabelo

2012-01-01

OBJECTIVE. Previous in vitro study has shown that TiF(4) varnish might reduce enamel erosion. No data regarding the effect of this experimental varnish on enamel erosion plus abrasion, however, are available so far. Thus, this in vitro study aimed to analyse the effect of TiF(4) compared with NaF varnishes and solutions, to protect against enamel erosion with or without abrasion. METHODS. Enamel specimens were pre-treated with experimental-TiF(4) (2.45% F), experimental-NaF (2.45% F), NaF-Duraphat (2.26% F), and placebo varnishes; NaF (2.26% F) and TiF(4) (2.45% F) solutions. Controls remained untreated. The erosive challenge was performed using a soft drink (pH 2.6) 4 × 90 s/day (ERO) and the toothbrushing abrasion (ERO+ABR) 2 × 10 s/day, for 5 days. Between the challenges, the specimens were exposed to artificial saliva. Enamel loss was measured profilometrically (μm). RESULTS. Kruskal-Wallis/Dunn tests showed that all fluoridated varnishes (TiF(4) -ERO:0.53 ± 0.20, ERO+ABR:0.65 ± 0.19/NaF-ERO:0.94 ± 0.18, ERO+ABR:1.74 ± 0.37/Duraphat-ERO:1.00 ± 0.37, ERO+ABR:1.72 ± 0.58) were able to significantly reduce enamel loss when compared with placebo varnish (ERO:3.45 ± 0.41/ERO+ABR:3.20 ± 0.66) (P < 0.0001). Placebo varnish, control (ERO:2.68 ± 0.53/ERO+ABR:3.01 ± 0.34), and fluoridated (NaF-ERO:2.84 ± 0.09/ERO+ABR:2.40 ± 0.21/TiF(4) -ERO:3.55 ± 0.59/ERO+ABR:4.10 ± 0.38) solutions did not significantly differ from each other. CONCLUSION. Based on the results, it can be concluded that the TiF(4) varnish seems to be a promising treatment to reduce enamel loss under mild erosive and abrasive conditions in vitro. © 2011 The Authors. International Journal of Paediatric Dentistry © 2011 BSPD, IAPD and Blackwell Publishing Ltd.

Erythrocyte and porcine intestinal glycosphingolipids recognized by F4 fimbriae of enterotoxigenic Escherichia coli.

PubMed

Coddens, Annelies; Valis, Erik; Benktander, John; Ångström, Jonas; Breimer, Michael E; Cox, Eric; Teneberg, Susann

2011-01-01

Enterotoxigenic F4-fimbriated Escherichia coli is associated with diarrheal disease in neonatal and postweaning pigs. The F4 fimbriae mediate attachment of the bacteria to the pig intestinal epithelium, enabling an efficient delivery of diarrhea-inducing enterotoxins to the target epithelial cells. There are three variants of F4 fimbriae designated F4ab, F4ac and F4ad, respectively, having different antigenic and adhesive properties. In the present study, the binding of isolated F4ab, F4ac and F4ad fimbriae, and F4ab/ac/ad-fimbriated E. coli, to glycosphingolipids from erythrocytes and from porcine small intestinal epithelium was examined, in order to get a comprehensive view of the F4-binding glycosphingolipids involved in F4-mediated hemagglutination and adhesion to the epithelial cells of porcine intestine. Specific interactions between the F4ab, F4ac and F4ad fimbriae and both acid and non-acid glycosphingolipids were obtained, and after isolation of binding-active glycosphingolipids and characterization by mass spectrometry and proton NMR, distinct carbohydrate binding patterns were defined for each fimbrial subtype. Two novel glycosphingolipids were isolated from chicken erythrocytes, and characterized as GalNAcα3GalNAcß3Galß4Glcß1Cer and GalNAcα3GalNAcß3Galß4GlcNAcß3Galß4Glcß1Cer. These two compounds, and lactosylceramide (Galß4Glcß1Cer) with phytosphingosine and hydroxy fatty acid, were recognized by all three variants of F4 fimbriae. No binding of the F4ad fimbriae or F4ad-fimbriated E. coli to the porcine intestinal glycosphingolipids occurred. However, for F4ab and F4ac two distinct binding patterns were observed. The F4ac fimbriae and the F4ac-expressing E. coli selectively bound to galactosylceramide (Galß1Cer) with sphingosine and hydroxy 24:0 fatty acid, while the porcine intestinal glycosphingolipids recognized by F4ab fimbriae and the F4ab-fimbriated bacteria were characterized as galactosylceramide, sulfatide (SO(3)-3Galß1Cer), sulf-lactosylceramide (SO(3)-3Galß4Glcß1Cer), and globotriaosylceramide (Galα4Galß4Glcß1Cer) with phytosphingosine and hydroxy 24:0 fatty acid. Finally, the F4ad fimbriae and the F4ad-fimbriated E. coli, but not the F4ab or F4ac subtypes, bound to reference gangliotriaosylceramide (GalNAcß4Galß4Glcß1Cer), gangliotetraosylceramide (Galß3GalNAcß4Galß4Glcß1Cer), isoglobotriaosylceramide (Galα3Galß4Glcß1Cer), and neolactotetraosylceramide (Galß4GlcNAcß3Galß4Glcß1Cer).

Erythrocyte and Porcine Intestinal Glycosphingolipids Recognized by F4 Fimbriae of Enterotoxigenic Escherichia coli

PubMed Central

Coddens, Annelies; Valis, Erik; Benktander, John; Ångström, Jonas; Breimer, Michael E.; Cox, Eric; Teneberg, Susann

2011-01-01

Enterotoxigenic F4-fimbriated Escherichia coli is associated with diarrheal disease in neonatal and postweaning pigs. The F4 fimbriae mediate attachment of the bacteria to the pig intestinal epithelium, enabling an efficient delivery of diarrhea-inducing enterotoxins to the target epithelial cells. There are three variants of F4 fimbriae designated F4ab, F4ac and F4ad, respectively, having different antigenic and adhesive properties. In the present study, the binding of isolated F4ab, F4ac and F4ad fimbriae, and F4ab/ac/ad-fimbriated E. coli, to glycosphingolipids from erythrocytes and from porcine small intestinal epithelium was examined, in order to get a comprehensive view of the F4-binding glycosphingolipids involved in F4-mediated hemagglutination and adhesion to the epithelial cells of porcine intestine. Specific interactions between the F4ab, F4ac and F4ad fimbriae and both acid and non-acid glycosphingolipids were obtained, and after isolation of binding-active glycosphingolipids and characterization by mass spectrometry and proton NMR, distinct carbohydrate binding patterns were defined for each fimbrial subtype. Two novel glycosphingolipids were isolated from chicken erythrocytes, and characterized as GalNAcα3GalNAcß3Galß4Glcß1Cer and GalNAcα3GalNAcß3Galß4GlcNAcß3Galß4Glcß1Cer. These two compounds, and lactosylceramide (Galß4Glcß1Cer) with phytosphingosine and hydroxy fatty acid, were recognized by all three variants of F4 fimbriae. No binding of the F4ad fimbriae or F4ad-fimbriated E. coli to the porcine intestinal glycosphingolipids occurred. However, for F4ab and F4ac two distinct binding patterns were observed. The F4ac fimbriae and the F4ac-expressing E. coli selectively bound to galactosylceramide (Galß1Cer) with sphingosine and hydroxy 24:0 fatty acid, while the porcine intestinal glycosphingolipids recognized by F4ab fimbriae and the F4ab-fimbriated bacteria were characterized as galactosylceramide, sulfatide (SO3-3Galß1Cer), sulf-lactosylceramide (SO3-3Galß4Glcß1Cer), and globotriaosylceramide (Galα4Galß4Glcß1Cer) with phytosphingosine and hydroxy 24:0 fatty acid. Finally, the F4ad fimbriae and the F4ad-fimbriated E. coli, but not the F4ab or F4ac subtypes, bound to reference gangliotriaosylceramide (GalNAcß4Galß4Glcß1Cer), gangliotetraosylceramide (Galß3GalNAcß4Galß4Glcß1Cer), isoglobotriaosylceramide (Galα3Galß4Glcß1Cer), and neolactotetraosylceramide (Galß4GlcNAcß3Galß4Glcß1Cer). PMID:21949679

Cooperativity of E-cadherin and Smad4 loss to promote diffuse-type gastric adenocarcinoma and metastasis.

PubMed

Park, Jun Won; Jang, Seok Hoon; Park, Dong Min; Lim, Na Jung; Deng, Chuxia; Kim, Dae Yong; Green, Jeffrey E; Kim, Hark Kyun

2014-08-01

Loss of E-cadherin (CDH1), Smad4, and p53 has been shown to play an integral role in gastric, intestinal, and breast cancer formation. Compound conditional knockout mice for Smad4, p53, and E-cadherin were generated to define and compare the roles of these genes in gastric, intestinal, and breast cancer development by crossing with Pdx-1-Cre, Villin-Cre, and MMTV-Cre transgenic mice. Interestingly, gastric adenocarcinoma was significantly more frequent in Pdx-1-Cre;Smad4(F/F);Trp53(F/F);Cdh1(F) (/+) mice than in Pdx-1-Cre;Smad4(F/F);Trp53(F/F);Cdh1(+/+) mice, demonstrating that Cdh1 heterozygosity accelerates the development and progression of gastric adenocarcinoma, in combination with loss of Smad4 and p53. Pdx-1-Cre;Smad4(F/F);Trp53(F/F);Cdh1(F) (/+) mice developed gastric adenocarcinomas without E-cadherin expression. However, intestinal and mammary adenocarcinomas with the same genetic background retained E-cadherin expression and were phenotypically similar to mice with both wild-type Cdh1 alleles. Lung metastases were identified in Pdx-1-Cre;Smad4(F/F);Trp53(F/F);Cdh1(F) (/+) mice, but not in the other genotypes. Nuclear β-catenin accumulation was identified at the invasive tumor front of gastric adenocarcinomas arising in Pdx-1-Cre;Smad4(F/F);Trp53(F/F);Cdh1(F) (/+) mice. This phenotype was less prominent in mice with intact E-cadherin or Smad4, indicating that the inhibition of β-catenin signaling by E-cadherin or Smad4 downregulates signaling pathways involved in metastases in Pdx-1-Cre;Smad4(F/F);Trp53(F/F);Cdh1(F) (/+) mice. Knockdown of β-catenin significantly inhibited the migratory activity of Pdx-1-Cre;Smad4(F/F);Trp53(F/F);Cdh1(F) (/+) cell lines. Thus, loss of E-cadherin and Smad4 cooperates with p53 loss to promote the development and metastatic progression of gastric adenocarcinomas, with similarities to human gastric adenocarcinoma. This study demonstrates that inhibition of β-catenin is a converging node for the antimetastatic signaling pathways driven by E-cadherin and Smad4 in Pdx-1-Cre;Smad4(F/F);Trp53(F/F);Cdh1(F) (/+) mice, providing novel insights into mechanisms for gastric cancer metastasis. ©2014 American Association for Cancer Research.

Estimation of hepatic extracellular volume fraction using multiphasic liver computed tomography for hepatic fibrosis grading.

PubMed

Yoon, Jeong Hee; Lee, Jeong Min; Klotz, Ernst; Jeon, Ju Hyun; Lee, Kyung-Bun; Han, Joon Koo; Choi, Byung Ihn

2015-04-01

The purpose of this study was to determine whether hepatic extracellular volume fractions (fECVs) measured using multiphasic liver computed tomography (CT) can be used to quantify the severity of hepatic fibrosis (HF). This retrospective study was approved by our institutional review board, and the requirement for informed consent was waived. A total of 141 patients (male-female ratio, 109:32; mean [SD] age, 59.4 [11.4] years) histologically diagnosed with HF (F0-F1 = 33 and F2-F4 = 108) underwent multiphasic liver CT. Absolute enhancements (in Hounsfield unit) of the liver parenchyma (Eliver) and aorta (Eaorta) 3 minutes after contrast administration were measured on subtraction images of precontrast and equilibrium phase scans using nonrigid registration software. The fECV was calculated using the following equation: fECV (%) = Eliver/Eaorta × (100 - Hematocrit [%]). Correlation between fECV and HF stage was evaluated using the Spearman correlation coefficient. The fECVs were compared between F0-F1 and ≥F2 as well as between child A and child B or C. Diagnostic performance of fECV in predicting significant HF (≥F2) was assessed using receiver operating curve analysis. The fECVs showed a significant correlation with pathologic HF staging (r = 0.493, P < 0.001). The F2-F4 showed significantly higher fECVs than did F0 to F1 (33.6% [4.7%] vs 27.7% [4.4%]; P < 0.001). The fECVs were significantly higher in the patients with child B or C than those with child A (35.2% [7.0%] vs 31.3% [4.2%]; P < 0.001). The fECV values higher than 28.76% provided 87.5% sensitivity and 71.0% specificity in detecting significant HF (area under the curve, 0.832; P < 0.0001). Because fECV was shown to increase along with HF progression, the estimation of fECV using routine multiphasic liver CT may have the potential to detect significant HF.

Intravoxel Incoherent Motion MR Imaging for Staging of Hepatic Fibrosis.

PubMed

Zhang, Bin; Liang, Long; Dong, Yuhao; Lian, Zhouyang; Chen, Wenbo; Liang, Changhong; Zhang, Shuixing

2016-01-01

To determine the potential of intravoxel incoherent motion (IVIM) MR imaging for staging of hepatic fibrosis (HF). We searched PubMed and EMBASE from their inception to 31 July 2015 to select studies reporting IVIM MR imaging and HF staging. We defined F1-2 as non-advanced HF, F3-4 as advanced HF, F0 as normal liver, F1 as very early HF, and F2-4 as significant HF. Then we compared stage F0 with F1, F0-1 with F2-3, and F1-2 with F3-4 using IVIM-derived parameters (pseudo-diffusion coefficient D*, perfusion fraction f, and pure molecular diffusion parameter D). The effect estimate was expressed as a pooled weighted mean difference (WMD) with 95% confidence interval (CI), using the fixed-effects model. Overall, we included six papers (406 patients) in this study. Significant differences in D* were observed between F0 and F1, F0-1 and F2-3, and F1-2 and F3-4 (WMD 2.46, 95% CI 0.83-4.09, P = 0.006; WMD 13.10, 95% CI 9.53-16.67, P < 0.001; WMD 14.34, 95% CI 10.26-18.42, P < 0.001, respectively). Significant differences in f were also found between F0 and F1, F0-1 and F2-3, and F1-2 and F3-4 (WMD 1.62, 95% CI 0.06-3.18, P = 0.027; WMD 5.63, 95% CI 2.74-8.52, P < 0.001; WMD 3.30, 95% CI 2.10-4.50, P < 0.001, respectively). However, D showed no differences between F0 and F1, F0-1 and F2-3, and F1-2 and F3-4 (WMD 0.05, 95% CI -0.01─0.11, P = 0.105; WMD 0.04, 95% CI -0.01─0.10, P = 0.230; WMD 0.02, 95% CI -0.02─0.06, P = 0.378, respectively). IVIM MR imaging provides an effective method of staging HF and can distinguish early HF from normal liver, significant HF from normal liver or very early HF, and advanced HF from non-advanced HF.

Center-of-gravity effects in the perception of high front vowels

NASA Astrophysics Data System (ADS)

Jacewicz, Ewa; Feth, Lawrence L.

2002-05-01

When two formant peaks are close in frequency, changing their amplitude ratio can shift the perceived vowel quality. This center-of-gravity effect (COG) was studied particularly in back vowels whose F1 and F2 are close in frequency. Chistovich and Lublinskaja (1979) show that the effect occurs when the frequency separation between the formants does not exceed 3.5 bark. The COG and critical distance effects were manifested when a two-formant reference signal was matched by a single-formant target of variable frequency. This study investigates whether the COG effect extends to closely spaced higher formants as in English /i/ and /I/. In /i/, the frequency separation between F2, F3, and F4 does not exceed 3.5 bark, suggesting the existence of one COG which may affect all three closely spaced formants (F2=2030, F3=2970, F4=3400 Hz). In /I/, each of the F2-F3 and F3-F4 separations is less than 3.5 bark but the F2-F4 separation exceeds the critical distance, indicating two COGs (F2=1780, F3=2578, F4=3400 Hz). We examine the COG effects using matching of four-formant reference signals, in which we change the amplitude ratios, by two-formant targets with variable frequency of F2. The double-staircase adaptive procedure is used. [Work supported by an INRS award from NIH to R. Fox.

Clostridium botulinum strains producing BoNT/F4 or BoNT/F5.

PubMed

Raphael, Brian H; Bradshaw, Marite; Kalb, Suzanne R; Joseph, Lavin A; Lúquez, Carolina; Barr, John R; Johnson, Eric A; Maslanka, Susan E

2014-05-01

Botulinum neurotoxin type F (BoNT/F) may be produced by Clostridium botulinum alone or in combination with another toxin type such as BoNT/A or BoNT/B. Type F neurotoxin gene sequences have been further classified into seven toxin subtypes. Recently, the genome sequence of one strain of C. botulinum (Af84) was shown to contain three neurotoxin genes (bont/F4, bont/F5, and bont/A2). In this study, eight strains containing bont/F4 and seven strains containing bont/F5 were examined. Culture supernatants produced by these strains were incubated with BoNT/F-specific peptide substrates. Cleavage products of these peptides were subjected to mass spectral analysis, allowing detection of the BoNT/F subtypes present in the culture supernatants. PCR analysis demonstrated that a plasmid-specific marker (PL-6) was observed only among strains containing bont/F5. Among these strains, Southern hybridization revealed the presence of an approximately 242-kb plasmid harboring bont/F5. Genome sequencing of four of these strains revealed that the genomic backgrounds of strains harboring either bont/F4 or bont/F5 are diverse. None of the strains analyzed in this study were shown to produce BoNT/F4 and BoNT/F5 simultaneously, suggesting that strain Af84 is unusual. Finally, these data support a role for the mobility of a bont/F5-carrying plasmid among strains of diverse genomic backgrounds.

N,N-dimethyl-2-(2-amino-4-(18)F-fluorophenylthio)-benzylamine (4-(18)F-ADAM): an improved PET radioligand for serotonin transporters.

PubMed

Shiue, Grace G; Choi, Seok-Rye; Fang, Ping; Hou, Catherine; Acton, Paul D; Cardi, Chris; Saffer, Janet R; Greenberg, Joel H; Karp, Joel S; Kung, Hank F; Shiue, Chyng-Yann

2003-12-01

There has been considerable interest in the development of PET radioligands that are useful for imaging serotonin transporter (SERT) in the living human brain. For the last decade, (11)C-(+)McN5652 has been the most promising PET agent for studying SERT in humans. However, this agent has some limitations. Recently, a new promising SERT PET radioligand, 3-(11)C-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile, has been reported. We recently reported the synthesis of a new (18)F-labeled SERT PET radioligand, N,N-dimethyl-2-(2-amino-4-(18)F-fluorophenylthio)benzylamine (4-(18)F-ADAM), which may have advantages over (11)C-labeled radioligands. The purpose of this study was to evaluate this newly developed (18)F-labeled PET radioligand as a promising agent for studying SERT in the living human brain. This agent was evaluated by studying its in vitro binding to different monoamine transporters, its in vivo biodistributions in rats, its integrity and pharmacologic profiles in rat brain, and its distribution in a female baboon brain. In vitro binding assays showed that 4-F-ADAM displayed high affinity to SERT sites (inhibition constant = 0.081 nmol/L, using membrane preparations of LLC-PK1 cells expressing the specific transporter) and showed more than 1,000- and 28,000-fold selectivity for SERT over norepinephrine transporter and dopamine transporter, respectively. Biodistribution of 4-(18)F-ADAM in rats showed a high initial uptake and slow clearance in the brain (2.13%, 1.90%, and 0.95% injected dose per organ at 2, 30, and 60 min after intravenous injection, respectively), with the specific binding peaking at 2 h after injection (hypothalamus/cerebellum = 12.49). The uptake in blood, muscle, lung, kidney, and liver was also initially high but cleared rapidly. The radioactivity in the femur increases with time for 4-(18)F-ADAM, indicating that in vivo defluorination may occur. In vivo metabolism studies in rats showed that 4-(18)F-ADAM was not metabolized in rat brain (>96% of radioactivity was recovered as parent compound at 1 h after injection). However, it metabolized rapidly in the blood. Less than 7% of the radioactivity recovered from plasma was the parent compound, with the majority of radioactivity in the plasma not extractable by ethyl acetate. Blocking studies showed significant decreases in the uptake of 4-(18)F-ADAM in the brain regions (hypothalamus, hippocampus, and striatum) where SERT concentrations are high when rats were pretreated with (+)McN5652 (2 mg/kg 5 min before intravenous injection of 4-(18)F-ADAM). However, changes in the uptake of 4-(18)F-ADAM in these brain regions were less significant when rats were pretreated with either methylphenidate or nisoxetine. The baboon study showed that uptake of 4-(18)F-ADAM in the midbrain peaked at approximately 1 h after injection and then declined slowly. The ratios of the radioactivity in the midbrain to that in the cerebellum (where the concentration of SERT is low) at 2 and 3 h after injection were 3.2 and 4.2, respectively. 4-(18)F-ADAM is suitable as a PET radioligand for studying SERT in the living brain. Further characterization of this new radioligand in humans is warranted.

Analytical variables affecting analysis of F2-isoprostanes and F4-neuroprostanes in human cerebrospinal fluid by gas chromatography/mass spectrometry.

PubMed

Yen, Hsiu-Chuan; Wei, Hsing-Ju; Chen, Ting-Wei

2013-01-01

F2-isoprostanes (F2-IsoPs) are a gold marker of lipid peroxidation in vivo, whereas F4-neuroprostanes (F4-NPs) measured in cerebrospinal fluid (CSF) or brain tissue selectively indicate neuronal oxidative damage. Gas chromatography/negative-ion chemical-ionization mass spectrometry (GC/NICI-MS) is the most sensitive and robust method for quantifying these compounds, which is essential for CSF samples because abundance of these compounds in CSF is very low. The present study revealed potential interferences on the analysis of F2-IsoPs and F4-NPs in CSF by GC/NICI-MS due to the use of improper analytical methods that have been employed in the literature. First, simultaneous quantification of F2-IsoPs and F4-NPs in CSF samples processed for F4-NPs analysis could cause poor chromatographic separation and falsely higher F2-IsoPs values for CSF samples with high levels of F2-IsoPs and F4-NPs. Second, retention of unknown substances in GC columns from CSF samples during F4-NPs analysis and from plasma samples during F2-IsoPs analysis might interfere with F4-NPs analysis of subsequent runs, which could be solved by holding columns at a high temperature for a period of time after data acquisition. Therefore, these special issues should be taken into consideration when performing analysis of F2-IsoPs and F4-NPs in CSF to avoid misleading results.

Analytical Variables Affecting Analysis of F2-Isoprostanes and F4-Neuroprostanes in Human Cerebrospinal Fluid by Gas Chromatography/Mass Spectrometry

PubMed Central

Yen, Hsiu-Chuan; Wei, Hsing-Ju; Chen, Ting-Wei

2013-01-01

F2-isoprostanes (F2-IsoPs) are a gold marker of lipid peroxidation in vivo, whereas F4-neuroprostanes (F4-NPs) measured in cerebrospinal fluid (CSF) or brain tissue selectively indicate neuronal oxidative damage. Gas chromatography/negative-ion chemical-ionization mass spectrometry (GC/NICI-MS) is the most sensitive and robust method for quantifying these compounds, which is essential for CSF samples because abundance of these compounds in CSF is very low. The present study revealed potential interferences on the analysis of F2-IsoPs and F4-NPs in CSF by GC/NICI-MS due to the use of improper analytical methods that have been employed in the literature. First, simultaneous quantification of F2-IsoPs and F4-NPs in CSF samples processed for F4-NPs analysis could cause poor chromatographic separation and falsely higher F2-IsoPs values for CSF samples with high levels of F2-IsoPs and F4-NPs. Second, retention of unknown substances in GC columns from CSF samples during F4-NPs analysis and from plasma samples during F2-IsoPs analysis might interfere with F4-NPs analysis of subsequent runs, which could be solved by holding columns at a high temperature for a period of time after data acquisition. Therefore, these special issues should be taken into consideration when performing analysis of F2-IsoPs and F4-NPs in CSF to avoid misleading results. PMID:23957004

High susceptibility to liver injury in IL-27 p28 conditional knockout mice involves intrinsic interferon-γ dysregulation of CD4+ T cells.

PubMed

Zhang, Song; Liang, Ruifang; Luo, Wei; Liu, Chang; Wu, Xiaoli; Gao, Yanan; Hao, Jianlei; Cao, Guangchao; Chen, Xi; Wei, Jun; Xia, Siyuan; Li, Zheng; Wen, Ti; Wu, Yunyun; Zhou, Xinglong; Wang, Puyue; Zhao, Liqing; Wu, Zhengzhou; Xiong, Sidong; Gao, Xiaoming; Gao, Xiang; Chen, Yongyan; Ge, Qing; Tian, Zhigang; Yin, Zhinan

2013-04-01

Interleukin (IL)-27, a newly discovered IL-12 family cytokine, is composed of p28 and EBI3. In this study, CD11c-p28(f/f) conditional knockout mice were generated to delete p28 specifically in dendritic cells (DCs). We demonstrated that in the absence of DC-derived p28, these mice were highly susceptible to both low and higher concentrations of concanavalin A (ConA) (5 mg/kg or 10 mg/kg), with extremely early and steady high levels of interferon-γ (IFN-γ) in sera. Neutralizing IFN-γ prevented ConA-induced liver damage in these mice, indicating a critical role of IFN-γ in this pathological process. Interestingly, the main source of the increased IFN-γ in CD11c-p28(f/f) mice was CD4+ T cells, but not natural killer T (NKT) cells. Depletion of CD4+ , but not NK1.1+ , cells completely abolished liver damage, whereas transferring CD4+ T cells from CD11c-p28(f/f) mice, but not from wild-type mice or CD11c-p28(f/f) -IFN-γ(-/-) double knockout mice to CD4(-/-) mice, restored the increased liver damage. Further studies defined higher levels of IFN-γ and T-bet messenger RNA in naïve CD4+ T cells from CD11c-p28(f/f) mice, and these CD4+ T cells were highly responsive to both low and higher concentrations of anti-CD3, indicating a programmed functional alternation of CD4+ T cells. We provide a unique model for studying the pathology of CD4+ T cell-mediated liver injury and reveal a novel function of DC-derived p28 on ConA-induced fulminant hepatitis through regulation of the intrinsic ability for IFN-γ production by CD4+ T cells. Copyright © 2012 American Association for the Study of Liver Diseases.

Electronic structure of the (Nd{sub 1−x}Dy{sub x}){sub 2}Fe{sub 14}B (0 ≤ x ≤ 1) system studied by X-ray photoelectron spectroscopy

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

Wang, Jing; Liang, Le; Yang, Bin

2015-09-15

Systematic characterization of electronic structures in the (Nd{sub 1−x}Dy{sub x}){sub 2}Fe{sub 14}B system, especially the 4f behavior, provides an insight to the physical nature of the evolution of magnetic properties. A series of X-ray photoelectron spectroscopy (XPS) core-level and valence-band spectra were used to study the electronic structures. It was found that substitution of Dy for Nd in Nd{sub 2}Fe{sub 14}B results in a nonlinear variation in the evolution of electronic structures. Only the finite coupling between the Nd 4f states and the Fe 3d states is found at both the Nd-rich regime and the Dy-rich regime. When the Dymore » concentration and the Nd concentration approach to be equal, a strong coupling between the Nd 4f states and the Fe 3d states is found, which results in a bonding state between them. Additionally, the 4f components in the (Nd{sub 1−x}Dy{sub x}){sub 2}Fe{sub 14}B system are ascribed to three parts: 1) the individual contribution of the Dy 4f states, which emerges just after the Dy-substitution; 2) the contribution of the coupling between the Nd 4f states and the Dy 4f states, which arises only when 0.4 ≤ x ≤ 0.6; 3) the associated contributions of the Nd 4f states and the Dy 4f states, where the contribution of the Nd 4f states and that of the Dy 4f states are prominent in the Nd-rich regime and Dy-rich regime, respectively.« less

Genome-wide meta-analysis identifies novel determinants of circulating serum progranulin.

PubMed

Tönjes, Anke; Scholz, Markus; Krüger, Jacqueline; Krause, Kerstin; Schleinitz, Dorit; Kirsten, Holger; Gebhardt, Claudia; Marzi, Carola; Grallert, Harald; Ladenvall, Claes; Heyne, Henrike; Laurila, Esa; Kriebel, Jennifer; Meisinger, Christa; Rathmann, Wolfgang; Gieger, Christian; Groop, Leif; Prokopenko, Inga; Isomaa, Bo; Beutner, Frank; Kratzsch, Jürgen; Fischer-Rosinsky, Antje; Pfeiffer, Andreas; Krohn, Knut; Spranger, Joachim; Thiery, Joachim; Blüher, Matthias; Stumvoll, Michael; Kovacs, Peter

2018-02-01

Progranulin is a secreted protein with important functions in processes including immune and inflammatory response, metabolism and embryonic development. The present study aimed at identification of genetic factors determining progranulin concentrations. We conducted a genome-wide association meta-analysis for serum progranulin in three independent cohorts from Europe: Sorbs (N = 848) and KORA (N = 1628) from Germany and PPP-Botnia (N = 335) from Finland (total N = 2811). Single nucleotide polymorphisms (SNPs) associated with progranulin levels were replicated in two additional German cohorts: LIFE-Heart Study (Leipzig; N = 967) and Metabolic Syndrome Berlin Potsdam (Berlin cohort; N = 833). We measured mRNA expression of genes in peripheral blood mononuclear cells (PBMC) by micro-arrays and performed mRNA expression quantitative trait and expression-progranulin association studies to functionally substantiate identified loci. Finally, we conducted siRNA silencing experiments in vitro to validate potential candidate genes within the associated loci. Heritability of circulating progranulin levels was estimated at 31.8% and 26.1% in the Sorbs and LIFE-Heart cohort, respectively. SNPs at three loci reached study-wide significance (rs660240 in CELSR2-PSRC1-MYBPHL-SORT1, rs4747197 in CDH23-PSAP and rs5848 in GRN) explaining 19.4%/15.0% of the variance and 61%/57% of total heritability in the Sorbs/LIFE-Heart Study. The strongest evidence for association was at rs660240 (P = 5.75 × 10-50), which was also associated with mRNA expression of PSRC1 in PBMC (P = 1.51 × 10-21). Psrc1 knockdown in murine preadipocytes led to a consecutive 30% reduction in progranulin secretion. In conclusion, the present meta-GWAS combined with mRNA expression identified three loci associated with progranulin and supports the role of PSRC1 in the regulation of progranulin secretion. © The Author(s) 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Variation in 12 porcine genes involved in the carbohydrate moiety assembly of glycosphingolipids does not account for differential binding of F4 Escherichia coli and their fimbriae.

PubMed

Goetstouwers, Tiphanie; Van Poucke, Mario; Coddens, Annelies; Nguyen, Van Ut; Melkebeek, Vesna; Deforce, Dieter; Cox, Eric; Peelman, Luc J

2014-10-03

Glycosphingolipids (GSLs) are important membrane components composed of a carbohydrate structure attached to a hydrophobic ceramide. They can serve as specific membrane receptors for microbes and microbial products, such as F4 Escherichia coli (F4 ETEC) and isolated F4 fimbriae. The aim of this study was to investigate the hypothesis that variation in genes involved in the assembly of the F4 binding carbohydrate moiety of GSLs (i.e. ARSA, B4GALT6, GAL3ST1, GALC, GBA, GLA, GLB1, GLB1L, NEU1, NEU2, UGCG, UGT8) could account for differential binding of F4 ETEC and their fimbriae. RT-PCR could not reveal any differential expression of the 12 genes in the jejunum of F4 receptor-positive (F4R(+)) and F4 receptor-negative (F4R(-)) pigs. Sequencing the complete open reading frame of the 11 expressed genes (NEU2 was not expressed) identified 72 mutations. Although some of them might have a structural effect, none of them could be associated with a F4R phenotype. We conclude that no regulatory or structural variation in any of the investigated genes is responsible for the genetic susceptibility of pigs towards F4 ETEC.

Sidedness of interfacial arginine residues and anti-atherogenicity of apolipoprotein A-I mimetic peptides

PubMed Central

Nayyar, Gaurav; Mishra, Vinod K.; Handattu, Shaila P.; Palgunachari, Mayakonda N.; Shin, Ronald; McPherson, David T.; Deivanayagam, Champion C. S.; Garber, David W.; Segrest, Jere P.; Anantharamaiah, G. M.

2012-01-01

To test the hypothesis that sidedness of interfacial arginine (Arg) in apoA-I mimetic peptides, similar to that observed in apoA-I (Bashtovyy, D. et al. 2011. Sequence conservation of apolipoprotein A-I affords novel insights into HDL structure-function. J. Lipid Res. 52: 435–450.), may be important for biological activity, we compared properties of 4F and analogs, [K4,15>R]4F and [K9,13>R]4F, with Lys>Arg substitutions on the right and left side, respectively, of the 4F amphipathic helix. Intraperitoneal administration of these peptides into female apoE null mice (n = 13 in each group) reduced en face lesions significantly compared with controls; 4F and [K4,15>R]4F were equally effective whereas [K9,13>R]4F was less effective. Turnover experiments indicated that [K4,15>R]4F reached the highest, whereas [K9,13>R]4F had the lowest, plasma peak levels with a similar half life as the [K4,15>R]4F analog. The half life of 4F was two times longer than the other two peptides. The order in their abilities to associate with HDL in human plasma, generation of apoA-I particles with pre-β mobility from isolated HDL, lipid associating ability, and sensitivity of lipid complexes to trypsin digestion was: 4F>[K4,15,>R]4F>[K9,13>R]4F. These studies support our hypothesis that the sidedness of interfacial Arg residues in the polar face of apoA-I mimetics results in differential biological properties. PMID:22377531

Distribution of Escherichia coli F4 adhesion phenotypes in pigs of 15 Chinese and Western breeds and a White DurocxErhualian intercross.

PubMed

Yan, Xueming; Huang, Xiang; Ren, Jun; Zou, Zhengzhi; Yang, Shujin; Ouyang, Jing; Zeng, Weihong; Yang, Bin; Xiao, Shijun; Huang, Lusheng

2009-08-01

Diarrhoea in newborn and weaned piglets is mainly caused by enterotoxigenic Escherichia coli (ETEC) with fimbriae F4. To investigate the prevalence of resistance to three fimbrial strains, F4ab, F4ac and F4ad, among Chinese indigenous pigs and Western commercial pigs introduced into China, we determined the ETEC F4 adhesion phenotypes in 292 pure-bred piglets from three Western commercial breeds and 12 Chinese indigenous breeds, and a total of 1093 adult pigs in a White DurocxErhualian intercross, by an in vitro microscopic adhesion assay. All the Tibet and Lantang pigs and a majority of the Erhualian and Rongchang pigs were resistant (nonadherent) to ETEC F4 whereas all the Laiwu pigs and most of the Jiangquhai and Tongcheng pigs were susceptible (adhesive) to at least one of the F4 strains. Yushan Black pigs were uniformly resistant to F4ab, and Jinhua pigs were predominantly resistant to F4ac. Susceptible and resistant animals were observed in the other breeds, indicating that diarrhoea caused by ETEC F4 could be prevalent in these breeds. This study confirmed the existence of eight previously reported F4 adhesion patterns, and supported the assumption that the three F4 receptors are encoded by distinct loci. Expression of the weakly adherent phenotype was observed in six pure-bred piglets and 90 adult F(2)/F(3) animals, and the inheritance of this phenotype and its correlation with susceptibility to disease are still not known.

A Radiofluorinated Divalent Cystine Knot Peptide for Tumor PET Imaging

DOE PAGES

Jiang, Lei; Kimura, Richard H.; Ma, Xiaowei; ...

2014-04-09

A divalent knottin containing two separate integrin binding epitopes (RGD) in the adjacent loops, 3-4A, was recently developed and reported in our previous publication. In the current study, 3-4A was radiofluorinated with a 4-nitrophenyl 2- 18F-fluoropropinate ( 18F-NFP) group and the resulting divalent positron emission tomography (PET) probe, 18F-FP–3-4A, was evaluated as a novel imaging probe to detect integrin αvβ3 positive tumors in living animals. Knottin 3-4A was synthesized by solid phase peptide synthesis, folded, and site-specifically conjugated with 18/19F-NFP to produce the fluorinated peptide 18/19F-fluoropropinate-3-4A ( 18/19F-FP–3-4A). The stability of 18F-FP–3-4A was tested in both phosphate buffered saline (PBS)more » buffer and mouse serum. Cell uptake assays of the radiolabeled peptides were performed using U87MG cells. In addition, small animal PET imaging and biodistribution studies of 18F-FP–3-4A were performed in U87MG tumor-bearing mice. The receptor targeting specificity of the radiolabeled peptide was also verified by coinjecting the probe with a blocking peptide cyclo(RGDyK). Our study showed that 18F-FP–3-4A exhibited excellent stability in PBS buffer (pH 7.4) and mouse serum. Small animal PET imaging and biodistribution data revealed that 18F-FP–3-4A exhibited rapid and good tumor uptake (3.76 ± 0.59% ID/g and 2.22 ± 0.62% ID/g at 0.5 and 1 h, respectively). 18F-FP–3-4A was rapidly cleared from the normal tissues, resulting in excellent tumor-to-normal tissue contrasts. For example, liver uptake was only 0.39 ± 0.07% ID/g and the tumor to liver ratio was 5.69 at 1 h p.i. Furthermore, coinjection of cyclo(RGDyK) with 18F-FP–3-4A significantly inhibited tumor uptake (0.41 ± 0.12 vs 1.02 ± 0.19% ID/g at 2.5 h) in U87MG xenograft models, demonstrating specific accumulation of the probe in the tumor. In summary, the divalent probe 18F-FP–3-4A is characterized by rapid and high tumor uptake and excellent tumor-to-normal tissue ratios. 18F-FP–3-4A is a highly promising knottin based PET probe for translating into clinical imaging of tumor angiogenesis.« less

Efficacy of a single oral dose of a live bivalent E. coli vaccine against post-weaning diarrhea due to F4 and F18-positive enterotoxigenic E. coli.

PubMed

Nadeau, É; Fairbrother, J M; Zentek, J; Bélanger, L; Tremblay, D; Tremblay, C-L; Röhe, I; Vahjen, W; Brunelle, M; Hellmann, K; Cvejić, D; Brunner, B; Schneider, C; Bauer, K; Wolf, R; Hidalgo, Á

2017-08-01

F4- and F18-positive enterotoxigenic E. coli strains (F4-ETEC and F18-ETEC) are important causes of post-weaning diarrhea (PWD) in pigs. F4 (antigenic variant ac) and F18 (ab and ac) fimbriae are major antigens that play an important role in the early stages of infection. Herein, the efficacy of a live oral vaccine consisting of two non-pathogenic E. coli strains, one F4ac- and one F18ac-positive, was evaluated using F4ac-ETEC and F18ab-ETEC challenge models. A randomized, masked, placebo-controlled, block design, parallel-group confirmatory study with two different vaccination-challenge intervals (7 and 21 days) was conducted for each challenge model. The vaccine was administered in one dose, to ≥18-day-old piglets via drinking water. Efficacy was assessed by evaluating diarrhea, clinical observations, weight gain and fecal shedding of F4-ETEC or F18-ETEC. Anti-F4 and anti-F18 immunoglobulins in blood were measured. The vaccination resulted in significant reductions in clinical PWD and fecal shedding of F4-ETEC and F18-ETEC after the 7- and 21-day-post-vaccination heterologous challenges, except for after the 21-day-post-vaccination F4-ETEC challenge, when the clinical PWD was too mild to demonstrate efficacy. A significant reduction of mortality and weight loss by vaccination were observed following the F18-ETEC challenge. The 7-day protection was associated with induction of anti-F4 and anti-F18 IgM, whereas the 21-day protection was mainly associated with anti-F4 and anti-F18 IgA. The 7-day onset and 21-day duration of protection induced by this vaccine administered once in drinking water to pigs of at least 18days of age were confirmed by protection against F4-ETEC and F18-ETEC, and induction of F4 and F18-specific immunity. Cross protection of the vaccine against F18ab-E. coli was demonstrated for both the 7- and 21-day F18-ETEC challenges. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effect of a single application of TiF(4) and NaF varnishes and solutions on dentin erosion in vitro.

PubMed

Magalhães, Ana Carolina; Levy, Flávia Mauad; Rios, Daniela; Buzalaf, Marília Afonso Rabelo

2010-02-01

This in vitro study aimed to analyse the effect of a single application of TiF(4) and NaF varnishes and solutions to protect against dentin erosion. Bovine root dentin samples were pre-treated with NaF-Duraphat varnish (2.26%F, pH 4.5), NaF/CaF(2)-Duofluorid varnish (5.63%F, pH 8.0), NaF-experimental varnish (2.45%F, pH 4.5), TiF(4)-experimental varnish (2.45%F, pH 1.2), NaF solution (2.26%F, pH 4.5), TiF(4) solution (2.45%F, pH 1.2) and placebo varnish (pH 5.0, no-F varnish control). Controls remained untreated. Ten samples in each group were then subjected to an erosive demineralisation (Sprite Zero, 4x 90s/day) and remineralisation (artificial saliva, between the erosive cycles) cycling for 5 days. Dentin loss was measured profilometrically after pre-treatment and after 1, 3 and 5 days of de-remineralisation cycling. The data were statistically analysed by two-way ANOVA and Bonferroni's post hoc test (p<0.05). After pre-treatment, TiF(4) solution significantly induced surface loss (1.08+/-0.53 microm). Only Duraphat reduced the dentin loss overtime, but it did not significantly differ from placebo varnish (at 3rd and 5th days) and TiF(4) varnish (at 3rd day). Duraphat varnish seems to be the best option to partially reduce dentin erosion. However, the maintenance of the effects of this treatment after successive erosive challenges is limited. Copyright 2009 Elsevier Ltd. All rights reserved.

Multicomponent diffusion in molten salt NaF-ZrF4: Dynamical correlations and Maxwell-Stefan diffusivities

NASA Astrophysics Data System (ADS)

Baig, Mohammad Saad; Chakraborty, Brahmananda; Ramaniah, Lavanya M.

2016-05-01

NaF-ZrF4 is used as a waste incinerator and as a coolant in Generation IV reactors.Structural and dynamical properties of molten NaF-ZrF4 system were studied along with Onsagercoefficients and Maxwell-Stefan (MS) Diffusivities applying Green-Kubo formalism and molecular dynamics (MD) simulations. The zirconium ions are found to be 8 fold coordinated with fluoride ions for all temperatures and concentrations. All the diffusive flux correlations show back-scattering. Even though the MS diffusivities are expected to depend very lightly on the composition because of decoupling of thermodynamic factor, the diffusivity ĐNa-F shows interesting behavior with the increase in concentration of ZrF4. This is because of network formation in NaF-ZrF4. Positive entropy constraints have been plotted to authenticate negative diffusivities observed.

Enamel demineralization and remineralization under plaque fluid-like conditions: a quantitative light-induced fluorescence study.

PubMed

Lippert, F; Butler, A; Lynch, R J M

2011-01-01

The present study investigated de- and remineralization in enamel lesions under plaque fluid (PF)-like conditions using quantitative light-induced fluorescence (QLF). Preformed lesions were exposed to partially saturated lactic acid solutions, varying in pH and fluoride concentration ([F]) based on a 5 × 3 factorial study design (0/0.1/0.5/1.5/4 ppm F; pH 4.9/5.2/5.5). Average fluorescence loss (ΔF) was monitored for 11 days. Subsequently, lesions were demineralized in a partially saturated acetic acid solution for two 24-hour periods. Data were analyzed using repeated measures analysis of covariance. Lesions exposed to PF at 4 ppm F and pH 5.5 showed not only the most remineralization (ΔΔF = 28.2 ± 14.0%) for all groups after 11 days, but also the most demineralization (ΔΔF = -19.3 ± 13.5%) after subsequent acetic acid exposure. Increased [F] resulted in more remineralization, regardless of pH. Higher pH values resulted in more remineralization. No remineralization was observed in lesions exposed to F-free solutions, regardless of pH. Remineralization was noticeable under the following conditions: pH 4.9 - [F] = 4 ppm, pH 5.2 - [F] ≥ 1.5 ppm, and pH 5.5 - [F] ≥ 0.5 ppm. Overall, [F] had a stronger effect on remineralization than pH. Subsequent demineralization showed that little protection was offered by PF-like solutions, and further demineralization compared with baseline was observed on lesions not remineralized initially. [F] had a stronger effect on net mineral change than pH. The present study has shown that QLF is a valuable tool in studying lesion de- and remineralization under PF-like conditions, where [F] was shown to be more important than pH. Copyright © 2011 S. Karger AG, Basel.

Supramolecular architectures with π-acidic 3,6-bis(2-pyridyl)-1,2,4,5-tetrazine cavities: role of anion-π interactions in the remarkable stability of Fe(II) metallacycles in solution.

PubMed

Chifotides, Helen T; Giles, Ian D; Dunbar, Kim R

2013-02-27

The comprehensive investigation reported herein provides compelling evidence that anion-π interactions are the main driving force in the formation of self-assembled Fe(II)-templated metallacycles with bptz [3,6-bis(2-pyridyl)-1,2,4,5-tetrazine] in high yields. It was demonstrated by X-ray crystallography, (1)H NMR, solution and solid-state MAS (19)F NMR spectroscopies, CV and MS studies that the anions [X](-) = [BF(4)](-), [ClO(4)](-) and the anions [Y](-) = [SbF(6)](-), [AsF(6)](-), [PF(6)](-) template molecular squares [Fe(4)(bptz)(4)(CH(3)CN)(8)][X](8) and pentagons [Fe(5)(bptz)(5)(CH(3)CN)(10)][Y](10), respectively. The X-ray structures of [{Fe(4)(bptz)(4)(CH(3)CN)(8)}⊂BF(4)][BF(4)](7) and [{Fe(5)(bptz)(5)(CH(3)CN)(10)}⊂2SbF(6)][SbF(6)](8) revealed that the [BF(4)](-) and [SbF(6)](-) anions occupy the π-acidic cavities, establishing close directional F···C(tetrazine) contacts with the tetrazine rings that are by ~0.4 Å shorter than the sum of the F···C van der Waals radii (ΣR(vdW) F···C = 3.17 Å). The number and strength of F···C(tetrazine) contacts are maximized; the F···C(tetrazine) distances and anion positioning versus the polygon opposing tetrazine rings are in agreement with DFT calculations for C(2)N(4)R(2)···[X](-)···C(2)N(4)R(2) (R = F, CN; [X](-) = [BF(4)](-), [PF(6)](-)). In unprecedented solid-state (19)F MAS NMR studies, the templating anions, engaged in anion-π interactions in the solid state, exhibit downfield chemical shifts Δδ((19)F) ≈ 3.5-4.0 ppm versus peripheral anions. NMR, CV, and MS studies also establish that the Fe(II) metallacycles remain intact in solution. Additionally, interconversion studies between the Fe(II) metallacycles in solution, monitored by (1)H NMR spectroscopy, underscore the remarkable stability of the metallapentacycles [Fe(5)(bptz)(5)(CH(3)CN)(10)][PF(6)](10) ≪ [Fe(5)(bptz)(5)(CH(3)CN)(10)][SbF(6)](10) < [Fe(5)(bptz)(5)(CH(3)CN)(10)][AsF(6)](10) versus [Fe(4)(bptz)(4)(CH(3)CN)(8)][BF(4)](8), given the inherent angle strain in five-membered rings. Finally, the low anion activation energies of encapsulation (ΔG(‡) ≈ 50 kJ/mol), determined from variable-temperature (19)F NMR studies for [Fe(5)(bptz)(5)(CH(3)CN)(10)][PF(6)](10) and [Zn(4)(bptz)(4)(CH(3)CN)(8)][BF(4)](8), confirm anion encapsulation in the π-acidic cavities by anion-π contacts (~20-70 kJ/mol).

Experimental and Theoretical Studies of High Power Plasma Filled Backward Wave Oscillators

DTIC Science & Technology

1991-02-01

excitation and amplification plasma may have a phase velocity vph ,, - c, allowing it of electromagnetic waves. This last area has been referred to be more...and (5): e x p lic i t f o r m ir f 12 ( + A f / f , 12 ) ] ( f=f(cosL,G) (2) Vph Cos_ I(B 2 -4C&f) _2-B]I2C), (4) where f is the frequency of the

Novel duplex vapor-electrochemical method for silicon solar cells

NASA Technical Reports Server (NTRS)

Nanis, L.; Sanjurjo, A.; Westphal, S.

1979-01-01

Optimization studies were carried out for the SiF4-Na reaction with solid Na feed. The goals of the study were the consistent production of high purity reaction products and the gathering of relevant information needed to scale-up the reactor. Parameters studied include: (1) effect of surface to volume ratio of Na slices on the extent of reaction; (2) effect of Na surface oxidation on the extent of reaction; (3) effect of external heating on the extent of SiF4-Na reaction; (4) effect of Na slice addition rate on extent of the reaction; and (5) SiF4-Na reaction - high pressure experiments. An investigation was also made of the possible role played by NaF as a fluxing agent during the separation of silicon by melting of the reaction product (Si + NaF) mixture. Since silicon can be produced by the thermite reaction between Na2SiF6 and Na, studies were initiated to gather information on parameters which control the efficiency of the thermite reaction.

First step in developing a 3D biodegradable fibrin scaffold for an artificial ovary

PubMed Central

2013-01-01

Background Although transplantation of cryopreserved ovarian tissue is a promising approach to restore fertility in cancer patients, it is not advisable for women at risk of ovarian involvement due to the threat of reintroducing malignant cells. The aim of this study was therefore to find an alternative for these patients by development of an artificial ovary. Methods For construction of the artificial ovary matrix, we used a central composite design to investigate nine combinations of fibrinogen (mg/ml) and thrombin (IU/mL) (F/T): F1/T4, F12.5/T1, F12.5/T20, F25/T0.1, F25/T4, F25/T500, F50/T1, F50/T20 and F100/T4. From the first qualitative analyses (handling and matrix size), five combinations (F12.5/T1, F25/T4, F50/T20, F50/T1 and F100/T4) yielded positive results. They were further evaluated in order to assess fibrin matrix degradation and homogeneous cell encapsulation (density), survival and proliferation (Ki67), and atresia (TUNEL) before and after 7 days of in vitro culture. To determine the best compromise between maximizing the dynamic density (Y1) and minimizing the apoptosis rate (Y2), we used the desirability function approach. Results Two combinations (F12.5/T1 and F25/T4) showed greater distribution of cells before in vitro culture, reproducible degradation of the fibrin network and adequate support for isolated human ovarian stromal cells, with a high proportion of Ki67-positive cells. SEM analysis revealed a network of fibers with regular pores and healthy stromal cells after in vitro culture with both F/T combinations. Conclusion This study reports two optimal F/T combinations that allow survival and proliferation of isolated human ovarian cells. Further studies are required to determine if such a scaffold will also be a suitable environment for isolated ovarian follicles. PMID:24274108

Characterization of a new TiF(4) and β-cyclodextrin inclusion complex and its in vitro evaluation on inhibiting enamel demineralization.

PubMed

Nassur, Camila; Alexandria, Adílis Kalina; Pomarico, Luciana; de Sousa, Valeria Pereira; Cabral, Lúcio Mendes; Maia, Lucianne Cople

2013-03-01

Titanium tetrafluoride (TiF(4)) is an effective but instable caries preventive agent. As the stability problems could be minimized through the use of drug carriers this study aimed to prepare and characterize a new TiF(4) nanoinclusion complex and to evaluate its potential in inhibiting enamel demineralization under pH cycling conditions. The TiF(4) nanosystems were prepared using β-cyclodextrin (βCD) and sodium montmorillonite (MMTNa). Bovine enamel blocks (n=48) with known surface microhardness (SMH), were randomly assigned to 4 groups (n=12) and submitted to one of the following treatments: distilled deionized water (as negative control) and solutions containing 1% βCD, 1% TiF(4) and TiF(4):βCD. The solutions were blinded applied once on the blocks with a microbrush(®) on the surface for 1min before pH-cycling. After that, samples were reavaluated by SMH, %SMH loss, cross-sectional microhardness (CSMH), scanning electron microscope (SEM) and energy dispersive spectrometry (EDX). The inclusion complex of TiF(4):βCD offered better protection against demineralization in the subsurface. The SEM analysis showed that TiF(4) and TiF(4):βCD samples presented the most intact enamel than the control. The EDX analysis identified titanium in TiF(4) and TiF(4):βCD groups. TiF(4):βCD has higher potential on inhibiting demineralization in the inner enamel. TiF(4):βCD is a new alternative to TiF(4) stabilization in order to reduce enamel subsurface demineralization. Copyright © 2012 Elsevier Ltd. All rights reserved.

A Comparative Study of the Hypoxia PET Tracers [{sup 18}F]HX4, [{sup 18}F]FAZA, and [{sup 18}F]FMISO in a Preclinical Tumor Model

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

Peeters, Sarah G.J.A., E-mail: sarah.peeters@maastrichtuniversity.nl; Zegers, Catharina M.L.; Lieuwes, Natasja G.

Purpose: Several individual clinical and preclinical studies have shown the possibility of evaluating tumor hypoxia by using noninvasive positron emission tomography (PET). The current study compared 3 hypoxia PET tracers frequently used in the clinic, [{sup 18}F]FMISO, [{sup 18}F]FAZA, and [{sup 18}F]HX4, in a preclinical tumor model. Tracer uptake was evaluated for the optimal time point for imaging, tumor-to-blood ratios (TBR), spatial reproducibility, and sensitivity to oxygen modification. Methods and Materials: PET/computed tomography (CT) images of rhabdomyosarcoma R1-bearing WAG/Rij rats were acquired at multiple time points post injection (p.i.) with one of the hypoxia tracers. TBR values were calculated, andmore » reproducibility was investigated by voxel-to-voxel analysis, represented as correlation coefficients (R) or Dice similarity coefficient of the high-uptake volume. Tumor oxygen modifications were induced by exposure to either carbogen/nicotinamide treatment or 7% oxygen breathing. Results: TBR was stabilized and maximal at 2 hours p.i. for [{sup 18}F]FAZA (4.0 ± 0.5) and at 3 hours p.i. for [{sup 18}F]HX4 (7.2 ± 0.7), whereas [{sup 18}F]FMISO showed a constant increasing TBR (9.0 ± 0.8 at 6 hours p.i.). High spatial reproducibility was observed by voxel-to-voxel comparisons and Dice similarity coefficient calculations on the 30% highest uptake volume for both [{sup 18}F]FMISO (R = 0.86; Dice coefficient = 0.76) and [{sup 18}F]HX4 (R = 0.76; Dice coefficient = 0.70), whereas [{sup 18}F]FAZA was less reproducible (R = 0.52; Dice coefficient = 0.49). Modifying the hypoxic fraction resulted in enhanced mean standardized uptake values for both [{sup 18}F]HX4 and [{sup 18}F]FAZA upon 7% oxygen breathing. Only [{sup 18}F]FMISO uptake was found to be reversible upon exposure to nicotinamide and carbogen. Conclusions: This study indicates that each tracer has its own strengths and, depending on the question to be answered, a different tracer can be put forward.« less

Superelectrophilic tetrakis(carbonyl)palladium(II)- and -platinum(II) undecafluorodiantimonate(V), [Pd(CO)4][Sb(2)F(11)]2 and [Pt(CO)4][Sb(2)F(11)]2: syntheses, physical and spectroscopic properties, their crystal, molecular, and extended structures, and density functional calculations: an experimental, computational, and comparative study .

PubMed

Willner, H; Bodenbinder, M; Bröchler, R; Hwang, G; Rettig, S J; Trotter, J; von Ahsen, B; Westphal, U; Jonas, V; Thiel, W; Aubke, F

2001-01-31

The salts [M(CO)(4)][Sb(2)F(11)](2), M = Pd, Pt, are prepared by reductive carbonylation of Pd[Pd(SO(3)F)(6)], Pt(SO(3)F)(4) or PtF(6) in liquid SbF(5), or HF-SbF(5). The resulting moisture-sensitive, colorless solids are thermally stable up to 140 degrees C (M = Pd) or 200 degrees C (M = Pt). Their thermal decompositions are studied by differential scanning calorimetry (DSC). Single crystals of both salts are suitable for an X-ray diffraction study at 180 K. Both isostructural salts crystallize in the monoclinic space group P2(1)/c (No. 14). The unit cell volume of [Pt(CO)(4)][Sb(2)F(11)](2) is smaller than that of [Pd(CO)(4)][Sb(2)F(11)](2) by about 0.4%. The cations [M(CO)(4)](2+), M = Pd, Pt, are square planar with only very slight angular and out-of-plane deviations from D(4)(h)() symmetry. The interatomic distances and bond angles for both cations are essentially identical. The [Sb(2)F(11)](-) anions in [M(CO)(4)][Sb(2)F(11)](2,) M = Pd, Pt, are not symmetry-related, and both pairs differ in their Sb-F-Sb bridge angles and their dihedral angles. There are in each salt four to five secondary interionic C- -F contacts per CO group. Of these, two contacts per CO group are significantly shorter than the sum of the van der Waals radii by 0.58 - 0.37 A. In addition, structural, and spectroscopic details of recently synthesized [Rh(CO)(4)][Al(2)Cl(7)] are reported. The cations [Rh(CO)(4)](+) and [M(CO)(4)](2+), M = Pd, Pt, are characterized by IR and Raman spectroscopy. Of the 16 vibrational modes (13 observable, 3 inactive) 10 (Pd, Pt) or 9 (Rh), respectively, are found experimentally. The vibrational assignments are supported by DFT calculations, which provide in addition to band positions also intensities of IR bands and Raman signals as well as internal force constants for the cations. (13)C NMR measurements complete the characterization of the square planar metal carbonyl cations. The extensive characterization of [M(CO)(4)][Sb(2)F(11)](2), M = Pd, Pt, reported here, allows a comparison to linear and octahedral [M(CO)(n)()][Sb(2)F(11)](2) salts [M = Hg (n = 2); Fe, Ru, Os (n = 6)] and their derivatives, which permit a deeper understanding of M-CO bonding in the solid state for superelectrophilic cations with [Sb(2)F(11)](-) or [SbF(6)](-) as anions.

Comparative expression analysis of POU4F1, POU4F2 and ISL1 in developing mouse cochleovestibular ganglion neurons

PubMed Central

Deng, Min; Yang, Hua; Xie, Xiaoling; Liang, Guoqing; Gan, Lin

2014-01-01

POU-homeodomain and LIM-homeodomain transcription factors are expressed in developing projection neurons within retina, inner ear, dorsal root ganglion, and trigeminal ganglion, and play synergistic roles in their differentiation and survival. Here, using immunohistochemistry, we present a comparative analysis of the spatiotemporal expression pattern of POU4F1, POU4F2, and ISL1 during the development of cochleovestibular ganglion (CVG) neurons in mouse inner ear. At early stages, when otic neurons are first detected in the otic epithelium (OE) and migrate into periotic mesenchyme to form the CVG, POU4F1 and ISL1 are co-expressed in a majority of the delaminated CVG neurons, which are marked by NEUROD1 expression, but POU4F1 is absent in the otic epithelium. The onset of POU4F2 expression starts after that of POU4F1 and ISL1, and is observed in the NEUROD1-negative, post-mitotic CVG neurons. When the CVG neurons innervate the vestibular and cochlear sensory organs, the expression of POU4F1, POU4F2, and ISL1 continues in both vestibular and spiral ganglion cells. Later in development, POU4F1 expression becomes down-regulated in a majority of spiral ganglion (SG) neurons and more neurons express POU4F2 expression while ISL1 expression is maintained. The differential as well as overlapping expression of POU4F1, POU4F2, and ISL1 combined with previous studies suggests possible functional interaction and regulatory relationship of these transcription factors in the development of inner ear neurons. PMID:24709358

Nicotinic α4β2 receptor imaging agents. Part IV. Synthesis and biological evaluation of 3-(2-(S)-3,4-dehydropyrrolinyl methoxy)-5-(3'-¹⁸F-fluoropropyl)pyridine (¹⁸F-Nifrolene) using PET.

PubMed

Pichika, Rama; Kuruvilla, Sharon A; Patel, Narmisha; Vu, Kenny; Sinha, Sangamitra; Easwaramoorthy, Balu; Narayanan, Tanjore K; Shi, Bingzhi; Christian, Bradley; Mukherjee, Jogeshwar

2013-01-01

Imaging agents for nicotinic α4β2 receptors in the brain have been under way for studying various CNS disorders. Previous studies from our laboratories have reported the successful development of agonist, ¹⁸F-nifene. In attempts to develop potential antagonists, ¹⁸F-nifrolidine and ¹⁸F-nifzetidine were previously reported. Further optimization of these fluoropropyl derivatives has now been carried out resulting in 3-(2-(S)-3,4-dehydropyrrolinylmethoxy)-5-(3'-Fluoropropyl)pyridine (nifrolene) as a new high affinity agent for nicotinic α4β2 receptors. Nifrolene in rat brain homogenate assays--labeled with ³H-cytisine--exhibited a binding affinity of 0.36 nM. The fluorine-18 analog, ¹⁸F-nifrolene, was synthesized in approximately 10%-20% yield and specific activity was estimated to be >2000 Ci/mmol. Rat brain slices indicated selective binding to anterior thalamic nuclei, thalamus, subiculum, striata, cortex and other regions consistent with α4β2 receptor distribution. This selective binding was displaced >90% by 300 μM nicotine. Thalamus to cerebellum ratio (>10) was the highest for ¹⁸F-nifrolene with several other regions showing selective binding. In vivo rat PET studies exhibited rapid uptake of ¹⁸F-nifrolene in the brain with specific retention in the thalamus and other brain regions while clearing out from the cerebellum. Thalamus to cerebellum ratio value in the rat was >4. Administration of nicotine caused a rapid decline in the thalamic ¹⁸F-nifrolene suggesting reversible binding to nicotinic receptors. PET imaging studies of ¹⁸F-nifrolene in anesthetized rhesus monkey revealed highest binding in the thalamus followed by regions of the lateral cingulated and temporal cortex. Cerebellum showed the least binding. Thalamus to cerebellum ratio in the monkey brain was >3 at 120 min. These ratios of ¹⁸F-nifrolene are higher than measured for ¹⁸F-nifrolidine and ¹⁸F-nifzetidine. ¹⁸F-Nifrolene thus shows promise as a new PET imaging agent for α4β2 nAChR. Copyright © 2013 Elsevier Inc. All rights reserved.

Follow-up of newborns of mothers with Graves' disease.

PubMed

Levy-Shraga, Yael; Tamir-Hostovsky, Liran; Boyko, Valentina; Lerner-Geva, Liat; Pinhas-Hamiel, Orit

2014-06-01

Overt neonatal Graves' disease is rare, but may be severe, even life threatening, with deleterious effects on neural development. The main objective of this study was to describe the course of thyrotropin (TSH) and free thyroxin (fT4) levels, as well as postnatal weight gain in relation to fT4 levels, in neonates born to women with Graves' disease without overt neonatal thyrotoxicosis. Such information is important to deduce the optimal schedule for evaluation. We conducted a retrospective chart review of neonates born to mothers with Graves' disease between January 2007 and December 2012. The records were reviewed for sex, gestational age, birth weight, maternal treatment during pregnancy, and maternal thyroid stimulating immunoglobulin (TSI) level. For each visit in the clinic, the data included growth parameters, presence of symptoms suspected for hyperthyroidism, blood test results (levels of TSH, fT4, and TSI), and treatment. Ninety-six neonates were included in the study (49 males), with a total of 320 measurements of thyroid function tests (TSH and fT4). Four neonates (4%) had overt neonatal Graves' disease; one of them along with nine others were born preterm. In 77 (92.9%) of the remaining 83 neonates (the subclinical group), fT4 levels were above the 95th percentile on day 5. All had normal fT4 on day 15. A negative association was found between fT4 and weight gain during the first two weeks. In this cohort, most neonates born to mothers with Graves' disease had a subclinical course with abnormal fT4 levels that peaked at day 5. After day 14, all measurements of fT4 returned to the normal range, although measurements of TSH remained suppressed for up to three months. Elevated fT4 was associated with poor weight gain.

Density Functional Study of Structures and Electron Affinities of BrO4F/BrO4F−

PubMed Central

Gong, Liangfa; Xiong, Jieming; Wu, Xinmin; Qi, Chuansong; Li, Wei; Guo, Wenli

2009-01-01

The structures, electron affinities and bond dissociation energies of BrO4F/BrO4F− species have been investigated with five density functional theory (DFT) methods with DZP++ basis sets. The planar F-Br…O2…O2 complexes possess 3A′ electronic state for neutral molecule and 4A′ state for the corresponding anion. Three types of the neutral-anion energy separations are the adiabatic electron affinity (EAad), the vertical electron affinity (EAvert), and the vertical detachment energy (VDE). The EAad value predicted by B3LYP method is 4.52 eV. The bond dissociation energies De (BrO4F → BrO4-mF + Om) (m = 1–4) and De− (BrO4F− → BrO4-mF− + Om and BrO4F− → BrO4-mF + Om−) are predicted. The adiabatic electron affinities (EAad) were predicted to be 4.52 eV for F-Br…O2…O2 (3A′←4A′) (B3LYP method). PMID:19742128

F4/80 inhibits osteoclast differentiation via downregulation of nuclear factor of activated T cells, cytoplasmic 1.

PubMed

Kang, Ju-Hee; Sim, Jung-Sun; Zheng, Ting; Yim, Mijung

2017-04-01

Osteoclastogenesis is an essential process in bone metabolism, which can be induced by RANKL stimulation. The F4/80 glycoprotein is a member of the EGF-transmembrane 7 (TM7) family and has been established as a specific cell-surface marker for murine macrophages. This study aimed to identify the role of F4/80 in osteoclastogenesis. Using mouse bone marrow-derived macrophages (BMMs), we observed that the mRNA level of F4/80 was dramatically reduced as these cells differentiated into osteoclasts. Furthermore, osteoclastogenesis was decreased in F4/80 high BMMs compared to F4/80 -/low BMMs. The inhibitory effect of F4/80 was associated with decreased expression of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1). Ectopic overexpression of a constitutively active form of NFATc1 rescued the anti-osteoclastogenic effect of F4/80 completely, suggesting that the anti-osteoclastogenic effect of F4/80 was mainly due to reduction in NFATc1 expression. As an underlying mechanism, we demonstrated that the presence of F4/80 abrogated the effect of RANKL on the phosphorylation of CREB and activated the expression of IFN-β, which are restored by cyclic AMP. Collectively, our results demonstrate that the presence of F4/80 suppresses RANKL-induced osteoclastogenesis by impairing the expression of NFATc1 via CREB and IFN-β. Therefore, F4/80 may hold therapeutic potential for bone destructive diseases.

Phase transitions in (NH4)2MoO2F4 crystal

NASA Astrophysics Data System (ADS)

Krylov, Alexander; Laptash, Natalia; Vtyurin, Alexander; Krylova, Svetlana

2016-11-01

The mechanisms of temperature and high pressure phase transitions have been studied by Raman spectroscopy. Room temperature (295 K) experiments under high hydrostatic pressure up to 3.6 GPa for (NH4)2 MoO2 F4 have been carried out. Experimental data indicates a phase transition into a new high-pressure phase for (NH4)2 MoO2 F4 at 1.2 GPa. This phase transition is related to the ordering anion octahedron groups [MoO2 F4]2- and is not associated with ammonium group. Raman spectra of small non-oriented crystals ranging from 10 to 350 K have been observed. The experiment shows anion groups [MoO2 F4]2- and ammonium in high temperature phase are disordered. The phase transition at T1 = 269.8 K is of the first-order, close to the tricritical point. The first temperature phase transition is related to the ordering anion octahedron groups [MoO2 F4]2-. Second phase transitions T2 = 180 K are associated with the ordering of ammonium. The data presented within this study demonstrate that 2D correlation analysis combined with traditional Raman spectroscopy are powerful tool to study phase transitions in the crystals.

Observation of EIA in closed and open caesium atomic system

NASA Astrophysics Data System (ADS)

Zhao, Jian-Ming; Zhao, Yan-Ting; Huang, Tao; Xiao, Lian-Tuan; Jia, Suo-Tang

2005-04-01

We present an experimental study on electromagnetically induced absorption (EIA) in the closed transition of a degenerate two-level Cs atomic system. The coupling and probe lasers coupled with the transition 6S1/2F=4 → 6P3/2F'=5 of caesium atom. The signal of EIA was obtained and the frequency detuning and intensity effect of the pumping laser were experimentally investigated. The EIA signal in 6S1/2 F=4 → 6P3/2 F'=4 and 6S1/2 F=4 → 6P3/2 F'=3 open transitions was also obtained. As the repumping laser couples with the transition of 6S1/2 F=3 → 6P3/2 F'=4, the EIA signal is increased due to the hyperfine optical pumping.

A Comparative Study on Physicochemical Characteristics of Raw Goat Milk Collected from Different Farms in Malaysia.

PubMed

Jaafar, Syarifah Hazirah Syd; Hashim, Roshada; Hassan, Zaiton; Arifin, Norlelawati

2018-03-01

This study was conducted to determine the physical and chemical composition of goat milk produced by eight local farms located in the central region of Malaysia. Farms 1 to 4 (F1-SC, F2-SP, F3-SP, F4-SBC) reared Saanen-type goats while farms 5 to 8 (F5-JK, F6-JPEC, F7-JTC, F8-JC), Jamnapari-type goats. The common feedstuffs used in all farms comprised of fresh or silage from Napier grass, feed pellets, and brans while two farms, F5-JK and F6-JPEC supplemented the feeds with soybean-based product. The total solid content, dry matter, and proximate composition of goat milk and feedstuffs from the different farms were determined and the results analysed using principal component analysis. Total solid content of goat milk from the Jamnapari crossbreed had the highest solid content ranging from 11.81% to 17.54% compared to milk from farms with Saanen and Saanen crossbreed (10.95% to 14.63%). Jamnapari-type goats from F5-JK, F6-JPEC, and F8-JC had significantly higher ( p < 0.05) milk fat and protein contents (7.36%, 7.14%, and 6.59% fat; 5.08%, 6.19%, and 4.23% protein, respectively) than milk from other farms but, milk produced by Saanen-type goats from F4-SBC contained similar protein content (4.34%) to that from F8-JC. Total ash and carbohydrate contents in milk ranged between 0.67% to 0.86% and 3.26% to 4.71%, respectively, regardless of goat breed. Feeding soybean-based products appear to have a positive influence on milk fat and protein content in Jamnaparitype goats.

A Comparative Study on Physicochemical Characteristics of Raw Goat Milk Collected from Different Farms in Malaysia

PubMed Central

Jaafar, Syarifah Hazirah Syd; Hashim, Roshada; Hassan, Zaiton; Arifin, Norlelawati

2018-01-01

This study was conducted to determine the physical and chemical composition of goat milk produced by eight local farms located in the central region of Malaysia. Farms 1 to 4 (F1-SC, F2-SP, F3-SP, F4-SBC) reared Saanen-type goats while farms 5 to 8 (F5-JK, F6-JPEC, F7-JTC, F8-JC), Jamnapari-type goats. The common feedstuffs used in all farms comprised of fresh or silage from Napier grass, feed pellets, and brans while two farms, F5-JK and F6-JPEC supplemented the feeds with soybean-based product. The total solid content, dry matter, and proximate composition of goat milk and feedstuffs from the different farms were determined and the results analysed using principal component analysis. Total solid content of goat milk from the Jamnapari crossbreed had the highest solid content ranging from 11.81% to 17.54% compared to milk from farms with Saanen and Saanen crossbreed (10.95% to 14.63%). Jamnapari-type goats from F5-JK, F6-JPEC, and F8-JC had significantly higher (p < 0.05) milk fat and protein contents (7.36%, 7.14%, and 6.59% fat; 5.08%, 6.19%, and 4.23% protein, respectively) than milk from other farms but, milk produced by Saanen-type goats from F4-SBC contained similar protein content (4.34%) to that from F8-JC. Total ash and carbohydrate contents in milk ranged between 0.67% to 0.86% and 3.26% to 4.71%, respectively, regardless of goat breed. Feeding soybean-based products appear to have a positive influence on milk fat and protein content in Jamnaparitype goats. PMID:29644024

Inactivation of the F4/80 glycoprotein in the mouse germ line.

PubMed

Schaller, Evelyne; Macfarlane, Alison J; Rupec, Rudolf A; Gordon, Siamon; McKnight, Andrew J; Pfeffer, Klaus

2002-11-01

Macrophages play a crucial role in the defense against pathogens. Distinct macrophage populations can be defined by the expression of restricted cell surface proteins. Resident tissue macrophages, encompassing Kupffer cells of the liver and red pulp macrophages of the spleen, characteristically express the F4/80 molecule, a cell surface glycoprotein related to the seven transmembrane-spanning family of hormone receptors. In this study, gene targeting was used to simultaneously inactivate the F4/80 molecule in the germ line of the mouse and to produce a mouse line that expresses the Cre recombinase under the direct control of the F4/80 promoter (F4/80-Cre knock-in). F4/80-deficient mice are healthy and fertile. Macrophage populations in tissues can develop in the absence of F4/80 expression. Functional analysis revealed that the generation of T-cell-independent B-cell responses and macrophage antimicrobial defense after infection with Listeria monocytogenes are not impaired in the absence of F4/80. Interestingly, tissues of F4/80-deficient mice could not be labeled with anti-BM8, another macrophage subset-specific marker with hitherto undefined molecular antigenic structure. Recombinant expression of a F4/80 cDNA in heterologous cells confirmed this observation, indicating that the targets recognized by the F4/80 and BM8 monoclonal antibodies are identical.

Antioxidant and Cytoprotective Activities of Fucus spiralis Seaweed on a Human Cell in Vitro Model.

PubMed

Pinteus, Susete; Silva, Joana; Alves, Celso; Horta, André; Thomas, Olivier P; Pedrosa, Rui

2017-01-29

Antioxidants play an important role as Reactive Oxygen Species (ROS) chelating agents and, therefore, the screening for potent antioxidants from natural sources as potential protective agents is of great relevance. The main aim of this study was to obtain antioxidant-enriched fractions from the common seaweed Fucus spiralis and evaluate their activity and efficiency in protecting human cells (MCF-7 cells) on an oxidative stress condition induced by H₂O₂. Five fractions, F1-F5, were obtained by reversed-phase vacuum liquid chromatography. F3, F4 and F5 revealed the highest phlorotannin content, also showing the strongest antioxidant effects. The cell death induced by H₂O₂ was reduced by all fractions following the potency order F4 > F2 > F3 > F5 > F1. Only fraction F4 completely inhibited the H₂O₂ effect. To understand the possible mechanisms of action of these fractions, the cellular production of H₂O₂, the mitochondrial membrane potential and the caspase 9 activity were studied. Fractions F3 and F4 presented the highest reduction on H₂O₂ cell production. All fractions decreased both caspase-9 activity and cell membrane depolarization (except F1). Taken all together, the edible F. spiralis reveal that they provide protection against oxidative stress induced by H₂O₂ on the human MCF-7 cellular model, probably acting as upstream blockers of apoptosis.

Sequence of phase transitions in (NH4)3SiF7.

PubMed

Mel'nikova, S V; Molokeev, M S; Laptash, N M; Pogoreltsev, E I; Misyul, S V; Flerov, I N

2017-02-21

Single crystals of silicon double salt (NH 4 ) 3 SiF 7 = (NH 4 ) 2 SiF 6 ·NH 4 F = (NH 4 ) 3 [SiF 6 ]F were grown and studied by the methods of polarization optics, X-ray diffraction and calorimetry. A sequence of symmetry transformations with the temperature change was established: P4/mbm (Z = 2) (G 1 ) ↔ Pbam (Z = 4) (G 2 ) ↔ P2 1 /c (Z = 4) (G 3 ) ↔ P1[combining macron] (Z = 4) (G 4 ) ↔ P2 1 /c (Z = 8) (G 5 ). Crystal structures of different phases were determined. The experimental data were also interpreted by a group-theoretical analysis of the complete condensate of order parameters taking into account critical and noncritical atomic displacements. Strengthening of the N-HF hydrogen bonds can be a driving force of the observed phase transitions.

Mechanism of Action of TiF4 on Dental Enamel Surface: SEM/EDX, KOH-Soluble F, and X-Ray Diffraction Analysis.

PubMed

Comar, Lívia P; Souza, Beatriz M; Al-Ahj, Luana P; Martins, Jessica; Grizzo, Larissa T; Piasentim, Isabelle S; Rios, Daniela; Buzalaf, Marília Afonso Rabelo; Magalhães, Ana Carolina

2017-10-12

This in vitro study aimed to evaluate the action of TiF4 on sound and carious bovine and human enamel. Sound (S) and pre-demineralised (DE) bovine and human (primary and permanent) enamel samples were treated with TiF4 (pH 1.0) or NaF varnishes (pH 5.0), containing 0.95, 1.95, or 2.45% F for 12 h. The enamel surfaces were analysed using SEM-EDX (scanning electron microscopy/energy-dispersive X-ray spectroscopy) (n = 10, 5 S and 5 DE) and KOH-soluble fluoride was quantified (n = 20, 10 S and 10 DE). Hydroxyapatite powder produced by precipitation method was treated with the corresponding fluoride solutions for 1 min (n = 2). The formed compounds were detected using X-ray diffraction (XRD). All TiF4 varnishes produced a coating layer rich in Ti and F on all types of enamel surface, with micro-cracks in its extension. TiF4 (1.95 and 2.45% F) provided higher fluoride deposition than NaF, especially for bovine enamel (p < 0.0001). It also induced a higher fluoride deposition on DE samples compared to S samples (p < 0.0001), except for primary enamel. The Ti content was higher for bovine and human primary enamel than human permanent enamel, with some differences between S and DE. The XRD analysis showed that TiF4 induced the formation of new compounds such as CaF2, TiO2, and Ti(HPO4)2·H2O. In conclusion, TiF4 (>0.95% F) interacts better, when compared to NaF, with bovine and human primary enamel than with human permanent enamel. TiF4 provoked higher F deposition compared to NaF. Carious enamel showed higher F uptake than sound enamel by TiF4 application, while Ti uptake was dependent on the enamel condition and origin. © 2017 S. Karger AG, Basel.

F4+ ETEC infection and oral immunization with F4 fimbriae elicits an IL-17-dominated immune response.

PubMed

Luo, Yu; Van Nguyen, Ut; de la Fe Rodriguez, Pedro Y; Devriendt, Bert; Cox, Eric

2015-10-21

Enterotoxigenic Escherichia coli (ETEC) are an important cause of post-weaning diarrhea (PWD) in piglets. Porcine-specific ETEC strains possess different fimbrial subtypes of which F4 fimbriae are the most frequently associated with ETEC-induced diarrhea in piglets. These F4 fimbriae are potent oral immunogens that induce protective F4-specific IgA antibody secreting cells at intestinal tissues. Recently, T-helper 17 (Th17) cells have been implicated in the protection of the host against extracellular pathogens. However, it remains unknown if Th17 effector responses are needed to clear ETEC infections. In the present study, we aimed to elucidate if ETEC elicits a Th17 response in piglets and if F4 fimbriae trigger a similar response. F4(+) ETEC infection upregulated IL-17A, IL-17F, IL-21 and IL-23p19, but not IL-12 and IFN-γ mRNA expression in the systemic and mucosal immune system. Similarly, oral immunization with F4 fimbriae triggered a Th17 signature evidenced by an upregulated mRNA expression of IL-17F, RORγt, IL-23p19 and IL-21 in the peripheral blood mononuclear cells (PBMCs). Intriguingly, IL-17A mRNA levels were unaltered. To further evaluate this difference between systemic and mucosal immune responses, we assayed the cytokine mRNA profile of F4 fimbriae stimulated PBMCs. F4 fimbriae induced IL-17A, IL-17F, IL-22 and IL-23p19, but downregulated IL-17B mRNA expression. Altogether, these data indicate a Th17 dominated response upon oral immunization with F4 fimbriae and F4(+) ETEC infection. Our work also highlights that IL-17B and IL-17F participate in the immune response to protect the host against F4(+) ETEC infection and could aid in the design of future ETEC vaccines.

Optical Studies of CaS:Eu, Sm Infrared Stimulable Phosphors

NASA Astrophysics Data System (ADS)

Tamura, Yasuaki; Shibukawa, Atsushi

1993-07-01

The photoluminescence (PL) and infrared stimulated luminescence (ISL) spectra of CaS:Eu,Sm infrared stimulable phosphors (ISPs) are studied. In addition, the concentration dependence of ISL intensity is examined. Sm3+- and Eu2+-related structures are found in both the PL excitation and emission spectra. Two types of Sm3+ are found, one of which exhibits strong emission at around 650 nm and the other, weak emission compared to the other emissions at around 565 nm and 605 nm. These are assigned to an asymmetric and a symmetric site, respectively. ISL excitation spectra coincide with the Eu2+ 4f7 to 4f65d1 and 4f66s1 transitions and range from 220 to 650 nm. ISL emission spectra coincide with the Eu2+ 4f65d1 to 4f7 transition and range from 550 to 750 nm. ISL stimulation spectra range from 0.8 μm to 1.7 μm and are thought to indicate the Sm2+ ion transition from 4f6 to 4f55d1. The maximum ISL intensity is obtained from a sample with Eu and Sm concentrations of 500 and 130 ppm, respectively.

High resolution FTIR spectroscopy of BaY2F8 single crystals doped with trivalent Er

NASA Astrophysics Data System (ADS)

Baraldi, A.; Capelletti, R.; Cornelli, M.; Ponzoni, A.; Ruffini, A.; Sperzagni, A.; Tonelli, M.

High resolution (0.04 cm-1) FTIR spectroscopy is applied to monoclinic Er3+-doped BaY2F8 single crystals in the wavenumber range 500-24000 cm-1 and temperature range 9-300 K to study the crystal field splitting of the fundamental 4I15/2 and of the excited 4I13/2, 4I11/2, 4I9/2, 4F9/2, 4S3/2, 2H11/2, 4F7/2, 4F5/2, and 4F3/2 states and the effects caused by increasing Er3+-concentrations (2-20% m.f.), such as inhomogeneous line-broadening and new lines due to Er3+-Er3+ interaction. In the framework of the electron-phonon interaction, the thermally induced line-broadening and -shift are detected and accounted for by the two-phonon Raman model and the vibronic replicas of a few lines are investigated.

Comparison of serological assessments in the diagnosis of liver fibrosis in bile duct ligation mice.

PubMed

Xie, Chengxia; Ma, Bo; Wang, Ning; Wan, Lin

2017-08-01

Liver fibrosis assessment is essential to make a prognosis and to determine the appropriate anti-fibrosis treatment. Non-invasive serum markers are widely studied in patients to assess liver fibrosis due to the limitations of liver biopsy. When using animal models to study the mechanism and intervention of hepatic fibrosis, serum markers might be useful for the continuous assessment of liver fibrosis in individual animals, which could avoid the influence of biological differences between individuals. However, it is unclear whether serum markers can assess hepatic fibrosis in the animal model. In the present study, we evaluated and compared the ability of four serum markers to assess liver fibrosis in bile duct ligation mice. According to the stages of liver fibrosis assessed by pathological changes, mice in this study were divided into five groups (F0, F1, F2, F3, and F4). Subsequently, four serum markers, aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis index based on the 4 factors (FIB-4), and Forns Index, were calculated for each group. Furthermore, the correlations between serum markers and pathological stages and the ability of serological markers to evaluate liver fibrosis were analyzed. AAR, APRI, FIB-4, and Forns Index could significantly distinguish F0-2 from F3-4 mice. APRI, FIB-4, and Forns Index could detect F0-3 from F4 mice. Among these four markers, FIB-4 was the best able to distinguish ≥F2 and ≥F3, with area under the curve values of 0.882 and 0.92, respectively. Forns Index was best for diagnosing F4 with area under the curve value of 0.879. These results demonstrated that serum markers could be used for assessing liver fibrosis in bile duct ligation mice, and therefore, these markers might lead to more accurate diagnostic and therapeutic studies through continuous monitoring in individual animals. Impact statement The assessment of liver fibrosis is essential for making a prognosis and determining the appropriate anti-fibrosis treatment. In studies focusing on the mechanism and treatment of liver fibrosis using animal models, it would be more accurate to continuously evaluate liver fibrosis in a single animal to avoid individual biological differences. Unfortunately, it is difficult to perform continuous assessment through liver biopsy in the most commonly used rodent models. It is unclear whether serum markers, which have been used in hepatic fibrosis patients, could be used in animal models. Our results demonstrate that serum markers could be used for assessing liver fibrosis in bile duct ligation mice. This study might contribute to more accurate diagnostic and therapeutic studies through continuous monitoring in individual animals.

Sex specificity of behavioral dominance and fasting endurance in wintering canvasbacks: Experimental results

USGS Publications Warehouse

Perry, M.C.; Nichols, J.D.; Conroy, M.J.; Obrecht, H.H.; Williams, B.K.; Weller, Milton W.

1988-01-01

Hand-reared canvasbacks (Aythya valisineria) of varying sex ratios were maintained in pens during winter 1980-81 (3M-3F, 6M-0F, 0M-6F) and winter 1981-82 (4M-2F, 2M-4F) and fed two diets (control and stress). They were observed during feeding trials to determine intrasexual and intersexual aggressive activity. There was little evidence that either diet or sex ratio affected the total number of aggressive encounters. Females fed both control and stress diets were more aggressive and spent more time in the small feeding areas than males in pens with 3M-3F, 4M-2F, and 2M-4F sex ratios. Stressed ducks tended to weigh less than controls throughout the study. Females in the 3M-3F and 4M-2F pens weighed less than those in the 0M-6F and 2M-4F pens, respectively. However, relative weight changes throughout the winter were similar for males and females. Thus, results of these experiments do not lead to conclusive rejection of either the behavioral dominance hypothesis or the fasting endurance hypothesis.

Rates and mechanism of fluoride and water exchange in UO(2)F(5)(3-) and [UO(2)F(4)(H(2)O)](2-) studied by NMR spectroscopy and wave function based methods.

PubMed

Vallet, Valérie; Wahlgren, Ulf; Szabó, Zoltán; Grenthe, Ingmar

2002-10-21

The reaction mechanism for the exchange of fluoride in UO(2)F(5)(3-) and UO(2)F(4)(H(2)O)(2-) has been investigated experimentally using (19)F NMR spectroscopy at -5 degrees C, by studying the line broadening of the free fluoride, UO(2)F(4)(2-)(aq) and UO(2)F(5)(3-), and theoretically using quantum chemical methods to calculate the activation energy for different pathways. The new experimental data allowed us to make a more detailed study of chemical equilibria and exchange mechanisms than in previous studies. From the integrals of the different individual peaks in the new NMR spectra, we obtained the stepwise stability constant K(5) = 0.60 +/- 0.05 M(-1) for UO(2)F(5)(3-). The theoretical results indicate that the fluoride exchange pathway of lowest activation energy, 71 kJ/mol, in UO(2)F(5)(3-) is water assisted. The pure dissociative pathway has an activation energy of 75 kJ/mol, while the associative mechanism can be excluded as there is no stable UO(2)F(6)(4-) intermediate. The quantum chemical calculations have been made at the SCF/MP2 levels, using a conductor-like polarizable continuum model (CPCM) to describe the solvent. The effects of different model assumptions on the activation energy have been studied. The activation energy is not strongly dependent on the cavity size or on interactions between the complex and Na(+) counterions. However, the solvation of the complex and the leaving fluoride results in substantial changes in the activation energy. The mechanism for water exchange in UO(2)F(4)(H(2)O)(2-) has also been studied. We could eliminate the associative mechanism, the dissociative mechanism had the lowest activation energy, 39 kJ/mol, while the interchange mechanism has an activation energy that is approximately 50 kJ/mol higher.

Molecular determinants for the high constitutive activity of the human histamine H4 receptor: functional studies on orthologues and mutants

PubMed Central

Wifling, D; Löffel, K; Nordemann, U; Strasser, A; Bernhardt, G; Dove, S; Seifert, R; Buschauer, A

2015-01-01

Background and Purpose Some histamine H4 receptor ligands act as inverse agonists at the human H4 receptor (hH4R), a receptor with exceptionally high constitutive activity, but as neutral antagonists or partial agonists at the constitutively inactive mouse H4 receptor (mH4R) and rat H4 receptor (rH4R). To study molecular determinants of constitutive activity, H4 receptor reciprocal mutants were constructed: single mutants: hH4R-F169V, mH4R-V171F, hH4R-S179A, hH4R-S179M; double mutants: hH4R-F169V+S179A, hH4R-F169V+S179M and mH4R-V171F+M181S. Experimental Approach Site-directed mutagenesis with pVL1392 plasmids containing hH4 or mH4 receptors were performed. Wild-type or mutant receptors were co-expressed with Gαi2 and Gβ1γ2 in Sf9 cells. Membranes were studied in saturation and competition binding assays ([3H]-histamine), and in functional [35S]-GTPγS assays with inverse, partial and full agonists of the hH4 receptor. Key Results Constitutive activity decreased from the hH4 receptor via the hH4R-F169V mutant to the hH4R-F169V+S179A and hH4R-F169V+S179M double mutants. F169 alone or in concert with S179 plays a major role in stabilizing a ligand-free active state of the hH4 receptor. Partial inverse hH4 receptor agonists like JNJ7777120 behaved as neutral antagonists or partial agonists at species orthologues with lower or no constitutive activity. Some partial and full hH4 receptor agonists showed decreased maximal effects and potencies at hH4R-F169V and double mutants. However, the mutation of S179 in the hH4 receptor to M as in mH4 receptor or A as in rH4 receptor did not significantly reduce constitutive activity. Conclusions and Implications F169 and S179 are key amino acids for the high constitutive activity of hH4 receptors and may also be of relevance for other constitutively active GPCRs. Linked Articles This article is part of a themed issue on Histamine Pharmacology Update published in volume 170 issue 1. To view the other articles in this issue visit http://onlinelibrary.wiley.com/doi/10.1111/bph.2013.170.issue-1/issuetoc PMID:24903527

Synthesis and preliminary evaluation of 18-(18)F-fluoro-4-thia-oleate as a PET probe of fatty acid oxidation.

PubMed

DeGrado, Timothy R; Bhattacharyya, Falguni; Pandey, Mukesh K; Belanger, Anthony P; Wang, Shuyan

2010-08-01

Fatty acid oxidation (FAO) is a major energy-providing process with important implications in cardiovascular, oncologic, neurologic, and metabolic diseases. A novel 4-thia oleate analog, 18-(18)F-fluoro-4-thia-oleate ((18)F-FTO), was evaluated in relationship to the previously developed palmitate analog 16-(18)F-fluoro-4-thia-palmitate ((18)F-FTP) as an FAO probe. (18)F-FTO was synthesized from a corresponding bromoester. Biodistribution and metabolite analysis studies were performed in rats. Preliminary small-animal PET studies were performed with (18)F-FTO and (18)F-FTP in rats. A practical synthesis of (18)F-FTO was developed, providing a radiotracer of high radiochemical purity (>99%). In fasted rats, myocardial uptake of (18)F-FTO (0.70 +/- 0.30% dose kg [body mass]/g [tissue mass]) was similar to that of (18)F-FTP at 30 min after injection. At 2 h, myocardial uptake of (18)F-FTO was maintained, whereas (18)F-FTP uptake in the heart was 82% reduced. Similar to (18)F-FTP, (18)F-FTO uptake by the heart was approximately 80% reduced at 30 min by pretreatment of rats with the CPT-I inhibitor etomoxir. Folch-type extraction analyses showed 70-90% protein-bound fractions in the heart, liver, and skeletal muscle, consistent with efficient trafficking of (18)F-FTO to the mitochondrion with subsequent metabolism to protein-bound species. Preliminary small-animal PET studies showed rapid blood clearance and avid extraction of (18)F-FTO and of (18)F-FTP into the heart and liver. Images of (18)F-FTO accumulation in the rat myocardium were clearly superior to those of (18)F-FTP. (18)F-FTO is shown to be a promising metabolically trapped FAO probe that warrants further evaluation.

E4F1 deficiency results in oxidative stress–mediated cell death of leukemic cells

PubMed Central

Hatchi, Elodie; Rodier, Genevieve; Lacroix, Matthieu; Caramel, Julie; Kirsh, Olivier; Jacquet, Chantal; Schrepfer, Emilie; Lagarrigue, Sylviane; Linares, Laetitia Karine; Lledo, Gwendaline; Tondeur, Sylvie; Dubus, Pierre

2011-01-01

The multifunctional E4F1 protein was originally discovered as a target of the E1A viral oncoprotein. Growing evidence indicates that E4F1 is involved in key signaling pathways commonly deregulated during cell transformation. In this study, we investigate the influence of E4F1 on tumorigenesis. Wild-type mice injected with fetal liver cells from mice lacking CDKN2A, the gene encoding Ink4a/Arf, developed histiocytic sarcomas (HSs), a tumor originating from the monocytic/macrophagic lineage. Cre-mediated deletion of E4F1 resulted in the death of HS cells and tumor regression in vivo and extended the lifespan of recipient animals. In murine and human HS cell lines, E4F1 inactivation resulted in mitochondrial defects and increased production of reactive oxygen species (ROS) that triggered massive cell death. Notably, these defects of E4F1 depletion were observed in HS cells but not healthy primary macrophages. Short hairpin RNA–mediated depletion of E4F1 induced mitochondrial defects and ROS-mediated death in several human myeloid leukemia cell lines. E4F1 protein is overexpressed in a large subset of human acute myeloid leukemia samples. Together, these data reveal a role for E4F1 in the survival of myeloid leukemic cells and support the notion that targeting E4F1 activities might have therapeutic interest. PMID:21708927

Effect of NaF and TiF(4) varnish and solution on bovine dentin erosion plus abrasion in vitro.

PubMed

Magalhães, Ana Carolina; Levy, Flávia Mauad; Rizzante, Fábio A; Rios, Daniela; Buzalaf, Marília Afonso Rabelo

2012-03-01

This in vitro study aimed to analyze the effect of TiF(4) compared to NaF varnishes and solutions, to protect against dentin erosion associated with abrasion. Bovine dentin specimens were pre-treated with NaF-Duraphat (2.26% F), NaF/CaF(2)-Duofluorid (5.63% F), experimental-NaF (2.45% F), experimental-TiF(4) (2.45% F) and placebo varnishes; NaF (2.26% F) and TiF(4) (2.45% F) solutions. Controls remained untreated. The erosive pH cycling was performed using a soft drink (pH 2.6) 4 × 90 s/day and the toothbrushing-abrasion 2 × 10 s/day, in vitro for 5 days. Between the challenges, the specimens were exposed to artificial saliva. Dentin tissue loss was measured profilometrically (μm). ANOVA/Tukey's test showed that all fluoridated varnishes (Duraphat, 7.5 ± 1.1; Duofluorid, 6.8 ± 1.1; NaF, 7.2 ± 1.9; TiF(4), 6.5 ± 1.0) were able to significantly reduce dentin tissue loss (40.7% reduction compared to control) when compared to placebo varnish (11.2 ± 1.3), control (11.8 ± 1.7) and fluoridated (NaF, 9.9 ± 1.8; TiF(4), 10.3 ± 2.1) solutions (p < 0.0001), which in turn did not significantly differ from each other. All fluoridated varnishes, but not the solutions, had a similar performance and a good potential to reduce dentin tissue loss under mild erosive and abrasive conditions in vitro. Risk patients for erosion and abrasion, especially those with exposed dentin, should benefit from this clinical preventive measure. Further research has to confirm this promising result in the clinical situation.

Identification of serum metabolites associated with risk of type 2 diabetes using a targeted metabolomic approach.

PubMed

Floegel, Anna; Stefan, Norbert; Yu, Zhonghao; Mühlenbruch, Kristin; Drogan, Dagmar; Joost, Hans-Georg; Fritsche, Andreas; Häring, Hans-Ulrich; Hrabě de Angelis, Martin; Peters, Annette; Roden, Michael; Prehn, Cornelia; Wang-Sattler, Rui; Illig, Thomas; Schulze, Matthias B; Adamski, Jerzy; Boeing, Heiner; Pischon, Tobias

2013-02-01

Metabolomic discovery of biomarkers of type 2 diabetes (T2D) risk may reveal etiological pathways and help to identify individuals at risk for disease. We prospectively investigated the association between serum metabolites measured by targeted metabolomics and risk of T2D in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam (27,548 adults) among all incident cases of T2D (n = 800, mean follow-up 7 years) and a randomly drawn subcohort (n = 2,282). Flow injection analysis tandem mass spectrometry was used to quantify 163 metabolites, including acylcarnitines, amino acids, hexose, and phospholipids, in baseline serum samples. Serum hexose; phenylalanine; and diacyl-phosphatidylcholines C32:1, C36:1, C38:3, and C40:5 were independently associated with increased risk of T2D and serum glycine; sphingomyelin C16:1; acyl-alkyl-phosphatidylcholines C34:3, C40:6, C42:5, C44:4, and C44:5; and lysophosphatidylcholine C18:2 with decreased risk. Variance of the metabolites was largely explained by two metabolite factors with opposing risk associations (factor 1 relative risk in extreme quintiles 0.31 [95% CI 0.21-0.44], factor 2 3.82 [2.64-5.52]). The metabolites significantly improved T2D prediction compared with established risk factors. They were further linked to insulin sensitivity and secretion in the Tübingen Family study and were partly replicated in the independent KORA (Cooperative Health Research in the Region of Augsburg) cohort. The data indicate that metabolic alterations, including sugar metabolites, amino acids, and choline-containing phospholipids, are associated early on with a higher risk of T2D.

Identification of Serum Metabolites Associated With Risk of Type 2 Diabetes Using a Targeted Metabolomic Approach

PubMed Central

Floegel, Anna; Stefan, Norbert; Yu, Zhonghao; Mühlenbruch, Kristin; Drogan, Dagmar; Joost, Hans-Georg; Fritsche, Andreas; Häring, Hans-Ulrich; Hrabě de Angelis, Martin; Peters, Annette; Roden, Michael; Prehn, Cornelia; Wang-Sattler, Rui; Illig, Thomas; Schulze, Matthias B.; Adamski, Jerzy; Boeing, Heiner; Pischon, Tobias

2013-01-01

Metabolomic discovery of biomarkers of type 2 diabetes (T2D) risk may reveal etiological pathways and help to identify individuals at risk for disease. We prospectively investigated the association between serum metabolites measured by targeted metabolomics and risk of T2D in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam (27,548 adults) among all incident cases of T2D (n = 800, mean follow-up 7 years) and a randomly drawn subcohort (n = 2,282). Flow injection analysis tandem mass spectrometry was used to quantify 163 metabolites, including acylcarnitines, amino acids, hexose, and phospholipids, in baseline serum samples. Serum hexose; phenylalanine; and diacyl-phosphatidylcholines C32:1, C36:1, C38:3, and C40:5 were independently associated with increased risk of T2D and serum glycine; sphingomyelin C16:1; acyl-alkyl-phosphatidylcholines C34:3, C40:6, C42:5, C44:4, and C44:5; and lysophosphatidylcholine C18:2 with decreased risk. Variance of the metabolites was largely explained by two metabolite factors with opposing risk associations (factor 1 relative risk in extreme quintiles 0.31 [95% CI 0.21–0.44], factor 2 3.82 [2.64–5.52]). The metabolites significantly improved T2D prediction compared with established risk factors. They were further linked to insulin sensitivity and secretion in the Tübingen Family study and were partly replicated in the independent KORA (Cooperative Health Research in the Region of Augsburg) cohort. The data indicate that metabolic alterations, including sugar metabolites, amino acids, and choline-containing phospholipids, are associated early on with a higher risk of T2D. PMID:23043162

Studies on electronic spectral parameters of doped Nd(III) ion with therapeutically important ligands in dioxane solvent

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

Bajaj, Annu, E-mail: annu.bajaj11@gmail.com; Jain, Sushma

2016-05-06

The present investigation is concerened with the studies on electronic spectral parameters viz. Oscillator strength (P), Judd-Ofelt T{sub λ} (λ=2,4,6), Slater-Condon(F{sub K}),Lande(ζ{sub 4F}),Nephelauxetic ratio(β), Bonding parameter (b{sup 1/2}) and Percent covalency parameter (δ%) for Nd(III) ion complexes with the ligands having Nitrogen,Oxygen Sulphur donor sites.The variation in the values of oscillator strength explicitly shows the relative sensitivities of the 4f-4f transition as well as the specific correlation between ligand structures and nature of Nd(III) ligand interaction.

Mobilities and leachabilities of heavy metals in sludge with humus soil.

PubMed

Zhu, Rui; Wu, Min; Yang, Jian

2011-01-01

Chemical forms of Zn, Ni, Cu, and Pb in municipal sewage sludge were investigated by adding humus soil to sludge and by performing sequential extraction procedures. In the final sludge mixtures, Zn and Ni were mainly found in Fe/Mn oxide-bound (F3) and organic matter/sulfide-bound (F4) forms. For Zn, exchangeable (F1), carbonate-bound (F2), and F3 forms were transformed to F4 and residual forms (F5). For Ni, F1 and F2 forms were transformed to F1, F2, and F3 forms. Both Cu and Pb were strongly associated with the stable forms F4 and F5. For Cu, F2 and F3 forms were major contributors, while for Pb, F3 and F4 forms were major contributors to F5. Humus soil dosage and pH conditions in the sludge were strongly correlated with the forms of heavy metals. Five forms were used to evaluate metal mobilities in the initial and final sludge mixtures. The mobilities of the four heavy metals studied decreased after 28 days. The metal mobilities in the final sludge mixtures were ranked in the following order: Ni > Zn > Cu = Pb. Leaching tests showed that the mobilities of Zn and Ni in lower pH conditions (pH 4) were higher than those in higher pH conditions (pH 8).

Evaluation of the biomarker candidate MFAP4 for non-invasive assessment of hepatic fibrosis in hepatitis C patients.

PubMed

Bracht, Thilo; Mölleken, Christian; Ahrens, Maike; Poschmann, Gereon; Schlosser, Anders; Eisenacher, Martin; Stühler, Kai; Meyer, Helmut E; Schmiegel, Wolff H; Holmskov, Uffe; Sorensen, Grith L; Sitek, Barbara

2016-07-04

The human microfibrillar-associated protein 4 (MFAP4) is located to extracellular matrix fibers and plays a role in disease-related tissue remodeling. Previously, we identified MFAP4 as a serum biomarker candidate for hepatic fibrosis and cirrhosis in hepatitis C patients. The aim of the present study was to elucidate the potential of MFAP4 as biomarker for hepatic fibrosis with a focus on the differentiation of no to moderate (F0-F2) and severe fibrosis stages and cirrhosis (F3 and F4, Desmet-Scheuer scoring system). MFAP4 levels were measured using an AlphaLISA immunoassay in a retrospective study including n = 542 hepatitis C patients. We applied a univariate logistic regression model based on MFAP4 serum levels and furthermore derived a multivariate model including also age and gender. Youden-optimal cutoffs for binary classification were determined for both models without restrictions and considering a lower limit of 80 % sensitivity (correct classification of F3 and F4), respectively. To assess the generalization error, leave-one-out cross validation (LOOCV) was performed. MFAP4 levels were shown to differ between no to moderate fibrosis stages F0-F2 and severe stages (F3 and F4) with high statistical significance (t test on log scale, p value <2.2·10(-16)). In the LOOCV, the univariate classification resulted in 85.8 % sensitivity and 54.9 % specificity while the multivariate model yielded 81.3 % sensitivity and 61.5 % specificity (restricted approaches). We confirmed the applicability of MFAP4 as a novel serum biomarker for assessment of hepatic fibrosis and identification of high-risk patients with severe fibrosis stages in hepatitis C. The combination of MFAP4 with existing tests might lead to a more accurate non-invasive diagnosis of hepatic fibrosis and allow a cost-effective disease management in the era of new direct acting antivirals.

F4/80: the macrophage-specific adhesion-GPCR and its role in immunoregulation.

PubMed

Lin, Hsi-Hsien; Stacey, Martin; Stein-Streilein, Joan; Gordon, Siamon

2010-01-01

As a macrophage-restricted reagent, the generation and application of the F4/80 mAb has greatly benefited the phenotypic characterization of mouse tissue macrophages for three decades. Following the molecular identification of the F4/80 antigen as an EGF-TM7 member of the adhesion-GPCR family, great interest was ignited to understand its cell type-specific expression pattern as well as its functional role in macrophage biology. Recent studies have shown that the F4/80 gene is regulated by a novel set of transcription factors that recognized a unique promoter sequence. Gene targeting experiments have produced two F4/80 knock out animal models and showed that F4/80 is not required for normal macrophage development. Nevertheless, the F4/80 receptor was found to be necessary for the induction of efferent CD8+ regulatory T cells responsible for peripheral immune tolerance. The identification of cellular ligands for F4/80 and delineation of its signaling pathway remain elusive but are critical to understand the in vivo role of this macrophage-specific adhesion-GPCR.

Study on Utilization of Super Grade Plutonium in Molten Salt Reactor FUJI-U3 using CITATION Code

NASA Astrophysics Data System (ADS)

Wulandari, Cici; Waris, Abdul; Pramuditya, Syeilendra; Asril, Pramutadi AM; Novitrian

2017-07-01

FUJI-U3 type of Molten Salt Reactor (MSR) has a unique design since it consists of three core regions in order to avoid the replacement of graphite as moderator. MSR uses floride as a nuclear fuel salt with the most popular chemical composition is LiF-BeF2-ThF4-233UF4. ThF4 and 233UF4 are the fertile and fissile materials, respectively. On the other hand, LiF and BeF2 working as both fuel and heat transfer medium. In this study, the super grade plutonium will be utilized as substitution of 233U since plutonium is easier to be obtained compared to 233U as main fuel. Neutronics calculation was performed by using PIJ and CITATION modules of SRAC 2002 code with JENDL 3.2 as nuclear data library.

Rigid 2',4'-difluororibonucleosides: synthesis, conformational analysis, and incorporation into nascent RNA by HCV polymerase.

PubMed

Martínez-Montero, Saúl; Deleavey, Glen F; Kulkarni, Anupriya; Martín-Pintado, Nerea; Lindovska, Petra; Thomson, Michael; González, Carlos; Götte, Matthias; Damha, Masad J

2014-06-20

We report on the synthesis and conformational properties of 2'-deoxy-2',4'-difluorouridine (2',4'-diF-rU) and cytidine (2',4'-diF-rC) nucleosides. NMR analysis and quantum mechanical calculations show that the strong stereoelectronic effects induced by the two fluorines essentially "lock" the conformation of the sugar in the North region of the pseudorotational cycle. Our studies also demonstrate that NS5B HCV RNA polymerase was able to accommodate 2',4'-diF-rU 5'-triphosphate (2',4'-diF-rUTP) and to link the monophosphate to the RNA primer strand. 2',4'-diF-rUTP inhibited RNA synthesis in dinucleotide-primed reactions, although with relatively high half-maximal inhibitory concentrations (IC50 > 50 μM). 2',4'-diF-rU/C represents rare examples of "locked" ribonucleoside mimics that lack a bicyclic ring structure.

Experimental and DFT Studies of the Electron-Withdrawing Ability of Perfluoroalkyl (R F) Groups: Electron Affinities of PAH(R F) n Increase Significantly with Increasing R F Chain Length

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

San, Long K.; Spisak, Sarah N.; Dubceac, Cristina

Two series of aromatic compounds with perfluoroalkyl (RF) groups of increasing length, 1,3,5,7-naphthalene(RF)4 and 1,3,5,7,9-corannulene(RF)5, have been prepared and their electronic properties studied by low-temperature PES (i.e., gas-phase electron affinity (EA) measurements). These and many related compounds were also studied by DFT calculations. The data demonstrate unambiguously that the electron-withdrawing ability of RF substituents increases significantly and uniformly from CF3 to C2F5 to n-C3F7 to n-C4F9.

Experimental and DFT Studies of the Electron-Withdrawing Ability of Perfluoroalkyl (R-F) Groups: Electron Affinities of PAH(R-F)(n) Increase Significantly with Increasing R-F Chain Length

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

San, Long K.; Spisak, Sarah N.; Dubceac, Cristina

2018-01-26

Two series of aromatic compounds with perfluoroalkyl (RF) groups of increasing length, 1,3,5,7-naphthalene(RF)4 and 1,3,5,7,9-corannulene(RF)5, have been prepared and their electronic properties studied by low-temperature PES (i.e., gas-phase electron affinity (EA) measurements). These and many related compounds were also studied by DFT calculations. The data demonstrate unambiguously that the electron-withdrawing ability of RF substituents increases significantly and uniformly from CF3 to C2F5 to n-C3F7 to n-C4F9.

Comparison of 4'-[methyl-(11)C]thiothymidine ((11)C-4DST) and 3'-deoxy-3'-[(18)F]fluorothymidine ((18)F-FLT) PET/CT in human brain glioma imaging.

PubMed

Toyota, Yasunori; Miyake, Keisuke; Kawai, Nobuyuki; Hatakeyama, Tetsuhiro; Yamamoto, Yuka; Toyohara, Jun; Nishiyama, Yoshihiro; Tamiya, Takashi

2015-01-01

3'-deoxy-3'-[(18)F]fluorothymidine ((18)F-FLT) has been used to evaluate tumor malignancy and cell proliferation in human brain gliomas. However, (18)F-FLT has several limitations in clinical use. Recently, (11)C-labeled thymidine analogue, 4'-[methyl-(11)C]thiothymidine ((11)C-4DST), became available as an in vivo cell proliferation positron emission tomography (PET) tracer. The present study was conducted to evaluate the usefulness of (11)C-4DST PET in the diagnosis of human brain gliomas by comparing with the images of (18)F-FLT PET. Twenty patients with primary and recurrent brain gliomas underwent (18)F-FLT and (11)C-4DST PET scans. The uptake values in the tumors were evaluated using the maximum standardized uptake value (SUVmax), the tumor-to-normal tissue uptake (T/N) ratio, and the tumor-to-blood uptake (T/B) ratio. These values were compared among different glioma grades. Correlation between the Ki-67 labeling index and the uptake values of (11)C-4DST and (18)F-FLT in the tumor was evaluated using linear regression analysis. The relationship between the individual (18)F-FLT and (11)C-4DST uptake values in the tumors was also examined. (11)C-4DST uptake was significantly higher than that of (18)F-FLT in the normal brain. The uptake values of (11)C-4DST in the tumor were similar to those of (18)F-FLT resulting in better visualization with (18)F-FLT. No significant differences in the uptake values of (18)F-FLT and (11)C-4DST were noted among different glioma grades. Linear regression analysis showed a significant correlation between the Ki-67 labeling index and the T/N ratio of (11)C-4DST (r = 0.50, P < 0.05) and (18)F-FLT (r = 0.50, P < 0.05). Significant correlations were also found between the Ki-67 labeling index and the T/B ratio of (11)C-4DST (r = 0.52, P < 0.05) and (18)F-FLT (r = 0.55, P < 0.05). A highly significant correlation was observed between the individual T/N ratio of (11)C-4DST and (18)F-FLT in the tumor (r = 0.79, P = 0.0001). The present study demonstrates that (11)C-4DST is useful for the imaging of human brain gliomas with PET. A relatively higher background uptake of (11)C-4DST in the normal brain compared to (18)F-FLT limits the detection of low-tracer-uptake tumors. Moreover, no superiority was found in (11)C-4DST over (18)F-FLT in the evaluation of cell proliferation.

Antioxidant and Cytoprotective Activities of Fucus spiralis Seaweed on a Human Cell in Vitro Model

PubMed Central

Pinteus, Susete; Silva, Joana; Alves, Celso; Horta, André; Thomas, Olivier P.; Pedrosa, Rui

2017-01-01

Antioxidants play an important role as Reactive Oxygen Species (ROS) chelating agents and, therefore, the screening for potent antioxidants from natural sources as potential protective agents is of great relevance. The main aim of this study was to obtain antioxidant-enriched fractions from the common seaweed Fucus spiralis and evaluate their activity and efficiency in protecting human cells (MCF-7 cells) on an oxidative stress condition induced by H2O2. Five fractions, F1–F5, were obtained by reversed-phase vacuum liquid chromatography. F3, F4 and F5 revealed the highest phlorotannin content, also showing the strongest antioxidant effects. The cell death induced by H2O2 was reduced by all fractions following the potency order F4 > F2 > F3 > F5 > F1. Only fraction F4 completely inhibited the H2O2 effect. To understand the possible mechanisms of action of these fractions, the cellular production of H2O2, the mitochondrial membrane potential and the caspase 9 activity were studied. Fractions F3 and F4 presented the highest reduction on H2O2 cell production. All fractions decreased both caspase-9 activity and cell membrane depolarization (except F1). Taken all together, the edible F. spiralis reveal that they provide protection against oxidative stress induced by H2O2 on the human MCF-7 cellular model, probably acting as upstream blockers of apoptosis. PMID:28146076

The roles of 4f- and 5f-orbitals in bonding: a magnetochemical, crystal field, density functional theory, and multi-reference wavefunction study

DOE PAGES

Lukens, W. W.; Speldrich, M.; Yang, P.; ...

2016-01-01

The electronic structures of 4f 3/5f 3Cp" 3M and Cp"sub>3M·alkylisocyanide complexes, where Cp" is 1,3-bis-(trimethylsilyl)cyclopentadienyl, are explored with a focus on the splitting of the f-orbitals, which provides information about the strengths of the metal–ligand interactions.

Identifying and sequencing a Mycobacterium sp. strain F4 as a potential bioremediation agent for quinclorac.

PubMed

Li, Yingying; Chen, Wu; Wang, Yunsheng; Luo, Kun; Li, Yue; Bai, Lianyang; Luo, Feng

2017-01-01

Quinclorac is a widely used herbicide in rice filed. Unfortunately, quinclorac residues are phytotoxic to many crops/vegetables. The degradation of quinclorac in nature is very slow. On the other hand, degradation of quinclorac using bacteria can be an effective and efficient method to reduce its contamination. In this study, we isolated a quinclorac bioremediation bacterium strain F4 from quinclorac contaminated soils. Based on morphological characteristics and 16S rRNA gene sequence analysis, we identified strain F4 as Mycobacterium sp. We investigated the effects of temperature, pH, inoculation size and initial quinclorac concentration on growth and degrading efficiency of F4 and determined the optimal quinclorac degrading condition of F4. Under optimal degrading conditions, F4 degraded 97.38% of quinclorac from an initial concentration of 50 mg/L in seven days. Our indoor pot experiment demonstrated that the degradation products were non-phytotoxic to tobacco. After analyzing the quinclorac degradation products of F4, we proposed that F4 could employ two pathways to degrade quinclorac: one is through methylation, the other is through dechlorination. Furthermore, we reconstructed the whole genome of F4 through single molecular sequencing and de novo assembly. We identified 77 methyltransferases and eight dehalogenases in the F4 genome to support our hypothesized degradation path.

Identifying and sequencing a Mycobacterium sp. strain F4 as a potential bioremediation agent for quinclorac

PubMed Central

Li, Yingying; Chen, Wu; Wang, Yunsheng; Luo, Kun; Li, Yue; Bai, Lianyang

2017-01-01

Quinclorac is a widely used herbicide in rice filed. Unfortunately, quinclorac residues are phytotoxic to many crops/vegetables. The degradation of quinclorac in nature is very slow. On the other hand, degradation of quinclorac using bacteria can be an effective and efficient method to reduce its contamination. In this study, we isolated a quinclorac bioremediation bacterium strain F4 from quinclorac contaminated soils. Based on morphological characteristics and 16S rRNA gene sequence analysis, we identified strain F4 as Mycobacterium sp. We investigated the effects of temperature, pH, inoculation size and initial quinclorac concentration on growth and degrading efficiency of F4 and determined the optimal quinclorac degrading condition of F4. Under optimal degrading conditions, F4 degraded 97.38% of quinclorac from an initial concentration of 50 mg/L in seven days. Our indoor pot experiment demonstrated that the degradation products were non-phytotoxic to tobacco. After analyzing the quinclorac degradation products of F4, we proposed that F4 could employ two pathways to degrade quinclorac: one is through methylation, the other is through dechlorination. Furthermore, we reconstructed the whole genome of F4 through single molecular sequencing and de novo assembly. We identified 77 methyltransferases and eight dehalogenases in the F4 genome to support our hypothesized degradation path. PMID:28968436

Comparative Study of Multiplet Structures of Mn4+ in K2SiF6, K2GeF6, and K2TiF6 Based on First-Principles Configuration-Interaction Calculations

NASA Astrophysics Data System (ADS)

Novita, Mega; Ogasawara, Kazuyoshi

2012-02-01

We performed first-principles configuration-interaction calculations of multiplet energies for Mn4+ in K2SiF6, K2GeF6, and K2TiF6 crystals. The results indicate that corrections based on a single-electron calculation are effective for the prediction of 4A2 → 4T2 and 4A2 → 4T1a transition energies, while such corrections are not necessary for the prediction of the 4A2 → 2E transition energy. The cluster size dependence of the multiplet energies is small. However, the 4A2 → 2E transition energy is slightly improved by using larger clusters including K ions. The theoretical multiplet energies are improved further by considering the lattice relaxation effect. As a result, the characteristic multiplet energy shifts depending on the host crystal are well reproduced without using any empirical parameters. Although K2GeF6 and K2TiF6 have lower symmetry than K2SiF6, the results indicate that the variation of the multiplet energy is mainly determined by the Mn-F bond length.

Conversion of iodine to fluorine-18 based on iodinated chalcone and evaluation for β-amyloid PET imaging.

PubMed

Kaide, Sho; Ono, Masahiro; Watanabe, Hiroyuki; Shimizu, Yoichi; Nakamoto, Yuji; Togashi, Kaori; Yamaguchi, Aiko; Hanaoka, Hirofumi; Saji, Hideo

2018-07-23

In the amyloid cascade hypothesis, β-amyloid (Aβ) plaques is one of the major pathological biomarkers in the Alzheimer's disease (AD) brain. We report the synthesis and evaluation of novel radiofluorinated chalcones, [ 18 F]4-dimethylamino-4'-fluoro-chalcone ([ 18 F]DMFC) and [ 18 F]4'-fluoro-4-methylamino-chalcone ([ 18 F]FMC), as Aβ imaging probes. The conversion of iodine directly introduced to the chalcone backbone into fluorine was successfully carried out by 18 F-labeling via the corresponding boronate precursors, achieving the direct introduction of fluorine-18 into the chalcone backbone to prepare [ 18 F]DMFC and [ 18 F]FMC. In a biodistribution study using normal mice, [ 18 F]DMFC and [ 18 F]FMC showed a higher initial uptake (4.43 and 5.47% ID/g at 2 min postinjection, respectively) into and more rapid clearance (0.52 and 0.66% ID/g at 30 min postinjection, respectively) from the brain than a Food and Drug Administration (FDA)-approved Aβ imaging agent ([ 18 F]Florbetapir), meaning the improvement of the probability of detecting Aβ plaques and the reduction of non-specific binding in the brain. In the in vitro binding studies using aggregates of recombinant Aβ peptides, [ 18 F]DMFC and [ 18 F]FMC showed high binding affinity to recombinant Aβ aggregates at the K d values of 4.47 and 6.50 nM, respectively. In the in vitro autoradiography (ARG) experiment with AD brain sections, [ 18 F]DMFC and [ 18 F]FMC markedly accumulated only in a region with abundant Aβ plaques, indicating that they clearly recognized human Aβ plaques in vitro. These encouraging results suggest that [ 18 F]DMFC and [ 18 F]FMC may be promising PET probes for the detection of an amyloid pathology and the early diagnosis of AD with marked accuracy. Copyright © 2018 Elsevier Ltd. All rights reserved.

TiF(4) and NaF at pH 1.2 but not at pH 3.5 are able to reduce dentin erosion.

PubMed

Wiegand, Annette; Magalhães, Ana Carolina; Sener, Beatrice; Waldheim, Elena; Attin, Thomas

2009-08-01

This study aimed to analyse and compare the protective effect of buffered (pH 3.5) and native (pH 1.2) TiF(4) in comparison to NaF solutions of same pH on dentin erosion. Bovine samples were pretreated with 1.50% TiF(4) or 2.02% NaF (both 0.48M F) solutions, each with a pH of 1.2 and 3.5. The control group received no fluoride pretreatment. Ten samples in each group were eroded with HCl (pH 2.6) for 10x60s. Erosion was analysed by determination of calcium release into the acid. Additionally, the surface and the elemental surface composition were examined by scanning electron microscopy (two samples in each group) and X-ray energy-dispersive spectroscopy in fluoridated but not eroded samples (six samples in each group). Cumulative calcium release (nmol/mm(2)) was statistically analysed by repeated measures ANOVA and one-way ANOVA at t=10min. TiF(4) and NaF at pH 1.2 decreased calcium release significantly, while TiF(4) and NaF at pH 3.5 were not effective. Samples treated with TiF(4) at pH 1.2 showed a significant increase of Ti, while NaF pretreatment increased F concentration significantly. TiF(4) at pH 1.2 led to the formation of globular precipitates occluding dentinal tubules, which could not be observed on samples treated with TiF(4) at pH 3.5. NaF at pH 1.2 but not at pH 3.5 induced the formation of surface precipitates covering dentinal tubules. Dentin erosion can be significantly reduced by TiF(4) and NaF at pH 1.2, but not at pH 3.5.

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

Baig, Mohammad Saad, E-mail: saad110baig@gmail.com; Chakraborty, Brahmananda; Ramaniah, Lavanya M.

NaF-ZrF{sub 4} is used as a waste incinerator and as a coolant in Generation IV reactors.Structural and dynamical properties of molten NaF-ZrF{sub 4} system were studied along with Onsagercoefficients and Maxwell–Stefan (MS) Diffusivities applying Green–Kubo formalism and molecular dynamics (MD) simulations. The zirconium ions are found to be 8 fold coordinated with fluoride ions for all temperatures and concentrations. All the diffusive flux correlations show back-scattering. Even though the MS diffusivities are expected to depend very lightly on the composition because of decoupling of thermodynamic factor, the diffusivity Đ{sub Na-F} shows interesting behavior with the increase in concentration of ZrF{submore » 4}. This is because of network formation in NaF-ZrF{sub 4}. Positive entropy constraints have been plotted to authenticate negative diffusivities observed.« less

Halide addition/abstraction in phosphido derivatives: isolation of the thallium and silver intermediates.

PubMed

Forniés, Juan; Fortuño, Consuelo; Ibáñez, Susana; Martín, Antonio

2008-07-07

Reaction of unsaturated (44e (-) skeleton) [PdPt 2(mu-PPh 2) 2(mu-P 2Ph 4)(R F) 4] 4 with Br (-) produces the saturated (48e (-) skeleton) complex [NBu 4][(R F) 2Pt(mu-PPh 2)(mu-Br)Pd(mu-PPh 2)(mu-P 2Ph 4)Pt(R F) 2] 5 without any M-M' bond. Attempts to eliminate Br (-) of 5 with Ag (+) in CH 2Cl 2 as a solvent gives a mixture of [(R F) 2Pt (III)(mu-PPh 2) 2Pt (III)(R F) 2] and some other unidentified products as a consequence of oxidation and partial fragmentation. However, when the reaction of 5 with Ag (+) is carried out in CH 3CN, no oxidation is observed but the elimination of Br (-) and the formation of [(R F) 2(CH 3CN)Pt(mu-PPh 2)Pd(mu-PPh 2)(mu-P 2Ph 4)Pt(R F) 2] 6 (46e (-) skeleton), a complex with a Pt-Pd bond, takes place. It is noteworthy that the reaction of 5 with TlPF 6 in CH 2Cl 2 does not precipitate TlBr but forms the adduct [(R F) 2PtTl(mu-PPh 2)(mu-Br)Pd(mu-PPh 2)(mu-P 2Ph 4)Pt(R F) 2] 7 with a Pt-Tl bond. Likewise, 5 reacts with [AgOClO 3(PPh 3)] in CH 2Cl 2 forming the adduct [AgPdPt 2(mu-Br)(mu-PPh 2) 2(mu-Ph 2P-PPh 2)(R F) 4(PPh 3)] 8, which contains a Pt-Ag bond. Both adducts are unstable in a CH 3CN solution, precipitating TlBr or AgBr and yielding the unsaturated 6. The treatment of [NBu 4] 2[(R F) 2Pt(mu-PPh 2) 2Pd(mu-PPh 2) 2Pt(R F) 2] in CH 3CN with I 2 (1:1 molar ratio) at 233 K yields a mixture of 4 and 6, which after recrystallization from CH 2Cl 2 is totally converted in 4. If the reaction with I 2 is carried out at room temperature, a mixture of the isomers [NBu 4][(R F) 2Pt(mu-PPh 2)(mu-I)Pd(mu-PPh 2)(mu-P 2Ph 4)Pt(R F) 2] 9 and [NBu 4][(R F)(PPh 2R F)Pt(mu-PPh 2)(mu-I)Pd(mu-PPh 2) 2Pt(R F) 2] 10 are obtained. The structures of the complexes have been established on the bases of NMR data, and the X-ray structures of 5- 8 have been studied. The relationship between the different complexes has been studied.

Fourier transform infrared study of the phase transitions in (NH4)3VO2FO4

NASA Astrophysics Data System (ADS)

de Waal, D.; Heyns, A. M.

1994-01-01

Ammonium oxofluorovanadate compounds are known to show some potential as ferroelectric materials. The whole series of ammonium and sodium oxofluorovanadate compounds including Na3VO2F4 have already been prepared and investigated by means of various techniques including x-ray diffraction, EPR, and vibrational spectroscopy. It was established that the pure ammonium compound shows the two above mentioned transitions from phase A (below 200 K) to phase B (between 200 and 400 K) and phase C (above 400 K) while Na(NH4)2VO2F4 has only one transition from phase A to phase B around 400 K4. In the present study various aspects regarding the nature of the structures of (NH4)3VO2F3 and Na(NH4)2VO2F4 and its influence on the phase transitions have been investigated.

E2F4 is required for early eye patterning.

PubMed

Ruzhynsky, Vladimir A; Furimsky, Marosh; Park, David S; Wallace, Valerie A; Slack, Ruth S

2009-01-01

Increasingly, studies reveal novel functions for cell cycle proteins during development. Here, we investigated the role of E2F4 in eye development. E2F4-deficient mouse embryos exhibit severe early eye patterning defects, which are evident from embryonic day 11.5 and characterized by aberrant shape of the optic cup, coloboma as well as abnormal eye pigmentation. Loss of E2F4 is associated with proximal-distal patterning defects in the optic vesicle. These defects are characterized by the expansion of optic stalk marker gene expression to the optic cup and reduced expression of ventral optic cup markers. These defects are associated with a split of Shh expression domain at the ventral midline of the forebrain and expansion of the Shh activity into the ventral optic cup. Despite these patterning defects, early neuronal differentiation and Shh expression in the retina are not affected by E2F4 deletion. Overall, the results of our studies show a novel role of E2F4 in the early eye development. 2009 S. Karger AG, Basel.

Structural study of the ammonium octafluoroneptunate, [NH 4] 4NpF 8

DOE PAGES

Poineau, Frederic; Silva, Chinthaka M.; Yeamans, Charles B.; ...

2016-04-21

The [NH 4] 4NpF 8 salt was prepared from the solid-state reaction of NpO 2 with NH 4HF 2 and characterized by powder X-ray diffraction and X-ray absorption fine structure spectroscopy. The diffraction results confirm the compound to be isostructural to [NH 4] 4UF 8 with the following lattice parameter (a = 13.054(4) Å, b = 6.681(2) Å, c = 13.676(5) Å, ß = 121.14 Å). For the first time, a Neptunium fluoride complex has been characterized by XAFS spectroscopy. The energy position of the white line and inflection of the XANES spectra of [NH 4] 4NpF 8 are consistentmore » with the presence of Np(IV). Adjustment of the EXAFS spectra indicates that the coordination number (7.4±1.5) and the average Np-F distance (2.26(1) Å) are consistent with the presence of the NpF8 dodecahedron. The average Np-F distance is ~0.02 Å shorter than the U-F distance in [NH 4] 4UF 8 and is a result of the actinide contraction.« less

Low Temperature Deposition of PECVD Polycrystalline Silicon Thin Films using SiF4 / SiH4 mixture

NASA Astrophysics Data System (ADS)

Syed, Moniruzzaman; Inokuma, Takao; Kurata, Yoshihiro; Hasegawa, Seiichi

2016-03-01

Polycrystalline silicon films with a strong (110) texture were prepared at 400°C by a plasma-enhanced chemical vapor deposition using different SiF4 flow rates ([SiF4] = 0-0.5 sccm) under a fixed SiH4 flow rate ([SiH4] = 1 or 0.15 sccm). The effects of the addition of SiF4 to SiH4 on the structural properties of the films were studied by Raman scattering, X-ray diffraction (XRD), Atomic force microscopy and stress measurements. For [SiH4] = 1 sccm, the crystallinity and the (110) XRD grain size monotonically increased with increasing [SiF4] and their respective maxima reach 90% and 900 Å. However, for [SiH4] = 0.15 sccm, both the crystallinity and the grain size decreased with [SiF4]. Mechanisms causing the change in crystallinity are discussed, and it was suggested that an improvement in the crystallinity, due to the addition of SiF4, is likely to be caused by the effect of a change in the surface morphology of the substrates along with the effect of in situ chemical cleaning.

Efficacy of thiolated eudragit microspheres as an oral vaccine delivery system to induce mucosal immunity against enterotoxigenic Escherichia coli in mice.

PubMed

Lee, Won-Jung; Cha, Seungbin; Shin, Minkyoung; Jung, Myunghwan; Islam, Mohammad Ariful; Cho, Chong-su; Yoo, Han Sang

2012-05-01

A vaccine delivery system based on thiolated eudragit microsphere (TEMS) was studied in vivo for its ability to elicit mucosal immunity against enterotoxigenic Escherichia coli (ETEC). Groups of mice were orally immunized with F4 or F18 fimbriae of ETEC and F4 or F18 loaded in TEMS. Mice that were orally administered with F4 or F18 loaded TEMS showed higher antigen-specific IgG antibody responses in serum and antigen-specific IgA in saliva and feces than mice that were immunized with antigens only. In addition, oral vaccination of F4 or F18 loaded TEMS resulted in higher numbers of IgG and IgA antigen-specific antibody secreting cells in the spleen, lamina propria, and Peyer's patches of immunized mice than other groups. Moreover, TEMS administration loaded with F4 or F18 induced mixed Th1 and Th2 type responses based on similarly increased levels of IgG1 and IgG2a. These results suggest that F4 or F18 loaded TEMS may be a promising candidate for an oral vaccine delivery system to elicit systemic and mucosal immunity against ETEC. Copyright © 2012 Elsevier B.V. All rights reserved.

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

Kanai, Dai; Ueda, Atsushi; Akagi, Tadayuki

Embryonic stem (ES) cells, derived from the inner cell mass of blastocysts, have a characteristic cell cycle with truncated G1 and G2 phases. Recent findings that suppression of Oct3/4 expression results in a reduced proliferation rate of ES cells suggest the involvement of Oct3/4 in the regulation of ES cell growth, although the underlying molecular mechanism remains unclear. In the present study, we identified E2F3a as a direct target gene of Oct3/4 in ES cells. Oct3/4 directly bound to the promoter region of the E2F3a gene and positively regulated expression of E2F3a in mouse ES cells. Suppression of E2F3a activitymore » by E2F6 overexpression led to the reduced proliferation in ES cells, which was relieved by co-expression of E2F3a. Furthermore, cell growth retardation caused by loss of Oct3/4 was rescued by E2F3a expression. These results suggest that Oct3/4 upregulates E2F3a expression to promote ES cell growth. - Highlights: • Oct3/4 positively regulates E2F3a expression in ES cells. • Oct3/4 binds to the promoter region of the E2F3a gene. • Overexpression of E2F6, an inhibitor of E2F3a, reduces ES cell growth. • E2F3a recovers growth retardation of ES cells caused by Oct3/4 reduction.« less

[18F](2S,4R)4-Fluoroglutamine PET Detects Glutamine Pool Size Changes in Triple Negative Breast Cancer in Response to Glutaminase Inhibition

PubMed Central

Pantel, Austin R.; Li, Shihong; Lieberman, Brian P.; Ploessl, Karl; Choi, Hoon; Blankemeyer, Eric; Lee, Hsiaoju; Kung, Hank F.; Mach, Robert H.

2017-01-01

Glutaminolysis is a metabolic pathway adapted by many aggressive cancers, including triple-negative breast cancers (TNBC), to utilize glutamine for survival and growth. In this study, we examined the utility of [18F](2S,4R)4-fluoroglutamine ([18F]4F-Gln) PET to measure tumor cellular glutamine pool size, whose change might reveal the pharmacodynamic (PD) effect of drugs targeting this cancer-specific metabolic pathway. High glutaminase (GLS) activity in TNBC tumors resulted in low cellular glutamine pool size assayed via high-resolution 1H magnetic resonance spectroscopy (MRS). GLS inhibition significantly increased glutamine pool size in TNBC tumors. MCF-7 tumors, with inherently low GLS activity compared to TNBC, displayed a larger baseline glutamine pool size that did not change as much in response to GLS inhibition. The tumor-to-blood-activity-ratios (T/B) obtained from [18F]4F-Gln PET images matched the distinct glutamine pool sizes of both tumor models at baseline. After a short course of GLS inhibitor treatment, the T/B values increased significantly in TNBC, but did not change in MCF-7 tumors. Across both tumor types and after GLS inhibitor or vehicle treatment, we observed a strong positive correlation between T/B values and tumor glutamine pool size measured using MRS (R2=0.71). In conclusion, [18F]4F-Gln PET tracked cellular glutamine pool size in breast cancers with differential GLS activity and detected increases in cellular glutamine pool size induced by GLS inhibitors. This study accomplished the first necessary step towards validating [18F]4F-Gln PET as a PD marker for glutaminase-targeting drugs. PMID:28202527

Optical studies of CaS:Eu,Sm infrared stimulable phosphors

NASA Astrophysics Data System (ADS)

Tamura, Yasuaki; Shibukawa, Atsushi

1993-07-01

The photoluminescence (PL) and infrared stimulated luminescence (ISL) spectra of CaS:Eu,Sm infrared stimulable phosphors (ISPs) are studied. In addition, the concentration dependence of ISL intensity is examined. Sm(3+) and Eu(2+) related structures are found in both the PL excitation and emission spectra. Two types of Sm(3+) are found, one of which exhibits strong emission at around 650 nm and the other weak emission compared to the other emissions at around 565 nm and 605 nm. These are assigned to an asymmetric and a symmetric site, respectively. ISL excitation spectra coincide with the Eu(2+) 4f(sup 7) to 4f(sup 6)5d(sup 1) and 4f(sup 6)6s(sup 1) transitions and range from 220 to 650 nm. ISL emission spectra coincide with the Eu(2+) 4f(sup 6)5d(sup 1) to 4f(sup 7) transition and range from 550 to 750 nm. ISL stimulation spectra range from 0.8 micron to 1.7 micron and are thought to indicate the Sm(2+) ion transition from 4f(sup 6) to 4f(sup 5)5d(sup 1). The maximum ISL intensity is obtained from a sample with Eu and Sm concentrations of 500 and 130 ppm, respectively.

Functional characterization of barley betaglucanless mutants demonstrates a unique role for CslF6 in (1,3;1,4)-β-D-glucan biosynthesis

PubMed Central

Taketa, Shin; Yuo, Takahisa; Tonooka, Takuji; Tsumuraya, Yoichi; Inagaki, Yoshiaki; Haruyama, Naoto; Larroque, Oscar; Jobling, Stephen A.

2012-01-01

(1,3;1,4)-β-D-glucans (mixed-linkage glucans) are found in tissues of members of the Poaceae (grasses), and are particularly high in barley (Hordeum vulgare) grains. The present study describes the isolation of three independent (1,3;1,4)-β-D-glucanless (betaglucanless; bgl) mutants of barley which completely lack (1,3;1,4)-β-D-glucan in all the tissues tested. The bgl phenotype cosegregates with the cellulose synthase like HvCslF6 gene on chromosome arm 7HL. Each of the bgl mutants has a single nucleotide substitution in the coding region of the HvCslF6 gene resulting in a change of a highly conserved amino acid residue of the HvCslF6 protein. Microsomal membranes isolated from developing endosperm of the bgl mutants lack detectable (1,3;1,4)-β-D-glucan synthase activity indicating that the HvCslF6 protein is inactive. This was confirmed by transient expression of the HvCslF6 cDNAs in Nicotiana benthamiana leaves. The wild-type HvCslF6 gene directed the synthesis of high levels of (1,3;1,4)-β-D-glucans, whereas the mutant HvCslF6 proteins completely lack the ability to synthesize (1,3;1,4)-β-D-glucans. The fine structure of the (1,3;1,4)-β-D-glucan produced in the tobacco leaf was also very different from that found in cereals having an extremely low DP3/DP4 ratio. These results demonstrate that, among the seven CslF and one CslH genes present in the barley genome, HvCslF6 has a unique role and is the key determinant controlling the biosynthesis of (1,3;1,4)-β-D-glucans. Natural allelic variation in the HvCslF6 gene was found predominantly within introns among 29 barley accessions studied. Genetic manipulation of the HvCslF6 gene could enable control of (1,3;1,4)-β-D-glucans in accordance with the purposes of use. PMID:21940720

Utility of recombinant Aspergillus fumigatus antigens in the diagnosis of allergic bronchopulmonary aspergillosis: a systematic review and diagnostic test accuracy meta-analysis.

PubMed

Muthu, Valliappan; Sehgal, Inderpaul Singh; Dhooria, Sahajal; Aggarwal, Ashutosh N; Agarwal, Ritesh

2018-06-21

The role of recombinant A.fumigatus (rAsp) antigens in the diagnosis of allergic bronchopulmonary aspergillosis (ABPA) has not been systematically evaluated. Herein, we evaluate the utility of recombinant A.fumigatus (rAsp) antigens in diagnosing ABPA. We systematically reviewed the PubMed, EmBase, and Scopus databases for studies evaluating rAsp antigens in ABPA. The QUADAS-2 tool and the GRADE approach were used to assess the risk of bias and the quality of evidence, respectively. The diagnostic performance of IgE or skin test against rAsp f1, f2, f3, f4, f6, and their combination was evaluated separately for ABPA complicating asthma or cystic fibrosis (CF), using an HSROC model. The reference standard for diagnosing ABPA was the composite (clinical, radiological, immunological) criteria. Our search yielded 26 studies (n=1,694) and 17 studies (n=1,131) for inclusion in the systematic review and meta-analysis, respectively. In asthmatics, the pooled sensitivity for diagnosing ABPA was best for IgE against a combination of rAsp f1 or f3 (96.7%; 95% confidence interval [CI], 87.6-99.2). The pooled specificity for diagnosing ABPA was highest (99.2%; 95% CI, 88.2-99.9) for IgE against a combination of f4 or f6. In CF patients, the pooled sensitivity of rAsp f1 or f3 was 93.3% (95% CI, 55.2-99.9) while the pooled specificity of rAsp f4 or f6 was 93.9% (95% CI, 68.8-99.9). The quality of evidence was low as per the GRADE approach. A combination of IgE against rAsp antigens (f1, f2, f3, f4, f6) are likely to be helpful in the diagnosis of ABPA. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Novel duplex vapor-electrochemical method for silicon solar cells. [reaction of fluorine and silicon compounds with sodium

NASA Technical Reports Server (NTRS)

Nanis, L.; Sanjurjo, A.; Sancier, K. M.; Bartlett, R.; Westphal, S.

1979-01-01

The dependence of the SiF4 Na reaction initiation time and of the efficiency of the reaction on Na particle size and reaction temperature were studied. Close to 100 percent utilization of Na was obtained, and formation of byproduct fluoro-silicate was decreased to below 10 percent. A SiF4 Na reactor was built to scale up the reaction by a factor of about four and is now being tested. A scaled up melting system was built and successfully used to separate Si from kilogram quantities of SiF4 NaF mixtures. Support studies of the volatilization of NaF performed in a smaller melting system indicated minimal loss of NaF as vapor at 1410 C. The wetting of graphite was also investigated to determine the constituents of the NaF phase which promote good wetting.

Effect of the addition of MgF2 and NaF on the thermal, optical and magnetic properties of fluoride glasses for sensing applications

NASA Astrophysics Data System (ADS)

Wang, Yujie; Wang, Shuangbao; Deng, Saifu; Liu, Jianting; Zhang, Jiahui

2017-10-01

Optical glass was very important for the development of optical fiber sensor. In this paper, a new type fluoride glass of ZrF4-BaF2-AlF3-NaF-MgF2(ZBANM) was synthesized for sensing application which has low loss and high magneto-optical coefficient, and it was found that the glass system had at least 60% transmittance from 3.5 μm to 7 μm and smallest verdet constant of 4.628E-5/(rad A-1) at 632.8 nm. The relationship among the compositions of sample glass with its thermal property, optical absorptivity and magnetic-optical coefficients was respectively studied with Thermal Gravimetric-Differential Thermal Analyzer, Fourier Transform infrared spectroscopy and a home-made magneto optical bench. The study indicated that transmittance of fluoride glass structure had been obviously improved after moderate content of Mg2+ and Na+ was doped. Simultaneously, with the molar ratio of alkaline-earth ions Mg increased, the Verdet constant of fluoride glass was increased. And the glass structure with composition of 48%ZrF4-24%BaF2-6%AlF3-8%NaF-14%MgF2 exhibited a small molar absorptivity and the largest Verdet constant of 2.853E-4/(rad A-1).

Validation of APRI and FIB-4 score in an Antwerp cohort of chronic hepatitis C patients.

PubMed

Verlinden, Wim; Bourgeois, Stefan; De Maeyer, Marc; Vonghia, Luisa; Vanwolleghem, Thomas; Michielsen, Peter; Francque, Sven

2015-12-01

Evaluation of liver fibrosis in chronic hepatitis C patients guides clinical decision-making. The aim of this study is to validate APRI and FIB-4, two easily calculated noninvasive tests to predict fibrosis, in chronic HCV patients using biopsy as a gold standard and to compare accuracy between HCV monoinfected and HIV/HCV coinfected patients. We retrospectively studied HCV patients of two centres who underwent liver biopsy. Liver fibrosis was staged according to METAVIR. 136 patients were included. The AUROC of FIB-4 (0.896) to discriminate F0-F2 vs. F3-F4 was significantly higher (p=0.0186) than the AUROC of APRI (0.842). The difference in AUROC between HIV-negative and positive patients was not significant for APRI (p=0.471), nor for FIB-4 (p=0.495). Performance status was lower in HIV-positive patients with 46.7% and 69.0% of patients correctly classified using APRI and FIB-4, compared to 56.6% and 73.6% in HIV-negative patients, respectively. Conversion of transaminase values from one hospital to the other did not significantly change the AUROC of FIB-4 (p=0.928). APRI and FIB-4 have a better performance status in HCV monoinfected patients compared to HIV/HCV coinfected patients. FIB-4 has a better AUROC compared to APRI and is the preferred noninvasive fibrosis score to discriminate between F0-F2 and F3-F4. Different hospitals should use their local absolute serum transaminase values without conversion. © Acta Gastro-Enterologica Belgica.

Dynamic Elastography in Diagnostics of Liver Fibrosis in Patients After Liver Transplantation Due to Cirrhosis in the Course of Hepatitis C.

PubMed

Mikołajczyk-Korniak, N; Tronina, O; Ślubowska, K; Perkowska-Ptasińska, A; Pacholczyk, M; Bączkowska, T; Durlik, M

2016-06-01

Assessment of the dynamics and degree of liver fibrosis in patients after liver transplantation is a basic element in the process of determining transplant survival prognosis. It allows planning and early initiation of prophylaxis or treatment, which translates into increased chances of preventing cirrhosis and of long-term optimal function of the graft. The aim of this study was to compare the results of biopsy and dynamic elastography in diagnostics of transplanted liver fibrosis, as well as determination of the stiffness cut-off point for assessment of significant fibrosis. The study included 36 patients who had undergone liver transplantation due to cirrhosis in the course of hepatitis C virus (HVC) infection. Fibrosis was assessed in bioptates according to the METAVIR score (F0-F4). Elastography was performed using FibroScan; receiver operating characteristic curve analysis was used to identify the cut-off point for significant fibrosis (≥F2). The median stiffness in kPa for the whole group F0-F4 was 6.3 (range 3.4-29.9); for ≥F2 it was 6.9 (3.4-29.9), whereas for F0-F1 it was 4.4 (3.5-8.0). It was demonstrated that the value of 4.7 kPa in elastography is a statistically significant cut-off point for differentiation between the groups F0-F1 and F2-F4 (sensitivity: 93%, specificity: 57%, positive predictive value: 90%, negative predictive value: 66%), area under the receiver operating characteristic curve: 0.746 (95% confidence interval: 0.53-0.95, P < .05). Elastography is a promising tool for noninvasive assessment of significant liver fibrosis in patients after transplantation due to cirrhosis in the course of hepatitis C; it allows reduction in the number of biopsies performed. Copyright © 2016 Elsevier Inc. All rights reserved.

Treatment of patients with cardiovascular disease with L-4F, an apo-A1 mimetic, did not improve select biomarkers of HDL function[S

PubMed Central

Watson, Catherine E.; Weissbach, Nicole; Kjems, Lise; Ayalasomayajula, Surya; Zhang, Yiming; Chang, Ih; Navab, Mohamad; Hama, Susan; Hough, Greg; Reddy, Srinivasa T.; Soffer, Daniel; Rader, Daniel J.; Fogelman, Alan M.; Schecter, Alison

2011-01-01

L-4F, an apolipoprotein A-I (apoA-I) mimetic peptide (also known as APL180), was administered daily by either intravenous (IV) infusion for 7 days or by subcutaneous (SC) injection for 28 days in patients with coronary heart disease in two distinct clinical studies. L-4F was well tolerated at all doses tested. Despite achieving plasma levels (mean maximal plasma concentration of 2,907 ng/ml and 395 ng/ml, following IV infusion and SC injection, respectively), that were effective in previously published animal models, treatment with L-4F, as assessed by biomarkers of HDL function such as HDL-inflammatory index (HII), and paraoxonase activity, did not improve. Paradoxically, there was a 49% increase in high-sensitivity C-reactive protein (hs-CRP) levels after seven IV infusions of 30 mg L-4F (P < 0.05; compared with placebo) and a trend for hs-CRP increase in subjects receiving 30 mg SC injection for 28 days. In a subsequent, ex vivo study, addition of L-4F at concentrations of 150, 375, or 1,000 ng/ml to plasma from subjects prior to L-4F treatment resulted in significant dose-dependent HII improvement. In conclusion, in vivo L-4F treatment, delivered by either SC injection or IV infusion, did not improve HDL functional biomarkers despite achieving plasma levels that improved identical biomarkers ex vivo and in animal models. PMID:21068008

Epidemiology in Germany-general development and personal experience.

PubMed

Wichmann, Heinz-Erich

2017-08-01

Did you ever hear about epidemiology in Germany? Starting from an epidemiological desert the discipline has grown remarkably, especially during the last 10-15 years: research institutes have been established, research funding has improved, multiple curriculae in Epidemiology and Public Health are offered. This increase has been quite steep, and now the epidemiological infrastructure is much better. Several medium-sized and even big population cohorts are ongoing, and the number and quality of publications from German epidemiologists has reached a respectable level. My own career in epidemiology started in the field of environmental health. After German reunification I concentrated for many years on environmental problems in East Germany and observed the health benefits after improvement of the situation. Later, I concentrated on population-based cohorts in newborns (GINI/LISA) and adults (KORA, German National Cohort), and on biobanking. This Essay describes the development in Germany after worldwar 2, illustrated by examples of research results and build-up of epidemiological infractructures worth mentioning.

Theoretical and experimental studies of the Nd3+ 4f3<-->4f25d transitions in monoclinic Nd:BaY2F8 crystal

NASA Astrophysics Data System (ADS)

Collombet, Annabelle; Guyot, Yannick; Joubert, Marie-France; Margerie, Jean; Moncorgé, Richard; Tkachuk, Alexandra

2004-11-01

Experimental spectroscopic results related to Nd3+-doped BaY2F8, are presented that include vacuum-ultraviolet ground-state absorption and excitation spectra as well as polarized emission and excited-state absorption spectra recorded in the near-ultraviolet spectral range at room and low temperatures. Calculations were performed to determine the positions of the 4f25d sublevels and the intensities and polarizations of the 4f3<-->4f25d optical transitions of the Nd3+ ions in the C2 symmetry sites of the biaxial host crystal. The simulated spectra agree well with the experimental spectra; in particular, the model that was used successfully reproduced the differences between the polarized spectra on one hand and between the spectra recorded at low and room temperatures on the other hand.

Efficient synthesis of a fluorine-18 labeled biotin derivative.

PubMed

Claesener, Michael; Breyholz, Hans-Jörg; Hermann, Sven; Faust, Andreas; Wagner, Stefan; Schober, Otmar; Schäfers, Michael; Kopka, Klaus

2012-11-01

The natural occurring vitamin biotin, also known as vitamin H or vitamin B(7), plays a major role in various metabolic reactions. Caused by its high binding affinity to the protein avidin with a dissociation constant of about 10(-15)M the biotin-avidin system was extensively examined for multiple applications. We have synthesized a fluorine-18 labeled biotin derivative [(18)F]4 for a potential application in positron emission tomography (PET). Mesylate precursor 3 was obtained by an efficient two-step reaction via a copper catalyzed azide-alkyne cycloaddition (CuAAC) from easily accessible starting materials. [(18)F]4 was successfully synthesized by a nucleophilic radiofluorination of precursor 3. A biodistribution study by means of small-animal PET imaging in wt-mice was performed and serum stability was examined. Compound [(18)F]4 was obtained from precursor compound 3 with an average specific activity of 16GBq/μmol within 45min and a radiochemical yield of 45±5% (decay corrected). [(18)F]4 demonstrated only negligible decomposition in human serum. A qualitative binding study revealed the high affinity of the synthesized biotin derivative to avidin. Blocking experiments with native biotin showed that binding was site-specific. Biodistribution studies showed that [(18)F]4 was cleared quickly and efficiently from the body by hepatobiliary and renal elimination. An efficient synthesis for [(18)F]4 was established. In vivo characteristics were determined and demonstrated the pharmacokinetic behaviour of [(18)F]4. Copyright © 2012 Elsevier Inc. All rights reserved.

Clinical Significance of the Number of Depressive Symptoms in Major Depressive Disorder: Results from the CRESCEND Study.

PubMed

Park, Seon-Cheol; Sakong, Jeongkyu; Koo, Bon Hoon; Kim, Jae-Min; Jun, Tae-Youn; Lee, Min-Soo; Kim, Jung-Bum; Yim, Hyeon-Woo; Park, Yong Chon

2016-04-01

Our study aimed to establish the relationship between the number of depressive symptoms and the clinical characteristics of major depressive disorder (MDD). This would enable us to predict the clinical significance of the number of depressive symptoms in MDD patients. Using data from the Clinical Research Center for Depression (CRESCEND) study in Korea, 853 patients with DSM-IV MDD were recruited. The baseline and clinical characteristics of groups with different numbers of depressive symptoms were compared using the χ(2) test for discrete variables and covariance (ANCOVA) for continuous variables. In addition, the scores of these groups on the measurement tools were compared by ANCOVA after adjusting the potential effects of confounding variables. After adjusting the effects of monthly income and history of depression, a larger number of depressive symptoms indicated higher overall severity of depression (F [4, 756] = 21.458, P < 0.001) and higher levels of depressive symptoms (F [4, 767] = 19.145, P < 0.001), anxiety symptoms (F [4, 765] = 12.890, P < 0.001) and suicidal ideation (F [4, 653] = 6.970, P < 0.001). It also indicated lower levels of social function (F [4, 760] = 13.343, P < 0.001), and quality of life (F [4, 656] = 11.975, P < 0.001). However, there were no significant differences in alcohol consumption (F [4, 656] = 11.975, P < 0.001). The number of depressive symptoms can be used as an index of greater illness burden in clinical psychiatry.

Temperature sensor based on ladder-level assisted thermal coupling and thermal-enhanced luminescence in NaYF4: Nd³⁺.

PubMed

Tian, Xiuna; Wei, Xiantao; Chen, Yonghu; Duan, Changkui; Yin, Min

2014-12-01

NaYF4: Nd³⁺ microprisms were synthesized by a hydrothermal method. The bands of near-infrared (NIR) luminescence originating from the 4F3/2, 4F5/2 and 4F7/2 levels of Nd³⁺ ions in NaYF4: Nd³⁺ microcrystals were measured under 574.8 nm excitation at various temperatures from 323 to 673 K. The fluorescence intensity ratios (FIRs) between any two of the three bands change monotonically with temperature and agree with the prediction assuming thermal couplings. A large relative temperature sensitivity of 1.12% K⁻¹ at 500K is reached with the FIR of 4F7/2 to 4F3/2 levels. In addition, anti-Stokes fluorescence from 4F5/2 level (740 nm) and 4F5/2,7/2 levels (740 nm and 803 nm) of Nd³⁺ ions was studied meticulously under 793.8 nm and 864.2 nm excitations, respectively. The intensities were shown to be greatly enhanced as temperature increases, and the 740 nm band from 4F7/2 level at 458 K increases in intensity by 170 fold relative to that at 298 K under the 793.8 nm excitation.

Spectroscopic and dielectric response of zinc bismuth phosphate glasses as a function of chromium content

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

Rao, P. Srinivasa; Babu, P. Ramesh; Vijay, R.

2014-09-15

Graphical abstract: 20ZnF{sub 2}–(20 − x)Bi{sub 2}O{sub 3}–60P{sub 2}O{sub 5}:xCr{sub 2}O{sub 3} (0 ≤ x ≤2 mol%) glasses are prepared by melt quenching technique. The optical absorption spectra of present glasses are analyzed as a function of chromium content. The absorption bands are assigned to {sup 4}A{sub 2g}(F) ⟶ {sup 4}T{sub 1g}(F), {sup 4}A{sub 2g}(F) ⟶ {sup 4}T{sub 2g}(F), {sup 4}A{sub 2g}(F) ⟶ {sup 2}T{sub 1g}(G) and {sup 4}A{sub 2g}(F) ⟶ {sup 2}E{sub g}(G) transitions of Cr{sup 3+} ions. - Highlights: • ZnF{sub 2}–Bi{sub 2}O{sub 3}–P{sub 2}O{sub 5}:Cr{sub 2}O{sub 3} glasses were prepared by melt quenching and annealing. • Spectroscopicmore » and dielectric properties of chromium ions were investigated. • ESR and optical absorption spectra indicate the co-existence of Cr{sup 6+} ions with Cr{sup 5+} ions and Cr{sup 3+} ions. • Cr{sup 3+} ions act as modifiers and influence the semiconducting nature of the glass system. - Abstract: 20ZnF{sub 2}–(20 − x)Bi{sub 2}O{sub 3}–60P{sub 2}O{sub 5}:xCr{sub 2}O{sub 3} (0 ≤ x ≤2 mol%) glasses are prepared by melt quenching technique. Amorphous nature of these samples is confirmed by X-ray diffraction (XRD) analysis. FTIR study reveals bands due to CrO{sub 6}(o{sub d}) and CrO{sub 4}{sup 2−}(T{sub d}) units along with conventional phosphate groups. The optical absorption and ESR studies of present glasses are analyzed as a function of chromium content. The absorption bands are assigned to {sup 4}A{sub 2g}(F) ⟶ {sup 4}T{sub 1g}(F), {sup 4}A{sub 2g}(F) ⟶ {sup 4}T{sub 2g}(F), {sup 4}A{sub 2g}(F) ⟶ {sup 2}T{sub 1g}(G) and {sup 4}A{sub 2g}(F) ⟶ {sup 2}E{sub g}(G) transitions of Cr{sup 3+} ions. The highest concentration of Cr{sup 3+} ions (in octahedral sites, with network modifying positions) is found in the sample with 2.0 mol% of Cr{sub 2}O{sub 3}. The analysis of dielectric properties indicates a gradual increase in semiconducting character with increase in the concentration of Cr{sub 2}O{sub 3} from 0.2 to 2.0 mol%. The studies on dielectric breakdown strength identify the highest insulating strength for lowest mol% of Cr{sub 2}O{sub 3} in the present samples.« less

The F4/AS01B HIV-1 Vaccine Candidate Is Safe and Immunogenic, But Does Not Show Viral Efficacy in Antiretroviral Therapy-Naive, HIV-1-Infected Adults

PubMed Central

Dinges, Warren; Girard, Pierre-Marie; Podzamczer, Daniel; Brockmeyer, Norbert H.; García, Felipe.; Harrer, Thomas; Lelievre, Jean-Daniel; Frank, Ian; Colin De Verdière, Nathalie; Yeni, Guy-Patrick; Ortega Gonzalez, Enrique; Rubio, Rafael; Clotet Sala, Bonaventura; DeJesus, Edwin; Pérez-Elias, Maria Jesus; Launay, Odile; Pialoux, Gilles; Slim, Jihad; Weiss, Laurence; Bouchaud, Olivier; Felizarta, Franco; Meurer, Anja; Raffi, François; Esser, Stefan; Katlama, Christine; Koletar, Susan L.; Mounzer, Karam; Swindells, Susan; Baxter, John D.; Schneider, Stefan; Chas, Julie; Molina, Jean-Michel; Koutsoukos, Marguerite; Collard, Alix; Bourguignon, Patricia; Roman, François

2016-01-01

Abstract The impact of the investigational human immunodeficiency virus type 1 (HIV-1) F4/AS01B vaccine on HIV-1 viral load (VL) was evaluated in antiretroviral therapy (ART)-naive HIV-1 infected adults. This phase IIb, observer-blind study (NCT01218113), included ART-naive HIV-1 infected adults aged 18 to 55 years. Participants were randomized to receive 2 (F4/AS01B_2 group, N = 64) or 3 (F4/AS01B_3 group, N = 62) doses of F4/AS01B or placebo (control group, N = 64) at weeks 0, 4, and 28. Efficacy (HIV-1 VL, CD4+ T-cell count, ART initiation, and HIV-related clinical events), safety, and immunogenicity (antibody and T-cell responses) were evaluated during 48 weeks. At week 48, based on a mixed model, no statistically significant difference in HIV-1 VL change from baseline was demonstrated between F4/AS01B_2 and control group (0.073 log10 copies/mL [97.5% confidence interval (CI): −0.088; 0.235]), or F4/AS01B_3 and control group (−0.096 log10 copies/mL [97.5% CI: −0.257; 0.065]). No differences between groups were observed in HIV-1 VL change, CD4+ T-cell count, ART initiation, or HIV-related clinical events at intermediate timepoints. Among F4/AS01B recipients, the most frequent solicited symptoms were pain at injection site (252/300 doses), fatigue (137/300 doses), myalgia (105/300 doses), and headache (90/300 doses). Twelve serious adverse events were reported in 6 participants; 1 was considered vaccine-related (F4/AS01B_2 group: angioedema). F4/AS01B induced polyfunctional F4-specific CD4+ T-cells, but had no significant impact on F4-specific CD8+ T-cell and anti-F4 antibody levels. F4/AS01B had a clinically acceptable safety profile, induced F4-specific CD4+ T-cell responses, but did not reduce HIV-1 VL, impact CD4+ T-cells count, delay ART initiation, or prevent HIV-1 related clinical events. PMID:26871794

The F4/AS01B HIV-1 Vaccine Candidate Is Safe and Immunogenic, But Does Not Show Viral Efficacy in Antiretroviral Therapy-Naive, HIV-1-Infected Adults: A Randomized Controlled Trial.

PubMed

Dinges, Warren; Girard, Pierre-Marie; Podzamczer, Daniel; Brockmeyer, Norbert H; García, Felipe; Harrer, Thomas; Lelievre, Jean-Daniel; Frank, Ian; Colin De Verdière, Nathalie; Yeni, Guy-Patrick; Ortega Gonzalez, Enrique; Rubio, Rafael; Clotet Sala, Bonaventura; DeJesus, Edwin; Pérez-Elias, Maria Jesus; Launay, Odile; Pialoux, Gilles; Slim, Jihad; Weiss, Laurence; Bouchaud, Olivier; Felizarta, Franco; Meurer, Anja; Raffi, François; Esser, Stefan; Katlama, Christine; Koletar, Susan L; Mounzer, Karam; Swindells, Susan; Baxter, John D; Schneider, Stefan; Chas, Julie; Molina, Jean-Michel; Koutsoukos, Marguerite; Collard, Alix; Bourguignon, Patricia; Roman, François

2016-02-01

The impact of the investigational human immunodeficiency virus type 1 (HIV-1) F4/AS01B vaccine on HIV-1 viral load (VL) was evaluated in antiretroviral therapy (ART)-naive HIV-1 infected adults.This phase IIb, observer-blind study (NCT01218113), included ART-naive HIV-1 infected adults aged 18 to 55 years. Participants were randomized to receive 2 (F4/AS01B_2 group, N = 64) or 3 (F4/AS01B_3 group, N = 62) doses of F4/AS01B or placebo (control group, N = 64) at weeks 0, 4, and 28. Efficacy (HIV-1 VL, CD4 T-cell count, ART initiation, and HIV-related clinical events), safety, and immunogenicity (antibody and T-cell responses) were evaluated during 48 weeks.At week 48, based on a mixed model, no statistically significant difference in HIV-1 VL change from baseline was demonstrated between F4/AS01B_2 and control group (0.073 log10 copies/mL [97.5% confidence interval (CI): -0.088; 0.235]), or F4/AS01B_3 and control group (-0.096 log10 copies/mL [97.5% CI: -0.257; 0.065]). No differences between groups were observed in HIV-1 VL change, CD4 T-cell count, ART initiation, or HIV-related clinical events at intermediate timepoints. Among F4/AS01B recipients, the most frequent solicited symptoms were pain at injection site (252/300 doses), fatigue (137/300 doses), myalgia (105/300 doses), and headache (90/300 doses). Twelve serious adverse events were reported in 6 participants; 1 was considered vaccine-related (F4/AS01B_2 group: angioedema). F4/AS01B induced polyfunctional F4-specific CD4 T-cells, but had no significant impact on F4-specific CD8 T-cell and anti-F4 antibody levels.F4/AS01B had a clinically acceptable safety profile, induced F4-specific CD4 T-cell responses, but did not reduce HIV-1 VL, impact CD4 T-cells count, delay ART initiation, or prevent HIV-1 related clinical events.

Susceptibility quantitative trait loci for pathogenic leucocytosis in SCG/Kj mice, a spontaneously occurring crescentic glomerulonephritis and vasculitis model

PubMed Central

Hamano, Y; Abe, M; Matsuoka, S; Zhang, D; Kondo, Y; Kagami, Y; Ishigami, A; Maruyama, N; Tsuruta, Y; Yumura, W; Suzuki, K

2014-01-01

The spontaneous crescentic glomerulonephritis-forming/Kinjoh (SCG/Kj) mouse, a model of human crescentic glomerulonephritis (CrGN) and systemic vasculitis, is characterized by the production of myeloperoxidase-specific anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) and marked leucocytosis. This study was performed to identify the specific populations of leucocytes associated with CrGN and susceptibility loci for pathogenic leucocytosis. Four hundred and twenty female (C57BL/6 × SCG/Kj) F2 intercross mice were subjected to serial flow cytometry examination of the peripheral blood (PB). Kidney granulocytes and monocytes were examined histopathologically. Linkage analyses were performed with 109 polymorphic microsatellite markers. Correlation studies revealed that increase of the granulocytes, F4/80+ cells, CD3+CD4−CD8− T cells and dendritic cells (DCs) in peripheral blood (PB) were associated significantly with glomerulonephritis, crescent formation and vasculitis. In kidney sections, F4/80low cells were observed in crescent, while F4/80high cells were around the Bowman's capsules and in the interstitium. Numbers of F4/80+ cells in crescents correlated significantly with F4/80+ cell numbers in PB, but not with numbers of F4/80+ cells in the interstitium. Genome-wide quantitative trait locus (QTL) mapping revealed three SCG/Kj-derived non-Fas QTLs for leucocytosis, two on chromosome 1 and one on chromosome 17. QTLs on chromosome 1 affected DCs, granulocytes and F4/80+ cells, but QTL on chromosome 17 affected DCs and granulocytes. We found CrGN-associated leucocytes and susceptibility QTLs with their positional candidate genes. F4/80+ cells in crescents are considered as recruited inflammatory macrophages. The results provide information for leucocytes to be targeted and genetic elements in CrGN and vasculitis. PMID:24654803

Enhancement of charge transport properties of small molecule semiconductors by controlling fluorine substitution and effects on photovoltaic properties of organic solar cells and perovskite solar cells.

PubMed

Yun, Jae Hoon; Park, Sungmin; Heo, Jin Hyuck; Lee, Hyo-Sang; Yoon, Seongwon; Kang, Jinback; Im, Sang Hyuk; Kim, Hyunjung; Lee, Wonmok; Kim, BongSoo; Ko, Min Jae; Chung, Dae Sung; Son, Hae Jung

2016-11-01

We prepared a series of small molecules based on 7,7'-(4,4-bis(2-ethylhexyl)-4 H -silolo[3,2- b :4,5- b ']dithiophene-2,6-diyl)bis(4-(5'-hexyl-[2,2'-bithiophene]-5-yl)benzo[ c ][1,2,5]thiadiazole) with different fluorine substitution patterns ( 0F-4F ). Depending on symmetricity and numbers of fluorine atoms incorporated in the benzo[ c ][1,2,5]thiadiazole unit, they show very different optical and morphological properties in a film. 2F and 4F , which featured symmetric and even-numbered fluorine substitution patterns, display improved molecular packing structures and higher crystalline properties in a film compared with 1F and 3F and thus, 2F achieved the highest OTFT mobility, which is followed by 4F . In the bulk heterojunction solar cell fabricated with PC 71 BM, 2F achieves the highest photovoltaic performance with an 8.14% efficiency and 0F shows the lowest efficiency of 1.28%. Moreover, the planar-type perovskite solar cell (PSC) prepared with 2F as a dopant-free hole transport material shows a high power conversion efficiency of 14.5% due to its high charge transporting properties, which were significantly improved compared with the corresponding PSC device obtained from 0F (8.5%). From the studies, it is demonstrated that low variation in the local dipole moment and the narrow distribution of 2F conformers make intermolecular interactions favorable, which may effectively drive crystal formations in the solid state and thus, higher charge transport properties compared with 1F and 3F .

Investigating the capability of ToF-SIMS to determine the oxidation state of Ce

NASA Astrophysics Data System (ADS)

Seed Ahmed, H. A. A.; Swart, H. C.; Kroon, R. E.

2018-04-01

The capability of time of flight secondary ion mass spectrometry (ToF-SIMS) to determine the oxidation state of Ce ions doped in a phosphor was investigated. Two samples of SiO2:Ce (4 mol%) with known Ce3+/Ce4+ relative concentrations were subjected to ToF-SIMS measurements. The spectra were very similar and no significant differences in the relative peak intensities were observed that would readily allow one to distinguish Ce3+ from Ce4+. Although ToF-SIMS was therefore not useful to distinguish the charge state of Ce ions doped in this phosphor material, the idea in principle was also tested on two other samples, namely CeF3 and CeF4 These contain Ce as part of the host (i.e. much higher concentration) and are fluorides, which is significant because ToF-SIMS has previously been reported to be able to distinguish Eu2+ from Eu3+ in Eu doped Sr5(PO4)3F phosphor. The spectrum of CeF4 contained a small peak related to Ce4+ which was not observed in the CeF3 spectrum, yet the peak related to the Ce3+ ions was found to be much more intense in the spectrum of CeF4 than CeF3, showing that the ToF-SIMS signals cannot be directly interpreted as retaining the charge state of the ions in the original material. Nevertheless, the significant differences in the Ce-related peaks in the ToF-SIMS spectra from CeF3 and CeF4 show that the charge state of Ce may be distinguished. This study shows that while in principle ToF-SIMS may be used to distinguish the charge state of Ce ions, this depends on the sample and it would not be easy to interpret the spectra without a standard or reference.

Jahn-Teller effect on the [TiF 4F 4F int] 6-(C 4v) and [NiF 4F 4F int] 7-(C 4v) clusters embedded into SrF 2 crystals

NASA Astrophysics Data System (ADS)

Ulanov, V. A.; Zhiteitcev, E. R.; Varlamov, A. G.

2007-07-01

By means of EPR method the associative [TiF 4F 4F int] 6-(C 4v) and [NiF 4F 4F int] 7-(C 4v) centers were revealed in the fluorite type SrF 2:Ti and SrF 2:Ni crystals grown by Bridgman method in helium atmosphere containing some amount of a fluorine gas. It was found that at low temperatures the local structures of these associative centers were exposed to a static rhombic distortion. The reasons of such distortions were accounted for by the assumption that the E ⊗ ( b1 + b2) vibronic interaction became effective due to that the ground orbital states of the [TiF 4F 4F int] 6-(C 4v) and [NiF 4F 4F int] 7-(C 4v) centers occurred to be doubly degenerated.

Nuclear donor cell lines considerably influence cloning efficiency and the incidence of large offspring syndrome in bovine somatic cell nuclear transfer.

PubMed

Liu, J; Wang, Y; Su, J; Luo, Y; Quan, F; Zhang, Y

2013-08-01

Total five ear skin fibroblast lines (named F1, F2, F3, F4 and F5) from different newborn Holstein cows have been used as nuclear donor cells for producing cloned cows by somatic cell nuclear transfer (SCNT). The effects of these cell lines on both in vitro and in vivo developmental rates of cloned embryos, post-natal survivability and incidence of large offspring syndrome (LOS) were examined in this study. We found that the different cell lines possessed the same capacity to support pre-implantation development of cloned embryos, the cleavage and blastocyst formation rates ranged from 80.2 ± 0.9 to 84.5 ± 2.5% and 28.5 ± 0.9 to 33.3 ± 1.4%, respectively. However, their capacities to support the in vivo development of SCNT embryos showed significant differences (p < 0.05). The pregnancy rates at 90 and 240 day were significantly lower in groups F2 (4.9% and 3.3%) and F3 (5.4% and 5.4%) compared to groups F1 (23.3% and 16.3%), F4 (25.7% and 18.6%) and F5 (25.9% and 19.8%) (p < 0.05). The cloning efficiency was significantly higher in group F5 than those in group F1, F2, F3 and F4 (9.3% vs 4.1%, 1.2%, 2.0% and 5.0%, respectively, p < 0.05). Moreover, large offspring syndrome (LOS) incidence in group F5 was significantly lower than those in other groups (p < 0.05). All cloned offspring from cell line F1, F2, F3 and F4 showed LOS and gestation length delay, while all cloned offspring from F5 showed normal birthweight and gestation length. We concluded that the nuclear donor cell lines have significant impact on the in vivo development of cloned embryos and the incidence of LOS in cloned calves. © 2013 Blackwell Verlag GmbH.

Biodistribution, pharmacokinetics and PET imaging of [(18)F]FMISO, [(18)F]FDG and [(18)F]FAc in a sarcoma- and inflammation-bearing mouse model.

PubMed

Liu, Ren-Shyan; Chou, Ta-Kai; Chang, Chih-Hsien; Wu, Chun-Yi; Chang, Chi-Wei; Chang, Tsui-Jung; Wang, Shih-Jen; Lin, Wuu-Jyh; Wang, Hsin-Ell

2009-04-01

2-Deoxy-2-[(18)F]fluoro-d-glucose ([(18)F]FDG), [(18)F]fluoroacetate ([(18)F]FAc) and [(18)F]fluoromisonidazole ([(18)F]FMISO) were all considered to be positron emission tomography (PET) probes for tumor diagnosis, though based on different rationale of tissue uptake. This study compared the biodistribution, pharmacokinetics and imaging of these three tracers in a sarcoma- and inflammation-bearing mouse model. C3H mice were inoculated with 2x10(5) KHT sarcoma cells in the right thigh on Day 0. Turpentine oil (0.1 ml) was injected in the left thigh on Day 11 to induce inflammatory lesion. Biodistribution, pharmacokinetics and microPET imaging of [(18)F]FMISO, [(18)F]FDG and [(18)F]FAc were performed on Day 14 after tumor inoculation. The inflammatory lesions were clearly visualized by [(18)F]FDG/microPET and autoradiography at 3 days after turpentine oil injection. The tumor-to-muscle and inflammatory lesion-to-muscle ratios derived from microPET imaging were 6.79 and 1.48 for [(18)F]FMISO, 8.12 and 4.69 for [(18)F]FDG and 3.72 and 3.19 for [(18)F]FAc at 4 h post injection, respectively. Among these, the tumor-to-inflammation ratio was the highest (4.57) for [(18)F]FMISO compared with that of [(18)F]FDG (1.73) and [(18)F]FAc (1.17), whereas [(18)F]FAc has the highest bioavailability (area under concentration of radiotracer vs. time curve, 116.2 hxpercentage of injected dose per gram of tissue). MicroPET images and biodistribution studies showed that the accumulation of [(18)F]FMISO in the tumor is significantly higher than that in inflammatory lesion at 4 h post injection. [(18)F]FDG and [(18)F]FAc delineated both tumor and inflammatory lesions. Our results demonstrated the potential of [(18)F]FMISO/PET in distinguishing tumor from inflammatory lesion.

In vivo and in vitro immunosuppressive effects of benzo[k]fluoranthene in female Balb/c mice.

PubMed

Jeon, Tae Won; Jin, Chun Hua; Lee, Sang Kyu; Lee, Dong Wook; Hyun, Sun Hee; Kim, Ghee Hwan; Jun, In Hye; Lee, Byung Mu; Yum, Young Na; Kim, Jun Kyou; Kim, Ok Hee; Jeong, Tae Cheon

2005-12-10

Although polycyclic aromatic hydrocarbons (PAHs) have been known to suppress immune responses, few studies have addressed the immunotoxicity of benzo[k]fluoranthene (B[k]F). In this study, we investigated the immunosuppression by B[k]F, both in vivo and in vitro, in female BALB/c mice. To assess the effects of B[k]F on humoral immunity as splenic antibody response to sheep red blood cells (SRBCs), B[k]F was given a single dose or once daily for 7 consecutive days po with 30, 60, and 120 micromol/kg. B[k]F reduced the number of antibody-forming cells (AFCs) in a dose-dependent manner. Subacute treatment with B[k]F caused weight increases in liver and decreases in spleen and thymus. The number of AFCs was dramatically decreased by B[k]F in a dose-dependent manner. In a subsequent study, mice were subacutely exposed to the same doses of B[k]F without an immunization with SRBCs, followed by splenic and thymic lymphocyte phenotypings using a flow cytometry and ex vivo mitogen-stimulated proliferation. B[k]F-exposed mice exhibited reduced splenic and thymic cellularity, decreased numbers of total T cells, CD4(+) cells, and CD8(+) cells in spleen, and immature CD4(+)CD8(+) cells, CD4(+)CD8(-) cells, and CD8(+)CD4(-) cells in thymus. The number of CD4(+) IL-2(+) cells was reduced by about 11%, 31%, and 53% following exposure of mice to 30, 60, and 120 micromol/kg of B[k]F, respectively. In the ex vivo lymphocyte proliferation assay, B[k]F inhibited splenocyte proliferation by LPS and Con A. In the in vitro mitogen-stimulated proliferation by untreated splenic suspensions, B[k]F only suppressed splenocyte proliferation to LPS. These results suggested that B[k]F-induced immunosuppression might be mediated, at least in part, through the IL-2 production, and caused by mechanisms associated with metabolic processes.

Biological and immunological characterization of a simian rotavirus SA11 variant with an altered genome segment 4.

PubMed

Burns, J W; Chen, D; Estes, M K; Ramig, R F

1989-04-01

We have studied a variant virus isolated from a stock of SA11 virus (H. G. Pereira, R. S. Azeredo, A. M. Fialho, and M. N. P. Vidal, 1984, J. Gen. Virol. 65, 815-818). This virus, designated 4F, was initially identified by its faster electrophoretic mobility for genome segment 4. The variant was analyzed to determine if the altered electrophoretic mobility of genome segment 4 could be correlated with phenotypic changes. Comparison of our standard laboratory SA11 virus (clone 3) with the 4F variant showed the following: (i) The 4F variant possesses a viral hemagglutinin (VP4) with a higher apparent molecular weight than clone 3. (ii) The 4F variant produces large plaques when assayed in vitro, as compared to clone 3. (iii) The 4F variant produces plaques in the absence of proteolytic enzymes, whereas clone 3 does not. (iv) The 4F variant reacts with serotype-specific neutralizing monoclonal antibodies to VP7, but fails to react with several neutralizing anti-VP4 monoclonal antibodies generated to SA11 clone 3. (v) The 4F variant grows to a higher titer and is more stable than clone 3. (vi) The 4F variant produces a VP4 that appears to be more susceptible to cleavage by trypsin than is the VP4 of clone 3. Further analyses with the 4F variant may lead to an understanding of the molecular basis for these altered phenotypes that appear to be related, at least in part, to the product of genome segment 4.

Rotamer-Specific Photoisomerization of Difluorostilbenes from Transient Absorption and Transient Raman Spectroscopy.

PubMed

Quick, M; Dobryakov, A L; Ioffe, I N; Berndt, F; Mahrwald, R; Ernsting, N P; Kovalenko, S A

2018-01-25

Photoisomerization of 2,2'-, 3,3'-, and 4,4'-difluorostilbene (F2, F3, F4, respectively) in n-hexane, perfluoro-n-hexane, and acetonitrile is studied with broadband transient absorption (TA) and femtosecond stimulated Raman (FSR) spectroscopy and by DFT/TDDFT calculations. F2 and F3 possess three rotamers (rotational isomers) each, while F4 has one single conformation only. These differences are reflected in TA and FSR spectra. Thus F4 reveals a monoexponential decay of TA with τ 1 = 172 ps in n-hexane, as expected for a single species. For F2 and F3, the decays are biexponential in all solvents, corresponding to two distinctly discerned rotamers or rotamer fractions. Specifically, for F2 in n-hexane, τ 1 = 357 ps (83%) and τ 2 = 62 ps (17%), and for F3 in the same solvent, τ 1 = 222 ps (57%), and τ 2 = 81 ps (43%). The weights in brackets agree with theoretically estimated ground-state abundances of the rotamers. Furthermore, a global fit of the TA and FSR data allows us to extract the spectra of the pure rotamers. The Raman spectra of S 0 and S 1 are in qualitative agreement with calculations.

Morphology evolution and pure red upconversion mechanism of β-NaLuF4 crystals.

PubMed

Lin, Hao; Xu, Dekang; Li, Anming; Teng, Dongdong; Yang, Shenghong; Zhang, Yueli

2016-06-16

A series of β-NaLuF4 crystals were synthesized via a hydrothermal method. Hexagonal phase microdisks, microprisms, and microtubes were achieved by simply changing the amount of citric acid in the initial reaction solution. Pure red upconversion (UC) luminescence can be observed in β-NaLuF4:Yb(3+), Tm(3+), Er(3+) and Li(+) doped β-NaLuF4:20% Yb(3+), 1% Tm(3+), 20% Er(3+). Based on the rate equations, we report the theoretical model about the pure red UC mechanism in Yb(3+)/Tm(3+)/Er(3+) doped system. It is proposed that the pure red UC luminescence is mainly ascribed to the energy transfer UC from Tm(3+):(3)F4 → (3)H6 to Er(3+):(4)I11/2 → (4)F9/2 and the cross-relaxation (CR) effect [Er(3+):(4)S3/2 + (4)I15/2 → (4)I9/2 + (4)I13/2] rather than the long-accepted mechanism [CR process among Er(3+):(4)F7/2 + (4)I11/2 → (4)F9/2 + (4)F9/2]. In addition, compared to the Li(+)-free counterpart, the pure red UC luminescence in β-NaLuF4:20% Yb(3+), 1% Tm(3+), 20% Er(3+) with 15 mol% Li(+) doping is enhanced by 13.7 times. This study provides a general and effective approach to obtain intense pure red UC luminescence, which can be applied to other synthetic strategies.

Morphology evolution and pure red upconversion mechanism of β-NaLuF4 crystals

PubMed Central

Lin, Hao; Xu, Dekang; Li, Anming; Teng, Dongdong; Yang, Shenghong; Zhang, Yueli

2016-01-01

A series of β-NaLuF4 crystals were synthesized via a hydrothermal method. Hexagonal phase microdisks, microprisms, and microtubes were achieved by simply changing the amount of citric acid in the initial reaction solution. Pure red upconversion (UC) luminescence can be observed in β-NaLuF4:Yb3+, Tm3+, Er3+ and Li+ doped β-NaLuF4:20% Yb3+, 1% Tm3+, 20% Er3+. Based on the rate equations, we report the theoretical model about the pure red UC mechanism in Yb3+/Tm3+/Er3+ doped system. It is proposed that the pure red UC luminescence is mainly ascribed to the energy transfer UC from Tm3+:3F4 → 3H6 to Er3+:4I11/2 → 4F9/2 and the cross-relaxation (CR) effect [Er3+:4S3/2 + 4I15/2 → 4I9/2 + 4I13/2] rather than the long-accepted mechanism [CR process among Er3+:4F7/2 + 4I11/2 → 4F9/2 + 4F9/2]. In addition, compared to the Li+-free counterpart, the pure red UC luminescence in β-NaLuF4:20% Yb3+, 1% Tm3+, 20% Er3+ with 15 mol% Li+ doping is enhanced by 13.7 times. This study provides a general and effective approach to obtain intense pure red UC luminescence, which can be applied to other synthetic strategies. PMID:27306720

Imaging Caspase-3 Activation as a Marker of Apoptosis-Targeted Treatment Response in Cancer

PubMed Central

Chen, Delphine L.; Engle, Jacquelyn T.; Griffin, Elizabeth A.; Miller, J. Philip; Chu, Wenhua; Zhou, Dong; Mach, Robert H.

2016-01-01

Purpose We tested whether positron emission tomography (PET) with the caspase-3 targeted isatin analog [18F]WC-4-116 could image caspase-3 activation in response to an apoptosis-inducing anticancer therapy. Procedures [18F]WC-4-116 uptake was determined in etoposide-treated EL4 cells. Biodistribution studies with [18F]WC-4-116 and [18F]ICMT-18, a non-caspase-3-targeted tracer, as well as [18F]WC-4-116 microPET imaging assessed responses in Colo205 tumor bearing mice treated with death receptor 5 (DR5) targeted agonist antibodies. Immunohistochemical staining and enzyme assays confirmed caspase-3 activation. Two-way analysis of variance or Student’s t-test assessed for treatment-related changes in tracer uptake. Results [18F]WC-4-116 increased 8 ± 2-fold in etoposide-treated cells. The [18F]WC-4-116 %ID/g also increased significantly in tumors with high caspase-3 enzyme activity (p < 0.05). [18F]ICMT-18 tumor uptake did not differ in tumors with high or low caspase-3 enzyme activity. Conclusions [18F]WC-4-116 uptake in vivo reflects increased caspase-3 activation and may be useful for detecting caspase-3 mediated apoptosis treatment responses in cancer. PMID:25344147

The polymeric stability of the Escherichia coli F4 (K88) fimbriae enhances its mucosal immunogenicity following oral immunization.

PubMed

Verdonck, Frank; Joensuu, Jussi Joonas; Stuyven, Edith; De Meyer, Julie; Muilu, Mikko; Pirhonen, Minna; Goddeeris, Bruno Maria; Mast, Jan; Niklander-Teeri, Viola; Cox, Eric

2008-10-23

Only a few vaccines are commercially available against intestinal infections since the induction of a protective intestinal immune response is difficult to achieve. For instance, oral administration of most proteins results in oral tolerance instead of an antigen-specific immune response. We have shown before that as a result of oral immunization of piglets with F4 fimbriae purified from pathogenic enterotoxigenic Escherichia coli (ETEC), the fimbriae bind to the F4 receptor (F4R) in the intestine and induce a protective F4-specific immune response. F4 fimbriae are very stable polymeric structures composed of some minor subunits and a major subunit FaeG that is also the fimbrial adhesin. In the present study, the mutagenesis experiments identified FaeG amino acids 97 (N to K) and 201 (I to V) as determinants for F4 polymeric stability. The interaction between the FaeG subunits in mutant F4 fimbriae is reduced but both mutant and wild type fimbriae behaved identically in F4R binding and showed equal stability in the gastro-intestinal lumen. Oral immunization experiments indicated that a higher degree of polymerisation of the fimbriae in the intestine was correlated with a better F4-specific mucosal immunogenicity. These data suggest that the mucosal immunogenicity of soluble virulence factors can be increased by the construction of stable polymeric structures and therefore help in the development of effective mucosal vaccines.

Synthesis and luminescence properties of Ca3Ga2Si3O12:RE3+ (RE = Eu/Tb) powder phosphors.

PubMed

Reddy, M Bhushana; Sailaja, S; Raju, K Vemasevana; Raju, C Nageswara; Giridhar, P; Rao, B Vengala; Reddy, B Sudhakar

2011-01-01

Rare earth ions (Eu(3+) or Tb(3+) )-activated Ca(3) Ga(2) Si(3) O(12) (CaGaSi) phosphors were synthesized by using a sol-gel method. Photoluminescence spectra of Eu(3+):CaGaSi phosphors exhibited five emission bands at 578, 592, 612, 652 and 701 nm, which were assigned to the transitions ((5)D(0) → (7)F(0), (7)F(1,)(7)F(2), (7)F(3) and (7)F(4)), respectively, with an excitation wavelength of λ(exci) = 392 nm. Among these, the transition (5) D(0) → (7) F(2) (612 nm) displayed bright red emission. In the case of Tb(3+):CaGaSi phosphors, four emission bands were observed at 488 ((5)D(4) → (7)F(6)), 543 ((5)D(4) → (7)F(5)), 584 ((5)D(4) → (7)F(4)) and 614 nm ((5)D(4) → (7) F(3) ) from the measurement of PL spectra with λ(exci) = 376 nm. Among these, the transition (5)D(4) → (7) F(5) at 543 nm displayed bright green emission. The structure and morphology of the phosphors were studied from the measurements of X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy-dispersive X-ray analysis (EDAX) results. Copyright © 2011 John Wiley & Sons, Ltd.

Quantitative and descriptive comparison of four acoustic analysis systems: vowel measurements.

PubMed

Burris, Carlyn; Vorperian, Houri K; Fourakis, Marios; Kent, Ray D; Bolt, Daniel M

2014-02-01

This study examines accuracy and comparability of 4 trademarked acoustic analysis software packages (AASPs): Praat, WaveSurfer, TF32, and CSL by using synthesized and natural vowels. Features of AASPs are also described. Synthesized and natural vowels were analyzed using each of the AASP's default settings to secure 9 acoustic measures: fundamental frequency (F0), formant frequencies (F1-F4), and formant bandwidths (B1-B4). The discrepancy between the software measured values and the input values (synthesized, previously reported, and manual measurements) was used to assess comparability and accuracy. Basic AASP features are described. Results indicate that Praat, WaveSurfer, and TF32 generate accurate and comparable F0 and F1-F4 data for synthesized vowels and adult male natural vowels. Results varied by vowel for women and children, with some serious errors. Bandwidth measurements by AASPs were highly inaccurate as compared with manual measurements and published data on formant bandwidths. Values of F0 and F1-F4 are generally consistent and fairly accurate for adult vowels and for some child vowels using the default settings in Praat, WaveSurfer, and TF32. Manipulation of default settings yields improved output values in TF32 and CSL. Caution is recommended especially before accepting F1-F4 results for children and B1-B4 results for all speakers.

DNA alterations and effects on growth and reproduction in Daphnia magna during chronic exposure to gamma radiation over three successive generations.

PubMed

Parisot, Florian; Bourdineaud, Jean-Paul; Plaire, Delphine; Adam-Guillermin, Christelle; Alonzo, Frédéric

2015-06-01

This study examined chronic effects of external Cs-137 gamma radiation on Daphnia magna exposed over three successive generations (F0, F1 and F2) to environmentally relevant dose rates (ranging from 0.007 to 35.4 mGy h(-1)). Investigated endpoints included survival, growth, reproduction and DNA alterations quantified using random-amplified polymorphic DNA polymerase chain reaction (RAPD-PCR). Results demonstrated that radiation effects on survival, growth and reproduction increased in severity from generation F0 to generation F2. Mortality after 21 days at 35.4 mGy h(-1) increased from 20% in F0 to 30% in F2. Growth was affected by a slight reduction in maximum length at 35.4 mGy h(-1) in F0 and by reductions of 5 and 13% in growth rate, respectively, at 4.70 and 35.4 mGy h(-1) in F2. Reproduction was affected by a reduction of 19% in 21 day-fecundity at 35.4 mGy h(-1) in F0 and by a delay of 1.9 days in brood release as low as 0.070 mGy h(-1) in F2. In parallel, DNA alterations became significant at decreasing dose rates over the course of F0 (from 4.70 mGy h(-1) at hatching to 0.007 mGy h(-1) after ∼21 days) and from F0 to F2 (0.070 mGy h(-1) at hatching to 0.007 mGy h(-1) after ∼21 days), demonstrating their rapid accumulation in F0 daphnids and their transmission to offspring generations. Transiently more efficient DNA repair leading to some recovery at the organism level was suggested in F1, with no effect on survival, a slight reduction of 12% in 21 day-fecundity at 35.4 mGy h(-1) and DNA alterations significant at highest dose rates only. The study improved our understanding of long term responses to low doses of radiation at the molecular and organismic levels in a non-human species for a better radioprotection of aquatic ecosystems. Copyright © 2015 Elsevier B.V. All rights reserved.

Synthesis, characterization and antimicrobial studies of new bispyrazolines linked via 3-aryl ring with aliphatic chains

NASA Astrophysics Data System (ADS)

Yusuf, Mohamad; Jain, Payal

2012-10-01

The bispyrazolines 4a(a'-f') and 4b(a'-f') built around the aliphatic chains of varying lengths have been prepared by refluxing bischalcones 3a(a'-f') and 3b(a'-f') with phenyl hydrazine in alcoholic medium. The reactions of chalcones 2a and 2b with suitable 1,ω-dibromoalkanes in the presence of anhydrous K2CO3/dry acetone and Bu4N+I- (PTC) provided 3a(a'-f') and 3b(a'-f'), respectively. The antibacterial and antifungal activities of the synthesized compounds were evaluated against five bacterial and four fungal strains. The compounds 3ba', 3bc', 3bd', 3be', 3af', 4aa' and 4ba' showed better MIC (μg/mL) against the tested microorganisms.

[Divisibility of warfarin and fluindione tablets tested in elderly patients and their family circle].

PubMed

Pautas, Eric; Despres, Jérémie; Peyron, Isabelle; Golmard, Jean-Louis; Grange, Jennifer; Koenig, Nelly; Gouronnec, Adeline; Mitha, Nathalie; Siguret, Virginie; Gouin-Thibault, Isabelle

2011-06-01

Vitamin K antagonist tablets are often split to fractionate the dose by elderly patients. We performed a study in order to assess the divisibility of one dosage strength of score-lined warfarin and of score-lined fluindione. Due to a recent change in the pharmaceutical form of fluindione in order to improve the divisibility, the study was performed over 2 different periods (with the « old » and with the « new » pharmaceutical form). In each period, 10 patients mean aged 82 years, 10 relatives, 10 nurses, 10 medical doctors) were asked to split in half warfarin tablets (W2 1(st) period et W2 2(d) period) and fluindione tablets (F2 et F'2), and to split fluindione tablets into 4 fragments (F4 et F'4). The first end-point was the accuracy of splitting estimated by the difference between the real and the expected weight of fragmented tablets. The statistical analysis was performed using an ANOVA test with 2 variables, subject and drug. The difference between the 2 periods were analyzed using an ANOVA test with 2 variables, subject and period. Over the 2 periods, the differences between real and expected weight were of 4.65% for W2 1(st) phase, 9.48% for F2, 15.35% for F4, 5.56% for W2 2(d )period, 4.30% for F'2, and 6.98% for F'4. The quality of splitting was statistically poorer in the elderly patient group compared to other subjects. This study was not design to assess the clinical relevance (bleeding or thromboembolism) or the anticoagulation control of the variations in drug mass due to inappropriate splitting of tablets. However, split form of drugs should be prescribe with caution to elderly patients.

¹¹¹In-anti-F4/80-A3-1 antibody: a novel tracer to image macrophages.

PubMed

Terry, Samantha Y A; Boerman, Otto C; Gerrits, Danny; Franssen, Gerben M; Metselaar, Josbert M; Lehmann, Steffi; Oyen, Wim J G; Gerdes, Christian A; Abiraj, Keelara

2015-08-01

Here, the expression of F4/80 on the cell surface of murine macrophages was exploited to develop a novel imaging tracer that could visualize macrophages in vivo. The immunoreactive fraction and IC50 of anti-F4/80-A3-1, conjugated with diethylenetriaminepentaacetic acid (DTPA) and radiolabelled with (111)In, were determined in vitro using murine bone marrow-derived macrophages. In vivo biodistribution studies were performed with (111)In-anti-F4/80-A3-1 and isotype-matched control antibody (111)In-rat IgG2b at 24 and 72 h post-injection (p.i.) in SCID/Beige mice bearing orthotopic MDA-MB-231 xenografts. In some studies mice were also treated with liposomal clodronate. Macrophage content in tissues was determined immunohistochemically. Micro-single photon emission computed tomography (SPECT)/CT images were also acquired. In vitro binding assays showed that (111)In-anti-F4/80-A3-1 specifically binds F4/80 receptor-positive macrophages. The immunoreactivity of anti-F4/80-A3-1 was 75 % and IC50 was 0.58 nM. In vivo, injection of 10 or 100 μg (111)In-anti-F4/80-A3-1 resulted in splenic uptake of 78 %ID/g and 31 %ID/g, respectively, and tumour uptake of 1.38 %ID/g and 4.08 %ID/g, respectively (72 h p.i.). Liposomal clodronate treatment reduced splenic uptake of 10 μg (111)In-anti-F4/80-A3-1 from 248 %ID/g to 114 %ID/g and reduced (111)In-anti-F4/80-A3-1 uptake in the liver and femur (24 h p.i.). Tracer retention in the blood and tumour uptake increased (24 h p.i.). Tumour uptake of (111)In-anti-F4/80-A3-1 was visualized by microSPECT/CT. Macrophage density in the spleen and liver decreased in mice treated with liposomal clodronate. Uptake of (111)In-rat IgG2b was lower in the spleen, liver and femur when compared to (111)In-anti-F4/80-A3-1. Radiolabelled anti-F4/80-A3-1 antibodies specifically localize in tissues infiltrated by macrophages in mice and can be used to visualize tumours. The liver and spleen act as antigen sink organs for macrophage-specific tracers.

Prime Contractors with Awards Over $25,000 by Name, Location, and Contract Number, Fiscal Year 1992 (International Const. Co. Ltd.-McKay Communications)

DTIC Science & Technology

1993-01-01

a4 a -- 0 a ,r 00 a.H Va CO u 0 0~ a. a . a 404~~ x- 4z. . . a a a. a~~~c. a WOw C6 Cr a D 00 - aa a a a3 a . Ca.~ ~ 0 acca rI a. az 0-. a 0 a 0 aD...4Ed V-4E ) F .4 ~ F 0.4 00. F4C n- F EL F: F3. xL O F-F,-.1~~~~F o)40 F en0 F (F 1. F 0 4 4 4 4 41 F6 F6 F8 a F6. 6 a 444~ F) 44 F) 4 0 4~~~ ccFF 0

Fluoride-induced thyroid dysfunction in rats: roles of dietary protein and calcium level.

PubMed

Wang, H; Yang, Z; Zhou, B; Gao, H; Yan, X; Wang, J

2009-02-01

To assess the roles of dietary protein (Pr) and calcium (Ca) level associated with excessive fluoride (F) intake and the impact of dietary Pr, Ca, and F on thyroid function, 144 30-day-old Wistar albino rats were randomly allotted to six groups of 24 (female:male = 1:1). The six groups were fed (1) a normal control (NC) diet (17.92% Pr, 0.85% Ca = NC group); (2) the NC diet and high F (338 mg NaF [=150 mg F ion]/L in their drinking water = NC+F group); (3) low Pr and low Ca diet (10.01% Pr, 0.24% Ca = LPrLCa group); (4) low Pr and low Ca diet plus high F = LPrLCa+F group; (5) high Pr and low Ca diet plus high F (25.52% Pr, 0.25% Ca = HPrLCa+F group); and (6) low Pr and high Ca diet plus high F (10.60% Pr, 1.93% Ca = LPrHCa+F group). The areas of thyroid follicles were determined by Image-Proplus 5.1, and triiodothyronine (T3), free T3 (FT3), thyroxine (T4), and free T4 (FT4) levels in serum were measured by radioimmunoassay. The histopathological study revealed obviously flatted follicular epithelia cells and hyperplastic nodules, consisting of thyroid parafollicular cells that appeared by excessive F ingestion, on the 120th day. Pr or Ca supplementation reverses the F-induced damage in malnutrition. The serum T3, FT3, T4, and FT4 levels in the NC+F group were significantly decreased and significantly increased in the LPrLCa+F group. Thus, excessive F administration induces thyroid dysfunction in rats; dietary Pr and Ca level play key roles in F-induced thyroid dysfunction.

Longitudinal analysis of low-molecular weight fluorophores in type 1 diabetes mellitus.

PubMed

Januszewski, Andrzej S; Thomas, Merlin C; Karschimkus, Connie S; Chung, Jasmine S; Rowley, Kevin G; Nelson, Craig L; O'Neal, David N; Dragicevic, George; Harper, Colin A; Best, James D; Jenkins, Alicia J

2008-02-01

Circulating low molecular weight (<10 kDa) fluorophores (LMW-F) measured by non-specific fluorescence spectroscopy may detect small advanced glycation end-products (AGEs) not recognized by other assays. This longitudinal study assessed correlates of LMW-F and predictive power of LMW-F levels for vascular health in Type 1 diabetes (T1DM) patients. Fasting patients with T1DM (n=37) were studied twice at intervals of 12-60 months (mean+/-SD, 33+/-15 months). LMW-F levels were also measured once in 112 healthy control subjects. Relative to controls, LMW-F levels were higher in diabetic subjects at initial and final time points (mean+/-SD), 5.4+/-1.9 AU/ml and 4.5+/-1.8 AU/ml respectively vs. 3.8+/-2.1 AU/ml; p=0.0001 and p=0.06). Baseline LMW-F levels predicted subsequent hs-CRP and oxLDL/LDL values. LMW-F levels decreased significantly over time in diabetes (5.4+/-1.9 vs. 4.5+/-1.8 AU/ml; p=0.02). Rises in LMW-F levels in individual diabetic subjects correlated significantly with worsening renal function (BUN), glycemia (HbA1c) and with vascular dysfunction (systemic vascular resistance). LMW-F levels predict levels of inflammation and oxidation in T1DM. Changes in LMW-F levels in T1DM reflect variations in glycemia and renal function. Biochemical characterization of LMW-F would facilitate understanding of the potential utility of LMW-F as a therapeutic target.

Why is walker-assisted gait metabolically expensive?

PubMed

Priebe, Jonathon R; Kram, Rodger

2011-06-01

Walker-assisted gait is reported to be ∼200% more metabolically expensive than normal bipedal walking. However, previous studies compared different walking speeds. Here, we compared the metabolic power consumption and basic stride temporal-spatial parameters for 10 young, healthy adults walking without assistance and using 2-wheeled (2W), 4-wheeled (4W) and 4-footed (4F) walker devices, all at the same speed, 0.30m/s. We also measured the metabolic power demand for walking without any assistive device using a step-to gait at 0.30m/s, walking normally at 1.25m/s, and for repeated lifting of the 4F walker mimicking the lifting pattern used during 4F walker-assisted gait. Similar to previous studies, we found that the cost per distance walked was 217% greater with a 4F walker at 0.30m/s compared to unassisted, bipedal walking at 1.25m/s. Compared at the same speed, 0.30m/s, using a 4F walker was still 82%, 74%, and 55% energetically more expensive than walking unassisted, with a 4W walker and a 2W walker respectively. The sum of the metabolic cost of step-to walking plus the cost of lifting itself was equivalent to the cost of walking with a 4F walker. Thus, we deduce that the high cost of 4F walker assisted gait is due to three factors: the slow walking speed, the step-to gait pattern and the repeated lifting of the walker. Copyright © 2011 Elsevier B.V. All rights reserved.

Non-invasive estimation of 10 B-4-borono-L-phenylalanine-derived boron concentration in tumors by PET using 4-borono-2-18 F-fluoro-phenylalanine.

PubMed

Yoshimoto, Mitsuyoshi; Honda, Natsuki; Kurihara, Hiroaki; Hiroi, Kenta; Nakamura, Satoshi; Ito, Masashi; Shikano, Naoto; Itami, Jun; Fujii, Hirofumi

2018-05-01

In boron neutron capture therapy (BNCT), 10 B-4-borono-L-phenylalanine (BPA) is commonly used as a 10 B carrier. PET using 4-borono-2- 18 F-fluoro-phenylalanine ( 18 F-FBPA PET) has been performed to estimate boron concentration and predict the therapeutic effects of BNCT; however, the association between tumor uptake of 18 F-FBPA and boron concentration in tumors remains unclear. The present study investigated the transport mechanism of 18 F-FBPA and BPA, and evaluated the utility of 18 F-FBPA PET in predicting boron concentration in tumors. The transporter assay revealed that 2-aminobicyclo-(2.2.1)-heptane-2-carboxylic acid, an inhibitor of the L-type amino acid transporter, significantly inhibited 18 F-FBPA and 14 C-4-borono-L-phenylalanine ( 14 C-BPA) uptake in FaDu and LN-229 human cancer cells. 18 F-FBPA uptake strongly correlated with 14 C-BPA uptake in 7 human tumor cell lines (r = .93; P < .01). PET experiments demonstrated that tumor uptake of 18 F-FBPA was independent of the administration method, and uptake of 18 F-FBPA by bolus injection correlated well with BPA uptake by continuous intravenous infusion. The results of this study revealed that evaluating tumor uptake of 18 F-FBPA by PET was useful for estimating 10 B concentration in tumors. © 2018 The Authors.Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Changes in absolute theta power in bipolar patients during a saccadic attention task.

PubMed

Cartier, Consuelo; Diniz, Claudia; Di Girogio, Luiza; Bittencourt, Juliana; Gongora, Mariana; Ken Tanaka, Guaraci; Teixeira, Silmar; Basile, Luis F; Novis, Fernanda; Angélica Silveira, Luciana; da Silva, Rafael de Assis; Cagy, Mauricio; Cheniaux, Elie; Ribeiro, Pedro; Velasques, Bruna

2015-08-30

The present study analyzed absolute theta power (ATP) in brain areas involved with attention in the three phase of BD while the patients performing a saccadic attention task. We hypothesized that patients in depression and mania states show a higher ATP compared to euthymic patients, since a higher ATP is indicative of attention deficit. We analyzed the frontal (F7, F3, Fz, F4 and F8) and central (C3, Cz and C4) areas. Thirty bipolar patients were enrolled in this study. The subjects performed a saccadic attention task while their brain activity pattern was recorded using quantitative electroencephalography (20 channels). Our results showed a main effect for group over C3, C4, Cz, F7, F4, F8 electrodes, and a main effect for moment over Cz, F7, F8 electrodes. These results indicate that both task and groups produce changes in theta activity in distinct cortical areas that participate in the organization of attention. Our results therefore demonstrate that, although it is well established in the literature that theta has a relevant role in the attention process, it is necessary to deepen the investigations to better understand the specifics of theta during visual processing tasks that have a demand for attention. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

C-F activation of fluorinated arenes using NHC-stabilized nickel(0) complexes: selectivity and mechanistic investigations.

PubMed

Schaub, Thomas; Fischer, Peter; Steffen, Andreas; Braun, Thomas; Radius, Udo; Mix, Andreas

2008-07-23

The reaction of [Ni2((i)Pr2Im)4(COD)] 1a or [Ni((i)Pr2Im)2(eta(2)-C2H4)] 1b with different fluorinated arenes is reported. These reactions occur with a high chemo- and regioselectivity. In the case of polyfluorinated aromatics of the type C6F5X such as hexafluorobenzene (X = F) octafluorotoluene (X = CF3), trimethyl(pentafluorophenyl)silane (X = SiMe3), or decafluorobiphenyl (X = C6F5) the C-F activation regioselectively takes place at the C-F bond in the para position to the X group to afford the complexes trans-[Ni((i)Pr2Im)2(F)(C6F5)]2, trans-[Ni((i)Pr2Im)2(F)(4-(CF3)C6F4)] 3, trans-[Ni((i)Pr2Im)2(F)(4-(C6F5)C6F4)] 4, and trans-[Ni((i)Pr2Im)2(F)(4-(SiMe3)C6F4)] 5. Complex 5 was structurally characterized by X-ray diffraction. The reaction of 1a with partially fluorinated aromatic substrates C6H(x)F(y) leads to the products of a C-F activation trans-[Ni((i)Pr2Im)2(F)(2-C6FH4)] 7, trans-[Ni((i)Pr2Im)2(F)(3,5-C6F2H3)] 8, trans-[Ni((i)Pr2Im)2(F)(2,3-C6F2H3)] 9a and trans-[Ni((i)Pr2Im)2(F)(2,6-C6F2H3)] 9b, trans-[Ni((i)Pr2Im)2(F)(2,5-C6F2H3)] 10, and trans-[Ni((i)Pr2Im)2(F)(2,3,5,6-C6F4H)] 11. The reaction of 1a with octafluoronaphthalene yields exclusively trans-[Ni((i)Pr2Im)2(F)(1,3,4,5,6,7,8-C10F7)] 6a, the product of an insertion into the C-F bond in the 2-position, whereas for the reaction of 1b with octafluoronaphthalene the two isomers trans-[Ni((i)Pr2Im)2(F)(1,3,4,5,6,7,8-C10F7)] 6a and trans-[Ni((i)Pr2Im)2(F)(2,3,4,5,6,7,8-C10F7)] 6b are formed in a ratio of 11:1. The reaction of 1a or of 1b with pentafluoropyridine at low temperatures affords trans-[Ni((i)Pr2Im)2(F)(4-C5NF4)] 12a as the sole product, whereas the reaction of 1b performed at room temperature leads to the generation of trans-[Ni((i)Pr2Im)2(F)(4-C5NF4)] 12a and trans-[Ni((i)Pr2Im)2(F)(2-C5NF4)] 12b in a ratio of approximately 1:2. The detection of intermediates as well as kinetic studies gives some insight into the mechanistic details for the activation of an aromatic carbon-fluorine bond at the {Ni((i)Pr2Im)2} complex fragment. The intermediates of the reaction of 1b with hexafluorobenzene and octafluoronaphthalene, [Ni((i)Pr2Im)2(eta(2)-C6F6)] 13 and [Ni((i)Pr2Im)2(eta(2)-C10F8)] 14, have been detected in solution. They convert into the C-F activation products. Complex 14 was structurally characterized by X-ray diffraction. The rates for the loss of 14 at different temperatures for the C-F activation of the coordinated naphthalene are first order and the estimated activation enthalpy Delta H(double dagger) for this process was determined to be Delta H(double dagger) = 116 +/- 8 kJ mol(-1) (Delta S(double dagger) = 37 +/- 25 J K(-1) mol(-1)). Furthermore, density functional theory calculations on the reaction of 1a with hexafluorobenzene, octafluoronaphthalene, octafluorotoluene, 1,2,4-trifluorobenzene, and 1,2,3-trifluorobenzene are presented.

Maternal immunity enhances systemic recall immune responses upon oral immunization of piglets with F4 fimbriae.

PubMed

Nguyen, Ut V; Melkebeek, Vesna; Devriendt, Bert; Goetstouwers, Tiphanie; Van Poucke, Mario; Peelman, Luc; Goddeeris, Bruno M; Cox, Eric

2015-06-23

F4 enterotoxigenic Escherichia coli (ETEC) cause diarrhoea and mortality in piglets leading to severe economic losses. Oral immunization of piglets with F4 fimbriae induces a protective intestinal immune response evidenced by an F4-specific serum and intestinal IgA response. However, successful oral immunization of pigs with F4 fimbriae in the presence of maternal immunity has not been demonstrated yet. In the present study we aimed to evaluate the effect of maternal immunity on the induction of a systemic immune response upon oral immunization of piglets. Whereas F4-specific IgG and IgA could be induced by oral immunization of pigs without maternal antibodies and by intramuscular immunization of pigs with maternal antibodies, no such response was seen in the orally immunized animals with maternal antibodies. Since maternal antibodies can mask an antibody response, we also looked by ELIspot assays for circulating F4-specific antibody secreting cells (ASCs). Enumerating the F4-specific ASCs within the circulating peripheral blood mononuclear cells, and the number of F4-specific IgA ASCs within the circulating IgA(+) B-cells revealed an F4-specific immune response in the orally immunized animals with maternal antibodies. Interestingly, results suggest a more robust IgA booster response by oral immunization of pigs with than without maternal antibodies. These results demonstrate that oral immunization of piglets with F4-specific maternal antibodies is feasible and that these maternal antibodies seem to enhance the secondary systemic immune response. Furthermore, our ELIspot assay on enriched IgA(+) B-cells could be used as a screening procedure to optimize mucosal immunization protocols in pigs with maternal immunity.

Oligonucleotide-genotyping as a method of detecting the HLA-DR2 (DRw15)-Dw2, -DR2 (DRw15)-Dw12, -DR4-Dw15, and -DR4-D"KT2" haplotypes in the Japanese population.

PubMed

Obata, F; Ito, I; Kaneko, T; Ohkubo, M; Ishimoto, A L; Abe, A; Kashiwagi, N

1989-05-01

We synthesized pairs of four different oligonucleotides, F22, F29, F42, and F158, to analyse the HLA-DR2 (DRw15) and -DR4 haplotypes in the Japanese population. After enzymatically amplifying the HLA-DRB1 gene, we hybridized the oligonucleotide probes with DNA extracted from 42 donors. Hybridization was completed between F22 and the DNA of haplotype DR2 (DRw15)-Dw2, between F29 and the DNA of DR2 (DRw15)-Dw12, between F42 and the DNA of DR4-D"KT2", and between F158 and the DNA of DR4-Dw15. In keeping with the nucleotide sequences of the probes, F29 hybridized also with DNA from the DR9-Dw23 haplotype and F158 with that from some of the DRw8 haplotypes (DRw8-Dw8.3) in the Japanese population. Results of this study demonstrate that the four oligonucleotides make useful probes for detecting the haplotypes above.

Lake Erie Water Level Study. Appendix A. Regulation. Volume II. Coordinated Basic Data and Computer Programs.

DTIC Science & Technology

1981-07-01

fu4 M04 IV6 ft4 464 ftf tn t i f vMfu f tf u 6f tf 1 t4aa -f t a P-o a~ Jb Pൽ 24%5 -4S 2 .8- 2 4 OW- am 4~ MO-0 onCP wa D 0 ~ 04~ ft03 ft f 430 o POI...0 m Vk. so.i 4 hh 2 .a c9 0o& - 009--90 9-V-9--P.09 a z W-~P0~0-~ a 091- M9 M P 9-90 m ~ t 1- 9, 1-9 r- a-99 44 40U949P999449 0 9W MCO4404-9-4 am -99...whole minutes of time of run. ITIME - Parameter of CALL HOUR (time in form: hh /mnVss). IYR - Output - year. JHR - Output - hour and minute of time of run

Cadmium biosorption by Streptomyces sp. F4 isolated from former uranium mine.

PubMed

Siñeriz, Manuel Louis; Kothe, Erika; Abate, Carlos Mauricio

2009-09-01

46 actinomycetes were isolated from two polluted sites and one unpolluted site. One strain, F4, was selected through primary qualitative screening assays because of its cadmium resistance, and physiologically and taxonomically characterized. F4 was able to grow at 7.5% NaCl and 100 microg/ml lysozyme and at a pH between 6 and 10. 16S rDNA sequence analysis showed that F4 was closely related to Streptomyces tendae. Growth of Streptomyces sp. F4 on culture medium with 8 mg/l Cd(2+) for 8 days showed 80% inhibition. Maximum specific biosorption was 41.7 mg Cd(2+)/g dry weight after 7 days of growth and highest Cd(2+ )concentration was found in the cell wall (41.2%). The exopolysaccharide layer only contained 7.4%, whereas 39.4% of Cd(2+) was found in the cytosolic fraction. Twelve % was found in the ribosomes and membrane fraction. This was verified with TEM, showing Streptomyces sp. F4 cytoplasm with dark granulate appearance. This study could present the potential capacity of Streptomyces sp. F4 for Cd(2+) bioremediation. Copyright 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sulfonyl fluoride-based prosthetic compounds as potential 18F labelling agents.

PubMed

Inkster, James A H; Liu, Kate; Ait-Mohand, Samia; Schaffer, Paul; Guérin, Brigitte; Ruth, Thomas J; Storr, Tim

2012-08-27

Nucleophilic incorporation of [(18)F]F(-) under aqueous conditions holds several advantages in radiopharmaceutical development, especially with the advent of complex biological pharmacophores. Sulfonyl fluorides can be prepared in water at room temperature, yet they have not been assayed as a potential means to (18)F-labelled biomarkers for PET chemistry. We developed a general route to prepare bifunctional 4-formyl-, 3-formyl-, 4-maleimido- and 4-oxylalkynl-arylsulfonyl [(18)F]fluorides from their sulfonyl chloride analogues in 1:1 mixtures of acetonitrile, THF, or tBuOH and Cs[(18)F]F/Cs(2)CO(3(aq.)) in a reaction time of 15 min at room temperature. With the exception of 4-N-maleimide-benzenesulfonyl fluoride (3), pyridine could be used to simplify radiotracer purification by selectively degrading the precursor without significantly affecting observed yields. The addition of pyridine at the start of [(18)F]fluorination (1:1:0.8 tBuOH/Cs(2)CO(3(aq.))/pyridine) did not negatively affect yields of 3-formyl-2,4,6-trimethylbenzenesulfonyl [(18)F]fluoride (2) and dramatically improved the yields of 4-(prop-2-ynyloxy)benzenesulfonyl [(18)F]fluoride (4). The N-arylsulfonyl-4-dimethylaminopyridinium derivative of 4 (14) can be prepared and incorporates (18)F efficiently in solutions of 100 % aqueous Cs(2)CO(3) (10 mg mL(-1)). As proof-of-principle, [(18)F]2 was synthesised in a preparative fashion [88(±8) % decay corrected (n=6) from start-of-synthesis] and used to radioactively label an oxyamino-modified bombesin(6-14) analogue [35(±6) % decay corrected (n=4) from start-of-synthesis]. Total preparation time was 105-109 min from start-of-synthesis. Although the (18)F-peptide exhibited evidence of proteolytic defluorination and modification, our study is the first step in developing an aqueous, room temperature (18)F labelling strategy. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis of [18F]-labelled Maltose Derivatives as PET Tracers for Imaging Bacterial Infection

PubMed Central

Namavari, Mohammad; Gowrishankar, Gayatri; Hoehne, Aileen; Jouannot, Erwan; Gambhir, Sanjiv S

2015-01-01

Purpose To develop novel positron emission tomography (PET) agents for visualization and therapy monitoring of bacterial infections. Procedures It is known that maltose and maltodextrins are energy sources for bacteria. Hence, 18F-labelled maltose derivatives could be a valuable tool for imaging bacterial infections. We have developed methods to synthesize 4-O-(α-D-glucopyranosyl)-6-deoxy-6-[18F]fluoro-D-glucopyranoside (6-[18F]fluoromaltose) and 4-O-(α-D-glucopyranosyl)-1-deoxy-1-[18F]fluoro-D-glucopyranoside (1-[18F]fluoromaltose) as bacterial infection PET imaging agents. 6-[18F]fluoromaltose was prepared from precursor 1,2,3-tri-O-acetyl-4-O-(2′,3′,-di-O-acetyl-4′,6′-benzylidene-α-D-glucopyranosyl)-6-deoxy-6-nosyl-D-glucopranoside (5). The synthesis involved the radio-fluorination of 5 followed by acidic and basic hydrolysis to give 6-[18F]fluoromaltose. In an analogous procedure, 1-[18F]fluoromaltose was synthesized from 2,3, 6-tri-O-acetyl-4-O-(2′,3′,4′,6-tetra-O-acetyl-α-D-glucopyranosyl)-1-deoxy-1-O-triflyl-D-glucopranoside (9). Stability of 6-[18F]fluoromaltose in phosphate-buffered saline (PBS) and human and mouse serum at 37 °C was determined. Escherichia coli uptake of 6-[18F]fluoromaltose was examined. Results A reliable synthesis of 1- and 6-[18F]fluoromaltose has been accomplished with 4–6 and 5–8 % radiochemical yields, respectively (decay-corrected with 95 % radiochemical purity). 6-[18F]fluoromaltose was sufficiently stable over the time span needed for PET studies (~96 % intact compound after 1-h and ~65 % after 2-h incubation in serum). Bacterial uptake experiments indicated that E. coli transports 6-[18F]fluoromaltose. Competition assays showed that the uptake of 6-[18F]fluoromaltose was completely blocked by co-incubation with 1 mM of the natural substrate maltose. Conclusion We have successfully synthesized 1- and 6-[18F]fluoromaltose via direct fluorination of appropriate protected maltose precursors. Bacterial uptake experiments in E. coli and stability studies suggest a possible application of 6-[18F]fluoromaltose as a new PET imaging agent for visualization and monitoring of bacterial infections. PMID:25277604

The protective effect of SnF2 containing toothpastes and solution on enamel surfaces subjected to erosion and abrasion in situ.

PubMed

Hove, L H; Stenhagen, K R; Holme, B; Tveit, A B

2014-08-01

Stannous fluoride solutions have shown promising protective effect against erosion/abrasion, but the effect of SnF2 toothpastes is uncertain. The aim of the study was to test the inhibiting effect of two SnF2 toothpastes and a SnF2 solution against erosive/abrasive wear in a single-blind, randomised in situ study, using a white light interferometer. Sixteen human molars were each divided into four specimens, mounted on mouth appliances and worn by 8 volunteers for 9 days. Specimens were brushed with toothpaste twice each day for 30 s either with fluoride-free toothpaste or toothpastes including SnF2. Toothpaste was left on the surface for 90 additional seconds. Group 1, fluoride-free toothpaste; Group 2, toothpaste A (0.4% SnF2, Solidox); Group 3, toothpaste B (0.454 % SnF2, Oral-B(®)); Group 4, brushed with fluoride-free toothpaste (30 s) and treated for 2 min with a 0.4 % SnF2 solution (1,000 ppm F). To mimic gastric reflux/vomit, specimens were etched for 2 min twice a day (0.01 M HCl). Procedures were performed extra-orally. The mean enamel wear (in μm) for the control specimens was: -29.2 ± SD 10.5; for group 2 -14.5 SD ± 9.3; for group 3 -33.3 SD ± 7.4, and for group 4 +0.4 SD ± 1.3. The specimens treated with SnF2 solution and toothpaste A showed significantly lower enamel wear than the control group. Toothpaste B gave no significant reduction in enamel wear. The SnF2 solution fully protected the enamel surface against erosive and abrasive challenges. The SnF2 toothpaste A (Solidox) showed less, but significant protection of the enamel, while no statistically significant protection was demonstrated by SnF2 toothpaste B (Oral-B(®) Pro-Expert).

Oral immunization with F4 fimbriae and CpG formulated with carboxymethyl starch enhances F4-specific mucosal immune response and modulates Th1 and Th2 cytokines in weaned pigs.

PubMed

Delisle, Benjamin; Calinescu, Carmen; Mateescu, Mircea Alexandru; Fairbrother, John Morris; Nadeau, Éric

2012-01-01

F4 fimbriae are a potential candidate for an oral subunit vaccine for prevention of post-weaning diarrhea in swine due to infection with F4-positive enterotoxigenic Escherichia coli. However, large quantities of F4 fimbriae are required to induce a specific antibody response. The aim of the present study was to evaluate the effect of supplementation of F4 fimbriae with Cytosine-phosphate-Guanosine-oligodeoxynucleotide (CpG-A D19) or with complete cholera toxin (CT) as adjuvants on the F4-specific antibody response and cytokine production in weaned pigs following oral administration of F4 fimbrial antigen formulated with Carboxymethyl Starch (CMS). Oral dosage forms of F4 fimbriae alone or supplemented with CpG-A D19 or with CT were formulated with CMS as monolithic tablets, obtained by direct compression, and administered to weaned pigs. Blood and faecal samples were collected to determine the systemic and mucosal immune status of animals at various times until necropsy. During necropsy, contents of the jejunum and ileum were collected for determination of mucosal F4 specific antibodies. Segments of jejunum and ileum were also used to measure mRNA cytokine production. The presence of CpG in the formulation of the fimbriae significantly increased F4-specific immunoglobulin (Ig) IgM and IgG levels in intestinal secretions, and enhanced Th1 (Interferon-gamma / IFN-γ, Tumour Necrosis Factor-alpha / TNF-α, Interleukin-12p40 / IL-12p40, IL-1β) and Th2 (IL-4, IL-6) cytokine production in intestinal tissues. Supplementation with CT did not result in induction of F4-specific antibodies in secretions, although a significant Th1 response (IFN-α, IFN-γ, IL-18) was detected in tissues. Neither F4-specific systemic antibodies, nor intestinally secreted IgA were detected throughout the immunization trial for all groups. CpG-A D19 appeared to be a promising adjuvant for an oral F4 subunit vaccine formulated with CMS excipient as monolithic tablets. This matrix afforded gastro-protection and delivered the F4 fimbriae at their intestinal sites.

Comparison of two plethysmography systems in assessment of forearm blood flow.

PubMed

Leslie, Stephen J; Attinà, Teresa; Hultsch, Ellen; Bolscher, Luc; Grossman, Matthias; Denvir, Martin A; Webb, David J

2004-05-01

Venous occlusion plethysmography is widely used to assess forearm blood flow (FBF). We compared the established Hokanson system (HEC4) with a newly developed Filtrass 2001 system (F2001). The HEC4 uses mercury-in-Silastic strain gauges, whereas F2001 detects volume changes with a nonmercury linear displacement device. The aim of this study was to evaluate the new F2001 against the HEC4 in terms of repeatability and systematic bias. Ten subjects were studied on 4 separate days in random order using either the HEC4 on both arms, the F2001 on both arms, the HEC4 on the right arm with the F2001 on the left, or the F2001 on the right arm and the HEC4 on the left. Stroop's colored word conflict test and postocclusive hyperemia were used to increase FBF, and lower body negative pressure was used to lower FBF. Stroop's colored word conflict test and lower body negative pressure increased (24.6 +/- 1.5%, n = 240, P < 0.0001) and decreased (18.7 +/- 0.8%, n = 240, P < 0.0001) FBF, respectively. Postocclusive hyperemia after occlusion times of 5, 8, and 13 min substantially increased FBF by 390 +/- 86, 756 +/- 217, and 851 +/- 132%, respectively. Repeatability was not different between the devices (0.10 +/- 2.37 vs. -0.47 +/- 1.92 l/min, n = 125, P > 0.05), and there was no systematic bias. The F2001 is a newly developed plethysmography system that does not utilize mercury and is suitable for assessing changes of FBF in physiological studies.

Case study of 4(f) litigation/rulings.

DOT National Transportation Integrated Search

2004-06-01

This study addresses issues related to compliance with Section 4(f). By referring to the manual Cabinet employees will be to: 1) Conduct an assessment of proposed alternatives to evaluate prudence and feasibility of a proposed project alternative; 2)...

Triiodothyronine and free thyroxine levels are differentially associated with metabolic profile and adiposity-related cardiovascular risk markers in euthyroid middle-aged subjects.

PubMed

Roef, Greet L; Rietzschel, Ernst R; Van Daele, Caroline M; Taes, Youri E; De Buyzere, Marc L; Gillebert, Thierry C; Kaufman, Jean-Marc

2014-02-01

We have previously shown that in healthy young men, a less favorable body composition is associated with higher free triiodothyronine (fT3) levels within the euthyroid range. Besides, a higher free-triiodothyronine-to-free-thyroxin (fT3-to-fT4) ratio has been related to a less favorable metabolic phenotype and more placental growth in pregnant women. In the present study, we therefore investigated whether serum thyrotropin (TSH), thyroid hormone levels, and the fT3-to-fT4 ratio are associated with metabolic and adiposity-related cardiovascular risk markers in a healthy population of middle-aged euthyroid men and women. Thyroid parameters were measured in 2524 generally healthy subjects from the Asklepios Study (35-55 years, mean age 46 years). Analyses were restricted to 2315 subjects (1138 women and 1177 men), not using thyroid medication, not having anti-TPO levels above clinical cutoff values or TSH levels outside the reference range (0.27-4.2 mU/L). Twenty-seven percent of the women and 47.5% of the men were overweight, while 13% of women and 17% of men were obese. Twenty percent of the subjects were active smokers. Serum thyroid function parameters were determined by electrochemiluminescence. fT3 and the fT3-to-fT4 ratio were positively related to body mass index (BMI), waist circumference, and components of metabolic syndrome, that is, triglycerides, systolic and diastolic blood pressure, and fasting plasma glucose, and negatively with HDL-cholesterol levels, whereas fT4 was negatively associated with BMI, waist circumference, and triglycerides (p<0.001). TSH related positively with total cholesterol levels (p<0.01), triglycerides, and systolic and diastolic blood pressure (p<0.001). The fT3-to-fT4 ratio was further positively associated with the adiposity-related inflammation markers interleukin-6 and high-sensitivity C-reactive protein and to pulse wave velocity. All associations were adjusted for sex, age, height, and smoking, and most associations persisted after additional adjustment for weight or waist circumference. In healthy euthyroid middle-aged men and women, higher fT3 levels, lower fT4 levels, and thus a higher fT3-to-fT4 ratio are consistently associated with various markers of unfavorable metabolic profile and cardiovascular risk.

An isocaloric increase of eating episodes in the morning contributes to decrease energy intake at lunch in lean men.

PubMed

Allirot, Xavier; Saulais, Laure; Seyssel, Kevin; Graeppi-Dulac, Julia; Roth, Hubert; Charrié, Anne; Drai, Jocelyne; Goudable, Joelle; Blond, Emilie; Disse, Emmanuel; Laville, Martine

2013-02-17

The effects of increasing eating frequency on human health are unclear. This study used an integrated approach to assess the short-term consequences on appetite and metabolism. Twenty normal-weight men participated in: (i) two sessions consisting of a breakfast consumed in one eating episode at T0 (F1), or in four isocaloric eating episodes at T0, T60, T120, and T180 min (F4), and followed by an ecological ad libitum buffet meal (T240) designed in an experimental restaurant. Intakes were assessed for the whole buffet meal and for each temporal quarter of the meal. (ii) two sessions consisting of the same two breakfasts F1 and F4 in a Clinical Investigation Centre. Blood sampling was performed to study the kinetics of ghrelin, glucagon-like peptide-1 (GLP-1), glucose, insulin, triglycerides and non-esterified fatty acids (NEFA). Substrate oxidation was measured by indirect calorimetry. During each of the 4 sessions, participants rated their appetite throughout the experiment. After F4, at T240 min, GLP-1 concentration was higher (P=0.006) while ghrelin concentration and hunger ratings were lower (P<0.001). We showed a trend for subjects to consume less energy (-88±61 kcal, P=0.08) at the buffet after F4, explained by a decrease in lipid intake (P=0.04). Marked differences in consumption were observed during the last temporal quarter of the meal for total energy and lipid intake (P=0.03). Mixed models highlighted differences between F1 and F4 for the kinetics of glucose, insulin and NEFA (P<0.001). The area under the curve was lower for insulin (P<0.001) and NEFA in F4 (P=0.03). Diet induced thermogenesis was reduced in F4 (P<0.05). This study demonstrated the beneficial short-term effect of increasing eating frequency on appetite in lean men considering subjective, physiological and behavioral data. However, the loss of the inter-prandial fast was associated with an inhibition of lipolysis, reflected by NEFA profiles, and a decrease in energy expenditure. Copyright © 2013 Elsevier Inc. All rights reserved.

Enhancement of luminescence properties in Er3+ doped TeO2-Na2O-PbX (X=O and F) ternary glasses.

PubMed

Kumar, Kaushal; Rai, S B; Rai, D K

2007-04-01

An enhancement of luminescence properties in Er3+ doped ternary glasses is observed on the addition of PbO/PbF2. The infrared to visible upconversion emission bands are observed at 410, 525, 550 and 658 nm, due to the 2H9/2-->4I15/2, 2H11/2-->4I15/2, 4S3/2-->4I15/2, 4F9/2-->4I15/2 transitions respectively, on excitation with 797 nm laser line. A detailed study reveals that the 2H9/2-->4I15/2 transition arises due to three step upconversion process while other transitions arise due to two step absorption. On excitation with 532 nm radiation, ultraviolet and violet upconversion bands centered at 380, 404, 410 and 475 nm wavelengths are observed along with one photon luminescence bands at 525, 550, 658 and 843 nm wavelengths. These bands are found due to the 4G11/2-->4I15/2, 2P3/2-->4I13/2, 2H9/2-->4I15/2, 2P3/2-->4I11/2, 2H11/2-->4I15/2, 4S3/2-->4I15/2, 4F9/2-->4I15/2 and 4S3/2-->4I13/2 transitions, respectively. Though incorporation of PbO and PbF2 both enhances fluorescence intensities however, PbF2 content has an important influence on upconversion luminescence emission. The incorporation of PbF2 enhances the red emission (658 nm) intensity by 1.5 times and the violet emission (410 nm) intensity by 2.0 times. A concentration dependence study of fluorescence reveals the rapid increase in the red (4F9/2-->4I15/2) emission intensity relative to the green (4S3/2-->4I15/2) emission with increase in the Er3+ ion concentration. This behaviour has been explained in terms of an energy transfer by relaxation between excited ions.

The Extracellular Loop 2 (ECL2) of the Human Histamine H4 Receptor Substantially Contributes to Ligand Binding and Constitutive Activity

PubMed Central

Wifling, David; Bernhardt, Günther; Dove, Stefan; Buschauer, Armin

2015-01-01

In contrast to the corresponding mouse and rat orthologs, the human histamine H4 receptor (hH4R) shows extraordinarily high constitutive activity. In the extracellular loop (ECL), replacement of F169 by V as in the mouse H4R significantly reduced constitutive activity. Stabilization of the inactive state was even more pronounced for a double mutant, in which, in addition to F169V, S179 in the ligand binding site was replaced by M. To study the role of the FF motif in ECL2, we generated the hH4R-F168A mutant. The receptor was co-expressed in Sf9 insect cells with the G-protein subunits Gαi2 and Gβ1γ2, and the membranes were studied in [3H]histamine binding and functional [35S]GTPγS assays. The potency of various ligands at the hH4R-F168A mutant decreased compared to the wild-type hH4R, for example by 30- and more than 100-fold in case of the H4R agonist UR-PI376 and histamine, respectively. The high constitutive activity of the hH4R was completely lost in the hH4R-F168A mutant, as reflected by neutral antagonism of thioperamide, a full inverse agonist at the wild-type hH4R. By analogy, JNJ7777120 was a partial inverse agonist at the hH4R, but a partial agonist at the hH4R-F168A mutant, again demonstrating the decrease in constitutive activity due to F168A mutation. Thus, F168 was proven to play a key role not only in ligand binding and potency, but also in the high constitutive activity of the hH4R. PMID:25629160

Behavior of fluorinated analogs of L-(3,4-dihydroxyphenyl)alanine and L-threo-(3,4-dihydroxyphenyl)serine as substrates for Dopa decarboxylase.

PubMed

Borri Voltattorni, Carla; Bertoldi, Mariarita; Bianconi, Silvia; Deng, Wei-ping; Wong, Kelli; Kim, InHo; Herbert, Brian; Kirk, Kenneth L

2002-07-05

We have determined the kinetic parameters for Dopa decarboxylase (DDC) of three ring-fluorinated analogs of 3,4-dihydroxyphenylalanine (Dopa). The rank order of catalytic efficiency of decarboxylation (k(cat)/K(m)) is Dopa>6-F-Dopa>2-F-Dopa>5-F-Dopa. This rank is consistent with previous in vivo and in vitro studies which indicate that, of the fluorinated analogs, 6-F-Dopa has pharmacokinetics that are most suited for positron emission tomographic (PET) evaluation of dopamine function. The effectiveness of PET as a diagnostic tool, the convenient half-life of (18)F (110 min) and the favorable pharmacokinetics of 6-[(18)F]FDOPA have combined to make this an extremely valuable reagent to study dopaminergic activity. The reactions of the related fluorinated DOPS analogs show that, while 6-F-threo-3,4-(dihydroxyphenyl)serine (DOPS) is decarboxylated at approximately the same rate as the non-fluorinated substrate, 2-F-threo-DOPS is not converted into the corresponding amine. In both cases a Pictet-Spengler condensation with the pyridoxal 5(')-phosphate (PLP) cofactor occurs to produce tetrahydroisoquinolines. Condensation of fluorinated catecholamines and catechol amino acids with endogenous aldehydes will be investigated as an approach to study possible mechanisms of L-Dopa-linked neurotoxicity. (c) 2002 Elsevier Science (USA).

Fluorescence Spectroscopy as a Tool for the Assessment of Liver Samples with Several Stages of Fibrosis.

PubMed

Fabila-Bustos, Diego A; Arroyo-Camarena, Úrsula D; López-Vancell, María D; Durán-Padilla, Marco A; Azuceno-García, Itzel; Stolik-Isakina, Suren; Valor-Reed, Alma; Ibarra-Coronado, Elizabeth; Hernández-Quintanar, Luis F; Escobedo, Galileo; de la Rosa-Vázquez, José M

2018-03-01

During the last years, fluorescence spectroscopy has been used as a potential tool for the evaluation and characterization of tissues with different disease conditions due to its low cost, high sensitivity, and minimally or noninvasive character. In this study, fluorescence spectroscopy was used to study 19 paraffin blocks containing human liver tissue from biopsies. All samples were previously analyzed by two senior pathologists in a single-blind trial. After their evaluation, four liver samples were classified as nonfibrosis (F0), four as initial fibrosis (F1-F2), four as advanced fibrosis (F3), and six as cirrhosis (F4). The fluorescence was induced at different wavelengths as follows: 330, 365, and 405 nm using a portable fiber-optic system. The fluorescence spectra were recorded in the range of 400-750 nm. A distinctive correlation between the shape of each spectrum and the level of fibrosis in the liver sample was detected. A multi-variate statistical analysis based on principal component analysis followed by linear discrimination analysis was applied to develop algorithms able to distinguish different stages of fibrosis based on the characteristics of fluorescence spectra. Pairwise comparisons were performed: F0 versus F1-F2, F1-F2 versus F3, F3 versus F4, and F1-F2 versus F4. The algorithms applied to each set of data yielded values of sensitivity and specificity that were higher than 90% and 95%, respectively, in all the analyzed cases. With this study, it is concluded that fluorescence spectroscopy can be used as a complementary tool for the assessment of liver fibrosis in liver tissue samples, which sets the stage for subsequent clinical trials.

Arachidonic acid and lipoxin A4 attenuate alloxan-induced cytotoxicity to RIN5F cells in vitro and type 1 diabetes mellitus in vivo.

PubMed

Gundala, Naveen K V; Naidu, Vegi G M; Das, Undurti N

2017-03-01

We studied whether polyunsaturated fatty acids (PUFAs) can protect rat insulinoma (RIN5F) cells against alloxan-induced apoptosis in vitro and type 1 diabetes mellitus (type 1 DM) in vivo and if so, mechanism of this beneficial action. In vitro study was conducted using RIN5F cells while in vivo study was performed in Wistar rats. The effect of PUFAs, cyclo-oxygenase and lipoxygenase inhibitors, various eicosanoids and PUFAs metabolites: lipoxin A4 (LXA4), resolvin D2 and protectin against alloxan-induced cytotoxicity to RIN5F cells and type 1 DM was studied. Expression of PDX1, P65 NF-kB and IKB in RIN5F cells and Nrf2, GLUT2, COX2, iNOS protein levels in the pancreatic tissue and plasma glucose, insulin and tumor necrosis factor-α and antioxidants, lipid peroxides and nitric oxide were measured. Of all, arachidonic acid (AA) was found to be the most effective against alloxan-induced cytotoxicity to RIN5F cells and preventing type 1 DM. Both cyclo-oxygenase and lipoxygenase inhibitors did not block the beneficial actions of AA in vitro and in vivo. Alloxan inhibited LXA4 production by RIN5F cells and in alloxan-induced type 1 DM Wistar rats. AA-treatment restored LXA4 levels to normal both in vitro and in vivo. LXA4 protected RIN5F cells against alloxan-induced cytotoxicity and prevented type 1 DM and restored expression of Nrf2, Glut2, COX2, and iNOS genes and abnormal antioxidants to near normal. AA seems to bring about its beneficial actions against alloxan-induced cytotoxicity and type 1 DM by enhancing the production of LXA4. © 2016 BioFactors, 43(2):251-271, 2017. © 2016 International Union of Biochemistry and Molecular Biology.

Exposure to polychlorinated biphenyls and the thyroid gland – examining and discussing possible longitudinal health effects in humans

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

Gaum, Petra M., E-mail: pgaum@ukaachen.de; Lang, Jessica; Esser, André

Background: Many previous studies have dealt with the effect of polychlorinated biphenyls (PCBs) on the thyroid gland, but their findings are inconsistent. One problem of these studies has been their use of cross-sectional designs. Objectives: The aim of the current study is to investigate longitudinal effects of PCBs on the thyroid gland, focusing on: morphological changes in thyroid tissue (i.e. thyroid volume), changes in thyroid hormones and in thyroid antibodies. Methods: A total of 122 individuals (M{sub age}=44.7) were examined over a period of four years (t{sup 1} until t{sup 4}). Medical history was collected via interviews, an ultrasound examinationmore » was performed and blood samples were taken to determine plasma PCB levels, thyroid stimulating hormone (TSH), free triiodthyronine (fT3), free thyroxine (fT4), thyroid peroxidase antibodies (TPOab), thyreoglobulin antibodies (TGab) and thyroid-stimulating hormone receptor antibodies (TSHRab). Rank correlation coefficients and mixed effect models were performed controlling for age and total lipids. Results: There were negative correlations between higher chlorinated biphenyls and fT3, cross-sectionally as well as longitudinally. We also found an interaction effect of higher-chlorinated PCBs over time for fT4 as well as TSHRab. In case of high exposure, a decrease in fT4 and an increase in TSHRab level were found over time. In regards to the other variables, our findings yielded no clear results in the examined time period. Conclusion: This is the first study to shows a PCB-related effect on fT3, fT4 and TSHRab over a four year period. The data also suggest that morphological and antibody findings remain inconsistent and do not allow for unambiguous interpretation. - Highlights: • This is a longitudinal study which includes data from four cross sections. • Higher-chlorinated biphenyls are negatively correlated with fT3. • There are interactions of time and higher-chlorinated biphenyls to TSHRab and fT4. • There is an interaction of time and dioxin-like polychlorinated biphenyls to fT4. • No consistent effects were found for thyroid volume, TSH, TPOab and TGab.« less

Intervalence charge transfer luminescence: Interplay between anomalous and 5d − 4f emissions in Yb-doped fluorite-type crystals

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

Barandiarán, Zoila, E-mail: zoila.barandiaran@uam.es; Seijo, Luis; Instituto Universitario de Ciencia de Materiales Nicolás Cabrera, Universidad Autónoma de Madrid, 28049 Madrid

2014-12-21

In this paper, we report the existence of intervalence charge transfer (IVCT) luminescence in Yb-doped fluorite-type crystals associated with Yb{sup 2+}–Yb{sup 3+} mixed valence pairs. By means of embedded cluster, wave function theory ab initio calculations, we show that the widely studied, very broad band, anomalous emission of Yb{sup 2+}-doped CaF{sub 2} and SrF{sub 2}, usually associated with impurity-trapped excitons, is, rather, an IVCT luminescence associated with Yb{sup 2+}–Yb{sup 3+} mixed valence pairs. The IVCT luminescence is very efficiently excited by a two-photon upconversion mechanism where each photon provokes the same strong 4f{sup 14}–1A{sub 1g}→ 4f{sup 13}({sup 2}F{sub 7/2})5de{sub g}–1T{submore » 1u} absorption in the Yb{sup 2+} part of the pair: the first one, from the pair ground state; the second one, from an excited state of the pair whose Yb{sup 3+} moiety is in the higher 4f{sup 13}({sup 2}F{sub 5/2}) multiplet. The Yb{sup 2+}–Yb{sup 3+} → Yb{sup 3+}–Yb{sup 2+} IVCT emission consists of an Yb{sup 2+} 5de{sub g} → Yb{sup 3+} 4f{sub 7/2} charge transfer accompanied by a 4f{sub 7/2} → 4f{sub 5/2} deexcitation within the Yb{sup 2+} 4f{sup 13} subshell: [{sup 2}F{sub 5/2}5de{sub g},{sup 2}F{sub 7/2}] → [{sup 2}F{sub 7/2},4f{sup 14}]. The IVCT vertical transition leaves the oxidized and reduced moieties of the pair after electron transfer very far from their equilibrium structures; this explains the unexpectedly large band width of the emission band and its low peak energy, because the large reorganization energies are subtracted from the normal emission. The IVCT energy diagrams resulting from the quantum mechanical calculations explain the different luminescent properties of Yb-doped CaF{sub 2}, SrF{sub 2}, BaF{sub 2}, and SrCl{sub 2}: the presence of IVCT luminescence in Yb-doped CaF{sub 2} and SrF{sub 2}; its coexistence with regular 5d-4f emission in SrF{sub 2}; its absence in BaF{sub 2} and SrCl{sub 2}; the quenching of all emissions in BaF{sub 2}; and the presence of additional 5d–4f emissions in SrCl{sub 2} which are absent in SrF{sub 2}. They also allow to interpret and reproduce recent experiments on transient photoluminescence enhancement in Yb{sup 2+}-doped CaF{sub 2} and SrF{sub 2}, the appearance of Yb{sup 2+} 4f–5d absorption bands in the excitation spectra of the IR Yb{sup 3+} emission in partly reduced CaF{sub 2}:Yb{sup 3+} samples, and to identify the broadband observed in the excitation spectrum of the so far called anomalous emission of SrF{sub 2}:Yb{sup 2+} as an IVCT absorption, which corresponds to an Yb{sup 2+} 4f{sub 5/2} → Yb{sup 3+} 4f{sub 7/2} electron transfer.« less

Use of spray-cooling technology for development of microencapsulated capsicum oleoresin for the growing pig as an alternative to in-feed antibiotics: a study of release using in vitro models.

PubMed

Meunier, J-P; Cardot, J-M; Manzanilla, E G; Wysshaar, M; Alric, M

2007-10-01

The aim of this study was to develop sustained release microspheres of capsicum oleoresin as an alternative to in-feed additives. Two spray-cooling technologies, a fluidized air bed using a spray nozzle system and a vibrating nozzle system placed on top of a cooling tower, were used to microencapsulate 20% of capsicum oleoresin in a hydrogenated, rapeseed oil matrix. Microencapsulation was intended to reduce the irritating effect of capsicum oleoresin and to control its release kinetics during consumption by the animal. Particles produced by the fluidized air bed process (batch F1) ranged from 180 to 1,000 microm in size. The impact of particle size on release of capsaicin, the main active compound of capsicum oleoresin, was studied after sieving batch F1 to obtain 4 formulations: F1a (180 to 250 microm), F1b (250 to 500 microm), F1c (500 to 710 microm), and F1d (710 to 1,000 microm). The vibrating nozzle system can produce a monodispersive particle size distribution. In this study, particles of 500 to 710 microm were made (batch F2). The release kinetics of the formulations was estimated in a flow-through cell dissolution apparatus (CFC). The time to achieve a 90% dissolution value (T90%) of capsaicin for subbatches of F1 increased with the increase in particle size (P < 0.05), with the greatest value of 165.5 +/- 13.2 min for F1d. The kinetics of dissolution of F2 was slower than all F1 subbatches, with a T90% of 422.7 +/- 30.0 min. Nevertheless, because CFC systems are ill suited for experiments with solid feed and thus limit their predictive values, follow-up studies were performed on F1c and F2 using an in vitro dynamic model that simulated more closely the digestive environment. For both formulations a lower quantity of capsaicin dialyzed was recorded under fed condition vs. fasting condition with 46.9% +/- 1.0 vs. 74.7% +/- 2.7 for F1c and 32.4% +/- 1.4 vs. 44.2% +/- 2.6 for F2, respectively. This suggests a possible interaction between capsaicin and the feed matrix. Moreover, 40.4 +/- 3.9% of the total capsaicin intake in F2 form was dialyzed after 8 h of digestion when feed had been granulated vs. 32.4 +/- 1.4% when feed had not been granulated, which suggests that the feed granulation process could lead to a partial degradation of the microspheres and to a limitation of the sustained release effect. This study demonstrates the potential and the limitations of spray-cooling technology to encapsulate feed additives.

Effect of Silver Nitrate and Sodium Fluoride with Tri-Calcium Phosphate on Streptococcus mutans and Demineralised Dentine.

PubMed

Yu, Ollie Yiru; Zhao, Irene Shuping; Mei, May Lei; Lo, Edward Chin-Man; Chu, Chun-Hung

2018-04-25

This study investigated the effect of 25% silver nitrate (AgNO₃) and 5% sodium fluoride (NaF) varnish with functionalized tri-calcium phosphate (fTCP) on a Streptococcus mutans ( S. mutans ) biofilm and dentine caries lesion. Demineralised dentine specimens were treated with 25% AgNO₃ and 5% NaF + fTCP (Group 1), 25% AgNO₃ and 5% NaF (Group 2), 25% AgNO₃ (Group 3), or water (Group 4). The specimens were subjected to a S. mutans biofilm challenge after treatment. The biofilm was then studied via scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), and colony forming units (CFU). The specimens were assessed by micro-computed tomography, X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). SEM and CLSM revealed less biofilm in Groups 1 to 3. The log 10 CFU of Groups 1 to 4 were 4.5 ± 0.7, 4.4 ± 0.9, 4.4 ± 0.9, and 6.7 ± 1.0, respectively (Groups 1, 2, 3 < 4, p < 0.001). The lesion depths of Groups 1 to 4 were 212.6 ± 20.1 µm, 280.8 ± 51.6 µm, 402.5 ± 61.7 µm, and 497.4 ± 67.2 µm, respectively (Groups 1 < 2 < 3 < 4, p < 0.001). XRD demonstrated silver chloride formation in Groups 1, 2, and 3. FTIR found the amide I: HPO₄ 2− values of the four groups were 0.22 ± 0.05, 0.25 ± 0.05, 0.41 ± 0.12, and 0.64 ± 0.14, respectively (Groups 1, 2 < 3 < 4; p < 0.001). In conclusion, this study revealed that AgNO₃ and NaF + fTCP reduced the damage of dentine caries by cariogenic biofilm.

Radiolabelling of isopeptide N epsilon-(gamma-glutamyl)-L-lysine by conjugation with N-succinimidyl-4-[18F]fluorobenzoate.

PubMed

Wüst, F; Hultsch, C; Bergmann, R; Johannsen, B; Henle, T

2003-07-01

The isopeptide N(epsilon)-(gamma-glutamyl)-L-lysine 4 was labelled with 18F via N-succinimidyl-4-[18F]fluorobenzoate ([18F]SFB). A modified approach for the convenient synthesis of [18F]SFB was used, and [18F]SFB could be obtained in decay-corrected radiochemical yields of 44-53% (n = 20) and radiochemical purity >95% within 40 min after EOB. For labelling N(epsilon)-(gamma-glutamyl)-L-lysine with [18F]SFB the effects of isopeptide concentration, temperature, and pH were studied to determine the optimum reaction conditions. The coupling reaction was shown to be temperature and pH independent while being strongly affected by the isopeptide concentration. Using the optimized labelling conditions, in a typical experiment 1.3GBq of [18F]SFB could be converted into 447MBq (46%, decay-corrected) of [18F]fluorobenzoylated isopeptide within 45 min, including HPLC purification.

Evaluation of the Tobacco Heating System 2.2. Part 4: 90-day OECD 413 rat inhalation study with systems toxicology endpoints demonstrates reduced exposure effects compared with cigarette smoke.

PubMed

Wong, Ee Tsin; Kogel, Ulrike; Veljkovic, Emilija; Martin, Florian; Xiang, Yang; Boue, Stephanie; Vuillaume, Gregory; Leroy, Patrice; Guedj, Emmanuel; Rodrigo, Gregory; Ivanov, Nikolai V; Hoeng, Julia; Peitsch, Manuel C; Vanscheeuwijck, Patrick

2016-11-30

The objective of the study was to characterize the toxicity from sub-chronic inhalation of test atmospheres from the candidate modified risk tobacco product (MRTP), Tobacco Heating System version 2.2 (THS2.2), and to compare it with that of the 3R4F reference cigarette. A 90-day nose-only inhalation study on Sprague-Dawley rats was performed, combining classical and systems toxicology approaches. Reduction in respiratory minute volume, degree of lung inflammation, and histopathological findings in the respiratory tract organs were significantly less pronounced in THS2.2-exposed groups compared with 3R4F-exposed groups. Transcriptomics data obtained from nasal epithelium and lung parenchyma showed concentration-dependent differential gene expression following 3R4F exposure that was less pronounced in the THS2.2-exposed groups. Molecular network analysis showed that inflammatory processes were the most affected by 3R4F, while the extent of THS2.2 impact was much lower. Most other toxicological endpoints evaluated did not show exposure-related effects. Where findings were observed, the effects were similar in 3R4F- and THS2.2-exposed animals. In summary, toxicological changes observed in the respiratory tract organs of THS2.2 aerosol-exposed rats were much less pronounced than in 3R4F-exposed rats while other toxicological endpoints either showed no exposure-related effects or were comparable to what was observed in the 3R4F-exposed rats. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Magnetic x-ray linear dichroism in resonant and non-resonant Gd 4f photoemission

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

Mishra, S.; Gammon, W.J.; Pappas, D.P.

1997-04-01

The enhancement of the magnetic linear dichroism in resonant 4f photoemission (MLDRPE) is studied from a 50 monolayer film of Gd/Y(0001). The ALS at beamline 7.0.1 provided the source of linearly polarized x-rays used in this study. The polarized light was incident at an angle of 30 degrees relative to the film plane, and the sample magnetization was perpendicular to the photon polarization. The linear dichroism of the 4f core levels is measured as the photon energy is tuned through the 4d-4f resonance. The authors find that the MLDRPE asymmetry is strongest at the resonance. Near the threshold the asymmetrymore » has several features which are out of phase with the fine structure of the total yield.« less

Laser-induced fluorescence studies of excited Sr reactions: II. Sr(3P1)+CH3F, C2H5F, C2H4F2

NASA Astrophysics Data System (ADS)

Teule, J. M.; Janssen, M. H. M.; Bulthuis, J.; Stolte, S.

1999-06-01

The vibrational and rotational energy distributions of ground state SrF(X 2Σ) formed in the reactions of electronically excited Sr(3P1) with methylfluoride, ethylfluoride, and 1,1-difluoroethane have been studied by laser-induced fluorescence. Although the reactions of ground state Sr with these reactants are exothermic, no SrF products are observed for those reactions in this study. The fraction of available energy disposed into the sum of rotational and vibrational energy of the SrF(X 2Σ) product is approximately the same for all three reactions, i.e., 40%. The reaction of Sr(3P1) with CH3F results in very low vibrational excitation in the SrF reaction product. The product vibration increases in going to C2H5F and C2H4F2. It is concluded that the alkyl group influences the energy disposal mechanism in these reactions, and some suggestions are given for a partial explanation of the observations.

Electron induced ionization of plasma processing gases: C4F x (x  =  1–8) and the isomers of C4F6 and C4F8

NASA Astrophysics Data System (ADS)

Gupta, Dhanoj; Choi, Heechol; Kwon, Deuk-Chul; Yoon, Jung-Sik; Song, Mi-Young

2018-04-01

The total ionization cross section (Q ion) for C4F x (x  =  1–8) fluorocarbons and the isomers of C4F6 and C4F8 molecules are calculated from ionization threshold to 5 keV using the binary-encounter bethe method. The targets are fully optimized using the Hartree–Fock (HF) method and density function theory (DFT) for their minimum energy structure and orbital parameters. The present Q ion with HF parameters showed good agreement with the experimental data for 1,3-C4F6, 2-C4F6, 2-C4F8 and 1-C4F8. On the other hand, the Q ion with DFT parameters are in good accordance with the recent theoretical results for 1,3-C4F6 and 2-C4F6. The Q ion for c-C4F8 showed much variation among the various results. The isomer effect in Q ion is negligible for the isomers of C4F6 and C4F8 molecules. The calculation of Q ion for C4F, C4F2, C4F3, C4F4, C4F5, c-C4F6, C4F7 and iso-C4F8 is a maiden attempt. The present cross section data are important quantities for low temperature plasma modeling especially related to the fluorocarbon plasmas.

Association between domains of physical activity and all-cause, cardiovascular and cancer mortality.

PubMed

Autenrieth, Christine S; Baumert, Jens; Baumeister, Sebastian E; Fischer, Beate; Peters, Annette; Döring, Angela; Thorand, Barbara

2011-02-01

Few studies have investigated the independent effects of domain-specific physical activity on mortality. We sought to investigate the association of physical activity performed in different domains of daily living on all-cause, cardiovascular (CVD) and cancer mortality. Using a prospective cohort design, 4,672 men and women, aged 25-74 years, who participated in the baseline examination of the MONICA/KORA Augsburg Survey 1989/1990 were classified according to their activity level (no, light, moderate, vigorous). Domains of self-reported physical activity (work, transportation, household, leisure time) and total activity were assessed by the validated MOSPA (MONICA Optional Study on Physical Activity) questionnaire. After a median follow-up of 17.8 years, a total of 995 deaths occurred, with 452 from CVD and 326 from cancer. For all-cause mortality, hazard ratios and 95% confidence interval (HR, 95% CI) of the highly active versus the inactive reference group were 0.69 (0.48-1.00) for work, 0.48 (0.36-0.65) for leisure time, and 0.73 (0.59-0.90) for total activity after multivariable adjustments. Reduced risks of CVD mortality were observed for high levels of work (0.54, 0.31-0.93), household (0.80, 0.54-1.19), leisure time (0.50, 0.31-0.79) and total activity (0.75, 0.55-1.03). Leisure time (0.36, 0.23-0.59) and total activity (0.62, 0.43-0.88) were associated with reduced risks of cancer mortality. Light household activity was related to lower all-cause (0.82, 0.71-0.95) and CVD (0.72, 0.58-0.89) mortality. No clear effects were found for transportation activities. Our findings suggest that work, household, leisure time and total physical activity, but not transportation activity, may protect from premature mortality.

Improving care of post-infarct patients: effects of disease management programmes and care according to international guidelines.

PubMed

Stark, Renee; Kirchberger, Inge; Hunger, Matthias; Heier, Margit; Leidl, Reiner; von Scheidt, Wolfgang; Meisinger, Christa; Holle, Rolf

2014-03-01

Cardiac disease management programmes (CHD-DMPs) and secondary cardiovascular prevention guidelines aim to improve complex care of post-myocardial infarction (MI) patients. In Germany, CHD-DMPs, in addition to incorporating medical care according to guidelines (guideline-care), also ensure regular quarterly follow-up. Thus, our aim was to examine whether CHD-DMPs increase the frequency of guideline-care and whether CHD-DMPs and guideline-care improve survival over 4 years. The study included 975 post-MI patients, registered by the KORA-MI Registry (Augsburg, Germany), who completed a questionnaire in 2006. CHD-DMP enrolment was reported by physicians. Guideline-care was based on patient reports regarding medical advice (smoking, diet, or exercise) and prescribed medications (statins and platelet aggregation inhibitors plus beta-blockers or renin-angiotensin inhibitors). All-cause mortality until December 31, 2010 was based on municipal registration data. Cox regression analyses were adjusted for age, sex, education, years since last MI, and smoking and diabetes. Physicians reported that 495 patients were CHD-DMP participants. CHD-DMP participation increased the likelihood of receiving guideline-care (odds ratio 1.55, 95% CI 1.20; 2.02) but did not significantly improve survival (hazard rate 0.90, 95% CI 0.64-1.27). Guideline-care significantly improved survival (HR 0.41, 95% CI 0.28; 0.59). Individual guideline-care components, which significantly improved survival, were beta-blockers, statins and platelet aggregation inhibitors. However, these improved survival less than guideline-care. This study shows that CHD-DMPs increase the likelihood of guideline care and that guideline care is the important component of CHD-DMPs for increasing survival. A relatively high percentage of usual care patients receiving guideline-care indicate high quality of care of post-MI patients. Reasons for not implementing guideline-care should be investigated.

Disruption of Mouse Cytochrome P450 4f14 (Cyp4f14 Gene) Causes Severe Perturbations in Vitamin E Metabolism*

PubMed Central

Bardowell, Sabrina A.; Duan, Faping; Manor, Danny; Swanson, Joy E.; Parker, Robert S.

2012-01-01

Vitamin E is a family of naturally occurring and structurally related lipophilic antioxidants, one of which, α-tocopherol (α-TOH), selectively accumulates in vertebrate tissues. The ω-hydroxylase cytochrome P450–4F2 (CYP4F2) is the only human enzyme shown to metabolize vitamin E. Using cDNA cloning, cell culture expression, and activity assays, we identified Cyp4f14 as a functional murine ortholog of CYP4F2. We then investigated the effect of Cyp4f14 deletion on vitamin E metabolism and status in vivo. Cyp4f14-null mice exhibited substrate-specific reductions in liver microsomal vitamin E-ω-hydroxylase activity ranging from 93% (γ-TOH) to 48% (γ-tocotrienol). In vivo data obtained from metabolic cage studies showed whole-body reductions in metabolism of γ-TOH of 90% and of 68% for δ- and α-TOH. This metabolic deficit in Cyp4f14−/− mice was partially offset by increased fecal excretion of nonmetabolized tocopherols and of novel ω-1- and ω-2-hydroxytocopherols. 12′-OH-γ-TOH represented 41% of whole-body production of γ-TOH metabolites in Cyp4f14−/− mice fed a soybean oil diet. Despite these counterbalancing mechanisms, Cyp4f14-null mice fed this diet for 6 weeks hyper-accumulated γ-TOH (2-fold increase over wild-type littermates) in all tissues and appeared normal. We conclude that CYP4F14 is the major but not the only vitamin E-ω-hydroxylase in mice. Its disruption significantly impairs whole-body vitamin E metabolism and alters the widely conserved phenotype of preferential tissue deposition of α-TOH. This model animal and its derivatives will be valuable in determining the biological actions of specific tocopherols and tocotrienols in vivo. PMID:22665481

Long-term follow-up of HIV-1-infected adults who received the F4/AS01B HIV-1 vaccine candidate in two randomised controlled trials.

PubMed

Harrer, Thomas; Dinges, Warren; Roman, François

2018-05-03

This Phase I/II, open, long-term follow-up study was conducted in antiretroviral therapy (ART)-naïve (N = 212) and ART-treated (N = 19) human immunodeficiency virus 1 (HIV-1)-infected adults, who received an HIV-1 investigational vaccine (F4/AS01 B ) or placebo in two previous studies (NCT00814762 and NCT01218113). After a minimum of two years and a maximum of four years of follow-up post-vaccination per patient, no significant differences were observed between F4/AS01 B and placebo groups in terms of viral load, CD4 + T-cell count and incidence of specific clinical events. Vaccine-induced polyfunctional CD4 + T-cells persisted up to study end and no relevant vaccine-related safety events were reported in F4/AS01 B groups. This study has been registered at ClinicalTrials.gov (NCT01092611). Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Bioimpacts of dialyzer variety on phosphorus level in Iranian hemodialysis patients

PubMed Central

Pezeshgi, Aiyoub; Moharrami, Bahareh; Kolifarhood, Goodarz; Sadeghi, Alireza; Asadi-Khiavi, Masoud

2016-01-01

Introduction: Cardiovascular events are the major cause of death in patients with chronic renal failure. About half of dialysis patients because of reduced phosphorus clearance have hyperphosphatemia. Hyperphosphatemia and following secondary hyperparathyroidism lead to some cardiovascular changes. Hemodialysis (HD) partly removes phosphorus during each dialysis session. Objectives: Presented study was designed to evaluate dialyzer variation effect on phosphorus level as a prognostic factor after dialysis using. Materials and Methods: Six kinds of dialyzer were used for dialysis; low flux (LF) dialyzer (F7 and F8), high flux (HF) dialyzer (F70 and F80) and finally hollow-fiber dialyzers including polyethersulfone (PES) 130 HF and polysulfone (PS) 13 LF. Fifty-seven patients were divided into 6 matched groups included three groups of 10 people and 3 groups of 9 persons in groups: A (F70), B (F80), C (F7), D (F8), E (PES 130 HF) and F (PS 13 LF). Patients were treated for one month with these dialyzers. At the end of the month, blood samples were taken again for phosphorus level before dialysis handling. Results: The mean pre-dialysis serum phosphorus was 5.03, 5.4, 5.2, 4.6, 4.95 and 5.1 mg/dl and the mean phosphorus was 5.43, 5.01, 4.9, 4.18, 4.17 and 5.3 mg/dl after one month of dialysis, respectively in groups A to F without any statistically differences between pre- and after one month dialysis values respectively. Discussion: The findings indicate dialyzer type in the control of serum phosphorus has not been effective in the short-term HD. We suggest a study with more duration time. PMID:27471742

Bioimpacts of dialyzer variety on phosphorus level in Iranian hemodialysis patients.

PubMed

Pezeshgi, Aiyoub; Moharrami, Bahareh; Kolifarhood, Goodarz; Sadeghi, Alireza; Asadi-Khiavi, Masoud

2016-01-01

Cardiovascular events are the major cause of death in patients with chronic renal failure. About half of dialysis patients because of reduced phosphorus clearance have hyperphosphatemia. Hyperphosphatemia and following secondary hyperparathyroidism lead to some cardiovascular changes. Hemodialysis (HD) partly removes phosphorus during each dialysis session. Presented study was designed to evaluate dialyzer variation effect on phosphorus level as a prognostic factor after dialysis using. Six kinds of dialyzer were used for dialysis; low flux (LF) dialyzer (F7 and F8), high flux (HF) dialyzer (F70 and F80) and finally hollow-fiber dialyzers including polyethersulfone (PES) 130 HF and polysulfone (PS) 13 LF. Fifty-seven patients were divided into 6 matched groups included three groups of 10 people and 3 groups of 9 persons in groups: A (F70), B (F80), C (F7), D (F8), E (PES 130 HF) and F (PS 13 LF). Patients were treated for one month with these dialyzers. At the end of the month, blood samples were taken again for phosphorus level before dialysis handling. The mean pre-dialysis serum phosphorus was 5.03, 5.4, 5.2, 4.6, 4.95 and 5.1 mg/dl and the mean phosphorus was 5.43, 5.01, 4.9, 4.18, 4.17 and 5.3 mg/dl after one month of dialysis, respectively in groups A to F without any statistically differences between pre- and after one month dialysis values respectively. The findings indicate dialyzer type in the control of serum phosphorus has not been effective in the short-term HD. We suggest a study with more duration time.

Peptide stabilized amphotericin B nanodisks

PubMed Central

Tufteland, Megan; Pesavento, Joseph B.; Bermingham, Rachelle L.; Hoeprich, Paul D.; Ryan, Robert O.

2007-01-01

Nanometer scale apolipoprotein A-I stabilized phospholipid disk complexes (nanodisks; ND) have been formulated with the polyene antibiotic amphotericin B (AMB). The present studies were designed to evaluate if a peptide can substitute for the function of the apolipoprotein component of ND with respect to particle formation and stability. An 18-residue synthetic amphipathic α-helical peptide, termed 4F (Ac-D-W-F-K-A-F-Y-D-K-V-A-E-K-F-K-E-A-F-NH2), solubilized vesicles comprised of egg phosphatidylcholine (egg PC), dipentadecanoyl PC or dimyristoylphosphatidylcholine (DMPC) at rates greater than or equal to solubilization rates observed with human apolipoprotein A-I (apoA-I; 243 amino acids). Characterization studies revealed that interaction with DMPC induced a near doubling of 4F tryptophan fluorescence emission quantum yield (excitation 280 nm) and a ~7 nm blue shift in emission wavelength maximum. Inclusion of AMB in the vesicle substrate resulted in formation of 4F AMB-ND. Spectra of AMB containing particles revealed the antibiotic is a highly effective quencher of 4F tryptophan fluorescence emission, giving rise to a Ksv = 7.7 × 104. Negative stain electron microscopy revealed that AMB-ND prepared with 4F possessed a disk shaped morphology similar to ND prepared without AMB or prepared with apoA-I. In yeast and pathogenic fungi growth inhibition assays, 4F AMB-ND was as effective as apoA-I AMB-ND. The data indicate that AMB-ND generated using an amphipathic peptide in lieu of apoA-I form a discrete population of particles that possess potent biological activity. Given their intrinsic versatility, peptides may be preferred for scale up and clinical application of AMB-ND. PMID:17293004

Semisolid matrix filled capsules: an approach to improve dissolution stability of phenytoin sodium formulation.

PubMed

El Massik, M A; Abdallah, O Y; Galal, S; Daabis, N A

2003-05-01

Seven semisolid fill bases were selected for the formulation of 24 capsule formulations, each containing 100 mg of phenytoin sodium. The fill materials were selected based on the water absorption capacity of their mixtures with phenytoin sodium. The fill matrices included lipophilic bases (castor oil, soya oil, and Gelucire (G) 33/01), amphiphilic bases (G 44/14 and Suppocire BP), and water-soluble bases (PEG 4000 and PEG 6000). The drug:base ratio was 1:2. Excipients such as lecithin, docusate sodium, and poloxamer 188 were added to some formulations. The dissolution rate study indicated that formulations containing lipophilic and amphiphilic bases showed the best release profiles. These are F4 (castor oil-1% docusate sodium); F10 (castor oil-3% poloxamer 188); F14 (G33/01-10% lecithin); F17 (G33/01-1% docusate sodium), and F20 (Suppocire BP). Further, the dissolution stability of the five formulations above was assessed by an accelerated stability study at 30 degrees C and 75% RH using standard Epanutin capsules for comparison. The study included the test and standard capsules either packed in the container of marketed Epanutin capsules (packed) or removed from their outer pack (unpacked). Release data indicated superior release rates of castor oil based formulations (F4 and F10) relative to standard capsules in both the unpacked and packed forms. For instance, the extent of drug release at 30 min after 1 month was 91% for F4 and F10 and 20% for standard capsules. Drug release from packed capsules after 6 months storage was 88% for both formulations F4 and F10 and 35% for standard capsules. In conclusion, the pharmaceutical quality of phenytoin sodium capsules can be improved by using a semisolid lipophilic matrix filled in hard gelatin capsules.

Binding of 2-[18F]fluoro-CP-118,954 to mouse acetylcholinesterase: microPET and ex vivo Cerenkov luminescence imaging studies.

PubMed

Kim, Dong Hyun; Choe, Yearn Seong; Choi, Joon Young; Lee, Kyung-Han; Kim, Byung-Tae

2011-05-01

Acetylcholinesterase (AChE) has been an important cholinergic factor for the diagnosis of Alzheimer's disease (AD), because of reduced AChE activity in the postmortem brains of AD patients. We previously developed 5,7-dihydro-3-(2-(1-(2-[(18)F]fluorobenzyl)-4-piperidinyl)ethyl)-6H-pyrrolo(3,2,f)-1,2-benzisoxazol-6-one (2-[(18)F]fluoro-CP-118,954) for in vivo studies of AChE in mice. In the present study, we automated the synthesis of 2-[(18)F]fluoro-CP-118,954 for the routine use and evaluated the radioligand by microPET and ex vivo Cerenkov luminescence imaging of mouse AChE. 4-[(18)F]Fluoro-donepezil, another AChE inhibitor, was used for comparison. Automated syntheses of 2-[(18)F]fluoro-CP-118,954 and 4-[(18)F]fluoro-donepezil resulted in high radiochemical yields (25-33% and 30-40%) and high specific activity (27.1-35.4 and 29.7-37.3 GBq/μmol). Brain microPET images of two ICR mice injected with 2-[(18)F]fluoro-CP-118,954 demonstrated high uptake in the striatum (ROI analysis: 5.1 %ID/g for the first 30 min and 4.1 %ID/g for another 30 min), and a blocking study with injection of CP-118,954 into one of the mice at 30 min after radioligand injection led to complete blocking of radioligand uptake in the striatum (ROI analysis: 1.9 %ID/g), whereas (18)F-labeled donepezil did not show specific uptake in the striatum. In another set of experiments, the brain tissues (striatum, parietal cortex, frontal cortex and cerebellum) were excised after brain microPET/CT imaging of mouse injected with 2-[(18)F]fluoro-CP-118,954, and a high striatal uptake was also detected in ex vivo optical and microPET images (ROI analysis: 1.4 %ID/g) and in γ-counting data (2.1 %ID/g at 50 min post-injection) of the brain tissues. Taken together, these results demonstrated that 2-[(18)F]fluoro-CP-118,954 specifically binds to AChE in mouse brains. Copyright © 2011 Elsevier Inc. All rights reserved.

Novel duplex vapor-electrochemical method for silicon solar cells

NASA Technical Reports Server (NTRS)

Kapur, V. K.; Nanis, L.; Sanjurjo, A.

1977-01-01

Silicon obtained by the SiF4-Na reaction was analyzed by spark source mass spectrometry (SSMS). Silicon samples prepared from induction melted powder were evaluated for electrical properties using four point probe conductivity and thermoelectric methods. SiF4-Na reaction under P sub SiF4 greater than 1 atmosphere. The amount of silicon produced was increased from 25 g per batch (in the glass reactor) to greater than 70 g per batch in the stainless steel reactor. The study of the effects of reaction variables such as P sub SiF4 and maximum temperature attained on the particle size of silicon powder showed that the silicon particle size tends to grow larger with increasing pressure of the SiF4 gas in the reaction system.

Cumulative Brain Injury from Motor Vehicle-Induced Whole-Body Vibration and Prevention by Human Apolipoprotein A-I Molecule Mimetic (4F) Peptide (an Apo A-I Mimetic)

PubMed Central

Yan, Ji-Geng; Zhang, Lin-ling; Agresti, Michael; Yan, Yuhui; LoGiudice, John; Sanger, James R.; Matloub, Hani S.; Pritchard, Kirkwood A.; Jaradeh, Safwan S.; Havlik, Robert

2017-01-01

Background Insidious cumulative brain injury from motor vehicle-induced whole-body vibration (MV-WBV) has not yet been studied. The objective of the present study is to validate whether whole-body vibration for long periods causes cumulative brain injury and impairment of the cerebral function. We also explored a preventive method for MV-WBV injury. Methods A study simulating whole-body vibration was conducted in 72 male Sprague-Dawley rats divided into 9 groups (N = 8): (1) 2-week normal control; (2) 2-week sham control (in the tube without vibration); (3) 2-week vibration (exposed to whole-body vibration at 30 Hz and .5 G acceleration for 4 hours/day, 5 days/week for 2 weeks; vibration parameters in the present study are similar to the most common driving conditions); (4) 4-week sham control; (5) 4-week vibration; (6) 4-week vibration with human apolipoprotein A-I molecule mimetic (4F)-preconditioning; (7) 8-week sham control; (8) 8-week vibration; and (9) 8-week 4F-preconditioning group. All the rats were evaluated by behavioral, physiological, and histological studies of the brain. Results Brain injury from vibration is a cumulative process starting with cerebral vasoconstriction, squeezing of the endothelial cells, increased free radicals, decreased nitric oxide, insufficient blood supply to the brain, and repeated reperfusion injury to brain neurons. In the 8-week vibration group, which indicated chronic brain edema, shrunken neuron numbers increased and whole neurons atrophied, which strongly correlated with neural functional impairment. There was no prominent brain neuronal injury in the 4F groups. Conclusions The present study demonstrated cumulative brain injury from MV-WBV and validated the preventive effects of 4F preconditioning. PMID:26433438

Thermodynamic assessment of the LiF-ThF4-PuF3-UF4 system

NASA Astrophysics Data System (ADS)

Capelli, E.; Beneš, O.; Konings, R. J. M.

2015-07-01

The LiF-ThF4-PuF3-UF4 system is the reference salt mixture considered for the Molten Salt Fast Reactor (MSFR) concept started with PuF3. In order to obtain the complete thermodynamic description of this quaternary system, two binary systems (ThF4-PuF3 and UF4-PuF3) and two ternary systems (LiF-ThF4-PuF3 and LiF-UF4-PuF3) have been assessed for the first time. The similarities between CeF3/PuF3 and ThF4/UF4 compounds have been taken into account for the presented optimization as well as in the experimental measurements performed, which have confirmed the temperatures predicted by the model. Moreover, the experimental results and the thermodynamic database developed have been used to identify potential compositions for the MSFR fuel and to evaluate the influence of partial substitution of ThF4 by UF4 in the salt.

Tumor cell-released TLR4 ligands stimulate Gr-1+CD11b+F4/80+ cells to induce apoptosis of activated T cells.

PubMed

Liu, Yan-Yan; Sun, Ling-Cong; Wei, Jing-Jing; Li, Dong; Yuan, Ye; Yan, Bin; Liang, Zhi-Hui; Zhu, Hui-Fen; Xu, Yong; Li, Bo; Song, Chuan-Wang; Liao, Sheng-Jun; Lei, Zhang; Zhang, Gui-Mei; Feng, Zuo-Hua

2010-09-01

Gr-1(+)CD11b(+)F4/80(+) cells play important roles in tumor development and have a negative effect on tumor immunotherapy. So far, the mechanisms underlying the regulation of their immunosuppressive phenotype by classical and alternative macrophage activation stimuli are not well elucidated. In this study, we found that molecules from necrotic tumor cells (NTC-Ms) stimulated Gr-1(+)CD11b(+)F4/80(+) cells to induce apoptosis of activated T cells but not nonstimulated T cells. The apoptosis-inducing capacity was determined by higher expression levels of arginase I and IL-10 relative to those of NO synthase 2 and IL-12 in Gr-1(+)CD11b(+)F4/80(+) cells, which were induced by NTC-Ms through TLR4 signaling. The apoptosis-inducing capacity of NTC-Ms-stimulated Gr-1(+)CD11b(+)F4/80(+) cells could be enhanced by IL-10. IFN-gamma may reduce the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells only if their response to IFN-gamma was not attenuated. However, the potential of Gr-1(+)CD11b(+)F4/80(+) cells to express IL-12 in response to IFN-gamma could be attenuated by tumor, partially due to the existence of active STAT3 in Gr-1(+)CD11b(+)F4/80(+) cells and NTC-Ms from tumor. In this situation, IFN-gamma could not effectively reduce the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells. Tumor immunotherapy with 4-1BBL/soluble programmed death-1 may significantly reduce, but not abolish the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells in local microenvironment. Blockade of TLR4 signaling could further reduce the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells and enhance the suppressive effect of 4-1BBL/soluble form of programmed death-1 on tumor growth. These findings indicate the relationship of distinct signaling pathways with apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells and emphasize the importance of blocking TLR4 signaling to prevent the induction of T cell apoptosis by Gr-1(+)CD11b(+)F4/80(+) cells.

Effect of Different Torque Settings on Crack Formation in Root Dentin.

PubMed

Dane, Asım; Capar, Ismail Davut; Arslan, Hakan; Akçay, Merve; Uysal, Banu

2016-02-01

The aim of the present study was to observe the incidence of cracks in root canal dentin using the ProTaper Universal system (Dentsply Maillefer, Ballaigues, Switzerland) at low- and high-torque settings. Sixty-nine mandibular premolar teeth that had been extracted for different reasons were selected. The teeth were divided into 3 groups: an unprepared control group, a low-torque settings group (SX = 3, S1 = 2, S2 = 1, F1 = 1.5, F2 = 2, F3 = 2, F4 = 2 N/cm), and a high-torque settings group (SX = 4, S1 = 4, S2 = 1.5, F1 = 2, F2 = 3, F3 = 3, F4 = 3 N/cm). After a root canal procedure, all the teeth were horizontally sectioned at 2, 4, 6, and 8 mm from the apex. Then, under a stereomicroscope, all the slices were examined to determine the presence of cracks. A chi-square test was used for data analysis. The significance level was set at P = .05. There were no cracks in the unprepared control group. Vertical root fractures were not observed in any of the groups. There were significantly fewer cracks (17.4% of the sections) in the low-torque group than in the high-torque group (29.4% of the sections) (P < .05). In this in vitro study, the instrumentation of root canals with the ProTaper Universal instrument caused more crack formation in root canal dentin at high-torque than at low-torque settings. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

[REAL TIME POLYMERASE CHAIN REACTION IN TULAREMIA LABORATORY DIAGNOSTICS].

PubMed

Kormilitsyna, M I; Mescheryakova, I S; Mikhailova, T V; Dobrovolsky, A A

2015-01-01

Enhancement of tularemia laboratory diagnostics by F. tularensis DNA determination in blood sera of patients using real time polymerase chain reaction (RT-PCR). 39 blood sera of patients obtained during transmissive epidemic outbreak of tularemia in Khanty-Mansiysk in 2013 were studied in agglutination reaction, passive hemagglutination, RT-PCR. Specific primers and fluorescent probes were used: ISFTu2F/R+ISFTu2P, Tu14GF/R+tul4-PR2. Advantages of using RT-PCR for early diagnostics of tularemia, when specific antibodies are not detected using traditional immunologic methods, were established. Use of a combination of primers and ISFTu2F/R+ISFTu2P probe allowed to detect F. tularensis DNA in 100% of sera, whereas Tul4G F/R+tul4-PR2 combination--92% of sera. The data were obtained when DNA was isolated from sera using "Proba Rapid" express method. Clinical-epidemiologic diagnosis oftularemia was confirmed by both immune-serologic and RT-PCR methods when sera were studied 3-4 weeks after the onset of the disease. RT-PCR with ISFTu2F/R primers and fluorescent probe ISFTu2P, having high sensitivity and specificity, allows to determine F. tularensis DNA in blood sera of patients at both the early stage and 3-4 weeks after the onset of the disease.

[Characteristics and comparative study of a new drinking-water defluoridation adsorbent Bio-F].

PubMed

Zhu, Chi; Zhao, Liang-Yuan; Yuan, Heng; Yang, Han-Ying; Li, Ang; Wang, Peng; Yang, Shao

2009-04-15

To evaluate the application potentiality pf a new type drinking-water defluoridation adsorbent Bio-F, comparative study on the defluoridation characteristics of common adsorbents activated alumina (AA), bone char (BC), activated clinoptilolite (AC) with Bio-F was conducted. The defluoridation characteristics under different conditions, such as particle diameter, pH, retention time, fluorine concentration, regeneration stability, were investigated by continuous-flow column experiments and static tests. The defluoridation efficiency of high fluoride underground water by four types of adsorbents was also compared. The results showed that F(-) adsorption kinetics of Bio-F fitted the Lagergren First-order equation (R2 = 0.9580). F(-) adsorption by Bio-F was found to fit the Langmuir adsorption isotherm (R2 = 0.9992). The results indicated that the static defluoridation capacity (DC) of Bio-F was 4.0883 mg x g(-1), which was about 1.8 folds and 5.8 folds of those of AA and AC respectively. DC of all four adsorbents was positively correlated with F(-) concentration and negatively correlated with particle size. High concentration of CO3(2-) and HCO3(-) reduced the DC of Bio-F (p < 0.05), while high concentration of Ca2+, NO3(-), HPO4(2-) favored defluoridation by Bio-F (p < 0.001). The optimal retention time of Bio-F was 3-4 min, which was less than that of AC (20 min) and AA (11 min). The DC of Bio-F remained relatively stable in pH 4.0-9.0 and in regeneration since the DC variation was not more than 15%. The above results indicated that Bio-F was superior to AA, BC and AC in drinking-water defluoridation.

Crystallization of heavy metal fluoride glasses

NASA Technical Reports Server (NTRS)

Bansal, Narottam P.; Bruce, Allan J.; Doremus, R. H.; Moynihan, C. T.

1984-01-01

The kinetics of crystallization of a number of fluorozirconate glasses were studied using isothermal and dynamic differential scanning calorimetry and X-ray diffraction. The addition of the fluorides LiF, NaF, AlF3, LaF3 to a base glass composition of ZrF4-BaF2 reduced the tendency to crystallize, probably by modifying the viscosity-temperature relation. ZrF4-BaF2-LaF3-AlF3-NaF glass was the most stable against devitrification and perhaps is the best composition for optical fibers with low scattering loss. Some glasses first crystallize out into metastable beta-BaZr2F10 and beta-BaZrF6 phases, which transform into the most stable alpha-phases when heated to higher temperatures. The size of the crystallites was estimated to be about 600 A from X-ray diffraction.

Metabolomic studies for the interaction Glycine max- Fusarium tucumaniae

USDA-ARS?s Scientific Manuscript database

Sudden-death syndrome (SDS) of soybean can be caused in Argentina by 4 different Fusarium species: F. brasiliense, F. crassistipitatum, F. tucumaniae and F. virguliforme. Fusarium tucumaniae and F. virguliforme are the primary etiological agents of soybean SDS in Argentina and United States, respect...

Techniques for the Analysis of Expendable Bathythermograph (XBT) Data with Applications to the South-Western Pacific Ocean.

DTIC Science & Technology

1981-09-01

F6 .O...4X,F5.2,5X,F5 .2,SX,F6.3,4X,F8.6,2X,F8.6,2X,F7.3, Z5X,F5.1,4X,F5.2,3X,F7.2,4X, F6 .3, 4X , F6 .4) 340 FORMAT( F6 .O,F5.2,F5.2,F6.3,F8.6,F8.6,F7.3, ZF5. 1...New York NY� 3 Data Courier Inc, Louisville Ky 40202 4 In Malaysia The Director, Defence Research Centre, Malaysia 5 In Australia Chief

TiF(4) varnish-A (19)F-NMR stability study and enamel reactivity evaluation.

PubMed

Nóbrega, Carolina Bezerra Cavalcanti; Fujiwara, Fred Yukio; Cury, Jaime Aparecido; Rosalen, Pedro Luiz

2008-01-01

The aim of this study was to develop a titanium tetrafluoride (TiF(4)) varnish and evaluate the stability of the formulation and its reactivity with dental enamel. The varnish was prepared in a resinous matrix using ethanol 96% as solvent. Samples (n=45) were aged at 65 degrees C and 30% of relativity humidity (RE n degrees 01/05-ANVISA) and after 3, 6, 9 and 12 months, nine samples were removed for evaluation and compared with fresh samples. Chemical stability of TiF(4) varnish was determinate by (19)F-NMR and the reactivity of the formulation was quantified by formation of fluoride loosely (CaF(2)) and firmly bound (fluorapatite; FA) to enamel. For reactivity comparisons, a varnish without TiF(4) was used as control. The loss of soluble fluoride was about 0.9% after one year of storage. The values of the reactivity (mean+/-S.D.) of fresh, aged at 3, 6, 9 and 12 months and control samples were: CaF(2) (microg F/mm(2)): 89.3+/-27.5(a); 54.5+/-14.3(b); 51.2+/-29.8(b); 69.3+/-21.3(a); 48.0+/-27.4(b); 0.10+/-0.07(c), FA (microg F/g): 2477.5+/-1044.0(a); 2484.8+/-992.0(a); 2580.0+/-1383.9(a); 2517.2+/-929.9(a); 2121.0+/-1059.2(a); 330.0+/-180.0(b), respectively. Means followed by distinct letters were statistically different (p<0.05). After one year of storage, the formulation was chemically stable and the levels of FA were maintained. However there was an initial decrease in the ability to form CaF(2).

Accuracy of transient elastography-FibroScan®, acoustic radiation force impulse (ARFI) imaging, the enhanced liver fibrosis (ELF) test, APRI, and the FIB-4 index compared with liver biopsy in patients with chronic hepatitis C.

PubMed

Ragazzo, Taisa Grotta; Paranagua-Vezozzo, Denise; Lima, Fabiana Roberto; de Campos Mazo, Daniel Ferraz; Pessoa, Mário Guimarães; Oliveira, Claudia Pinto; Alves, Venancio Avancini Ferreira; Carrilho, Flair José

2017-10-01

Although liver biopsy is the gold standard for determining the degree of liver fibrosis, issues regarding its invasiveness and the small amount of liver tissue evaluated can limit its applicability and interpretation in clinical practice. Non-invasive evaluation methods for liver fibrosis can address some of these limitations. The aim of this study was to evaluate the accuracy of transient elastography-FibroScan®, acoustic radiation force impulse (ARFI), enhanced liver fibrosis (ELF), the aspartate aminotransferase-to-platelet ratio index (APRI), and the FIB-4 index compared with liver biopsy in hepatitis C. We evaluated chronic hepatitis C patients who were followed at the Division of Clinical Gastroenterology and Hepatology, Hospital das Clínicas, Department of Gastroenterology of University of São Paulo School of Medicine, São Paulo, Brazil, and who underwent liver biopsy. The accuracy of each method was determined by a receiver operating characteristic (ROC) curve analysis, and fibrosis was classified as significant fibrosis (≥F2), advanced fibrosis (≥F3), or cirrhosis (F4). The Obuchowski method was also used to determine the diagnostic accuracy of each method at the various stages of fibrosis. In total, 107 FibroScan®, 51 ARFI, 68 ELF, 106 APRI, and 106 FIB-4 analyses were performed. A total of 107 patients were included in the study. The areas under the ROC curve (AUROCs) according to fibrosis degree were as follows: significant fibrosis (≥F2): FibroScan®: 0.83, FIB-4: 0.76, ELF: 0.70, APRI: 0.69, and ARFI: 0.67; advanced fibrosis (≥F3): FibroScan®: 0.85, ELF: 0.82, FIB-4: 0.77, ARFI: 0.74, and APRI: 0.71; and cirrhosis (F4): APRI: 1, FIB-4: 1, FibroScan®: 0.99, ARFI: 0.96, and ELF: 0.94. The accuracies of transient elastography, ARFI, ELF, APRI and FIB-4 determined by the Obuchowski method were F0-F1: 0.81, 0.78, 0.44, 0.72 and 0.67, respectively; F1-F2: 0.73, 0.53, 0.62, 0.60, and 0.68, respectively; F2-F3: 0.70, 0.64, 0.77, 0.60, and 0.67, respectively; and F3-F4: 0.98, 0.96, 0.82, 1, and 1, respectively. Transient elastography remained the most effective method for evaluating all degrees of fibrosis. The accuracy of all methodologies was best at F4.

Ion chemistry in germane/fluorocompounds gaseous mixtures: a mass spectrometric and theoretical study.

PubMed

Antoniotti, Paola; Rabezzana, Roberto; Turco, Francesca; Borocci, Stefano; Giordani, Maria; Grandinetti, Felice

2008-10-01

The ion-molecule reactions occurring in GeH(4)/NF(3), GeH(4)/SF(6), and GeH(4)/SiF(4) gaseous mixtures have been investigated by ion trap mass spectrometry and ab initio calculations. While the NF(x)(+) (x=1-3) react with GeH(4) mainly by the exothermic charge transfer, the open-shell Ge(+) and GeH(2)(+) undergo the efficient F-atom abstraction from NF(3) and form GeF(+) and F-GeH(2)(+) as the only ionic products. The mechanisms of these two processes are quite similar and involve the formation of the fluorine-coordinated complexes Ge-F-NF(2)(+) and H(2)Ge-F-NF(2)(+), their subsequent crossing to the significantly more stable isomers FGe-NF(2)(+) and F-GeH(2)-NF(2)(+), and the eventual dissociation of these ions into GeF(+) (or F-GeH(2)(+)) and NF(2). The closed-shell GeH(+) and GeH(3)(+) are instead much less reactive towards NF(3), and the only observed process is the less efficient formation of GeF(+) from GeH(+). The theoretical investigation of this unusual H/F exchange reaction suggests the involvement of vibrationally-hot GeH(+). Passing from NF(3) to SF(6) and SiF(4), the average strength of the M-F bond increases from 70 to 79 and 142 kcal mol(-1), and in fact the only process observed by reacting GeH(n)(+) (n=0-3) with SF(6) and SiF(4) is the little efficient F-atom abstraction from SF(6) by Ge(+). Irrespective of the experimental conditions, we did not observe any ionic product of Ge-N, Ge-S, or Ge-Si connectivity. This is in line with the previously observed exclusive formation of GeF(+) from the reaction between Ge(+) and C-F compounds such as CH(3)F. Additionally observed processes include in particular the conceivable formation of the elusive thiohypofluorous acid FSH from the reaction between SF(+) and GeH(4).

Psychoneuropharmacological activities and chemical composition of essential oil of fresh fruits of Piper guineense (Piperaceae) in mice.

PubMed

Oyemitan, Idris Ajayi; Olayera, Omotola Aanuoluwa; Alabi, Akeeb; Abass, Luqman Adewale; Elusiyan, Christianah Abimbola; Oyedeji, Adebola Omowumi; Akanmu, Moses Atanda

2015-05-26

Piper guineense Schum & Thonn (Piperaceae) is a medicinal plant used in the Southern States of Nigeria to treat fever, mental disorders and febrile convulsions. This study aims at determining the chemical composition and the central nervous system (CNS) activities of the essential oil obtained from the plant׳s fresh fruits in order to rationalize its folkloric use. Essential oil of P. guineense (EOPG) obtained by hydrodistillation was analysed by GC/MS. EOPG (50-200mg/kg, i.p.) was evaluated for behavioural, hypothermic, sedative, muscle relaxant, anti-psychotic and anticonvulsant activities using standard procedures. Analysis of the oil reveals 44 compounds of which 30 compounds constituting 84.7% were identified. The oil was characterized by sesquiterpenoids (64.4%) while only four monoterpeneoids (21.3%) were found present in the oil. Major compounds identified were β-sesquiphellandrene (20.9%), linalool (6.1%), limonene (5.8%), Z-β-bisabolene (5.4%) and α-pinene (5.3%). The EOPG (50-200mg/kg, i.p.) caused significant (p<0.01) inhibition on rearing {F(4,20)=43}, locomotor {F(4,20)=22} activity and decreased head dips in hole board {F(4,20)=7} indicating CNS depressant effect; decreased rectal temperature {F(4,20)=7-16}, signifying hypothermic activity; decreased ketamine-induced sleep latency {F(4,20)=7.8} and prolonged total sleeping time {F(4,20)=8.8}, indicating sedative effect; reduced muscular tone on the hind-limb grip test {F(4,20)=22}, inclined board {F(4,20)=4-49} and rota rod {F(4,20)=13-106}, implying muscle relaxant activity; induced catalepsy {F(4,20)=47-136}, inhibited apomorphine-induced climbing behaviour {F(4,20)=9} and inhibited apomorphine-induced locomotor {F(4,20)=16}, suggesting anti-psychotic effect; and protected mice against pentylenetetrazole-induced convulsions, indicating anticonvulsant potential. The most abundant component of the fresh fruits essential oil of P. guineense was β-sesquiphellandrene (20.9%); and the oil possesses CNS depressant, hypothermic, sedative, muscle relaxant, antipsychotic and anticonvulsant activities, thus providing scientific basis for its ethnomedicinal applications. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Peracetylated 4-Fluoro-glucosamine Reduces the Content and Repertoire of N- and O-Glycans without Direct Incorporation*

PubMed Central

Barthel, Steven R.; Antonopoulos, Aristotelis; Cedeno-Laurent, Filiberto; Schaffer, Lana; Hernandez, Gilberto; Patil, Shilpa A.; North, Simon J.; Dell, Anne; Matta, Khushi L.; Neelamegham, Sriram; Haslam, Stuart M.; Dimitroff, Charles J.

2011-01-01

Prior studies have shown that treatment with the peracetylated 4-fluorinated analog of glucosamine (4-F-GlcNAc) elicits anti-skin inflammatory activity by ablating N-acetyllactosamine (LacNAc), sialyl Lewis X (sLeX), and related lectin ligands on effector leukocytes. Based on anti-sLeX antibody and lectin probing experiments on 4-F-GlcNAc-treated leukocytes, it was hypothesized that 4-F-GlcNAc inhibited sLeX formation by incorporating into LacNAc and blocking the addition of galactose or fucose at the carbon 4-position of 4-F-GlcNAc. To test this hypothesis, we determined whether 4-F-GlcNAc is directly incorporated into N- and O-glycans released from 4-F-GlcNAc-treated human sLeX (+) T cells and leukemic KG1a cells. At concentrations that abrogated galectin-1 (Gal-1) ligand and E-selectin ligand expression and related LacNAc and sLeX structures, MALDI-TOF and MALDI-TOF/TOF mass spectrometry analyses showed that 4-F-GlcNAc 1) reduced content and structural diversity of tri- and tetra-antennary N-glycans and of O-glycans, 2) increased biantennary N-glycans, and 3) reduced LacNAc and sLeX on N-glycans and on core 2 O-glycans. Moreover, MALDI-TOF MS did not reveal any m/z ratios relating to the presence of fluorine atoms, indicating that 4-F-GlcNAc did not incorporate into glycans. Further analysis showed that 4-F-GlcNAc treatment had minimal effect on expression of 1200 glycome-related genes and did not alter the activity of LacNAc-synthesizing enzymes. However, 4-F-GlcNAc dramatically reduced intracellular levels of uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc), a key precursor of LacNAc synthesis. These data show that Gal-1 and E-selectin ligand reduction by 4-F-GlcNAc is not caused by direct 4-F-GlcNAc glycan incorporation and consequent chain termination but rather by interference with UDP-GlcNAc synthesis. PMID:21493714

AST-platelet ratio index, Forns index and FIB-4 in the prediction of significant fibrosis and cirrhosis in patients with chronic hepatitis C.

PubMed

Güzelbulut, Fatih; Çetınkaya, Züleyha Akkan; Sezıklı, Mesut; Yaşar, Bülent; Ozkara, Selvinaz; Övünç, Ayşe Oya Kurdaş

2011-06-01

The aim of this study was to evaluate the diagnostic accuracy of aspartate aminotransferase-platelet ratio index, the Forns index and FIB-4 for the assessment of hepatic fibrosis in chronic hepatitis C patients by comparison with liver biopsy. We retrospectively reviewed our computerized data of chronic hepatitis C patients who admitted to the Gastroenterology Clinic between 2004 and 2008. Treatment-naive chronic hepatitis C patients who had undergone liver biopsy and had laboratory test results allowing the calculation of aspartate aminotransferase-platelet ratio index, the Forns index and FIB-4 were included in this study. The degree of fibrosis was scored according to the METAVIR staging system. Significant fibrosis was defined as F2-4 and cirrhosis as F4. Aspartate aminotransferase-platelet ratio index, the Forns index and FIB-4 were calculated based on the original studies. Tests results were compared between groups F0-1 (no or mild fibrosis) versus F2-4 (significant fibrosis) and F03 (no cirrhosis) versus F4 (cirrhosis). One hundred and fifty patients with chronic hepatitis C were included in this study. The areas under the ROC curves of the Forns index, aspartate aminotransferase-platelet ratio index and FIB-4 to predict significant fibrosis were 0.795, 0.774 and 0.764, respectively. The area under the ROC curves of the Forns index, aspartate aminotransferase-platelet ratio index and FIB-4 to predict cirrhosis were 0.879, 0.839 and 0.874, respectively. The Forns index, aspartate aminotransferase-platelet ratio index and FIB-4 were accurate noninvasive blood tests to predict the presence or absence of significant fibrosis and cirrhosis in half of the chronic hepatitis C patients. The Forns index was slightly better than the aspartate aminotransferase-platelet ratio index and FIB-4 in the prediction of significant fibrosis and cirrhosis.

In vitro and in vivo anti-inflammatory activities of high molecular weight sulfated polysaccharide; containing fucose separated from Sargassum horneri: Short communication.

PubMed

Sanjeewa, K K Asanka; Fernando, I P S; Kim, Seo-Young; Kim, Hyun-Soo; Ahn, Ginnae; Jee, Youngheun; Jeon, You-Jin

2018-02-01

Recent studies on crude and pure compounds from Sargassum horneri have shown promising bioactive properties. However, anti-inflammatory potentials of fucose-rich sulfated polysaccharides from S. horneri have not yet been discovered. In the present study, we evaluated the in vitro and in vivo anti-inflammatory activities of four polysaccharide fractions separated from membrane filters according to their molecular weights (<5kDa (f1), 5-10kDa (f2), 10-30kDa (f3), and >30kDa (f4)). According to the results, F4 fraction inhibited the lipopolysaccharides (LPS)-induced nitric oxide (NO) (IC 50 =87.12μg/mL) and prostaglandin E 2 production as well as pro-inflammatory cytokine production in RAW 264.7 cells through down-regulating nuclear factor-κB signaling cascade. According to the results, f4 has a potential to down-regulate LPS-induced toxicity, cell death and NO production levels in LPS-induced in vivo zebrafish embryo model. These results suggest that f4 fraction has the potential to develop functional materials or drugs to treat inflammatory diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of zirconia based phosphors for application in lighting and as luminescent bioprobes =

NASA Astrophysics Data System (ADS)

Soares, Maria Rosa Nunes

The strong progress evidenced in photonic and optoelectronic areas, accompanied by an exponential development in the nanoscience and nanotechnology, gave rise to an increasing demand for efficient luminescent materials with more and more exigent characteristics. In this field, wide band gap hosts doped with lanthanide ions represent a class of luminescent materials with a strong technological importance. Within wide band gap material, zirconia owns a combination of physical and chemical properties that potentiate it as an excellent host for the aforementioned ions, envisaging its use in different areas, including in lighting and optical sensors applications, such as pressure sensors and biosensors. Following the demand for outstanding luminescent materials, there is also a request for fast, economic and an easy scale-up process for their production. Regarding these demands, laser floating zone, solution combustion synthesis and pulsed laser ablation in liquid techniques are explored in this thesis for the production of single crystals, nanopowders and nanoparticles of lanthanides doped zirconia based hosts. Simultaneously, a detailed study of the morphological, structural and optical properties of the produced materials is made. The luminescent characteristics of zirconia and yttria stabilized zirconia (YSZ) doped with different lanthanide ions (Ce3+ (4f1), Pr3+ (4f2), Sm3+ (4f5), Eu3+ (4f6), Tb3+ (4f8), Dy3+ (4f9), Er3+ (4f11), Tm3+ (4f12), Yb3+ (4f13)) and co-doped with Er3+,Yb3+ and Tm3+,Yb3+ are analysed. Besides the Stokes luminescence, the anti- Stokes emission upon infrared excitation (upconversion and black body radiation) is also analysed and discussed. The comparison of the luminescence characteristics in materials with different dimensions allowed to analyse the effect of size in the luminescent properties of the dopant lanthanide ions. The potentialities of application of the produced luminescent materials in solid state light, biosensors and pressure sensors are explored taking into account their studied characteristics.

Reverse-D-4F Increases the Number of Endothelial Progenitor Cells and Improves Endothelial Progenitor Cell Dysfunctions in High Fat Diet Mice.

PubMed

Nana, Yang; Peng, Jiao; Jianlin, Zhang; Xiangjian, Zhang; Shutong, Yao; Enxin, Zhan; Bin, Li; Chuanlong, Zong; Hua, Tian; Yanhong, Si; Yunsai, Du; Shucun, Qin; Hui, Wang

2015-01-01

Although high density lipoprotein (HDL) improves the functions of endothelial progenitor cells (EPCs), the effect of HDL ApoAI mimetic peptide reverse-D-4F (Rev-D4F) on EPC mobilization and repair of EPC dysfunctions remains to be studied. In this study, we investigated the effects of Rev-D4F on peripheral blood cell subpopulations in C57 mice treated with a high fat diet and the mechanism of Rev-D4F in improving the function of EPCs impaired by tumor necrosis factor-α (TNF-α). The high fat diet significantly decreased the number of EPCs, EPC migratory functions, and the percentage of lymphocytes in the white blood cells. However, it significantly increased the number of white blood cells, the percentage of monocytes in the white blood cells, and the level of vascular endothelial growth factor (VEGF) and TNF-α in the plasma. Rev-D4F clearly inhibited the effect of the high fat diet on the quantification of peripheral blood cell subpopulations and cytokine levels, and increased stromal cell derived factor 1α (SDF-1α) in the plasma. We provided in vitro evidence that TNF-α impaired EPC proliferation, migration, and tube formation through inactive AKT and eNOS, which was restored by Rev-D4F treatment. In contrast, both the PI3-kinase (PI3K) inhibitor (LY294002) and AKT inhibitor (perifosine) obviously inhibited the restoration of Rev-4F on EPCs impaired by TNF-α. Our results suggested that Rev-D4F increases the quantity of endothelial progenitor cells through increasing the SDF-1α levels and decreasing the TNF-α level of peripheral blood in high fat diet-induced C57BL/6J mice, and restores TNF-α induced dysfunctions of EPCs partly through stimulating the PI3K/AKT signal pathway.

3d-4f magnetic interaction with density functional theory plus u approach: local Coulomb correlation and exchange pathways.

PubMed

Zhang, Yachao; Yang, Yang; Jiang, Hong

2013-12-12

The 3d-4f exchange interaction plays an important role in many lanthanide based molecular magnetic materials such as single-molecule magnets and magnetic refrigerants. In this work, we study the 3d-4f magnetic exchange interactions in a series of Cu(II)-Gd(III) (3d(9)-4f(7)) dinuclear complexes based on the numerical atomic basis-norm-conserving pseudopotential method and density functional theory plus the Hubbard U correction approach (DFT+U). We obtain improved description of the 4f electrons by including the semicore 5s5p states in the valence part of the Gd-pseudopotential. The Hubbard U correction is employed to treat the strongly correlated Cu-3d and Gd-4f electrons, which significantly improve the agreement of the predicted exchange constants, J, with experiment, indicating the importance of accurate description of the local Coulomb correlation. The high efficiency of the DFT+U approach enables us to perform calculations with molecular crystals, which in general improve the agreement between theory and experiment, achieving a mean absolute error smaller than 2 cm(-1). In addition, through analyzing the physical effects of U, we identify two magnetic exchange pathways. One is ferromagnetic and involves an interaction between the Cu-3d, O-2p (bridge ligand), and the majority-spin Gd-5d orbitals. The other one is antiferromagnetic and involves Cu-3d, O-2p, and the empty minority-spin Gd-4f orbitals, which is suppressed by the planar Cu-O-O-Gd structure. This study demonstrates the accuracy of the DFT+U method for evaluating the 3d-4f exchange interactions, provides a better understanding of the exchange mechanism in the Cu(II)-Gd(III) complexes, and paves the way for exploiting the magnetic properties of the 3d-4f compounds containing lanthanides other than Gd.

Susceptibility quantitative trait loci for pathogenic leucocytosis in SCG/Kj mice, a spontaneously occurring crescentic glomerulonephritis and vasculitis model.

PubMed

Hamano, Y; Abe, M; Matsuoka, S; Zhang, D; Kondo, Y; Kagami, Y; Ishigami, A; Maruyama, N; Tsuruta, Y; Yumura, W; Suzuki, K

2014-07-01

The spontaneous crescentic glomerulonephritis-forming/Kinjoh (SCG/Kj) mouse, a model of human crescentic glomerulonephritis (CrGN) and systemic vasculitis, is characterized by the production of myeloperoxidase-specific anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) and marked leucocytosis. This study was performed to identify the specific populations of leucocytes associated with CrGN and susceptibility loci for pathogenic leucocytosis. Four hundred and twenty female (C57BL/6 × SCG/Kj) F2 intercross mice were subjected to serial flow cytometry examination of the peripheral blood (PB). Kidney granulocytes and monocytes were examined histopathologically. Linkage analyses were performed with 109 polymorphic microsatellite markers. Correlation studies revealed that increase of the granulocytes, F4/80(+) cells, CD3(+) CD4(-) CD8(-) T cells and dendritic cells (DCs) in peripheral blood (PB) were associated significantly with glomerulonephritis, crescent formation and vasculitis. In kidney sections, F4/80(low) cells were observed in crescent, while F4/80(high) cells were around the Bowman's capsules and in the interstitium. Numbers of F4/80(+) cells in crescents correlated significantly with F4/80(+) cell numbers in PB, but not with numbers of F4/80(+) cells in the interstitium. Genome-wide quantitative trait locus (QTL) mapping revealed three SCG/Kj-derived non-Fas QTLs for leucocytosis, two on chromosome 1 and one on chromosome 17. QTLs on chromosome 1 affected DCs, granulocytes and F4/80(+) cells, but QTL on chromosome 17 affected DCs and granulocytes. We found CrGN-associated leucocytes and susceptibility QTLs with their positional candidate genes. F4/80(+) cells in crescents are considered as recruited inflammatory macrophages. The results provide information for leucocytes to be targeted and genetic elements in CrGN and vasculitis. © 2014 British Society for Immunology.

Ability of Cytokeratin-18 Fragments and FIB-4 Index to Diagnose Overall and Mild Fibrosis Nonalcoholic Steatohepatitis in Japanese Nonalcoholic Fatty Liver Disease Patients.

PubMed

Kobayashi, Natsuko; Kumada, Takashi; Toyoda, Hidenori; Tada, Toshifumi; Ito, Takanori; Kage, Masayoshi; Okanoue, Takeshi; Kudo, Masatoshi

2017-01-01

Several laboratory markers used in lieu of liver biopsy are reportedly useful in the diagnosis of nonalcoholic steatohepatitis (NASH). In the present study, we investigated the diagnostic impact of various non-invasive markers for predicting NASH. A total of 229 nonalcoholic fatty liver disease (NAFLD) patients who underwent liver biopsy were enrolled for the study. The diagnostic ability of various markers to diagnose NASH from NAFLD was investigated. A total of 140 patients were histologically diagnosed with NASH. Of these, 104 had degree 0-2 fibrosis (F0-2), and 36 had degree 3-4 fibrosis (F3-4). Multiple logistic regression analysis identified hyaluronic acid (HA) (OR 1.014; 95% CI 1.002-1.026; p = 0.024), FIB-4 index (OR 2.097; 95% CI 1.177-3.735; p = 0.012), and cytokeratin-18 fragments (CK-18F) (OR 1.002; 95% CI 1.001-1.002; p < 0.001) as factors independently associated with the diagnosis of NASH. The areas under the receiver operating characteristic curves (AUROCs) of HA, FIB-4 index, and CK-18F for the diagnosis of NASH were 0.77, 0.76, and 0.72, respectively. In addition, FIB-4 index (OR 1.907; 95% CI 1.063-3.419; p = 0.03) and CK-18F (OR 1.002; 95% CI 1.001-1.002; p < 0.001) could differentiate between NASH and NAFL, even when NASH patients with advanced fibrosis (F3-4) were excluded. AUROCs of FIB-4 index and CK-18F for the diagnosis of NASH with mild fibrosis (F0-2) from NAFLD were 0.70 and 0.70, respectively. FIB-4 index and CK-18F have good diagnostic abilities not only for NASH overall, but also for NASH with mild fibrosis. © 2017 S. Karger AG, Basel.

Oxygen Buffering in High Pressure Solid Media Assemblies: New Approach Enabling Study of fO2 from IW-4 to IW+4.5

NASA Technical Reports Server (NTRS)

Righter, K.; Pando, K. M.; Ross, D. K.; Butterworth, A. L.; Gainsforth, Z.; Jilly-Rehak, C. E.; Westphal, A. J.

2017-01-01

Oxygen fugacity is an intensive parameter that controls some fundamental chemical and physical properties in planetary materials. In terrestrial magmas high fO2 promotes magnetite stability and low fO2 causes Fe-enrichment due to magnetite suppression. In lunar and asteroidal basalts, low fO2 can allow metal to be stable. Experimental studies will therefore be most useful if they are done at a specific and relevant fO2 for the samples under consideration. Control of fO2 in the solid media apparatus (piston cylinder multi-anvil) has relied on either sliding sensors or graphite capsule buffering, which are of limited application to the wide range of fO2 recorded in planetary or astromaterials. Here we describe a new approach that allows fO2 to be specified across a wide range of values relevant to natural samples.

The OsO(3)F(+) and mu-F(OsO(3)F)(2)(+) cations: their syntheses and study by Raman and (19)F NMR spectroscopy and electron structure calculations and X-ray crystal structures of [OsO(3)F][PnF(6)] (Pn = As, Sb), [OsO(3)F][HF](2)[AsF(6)], [OsO(3)F][HF][SbF(6)], and [OsO(3)F][Sb(3)F(16)].

PubMed

Gerken, Michael; Dixon, David A; Schrobilgen, Gary J

2002-01-28

The fluoride ion donor properties of OsO(3)F(2) have been investigated. The salts [OsO(3)F][AsF(6)], [OsO(3)F][HF](2)[AsF(6)], mu-F(OsO(3)F)(2)[AsF(6)], [OsO(3)F][HF](2)[SbF(6)], and [OsO(3)F][HF][SbF(6)] have been prepared by reaction of OsO(3)F(2) with AsF(5) and SbF(5) in HF solvent and have been characterized in the solid state by Raman spectroscopy. The single-crystal X-ray diffraction studies of [OsO(3)F][AsF(6)] (P2(1)/n, a = 7.0001(11) A, c = 8.8629(13) A, beta = 92.270(7) degrees, Z = 4, and R(1) = 0.0401 at -126 degrees C), [OsO(3)F][SbF(6)] (P2(1)/c, a = 5.4772(14) A, b = 10.115(3) A, c = 12.234(3) A, beta = 99.321(5) degrees, Z = 4, and R(1) = 0.0325 at -173 degrees C), [OsO(3)F][HF](2)[AsF(6)] (P2(1)/n, a = 5.1491(9) A, b = 8.129(2) A, c = 19.636(7) A, beta = 95.099(7) degrees, Z = 4, and R(1) = 0.0348 at -117 degrees C), and [OsO(3)F][HF][SbF(6)] (Pc, a = 5.244(4) A, b = 9.646(6) A, c = 15.269(10) A, beta = 97.154(13) degrees, Z = 4, and R(1) = 0.0558 at -133 degrees C) have shown that the OsO(3)F(+) cations exhibit strong contacts to the anions and HF solvent molecules giving rise to cyclic, dimeric structures in which the osmium atoms have coordination numbers of 6. The reaction of OsO(3)F(2) with neat SbF(5) yielded [OsO(3)F][Sb(3)F(16)], which has been characterized by (19)F NMR spectroscopy in SbF(5) and SO(2)ClF solvents and by Raman spectroscopy and single-crystal X-ray diffraction in the solid state (P4(1)m, a = 10.076(6) A, c = 7.585(8) A, Z = 2, and R(1) = 0.0858 at -113 degrees C). The weak fluoride ion basicity of the Sb(3)F(16)(-) anion resulted in an OsO(3)F(+) cation (C(3)(v) point symmetry) that is well isolated from the anion and in which the osmium is four-coordinate. The geometrical parameters and vibrational frequencies of OsO(3)F(+), ReO(3)F, mu-F(OsO(3)F)(2)(+), (FO(3)Os--FPnF(5))(2), and (FO(3)Os--(HF)(2)--FPnF(5))(2) (Pn = As, Sb) have been calculated using density functional theory methods.

Modeling EEG fractal dimension changes in wake and drowsy states in humans--a preliminary study.

PubMed

Bojić, Tijana; Vuckovic, Aleksandra; Kalauzi, Aleksandar

2010-01-21

Aim of this preliminary study was to examine and compare topographic distribution of Higuchi's fractal dimension (FD, measure of signal complexity) of EEG signals between states of relaxed wakefulness and drowsiness, as well as their FD differences. The experiments were performed on 10 healthy individuals using a fourteen-channel montage. An explanation is offered on the causes of the detected FD changes. FD values of 60s records belonging to wake (Hori's stage 1) and drowsy (Hori's stages 2-4) states were calculated for each channel and each subject. In 136 out of 140 epochs an increase in FD was obtained. Relationship between signal FD and its relative alpha amplitude was mathematically modeled and we quantitatively demonstrated that the increase in FD was predominantly due to a reduction in alpha activity. The model was generalized to include other EEG oscillations. By averaging FD values for each channel across 10 subjects, four clusters (O2O1; T6P4T5P3; C3F3F4C4F8F7; T4T3) for the wake and two clusters (O2O1P3T6P4T5; C3C4F4F3F8T4T3F7) for the drowsy state were statistically verified. Topographic distribution of FD values in wakefulness showed a lateral symmetry and a partial fronto-occipital gradient. In drowsiness, a reduction in the number of clusters was detected, due to regrouping of channels T3, T4, O1 and O2. Topographic distribution of absolute FD differences revealed largest values at F7, O1 and F3. Reorganization of channel clusters showed that regionalized brain activity, specific for wakefulness, became more global by entering into drowsiness. Since the global increase in FD during wake-to-drowsy transition correlated with the decrease of alpha power, we inferred that increase of EEG complexity may not necessarily be an index of brain activation.

Structural and energetic properties of acetonitrile-Group IV (A & B) halide complexes.

PubMed

Helminiak, Heather M; Knauf, Robin R; Danforth, Samuel J; Phillips, James A

2014-06-19

We have conducted an extensive computational study of the structural and energetic properties of select acetonitrile-Group IV (A & B) tetrahalide complexes, both CH3CN-MX4 and (CH3CN)2-MX4 (M = Si, Ge, Ti; X = F, Cl). We have also examined the reactivity of CH3CN with SiF4, SiCl4, GeCl4, and TiCl4, and measured low-temperature IR spectra of thin films containing CH3CN with SiF4, GeCl4, or TiCl4. The six 1:1 complexes fall into two general structural classes. CH3CN-TiCl4, CH3CN-TiF4, and CH3CN-GeF4, exhibit relatively short M-N bonds (~2.3 Å), an intermediate degree of distortion in the MX4 subunit, and binding energies ranging from 11.0 to 13.0 kcal/mol. Conversely, CH3CN-GeCl4, CH3CN-SiF4, and CH3CN-SiCl4, are weakly bonded systems, with long M-N distances (>3.0 Å), little distortion in the MX4 subunit, and binding energies ranging from 3.0 to 4.4 kcal/mol. The structural features of analogous 2:1 systems resemble those of their 1:1 counterparts, whereas the binding energies (relative to three isolated fragments) are roughly twice as large. Calculated M-N potential curves in the gas phase and bulk, dielectric media are reported for all 1:1 complexes, and for two systems, CH3CN-GeF4 and CH3CN-SiF4, these data predict significant condensed-phase structural changes. The effect on the CH3CN-SiF4 potential is extreme; the curve becomes quite flat over a broad range in dielectric media, and at higher ε values, the global minimum shifts inward by about 1.0 Å. In bulk reactivity experiments, no reaction was observed between CH3CN and SiF4, SiCl4, or GeCl4, whereas CH3CN and TiCl4 were found to react immediately upon contact. Also, thin-film IR spectra indicate a strong interaction between CH3CN and TiCl4, yet only weak interactions between CH3CN and GeCl4 or SiF4 in the solid state.

In situ investigation of the effect of TiF4 and CO2 laser irradiation on the permeability of eroded enamel.

PubMed

Lepri, Taísa Penazzo; Colucci, Vivian; Turssi, Cecília Pedroso; Corona, Silmara Aparecida Milori

2015-06-01

Interest in erosion and its role in tooth wear has increased considerably. Due to the limited contribution of patients in modifying their dietary habits, therapeutic resources aiming to reduce the progression of erosion-like lesions have been discussed. This study sought to evaluate the effect of TiF4 and CO2 laser in controlling the permeability of in situ eroded enamel. Ten volunteers wore an intraoral palatal device containing two enamel slabs, treated with TiF4 gel and TiF4 gel + CO2 or placebo gel and placebo gel + CO2. After the washout period, volunteers were crossed over to the other treatment. During both phases, specimens were submitted to erosive challenges and then evaluated for permeability measured as the percentage of copper ion penetration over the total enamel thickness. Two-way analysis of variance (ANOVA) revealed that there was a significant interaction between the factors under study (p = 0.0002). Tukey's test showed that TiF4 significantly reduced the enamel permeability of eroded enamel specimens, regardless of whether CO2 laser irradiation was performed. It may be concluded that when the placebo gel was applied, CO2 laser was able to reduce enamel permeability; however, when TiF4 was applied, laser irradiation did not imply a reduction in permeability. TiF4 provided a lower permeability of eroded enamel, regardless of whether the CO2 laser was used. Copyright © 2015 Elsevier Ltd. All rights reserved.

Vinclozolin--no transgenerational inheritance of anti-androgenic effects after maternal exposure during organogenesis via the intraperitoneal route.

PubMed

Schneider, Steffen; Marxfeld, Heike; Gröters, Sibylle; Buesen, Roland; van Ravenzwaay, Bennard

2013-06-01

The goal of this study was to examine the potential transgenerational inheritance of anti-androgenic effects induced by Vinclozolin administered intraperitoneally to pregnant Wistar rats (Crl:WI[Han]). Dams were dosed with Vinclozolin at 0, 4 or 100mg/kg bw/d on gestation days 6-15. Male offspring of F1-F3 generations were bred with untreated females to yield F2-F4 offspring. No evident anti-androgenic effects were observed at 4mg/kg bw/d, but a case of hypospadias as well as delayed sexual maturation in F1 male offspring was observed as a sign of anti-androgenicity at 100mg/kg bw/d. However, F1-F3 males developed normally to sexual maturity and were able to mate and to generate healthy progeny. Sperm count, morphology and motility were not affected in F1-F4 generation male offspring. In conclusion, transgenerational inheritance of Vinclozolin's anti-androgenic effects was not evident in outbred Wistar rats. Copyright © 2013 Elsevier Inc. All rights reserved.

DNA Binding Behavior, Sensor Studies, Antimicrobial, Photocleavage and In vitro Cytotoxicity of Synthesized Ru(II) Complexes with Assorted Intercalating Polypyridyl Ligands.

PubMed

Mallepally, Rajender Reddy; Putta, Venkat Reddy; Chintakuntla, Nagamani; Vuradi, Ravi Kumar; Kotha, Laxma Reddy; Sirasani, Satyanarayana

2016-05-01

The four novel Ru(II) polypyridyl complexes of [Ru(Hdpa)2dmbip](2+) (1), [Ru(Hdpa)2NO2-dmbip](2+) (2), [Ru(Hdpa)2debip](2+) (3) and [Ru(Hdpa)2OH-debip](2+) (4) where Hdpa = 2,2'-bipyridylamine, dmbip = 2-(4-N,N-dimethylbenzenamine)1H-imidazo[4,5-f][1,10]phenanthroline, debip = 2-(4-N,N-diethylbenzenamine)1H-imidazo[4,5-f][1,10]phenanthroline, NO2-dmbip = NO2-2-(4-N,N-dimethylbenzenamine)1H-imidazo[4,5-f][1,10]phenanthroline, OH-debip = OH-2-(4-N,N-diethylbenzenamine)1H-imidazo[4,5-f][1,10]phenanthroline were synthesized and fully characterized using elemental analysis, Mass, NMR and FT-IR. The DNA binding behavior of all synthesized complexes were investigated by using electronic absorption spectra, emission spectra, cyclic light switch on and off, sensor studies, electrochemical method and viscosity titrations. Docking studies were performed with human DNA TOP1 by using LibDock. Furthermore explore antimicrobial activity, photocleavage and in vitro cytotoxicity assay of four Ru(II) complexes.

Total and free iodothyronine changes in response to transport of Equidae (Equus asinus and Equus caballus).

PubMed

Fazio, Esterina; Medica, Pietro; Cravana, Cristina; Ferlazzo, Adriana

2017-03-31

In this study the effects of short distance road transport on total and free iodothyronine changes in 12 stallions (Equus asinus and Equus caballus) were evaluated. Donkeys (n = 6) and horses (n = 6) were transported for a distance of 50 km. Blood samples were collected 1 week before transport in basal conditions, 1 week later immediately before loading, and after transport and unloading. After transport, donkeys showed significant increases in circulating T4 (P≤0.01), fT3 (P≤0.001), and fT4 (P≤0.01) levels; while horses had significant increases in circulating T3, fT3 and fT4 (P≤0.01) levels. Compared to donkeys' values, horses showed lower T4 values in basal condition, before and after transport (P≤0.001); higher fT3 values in basal condition and before (P≤0.001), and lower values (P≤0.001) after transport; higher fT4 values (P≤0.001) in basal condition. The results indicate that short road transport of donkeys and horses induces the activation of the thyroid gland, with the same release of fT3 and fT4 iodothyronines, but with different preferential release of T3 in horses and T4 in donkeys after transport.

Utility of 18F-fluorodeoxy glucose and 18F-sodium fluoride positron emission tomography/computed tomography in the diagnosis of medication-related osteonecrosis of the jaw: A preclinical study in a rat model.

PubMed

Kim, Yemi; Lee, Ho-Young; Yoon, Hai-Jeon; Kim, Bom Sahn

2016-04-01

The aim of this study was to determine the clinical utility of positron emission tomography/computed tomography (PET/CT) using 18F-FDG and 18F-NaF for the diagnosis of osteonecrosis of the jaw (ONJ), by observing characteristics in rat models treated with zoledronic acid (ZA) and/or dexamethasone (DX) followed by tooth extraction. A total of 48 rats were divided randomly into four groups: Group 1, rats treated with ZA and DX; Group 2, rats treated with ZA; Group 3, rats treated with DX; and Group 4, rats treated with vehicle as normal controls. They underwent examinations with both 18F-FDG and 18F-NaF PET/CT at 4 weeks prior to tooth extraction (baseline) and 4 weeks after tooth extraction. Rats were then sacrificed to evaluate the histological incidence and characteristics of ONJ. Histological and radiological characteristics of all groups were compared to assess the effects of medication and tooth extraction. Baseline PET/CT studies using 18F-FDG and 18F-NaF showed no difference in uptake among the groups. However, 18F-FDG PET/CT performed at 4 weeks after tooth extraction showed increased glucose metabolism at the extraction site in both the ZA/DX and the ZA-only groups compared with that in the vehicle-treated group, in accordance with the higher incidence of histological ONJ (p < 0.05, respectively). 18F-NaF PET/CT performed at 4 weeks after tooth extraction showed decreased bone uptake in the extraction site in the ZA/DX, ZA, and DX groups versus the vehicle group (all p < 0.05), but this was not correlated with the incidence of histological ONJ. The incidence of ONJ was highest in the ZA/DX group (66.7%), followed by the ZA group, both of which were significantly higher than in the DX and vehicle groups (both p < 0.05). 18F-FDG PET/CT as an inflammatory marker appeared to be a more appropriate imaging modality than 18F-NaF PET/CT in diagnosing ONJ in a rat model including a ZA/DX group. However, the decreased bone remodeling tendency highlighted by 18F-NaF PET/CT may be an indicator of a possible risk of ONJ before the onset of clinical signs and symptoms. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Prime Contractors with Awards Over $25,000 by Name, Location, and Contract Number, Fiscal Year 87. Part 6. HI Desert Eagle Corporation-Kingsley Machine Company, Incorporated.

DTIC Science & Technology

1987-01-01

a a . c - 4 ) ) x’ m~ a4 a. a a J~C 0. ~a.L a. a m ac zz acca > a0 0 a0 a 0o~ a a 7- .CLa - cF 4 0 - HH u H auH. z~ -a a A wa a a~~~ a w .Laa.4 w...FF cc>C ~ ~ ~ ~ F o F ,.FF X1 F F -C F) F F -IC 0~~ 3 F F F3 Lo3F< 4 FF 4 0 F F . F 0 F 4 F * 0 0 OFUF 0 C 0 1 F CZFCi F7 Zl F C ,O D O C F - F F F...8217. ZU)to -At-4 - ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ k OD.-.-- - - - - - -.. -. . .~- - - r ~rwr y vva v- - - .3l f3 . ~ r.- (SOc Cr J m- OD( N t--C m m

On the Ground Electronic States of TiF and TiCl

NASA Astrophysics Data System (ADS)

Boldyrev, Alexander I.; Simons, Jack

1998-04-01

The low-lying electronic states of TiF and TiCl have been studied using high levelab initiotechniques. Both are found to have two low-lying excited electronic states,4Σ-(0.080 eV (TiF) and 0.236 eV (TiCl)) and2Δ (0.266 eV (TiF) and 0.348 eV (TiCl)), and4Φ ground states at the highest CCSD(T)/6-311++G(2d,2f) level of theory. Our theoretical predictions of4Φ ground electronic states for TiF and TiCl support recent experimental findings by Ram and Bernath, and our calculated bond lengths and vibrational frequencies are in reasonable agreement with their experimental data.

Pou4f1 and Pou4f2 Are Dispensable for the Long-Term Survival of Adult Retinal Ganglion Cells in Mice

PubMed Central

Huang, Liang; Hu, Fang; Xie, Xiaoling; Harder, Jeffery; Fernandes, Kimberly; Zeng, Xiang-yun; Libby, Richard; Gan, Lin

2014-01-01

Purpose To investigate the role of Pou4f1 and Pou4f2 in the survival of adult retinal ganglion cells (RGCs). Methods Conditional alleles of Pou4f1 and Pou4f2 were generated (Pou4f1loxP and Pou4f2loxP respectively) for the removal of Pou4f1 and Pou4f2 in adult retinas. A tamoxifen-inducible Cre was used to delete Pou4f1 and Pou4f2 in adult mice and retinal sections and flat mounts were subjected to immunohistochemistry to confirm the deletion of both alleles and to quantify the changes in the number of RGCs and other retinal neurons. To determine the effect of loss of Pou4f1 and Pou4f2 on RGC survival after axonal injury, controlled optic nerve crush (CONC) was performed and RGC death was assessed. Results Pou4f1 and Pou4f2 were ablated two weeks after tamoxifen treatment. Retinal interneurons and Müller glial cells are not affected by the ablation of Pou4f1 or Pou4f2 or both. Although the deletion of both Pou4f1 and Pou4f2 slightly delays the death of RGCs at 3 days post-CONC in adult mice, it does not affect the cell death progress afterwards. Moreoever, deletion of Pou4f1 or Pou4f2 or both has no impact on the long-term viability of RGCs at up to 6 months post-tamoxifen treatment. Conclusion Pou4f1 and Pou4f2 are involved in the acute response to damage to RGCs but are dispensable for the long-term survival of adult RGC in mice. PMID:24736625

Cell cycle regulator E2F4 is essential for the development of the ventral telencephalon.

PubMed

Ruzhynsky, Vladimir A; McClellan, Kelly A; Vanderluit, Jacqueline L; Jeong, Yongsu; Furimsky, Marosh; Park, David S; Epstein, Douglas J; Wallace, Valerie A; Slack, Ruth S

2007-05-30

Early forebrain development is characterized by extensive proliferation of neural precursors coupled with complex structural transformations; however, little is known regarding the mechanisms by which these processes are integrated. Here, we show that deficiency of the cell cycle regulatory protein, E2F4, results in the loss of ventral telencephalic structures and impaired self-renewal of neural precursor cells. The mechanism underlying aberrant ventral patterning lies in a dramatic loss of Sonic hedgehog (Shh) expression specifically in this region. The E2F4-deficient phenotype can be recapitulated by interbreeding mice heterozygous for E2F4 with those lacking one allele of Shh, suggesting a genetic interaction between these pathways. Treatment of E2F4-deficient cells with a Hh agonist rescues stem cell self-renewal and cells expressing the homeodomain proteins that specify the ventral telencephalic structures. Finally, we show that E2F4 deficiency results in impaired activity of Shh forebrain-specific enhancers. In conclusion, these studies establish a novel requirement for the cell cycle regulatory protein, E2F4, in the development of the ventral telencephalon.

Edoxaban effects on bleeding following punch biopsy and reversal by a 4-factor prothrombin complex concentrate.

PubMed

Zahir, Hamim; Brown, Karen S; Vandell, Alexander G; Desai, Madhuri; Maa, Jen-Fue; Dishy, Victor; Lomeli, Barbara; Feussner, Annette; Feng, Wenqin; He, Ling; Grosso, Michael A; Lanz, Hans J; Antman, Elliott M

2015-01-06

The oral factor Xa inhibitor edoxaban has demonstrated safety and efficacy in stroke prevention in patients with atrial fibrillation and in the treatment and secondary prevention of venous thromboembolism. This study investigated the reversal of edoxaban's effects on bleeding measures and biomarkers by using a 4-factor prothrombin complex concentrate (4F-PCC). This was a phase 1 study conducted at a single site. This was a double-blind, randomized, placebo-controlled, 2-way crossover study to determine the reversal effect of descending doses of 4F-PCC on bleeding duration and bleeding volume following edoxaban treatment. A total of 110 subjects (17 in part 1, 93 in part 2) were treated. Intravenous administration of 4F-PCC 50, 25, or 10 IU/kg following administration of edoxaban (60 mg) dose-dependently reversed edoxaban's effects on bleeding duration and endogenous thrombin potential, with complete reversal at 50 IU/kg. Effects on prothrombin time were partially reversed at 50 IU/kg. A similar trend was seen for bleeding volume. The 4F-PCC dose-dependently reversed the effects of edoxaban (60 mg), with complete reversal of bleeding duration and endogenous thrombin potential and partial reversal of prothrombin time following 50 IU/kg. Edoxaban alone and in combination with 4F-PCC was safe and well tolerated in these healthy subjects. A dose of 50 IU/kg 4F-PCC may be suitable for reversing edoxaban anticoagulation. http://www.clinicaltrials.gov. Unique identifier: NCT02047565. © 2014 American Heart Association, Inc.

Imide modified epoxy matrix resins

NASA Technical Reports Server (NTRS)

Scola, D. A.

1982-01-01

Results of a program designed to develop tough imide modified epoxy (IME) resins cured by bisimide amine (BIA) hardeners are presented. State of the art epoxy resin, MY720, was used. Three aromatic bisimide amines and one aromatic aliphatic BIA were evaluated. BIA's derived from 6F anhydride (3,3 prime 4,4 prime-(hexafluoro isopropyl idene) bis (phthalic anhydride) and diamines, 3,3 prime-diam nodiphenyl sulfone (3,3 prime-DDS), 4,4 prime-diamino diphenyl sulfone (4,4 prime-DDS), 1.12-dodecane diamine (1,12-DDA) were used. BIA's were abbreviated 6F-3,3 prime-DDS, 6F-4,4 prime-DDS, 6F-3,3 prime-DDS-4,4 prime DDS, and 6F-3,3 prime-DDS-1,12-DDA corresponding to 6F anhydride and diamines mentioned. Epoxy resin and BIA's (MY720/6F-3,3 prime-DDS, MY720/6F-3,3 prime-DDS-4,4 prime-DDS, MY720/6F-3,3 prime-DDS-1,12-DDA and a 50:50 mixture of a BIA and parent diamine, MY720/6F-3,3 prime-DDS/3,3 prime-DDS, MY720/6F-3,3 prime-DDS-4,4 prime-DDS/3,3 prime-DDS, MY720/6F-3,3 prime-DDS-1,12-DDA/3,3 prime-DDS were studied to determine effect of structure and composition. Effect of the addition of two commercial epoxies, glyamine 200 and glyamine 100 on the properties of several formulations was evaluated. Bisimide amine cured epoxies were designated IME's (imide modified epoxy). Physical, thermal and mechanical properties of these resins were determined. Moisture absorption in boiling water exhibited by several of the IME's was considerably lower than the state of the art epoxies (from 3.2% for the control and state of the art to 2.0 wt% moisture absorption). Char yields are increased from 20% for control and state of the art epoxies to 40% for IME resins. Relative toughness characteristics of IME resins were measured by 10 deg off axis tensile tests of Celion 6000/IME composites. Results show that IME's containing 6F-3,3 prime-DDS or 6F-3,3 prime-DDS-1,12-DDA improved the "toughness" characteristics of composites by about 35% (tensile strength), about 35% (intralaminar shear strength), and about 78% (shear strain to failure) relative to the control composite.

Combined use of (18)F-FDG and (18)F-FMISO in unresectable non-small cell lung cancer patients planned for radiotherapy: a dynamic PET/CT study.

PubMed

Sachpekidis, Christos; Thieke, Christian; Askoxylakis, Vasileios; Nicolay, Nils H; Huber, Peter E; Thomas, Michael; Dimitrakopoulou, Georgia; Debus, Juergen; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

2015-01-01

Aim of this study was to evaluate and compare, by means of dynamic and static PET/CT, the distribution patterns and pharmacokinetics of fluorine-18 fluorodeoxyglucose ((18)F-FDG) and of fluorine-18-fluoromisonidazole ((18)F-FMISO) in non-small cell lung cancer (NSCLC) patients scheduled for intensity modulated radiation therapy (IMRT). Thirteen patients suffering from inoperable stage III NSCLC underwent PET/CTs with (18)F-FDG and (18)F-FMISO for tumor metabolism and hypoxia assessment accordingly. Evaluation of PET/CT studies was based on visual analysis, semi-quantitative (SUV) calculations and absolute quantitative estimations, after application of a two-tissue compartment model and a non-compartmental approach. (18)F-FDG PET/CT revealed all thirteen primary lung tumors as sites of increased (18)F-FDG uptake. Six patients demonstrated also in total 43 (18)F-FDG avid metastases; these patients were excluded from radiotherapy. (18)F-MISO PET/CT demonstrated 12/13 primary lung tumors with faint tracer uptake. Only one tumor was clearly (18)F-FMISO avid, (SUVaverage = 3.4, SUVmax = 5.0). Mean values for (18)F-FDG, as derived from dPET/CT data, were SUVaverage = 8.9, SUVmax = 15.1, K1 = 0.23, k2 = 0.53, k3 = 0.17, k4 = 0.02, influx = 0.05 and fractal dimension (FD) = 1.25 for the primary tumors. The respective values for (18)F-FMISO were SUVaverage = 1.4, SUVmax = 2.2, K1 = 0.26, k2 = 0.56, k3 = 0.06, k4 = 0.06, influx = 0.02 and FD = 1.14. No statistically significant correlation was observed between the two tracers. (18)F-FDG PET/CT changed therapy management in six patients, by excluding them from planned IMRT. (18)F-FMISO PET/CT revealed absence of significant tracer uptake in the majority of the (18)F-FDG avid NSCLCs. Lack of correlation between the two tracers' kinetics indicates that they reflect different molecular mechanisms and implies the discordance between increased glycolysis and hypoxia in the malignancy.

Combined use of 18F-FDG and 18F-FMISO in unresectable non-small cell lung cancer patients planned for radiotherapy: a dynamic PET/CT study

PubMed Central

Sachpekidis, Christos; Thieke, Christian; Askoxylakis, Vasileios; Nicolay, Nils H; Huber, Peter E; Thomas, Michael; Dimitrakopoulou, Georgia; Debus, Juergen; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

2015-01-01

Aim of this study was to evaluate and compare, by means of dynamic and static PET/CT, the distribution patterns and pharmacokinetics of fluorine-18 fluorodeoxyglucose (18F-FDG) and of fluorine-18-fluoromisonidazole (18F-FMISO) in non-small cell lung cancer (NSCLC) patients scheduled for intensity modulated radiation therapy (IMRT). Thirteen patients suffering from inoperable stage III NSCLC underwent PET/CTs with 18F-FDG and 18F-FMISO for tumor metabolism and hypoxia assessment accordingly. Evaluation of PET/CT studies was based on visual analysis, semi-quantitative (SUV) calculations and absolute quantitative estimations, after application of a two-tissue compartment model and a non-compartmental approach. 18F-FDG PET/CT revealed all thirteen primary lung tumors as sites of increased 18F-FDG uptake. Six patients demonstrated also in total 43 18F-FDG avid metastases; these patients were excluded from radiotherapy. 18F-MISO PET/CT demonstrated 12/13 primary lung tumors with faint tracer uptake. Only one tumor was clearly 18F-FMISO avid, (SUVaverage = 3.4, SUVmax = 5.0). Mean values for 18F-FDG, as derived from dPET/CT data, were SUVaverage = 8.9, SUVmax = 15.1, K1 = 0.23, k2 = 0.53, k3 = 0.17, k4 = 0.02, influx = 0.05 and fractal dimension (FD) = 1.25 for the primary tumors. The respective values for 18F-FMISO were SUVaverage = 1.4, SUVmax = 2.2, K1 = 0.26, k2 = 0.56, k3 = 0.06, k4 = 0.06, influx = 0.02 and FD = 1.14. No statistically significant correlation was observed between the two tracers. 18F-FDG PET/CT changed therapy management in six patients, by excluding them from planned IMRT. 18F-FMISO PET/CT revealed absence of significant tracer uptake in the majority of the 18F-FDG avid NSCLCs. Lack of correlation between the two tracers’ kinetics indicates that they reflect different molecular mechanisms and implies the discordance between increased glycolysis and hypoxia in the malignancy. PMID:25973334

Interactions of praseodymium and neodymium with nucleosides and nucleotides: absorption difference and comparative absorption spectral study.

PubMed

Misra, S N; Anjaiah, K; Joseph, G; Abdi, S H

1992-02-01

The interactions of praseodymium(III) and neodymium(III) with nucleosides and nucleotides have been studied in different stoichiometry in water and water-DMF mixtures by employing absorption difference and comparative absorption spectrophotometry. The 4f-4f bands were analysed by linear curve analysis followed by gaussian curve analysis, and various spectral parameters were computed, using partial and multiple regression method. The magnitude of changes in both energy interaction and intensity were used to explore the degree of outer and inner sphere coordination, incidence of covalency and the extent of metal 4f-orbital involvement in chemical bonding. Crystalline complexes of the type [Ln(nucleotide)2(H2O)2]- (where nucleotide--GMP or IMP) were characterized by IR, 1H NMR, 31P NMR data. These studies indicated that the binding of the nucleotide is through phosphate oxygen in a bidentate manner and the complexes undergo substantial ionisation in aqueous medium, thereby supporting the observed weak 4f-4f bands and lower values for nephelauxetic effect (1-beta), bonding (b) and covalency (delta) parameters derived from coulombic and spin orbit interaction parameters.

Initial in vivo PET imaging of 5-HT1A receptors with 3-[18F]mefway

PubMed Central

Wooten, Dustin W; Hillmer, Ansel T; Murali, Dhanabalan; Barnhart, Todd E; Thio, Joanne P; Bajwa, Alisha K; Bonab, Ali A; Normandin, Marc D; Schneider, Mary L; Mukherjee, Jogeshwar; Christian, Bradley T

2014-01-01

4-trans-[18F]Mefway is a PET radiotracer with high affinity for 5-HT1A receptors. Our preliminary work indicated the positional isomer, 3-[18F]mefway, would be suitable for PET imaging of 5-HT1A receptors. We now compare the in vivo behaviour of 3-mefway with 4-mefway to evaluate 3-[18F]mefway as a potential 5-HT1A PET radiotracer. Two male rhesus macaques were given bolus injections of both 3- and 4-trans-[18F]mefway in separate experiments. 90 minute dynamic PET scans were acquired. TACs were extracted in the mesial temporal lobe (MTL) and caudal anterior cingulate gyrus (cACg). The cerebellum (CB) was used as a reference region. In vivo behavior of the radiotracers in the CB was compared based upon the ratio of normalized PET uptake for 3- and 4-trans-[18F]mefway. Specific binding was compared by examining MTL/CB and cACg/CB ratios. The subject-averaged ratio of 3-[18F]mefway to 4-trans-[18F]mefway in the cerebellum was 0.96 for 60-90 minutes. MTL/CB reached plateaus of ~2.7 and ~6 by 40 minutes and 90 minutes for 3- and 4-trans-[18F]mefway, respectively. cACg/CB reached plateaus of ~2.5 and ~6 by 40 minutes and 70 minutes for 3- and 4-trans-[18F]mefway, respectively. The short pseudoequilibration times and sufficient uptake of 3-[18F]mefway may be useful in studies requiring short scan times. Furthermore, the similar nondisplaceable clearance in the CB to 4-trans-[18F]mefway suggests the lower BPND of 3-[18F]mefway is due to a lower affinity. The lower affinity of 3-[18F]mefway may make it useful for measuring changes in endogenous 5-HT levels, however, this remains to be ascertained. PMID:25143866

Involvement of CYP4F2 in the Metabolism of a Novel Monophosphate Ester Prodrug of Gemcitabine and Its Interaction Potential In Vitro.

PubMed

Wang, Yedong; Li, Yuan; Lu, Jia; Qi, Huixin; Cheng, Isabel; Zhang, Hongjian

2018-05-16

Compound- 3 is an oral monophosphate prodrug of gemcitabine. Previous data showed that Compound- 3 was more potent than gemcitabine and it was orally active in a tumor xenograft model. In the present study, the metabolism of Compound- 3 was investigated in several well-known in vitro matrices. While relatively stable in human and rat plasma, Compound- 3 demonstrated noticeable metabolism in liver and intestinal microsomes in the presence of NADPH and human hepatocytes. Compound- 3 could also be hydrolyzed by alkaline phosphatase, leading to gemcitabine formation. Metabolite identification using accurate mass- and information-based scan techniques revealed that Compound- 3 was subjected to sequential metabolism, forming alcohol, aldehyde and carboxylic acid metabolites, respectively. Results from reaction phenotyping studies indicated that cytochrome P450 4F2 (CYP4F2) was a key CYP isozyme involved in Compound- 3 metabolism. Interaction assays suggested that CYP4F2 activity could be inhibited by Compound- 3 or an antiparasitic prodrug pafuramidine. Because CYP4F2 is a key CYP isozyme involved in the metabolism of eicosanoids and therapeutic drugs, clinical relevance of drug-drug interactions mediated via CYP4F2 inhibition warrants further investigation.

Evaluation of dermatological effects of cosmetic formulations containing Saccharomyces cerevisiae extract and vitamins.

PubMed

Gaspar, L R; Camargo, F B; Gianeti, M D; Maia Campos, P M B G

2008-11-01

Saccharomyces cerevisiae extract (SCE) is used in cosmetics since it can act in oxidative stress and improve skin conditions. This study investigated dermatological effects of cosmetic formulations containing SCE and/or vitamins A, C and E. The formulation studied was supplemented or not (F1: vehicle) with vitamins A, C and E esters (F2) or with SCE (F3) or with the combination of vitamins and SCE (F4). Formulations were patch tested on back skin of volunteers. For efficacy studies, formulations were applied on volunteers and transepidermal water loss (TEWL), skin moisture (SM), skin microrelief (SMR) and free radicals protection were analysed after 3h, 15 and 30 days of application. Volunteers were also asked about efficacy perception. It was observed that F4 provoked a slight erythema in one volunteer. All formulations enhanced forearm SM. Only F3 and F4 presented long term effects on SMR and showed higher texture values; F3 had the highest brightness values. Our results suggest that vitamins and SCE showed effects in SM and SMR. Only formulations containing SC had long term effects in the improvement of SMR. Thus, these kinds of evaluations are very important in cosmetics development to evaluate the best risk and benefit correlation.

The effectiveness of German disease management programs (DMPs) in patients with type 2 diabetes mellitus and coronary heart disease: results from an observational longitudinal study.

PubMed

Laxy, Michael; Stark, Renée; Meisinger, Christa; Kirchberger, Inge; Heier, Margit; von Scheidt, Wolfgang; Holle, Rolf

2015-01-01

Although the population-based German disease management programs (DMPs) for diabetes mellitus (DM) and coronary heart disease (CHD) are among the biggest worldwide, evidence on the effectiveness of these programs is still inconclusive or missing, particularly for high risk patients with comorbidities. The objective of this study was therefore to analyze the impact of DMPs on process and outcome parameters in patients with both, type 2 DM and CHD. Analyses are based on two postal surveys of patients from the KORA myocardial infarction registry (southern Germany) with type 2 DM and on two postal validation studies with patients' general physicians (2006, n = 312 and 2011, n = 212). The association between DMP enrollment (being enrolled in either DMP-DM or DMP-CHD) and guideline care (defined by several process indicators) at baseline (2006) and its development until follow-up (2011) was analyzed using logistic regression models accounting for the repeated measurements structure. The impact of DMP enrollment/guideline care on cumulated (quality-adjusted) life years ((QA)LYs) over a 4-year time horizon (2006-2010) was assessed using multiple linear regression methods. Logistic regression models were applied to analyze the association between DMP status and patient self-management at follow-up. Being enrolled in a DMP was associated with better guideline care at baseline [OR = 2.3 (95 % CI 1.27-4.03)], but not at follow-up [OR = 0.80 (95 % CI 0.40-1.58); p value for time-interaction <0.01]. DMP enrollment was not significantly [+0.15 LYs (95 % CI -0.07, 0.37); +0.06 QALYs (95 % CI -0.15, 0.26)], but treatment according to guideline care significantly [+0.40 LYs (95 % CI 0.21-0.60); +0.28 QALYs (95 % CI 0.10-0.45)] associated with higher (quality-adjusted) survival over the 4-year follow-up period. DMP enrollees further reported a somewhat better self-management than patients not being enrolled into a DMP. The results of this study concerning the effectiveness of DMPs in patients with DM and CHD are mixed, but are weakly in favor of DMPs. However, we found a clear positive impact of guideline care on quality adjusted survival in this patient group. The development of the association between DMP enrollment and guideline care over the follow-up time indicates some external effects, which should be the subject of further investigations.

TiF4 varnish protects the retention of brackets to enamel after in vitro mild erosive challenge.

PubMed

Medeiros, Maria Isabel Dantas de; Carlo, Hugo Lemes; Santos, Rogério Lacerda Dos; Sousa, Frederico Barbosa; Castro, Ricardo Dias de; França, Renata Cristina Sobreira; Carvalho, Fabíola Galbiatti de

2018-05-14

The effect of fluoride agents on the retention of orthodontic brackets to enamel under erosive challenge is little investigated. The aim of this study was to evaluate the effect of titanium tetrafluoride (TiF4) and sodium fluoride (NaF) agents on the shear bond strength of brackets to enamel and on the enamel microhardness around brackets under erosive challenge. Brackets were bonded to bovine incisors. Five groups were formed according to fluoride application (n=10): TiF4 varnish, TiF4 solution, NaF varnish, NaF solution and control (without application). The specimens were submitted to erosive challenge (90 s cola drink/2h artificial saliva, 4x per day for 7 days). Solutions were applied before each erosive cycle and varnishes were applied once. Vickers Microhardness (VHN) was obtained before and after all cycles of erosion and the percentage of microhardness loss was calculated. Shear bond strength, adhesive remnant index and polarized light microscopy were conducted after erosion. The data were analyzed by ANOVA, Tukey, Kruskal-Wallis and Mann-Whitney U tests (α=0.05). The %VHN had no statistically significant differences among the experimental groups. However, considering the comparisons of all groups with the control group, TiF4 varnish showed the highest protection from enamel demineralization (effect size of 2.94, while the effect size for the other groups was >2.4). The TiF4 varnish group had significantly higher shear bond strength compared to other groups. There was no difference among groups for adhesive remnant index. Polarized light microscopy showed higher demineralization depth for the control group. Application of NaF and TiF4 agents during mild erosive challenge minimized the enamel mineral loss around brackets, however only the experimental TiF4 varnish was able to prevent the reduction of shear bond strength of brackets to enamel.

Synthesis of new unsymmetrical 4,5-dihydroxy-2-imidazolidinones. Dynamic NMR spectroscopic study of the prototropic tautomerism in 1-(2-benzimidazolyl)-3-phenyl-4,5-dihydroxy-2-imidazolidinone.

PubMed

Ghandi, Mehdi; Olyaei, Abolfazl; Salimi, Farshid

2006-10-19

The acid-catalyzed cyclocondensation in refluxing acetonitrile of aqueous glyoxal with N-heteroaryl-N'-phenylureas 4a-f (heteroaryl = 2-thiazolyl, 2-pyrimidinyl,2-pyrazinyl, 2-pyridinyl, 3-pyridinyl and 2-benzimidazolyl) led to the formation of the corresponding 1-heteroaryl-3-phenyl-4,5-dihydroxy-2-imidazolidinones 5a-f. All the products were characterized by elemental and spectroscopic analyses. The free-energy barrier (Delta G not equal) for prototropic tautomerism in 1-(2-benzimidazolyl)-3-phenyl-4,5-dihydroxy-2-imidazolidinone (5f) was determined by dynamic NMR studies to be 81 +/- 2 KJ mol(-1).

A semifluorinated alkane (F4H5) as novel carrier for cyclosporine A: a promising therapeutic and prophylactic option for topical treatment of dry eye.

PubMed

Gehlsen, Uta; Braun, Tobias; Notara, Maria; Krösser, Sonja; Steven, Philipp

2017-04-01

Cyclosporine A (Cs) has been used as effective topical therapy for inflammatory dry eye disease since more than a decade. However, due to its lipophilic character, Cs is formulated as emulsions or oily solutions for topical application. This experimental study aimed to test if the use of semifluorinated alkanes (SFAs) as a preservative-free, well-tolerated non-stinging or burning vehicle maintains or even improves the benefits of Cs in the topical therapy of dry-eye disease. Desiccating stress was applied to C57BL/6 mice for 14 consecutive days to induce experimental dry-eye. Cs dissolved in SFA (perfluorobutylpentane = F4H5with 0.5% Ethanol), F4H5 with 0.5% ethanol only, 0.05% Cs (Restasis®), and dexamethasone (Monodex®) were applied three times daily beginning either at day 4 or day 11 of desiccating stress for up to 3 weeks after end of dry-eye induction. In comparison to other groups, Cs/F4H5 demonstrated high efficacy and earlier reduction of corneal staining. In this study, Cs/F4H5 had the ability to maintain conjunctival goblet cell density once applied on day 4. Flow cytometry analysis from cervical lymphnodes demonstrated a significantly lower CD4+ and CD8+ T-cells in the Cs/F4H5 group following 3 weeks of therapy than at baseline, but no difference in regulatory T cells from regional lymphnodes were seen. Overall, compared to a commercially available Cs formulation (Restasis®) and dexamethasone, Cs/F4H5 was shown to be equally effective but with a significantly faster therapeutic response in reducing signs of dry-eye disease in an experimental mouse model.

MIG-6 negatively regulates STAT3 phosphorylation in uterine epithelial cells

PubMed Central

Yoo, Jung-Yoon; Yang, Woo Sub; Lee, Jae Hee; Kim, Byung Gak; Broaddus, Russell R.; Lim, Jeong M.; Kim, Tae Hoon; Jeong, Jae-Wook

2017-01-01

Endometrial cancer is the most common malignancy of the female genital tract. Progesterone (P4) has been used for several decades in endometrial cancer treatment, especially in women who wish to retain fertility. However, it is unpredictable which patients will respond to P4 treatment and which may have a P4 resistant cancer. Therefore, identifying the mechanism of P4 resistance is essential to improve the therapies for endometrial cancer. Mitogen-inducible gene 6 (Mig-6) is a critical mediator of progesterone receptor (PGR) action in the uterus. In order to study the function of Mig-6 in P4 resistance, we generated a mouse model in which we specifically ablated Mig-6 in uterine epithelial cells using Sprr2f-cre mice (Sprr2fcre+Mig-6f/f). Female mutant mice develop endometrial hyperplasia due to aberrant phosphorylation of STAT3 and proliferation of the endometrial epithelial cells. The results from our immunoprecipitation and cell culture experiments showed that MIG-6 inhibited phosphorylation of STAT3 via protein interactions. Our previous study showed P4 resistance in mice with Mig-6 ablation in Pgr positive cells (Pgrcre/+Mig-6f/f). However, Sprr2fcre+Mig-6f/f mice were P4 responsive. P4 treatment significantly decreased STAT3 phosphorylation and epithelial proliferation in the uterus of mutant mice. We showed that Mig-6 has an important function of tumor suppressor via inhibition of STAT3 phosphorylation in uterine epithelial cells and the anti-tumor effects of P4 are mediated by the endometrial stroma. This data helps to develop a new signaling pathway in the regulation of steroid hormones in the uterus, and to overcome P4 resistance in human reproductive diseases, such as endometrial cancer. PMID:28925396

Sodium fluoride mouthrinse used twice daily increased incipient caries lesion remineralization in an in situ model.

PubMed

Songsiripradubboon, Siriporn; Hamba, Hidenori; Trairatvorakul, Chutima; Tagami, Junji

2014-03-01

To investigate the remineralizing effects of fluoride mouthrinses used at different times and frequency in addition to fluoride toothpaste. A randomized crossover single blinded study comprised 4 experimental phases of 21 days each. Twelve orthodontic volunteers were fixed with an orthodontic bracket containing an artificial carious enamel slab, which was from the same tooth in all 4 phases, and were randomly assigned to the following groups: (1) brushing with F toothpaste 2× per day (F- brush), (2) F- brush+rinsing with 0.05% NaF (F- rinse) after lunch, (3) F- brush+F-rinse before bedtime, and (4) F- brush+F- rinse 2× per day. Mean mineral gain after each phase was determined from mineral density profiles obtained using Micro-CT. The mean mineral gain in all treatments with F- brush and F-rinse were significantly greater than those in F- brush (p<0.05). Moreover F- rinse 2× per day increased lesion remineralization more than F- rinse once a day. The twice-daily use of 0.05% NaF mouthrinse combined with twice-daily regular use of fluoride toothpaste resulted in the greatest remineralization of incipient caries. These data indicate that rinsing frequency is a factor affecting the effectiveness of fluoride mouthrinse. The rinsing frequency of NaF mouthrinse, when used with fluoride toothpaste, also affects the remineralization. This finding, if confirmed by a clinical study, would lead to a new recommendation for fluoride mouthrinse used in high caries risk patients who could benefit from using it twice a day. Copyright © 2014 Elsevier Ltd. All rights reserved.

Investigation of XoxF methanol dehydrogenases reveals new methylotrophic bacteria in pelagic marine and freshwater ecosystems.

PubMed

Ramachandran, Arthi; Walsh, David A

2015-10-01

The diversity and distribution of methylotrophic bacteria have been investigated in the oceans and lakes using the methanol dehydrogenase mxaF gene as a functional marker. However, pelagic marine (OM43) and freshwater (LD28 and PRD01a001B) methylotrophs within the Betaproteobacteria lack mxaF, instead possessing a related xoxF4-encoded methanol dehydrogenase. Here, we developed and employed xoxF4 as a complementary functional gene marker to mxaF for studying methylotrophs in aquatic environment. Using xoxF4, we detected OM43-related and LD28-related methylotrophs in the ocean and freshwaters of North America, respectively, and showed the coexistence of these two lineages in a large estuarine system (St Lawrence Estuary). Gene expression patterns of xoxF4 supported a positive relationship between xoxF4-containing methylotroph activity and spring time productivity, suggesting phytoplankton blooms are a source of methylotrophic substrates. Further investigation of methanol dehydrogenase diversity in pelagic ecosystems using comparative metagenomics provided strong support for a widespread distribution of xoxF4 (as well as several distinct xoxF5) containing methylotrophs in marine and freshwater surface waters. In total, these results demonstrate a geographical distribution of OM43/LD28-related methylotrophs that includes marine and freshwaters and suggest that methylotrophy occurring in the water column is an important component of lake and estuary carbon cycling and biogeochemistry. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Water consumption, grain yield, and water productivity in response to field water management in double rice systems in China.

PubMed

Wu, Xiao Hong; Wang, Wei; Yin, Chun Mei; Hou, Hai Jun; Xie, Ke Jun; Xie, Xiao Li

2017-01-01

Rice cultivation has been challenged by increasing food demand and water scarcity. We examined the responses of water use, grain yield, and water productivity to various modes of field water managements in Chinese double rice systems. Four treatments were studied in a long-term field experiment (1998-2015): continuous flooding (CF), flooding-midseason drying-flooding (F-D-F), flooding-midseason drying-intermittent irrigation without obvious standing water (F-D-S), and flooding-rain-fed (F-RF). The average precipitation was 483 mm in early-rice season and 397 mm in late-rice season. The irrigated water for CF, F-D-F, F-D-S, and F-RF, respectively, was 263, 340, 279, and 170 mm in early-rice season, and 484, 528, 422, and 206 mm in late-rice season. Grain yield for CF, F-D-F, F-D-S, and F-RF, respectively, was 4,722, 4,597, 4,479, and 4,232 kgha-1 in early-rice season, and 5,420, 5,402, 5,366, and 4,498 kgha-1 in late-rice season. Compared with CF, F-D-F consumed more irrigated water, which still decreased grain yield, leading to a decrease in water productivity by 25% in early-rice season and by 8% in late-rice season. Compared with F-D-F, F-D-S saved much irrigated water with a small yield reduction, leading to an increase in water productivity by 22% in early-rice season and by 26% in late-rice season. The results indicate that CF is best for early-rice and FDS is best for late-rice in terms of grain yield and water productivity.

Molecular Self-Assembly in a Poorly Screened Environment: F4TCNQ on Graphene/BN

PubMed Central

2015-01-01

We report a scanning tunneling microscopy and noncontact atomic force microscopy study of close-packed 2D islands of tetrafluorotetracyanoquinodimethane (F4TCNQ) molecules at the surface of a graphene layer supported by boron nitride. While F4TCNQ molecules are known to form cohesive 3D solids, the intermolecular interactions that are attractive for F4TCNQ in 3D are repulsive in 2D. Our experimental observation of cohesive molecular behavior for F4TCNQ on graphene is thus unexpected. This self-assembly behavior can be explained by a novel solid formation mechanism that occurs when charged molecules are placed in a poorly screened environment. As negatively charged molecules coalesce, the local work function increases, causing electrons to flow into the coalescing molecular island and increase its cohesive binding energy. PMID:26482218

Guide wire entrapment by inferior vena cava filters: an experimental study.

PubMed

Rosen, Michael J; Burns, Justin M; Cobb, William S; Jacobs, David G; Heniford, B Todd; Sing, Ronald F

2005-09-01

In situ vena cava filters are at risk for complications with the use of J-tipped guide wires. The purpose of this study was to evaluate the impact of two commonly used J-tipped guide wires on the stability of the four most recently released vena cava filters in an in vitro flow model. Four filters (OptEase [F1], Günther Tulip [F2], Vena Tech LP [F3], and Recovery [F4]) were inserted into an in vitro flow model. Two J-tipped guide wires (0.032-inch [GW-1], 0.035-inch [GW-2]) were passed through each filter (n = 50 passes per wire) for a distance of 10 cm. The inserter was blind as to the effects of the wire. The filters were monitored by an independent observer for adverse events occurring between the filters and the guide wires. These were defined as: migrations (>1 cm), change of position (tilt>10 degrees), and entrapment of the wire (unable to remove wire). Descriptive statistics, chi-square, and Fisher's exact test were used (p < 0.05 considered significant). GW-1 resulted in a lower incidence of entrapment, migration, and tilt for all filters compared with GW-2 (F1, p = 0.003; F2, p < 0.0001; F3, p < 0.0001; F4, p = 0.0004). GW-1 resulted in entrapment in 0%, migration in 7.5%, and tilt in 10.5% of insertions. GW-2 resulted in entrapment in 1%, migration in 26.5%, and tilt in 5.5% of insertions. The incidence of adverse events for GW-1 was significantly different compared with all filters (F1, 0%; F2, 46%; F3, 4%; and F4, 22%; p < 0.0001). Similarly, the incidence of adverse events for GW-2 was significantly different when evaluating all filters (F1, 12%; F2, 48%; F3, 22%; F4 60%; p < 0.0001). The smaller-diameter guide wire resulted in a decreased incidence of adverse events for all filters, but there is still risk for complications. Knowledge of potential complications associated with vena cava filters and the postinsertion use of guide wires are essential to avoid potential mishaps.

F4 (K88) fimbrial adhesin FaeG expressed in alfalfa reduces F4+ enterotoxigenic Escherichia coli excretion in weaned piglets.

PubMed

Joensuu, J J; Verdonck, F; Ehrström, A; Peltola, M; Siljander-Rasi, H; Nuutila, A M; Oksman-Caldentey, K-M; Teeri, T H; Cox, E; Goddeeris, B M; Niklander-Teeri, V

2006-03-20

Transgenic plants are attractive bioreactors to large-scale production of recombinant proteins because of their relatively low cost. This study reports for the first time the use of transgenic plants to reduce enterotoxigenic Escherichia coli (ETEC) excretion in its natural host species. The DNA sequence encoding the major subunit and adhesin FaeG of F4+ ETEC was transformed into edible alfalfa plants. Targeting of FaeG production to chloroplasts led to FaeG levels of up to 1% of the total soluble protein fraction of the transgenic alfalfa. Recombinant plant-produced FaeG (pFaeG) remained stable for 2 years when the plant material was dried and stored at room temperature. Intragastric immunization of piglets with pFaeG induced a weak F4-specific humoral response. Co-administration of pFaeG and the mucosal adjuvant cholera toxin (CT) enhanced the immune response against FaeG, reflected a better induction of an F4-specific immune response. In addition, the intragastric co-administration of CT with pFaeG significantly reduced F4+ E. coli excretion following F4+ ETEC challenge as compared with pigs that had received nontransgenic plant material. In conclusion, transgenic plants producing the FaeG subunit protein could be used for production and delivery of oral vaccines against F4+ ETEC infections.

Using Personnel Distribution Models.

DTIC Science & Technology

1980-02-01

for a steady-state system can be repre- sented algebraically by any two of the three equations flI + f 2 = i + 12 (1) fl + f4 = f3 + 2 f2 + f 3 = f4...of stock to the other category is cbf and the losses are (l-cb)f. Applying this argument to both categories gives f4 = ca(f2+ f3 ca(f 4 + 1 ) f3 = cb...f+f) = cb (f 3 + 12) These equations allow us to eliminate f3 and f4 in (1) to obtain the equations f + f-1- 2 =0 5 _ _ _ _ _ _ _ _ _ -La f 1 (l a 3

Zinc fractionation in contaminated soils by sequential and single extractions: influence of soil properties and zinc content.

PubMed

Voegelin, Andreas; Tokpa, Gerome; Jacquat, Olivier; Barmettler, Kurt; Kretzschmar, Ruben

2008-01-01

We studied the fractionation of zinc (Zn) in 49 contaminated soils as influenced by Zn content and soil properties using a seven-step sequential extraction procedure (F1: NH4NO3; F2: NH4-acetate, pH 6; F3: NH3OHCl, pH 6; F4: NH4-EDTA, pH 4.6; F5: NH4-oxalate, pH 3; F6: NH4-oxalate/ascorbic acid, pH 3; F7: residual). The soils had developed from different geologic materials and covered a wide range in soil pH (4.0-7.3), organic C content (9.3-102 g kg(-1)), and clay content (38-451 g kg(-1)). Input of aqueous Zn with runoff water from electricity towers during 26 to 74 yr resulted in total soil Zn contents of 3.8 to 460 mmol kg(-1). In acidic soils (n = 24; pH <6.0), Zn was mainly found in the mobile fraction (F1) and the last two fractions (F6 and F7). In neutral soils (n = 25; pH > or =6.0), most Zn was extracted in the mobilizable fraction (F2) and the intermediate fractions (F4 and F5). The extractability of Zn increased with increasing Zn contamination of the soils. The sum of mobile (F1) and mobilizable (F2) Zn was independent of soil pH, the ratio of Zn in F1 over F1+F2 plotted against soil pH, exhibited the typical shape of a pH sorption edge and markedly increased from pH 6 to pH 5, reflecting the increasing lability of mobilizable Zn with decreasing soil pH. In conclusion, the extractability of Zn from soils contaminated with aqueous Zn after decades of aging under field conditions systematically varied with soil pH and Zn content. The same trends are expected to apply to aqueous Zn released from decomposing Zn-bearing contaminants, such as sewage sludge or smelter slag. The systematic trends in Zn fractionation with varying soil pH and Zn content indicate the paramount effect of these two factors on molecular scale Zn speciation. Further research is required to characterize the link between the fractionation and speciation of Zn and to determine how Zn loading and soil physicochemical properties affect Zn speciation in soils.

Impact of hepatitis C virus genotype-4 eradication following direct acting antivirals on liver stiffness measurement.

PubMed

Tag-Adeen, Mohammed; Sabra, Ahlam Mohamed; Akazawa, Yuko; Ohnita, Ken; Nakao, Kazuhiko

2017-01-01

Liver fibrosis is the most important prognostic factor in chronic hepatitis C virus (HCV) patients, and Egypt shows the highest worldwide HCV prevalence with genotype-4 pre-dominance. The aim of this study was to investigate the degree of liver stiffness measurement (LSM) improvement after successful HCV eradication. The study included 84 chronic HCV Egyptian patients, and was conducted at Qena University Hospital from November 1, 2015 till October 31, 2016. LSM was obtained by FibroScan® before starting direct acting antiviral (DAA) treatment and after achieving sustained virologic response-24 (SVR-24). Based on baseline LSM, patients were stratified into F0-F1, F2, F3 and F4 groups (METAVIR). LSM and laboratory data after achieving SVR-24 was compared with that before starting therapy in each fibrosis group (F0-F4), p -value <0.05 was statistically significant. Following DAA treatment, 80 patients achieved SVR-24; of these, 50 were males (62.5%), mean age: 54.2±7.6 years, and mean body mass index: 28.6±2.2 kg/m 2 . Mean baseline LSM dropped from 15.6±10.8 to 12.1±8.7 kPa post-SVR; the maximum change of -5.8 occurred in F4 versus -2.79, -1.28 and +0.08 in F3, F2 and F0-F1 respectively ( p <0.0001). At baseline, 41 patients were in the F4 group; only 16 (39%) regressed to non-cirrhotic range (<12.5 kPa), while 25 (61%) were still cirrhotic despite achieving SVR-24 ( p <0.0001). Patients who achieved LSM improvement (n=64) have had significantly higher baseline aspartate transferase (AST) and alanine transaminase (ALT). Also, those patients showed significant improvement in AST, AST/platelets ratio index (APRI) and fibrosis-4 index (Fib-4) after achieving SVR; 91% showed AST improvement ( p =0.01) and APRI improvement ( p =0.01) and 81% showed Fib-4 improvement ( p =0.04). Females, diabetics, patients with S3 steatosis and patients older than 50 years showed less LSM improvements than their counterparts. Baseline LSM ≥9 kPa, bilirubin ≥1 mg/dl, ALT ≥36 U/L and AST ≥31 U/L were significant predictors for LSM improvement. Successful HCV genotype-4 eradication results in significant LSM improvement; the best improvement occurs in F4 patients. But as the majority of cirrhotics are still at risk for liver decompensation and hepatocellular carcinoma development despite achieving SVR-24, early detection and treatment are highly recommended.

Ion beam induced 18F-radiofluorination: straightforward synthesis of gaseous radiotracers for the assessment of regional lung ventilation using positron emission tomography.

PubMed

Gómez-Vallejo, V; Lekuona, A; Baz, Z; Szczupak, B; Cossío, U; Llop, J

2016-09-29

A simple, straightforward and efficient method for the synthesis of [ 18 F]CF 4 and [ 18 F]SF 6 based on an ion beam-induced isotopic exchange reaction is presented. Positron emission tomography ventilation studies in rodents using [ 18 F]CF 4 showed a uniform distribution of the radiofluorinated gas within the lungs and rapid elimination after discontinuation of the administration.

Evaluation of an [(18)F]AlF-NOTA Analog of Exendin-4 for Imaging of GLP-1 Receptor in Insulinoma.

PubMed

Kiesewetter, Dale O; Guo, Ning; Guo, Jinxia; Gao, Haokao; Zhu, Lei; Ma, Ying; Niu, Gang; Chen, Xiaoyuan

2012-01-01

The GLP-1 receptor plays an important role in glucose homeostasis and thus is a very important target for diabetes therapy. The receptor is also overexpressed in insulinoma, a tumor of pancreatic beta-cells. We previously evaluated two fluorine-18-labeled analogs of exendin-4 prepared by conjugation with [(18)F]FBEM (N-[2-(4-[(18)F]fluorobenzamide)ethyl]maleimide). Both compounds demonstrated good tumor uptake, but the synthesis of the radiotracers was time consuming. To overcome this challenge, we developed a NOTA analog and performed radiolabeling using aluminum [(18)F]fluoride complexation. Cys(40)-exendin-4 was conjugated with NOTA mono N-ethylmaleimide. [(18)F]AlF conjugation was conducted and the radiolabeled product purified by preparative HPLC. Dynamic and static PET imaging scans were conducted on nude mice with established INS-1 xenografts. Uptake of tumor and other major organs in static images was quantitated (%ID/g) and comparison with blocking studies was made. PET quantification was also compared with ex vivo biodistribution results. The radiosynthesis provided [(18)F]AlF-NOTA-MAL-cys(40)-exendin-4 in 23.6 ± 2.4 % radiochemical yield (uncorrected, n = 3) after HPLC; the process required about 55 min. The specific activity at time of injection ranged from 19.6 to 31.4 GBq (0.53-0.85 Ci)/µmol. Tumor uptake had reached its maximum (16.09 ± 1.18% ID/g, n = 4) by 5 min and remained nearly constant for the duration of the study. Kidney uptake continued to increase throughout the entire one hour time course. Pre-injection of exendin-4 caused a marked reduction in tissue uptake with the major exception of liver and kidneys, in which uptake was not affected. HPLC analysis of the radioactive components in extracts of the tumor and plasma showed primarily parent compound at 60 min post-injection, whereas extracts of kidney and urine contained exclusively one polar radioactive component. The radiotracer is prepared in a simple one-step procedure and obtained in high specific activity after HPLC purification. [(18)F]AlF-NOTA-MAL-exendin-4 shows high tumor uptake and highly selective GLP-1 tissue uptake (INS-1 tumor, lung, pancreas), but still suffers from high kidney uptake.

Prevalence of adhesin and toxin genes in E. coli strains isolated from diarrheic and non-diarrheic pigs from smallholder herds in northern and eastern Uganda.

PubMed

Ikwap, Kokas; Larsson, Jenny; Jacobson, Magdalena; Owiny, David Okello; Nasinyama, George William; Nabukenya, Immaculate; Mattsson, Sigbrit; Aspan, Anna; Erume, Joseph

2016-08-05

Enterotoxigenic E. coli (ETEC) significantly contribute to diarrhea in piglets and weaners. The smallholder pig producers in Uganda identified diarrhea as one of the major problems especially in piglets. The aim of this study was to; i) characterize the virulence factors of E. coli strains isolated from diarrheic and non-diarrheic suckling piglets and weaners from smallholder herds in northern and eastern Uganda and ii) identify and describe the post-mortem picture of ETEC infection in severely diarrheic piglets. Rectal swab samples were collected from 83 piglets and weaners in 20 herds and isolated E. coli were characterized by PCR, serotyping and hemolysis. The E. coli strains carried genes for the heat stable toxins STa, STb and EAST1 and adhesins F4 and AIDA-I. The genes for the heat labile toxin LT and adhesins F5, F6, F18 and F41 were not detected in any of the E. coli isolates. Where the serogroup could be identified, E. coli isolates from the same diarrheic pig belonged to the same serogroup. The prevalence of EAST1, STb, Stx2e, STa, AIDA-I, and F4 in the E. coli isolates from suckling piglets and weaners (diarrheic and non-diarrheic combined) was 29, 26.5, 2.4, 1.2, 16, and 8.4 %, respectively. However the prevalence of F4 and AIDA-I in E. coli from diarrheic suckling piglets alone was 22.2 and 20 %, respectively. There was no significant difference in the prevalence of the individual virulence factors in E. coli from the diarrheic and non-diarrheic pigs (p > 0.05). The main ETEC strains isolated from diarrheic and non-diarrheic pigs included F4/STb/EAST1 (7.2 %), F4/STb (1.2 %), AIDA/STb/EAST1 (8 %) and AIDA/STb (8 %). At post-mortem, two diarrheic suckling piglets carrying ETEC showed intact intestinal villi, enterocytes and brush border but with a layer of cells attached to the brush border, suggestive of ETEC infections. This study has shown that the F4 fimbriae is the most predominant in E. coli from diarrheic piglets in the study area and therefore an F4-based vaccine should be considered one of the preventive measures for controlling ETEC infections in the piglets in northern and eastern Uganda.

Pharmacological characterization of canine melancortin-4 receptor and its natural variant V213F.

PubMed

Yan, J; Tao, Y-X

2011-08-01

Dogs have become one of the most important companion animals in modern society. However, it is estimated that 20% to 40% of owned dogs are obese, suggesting that obesity has become one of the most important canine health problem. In addition, obesity in dogs also leads to type II diabetes. Because the melanocortin-4 receptor (MC4R) has been shown to be essential in maintaining energy homeostasis in several different species, including rodents and humans, we initiated studies toward elucidating the roles of MC4R in obesity pathogenesis in dogs. Canine MC4R has been cloned, and a missense variant V213F was identified. We designed primers and successfully cloned canine MC4R and generated the variant V213F by site-directed mutagenesis. The objective of this study was to investigate the pharmacological properties of canine MC4R and its natural variant V213F. We measured ligand binding and signaling properties with the use of both natural and synthetic ligands. Human MC4R was also included in the experiments for comparison. Both wild-type canine MC4R and its natural variant V213F functioned normally in terms of binding and signaling. Of the ligands we used, [Nle(4), D-Phe(7)]-α-melanocyte-stimulating hormone is the most potent ligand. We conclude that the cloned canine MC4R is a functional receptor, and the natural variant V213F does not have any functional defect and therefore is not likely to cause obesity in dogs. Copyright © 2011 Elsevier Inc. All rights reserved.

Synthesis and evaluation of novel 18 F-labeled quinazoline derivatives with low lipophilicity for tumor PET imaging.

PubMed

Chong, Yan; Chang, Jin; Zhao, Wenwen; He, Yong; Li, Yuqiao; Zhang, Huabei; Qi, Chuanmin

2018-02-01

Four novel 18 F-labeled quinazoline derivatives with low lipophilicity, [ 18 F]4-(2-fluoroethoxy)-6,7-dimethoxyquinazoline ([ 18 F]I), [ 18 F]4-(3-((4-(2-fluoroethoxy)-7-methoxyquinazolin-6-yl)oxy)propyl)morpholine ([ 18 F]II), [ 18 F]4-(2-fluoroethoxy)-7-methoxy-6-(2-methoxyethoxy)quinazoline ([ 18 F]III), and [ 18 F]4-(2-fluoroethoxy)-6,7-bis(2-methoxyethoxy)quinazoline ([ 18 F]IV), were synthesized via a 2-step radiosynthesis procedure with an overall radiochemical yield of 10% to 38% (without decay correction) and radiochemical purities of >98%. The lipophilicity and stability of labeled compounds were tested in vitro. The log P values of the 4 radiotracers ranged from 0.52 to 1.07. We then performed ELISA to measure their affinities to EGFR-TK; ELISA assay results indicated that each inhibitor was specifically bounded to EGFR-TK in a dose-dependent manner. The EGFR-TK autophosphorylation IC 50 values of [ 18 F]I, [ 18 F]II, [ 18 F]III, and [ 18 F]IV were 7.732, 0.4698, 0.1174, and 0.1176 μM, respectively. All labeled compounds were evaluated via cellular uptake and blocking studies in HepG2 cell lines in vitro. Cellular uptake and blocking experiment results indicated that [ 18 F]I and [ 18 F]III had excellent cellular uptake at 120-minute postinjection in HepG2 carcinoma cells (51.80 ± 3.42%ID/mg protein and 27.31 ± 1.94%ID/mg protein, respectively). Additionally, biodistribution experiments in S180 tumor-bearing mice in vivo indicated that [ 18 F]I had a very fast clearance in blood and a relatively high uptake ratio of tumor to blood (4.76) and tumor to muscle (1.82) at 60-minute postinjection. [ 18 F]III had a quick clearance in plasma, and its highest uptake ratio of tumor to muscle was 2.55 at 15-minute postinjection. These experimental results and experiences were valuable for the further exploration of novel radiotracers of quinazoline derivatives. Copyright © 2017 John Wiley & Sons, Ltd.

Design, synthesis, kinetic mechanism and molecular docking studies of novel 1-pentanoyl-3-arylthioureas as inhibitors of mushroom tyrosinase and free radical scavengers.

PubMed

Larik, Fayaz Ali; Saeed, Aamer; Channar, Pervaiz Ali; Muqadar, Urooj; Abbas, Qamar; Hassan, Mubashir; Seo, Sung-Yum; Bolte, Michael

2017-12-01

A series of novel 1-pentanoyl-3-arylthioureas was designed as new mushroom tyrosinase inhibitors and free radical scavengers. The title compounds were obtained in excellent yield and characterized by FTIR, 1 H NMR, 13 C NMR and X-ray crystallography in case of compound (4a). The inhibitory effects on mushroom tyrosinase and DPPH were evaluated and it was observed that 1-Pentanoyl-3-(4-methoxyphenyl) thiourea (4f) showed tyrosinase inhibitory activity (IC 50 1.568 ± 0.01 mM) comparable to Kojic acid (IC 50 16.051 ± 1.27 mM). Interestingly compound 4f exhibited higher antioxidant potential compared to other derivatives. The docking studies of synthesized 1-Pentanoyl-3-arylthioureas analogues were also carried out against tyrosinase protein (PDBID 2ZMX) to compare the binding affinities with IC 50 values. The predicted binding affinities are in good agreement with the IC 50 values as compound (4f) showed highest binding affinity (-7.50 kcal/mol) compared to others derivatives. The kinetic mechanism analyzed by Line-weavere Burk plots exhibited that compound (4f) inhibit the enzyme inhibits the tyrosinase non-competitively to form an enzyme inhibitor complex. The inhibition constants Ki calculated from Dixon plots for compound (4f) is 1.10 μM. It was also found from kinetic analysis that derivative 4f irreversible enzyme inhibitor complex. It is proposed on the basis of our investigation that title compound (4f) may serve as lead structure for the design of more potent tyrosinase inhibitors. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Development and Initial Evaluation of a Telephone-Delivered, Behavioral Activation and Problem-solving Treatment Program to Address Functional Goals of Breast Cancer Survivors

PubMed Central

Lyons, Kathleen D.; Hull, Jay G.; Kaufman, Peter A.; Li, Zhongze; Seville, Janette L.; Ahles, Tim A.; Kornblith, Alice B.; Hegel, Mark T.

2015-01-01

The purpose of this research was to develop and pilot test an intervention to optimize functional recovery for breast cancer survivors. Over two studies, 31 women enrolled in a goal-setting program via telephone. All eligible women enrolled (37% of those screened) and 66% completed all study activities. Completers were highly satisfied with the intervention, using it to address, on average, four different challenging activities. The longitudinal analysis showed a main effect of time for overall quality of life (F(5, 43.1) = 5.1, p = 0.001) and improvements in active coping (F (3, 31.7) = 4.9, p = 0.007), planning (F (3, 36.0) = 4.1, p = 0.01), reframing (F (3, 29.3) = 8.5, p < 0.001), and decreases in self-blame (F (3,31.6) = 4.3, p = 0.01). The intervention is feasible and warrants further study to determine its efficacy in fostering recovery and maximizing activity engagement after cancer treatment. PMID:25668509

Thyroid Signaling, Insulin Resistance, and 2 Diabetes Mellitus: A Mendelian Randomization Study.

PubMed

Bos, Maxime M; Smit, Roelof A J; Trompet, Stella; van Heemst, Diana; Noordam, Raymond

2017-06-01

Increasing evidence suggests an association between thyroid-stimulating hormone (TSH), free thyroxine (fT4), and deiodinases with insulin resistance and type 2 diabetes mellitus (T2D). We examined whether TSH and fT4 levels and deiodinases are causally associated with insulin resistance and T2D, using Mendelian randomization. We selected 20 genetic variants for TSH level and four for fT4 level (identified in a genome-wide association study (GWAS) meta-analysis of European-ancestry cohorts) as instrumental variables for TSH and fT4 levels, respectively. We used summary data from GWASs on the outcomes T2D [Diabetes, Genetics Replication and Meta-analysis (DIAGRAM), n = 12,171 cases and n = 56,862 control subjects] and glycemic traits in patients without diabetes [Meta-Analyses of Glucose and Insulin-Related Traits Consortium (MAGIC), n = 46,186 for fasting glucose and insulin and n = 46,368 for hemoglobin A1c]. To examine whether the associations between TSH/fT4 levels and the study outcomes were causal, we combined the effects of the genetic instruments. Furthermore, we examined the associations among 16 variants in DIO1, DIO2, DIO3, and T2D and glycemic traits. We found no evidence for an association between the combined genetic instrumental variables for TSH and fT4 and the study outcomes. For example, we did not observe a genetically determined association between high TSH level and T2D (odds ratio, 0.91 per standard deviation TSH increase; 95% confidence interval, 0.78 to 1.07). Selected genetic variants in DIO1 (e.g., rs7527713) were associated with measures of insulin resistance. We found no evidence for a causal association between circulatory levels of TSH and fT4 with insulin resistance and T2D, but we found suggestive evidence that DIO1 affects glucose metabolism. Copyright © 2017 by the Endocrine Society

Increasing Polymer Solar Cell Fill Factor by Trap-Filling with F4-TCNQ at Parts Per Thousand Concentration.

PubMed

Yan, Han; Manion, Joseph G; Yuan, Mingjian; García de Arquer, F Pelayo; McKeown, George R; Beaupré, Serge; Leclerc, Mario; Sargent, Edward H; Seferos, Dwight S

2016-08-01

Intrinsic traps in organic semiconductors can be eliminated by trap-filling with F4-TCNQ. Photovoltaic tests show that devices with F4-TCNQ at parts per thousand concentration outperform control devices due to an improved fill factor. Further studies confirm the trap-filling pathway and demonstrate the general nature of this finding. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Near-resonant vibration. -->. vibration energy transfer under single-collision conditions. [Propynal

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

Breener, D M

1981-01-01

Energy transfer in single collisions of propynal (HC triple bond C-CHO) subsequent to ir multiphonon absorption (CO/sub 2/ laser) was studied. SiF/sub 4/, CH/sub 3/F, CCl/sub 4/, and CH/sub 4/ were added. (DLC)

A phase I study of vaccination with NY-ESO-1f peptide mixed with Picibanil OK-432 and Montanide ISA-51 in patients with cancers expressing the NY-ESO-1 antigen.

PubMed

Kakimi, Kazuhiro; Isobe, Midori; Uenaka, Akiko; Wada, Hisashi; Sato, Eiichi; Doki, Yuichiro; Nakajima, Jun; Seto, Yasuyuki; Yamatsuji, Tomoki; Naomoto, Yoshio; Shiraishi, Kenshiro; Takigawa, Nagio; Kiura, Katsuyuki; Tsuji, Kazuhide; Iwatsuki, Keiji; Oka, Mikio; Pan, Linda; Hoffman, Eric W; Old, Lloyd J; Nakayama, Eiichi

2011-12-15

We conducted a phase I clinical trial of a cancer vaccine using a 20-mer NY-ESO-1f peptide (NY-ESO-1 91-110) that includes multiple epitopes recognized by antibodies, and CD4 and CD8 T cells. Ten patients were immunized with 600 μg of NY-ESO-1f peptide mixed with 0.2 KE Picibanil OK-432 and 1.25 ml Montanide ISA-51. Primary end points of the study were safety and immune response. Subcutaneous injection of the NY-ESO-1f peptide vaccine was well tolerated. Vaccine-related adverse events observed were fever (Grade 1), injection-site reaction (Grade 1 or 2) and induration (Grade 2). Vaccination with the NY-ESO-1f peptide resulted in an increase or induction of NY-ESO-1 antibody responses in nine of ten patients. The sera reacted with recombinant NY-ESO-1 whole protein as well as the NY-ESO-1f peptide. An increase in CD4 and CD8 T cell responses was observed in nine of ten patients. Vaccine-induced CD4 and CD8 T cells responded to NY-ESO-1 91-108 in all patients with various HLA types with a less frequent response to neighboring peptides. The findings indicate that the 20-mer NY-ESO-1f peptide includes multiple epitopes recognized by CD4 and CD8 T cells with distinct specificity. Of ten patients, two with lung cancer and one with esophageal cancer showed stable disease. Our study shows that the NY-ESO-1f peptide vaccine was well tolerated and elicited humoral, CD4 and CD8 T cell responses in immunized patients. Copyright © 2011 UICC.

Structure, stability, and photoluminescence in the anti-perovskites Na{sub 3}W{sub 1−x}Mo{sub x}O{sub 4}F (0≤x≤1)

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

Sullivan, Eirin, E-mail: esulliv@ilstu.edu; Avdeev, Maxim; Blom, Douglas A.

2015-10-15

Single-phase ordered oxyfluorides Na{sub 3}WO{sub 4}F, Na{sub 3}MoO{sub 4}F and their mixed members Na{sub 3}W{sub 1−x}Mo{sub x}O{sub 4}F can be prepared via facile solid state reaction of Na{sub 2}MO{sub 4}·2H{sub 2}O (M=W, Mo) and NaF. Phases produced from incongruent melts are metastable, but lower temperatures allow for a facile one-step synthesis. In polycrystalline samples of Na{sub 3}W{sub 1−x}Mo{sub x}O{sub 4}F, the presence of Mo stabilizes the structure against decomposition to spinel phases. Photoluminescence studies show that upon excitation with λ=254 nm and λ=365 nm, Na{sub 3}WO{sub 4}F and Na{sub 3}MoO{sub 4}F exhibit broad emission maxima centered around 485 nm. Thesemore » materials constitute new members of the family of self-activating ordered oxyfluoride phosphors with anti-perovskite structures which are amenable to doping with emitters such as Eu{sup 3+}. - Graphical abstract: Directed synthesis of the ordered oxyfluorides Na{sub 3}W{sub 1−x}Mo{sub x}O{sub 4}F (0≤x≤1) has shown that a complete solid solution is attainable and provides the first example of photoluminescence in these materials. - Highlights: • Na{sub 3}W{sub 1−x}Mo{sub x}O{sub 4}F is a complete solid solution with hexagonal anti-perovskite structure. • The presence of even small amounts of Mo stabilizes the structure against decomposition. • Na{sub 3}W{sub 1−x}Mo{sub x}O{sub 4}F has broad emissions centered ≈485 nm (λ{sub ex}=254 nm and λ{sub ex}=365 nm). • These materials constitute a new family of self-activated oxyfluoride phosphors. • Na{sub 3}W{sub 1−x}Mo{sub x}O{sub 4}F materials are amenable to doping with emitters such as Eu{sup 3+}.« less

The role of selenium in iodine metabolism in children with goiter.

PubMed Central

Zagrodzki, P; Szmigiel, H; Ratajczak, R; Szybinski, Z; Zachwieja, Z

2000-01-01

Possible interactions between selenium and iodine metabolism were investigated in 7- to 16-year-old children with goiter (n = 136) living in southeastern Poland in iodine-deficient areas influenced by a sulfur industry. The Se-iodine interactions in these children were compared to the interactions in children from outside of that region (n = 38). Blood selenium (BSe) concentration and plasma glutathione peroxidase activity were much lower in the study group (64.1 +/- 15.7 microg/L; 111.0 +/- 27.6 U/L) than in the control group (85.3 +/- 19.6 microg/L; 182.4 +/- 35.6 U/L). Almost all of the data [plasma thyroid-stimulating hormone (TSH) concentration, plasma free thyroxine (fT(4)) concentration] fell within the reference limits. There was no statistically significant difference between the control and the study groups with respect to fT(4) and TSH. However, statistically significant differences of fT(4) and TSH in the study group were revealed between females belonging to the lower (n = 21; fT(4), 16.1 +/- 3.3 pmol/L; TSH, 1.83 +/- 1.05 mU/L) and upper Se quartiles (n = 24; fT(4), 14.5 +/- 2.2 pmol/L; TSH, 1. 26 +/- 0.90 mU/L), p < 0.05. Neither group differed in iodine in urine concentration, age, and body mass index. The difference in fT(4) concentrations can be attributed to an Se deficiency. The relationship exists only for females, which suggests a sex-linked hormonal response to concomitant Se and iodine deficiencies. Images Figure 1 Figure 2 PMID:10620526

The SHAFT Book (Design Charts for Torsional Properties of Non-Circular Shafts)

DTIC Science & Technology

1980-03-01

7870 .7906 .7944 .7864 .7903 .7968 .8048 . 7845 .7874 .7933 .8035 .8189 .7852 .7899 .7993 .8143 .8362 .7857 .7918 .8059 .8270 .8580 .7862 .7950 .8113...similar manner to equation 4): Ch h2V2f0= A(f1 +f3) +B(f2 +f4) +— (f2-f4) 2Rr - (A + B)2 f0 = h’D Eq (12) See figure A-6. 73 IRREGULAR...b2+b4) 4 1 Ch ba f k Ro b2(b2+b4) 2 b4(b2+b4) i Z2 f + r ] 1 2A_ ^ ^B_ _ Ch cb«-b4 j f ! bjbj b2b4

Phase equilibria in the NaF-CdO-NaPO{sub 3} system at 873 K and crystal structure and physico-chemical characterizations of the new Na{sub 2}CdPO{sub 4}F fluorophosphate

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

Aboussatar, Mohamed; Laboratoire de Physico-Chimie de l’État Solide, Faculté des Sciences de Sfax, Université de Sfax, BP 1171, 3000 Sfax; Mbarek, Aïcha

Isothermal sections of the diagram representing phase relationships in the NaF-CdO-NaPO{sub 3} system have been investigated by solid state reactions and powder X-ray diffraction. This phase diagram investigation confirms the polymorphism of the NaCdPO{sub 4} side component and the structure of the ß high temperature polymorph (orthorhombic, space group Pnma and unit cell parameters a=9.3118(2), b=7.0459(1), c=5.1849(1) Å has been refined. A new fluorophosphate, Na{sub 2}CdPO{sub 4}F, has been discovered and its crystal structure determined and refined from powder X-ray diffraction data. It exhibits a new 3D structure with orthorhombic symmetry, space group Pnma and unit cell parameters a=5.3731(1), b=6.8530(1),more » c=12.2691(2) Å. The structure is closely related to those of the high temperature polymorph of the nacaphite Na{sub 2}CaPO{sub 4}F and the fluorosilicate Ca{sub 2}NaSiO{sub 4}F but differs essentially in the cationic repartition since the structure is fully ordered with one Na site (8d) and one Cd site (4c). Relationships with other Na{sub 2}M{sup II}PO{sub 4}F (M{sup II}=Mg, Ca, Mn, Fe, Co, Ni) have been examined and the crystal-chemical and topographical analysis of these fluorophosphates is briefly reviewed. IR, Raman, optical and {sup 19}F, {sup 23}Na, {sup 31}P MAS NMR characterizations of Na{sub 2}CdPO{sub 4}F have been investigated. - Graphical abstract: The structure of the compound Na{sub 2}CdPO{sub 4}F, discovered during the study of the phase relationships in the NaF-CdO-NaPO{sub 3} system, has been determined and compared with other Na{sub 2}M{sup II}PO{sub 4}F fluorophosphates. - Highlights: • XRD analysis of the isothermal section of the NaF-CdO-NaPO{sub 3} system at 923 K. • Rietveld refinement of the high temperature polymorph β-NaCdPO{sub 4}. • Crystal structure of the new Na{sub 2}CdPO{sub 4}F fluorophosphate determined from powder XRD. • Crystal structure - composition relationships of Na{sub 2}M{sup II}PO{sub 4}F compounds are reviewed. • IR, Raman, optical and {sup 19}F, {sup 23}Na, {sup 31}P MAS NMR characterizations of Na{sub 2}CdPO{sub 4}F.« less

Room temperature synthesis of β-NaGdF 4 : RE 3+ (RE= Eu, Er) nanocrystallites and their luminescence

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

Tessitore, Gabriella; Mudring, Anja-Verena; Kr?mer, Karl W.

In this study, a room temperature synthesis was developed for phase pure β-NaGdF 4 nanocrystallites as well as 5, 10, and 20% Eu 3+ or 5% Er 3+ doped material. Rare earth acetates and NaCl react in a 1:2 M ratio with a variable excess of NH 4F in ethylene glycol within 24 hours. Since the thermodynamic stability of the hexagonal phase decreases along the lanthanide series, a larger excess of NH 4F was required for the synthesis of luminescent samples doped with the smaller Er 3+ ions than for Eu 3+ doped or pure β-NaGdF 4. The materials weremore » characterized by powder X-ray diffraction, electron microscopy, and luminescence spectroscopy. The Eu 3+-doped samples show 5D 0→ 7F J and 5D 1→ 7F J luminescence after Eu 3+ excitation at 394 nm or Gd 3+ excitation at 273 nm and 308 nm. The ratio of 5D 1 vs. 5D 0 luminescence is influenced by the excitation wavelength and the Eu 3+ concentration. Lastly, the Er 3+-doped samples show green and red upconversion luminescence, respectively, from the 2H 11/2+ 4S 3/2→ 4I 15/2 and 4F 9/2→ 4I 15/2 transitions after 970 nm excitation.« less

Room temperature synthesis of β-NaGdF 4 : RE 3+ (RE= Eu, Er) nanocrystallites and their luminescence

DOE PAGES

Tessitore, Gabriella; Mudring, Anja-Verena; Kr?mer, Karl W.

2017-09-01

In this study, a room temperature synthesis was developed for phase pure β-NaGdF 4 nanocrystallites as well as 5, 10, and 20% Eu 3+ or 5% Er 3+ doped material. Rare earth acetates and NaCl react in a 1:2 M ratio with a variable excess of NH 4F in ethylene glycol within 24 hours. Since the thermodynamic stability of the hexagonal phase decreases along the lanthanide series, a larger excess of NH 4F was required for the synthesis of luminescent samples doped with the smaller Er 3+ ions than for Eu 3+ doped or pure β-NaGdF 4. The materials weremore » characterized by powder X-ray diffraction, electron microscopy, and luminescence spectroscopy. The Eu 3+-doped samples show 5D 0→ 7F J and 5D 1→ 7F J luminescence after Eu 3+ excitation at 394 nm or Gd 3+ excitation at 273 nm and 308 nm. The ratio of 5D 1 vs. 5D 0 luminescence is influenced by the excitation wavelength and the Eu 3+ concentration. Lastly, the Er 3+-doped samples show green and red upconversion luminescence, respectively, from the 2H 11/2+ 4S 3/2→ 4I 15/2 and 4F 9/2→ 4I 15/2 transitions after 970 nm excitation.« less

On the Ground Electronic States of TiF and TiCl

PubMed

Boldyrev; Simons

1998-04-01

The low-lying electronic states of TiF and TiCl have been studied using high level ab initio techniques. Both are found to have two low-lying excited electronic states, 4Sigma- (0.080 eV (TiF) and 0.236 eV (TiCl)) and 2Delta (0.266 eV (TiF) and 0.348 eV (TiCl)), and 4Phi ground states at the highest CCSD(T)/6-311++G(2d,2f) level of theory. Our theoretical predictions of 4Phi ground electronic states for TiF and TiCl support recent experimental findings by Ram and Bernath, and our calculated bond lengths and vibrational frequencies are in reasonable agreement with their experimental data. Copyright 1998 Academic Press.

Bone marrow CD11b(+)F4/80(+) dendritic cells ameliorate collagen-induced arthritis through modulating the balance between Treg and Th17.

PubMed

Zhang, Lingling; Fu, Jingjing; Sheng, Kangliang; Li, Ying; Song, Shanshan; Li, Peipei; Song, Shasha; Wang, Qingtong; Chen, Jingyu; Yu, Jianhua; Wei, Wei

2015-03-01

Tolerogenic dendritic cells (DCs) are well-known to show an immunosuppressive function. In this study we determine the therapeutic effects and potential mechanisms of transferred bone marrow (BM) CD11b(+)F4/80(+) DCs on collagen-induced arthritis (CIA) in mice. Murine BM CD11b(+)F4/80(+) DCs were generated under the stimulation of GM-CSF and IL-4, and the function of BM CD11b(+) F4/80(+) DCs was identified by measuring the levels of IL-10, TGF-beta and indoleamine 2,3-dioxygenase (IDO). BM CD11b(+)F4/80(+) DCs were transferred to CIA mice by intravenous injections. The histopathology of joint and spleen were evaluated. T lymphocyte proliferation, Treg and Th17 subsets were analyzed. The expressions of Foxp3, Helios and RORγt in T lymphocytes co-cultured with BM CD11b(+)F4/80(+) DCs were measured in vitro. We found that BM CD11b(+)F4/80(+) DCs induced by GM-CSF and IL-4 could express high levels of IL-10, TGF-beta and IDO. BM CD11b(+)F4/80(+) DCs significantly reduced the pathologic scores in joints and spleens, which correlated significantly with the reduced T lymphocyte proliferation and Th17 cell number, and with the increased Tregs number. In vitro, OVA-pulsed BM CD11b(+)F4/80(+) DCs promoted Treg cell expansion, enhanced IL-10 and CTLA-4 protein expression, augmented Foxp3 and Helios mRNA expression, and inhibited RORγt and IL-17 mRNA expression. Taken together, BM CD11b(+)F4/80(+) DCs are able to ameliorate the development and severity of CIA, at least partly by inducing Foxp3(+) Treg cell expansion and suppressing Th17 function. The BM CD11b(+)F4/80(+) DCs might have a promising immunotherapeutic potential for autoimmune arthritis. Copyright © 2015 Elsevier B.V. All rights reserved.

Cost-effectiveness analysis of ledipasvir/sofosbuvir in patients with chronic hepatitis C: Treatment of patients with absence or mild fibrosis compared to patients with advanced fibrosis.

PubMed

Buti, M; Domínguez-Hernández, R; Oyagüez, I; Casado, M A; Esteban, R

2017-09-01

To evaluate the cost-effectiveness of ledipasvir/sofosbuvir (LDV/SOF) in treatment-naïve patients with chronic hepatitis C (CHC) genotype 1 (GT1) in the absence or mild fibrosis (F0-F1) versus advanced fibrosis (F2-F4), from the perspective of the Spanish Health System. A Markov model was developed to simulate disease progression, estimating costs and outcomes [life years gained (LYG) and quality-adjusted life years (QALY)] derived from starting with LDV/SOF in patients with F0-F1 compared with F2-F4. Therapy duration was 8 weeks in noncirrhotic patients with viral load <6 million IU/mL and 12 weeks in the remaining patients. Sustained virologic response rates were obtained from real-world cohort studies. Transition probabilities, utilities and direct costs were obtained from the literature. A 3% annual discount rate was applied to costs and outcomes. Sensitivity analyses were performed. LDV/SOF in F0-F1 patients was a dominant strategy, being more effective (19.85 LYG and 19.80 QALY) than beginning treatment in F2-F4 patients (18.63 LYG and 16.25 QALY), generating savings of €9228 per patient (€3661 due to disease management and monitoring). In a cohort of 1000 patients, LDV/SOF in F0-F1 patients decreased the number of cases of decompensated cirrhosis (93%), hepatocellular carcinoma (97%) and liver-related deaths (95%) and prevented 6 liver transplants compared to initiating LDV/SOF in F2-F4 patients. In CHC treatment-naïve GT1 patients, starting treatment with LDV/SOF in patients with F0-F1 compared to those with F2-F4 increases effectiveness by 1.22 LYG and 3.55 QALY gained and reduces disease burden and it is associated with cost savings. © 2017 John Wiley & Sons Ltd.

The 4d8-(4d74f + 4d76p + 4p54d9) transitions in the spectrum of five times ionized indium (In VI)

NASA Astrophysics Data System (ADS)

Ryabtsev, A. N.; Tauheed, A.; Swapnil; Kildiyarova, R. R.; Kononov, E. Ya

2018-06-01

The spectrum of five times ionized indium excited in a vacuum spark has been studied in the wavelength region 180-250 Å using a 3 m grazing incidence spectrograph. Transitions from highly excited interacting configurations 4d74f + 4d76p + 4p54d9 to the ground state 4d8 configuration were studied. 165 spectral lines were identified and 81 levels of the excited configurations were found.

Novel Catanionic Surfactant Vesicle Vaccines Protect against Francisella tularensis LVS and Confer Significant Partial Protection against F. tularensis Schu S4 Strain

PubMed Central

Richard, Katharina; Mann, Barbara J.; Stocker, Lenea; Barry, Eileen M.; Qin, Aiping; Cole, Leah E.; Hurley, Matthew T.; Ernst, Robert K.; Michalek, Suzanne M.; Stein, Daniel C.; DeShong, Philip

2014-01-01

Francisella tularensis is a Gram-negative immune-evasive coccobacillus that causes tularemia in humans and animals. A safe and efficacious vaccine that is protective against multiple F. tularensis strains has yet to be developed. In this study, we tested a novel vaccine approach using artificial pathogens, synthetic nanoparticles made from catanionic surfactant vesicles that are functionalized by the incorporation of either F. tularensis type B live vaccine strain (F. tularensis LVS [LVS-V]) or F. tularensis type A Schu S4 strain (F. tularensis Schu S4 [Schu S4-V]) components. The immunization of C57BL/6 mice with “bare” vesicles, which did not express F. tularensis components, partially protected against F. tularensis LVS, presumably through activation of the innate immune response, and yet it failed to protect against the F. tularensis Schu S4 strain. In contrast, immunization with LVS-V fully protected mice against intraperitoneal (i.p.) F. tularensis LVS challenge, while immunization of mice with either LVS-V or Schu S4-V partially protected C57BL/6 mice against an intranasal (i.n.) F. tularensis Schu S4 challenge and significantly increased the mean time to death for nonsurvivors, particularly following the i.n. and heterologous (i.e., i.p./i.n.) routes of immunization. LVS-V immunization, but not immunization with empty vesicles, elicited high levels of IgG against nonlipopolysaccharide (non-LPS) epitopes that were increased after F. tularensis LVS challenge and significantly increased early cytokine production. Antisera from LVS-V-immunized mice conferred passive protection against challenge with F. tularensis LVS. Together, these data indicate that functionalized catanionic surfactant vesicles represent an important and novel tool for the development of a safe and effective F. tularensis subunit vaccine and may be applicable for use with other pathogens. PMID:24351755

The roles of 4f- and 5f-orbitals in bonding: A magnetochemical, crystal field, density functional theory, and multi-reference wavefunction study

DOE PAGES

Lukens, Wayne W.; Speldrich, Manfred; Yang, Ping; ...

2016-05-31

The electronic structures of 4f 3/5f 3 Cp" 3M and Cp" 3M·alkylisocyanide complexes, where Cp" is 1,3-bis-(trimethylsilyl)cyclopentadienyl, are explored with a focus on the splitting of the f-orbitals, which provides information about the strengths of the metal–ligand interactions. While the f-orbital splitting in many lanthanide complexes has been reported in detail, experimental determination of the f-orbital splitting in actinide complexes remains rare in systems other than halide and oxide compounds, since the experimental approach, crystal field analysis, is generally significantly more difficult for actinide complexes than for lanthanide complexes. In this study, a set of analogous neodymium(III) and uranium(III) tris-cyclopentadienylmore » complexes and their isocyanide adducts was characterized by electron paramagnetic resonance (EPR) spectroscopy and magnetic susceptibility. The crystal field model was parameterized by combined fitting of EPR and susceptibility data, yielding an accurate description of f-orbital splitting. The isocyanide derivatives were also studied using density functional theory, resulting in f-orbital splitting that is consistent with crystal field fitting, and by multi-reference wavefunction calculations that support the electronic structure analysis derived from the crystal-field calculations. The results highlight that the 5f-orbitals, but not the 4f-orbitals, are significantly involved in bonding to the isocyanide ligands. The main interaction between isocyanide ligand and the metal center is a σ-bond, with additional 5f to π* donation for the uranium complexes. As a result, while interaction with the isocyanide π*-orbitals lowers the energies of the 5f xz2 and 5f yz2-orbitals, spin–orbit coupling greatly reduces the population of 5f xz2 and 5f yz2 in the ground state.« less

Exposure to polychlorinated biphenyls and the thyroid gland - examining and discussing possible longitudinal health effects in humans.

PubMed

Gaum, Petra M; Lang, Jessica; Esser, André; Schettgen, Thomas; Neulen, Joseph; Kraus, Thomas; Gube, Monika

2016-07-01

Many previous studies have dealt with the effect of polychlorinated biphenyls (PCBs) on the thyroid gland, but their findings are inconsistent. One problem of these studies has been their use of cross-sectional designs. The aim of the current study is to investigate longitudinal effects of PCBs on the thyroid gland, focusing on: morphological changes in thyroid tissue (i.e. thyroid volume), changes in thyroid hormones and in thyroid antibodies. A total of 122 individuals (Mage=44.7) were examined over a period of four years (t(1) until t(4)). Medical history was collected via interviews, an ultrasound examination was performed and blood samples were taken to determine plasma PCB levels, thyroid stimulating hormone (TSH), free triiodthyronine (fT3), free thyroxine (fT4), thyroid peroxidase antibodies (TPOab), thyreoglobulin antibodies (TGab) and thyroid-stimulating hormone receptor antibodies (TSHRab). Rank correlation coefficients and mixed effect models were performed controlling for age and total lipids. There were negative correlations between higher chlorinated biphenyls and fT3, cross-sectionally as well as longitudinally. We also found an interaction effect of higher-chlorinated PCBs over time for fT4 as well as TSHRab. In case of high exposure, a decrease in fT4 and an increase in TSHRab level were found over time. In regards to the other variables, our findings yielded no clear results in the examined time period. This is the first study to shows a PCB-related effect on fT3, fT4 and TSHRab over a four year period. The data also suggest that morphological and antibody findings remain inconsistent and do not allow for unambiguous interpretation. Copyright © 2016 Elsevier Inc. All rights reserved.

Validation of the FIB-4 index for evaluation of fibrosis in patients with recurrent hepatitis C after living donor liver transplantation: A single center experience.

PubMed

Kitajima, Toshihiro; Kaido, Toshimi; Hamaguchi, Yuhei; Yagi, Shintaro; Taura, Kojiro; Fujimoto, Yasuhiro; Hatano, Etsuro; Okajima, Hideaki; Haga, Hironori; Uemoto, Shinji

2016-07-01

The FIB-4 index has been proposed as a simple, non-invasive surrogate marker of liver fibrosis in patients with hepatitis C virus (HCV). However, the utility of FIB-4 in HCV positive patients after living donor liver transplantation (LDLT) has not been assessed. The aim of this study was to evaluate the efficacy of FIB-4 in the detection of significant liver graft fibrosis caused by recurrent HCV infection after LDLT compared with other simple fibrosis markers. A total of 259 liver biopsies (LB) with evidence of recurrent HCV were taken from 110 HCV positive LDLT patients who had undergone concomitant splenectomy before administration of antiviral therapy. In LB performed at 3 months or later after LT (n = 202, subject group), FIB-4 was compared between fibrosis stages and the accuracy of FIB-4 in predicting significant fibrosis (METAVIR, F ≥ 2) was assessed compared with aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio, age-platelet index, and AST to platelet ratio index (APRI). FIB-4 was significantly different between all fibrosis stages (F0 and F1-F4, P = 0.022; F0/1 and F2-F4, P < 0.0005; and F0-F2 and F3F4, P = 0.034) and provided the best area under the receiver-operator curve (AUROC) compared with other markers (FIB-4, 0.711; APRI, 0.693; age-platelet index, 0.663; and AST to ALT ratio, 0.562). The optimal cut-off value to identify significant fibrosis was 2.20 with 65% sensitivity and 69% specificity. FIB-4 is a more reliable marker for diagnosing significant liver fibrosis than APRI, age-platelet index, and AST to ALT ratio in LDLT patients with HCV. © 2015 The Japan Society of Hepatology.

The CRUTEM4 land-surface air temperature data set: construction, previous versions and dissemination via Google Earth

NASA Astrophysics Data System (ADS)

Osborn, T. J.; Jones, P. D.

2014-02-01

The CRUTEM4 (Climatic Research Unit Temperature, version 4) land-surface air temperature data set is one of the most widely used records of the climate system. Here we provide an important additional dissemination route for this data set: online access to monthly, seasonal and annual data values and time series graphs via Google Earth. This is achieved via an interface written in Keyhole Markup Language (KML) and also provides access to the underlying weather station data used to construct the CRUTEM4 data set. A mathematical description of the construction of the CRUTEM4 data set (and its predecessor versions) is also provided, together with an archive of some previous versions and a recommendation for identifying the precise version of the data set used in a particular study. The CRUTEM4 data set used here is available from doi:10.5285/EECBA94F-62F9-4B7C-88D3-482F2C93C468.

Detection of inflamed atherosclerotic lesions with diadenosine-5',5'''-P1,P4-tetraphosphate (Ap4A) and positron-emission tomography.

PubMed

Elmaleh, D R; Fischman, A J; Tawakol, A; Zhu, A; Shoup, T M; Hoffmann, U; Brownell, A-L; Zamecnik, P C

2006-10-24

Diadenosine-5',5'''-P(1),P(4)-tetraphosphate (Ap(4)A) and its analog P(2),P(3)-monochloromethylene diadenosine-5',5'''-P(1),P(4)-tetraphosphate (AppCHClppA) are competitive inhibitors of adenosine diphosphate-induced platelet aggregation, which plays a central role in arterial thrombosis and plaque formation. In this study, we evaluate the imaging capabilities of positron-emission tomography (PET) with P(2),P(3)-[(18)F]monofluoromethylene diadenosine-5',5'''-P(1),P(4)-tetraphosphate ([(18)F]AppCHFppA) to detect atherosclerotic lesions in male New Zealand White rabbits. Three to six months after balloon injury to the aorta, the rabbits were injected with [(18)F]AppCHFppA, and microPET imaging showed rapid accumulation of this radiopharmaceutical in the atherosclerotic abdominal aorta, with lesions clearly visible 30 min after injection. Computed tomographic images were coregistered with PET images to improve delineation of aortoiliac tracer activity. Plaque macrophage density, quantified by immunostaining with RAM11 against rabbit macrophages, correlated with PET measurements of [(18)F]AppCHFppA uptake (r = 0.87, P < 0.0001), whereas smooth-muscle cell density, quantified by immunostaining with 1A4 against smooth muscle actin, did not. Biodistribution studies of [(18)F]AppCHFppA in normal rats indicated typical adenosine dinucleotide behavior with insignificant myocardial uptake and fast kidney clearance. The accumulation of [(18)F]AppCHFppA in macrophage-rich atherosclerotic plaques can be quantified noninvasively with PET. Hence, [(18)F]AppCHFppA holds promise for the noninvasive characterization of vascular inflammation.

Synthesis and characterization of polyaniline/MnWO4 nanocomposites as electrodes for pseudocapacitors

NASA Astrophysics Data System (ADS)

Saranya, S.; Selvan, R. Kalai; Priyadharsini, N.

2012-03-01

Polyaniline (PAni)/MnWO4 nanocomposite was successfully synthesized by in situ polymerization method under ultrasonication and the MnWO4 was prepared by surfactant assisted ultrasonication method. The thermal stability of PAni was determined by TG/DTA (Thermo Gravimetric/ Differential thermal analysis). The structural and morphological features of PAni, MnWO4 and PAni/MnWO4 composite was analyzed using Fourier transform infrared spectrometry, X-ray diffraction (XRD), scanning electron microscope (SEM) and Transmission electron microscope (TEM) images. The electro-chemical properties of PAni, MnWO4 and its composites with different weight percentage of MnWO4 loading were studied through cyclic voltammetry (CV) for the application of supercapacitors as active electrode materials. From the cyclic voltammogram, 50% of MnWO4 impregnated PAni showed a high specific capacitance (SC) of 481 F/g than their individual counterparts of PAni (396 F/g) and MnWO4 (18 F/g). The galvanostatic charge-discharge studies indicate the in situ polymerized composite shows greater specific capacitance (475 F/g) than the physical mixture (346 F/g) at a constant discharge current of 1 mA/cm2 with reasonable cycling stability. The charge transfer resistance (Rct) of PAni/MnWO4 composite (22 ohm) was calculated using electrochemical impedance spectroscopy (EIS) and compared with its physical mixture (58 ohm).

Decreased intelligence in children and exposure to fluoride and arsenic in drinking water.

PubMed

Rocha-Amador, Diana; Navarro, Maria Elena; Carrizales, Leticia; Morales, Raúl; Calderón, Jaqueline

2007-01-01

Recent evidence suggests that fluoride (F) and arsenic (As) may adversely affect intelligence quotient (IQ) scores. We explore the association between exposure to F and As in drinking water and intelligence in children. Three rural communities in Mexico with contrasting levels of F and As in drinking water were studied: Moctezuma (F 0.8+/-1.4 mg/L; As 5.8+/-1.3 microg/L); Salitral (F 5.3+/-0.9 mg/L; As 169+/-0.9 microg/L) and 5 de Febrero (F 9.4+/-0.9 mg/L; As 194+/-1.3 microg/L). The final study sample consisted of 132 children from 6 to 10 years old. After controlling for confounders, an inverse association was observed between F in urine and Performance, Verbal, and Full IQ scores (beta values = -13, -15.6, -16.9, respectively). Similar results were observed for F in drinking water (beta values = -6.7, -11.2, -10.2, respectively) and As in drinking water (beta values= -4.30, -6.40, -6.15, respectively). The p-values for all cases were < 0.001. A significant association was observed between As in urine and Full IQ scores (beta = -5.72, p = 0.003). These data suggest that children exposed to either F or As have increased risks of reduced IQ scores.

Vitamin D levels do not predict the stage of hepatic fibrosis in patients with non-alcoholic fatty liver disease: A PRISMA compliant systematic review and meta-analysis of pooled data

PubMed Central

Saberi, Behnam; Dadabhai, Alia S; Nanavati, Julie; Wang, Lin; Shinohara, Russell T; Mullin, Gerard E

2018-01-01

AIM To investigate the relationship between 25-hydroxyvitamin D [25(OH)D] levels and fibrosis stage in patients with non-alcoholic fatty liver disease (NAFLD). METHODS Two individual reviewers identified relevant studies using the PubMed, EMBASE, Cochrane, and Scopus databases. Inclusion criteria were as follows: (1) Studies that evaluated adults with NAFLD and serum or plasma 25(OH)D levels; and (2) assessed fibrosis stage using liver biopsy. A rigorous analysis yielded six articles as having sufficient data to employ in evaluating the association of serum vitamin D levels in patients with NAFLD based on their liver fibrosis stage by histopathological analysis. The lead investigators of each of the six studies were contacted and the data were collected. To meta-analyze vitamin D levels in F0-F2 vs F3-F4 fibrosis, a random-effects meta-analysis fit using restricted maximum likelihood was applied. To examine trends across each stage of fibrosis with respect to vitamin D levels, a meta-regression was performed. P < 0.05 was considered statistically significant. RESULTS A total of 937 subjects from six studies were included in the final analysis to evaluate the association of serum vitamin D levels in patients with NAFLD based on their liver fibrosis stage by histopathological analysis. The lead investigators of each of the six studies were contacted and the data were collected. First, the investigators performed a meta-analysis to compare serum vitamin D levels in patients with NAFLD with stage F0-F2 compared to F3-F4, which did not show significance [meta-estimate of the pooled mean difference = -0.86, P = 0.08 (-4.17, 2.46)]. A meta-regression evaluation of serum vitamin 25 (OH)D levels across the individual stages (F0-F4) of fibrosis did not show an association for the six included studies. CONCLUSION Low vitamin D status is not associated with higher stages of liver fibrosis in patients with NAFLD. PMID:29399288

Vitamin D levels do not predict the stage of hepatic fibrosis in patients with non-alcoholic fatty liver disease: A PRISMA compliant systematic review and meta-analysis of pooled data.

PubMed

Saberi, Behnam; Dadabhai, Alia S; Nanavati, Julie; Wang, Lin; Shinohara, Russell T; Mullin, Gerard E

2018-01-27

To investigate the relationship between 25-hydroxyvitamin D [25(OH)D] levels and fibrosis stage in patients with non-alcoholic fatty liver disease (NAFLD). Two individual reviewers identified relevant studies using the PubMed, EMBASE, Cochrane, and Scopus databases. Inclusion criteria were as follows: (1) Studies that evaluated adults with NAFLD and serum or plasma 25(OH)D levels; and (2) assessed fibrosis stage using liver biopsy. A rigorous analysis yielded six articles as having sufficient data to employ in evaluating the association of serum vitamin D levels in patients with NAFLD based on their liver fibrosis stage by histopathological analysis. The lead investigators of each of the six studies were contacted and the data were collected. To meta-analyze vitamin D levels in F0-F2 vs F3-F4 fibrosis, a random-effects meta-analysis fit using restricted maximum likelihood was applied. To examine trends across each stage of fibrosis with respect to vitamin D levels, a meta-regression was performed. P < 0.05 was considered statistically significant. A total of 937 subjects from six studies were included in the final analysis to evaluate the association of serum vitamin D levels in patients with NAFLD based on their liver fibrosis stage by histopathological analysis. The lead investigators of each of the six studies were contacted and the data were collected. First, the investigators performed a meta-analysis to compare serum vitamin D levels in patients with NAFLD with stage F0-F2 compared to F3-F4, which did not show significance [meta-estimate of the pooled mean difference = -0.86, P = 0.08 (-4.17, 2.46)]. A meta-regression evaluation of serum vitamin 25 (OH)D levels across the individual stages (F0-F4) of fibrosis did not show an association for the six included studies. Low vitamin D status is not associated with higher stages of liver fibrosis in patients with NAFLD.

Molecular Self-Assembly in a Poorly Screened Environment: F 4TCNQ on Graphene/BN

DOE PAGES

Tsai, Hsin-Zon; Omrani, Arash A.; Coh, Sinisa; ...

2015-10-20

Here we report a scanning tunneling microscopy and noncontact atomic force microscopy study of close-packed 2D islands of tetrafluoro-tetracyanoquinodimethane (F 4TCNQ) molecules at the surface of a graphene layer supported by boron nitride. While F 4TCNQ molecules are known to form cohesive 3D solids, the intermolecular interactions that are attractive for F 4TCNQ in 3D are repulsive in 2D. Our experimental observation of cohesive molecular behavior for F 4TCNQ on graphene is thus unexpected. This self-assembly behavior can be explained by a novel solid formation mechanism that occurs when charged molecules are placed in a poorly screened environment. As negativelymore » charged molecules coalesce, the local work function increases, causing electrons to flow into the coalescing molecular island and increase its cohesive binding energy.« less

Development of Solid State Laser Materials for Application in Lasers for Atmospheric Ozone and Water Vapor Sensing

NASA Technical Reports Server (NTRS)

Noginov, Makhail A.; Loutts, G. B.

2002-01-01

We have grown neodymium doped mixed apatite crystals, (Sr(x)Ba(l-x)5(PO4)3F, Sr5(P(1-x)V(x)O4)3F, and Ba5(P(1-x)V(x)O4)3F, and spectroscopically studied them as potential gain media for a laser source for atmospheric water sensing operating at 944.11 nm0. We conclude that an appropriate apatite host material for a 944.11 nm laser should be a mixture of Sr5(PO4)3F with a small fraction of Ba5(PO4)3F. The precise wavelength tuning around 944.11 nm can be accomplished by varying the host composition, temperature, and threshold population inversion. In apatite crystals of mixed composition, the Amplified Spontaneous Emission (ASE) loss at 1.06 microns is predicted to be significantly smaller than that in the end members.

Investigation of cis-4-[18F]Fluoro-D-Proline Uptake in Human Brain Tumors After Multimodal Treatment.

PubMed

Verger, Antoine; Stoffels, Gabriele; Galldiks, Norbert; Lohmann, Philipp; Willuweit, Antje; Neumaier, Bernd; Geisler, Stefanie; Langen, Karl-Josef

2018-04-23

Cis-4-[ 18 F]fluoro-D-proline (D-cis-[ 18 F]FPro) has been shown to pass the intact blood-brain barrier and to accumulate in areas of secondary neurodegeneration and necrosis in the rat brain while uptake in experimental brain tumors is low. This pilot study explores the uptake behavior of D-cis-[ 18 F]FPro in human brain tumors after multimodal treatment. In a prospective study, 27 patients with suspected recurrent brain tumor after treatment with surgery, radiotherapy, and/or chemotherapy (SRC) were investigated by dynamic positron emission tomography (PET) using D-cis-[ 18 F]FPro (22 high-grade gliomas, one unspecified glioma, and 4 metastases). Furthermore, two patients with untreated lesions were included (one glioblastoma, one reactive astrogliosis). Data were compared with the results of PET using O-(2-[ 18 F]fluoroethyl)-L-tyrosine ([ 18 F]FET) which detects viable tumor tissue. Tracer distribution, mean and maximum lesion-to-brain ratios (LBR mean , LBR max ), and time-to-peak (TTP) of the time activity curve (TAC) of tracer uptake were evaluated. Final diagnosis was determined by histology (n = 9), clinical follow-up (n = 10), or by [ 18 F]FET PET (n = 10). D-cis-[ 18 F]FPro showed high uptake in both recurrent brain tumors (n = 11) and lesions classified as treatment-related changes (TRC) only (n = 16) (LBR mean 2.2 ± 0.7 and 2.1 ± 0.6, n.s.; LBR max 3.4 ± 1.2 and 3.2 ± 1.3, n.s.). The untreated glioblastoma and the lesion showing reactive astrogliosis exhibited low D-cis-[ 18 F]FPro uptake. Distribution of [ 18 F]FET and D-cis-[ 18 F]FPro uptake was discordant in 21/29 cases indicating that the uptake mechanisms are different. The high accumulation of D-cis-[ 18 F]FPro in pretreated brain tumors and TRC supports the hypothesis that tracer uptake is related to cell death. Further studies before and after therapy are needed to assess the potential of D-cis-[ 18 F]FPro for treatment monitoring.

The PAPAS index: a novel index for the prediction of hepatitis C-related fibrosis.

PubMed

Ozel, Banu D; Poyrazoğlu, Orhan K; Karaman, Ahmet; Karaman, Hatice; Altinkaya, Engin; Sevinç, Eylem; Zararsiz, Gökmen

2015-08-01

Several noninvasive tests have been developed to determine the degree of hepatic fibrosis in patients with chronic hepatitis C (CHC) without performing liver biopsy. This study aimed to determine the performance of the PAPAS (Platelet/Age/Phosphatase/AFP/AST) index in patients with CHC for the prediction of significant fibrosis and cirrhosis and to compare it with other noninvasive tests. To date, no study has evaluated the application of the PAPAS index in CHC-associated liver fibrosis. This retrospective study included 137 consecutive patients with CHC who had undergone a percutaneous liver biopsy before treatment. The aspartate aminotransferase/platelet ratio (APRI), aspartate aminotransferase/alanine transaminase ratio (AAR), age-platelet index (API), FIB4, cirrhosis discriminate score (CDS), the Göteborg University cirrhosis index (GUCI), and PAPAS were calculated and compared with the diagnostic accuracies of all fibrosis indices between the groups F0-F2 (no-mild fibrosis) versus F3-F6 (significant fibrosis) and F0-F4 (no cirrhosis) versus F5-F6 (cirrhosis). To predict significant fibrosis, the area under curve (95% confidence interval) for FIB4 was 0.727 followed by GUCI (0.721), PAPAS≈APRI≈CDS (0.716), and API (0.68). To predict cirrhosis, the area under curve (95% confidence interval) for FIB4 was calculated to be 0.735, followed by GUCI (0.723), PAPAS≈APRI≈CDS≈(0.71), and API (0.66). No statistically significant difference was observed among these predictors to exclude both significant fibrosis and cirrhosis (P>0.05). The diagnostic capability of the PAPAS index has moderate efficiency and was not superior to other fibrosis markers for the identification of fibrosis in CHC patients. There is a need for more comprehensive prospective studies to help determine the diagnostic value of PAPAS for liver fibrosis.

CXCR4-mediated osteosarcoma growth and pulmonary metastasis is promoted by mesenchymal stem cells through VEGF.

PubMed

Zhang, Peng; Dong, Ling; Yan, Kang; Long, Hua; Yang, Tong-Tao; Dong, Ming-Qing; Zhou, Yong; Fan, Qing-Yu; Ma, Bao-An

2013-10-01

Chemokines and chemokine receptor 4 (CXCR4) play an important role in metastasis. CXCR4 is also expressed in the human osteosarcoma cell line 9607-F5M2 (F5M2), which has a high tumorigenic ability and potential for spontaneous pulmonary metastasis. Mesenchymal stem cells (MSCs) contribute to the formation of the tumor stroma and promote metastasis. However, mechanisms underlying the promotion of osteosarcoma growth and pulmonary metastasis by MSCs are still elusive. Our study co-injected the human MSCs and F5M2 cells into the caudal vein of nude mice. The total number of tumor nodules per lung was significantly increased in the F5M2+MSC group compared to the other groups (control, F5M2 cells alone and MSCs alone) at week six. Moreover, a high number of Dil-labeled MSCs was present also at the osteosarcoma metastasis sites in the lung. Using Transwell assays, we found that F5M2 cells migrate towards MSCs, while the CXCR4 inhibitor AMD3100 decreased the migration potential of F5M2 cells towards MSCs. Furthermore, upon treatment with F5M2-conditioned medium, MSCs expressed and secreted higher levels of VEGF as determined by immunohistochemistry, western blotting and ELISA, respectively. Importantly, co-cultured with F5M2 cells, MSCs expressed and secreted higher VEGF levels, while AMD3100 dramatically decreased the VEGF secretion by MSCs. However, CXCR4 expression on F5M2 cells was not significantly increased in the co-culture system. Additionally, VEGF increased the proliferation of both MSCs and F5M2 cells. These findings suggest that CXCR4-mediated osteosarcoma growth and pulmonary metastasis are promoted by MSCs through VEGF.

Inelastic Neutron Scattering Study of the Specific Features of the Phase Transitions in (NH4)2WO2F4

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

Smirnov, Lev S; Kolesnikov, Alexander I; Flerov, I. N.

2009-01-01

Oxyfluoride (NH4)2WO2F4 has been studied by the inelastic neutron scattering method over a wide temperature range 10 300 K at two initial neutron energies of 15 and 60 meV. The role of tetrahedral ammonium groups in the mechanism of sequential phase transitions at T1 = 201 K and T2 = 160 K has been discussed.

A non-typical sequence of phase transitions in (NH4)3GeF7: optical and structural characterization.

PubMed

Mel'nikova, S V; Molokeev, M S; Laptash, N M; Misyul, S V

2016-03-28

Single crystals of germanium double salt (NH4)3GeF7 = (NH4)2GeF6·NH4F = (NH4)3[GeF6]F were grown and studied by the methods of polarization optics and X-ray diffraction. The birefringence Δn = (no - ne), the rotation angle of the optical indicatrix ϕ(T) and unit cell parameters were measured in the temperature range 100-400 K. Three structural phase transitions were found at the temperatures: T1↓ = 279.2 K (T1↑ = 279.4 K), T2↑ = 270 K (T2↓ = 268.9 K), T3↓ = 218 K (T3↑ = 227 K). An unusual sequence of symmetry transformations with temperature change was established: P4/mbm (Z = 2) (G1) ↔ Pbam (Z = 4) (G2) ↔ P21/c (Z = 4) (G3) ↔ Pa3[combining macron] (Z = 8) (G4). The crystal structures of different phases were determined. The experimental data were additionally interpreted by a group-theoretical analysis of the complete condensate of order parameters taking into account the critical and noncritical atomic displacements. Strengthening of the N-HF hydrogen bonds can be a driving force of the observed phase transitions.

The Effect of Titanium Tetrafluoride and Sodium Hypochlorite on the Shear Bond Strength of Methacrylate and Silorane Based Composite Resins: an In-Vitro Study.

PubMed

Sharafeddin, Farahnaz; Koohpeima, Fatemeh; Razazan, Nader

2017-06-01

The bond strength of composites with different adhesive systems with dentin is an important factor in long term durability of composite restorations. The effect of titanium tetrafluoride (TiF 4 ) as anti caries agent and sodium hypochlorite (NaOCl) as disinfectant on the shear bond of nanofilled and silorane based composite resins have not been investigated in previous studies. This study was conducted to determine bond strength between dentin and two composite systems, by means of shear bond test using TiF 4 and NaOCl. Middle dentin of 60 intact extracted maxillary premolar teeth were exposed by sectioning the crowns at a depth of 2mm from central groove and parallel to the occlusal surface. Standardized smear layer was created using a 600-grit silicon carbide paper and then samples were embedded in acrylic resin blocks. Then the samples were randomly divided into 6 \\groups summarized as Group I: Z350, Group II: Z350+ NaOCl, Group III: Z350+ TiF 4 , Group IV: P90, Group V: P90+ NaOCl, Group VI: P90+ TiF 4 according to manufacturer's instruction. Then samples were subjected to shear bond strength (SBS) test using universal testing machine and data were analyzed using ANOVA and Tukey tests ( p < 0.05). Application of 5% NaOCl caused a significant decrease in SBS of nanofilled composite resin ( p = 0.004), and also silorane based composite resin ( p = 0.006). Application of 4% TiF 4 caused a significant increase in SBS of silorane based composite resin ( p = 0.001). The effect of TiF 4 on nanofilled composite was not statistically significant. Using TiF 4 has a positive effect on increasing the shear bond while NaOCl has negative effect on bond strength.

Melanocortin-4 receptor pathway dysfunction in obesity: Patient stratification aimed at MC4R agonist treatment.

PubMed

Ayers, Kristin L; Glicksberg, Benjamin S; Garfield, Alastair S; Longerich, Simonne; White, Joseph A; Yang, Pengwei; Du, Lei; Chittenden, Thomas W; Gulcher, Jeffery R; Roy, Sophie; Fiedorek, Fred; Gottesdiener, Keith; Cohen, Sarah; North, Kari E; Schadt, Eric E; Li, Shuyu D; Chen, Rong; Van der Ploeg, Lex H T

2018-05-02

The hypothalamic melanocortin 4 receptor (MC4R)-pathway serves a critical role in regulating bodyweight. Loss of function (LoF) mutations in the MC4R pathway including mutations in the POMC (1), PCSK1, LEPR (2) or the MC4R genes (3) have been shown to be causative of early-onset severe obesity. Through a comprehensive epidemiological analysis of known and predicted LoF variants in the POMC, PCSK1 and LEPR genes, we sought to estimate the number of US individuals with bi-allelic MC4R pathway LoF variants. We predict approximately 650 α-MSH/POMC, 8,500 PCSK1 and 3,600 LEPR homozygous and compound heterozygous individuals in the US, cumulatively enumerating over 12,800 MC4R pathway deficient obese patients. Very few of these have been genetically diagnosed to date. These estimates increase when we include a small subset of less rare variants: β-MSH/POMC, PCSK1 N221D, and a novel PCSK1 LoF variant (T640A). To further define the MC4R pathway and its potential impact on obesity we tested associations between body-mass index (BMI) and LoF mutation-burden in the POMC, PCSK1 and LEPR genes in various populations. We show that the cumulative allele burden in individuals with two or more LoF alleles in one or more genes in the MC4R pathway predisposes to a higher BMI than non-carriers or heterozygous LoF carriers with a defect in only one gene. Our analysis represents a genetically-rationalized study of the hypothalamic MC4R pathway aimed at genetic patient stratification to determine which obese sub-populations should be studied to understand MC4R agonist (e.g., setmelanotide) treatment responsiveness.

Optical characterization of Eu3+ and Tb3+ ions doped zinc lead borate glasses.

PubMed

Thulasiramudu, A; Buddhudu, S

2007-02-01

This paper reports on the spectral analysis of Eu3+ or Tb3+ ions (0.5 mol%) doped heavy metal oxide (HMO) based zinc lead borate glasses from the measurement of their absorption, emission spectra and also different physical properties. From the XRD, DSC profiles, the glass nature and glass thermal properties have been studied. The measured emission spectrum of Eu3+ glass has revealed five transitions (5D0-->7F0, 7F1, 7F2, 7F3 and 7F4) at 578, 591, 613, 654 and 702 nm, respectively, with lambdaexci=392 nm (7F0-->5L6). In the case of Tb3+:ZLB glass, four emission transitions such as (5D4-->7F6, 7F5, 7F4 and 7F3) that are located at 489, 542, 585 and 622 nm, respectively, have been measured with lambdaexci=374 nm. For all these emission bands decay curves have been plotted to evaluate their lifetimes and the emission processes that arise in the glasses have been explained in terms of energy level schemes.

Polymorphs of LiFeSO4F as cathode materials for lithium ion batteries - a first principle computational study.

PubMed

Chung, Sai Cheong; Barpanda, Prabeer; Nishimura, Shin-Ichi; Yamada, Yuki; Yamada, Atsuo

2012-06-28

We have investigated polymorphs of LiFeSO4F, tavorite and triplite, which have been reported as cathode materials for lithium ion batteries. The predicted voltages are 3.64 and 3.90 V for tavorite and triplite, respectively, which agreed excellently with experimental data. It is found that the lithiated states (LiFeSO4F) of the polymorphs are almost degenerate in energy. The difference in voltage is mainly due to the difference in the stabilities of the delithiated states (FeSO4F). This is rationalized by the Fe(3+)-Fe(3+) repulsion in the edge sharing geometry of the triplite structure.

A population pharmacokinetic analysis of sildenafil citrate in patients with erectile dysfunction

PubMed Central

Milligan, Peter A; Marshall, Scott F; Karlsson, Mats O

2002-01-01

Aims To analyse the pharmacokinetics of sildenafil citrate in patients with erectile dysfunction in order to characterize covariate relationships and assist in the development of rational dosage strategies. Methods A population pharmacokinetic sampling strategy was incorporated into five phase III clinical study protocols. Overall, 2077 patients, 1335 of whom received sildenafil, were asked to take an additional dose of study drug before their scheduled clinic visits on four or five occasions throughout the study duration. A single plasma sample was obtained at random times postdose (range 1–7 h), and a total of 4582 samples were assayed (average 3.4 samples per individual). Results For the population average patient (age 58 years; aspartate transaminase [AST], 24 IU l−1; weight, 87 kg; not receiving CYP3A4 potential inhibitors), typical values for sildenafil (mean±SE) were 58.5±1.4 l h−1 for apparent clearance (CL/F), 310±6.92 l for volume of distribution (V/F), and 2.6±0.176 h−1 for first-order absorption constant (ka). The value for ka is associated with meal consumption within 2 h predose, at all other times ka was equivalent to an instantaneous bolus administration. The interindividual variabilities were 29% for CL/F, 20% for V/F, and 210% for ka. Over a dose range of 25–100 mg sildenafil, the pharmacokinetics exhibited dose proportionality. There was evidence of nonproportionality (40% increase on average) in relative bioavailability with respect to the 200-mg dose (P < 0.001) relative to the other doses. Age, AST concentration, and co-administration with CYP3A4 potential inhibitors significantly influenced CL/F of sildenafil (P < 0.001, for each relationship). For age and AST, the extent of the linear relationships (extrapolated from population average values) included a 4% decrease in CL/F for every decade increase and a 6% decrease in CL/F for every 10-unit increase, respectively. Following co-administration of CYP3A4 potential inhibitors, a 14% decrease in CL/F was estimated. Only body weight was found to significantly (P < 0.001) influence V/F (a 6% increase in V/F for every 10-kg increase). Conclusions The pharmacokinetics of, and covariate influences on, sildenafil in patients with erectile dysfunction were shown to be consistent with those demonstrated in phase I volunteer studies. PMID:11879259

Differentiation of F4 receptor profiles in pigs based on their mucin 4 polymorphism, responsiveness to oral F4 immunization and in vitro binding of F4 to villi.

PubMed

Nguyen, V U; Goetstouwers, T; Coddens, A; Van Poucke, M; Peelman, L; Deforce, D; Melkebeek, V; Cox, E

2013-03-15

F4(+) enterotoxigenic Escherichia coli (F4(+) ETEC) are an important cause of diarrhoea and mortality in piglets. F4(+) ETEC use their F4 fimbriae to adhere to specific receptors (F4Rs) on small intestinal brush borders, resulting in colonization of the small intestine. To prevent pigs from post-weaning diarrhoea, pigs should be vaccinated during the suckling period. Previously, we demonstrated that F4acR(+), but not F4acR(-) piglets could be orally immunized with purified F4 fimbriae resulting in a protective immunity against F4(+) ETEC infections, indicating that this immune response was F4R dependent. Recently, aminopeptidase N has been identified as a glycoprotein receptor important for this oral immune response. However, in some oral immunization experiments, a few F4acR(+) piglets did not show an antibody response upon oral immunization, suggesting additional receptors. Therefore, the binding profile of F4 to brush border membrane (glyco)proteins was determined for pigs differing in F4-specific antibody response upon oral immunization, in in vitro adhesion of F4(+)E. coli to small intestinal villi, and in Muc4 genotype. Six groups of pigs could be identified. Only two groups positive in all three assays showed two high molecular weight (MW) glycoprotein bands (>250kDa) suggesting that these high MW bands are linked to the MUC4 susceptible genotype. The fact that these bands were absent in the MUC4 resistant group which showed a positive immune response against F4 and was positive in the adhesion test confirm that at least one or perhaps more other F4Rs exist. Interestingly, two pigs that were positive in the villous adhesion assay did not show an immune response against F4 fimbriae. This suggests that a third receptor category might exist which allows the bacteria to adhere but does not allow effective immunization with soluble F4 fimbriae. Future research will be necessary to confirm or reveal the identity of these receptors. Copyright © 2012 Elsevier B.V. All rights reserved.

Corrosive effects of fluoride on titanium: investigation by X-ray photoelectron spectroscopy, atomic force microscopy, and human epithelial cell culturing.

PubMed

Stájer, Anette; Ungvári, Krisztina; Pelsoczi, István K; Polyánka, Hilda; Oszkó, Albert; Mihalik, Erzsébet; Rakonczay, Zoltán; Radnai, Márta; Kemény, Lajos; Fazekas, András; Turzó, Kinga

2008-11-01

High fluoride (F(-)) concentrations and acidic pH impair the corrosion resistance of titanium (Ti). Effects of F(-)-containing caries-preventive prophylactic rinses, and gels on Ti were investigated by X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). Human epithelial cell attachment and proliferation were investigated by dimethylthiazol-diphenyl tetrazolium bromide (MTT) and protein content assays. Aqueous 1% NaF solution (3800 ppm F(-), pH 4.5) or high (12,500 ppm) F(-) content gel (pH 4.8) strongly corroded the surface and modified its composition. XPS revealed formation of a strongly bound F(-)-containing complex (Na(2)TiF(6)). AFM indicated an increase in roughness (R(a)) of the surfaces: 10-fold for the NaF solution and smaller for the gel or a mouthwash (250 ppm F(-), pH 4.4). MTT revealed that cell attachment was significantly increased by the gel, but was not disturbed by either the mouthwash or the NaF. Cell proliferation determined by MTT decreased significantly only for the NaF-treated samples; protein content assay experiments showed no such effect. This study indicates that epithelial cell culturing results can depend on the method used, and the adverse effects of a high F(-) concentration and low pH should be considered when prophylactic gels are applied by patients with Ti implants or other dental devices.

Oral Administration of a Select Mixture of Bacillus Probiotics Affects the Gut Microbiota and Goblet Cell Function following Escherichia coli Challenge in Newly Weaned Pigs of Genotype MUC4 That Are Supposed To Be Enterotoxigenic E. coli F4ab/ac Receptor Negative.

PubMed

Zhang, Wei; Zhu, Yao-Hong; Zhou, Dong; Wu, Qiong; Song, Dan; Dicksved, Johan; Wang, Jiu-Feng

2017-02-01

Structural disruption of the gut microbiota and impaired goblet cell function are collateral etiologic factors in enteric diseases. Low, moderate, or high doses of a Bacillus licheniformis-B. subtilis mixture (BLS mix) were orally administered to piglets of genotype MUC4 that are supposed to be F4-expressing enterotoxigenic Escherichia coli strain (F4 + ETEC) F4ab/ac receptor negative (i.e., MUC4-resistant piglets) for 1 week before F4 + ETEC challenge. The luminal contents were collected from the mucosa of the colon on day 8 after F4 + ETEC challenge. The BLS mix attenuated E. coli-induced expansion of Bacteroides uniformis, Eubacterium eligens, Acetanaerobacterium, and Sporobacter populations. Clostridium and Turicibacter populations increased following F4 + ETEC challenge in pigs pretreated with low-dose BLS mix. Lactobacillus gasseri and Lactobacillus salivarius populations increased after administration of BLS mix during E. coli infection. The beneficial effects of BLS mix were due in part to the expansion of certain Clostridium, Lactobacillus, and Turicibacter populations, with a corresponding increase in the number of goblet cells in the ileum via upregulated Atoh1 expression, in turn increasing MUC2 production and thus preserving the mucus barrier and enhancing host defenses against enteropathogenic bacteria. However, excessive BLS mix consumption may increase the risk for enteritis, partly through disruption of colonic microbial ecology, characterized by expansion of Proteobacteria and impaired goblet cell function in the ileum. Our findings suggest that oral administration of BLS mix reprograms the gut microbiota and enhances goblet cell function to ameliorate enteritis. The present study is important for improving our understanding of the protective role of probiotics against Escherichia coli infection in piglets. Structural disruption of the gut microbiota and impaired goblet cell function are collateral etiologic factors in enteric diseases. In this study, low, moderate, or high doses of a Bacillus licheniformis-B. subtilis mixture (BLS mix) were orally administered to MUC4-resistant piglets for 1 week before the F4-expressing ETEC strain (F4 + ETEC) challenge. Our findings suggest that oral administration of BLS mix reprograms the gut microbiota and enhances goblet cell function to ameliorate enteritis. Copyright © 2017 American Society for Microbiology.

Oral Administration of a Select Mixture of Bacillus Probiotics Affects the Gut Microbiota and Goblet Cell Function following Escherichia coli Challenge in Newly Weaned Pigs of Genotype MUC4 That Are Supposed To Be Enterotoxigenic E. coli F4ab/ac Receptor Negative

PubMed Central

Zhang, Wei; Zhou, Dong; Wu, Qiong; Song, Dan; Dicksved, Johan; Wang, Jiu-Feng

2016-01-01

ABSTRACT Structural disruption of the gut microbiota and impaired goblet cell function are collateral etiologic factors in enteric diseases. Low, moderate, or high doses of a Bacillus licheniformis-B. subtilis mixture (BLS mix) were orally administered to piglets of genotype MUC4 that are supposed to be F4-expressing enterotoxigenic Escherichia coli strain (F4+ ETEC) F4ab/ac receptor negative (i.e., MUC4-resistant piglets) for 1 week before F4+ ETEC challenge. The luminal contents were collected from the mucosa of the colon on day 8 after F4+ ETEC challenge. The BLS mix attenuated E. coli-induced expansion of Bacteroides uniformis, Eubacterium eligens, Acetanaerobacterium, and Sporobacter populations. Clostridium and Turicibacter populations increased following F4+ ETEC challenge in pigs pretreated with low-dose BLS mix. Lactobacillus gasseri and Lactobacillus salivarius populations increased after administration of BLS mix during E. coli infection. The beneficial effects of BLS mix were due in part to the expansion of certain Clostridium, Lactobacillus, and Turicibacter populations, with a corresponding increase in the number of goblet cells in the ileum via upregulated Atoh1 expression, in turn increasing MUC2 production and thus preserving the mucus barrier and enhancing host defenses against enteropathogenic bacteria. However, excessive BLS mix consumption may increase the risk for enteritis, partly through disruption of colonic microbial ecology, characterized by expansion of Proteobacteria and impaired goblet cell function in the ileum. Our findings suggest that oral administration of BLS mix reprograms the gut microbiota and enhances goblet cell function to ameliorate enteritis. IMPORTANCE The present study is important for improving our understanding of the protective role of probiotics against Escherichia coli infection in piglets. Structural disruption of the gut microbiota and impaired goblet cell function are collateral etiologic factors in enteric diseases. In this study, low, moderate, or high doses of a Bacillus licheniformis-B. subtilis mixture (BLS mix) were orally administered to MUC4-resistant piglets for 1 week before the F4-expressing ETEC strain (F4+ ETEC) challenge. Our findings suggest that oral administration of BLS mix reprograms the gut microbiota and enhances goblet cell function to ameliorate enteritis. PMID:27881419

Antibody-based targeted delivery of interleukin-4 synergizes with dexamethasone for the reduction of inflammation in arthritis.

PubMed

Schmid, Anja Sophie; Hemmerle, Teresa; Pretto, Francesca; Kipar, Anja; Neri, Dario

2018-04-01

We have previously reported that F8-IL4, a fusion protein consisting of the F8 antibody specific to the alternatively-spliced extra domain A of fibronectin and of murine IL-4, cures mice with established arthritis, when used in combination with dexamethasone (DXM). The goal of this study was to assess whether other therapeutic agents, besides DXM, could induce cures in combination with F8-IL4 and to elucidate which leucocytes are most affected by the pharmacological treatment. We performed therapy experiments in mice with CIA, using intravenous administrations of F8-IL4 in combination with DXM, MTX, murine cytotoxic T-lymphocyte-associated protein 4 fused to the fragment crystallizable portion of murine IgG2a, as well as mAbs to murine IL17A or the p40 subunit of murine IL12/IL23. Histology and immunohistochemistry for the identification of the various leucocytes were performed on the paws of mice euthanized at different therapy time points. Only the use of F8-IL4 in combination with DXM induced complete remissions, while all other combinations did not lead to cures. The light microscopical evaluation of paws with arthritis revealed a predominant infiltration of neutrophils, which substantially decreased 24 h after treatment with F8-IL4 and DXM. The combination of F8-IL4 with DXM promotes a rapid anti-arthritic action by potently inhibiting neutrophil activity. A fully human analogue of F8-IL4 may find clinical utility for the treatment of neutrophil-driven chronic inflammatory conditions.

Eukaryotic Initiation Factor (eIF) 4F Binding to Barley Yellow Dwarf Virus (BYDV) 3′-Untranslated Region Correlates with Translation Efficiency*

PubMed Central

Banerjee, Bidisha; Goss, Dixie J.

2014-01-01

Eukaryotic initiation factor (eIF) 4F binding to mRNA is the first committed step in cap-dependent protein synthesis. Barley yellow dwarf virus (BYDV) employs a cap-independent mechanism of translation initiation that is mediated by a structural BYDV translation element (BTE) located in the 3′-UTR of its mRNA. eIF4F bound the BTE and a translationally inactive mutant with high affinity, thus questioning the role of eIF4F in translation of BYDV. To examine the effects of eIF4F in BYDV translation initiation, BTE mutants with widely different in vitro translation efficiencies ranging from 5 to 164% compared with WT were studied. Using fluorescence anisotropy to obtain quantitative data, we show 1) the equilibrium binding affinity (complex stability) correlated well with translation efficiency, whereas the “on” rate of binding did not; 2) other unidentified proteins or small molecules in wheat germ extract prevented eIF4F binding to mutant BTE but not WT BTE; 3) BTE mutant-eIF4F interactions were found to be both enthalpically and entropically favorable with an enthalpic contribution of 52–90% to ΔG° at 25 °C, suggesting that hydrogen bonding contributes to stability; and 4) in contrast to cap-dependent and tobacco etch virus internal ribosome entry site interaction with eIF4F, poly(A)-binding protein did not increase eIF4F binding. Further, the eIF4F bound to the 3′ BTE with higher affinity than for either m7G cap or tobacco etch virus internal ribosome entry site, suggesting that the 3′ BTE may play a role in sequestering host cell initiation factors and possibly regulating the switch from replication to translation. PMID:24379412

Self-assembly of PEGylated tetra-phenylalanine derivatives: structural insights from solution and solid state studies

PubMed Central

Diaferia, Carlo; Mercurio, Flavia Anna; Giannini, Cinzia; Sibillano, Teresa; Morelli, Giancarlo; Leone, Marilisa; Accardo, Antonella

2016-01-01

Water soluble fibers of PEGylated tetra-phenylalanine (F4), chemically modified at the N-terminus with the DOTA chelating agent, have been proposed as innovative contrast agent (CA) in Magnetic Resonance Imaging (MRI) upon complexation of the gadolinium ion. An in-depth structural characterization of PEGylated F4-fibers, in presence (DOTA-L6-F4) and in absence of DOTA (L6-F4), is reported in solution and at the solid state, by a multiplicity of techniques including CD, FTIR, NMR, DLS, WAXS and SAXS. This study aims to better understand how the aggregation process influences the performance of nanostructures as MRI CAs. Critical aggregation concentrations for L6-F4 (43 μM) and DOTA-L6-F4 (75 μM) indicate that self-aggregation process occurs in the same concentration range, independently of the presence of the CA. The driving force for the aggregation is the π-stacking between the side chains of the aromatic framework. CD, FTIR and WAXS measurements indicate an antiparallel β-sheet organization of the monomers in the resulting fibers. Moreover, WAXS and FTIR experiments point out that in solution the nanomaterials retain the same morphology and monomer organizations of the solid state, although the addition of the DOTA chelating agent affects the size and the degree of order of the fibers. PMID:27220817

Remineralizing Potential of a Low Fluoride Toothpaste with Sodium Trimetaphosphate: An in situ Study.

PubMed

Takeshita, Eliana M; Danelon, Marcelle; Castro, Luciene P; Cunha, Robson F; Delbem, Alberto C B

2016-01-01

To evaluate the effect of a low-fluoride (F) toothpaste supplemented with sodium trimetaphosphate (TMP) on enamel remineralization in situ. Bovine enamel blocks were selected on the basis of their surface hardness (SH) after caries-like lesions had been induced, and randomly divided into 4 treatment groups, according to the toothpastes used: without F or TMP (placebo); 500 ppm F; 500 ppm F plus 1% TMP; and 1,100 ppm F. The study design was blinded and crossover and performed in 4 phases of 3 days each. Eleven subjects used palatal appliances containing 4 bovine enamel blocks which were treated 3 times per day during 1 min each time, with natural slurries of saliva and toothpaste formed in the oral cavity during toothbrushing. After each phase, the percentages of surface (%SHR) and subsurface hardness recovery (%ΔKHNR) were calculated. F, calcium (Ca), and phosphorus (Pi) contents in enamel were also determined. Data were analyzed by 1-way, repeated-measures ANOVA, followed by the Student-Newman-Keuls test (p < 0.05). Toothpaste with 500 ppm F + TMP and 1,100 ppm F showed similar %SHR and %ΔKHNR as well as enamel F, Ca, and Pi concentrations. The addition of TMP to a low-fluoride toothpaste promoted a similar remineralizing capacity to that of a standard (1,100 ppm F) toothpaste in situ. © 2016 S. Karger AG, Basel.

Theoretical study of local structure for Ni2+ ions at tetragonal sites in K2ZnF4:Ni2+ system.

PubMed

Wang, Su-Juan; Kuang, Xiao-Yu; Lu, Cheng

2008-12-15

A theoretical method for studying the local lattice structure of Ni2+ ions in (NiF6)(4-) coordination complex is presented. Using the ligand-field model, the formulas relating the microscopic spin Hamiltonian parameters with the crystal structure parameters are derived. Based on the theoretical formulas, the 45 x 45 complete energy matrices for d8 (d2) configuration ions in a tetragonal ligand-field are constructed. By diagonalizing the complete energy matrices, the local distortion structure parameters (R perpendicular and R || ) of Ni2+ ions in K2ZnF4:Ni2+ system have been investigated. The theoretical results are accorded well with the experimental values. Moreover, to understand the detailed physical and chemical properties of the fluoroperovskite crystals, the theoretical values of the g factor of K2ZnF4:Ni2+ system at 78 and 290 K are reported first.

Theoretical study of local structure for Ni 2+ ions at tetragonal sites in K 2ZnF 4:Ni 2+ system

NASA Astrophysics Data System (ADS)

Wang, Su-Juan; Kuang, Xiao-Yu; Lu, Cheng

2008-12-01

A theoretical method for studying the local lattice structure of Ni 2+ ions in (NiF 6) 4- coordination complex is presented. Using the ligand-field model, the formulas relating the microscopic spin Hamiltonian parameters with the crystal structure parameters are derived. Based on the theoretical formulas, the 45 × 45 complete energy matrices for d8 ( d2) configuration ions in a tetragonal ligand-field are constructed. By diagonalizing the complete energy matrices, the local distortion structure parameters ( R⊥ and R||) of Ni 2+ ions in K 2ZnF 4:Ni 2+ system have been investigated. The theoretical results are accorded well with the experimental values. Moreover, to understand the detailed physical and chemical properties of the fluoroperovskite crystals, the theoretical values of the g factor of K 2ZnF 4:Ni 2+ system at 78 and 290 K are reported first.

Magnetooptics of the luminescent transitions in Tb3+:Gd3Ga5O12

NASA Astrophysics Data System (ADS)

Valiev, Uygun V.; Gruber, John B.; Ivanov, Igor'A.; Burdick, Gary W.; Liang, Hongbin; Zhou, Lei; Fu, Dejun; Pelenovich, Oleg V.; Pelenovich, Vasiliy O.; Lin, Zhou

2015-08-01

The spectra of the luminescence and magnetic circular polarization of luminescence in terbium-gadolinium gallium garnet Tb3+:Gd3Ga5O12 (Tb3+:GGG) were studied within the visible spectral range at temperatures T = 90 and 300 K in an external magnetic field of 0.45 T. The Zeeman effect in the luminescence "green" band associated with 4f → 4f transition 5D4 → 7F5 of Tb3+:GGG was also studied at T = 90 K in an external field of 0.55 T. Measurement of the Zeeman effect in Tb3+:GGG carried out for some doublet lines of the luminescence band 5D4 → 7F5 at T = 90 K shows that a magnetooptical effect of the intensity change of the emitted light is observed on these lines, in contrast to pure Zeeman splitting of the emission lines measured in the luminescence band 5D4 → 7F6. For the systems we have studied, the maximal value of the magnetooptical effect of the intensity change of the luminescence line at low temperatures has been achieved in paramagnetic garnet Tb0.2Y2.8Al5O12 at comparatively low magnetic fields.

Structures and electron affinities of the di-arsenic fluorides As2Fn/As2Fn- (n=1-8).

PubMed

Kasalová, Veronika; Schaefer, Henry F

2005-04-15

Developments in the preparation of new materials for microelectronics are focusing new attention on molecular systems incorporating several arsenic atoms. A systematic investigation of the As2Fn/As2Fn- systems was carried out using Density Functional Theory methods and a DZP++ quality basis set. Global and low-lying local geometric minima and relative energies are discussed and compared. The three types of neutral-anion separations reported in this work are: the adiabatic electron affinity (EAad), the vertical electron affinity (EAvert), and the vertical detachment energy (VDE). Harmonic vibrational frequencies pertaining to the global minimum for each compound are reported. From the first four studied species (As2Fn, n=1-4), all neutral molecules and their anions are shown to be stable with respect to As-As bond breaking. The neutral As2F molecule and its anion are predicted to have Cs symmetry. We find the trans F-As-As-F isomer of C2h symmetry and a pyramidalized vinylidene-like As-As-F2- isomer of Cs symmetry to be the global minima for the As2F2 and As2F2- species, respectively. The lowest lying minima of As2F3 and As2F3- are vinyl radical-like structures F-As-As-F2 of Cs symmetry. The neutral As2F4 global minimum is a trans-bent (like Si2H4) F2-As-As-F2 isomer of C2 symmetry, while its anion is predicted to have an unusual fluorine-bridged (C(1)) structure. The global minima of the neutral As2Fn species, n=5-8, are weakly bound complexes, held together by dipole-dipole interactions. All such structures have the AsFm-AsFn form, where (m,n) is (2,3) for As2F5, (3,3) for As2F6, (4,3) for As2F7), and (5,3) for As2F8. For As2F8 the beautiful pentavalent F4As-AsF4 structure (analogous to the stable AsF5 molecule) lies about 30 kcal/mol above the AsF3 . . . AsF5 complex. The stability of AsF(5) depends crucially on the strong As-F bonds, and replacing one of these with an As-As bond (in F4As-AsF4) has a very negative impact on the molecule's stability. The anions As2Fn-, n=5-8, are shown to be stable with respect to the As-As bond breaking, and we predict that all of them have fluorine-bridged or fluorine-linked structures. The zero-point vibrational energy corrected adiabatic electron affinities are predicted to be 2.28 eV (As2F), 1.95 eV (As2F2), 2.39 eV (As2F3), 1.71 eV (As2F4), 2.72 eV (As2F5), 1.79 eV (As2F6), 5.26 eV (As2F7), and 3.40 eV (As2F8) from the BHLYP method. Vertical detachment energies are rather large, especially for species with fluorine-bridged global minima, having values up to 6.45 eV (As2F7, BHLYP).

In vivo assessment and dosimetry of 2 novel PDE10A PET radiotracers in humans: 18F-MNI-659 and 18F-MNI-654.

PubMed

Barret, Olivier; Thomae, David; Tavares, Adriana; Alagille, David; Papin, Caroline; Waterhouse, Rikki; McCarthy, Timothy; Jennings, Danna; Marek, Ken; Russell, David; Seibyl, John; Tamagnan, Gilles

2014-08-01

Phosphodiesterase (PDE) 10A is an enzyme involved in the regulation of cyclic adenosine monophosphate and cyclic guanosine monophosphate and is highly expressed in medium-sized spiny neurons of the striatum, making it an attractive target for novel therapies for a variety of neurologic and psychiatric disorders that involve striatal function. Potential ligands for PET imaging of PDE10A have been reported. Here, we report the first-in-human characterization of 2 new PDE10A radioligands, 2-(2-(3-(1-(2-fluoroethyl)-1H-indazol-6-yl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione ((18)F-MNI-654) and 2-(2-(3-(4-(2-fluoroethoxy)phenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione ((18)F-MNI-659), with the goal of selecting the best one for use in future studies interrogating pathophysiologic changes in neuropsychiatric disorders and aiding pharmaceutical development targeting PDE10A. Eleven healthy volunteers participated in this study ((18)F-MNI-654 test-retest, 2 men; (18)F-MNI-659 test-retest, 4 men and 1 woman; (18)F-MNI-659 dosimetry, 2 men and 2 women). Brain PET images were acquired over 5.5 h for (18)F-MNI-654 and over 3.5 h for (18)F-MNI-659, and pharmacokinetic modeling with plasma- and reference-region (cerebellar cortex)-based methods was performed. Whole-body PET images were acquired over 6 h for (18)F-MNI-659 and radiation dosimetry estimated with OLINDA. Both radiotracers were similarly metabolized, with about 20% of intact parent remaining at 120 min after injection. PET time-activity data demonstrated that (18)F-MNI-654 kinetics were much slower than (18)F-MNI-659 kinetics. For (18)F-MNI-659, there was good agreement between the Logan and simplified reference tissue models for nondisplaceable binding potential (BPND), supporting noninvasive quantification, with test-retest variability less than 10% and intraclass correlation greater than 0.9. The (18)F-MNI-659 effective dose was estimated at 0.024 mSv/MBq. PET imaging in the human brain with 2 novel PDE10A (18)F tracers is being reported. Noninvasive quantification of (18)F-MNI-659 with the simplified reference tissue model using the cerebellum as a reference is possible. In addition, (18)F-MNI-659 kinetics are fast enough for a good estimate of BPND with 90 min of data, with values around 3.0 in the basal ganglia. Finally, (18)F-MNI-659 dosimetry is favorable and consistent with values reported for other PET radiotracers currently used in humans. © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

In vivo therapeutic efficacy and pharmacokinetics of colistin sulfate in an experimental model of enterotoxigenic Escherichia coli infection in weaned pigs.

PubMed

Rhouma, Mohamed; Beaudry, Francis; Thériault, William; Bergeron, Nadia; Beauchamp, Guy; Laurent-Lewandowski, Sylvette; Fairbrother, John Morris; Letellier, Ann

2016-05-27

Enterotoxigenic Escherichia coli (ETEC: F4) associated with post-weaning diarrhea (PWD) in pigs has developed resistance against several antimicrobial families, leading to increased use of colistin sulfate (CS) for the treatment of this disease. The objective of this study was to determine the efficacy of oral CS treatment in experimental PWD due to ETEC: F4 challenge and determine the effect of this challenge on CS intestinal absorption. In this study, 96 pigs were divided into two trials based on CS dose (100 000 or 50 000 IU/kg). Fecal shedding of ETEC: F4, total E. coli, and CS-resistant E. coli, diarrhea scores, and weight changes were evaluated. Colistin sulfate plasma concentrations were determined by HPLC-MS/MS. Regardless of the dose, CS treatment resulted in a reduction of fecal ETEC: F4 and total E. coli shedding, and in diarrhea scores but only during the treatment period. However, CS treatment resulted in a slight increase in fecal shedding of CS resistant E. coli and did not prevent weight loss in challenged pigs. In addition, challenge with ETEC: F4 resulted in an increase of CS intestinal absorption. Our study is among the first to demonstrate that under controlled conditions, CS was effective in reducing fecal shedding of ETEC: F4 and total E. coli in experimental PWD. However, CS treatment was associated with a slight selection pressure on E. coli and did not prevent pig weight loss. Further studies are needed in field conditions, to better characterize CS therapeutic regimen efficacy and bacterial resistance dissemination.

The over expression of long non-coding RNA ANRIL promotes epithelial-mesenchymal transition by activating the ATM-E2F1 signaling pathway in pancreatic cancer: An in vivo and in vitro study.

PubMed

Chen, Shi; Zhang, Jia-Qiang; Chen, Jiang-Zhi; Chen, Hui-Xing; Qiu, Fu-Nan; Yan, Mao-Lin; Chen, Yan-Ling; Peng, Cheng-Hong; Tian, Yi-Feng; Wang, Yao-Dong

2017-09-01

This study aims to investigate the roles of lncRNA ANRIL in epithelial-mesenchymal transition (EMT) by regulating the ATM-E2F1 signaling pathway in pancreatic cancer (PC). PC rat models were established and ANRIL overexpression and interference plasmids were transfected. The expression of ANRIL, EMT markers (E-cadherin, N-cadherin and Vimentin) and ATM-E2F1 signaling pathway-related proteins (ATM, E2F1, INK4A, INK4B and ARF) were detected. Small molecule drugs were applied to activate and inhibit the ATM-E2F1 signaling pathway. Transwell assay and the scratch test were adopted to detect cell invasion and migration abilities. ANRIL expression in the PC cells was higher than in normal pancreatic duct epithelial cells. In the PC rat models and PC cells, ANRIL interference promoted the expressions of INK4B, INK4A, ARF and E-cadherin, while reduced N-cadherin and Vimentin expression. Over-expressed ANRIL decreased the expression of INK4B, INK4A, ARF and E-cadherin, but raised N-cadherin and Vimentin expressions. By inhibiting the ATM-E2F1 signaling pathway in PC cells, E-cadherin expression increased but N-cadherin and Vimentin expressions decreased. After ANRIL was silenced or the ATM-E2F1 signaling pathway inhibited, PC cell migration and invasion abilities were decreased. In conclusion, over-expression of lncRNA ANRIL can promote EMT of PC cells by activating the ATM-E2F1 signaling pathway. Copyright © 2017 Elsevier B.V. All rights reserved.

Cumulative Brain Injury from Motor Vehicle-Induced Whole-Body Vibration and Prevention by Human Apolipoprotein A-I Molecule Mimetic (4F) Peptide (an Apo A-I Mimetic).

PubMed

Yan, Ji-Geng; Zhang, Lin-ling; Agresti, Michael; Yan, Yuhui; LoGiudice, John; Sanger, James R; Matloub, Hani S; Pritchard, Kirkwood A; Jaradeh, Safwan S; Havlik, Robert

2015-12-01

Insidious cumulative brain injury from motor vehicle-induced whole-body vibration (MV-WBV) has not yet been studied. The objective of the present study is to validate whether whole-body vibration for long periods causes cumulative brain injury and impairment of the cerebral function. We also explored a preventive method for MV-WBV injury. A study simulating whole-body vibration was conducted in 72 male Sprague-Dawley rats divided into 9 groups (N = 8): (1) 2-week normal control; (2) 2-week sham control (in the tube without vibration); (3) 2-week vibration (exposed to whole-body vibration at 30 Hz and .5 G acceleration for 4 hours/day, 5 days/week for 2 weeks; vibration parameters in the present study are similar to the most common driving conditions); (4) 4-week sham control; (5) 4-week vibration; (6) 4-week vibration with human apolipoprotein A-I molecule mimetic (4F)-preconditioning; (7) 8-week sham control; (8) 8-week vibration; and (9) 8-week 4F-preconditioning group. All the rats were evaluated by behavioral, physiological, and histological studies of the brain. Brain injury from vibration is a cumulative process starting with cerebral vasoconstriction, squeezing of the endothelial cells, increased free radicals, decreased nitric oxide, insufficient blood supply to the brain, and repeated reperfusion injury to brain neurons. In the 8-week vibration group, which indicated chronic brain edema, shrunken neuron numbers increased and whole neurons atrophied, which strongly correlated with neural functional impairment. There was no prominent brain neuronal injury in the 4F groups. The present study demonstrated cumulative brain injury from MV-WBV and validated the preventive effects of 4F preconditioning. Copyright © 2015 National Stroke Association. All rights reserved.

In vivo evaluation of 18F-MNI698: an 18F-labeled radiotracer for imaging of serotonin 4 receptors in brain.

PubMed

Tavares, Adriana Alexandre S; Caillé, Fabien; Barret, Olivier; Papin, Caroline; Lee, Hsiaoju; Morley, Thomas J; Fowles, Krista; Holden, Daniel; Seibyl, John P; Alagille, David; Tamagnan, Gilles D

2014-05-01

Serotonin 4 receptors (5-hydroxytryptamine receptor 4 [5HT4R]) hold promise as a novel therapeutic approach to multiple brain disorders, including Alzheimer and Huntington disease. In vivo imaging of these receptors with selective 5HT4R radiotracers and PET would be valuable to investigate alterations in 5HT4R in different brain disorders and to assist drug discovery. In this study, (18)F-MNI698 was evaluated as a potential PET radiotracer for imaging of 5HT4R in the brain. Eighteen PET studies were performed in 3 adult rhesus monkeys. The radiotracer was administered as a bolus intravenous injection or bolus plus constant infusion (time that would be required to inject the bolus at the infusion rate = 60 min), and arterial blood was collected for data quantification. Kinetic models were used to estimate distribution volumes and binding potentials, for which the cerebellum was used as a reference region. (18)F-MNI698 test-retest variability and upper mass dose limits were determined. Preblocking studies using several doses of SB204070, a selective 5HT4R antagonist, were performed. (18)F-MNI698 avidly entered the monkey brain (peak percentage injected dose of ∼ 6.6%), and its brain distribution was consistent with known 5HT4R densities. At 120 min after bolus injection and after the start of radiotracer infusion, only less than 5% and approximately 10% parent compound was present in blood, respectively. Measured binding potentials were underestimated by 22%-36% when noninvasive methods were used for data quantification in comparison with invasive methods. A good agreement was found between test-retest measurements. The radiotracer upper mass dose limit (<5% occupancy) was determined to be 13.1 μg per 70 kg of body weight. SB204070 blocked the radiotracer binding in a dose-dependent manner. Data indicate that (18)F-MNI698 is a promising PET radiotracer for imaging of 5HT4R in the brain, and human studies are warranted based on these study results.

Identification of estrogenic and antiestrogenic activities of respirable diesel exhaust particles by bioassay-directed fractionation.

PubMed

Oh, Seung Min; Ryu, Byung Taek; Chung, Kyu Hyuck

2008-01-01

Bioassay-directed fractionation was performed to identify causative chemical groups of DEPs with estrogenic and antiestrogenic activities. Bioassay-directed fractionation consists of a cell bioassay (E-SCREEN) in conjunction with acid-base partitioning (F1 and F2) and silica gel column fractionation of neutral fractions (F3-F7). Crude extract (CE) of DEPs in dichloromethane (DCM) exhibited both estrogenic and antiestrogenic activity. Estrogenic activity of CE and some fractions (F1, F2, F3, F5 and F6) was induced through estrogen receptor (ER)-mediated pathways. In particular, the acid polar fraction (F2) of DEPs, which contains phenols, induced high levels of estrogenic activity compared to other fractions. The estrogenic activity of F2 (610.80 pg-bio-EEQ/g-DEPs) was higher than that of the total estrogenic activity of CE (222.22 pg-bio-EEQ/g-DEPs). This result indicates that the estrogenic activity induced by causative estrogenic fraction (F2) may be antagonized by unidentified chemicals in DEPs. On the other hand, non-polar fractions (F3 and F4) of DEPs include aliphatic and chlorinated hydrocarbon, polyaromatic hydrocarbons, and their alkyl derivatives, which play an important role in the antiestrogenic activity of DEPs. In particular, F4, which contains PAH and its derivatives, showed the highest antiestrogenic activity. Since in our previous study, dibenzo(a, h)anthracene and chrysene were identified in F4, and these chemicals have antiestrogenic activity, we assume that these chemicals are the major causative chemicals with antiestrogenic activity in DEPs. In contrast to the estrogenic activity of DEPs, antiestrogenic activity of CE was stronger than that of antiestrogenic fractions (F3 and F4) at non-cytotoxic concentrations, indicating that additive or synergistic effects by unidentified chemicals contained in DEPs occurred.

Maternal thyroid dysfunction during gestation, preterm delivery, and birthweight. The Infancia y Medio Ambiente Cohort, Spain.

PubMed

León, Gemma; Murcia, Mario; Rebagliato, Marisa; Álvarez-Pedrerol, Mar; Castilla, Ane M; Basterrechea, Mikel; Iñiguez, Carmen; Fernández-Somoano, Ana; Blarduni, Elizabeth; Foradada, Carles M; Tardón, Adonina; Vioque, Jesús

2015-03-01

Maternal clinical thyroid disorders can cause reproductive complications. However, the effects of mild thyroid dysfunctions are not yet well established. The aim was to evaluate the association of maternal thyroid function during the first half of pregnancy with birthweight and preterm delivery. We analysed data on 2170 pregnant women and their children from a prospective population-based cohort study in four Spanish areas. Mid-gestation maternal serum and urine samples were gathered to determine thyroid-stimulating hormone (TSH), free thyroxine (fT4 ), and urinary iodine concentration (UIC). Thyroid status was defined according to percentile distribution as: euthyroid (TSH and fT4 >5th and <95th percentiles); hypothyroxinaemia (fT4  < 5 th percentile and TSH normal), hypothyroidism (TSH > 95th percentile and fT4 normal or <5th percentile), hyperthyroxinaemia (fT4  > 95 th percentile and TSH normal), and hyperthyroidism (TSH < 5 th percentile and fT4 normal or >95th percentile). Response variables were birthweight, small and large for gestational age (SGA/LGA), and preterm delivery. An inverse association of fT4 and TSH with birthweight was found, the former remaining when restricted to euthyroid women. High fT4 levels were also associated with an increased risk of SGA [odds ratio, 95% confidence interval (CI) 1.28 (95% CI 1.08, 1.51)]. Mean birthweight was higher in the hypothyroxinaemic group (β = 109, P < 0.01). Iodine intake and UIC were not associated with birth outcomes. High maternal fT4 levels during the first half of pregnancy were related to lower birthweight and increased risk of SGA newborns, suggesting that maternal thyroid function may affect fetal growth, even within the normal range. © 2015 John Wiley & Sons Ltd.

Biofilm community diversity after exposure to 0·4% stannous fluoride gels.

PubMed

Reilly, C; Rasmussen, K; Selberg, T; Stevens, J; Jones, R S

2014-12-01

To test the effect of 0·4% stannous fluoride (SnF2 ) glycerine-based gels on specific portions of the bacterial community in both a clinical observational study and in vitro multispecies plaque-derived (MSPD) biofilm model. Potential changes to specific portions of the bacterial community were determined through the Human Oral Microbial Identification Microarray (HOMIM). Both the observational clinical study and the biofilm model showed that short-term use of 0·4% SnF2 gel has little effect on the bacterial community depicted by hierarchical cluster analysis. The amount of plaque accumulation on a subject's teeth, which was measured by plaque index scores, failed to show statistical significant changes over the two baselines or after treatment (P = 0·9928). The in vitro results were similar when examining the effect of 0·4% SnF2 gels on biofilm adherence through a crystal violet assay (P = 0·1157). The bacteria within the dental biofilms showed resilience in maintaining the overall community diversity after exposure to 0·4% SnF2 topical gels. The study supports that the immediate benefits of using 0·4% SnF2 gels in children may be strictly from fluoride ions inhibiting tooth demineralization rather than delivering substantial antimicrobial effects. © 2014 The Society for Applied Microbiology.

Synthesis and Evaluation of 15-(4-(2-[18F]Fluoroethoxy)phenyl)pentadecanoic Acid: a Potential PET Tracer for Studying Myocardial Fatty Acid Metabolism

PubMed Central

Tu, Zhude; Li, Shihong; Sharp, Terry L.; Herrero, Pilar; Dence, Carmen S.; Gropler, Robert J.; Mach, Robert H.

2010-01-01

15-(4-(2-[18F]fluoroethoxy)phenyl)pentadecanoic acid ([18F]7) was synthesized as a PET probe for assessing myocardial fatty acid metabolism. The radiosynthesis of [18F]7 was accomplished using a two step reaction, starting with the corresponding tosylate ester, methyl 15-(4-(2-(tosyloxy)ethoxy)phenyl)pentadecanoate (5) and gave the radiolabeled fatty acid, [18F]7 in a radiolabeling yield of 55 – 60% and a specific activity of > 2,000 Ci/mmol (decay corrected to EOB). The biological evaluation of [18F]7 in rats displayed high uptake in heart (1.94%.ID/g at 5 min), which was higher than the uptake (%ID/g) in blood, lung, muscle, pancreas and brain. MicroPET studies of [18F]7 in Sprague-Dawley rats demonstrated excellent images of the myocardium when compared with [11C]palmitate images in the same animal. Moreover, the tracer kinetics of [18F]7 paralleled those seen with [11C]palmitate, with an early peak followed by biphasic washout. When compared to [11C]palmitate, [18F]7 exhibited a slower early clearance (0.17 ± 0.01 vs. 0.30 ± 0.02, P < 0.0001) and a significantly higher late clearance (0.0030 ± 0.0005 vs. 0.0006 ± 0.00013, P < 0.01). These initial studies suggest that [18F]7 could be a potentially useful clinical PET tracer to assess abnormal myocardial fatty acid metabolism. PMID:21070001

Structure-Activity Comparison of Hydrazine to Other Nasotoxic Chemicals

DTIC Science & Technology

1992-08-01

Carcinogenesis bioassay of 1,2-dibromo-3- chloropropane (CAS No. 96-12-8) in F344/N rats and B6C3F 1 mice (inhalation studies). Technical Report No. 206...1204. Arfrndtdtt. VA 22O2014301 and to the Oflioe of M~n4’jrtrtn’ and 13r~dget, f,4perfoon Ket-Jrlon Prutect (0 104 0 t~ft Vt.,frrjngtot1.( 20SOJ 1 ... 1 LIST O F FIG URES ..................................................................... 3 INTRO DUCTI3N

Asymmetric flavone-based liquid crystals: synthesis and properties

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

Timmons, Daren J.; Jordan, Abraham J.; Kirchon, Angelo A.

2017-02-01

A series of flavones (n-F) substituted at the 4', and 6 positions was prepared, characterised by NMR (1H,13C), HRMS, and studied for liquid crystal properties. The 4'-alkoxy,6-methoxyflavones (4-F–16-F) exhibit varying ranges of nematic and smectic A phases as evidenced by polarised optical microscopy and differential scanning calorimetry (DSC). As the tail length is increased, the smectic phase becomes more prevalent. Smectic phases for (8-F–16-F) were further analysed by powder X-ray diffraction (XRD), and the rate of structural transformations was explored by combined DSC/XRD studies. Flavonol 6-F–OH was also prepared but no mesogenic behaviour was observed. The molecular structures of 6-Fmore » and 6-F–OH were determined by single-crystal XRD and help to explain the differences in material properties. Additionally, fluorescence and electrochemical studies were conducted on solutions of n-F.« less

Dietary patterns as predictors of body fat and BMI in women: a factor analytic study.

PubMed

Tucker, Larry A; Tucker, Jared M; Bailey, Bruce W; LeCheminant, James D

2015-01-01

To identify independent patterns of diet using factor analysis to determine the extent to which dietary patterns account for differences in body fat percentage (BF%) and body mass index (BMI). Also, to ascertain the extent to which the associations are influenced by age, education, menopause, energy intake, and physical activity. Study design was cross-sectional. Study setting was approximately 20 cities in the Mountain West. The study included 281 apparently healthy female nonsmokers. Diet was assessed using 7-day weighed food records, and foods were categorized using the American Diabetes and American Dietetic Associations Exchange Lists and expressed as servings per 1000 kcal. BF% was measured using the Bod Pod, and physical activity was estimated using accelerometers worn for 1 week. We used factor analysis, general linear models, and partial correlations. Three dietary patterns were identified: (1) Prudent Pattern, (2) Low-fat Milk, and (3) Meat. Higher consumption of the Prudent Pattern corresponded with significantly lower BF% (F = 8.5, p = .0038) and BMI (F = 4.4, p = .0363). The Low-fat Milk pattern was inversely related to BF% (F = 5.4, p = .0207) and BMI (F = 9.5, p = .0023). Higher intake of the Meat pattern was related to higher levels of BF% (F = 4.5, p = .0346) and BMI (F = 4.2, p = .0418). These findings support an association between dietary patterns and body composition. Dietary patterns reflect the complex interrelationships inherent in day-to-day eating and are strongly related to differences in BF% and BMI in women.

Serum MicroRNAs as Potential Biomarkers for Early Diagnosis of Hepatitis C Virus-Related Hepatocellular Carcinoma in Egyptian Patients

PubMed Central

Motawi, Tarek K.; Shaker, Olfat G.; El-Maraghy, Shohda A.; Senousy, Mahmoud A.

2015-01-01

Circulating microRNAs are deregulated in liver fibrosis and hepatocellular carcinoma (HCC) and are candidate biomarkers. This study investigated the potential of serum microRNAs; miR-19a, miR-296, miR-130a, miR-195, miR-192, miR-34a, and miR-146a as early diagnostic biomarkers for hepatitis C virus (HCV)-related HCC. As how these microRNAs change during liver fibrosis progression is not clear, we explored their serum levels during fibrosis progression in HCV-associated chronic liver disease (CLD) and if they could serve as non-invasive biomarkers for fibrosis progression to HCC. 112 Egyptian HCV-HCC patients, 125 non-malignant HCV-CLD patients, and 42 healthy controls were included. CLD patients were subdivided according to Metavir fibrosis-scoring. Serum microRNAs were measured by qRT-PCR custom array. Serum microRNAs were deregulated in HCC versus controls, and except miR-130a, they were differentially expressed between HCC and CLD or late fibrosis (F3-F4) subgroup. Serum microRNAs were not significantly different between individual fibrosis-stages or between F1-F2 (early/moderate fibrosis) and F3-F4. Only miR-19a was significantly downregulated from liver fibrosis (F1-F3) to cirrhosis (F4) to HCC. Individual microRNAs discriminated HCC from controls, and except miR-130a, they distinguished HCC from CLD or F3-F4 patients by receiver-operating-characteristic analysis. Multivariate logistic analysis revealed a panel of four microRNAs (miR-19a, miR-195, miR-192, and miR-146a) with high diagnostic accuracy for HCC (AUC = 0.946). The microRNA panel also discriminated HCC from controls (AUC = 0.949), CLD (AUC = 0.945), and F3-F4 (AUC = 0.955). Studied microRNAs were positively correlated in HCC group. miR-19a and miR-34a were correlated with portal vein thrombosis and HCC staging scores, respectively. In conclusion, studied microRNAs, but not miR-130a, could serve as potential early biomarkers for HCC in high-risk groups, with miR-19a as a biomarker for liver fibrosis progression to cirrhosis to HCC. We identified a panel of four serum microRNAs with high accuracy in HCC diagnosis. Additional studies are required to confirm this panel and test its prognostic significance. PMID:26352740

Colchicum autumnale in Patients with Goitre with Euthyroidism or Mild Hyperthyroidism: Indications for a Therapeutic Regulative Effect—Results of an Observational Study

PubMed Central

Scheffer, Christian; Debus, Marion; Heckmann, Christian; Cysarz, Dirk; Girke, Matthias

2016-01-01

Introduction. Goitre with euthyroid function or with subclinical or mild hyperthyroidism due to thyroid autonomy is common. In anthroposophic medicine various thyroid disorders are treated with Colchicum autumnale (CAU). We examined the effects of CAU in patients with goitre of both functional states. Patients and methods. In an observational study, 24 patients with goitre having suppressed thyroid stimulating hormone (TSH) levels with normal or slightly elevated free thyroxine (fT4) and free triiodothyronine (fT3) (group 1, n = 12) or normal TSH, fT3, and fT4 (group 2, n = 12) were included. After 3 months and after 6 to 12 months of CAU treatment, we investigated clinical pathology using the Hyperthyroid Symptom Scale (HSS), hormone status (TSH, fT4, and fT3), and thyroidal volume (tV). Results. After treatment with CAU, in group 1 the median HSS decreased from 4.5 (2.3–11.8) to 2 (1.3–3) (p < 0.01) and fT3 decreased from 3.85 (3.5–4.78) to 3.45 (3.3–3.78) pg/mL (p < 0.05). In group 2 tV (13.9% (18.5%–6.1%)) and TSH (p < 0.01) were reduced. Linear regression for TSH and fT3 in both groups indicated a regulative therapeutic effect of CAU. Conclusions. CAU positively changed the clinical pathology of subclinical hyperthyroidism and thyroidal volume in patients with euthyroid goitre by normalization of the regulation of thyroidal hormones. PMID:26955394

Colchicum autumnale in Patients with Goitre with Euthyroidism or Mild Hyperthyroidism: Indications for a Therapeutic Regulative Effect-Results of an Observational Study.

PubMed

Scheffer, Christian; Debus, Marion; Heckmann, Christian; Cysarz, Dirk; Girke, Matthias

2016-01-01

Introduction. Goitre with euthyroid function or with subclinical or mild hyperthyroidism due to thyroid autonomy is common. In anthroposophic medicine various thyroid disorders are treated with Colchicum autumnale (CAU). We examined the effects of CAU in patients with goitre of both functional states. Patients and methods. In an observational study, 24 patients with goitre having suppressed thyroid stimulating hormone (TSH) levels with normal or slightly elevated free thyroxine (fT4) and free triiodothyronine (fT3) (group 1, n = 12) or normal TSH, fT3, and fT4 (group 2, n = 12) were included. After 3 months and after 6 to 12 months of CAU treatment, we investigated clinical pathology using the Hyperthyroid Symptom Scale (HSS), hormone status (TSH, fT4, and fT3), and thyroidal volume (tV). Results. After treatment with CAU, in group 1 the median HSS decreased from 4.5 (2.3-11.8) to 2 (1.3-3) (p < 0.01) and fT3 decreased from 3.85 (3.5-4.78) to 3.45 (3.3-3.78) pg/mL (p < 0.05). In group 2 tV (13.9% (18.5%-6.1%)) and TSH (p < 0.01) were reduced. Linear regression for TSH and fT3 in both groups indicated a regulative therapeutic effect of CAU. Conclusions. CAU positively changed the clinical pathology of subclinical hyperthyroidism and thyroidal volume in patients with euthyroid goitre by normalization of the regulation of thyroidal hormones.

In situ monitoring, separation, and characterization of gold nanorod transformation during seed-mediated synthesis.

PubMed

Nguyen, Thao M; Pettibone, John M; Gigault, Julien; Hackley, Vincent A

2016-03-01

The control of gold nanorod (GNR) solution-based syntheses has been hindered in part by the inability to examine and control the conversion of precursor seed populations to anisotropic materials, which have resulted in low yields of desired products and limited their commercial viability. The advantages offered by tandem separation and characterization methods utilizing asymmetric-flow field flow fractionation (A4F) are principally achieved as a result of their non-disruptive nature (minimizing artefacts), fast throughput, and in-situ analysis. With hyphenated A4F methods, resolved populations of seeds and secondary products, up to long aspect ratio rods, have been achieved and exemplify progress towards elucidating mechanistic aspects of formation and thus rational design. While there have been previously reported studies on A4F separation of GNRs, to our knowledge, this is the first published investigation of in situ GNR growth, separation, and characterization based on A4F, where its utilization in this capacity goes beyond traditional separation analysis. By using hydroquinone as the reducing agent, the conversion of the initial seed population to a distribution of products, including the GNRs, could be monitored in real time using A4F hyphenated with a diode array detector. Transmission electron microscopy confirms that the number of peaks observed during fractionation corresponds with size and shape dispersity. This proof-of-principle study introduces A4F as a technique that establishes a foundation for future mechanistic studies on the growth of GNRs from gold seeds, including conversion of the seed population to initial products, a topic highly relevant to advancing progress in nanomanufacturing.

Synthesis, characterization, and application of two Al(OR(F))3 Lewis superacids.

PubMed

Kraft, Anne; Trapp, Nils; Himmel, Daniel; Böhrer, Hannes; Schlüter, Peter; Scherer, Harald; Krossing, Ingo

2012-07-23

We report herein the synthesis and full characterization of the donor-free Lewis superacids Al(OR(F))(3) with OR(F) = OC(CF(3))(3) (1) and OC(C(5)F(10))C(6)F(5) (2), the stabilization of 1 as adducts with the very weak Lewis bases PhF, 1,2-F(2)C(6)H(4), and SO(2), as well as the internal C-F activation pathway of 1 leading to Al(2)(F)(OR(F))(5) (4) and trimeric [FAl(OR(F))(2)](3) (5, OR(F) = OC(CF(3))(3)). Insights have been gained from NMR studies, single-crystal structure determinations, and DFT calculations. The usefulness of these Lewis acids for halide abstractions has been demonstrated by reactions with trityl chloride (NMR; crystal structures). The trityl salts allow the introduction of new, heteroleptic weakly coordinating [Cl-Al(OR(F))(3)](-) anions, for example, by hydride or alkyl abstraction reactions. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Time-of-flight neutron powder diffraction study on the third row transition metal hexafluorides WF6, OsF6, and PtF6

NASA Astrophysics Data System (ADS)

Marx, R.; Seppelt, K.; Ibberson, R. M.

1996-05-01

A neutron diffraction study on the third-row transition metal hexafluorides MF6 (M≡W, Os, Pt) has been performed using the high resolution neutron powder diffractometer (HRPD) at the spallation source ISIS, England. The previously unknown structures of the low-temperature phases of OsF6 and PtF6 are reported. WF6, OsF6, and PtF6, which exhibit a (5dt2g)0, (5dt2g)2, and (5dt2g)4 electronic configuration, respectively, are found to be isostructural and crystallize in the UF6 structure, space group Pmnb, (No. 62). The geometry of the MF6 molecules is to good approximation octahedral for each compound, the mean M-F bond length increasing only slightly from 182.5 (W) to 185.0 (Pt). For WF6 deviations from ideal octahedral geometry are only marginally significant [181.8(2) to 183.2(2) pm] and may be interpreted on the basis of packing effects. Deviations for the d2 complex OsF6 are somewhat larger [181.5(2) to 184.4(3) pm] and may be assumed to be caused by packing effects essentially the same as for WF6, in addition to a first-order Jahn-Teller effect arising from the (5dt2g)2 electronic configuration. While eliminating the effects of packing by a comparison of individual M-F bond lengths for WF6 and OsF6, the OsF6 molecule shows to have D4h symmetry with two apical M-F bonds about 1.8 pm longer than the four equatorial bonds as a result of the Jahn-Teller distortion. Only small deviations from ideal octahedral geometry [184.4(3) to 185.8(3) pm] are found for the d4 complex PtF6. Within the series W to Pt a substantial shortening of the F...F van der Waals contact distances is observed. This shortening more than compensates for the increase in the M-F bond lengths and leads to unit cell volumes and cell parameters decreasing continuously from W to Pt. The variation of F...F contact distances and M-F bond lengths may be rationalized in terms of polarization of the F-ligands in the field of the highly charged nuclei of the central atoms which are only incompletely shielded by the 5d electrons.

Depletion of kidney CD11c+ F4/80+ cells impairs the recovery process in ischaemia/reperfusion-induced acute kidney injury.

PubMed

Kim, Myung-Gyu; Boo, Chang Su; Ko, Yoon Sook; Lee, Hee Young; Cho, Won Yong; Kim, Hyoung Kyu; Jo, Sang-Kyung

2010-09-01

Recent studies provided evidence of the potential role of CD11c(+) F4/80(+) dendritic subset in mediating injury and repair. The purpose of this study was to examine the role of kidney CD11c(+) F4/80(+) dendritic subset in the recovery phase of ischaemia/reperfusion injury (IRI). Following ischaemia/reperfusion (I/R), liposome clodronate or phosphate buffered saline (PBS) was administered, and on day 7 biochemical and histologic kidney damage was assessed. Activation and depletion of CD11c(+) F4/80(+) dendritic subset were confirmed by flow cytometry. Isolation of kidney CD11c(+) cells on days 1 and 7 with in vitro culture for measuring cytokines was performed to define functional characteristics of these cells, and adoptive transfer of CD11c(+) cells was also done. Following kidney IRI, the percentage of CD11c(+) F4/80(+) kidney dendritic cell subset that co-expresses maturation marker increased. Liposome clodronate injection after I/R resulted in preferential depletion of CD11c(+) F4/80(+) kidney dendritic subset, and depletion of these cells was associated with persistent kidney injury, more apoptosis, inflammation and impaired tubular cell proliferation. CD11c(+) F4/80(+) cell depletion was also associated with higher tissue levels of pro-inflammatory cytokines and lower level of IL-10, indicating the persistence of inflammatory milieu. Isolated kidney CD11c(+) cells on day 7 showed different phenotype with increased production of IL-10 compared with those on day 1. Adoptive transfer of CD11c(+) cells partially reversed impaired tissue recovery. Our results suggest that kidney CD11c(+) F4/80(+) dendritic subset might contribute to the recovery process by dynamic phenotypic change from pro-inflammatory to anti-inflammatory with modulation of immune response.

Detailed investigation of thermal and electron transport properties in strongly correlated compound Ce6Pd12In5 and its nonmagnetic analog La6Pd12In5

NASA Astrophysics Data System (ADS)

Falkowski, M.; Krychowski, D.; Strydom, A. M.

2016-11-01

An in-depth study of thermal and electron transport properties including thermal conductivity κ(T), thermoelectric power S(T), and electrical resistivity ρ(T) of the heavy fermion Kondo lattice Ce6Pd12In5 and its nonmagnetic reference compound La6Pd12In5 is presented. The absolute κ(T) value of Ce6Pd12In5 is smaller that than of La6Pd12In5, which indicates that conduction electron-4f electron scattering has a large impact on the reduction of thermal conductivity. The isolated 4f electron contributions to the electrical resistivity ρ 4 f (T), electronic thermal resistivity displayed in the form W e l , 4 f (T) .T, and thermoelectric power S 4 f (T) reveal a low- and high-temperature -lnT behaviour characteristic of Kondo systems with strong crystal-electric field (CEF) interactions. The analysis of phonon scattering processes of lattice thermal conductivity κph(T) in (Ce, La)6Pd12In5 was performed over the whole accessible temperature range according to the Callaway model. In the scope of a theoretical approach based on the perturbation type calculation, we were able to describe our experimental data of ρ 4 f (T) and W e l , 4 f (T) .T by using the model incorporating simultaneously the Kondo effect in the presence of the CEF splitting, as it is foreseen in the framework of the Cornut-Coqblin and Bhattacharjee-Coqblin theory. Considering the fact that there are not many cases of similar studies at all, we also show the numerical calculations of temperature-dependent behaviour of spin-disorder resistivity ρs(T), magnetic resistivity ρ 4 f (T), and occupation number ⟨ N i ⟩ due to the various types of degeneracy of the ground state multiplet of Ce 3 + (J = 5/2).

Reevaluation and Classification of Duodenal Lesions in B6C3F1 Mice and F344 Rats from 4 Studies of Hexavalent Chromium in Drinking Water.

PubMed

Cullen, John M; Ward, Jerrold M; Thompson, Chad M

2016-02-01

Thirteen-week and 2-year drinking water studies conducted by the National Toxicology Program (NTP) reported that hexavalent chromium (Cr(VI)) induced diffuse epithelial hyperplasia in the duodenum of B6C3F1 mice but not F344 rats. In the 2-year study, Cr(VI) exposure was additionally associated with duodenal adenomas and carcinomas in mice only. Subsequent 13-week Cr(VI) studies conducted by another group demonstrated non-neoplastic duodenal lesions in B6C3F1 mice similar to those of the NTP study as well as mild duodenal hyperplasia in F344 rats. Because intestinal lesions in mice are the basis for proposed safety standards for Cr(VI), and the histopathology data are relevant to the mode of action, consistency (an important Hill criterion for causality) was assessed across the aforementioned studies. Two veterinary pathologists applied uniform diagnostic criteria to the duodenal lesions in rats and mice from the 4 repeated-dose studies. Comparable non-neoplastic intestinal lesions were evident in mice and rats from all 4 studies; however, the incidence and severity of intestinal lesions were greater in mice than rats. These findings demonstrate consistency across studies and species and highlight the importance of standardized nomenclature for intestinal pathology. The differences in the severity of non-neoplastic lesions also likely contribute to the differential tumor response. © The Author(s) 2015.

Reevaluation and Classification of Duodenal Lesions in B6C3F1 Mice and F344 Rats from 4 Studies of Hexavalent Chromium in Drinking Water

PubMed Central

Cullen, John M.; Ward, Jerrold M.

2015-01-01

Thirteen-week and 2-year drinking water studies conducted by the National Toxicology Program (NTP) reported that hexavalent chromium (Cr(VI)) induced diffuse epithelial hyperplasia in the duodenum of B6C3F1 mice but not F344 rats. In the 2-year study, Cr(VI) exposure was additionally associated with duodenal adenomas and carcinomas in mice only. Subsequent 13-week Cr(VI) studies conducted by another group demonstrated non-neoplastic duodenal lesions in B6C3F1 mice similar to those of the NTP study as well as mild duodenal hyperplasia in F344 rats. Because intestinal lesions in mice are the basis for proposed safety standards for Cr(VI), and the histopathology data are relevant to the mode of action, consistency (an important Hill criterion for causality) was assessed across the aforementioned studies. Two veterinary pathologists applied uniform diagnostic criteria to the duodenal lesions in rats and mice from the 4 repeated-dose studies. Comparable non-neoplastic intestinal lesions were evident in mice and rats from all 4 studies; however, the incidence and severity of intestinal lesions were greater in mice than rats. These findings demonstrate consistency across studies and species and highlight the importance of standardized nomenclature for intestinal pathology. The differences in the severity of non-neoplastic lesions also likely contribute to the differential tumor response. PMID:26538584

Engine Rotor Dynamics, Synchronous and Nonsynchronous Whirl Control

DTIC Science & Technology

1979-02-01

models and experimental tests, a method of design optimization was de -, loped to obtain the best trade-off between all the rotor design variables...onsnchrorous What Task X Dphrmiaatoos * Conxduct u rede Study to Determine Sat Comnpromise Damper Support F~ure 1, Rotor Dyna micso Powe agrbin Overview 12 Tlsv...Program - Pj,k-I + l P-l -2 +. + 2 " 1jk Pjjkll + 1+’- + + 2 flJk Pj+I,k (20) where Rj,k = f3,j-,d- + f4j.k de and f3j, k I f4j,k are the functions

76 FR 19724 - Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-08

... B4-600, B4-600R, and F4-600R Series Airplanes, and Model C4-605R Variant F Airplanes (Collectively... F4-605R and F4-622R airplanes, and Model A300 C4-605R Variant F airplanes; and Model A310-203, -204...

Sedimentary Facies of the West Crocker Formation North Kota Kinabalu-Tuaran Area, Sabah, Malaysia

NASA Astrophysics Data System (ADS)

Mohamed, Azfar; Hadi Abd Rahman, Abdul; Suhaili Ismail, Mohd

2016-02-01

Newly outcrops exposed in the West Crocker Formation have led to the detail sedimentolgical analysis of the formation. Eight sedimentary facies have been recognised in which it was divided into three main groups: (1) sand-dominated facies (F1-F2), (2) poorly- sorted unit mixed sand and mud-dominated facies (F3), and (3) mud-dominated facies (F4-F5). These are: F1- graded sandstone (massive to planar laminated), F2-ripple-cross laminated, wavy and convolute lamination sandstone, F3-chaotic beds of mixed sandstone and mudstone blocks and clasts, F4-lenticular bedded of sandstone, and F5-shale. The studies of the formation has come out that it was deposited in a sand-rich submarine fan with specific location located at (1) inner fan channel-levee complex; (2) mid-fan channelised lobes, and (3) outer fan.

Undergraduate Social Work Students: Learning Interviewing Skills in a Hybrid Practice Class

ERIC Educational Resources Information Center

Barclay, Barbara

2012-01-01

This action research case study explored undergraduate social work students' perceived learning of interviewing skills in a hybrid environment course delivery. The single case study consisted of 19 students enrolled in a practice course blending web-based and face-to-face (f2f) meetings (4 of 15 f2f) within a large urban college. As part of…

Developing a Small-Scale De-Fluoridation Filter for Use in Rural Northern Ghana with Activated Alumina As the Sorbent

NASA Astrophysics Data System (ADS)

Craig, L.; Stillings, L. L.

2014-12-01

In northern Ghana, groundwater is the main source of household water and is generally considered safe to drink. However in some areas it contains fluoride (F-) concentrations above the 1.5 ppm limit recommended by the World Health Organization, putting the users at risk of fluorosis. The study area in the Upper East Region of Ghana has pockets of groundwater F- up to 4.6 ppm and, as a result, also has a high percentage of residents with dental fluorosis. They have no alternative water source and, because of poverty and limited access to technology, lack the capacity to set up advanced treatment systems. One proposed solution is to attach F- adsorption filters to the wells, since adsorption is considered a simple and cost effective approach for treating high F-drinking water. This study evaluates activated alumina as a sorbent for use in de-fluoridation filters in the study area. We evaluated the long-term adsorption capacity of activated alumina, and changes in F- adsorption rate and capacity with grain size. We measured differences in positive surface charge (C m-2) via slow acid titration, as well as F- loading with varied prior hydration time. Results from this research show no notable change in F- adsorption or positive surface charge when the activated alumina surface was pre-equilibrated in distilled water from 24 hours to 30 weeks. The results of F- loading show a maximum of ~3.4 mg F- sorbed per gm activated alumina (initial pH ~6.9, initial F- 1 to 60 ppm, 20 hr reaction time). The pH dependent surface charge is ~0.14 C m-2 at pH of ~4.4 and is zero at pH ~8.6. F- loading experiments were conducted with grain size 0.125 to 0.250 mm and 0.5 to 1.0 mm to evaluate changes in F- adsorption rate (initial pH ~6.9, initial F- 10 ppm) and F- loading (initial pH ~6.9, initial F- 1 to 60 ppm, 20 hr reaction time). The F- loading did not change with grain size. However time to equilibrium increased dramatically with a decrease in grain size - after one hour of reaction time, the larger grain size adsorbed only 59% of F-, while at the finer grain size 90% was adsorbed. Future work will determine the volume of high F- water that can be treated before activated alumina needs to be regenerated or changed. These data will aid in the design of a small-scale F- adsorption filter in the study area, and will predict the longevity of activated alumina as the sorbent.

N-(4-[18F]fluorobenzyl)cholylglycine, a novel tracer for PET of enterohepatic circulation of bile acids: Radiosynthesis and proof-of-concept studies in rats.

PubMed

Frisch, Kim; Stimson, Damion H R; Venkatachalam, Taracad; Pierens, Gregory K; Keiding, Susanne; Reutens, David; Bhalla, Rajiv

2018-05-04

Enterohepatic circulation (EHC) of conjugated bile acids is an important physiological process crucial for regulation of intracellular concentrations of bile acids and their function as detergents and signal carriers. Only few bile acid-derived imaging agents have been synthesized and hitherto none have been evaluated for studies of EHC. We hypothesized that N-(4-[ 18 F]fluorobenzyl)cholylglycine ([ 18 F]FBCGly), a novel fluorine-18 labeled derivative of endogenous cholylglycine, would be a suitable tracer for PET of the EHC of conjugated bile acids, and we report here a radiosynthesis of [ 18 F]FBCGly and a proof-of-concept study by PET/MR in rats. A radiosynthesis of [ 18 F]FBCGly was developed based on reductive alkylation of glycine with 4-[ 18 F]fluorobenzaldehyde followed by coupling to cholic acid. [ 18 F]FBCGly was investigated in vivo by dynamic PET/MR in anesthetized rats; untreated or treated with cholyltaurine or rifampicin. Possible in vivo metabolites of [ 18 F]FBCGly were investigated by analysis of blood and bile samples, and the stability of [ 18 F]FBCGly towards enzymatic de-conjugation by Cholylglycine Hydrolase was tested in vitro. [ 18 F]FBCGly was produced with a radiochemical purity of 96% ± 1% and a non-decay corrected radiochemical yield of 1.0% ± 0.3% (mean ± SD; n = 12). PET/MR studies showed that i.v.-administrated [ 18 F]FBCGly underwent EHC within 40-60 min with a rapid transhepatic transport from blood to bile. In untreated rats, the radioactivity concentration of [ 18 F]FBCGly was approximately 15 times higher in bile than in liver tissue. Cholyltaurine and rifampicin inhibited the biliary secretion of [ 18 F]FBCGly. No fluorine-18 metabolites of [ 18 F]FBCGly were observed. We have developed a radiosynthesis of a novel fluorine-18 labeled bile acid derivative, [ 18 F]FBCGly, and shown by PET/MR that [ 18 F]FBCGly undergoes continuous EHC in rats without metabolizing. This novel tracer may prove useful in PET studies on the effect of drugs or diseases on the EHC of conjugated bile acids. Copyright © 2018 Elsevier Inc. All rights reserved.

Testing Properties of Boolean Functions

DTIC Science & Technology

2012-01-01

Applying the Hermite decomposition of f and linearity of expectation, E x,y [f(x)f(y) 〈x, y〉] = n∑ i=1 ∑ S,T∈Nn f̂(S)f̂(T )E x [HS(x)xi]E y [ HT (y)yi...otherwise it takes the value 0. Similarly, Ey[ HT (y)yi] = 1 iff T = ei. 38 Part I Exact Query Complexity 39 Chapter 5 Testing Juntas We begin by studying the...1− 2e− 6m /2 = 1− 2e−O( √ n). The estimate ν̃ is a U-statistic with kernel ψ∗f . This kernel satisfies ‖ψ∗f − Eψ∗f‖∞ ≤ 2‖ψ∗f‖∞ = 2 √ 4n log(4n/3

[Ni(cod) 2][Al(OR F) 4], a Source for Naked Nickel(I) Chemistry

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

Schwab, Miriam M.; Himmel, Daniel; Kacprzak, Sylwia

The straightforward synthesis of the cationic, purely organometallic Ni I salt [Ni(cod) 2] +[Al(OR F) 4] - was realized through a reaction between [Ni(cod) 2] and Ag[Al(OR F) 4] (cod=1,5-cyclooctadiene). Crystal-structure analysis and EPR, XANES, and cyclic voltammetry studies confirmed the presence of a homoleptic NiI olefin complex. Weak interactions between the metal center, the ligands, and the anion provide a good starting material for further cationic NiI complexes.

New High Temperature Cross Linking Monomers

NASA Technical Reports Server (NTRS)

Scola, Daniel A.

1978-01-01

This report describes the results of a one-year program designed to synthesize new, nonvolatile crosslinking monomers and to prove their feasibility in the development of lower temperature curing PMR-polyimide resins with high temperature capability. The objective of this program is to develop PMR-polyimide resins capable of being processed at a maximum temperature of 232C to 288C (450F to 500F) without sacrifice of the high temperature 316C (600F) capability of the state-of-the-art PMR-15 polyimide resin. Four monomethyl esters were synthesized and characterized for use in the crosslinking studies. It was found that all four crosslinkers were capable of entering into a crosslinking reaction to produce polymer specimens which were strong, dense and free of voids. The infrared and DSC studies of each crosslinker with monomers 4,4'-methylenedianiline (MDA) and the dimethyl ester of 3,3',4,4'-benzophenonetetracarboxylic acid (BTDE) comprising the resin systems, crosslinker/MDA/BTDE suggested that curing could be accomplished at 288C (550F). However, fabrication of dense, void free polymer specimens required a temperature of 316C (600F) and a pressure of 0.69 MPa (100 psi). The crosslinkers, monomethyl ester of 2,5-bicyclo[2.2.1]heptadiene-2,3-dicarboxylic acid (NDE) and monomethyl ester of maleic acid (MAE) were selected for evaluation in Celion 6000/PMR polyimide composites. These composites were characterized at RT, 288C (550F) and 316C (600F) initially and after isothermal aging at 288C (550F) and 316C (600F) for several hundred hours. The results of the isothermal aging studies suggested that both PMR systems NDE-MDA-BTDE and MAE-MDA-BTDE are promising candidates as matrices for addition type polyimide composites. These studies demonstrated that alternate crosslinkers to NE/MDA/BTDE are feasible, but mechanisms to lower the crosslinking temperature must be developed to provide lower temperature processing PMR-type polyimides.

Novel non-invasive biological predictive index for liver fibrosis in hepatitis C virus genotype 4 patients

PubMed Central

Khattab, Mahmoud; Sakr, Mohamed Amin; Fattah, Mohamed Abdel; Mousa, Youssef; Soliman, Elwy; Breedy, Ashraf; Fathi, Mona; Gaber, Salwa; Altaweil, Ahmed; Osman, Ashraf; Hassouna, Ahmed; Motawea, Ibrahim

2016-01-01

AIM To investigate the diagnostic ability of a non-invasive biological marker to predict liver fibrosis in hepatitis C genotype 4 patients with high accuracy. METHODS A cohort of 332 patients infected with hepatitis C genotype 4 was included in this cross-sectional study. Fasting plasma glucose, insulin, C-peptide, and angiotensin-converting enzyme serum levels were measured. Insulin resistance was mathematically calculated using the homeostasis model of insulin resistance (HOMA-IR). RESULTS Fibrosis stages were distributed based on Metavir score as follows: F0 = 43, F1 = 136, F2 = 64, F3 = 45 and F4 = 44. Statistical analysis relied upon reclassification of fibrosis stages into mild fibrosis (F0-F) = 179, moderate fibrosis (F2) = 64, and advanced fibrosis (F3-F4) = 89. Univariate analysis indicated that age, log aspartate amino transaminase, log HOMA-IR and log platelet count were independent predictors of liver fibrosis stage (P < 0.0001). A stepwise multivariate discriminant functional analysis was used to drive a discriminative model for liver fibrosis. Our index used cut-off values of ≥ 0.86 and ≤ -0.31 to diagnose advanced and mild fibrosis, respectively, with receiving operating characteristics of 0.91 and 0.88, respectively. The sensitivity, specificity, positive predictive value, negative predictive value and positive likelihood ratio were: 73%, 91%, 75%, 90% and 8.0 respectively for advanced fibrosis, and 67%, 88%, 84%, 70% and 4.9, respectively, for mild fibrosis. CONCLUSION Our predictive model is easily available and reproducible, and predicted liver fibrosis with acceptable accuracy. PMID:27917265

Novel non-invasive biological predictive index for liver fibrosis in hepatitis C virus genotype 4 patients.

PubMed

Khattab, Mahmoud; Sakr, Mohamed Amin; Fattah, Mohamed Abdel; Mousa, Youssef; Soliman, Elwy; Breedy, Ashraf; Fathi, Mona; Gaber, Salwa; Altaweil, Ahmed; Osman, Ashraf; Hassouna, Ahmed; Motawea, Ibrahim

2016-11-18

To investigate the diagnostic ability of a non-invasive biological marker to predict liver fibrosis in hepatitis C genotype 4 patients with high accuracy. A cohort of 332 patients infected with hepatitis C genotype 4 was included in this cross-sectional study. Fasting plasma glucose, insulin, C-peptide, and angiotensin-converting enzyme serum levels were measured. Insulin resistance was mathematically calculated using the homeostasis model of insulin resistance (HOMA-IR). Fibrosis stages were distributed based on Metavir score as follows: F0 = 43, F1 = 136, F2 = 64, F3 = 45 and F4 = 44. Statistical analysis relied upon reclassification of fibrosis stages into mild fibrosis (F0-F) = 179, moderate fibrosis (F2) = 64, and advanced fibrosis (F3-F4) = 89. Univariate analysis indicated that age, log aspartate amino transaminase, log HOMA-IR and log platelet count were independent predictors of liver fibrosis stage ( P < 0.0001). A stepwise multivariate discriminant functional analysis was used to drive a discriminative model for liver fibrosis. Our index used cut-off values of ≥ 0.86 and ≤ -0.31 to diagnose advanced and mild fibrosis, respectively, with receiving operating characteristics of 0.91 and 0.88, respectively. The sensitivity, specificity, positive predictive value, negative predictive value and positive likelihood ratio were: 73%, 91%, 75%, 90% and 8.0 respectively for advanced fibrosis, and 67%, 88%, 84%, 70% and 4.9, respectively, for mild fibrosis. Our predictive model is easily available and reproducible, and predicted liver fibrosis with acceptable accuracy.

Crystal Phases Formed in a CaO-Fe2O3 System Under a High Cooling Rate in Air

NASA Astrophysics Data System (ADS)

Kashiwaya, Yoshiaki

2017-12-01

A CaO-Fe2O3 system is a fundamental binary system for the iron ore sintering process. Although the basic reactions have been investigated since the 1960s, melting and solidification caused by the combustion of coke results in an unstable state owing to extreme temperature variations. In this study, using a hot thermocouple method, samples of 10 pct CaO-90 pct Fe2O3 and 20 pct CaO-80 pct Fe2O3 were melted on a thermocouple and quenched with several techniques. The obtained samples were precisely examined by XRD. It was found that the sample containing 10 pct CaO-90 pct Fe2O3 changed to 10 pct CaO-13 pct FeO-77 pct Fe2O3 under an oxygen partial pressure ( P_{{{O}2 }} ) of 0.21 during melting. For the 10 pct CaO sample, the crystal phases found at a low cooling rate (509 K/s) were WFss, C4WF8 (C: CaO, W: FeO, F: Fe2O3), and C2W4F9. When the sample composition was 20 pct CaO, the precipitated crystal phases were C4WF4, C4F7, and C4WF8. On the other hand, the crystal phases for high cooling rates (1590 and 7900 K/s) with 10 pct CaO were WFss (solid solution of WF and F), F, and C2W4F9. The formation of the equilibrium phases WFss, F, C4WF4, and C4WF8 can be understood by examining the isothermal section of the phase diagrams, while the unstable phases C2W4F9 and C4F7 are discussed on the basis of the reactions under an equilibrium state.

Role of TiF4 in Microleakage of Silorane and Methacrylate-based Composite Resins in Class V Cavities.

PubMed

Koohpeima, Fatemeh; Sharafeddin, Farahnaz; Jowkar, Zahra; Ahmadzadeh, Samaneh; Mokhtari, Mohammad Javad; Azarian, Babak

2016-03-01

This study investigated the effect of TiF4 solution pretreat-ment on microleakage of silorane and nanofilled methacrylate-based composites in class V cavities. Forty-eight intact premolar teeth were randomly allocated to four groups of 12 teeth. Restorative techniques after standard class V tooth preparations were as follows: Group 1, Filtek P90 composite; group 2, Filtek Z350 XT; group 3, TiF4 solution pretreatment and Filtek P90 composite; group 4, TiF4 solution pretreatment and Filtek Z350 XT. After storing the specimens in distilled water at 37°C for 24 hours and followed by immersion of the specimens in a 0.5% basic-fuchsin solution for 24 hours, they were sectioned buccolingually to obtain four surfaces for each specimen for analysis of microleakage using a stereomicroscope. Data analysis was performed using Kruskal-Wallis test to compare the four groups and the Mann-Whitney test for paired comparisons with Statistical Package for the Social Sciences (SPSS) version 17 software. At the enamel margins, microleakage score of the Filtek Z350 XT group was lower than those of the Filtek P90 with and without the application of the TiF4 (p = 0.009 and p = 0.031 respectively). At the dentin margins, groups 3 and 4 (TiF4+Filtek P90 and TiF4+Filtek z350 XT respectively) showed significantly lower microleakage than group 1 (Filtek P90). However, there was no significant difference between other groups (p > 0.05). At the enamel margins, microleakage score of the silorane-based composite was more than that of the nanofilled composite. No significant differences were observed between the other groups. At the dentin margins, for the silorane-based composite restorations, TiF4 solution pretreatment resulted in significantly lower microleakage. However, the similar result was not observed for Filtek Z350 XT. Also, no significant difference was observed between microleakage scores of Filtek P90 and Filtek Z350 XT with or without TiF4 pretreatment. In spite of better mechanical and physical properties of modern composites than earlier methacrylate-based composites, polymerization shrinkage has been remaining as one of the main shortcomings of them. Different methods, such as using new low shrinkage resin composites and different dentin pretreatments, have been suggested to overcome this problem. This study evaluated the effect of TiF4 as pretreatment on microleakage of class V tooth preparations restored with a nanocomposite and a silorane-based resin composite.

[The influence of hypothyroidism on the conversion and binding of thyroid hormones in patients with end-stage renal disease].

PubMed

Dubczak, Iwanna; Niemczyk, Longin; Bartoszewicz, Zbigniew; Szamotulska, Katarzyna; Saracyn, Marek; Niemczyk, Stanisław

2017-03-21

Hypothyroidism in patients with renal failure (RF) causes many metabolic and clinical problems, and both these diseases can mutually exacerbate their disturbances. The aim of this study was to evaluate the effect of hypothyroidism, and end-stage renal disease (ESRD) on conversion of thyroid hormones (TH) in patients with ESRD treated with chronic hemodialysis (HD). The study was performed in 74 patients, including 41 women (K) and 33 men (M) aged 28-83 y.o. in 4 groups: G1 - 12 people with ESRD treated with HD and with newly diagnosed hypothyroidism without substitution (6 K and M 6) aged 66,83±12,90 y.o., G2 - 26 patients with ESRD treated with HD without hypothyroidism (10 F, 16 M) aged 58,85±15,52 y.o., G3 - 11 hypothyroid patients without RF (9 K, 2 M) aged 54,73±21,26 y.o., G4 - 25-persons from control group of healthy subjects (16 M, 9 M) aged 51,24±12,58 y.o. In all subjects the concentration of TSH and TH (T4, T3, fT4, TSH, FT3, rT3) were measured and values of conversion factors (T3/T4, FT3/ fT4, rT3/fT4 and rT3/fT3) and binding TH to protein factors (fT4/T4 and fT3/T3) were calculated. Lower concentration of T3 (p=0.012), fT3 (p<0.001) i fT4 (p=0.014) was found in patients without hypothyroidism than in healthy subjects. Renal failure with concomitant hypothyroidism intensify the disturbances of T4 to T3 conversion (p=0.034) and hypothyroidism with concomitant renal failure disrupts binding of T3 to proteins (p=0.001). FT3 to fT4 ratio in renal failure with concomitant hypothyroidism group was significantly lower than in each other group. rT3 concentrations were the highest in healthy subjects. Concomitance of hypothyroidism and end-stage renal disease reduces the conversion of thyroxine to triiodothyronine, but does not increase the production of rT3. Hypothyroidism significantly increases the disorders of thyroid hormones in end-stage renal disease. There is decreased tendency to bind of thyroid hormone to protein in hypothyroidism in patients with end-stage renal disease.

The Impact of School Gardening on Cree Children's Knowledge and Attitudes toward Vegetables and Fruit.

PubMed

Hanbazaza, Mahitab A; Triador, Lucila; Ball, Geoff D C; Farmer, Anna; Maximova, Katerina; Alexander First Nation; Willows, Noreen D

2015-09-01

School-based interventions may increase children's preferences for vegetables and fruit (V&F). This Canadian study measured changes in Indigenous First Nations schoolchildren's V&F knowledge, preferences, and home consumption following the implementation of a gardening and V&F snack program. At baseline, 7 months, and 18 months, children in grades 1-6 (i) listed at least 5 V&F they knew, (ii) tasted and indicated their preferences towards 9 vegetables and 8 fruit using a 6-point Likert scale, and (iii) indicated their home consumption of 17 V&F. At all 3 time points, 56.8% (n = 66/116) of children provided data. Children listed a greater number of V&F at 18 months (4.9 ± 0.1) than at baseline (4.5 ± 1.0) or 7 months (4.7 ± .07) (F(1.6,105.6) = 6.225, P < 0.05). Vegetable preferences became more positive between baseline (37.9 ± 9.3) and 7 months (39.9 ± 9.2), but returned to baseline levels at 18 months (37.3 ± 8.7) (F(1.6,105.8) = 4.581, P < 0.05). Fruit preferences at 18 months (42.7 ± 3.0) were greater than at baseline (41.1 ± 4.3) and at 7 months (41.9 ± 5.1) (F(1.7,113.3) = 3.409, P < 0.05). No change in V&F consumption occurred at home. Despite improvements in V&F knowledge and preferences, home consumption of V&F did not occur. Complementing school-based programs with home-based components may be needed to influence V&F intake of children.

Studies of Solar Flares and Coronal Loops.

DTIC Science & Technology

1984-07-10

i( Tipo + T pl) and equations (5) and (8), we get P (D - w t P = + 0 (9j where 0 = o ’-, +T (k" -B,)- (o fTQ 10R B0 . G!) = ( - 1 ) R p + T ( k...andStegun. 1 . eds. 1970. HandhoolMathemarical Davis. J. M., and Webb. D F 1981. Bull • 4.4S. 13. -21 F!,n,; .ns INew York Do’er). p. 17 Einaudi. G...Sakanaka. P H 19-4. Ph s fIhids. 17, SIX 1951. Proc Ros Sit London. 1. 244. 17. Harsey. K. L. 1981. Bull . 44S. 13. ,90 tiider. C. Einaudi. G. and

Aircraft Avionics and Missile System Installation Cost Study. Volume 2. Appendices F and G.

DTIC Science & Technology

1988-02-12

C WING STRUCTUAL FAITIGU LIFI ENBANCEMEINT 3 25 983 81018 F-4 AFPSOOSBR Al A F-4S A/C STRUCTUAL NOD 3 26 200 81019 F-4 AFPS00674 Al A A1N-7N SPARROW...INTERFACE CONPATIBILITY 3 25 18 81019 YCA542523 A1 B AIAING-1OA TECHICAI L OBSOLESCEICE PROGR AM 3 200000 39 1336 34 328 811 C522 2Bh/W-10A TECHNICAL...OBSOLESENCE PROGRAM 3 196000 00 0 328* 81019 YCA542523 B1 B AN/AWG-IOA TECHNICAL OBSOLESENCE PROGRAN 3 2210 2 82 41 29 81019 YCA542523 B2 B ANANG

Health promotion across occupational groups: one size does not fit all.

PubMed

Tsiga, E; Panagopoulou, E; Niakas, D

2015-10-01

Although several studies have examined the link between specific working conditions and health behaviours, very few have comparatively assessed the health behaviours of different occupational groups. To compare protective and risky health behaviours among police officers, ambulance workers, hospital staff (doctors and nurses) and office workers, prompted by the need to identify key areas for interventions tailored to the needs of different occupational groups. A cross-sectional postal survey using the Health Behaviours Inventory, assessing health behaviours which are risky (alcohol intake, smoking, coffee consumption, fast food meals and painkiller consumption) and protective (physical activity, eating breakfast and hours of sleep). The sample consisted of 1451 employees. Ambulance workers smoked the most cigarettes per day (F (4, 1405) = 8.63, P < 0.01), while doctors consumed twice as many fast food meals as any other occupational group (F (4, 1415) = 78.45, P < 0.01) and had the highest daily caffeine consumption (F (4, 1440) = 11.17, P < 0.01). Ambulance workers and doctors reported the highest frequency of alcohol consumption per week (F (4, 1421) = 10.13, P < 0.01). In regard to protective health behaviours, office workers reported the highest number of breakfast meals per week (F (4, 1431) = 5.7, P < 0.01) and sleeping hours per night (F (4, 1438) = 170.34, P < 0.01), while police officers and ambulance workers exercised more frequently (F (4, 1420) = 5.764, P < 0.01). The results of the study highlight key priorities for health promotion for different occupational groups which need to be taken into consideration in policy making and developing workplace interventions. © The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Detection of inflamed atherosclerotic lesions with diadenosine-5′,5‴-P1,P4-tetraphosphate (Ap4A) and positron-emission tomography

PubMed Central

Elmaleh, D. R.; Fischman, A. J.; Tawakol, A.; Zhu, A.; Shoup, T. M.; Hoffmann, U.; Brownell, A.-L.; Zamecnik, P. C.

2006-01-01

Diadenosine-5′,5‴-P1,P4-tetraphosphate (Ap4A) and its analog P2,P3-monochloromethylene diadenosine-5′,5‴-P1,P4-tetraphosphate (AppCHClppA) are competitive inhibitors of adenosine diphosphate-induced platelet aggregation, which plays a central role in arterial thrombosis and plaque formation. In this study, we evaluate the imaging capabilities of positron-emission tomography (PET) with P2,P3-[18F]monofluoromethylene diadenosine-5′,5‴-P1,P4-tetraphosphate ([18F]AppCHFppA) to detect atherosclerotic lesions in male New Zealand White rabbits. Three to six months after balloon injury to the aorta, the rabbits were injected with [18F]AppCHFppA, and microPET imaging showed rapid accumulation of this radiopharmaceutical in the atherosclerotic abdominal aorta, with lesions clearly visible 30 min after injection. Computed tomographic images were coregistered with PET images to improve delineation of aortoiliac tracer activity. Plaque macrophage density, quantified by immunostaining with RAM11 against rabbit macrophages, correlated with PET measurements of [18F]AppCHFppA uptake (r = 0.87, P < 0.0001), whereas smooth-muscle cell density, quantified by immunostaining with 1A4 against smooth muscle actin, did not. Biodistribution studies of [18F]AppCHFppA in normal rats indicated typical adenosine dinucleotide behavior with insignificant myocardial uptake and fast kidney clearance. The accumulation of [18F]AppCHFppA in macrophage-rich atherosclerotic plaques can be quantified noninvasively with PET. Hence, [18F]AppCHFppA holds promise for the noninvasive characterization of vascular inflammation. PMID:17038498

Three-phase heterostructures f-NiFe2O4/PANI/PI EMI shielding fabric with high Microwave Absorption Performance

NASA Astrophysics Data System (ADS)

Wang, Yu; Wang, Wei; Yu, Dan

2017-12-01

In this work, a three-phase heterostructures f-NiFe2O4/PANI/PI EMI shielding fabric with a layer by layer structure was designed and prepared to obtain excellent microwave attenuation performance. Firstly, PANI/PI fabric was prepared via in-situ deposition method. Then, the NiFe2O4 nanoparticles functionalized by oleic acid were uniformly dispersed in epoxy resin and coated on the top and bottom of PANI/PI fabric with 0.041 mm total thickness. The investigation of chemical structure and surface morphologies indicated the composite structure of f-NiFe2O4/PANI/PI fabric. Various parameters like magnetic property, reflection loss and attenuation constant were used to evaluate its microwave attenuation performance. The results demonstrated that the 30f-NiFe2O4/PANI/PI fabric had a highest attenuation effectiveness with the minimum reflection loss value of -42.5 dB (>90% attenuation) at 12.5 GHz and the effective absorption bandwidth was 3.4 GHz. The study of attenuation mechanism indicated that the dielectric loss from PANI, the magnetic loss caused by f-NiFe2O4 and the layer by layer structure effectively improved microwave attenuation performance of composite fabric. Furthermore, the favorable flexibility and dimensional stability of this resultant fabric would allow the composite fabric for a long time service under pressure or foldable conditions. In sum, the study clearly indicated that three-phase heterostructures f-NiFe2O4/PANI/PI fabric was a good candidate as electromagnetic shielding materials in many fields.

Synthesis and isomerization of acridine substituted 1,3-thiazolidin-4-ones and 4-oxo-1,3-thiazolidin-5-ylidene acetates. An experimental and computational study

NASA Astrophysics Data System (ADS)

Bečka, Michal; Vilková, Mária; Šoral, Michal; Potočňák, Ivan; Breza, Martin; Béres, Tibor; Imrich, Ján

2018-02-01

Acridine thiosemicarbazones 3a-g, obtained through a two-step reaction between aromatic isothiocyanates and hydrazine followed by the treatment with acridin-9-carbaldehyde, in reaction with bifunctional reagents; methyl bromoacetate (MBA) and diethyl acetylenedicarboxylate (DEAD) afforded acridin-thiazolidinone derivatives 4a-g and 7a-f and not their regioisomers 6a-g and 9a-f. Derivatives 4a-g and 7a-f exhibit ZC2N6EN7C8 configuration. Upon standing in DMSO-d6 the thiazolidinones 4a-g and 7a-f spontaneously isomerized into ZC2N6ZN7C8 isomers 5a-g and 8a-f to give a mixture of the both stereoisomers. All compounds were fully characterized by multinuclear NMR, mass spectrometry (MS) and X-ray crystal structure of 4b is also described. X-ray diffraction study revealed that the representative compound 4b crystallized in the monoclinic crystal system with the C2/c space group and Z = 4. Intramolecular C1‧sbnd H1‧⋯N-7 hydrogen bond between the acridine proton H-1‧ and nitrogen N-7 of linker existed. This hydrogen bond is responsible for the E isomerism on C-8 atom which was observed in the NMR experiments. Quantum-chemical calculations and NOESY experiments confirmed ZC2N6ZN7C8 configuration of the transformed stereoisomers 5a-g and 8a-f.

Compressed Sensing for fMRI: Feasibility Study on the Acceleration of Non-EPI fMRI at 9.4T

PubMed Central

Kim, Seong-Gi; Ye, Jong Chul

2015-01-01

Conventional functional magnetic resonance imaging (fMRI) technique known as gradient-recalled echo (GRE) echo-planar imaging (EPI) is sensitive to image distortion and degradation caused by local magnetic field inhomogeneity at high magnetic fields. Non-EPI sequences such as spoiled gradient echo and balanced steady-state free precession (bSSFP) have been proposed as an alternative high-resolution fMRI technique; however, the temporal resolution of these sequences is lower than the typically used GRE-EPI fMRI. One potential approach to improve the temporal resolution is to use compressed sensing (CS). In this study, we tested the feasibility of k-t FOCUSS—one of the high performance CS algorithms for dynamic MRI—for non-EPI fMRI at 9.4T using the model of rat somatosensory stimulation. To optimize the performance of CS reconstruction, different sampling patterns and k-t FOCUSS variations were investigated. Experimental results show that an optimized k-t FOCUSS algorithm with acceleration by a factor of 4 works well for non-EPI fMRI at high field under various statistical criteria, which confirms that a combination of CS and a non-EPI sequence may be a good solution for high-resolution fMRI at high fields. PMID:26413503

Neighborhood and healthy aging in a German city: distances to green space and senior service centers and their associations with physical constitution, disability, and health-related quality of life.

PubMed

Vogt, Susanne; Mielck, Andreas; Berger, Ursula; Grill, Eva; Peters, Annette; Döring, Angela; Holle, Rolf; Strobl, Ralf; Zimmermann, Anja-Kerstin; Linkohr, Birgit; Wolf, Kathrin; Kneißl, Klaus; Maier, Werner

2015-12-01

The composition of the residential environment may have an independent influence on health, especially in older adults. In this cross-sectional study, we examined the associations between proximity to two features of the residential environment (green space and senior service centers) and three aspects of healthy aging (self-rated physical constitution, disability, and health-related quality of life). We included 1711 inhabitants from the city of Augsburg, Germany, aged 65 years or older, who participated in the KORA-Age study conducted in 2008/2009. We calculated the Euclidian distances between each participant's residential address and the nearest green space or senior service center, using a geographic information system. Multilevel logistic regression models were fitted to analyze the associations, controlling for demographic and socioeconomic factors. Contrary to expectations, we did not find clear associations between the distances to the nearest green space or senior service center and any of the examined aspects of healthy aging. The importance of living close to green space may largely depend on the study location. The city of Augsburg is relatively small (about 267,000 inhabitants) and has a high proportion of greenness. Thus, proximity to green space may not be as important as in a densely populated metropolitan area. Moreover, an objectively defined measure of access such as Euclidian distance may not reflect the actual use. Future studies should try to assess the importance of resources of the residential environment not only objectively, but also from the resident's perspective.

EFFECTIVE INDICES FOR MONITORING MENTAL WORKLOAD WHILE PERFORMING MULTIPLE TASKS.

PubMed

Hsu, Bin-Wei; Wang, Mao-Jiun J; Chen, Chi-Yuan; Chen, Fang

2015-08-01

This study identified several physiological indices that can accurately monitor mental workload while participants performed multiple tasks with the strategy of maintaining stable performance and maximizing accuracy. Thirty male participants completed three 10-min. simulated multitasks: MATB (Multi-Attribute Task Battery) with three workload levels. Twenty-five commonly used mental workload measures were collected, including heart rate, 12 HRV (heart rate variability), 10 EEG (electroencephalography) indices (α, β, θ, α/θ, θ/β from O1-O2 and F4-C4), and two subjective measures. Analyses of index sensitivity showed that two EEG indices, θ and α/θ (F4-C4), one time-domain HRV-SDNN (standard deviation of inter-beat intervals), and four frequency-domain HRV: VLF (very low frequency), LF (low frequency), %HF (percentage of high frequency), and LF/HF were sensitive to differentiate high workload. EEG α/θ (F4-C4) and LF/HF were most effective for monitoring high mental workload. LF/HF showed the highest correlations with other physiological indices. EEG α/θ (F4-C4) showed strong correlations with subjective measures across different mental workload levels. Operation strategy would affect the sensitivity of EEG α (F4-C4) and HF.

Preliminary research on 1-(4-bromo-2-nitroimidazol-1-yl)-3-[(18)F]fluoropropan-2-ol as a novel brain hypoxia PET tracer in a rodent model of stroke.

PubMed

Nieto, Elena; Delgado, Mercedes; Sobrado, Mónica; de Ceballos, María L; Alajarín, Ramón; García-García, Luis; Kelly, James; Lizasoain, Ignacio; Pozo, Miguel A; Álvarez-Builla, Julio

2015-08-28

The synthesis of the new radiotracer precursor 4-Br-NITTP and the radiolabeling of the new tracer 1-(4-bromo-2-nitroimidazol-1-yl)-3-[(18)F]fluoropropan-2-ol (4-Br-[(18)F]FMISO) is reported. The cyclic voltammetry behaviour, neuronal cell toxicity, transport through the brain endothelial cell monolayer, in vivo PET imaging and preliminary calculations of the tracer uptake for a rodent model of stroke were studied for the new compound and the results were compared to those obtained with [(18)F]FMISO, the current gold standard PET hypoxia tracer. The new PET brain hypoxia tracer is more easily reduced, has higher CLogP than [(18)F]FMISO and it diffuses more rapidly through brain endothelial cells. The new compound is non-toxic to neuronal cells and it allows the in vivo mapping of stroke in mice with higher sensitivity. 4-Br-[(18)F]FMISO is a good candidate for further development in ischemic stroke. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

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

Guo Yicheng; Barro, Guillermo; Faber, Sandra M.

We present a UV to mid-infrared multi-wavelength catalog in the CANDELS/GOODS-S field, combining the newly obtained CANDELS HST/WFC3 F105W, F125W, and F160W data with existing public data. The catalog is based on source detection in the WFC3 F160W band. The F160W mosaic includes the data from CANDELS deep and wide observations as well as previous ERS and HUDF09 programs. The mosaic reaches a 5{sigma} limiting depth (within an aperture of radius 0.''17) of 27.4, 28.2, and 29.7 AB for CANDELS wide, deep, and HUDF regions, respectively. The catalog contains 34,930 sources with the representative 50% completeness reaching 25.9, 26.6, andmore » 28.1 AB in the F160W band for the three regions. In addition to WFC3 bands, the catalog also includes data from UV (U band from both CTIO/MOSAIC and VLT/VIMOS), optical (HST/ACS F435W, F606W, F775W, F814W, and F850LP), and infrared (HST/WFC3 F098M, VLT/ISAAC Ks, VLT/HAWK-I Ks, and Spitzer/IRAC 3.6, 4.5, 5.8, 8.0 {mu}m) observations. The catalog is validated via stellar colors, comparison with other published catalogs, zero-point offsets determined from the best-fit templates of the spectral energy distribution of spectroscopically observed objects, and the accuracy of photometric redshifts. The catalog is able to detect unreddened star-forming (passive) galaxies with stellar mass of 10{sup 10} M{sub Sun} at a 50% completeness level to z {approx} 3.4 (2.8), 4.6 (3.2), and 7.0 (4.2) in the three regions. As an example of application, the catalog is used to select both star-forming and passive galaxies at z {approx} 2-4 via the Balmer break. It is also used to study the color-magnitude diagram of galaxies at 0 < z < 4.« less

[The clinical efficacy and safety study of Esculin and Digitalis glycosides Eye Drops in treating ametropic asthenopia].

PubMed

Jiang, Zhen-ying; Qu, Xiao-mei; Li, Xiao-xin; Liu, Yu-ling; Shen, Nian-ci; Zhang, Lin; Ke, Bi-lian; Zhao, Pei-quan; Jiang, Jun; Yao, Ke; Zeng, Jin; Yang, Xiao; Chu, Ren-yuan

2010-12-01

To study the clinical efficacy and safety of the Esculin and Digitalis glycosides Eye Drops used in the patients of ametropic asthenopia. Multicenter clinical trial. Asthenopia patients were chosen from eleven hospitals cross China from July, 2008 to January, 2009. The experiment was conducted asthenopia patients who used the Esculin and Digitalis glycosides Eye Drops for 4 weeks continuously. Symptoms of asthenopia, UCVA (uncorrected vision acuity), refraction, amplitude of accommodation, accommodative lag, accommodative sensitivity and positive/negative relative accommodation were measured at different time points, such as treated before, 1 week and 4 week in treated after. After the 4-week's use of Esculin and Digitalis glycosides Eye Drops, each subjective symptom of the patients was decreased significantly (F=353.30, P<0.05). In addition, most of the objective exams of accommodation ability were significantly improved, such as UCVA (left eye: F=23.39, P<0.05; right eye: F=15.62, P<0.05), refraction (left eye: F=10.34, P<0.05; right eye: F=17.13, P<0.05), amplitude of accommodation (left eye: F=14.46, P<0.05; right eye: F=8.29, P<0.05; eyes: F=13.86, P<0.05), accommodative lag (F=14.89, P<0.05) and accommodative sensitivity (left eye: F=62.67, P<0.05; right eye: F=68.77, P<0.05; eyes: F=82.74, P<0.05). And no patient appeared any adverse reaction in whole experiment. Esculin and Digitalis glycosides Eye Drops is effective and safety for use in the patients of ametropia asthenopia.

Prime Contractors with Awards Over $25,000 by Name, Location, and Contract Number, Fiscal Year 1992 (Daubert Industries, Inc.-Gaylord Industries, Inc.)

DTIC Science & Technology

1993-01-01

a0 m~ ar (0 - a 0 a4 04 H50 4 a 4 C-1 am a C3 L) 0ý an 0 a n c Za4 00 C.ým 4Lo j I N O Nol 0IS)0 cl r- m - anNe t"I ý ý Ll2 an N -z Do~ acca -fN- 0a’J...c to aQ Coo," I "o o) " ’ mC, ,I e nnI to a) ammc)oc Il I I L) o c wo x I Ca u m2 a. U r-7f cc ~ nl.< C0C) -*4~-0na-ao " 0 ELI ao (v acCa ’’ a~al~ nal...Fw IE~ 1. E F1 F4 o F. c4I F 4 F OF. F7 )I - F ~-4 .F 4 F 41) w 10 A F F W)( o4 v7- m ’mo7 l T =444 45 o o .7 c> S . o Lc4 mo - 04 NNr a)0 lo 7 1 7 o

Dendritic Cell Subset Distributions in the Aorta in Healthy and Atherosclerotic Mice

PubMed Central

Lutz, Manfred B.; Zernecke, Alma

2014-01-01

Dendritic cells (DCs) can be sub-divided into various subsets that play specialized roles in priming of adaptive immune responses. Atherosclerosis is regarded as a chronic inflammatory disease of the vessel wall and DCs can be found in non-inflamed and diseased arteries. We here performed a systematic analyses of DCs subsets during atherogenesis. Our data indicate that distinct DC subsets can be localized in the vessel wall. In C57BL/6 and low density lipoprotein receptor-deficient (Ldlr −/−) mice, CD11c+ MHCII+ DCs could be discriminated into CD103− CD11b+F4/80+, CD11b+F4/80− and CD11b−F4/80− DCs and CD103+ CD11b−F4/80− DCs. Except for CD103− CD11b− F4/80− DCs, these subsets expanded in high fat diet-fed Ldlr −/− mice. Signal-regulatory protein (Sirp)-α was detected on aortic macrophages, CD11b+ DCs, and partially on CD103− CD11b− F4/80− but not on CD103+ DCs. Notably, in FMS-like tyrosine kinase 3-ligand-deficient (Flt3l −/−) mice, a specific loss of CD103+ DCs but also CD103− CD11b+ F4/80− DCs was evidenced. Aortic CD103+ and CD11b+ F4/80− CD103− DCs may thus belong to conventional rather than monocyte-derived DCs, given their dependence on Flt3L-signalling. CD64, postulated to distinguish macrophages from DCs, could not be detected on DC subsets under physiological conditions, but appeared in a fraction of CD103− CD11b+ F4/80− and CD11b+ F4/80+ cells in atherosclerotic Ldlr −/− mice. The emergence of CD64 expression in atherosclerosis may indicate that CD11b+ F4/80− DCs similar to CD11b+ F4/80+ DCs are at least in part derived from immigrated monocytes during atherosclerotic lesion formation. Our data advance our knowledge about the presence of distinct DC subsets and their accumulation characteristics in atherosclerosis, and may help to assist in future studies aiming at specific DC-based therapeutic strategies for the treatment of chronic vascular inflammation. PMID:24551105

Nanostructured F doped IrO2 electro-catalyst powders for PEM based water electrolysis

NASA Astrophysics Data System (ADS)

Kadakia, Karan Sandeep; Jampani, Prashanth H.; Velikokhatnyi, Oleg I.; Datta, Moni Kanchan; Park, Sung Kyoo; Hong, Dae Ho; Chung, Sung Jae; Kumta, Prashant N.

2014-12-01

Fluorine doped iridium oxide (IrO2:F) powders with varying F content ranging from 0 to 20 wt.% has been synthesized by using a modification of the Adams fusion method. The precursors (IrCl4 and NH4F) are mixed with NaNO3 and heated to elevated temperatures to form high surface area nanomaterials as electro-catalysts for PEM based water electrolysis. The catalysts were then coated on a porous Ti substrate and have been studied for the oxygen evolution reaction in PEM based water electrolysis. The IrO2:F with an optimum composition of IrO2:10 wt.% F shows remarkably superior electrochemical activity and chemical stability compared to pure IrO2. The results have also been supported via kinetic studies by conducting rotating disk electrode (RDE) experiments. The RDE studies confirm that the electro-catalysts follow the two electron transfer reaction for electrolysis with calculated activation energy of ∼25 kJ mol-1. Single full cell tests conducted also validate the superior electrochemical activity of the 10 wt.% F doped IrO2.

Radiosynthesis and biological evaluation of N-(2-[18F]fluoropropionyl)-3,4-dihydroxy-l-phenylalanine as a PET tracer for oncologic imaging.

PubMed

Tang, Caihua; Nie, Dahong; Tang, Ganghua; Gao, Siyuan; Liu, Shaoyu; Wen, Fuhua; Tang, Xiaolan

2017-07-01

Several 11 C and 18 F labeled 3,4-dihydroxy-l-phenylalanine (l-DOPA) analogues have been used for neurologic and oncologic diseases, especially for brain tumors and neuroendocrine tumors PET imaging. However, 18 F-labeled N-substituted l-DOPA analogues have not been reported so far. In the current study, radiosynthesis and biological evaluation of a new 18 F-labeled l-DOPA analogue, N-(2-[ 18 F]fluoropropionyl)-3,4-dihydroxy-l-phenylalanine ([ 18 F]FPDOPA) for tumor PET imaging are performed. The synthesis of [ 18 F]FPDOPA was via a two-step reaction sequence from 4-nitrophenyl-2-[ 18 F]fluoropropionate ([ 18 F]NFP). The biodistribution of [ 18 F]FPDOPA was determined in normal Kunming mice. In vitro competitive inhibition and protein incorporation experiments were performed with SPC-A-1 lung adenocarcinoma cell lines. PET/CT studies of [ 18 F]FPDOPA were conducted in C6 rat glioma and SPC-A-1 human lung adenocarcinoma and H460 human large cell lung cancer-bearing nude mice. [ 18 F]FPDOPA was prepared with a decay-corrected radiochemical yield of 28±5% and a specific activity of 50±15GBq/μmol (n=10) within 125min. In vitro cell experiments showed that [ 18 F]FPDOPA uptake in SPC-A-1 cells was primarily transported through Na + -independent system L, with Na + -dependent system B 0,+ and system ASC partly involved in it. Biodistribution data in mice showed that renal-bladder route was the main excretory system of [ 18 F]FPDOPA. PET imaging demonstrated intense accumulation of [ 18 F]FPDOPA in several tumor xenografts, with (8.50±0.40)%ID/g in C6 glioma, (6.30±0.12)%ID/g in SPC-A-1 lung adenocarcinoma, and (6.50±0.10)%ID/g in H460 large cell lung cancer, respectively. A novel N-substituted 18 F-labeled L-DOPA analogue [ 18 F]FPDOPA is synthesized and evaluated in vitro and in vivo. The results support that [ 18 F]FPDOPA seems to be a potential PET tracer for tumor imaging, especially be a better potential PET tracer than [ 18 F]fluoro-2-deoxy-d-glucose ([ 18 F]FDG) for brain tumor imaging. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of the sensitivity of the novel α4β2* nicotinic acetylcholine receptor PET radioligand 18F-(-)-NCFHEB to increases in synaptic acetylcholine levels in rhesus monkeys.

PubMed

Gallezot, Jean-Dominique; Esterlis, Irina; Bois, Frederic; Zheng, Ming-Qiang; Lin, Shu-Fei; Kloczynski, Tracy; Krystal, John H; Huang, Yiyun; Sabri, Osama; Carson, Richard E; Cosgrove, Kelly P

2014-11-01

18F-(-)-NCFHEB (also known as 18F-(-)-Flubatine) is a new radioligand to image α4β2* nicotinic acetylcholine receptors in vivo with positron emission tomography (PET), with faster kinetics than previous radioligands such as 18F-2-F-A85380. The goal of this study was to assess the sensitivity of 18F-(-)-NCFHEB-PET to increases in synaptic acetylcholine concentration induced by acetylcholinesterase inhibitors. Two rhesus monkeys were scanned four times each on a Focus 220 scanner: first at baseline, then during two bolus plus infusions of physostigmine (0.06-0.28 mg/kg), and finally following a bolus injection of donepezil (0.25 mg/kg). The arterial input function and the plasma free fraction fP were measured. 18F-(-)-NCFHEB volume of distribution VT was estimated using the multilinear analysis MA1 and then normalized by plasma free fraction fP . 18F-(-)-NCFHEB fP was 0.89±0.04. At baseline, 18F-(-)-NCFHEB VT /fP ranged from 7.9±1.3 mL plasma/cm3 tissue in the cerebellum to 34.3±8.4 mL plasma/cm3 tissue in the thalamus. Physostigmine induced a dose-dependent reduction of 18F-(-)-NCFHEB VT /fP of 34±9% in the putamen, 32±8% in the thalamus, 25±8% in the cortex, and 23±10% in the hippocampus. With donepezil, 18F-(-)-NCFHEB VT /fP was reduced by 24±2%, 14+3% and 14±5%, 10±6% in the same regions. 18F-(-)-NCFHEB can be used to detect changes in synaptic acetylcholine concentration and is a promising tracer to study acetylcholine dynamics with shorter scan durations than previous radioligands. © 2014 Wiley Periodicals, Inc.

Anti-inflammatory effects, nuclear magnetic resonance identification, and high-performance liquid chromatography isolation of the total flavonoids from Artemisia frigida.

PubMed

Wang, Qinghu; Jin, Jinmei; Dai, Nayintai; Han, Narenchaoketu; Han, Jingjing; Bao, Baiyinmuqier

2016-04-01

The aerial parts of Artemisia frigida Willd. are used to treat joint swelling, renal heat, abnormal menstruation, and sore carbuncle. The anti-inflammatory effects of A. frigida have been well-known in folk medicine, suggesting that components extracted from A. frigida could potentially treat inflammatory disease. With the aim of discovering bioactive compounds, in this study, we extracted total flavonoids from the aerial parts of A. frigida and investigated their anti-inflammatory effects against inflammation induced by carrageenan and egg albumin in rats. At the doses studied, total flavonoids (100 mg/kg, 200 mg/kg, and 400 mg/kg) and some isolated compounds (30 mg/kg) showed significant and dose-dependent anti-inflammatory effects. According to the high-performance liquid chromatography analysis of the total flavonoids from A. frigida, there are five major compounds, namely, 5-hydroxy-3',4'-dimethoxy-7-O-β-d-glucuronide (F1), 5-hydroxy-3',4',5'-trimethoxy-7-O-β-d-glucuronide (F2), 5,7,3'-trihydroxy-6,4'-dimethoxyflavone (F3), 5,3'-dihydroxy-6,7,4'-trimethoxyflavone (F4), and 5,3'-dihydroxy-3,6,7,4'-tetramethoxyflavone (F5), which may explain the anti-inflammatory activity. Copyright © 2016. Published by Elsevier B.V.

A study of low threshold and high gain Nd3+ ions doped SiO2-B2O3-Na2CO3-NaF-CaF2 glasses for NIR laser applications

NASA Astrophysics Data System (ADS)

Megala, Rajesh; Gowthami, T.; John Sushma, N.; Kamala, S.; Deva Prasad Raju, B.

2018-05-01

Fluoroborosilicate glasses of composition 35SiO2-25B2O3-10Na2CO3-15NaF-15CaF2-xNd2O3 (where x = 0.1, 0.5. 1.0, 2.0 mol%) were prepared by melt quenching technique and various physical properties have been calculated. From the absorption spectra J-O Intensity parameters Ωλ (λ = 2, 4, 6) and radiative properties are evaluated by using J-O theory. The high values of Ω2 = 4.213 × 10-20 cm2, Ω4 = 5.345 × 10-20 cm2, Ω6 = 5.526 × 10-20 cm2 suggest that among the prepared glasses 0.5 mol% Nd glass is more asymmetric, more covalent and rigid in nature. The emission spectra were recorded with 808 nm laser as excitation source. The strong NIR emissions were observed at 876 nm, 1056 nm, 1328 nm corresponding to the transitions 4F3/2 → 4I9/2, 4F3/2 → 4I11/2, 4F3/2 → 4I13/2 respectively. Stimulated emission cross -section (σemi) and Gain bandwidth (σemi × Δλeff) were calculated. For 0.5 mol% Nd these values are found to be 3.30 × 10-20 cm2, 11 × 10-26 cm2. From the decay curve analysis the lifetime values for 4F3/2 level have been determined and these values are decreased with increase in Nd3+ ions concentration. These results may suggest that the prepared SBNCNd05 (Nd = 0.5 mol%) glass could be useful for 1056 nm laser applications.

The Science of Science Policy: A Federal Research Roadmap

DTIC Science & Technology

2008-11-01

and Atmospheric Administra on, h p://www.ncdc.noaa.gov/ oa /climate/globalwarming.html#q4. T S S P : A F R R4 maintain the na on’s dominance...econometric studies, surveys, case studies, and retrospec ve analyses. Econometric studies include the macroeconomic growth models pioneered by Robert...R A W ha t a re th e be ha vi or al fo un da o ns o f i nn ov a- o n? U nd er st an di ng th e be ha vi or o f i nd iv id ua ls an d

Triggering of acute myocardial infarction by different means of transportation.

PubMed

Peters, Annette; von Klot, Stephanie; Mittleman, Murray A; Meisinger, Christine; Hörmann, Allmut; Kuch, Bernhard; Wichmann, H Erich

2013-10-01

Prior studies have reported an association between traffic-related air pollution in urban areas and exacerbation of cardiovascular disease. We assess here whether time spent in different modes of transportation can trigger the onset of acute myocardial infarction (AMI). We performed a case-crossover study. We interviewed consecutive cases of AMI in the KORA Myocardial Infarction Registry in Augsburg, Southern Germany between February 1999 and December 2003 eliciting data on potential triggers in the four days preceding myocardial infarction onset. A total of 1459 cases with known date and time of AMI symptom onset, who had survived 24 hours after the onset, completed the registry's standard interview on potential triggers of AMI. An association between exposure to traffic and AMI onset 1 hour later was observed (odds ratio: 3.2; 95% confidence interval [CI]: 2.7-3.9, p < 0.001). Using a car was the most common source of traffic exposure; nevertheless, times spent in public transport or on a bicycle were similarly associated with AMI onset 1 hour later. While the highest risk for AMI onset was within 1 hour of exposure to traffic, the elevated risk persisted for up to 6 hours. Women, patients aged 65 years or older, patients not part of the workforce, and those with a history of angina or diabetes exhibited the largest associations between times spent in traffic and AMI onset 1 hour later. The data suggest that transient exposure to traffic regardless of the means of transportation may increase the risk of AMI transiently.

pulver: an R package for parallel ultra-rapid p-value computation for linear regression interaction terms.

PubMed

Molnos, Sophie; Baumbach, Clemens; Wahl, Simone; Müller-Nurasyid, Martina; Strauch, Konstantin; Wang-Sattler, Rui; Waldenberger, Melanie; Meitinger, Thomas; Adamski, Jerzy; Kastenmüller, Gabi; Suhre, Karsten; Peters, Annette; Grallert, Harald; Theis, Fabian J; Gieger, Christian

2017-09-29

Genome-wide association studies allow us to understand the genetics of complex diseases. Human metabolism provides information about the disease-causing mechanisms, so it is usual to investigate the associations between genetic variants and metabolite levels. However, only considering genetic variants and their effects on one trait ignores the possible interplay between different "omics" layers. Existing tools only consider single-nucleotide polymorphism (SNP)-SNP interactions, and no practical tool is available for large-scale investigations of the interactions between pairs of arbitrary quantitative variables. We developed an R package called pulver to compute p-values for the interaction term in a very large number of linear regression models. Comparisons based on simulated data showed that pulver is much faster than the existing tools. This is achieved by using the correlation coefficient to test the null-hypothesis, which avoids the costly computation of inversions. Additional tricks are a rearrangement of the order, when iterating through the different "omics" layers, and implementing this algorithm in the fast programming language C++. Furthermore, we applied our algorithm to data from the German KORA study to investigate a real-world problem involving the interplay among DNA methylation, genetic variants, and metabolite levels. The pulver package is a convenient and rapid tool for screening huge numbers of linear regression models for significant interaction terms in arbitrary pairs of quantitative variables. pulver is written in R and C++, and can be downloaded freely from CRAN at https://cran.r-project.org/web/packages/pulver/ .

An easy prepared dual-channel chemosensor for selective and instant detection of fluoride based on double Schiff-base

NASA Astrophysics Data System (ADS)

Leng, Yan-Li; Zhang, Jian-Hui; Li, Qiao; Zhang, You-Ming; Lin, Qi; Yao, Hong; Wei, Tai-Bao

2016-10-01

A colorimetric and fluorescent dual-channel fluoride chemosensor N,N‧-bis (4-diethylaminosalicylidene) hydrazine (sensor S) bearing two imine groups has been designed and synthesized. This structurally simple probe displays rapid response and high selectivity for fluoride over other common anions (Cl-, Br-, I-, AcO-, H2PO4-, HSO4-, ClO4-, CN- and SCN-) in a highly polar aqueous DMSO solution. Mechanism studies suggested that the sensor firstly combined with F- through hydrogen bonds and then experienced the deprotonation process at higher concentrations of F- anion to the two Ar-OH groups. The detection limit was 5.78 × 10- 7 M of F-, which points to the high detection sensitivity. Test strips based on sensor S were fabricated, which could act as a convenient and efficient F- test kit to detect F- for ;in-the-field; measurement.

Reproducibility of shear wave elastography (SWE) in patients with chronic liver disease

PubMed Central

Salomone Megna, Angelo; Ragucci, Monica; De Luca, Massimo; Marino Marsilia, Giuseppina; Nardone, Gerardo; Coccoli, Pietro; Prinster, Anna; Mannelli, Lorenzo; Vergara, Emilia; Monti, Serena; Liuzzi, Raffaele; Incoronato, Mariarosaria

2017-01-01

The presence of significant fibrosis is an indicator for liver disease staging and prognosis. The aim of the study was to determine reproducibility of real-time shear wave elastography using a hepatic biopsy as the reference standard to identify patients with chronic liver disease. Forty patients with chronic liver disease and 12 normal subjects received shear wave elastography performed by skilled operators. Interoperator reproducibility was studied in 29 patients. Fibrosis was evaluated using the Metavir score. The median and range shear wave elastography values in chronic liver disease subjects were 6.15 kPa and 3.14–16.7 kPa and were 4.49 kPa and 2.92–7.32 kPa in normal subjects, respectively. With respect to fibrosis detected by liver biopsy, shear wave elastography did not change significantly between F0 and F1 (p = 0.334), F1 and F2 (p = 0.611), or F3 and F4 (0.327); a significant difference was observed between the F0-F2 and F3-F4 groups (p = 0.002). SWE also correlated with inflammatory activity (Rs = 0.443, p = 0.0023) and ALT levels (Rs = 0.287, p = 0.0804). Age, sex and body mass index did not affect shear wave elastography measurements. Using receiver operator characteristic curves, two threshold values for shear wave elastography were identified: 5.62 kPa for patients with fibrosis (≥F2; sensitivity 80%, specificity 69.4%, and accuracy 77%) and 7.04 kPa for patients with severe fibrosis (≥F3; sensitivity 88.9%, specificity 81%, and accuracy 89%). Overall interobserver agreement was excellent and was analysed using an interclass correlation coefficient (0.94; CI 0.87–0.97).This study shows that shear wave elastography executed by skilled operators can be performed on almost all chronic liver disease patients with high reproducibility. It is not influenced by age, sex or body mass index, identifies severely fibrotic patients and is also related to inflammatory activity. PMID:29023554

Probing the early development of visual working memory capacity with functional near-infrared spectroscopy

PubMed Central

Buss, Aaron T.; Fox, Nicholas; Boas, David A.; Spencer, John P.

2013-01-01

Visual working memory (VWM) is a core cognitive system with a highly limited capacity. The present study is the first to examine VWM capacity limits in early development using functional neuroimaging. We recorded optical neuroimaging data while 3- and 4-year-olds completed a change detection task where they detected changes in the shapes of objects after a brief delay. Near-infrared sources and detectors were placed over the following 10–20 positions: F3 and F5 in left frontal cortex, F4 and F6 in right frontal cortex, P3 and P5 in left parietal cortex, and P4 and P6 in right parietal cortex. The first question was whether we would see robust task-specific activation of the frontal-parietal network identified in the adult fMRI literature. This was indeed the case: three left frontal channels and 11 of 12 parietal channels showed a statistically robust difference between the concentration of oxygenated and deoxygenated hemoglobin following the presentation of the sample array. Moreover, four channels in the left hemisphere near P3, P5, and F5 showed a robust increase as the working memory load increased from 1–3 items. Notably, the hemodynamic response did not asymptote at 1–2 items as expected from previous fMRI studies with adults. Finally, 4-year-olds showed a more robust parietal response relative to 3-year-olds, and an increasing sensitivity to the memory load manipulation. These results demonstrate that fNIRS is an effective tool to study the neural processes that underlie the early development of VWM capacity. PMID:23707803

Probing the early development of visual working memory capacity with functional near-infrared spectroscopy.

PubMed

Buss, Aaron T; Fox, Nicholas; Boas, David A; Spencer, John P

2014-01-15

Visual working memory (VWM) is a core cognitive system with a highly limited capacity. The present study is the first to examine VWM capacity limits in early development using functional neuroimaging. We recorded optical neuroimaging data while 3- and 4-year-olds completed a change detection task where they detected changes in the shapes of objects after a brief delay. Near-infrared sources and detectors were placed over the following 10-20 positions: F3 and F5 in left frontal cortex, F4 and F6 in right frontal cortex, P3 and P5 in left parietal cortex, and P4 and P6 in right parietal cortex. The first question was whether we would see robust task-specific activation of the frontal-parietal network identified in the adult fMRI literature. This was indeed the case: three left frontal channels and 11 of 12 parietal channels showed a statistically robust difference between the concentration of oxygenated and deoxygenated hemoglobin following the presentation of the sample array. Moreover, four channels in the left hemisphere near P3, P5, and F5 showed a robust increase as the working memory load increased from 1 to 3 items. Notably, the hemodynamic response did not asymptote at 1-2 items as expected from previous fMRI studies with adults. Finally, 4-year-olds showed a more robust parietal response relative to 3-year-olds, and an increasing sensitivity to the memory load manipulation. These results demonstrate that fNIRS is an effective tool to study the neural processes that underlie the early development of VWM capacity. Copyright © 2013 Elsevier Inc. All rights reserved.

How useful are ARFI elastography cut-off values proposed by meta-analysis for predicting the significant fibrosis and compensated liver cirrhosis?

PubMed

Bota, Simona; Sporea, Ioan; Sirli, Roxana; Popescu, Alina; Gradinaru-Tascau, Oana

2015-06-01

To evaluate how often do we "miss" chronic hepatitis C patients with at least significant fibrosis (F>/=2) and those with compensated cirrhosis, by using Acoustic Radiation Force Impulse (ARFI) elastography cut-off values proposed by meta-analysis. Our study included 132 patients with chronic hepatitis C, evaluated by means of ARFI and liver biopsy (LB), in the same session. Reliable measurements were defined as: median value of 10 liver stiffness (LS) measurements with a success rate>/=60% and an interquartile range interval<30%. For predicting F>/=2 and F=4 we used the LS cut-offs proposed in the last published meta-analysis: 1.35 m/s and 1.87 m/s, respectively. Reliable LS measurements by means of ARFI were obtained in 117 patients (87.9%). In our study, 58 patients (49.6%) had LS values <1.35 m/s; from these 75.8% had F>/=2 in LB. From the 59 patients (50.4%) with LS values>/=1.35 m/s, only 6.8% had F0 or F1 in LB. Also, in our study, 88 patients (75.3%) had LS values <1.87 m/s; from these only 2.2 % had F4 in LB. From the 29 patients (24.7%) with LS values>/=1.87 m/s, 41.3% had F4 in LB. Both for prediction of at least significant fibrosis and liver cirrhosis, higher aminotransferases levels were associated with wrongly classified patients, in univariate and multivariate analysis. ARFI elastography had a very good positive predictive value (93.2%) for predicting the presence of significant fibrosis and excellent negative predictive value (97.8%) for excluding the presence of compensated liver cirrhosis.

Prime Contractors with Awards Over $25,000 by Name, Location, and Contract Number, Fiscal Year 1992 (Bituminous Paving, Inc.-Datum Maching Services, Inc.)

DTIC Science & Technology

1993-01-01

Fa U ~ 4 0 F0 co00 F 0~ 0~~~ z CC FF; F F (0 FEFn E3 >w 40 pa P4 PO FPi 40~~ ~ 0 HC F F 0 Z 4 F < OF C Z N N z w to F3 C) i3Z 0 CO Q F. 0 r. F0 0 4h...3331*7.30-.4 0 ~ ~ ~ ~ ~ ~ ~ ~ a m x3 Fx3. (󈧥- F3 3 0 (3 .~0 IHC ~ - r 2 00 0.00 F ’> F .0-.. 0co 33.. 13 F 0 1 ~ CO F- 3 F - 2431~~~~~~~~~~~ U)4X 0o F...0( F3 00 0 n ;r3 000 r0o ( -- N r.’- m -- a, m w "D 00 N C> (n0r 0 0) 0 0 , ~ 1 (0.5 0 4CNC, i n ) ~ 04 3 I- F I~~~~C C,) F 0 0o’e

[A study on the concentration quenching of Tm3+ upconversion luminescence].

PubMed

Chen, B; Wang, H; Huang, S

2001-06-01

In this work, we have a designation and preparation of MFT glasses for upconversion, the glasses consisted of TeO2 and fluoride: PbF2, AlF3, BaF2, NaF and the impurity Tm2O3. In this glass system the oxide improve forming ability, the fluorides improve the microscopic environment around RE ions in glasses. In this glass host the content of Tm2O3 achieves to 4% mol and crystallization no occurred. A detail study on the concentration quenching of upconversion luminescence for 1G4-->3H6 and 1D2-->3H4 transitions was completed. The experimental results directed that the quenching concentration was 0.6 mol.% and higher 3 times than in other glasses materials. The cross relaxation and mechanism of concentration quenching were discussed.

Medaka extended one-generation reproduction test evaluating 4-nonylphenol.

PubMed

Watanabe, Haruna; Horie, Yoshifumi; Takanobu, Hitomi; Koshio, Masaaki; Flynn, Kevin; Iguchi, Taisen; Tatarazako, Norihisa

2017-12-01

The medaka extended one-generation test (MEOGRT) was developed as a multigenerational toxicity test for chemicals, particularly endocrine-disrupting chemicals. Briefly, 3 generations of Japanese medaka (Oryzias latipes) are exposed to a chemical over a 20-wk period: 3 wk in the parental generation (F0), 15 wk in the first generation (F1), and 2 wk in the second generation (F2). The present study reports the first MEOGRT results concerning branched isomer mixtures of 4-nonylphenol (NP). Adult F0 medaka exposed to NP at 5 actual concentrations (1.27, 2.95, 9.81, 27.8, 89.4 µg/L) were unaffected in terms of reproduction, although vitellogenin in the male liver was increased dose-dependently at concentration of 2.95 µg/L and higher. In F1, in contrast, total egg (fecundity), fertile egg, and fertility decreased as NP increased; lowest-observed-effect concentrations (LOECs) for total egg, fertile egg, and fertility were 1.27, 1.27, 27.8 µg/L, respectively. In F1, but not in F0, secondary sex characteristics (i.e., anal fin papillae in males) were suppressed at 27.8 µg/L NP. Vitellogenin induction in adult male fish was slightly weaker in F1 than it was in F0, however. Gonadal sex abnormality and sex reversal occurred at 27.8 and 89.4 µg/L NP in F1 subadults. At 89.4 µg/L NP, all genotypic F1 males in breeding pairs had female phenotype, and some even demonstrated spawning. Concentrations of NP lower than 89.4 µg/L did not affect F2 survival or hatching. The highest detected NP level in environmental freshwater in Japan was approximately a half of the LOEC (1.27 µg/L for F1 fecundity); in other countries, however, environmental concentrations above the LOEC are reported, suggesting that NP may be affecting fish populations. Environ Toxicol Chem 2017;36:3254-3266. © 2017 SETAC. © 2017 SETAC.

TOXICITY OF TETRYL (N-METHYL-N,2,4,6-TETRANITROANILINE) IN F344 RATS

EPA Science Inventory

The toxicity of tetryl (N-methyl-N,2,4,6-tetranitroaniline) in male and female F344 rats was evaluated after adminstration in the diet for 14 or 90 days. The 14-day study diet concentrations used were 0, 500, 1250, 2000, 2500, and 5000 ppm; the 90-day study diet concentrations we...

Lack of association of MRI determined subclinical cardiovascular disease with dizziness and vertigo in a cross-sectional population-based study.

PubMed

Lorbeer, Roberto; Hetterich, Holger; Strobl, Ralf; Schafnitzel, Anina; Patscheider, Hannah; Schindler, Andreas; Müller-Peltzer, Katharina; Sommer, Wieland; Peters, Annette; Meisinger, Christa; Heier, Margit; Rathmann, Wolfgang; Bamberg, Fabian; Grill, Eva

2017-01-01

We investigated the association between subclinical cardiovascular diseases assessed by MRI examination and symptoms of dizziness and vertigo in participants of a population-based sample. Data from 400 participants (169 women) aged from 39 to 73 of a cross-sectional MRI sub-study of the "Kooperative Gesundheitsforschung in der Region Augsburg" (KORA) FF4 study from the south of Germany was used. MRI determined subclinical cardiovascular diseases include left and right ventricular structure and function as well as the presence of carotid plaque and carotid wall thickness. Cerebrum diseases include white matter lesions (WML) and cerebral microbleeds (CMB). The main outcomes of dizziness and vertigo were assessed by standardized interview. Logistic regression models were applied and adjusted odds ratios (OR) with 95% confidence intervals (CI) were provided. Lifetime and 12-month prevalence of dizziness and vertigo were 30% (95%CI 26% to 35%) and 21% (95%CI 17% to 26%) respectively in this sample. On multivariable analysis, cardiac and carotid measurements were not associated with dizziness and vertigo excluding orthostatic vertigo (20%, 95CI 16% to 24%). Only in male participants, there was a significant association between WML and the presence of dizziness and vertigo (OR = 2.95, 95%CI 1.08 to 8.07). There was no significant association of CMB with dizziness and vertigo. However, CMB and WML were tending to associate with a higher risk of dizziness and vertigo in the whole sample (CMB: OR = 1.48, 95%CI 0.70; 3.15; WML: OR = 1.71, 95%CI 0.80 to 3.67;), in persons with prediabetes and diabetes (WML: OR = 2.71, 95%CI 0.89 to 8.23) and in men with normal glucose metabolism (CMB: OR = 2.60, 95%CI 0.56 to 12.0; WML: OR = 3.08, 95%CI 0.58 to 16.5). In this sample of participants without manifest cardiovascular diseases, subclinical left and right ventricular function and carotid structure were consistently not associated with dizziness and vertigo. Subclinical cerebrum measurements, however, tend to increase the risk for dizziness and vertigo, especially in men and in persons with prediabetes or diabetes.

CLEC4F Is an Inducible C-Type Lectin in F4/80-Positive Cells and Is Involved in Alpha-Galactosylceramide Presentation in Liver

PubMed Central

Yang, Chih-Ya; Chen, Jiun-Bo; Tsai, Ting-Fen; Tsai, Yi-Chen; Tsai, Ching-Yen; Liang, Pi-Hui; Hsu, Tsui-Ling; Wu, Chung-Yi; Netea, Mihai G.; Wong, Chi-Huey; Hsieh, Shie-Liang

2013-01-01

CLEC4F, a member of C-type lectin, was first purified from rat liver extract with high binding affinity to fucose, galactose (Gal), N-acetylgalactosamine (GalNAc), and un-sialylated glucosphingolipids with GalNAc or Gal terminus. However, the biological functions of CLEC4F have not been elucidated. To address this question, we examined the expression and distribution of murine CLEC4F, determined its binding specificity by glycan array, and investigated its function using CLEC4F knockout (Clec4f−/−) mice. We found that CLEC4F is a heavily glycosylated membrane protein co-expressed with F4/80 on Kupffer cells. In contrast to F4/80, CLEC4F is detectable in fetal livers at embryonic day 11.5 (E11.5) but not in yolk sac, suggesting the expression of CLEC4F is induced as cells migrate from yolk cells to the liver. Even though CLEC4F is not detectable in tissues outside liver, both residential Kupffer cells and infiltrating mononuclear cells surrounding liver abscesses are CLEC4F-positive upon Listeria monocytogenes (L. monocytogenes) infection. While CLEC4F has strong binding to Gal and GalNAc, terminal fucosylation inhibits CLEC4F recognition to several glycans such as Fucosyl GM1, Globo H, Bb3∼4 and other fucosyl-glycans. Moreover, CLEC4F interacts with alpha-galactosylceramide (α-GalCer) in a calcium-dependent manner and participates in the presentation of α-GalCer to natural killer T (NKT) cells. This suggests that CLEC4F is a C-type lectin with diverse binding specificity expressed on residential Kupffer cells and infiltrating monocytes in the liver, and may play an important role to modulate glycolipids presentation on Kupffer cells. PMID:23762286

Identification of Escherichia coli F4ac-binding proteins in porcine milk fat globule membrane

PubMed Central

Novakovic, Predrag; Huang, Yanyun Y.; Lockerbie, Betty; Shahriar, Farshid; Kelly, John; Gordon, John R.; Middleton, Dorothy M.; Loewen, Matthew E.; Kidney, Beverly A.; Simko, Elemir

2015-01-01

F4ac-positive enterotoxigenic Escherichia coli (ETEC) must attach to the intestinal mucosa to cause diarrhea in piglets. Prevention of bacterial attachment to the intestinal mucosa is the most effective defense against ETEC-induced diarrhea. Porcine milk fat globule membranes (MFGM) were shown to be able to inhibit attachment of ETEC to the intestinal brush border; however, the specific components of porcine MFGM that inhibited attachment of ETEC to enterocytes were not identified. Accordingly, the purpose of this study was to identify F4ac-binding MFGM proteins by overlay Western blot and affinity chromatography. The proteome of porcine MFGM was characterized and the following F4ac-binding proteins were detected by overlay Western blot and affinity chromatography: lactadherin, butyrophilin, adipophilin, acyl-CoA synthetase 3, and fatty acid-binding protein 3. The biological function of these proteins was not investigated but it is possible that their interaction with F4ac fimbria interferes with bacterial attachment and colonization. PMID:25852227

Effects of condensed tannin fractions of different molecular weights from a Leucaena leucocephala hybrid on in vitro methane production and rumen fermentation.

PubMed

Saminathan, Mookiah; Sieo, Chin Chin; Abdullah, Norhani; Wong, Clemente Michael Vui Ling; Ho, Yin Wan

2015-10-01

Molecular weights (MWs) and their chemical structures are the primary factors determining the influence of condensed tannins (CTs) on animal nutrition and methane (CH4 ) production in ruminants. In this study the MWs of five CT fractions from Leucaena leucocephala hybrid-Rendang (LLR) were determined and the CT fractions were investigated for their effects on CH4 production and rumen fermentation. The number-average molecular weight (Mn ) of fraction F1 (1265.8 Da), which was eluted first, was the highest, followed by those of fractions F2 (1028.6 Da), F3 (652.2 Da), F4 (562.2 Da) and F5 (469.6 Da). The total gas (mL g(-1) dry matter (DM)) and CH4 production decreased significantly (P < 0.05) with increasing MWs of the CT fractions, but there were no significant (P > 0.05) differences between the CT fractions and control on DM degradation. However, the in vitro N disappearance decreased significantly (P < 0.05) with the inclusion of CT fraction F1 (highest MW) compared with the control and other fractions (F2-F5). The inclusion of CT fraction F1 also significantly decreased (P < 0.05) total volatile fatty acid and acetic acid concentrations compared with the control. The acetic/propionic acid ratio was significantly decreased (P < 0.05) by fraction F1 but not by the control and other fractions (F2-F5). The CT fractions of different MWs from LLR could affect rumen fermentation and CH4 production, and the impact was more pronounced for the CT fraction with a higher MW. © 2014 Society of Chemical Industry.

Elevated TSH in adults treated for hypothyroidism is associated with increased mortality.

PubMed

Akirov, Amit; Gimbel, Hannah; Grossman, Alon; Shochat, Tzipora; Shimon, Ilan

2017-01-01

Numerous studies investigated the link between hypothyroidism and mortality, but a definite conclusion is hard to reach as these were limited by a number of factors, including age of participants, comorbidities and single measurement of thyroid function. To evaluate the association between TSH and fT4 levels and mortality in patients with levothyroxine-treated hypothyroidism. Observational data of hospitalized patients (2011-2014). TSH and fT4 levels obtained between at least 30 days after discharge and until death or end of follow-up were collected. Median TSH and fT4 levels were stratified into categories. In total, 611 patients with treated hypothyroidism, aged 60-80 years (72% females, mean age 71 ± 6 years) were included in the study. All-cause mortality up to 66 months after discharge, by TSH and fT4 categories. During follow-up, the average numbers of TSH and fT4 measurements were 5.5 ± 3.8 and 2.5 ± 4.2 per patient respectively. Mortality rates were 28%, 29% and 54% with median TSH of 0.5-2.5, 2.5-5.0 and 5.0-10.0 IU/L respectively. Adjusted hazard ratios for mortality with median TSH between 5.0 and 10.0 IU/L were 2.3 (95% CI: 1.6-3.4) and 2.2 (95% CI: 1.6-3.2) compared with patients with TSH between 0.5-2.5 IU/L and 2.5-5 IU/L respectively. There was no difference in mortality between patients with median fT4 10-15 or 15-20 pmol/L. In treated hypothyroid adult patients and serial measurements of thyroid function tests, median TSH levels of 5-10 IU/L are associated with increased mortality with no effect of fT4 levels. Treatment should aim at achieving euthyroidism to improve survival. © 2017 European Society of Endocrinology.

Dietary exposure to heterocyclic amines in high-temperature cooked meat and fish in Malaysia.

PubMed

Jahurul, M H A; Jinap, S; Ang, S J; Abdul-Hamid, A; Hajeb, P; Lioe, H N; Zaidul, I S M

2010-08-01

The intake of heterocyclic amines is influenced by the amount and type of meat and fish ingested, frequency of consumption, cooking methods, cooking temperature, and duration of cooking. In this study, the dietary intake of heterocyclic amines in Malaysia and their main sources were investigated. Forty-two samples of meat and fish were analysed by high-performance liquid chromatography with photodiode array detector to determine the concentration of the six predominant heterocyclic amines, namely: 2-amino-3-methylimidazo[4,5-f] quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f] quinoline(MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f] quinoxaline (4,8-DiMeIQx), 2-amino-3,7,8-trimethylimidazo[4,5-f] quinoxaline (7,8-DiMeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Dietary intake data were obtained using a food-frequency questionnaire when interviewing 600 Malaysian respondents. The level of total heterocyclic amines in food samples studies ranged from not detected to 38.7 ng g(-1). The average daily intake level of heterocyclic amine was 553.7 ng per capita day(-1). The intake of PhIP was the highest, followed by MeIQx and MeIQ. The results reveal that fried and grilled chicken were the major dietary source of heterocyclic amines in Malaysia. However, the heterocyclic amine intake by the Malaysian population was lower than those reported from other regions.

Preparation of high density heavy metal fluoride glasses with extended ultraviolet and infra red ranges, and such high density heavy metal fluoride glasses

NASA Technical Reports Server (NTRS)

Martin, Steven W. (Inventor); Huebsch, Jesse (Inventor)

2001-01-01

A heavy metal fluoride glass composition range (in mol percent) consisting essentially of: (16-30)BaF.sub.2.(8-26)HfF.sub.4.(6-24)InF.sub.3 or GaF.sub.3.(4-16)CdF.sub.2.(6-24)YbF.sub.3.(4-22)ZnF.sub.2. In an alternative embodiment, a heavy metal fluoride glass composition range (in mol percent) comprises (16-30)BaF.sub.2.(8-26)HfF.sub.4.(6-24) of (0-24)InF.sub.3, (0-24)GaF.sub.3 and (0-19)AlF.sub.3.(1-16)CdF.sub.2.(6-24)YbF.sub.3.(4-26)ZnF.sub.2. A preferred heavy metal fluoride glass produced in accordance with the present invention comprises a composition (in mol %) and comprises about 26BaF.sub.2.18HfF.sub.4.7InF.sub.3.5GaF.sub.3.10CdF.sub.2.18YbF.sub.3. 16ZnF.sub.2. A preferred heavy metal fluoride glass has maximum thickness of most preferably about 3 mm. Another preferred heavy metal fluoride glass comprises a composition (in mol %) and comprises about 26BaF.sub.2.18HfF.sub.4.12AlF.sub.3.10CdF.sub.2.18YbF.sub.3.16ZnF.sub.2.

A comparative evaluation to assess the efficacy of 5% sodium fluoride varnish and diode laser and their combined application in the treatment of dentin hypersensitivity

PubMed Central

Suri, Isha; Singh, Poonam; Shakir, Quaid Johar; Shetty, Arvind; Bapat, Ranjeet; Thakur, Roshani

2016-01-01

Background: Dentin hypersensitivity (DH) is an age old complaint with a great number of treatment modalities, but none of these are totally effective till date. Lasers being one of the latest treatment options in periodontics, a study was conducted to test the efficacy of diode laser (DL) in DH alone and in comparison with 5% sodium fluoride (NaF) varnish. Aim: The aim of the present study was to compare the effectiveness of 5% topical NaF varnish and 980 nm gallium aluminum arsenide (GaAlAs) DL alone and combination of 5% NaF + 980 nm GaAlAs DL in the management of DH. Materials and Methods: The study was conducted on 120 teeth in thirty patients with DH assessed by tactile and air blast (AB) stimuli measured by visual analog scale (VAS). Teeth were randomly divided into Group 1 (P) placebo-treated control group, Group 2 (NaF) treated by 5% NaF varnish, Group 3 (DL) treated with 980 nm DL, and Group 4 (NaF + DL) treated with both 5% NaF varnish and 980 nm DL (combination group). Results: There was a significant reduction in DH. The VAS reduction percentages were calculated, and there was a significant decrease in DH above all in G4 (NaF + DL) than G3 (DL) and G2 (NaF). Conclusion: Even though all the three groups (2, 3, and 4) showed improvement in terms of DH reduction, 5% NaF varnish with DL showed the best results among all the groups. PMID:27563205

Scientific and Engineering Studies, Compiled 1989. Signal Processing Studies

DTIC Science & Technology

1989-01-01

Version W(t,f) . . . . . .......... 25 3 W(t,f) for Real Waveform s(t) ............... 25 4 Contour of WDF (72) at l/e Relative Level . . . . . . . . . 30...spectral level , (189) B Passband of filter H, figure 8 Duration of weighting v, figure 8 LFM Linear Frequency Modulation sgn(x) 1 for x > 0, -1 for x...figure 4. the area of thl parir( Iua level ellipse is 1/2 In the t.f Vifne Wher this area i *, rlt IVe! bl ty e peak height of ?[, the product Is . *ýich

IDA/OSD(Institute for Defense Analyses/Office of the Secretary of Defense) Reliability and Maintainability Study. Volume 3. Case Study Analysis.

DTIC Science & Technology

1983-11-01

Isolation FIT Fault Isolation Test FMC Fully Mission Capable FMEA Failure Modes and Effects Analysis FMECA Failure Modes, Effects and Criticality...8217 ..* ,/- " , " A ’’"""¢ 9 % ’ k " . " ~ .[:, .- v," . , , .’ % , o4,o 100 92 88 0 80 76 PERCENT -- __ OF F-16 60 FLIGHTS WITHOUT NATO NATO RADAR HILL BASE BASE...to manage a growth program adequately. 822/1-13 IV-13 %. - 70 60 F-ill 50 F-1 5 40- CL. C.c 30 - IF-1 S20 ICIC p 10 I~* -. -. - - -____ F-5E -4 -3 -2

Liver Stiffness Measurements Using Acoustic Radiation Force Impulse in Recipients of Living-Donor and Deceased-Donor Orthotopic Liver Transplant.

PubMed

Haberal, Kemal Murat; Turnaoğlu, Hale; Özdemir, Adnan; Uslu, Nihal; Haberal Reyhan, Asuman Nihan; Moray, Gökhan; Haberal, Mehmet

2017-08-24

The aim of this study was to evaluate the diagnostic efficiency of the acoustic radiation force impulse (Siemens Medical Solutions, Erlangen, Germany) elastography in assessment of fibrosis in orthotopic liver transplant patients. We enrolled 28 orthotopic liver transplant patients (deceased and living donors), whose biopsy decision had been prospectively given clinically. Ten acoustic radiation force impulse elastographic measurements were applied before the biopsy or within 3 days after the biopsy by 2 radiologists. After the core tissue needle biopsy, specimens of all patients were analyzed according to the modified Ishak scoring system. Measurements of acoustic radiation force impulse elastography and pathology specimen results were compared. From 28 biopsies, fibrosis scores of 4 biopsies were evaluated as F0 (14.3%), 16 as F1 (57.1%), 4 as F2 (14.3%), and 4 as F3 (14.3%). Mean results of acoustic radiation force impulse measurements were calculated as 1.4 ± 0.07 in F0, 1.74 ± 0.57 in F1, 2.19 ± 0.7 in F2, and 2.18 ± 0.35 in F3. There were no significant correlations of mean acoustic radiation force impulse values between the F0 versus F1 (P = .956) and F0 versus F2 stages (P = .234). A statistically significant correlation of mean acoustic radiation force impulse values was found between the F0 and F3 fibrosis stages (P = .046). Acoustic radiation force impulse imaging is a promising screening test for detecting significant liver fibrosis (≥ F3 in modified Ishak) in living-donor or deceased-donor orthotopic liver transplant recipients.

Laser performance of in-band pumped Er : LiYF4 and Er : LiLuF4 crystals

NASA Astrophysics Data System (ADS)

Gorbachenya, K. N.; Kurilchik, S. V.; Kisel, V. E.; Yasukevich, A. S.; Kuleshov, N. V.; Nizamutdinov, A. S.; Korableva, S. L.; Semashko, V. V.

2016-02-01

Spectroscopic properties of Er : LiLuF4 and Er : LiYF4 crystals in the spectral region near 1.5 μm and the lasing characteristics of these crystals under in-band pumping at a wavelength of 1522 nm are studied. With the Er : LiLuF4 crystal, the maximum slope efficiency with respect to the absorbed pump power was 44% at a wavelength of 1609 nm. Continuous-wave operation of an inband pumped Er : LiYF4 laser is obtained for the first time. The output power at a wavelength of 1606 nm was 58 mW with a slope efficiency of 21%.

75 FR 27956 - Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-19

... B4-600, B4-600R, and F4-600R Series Airplanes, and Model C4-605R Variant F Airplanes (Collectively...-203, and B4-203 airplanes; Model A300 B4-601, B4- 603, B4-620, B4-622, B4-605R, B4-622R, F4-605R, F4...

The structure of SpnF a standalone enzyme that catalyzes [4 + 2] cycloaddition

DOE PAGES

Fage, Christopher D.; Isiorho, Eta A.; Liu, Yungnan; ...

2015-03-02

In the biosynthetic pathway of the spinosyn insecticides, the tailoring enzyme SpnF performs a [4 + 2] cycloaddition on a 22-membered macrolactone to forge an embedded cyclohexene ring. To learn more about this reaction, which could potentially proceed through a Diels-Alder mechanism, in this paper we determined the 1.50-Å-resolution crystal structure of SpnF bound to S-adenosylhomocysteine. Finally, this sets the stage for advanced experimental and computational studies to determine the precise mechanism of SpnF-mediated cyclization.

Synthesis and structural characterization of the hexagonal anti-perovskite Na{sub 2}CaVO{sub 4}F

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

Green, Robert L., E-mail: rgreen@flpoly.org; Avdeev, Maxim; School of Chemistry, The University of Sydney, Sydney, NSW 2006

The structural details of the ordered hexagonal oxyfluoride Na{sub 2}CaVO{sub 4}F prepared by solid-state synthesis using stoichiometric amounts of V{sub 2}O{sub 5}, CaCO{sub 3}, Na{sub 2}CO{sub 3} and NaF were characterized using high-resolution neutron powder diffraction. The structural changes between 25 °C and 750 °C revealed that the two structural subunits in this material behave different when heated: there is an expansion of the face-shared FNa{sub 4}Ca{sub 2} octahedra while the VO{sub 4} tetrahedra due to increased thermal disorder reveal marginal bond contractions. Bond valences and the global instability index point to significant structural disorder at 750 °C. - Graphicalmore » abstract: The structure of the novel oxyfluoride Na{sub 2}CaVO{sub 4}F is studied at room temperature and high-temperatures. The structure can be viewed as layers of compression and elongation of polyhedral subunits, which change as a function of temperature. - Highlights: • The novel oxyfluoride, Na{sub 2}CaVO{sub 4}F, is synthesized via solid-state method. • High-resolution neutron diffraction data is used to analyze the structure of Na{sub 2}CaVO{sub 4}F. • Structural subunits exhibit expansion and contraction with increasing temperature. • Higher temperatures increase instability within the structure of Na{sub 2}CaVO{sub 4}F.« less

Biodistribution and radiation dosimetry of the hypoxia marker 18F-HX4 in monkeys and humans determined by using whole-body PET/CT.

PubMed

Doss, Mohan; Zhang, James J; Bélanger, Marie-José; Stubbs, James B; Hostetler, Eric D; Alpaugh, Katherine; Kolb, Hartmuth C; Yu, Jian Q

2010-12-01

F-HX4 is a novel positron emission tomography (PET) tracer for imaging hypoxia. The purpose of this study was to determine the biodistribution and estimate the radiation dose of F-HX4 using whole-body PET/computed tomography (CT) scans in monkeys and humans. Successive whole-body PET/CT scans were done after the injection of F-HX4 in four healthy humans (422±142 MBq) and in three rhesus monkeys (189±3 MBq). Biodistribution was determined from PET images and organ doses were estimated using OLINDA/EXM software. The bladder, liver, and kidneys showed the highest percentage of the injected radioactivity for humans and monkeys. For humans, approximately 45% of the activity is eliminated by bladder voiding in 3.6 h, and for monkeys 60% is in the bladder content after 3 h. The critical organ is the urinary bladder wall with the highest absorbed radiation dose of 415±18 (monkeys) and 299±38 μGy/MBq (humans), in the 4.8-h bladder voiding interval model. The average value of effective dose for the adult male was estimated at 42±4.2 μSv/MBq from monkey data and 27±2 μSv/MBq from human data. Bladder, kidneys, and liver have the highest uptake of injected F-HX4 activity for both monkeys and humans. The urinary bladder wall receives the highest dose of F-HX4 and is the critical organ. Thus, patients should be encouraged to maintain adequate hydration and void frequently. The effective dose of F-HX4 is comparable with that of other F-based imaging agents.

Administration of probiotics influences F4 (K88)-positive enterotoxigenic Escherichia coli attachment and intestinal cytokine expression in weaned pigs.

PubMed

Daudelin, Jean-François; Lessard, Martin; Beaudoin, Frédéric; Nadeau, Eric; Bissonnette, Nathalie; Boutin, Yvan; Brousseau, Jean-Philippe; Lauzon, Karoline; Fairbrother, John Morris

2011-05-23

This study evaluated the effect of the probiotics Pediococcus acidilactici and Saccharomyces cerevisiae boulardii on the intestinal colonization of O149 enterotoxigenic Escherichia coli harbouring the F4 (K88) fimbriae (ETEC F4) and on the expression of ileal cytokines in weaned pigs. At birth, different litters of pigs were randomly assigned to one of the following treatments: 1) control without antibiotics or probiotics (CTRL); 2) reference group in which chlortetracycline and tiamulin were added to weanling feed (ATB); 3) P. acidilactici; 4) S. cerevisiae boulardii; or 5) P. acidilactici + S. cerevisiae boulardii. Probiotics were administered daily (1 × 10(9) CFU per pig) during the lactation period and after weaning (day 21). At 28 days of age, all pigs were orally challenged with an ETEC F4 strain, and a necropsy was performed 24 h later. Intestinal segments were collected to evaluate bacterial colonization in the small intestine and ileal cytokine expressions. Attachment of ETEC F4 to the intestinal mucosa was significantly reduced in pigs treated with P. acidilactici or S. cerevisiae boulardii in comparison with the ATB group (P = 0.01 and P = 0.03, respectively). In addition, proinflammatory cytokines, such as IL-6, were upregulated in ETEC F4 challenged pigs treated with P. acidilactici alone or in combination with S. cerevisiae boulardii compared with the CTRL group. In conclusion, the administration of P. acidilactici or S. cerevisiae boulardii was effective in reducing ETEC F4 attachment to the ileal mucosa, whereas the presence of P. acidilactici was required to modulate the expression of intestinal inflammatory cytokines in pigs challenged with ETEC F4.

Kinetics of Cathode Processes in Separation of Thorium from Molten Salts. Part I. Investigation of ThF$sub 4$ and ThF$sub 4$-CaF$sub 2$; KINETYKA PROCESU KATODOWEGO PRZY OSADZANIU TORU ZE STOPIONYCH SOLI. CZESC I. BADANIA ThF$sub 4$ I ThF$sub 4$-CaF$sub 2$

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

Mints, S.; Rafal'skii, V.

1961-09-01

The current-intensity curves of non-electrolyzed salts and the curves of time-intensity and current-intensity in electrolyzed salts were plotted for molten ThF/sub 4/ and ThF /sub 4/CaF/sub 2/. The intensity of salt disintegration was determined, and electric conductivity in electrolyte was observed. (trauth)

Properties and Crystallization Phenomena in Li2Si2O5-Ca5(PO4)3F and Li2Si2O5-Sr5(PO4)3F Glass-Ceramics Via Twofold Internal Crystallization.

PubMed

Rampf, Markus; Dittmer, Marc; Ritzberger, Christian; Schweiger, Marcel; Höland, Wolfram

2015-01-01

The combination of specific mechanical, esthetic, and chemical properties is decisive for the application of materials in prosthodontics. Controlled twofold crystallization provides a powerful tool to produce special property combinations for glass-ceramic materials. The present study outlines the potential of precipitating Ca5(PO4)3F as well as Sr5(PO4)3F as minor crystal phases in Li2Si2O5 glass-ceramics. Base glasses with different contents of CaO/SrO, P2O5, and F(-) were prepared within the glasses of the SiO2-Li2O-K2O-CaO/SrO-Al2O3-P2O5-F system. Preliminary studies of nucleation by means of XRD and scanning electron microscopy (SEM) of the nucleated base glasses revealed X-ray amorphous phase separation phenomena. Qualitative and quantitative crystal phase analyses after crystallization were conducted using XRD in combination with Rietveld refinement. As a main result, a direct proportional relationship between the content of apatite-forming components in the base glasses and the content of apatite in the glass-ceramics was established. The microstructures of the glass-ceramics were investigated using SEM. Microstructural and mechanical properties were found to be dominated by Li2Si2O5 crystals and quite independent of the content of the apatite present in the glass-ceramics. Biaxial strengths of up to 540 MPa were detected. Ca5(PO4)3F and Sr5(PO4)3F influence the translucency of the glass-ceramics and, hence, help to precisely tailor the properties of Li2Si2O5 glass-ceramics. The authors conclude that the twofold crystallization of Li2Si2O5-Ca5(PO4)3F or Li2Si2O5-Sr5(PO4)3F glass-ceramics involves independent solid-state reactions, which can be controlled via the chemical composition of the base glasses. The influence of the minor apatite phase on the optical properties helps to achieve new combinations of features of the glass-ceramics and, hence, displays new potential for dental applications.

Tuning of the ionization potential of paddlewheel diruthenium(II, II) complexes with fluorine atoms on the benzoate ligands.

PubMed

Miyasaka, Hitoshi; Motokawa, Natsuko; Atsuumi, Ryo; Kamo, Hiromichi; Asai, Yuichiro; Yamashita, Masahiro

2011-01-21

A series of paddlewheel diruthenium(ii, ii) complexes with various fluorine-substituted benzoate ligands were isolated as THF adducts and structurally characterized: [Ru(2)(F(x)PhCO(2))(4)(THF)(2)] (F(x)PhCO(2)(-) = o-fluorobenzoate, o-F; m-fluorobenzoate, m-F; p-fluorobenzoate, p-F; 2,6-difluorobenzoate, 2,6-F(2); 3,4-difluorobenzoate, 3,4-F(2); 3,5-difluorobenzoate, 3,5-F(2); 2,3,4-trifluorobenzoate, 2,3,4-F(3); 2,3,6-trifluorobenzoate, 2,3,6-F(3); 2,4,5-trifluorobenzoate, 2,4,5-F(3); 2,4,6-trifluorobenzoate, 2,4,6-F(3); 3,4,5-trifluorobenzoate, 3,4,5-F(3); 2,3,4,5-tetrafluorobenzoate, 2,3,4,5-F(4); 2,3,5,6-tetrafluorobenzoate, 2,3,5,6-F(4); pentafluorobenzoate, F(5)). By adding fluorine atoms on the benzoate ligands, it was possible to tune the redox potential (E(1/2)) for [Ru(2)(II,II)]/[Ru(2)(II,III)](+) over a wide range of potentials from -40 mV to 350 mV (vs. Ag/Ag(+) in THF). 2,3,6-F(3), 2,3,4,5-F(4), 2,3,5,6-F(4) and F(5) were relatively air-stable compounds even though they are [Ru(2)(II,II)] species. The redox potential in THF was dependent on an electronic effect rather than on a structural (steric) effect of the o-F atoms, although more than one substituent in the m- and p-positions shifted E(1/2) to higher potentials in relation to the general Hammett equation. A quasi-Hammett parameter for an o-F atom (σ(o)) was estimated to be ∼0.2, and a plot of E(1/2)vs. a sum of Hammett parameters including σ(o) was linear. In addition, the HOMO energy levels, which was calculated based on atomic coordinates of solid-state structures, as well as the redox potential were affected by adding F atoms. Nevertheless, a steric contribution stabilizing their static structures in the solid state was present in addition to the electronic effect. On the basis of the electronic effect, the redox potential of these complexes is correlated to the HOMO energy level, and the electronic effect of F atoms is the main factor controlling the ionization potential of the complexes with ligands free from the rotational constraint, i.e. complexes in solution.

F4+ enterotoxigenic Escherichia coli (ETEC) adhesion mediated by the major fimbrial subunit FaeG.

PubMed

Xia, Pengpeng; Song, Yujie; Zou, Yajie; Yang, Ying; Zhu, Guoqiang

2015-09-01

The FaeG subunit is the major constituent of F4(+) fimbriae, associated with glycoprotein and/or glycolipid receptor recognition and majorly contributes to the pathogen attachment to the host cells. To investigate the key factor involved in the fimbrial binding of F4(+) Escherichia coli, both the recombinant E. coli SE5000 strains carrying the fae operon gene clusters that express the different types of fimbriae in vitro, named as rF4ab, rF4ac, and rF4ad, respectively, corresponding to the fimbrial types F4ab, F4ac, and F4ad, and the three isogenic in-frame faeG gene deletion mutants were constructed. The adhesion assays and adhesion inhibition assays showed that ΔfaeG mutants had a significant reduction in the binding to porcine brush border as well as the intestinal epithelial cell lines, while the complemented strain ΔfaeG/pfaeG restored the adhesion function. The recombinant bacterial strains rF4ab, rF4ac, and rF4ad have the same binding property as wild-type F4(+) E. coli strains do and improvement in terms of binding to porcine brush border and the intestinal epithelial cells, and the adherence was blocked by the monoclonal antibody anti-F4 fimbriae. These data demonstrate that the fimbrial binding of F4(+) E. coli is directly mediated by the major FaeG subunit. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Medical Acquisition shelf-Life System (MASS) Decision Support Model Systems Documentation

DTIC Science & Technology

1989-05-01

9 I INTRODUCTI ON A. Background In October 1987, LTG Russo hosted a conference with the Military Service Logistics Chiefs...A42,F6.3,F6.2,F9.2,F3.1,AIS,F9.1,A9,F9.0,AI7,F9.0,A9, 00032220 + F5.4,F5.4,F7.4, FIO .0) 00032320 IF(ADQ.EQ.0.O)THEN 00032420 ADQ=QFD*4.0 00032520 END

Synthesis and evaluation of 18F-labeled CJ-042794 for imaging prostanoid EP4 receptor expression in cancer with positron emission tomography.

PubMed

Zhang, Zhengxing; Lau, Joseph; Kuo, Hsiou-Ting; Zhang, Chengcheng; Colpo, Nadine; Bénard, François; Lin, Kuo-Shyan

2017-05-15

The potent and selective prostanoid EP4 receptor antagonist CJ-042794 was radiolabeled with 18 F, and evaluated for imaging EP4 receptor expression in cancer with positron emission tomography (PET). The fluorination precursor, arylboronic acid pinacol ester 4, was prepared in 4 steps with 42% overall yield. 18 F-CJ-042794 was synthesized via a copper-mediated 18 F-fluorination reaction followed by base hydrolysis, and was obtained in 1.5±1.1% (n=2) decay-corrected radiochemical yield. PET/CT imaging and biodistribution studies in mice showed that 18 F-CJ-042794 was excreted through both renal and hepatobiliary pathways with significant retention in blood. The EP4-receptor-expressing LNCaP prostate cancer xenografts were clearly visualized in PET images with 1.12±0.08%ID/g (n=5) uptake value and moderate tumour-to-muscle contrast ratio (2.73±0.22) at 1h post-injection. However, the tumour uptake was nonspecific as it could not be blocked by co-injection of cold standard, precluding the application of 18 F-CJ-042794 for PET imaging of EP4 receptor expression in cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Production a monoclonal antibody specific to granulocytes of swimming crab (Portunus trituberculatus) and its cross reactivity with other crustaceans.

PubMed

Cheng, Shun-Feng; Wu, Xiao-Chun; Zhang, Min

2016-10-01

In this study, a monoclonal antibody (mAb) 3F4 specific to granulocytes of swimming crab, Portunus trituberculatus, was obtained by immunizing mice with whole haemocytes. mAb 3F4 showed strong immunofluorescent reaction with granulocytes, but no reaction with hyalinocytes. The positive cell percentage of granulocytes was 86.3% detected by Flow cytometry (FCM). A special antigen with molecular weight of about 26kDa was further recognized by mAb 3F4 in haemocytes of P. trituberculatus. mAb 3F4 also showed strong cross-reactivity with haemocytes of Eriocheir sinensis and Petalomera japonica, but no reaction with other crustaceans tested. In E. sinensis, the positive cell percentage was 73.4% for granulocytes and 59.8% for hyalinocytes; while in P. japonica, the positive cell percentage was 81.2% for granulocytes and 7.1% for hyalinocytes. There was also a special antigen with molecular weight of about 31kDa identified by mAb 3F4 in haemocytes of E.sinensis, but no corresponding protein band in P. japonica haemocytes. These results demonstrated that mAb 3F4 can be used as a marker for granulocytes of crabs. Copyright © 2016 Elsevier B.V. All rights reserved.

Copper Causes Regiospecific Formation of C4F8-Containing Six-Membered Rings and their Defluorination/Aromatization to C4F4-Containing Rings in Triphenylene/1,4-C4F8I2 Reactions

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

Rippy, Kerry C.; Bukovsky, Eric V.; Clikeman, Tyler T.

The presence of Cu in reactions of triphenylene (TRPH) and 1,4-C4F8I2 at 360 °C led to regiospecific substitution of TRPH ortho C(β) atoms to form C4F8-containing rings, completely suppressing substitution on C(α) atoms. In addition, Cu caused selective reductive-defluorination/aromatization (RD/A) to form C4F4- containing aromatic rings. Without Cu, the reactions of TRPH and 1,4- C4F8I2 were not regiospecific and no RD/A was observed. These results, supported by DFT calculations, are the first examples of Cupromoted (i) regiospecific perfluoroannulation, (ii) preparative C–F activation, and (iii) RD/A. HPLC-purified products were characterized by X-ray diffraction, low-temperature PES, and 1H/19F NMR.

Fully automated synthesis of 4-[18F]fluorobenzylamine based on borohydride/NiCl2 reduction.

PubMed

Way, Jenilee; Wuest, Frank

2013-04-01

4-[(18)F]Fluorobenzylamine ([(18)F]FBA) is an important building block for the synthesis of (18)F-labeled compounds. Synthesis of [(18)F]FBA usually involves application of strong reducing agents like LiAlH4 which is challenging to handle in automated synthesis units (ASUs). Therefore, alternative methods for the preparation of [(18)F]FBA compatible with remotely-controlled syntheses in ASUs are needed. (18)F]FBA was prepared in a remotely-controlled synthesis unit (GE TRACERlab™ FX) based on Ni(II)-mediated borohydride exchange resin (BER) reduction of 4-[(18)F]fluorobenzonitrile ([(18)F]FBN). [(18)F]FBA was used for the synthesis of novel thiol-reactive prosthetic group 4-[(18)F]fluorobenzyl)maleimide [(18)F]FBM and Hsp90 inhibitor 17-(4-[(18)F]fluorobenzylamino)-17-demethoxy-geldanamycin [(18)F] GA. [(18)F]FBA could be prepared in high radiochemical yield greater than 80% (decay-corrected) within 60min. In a typical experiment, 7.4GBq of [(18)F]FBA could be obtained in high radiochemical purity of greater than 95% starting from 10GBq of cyclotron-produced n.c.a. [(18)F]fluoride. [(18)F]FBA was used for the preparation of 4-[(18)F]fluorobenzyl)maleimide as a novel prosthetic group for labeling of thiol groups as demonstrated with tripeptide glutathione. [(18)F]FBA was also used as building block for the syntheses of small molecules as exemplified by the preparation of Hsp90 inhibitor 17-(4-[(18)F]fluorobenzylamino)-17-demethoxy-geldanamycin. The described remotely-controlled synthesis of [(18)F]FBA will significantly improve the availability of [(18)F]FBA as an important and versatile building block for the development of novel (18)F-labeled compounds containing a fluorobenzylamine moiety. Copyright © 2013 Elsevier Inc. All rights reserved.

Syntheses, crystal structures and Raman spectra of Ba(BF{sub 4})(PF{sub 6}), Ba(BF{sub 4})(AsF{sub 6}) and Ba{sub 2}(BF{sub 4}){sub 2}(AsF{sub 6})(H{sub 3}F{sub 4}); the first examples of metal salts containing simultaneously tetrahedral BF{sub 4}{sup -} and octahedral AF{sub 6}{sup -} anions

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

Lozinsek, Matic; Bunic, Tina; Goreshnik, Evgeny, E-mail: evgeny.goreshnik@ijs.s

2009-10-15

In the system BaF{sub 2}/BF{sub 3}/PF{sub 5}/anhydrous hydrogen fluoride (aHF) a compound Ba(BF{sub 4})(PF{sub 6}) was isolated and characterized by Raman spectroscopy and X-ray diffraction on the single crystal. Ba(BF{sub 4})(PF{sub 6}) crystallizes in a hexagonal P6-bar2m space group with a=10.2251(4) A, c=6.1535(4) A, V=557.17(5) A{sup 3} at 200 K, and Z=3. Both crystallographically independent Ba atoms possess coordination polyhedra in the shape of tri-capped trigonal prisms, which include F atoms from BF{sub 4}{sup -} and PF{sub 6}{sup -} anions. In the analogous system with AsF{sub 5} instead of PF{sub 5} the compound Ba(BF{sub 4})(AsF{sub 6}) was isolated and characterized.more » It crystallizes in an orthorhombic Pnma space group with a=10.415(2) A, b=6.325(3) A, c=11.8297(17) A, V=779.3(4) A{sup 3} at 200 K, and Z=4. The coordination around Ba atom is in the shape of slightly distorted tri-capped trigonal prism which includes five F atoms from AsF{sub 6}{sup -} and four F atoms from BF{sub 4}{sup -} anions. When the system BaF{sub 2}/BF{sub 3}/AsF{sub 5}/aHF is made basic with an extra addition of BaF{sub 2}, the compound Ba{sub 2}(BF{sub 4}){sub 2}(AsF{sub 6})(H{sub 3}F{sub 4}) was obtained. It crystallizes in a hexagonal P6{sub 3}/mmc space group with a=6.8709(9) A, c=17.327(8) A, V=708.4(4) A{sup 3} at 200 K, and Z=2. The barium environment in the shape of tetra-capped distorted trigonal prism involves 10 F atoms from four BF{sub 4}{sup -}, three AsF{sub 6}{sup -} and three H{sub 3}F{sub 4}{sup -} anions. All F atoms, except the central atom in H{sub 3}F{sub 4} moiety, act as mu{sub 2}-bridges yielding a complex 3-D structural network. - Graphical abstract: The first three compounds, containing simultaneously tetrahedral BF{sub 4}{sup -} and octahedral AF{sub 6}{sup -} (A=P, As) anions have been synthesized and characterized by Raman spectroscopy and X-ray single crystal diffraction. In the system BaF{sub 2}/BF{sub 3}/PF{sub 5}/anhydrous hydrogen fluoride (aHF) the compound Ba(BF{sub 4})(PF{sub 6}) was isolated. In the analogous system with AsF{sub 5} instead of PF{sub 5} the compound Ba(BF{sub 4})(AsF{sub 6}) was obtained. When the system BaF{sub 2}/BF{sub 3}/AsF{sub 5}/aHF is made basic with an extra addition of BaF{sub 2}, the compound Ba{sub 2}(BF{sub 4}){sub 2}(AsF{sub 6})(H{sub 3}F{sub 4}) was prepared.« less

Influence of Toothbrushing on the Antierosive Effect of Film-Forming Agents.

PubMed

Scaramucci, Taís; João-Souza, Samira Helena; Lippert, Frank; Eckert, George J; Aoki, Idalina V; Hara, Anderson T

2016-01-01

This study evaluated the influence of toothbrushing on the antierosive effect of solutions containing sodium fluoride (225 ppm/F), stannous chloride (800 ppm/Sn), sodium linear polyphosphate (2%/LPP), and their combinations, and deionized water as negative control (C). Solutions were tested in a 5-day erosion-remineralization-abrasion cycling model, using enamel and dentin specimens (n = 8). Erosion was performed 6 times/day for 5 min, exposure to the test solutions 3 times/day for 2min, and toothbrushing (or not) with toothpaste slurry 2 times/day for 2 min (45 strokes). Surface loss (SL) was determined by noncontact profilometry. Data were analyzed using three-way ANOVA (α = 0.05). Brushing caused more SL than no brushing for enamel (mean ± SD, in micrometers: 52.7 ± 6.6 and 33.0 ± 4.5, respectively), but not for dentin (28.2 ± 1.9 and 26.6 ± 1.8, respectively). For enamel without brushing, F+LPP+Sn showed the lowest SL (23.8 ± 3.4), followed by F+Sn (30.6 ± 4.9) and F+LPP (31.7 ± 1.7), which did not differ from each other. No differences were found between the other groups and C (37.8 ± 2.1). When brushing, F+LPP+Sn exhibited the lowest SL (36.7 ± 2.4), not differing from F+LPP (39.1 ± 1.8). F, F+Sn and LPP+Sn were similar (46.7 ± 2.9, 42.1 ± 2.8 and 45.3 ± 4.6, respectively) and better than C (52.7 ± 4.3). Sn (55.0 ± 2.4) and LPP (51.0 ± 4.3) did not differ from C. For dentin, neither groups differed from C, regardless of brushing. In conclusion, toothbrushing did not affect the antierosive effect of F+Sn, F+LPP and F+LPP+Sn on enamel, although overall it led to more erosion than nonbrushing. F and LPP+Sn showed a protective effect only under brushing conditions, whereas Sn and LPP did not exhibit any protection. For dentin, neither toothbrushing nor the test solutions influenced the development of erosion. © 2016 S. Karger AG, Basel.