Performance-based financing in the context of selective free health-care: an evaluation of its effects on the use of primary health-care services in Burundi using routine data.

PubMed

Falisse, Jean-Benoît; Ndayishimiye, Juvenal; Kamenyero, Vincent; Bossuyt, Michel

2015-12-01

Performance-based financing (PBF) is an increasingly adopted strategy in low- and middle-income countries. PBF pilot projects started in Burundi in 2006, at the same time when a national policy removed user fees for pregnant women and children below 5 years old. PBF was gradually extended to the 17 provinces of the country. This roll-out and data from the national health information system are exploited to assess the impact of PBF on the use of health-care services. PBF is associated with an increase in the number of anti-tetanus vaccination of pregnant women (around +20 percentage points in target population, P < 0.10). Non-robust positive effects are also found on institutional deliveries and prenatal consultations. Changes in outpatient visits, postnatal visits and children vaccinations are not significantly correlated with PBF. It is also found that more qualified nurses headed to PBF-supported provinces. The limited quality of the data and the restricted size of the sample have to be taken into account when interpreting these results. Health facility-level figures from PBF-supported provinces show that most indicators but those relative to preventive care are growing through time. The dataset does not include indicators of the quality of care and does not allow to assess whether changes associated with PBF are resource-driven or due to the incentive mechanism itself. The results are largely consistent with other impact evaluations conducted in Burundi and Rwanda. The fact that PBF is mostly associated with positive changes in the use of services that became free suggests an important interaction effect between the two strategies. A possible explanation is that the removal of user fees increases accessibility to health care and acts on the demand side while PBF gives medical staffs incentives for improving the provision of services. More empirical research is needed to understand the sustainability of (the incentive mechanism of) PBF and the interaction between PBF and other health policies. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine © The Author 2014; all rights reserved.

Are health workers motivated by income? Job motivation of Cambodian primary health workers implementing performance-based financing

PubMed Central

Khim, Keovathanak

2016-01-01

Background Financial incentives are widely used in performance-based financing (PBF) schemes, but their contribution to health workers’ incomes and job motivation is poorly understood. Cambodia undertook health sector reform from the middle of 2009 and PBF was employed as a part of the reform process. Objective This study examines job motivation for primary health workers (PHWs) under PBF reform in Cambodia and assesses the relationship between job motivation and income. Design A cross-sectional self-administered survey was conducted on 266 PHWs, from 54 health centers in the 15 districts involved in the reform. The health workers were asked to report all sources of income from public sector jobs and provide answers to 20 items related to job motivation. Factor analysis was conducted to identify the latent variables of job motivation. Factors associated with motivation were identified through multivariable regression. Results PHWs reported multiple sources of income and an average total income of US$190 per month. Financial incentives under the PBF scheme account for 42% of the average total income. PHWs had an index motivation score of 4.9 (on a scale from one to six), suggesting they had generally high job motivation that was related to a sense of community service, respect, and job benefits. Regression analysis indicated that income and the perception of a fair distribution of incentives were both statistically significant in association with higher job motivation scores. Conclusions Financial incentives used in the reform formed a significant part of health workers’ income and influenced their job motivation. Improving job motivation requires fixing payment mechanisms and increasing the size of incentives. PBF is more likely to succeed when income, training needs, and the desire for a sense of community service are addressed and institutionalized within the health system. PMID:27319575

Performance-based financing in low-income and middle-income countries: isn’t it time for a rethink?

PubMed Central

Albert, Lucien; Bisala, Badibanga N’Sambuka; Bodson, Oriane; Bonnet, Emmanuel; Bossyns, Paul; Colombo, Sandro; De Brouwere, Vincent; Dumont, Alexandre; Eclou, Dieudonné Sèdjro; Gyselinck, Karel; Hane, Fatoumata; Marchal, Bruno; Meloni, Remo; Noirhomme, Mathieu; Noterman, Jean-Pierre; Samb, Oumar Mallé; Ssengooba, Freddie; Touré, Laurence; Turcotte-Tremblay, Anne-Marie; Van Belle, Sara; Vinard, Philippe

2018-01-01

This paper questions the view that performance-based financing (PBF) in the health sector is an effective, efficient and equitable approach to improving the performance of health systems in low-income and middle-income countries (LMICs). PBF was conceived as an open approach adapted to specific country needs, having the potential to foster system-wide reforms. However, as with many strategies and tools, there is a gap between what was planned and what is actually implemented. This paper argues that PBF as it is currently implemented in many contexts does not satisfy the promises. First, since the start of PBF implementation in LMICs, concerns have been raised on the basis of empirical evidence from different settings and disciplines that indicated the risks, cost and perverse effects. However, PBF implementation was rushed despite insufficient evidence of its effectiveness. Second, there is a lack of domestic ownership of PBF. Considering the amounts of time and money it now absorbs, and the lack of evidence of effectiveness and efficiency, PBF can be characterised as a donor fad. Third, by presenting itself as a comprehensive approach that makes it possible to address all aspects of the health system in any context, PBF monopolises attention and focuses policy dialogue on the short-term results of PBF programmes while diverting attention and resources from broader processes of change and necessary reforms. Too little care is given to system-wide and long-term effects, so that PBF can actually damage health services and systems. This paper ends by proposing entry points for alternative approaches. PMID:29564163

Body fat and body-mass index among a multiethnic sample of college-age men and women.

PubMed

Carpenter, Catherine L; Yan, Eric; Chen, Steve; Hong, Kurt; Arechiga, Adam; Kim, Woo S; Deng, Max; Li, Zhaoping; Heber, David

2013-01-01

Obesity prevalence and average body composition vary by US race and gender. Asian Americans have the lowest prevalence of obesity. Relying on body-mass index (BMI) to estimate obesity prevalence may misclassify subgroups that appear normally weighted but have excess body fat. We evaluated percentage body fat (PBF) and BMI to determine whether BMI reflects PBF consistently across different races. 940 college students were recruited from a local public university over four consecutive years. We measured PBF by bioelectrical impedance analysis (BIA), weight by physicians' scales, and height with stadiometers. Our sample comprised Asians (49%), Caucasians (23%), Hispanics (7%), and Other (21%). Participants averaged 21.4 years old; BMI was 22.9 kg/m(2); PBF was 24.8%. BMI and PBF varied significantly by race and gender (P value = 0.002 and 0.005 for men; 0.0009 and 0.0008 for women). Asian-American women had the lowest BMI (21.5 kg/m(2)) but the second highest PBF (27.8%). Linear association between BMI and PBF was the weakest (r (2) = 0.09) among Asian-American women and BMI had the poorest sensitivity (37%) to detect PBF. The high PBF with low BMI pattern exhibited by Asian-American women suggests that they could escape detection for obesity-related disease if BMI is the sole measure that estimates body composition.

Performance-based financing: the same is different.

PubMed

Renmans, Dimitri; Holvoet, Nathalie; Criel, Bart; Meessen, Bruno

2017-07-01

Although it is increasingly acknowledged within the Performance-Based Financing (PBF) research community that PBF is more than just payments based on outputs verified for quality, this narrow definition of PBF is still very present in many studies and evaluations. This leads to missed opportunities, misunderstandings and an unhelpful debate. Therefore, we reinforce the claim that PBF should be viewed as a reform package focused on targeted services with many different aspects that go beyond the health worker level. Failing to acknowledge the importance of the different elements of PBF negatively influences the task of practitioners, researchers and policymakers alike. After making the case for this wider definition, we propose three research pathways (describing, understanding and framing PBF) and give a short and tentative starting point for future research, leaving the floor open for more in-depth discussions. From these three vantage points it appears that when it comes to PBF 'the same is different'. Notwithstanding the increased complexity due to the use of the wider definition, progress on these three different research pathways will strongly improve our knowledge, lead to better adapted PBF programs and create a more nuanced debate on PBF. © The Author 2017. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Performance-based financing in the context of the complex remuneration of health workers: findings from a mixed-method study in rural Sierra Leone.

PubMed

Bertone, Maria Paola; Lagarde, Mylene; Witter, Sophie

2016-07-19

There is growing interest on the impact of performance-based financing (PBF) on health workers' motivation and performance. However, the literature so far tends to look at PBF payments in isolation, without reference to the overall remuneration of health workers. Taking the case of Sierra Leone, where PBF was introduced in 2011, this study investigates the absolute and relative contribution of PBF to health workers' income and explores their views on PBF bonuses, in comparison to and interaction with other incomes. The study is based on a mixed-methods research consisting in a survey and an 8-week longitudinal logbook collecting data on the incomes of primary health workers (n = 266) and 39 in-depth interviews with a subsample of the same workers, carried out in three districts of Sierra Leone (Bo, Kenema and Moyamba). Our results show that in this setting PBF contributes about 10 % of the total income of health workers. Despite this relatively low contribution, their views on the bonuses are positive, especially compared to the negative views on salary. We find that this is because PBF is seen as a complement, with less sense of entitlement compared to the official salary. Moreover, PBF has a specific role within the income utilization strategies enacted by health workers, as it provides extra money which can be used for emergencies or reinvested in income generating activities. However, implementation issues with the PBF scheme, such as delays in payment and difficulties in access, cause a series of problems that limit the motivational effects of the incentives. Overall, staff still favor salary increases over increases in PBF. The study confirms that the remuneration of health workers is complex and interrelated so that the different financial incentives cannot be examined independently from one. It also shows that the implementation of PBF schemes has an impact on the way it does or does not motivate health workers, and must be thoroughly researched in order to assess the impact of PBF.

An equity analysis of performance-based financing in Rwanda: are services reaching the poorest women?

PubMed

Priedeman Skiles, Martha; Curtis, Siân L; Basinga, Paulin; Angeles, Gustavo

2013-12-01

Maternal health services continue to favour the wealthiest in lower and middle income countries. Debate about the potential of performance-based financing (PBF) to address these disparities continues. As PBF is adopted by countries, it is critical to understand the equity effects for maternal services. The aim of this study is to examine the effects of PBF on equity in maternal health service use when no specific provisions target the poorest in the population. In Rwanda, PBF was designed to increase health service use, which was universally low. Paired districts were randomly assigned to intervention and control for PBF implementation. Using Rwanda's Demographic Health Survey data from 2005 (pre-intervention) and 2007-8 (post-intervention), a cluster-level panel dataset of 7899 women 15-49 years of age from intervention (4477) and control districts (3422) was created. The impact of PBF on reported use of facility deliveries, antenatal care (ANC) and modern contraceptive use was estimated using a difference-in-differences model with community fixed effects. Interaction terms between wealth quintiles and PBF were estimated to identify the differential effect of PBF among poorer women. The probability of a facility delivery increased by 10 percentage points in the intervention when compared with the control districts (P = 0.014), while no significant effects were noted for ANC visits or modern contraceptive use. Service use increased for intervention and control populations and across all wealth quintiles from 2005 to 2007, with no evidence that PBF was a pro-poor or a pro-rich strategy. Insurance remained a positive predictor of service use. This research suggests that if service use is uniformly low then a PBF programme that incentivizes select services, such as facility deliveries, may improve service use overall. However, if the equity gap is extreme, then a PBF programme without equity targets will do little to alleviate disparities.

How does performance-based financing affect health workers' intrinsic motivation? A Self-Determination Theory-based mixed-methods study in Malawi.

PubMed

Lohmann, Julia; Muula, Adamson S; Houlfort, Nathalie; De Allegri, Manuela

2018-07-01

"Intrinsic motivation crowding out", the erosion of high-quality, sustainable motivation through the introduction of financial incentives, is one of the most frequently discussed but yet little researched potential unfavorable consequence of Performance-based Financing (PBF). We used the opportunity of the introduction of PBF in Malawi to investigate whether and how PBF affected intrinsic motivation, using a mixed-methods research design theoretically grounded in Self-Determination Theory (SDT). The quantitative component served to estimate the impact of PBF on intrinsic motivation, relying on a controlled pre- and post-test design, with data collected from health workers in 23 intervention and 10 comparison facilities before (March/April 2013; n = 70) and approximately two years after (June/July 2015; n = 71) the start of the intervention. The qualitative component, relying on in-depth interviews with health workers in selected intervention facilities one (April 2014; n = 21) and two (September 2015; n = 20) years after the start of PBF, served to understand how PBF did or did not bring about change in intrinsic motivation. Specifically, it allowed us to examine how the various motivation-relevant elements and consequences of PBF impacted health workers' basic psychological needs for autonomy, competence, and relatedness, which SDT postulates as central to intrinsic motivation. Our results suggest that PBF did not affect health workers' overall intrinsic motivation levels, with the intervention having had both positive and negative effects on psychological needs satisfaction. To maximize positive PBF effects on intrinsic motivation, our results underline the potential value of explicit strategies to mitigate unintended negative impact of unavoidable design, implementation, and contextual challenges, for instance by building autonomy support activities into PBF designs. Copyright © 2018 Elsevier Ltd. All rights reserved.

Pulmonary blood flow redistribution by increased gravitational force

NASA Technical Reports Server (NTRS)

Hlastala, M. P.; Chornuk, M. A.; Self, D. A.; Kallas, H. J.; Burns, J. W.; Bernard, S.; Polissar, N. L.; Glenny, R. W.

1998-01-01

This study was undertaken to assess the influence of gravity on the distribution of pulmonary blood flow (PBF) using increased inertial force as a perturbation. PBF was studied in unanesthetized swine exposed to -Gx (dorsal-to-ventral direction, prone position), where G is the magnitude of the force of gravity at the surface of the Earth, on the Armstrong Laboratory Centrifuge at Brooks Air Force Base. PBF was measured using 15-micron fluorescent microspheres, a method with markedly enhanced spatial resolution. Each animal was exposed randomly to -1, -2, and -3 Gx. Pulmonary vascular pressures, cardiac output, heart rate, arterial blood gases, and PBF distribution were measured at each G level. Heterogeneity of PBF distribution as measured by the coefficient of variation of PBF distribution increased from 0.38 +/- 0.05 to 0.55 +/- 0.11 to 0.72 +/- 0.16 at -1, -2, and -3 Gx, respectively. At -1 Gx, PBF was greatest in the ventral and cranial and lowest in the dorsal and caudal regions of the lung. With increased -Gx, this gradient was augmented in both directions. Extrapolation of these values to 0 G predicts a slight dorsal (nondependent) region dominance of PBF and a coefficient of variation of 0.22 in microgravity. Analysis of variance revealed that a fixed component (vascular structure) accounted for 81% and nonstructure components (including gravity) accounted for the remaining 19% of the PBF variance across the entire experiment (all 3 gravitational levels). The results are inconsistent with the predictions of the zone model.

Kinetic Risk Factors of Running-Related Injuries in Female Recreational Runners.

PubMed

Napier, Christopher; MacLean, Christopher L; Maurer, Jessica; Taunton, Jack E; Hunt, Michael A

2018-05-30

Our objective was to prospectively investigate the association of kinetic variables with running-related injury (RRI) risk. Seventy-four healthy female recreational runners ran on an instrumented treadmill while 3D kinetic and kinematic data were collected. Kinetic outcomes were vertical impact transient, average vertical loading rate, instantaneous vertical loading rate, active peak, vertical impulse, and peak braking force (PBF). Participants followed a 15-week half-marathon training program. Exposure time (hours of running) was calculated from start of program until onset of injury, loss to follow-up, or end of program. After converting kinetic variables from continuous to ordinal variables based on tertiles, Cox proportional hazard models with competing risks were fit for each variable independently, before analysis in a forward stepwise multivariable model. Sixty-five participants were included in the final analysis, with a 33.8% injury rate. PBF was the only kinetic variable that was a significant predictor of RRI. Runners in the highest tertile (PBF <-0.27 BW) were injured at 5.08 times the rate of those in the middle tertile and 7.98 times the rate of those in the lowest tertile. When analyzed in the multivariable model, no kinetic variables made a significant contribution to predicting injury beyond what had already been accounted for by PBF alone. Findings from this study suggest PBF is associated with a significantly higher injury hazard ratio in female recreational runners and should be considered as a target for gait retraining interventions. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Improved oral bioavalability of mebudipine upon administration in PhytoSolve and Phosal-based formulation (PBF).

PubMed

Khani, Samira; Keyhanfar, Fariborz

2014-02-01

The aim of this investigation was to examine the efficacy of PhytoSolve and Phosal-based formulation (PBF) to enhance the oral bioavailability of mebudipine, which is a poorly water-soluble calcium channel blocker. The solubility of mebudipine in various oils was determined. PhytoSolve was prepared with a medium-chain triglyceride (MCT) oil (20%), soybean phospholipids (5%), and a 70% fructose solution (75%). The influence of the weight ratio of Phosal 50PG to glycerol in PBF on the mean globule size was studied with dynamic light scattering. The optimized formulation was evaluated for robustness toward dilution, transparency, droplet size, and zeta potential. The in vivo oral absorption of different mebudipine formulations (PhytoSolve, PBF, oily solution, and suspension) were evaluated in rats. The optimized PBF contained Phosal 50PG/glycerol in a 6:4 ratio (w/w). The PBF and PhytoSolve formulations were miscible with water in any ratio and did not demonstrate any phase separation or drug precipitation over 1 month of storage. The mean particle size of PhytoSolve and PBF were 138.5 ± 9.0 and 74.4 ± 2.5 nm, respectively. The in vivo study demonstrated that the oral bioavailability of PhytoSolve and PBF in rats was significantly higher than that of the other formulations. The PhytoSolve and PBF formulations of mebudipine are found to be more bioavailable compared with suspension and oily solutions during an in vivo study in rats. These formulations might be new alternative carriers that increase the oral bioavailability of poorly water-soluble molecules, such as mebudipine.

High protein buckwheat flour suppresses hypercholesterolemia in rats and gallstone formation in mice by hypercholesterolemic diet and body fat in rats because of its low protein digestibility.

PubMed

Tomotake, Hiroyuki; Yamamoto, Naoe; Yanaka, Noriyuki; Ohinata, Hiroshi; Yamazaki, Rikio; Kayashita, Jun; Kato, Norihisa

2006-02-01

This study evaluated the physiologic properties of high protein buckwheat flour (PBF) by examining its effects on serum cholesterol and body fat in rats and on cholesterol gallstone formation in mice. Animals were fed experimental diets that contained casein, buckwheat protein extract (BWP), or PBF as a protein source (net protein content 200 g/kg). In experiment 1, consumption of PBF and BWP for 10 d caused 33% and 31% decreases, respectively, in serum cholesterol of rats fed cholesterol-enriched diets when compared with consumption of casein (P < 0.05). Dietary PBF caused a significant decrease in liver cholesterol, whereas dietary BWP caused only a slight decrease (P > 0.05). Fecal excretion of neutral and acidic steroids in the PBF group was significantly higher than those in the BWP and casein groups. In experiment 2, consumption of PBF for 10 d significantly suppressed adipose tissue weight and hepatic activity of fatty acid synthase in rats fed cholesterol-free diets compared with consumption of casein (P < 0.05), whereas that of BWP for this period caused only a slight decrease in adipose tissue weight (P > 0.05). In experiment 3, dietary PBF and BWP significantly decreased the incidence of cholesterol gallstones and lithogenic index in mice fed cholesterol-enriched diets for 27 d, which was associated with increased fecal excretion of acidic steroids. This study demonstrated that PBF has strong activities against hypercholesterolemia, obesity, and gallstone formation, suggesting a potential usefulness of PBF as functional ingredient.

Efficiency of herbal medicine Dai-kenchu-to on portal blood flow in rat models.

PubMed

Muraoka, Izumi; Takatsuki, Mitsuhisa; Soyama, Akihiko; Yamaguchi, Izumi; Tanaka, Shiro; Tanaka, Takayuki; Kinoshita, Ayaka; Hara, Takanobu; Kuroki, Tamotsu; Eguchi, Susumu

2015-09-01

To clarify the influence of Dai-Kenchu-To (DKT) on portal blood flow (PBF), PBF was continuously measured with Doppler ultrasound. Normal liver rats were divided into a DKT 90 mg/kg, DKT 270 mg/kg administered group, and control, while cirrhotic liver rats were divided into a DKT-LC 90 mg/kg administered group and Control-LC. The PBF was measured after the administration of either DKT or water for 60 min by laser Doppler flowmetry system. The PBF in the DKT 90 increased approximately 10 min after DKT was administrated, and elevated levels were maintained for approximately 10 min. A comparison of the increase in PBF by the calculating the area under the curve (AUC) revealed that flow was significantly higher in the DKT 90 compared to either the control or the DKT 270 (p < 0.05). The cirrhotic liver group showed stable PBF in both the DKT-LC and Control-LC. The AUC, revealed no significant difference between the DKT-LC and Control-LC. DKT induced an increase in PBF in normal livers; however, its effects were insufficient to increase PBF in the cirrhotic livers. No increase in the portal blood flow in the cirrhotic liver rats was probably the result of the cirrhotic liver, which had fibrotic change, and, therefore, may not have had sufficient compliance to accept the increasing blood flow volume from the intestinal tract. We suggested DKT has the potential to protect the liver by increasing PBF when the liver has either normal or mild to moderate dysfunction.

PBF Reactor Building (PER620). Fuel rod test assembly is on ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Reactor Building (PER-620). Fuel rod test assembly is on display at PBF. Date: 1982. INEEL negative no. 82-4893 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

SPERTI/PBF. Contextual aerial view after PBF had begun operating, but ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

SPERT-I/PBF. Contextual aerial view after PBF had begun operating, but prior to expansion of southwest corner of Reactor Building (PER-620). Camera facing northeast. Reactor Building in center of view. Cooling Tower (PER-720) to its left. Warehouse (PER-625) at lower left was built in 1966. SPERT-I Reactor Building (PER-605) and Instrument Cell Building (PER-604) at right of view. Buried cables and piping proceed from PBF toward lower edge of view to Control Building further south and out of view. Photographer: Farmer. Date: March 26, 1976. INEEL negative no. 76-1344 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

Residual stress prediction in a powder bed fusion manufactured Ti6Al4V hip stem

NASA Astrophysics Data System (ADS)

Barrett, Richard A.; Etienne, Titouan; Duddy, Cormac; Harrison, Noel M.

2017-10-01

Powder bed fusion (PBF) is a category of additive manufacturing (AM) that is particularly suitable for the production of 3D metallic components. In PBF, only material in the current build layer is at the required melt temperature, with the previously melted and solidified layers reducing in temperature, thus generating a significant thermal gradient within the metallic component, particularly for laser based PBF components. The internal thermal stresses are subsequently relieved in a post-processing heat-treatment step. Failure to adequately remove these stresses can result in cracking and component failure. A prototype hip stem was manufactured from Ti6Al4V via laser PBF but was found to have fractured during over-seas shipping. This study examines the evolution of thermal stresses during the laser PBF manufacturing and heat treatment processes of the hip stem in a 2D finite element analysis (FEA) and compares it to an electron beam PBF process. A custom written script for the automatic conversion of a gross geometry finite element model into a thin layer- by-layer finite element model was developed. The build process, heat treatment (for laser PBF) and the subsequent cooling were simulated at the component level. The results demonstrate the effectiveness of the heat treatment in reducing PBF induced thermal stresses, and the concentration of stresses in the region that fractured.

PULPAL BLOOD FLOW CHANGES IN ABUTMENT TEETH OF REMOVABLE PARTIAL DENTURES

PubMed Central

Kunt, Göknil Ergün; Kökçü, Deniz; Ceylan, Gözlem; Yılmaz, Nergiz; Güler, Ahmet Umut

2009-01-01

The purpose of this study was to investigate the effect of tooth supported (TSD) and toothtissue supported (TTSD) removable partial denture wearing on pulpal blood flow (PBF) of the abutment teeth by using Laser Doppler Flowmeter (LDF). Measurements were carried out on 60 teeth of 28 patients (28 teeth and 12 patients of TTSD group, 32 teeth and 16 patients of TSD group) who had not worn any type of removable partial dentures before, had no systemic problems and were non smokers. PBF values were recorded by LDF before insertion (day 0) and after insertion of dentures at day 1, day 7 and day 30. Statistical analysis was performed by student t test and covariance analyses of repeated measurements. In the group TTSD, the mean values of PBF decreased statistically significantly at day 1 after insertion when compared with PBF values before insertion (p<0,01). There was no statistically significant difference among PBF mean values on 1st, 7th and 30th day. However, in the group TSD, there was no statistically significant difference among PBF mean values before insertion and on 1st, 7th and 30th day. In other words, PBF mean values in group TSD continued without changing statistically significant on 1st, 7th and 30th day. TTSD wearing may show negative effect on the abutment teeth due to decreasing basal PBF. PMID:20001995

Incentives to change: effects of performance-based financing on health workers in Zambia.

PubMed

Shen, Gordon C; Nguyen, Ha Thi Hong; Das, Ashis; Sachingongu, Nkenda; Chansa, Collins; Qamruddin, Jumana; Friedman, Jed

2017-02-28

Performance-based financing (PBF) has been implemented in a number of countries with the aim of transforming health systems and improving maternal and child health. This paper examines the effect of PBF on health workers' job satisfaction, motivation, and attrition in Zambia. It uses a randomized intervention/control design to evaluate before-after changes for three groups: intervention (PBF) group, control 1 (C1; enhanced financing) group, and control 2 (C2; pure control) group. Mixed methods are employed. The quantitative portion comprises of a baseline and an endline survey. The survey and sampling scheme were designed to allow for a rigorous impact evaluation of PBF or C1 on several key performance indicators. The qualitative portion seeks to explain the pathways underlying the observed differences through interviews conducted at the beginning and at the three-year mark of the PBF program. Econometric analysis shows that PBF led to increased job satisfaction and decreased attrition on a subset of measures, with little effect on motivation. The C1 group also experienced some positive effects on job satisfaction. The null results of the quantitative assessment of motivation cohere with those of the qualitative assessment, which revealed that workers remain motivated by their dedication to the profession and to provide health care to the community rather than by financial incentives. The qualitative evidence also provides two explanations for higher overall job satisfaction in the C1 than in the PBF group: better working conditions and more effective supervision from the District Medical Office. The PBF group had higher satisfaction with compensation than both control groups because they have higher compensation and financial autonomy, which was intended to be part of the PBF intervention. While PBF could not address all the reasons for attrition, it did lower turnover because those health centers were staffed with qualified personnel and the personnel had role clarity. In Zambia, the implementation of PBF schemes brought about a significant increase in job satisfaction and a decrease in attrition, but had no significant effect on motivation. Enhanced health financing also increased stated job satisfaction.

PBF contextual view shows relationship between PBF Control Building (PER619, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF contextual view shows relationship between PBF Control Building (PER-619, in foreground at right) and SPERT-I Control Building (PER-601). Walkway with railing connects to waste reduction operations support building (PER-632), built in 1981. Note paneled stucco siding applied to PER-619 after 1980. Original concrete block is exposed at corner. Date: July 2004. INEEL negative no. HD-41-9-2 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

Impact of implementing performance-based financing on childhood malnutrition in Rwanda.

PubMed

Binagwaho, Agnes; Condo, Jeanine; Wagner, Claire; Ngabo, Fidele; Karema, Corine; Kanters, Steve; Forrest, Jamie I; Bizimana, Jean de Dieu

2014-11-04

Malnutrition remains a serious concern in Rwanda, particularly among children under-5 years. Performance-based financing (PBF), an innovative health systems financing strategy, has been implemented at the national level since 2008. This study aimed to assess the impact of PBF and other factors associated with the prevalence of three classifications of malnutrition (stunting, wasting and underweight) in children under-5 years in Rwanda. The study is a cross-sectional study comprising of 713 children under five years old from 557 households, whose anthropometric measurements (height, weight and age) had been obtained as part of the 2008 Rwanda General Health and HIV household survey. Z-scores for height-for-age, weight-for-age, weight-for-height, and body mass index-for-age were analyzed according to the World Health Organization 2006 Child Growth Standards. Random intercept logistic regression models were used to regress each anthropometric measure (WAZ, HAZ and WHZ) against child, maternal and household characteristics. Child participants ranged in age from 0 to 60 months, 20.2% of children were under 12 months and 5.1% were HIV positive. The prevalence of wasting was 8.8%; of stunting was 58.4%; and of underweight status was 20.7%. Maternal emotional and social wellbeing was protective of wasting in children under-5 years of age. Living in districts implementing PBF was protective of wasting (Adjusted Odds Ratio: 0.43; 95% confidence interval: 0.19-0.97). Living in a district with PBF was not found to be associated with either stunting or underweight status among children under-5. PBF may have a protective association with particular forms of malnutrition among children under-5 years in Rwanda. These findings warrant further investigation in relation to the impact of implementing innovative financing schemes on health outcomes.

Efficiency of herbal medicine Dai-kenchu-to on portal blood flow in rat models

PubMed Central

Muraoka, Izumi; Takatsuki, Mitsuhisa; Soyama, Akihiko; Yamaguchi, Izumi; Tanaka, Shiro; Tanaka, Takayuki; Kinoshita, Ayaka; Hara, Takanobu; Kuroki, Tamotsu; Eguchi, Susumu

2015-01-01

Introduction To clarify the influence of Dai-Kenchu-To (DKT) on portal blood flow (PBF), PBF was continuously measured with Doppler ultrasound. Methods Normal liver rats were divided into a DKT 90 mg/kg, DKT 270 mg/kg administered group, and control, while cirrhotic liver rats were divided into a DKT-LC 90 mg/kg administered group and Control-LC. The PBF was measured after the administration of either DKT or water for 60 min by laser Doppler flowmetry system. Results The PBF in the DKT 90 increased approximately 10 min after DKT was administrated, and elevated levels were maintained for approximately 10 min. A comparison of the increase in PBF by the calculating the area under the curve (AUC) revealed that flow was significantly higher in the DKT 90 compared to either the control or the DKT 270 (p < 0.05). The cirrhotic liver group showed stable PBF in both the DKT-LC and Control-LC. The AUC, revealed no significant difference between the DKT-LC and Control-LC. Discussion DKT induced an increase in PBF in normal livers; however, its effects were insufficient to increase PBF in the cirrhotic livers. No increase in the portal blood flow in the cirrhotic liver rats was probably the result of the cirrhotic liver, which had fibrotic change, and, therefore, may not have had sufficient compliance to accept the increasing blood flow volume from the intestinal tract. Conclusion We suggested DKT has the potential to protect the liver by increasing PBF when the liver has either normal or mild to moderate dysfunction. PMID:26155361

Analysis of association of gene variants with obesity traits in New Zealand European children at 6 years of age.

PubMed

Krishnan, Mohanraj; Thompson, John M D; Mitchell, Edwin A; Murphy, Rinki; McCowan, Lesley M E; Shelling, Andrew N; On Behalf Of The Children Of Scope Study Group, G

2017-07-25

Childhood obesity is a public health problem, which is associated with a long-term increased risk of cardiovascular disease and premature mortality. Several gene variants have previously been identified that have provided novel insights into biological factors that contribute to the development of obesity. As obesity tracks through childhood into adulthood, identification of the genetic factors for obesity in early life is important. The objective of this study was to identify putative associations between genetic variants and obesity traits in children at 6 years of age. We recruited 1208 children of mothers from the New Zealand centre of the international Screening for Pregnancy Endpoints (SCOPE) study. Eighty common genetic variants associated with obesity traits were evaluated by the Sequenom assay. Body mass index standardised scores (BMI z-scores) and percentage body fat (PBF; measured by bio-impedance assay (BIA)) were used as anthropometric measures of obesity. A positive correlation was found between BMI z-scores and PBF (p < 0.001, r = 0.756). Two subsets of gene variants were associated with BMI z-scores (HOXB5-rs9299, SH2B1-rs7498665, NPC1-rs1805081 and MSRA-rs545854) and PBF (TMEM18-rs6548238, NPY-rs17149106, ETV-rs7647305, NPY-rs16139, TIMELESS-rs4630333, FTO-rs9939609, UCP2-rs659366, MAP2K5-rs2241423 and FAIM2-rs7138803) in the genotype models. However, there was an absence of overlapping association between any of the gene variants with BMI z-scores and PBF. A further five variants were associated with BMI z-scores (TMEM18-rs6548238, FTO-rs9939609 and MC4R-rs17782313) and PBF (SH2B1-rs7498665 and FTO-rs1421085) once separated by genetic models (additive, recessive and dominant) of inheritance. This study has identified significant associations between numerous gene variants selected on the basis of prior association with obesity and obesity traits in New Zealand European children.

Association between body mass index and body fat in 9-11-year-old children from countries spanning a range of human development.

PubMed

Katzmarzyk, P T; Barreira, T V; Broyles, S T; Chaput, J-P; Fogelholm, M; Hu, G; Kuriyan, R; Kurpad, A; Lambert, E V; Maher, C; Maia, J; Matsudo, V; Olds, T; Onywera, V; Sarmiento, O L; Standage, M; Tremblay, M S; Tudor-Locke, C; Zhao, P; Church, T S

2015-12-01

The purpose was to assess associations between body mass index (BMI) and body fat in a multinational sample of 9-11-year-old children. The sample included 7265 children from countries ranging in human development. Total body fat (TBF) and percentage body fat (PBF) were measured with a Tanita SC-240 scale and BMI z-scores (BMIz) and percentiles were computed using reference data from the World Health Organization and the U.S. Centers for Disease Control and Prevention, respectively. Mean PBF at BMIz values of -1, 0 and +1 were estimated using multilevel models. Correlations between BMI and TBF were >0.90 in all countries, and correlations between BMI and PBF ranged from 0.76 to 0.96. Boys from India had higher PBF than boys from several other countries at all levels of BMIz. Kenyan girls had lower levels of PBF than girls from several other countries at all levels of BMIz. Boys and girls from Colombia had higher values of PBF at BMIz=-1, whereas Colombian boys at BMIz 0 and +1 also had higher values of PBF than boys in other countries. Our results show a consistently high correlation between BMI and adiposity in children from countries representing a wide range of human development.

Performance-Based Financing to Strengthen the Health System in Benin: Challenging the Mainstream Approach

PubMed Central

Paul, Elisabeth; Lamine Dramé, Mohamed; Kashala, Jean-Pierre; Ekambi Ndema, Armand; Kounnou, Marcel; Codjovi Aïssan, Julien; Gyselinck, Karel

2018-01-01

Background: Performance-based financing (PBF) is often proposed as a way to improve health system performance. In Benin, PBF was launched in 2012 through a World Bank-supported project. The Belgian Development Agency (BTC) followed suit through a health system strengthening (HSS) project. This paper analyses and draws lessons from the experience of BTC-supported PBF alternative approach – especially with regards to institutional aspects, the role of demand-side actors, ownership, and cost-effectiveness – and explores the mechanisms at stake so as to better understand how the "PBF package" functions and produces effects Methods: An exploratory, theory-driven evaluation approach was adopted. Causal mechanisms through which PBF is hypothesised to impact on results were singled out and explored. This paper stems from the co-authors’ capitalisation of experiences; mixed methods were used to collect, triangulate and analyse information. Results are structured along Witter et al framework. Results: Influence of context is strong over PBF in Benin; the policy is donor-driven. BTC did not adopt the World Bank’s mainstream PBF model, but developed an alternative approach in line with its HSS support programme, which is grounded on existing domestic institutions. The main features of this approach are described (decentralised governance, peer review verification, counter-verification entrusted to health service users’ platforms), as well as its adaptive process. PBF has contributed to strengthen various aspects of the health system and led to modest progress in utilisation of health services, but noticeable improvements in healthcare quality. Three mechanisms explaining observed outcomes within the context are described: comprehensive HSS at district level; acting on health workers’ motivation through a complex package of incentives; and increased accountability by reinforcing dialogue with demand-side actors. Cost-effectiveness and sustainability issues are also discussed. Conclusion: BTC’s alternative PBF approach is both promising in terms of effects, ownership and sustainability, and less resource consuming. This experience testifies that PBF is not a uniform or rigid model, and opens the policy ground for recipient governments to put their own emphasis and priorities and design ad hoc models adapted to their context specificities. However, integrating PBF within the normal functioning of local health systems, in line with other reforms, is a big challenge. PMID:29325401

PBF Reactor Building (PER620). Reactor vessel arrives from gate city ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Reactor Building (PER-620). Reactor vessel arrives from gate city steel at door of PBF. On flatbed, it is too high to fit under door. Photographer: Larry Page. Date: February 13, 1970. INEEL negative no. 70-737 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Reactor Building (PER620). Detail of arrangement of highdensity blocks ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Reactor Building (PER-620). Detail of arrangement of high-density blocks and other basement shielding. Date: February 1966. Ebasco Services 1205 PER/PBF 620-A-7. INEEL index no. 761-0620-00-205-123070 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

Reduced thermal sensitivity of hybrid air-core photonic band-gap fiber ring resonator

NASA Astrophysics Data System (ADS)

Feng, Li-shuang; Wang, Kai; Jiao, Hong-chen; Wang, Jun-jie; Liu, Dan-ni; Yang, Zhao-hua

2018-01-01

A novel hybrid air-core photonic band-gap fiber (PBF) ring resonator with twin 90° polarization-axis rotated splices is proposed and demonstrated. Frist, we measure the temperature dependent birefringence coefficient of air-core PBF and Panda fiber. Experimental results show that the relative temperature dependent birefringence coefficient of air-core PBF is 1.42×10-8/°C, which is typically 16 times less than that of Panda fiber. Then, we extract the geometry profile of air-core PBF from scanning electron microscope (SEM) images. Numerical modal is built to distinguish the fast axis and slow axis in the fiber. By precisely setting the length difference in air-core PBF and Panda fiber between two 90° polarization-axis rotated splicing points, the hybrid air-core PBF ring resonator is constructed, and the finesse of the resonator is 8.4. Environmental birefringence variation induced by temperature change can be well compensated, and experimental results show an 18-fold reduction in thermal sensitivity, compared with resonator with twin 0° polarization-axis rotated splices.

Improving health worker performance: The patient-perspective from a PBF program in Rwanda.

PubMed

Lannes, Laurence

2015-08-01

The effect of performance-based financing (PBF) on patients' perception of primary health care services in developing countries in not well documented. Data from a randomized impact evaluation in Rwanda conducted between 2006 and 2008 in 157 primary level facilities is used to explore patients' satisfaction with clinical and non-clinical services and quantify the contribution of individual and facility characteristics to satisfaction including PBF. Improvements in productivity, availability and competences of the health workforce following the implementation of PBF have a positive effect on patients' satisfaction with clinical services even if patients' satisfaction is not tied to a reward. The positive effect of PBF on non-clinical dimensions of satisfaction also suggests that PBF incentivizes providers to raise patients' satisfaction with non-clinical services if it is associated with future financial gains. It is recommended that low and middle income countries build on the experience from high income countries to better listen to patients' voice in general and include an assessment of patients' satisfaction in incentive mechanisms as a way to increase the benefits of the strategy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Does performance-based financing increase value for money in low- and middle- income countries? A systematic review.

PubMed

Turcotte-Tremblay, Anne-Marie; Spagnolo, Jessica; De Allegri, Manuela; Ridde, Valéry

2016-12-01

Governments of low- and middle-income countries (LMICs) are widely implementing performance-based financing (PBF) to improve healthcare services. However, it is unclear whether PBF provides good value for money compared to status quo or other interventions aimed at strengthening the healthcare system in LMICs. The objective of this systematic review is to identify and synthesize the existing literature that examines whether PBF represents an efficient manner of investing resources. We considered PBF to be efficient when improved care quality or quantity was achieved with equal or lower costs, or alternatively, when the same quality of care was achieved using less financial resources. A manual search of the reference lists of two recent systematic reviews on economic evaluations of PBF was conducted to identify articles that met our inclusion and exclusion criteria. Subsequently, a search strategy was developed with the help of a librarian. The following databases and search engines were used: PubMed, EconLit, Google Scholar and Google. Experts on economic evaluations were consulted for validation of the selected studies. A total of seven articles from five LMICs were selected for this review. We found the overall strength of the evidence to be weak. None of the articles were full economic evaluations; they did not make clear connections between the costs and effects of PBF. Only one study reported using a randomized controlled trial, but issues with the randomization procedure were reported. Important alternative interventions to strengthen the capacities of the healthcare system have not been considered. Few studies examined the costs and consequences of PBF in the long term. Important costs and consequences were omitted from the evaluations. Few LMICs are represented in the literature, despite wide implementation. Lastly, most articles had at least one author employed by an organization involved in the implementation of PBF, thereby resulting in potential conflicts of interest. Stronger empirical evidence on whether PBF represents good value for money in LMICs is needed.

Reduced pulmonary blood flow in regions of injury 2 hours after acid aspiration in rats.

PubMed

Richter, Torsten; Bergmann, Ralf; Musch, Guido; Pietzsch, Jens; Koch, Thea

2015-01-01

Aspiration-induced lung injury can decrease gas exchange and increase mortality. Acute lung injury following acid aspiration is characterized by elevated pulmonary blood flow (PBF) in damaged lung areas in the early inflammation stage. Knowledge of PBF patterns after acid aspiration is important for targeting intravenous treatments. We examined PBF in an experimental model at a later stage (2 hours after injury). Anesthetized Wistar-Unilever rats (n = 5) underwent unilateral endobronchial instillation of hydrochloric acid. The PBF distribution was compared between injured and uninjured sides and with that of untreated control animals (n = 6). Changes in lung density after injury were measured using computed tomography (CT). Regional PBF distribution was determined quantitatively in vivo 2 hours after acid instillation by measuring the concentration of [(68)Ga]-radiolabeled microspheres using positron emission tomography. CT scans revealed increased lung density in areas of acid aspiration. Lung injury was accompanied by impaired gas exchange. Acid aspiration decreased the arterial pressure of oxygen from 157 mmHg [139;165] to 74 mmHg [67;86] at 20 minutes and tended toward restoration to 109 mmHg [69;114] at 110 minutes (P < 0.001). The PBF ratio of the middle region of the injured versus uninjured lungs of the aspiration group (0.86 [0.7;0.9], median [25%;75%]) was significantly lower than the PBF ratio in the left versus right lung of the control group (1.02 [1.0;1.05]; P = 0.016). The PBF pattern 2 hours after aspiration-induced lung injury showed a redistribution of PBF away from injured regions that was likely responsible for the partial recovery from hypoxemia over time. Treatments given intravenously 2 hours after acid-induced lung injury may not preferentially reach the injured lung regions, contrary to what occurs during the first hour of inflammation. Please see related article: http://dx.doi.org/10.1186/s12871-015-0014-z.

Motivating health workers up to a limit: partial effects of performance-based financing on working environments in Nigeria.

PubMed

Bhatnagar, Aarushi; George, Asha S

2016-09-01

In 2012, the Nigerian government launched performance-based financing (PBF) in three districts providing financial incentives to health workers based on the quantity and quality of service provision. They were given autonomy to use funds for operational costs and performance bonuses. This study aims to understand changes in perceived motivation among health workers with the introduction of PBF in Wamba district, Nigeria. The study used a qualitative research design to compare perceptions of health workers in facilities receiving PBF payments in the pilot district of Wamba to those that were not. In-depth semi-structured interviews (n = 39) were conducted with health workers from PBF and non-PBF facilities along with managers of the PBF project. Framework analysis was used to identify patterns and variations in responses. Facility records were collated and triangulated with qualitative data. Health workers receiving PBF payments reported to be 'awakened' by performance bonuses and improved working environments including routine supportive supervision and availability of essential drugs. They recounted being more punctual, hard working and proud of providing better services to their communities. In comparison, health workers in non-PBF facilities complained about the dearth of basic equipment and lack of motivating strategies. However, health workers from both sets of facilities considered there to be a severe shortage of manpower resulting in excessive workload, fatigue and general dissatisfaction. PBF strategies can succeed in motivating health workers by bringing about a change in incentives and working conditions. However, such programmes need to be aligned with human resource reforms including timely recruitment and appropriate distribution of health workers to prevent burn out and attrition. As people working on the frontline of constrained health systems, health workers are responsive to improved incentives and working conditions, but need more comprehensive support. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The effect of performance-based financing on illness, care-seeking and treatment among children: an impact evaluation in Rwanda.

PubMed

Skiles, Martha Priedeman; Curtis, Siân L; Basinga, Paulin; Angeles, Gustavo; Thirumurthy, Harsha

2015-09-14

Performance-based financing (PBF) strategies are promoted as a supply-side, results-based financing mechanism to improve primary health care. This study estimated the effects of Rwanda's PBF program on less-incentivized child health services and examined the differential program impact by household poverty. Districts were allocated to intervention and comparison for PBF implementation in Rwanda. Using Demographic Health Survey data from 2005 to 2007-08, a community-level panel dataset of 5781 children less than 5 years of age from intervention and comparison districts was created. The impacts of PBF on reported childhood illness, facility care-seeking, and treatment received were estimated using a difference-in-differences model with community fixed effects. An interaction term between poverty and the program was estimated to identify the differential effect of PBF among children from poorer families. There was no measurable difference in estimated probability of reporting illness with diarrhea, fever or acute respiratory infections between the intervention and comparison groups. Seeking care at a facility for these illnesses increased over time, however no differential effect by PBF was seen. The estimated effect of PBF on receipt of treatment for poor children is 45 percentage points higher (p = 0.047) compared to the non-poor children seeking care for diarrhea or fever. PBF, a supply-side incentive program, improved the quality of treatment received by poor children conditional on patients seeking care, but it did not impact the propensity to seek care. These findings provide additional evidence that PBF incentivizes the critical role staff play in assuring quality services, but does little to influence consumer demand for these services. Efforts to improve child health need to address both supply and demand, with additional attention to barriers due to poverty if equity in service use is a concern.

Association between body mass index and body fat in 9–11-year-old children from countries spanning a range of human development

PubMed Central

Katzmarzyk, P T; Barreira, T V; Broyles, S T; Chaput, J-P; Fogelholm, M; Hu, G; Kuriyan, R; Kurpad, A; Lambert, E V; Maher, C; Maia, J; Matsudo, V; Olds, T; Onywera, V; Sarmiento, O L; Standage, M; Tremblay, M S; Tudor-Locke, C; Zhao, P; Church, T S

2015-01-01

The purpose was to assess associations between body mass index (BMI) and body fat in a multinational sample of 9–11-year-old children. The sample included 7265 children from countries ranging in human development. Total body fat (TBF) and percentage body fat (PBF) were measured with a Tanita SC-240 scale and BMI z-scores (BMIz) and percentiles were computed using reference data from the World Health Organization and the U.S. Centers for Disease Control and Prevention, respectively. Mean PBF at BMIz values of −1, 0 and +1 were estimated using multilevel models. Correlations between BMI and TBF were >0.90 in all countries, and correlations between BMI and PBF ranged from 0.76 to 0.96. Boys from India had higher PBF than boys from several other countries at all levels of BMIz. Kenyan girls had lower levels of PBF than girls from several other countries at all levels of BMIz. Boys and girls from Colombia had higher values of PBF at BMIz=−1, whereas Colombian boys at BMIz 0 and +1 also had higher values of PBF than boys in other countries. Our results show a consistently high correlation between BMI and adiposity in children from countries representing a wide range of human development. PMID:27152184

PBF Control Building (PER619). Interior detail of control room's severe ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Control Building (PER-619). Interior detail of control room's severe fuel damage instrument panel. Indicators provided real-time information about test underway in PBF reactor. Note audio speaker. Date: May 2004. INEEL negative no, HD-41-7-4 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

General layout of reactor and control areas upon advent of ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

General layout of reactor and control areas upon advent of power burst facility (PBF). Shows relationship of PBF to SPERT-I, -II, -III, and -IV. Ebasco Services 1205-PER/PBF-U-102. Date: July 1965. INEEL index no. 761-0100-00-205-123006 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

Performance-Based Financing to Strengthen the Health System in Benin: Challenging the Mainstream Approach.

PubMed

Paul, Elisabeth; Lamine Dramé, Mohamed; Kashala, Jean-Pierre; Ekambi Ndema, Armand; Kounnou, Marcel; Codjovi Aïssan, Julien; Gyselinck, Karel

2017-04-15

Performance-based financing (PBF) is often proposed as a way to improve health system performance. In Benin, PBF was launched in 2012 through a World Bank-supported project. The Belgian Development Agency (BTC) followed suit through a health system strengthening (HSS) project. This paper analyses and draws lessons from the experience of BTC-supported PBF alternative approach - especially with regards to institutional aspects, the role of demand-side actors, ownership, and cost-effectiveness - and explores the mechanisms at stake so as to better understand how the "PBF package" functions and produces effects. An exploratory, theory-driven evaluation approach was adopted. Causal mechanisms through which PBF is hypothesised to impact on results were singled out and explored. This paper stems from the co-authors' capitalisation of experiences; mixed methods were used to collect, triangulate and analyse information. Results are structured along Witter et al framework. Influence of context is strong over PBF in Benin; the policy is donor-driven. BTC did not adopt the World Bank's mainstream PBF model, but developed an alternative approach in line with its HSS support programme, which is grounded on existing domestic institutions. The main features of this approach are described (decentralised governance, peer review verification, counter-verification entrusted to health service users' platforms), as well as its adaptive process. PBF has contributed to strengthen various aspects of the health system and led to modest progress in utilisation of health services, but noticeable improvements in healthcare quality. Three mechanisms explaining observed outcomes within the context are described: comprehensive HSS at district level; acting on health workers' motivation through a complex package of incentives; and increased accountability by reinforcing dialogue with demand-side actors. Cost-effectiveness and sustainability issues are also discussed. BTC's alternative PBF approach is both promising in terms of effects, ownership and sustainability, and less resource consuming. This experience testifies that PBF is not a uniform or rigid model, and opens the policy ground for recipient governments to put their own emphasis and priorities and design ad hoc models adapted to their context specificities. However, integrating PBF within the normal functioning of local health systems, in line with other reforms, is a big challenge. © 2018 The Author(s); Published by Kerman University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

The effect of intraosseous local anesthesia of 4% articaine with 1:100,000 epinephrine on pulpal blood flow and pulpal anesthesia of mandibular molars and canines.

PubMed

Vongsavan, Kadkao; Samdrup, Tshering; Kijsamanmith, Kanittha; Rirattanapong, Praphasri; Vongsavan, Noppakun

2018-05-10

The aim of this study was to determine the effect of intraosseous (IO) anesthesia with 4% articaine and 1:100,000 epinephrine on pulpal blood flow (PBF) and pulpal anesthesia of mandibular first molars and canines in human subjects. Ten healthy volunteers with intact mandibular first molar and canine were given an osteocentral technique of IO injection using the Quick Sleeper 5 system and 4% articaine with 1:100,000 epinephrine at distal site of mandibular first molar. The PBF was monitored by a laser Doppler flowmeter (LDF). Pulpal anesthesia was assessed with an electric pulp tester (EPT). IO injection caused a decrease in PBF in molars from 6.31 ± 3.85 perfusion units (P.U.) before injection to 2.51 ± 2.53 P.U. 1 min after injection (P < 0.001). The percentage reduction in PBF was 60% after 1 min and PBF returned back to the baseline after 45 min. No significant reduction in PBF was observed in the canines (P = 0.212). For pulpal anesthesia in the molars, the mean onset was 2.40 ± 0.84 min and the mean duration was 38 ± 16.19 min. In the canines, there was a decrease in the sensitivity to EPT but complete pulpal anesthesia was not achieved. IO injection distal to mandibular first molar caused a decrease in PBF and successful pulpal anesthesia in first molar, but not in canine. Both PBF and EPT readings returned to normal, suggesting that pulpal ischemia may not occur. IO anesthesia is safe to use as a primary technique in teeth with normal pulp.

Impact of performance-based financing on primary health care services in Haiti.

PubMed

Zeng, Wu; Cros, Marion; Wright, Katherine D; Shepard, Donald S

2013-09-01

To strengthen Haiti's primary health care (PHC) system, the country first piloted performance-based financing (PBF) in 1999 and subsequently expanded the approach to most internationally funded non-government organizations. PBF complements support (training and technical assistance). This study evaluates (a) the separate impact of PBF and international support on PHC's service delivery; (b) the combined impact of PBF and technical assistance on PHC's service delivery; and (c) the costs of PBF implementation in Haiti. To minimize the risk of facilities neglecting potential non-incentivized services, the incentivized indicators were randomly chosen at the end of each year. We obtained quantities of key services from four departments for 217 health centres (15 with PBF and 202 without) from 2008 through 2010, computed quarterly growth rates and analysed the results using a difference-in-differences approach by comparing the growth of incentivized and non-incentivized services between PBF and non-PBF facilities. To interpret the statistical analyses, we also interviewed staff in four facilities. Whereas international support added 39% to base costs of PHC, incentive payments added only 6%. Support alone increased the quantities of PHC services over 3 years by 35% (2.7%/quarter). However, support plus incentives increased these amounts by 87% over 3 years (5.7%/quarter) compared with facilities with neither input. Incentives alone was associated with a net 39% increase over this period, and more than doubled the growth of services (P < 0.05). Interview findings found no adverse impacts and, in fact, indicated beneficial impacts on quality. Incentives proved to be a relatively inexpensive, well accepted and very effective complement to support, suggesting that a small amount of money, strategically used, can substantially improve PHC. Haiti's experience, after more than a decade of use, indicates that incentives are an effective tool to strengthen PHC.

Near-degeneracy in Excited Vibrational States of 207PbF

NASA Astrophysics Data System (ADS)

Mawhorter, Richard; Nguyen, Alexander; Kim, Yongrak; Biekert, Andreas; Sears, Trevor; Grabow, Jens-Uwe; Kudashov, A. D.; Skripnikov, L. V.; Titov, A. V.; Petrov, A. N.

2017-04-01

High-resolution Fourier transform microwave (FTMW) spectroscopy studies of 207PbF have demonstrated the near-degeneracy of two levels of opposite parity. These have attracted attention for the study of parity violation effects and the variation of fundamental constants using 207PbF. Further theoretical work has improved our detailed understanding of both 207PbF and 208PbF, and furthermore recently indicated that the finely split +/- parity levels grow monotonically closer for higher vibrational states. Our experimental results for v = 0-3 confirm this, and are in excellent agreement with our extended theoretical calculations up to v = 4; both will be presented. TJS acknowledges support from Contract No. DE-SC0012704 with the U.S. Department of Energy, Office of Science, supported by its Division of Chemical Sciences, Geosciences and Biosciences within the Office of Basic Energy Sciences., as do RM, AB, YK, & AN from Pomona College & J-UG from the Deutsche Forschungsgemeinschaft (DFG).

Changes in Maxillary Canine Pulpal Blood Flow During Dentoalveolar Distraction Osteogenesis.

PubMed

Ersahan, Seyda; Sabuncuoglu, Fidan Alakus

2016-05-01

The aim of this study was to assess the effects of dentoalveolar distraction osteogenesis (DD) on the pulpal blood flow (PBF) of maxillary canines. A laser Doppler flowmeter (LDF) was used to measure PBF in maxillary canines of 10 patients undergoing DD (study group) and 10 nonsurgical subjects who received no orthodontic treatment (control group). PBF was measured at baseline, at 4 and 7 days postoperatively, at the end of distraction and at the end of consolidation in the study group and at similar time-points in nonsurgical control subjects. Data were analyzed using paired and Student t tests, with the significance level set at 0.05. Study findings showed that baseline PBF values did not differ significantly between groups. PBF in the control group did not vary over time; however, in the study group, an initial decrease in PBF was observed at 4 days postoperatively and was followed by a gradual increase to preoperative levels at the end of distraction. During the DD latency period, there appears to be a short-lived ischemic phase when perfusion of pulp tissue declines; however, blood-flow returns to normal by the end of distraction.

Waist circumference cut-off in relation to body mass index and percentage of body fat in adult women from Merida, Mexico.

PubMed

Datta Banik, Sudip; Dickinson, Federico

2015-01-01

Waist circumference (WC) as an index of central obesity is related to body mass index (BMI) and percent body fat (PBF). Waist circumference data were analyzed to identify a WC cut-off for adult women with respect to BMI-based obesity (≥ 30 kg/m²) and PBF. The sample was 138 women aged 22 to 41 years with Maya ancestry (based on surnames) in Merida, Yucatan, measured during 2011 - 2013. Anthropometric parameters included height, body weight (BW), and BMI. The PBF was estimated by bioelectrical impedance. Estimated cut-offs per centimeter WC (80 - 99 cm) were predicted by BMI for obesity (≥ 30 kg m⁻²; binomial: Yes = 1, No = 0) and PBF (continuous variable) using binary logistic regression analyses. Mean age was 32 years, mean BMI was 29 kg m(-2) and mean WC was 89 cm. The sample exhibited high PBF (44 %), and high rates of overweight (44%) and obesity (40%). The threshold WC (≥ 93 cm) had high sensitivity (80%), specificity (82%), Youden Index value (0.62), and correct classification rate (82%). The area under the receiver operating characteristic curve was 88 %. The WC ≥ 93 cm cut-off had corresponding values for mean BMI (34 kg m⁻²) and PBF (47%). The optimal WC cut-off at 93 cm significantly identified central obesity for BMI ≥ 30 kg m⁻² and PBF for this sample.

Increasing maternal percentage body fat in early second trimester: a risk factor for preeclampsia.

PubMed

Wang, Yanxia; Qiu, Jie; Zhou, Min; Wang, Youjie; Du, Yukai

2015-02-01

To determine if maternal percentage body fat (PBF) or fat free mass (FFM) in the early second trimester of pregnancy influenced the development of preeclampsia. A matched nested case-control study was conducted from a cohort study of 1668 women at Gansu provincial maternal and child care hospital from July 2007 to August 2011 in China. Maternal PBF and FFM were assessed by bioelectrical impedance analysis during 12th-16th gestational week. The demographic characteristics were all chart abstracted. After childbirth, 70 cases of preeclampsia were matched by race/age with 140 uncomplicated pregnancies women. Multivariate logistic regression analysis was performed to determine the associated risk factors. Pre-pregnancy body mass index were higher in women who subsequently developed preeclampsia compared with controls (p < 0.001). During 12th-16th gestational week, there were nearly 7-fold increase in the odds of preeclampsia (adjusted OR: 6.84, 95% CI: 4.15-41.60) among women with PBF ≥ 40% versus women with PBF < 40%. But FFM were not at further increased risk of the development of preeclampsia (adjusted OR, 1.02; 95% CI, 0.6-3.6). Maternal PBF but not FFM is a predictor of preeclampsia in the early second trimester. Excessive adipose tissue possibly played an important role in developing of preeclampsia.

PBF Reactor Building (PER620). Construction view shows native lava rock ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Reactor Building (PER-620). Construction view shows native lava rock surrounding basement excavation and general complexity of planning required to build the PBF. A three-inch low-pressure air line protrudes from wall just below left center. Date: February 21, 1967. Photographer: Larry Page. INEEL negative no. 67-1125 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

SPERTI contextual view of instrument cell building, PER606. South facade. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

SPERT-I contextual view of instrument cell building, PER-606. South facade. Camera facing northwest. PBF Cooling Tower in view at right. High bay of PBF Reactor Building, PER-602, is further to right. PBF-625 at left edge of view. Date: August 2003. INEEL negative no. HD-35-3-4 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

The impact of the Bolsa Família Program on food consumption: a comparative study of the southeast and northeast regions of Brazil.

PubMed

Sperandio, Naiara; Rodrigues, Cristiana Tristão; Franceschini, Sylvia do Carmo Castro; Priore, Silvia Eloiza

2017-06-01

The aim of this study was to evaluate the impact of the Bolsa Família Program (PBF) on food consumption in the northeast and southeast regions of Brazil. The database was obtained from the individual food consumption module of the Household Budget Survey conducted in 2008-09. Consumption was assessed through two food records. The food was categorized into four groups: fresh or minimally processed food; culinary ingredients; processed food; and ultra-processed food. To analyze the impact, the propensity score matching method was used, which compares the individual recipients and non-recipients of the PBF in relation to a group of socioeconomic characteristics. After the propensity score was calculated, the impact of the PBF was estimated through the nearest-neighbor matching algorithm. In both regions, more than 60% of the daily total calories consumed by PBF recipients came from foods that had not undergone industrial processing. The recipients of PBF had a low level of consumption of processed and ultra-processed food in both regions, and an increased level of consumption of fresh or minimally processed food in the northeast. The results indicate the importance of adopting intersectoral policies in parallel to the PBF in order to strengthen healthy eating practices.

Assessment of EchoMRI-AH versus dual-energy X-ray absorptiometry by iDXA to measure human body composition.

PubMed

Marlatt, K L; Greenway, F L; Ravussin, E

2017-04-01

Comparison of percent fat mass across different body composition analysis devices is important given variation in technology accuracy and precision, as well as the growing need for cross-validation of devices often applied across longitudinal studies. We compared EchoMRI-AH and Lunar iDXA quantification of percent body fat (PBF) in 84 adults (43M, 41F), with the mean age 39.7±15.9 years and body mass index (BMI) 26.2±5.3 kg/m 2 . PBF correlated strongly between devices (r>0.95, P<0.0001). A prediction equation was derived in half of the subjects, and the other half were used to cross-validate the proposed equation (EchoMRI-AH PBF=[(0.94 × iDXA PBF)+(0.14 × Age)+(3.3 × Female)-8.83). The mean PBF difference (predicted-measured) in the validation group was not different from 0 (diff=0.27%, 95% confidence interval: -0.42-0.96, P=0.430). Bland-Altman plots showed a bias with higher measured PBF on EchoMRI-AH versus iDXA in all 84 subjects (β=0.13, P<0.0001). The proposed prediction equation was valid in our cross-validation sample, and it has the potential to be applied across multicenter studies.

Relationship between body mass index and adiposity in prepubertal children: ethnic and geographic comparisons between New York City and Jinan City (China)

PubMed Central

Navder, Khursheed P.; He, Qing; Zhang, Xiaojing; He, Suyuan; Gong, Luxia; Sun, Yungao; Deckelbaum, Richard J.; Thornton, John; Gallagher, Dympna

2009-01-01

Body mass index (BMI) is often used as a surrogate estimate of percent body fat in epidemiological studies. This study tested the hypothesis that BMI is representative of body fatness independent of age, sex, ethnicity, and geographic location in prepubertal children. The study sample included a total of 605 prepubertal children (275 girls and 330 boys) of which 247 were Chinese from Jinan, Shandong, Mainland China, and 358 children were from various ethnic backgrounds in New York City (NYC): 121 Caucasians, 94 African Americans, and 143 Asians (Chinese and Korean). In this cross-sectional study, dual energy X-ray absorptiometry was used to quantify total body fat (TBF) and percent body fat (PBF). Prepubertal status was assessed by the criteria of Tanner. Multiple regression models were developed with TBF and PBF as the dependent variables and BMI, age, sex, and ethnicity as independent variables. Multiple regression analysis showed that BMI alone explained 85% and 69% of between-subject variance for TBF and PBF, respectively. Sex was a significant contributor to the models (P < 0.001) with girls having higher TBF and PBF than boys. Ethnicity and geographic location were significant contributors to the model (P < 0.0001) with Asians (Jinan and NYC Asians) having higher PBF than all non-Asian groups (P < 0.0001), and Jinan Asians having higher TBF and PBF than NYC-Asians. Among prepubertal children, for the same BMI, Asians have significantly higher PBF compared with African Americans and Caucasians. Caution is warranted when applying BMI across sex and ethnic prepubertal groups. PMID:19541740

Prediction of microstructure, residual stress, and deformation in laser powder bed fusion process

NASA Astrophysics Data System (ADS)

Yang, Y. P.; Jamshidinia, M.; Boulware, P.; Kelly, S. M.

2018-05-01

Laser powder bed fusion (L-PBF) process has been investigated significantly to build production parts with a complex shape. Modeling tools, which can be used in a part level, are essential to allow engineers to fine tune the shape design and process parameters for additive manufacturing. This study focuses on developing modeling methods to predict microstructure, hardness, residual stress, and deformation in large L-PBF built parts. A transient sequentially coupled thermal and metallurgical analysis method was developed to predict microstructure and hardness on L-PBF built high-strength, low-alloy steel parts. A moving heat-source model was used in this analysis to accurately predict the temperature history. A kinetics based model which was developed to predict microstructure in the heat-affected zone of a welded joint was extended to predict the microstructure and hardness in an L-PBF build by inputting the predicted temperature history. The tempering effect resulting from the following built layers on the current-layer microstructural phases were modeled, which is the key to predict the final hardness correctly. It was also found that the top layers of a build part have higher hardness because of the lack of the tempering effect. A sequentially coupled thermal and mechanical analysis method was developed to predict residual stress and deformation for an L-PBF build part. It was found that a line-heating model is not suitable for analyzing a large L-PBF built part. The layer heating method is a potential method for analyzing a large L-PBF built part. The experiment was conducted to validate the model predictions.

Mindful eating reduces impulsive food choice in adolescents and adults.

PubMed

Hendrickson, Kelsie L; Rasmussen, Erin B

2017-03-01

The present study tested the extent to which age and obesity predicted impulsive choices for food and monetary outcomes and tested how a brief mindful-eating training would alter delay discounting for food and money choices compared with control groups. First, 172 adolescents (M age = 13.13 years) and 176 (M age = 23.33 years) adults completed the Food Choice Questionnaire (FCQ) and Monetary Choice Questionnaire (MCQ) as measures of food and money delay discounting, respectively. Then, participants returned to the lab and were randomly assigned to complete a brief mindful-eating training, watch a DVD on nutrition, or serve as a control. Participants completed the FCQ and MCQ again as a postmanipulation measure. Participants with high percent body fat (PBF) were more impulsive for food than those with low PBF. Adults with high PBF were also more impulsive for money compared with adults with low PBF; no PBF-related differences were found for adolescents. Participants in the mindful-eating group exhibited more self-controlled choices for food, but not for money. The control conditions did not exhibit changes. The study suggests that individuals with high PBF make more impulsive food choices relative to those with low PBF, which could increase the risk of obesity over time. It also is the first to demonstrate shifts in choice patterns for food and money using a brief mindful-eating training with adolescents. Mindful eating is a beneficial strategy to reduce impulsive food choice, at least temporarily, that may impede weight gain. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Can performance-based financing help reaching the poor with maternal and child health services? The experience of rural Rwanda.

PubMed

Lannes, Laurence; Meessen, Bruno; Soucat, Agnes; Basinga, Paulin

2016-07-01

More than 20 countries in Africa are scaling up performance-based financing (PBF), but its impact on equity in access to health services remains to be documented. This paper draws on evidence from Rwanda to examine the capacity of PBF to ensure equal access to key health interventions especially in rural areas where most of the poor live. Specifically, it focuses on maternal and child health services, distinguishing two wealth groups, and uses data from a rigorous impact evaluation. Difference-in-difference technique is used, and different model specifications are tested: control for unobserved heterogeneity and common random error using linear probability model, seemingly unrelated regression equations, and clustering and fixed effects. Results suggest that in Rwanda, PBF improved efficiency rather than equity for most health services. We find that PBF achieved efficiency gains by improving access to health services for those easier to reach, generally the relatively more affluent. It turns out to be less effective in reaching the poorest. Our results illustrate the advantages of rigorous randomized impact evaluation data as results published earlier using a nationally representative survey (Demographic and Health Survey) were not able to capture the pro-rich nature of the PBF scheme in Rwanda. Our paper advocates for building mechanisms targeting the vulnerable groups in PBF strategies. It also highlights the need to understand the impact of PBF together with the specific development of health insurance coverage and the organization of the health system. Copyright © 2015 John Wiley & Sons, Ltd.

Comparison of Eight Equations That Predict Percent Body Fat Using Skinfolds in American Youth

PubMed Central

Roberts, Amy; Cai, Jianwen; Berge, Jerica M.; Stevens, June

2016-01-01

Abstract Background: Skinfolds are often used in equations to predict percent body fat (PBF) in youth. Although there are numerous such equations published, there is limited information to help researchers determine which equation to use for their sample. Methods: Using data from the 1999–2006 National Health and Nutrition Examination Surveys (NHANES), we compared eight published equations for prediction of PBF. These published equations all included triceps and/or subscapular skinfold measurements. We examined the PBF equations in a nationally representative sample of American youth that was matched by age, sex, and race/ethnicity to the original equation development population and a full sample of 8- to 18-year-olds. We compared the equation-predicted PBF to the dual-emission X-ray absorptiometry (DXA)-measured PBF. The adjusted R2, root mean square error (RMSE), and mean signed difference (MSD) were compared. The MSDs were used to examine accuracy and differential bias by age, sex, and race/ethnicity. Results: When applied to the full range of 8- 18-year-old youth, the R2 values ranged from 0.495 to 0.738. The MSD between predicted and DXA-measured PBF indicated high average accuracy (MSD between −1.0 and 1.0) for only three equations (Bray subscapular equation and Dezenberg equations [with and without race/ethnicity]). The majority of the equations showed differential bias by sex, race/ethnicity, weight status, or age. Conclusions: These findings indicate that investigators should use caution in the selection of an equation to predict PBF in youth given that results may vary systematically in important subgroups. PMID:27045618

Liver stiffness and portal blood flow modifications induced by a liquid meal consumption: pathogenetic mechanisms and clinical relevance.

PubMed

Barone, Michele; Iannone, Andrea; Brunetti, Natale Daniele; Sebastiani, Francesco; Cecere, Onofrio; Berardi, Elsa; Antonica, Gianfranco; Di Leo, Alfredo

2015-05-01

The correlation between liver stiffness (LS) variations and portal blood flow (PBF) modifications induced by a standardized liquid meal consumption and the clinical relevance of this matter are two aspects not yet fully elucidated. Herein, we evaluated the variations of LS and PBF after a standardized liquid meal intake in patients with chronic liver disease. PBF and LS were determined after an overnight fasting period in 54 patients. They were divided in three groups according to baseline LS (absent, moderate, and severe). They consumed 200 ml of water and a standardized liquid meal (300 Kcal/200 ml) after 60 min. PBF and LS were measured at 30 min after water and liquid meal consumption. In all groups, LS and PBF values significantly increased only after meal consumption. A significant correlation between baseline LS values and post-meal increase of LS was observed. Moreover, higher basal stiffness values were associated to a larger increase of LS variation after meal consumption. The effect of the meal on LS remained statistically significant after multiple regression analysis. A significant correlation between increase of LS and PBF was found in patients with absent and moderate baseline LS. Nine patients (17%) switched from a lower to a higher level of LS after meal consumption. A low calories/low-volume meal is capable of significantly increasing LS regardless of the grade of stiffness, determining a reclassification rate of 17%. In presence of minimal or moderate stiffness, the increase of LS is significantly correlated with the augment of PBF.

Prediction of microstructure, residual stress, and deformation in laser powder bed fusion process

NASA Astrophysics Data System (ADS)

Yang, Y. P.; Jamshidinia, M.; Boulware, P.; Kelly, S. M.

2017-12-01

Laser powder bed fusion (L-PBF) process has been investigated significantly to build production parts with a complex shape. Modeling tools, which can be used in a part level, are essential to allow engineers to fine tune the shape design and process parameters for additive manufacturing. This study focuses on developing modeling methods to predict microstructure, hardness, residual stress, and deformation in large L-PBF built parts. A transient sequentially coupled thermal and metallurgical analysis method was developed to predict microstructure and hardness on L-PBF built high-strength, low-alloy steel parts. A moving heat-source model was used in this analysis to accurately predict the temperature history. A kinetics based model which was developed to predict microstructure in the heat-affected zone of a welded joint was extended to predict the microstructure and hardness in an L-PBF build by inputting the predicted temperature history. The tempering effect resulting from the following built layers on the current-layer microstructural phases were modeled, which is the key to predict the final hardness correctly. It was also found that the top layers of a build part have higher hardness because of the lack of the tempering effect. A sequentially coupled thermal and mechanical analysis method was developed to predict residual stress and deformation for an L-PBF build part. It was found that a line-heating model is not suitable for analyzing a large L-PBF built part. The layer heating method is a potential method for analyzing a large L-PBF built part. The experiment was conducted to validate the model predictions.

Comparison of Eight Equations That Predict Percent Body Fat Using Skinfolds in American Youth.

PubMed

Truesdale, Kimberly P; Roberts, Amy; Cai, Jianwen; Berge, Jerica M; Stevens, June

2016-08-01

Skinfolds are often used in equations to predict percent body fat (PBF) in youth. Although there are numerous such equations published, there is limited information to help researchers determine which equation to use for their sample. Using data from the 1999-2006 National Health and Nutrition Examination Surveys (NHANES), we compared eight published equations for prediction of PBF. These published equations all included triceps and/or subscapular skinfold measurements. We examined the PBF equations in a nationally representative sample of American youth that was matched by age, sex, and race/ethnicity to the original equation development population and a full sample of 8- to 18-year-olds. We compared the equation-predicted PBF to the dual-emission X-ray absorptiometry (DXA)-measured PBF. The adjusted R(2), root mean square error (RMSE), and mean signed difference (MSD) were compared. The MSDs were used to examine accuracy and differential bias by age, sex, and race/ethnicity. When applied to the full range of 8- 18-year-old youth, the R(2) values ranged from 0.495 to 0.738. The MSD between predicted and DXA-measured PBF indicated high average accuracy (MSD between -1.0 and 1.0) for only three equations (Bray subscapular equation and Dezenberg equations [with and without race/ethnicity]). The majority of the equations showed differential bias by sex, race/ethnicity, weight status, or age. These findings indicate that investigators should use caution in the selection of an equation to predict PBF in youth given that results may vary systematically in important subgroups.

Performance-based financing with GAVI health system strengthening funding in rural Cambodia: a brief assessment of the impact.

PubMed

Matsuoka, Sadatoshi; Obara, Hiromi; Nagai, Mari; Murakami, Hitoshi; Chan Lon, Rasmey

2014-07-01

Though Cambodia made impressive gains in immunization coverage between the years 2000 and 2005, it recognized several health system challenges to greater coverage of immunization and sustainability. The Global Alliance for Vaccines and Immunization (GAVI) opened a Health System Strengthening (HSS) funding window in 2006. To address the health system challenges, Cambodia has been receiving the GAVI HSS fund since October 2007. The major component of the support is performance-based financing (PBF) for maternal, neonatal and child health (MNCH) services. To examine the impact of the PBF scheme on MNCH services and administrative management in rural Cambodia. Quantitative and qualitative studies were conducted in Kroch Chhmar Operational District (OD), Cambodia. Quantitative analyses were conducted on the trends of the numbers of MNCH services. A brief analysis was conducted using qualitative data. After the commencement of the PBF support, the volume of MNCH services was significantly boosted. In addition, strengthened financial and operational management was observed in the study area. However, the quality of the MNCH services was not ensured. Technical assistance, rather than the PBF scheme, was perceived by stakeholders to play a vital role in increasing the quality of the services. To improve the quality of the health services provided, it is better to include indicators on the quality of care in the PBF scheme. Mutual co-operation between PBF models and technical assistance may ensure better service quality while boosting the quantity. A robust but feasible data validation mechanism should be in place, as a PBF could incentivize inaccurate reporting. The capacity for financial management should be strengthened in PBF recipient ODs. To address the broader aspects of MNCH, a balanced input of resources and strengthening of all six building blocks of a health system are necessary. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine © The Author 2013; all rights reserved.

PBF Reactor Building (PER620). After lowering reactor vessel onto blocks, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Reactor Building (PER-620). After lowering reactor vessel onto blocks, it is rolled on logs into PBF. Metal framework under vessel is handling device. Various penetrations in reactor bottom were for instrumentation, poison injection, drains. Large one, below center "manhole" was for primary coolant. Photographer: Larry Page. Date: February 13, 1970. INEEL negative no. 70-736 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

Changes in human pulp blood flow during canine retraction.

PubMed

Sabuncuoglu, Fidan Alakus; Ersahan, Seyda

2016-08-01

To evaluate the effects of maxillary canine retraction on pulpal blood flow (PBF) in humans as recorded by laser Doppler flowmetry (LDF). Maxillary canines of 24 participants were divided into two groups (n = 12 each). Teeth in the study group underwent maxillary canine retraction using mini-implants as anchorage for approximately 4 months, with 100 g of force applied via coil springs. Subjects in the control group received no orthodontic treatment. LDF measurements were recorded at baseline (T0); during retraction, at 24 hours (T1), 3 days (T2), 7 days (T3) and 1 month (T4); and at the end of retraction (T5) in the study group and at similar time-points in control subjects. Data were analyzed using the Friedman, Wilcoxon signed rank and Mann-Whitney U tests, with the significance level set at 0.05. No significant changes in PBF perfusion units (PU) were observed in the control group over the course of the study. However, PBF in the study group increased significantly from T0 (3.6 ± 0.2 PU) to T1 (3.7 ± 0.2 PU, p < 0.001) and decreased severely from T1 to T2 (3.3 ± 0.1, p < 0.001). PBF in the study group was still significantly lower at T3 (3.4 ± 0.1 PU, p < 0.001) in comparison to T0; however, at T4 and T5, PBF was found to have returned to pre-retraction levels. The fact that PBF values returned to initial levels within one month of the initiation of retraction despite short-term, hyperaemic, regressive changes demonstrates that the changes observed in PBF during canine retraction are reversible.

Effects of photoperiod on wheat growth, development and yield in CELSS

NASA Astrophysics Data System (ADS)

Yunze, Shen; Shuangsheng, Guo

2014-12-01

A Controlled Ecological Life Support System (CELSS) is a sealed system used in spaceflight in order to provide astronauts with food and O2 by plants. It is of great significance to increase the energy-using efficiency because energy is extremely deficient in the space. Therefore, the objective of this research was to increase the energy-using efficiency of wheat by regulating the photoperiod. Sixteen treatments were set in total: four photoperiods before flowering (PBF) combined with four photoperiods after flowering (PAF) of 12 h, 16 h, 20 h and 24 h. The light source was red-blue LED (90% red+10% blue). As a result, the growth period of wheat was largely extended by shorter PBF, particularly the number of days from tillering to jointing and from jointing to heading. The period from flowering to maturity was extended by shorter PAF. Shorter PBF and longer PAF could increase not only the yield but also the energy-using efficiency of wheat. As for the nutritional quality, longer photoperiod (both PBF and PAF) increased starch concentration as well as decreased protein concentration of seeds. The effects of PBF and PAF were interactional. The lighting strategy with PBF of 12 h and PAF of 24 h was proved to be the optimum photoperiod for wheat cultivation in CELSS. The mechanisms of photoperiod effect contain two aspects. Firstly, photoperiod is a signal for many processes in plant growth, particularly the process of ear differentiation. Shorter PBF promoted the ear differentiation of wheat, increasing the spikelet number, floret number and seed number and thus enhancing the yield. Secondly, longer photoperiod leads to more light energy input and longer time of photosynthesis, so that longer PAF provided more photosynthate and increased seed yield.

Performance-based financing for improving HIV/AIDS service delivery: a systematic review.

PubMed

Suthar, Amitabh B; Nagata, Jason M; Nsanzimana, Sabin; Bärnighausen, Till; Negussie, Eyerusalem K; Doherty, Meg C

2017-01-04

Although domestic HIV/AIDS financing is increasing, international HIV/AIDS financing has plateaued. Providing incentives for the health system (i.e. performance-based financing [PBF]) may help countries achieve more with available resources. We systematically reviewed effects of PBF on HIV/AIDS service delivery to inform WHO guidelines. PubMed, WHO Index Medicus, conference databases, and clinical trial registries were searched in April 2015 for randomised trials, comparative contemporaneous studies, or time-series studies. Studies evaluating PBF in people with HIV were included when they reported service quality, access, or cost. Meta-analyses were not possible due to limited data. This study is registered with PROSPERO, number CRD42015023207. Four studies, published from 2009 to 2015 and including 173,262 people, met the eligibility criteria. All studies were from Sub-Saharan Africa. PBF did not improve individual testing coverage (relative risk [RR], 1.00, 95% confidence interval [CI] 0.89 to 1.13), improved couples testing coverage (RR 1.11, 95% CI 1.02 to 1.20), and improved pregnant women testing coverage (RR 1.29, 95% CI 1.28-1.30). PBF improved coverage of antiretrovirals in pregnant women (RR 1.55, 95% CI 1.50 to 1.59), infants (RR 1.92, 95% CI 1.84 to 2.01), and adults (RR 1.74, 1.64 to 1.85). PBF reduced attrition (RR 0.84, 95% CI 0.74 to 0.96) and treatment failure (odds ratio 0.55, 95% CI 0.32 to 0.97). Potential harms were not reported. Although the limited data suggests PBF positively affected HIV service access and quality, critical health system and governance knowledge gaps remain. More research is needed to inform national policymaking.

Opening the 'black box' of performance-based financing in low- and lower middle-income countries: a review of the literature.

PubMed

Renmans, Dimitri; Holvoet, Nathalie; Orach, Christopher Garimoi; Criel, Bart

2016-11-01

Although performance-based financing (PBF) receives increasing attention in the literature, a lot remains unknown about the exact mechanisms triggered by PBF arrangements. This article aims to summarize current knowledge on how PBF works, set out what still needs to be investigated and formulate recommendations for researchers and policymakers from donor and recipient countries alike. Drawing on an extensive systematic literature review of peer-reviewed journals, we analysed 35 relevant articles. To guide us through this variety of studies, point out relevant issues and structure findings, we use a comprehensive analytical framework based on eight dimensions. The review inter alia indicates that PBF is generally welcomed by the main actors (patients, health workers and health managers), yet what PBF actually entails is less straightforward. More research is needed on the exact mechanisms through which not only incentives but also ancillary components operate. This knowledge is essential if we really want to appreciate the effectiveness, desirability and appropriate format of PBF as one of the possible answers to the challenges in the health sector of low-and lower middle-income countries. A clear definition of the research constructs is a primordial starting point for such research. © The Author 2016. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Case formulation and management using pattern-based formulation (PBF) methodology: clinical case 1.

PubMed

Fernando, Irosh; Cohen, Martin

2014-02-01

A tool for psychiatric case formulation known as pattern-based formulation (PBF) has been recently introduced. This paper presents an application of this methodology in formulating and managing complex clinical cases. The symptomatology of the clinical presentation has been parsed into individual clinical phenomena and interpreted by selecting explanatory models. The clinical presentation demonstrates how PBF has been used as a clinical tool to guide clinicians' thinking, that takes a structured approach to manage multiple issues using a broad range of management strategies. In doing so, the paper also introduces a number of patterns related to the observed clinical phenomena that can be re-used as explanatory models when formulating other clinical cases. It is expected that this paper will assist clinicians, and particularly trainees, to better understand PBF methodology and apply it to improve their formulation skills.

Percentage body fat in apparently healthy school children from northern India.

PubMed

Khadgawat, R; Marwaha, R K; Tandon, N; Mehan, N; Upadhyay, A D; Sastry, A; Bhadra, K

2013-09-01

Increased prevalence of obesity in childhood and adolescence, defined by the use of body mass index (BMI), has drawn attention towards direct measurement of body fat. To develop age-and sex-specific reference distribution of body fat in apparently healthy North-Indian children in the age group of 7-17 years and to assess agreement between obesity (defined by BMI) and excess body fat. Study subjects for this cross sectional study included 1640 apparently healthy school children (825 boys; 815 girls) aged 7-17 years. Total body fat was measured by dual energy X-rays absorptiometry (DXA). The excess body fat by DXA was defined by two methods, prevalence matching and with the use of 85th and 95th centile cutoffs. The mean ± SD, 3rd, 10th, 25th, 50th, 75th, 90th and 97th centile values of percentage body fat (PBF) are presented. PBF was highly correlated with BMI in both boys and girls (all boys: r=0.76, P<0.0001; all girls r=0.81, P<0.0001). There was no significant difference noted in PBF between boys and girls at the age of 7-8 years. From 9 years onwards, girls had significantly higher PBF than boys. Moderate degree of agreement was observed between BMI and PBF by DXA by both methods. Smoothened reference distribution of PBF for North-Indian children and adolescents in Delhi are provided. Indian children accumulate more body fat during peri-pubertal years in comparison with US children.

Body Fat Measurements in Singaporean Adults Using Four Methods

PubMed Central

Bi, Xinyan; Loo, Yi Ting

2018-01-01

Few studies have been conducted to measure body composition in Asian populations. In this study, we determined the percent body fat (PBF) by using dual-energy X-ray absorptiometry (DEXA), air-displacement plethysmography (ADP or BOD POD), bioelectrical impedance analysis (BIA) and skinfold (SKF) in 445 healthy Singaporean adults. We observed that the BOD POD, BIA and SKF estimates of PBF were highly correlated with that from DEXA (as a reference method) among Singaporean adults. However, they all underestimated PBF (differences of 3.9% for BOD POD, 5.6% for BIA and 12.5% for SKF). Our results filled a gap in the literature by testing the relationships between DEXA and BOD POD, BIA and SKF in a large sample with a wide range of body mass index (BMI) from 16.1 to 37.5 kg/m2 and age from 21 to 69.2 years. The differences of PBF measured by different methods were dependent on age, gender and ethnicity. No significant difference was observed between DEXA and BOD POD in men aged > 40 or in BMI tertile 3. However, the mean difference between DEXA and BOD POD was significant in women. Different measuring methods of estimating PBF therefore must be cautiously interpreted. PMID:29510545

PbF2-based single crystals and phase diagrams of PbF2-MF2 systems (M = Mg, Ca, Sr, Ba, Cd)

NASA Astrophysics Data System (ADS)

Buchinskaya, I. I.; Fedorov, Pavel P.; Sobolev, B. P.

1997-07-01

Optical grade single crystals of Pb0.67Cd0.33F2 and Pb1-xCaxF2 (x less than 0.05) were grown by the Bridgman technique in graphite crucibles under fluorinating atmosphere of teflon pyrolysis products. For determinations of concentration areas of solid solutions, suitable for crystal growth, the phase interactions in the systems PbF2 with fluorides of alkaline-earth elements and Cd were studied by DTA and x-ray powder diffraction techniques. Phase diagrams were described by corresponding thermodynamic models. Transition from pure PbF2 to two- component Pb0.67Cd0.33F2 crystal is accompanied by some increase in radiation hardness of the latter and positive changes of mechanical characteristics (the Pb0.67Cd0.33F2 composition microhardness is 147 plus or minus 5 kg/mm2 that is 5 times that of a pure lead fluoride, 28 plus or minus 4 kg/mm2). These solid solutions have a cubic Fm3m fluorite-type lattice as a high-temperature modification of PbF2.

PBF (PER620) interior, basement level. Sampling equipment. Date: May 2004. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF (PER-620) interior, basement level. Sampling equipment. Date: May 2004. INEEL negative no. HD-41-5-4 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF (PER620) interior. Counting room, main floor. Date: May 2004. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF (PER-620) interior. Counting room, main floor. Date: May 2004. INEEL negative no. HD-41-6-1 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Reactor Building (PER620). Plot plan shows layout, including auxiliary ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Reactor Building (PER-620). Plot plan shows layout, including auxiliary buildings: Emergency Generator (621), Hose House (622), Cooling Tower Auxiliary (624), Maintenance and Storage Warehouse (625), Gas Cylinder Storage (627), Hose House (628), Cooling Tower (720), Substation (719), and other features. Road connections between PBF Reactor, its control building, and SPERT-I site. Note cable trenches along road to control building. Date: July 1965. Ebasco Services, PER-U-101. INEEL index no. 761-0100-00-205-123005 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

Similarity in percent body fat between white and Vietnamese women: implication for a universal definition of obesity.

PubMed

Ho-Pham, Lan T; Lai, Thai Q; Nguyen, Nguyen D; Barrett-Connor, Elizabeth; Nguyen, Tuan V

2010-06-01

It has been widely assumed that for a given BMI, Asians have higher percent body fat (PBF) than whites, and that the BMI threshold for defining obesity in Asians should be lower than the threshold for whites. This study sought to test this assumption by comparing the PBF between US white and Vietnamese women. The study was designed as a comparative cross-sectional investigation. In the first study, 210 Vietnamese women ages between 50 and 85 were randomly selected from various districts in Ho Chi Minh City (Vietnam). In the second study, 419 women of the same age range were randomly selected from the Rancho Bernardo Study (San Diego, CA). In both studies, lean mass (LM) and fat mass (FM) were measured by dual-energy X-ray absorptiometry (DXA) (QDR 4500; Hologic). PBF was derived as FM over body weight. Compared with Vietnamese women, white women had much more FM (24.8 +/- 8.1 kg vs. 18.8 +/- 4.9 kg; P < 0.0001) and greater PBF (36.4 +/- 6.5% vs. 35.0 +/- 6.2%; P = 0.012). However, there was no significant difference in PBF between the two groups after matching for BMI (35.1 +/- 6.2% vs. 35.0 +/- 5.7%; P = 0.87) or for age and BMI (35.6 +/- 5.1% vs. 35.8 +/- 5.9%; P = 0.79). Using the criteria of BMI >or=30, 19% of US white women and 5% of Vietnamese women were classified as obese. Approximately 54% of US white women and 53% of Vietnamese women had their PBF >35% (P = 0.80). Although white women had greater BMI, body weight, and FM than Vietnamese women, their PBF was virtually identical. Further research is required to derive a more appropriate BMI threshold for defining obesity for Asian women.

Nitric oxide, prostaglandins and angiotensin II in the regulation of renal medullary blood flow during volume expansion.

PubMed

Moreno, Carol; Llinás, María T; Rodriguez, Francisca; Moreno, Juan M; Salazar, F Javier

2016-03-01

Regulation of medullary blood flow (MBF) is essential in maintaining renal function and blood pressure. However, it is unknown whether outer MBF (OMBF) and papillary blood flow (PBF) are regulated independently when extracellular volume (ECV) is enhanced. The aim of this study was to determine whether OMBF and PBF are differently regulated and whether there is an interaction between nitric oxide (NO), prostaglandins (PGs) and angiotensin II (Ang II) in regulating OMBF and PBF when ECV is enhanced. To achieve these goals, OMBF and PBF were measured by laser-Doppler in volume-expanded rats treated with a cyclooxygenase inhibitor (meclofenamate, 3 mg/kg) and/or a NO synthesis inhibitor (L-nitro-arginine methyl ester (L-NAME), 3 μg/kg/min) and/or Ang II (10 ng/kg/min). OMBF was unchanged by NO or PGs synthesis inhibition but decreased by 36 % (P < 0.05) when L-NAME and meclofenamate were infused simultaneously. PBF was similarly reduced by L-NAME (12 %), meclofenamate (17 %) or L-NAME + meclofenamate (19 %). Ang II did not modify OMBF, but it led to a similar decrease (P < 0.05) in OMBF when it was administered to rats with reduced NO (32 %), PGs (36 %) or NO and PGs (37 %) synthesis. In contrast, the fall in PBF induced by Ang II (12 %) was enhanced (P < 0.05) by the simultaneous PGs (30 %) or PGs and NO (31 %) synthesis inhibition but not in L-NAME-treated rats (20 %). This study presents novel findings suggesting that blood flows to the outer medulla and renal papilla are differently regulated and showing that there is a complex interaction between NO, PGs and Ang II in regulating OMBF and PBF when ECV is enhanced.

PBF (PER620) interior, first basement level. Sampling equipment. Date: March ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF (PER-620) interior, first basement level. Sampling equipment. Date: March 2004. INEEL negative no. HD-41-4-1 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF (PER620) interior, basement level. Detail of coolant piping. Date: ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF (PER-620) interior, basement level. Detail of coolant piping. Date: May 2004. INEEL negative no. HD-41-5-2 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

Alternative methods for measuring obesity in African American women.

PubMed

Clark, Ashley E; Taylor, Jacquelyn Y; Wu, Chun Yi; Smith, Jennifer A

2013-03-01

The use of body mass index (BMI) may not be the most appropriate measurement tool in determining obesity in diverse populations. We studied a convenience sample of 108 African American (AA) women to determine the best method for measuring obesity in this at-risk population. The purpose of this study was to determine if percent body fat (PBF) and percent body water (PBW) could be used as alternatives to BMI in predicting obesity and risk for hypertension (HTN) among AA women. After accounting for age, BMI, and the use of anti-hypertensive medication, PBF (p = 0.0125) and PBW (p = 0.0297) were significantly associated with systolic blood pressure, while BMI was not. Likewise, PBF (p = 0.0316) was significantly associated with diastolic blood pressure, while PBW and BMI were not. Thus, health care practitioners should consider alternative anthropometric measurements such as PBF when assessing obesity in AA women.

Simple anthropometrics are more correlated with health variables than are estimates of body composition in Yup'ik people.

PubMed

Bray, Maria; Pomeroy, Jeremy; Knowler, William C; Bersamin, Andrea; Hopkins, Scarlett; Brage, Søren; Stanhope, Kimber; Havel, Peter J; Boyer, Bert B

2013-09-01

To (1) evaluate the relationships between several indices of obesity with obesity-related risk factors; (2) compare the accuracy of body composition estimates derived from anthropometry and bioimpedance analysis (BIA) to estimates of body composition assessed by doubly-labeled water (DLW); and (3) establish equations for estimating fat mass (FM), fat-free mass (FFM), and percent body fat (PBF) in Yup'ik people. Participants included 1,056 adult Yup'ik people from 11 communities in Southwestern Alaska. In a sub-study of 30 participants, we developed population-specific linear regression models for estimating FM, FFM, and PBF from anthropometrics, age, sex, and BIA against criterion measures derived from total body water assessed with DLW. These models were then used with the population cohort and we analyzed the relationships between obesity indices and several health-related and disease status variables: (1) fasting plasma lipids, (2) glucose, (3) HbA1c, (4) adiponectin, (5) blood pressure, (6) diabetes (DM), and (7) cerebrocoronary vascular disease (CCVD) which includes stroke and heart disease. The best model for estimating FM in the sub-study used only three variables-sex, waist circumference (WC), and hip circumference and had multiple R(2) = 0.9730. FFM and PBF were calculated from FM and body weight. WC and other anthropometrics were more highly correlated with a number of obesity-related risk factors than were direct estimates of body composition. Body composition in Yup'ik people can be accurately estimated from simple anthropometrics. Copyright © 2012 The Obesity Society.

Simple Anthropometrics Are More Correlated with Health Variables than Are Estimates of Body Composition in Yup’ik People

PubMed Central

Bray, Maria; Pomeroy, Jeremy; Knowler, William C.; Bersamin, Andrea; Hopkins, Scarlett; Brage, Søren; Stanhope, Kimber; Havel, Peter J.; Boyer, Bert B.

2012-01-01

We aimed to: 1) evaluate the relationships between several indices of obesity with obesity-related risk factors; 2) compare the accuracy of body composition estimates derived from anthropometry and bioimpedance analysis (BIA) to estimates of body composition assessed by doubly-labeled water (DLW); and 3) establish equations for estimating fat mass (FM), fat-free mass (FFM), and percent body fat (PBF) in Yup’ik Eskimo people. Participants included 1056 adult Yup’ik People from 11 communities in Southwestern Alaska. In a substudy of 30 participants, we developed population-specific linear regression models for estimating FM, FFM, and PBF from anthropometrics, age, sex, and BIA against criterion measures derived from total body water assessed with DLW. These models were then used with the population cohort and we analyzed the relationships between obesity indices and several health-related and disease status variables: 1. fasting plasma lipids, 2. glucose, 3. HbA1c, 4. adiponectin, 5. blood pressure, 6) diabetes (DM), and 7) cerebrocoronary vascular disease (CCVD) which includes stroke and heart disease. The best model for estimating FM in the substudy used only three variables – sex, waist circumference (WC), and hip circumference and had multiple R2=0.9730. FFM and PBF were calculated from FM and body weight. WC and other anthropometrics were more highly correlated with a number of obesity-related risk factors than were direct estimates of body composition. We conclude that body composition in Yup’ik People can be accurately estimated from simple anthropometrics. PMID:23666898

PBF (PER620) interior. System control racks, secondary control and equipment ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF (PER-620) interior. System control racks, secondary control and equipment room. Date: May 2004. INEEL negative no. HD-41-6-2 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

Performance-based financing as a health system reform: mapping the key dimensions for monitoring and evaluation.

PubMed

Witter, Sophie; Toonen, Jurrien; Meessen, Bruno; Kagubare, Jean; Fritsche, György; Vaughan, Kelsey

2013-09-29

Performance-based financing is increasingly being applied in a variety of contexts, with the expectation that it can improve the performance of health systems. However, while there is a growing literature on implementation issues and effects on outputs, there has been relatively little focus on interactions between PBF and health systems and how these should be studied. This paper aims to contribute to filling that gap by developing a framework for assessing the interactions between PBF and health systems, focusing on low and middle income countries. In doing so, it elaborates a general framework for monitoring and evaluating health system reforms in general. This paper is based on an exploratory literature review and on the work of a group of academics and PBF practitioners. The group developed ideas for the monitoring and evaluation framework through exchange of emails and working documents. Ideas were further refined through discussion at the Health Systems Research symposium in Beijing in October 2012, through comments from members of the online PBF Community of Practice and Beijing participants, and through discussion with PBF experts in Bergen in June 2013. The paper starts with a discussion of definitions, to clarify the core concept of PBF and how the different terms are used. It then develops a framework for monitoring its interactions with the health system, structured around five domains of context, the development process, design, implementation and effects. Some of the key questions for monitoring and evaluation are highlighted, and a systematic approach to monitoring effects proposed, structured according to the health system pillars, but also according to inputs, processes and outputs. The paper lays out a broad framework within which indicators can be prioritised for monitoring and evaluation of PBF or other health system reforms. It highlights the dynamic linkages between the domains and the different pillars. All of these are also framed within inter-sectoral and wider societal contexts. It highlights the importance of differentiating short term and long term effects, and also effects (intended and unintended) at different levels of the health system, and for different sectors and areas of the country. Outstanding work will include using and refining the framework and agreeing on the most important hypotheses to test using it, in relation to PBF but also other purchasing and provider payment reforms, as well as appropriate research methods to use for this task.

75 FR 50746 - Endangered and Threatened Species; Take of Anadromous Fish

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-17

... and Threatened Species; Take of Anadromous Fish AGENCY: National Marine Fisheries Service (NMFS.... 1531 et seq.) and regulations governing listed fish and wildlife permits (50 CFR Parts 222-226). NMFS... is to evaluate factors limiting fish distribution and water quality in streams owned by PBF. The...

Phase sensitivity of fundamental mode to external atmospheric pressure for hollow-core photonic bandgap fiber

NASA Astrophysics Data System (ADS)

Xu, Xiaobin; Liu, Yangqian; Gao, Fuyu; Song, Ningfang

2018-07-01

Hollow-core photonic bandgap fibers (HC-PBFs) are suitable for spaceborne fiber optical gyroscopes owing to their excellent environmental adaptability. However, hundreds of small holes full of air at one atmosphere of pressure can make the HC-PBF sensitive to external atmospheric pressure. In this study, we investigated the phase sensitivity of the fundamental mode to external atmospheric pressure for the HC-PBF, and the experimental result indicates that the phase sensitivity is approximately 1.6 × 10-5 ppm/Pa, which is mostly contributed by the change in the pressure-induced length. Through the choice of coating, the phase sensitivity to external atmospheric pressure can be reduced by about a factor of five compared to current HC-PBFs, and the excellent temperature performance can be maintained at the same time.

Preliminary Investigation on Life Cycle Inventory of Powder Bed Fusion of Stainless Steel

NASA Astrophysics Data System (ADS)

Nyamekye, Patricia; Piili, Heidi; Leino, Maija; Salminen, Antti

Manufacturing of work pieces from stainless steel with laser additive manufacturing, known also as laser sintering or 3D printing may increase energy and material efficiency. The use of powder bed fusion offers advantages to make parts for dynamic applications of light weight and near-net-shape products. Due to these advantages among others, PBF may also reduce emissions and operational cost in various applications. However, there are only few life cycle assessment studies examining this subject despite its prospect to business opportunity. The application of Life Cycle Inventory (LCI) in Powder Bed Fusion (PBF) provides a distinct evaluation of material and energy consumption. LCI offers a possibility to improve knowledge of process efficiency. This study investigates effect of process sustainability in terms of raw material, energy and time consumption with PBF and CNC machining. The results of the experimental study indicated lower energy efficiency in the production process with PBF. This study revealed that specific energy consumption in PBF decreased when several components are built simultaneously than if they would be built individually. This is due to fact that energy consumption per part is lower. On the contrary, amount of energy needed to machine on part in case of CNC machining is lower when parts are done separately.

Spatial and temporal variability in the trans-Pacific migration of Pacific bluefin tuna (Thunnus orientalis) revealed by archival tags

NASA Astrophysics Data System (ADS)

Fujioka, Ko; Fukuda, Hiromu; Tei, Yaoki; Okamoto, Suguru; Kiyofuji, Hidetada; Furukawa, Seishiro; Takagi, Junichi; Estess, Ethan; Farwell, Charles J.; Fuller, Daniel W.; Suzuki, Nobuaki; Ohshimo, Seiji; Kitagawa, Takashi

2018-03-01

Archival electronic tags were internally implanted in 713 age-0 Pacific bluefin tuna (PBF) caught in their nursery waters off the southern coast of Japan and in the East China Sea over an extended study period (1995-2015) to clarify the spatial and temporal variability of their trans-Pacific migration. Two hundred twenty-five of these tagged tuna were recaptured by fisheries (31.6%), and we successfully retrieved tag data from 14 of 21 individuals recovered in the Eastern pacific. Furthermore, one archival tag recovered in the Western Pacific revealed that the individual had performed a trans-Pacific migration, so in total 21 tagged PBF were shown to have migrated to the Eastern Pacific (2.9% of the total tags released). We successfully downloaded data from 15 of these 21 archival tags, which revealed that some age-1 PBF migrate rapidly (123.9 ± 82.8 km day-1) and directly from waters offshore of Japan to the eastern Pacific (160.0°E to 130.0°W), a journey that takes an average of 2.5 months (ranging from 1.2 to 5.5 months) through relatively cool waters (14.7 ± 2.0 °C). All juvenile PBF began their trans-Pacific migration shortly after exposure to cooler water temperatures (<14 °C), suggesting that sustained residence in lower water temperatures presents a physiological challenge for this age class. Three patterns were identified in the timing of the departure of juvenile PBF from the western Pacific: departing 12-14 months post-hatch (N = 7) in early summer (May-July), departing 17-19 months post-hatch (N = 7) in late autumn (October-December), and departing 21 months post-hatch (N = 1) in late winter (February). The PBF tagged along the southern coast of Japan (SCJ) arrived in the eastern Pacific earlier than those tagged in the East China Sea (ECS), most likely due to the shorter travel distance. Additionally, the PBF that began their trans-Pacific migration in the earlier period remained in an offshore foraging zone (the Kuroshio-Oyashio transition region) for shorter periods (2.8 months on average) and at lower latitudes (35.0°N) during the spring, while the PBF that delayed their migration spent more time (6.7 months on average) in the productive waters between 35.0 and 45.0°N during the spring-autumn months. The variability in the departure timing of the trans-Pacific migration of age-1 PBF may be related to geographic differences between nursery areas in addition to oceanographic conditions and foraging opportunities encountered by the tuna in the offshore waters of Japan during their first year.

PBF Cooling Tower (PER720). Camera faces south to show north ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Cooling Tower (PER-720). Camera faces south to show north facade. Note enclosed stairway. Date: August 2003. INEEL negative no. HD-35-10-3 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Reactor Building (PER620). Canal takes shape, with rebar and ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Reactor Building (PER-620). Canal takes shape, with rebar and concrete placement underway. Photographer: John Capek. Date: August 16, 1967. INEEL negative no. 67-4370 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Cooling Tower (PER720). Closeup detail of louvered wall panels ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Cooling Tower (PER-720). Close-up detail of louvered wall panels on south facade. Date: August 2003. INEEL negative no. HD-35-11-1 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Control Building auxiliary features, including fire hose house and ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Control Building auxiliary features, including fire hose house and sewage system. Ebasco Services 1205 PER/PER-A-4. INEEL undex no. 760-0619-00-205-123024 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

Increase in pulmonary blood flow at birth: role of oxygen and lung aeration.

PubMed

Lang, Justin A R; Pearson, James T; Binder-Heschl, Corinna; Wallace, Megan J; Siew, Melissa L; Kitchen, Marcus J; te Pas, Arjan B; Fouras, Andreas; Lewis, Robert A; Polglase, Graeme R; Shirai, Mikiyasu; Hooper, Stuart B

2016-03-01

Lung aeration stimulates the increase in pulmonary blood flow (PBF) at birth, but the spatial relationships between PBF and lung aeration and the role of increased oxygenation remain unclear. Using simultaneous phase-contrast X-ray imaging and angiography, we have investigated the separate roles of lung aeration and increased oxygenation in PBF changes at birth using near-term (30 days of gestation) rabbit kits (n = 18). Rabbits were imaged before ventilation, then the right lung was ventilated with 100% nitrogen (N2), air or 100% O2 (oxygen), before all kits were switched to ventilation in air, followed by ventilation of both lungs using air. Unilateral ventilation of the right lung with 100% N2 significantly increased heart rate (from 69.4 ± 4.9 to 93.0 ± 15.0 bpm), the diameters of both left and right pulmonary axial arteries, number of visible vessels in both left and right lungs, relative PBF index in both pulmonary arteries, and reduced bolus transit time for both left and right axial arteries (from 1.34 ± 0.39 and 1.81 ± 0.43 s to 0.52 ± 0.17 and 0.89 ± 0.21 s in the left and right axial arteries, respectively). Similar changes were observed with 100% oxygen, but increases in visible vessel number and vessel diameter of the axial arteries were greater in the ventilated right lung during unilateral ventilation. These findings confirm that PBF increase at birth is not spatially related to lung aeration and that the increase in PBF to unventilated regions is unrelated to oxygenation, although oxygen can potentiate this increase. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Physicians' and nurses' attitudes towards performance-based financial incentives in Burundi: a qualitative study in the province of Gitega.

PubMed

Rudasingwa, Martin; Uwizeye, Marie Rose

2017-01-01

Performance-based financing (PBF) was first implemented in Burundi in 2006 as a pilot programme in three provinces and was rolled out nationwide in 2010. PBF is a reform approach to improve the quality, quantity, and equity of health services and aims at achieving universal health coverage. It focuses on how to best motivate health practitioners. To elicit physicians' and nurses' experiences and views on how PBF influenced and helped them in healthcare delivery. A qualitative cross-sectional study was carried out among frontline health workers such as physicians and nurses. The data was gathered through individual face-to-face, in-depth, semi-structured interviews with 6 physicians and 30 nurses from February to March 2011 in three hospitals in Gitega Province. A simple framework approach and thematic analysis using a combination of manual technique and MAXQDA software guided the analysis of the interview data. Overall, the interviewees felt that the PBF scheme had provided positive motivation to improve the quality of care, mainly in the structures and process of care. The utilization of health services and the relationship between health practitioners and patients also improved. The salary top-ups were recognized as the most significant impetus to increase effort in improving the quality of care. The small and sometimes delayed financial incentives paid to physicians and nurses were criticized. The findings of this study also indicate that the positive interaction between performance-based incentive schemes and other health policies is crucial in achieving comprehensive improvement in healthcare delivery. PBF has the potential to motivate medical staff to improve healthcare provision. The views of medical staff and the context of the area of implementation have to be taken into consideration when designing and implementing PBF schemes.

76 FR 4341 - Combined Notice of Filings #1

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-25

... Time on Thursday, February 03, 2011. Docket Numbers: ER10-2077-004. Applicants: PBF Power Marketing LLC. Description: Supplemental Information/Request Change-in-Status Notification of PBF Power Marketing LLC. Filed...-certification [or self-recertification] listed above, do not institute a proceeding regarding qualifying...

PBF Reactor Building (PER620). Floor at left of view is ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Reactor Building (PER-620). Floor at left of view is floor of first basement. Photographer: Farmer/Capek. Date: March 17, 1967. INEEL negative no. 67-1753 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Cooling Tower detail. Camera facing southwest. Wood fill rises ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Cooling Tower detail. Camera facing southwest. Wood fill rises from foundation piers of cold water basin. Photographer: Kirsh. Date: May 1, 1969. INEEL negative no. 69-2826 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF (PER620) west facade. Camera facing east. Note 1980 addition ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF (PER-620) west facade. Camera facing east. Note 1980 addition on south side of west wall. Date: March 2004. INEEL negative no. HD-41-3-3 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

The Quality Improvement of Emulsion-type Pork Sausages Formulated by Substituting Pork Back fat with Rice Bran Oil

PubMed Central

Yum, Hyeon-Woong; Seo, Jin-Kyu; Jeong, Jin-Yeon; Kim, Gap-Don; Rahman, M. Shafiur; Yang, Han-Sul

2018-01-01

The effects of pork back fat (PBF) substitution with various concentrations of rice bran oil (RBO) (50%, 45%, 40% and 35%) on the physicochemical characteristics and sensory attributes of emulsion-type pork sausages were studied. The modified pork sausages were compared with control sausages produced using PBF only. The sausages with RBO had significantly lower (p<0.05) moisture content than the control sausages. Sausages made from PBF substituted with 40% RBO showed the lowest cooking loss. Substitution of PBF with RBO had no significant effect on the emulsion stability of pork sausages. All sausages with RBO showed significantly lower (p<0.05) hardness values than control sausages. Sausages with RBO also had significantly higher values (p<0.05) of unsaturated fatty acid and polyunsaturated to saturated fatty acid contents than the controls. RBO substitution had no effect on the flavor intensity of sausages, but it improved the tenderness and produced a softer texture. PMID:29725230

Elucidating the Relations Between Monotonic and Fatigue Properties of Laser Powder Bed Fusion Stainless Steel 316L

NASA Astrophysics Data System (ADS)

Zhang, Meng; Sun, Chen-Nan; Zhang, Xiang; Goh, Phoi Chin; Wei, Jun; Li, Hua; Hardacre, David

2018-03-01

The laser powder bed fusion (L-PBF) technique builds parts with higher static strength than the conventional manufacturing processes through the formation of ultrafine grains. However, its fatigue endurance strength σ f does not match the increased monotonic tensile strength σ b. This work examines the monotonic and fatigue properties of as-built and heat-treated L-PBF stainless steel 316L. It was found that the general linear relation σ f = mσ b for describing conventional ferrous materials is not applicable to L-PBF parts because of the influence of porosity. Instead, the ductility parameter correlated linearly with fatigue strength and was proposed as the new fatigue assessment criterion for porous L-PBF parts. Annealed parts conformed to the strength-ductility trade-off. Fatigue resistance was reduced at short lives, but the effect was partially offset by the higher ductility such that comparing with an as-built part of equivalent monotonic strength, the heat-treated parts were more fatigue resistant.

Improving quality through performance-based financing in district hospitals in Rwanda between 2006 and 2010: a 5-year experience.

PubMed

Janssen, Willy; Ngirabega, Jean de Dieu; Matungwa, Michel; Van Bastelaere, Stefaan

2015-01-01

Since 2000 performance-based financing (PBF) made its way to sub-Saharan health systems in an attempt to improve service delivery. In Rwanda initial experiences in 2001 and 2002 led to a scaling up of the initiative to all health centres (HC) and district hospitals (DH). In 2008 PBF became national strategy. PBF was introduced in Rwanda in 2006 at the DH level. Evaluation on their service delivery was carried out quarterly in the following areas: hospital management, support to the health centres and clinical activities. We studied four DHs. After 5 years, an improvement in the quantity of clinical activities was observed, as well as quality in hospital management, in HC support and in clinical activities. PBF proves to be a promising approach in strengthening and maintaining quality service delivery in the sub-Saharan district hospitals. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Nd3+-doped TeO2-PbF2-AlF3 glasses for laser applications

NASA Astrophysics Data System (ADS)

Lalla, E. A.; Rodríguez-Mendoza, U. R.; Lozano-Gorrín, A. D.; Sanz-Arranz, A.; Rull, F.; Lavín, V.

2016-01-01

A study of the optical properties of Nd3+ ion in TeO2-PbF2-AlF3 glasses has been carried out for different Nd3+ concentrations. Based on the Judd-Ofelt theory, intensity parameters and radiative properties were determined from the absorption spectra. Focusing on the suitability of this host for laser applications, the spectroscopic quality factor χ was obtained with a value of 1.07, a value of the order of other compositions proposed as laser hosts. For the most intense emission corresponding with the 4F3/2 → 4I11/2 transition (1.06 μm), the absorption and emission and have been calculated with values of 1.20 × 10-20 cm2, 2.08 × 10-20 cm2. A positive value for the gain cross-sections has been found for a population inversion factor γ of 0.4 in the spectral range from 1060 to 1110 nm. All these results suggest the potentially use of this system as a laser host.

PBF (PER620) north facade. Camera facing south. Small metal shed ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF (PER-620) north facade. Camera facing south. Small metal shed at right is Stack Gas Monitor Building, PER-629. Date: March 2004. INEEL negative no. HD-41-2-4 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Control Building (PER619). Interior in data acquisition room showing ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Control Building (PER-619). Interior in data acquisition room showing data racks. The system recorded multiple channels of data during tests. INEEL negative no. HD-41-8-1 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Control Building (PER619) south facade. Camera faces north. Note ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Control Building (PER-619) south facade. Camera faces north. Note buried tanks with bollards protecting their access hatches. Date: July 2004. INEEL negative no. HD-41-10-4 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

Performance-based financing as a health system reform: mapping the key dimensions for monitoring and evaluation

PubMed Central

2013-01-01

Background Performance-based financing is increasingly being applied in a variety of contexts, with the expectation that it can improve the performance of health systems. However, while there is a growing literature on implementation issues and effects on outputs, there has been relatively little focus on interactions between PBF and health systems and how these should be studied. This paper aims to contribute to filling that gap by developing a framework for assessing the interactions between PBF and health systems, focusing on low and middle income countries. In doing so, it elaborates a general framework for monitoring and evaluating health system reforms in general. Methods This paper is based on an exploratory literature review and on the work of a group of academics and PBF practitioners. The group developed ideas for the monitoring and evaluation framework through exchange of emails and working documents. Ideas were further refined through discussion at the Health Systems Research symposium in Beijing in October 2012, through comments from members of the online PBF Community of Practice and Beijing participants, and through discussion with PBF experts in Bergen in June 2013. Results The paper starts with a discussion of definitions, to clarify the core concept of PBF and how the different terms are used. It then develops a framework for monitoring its interactions with the health system, structured around five domains of context, the development process, design, implementation and effects. Some of the key questions for monitoring and evaluation are highlighted, and a systematic approach to monitoring effects proposed, structured according to the health system pillars, but also according to inputs, processes and outputs. Conclusions The paper lays out a broad framework within which indicators can be prioritised for monitoring and evaluation of PBF or other health system reforms. It highlights the dynamic linkages between the domains and the different pillars. All of these are also framed within inter-sectoral and wider societal contexts. It highlights the importance of differentiating short term and long term effects, and also effects (intended and unintended) at different levels of the health system, and for different sectors and areas of the country. Outstanding work will include using and refining the framework and agreeing on the most important hypotheses to test using it, in relation to PBF but also other purchasing and provider payment reforms, as well as appropriate research methods to use for this task. PMID:24073625

75 FR 32453 - Combined Notice of Filings #1

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-08

... Wednesday, June 16, 2010. Docket Numbers: ER10-1097-001. Applicants: PBF Power Marketing LLC. Description: PBF Power Marketing LLC submits tariff filing per 35.17(b): Amended MBR Application, to be effective 6...-recertification] listed above, do not institute a proceeding regarding qualifying facility status. A notice of...

PBF Reactor Building (PER620). Camera in first basement, facing south ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Reactor Building (PER-620). Camera in first basement, facing south and upward toward main floor. Cable trays being erected. Photographer: Kirsh. Date: May 20, 1969. INEEL negative no. 69-3110 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF (PER620) interior, second basement level. Coolant and tank piping. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF (PER-620) interior, second basement level. Coolant and tank piping. Mark on vertical pipe says, "H.P. Demin. Water." (High pressure demineralized water.) Date: March 2004. INEEL negative no. HD-41-4-3 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF (PER620) interior, basement level. Concrete wall shows outline of ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF (PER-620) interior, basement level. Concrete wall shows outline of reactor basin. Sign says, "Flashing Light - Reactor On - Evacuate Area." Date: May 2004. INEEL negative no. HD-41-5-3 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF (PER620) south facade. Camera facing north. Note pedestrian bridge ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF (PER-620) south facade. Camera facing north. Note pedestrian bridge crossing over conduit. Central high bay contains reactor room and canal. Date: March 2004. INEEL negative no. HD-41-2-1 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Control Building (PER619). Interior of control room shows control ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Control Building (PER-619). Interior of control room shows control console from direction facing visitors room and its observation window. Camera facing northeast. Date: May 2004. INEEL negative no. HD-41-7-1 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Cooling Tower Auxiliary Building (PER624) interior. Camera facing north. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Cooling Tower Auxiliary Building (PER-624) interior. Camera facing north. Deluge valves and automatic fire protection piping for Cooling Tower. Photographer: Holmes. Date: May 20, 1970. INEEL negative no. 70-2323 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

INEL BNCT Program

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

Ackermann, A.L.

1991-08-01

This Bulletin presents a summary of accomplishments and highlights in the Idaho National Engineering Laboratory's (INEL) Boron Neutron Capture Therapy (BNCT) Program for August 1991. This bulletin includes information on the brain tumor and melanoma research programs, Power Burst Facility (PBF) technical support and modifications, PBF operations, and updates to the animal data charts.

PBF Reactor Building (PER620) Cubicle 13. Plan, section, details. Note ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Reactor Building (PER-620) Cubicle 13. Plan, section, details. Note "quality assurance" code at bottom of drawing. Aerojet Nuclear Company. Date: May 1976. INEEL index no. 761-0620-00-400-195279 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Cubicle 13. Shield wall details illustrate shielding technique of ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Cubicle 13. Shield wall details illustrate shielding technique of stepped penetrations and brick layout scheme for valve stem extension sleeve. Aerojet Nuclear Company. Date: May 1976. INEEL index no. 761-0620-00-400-195280 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF (PER620) interior, first basement. Detail of valves and other ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF (PER-620) interior, first basement. Detail of valves and other penetrations along wall. Bricks are made of high density shielding materials. Date: March 2004. INEEL negative no. HD-41-4-2 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Cooling Tower. View of stairway to fan deck. Vents ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Cooling Tower. View of stairway to fan deck. Vents are made of redwood. Camera facing southwest toward north side of Cooling Tower. Siding is corrugated asbestos concrete. Photographer: Kirsh. Date: June 6, 1969. INEEL negative no. 69-3463 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Reactor Building (PER620). Camera in second basement near subpile ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Reactor Building (PER-620). Camera in second basement near sub-pile room (directly below reactor vessel). Door and penetrations lead to sub-pile room. Date: August 15, 1969. Photographer: Larry Page. INEEL negative no. 69-4310 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Cooling Tower contextual view. Camera facing southwest. West wing ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Cooling Tower contextual view. Camera facing southwest. West wing and north facade (rear) of Reactor Building (PER-620) is at left; Cooling Tower to right. Photographer: Kirsh. Date: November 2, 1970. INEEL negative no. 70-4913 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF (PER620) interior. Detail view of door in north wall ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF (PER-620) interior. Detail view of door in north wall of reactor bay. Camera facing north. Note tonnage weighting of hatch covers in floor. Date: May 2004. INEEL negative no. HD-41-8-2 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF (PER620) interior. Detail view of actuator platform and control ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF (PER-620) interior. Detail view of actuator platform and control rod mechanism. Camera facing easterly from floor level. Reactor pool at lower left of view. Date: March 2004. INEEL negative no. HD-41-3-3 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Reactor Building (PER620). Camera faces southeast. Concrete placement will ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Reactor Building (PER-620). Camera faces southeast. Concrete placement will leave opening for neutron camera to be installed later. Note vertical piping within rebar. Photographer: John Capek. Date: July 6, 1967. INEEL negative no. 67-3514 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Reactor Building (PER620). Aerial view of early construction. Camera ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Reactor Building (PER-620). Aerial view of early construction. Camera facing northwest. Excavation and concrete placement in two basements are underway. Note exposed lava rock. Photographer: Farmer. Date: March 22, 1965. INEEL negative no. 65-2219 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Reactor Building (PER620). Camera faces north into highbay/reactor pit ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Reactor Building (PER-620). Camera faces north into high-bay/reactor pit area. Inside from for reactor enclosure is in place. Photographer: John Capek. Date: March 15, 1967. INEEL negative no. 67-1769 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Reactor Building (PER620). Camera facing south end of high ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Reactor Building (PER-620). Camera facing south end of high bay. Vertical-lift door is being installed. Later, pneumatic seals will be installed around door. Photographer: Kirsh. Date: September 31, 1968. INEEL negative no. 68-3176 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Reactor Building (PER620) as seen from control room window ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Reactor Building (PER-620) as seen from control room window in PER-619. Photographer stood just outside window. Note exposed communication cables on desert surface. Date: July 2004. INEEL negative no. HD-41-9-3 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Cooling Tower. Camera facing southwest. Round piers will support ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Cooling Tower. Camera facing southwest. Round piers will support Tower's wood "fill" or "packing." Black-topped stack in far distance is at Idaho Chemical Processing Plant. Photographer: John Capek. Date: October 16, 1968. INEEL negative no. 68-4097 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Reactor Building (PER620). Cubicle 10 detail. Camera facing west ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Reactor Building (PER-620). Cubicle 10 detail. Camera facing west toward brick shield wall. Valve stems against wall penetrate through east wall of cubicle. Photographer: John Capek. Date: August 19, 1970. INEEL negative no. 70-3469 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

INEL BNCT Program: Volume 5, No. 9

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

Ackermann, A.L.

1991-01-01

This Bulletin presents a summary of accomplishments and highlights of the Idaho National Engineering Laboratory's (INEL) Boron Neutron Capture Therapy (BNCT) Program for September 1991. This bulletin includes information on the brain tumor and melanoma research programs, Power Burst Facility (PBF) technical support and modifications, PBF operations, and updates to the animal data charts.

75 FR 24941 - PBF Power Marketing LLC; Supplemental Notice That Initial Market-Based Rate Filing Includes...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-06

... Marketing LLC; Supplemental Notice That Initial Market- Based Rate Filing Includes Request for Blanket... of PBF Power Marketing LLC's application for market-based rate authority, with an accompanying rate... protests and interventions in lieu of paper, using the FERC Online links at http://www.ferc.gov . To...

Gas phase bio-filter for the removal of triethylamine (TEA) from air: microbial diversity analysis with reference to design parameters.

PubMed

Gandu, Bharath; Sandhya, K; Gangagni Rao, A; Swamy, Y V

2013-07-01

Biotic (packed bio-filter; PBF) and abiotic (packed filter; PF) studies were carried out on two similar 2L gas phase filters for the removal of triethylamine (TEA) at inlet concentration in the range of 250-280 ppmV. Removal efficiency (RE) of PBF remained in the range of 90-99% during the stable period of operation (170 days) whereas RE of PF dropped gradually to 10% in a span of 90 days. Five different bacterial species viz; Aeromonas sp., Alcaligenes sp., Arthrobacter sp., Klebsiella sp., and Pseudomonas sp., were identified in PBF. It was observed that diethyl amine, ethylamine and nitrate were formed as metabolites during the degradation pathway. Empty bed residence time of 20s, mass loading rate of 202.26 g/m(3)/h, space velocity of 178.82 m(3)/m(3)/h and elimination capacity of 201.52 g/m(3)/h were found to be optimum design parameters for PBF to get RE in the range of 90-99%. Copyright © 2013 Elsevier Ltd. All rights reserved.

Dynamic Network Communication in the Human Functional Connectome Predicts Perceptual Variability in Visual Illusion.

PubMed

Wang, Zhiwei; Zeljic, Kristina; Jiang, Qinying; Gu, Yong; Wang, Wei; Wang, Zheng

2018-01-01

Ubiquitous variability between individuals in visual perception is difficult to standardize and has thus essentially been ignored. Here we construct a quantitative psychophysical measure of illusory rotary motion based on the Pinna-Brelstaff figure (PBF) in 73 healthy volunteers and investigate the neural circuit mechanisms underlying perceptual variation using functional magnetic resonance imaging (fMRI). We acquired fMRI data from a subset of 42 subjects during spontaneous and 3 stimulus conditions: expanding PBF, expanding modified-PBF (illusion-free) and expanding modified-PBF with physical rotation. Brain-wide graph analysis of stimulus-evoked functional connectivity patterns yielded a functionally segregated architecture containing 3 discrete hierarchical networks, commonly shared between rest and stimulation conditions. Strikingly, communication efficiency and strength between 2 networks predominantly located in visual areas robustly predicted individual perceptual differences solely in the illusory stimulus condition. These unprecedented findings demonstrate that stimulus-dependent, not spontaneous, dynamic functional integration between distributed brain networks contributes to perceptual variability in humans. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Efectos combinados de la ampliación de la atención primaria de salud y de las transferencias condicionadas de dinero en efectivo sobre la mortalidad infantil en Brasil, 1998–2010*

PubMed Central

Guanais, Frederico C.

2015-01-01

Objetivos. Examiné los efectos combinados del acceso a la atención primaria mediante el Programa de Salud Familiar (PSF) y las transferencias condicionadas de dinero en efectivo del Programa Bolsa Familia (PBF) sobre la mortalidad infantil posneonatal (MIPN) en Brasil. Métodos. Empleé un análisis ecológico longitudinal usando datos en panel de 4 583 municipios brasileños de 1998 al 2010, con 54 253 observaciones en total. Estimé modelos de regresión de efectos fijos por mínimos cuadrados ordinarios, con la tasa de MIPN como la variable dependiente y el PSF, el PBF y sus interacciones como las principales variables independientes de interés. Resultados. La asociación de una mayor cobertura del PSF con una menor tasa de MIPN se volvió más fuerte conforme aumentaba la cobertura del PBF. En los promedios de todas las demás variables, cuando la cobertura de PBF era 25%, la MIPN predicha fue 5,24 (intervalo de confianza [IC] de 95% = 4,95, 5,53) para una cobertura del PSF de 0%, y de 3,54 (IC de 95% = 2,77, 4,31) para una cobertura del PSF de 100%. Cuando la cobertura del PBF era de 60%, la MIPN predicha fue 4,65 (IC de 95% = 4,36, 4,94) para una cobertura del PSF de 0%, y de 1,38 (IC de 95% = 0,88, 1,89) para una cobertura del PSF de 100%. Conclusiones. El efecto del PSF depende de la ampliación del PBF. Para las poblaciones empobrecidas y subatendidas, la combinación de intervenciones tanto del lado de la oferta como del lado de la demanda podría ser necesaria para mejorar los resultados en salud.

Obesity in Korean pre-adolescent school children: comparison of various anthropometric measurements based on bioelectrical impedance analysis.

PubMed

Yoo, S; Lee, S-Y; Kim, K-N; Sung, E

2006-07-01

To examine the relationships between body mass index (BMI), percentage-weight-for-height (PWH) and percentage body fat (PBF), and to compare their validity based on PBF with the BMI criteria of International Obesity Task Force (IOTF) for childhood obesity in Korean pre-adolescent school children. Statistical comparative analysis for anthropometric measures. Korean pre-adolescent children (438 boys and 454 girls, aged 8-12 years, mean BMI 19.5+/-3.4 kg/m2). Body mass index and PWH were calculated as body size indices from height and weight. Hand-to-foot bioelectrical impedance analysis (BIA) was performed to obtain PBF values, with obese children defined as PBF above 35%. Sensitivity and specificity were displayed with the gold standard of PBF, and receiver operating characteristic (ROC) curves were used to assess the performance of BMI and PWH in detecting obesity. The prevalence of obesity varied by the criteria: 18.8% by Korean BMI standards for 95 percentile, 11% by the IOTF-BMI 30 kg/m2 and 29.4% by Korean PWH cutoffs. Body mass index and PWH were significantly correlated with PBF after adjusting for age, 0.910 (P<0.01) and 0.915 (P<0.01), respectively. The sensitivity and specificity of the PWH cutoffs were 0.909 and 0.882, respectively. The local BMI 95 percentiles had lower sensitivity (0.714) and specificity (0.790). The IOTF-BMI definition showed much lower sensitivity (0.457) and higher specificity (0.990). The BMI cutoffs corresponding with the highest accuracy were smaller than IOTF-BMI 30 kg/m2 for all age groups in both boys and girls. The prevalence of obesity among Korean pre-adolescent children widely varied according to the diagnostic criteria applied. Universally recommended cutoffs for children by IOTF showed the lowest sensitivity among the criteria used, and may therefore underestimate obesity in this population.

Physicians’ and nurses’ attitudes towards performance-based financial incentives in Burundi: a qualitative study in the province of Gitega

PubMed Central

Rudasingwa, Martin; Uwizeye, Marie Rose

2017-01-01

ABSTRACT Background: Performance-based financing (PBF) was first implemented in Burundi in 2006 as a pilot programme in three provinces and was rolled out nationwide in 2010. PBF is a reform approach to improve the quality, quantity, and equity of health services and aims at achieving universal health coverage. It focuses on how to best motivate health practitioners. Objective: To elicit physicians’ and nurses’ experiences and views on how PBF influenced and helped them in healthcare delivery. Methods: A qualitative cross-sectional study was carried out among frontline health workers such as physicians and nurses. The data was gathered through individual face-to-face, in-depth, semi-structured interviews with 6 physicians and 30 nurses from February to March 2011 in three hospitals in Gitega Province. A simple framework approach and thematic analysis using a combination of manual technique and MAXQDA software guided the analysis of the interview data. Results: Overall, the interviewees felt that the PBF scheme had provided positive motivation to improve the quality of care, mainly in the structures and process of care. The utilization of health services and the relationship between health practitioners and patients also improved. The salary top-ups were recognized as the most significant impetus to increase effort in improving the quality of care. The small and sometimes delayed financial incentives paid to physicians and nurses were criticized. The findings of this study also indicate that the positive interaction between performance-based incentive schemes and other health policies is crucial in achieving comprehensive improvement in healthcare delivery. Conclusions: PBF has the potential to motivate medical staff to improve healthcare provision. The views of medical staff and the context of the area of implementation have to be taken into consideration when designing and implementing PBF schemes. PMID:28452651

'The money can be a motivator, to me a little, but mostly PBF just helps me to do better in my job.' An exploration of the motivational mechanisms of performance-based financing for health workers in Malawi.

PubMed

Lohmann, Julia; Wilhelm, Danielle; Kambala, Christabel; Brenner, Stephan; Muula, Adamson S; De Allegri, Manuela

2018-03-01

Performance-based financing (PBF) is assumed to improve health care delivery by motivating health workers to enhance their work performance. However, the exact motivational mechanisms through which PBF is assumed to produce such changes are poorly understood to date. Although PBF is increasingly recognized as a complex health systems intervention, its motivational effect for individual health workers is still often reduced to financial 'carrots and sticks' in the literature and discourse. Aiming to contribute to the development of a more comprehensive understanding of the motivational mechanisms, we explored how PBF impacted health worker motivation in the context of the Malawian Results-based Financing for Maternal and Newborn Health (RBF4MNH) Initiative. We conducted in-depth interviews with 41 nurses, medical assistants and clinical officers from primary- and secondary-level health facilities 1 and 2 years after the introduction of RBF4MNH in 2013. Six categories of motivational mechanisms emerged: RBF4MNH motivated health workers to improve their performance (1) by acting as a periodic wake-up call to deficiencies in their day-to-day practice; (2) by providing direction and goals to work towards; (3) by strengthening perceived ability to perform successfully at work and triggering a sense of accomplishment; (4) by instilling feelings of recognition; (5) by altering social dynamics, improving team work towards a common goal, but also introducing social pressure; and (6) by offering a 'nice to have' opportunity to earn extra income. However, respondents also perceived weaknesses of the intervention design, implementation-related challenges and contextual constraints that kept RBF4MNH from developing its full motivating potential. Our results underline PBF's potential to affect health workers' motivation in ways which go far beyond the direct effects of financial rewards to individuals. We strongly recommend considering all motivational mechanisms more explicitly in future PBF design to fully exploit the approach's capacity for enhancing health worker performance. © The Author 2017. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PBF Reactor Building (PER620). Cubicle 10 area in basement. Highdensity ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Reactor Building (PER-620). Cubicle 10 area in basement. High-density shielding bricks will protect personnel from radiation coming from in-pile-tube coolant and blowdown tank. Photographer: John Capek. Date: January 26, 1970. INEEL negative no. 70-348 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Reactor Building (PER620). Detail of fuel test assembly in ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Reactor Building (PER-620). Detail of fuel test assembly in preparation for test. When complete, it will fit into in-pile tube. The maximum outside diameter of which must be about 8.25 inches. Date: 1982. INEEL negative no. 82-4908 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF (PER620) interior. Detail view across top of reactor tank. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF (PER-620) interior. Detail view across top of reactor tank. Camera facing northeast. Ait tubing is cleanup equipment. Note projections from reactor structure above water level in tank. Date: May 2004. INEEL negative no. HD-41-5-1 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Cooling Tower (PER720) and its Auxiliary Building (PER625). Camera ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Cooling Tower (PER-720) and its Auxiliary Building (PER-625). Camera facing west shows east facades. Center pipe carried secondary coolant water from reactor. Building to distributor basin. Date: August 2003. INEEL negative no. HD-35-10-1 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Cooling Tower (PER720), and Auxiliary Building (PER624). Camera faces ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Cooling Tower (PER-720), and Auxiliary Building (PER-624). Camera faces north to show south facades. Oblong vertical structure at left of center is weather shield for stairway. Date: August 2003. INEEL negative no. HD-35-10-4 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

INEL BNCT Program: Volume 5, No. 9. Bulletin, September 1991

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

Ackermann, A.L.

1991-12-31

This Bulletin presents a summary of accomplishments and highlights of the Idaho National Engineering Laboratory`s (INEL) Boron Neutron Capture Therapy (BNCT) Program for September 1991. This bulletin includes information on the brain tumor and melanoma research programs, Power Burst Facility (PBF) technical support and modifications, PBF operations, and updates to the animal data charts.

PBF Control Building (PER619) floor plan and elevations. Room numbers ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Control Building (PER-619) floor plan and elevations. Room numbers and functions. Roof plans for "high" roof and rest of roof. Ebasco Services 1205-PER/PER 619-A-1. Date: July 1965. INEEL index no. 760-0619-00-205-123022 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

Infrared-to-visible conversion luminescence of Er 3+ ions in lead borate transparent glass-ceramics

NASA Astrophysics Data System (ADS)

Pisarski, Wojciech A.; Pisarska, Joanna; Lisiecki, Radosław; Grobelny, Łukasz; Dominiak-Dzik, Grażyna; Ryba-Romanowski, Witold

2009-10-01

Transparent glass-ceramics were successfully prepared during controlled heat treatment of lead borate glasses. The PbF 2 particles were dispersed into a borate glass matrix which was evidenced by X-ray diffraction analysis. The phase identification revealed that crystalline peaks can be related to the orthorhombic PbF 2 phase. Green up-conversion luminescence due to the 4S 3/2- 4I 15/2 transition of Er 3+ ions was registered. In comparison to the precursor glass the luminescence intensity was considerably higher, whereas the luminescence linewidth slightly decreased in the studied oxyfluoride transparent glass-ceramics. It indicated that a part of the trivalent erbium was incorporated into the PbF 2 crystalline phase.

[Social exclusion and health inequity: a case study based on a cash distribution program (Bolsa Família) in Brazil].

PubMed

Alves, Hayda; Escorel, Sarah

2013-12-01

To understand the impact of Bolsa Família (PBF), a federal cash transfer program, and to analyze its effects on social inclusion and exclusion processes experienced by low-income families in Brazil, with a focus on the program's potential to help overcome health inequity. This qualitative investigation used a case study methodology including observant participation, review of documents, and semi-structured interviews with current and former PBF beneficiaries, as well as with the program's local managers. The study was conducted in a small city in the state of Rio de Janeiro with a high social exclusion index and 100% coverage by the Family Health Strategy (Estratégia Saúde da Família, ESF) program. The economic, political, social, and cultural dimensions of social exclusion and inclusion processes were used to guide data collection and analysis. The program facilitated social inclusion of low-income families, especially in the economic and social dimensions. Nevertheless, it did not produce the changes desired by the beneficiaries in the work dimension. The effects on the political dimension were limited by the insufficient social engagement of the PBF. The interviewees underscored the positive effects of the ESF, which allowed them to exercise their right to health by granting them wider access to primary health care services. However, these effects appeared to be unrelated to the PBF. The results reveal effects, limitations, and challenges of the PBF towards modifying the social determinants of health inequity, in order to promote more effective changes in the social exclusion/inclusion dynamics affecting low-income families.

Foot-to-foot bioelectrical impedance analysis: a valuable tool for the measurement of body composition in children.

PubMed

Tyrrell, V J; Richards, G; Hofman, P; Gillies, G F; Robinson, E; Cutfield, W S

2001-02-01

To determine the accuracy of foot-to-foot bioelectrical impedance analysis (BIA) and anthropometric indices as measures of body composition in children. Comparison of foot-to-foot BIA and anthropometry to dual-energy X-ray absorptiometry (DEXA)-derived body composition in a multi-ethnic group of children. : Eighty-two European, NZ Maori and Pacific Island children aged 4.9-10.9 y. DEXA body composition, foot-to-foot bioelectrical impedance, height, weight, hip and waist measurements. Using a BIA prediction equation derived from our study population we found a high correlation between DEXA and BIA in the estimation of fat-free mass (FFM), fat mass (FM) and percentage body fat (PBF) (r=0.98, 0.98 and 0.94, respectively). BIA-FFM underestimated DEXA-FFM by a mean of 0.75 kg, BIA-FM overestimated DEXA-FM by a mean of 1.02 kg and BIA-PBF overestimated DEXA-PBF by a mean of 2.53%. The correlation between six anthropometric indices (body mass index (BMI), ponderal index, Chinn's weight-for-height index, BMI standard deviation score, weight-for-length index and Cole's weight-for-height index) and DEXA were also examined. The correlation of these indices with PBF was remarkably similar (r=0.85-0.87), more variable with FM (r=0.77-0.94) and poor with FFM (r=0.41-0.75). BIA correlated better than anthropometric indices in the estimation of FFM, FM and PBF. Foot-to-foot BIA is an accurate technique in the measurement of body composition.

Pulpal and Periodontal Tissues Changes Associated with Le Fort I and Sagittal Split Ramus Osteotomies: A review

PubMed Central

Lazaridis, Konstantinos; Athanasiou, Athanasios E.

2018-01-01

Introduction: Le Fort I and sagittal split ramus osteotomies are the most commonly performed orthognathic surgery procedures on the maxilla and mandible, respectively. Techniques: Despite progress in the techniques, these procedures may still be associated with morbidity, expressed as inflammation, inadequate bony union, periodontal damages or in extreme cases even total bone loss. Discussion: Through a comprehensive review of the literature, the influences of maxillary and mandibular surgery on Pulpal Blood Flow (PBF), pulp sensitivity and pulp vitality are examined. Moreover, adverse effects of maxillary surgery on tooth color and periodontal tissues are also reported. The effects had a variety of expression. Concerning maxillary surgery, some studies showed an initial increase in PBF followed by a decrease to the baseline or even lower levels after 1-3 months. Other studies found an initial decrease in PBF followed by an increase soon after. There were also studies that showed no significant PBF changes, in contrast. Conclusion: Concerning mandibular surgery, a recent study showed a decrease in PBF immediately after sagittal split ramus osteotomy. Some authors detected tooth discoloration of maxillary teeth after Le Fort I osteotomy. Root resorption and root injury were also detected, but were of minor significance. Usually, these adverse effects derive from injury of the vessels of the palatal pedicle. This pedicle should be maintained intact for the avoidance of blood flow impairments. In addition, the descending palatine artery should be protected during maxillary surgery procedures in order to maintain the highest possible blood flow on the maxillary teeth. PMID:29456771

PBF Cooling Tower (PER720). Camera faces east to show west ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Cooling Tower (PER-720). Camera faces east to show west facade. Sloped (louvered) panels in this and opposite facade allow air to enter tower and cool water falling on splash bars within. Date: August 2003. INEEL negative no. HD-35-10-2 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF detail of metal pedestrian bridge over exposed control cables, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF detail of metal pedestrian bridge over exposed control cables, which run between Control (PER-619) and Reactor Buildings (PER-620). Camera facing northwest. Southwest corner of PER-620 at upper right of view. Date: May 2004. INEEL negative no. HD-41-6-3 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Reactor Building (PER620). Camera facing north toward south facade. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Reactor Building (PER-620). Camera facing north toward south facade. Note west-wing siding on concrete block; high-bay siding of metal. Excavation and forms for signal and cable trenches proceed from building. Photographer: Kirsh. Date August 20, 1968. INEEL negative no. 68-3332 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

Power Burst Facility (PBF), PER620, contextual and oblique view. Camera ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Power Burst Facility (PBF), PER-620, contextual and oblique view. Camera facing northwest. South and east facade. The 1980 west-wing expansion is left of center bay. Concrete structure at right is PER-730. Date: March 2004. INEEL negative no. HD-41-2-3 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Control Building (PER619). Interior of control room. Control console ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Control Building (PER-619). Interior of control room. Control console in center of room. Indicator panels along walls. Window shown in ID-33-F-120 is between control panels at left. Camera facing northwest. Date: May 2004. INEEL negative no. HD-41-7-3 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Reactor Building (PER620). Camera is facing east and down ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Reactor Building (PER-620). Camera is facing east and down into canal and storage pit for fuel rod assemblies. Stainless steel liner is being applied, temporarily covered with plywood for protection. Photographer: John Capek. Date: August 29, 1969. INEEL negative no. 69-4641 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Reactor Building (PER620). Cubicle 10. Camera facing southeast. Loop ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Reactor Building (PER-620). Cubicle 10. Camera facing southeast. Loop pressurizer on right. Other equipment includes loop strained, control valves, loop piping, pressurizer interchanger, and cleanup system cooler. High-density shielding brick walls. Photographer: Kirsh. Date: November 2, 1970. INEEL negative no. 70-4908 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

Institutional Characteristics That Lead to Increased Student Success Points for Community Colleges in Texas

ERIC Educational Resources Information Center

Hanes, Carol Moore

2017-01-01

Over 40% of undergraduates in the United States attend a community college; however, fewer than 50% complete a degree or certificate within 6 years. As a result, national and state leaders have endorsed completion agenda initiatives, including performance-based funding (PBF). Texas implemented a form of PBF for the 2014-2015 Academic Year (AY)…

Er-doped lead borate glasses and transparent glass ceramics for near-infrared luminescence and up-conversion applications.

PubMed

Pisarski, Wojciech A; Goryczka, Tomasz; Pisarska, Joanna; Ryba-Romanowski, Witold

2007-03-15

Lead borate based glasses have been analyzed using Raman and infrared spectroscopy. The formation of different borate groups and the direction of BO3 <--> BO4 conversion strongly depends on the PbO- and/or PbF2-to-B2O3 ratio in chemical composition. PbF2-PbO-B2O3 based glasses containing Er3+ ions have been studied after annealing. The orthorhombic PbF2 crystallites are formed during thermal treatment, which was evidenced by X-ray diffraction analysis. Near-infrared luminescence at 1530 nm and green up-conversion at 545 nm have been registered for samples before and after annealing. The luminescence bands correspond to 4I13/2-4I15/2 and 4S3/2-4I15/2 transitions of Er3+ ions, respectively. In comparison to the precursor glasses, the luminescence intensities are higher in the studied transparent oxyfluoride glass ceramics. Simultaneously, the half-width of the luminescence lines slightly decreases. It can be the evidence that a small amount of the Er3+ ions is incorporated into the orthorhombic PbF2 phase.

Performance Based Financing and Uptake of Maternal and Child Health Services in Yobe Sate, Northern Nigeria

PubMed Central

Ashir, Garba M.; Doctor, Henry V.; Afenyadu, Godwin Y.

2013-01-01

Reported maternal and child health (MCH) outcomes in Nigeria are amongst the worst in the world, with Nigeria second only to India in the number of maternal deaths. At the national level, maternal mortality ratios (MMRs) are estimated at 630 deaths per 100,000 live births (LBs) but vary from as low as 370 deaths per 100,000 LBs in the southern states to over 1,000 deaths per 100,000 LBs in the northern states. We report findings from a performance based financing (PBF) pilot study in Yobe State, northern Nigeria aimed at improving MCH outcomes as part of efforts to find strategies aimed at accelerating attainment of Millennium Development Goals for MCH. Results show that the demand-side PBF led to increased utilization of key MCH services (antenatal care and skilled delivery) but had no significant effect on completion of child immunization using measles as a proxy indicator. We discuss these results within the context of PBF schemes and the need for a careful consideration of all the critical processes and risks associated with demand-side PBF schemes in improving MCH outcomes in the study area and similar settings. PMID:23618473

Third strike for Idaho reactor

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

Crawford, M.

Differing opinions concerning the modification of the Power Burst Facility (PBF) at Idaho Falls to turn the facility into a research and cancer treatment center are reported. Energy Secretary James Watkins convened an independent panel to examine once again the merits of converting the PBF, and the committee concluded that there is neither enough information currently available sufficiently encouraging to convert the PBF or to maintain it for this purpose. Idaho legislators have used their influence to include $13 million in the Department of Energy 1991 budget for design studies, limited reactor modifications, and maintenance. After the report of themore » committee, Secretary Watkins must decide to either ask congress to rescind the $13 million appropriated for 1991 or spend money to close down the reactor in 1992.« less

PBF Reactor Building (PER620). Camera faces south toward verticallift door, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Reactor Building (PER-620). Camera faces south toward vertical-lift door, which is closed. Note crane and its trolley positioned near door; its rails along side walls. Reactor vessel and lifting beams are positioned above reactor pit. Photographer: John Capek. Date: January 9, 1970. INEEL negative no. 70-132 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Cooling Tower under construction. Cold water basin is five ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Cooling Tower under construction. Cold water basin is five feet deep. Foundation and basin walls are reinforced concrete. Camera facing west. Pipe openings through wall in front are outlets for return flow of cool water to reactor building. Photographer: John Capek. Date: September 4, 1968. INEEL negative no. 68-3473 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Cooling Tower. Hot deck of Cooling Tower with fan ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Cooling Tower. Hot deck of Cooling Tower with fan motors in place. Fan's propeller blades (not in view) rotate within lower portion of vents. Inlet pipe is a left of view. Contractor's construction buildings in view to right. Photographer: Larry Page. Date: June 30, 1969. INEEL negative no. 69-3781 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

Washington's Community and Technical Colleges' Student Achievement Initiative: Lessons Learned since the 2012 Revision and Considerations for New Allocation Model. Research Report 16-1

ERIC Educational Resources Information Center

Washington State Board for Community and Technical Colleges, 2016

2016-01-01

In January 2012, a system-wide task force came together for a nearly year-long process of revising the community and technical college system's performance-based funding (PBF) system, the Student Achievement Initiative. This review was consistent with national experts' recommendations for continuous evaluation of PBF systems to ensure overall…

Quality of Care in Performance-Based Financing: How It Is Incorporated in 32 Programs Across 28 Countries

PubMed Central

Gergen, Jessica; Josephson, Erik; Coe, Martha; Ski, Samantha; Madhavan, Supriya; Bauhoff, Sebastian

2017-01-01

ABSTRACT Objective: To describe how quality of care is incorporated into performance-based financing (PBF) programs, what quality indicators are being used, and how these indicators are measured and verified. Methods: An exploratory scoping methodology was used to characterize the full range of quality components in 32 PBF programs, initiated between 2008 and 2015 in 28 low- and middle-income countries, totaling 68 quality tools and 8,490 quality indicators. The programs were identified through a review of the peer-reviewed and gray literature as well as through expert consultation with key donor representatives. Findings: Most of the PBF programs were implemented in sub-Saharan Africa and most were funded primarily by the World Bank. On average, PBF quality tools contained 125 indicators predominately assessing maternal, newborn, and child health and facility management and infrastructure. Indicators were primarily measured via checklists (78%, or 6,656 of 8,490 indicators), which largely (over 90%) measured structural aspects of quality, such as equipment, beds, and infrastructure. Of the most common indicators across checklists, 74% measured structural aspects and 24% measured processes of clinical care. The quality portion of the payment formulas were in the form of bonuses (59%), penalties (27%), or both (hybrid) (14%). The median percentage (of a performance payment) allocated to health facilities was 60%, ranging from 10% to 100%, while the median percentage allocated to health care providers was 55%, ranging from 20% to 80%. Nearly all of the programs included in the analysis (91%, n=29) verified quality scores quarterly (every 3 months), typically by regional government teams. Conclusion: PBF is a potentially appealing instrument to address shortfalls in quality of care by linking verified performance measurement with strategic incentives and could ultimately help meet policy priorities at the country and global levels, including the ambitious Sustainable Development Goals. The substantial variation and complexity in how PBF programs incorporate quality of care considerations suggests a need to further examine whether differences in design are associated with differential program impacts. PMID:28298338

Quality of Care in Performance-Based Financing: How It Is Incorporated in 32 Programs Across 28 Countries.

PubMed

Gergen, Jessica; Josephson, Erik; Coe, Martha; Ski, Samantha; Madhavan, Supriya; Bauhoff, Sebastian

2017-03-24

To describe how quality of care is incorporated into performance-based financing (PBF) programs, what quality indicators are being used, and how these indicators are measured and verified. An exploratory scoping methodology was used to characterize the full range of quality components in 32 PBF programs, initiated between 2008 and 2015 in 28 low- and middle-income countries, totaling 68 quality tools and 8,490 quality indicators. The programs were identified through a review of the peer-reviewed and gray literature as well as through expert consultation with key donor representatives. Most of the PBF programs were implemented in sub-Saharan Africa and most were funded primarily by the World Bank. On average, PBF quality tools contained 125 indicators predominately assessing maternal, newborn, and child health and facility management and infrastructure. Indicators were primarily measured via checklists (78%, or 6,656 of 8,490 indicators), which largely (over 90%) measured structural aspects of quality, such as equipment, beds, and infrastructure. Of the most common indicators across checklists, 74% measured structural aspects and 24% measured processes of clinical care. The quality portion of the payment formulas were in the form of bonuses (59%), penalties (27%), or both (hybrid) (14%). The median percentage (of a performance payment) allocated to health facilities was 60%, ranging from 10% to 100%, while the median percentage allocated to health care providers was 55%, ranging from 20% to 80%. Nearly all of the programs included in the analysis (91%, n=29) verified quality scores quarterly (every 3 months), typically by regional government teams. PBF is a potentially appealing instrument to address shortfalls in quality of care by linking verified performance measurement with strategic incentives and could ultimately help meet policy priorities at the country and global levels, including the ambitious Sustainable Development Goals. The substantial variation and complexity in how PBF programs incorporate quality of care considerations suggests a need to further examine whether differences in design are associated with differential program impacts. © Gergen et al.

Overweight in children and adolescents associated with TV viewing and parental weight: Project HeartBeat!

PubMed

Steffen, Lyn M; Dai, Shifan; Fulton, Janet E; Labarthe, Darwin R

2009-07-01

Parental obesity and TV viewing are risk factors for childhood obesity. This study assessed the association of children's TV viewing and computer use with body mass and examined whether parental weight status modified the association. Cross-sectional associations of parental weight status, hours of TV viewing and computer use, and children's body composition were studied in a subsample of 526 black and nonblack children, aged 8, 11, and 14 years at baseline, enrolled in Project HeartBeat!, a longitudinal study of cardiovascular disease risk factors, 1991-1995. BMI, fat-free mass (FFM), and percent body fat (PBF) were calculated from children's body composition measured at baseline. Children's TV viewing and computer use habits and parental height and weight were self-reported. Multivariate regression analysis was used in assessing inter-relations of parental weight status and child's TV viewing and computer use habits with BMI, FFM, PBF, and risk for overweight status (BMI > or =85th percentile), adjusting for age, gender, race, and Tanner stage. Children of one or two overweight/obese parents watched an average of 22+/-6 minutes or 30+/-11 minutes more TV per day than children of normal-weight parents, respectively (both p<0.01). In multivariate regression analyses, BMI and PBF increased significantly by 0.42 kg/m(2) and 1.14% (both p<0.001), respectively, for each hour of TV watched among children with overweight parents, but not for those with normal-weight parents (p(interaction)<0.05). Similar results were observed for total screen time. These study findings are consistent with a genetic contribution of parental weight; however, overweight/obese parents may also exhibit behavior patterns that negatively influence children's TV viewing and have an impact on child overweight status. The effect of parental BMI on children's BMI may have both a genetic and an environmental linkage.

Prescribing patterns and associated factors of antibiotic prescription in primary health care facilities of Kumbo East and Kumbo West Health Districts, North West Cameroon

PubMed Central

Chem, Elvis Dzelamonyuy; Anong, Damian Nota; Akoachere, Jane-Francis K. T.

2018-01-01

Background Inappropriate use of antibiotics is a global public health challenge and has been associated with antibiotic resistance. WHO reports show that efforts to promote rational antibiotic use in developing countries are poor. With the growing number of infections with antibiotic resistant bacteria, rational drug use becomes imperative and studies that promote rational drug use are highly necessary. Considering this, we investigated prescribing patterns and predictors of antibiotic prescription in primary health care facilities in Kumbo East (KE) and Kumbo West (KW) health districts in North West Cameroon, to contribute data which could influence policy on antibiotic use. Methods and findings A cross sectional retrospective study was conducted from April 2014 to April 2015 in 26 randomly selected primary care facilities. Questionnaires were administered to 59 antibiotic prescribers to determine factors that predict antibiotic prescribing. Data on antibiotic prescription were collected by review of consultation registers. Prescription rates and demographics, prescriber and institution factors were analyzed using ANOVA. The best predictor of prescription was determined using multiple linear regression analysis. Results A total of 30,096 prescriptions were reviewed. Overall antibiotic prescription rate was 36.71%, with a mean of 1.14 antibiotics prescribed per patient. Amoxicillin was the most prescribed (29.9%). The most prevalent indications for prescribing were respiratory tract infections (21.27%). All antibiotics prescribed were broad-spectrum. Antibiotics were prescribed for patients with malaria and also in situations where diagnosis was uncertain. Prescribing by generic name was 98.36% while 99.87% was from Essential Drug List. Use of laboratory results, patient turnout and Performance Based Financing (PBF) were significantly associated with antibiotic prescribing rates (p < 0.05). PBF moderated prescribing. Conclusion There was misuse of antibiotics in primary care facilities in study area. We recommend all primary care health facilities in study area to be included in the PBF scheme and that prescribing should only be done by physicians as the have adequate training. PMID:29505584

A study on the implementation fidelity of the performance-based financing policy in Burkina Faso after 12 months.

PubMed

Bodson, Oriane; Barro, Ahmed; Turcotte-Tremblay, Anne-Marie; Zanté, Nestor; Somé, Paul-André; Ridde, Valéry

2018-01-01

Performance-based financing (PBF) in the health sector has recently gained momentum in low- and middle-income countries (LMICs) as one of the ways forward for achieving Universal Health Coverage. The major principle underlying PBF is that health centers are remunerated based on the quantity and quality of services they provide. PBF has been operating in Burkina Faso since 2011, and as a pilot project since 2014 in 15 health districts randomly assigned into four different models, before an eventual scale-up. Despite the need for expeditious documentation of the impact of PBF, caution is advised to avoid adopting hasty conclusions. Above all, it is crucial to understand why and how an impact is produced or not. Our implementation fidelity study approached this inquiry by comparing, after 12 months of operation, the activities implemented against what was planned initially and will make it possible later to establish links with the policy's impacts. Our study compared, in 21 health centers from three health districts, the implementation of activities that were core to the process in terms of content, coverage, and temporality. Data were collected through document analysis, as well as from individual interviews and focus groups with key informants. In the first year of implementation, solid foundations were put in place for the intervention. Even so, implementation deficiencies and delays were observed with respect to certain performance auditing procedures, as well as in payments of PBF subsidies, which compromised the incentive-based rationale to some extent. Over next months, efforts should be made to adjust the intervention more closely to context and to the original planning.

Performance-based financing to increase utilization of maternal health services: Evidence from Burkina Faso.

PubMed

Steenland, Maria; Robyn, Paul Jacob; Compaore, Philippe; Kabore, Moussa; Tapsoba, Boukary; Zongo, Aloys; Haidara, Ousmane Diadie; Fink, Günther

2017-12-01

Performance-based financing (PBF) programs are increasingly implemented in low and middle-income countries to improve health service quality and utilization. In April 2011, a PBF pilot program was launched in Boulsa, Leo and Titao districts in Burkina Faso with the objective of increasing the provision and quality of maternal health services. We evaluate the impact of this program using facility-level administrative data from the national health management information system (HMIS). Primary outcomes were the number of antenatal care visits, the proportion of antenatal care visits that occurred during the first trimester of pregnancy, the number of institutional deliveries and the number of postnatal care visits. To assess program impact we use a difference-in-differences approach, comparing changes in health service provision post-introduction with changes in matched comparison areas. All models were estimated using ordinary least squares (OLS) regression models with standard errors clustered at the facility level. On average, PBF facilities had 2.3 more antenatal care visits (95% CI [0.446-4.225]), 2.1 more deliveries (95% CI [0.034-4.069]) and 9.5 more postnatal care visits (95% CI [6.099, 12.903]) each month after the introduction of PBF. Compared to the service provision levels prior to the interventions, this implies a relative increase of 27.7 percent for ANC, of 9.2 percent for deliveries, and of 118.7 percent for postnatal care. Given the positive results observed during the pre-pilot period and the limited resources available in the health sector, the PBF program in Burkina Faso may be a low-cost, high impact intervention to improve maternal and child health.

Examining the Associations among Fibrocystic Breast Change, Total Lean Mass, and Percent Body Fat.

PubMed

Chen, Yuan-Yuei; Fang, Wen-Hui; Wang, Chung-Ching; Kao, Tung-Wei; Chang, Yaw-Wen; Yang, Hui-Fang; Wu, Chen-Jung; Sun, Yu-Shan; Chen, Wei-Liang

2018-06-15

Fibrocystic breast change (FBC) is extremely common and occurrs in 90% of women during their lives. The association between body composition and risk of breast cancer is well established. We hypothesized that the effect might exist during the development of FBC. Our aim was to examine the relationships of total lean mass (TLM) and percent body fat (PBF) with FBC in a general female population. In total, 8477 female subjects aged 20 years or older were enrolled in the study at the Tri-Service General Hospital in Taiwan from 2011 to 2016. Comprehensive examinations including biochemical data, measurements of body composition and breast ultrasound were performed. PBF was positively associated with the presence of FBC (OR = 1.039, 95%CI: 1.018-1.060), and TLM showed the opposite result (OR = 0.893, 95%CI: 0.861-0.926). Condition of metabolic syndrome (MetS), diabetes (DM) and fatty liver modified the association between PBF and FBC (P < 0.001, P = 0.032 and P = 0.007, respectively). Female subjects diagnosed with MetS, DM, and fatty liver had higher risk of developing FBC than control subjects (OR = 1.110, 95%CI: 1.052-1.171; OR = 1.144, 95%CI: 1.024-1.278; OR = 1.049, 95%CI: 1.019, 1.080). Those with higher PBF (for highest quartile versus lowest, OR = 2.451, 95%CI: 1.523-3.944) or lower TLM (for highest quartile versus lowest, OR = 0.279, 95%CI: 0.171-0.455) had increased risk of developing FBC. In conclusion, increased PBF and reduced TLM were likely to predict the risk of the presence of FBC in a general female population.

PBF Reactor Building (PER620). Camera is in cab of electricpowered ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Reactor Building (PER-620). Camera is in cab of electric-powered rail crane and facing east. Reactor pit and storage canal have been shaped. Floors for wings on east and west side are above and below reactor in view. Photographer: Larry Page. Date: August 23, 1967. INEEL negative no. 67-4403 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

Twelve months of implementation of health care performance‐based financing in Burkina Faso: A qualitative multiple case study

PubMed Central

Yaogo, Maurice; Zongo, Sylvie; Somé, Paul‐André; Turcotte‐Tremblay, Anne‐Marie

2017-01-01

Abstract To improve health services' quantity and quality, African countries are increasingly engaging in performance‐based financing (PBF) interventions. Studies to understand their implementation in francophone West Africa are rare. This study analysed PBF implementation in Burkina Faso 12 months post‐launch in late 2014. The design was a multiple and contrasted case study involving 18 cases (health centres). Empirical data were collected from observations, informal (n = 224) and formal (n = 459) interviews, and documents. Outside the circle of persons trained in PBF, few in the community had knowledge of it. In some health centres, the fact that staff were receiving bonuses was intentionally not announced to populations and community leaders. Most local actors thought PBF was just another project, but the majority appreciated it. There were significant delays in setting up agencies for performance monitoring, auditing, and contracting, as well as in the payment. The first audits led rapidly to coping strategies among health workers and occasionally to some staging beforehand. No community‐based audits had yet been done. Distribution of bonuses varied from one centre to another. This study shows the importance of understanding the implementation of public health interventions in Africa and of uncovering coping strategies. PMID:28671285

Blood-flow change and recovery of sensibility in the maxillary dental pulp during and after maxillary distraction: a pilot study.

PubMed

Harada, Kiyoshi; Sato, Masaru; Omura, Ken

2004-11-01

To examine the change in blood flow and recovery of sensibility in the maxillary dental pulp during and after maxillary distraction. The subjects included 5 patients undergoing high Le Fort I osteotomy and maxillary distraction (D-group) and a reference group of 14 patients who underwent a common single-segment Le Fort I osteotomy, 1-stage maxillary advancement, and mandibular setback surgery (C-group). Eleven (D-group) and 54 (C-group) maxillary incisors were assessed preoperatively and at 1-7 days, 14 days, and 3 months postoperatively. Pulpal blood flow (PBF) was measured by laser Doppler flowmetry, and pulpal sensibility (PS) was investigated by electrodiagnostics. From postoperative days 1 to 5 (the latency period), the PBF tended to be higher in the D-group than in the C-group. From day 6 to 3 months postoperatively (during and after maxillary distraction), the PBF values of the 2 groups were similar. The PS remained negative up to 14 days postoperatively in both groups. However, at 3 months after the operation, a higher proportion (90.9%) of teeth in the D-group was positive for PS. These results suggest that maxillary distraction is a favorable technique for maintenance of PBF and recovery of PS in the maxillary teeth after surgery.

PBF Reactor Building (PER620). Camera faces south along west wall. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Reactor Building (PER-620). Camera faces south along west wall. Gap between native lava rock and concrete basement walls is being backfilled and compacted. Wire mesh protects workers from falling rock. Note penetrations for piping that will carry secondary coolant water to Cooling Tower. Photographer: Holmes. Date: June 15, 1967. INEEL negative no. 67-3665 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Cooling Tower and it Auxiliary Building (PER624) to left ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Cooling Tower and it Auxiliary Building (PER-624) to left of tower. Camera facing west and the east louvered face of the tower. Details include secondary coolant water riser piping and flow control valves (butterfly valves) to distribute water evenly to all sections of tower. Photographer: Holmes. Date: May, 20, 1970. INEEL negative no. 70-2322 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

OPAQUE11 Is a Central Hub of the Regulatory Network for Maize Endosperm Development and Nutrient Metabolism[OPEN

PubMed Central

Feng, Fan; Qi, Weiwei; Lv, Yuanda; Yan, Shumei; Xu, Liming; Yang, Wenyao; Yuan, Yue; Chen, Yihan

2018-01-01

Maize (Zea mays) endosperm is a primary tissue for nutrient storage and is highly differentiated during development. However, the regulatory networks of endosperm development and nutrient metabolism remain largely unknown. Maize opaque11 (o11) is a classic seed mutant with a small and opaque endosperm showing decreased starch and protein accumulation. We cloned O11 and found that it encodes an endosperm-specific bHLH transcription factor (TF). Loss of function of O11 significantly affected transcription of carbohydrate/amino acid metabolism and stress response genes. Genome-wide binding site analysis revealed 9885 O11 binding sites distributed over 6033 genes. Using chromatin immunoprecipitation sequencing (ChIP-seq) coupled with RNA sequencing (RNA-seq) assays, we identified 259 O11-modulated target genes. O11 was found to directly regulate key TFs in endosperm development (NKD2 and ZmDOF3) and nutrient metabolism (O2 and PBF). Moreover, O11 directly regulates cyPPDKs and multiple carbohydrate metabolic enzymes. O11 is an activator of ZmYoda, suggesting its regulatory function through the MAPK pathway in endosperm development. Many stress-response genes are also direct targets of O11. In addition, 11 O11-interacting proteins were identified, including ZmIce1, which coregulates stress response targets and ZmYoda with O11. Therefore, this study reveals an endosperm regulatory network centered around O11, which coordinates endosperm development, metabolism and stress responses. PMID:29436476

Thermographic Measurements of the Commercial Laser Powder Bed Fusion Process at NIST

PubMed Central

Lane, Brandon; Moylan, Shawn; Whitenton, Eric; Ma, Li

2016-01-01

Measurement of the high-temperature melt pool region in the laser powder bed fusion (L-PBF) process is a primary focus of researchers to further understand the dynamic physics of the heating, melting, adhesion, and cooling which define this commercially popular additive manufacturing process. This paper will detail the design, execution, and results of high speed, high magnification in-situ thermographic measurements conducted at the National Institute of Standards and Technology (NIST) focusing on the melt pool region of a commercial L-PBF process. Multiple phenomena are observed including plasma plume and hot particle ejection from the melt region. The thermographic measurement process will be detailed with emphasis on the ‘measurability’ of observed phenomena and the sources of measurement uncertainty. Further discussion will relate these thermographic results to other efforts at NIST towards L-PBF process finite element simulation and development of in-situ sensing and control methodologies. PMID:28058036

Thermographic Measurements of the Commercial Laser Powder Bed Fusion Process at NIST.

PubMed

Lane, Brandon; Moylan, Shawn; Whitenton, Eric; Ma, Li

2016-01-01

Measurement of the high-temperature melt pool region in the laser powder bed fusion (L-PBF) process is a primary focus of researchers to further understand the dynamic physics of the heating, melting, adhesion, and cooling which define this commercially popular additive manufacturing process. This paper will detail the design, execution, and results of high speed, high magnification in-situ thermographic measurements conducted at the National Institute of Standards and Technology (NIST) focusing on the melt pool region of a commercial L-PBF process. Multiple phenomena are observed including plasma plume and hot particle ejection from the melt region. The thermographic measurement process will be detailed with emphasis on the 'measurability' of observed phenomena and the sources of measurement uncertainty. Further discussion will relate these thermographic results to other efforts at NIST towards L-PBF process finite element simulation and development of in-situ sensing and control methodologies.

Tracking Global Fund HIV/AIDS resources used for sexual and reproductive health service integration: case study from Ethiopia.

PubMed

Mookherji, Sangeeta; Ski, Samantha; Huntington, Dale

2015-05-27

The Global Fund to Fight AIDS, Tuberculosis & Malaria (GF) strives for high value for money, encouraging countries to integrate synergistic services and systems strengthening to maximize investments. The GF needs to show how, and how much, its grants support more than just HIV/AIDS, TB and malaria. Sexual and Reproductive Health (SRH) has been part of HIV/AIDS grants since 2007. Previous studies showed the GF PBF system does not allow resource tracking for SRH integration within HIV/AIDS grants. We present findings from a resource tracking case study using primary data collected at country level. Ethiopia was the study site. We reviewed data from four HIV/AIDS grants from January 2009-June 2011 and categorized SDAs and activities as directly, indirectly, or not related to SRH integration. Data included: GF PBF data; financial, performance, in-depth interview and facility observation data from Ethiopia. All HIV/AIDS grants in Ethiopia support SRH integration activities (12-100%). Using activities within SDAs, expenditures directly supporting SRH integration increased from 25% to 66% for the largest HIV/AIDS grant, and from 21% to 34% for the smaller PMTCT-focused grant. Using SDAs to categorize expenditures underestimated direct investments in SRH integration; activity-based categorization is more accurate. The important finding is that primary data collection could not resolve the limitations in using GF GPR data for resource tracking. The remedy is to require existing activity-based budgets and expenditure reports as part of PBF reporting requirements, and make them available in the grant portfolio database. The GF should do this quickly, as it is a serious shortfall in the GF guiding principle of transparency. Showing high value for money is important for maximizing impact and replenishments. The Global Fund should routinely track HIV/AIDs grant expenditures to disease control, service integration, and overall health systems strengthening. The current PBF system will not allow this. Real-time expenditure analysis could be achieved by integrating existing activity-based financial data into the routine PBF system. The GF's New Funding Model and the 2012-2016 strategy present good opportunities for over-hauling the PBF system to improve transparency and allow the GF to monitor and maximize value for money.

Prenatal Stress, Methylation in Inflammation-Related Genes, and Adiposity Measures in Early Childhood: the Programming Research in Obesity, Growth Environment and Social Stress Cohort Study.

PubMed

Wu, Shaowei; Gennings, Chris; Wright, Rosalind J; Wilson, Ander; Burris, Heather H; Just, Allan C; Braun, Joseph M; Svensson, Katherine; Zhong, Jia; Brennan, Kasey J M; Dereix, Alexandra; Cantoral, Alejandra; Schnaas, Lourdes; Téllez-Rojo, Martha Maria; Wright, Robert O; Baccarelli, Andrea A

2018-01-01

Maternal stress during pregnancy may influence childhood growth and adiposity, possibly through immune/inflammatory programming. We investigated whether exposure to prenatal stress and methylation in inflammation-related genes were associated with childhood adiposity in 424 mother-child pairs in Mexico City, Mexico. A stress index was created based on four prenatally administered stress-related scales (Exposure to Violence, Crisis in Family Systems, State-Trait Anxiety Inventory, and Edinburgh Postnatal Depression Scale). We measured weight, height, body fat mass (BFM), percentage body fat (PBF), and waist circumference in early childhood (age range, 4-6 years). Body mass index (BMI) z scores were calculated according to World Health Organization standards. DNA methylation in gene promoters of tumor necrosis factor α, interleukin 8, and interleukin 6 (IL6) in umbilical cord blood were determined by pyrosequencing. An interquartile range increase in stress index (27.3) was associated with decreases of 0.14 unit in BMI z score (95% confidence interval [CI] = -0.28 to -0.005), 5.6% in BFM (95% CI = -9.7 to -1.4), 3.5% in PBF (95% CI = -6.3 to -0.5), and 1.2% in waist circumference (95% CI = -2.4 to -0.04) in multivariable-adjusted models. An interquartile range increase in IL6 methylation (3.9%) was associated with increases of 0.23 unit in BMI z score (95% CI = 0.06-0.40), 8.1% (95% CI = 2.3-14.3) in BFM, 5.5% (95% CI = 1.7-9.5) in PBF, and 1.7% (95% CI = 0.2-3.3) in waist circumference. Prenatal stress was associated with decreased childhood adiposity, whereas cord blood IL6 methylation was associated with increased childhood adiposity in Mexican children.

PBF Cooling Tower. View from highbay roof of Reactor Building ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Cooling Tower. View from high-bay roof of Reactor Building (PER-620). Camera faces northwest. East louvered face has been installed. Inlet pipes protrude from fan deck. Two redwood vents under construction at top. Note piping, control, and power lines at sub-grade level in trench leading to Reactor Building. Photographer: Kirsh. Date: June 6, 1969. INEEL negative no. 69-3466 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Reactor Building (PER620). Camera facing southeast in second basement. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Reactor Building (PER-620). Camera facing southeast in second basement. Round form and reinforcing steel surround reactor vessel pit, which will be heavily shielded by several feet of concrete. Block-out is for door to sub-pile room. Rectangular form and rebar beyond pit is for canal wall. Photographer: John Capek. Date: March 10, 1967. INEEL negative no. 67-1643 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

Single-Event Effect Testing of the Linear Technology LTC6103HMS8#PBF Current Sense Amplifier

NASA Technical Reports Server (NTRS)

Yau, Ka-Yen; Campola, Michael J.; Wilcox, Edward

2016-01-01

The LTC6103HMS8#PBF (henceforth abbreviated as LTC6103) current sense amplifier from Linear Technology was tested for both destructive and non-destructive single-event effects (SEE) using the heavy-ion cyclotron accelerator beam at Lawrence Berkeley National Laboratory (LBNL) Berkeley Accelerator Effects (BASE) facility. During testing, the input voltages and output currents were monitored to detect single event latch-up (SEL) and single-event transients (SETs).

Twelve months of implementation of health care performance-based financing in Burkina Faso: A qualitative multiple case study.

PubMed

Ridde, Valéry; Yaogo, Maurice; Zongo, Sylvie; Somé, Paul-André; Turcotte-Tremblay, Anne-Marie

2018-01-01

To improve health services' quantity and quality, African countries are increasingly engaging in performance-based financing (PBF) interventions. Studies to understand their implementation in francophone West Africa are rare. This study analysed PBF implementation in Burkina Faso 12 months post-launch in late 2014. The design was a multiple and contrasted case study involving 18 cases (health centres). Empirical data were collected from observations, informal (n = 224) and formal (n = 459) interviews, and documents. Outside the circle of persons trained in PBF, few in the community had knowledge of it. In some health centres, the fact that staff were receiving bonuses was intentionally not announced to populations and community leaders. Most local actors thought PBF was just another project, but the majority appreciated it. There were significant delays in setting up agencies for performance monitoring, auditing, and contracting, as well as in the payment. The first audits led rapidly to coping strategies among health workers and occasionally to some staging beforehand. No community-based audits had yet been done. Distribution of bonuses varied from one centre to another. This study shows the importance of understanding the implementation of public health interventions in Africa and of uncovering coping strategies. © 2017 The Authors. The International Journal of Health Planning and Management Published by John Wiley & Sons Ltd.

A Metallurgical Evaluation of the Powder-Bed Laser Additive Manufactured 4140 Steel Material

NASA Astrophysics Data System (ADS)

Wang, Wesley; Kelly, Shawn

2016-03-01

Using laser powder bed fusion (PBF-L) additive manufacturing (AM) process for steel or iron powder has been attempted for decades. This work used a medium carbon steel (AISI 4140) powder to explore the feasibility of AM. The high carbon equivalent of 4140 steel (CEIIW ≈ 0.83) has a strong tendency toward cold cracking. As such, the process parameters must be carefully controlled to ensure the AM build quality. Through an orthogonally designed experimental matrix, a laser-welding procedure was successfully developed to produce 4140 steel AM builds with no welding defects. In addition, the microstructure and micro-cleanliness of the as-welded PBF-L AM builds were also examined. The results showed an ultra-fine martensite lath structure and an ultra-clean internal quality with minimal oxide inclusion distribution. After optimizing the PBF-L AM process parameters, including the laser power and scan speed, the as-welded AM builds yielded an average tensile strength higher than 1482 MPa and an average 33 J Charpy V-notch impact toughness at -18°C. The surface quality, tensile strength, and Charpy V-notch impact toughness of AM builds were comparable to the wrought 4140 steel. The excellent mechanical properties of 4140 steel builds created by the PBF-L AM AM process make industrial production more feasible, which shows great potential for application in the aerospace, automobile, and machinery industries.

Performance-based financing contributes to the resilience of health services affected by the Liberian Ebola outbreak

PubMed Central

Mapleh, L.; Ade, S.; Harries, A. D.; Bhat, P.; Kateh, F.; Dahn, B.

2017-01-01

Setting: The Liberian counties of Bong, with performance-based financing (PBF) for all 36 public primary-care facilities, and Margibi, with no PBF for its 24 public primary-care facilities. Objective: To compare whether specific maternal and child health indicators changed in the two counties during the pre-Ebola (2013), Ebola (2014) and post-Ebola (2015) disease outbreak periods from July to September each year. Design: This was a cross-sectional study. Results: For pregnant women, the numbers of antenatal visits, intermittent preventive malaria treatments, human immunodeficiency virus (HIV) tests and facility-based births with skilled attendants all fell during the Ebola period, with decreases being significantly more marked in Margibi County. Apart from HIV testing, which remained low in both counties, these indicators increased in the post-Ebola period, with increases significantly more marked in Bong than in Margibi. The number of childhood immunisations decreased significantly in Bong in the Ebola period compared with the pre-Ebola period, but increased to above pre-Ebola levels in the post-Ebola period. There were markedly larger decreases in childhood immunisations in Margibi County during the Ebola period, which remained significantly lower in the post-Ebola period compared with Bong County. Conclusion: In a PBF-supported county, selected maternal and childhood health indicators showed less deterioration during Ebola and better recovery post-Ebola than in a non-PBF-supported county. PMID:28744447

Performance-based financing contributes to the resilience of health services affected by the Liberian Ebola outbreak.

PubMed

Mussah, V G; Mapleh, L; Ade, S; Harries, A D; Bhat, P; Kateh, F; Dahn, B

2017-06-21

Setting: The Liberian counties of Bong, with performance-based financing (PBF) for all 36 public primary-care facilities, and Margibi, with no PBF for its 24 public primary-care facilities. Objective: To compare whether specific maternal and child health indicators changed in the two counties during the pre-Ebola (2013), Ebola (2014) and post-Ebola (2015) disease outbreak periods from July to September each year. Design: This was a cross-sectional study. Results: For pregnant women, the numbers of antenatal visits, intermittent preventive malaria treatments, human immunodeficiency virus (HIV) tests and facility-based births with skilled attendants all fell during the Ebola period, with decreases being significantly more marked in Margibi County. Apart from HIV testing, which remained low in both counties, these indicators increased in the post-Ebola period, with increases significantly more marked in Bong than in Margibi. The number of childhood immunisations decreased significantly in Bong in the Ebola period compared with the pre-Ebola period, but increased to above pre-Ebola levels in the post-Ebola period. There were markedly larger decreases in childhood immunisations in Margibi County during the Ebola period, which remained significantly lower in the post-Ebola period compared with Bong County. Conclusion: In a PBF-supported county, selected maternal and childhood health indicators showed less deterioration during Ebola and better recovery post-Ebola than in a non-PBF-supported county.

Slow neutron total cross-section, transmission and reflection calculation for poly- and mono-NaCl and PbF2 crystals

NASA Astrophysics Data System (ADS)

Mansy, Muhammad S.; Adib, M.; Habib, N.; Bashter, I. I.; Morcos, H. N.; El-Mesiry, M. S.

2016-10-01

A detailed study about the calculation of total neutron cross-section, transmission and reflection from crystalline materials was performed. The developed computer code is approved to be sufficient for the required calculations, also an excellent agreement has been shown when comparing the code results with the other calculated and measured values. The optimal monochromator and filter parameters were discussed in terms of crystal orientation, mosaic spread, and thickness. Calculations show that 30 cm thick of PbF2 poly-crystal is an excellent cold neutron filter producing neutron wavelengths longer than 0.66 nm needed for the investigation of magnetic structure experiments. While mono-crystal filter PbF2 cut along its (1 1 1), having mosaic spread (η = 0.5°) and thickness 10 cm can only transmit thermal neutrons of the desired wavelengths and suppress epithermal and γ-rays forming unwanted background, when it is cooled to liquid nitrogen temperature. NaCl (2 0 0) and PbF2 (1 1 1) monochromator crystals having mosaic spread (η = 0.5°) and thickness 10 mm shows high neutron reflectivity for neutron wavelengths (λ = 0.114 nm and λ = 0.43 nm) when they used as a thermal and cold neutron monochromators respectively with very low contamination from higher order reflections.

Trend of Body Compositions with Aging among Chinese Adolescents, Adults and Elders.

PubMed

Xu, T; Zhu, G; Han, S

2015-12-01

Rare reports can be found about sex- and age-specific body composition survey among Chinese population. The aim of this study is to explore the change of sex-specific body compositions with aging among Chinese adolescents, adults and elders. In a large-scale population survey about physiological constants and health conditions, 75,714 subjects who aged from 8 to 80 completed body composition array. Body mass index (BMI), percentage body fat (PBF), water percentage of body weight (WPBW), water percentage of lean body mass (WPLBM), fat-free mass index (FFMI) and basic metabolic rate were examined with Biodynamics BI-310 body composition analyzer. General obesity is defined as BMI equal to or greater than 28 kg/m2. The prevalence rates of general obesity were 9.4% for males and 7.7% for females respectively. With aging, PBF and FMI showed a U-shape curvilinear trend and WPBW showed a parabolic trend for males. At same age group: 18-19 age groups, PBF and FMI declined to the valley and WPBW rose to the peak. For females, PBF, WPBW and FMI changed in a linear trend. The values of WPLBM and FFMI showed same curvilinear trend for two genders. WPLBM changed in a U-shape trend and touched the valley in twenties for males and in 18-19 age groups for females. The value of FFMI was larger for older age groups in the younger generation but smaller in the older generation. A parabolic trend peaking was seen in the thirties for males and in the forties for females. Regression models with age as independent variable showed that the larger rate of increase of PBF and smaller rates of increase for WPBM and WPLBM with aging for males. This study presents detailed data about sex-specific body composition conditions. Different change trend with aging was found about body composition conditions.

Application of receiver operating characteristic curve in the assessment of the value of body mass index, waist circumference and percentage of body fat in the Diagnosis of Polycystic Ovary Syndrome in childbearing women.

PubMed

Dou, Pan; Ju, Huiyan; Shang, Jing; Li, Xueying; Xue, Qing; Xu, Yang; Guo, Xiaohui

2016-08-24

There are various parameters to analyze obesity, however, no standard reference to predict, screen or diagnose PCOS with various obesity parameters has been established, and the accuracy of these parameters still needs to be studied.This study was to use the receiver operating characteristic (ROC) curve to explore the different values of three obesity parameters, body mass index (BMI), waist circumference (WC) and percentage of body fat (PBF) in the diagnosis of polycystic ovary syndrome (PCOS) in Chinese childbearing women. Three hundred patients who were diagnosed with PCOS at Center of Reproductive Medicine and Genetics of Peking University First Hospital were enrolled in this study, and 110 healthy age-matched women were enrolled as controls. The characteristics of BMI, WC and PBF in PCOS patients were analyzed. Compared with the control group, all the three obesity parameters were significantly increased in PCOS group. In terms of ROC area under the curve, WC > PBF > BMI, and they were all significantly different from those of the control. At a cut-off point of 80.5 cm, WC has a sensitivity of 73.6 % and a specificity of 85 % in diagnosis of PCOS; At a cut-off point of 29 %, PBF has a sensitivity of 88.2 % and a specificity of 57.7 % in diagnosis of PCOS; and at a cut-off point of 26.6 kg/m(2), BMI has a sensitivity of 54.5 % and a specificity of 98 % in diagnosis of PCOS. WC, BMI and PBF are valuable in screening and diagnosis of PCOS in Chinese childbearing women. PBF can be used to screen PCOS as it has a better sensitivity, while BMI can be used in the diagnosis of PCOS as it has a better specificity.

Setting performance-based financing in the health sector agenda: a case study in Cameroon.

PubMed

Sieleunou, Isidore; Turcotte-Tremblay, Anne-Marie; Fotso, Jean-Claude Taptué; Tamga, Denise Magne; Yumo, Habakkuk Azinyui; Kouokam, Estelle; Ridde, Valery

2017-08-01

More than 30 countries in sub-Saharan Africa have introduced performance-based financing (PBF) in their healthcare systems. Yet, there has been little research on the process by which PBF was put on the national policy agenda in Africa. This study examines the policy process behind the introduction of PBF program in Cameroon. The research is an explanatory case study using the Kingdon multiple streams framework. We conducted a document review and 25 interviews with various types of actors involved in the policy process. We conducted thematic analysis using a hybrid deductive-inductive approach for data analysis. By 2004, several reports and events had provided evidence on the state of the poor health outcomes and health financing in the country, thereby raising awareness of the situation. As a result, decision-makers identified the lack of a suitable health financing policy as an important issue that needed to be addressed. The change in the political discourse toward more accountability made room to test new mechanisms. A group of policy entrepreneurs from the World Bank, through numerous forms of influence (financial, ideational, network and knowledge-based) and building on several ongoing reforms, collaborated with senior government officials to place the PBF program on the agenda. The policy changes occurred as the result of two open policy windows (i.e. national and international), and in both instances, policy entrepreneurs were able to couple the policy streams to effect change. The policy agenda of PBF in Cameroon underlined the importance of a perceived crisis in the policy reform process and the advantage of building a team to carry forward the policy process. It also highlighted the role of other sources of information alongside scientific evidence (eg.: workshop and study tour), as well as the role of previous policies and experiences, in shaping or influencing respectively the way issues are framed and reformers' actions and choices.

The effect of oxygen content during an initial sustained inflation on heart rate in asphyxiated near-term lambs.

PubMed

Sobotka, K S; Ong, T; Polglase, G R; Crossley, K J; Moss, T J M; Hooper, S B

2015-07-01

At birth, an initial sustained inflation (SI) uniformly aerates the lungs, increases arterial oxygenation and rapidly improves circulatory recovery in asphyxiated newborns. We hypothesised that lung aeration, in the absence of an increase in arterial oxygenation, can increase heart rate (HR) in asphyxiated near-term lambs. Lambs were delivered and instrumented at 139±2 days of gestation. Asphyxia was induced by umbilical cord clamping and then delaying the onset of ventilation until mean carotid arterial pressures (CAPs) had decreased <20 mm Hg. Lambs then received a single 30-s SI using nitrogen (N2; n=6), 5% oxygen (O2; n=6), 21% O2 (n=6) or 100% O2 (n=6) followed by ventilation in air for 30 min. HR, CAP and pulmonary blood flow (PBF) were continuously recorded. HR and PBF increased more quickly in lambs resuscitated with 100% and 21% O2 than with 5% O2 or N2. HR and PBF recovery in the 5% O2 group was delayed relative to all other oxygen SI groups. HR in 5%, 21% and 100% O2 groups reached 100 bpm before the SI was complete. HR and PBF in the N2 group did not increase until 10 s after the SI was completed and ventilation was initiated with air. CAP tended to increase quicker in all O2 groups than in N2 group. Oxygen content during an SI is important for circulatory recovery in asphyxiated lambs. This increase in HR is likely driven by the increase in PBF and venous return to the heart. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

PBF Reactor Building (PER620). In subpile room, camera faces southeast ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Reactor Building (PER-620). In sub-pile room, camera faces southeast and looks up toward bottom of reactor vessel. Upper assembly in center of view is in-pile tube as it connects to vessel. Lower lateral constraints and rotating control cable are in position. Other connections have been bolted together. Note light bulbs for scale. Photographer: John Capek. Date: August 21, 1970. INEEL negative no. 70-3494 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Reactor Building (PER620) basement, inside cubicle 13. Lead bricks ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Reactor Building (PER-620) basement, inside cubicle 13. Lead bricks shield the fission product detection system (FPDS). The system detected fission products in pressure loop from in-pile tube. shielding was to prevent other radiation in cubicle from interfering. Assembly of bricks in foreground will slide back to enclose and shield equipment in the three chambers. Date: 1982. INEEL negative no. 82-6376 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

PBF Reactor Building (PER620). Camera on main floor faces south ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Reactor Building (PER-620). Camera on main floor faces south (open) doorway. In foreground is canal gate, lined with stainless steel and painted with protective coatings. Reactor pit is round with protective coatings. Reactor put is round form discernible beyond. Lifting beams and rigging are in place for a load test before reactor vessel arrives. Photographer: John Capek. Date: January 26, 1970. INEEL negative no. 70-347 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

The prevalence of obesity in children and young people with Down syndrome.

PubMed

O' Shea, Muireann; O' Shea, Carol; Gibson, Louise; Leo, Jennifer; Carty, Catherine

2018-05-15

Overweight and obesity is a growing concern among individuals with intellectual disabilities; however, little is known about the prevalence among children and youth with Down syndrome (CYDS). The purpose of this study was to determine the prevalence of overweight/obesity among CYDS in South West Ireland. This cross-sectional study measured height and weight of 61 CYDS aged 4-16 years. Body mass index (BMI) was calculated and percentage body fat (PBF) was measured using bio-electrical impendence analysis (BIA). Using the International Obesity Task Force BMI cut-offs, 51.6% of males and 40% of females were overweight/obese compared to 32% and 14.8%, respectively, using PBF. The mean PBF for males was 18.76 versus females 22.38 (p < .05). There is a higher prevalence of overweight/obesity, particularly in males, compared to the general population of children. The difference in estimation of overweight/obesity between BMI and BIA has implications for research and clinical practice. © 2018 John Wiley & Sons Ltd.

Posttest calculation of the PBF LOC-11B and LOC-11C experiments using RELAP4/MOD6. [PWR

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

Hendrix, C.E.

Comparisons between RELAP4/MOD6, Update 4 code-calculated and measured experimental data are presented for the PBF LOC-11C and LOC-11B experiments. Independent code verification techniques are now being developed and this study represents a preliminary effort applying structured criteria for developing computer models, selecting code input, and performing base-run analyses. Where deficiencies are indicated in the base-case representation of the experiment, methods of code and criteria improvement are developed and appropriate recommendations are made.

PBF Reactor Building (PER620) under construction. Aerial view with camera ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Reactor Building (PER-620) under construction. Aerial view with camera facing northeast. Steel framework is exposed for west wing and high bay. Concrete block siding on east wing. Railroad crane set up on west side. Note trenches proceeding from front of building. Left trench is for secondary coolant and will lead to Cooling Tower. Shorter trench will contain cables leading to control area. Photographer: Larry Page. Date: March 22, 1967. INEEL negative no. 67-5025 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

All-fiber gas sensor with intracavity photothermal spectroscopy.

PubMed

Zhao, Yan; Jin, Wei; Lin, Yuechuan; Yang, Fan; Ho, Hoi Lut

2018-04-01

We present an all-fiber intracavity photothermal (IC-PT) spectroscopic gas sensor with a hollow-core photonic bandgap fiber (HC-PBF) gas cell. The gas cell is placed inside a fiber-ring laser cavity to achieve higher laser light intensity in the hollow core and hence higher PT modulation signal. An experiment with a 0.62-m-long HC-PBF gas cell demonstrated a noise equivalent concentration of 176 ppb acetylene. Theoretical modeling shows that the IC-PT sensor has the potential of achieving sub-ppb (parts-per-billion) acetylene detection sensitivity.

Measuring and understanding the effects of a performance based financing scheme applied to nutrition services in Burundi-a mixed method impact evaluation design.

PubMed

Nimpagaritse, Manassé; Korachais, Catherine; Roberfroid, Dominique; Kolsteren, Patrick; Zine Eddine El Idrissi, Moulay Driss; Meessen, Bruno

2016-06-14

Malnutrition is a huge problem in Burundi. In order to improve the provision of services at hospital, health centre and community levels, the Ministry of Health is piloting the introduction of malnutrition prevention and care indicators within its performance based financing (PBF) scheme. Paying for units of services and for qualitative indicators is expected to enhance provision and quality of these nutrition services, as PBF has done, in Burundi and elsewhere, for several other services. This paper presents the protocol for the impact evaluation of the PBF scheme applied to malnutrition. The research design consists in a mixed methods model adopting a sequential explanatory design. The quantitative component is a cluster-randomized controlled evaluation design: among the 90 health centres selected for the study, half receive payment related to their results in malnutrition activities, while the other half get a budget allocation. Qualitative research will be carried out both during the intervention period and at the end of the quantitative evaluation. Data are collected from 1) baseline and follow-up surveys of 90 health centres and 6,480 households with children aged 6 to 23 months, 2) logbooks filled in weekly in health centres, and 3) in-depth interviews and focus group discussions. The evaluation aims to provide the best estimate of the impact of the project on malnutrition outcomes in the community as well as outputs at the health centre level (malnutrition care outputs) and to describe quantitatively and qualitatively the changes that took place (or did not take place) within health centres as a result of the program. Although PBF schemes are blooming in low in-come countries, there is still a need for evidence, especially on the impact of revising the list of remunerated indicators. It is expected that this impact evaluation will be helpful for the national policy dialogue in Burundi, but it will also provide key evidence for countries with an existing PBF scheme and confronted with malnutrition problems on the appropriateness to extend the strategy to nutrition services. ClinicalTrials.gov PRS Identifier: NCT02721160; registered March 2016.

Adiposity, fractional exhaled nitric oxide, and asthma in U.S. children.

PubMed

Han, Yueh-Ying; Forno, Erick; Celedón, Juan C

2014-07-01

Whether allergic airway inflammation mediates the association between overweight or obesity and childhood asthma is unknown. To examine adiposity, asthma, and fractional exhaled nitric oxide (FeNO) in U.S. children. Cross-sectional study of indicators of adiposity or obesity, FeNO (a biomarker of eosinophilic airway inflammation), and asthma in 2,681 children aged 6-17 years in the 2007-2010 National Health and Nutrition Examination Survey. Adiposity measures included body mass index (BMI), percent body fat (PBF), and waist circumference (WC). BMI, PBF, and WC were associated with asthma among children with low FeNO (odds ratio, 1.54-1.68; P < 0.01), but not among children with increased FeNO. Among children without asthma, BMI, PBF, and WC were associated with higher FEV1 and FVC, and lower FEV1/FVC. Among children with asthma and a high FeNO, all adiposity indicators were associated with decreased FEV1/FVC (β = -1.5% to -1.7% per z score) but not with FEV1 or FVC. Higher BMI or PBF was associated with worse asthma severity or control in children with asthma and increased FeNO, but not in children with asthma and low FeNO. Similar results were obtained in a secondary multivariate analysis of overweight or obesity (defined as BMI ≥85th percentile) and asthma or indicators of asthma severity or control, stratified by FeNO level. Adiposity indicators are associated with asthma in children with low FeNO. Among children with asthma, adiposity indicators are associated with worse asthma severity or control in those with high FeNO.

Variations in respiratory excretion of carbon dioxide can be used to calculate pulmonary blood flow.

PubMed

Preiss, David A; Azami, Takafumi; Urman, Richard D

2015-02-01

A non-invasive means of measuring pulmonary blood flow (PBF) would have numerous benefits in medicine. Traditionally, respiratory-based methods require breathing maneuvers, partial rebreathing, or foreign gas mixing because exhaled CO2 volume on a per-breath basis does not accurately represent alveolar exchange of CO2. We hypothesized that if the dilutional effect of the functional residual capacity was accounted for, the relationship between the calculated volume of CO2 removed per breath and the alveolar partial pressure of CO2 would be reversely linear. A computer model was developed that uses variable tidal breathing to calculate CO2 removal per breath at the level of the alveoli. We iterated estimates for functional residual capacity to create the best linear fit of alveolar CO2 pressure and CO2 elimination for 10 minutes of breathing and incorporated the volume of CO2 elimination into the Fick equation to calculate PBF. The relationship between alveolar pressure of CO2 and CO2 elimination produced an R(2) = 0.83. The optimal functional residual capacity differed from the "actual" capacity by 0.25 L (8.3%). The repeatability coefficient leveled at 0.09 at 10 breaths and the difference between the PBF calculated by the model and the preset blood flow was 0.62 ± 0.53 L/minute. With variations in tidal breathing, a linear relationship exists between alveolar CO2 pressure and CO2 elimination. Existing technology may be used to calculate CO2 elimination during quiet breathing and might therefore be used to accurately calculate PBF in humans with healthy lungs.

POWER-BURST FACILITY (PBF) CONCEPTUAL DESIGN

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

Wasserman, A.A.; Johnson, S.O.; Heffner, R.E.

1963-06-21

A description is presented of the conceptual design of a high- performance, pulsed reactor called the Power Burst Facility (PBF). This reactor is designed to generate power bursts with initial asymptotic periods as short as 1 msec, producing energy releases large enough to destroy entire fuel subassemblies placed in a capsule or flow loop mounted in the reactor, all without damage to the reactor itself. It will be used primarily to evaluate the consequences and hazards of very rapid destructive accidents in reactors representing the entire range of current nuclear technology as applied to power generation, propulsion, and testing. Itmore » will also be used to carry out detailed studies of nondestructive reactivity feedback mechanisms in the shortperiod domain. The facility was designed to be sufficiently flexible to accommodate future cores of even more advanced design. The design for the first reactor core is based upon proven technology; hence, completion of the final design of this core will involve no significant development delays. Construction of the PBF is proposed to begin in September 1984, and is expected to take approximately 20 months to complete. (auth)« less

Pulsed photothermal interferometry for spectroscopic gas detection with hollow-core optical fibre

PubMed Central

Lin, Yuechuan; Jin, Wei; Yang, Fan; Ma, Jun; Wang, Chao; Ho, Hoi Lut; Liu, Yang

2016-01-01

Gas detection with hollow-core photonic bandgap fibre (HC-PBF) and pulsed photothermal (PT) interferometry spectroscopy are studied theoretically and experimentally. A theoretical model is developed and used to compute the gas-absorption-induced temperature and phase modulation in a HC-PBF filled with low-concentration of C2H2 in nitrogen. The PT phase modulation dynamics for different pulse duration, peak power and energy of pump beam are numerically modelled, which are supported by the experimental results obtained around the P(9) absorption line of C2H2 at 1530.371 nm. Thermal conduction is identified as the main process responsible for the phase modulation dynamics. For a constant peak pump power level, the phase modulation is found to increase with pulse duration up to ~1.2 μs, while it increases with decreasing pulse duration for a constant pulse energy. It is theoretically possible to achieve ppb level detection of C2H2 with ~1 m length HC-PBF and a pump beam with ~10 ns pulse duration and ~100 nJ pulse energy. PMID:28009011

Pulsed photothermal interferometry for spectroscopic gas detection with hollow-core optical fibre.

PubMed

Lin, Yuechuan; Jin, Wei; Yang, Fan; Ma, Jun; Wang, Chao; Ho, Hoi Lut; Liu, Yang

2016-12-23

Gas detection with hollow-core photonic bandgap fibre (HC-PBF) and pulsed photothermal (PT) interferometry spectroscopy are studied theoretically and experimentally. A theoretical model is developed and used to compute the gas-absorption-induced temperature and phase modulation in a HC-PBF filled with low-concentration of C 2 H 2 in nitrogen. The PT phase modulation dynamics for different pulse duration, peak power and energy of pump beam are numerically modelled, which are supported by the experimental results obtained around the P(9) absorption line of C 2 H 2 at 1530.371 nm. Thermal conduction is identified as the main process responsible for the phase modulation dynamics. For a constant peak pump power level, the phase modulation is found to increase with pulse duration up to ~1.2 μs, while it increases with decreasing pulse duration for a constant pulse energy. It is theoretically possible to achieve ppb level detection of C 2 H 2 with ~1 m length HC-PBF and a pump beam with ~10 ns pulse duration and ~100 nJ pulse energy.

PBF Reactor Building (PER620) basement. Workers wearing protective gear work ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Reactor Building (PER-620) basement. Workers wearing protective gear work inside cubicle 13 on the fission product detection system. Man on left is atop shielded box shown in previous photo. Posture of second man illustrates waist-high height of shielding box. His hand rests on the access panel, which has been filled with lead bricks and which has been slid shut to enclose detection instruments within box. Photographer: John Capek. Date: January 24, 1983. INEEL negative no. 83-41-3-5 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

Composition dependent structural and optical properties of PbF₂-TeO₂-B₂O₃-Eu₂O₃ glasses.

PubMed

Wagh, Akshatha; Raviprakash, Y; Upadhyaya, Vyasa; Kamath, Sudha D

2015-12-05

Boric oxide based quaternary glasses in the system PbF2-TeO2-B2O3-Eu2O3 have been prepared by melt quenching technique. Density, molar volume, FTIR, UV-Vis techniques were used to probe the structural modifications with incorporation of europium ions in the glass network. An increase in glass density & decrease in molar volume (Vm) values proved the structural changes occurring in coordination of boron atom [conversion of BO3 units to BO4]. This resulted in the increase of the compaction of the prepared glasses with increase in Eu2O3 contents. The amorphous natures of the samples were ascertained by XRD and metallization criterion (M) studies. XPS study showed the values of core-level binding energy [O1s, Eu3d, Eu4d, Te3d, Te4d, Pd4f, Pb5d, O1s, and F1s] of (PbF2-TeO2-B2O3-Eu2O3) the glass matrix. The frequency and temperature dependence of dielectric properties of present glasses were investigated in the frequency range of 1 Hz-10 MHz and temperature range of 313-773K. The study of dielectric measurements proved good insulating and thermal stability of the prepared glasses. At room temperature, dielectric loss [tanδ] values were negligibly small for prepared glasses and increased with increase in temperature. FTIR spectroscopy results were in good agreement with optical band energy gap, density, molar volume and hardness values revealing network modifications caused by europium ions in the glass structure. Copyright © 2015 Elsevier B.V. All rights reserved.

Adiposity, Fractional Exhaled Nitric Oxide, and Asthma in U.S. Children

PubMed Central

Han, Yueh-Ying; Forno, Erick

2014-01-01

Rationale: Whether allergic airway inflammation mediates the association between overweight or obesity and childhood asthma is unknown. Objectives: To examine adiposity, asthma, and fractional exhaled nitric oxide (FeNO) in U.S. children. Methods: Cross-sectional study of indicators of adiposity or obesity, FeNO (a biomarker of eosinophilic airway inflammation), and asthma in 2,681 children aged 6–17 years in the 2007–2010 National Health and Nutrition Examination Survey. Adiposity measures included body mass index (BMI), percent body fat (PBF), and waist circumference (WC). Measurements and Main Results: BMI, PBF, and WC were associated with asthma among children with low FeNO (odds ratio, 1.54–1.68; P < 0.01), but not among children with increased FeNO. Among children without asthma, BMI, PBF, and WC were associated with higher FEV1 and FVC, and lower FEV1/FVC. Among children with asthma and a high FeNO, all adiposity indicators were associated with decreased FEV1/FVC (β = −1.5% to −1.7% per z score) but not with FEV1 or FVC. Higher BMI or PBF was associated with worse asthma severity or control in children with asthma and increased FeNO, but not in children with asthma and low FeNO. Similar results were obtained in a secondary multivariate analysis of overweight or obesity (defined as BMI ≥85th percentile) and asthma or indicators of asthma severity or control, stratified by FeNO level. Conclusions: Adiposity indicators are associated with asthma in children with low FeNO. Among children with asthma, adiposity indicators are associated with worse asthma severity or control in those with high FeNO. PMID:24922361

How do performance-based financing programmes measure quality of care? A descriptive analysis of 68 quality checklists from 28 low- and middle-income countries

PubMed Central

Josephson, Erik; Gergen, Jessica; Coe, Martha; Ski, Samantha; Madhavan, Supriya; Bauhoff, Sebastian

2017-01-01

Abstract This paper seeks to systematically describe the length and content of quality checklists used in performance-based financing programmes, their similarities and differences, and how checklists have evolved over time. We compiled a list of supply-side, health facility-based performance-based financing (PBF) programmes in low- and lower middle-income countries based on a document review. We then solicited PBF manuals and quality checklists from implementers and donors of these PBF mechanisms. We entered each indicator from each quality checklist into a database verbatim in English, and translated into English from French where appropriate, and categorized each indicator according to the Donabedian framework and an author-derived categorization. We extracted 8,490 quality indicators from 68 quality checklists across 32 PBF implementations in 28 countries. On average, checklists contained 125 indicators; within the same program, checklists tend to grow as they are updated. Using the Donabedian framework, 80% of indicators were structure-type, 19% process-type, and less than 1% outcome-type. The author-derived categorization showed that 57% of indicators relate to availability of resources, 24% to managing the facility and 17% assess knowledge and effort. There is a high degree of similarity in a narrow set of indicators used in checklists for common service types such as maternal, neonatal and child health. We conclude that performance-based financing offers an appealing approach to targeting specific quality shortfalls and advancing toward the Sustainable Development Goals of high quality coverage. Currently most indicators focus on structural issues and resource availability. There is scope to rationalize and evolve the quality checklists of these programs to help achieve national and global goals to improve quality of care. PMID:28549142

A 5-mm piezo-scanning fiber device for high speed ultrafast laser microsurgery

PubMed Central

Ferhanoglu, Onur; Yildirim, Murat; Subramanian, Kaushik; Ben-Yakar, Adela

2014-01-01

Towards developing precise microsurgery tools for the clinic, we previously developed image-guided miniaturized devices using low repetition rate amplified ultrafast lasers for surgery. To improve the speed of tissue removal while reducing device diameter, here we present a new 5-mm diameter device that delivers high-repetition rate laser pulses for high speed ultrafast laser microsurgery. The device consists of an air-core photonic bandgap fiber (PBF) for the delivery of high energy pulses, a piezoelectric tube actuator for fiber scanning, and two aspheric lenses for focusing the light. Its inline optical architecture provides easy alignment and substantial size reduction to 5 mm diameter as compared to our previous MEMS-scanning devices while realizing improved intensity squared (two-photon) lateral and axial resolutions of 1.16 μm and 11.46 μm, respectively. Our study also sheds light on the maximum pulse energies that can be delivered through the air-core PBF and identifies cladding damage at the input facet of the fiber as the limiting factor. We have achieved a maximum energy delivery larger than 700 nJ at 92% coupling efficiency. An in depth analysis reveals how this value is greatly affected by possible slight misalignments of the beam during coupling and the measured small beam pointing fluctuations. In the absence of these imperfections, self-phase modulation becomes the limiting factor for the maximum energy delivery, setting the theoretical upper bound to near 2 μJ for a 1-m long, 7-μm, air-core PBF. Finally, the use of a 300 kHz repetition rate fiber laser enabled rapid ablation of 150 µm x 150 µm area within only 50 ms. Such ablation speeds can now allow the surgeons to translate the surgery device as fast as ~4 mm/s to continuously remove a thin layer of a 150 µm wide tissue. Thanks to a high optical transmission efficiency of the in-line optical architecture of the device and improved resolution, we could successfully perform ablation of scarred cheek pouch tissue, drilling through a thin slice. With further development, this device can serve as a precise and high speed ultrafast laser scalpel in the clinic. PMID:25071946

PBF Cooling Tower detail. Camera facing southwest into north side ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Cooling Tower detail. Camera facing southwest into north side of Tower. Five horizontal layers of splash bars constitute fill decks, which will break up falling water into droplets, promoting evaporative cooling. Louvered faces, through which air enters tower, are on east and west sides. Louvers have been installed. Support framework for one of two venturi-shaped fan stacks (or "vents") is in center top. Orifices in hot basins (not in view) will distribute water over fill. Photographer: Kirsh. Date: May 15, 1969. INEEL negative no. 69-3032 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

A novel Streptomyces spp. integration vector derived from the S. venezuelae phage, SV1.

PubMed

Fayed, Bahgat; Younger, Ellen; Taylor, Gabrielle; Smith, Margaret C M

2014-05-30

Integrating vectors based on the int/attP loci of temperate phages are convenient and used widely, particularly for cloning genes in Streptomyces spp. We have constructed and tested a novel integrating vector based on g27, encoding integrase, and attP site from the phage, SV1. This plasmid, pBF3 integrates efficiently in S. coelicolor and S. lividans but surprisingly fails to generate stable integrants in S. venezuelae, the natural host for phage SV1. pBF3 promises to be a useful addition to the range of integrating vectors currently available for Streptomyces molecular genetics.

Comparison of arsenic content in pelletized poultry house waste and biosolids fertilizer.

PubMed

Nachman, Keeve E; Mihalic, Jana N; Burke, Thomas A; Geyh, Alison S

2008-03-01

Managers of human biosolids have been incorporating the practice of waste pelletization for use as fertilizer since the mid 1920s, and waste pelletization has recently been embraced by some poultry producers as a way to move nutrients away from saturated agricultural land. However, the presence of arsenic in pelletized poultry house waste (PPHW) resulting from the use of organoarsenical antimicrobial drugs in poultry production raises concerns regarding additional incremental population exposures. Arsenic concentrations were determined in PPHW and pelletized biosolids fertilizer (PBF) samples. Pellets were processed using strong acid microwave digestion and analyzed by graphite furnace atomic absorption spectroscopy. The mean arsenic concentration in PPHW (20.1 ppm) fell within the lower part of the range of previously report arsenic concentrations in unpelletized poultry house waste. Arsenic concentrations in PBF, the source of which is less clear than for PPHW, were approximately a factor of 5 times lower than those in PPHW, with a mean concentration of 4.1 ppm. The pelletization and sale of these biological waste fertilizers present new pathways of exposure to arsenic in consumer populations who would otherwise not come into contact with these wastes. Arsenic exposures in humans resulting from use of these fertilizer pellets should be quantified to avoid potential unintended negative consequences of managing wastes through pelletization.

High temperature thermoplastic elastomers synthesized by living anionic polymerization in hydrocarbon solvent at room temperature

DOE PAGES

Schlegel, Ralf; Williams, Katherine; Voyloy, Dimitry; ...

2016-03-30

We present the synthesis and characterization of a new class of high temperature thermoplastic elastomers composed of polybenzofulvene–polyisoprene–polybenzofulvene (FIF) triblock copolymers. All copolymers were prepared by living anionic polymerization in benzene at room temperature. Homopolymerization and effects of additives on the glass transition temperature (T g) of polybenzofulvene (PBF) were also investigated. Among all triblock copolymers studied, FIF with 14 vol % of PBF exhibited a maximum stress of 14.3 ± 1.3 MPa and strain at break of 1390 ± 66% from tensile tests. The stress–strain curves of FIF-10 and 14 were analyzed by a statistical molecular approach using amore » nonaffine tube model to estimate the thermoplastic elastomer behavior. Dynamic mechanical analysis showed that the softening temperature of PBF in FIF was 145 °C, much higher than that of thermoplastic elastomers with polystyrene hard blocks. Microphase separation of FIF triblock copolymers was observed by small-angle X-ray scattering, even though long-range order was not achieved under the annealing conditions employed. Additionally, the microphase separation of the resulting triblock copolymers was examined by atomic force microscopy.« less

High temperature thermoplastic elastomers synthesized by living anionic polymerization in hydrocarbon solvent at room temperature

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

Schlegel, Ralf; Williams, Katherine; Voyloy, Dimitry

We present the synthesis and characterization of a new class of high temperature thermoplastic elastomers composed of polybenzofulvene–polyisoprene–polybenzofulvene (FIF) triblock copolymers. All copolymers were prepared by living anionic polymerization in benzene at room temperature. Homopolymerization and effects of additives on the glass transition temperature (T g) of polybenzofulvene (PBF) were also investigated. Among all triblock copolymers studied, FIF with 14 vol % of PBF exhibited a maximum stress of 14.3 ± 1.3 MPa and strain at break of 1390 ± 66% from tensile tests. The stress–strain curves of FIF-10 and 14 were analyzed by a statistical molecular approach using amore » nonaffine tube model to estimate the thermoplastic elastomer behavior. Dynamic mechanical analysis showed that the softening temperature of PBF in FIF was 145 °C, much higher than that of thermoplastic elastomers with polystyrene hard blocks. Microphase separation of FIF triblock copolymers was observed by small-angle X-ray scattering, even though long-range order was not achieved under the annealing conditions employed. Additionally, the microphase separation of the resulting triblock copolymers was examined by atomic force microscopy.« less

Effect of furosemide on pulmonary blood flow distribution in resting and exercising horses

NASA Technical Reports Server (NTRS)

Erickson, H. H.; Bernard, S. L.; Glenny, R. W.; Fedde, M. R.; Polissar, N. L.; Basaraba, R. J.; Walther, S. M.; Gaughan, E. M.; McMurphy, R.; Hlastala, M. P.

1999-01-01

We determined the spatial distribution of pulmonary blood flow (PBF) with 15-micron fluorescent-labeled microspheres during rest and exercise in five Thoroughbred horses before and 4 h after furosemide administration (0.5 mg/kg iv). The primary finding of this study was that PBF redistribution occurred from rest to exercise, both with and without furosemide. However, there was less blood flow to the dorsal portion of the lung during exercise postfurosemide compared with prefurosemide. Furosemide did alter the resting perfusion distribution by increasing the flow to the ventral regions of the lung; however, that increase in flow was abated with exercise. Other findings included 1) unchanged gas exchange and cardiac output during rest and exercise after vs. before furosemide, 2) a decrease in pulmonary arterial pressure after furosemide, 3) an increase in the slope of the relationship of PBF vs. vertical height up the lung during exercise, both with and without furosemide, and 4) a decrease in blood flow to the dorsal region of the lung at rest after furosemide. Pulmonary perfusion variability within the lung may be a function of the anatomy of the pulmonary vessels that results in a predominantly fixed spatial pattern of flow distribution.

Distributed gas sensing with optical fibre photothermal interferometry.

PubMed

Lin, Yuechuan; Liu, Fei; He, Xiangge; Jin, Wei; Zhang, Min; Yang, Fan; Ho, Hoi Lut; Tan, Yanzhen; Gu, Lijuan

2017-12-11

We report the first distributed optical fibre trace-gas detection system based on photothermal interferometry (PTI) in a hollow-core photonic bandgap fibre (HC-PBF). Absorption of a modulated pump propagating in the gas-filled HC-PBF generates distributed phase modulation along the fibre, which is detected by a dual-pulse heterodyne phase-sensitive optical time-domain reflectometry (OTDR) system. Quasi-distributed sensing experiment with two 28-meter-long HC-PBF sensing sections connected by single-mode transmission fibres demonstrated a limit of detection (LOD) of ∼10 ppb acetylene with a pump power level of 55 mW and an effective noise bandwidth (ENBW) of 0.01 Hz, corresponding to a normalized detection limit of 5.5ppb⋅W/Hz. Distributed sensing experiment over a 200-meter-long sensing cable made of serially connected HC-PBFs demonstrated a LOD of ∼ 5 ppm with 62.5 mW peak pump power and 11.8 Hz ENBW, or a normalized detection limit of 312ppb⋅W/Hz. The spatial resolution of the current distributed detection system is limited to ∼ 30 m, but it is possible to reduce down to 1 meter or smaller by optimizing the phase detection system.

Impact of Performance-Based Financing in a Low-Resource Setting: A Decade of Experience in Cambodia.

PubMed

Van de Poel, Ellen; Flores, Gabriela; Ir, Por; O'Donnell, Owen

2016-06-01

This paper exploits the geographic expansion of performance-based financing (PBF) in Cambodia over a decade to estimate its effect on the utilization of maternal and child health services. PBF is estimated to raise the proportion of births occurring in incentivized public health facilities by 7.5 percentage points (25%). A substantial part of this effect arises from switching the location of institutional births from private to public facilities; there is no significant impact on deliveries supervised by a skilled birth attendant, nor is there any significant effect on neonatal mortality, antenatal care and vaccination rates. The impact on births in public facilities is much greater if PBF is accompanied by maternity vouchers that cover user fees, but there is no significant effect among the poorest women. Heterogeneous effects across schemes differing in design suggest that maintaining management authority within a health district while giving explicit service targets to facilities is more effective in raising utilization than contracting management to a non-governmental organization while denying it full autonomy and leaving financial penalties vague. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Experimental and Theoretical Studies of the Pure Rotational Spectra of Lead Halides: PbF and PbCl

NASA Astrophysics Data System (ADS)

Norman, Spencer; Dawes, Richard; Grubbs, G. S., II; Cooke, S. A.; Long, B. E.; Dewberry, Chris

2014-06-01

The pure rotational spectrum of lead monochloride, PbCl, has been measured and analyzed using chirped pulse and cavity Fourier transform microwave (CP-FTMW and FTMW) spectrometers equipped with an ablation source. Refined parameters of an effective Hamiltonian including fine and hyperfine interactions similar to those previously reported by Fink et al. [1] were determined. Dynamically-weighted, explicitly-correlated MRCI-F12 calculations [2] were performed for both PbF and the valence isoelectronic PbCl to predict potential energy curves (PEC). Spin-orbit coupling was included in the calculations, which is known to split the X12Π1/2 and X22Π3/2 components of the ground electronic state by roughly 8280 wn in both lead halide systems. Calculated rotational levels were obtained using the PECs and compared with experiment including previously published results for PbF [3]. References: 1- K. Ziebarth, K. D. Setzer, O. Shestakov,1 and E. H. Fink, J. Mol. Spec. 191, 108 (1998). 2- B. J. Barker et al. J. Chem. Phys. 137, 214313 (2012). 3- R. J. Mawhorter et al. Phys. Rev. A 84, 022508 (2011).

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

Stan, Camelia V.; Dutta, Rajkrishna; White, Claire E.

Lead fluoride, PbF 2, was investigated experimentally in the laser-heated diamond anvil cell by x-ray diffraction to pressures of 75 GPa at room temperature and to 64.5 GPa and 2430 K, as well as through first-principles density functional theory calculations up to 70 GPa. During room temperature compression, no discontinuous changes in the x-ray diffraction pattern or volume were observed, but the lattice parameters displayed highly anomalous trends between 10-22 GPa with enhanced compressibility along the a direction and reduced or even negative compressibility along b and c. Theoretical calculations of valence electron densities at 22 GPa showed that α-PbFmore » 2 underwent a pressure-induced isosymmetric phase transition to a postcotunnite Co 2Si structure and also revealed the detailed atomic rearrangements associated with the development of an extra Pb-F bond in the high-pressure phase. Our x-ray results and theoretical calculations are consistent with an isosymmetric phase transition smoothly occurring over 10-22 GPa rather than abruptly as previously suggested. The characteristic values for the cell constants a/c and (a+c)/b, which are used to distinguish among cotunnite-, Co 2Si-, and Ni 2In-type phases, require modification based on our results. An equation of state fit yields a bulk modulus, K 0, of 72(3) GPa for the cotunnite-type, and an ambient-pressure volume, V 0, of 182(2)Å 3, and K 0=81(4)GPa for the Co 2Si-type phase when fixing the pressure derivative of the bulk modulus, K 0'=4. Upon heating above 1200 K at pressures at or above 25.9 GPa, PbF 2 partially transformed to the hexagonal Ni 2In-type phase but wholly or partially reverted back to Co 2Si-type phase upon temperature quench. From 43-65 GPa, nearly complete transformation to the Ni 2In-type PbF 2 was observed at high temperature, but the material partially transformed back to the orthorhombic phase upon temperature quench. Our results show that high-pressure behavior of PbF 2 is distinct from that of the alkaline earth fluorides with similar ionic radii. These results also have relevance to understanding the behavior of lanthanide and actinide dioxides, which have been predicted theoretically to exhibit similar isosymmetric transitions at Mbar pressures.« less

Slowing and cooling of heavy or light (even with a tiny electric dipole moment) polar molecules using a novel, versatile electrostatic Stark decelerator.

PubMed

Wang, Qin; Hou, Shunyong; Xu, Liang; Yin, Jianping

2016-02-21

To meet some demands for realizing precise measurements of an electric dipole moment of electron (eEDM) and examining cold collisions or cold chemical physics, we have proposed a novel, versatile electrostatic Stark decelerator with an array of true 3D electric potential wells, which are created by a series of horizontally-oriented, U-shaped electrodes with time-sequence controlling high voltages (± HV) and two guiding electrodes with a constant voltage. We have calculated the 2D electric field distribution, the Stark shifts of the four lowest rotational sub-levels of PbF molecules in the X1(2)Π1/2(v = 0) electronic and vibrational ground states as well as the population in the different rotational levels. We have discussed the 2D longitudinal and transverse phase-space acceptances of PbF molecules in our decelerator. Subsequently, we have simulated the dynamic processes of the decelerated PbF molecules using the 3D Monte-Carlo method, and have found that a supersonic PbF beam with a velocity of 300 m s(-1) can be efficiently slowed to about 5 m s(-1), which will greatly enhance the sensitivities to research a parity violation and measure an eEDM. In addition, we have investigated the dependences of the longitudinal velocity spread, longitudinal temperature and bunching efficiency on both the number of guiding stages and high voltages, and found that after bunching, a cold packet of PbF molecules in the J = 7/2, MΩ = -7/4 state with a longitudinal velocity spread of 0.69 m s(-1) (corresponding to a longitudinal temperature of 2.35 mK) will be produced by our high-efficient decelerator, which will generate a high energy-resolution molecular beam for studying cold collision physics. Finally, our novel decelerator can also be used to efficiently slow NO molecules with a tiny electric dipole moment (EDM) of 0.16 D from 315 m s(-1) to 28 m s(-1). It is clear that our proposed new decelerator has a good slowing performance and experimental feasibility as well as wide applications in the field of precise measurements and cold molecule physics.

High-pressure polymorphism of Pb F 2 to 75 GPa

DOE PAGES

Stan, Camelia V.; Dutta, Rajkrishna; White, Claire E.; ...

2016-07-06

Lead fluoride, PbF 2, was investigated experimentally in the laser-heated diamond anvil cell by x-ray diffraction to pressures of 75 GPa at room temperature and to 64.5 GPa and 2430 K, as well as through first-principles density functional theory calculations up to 70 GPa. During room temperature compression, no discontinuous changes in the x-ray diffraction pattern or volume were observed, but the lattice parameters displayed highly anomalous trends between 10-22 GPa with enhanced compressibility along the a direction and reduced or even negative compressibility along b and c. Theoretical calculations of valence electron densities at 22 GPa showed that α-PbFmore » 2 underwent a pressure-induced isosymmetric phase transition to a postcotunnite Co 2Si structure and also revealed the detailed atomic rearrangements associated with the development of an extra Pb-F bond in the high-pressure phase. Our x-ray results and theoretical calculations are consistent with an isosymmetric phase transition smoothly occurring over 10-22 GPa rather than abruptly as previously suggested. The characteristic values for the cell constants a/c and (a+c)/b, which are used to distinguish among cotunnite-, Co 2Si-, and Ni 2In-type phases, require modification based on our results. An equation of state fit yields a bulk modulus, K 0, of 72(3) GPa for the cotunnite-type, and an ambient-pressure volume, V 0, of 182(2)Å 3, and K 0=81(4)GPa for the Co 2Si-type phase when fixing the pressure derivative of the bulk modulus, K 0'=4. Upon heating above 1200 K at pressures at or above 25.9 GPa, PbF 2 partially transformed to the hexagonal Ni 2In-type phase but wholly or partially reverted back to Co 2Si-type phase upon temperature quench. From 43-65 GPa, nearly complete transformation to the Ni 2In-type PbF 2 was observed at high temperature, but the material partially transformed back to the orthorhombic phase upon temperature quench. Our results show that high-pressure behavior of PbF 2 is distinct from that of the alkaline earth fluorides with similar ionic radii. These results also have relevance to understanding the behavior of lanthanide and actinide dioxides, which have been predicted theoretically to exhibit similar isosymmetric transitions at Mbar pressures.« less

The structural properties of PbF2 by molecular dynamics

NASA Astrophysics Data System (ADS)

Chergui, Y.; Nehaoua, N.; Telghemti, B.; Guemid, S.; Deraddji, N. E.; Belkhir, H.; Mekki, D. E.

2010-08-01

This work presents the use of molecular dynamics (MD) and the code of Dl_Poly, in order to study the structure of fluoride glass after melting and quenching. We are realized the processing phase liquid-phase, simulating rapid quenching at different speeds to see the effect of quenching rate on the operation of the devitrification. This technique of simulation has become a powerful tool for investigating the microscopic behaviour of matter as well as for calculating macroscopic observable quantities. As basic results, we calculated the interatomic distance, angles and statistics, which help us to know the geometric form and the structure of PbF2. These results are in experimental agreement to those reported in literature.

PBF (PER620) interior of Reactor Room. Camera facing south from ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF (PER-620) interior of Reactor Room. Camera facing south from stairway platform in southwest corner (similar to platform in view at left). Reactor was beneath water in circular tank. Fuel was stored in the canal north of it. Platform and apparatus at right is reactor bridge with control rod mechanisms and actuators. The entire apparatus swung over the reactor and pool during operations. Personnel in view are involved with decontamination and preparation of facility for demolition. Note rails near ceiling for crane; motor for rollup door at upper center of view. Date: March 2004. INEEL negative no. HD-41-3-2 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

Community participation and voice mechanisms under performance-based financing schemes in Burundi.

PubMed

Falisse, Jean-Benoît; Meessen, Bruno; Ndayishimiye, Juvénal; Bossuyt, Michel

2012-05-01

Community participation is often described as a key for primary health care in low-income countries. Recent performance-based financing (PBF) initiatives have renewed the interest in this strategy by questioning the accountability of those in charge at the health centre (HC) level. We analyse the place of two downward accountability mechanisms in a PBF scheme: health committees elected among the communities and community-based organizations (CBOs) contracted as verifiers of health facilities' performance. We evaluated 100 health committees and 79 CBOs using original data collected in six Burundi provinces (2009-2010) and a framework based on the literature on community participation in health and New Institutional Economics. Health committees appear to be rather ineffective, focusing on supporting the medical staff and not on representing the population. CBOs do convey information about the concerns of the population to the health authorities; yet, they represent only a few users and lack the ability to force changes. PBF does not automatically imply more 'voice' from the population, but introduces an interesting complement to health committees with CBOs. However, important efforts remain necessary to make both mechanisms work. More experiments and analysis are needed to develop truly efficient 'downward' mechanisms of accountability at the HC level. © 2012 Blackwell Publishing Ltd.

Suppression of pulmonary vasculature in lung perfusion MRI using correlation analysis.

PubMed

Risse, Frank; Kuder, Tristan A; Kauczor, Hans-Ulrich; Semmler, Wolfhard; Fink, Christian

2009-11-01

The purpose of the study was to evaluate the feasibility of suppressing the pulmonary vasculature in lung perfusion MRI using cross-correlation analysis (CCA). Perfusion magnetic resonance imaging (MRI) (3D FLASH, TR/TE/flip angle: 0.8 ms/2.1 ms/40 degrees ) of the lungs was performed in seven healthy volunteers at 1.5 Tesla after injection of Gd-DTPA. CCA was performed pixel-wise in lung segmentations using the signal time-course of the main pulmonary artery and left atrium as references. Pixels with high correlation coefficients were considered as arterial or venous and excluded from further analysis. Quantitative perfusion parameters [pulmonary blood flow (PBF) and volume (PBV)] were calculated for manual lung segmentations separately, with the entire left and right lung with all intrapulmonary vessels (IPV) included, excluded manually or excluded using CCA. The application of CCA allowed reliable suppression of hilar and large IPVs. Using vascular suppression by CCA, perfusion parameters were significantly reduced (p

Gaussian process-based surrogate modeling framework for process planning in laser powder-bed fusion additive manufacturing of 316L stainless steel

DOE PAGES

Tapia, Gustavo; Khairallah, Saad A.; Matthews, Manyalibo J.; ...

2017-09-22

Here, Laser Powder-Bed Fusion (L-PBF) metal-based additive manufacturing (AM) is complex and not fully understood. Successful processing for one material, might not necessarily apply to a different material. This paper describes a workflow process that aims at creating a material data sheet standard that describes regimes where the process can be expected to be robust. The procedure consists of building a Gaussian process-based surrogate model of the L-PBF process that predicts melt pool depth in single-track experiments given a laser power, scan speed, and laser beam size combination. The predictions are then mapped onto a power versus scan speed diagrammore » delimiting the conduction from the keyhole melting controlled regimes. This statistical framework is shown to be robust even for cases where experimental training data might be suboptimal in quality, if appropriate physics-based filters are applied. Additionally, it is demonstrated that a high-fidelity simulation model of L-PBF can equally be successfully used for building a surrogate model, which is beneficial since simulations are getting more efficient and are more practical to study the response of different materials, than to re-tool an AM machine for new material powder.« less

Gaussian process-based surrogate modeling framework for process planning in laser powder-bed fusion additive manufacturing of 316L stainless steel

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

Tapia, Gustavo; Khairallah, Saad A.; Matthews, Manyalibo J.

Here, Laser Powder-Bed Fusion (L-PBF) metal-based additive manufacturing (AM) is complex and not fully understood. Successful processing for one material, might not necessarily apply to a different material. This paper describes a workflow process that aims at creating a material data sheet standard that describes regimes where the process can be expected to be robust. The procedure consists of building a Gaussian process-based surrogate model of the L-PBF process that predicts melt pool depth in single-track experiments given a laser power, scan speed, and laser beam size combination. The predictions are then mapped onto a power versus scan speed diagrammore » delimiting the conduction from the keyhole melting controlled regimes. This statistical framework is shown to be robust even for cases where experimental training data might be suboptimal in quality, if appropriate physics-based filters are applied. Additionally, it is demonstrated that a high-fidelity simulation model of L-PBF can equally be successfully used for building a surrogate model, which is beneficial since simulations are getting more efficient and are more practical to study the response of different materials, than to re-tool an AM machine for new material powder.« less

Glutamate control of pulpal blood flow in the incisor dental pulp of the rat.

PubMed

Zerari-Mailly, Fouzia; Braud, Adeline; Davido, Nicolas; Touré, Babacar; Azérad, Jean; Boucher, Yves

2012-10-01

Glutamate is present in primary sensory afferents innervating the dental pulp and is known to exert vasoactive effects. The aims of this study were (i) to assess pulpal blood flow (PBF) after glutamate infusion in the dental pulp and (ii) to observe the distribution of glutamatergic nerve fibers expressing the vesicular transporters of glutamate (VGluT). The PBF was monitored with laser Doppler flowmetry before and after glutamate (0.5 M) infusion in the dental pulp vs. saline infusion. Immunochemistry for VGluT1, 2, and 3 was performed in addition to immunochemistry for the vascular and neuronal markers smooth-muscle actin (SMA), isolectin B4 (IB4), and calcitonin gene-related peptide (CGRP). Glutamate infusion resulted in a PBF increase that lasted for 60 s. Positive immunolabeling was observed for the three glutamate transporters, but was more pronounced for VGluT3. Moreover, VGluT3 immunoreactivity was observed within nerve fibers entering the dental pulp and terminating at the periphery and at the vicinity of odontoblasts. Also, VGluT3 was colocalized with the vascular marker SMA, and in some nerve fibers with IB4, but not with CGRP. This study provides support for a control of dental pulp microcirculation by neurons expressing VGluT3. © 2012 Eur J Oral Sci.

The structure of Er3+-doped oxy-fluoride transparent glass-ceramics studied by Raman scattering

NASA Astrophysics Data System (ADS)

Tikhomirov, V. K.; Seddon, A. B.; Ferrari, M.; Montagna, M.; Santos, L. F.; Almeida, R. M.

2003-11-01

We show that the structure of transparent oxy-fluoride glass-ceramics formed by heat treatment of glasses of typical composition 32(SiO2):9(AlO1.5):31.5(CdF2):18.5(PbF2): 5.5(ZnF2):3.5(ErF3) mol% consists of ~ 12 nm diameter, Er3+-doped, β-PbF2 nano-crystals embedded in a silica-based glass network and connected to it via non-bridging O and F anions, or fluorine linkages such as Pb-F-Cd and Pb-F-Zn. It is proposed that the glass network structure is mostly chain-like and dominated by Si(O,F)4 tetrahedra with two bridging O and two non-bridging O and/or F atoms (Q2 units). SiO4 tetrahedra with zero and one bridging O (Q0 and Q1 units, respectively) are also present in the glass structure, in the approximate proportion Q0:Q1:Q2 = 1:1:3, a characteristic which appears to be of primary importance. The flexible, chain-like glass-network, with many broken bonds, results in easy accommodation of the Er3+-doped PbF2 nano-crystals, which are grown by heat-treatment of the precursor glass. The boson peak in the Raman spectrum of the precursor glass decreases in intensity upon ceramming and is partly converted to narrow crystalline peaks at lower frequency, consistent with the precipitation of PbF2 crystalline nano-particles. It is suggested that the boson peak involves localized vibrations of broken or stretched Pb-F bonds. The mean free path for these vibrations increases with ceramming, which involves partial crystallization of the glass network, resulting in a shift of the boson peak vibrations to lower-frequency crystalline peaks.

Effect of lead fluoride incorporation on the structure and luminescence properties of tungsten sodium phosphate glasses

NASA Astrophysics Data System (ADS)

Nardi, Rachel Prado Russo Delorenzo; Braz, Celso Eduardo; de Camargo, Andrea S. S.; Ribeiro, Sidney J. L.; Rocha, Lucas A.; Cassanjes, Fábia Castro; Poirier, Gael

2015-11-01

Tungsten phosphate glasses are known to be promising materials for several applications in optics such as non linear optical properties, lower phonon energy or photochromic effects related with tungsten oxide incorporation inside the phosphate network. In this study, lead fluoride has been incorporated in a 60NaPO3-40WO3 glass composition according to the ternary molar compositions (100 - x)[0.6NaPO3-0.4WO3]-xPbF2 with x varying from 0 to 60 mol%. The structural changes as a function of composition were investigated by thermal analysis, UV-visible absorption, Raman spectroscopy, X-ray diffraction of the crystallized samples, and Eu3+ emission in the visible. While DSC analyzes points out a strong decrease in the glass network connectivity and higher crystallization tendency with increasing PbF2 contents, Raman spectra clearly identify a progressive incorporation of PbF2 in the phosphate network with the formation of terminal Psbnd F and Wsbnd F bonds. These results are also in agreement with the crystallization of β-PbF2 observed for the most lead fluoride concentrated samples. Investigation of Eu3+ emission data in the visible showed longer 5D0 excited state lifetime values and higher quantum efficiencies. These results are discussed in terms of the assumption of higher local symmetry around Eu3+ with increasing PbF2 contents.

Pathways to high and low performance: factors differentiating primary care facilities under performance-based financing in Nigeria

PubMed Central

Mabuchi, Shunsuke; Sesan, Temilade; Bennett, Sara C

2018-01-01

Abstract The determinants of primary health facility performance in developing countries have not been well studied. One of the most under-researched areas is health facility management. This study investigated health facilities under the pilot performance-based financing (PBF) scheme in Nigeria, and aimed to understand which factors differentiated primary health care centres (PHCCs) which had performed well, vs those which had not, with a focus on health facility management practices. We used a multiple case study where we compared two high-performing PHCCs and two low-performing PHCCs for each of the two PBF target states. Two teams of two trained local researchers spent 1 week at each PHCC and collected semi-structured interview, observation and documentary data. Data from interviews were transcribed, translated and coded using a framework approach. The data for each PHCC were synthesized to understand dynamic interactions of different elements in each case. We then compared the characteristics of high and low performers. The areas in which critical differences between high and low-performers emerged were: community engagement and support; and performance and staff management. We also found that (i) contextual and health system factors particularly staffing, access and competition with other providers; (ii) health centre management including community engagement, performance management and staff management; and (iii) community leader support interacted and drove performance improvement among the PHCCs. Among them, we found that good health centre management can overcome some contextual and health system barriers and enhance community leader support. This study findings suggest a strong need to select capable and motivated health centre managers, provide long-term coaching in managerial skills, and motivate them to improve their practices. The study also highlights the need to position engagement with community leaders as a key management practice and a central element of interventions to improve PHCC performance. PMID:29077844

HABIT CHANGES OF Y3Al5O12 AND Y3Ga5O12 GROWN FROM A PbO-PbF2 FLUX,

DTIC Science & Technology

Al2O3 or - Ga2O3 ratio in the melt. Y3Ga5O12 crystals have a pure (211) habit when grown from either a Y2O3- or PbO-rich melt. The crystals develop...small (110) faces when grown from a Ga2O3 - or PbF2-rich melt. Y3Al5O12 crystals have a pure (110) when grown from either a PbF2- or Al2O3-rich melt... Ga2O3 -rich melts. It is believed that the habit variations are caused by changes in either the surface diffusion or step propagation, due to Pb

Further investigation of g factors for the lead monofluoride ground state

DOE PAGES

Skripnikov, L. V.; Petrov, A. N.; Titov, A. V.; ...

2015-09-15

We report the results of our theoretical study and analysis of earlier experimental data for the g-factor tensor components of the ground 2II 1/2 state of the free PbF radical. These values obtained both within the relativistic coupled-cluster method combined with the generalized relativistic effective core potential approach and with our fit of the experimental data from [R. J. Mawhorter, B. S. Murphy, A. L. Baum, T. J. Sears, T. Yang, P. M. Rupasinghe, C. P. McRaven, N. E. Shafer-Ray, L. D. Alphei, and J.-U. Grabow, Phys. Rev. A 84, 022508 (2011); A. L. Baum, B.A. thesis, Pomona College, 2011].more » The obtained results agree very well with each other but contradict the previous fit performed in the cited works. Our final prediction for g factors is G ∥=0.081(5),G ⊥=–0.27(1).« less

Further investigation of g factors for the lead monofluoride ground state

NASA Astrophysics Data System (ADS)

Skripnikov, L. V.; Petrov, A. N.; Titov, A. V.; Mawhorter, R. J.; Baum, A. L.; Sears, T. J.; Grabow, J.-U.

2015-09-01

We report the results of our theoretical study and analysis of earlier experimental data for the g -factor tensor components of the ground 2Π1 /2 state of the free PbF radical. The values were obtained both within the relativistic coupled-cluster method combined with the generalized relativistic effective core potential approach and with our fit of the experimental data from [R. J. Mawhorter, B. S. Murphy, A. L. Baum, T. J. Sears, T. Yang, P. M. Rupasinghe, C. P. McRaven, N. E. Shafer-Ray, L. D. Alphei, and J.-U. Grabow, Phys. Rev. A 84, 022508 (2011), 10.1103/PhysRevA.84.022508; A. L. Baum, B.A. thesis, Pomona College, 2011]. The obtained results agree very well with each other but contradict the previous fit performed in the cited works. Our final prediction for g factors is G∥=0.081 (5 ) ,G⊥=-0.27 (1 ) .

Thermal and refining processes, not fermentation, tend to reduce lipotropic capacity of plant-based foods.

PubMed

Fardet, Anthony; Martin, Jean-François; Chardigny, Jean-Michel

2011-08-01

Plant-based foods (PBF) are relevant and diversified sources of lipotropes, which are compounds preventing excess hepatic fat deposits. In a first study, we defined the lipotropic capacity (LC, %) of raw PBF as the means of 8 lipotrope densities (LD, mg/100 kcal), each expressed relative to that of a reference food ranking the highest considering its mean 8 LD ranks (LC(raw asparagus)=100%) (A. Fardet, J.-F. Martin and J. M. Chardigny, J. Food Comp. Anal., 2011, DOI: 10.1016/j.jfca.2011.1003.1013). We showed that vegetables appeared as the best source of lipotropes on a 100 kcal-basis compared to legumes, cereals, fruits and nuts. The main objective of this second study was to quantify the effect of processing on LD and LC of raw PBF based on lipotrope contents collected in a USDA (United State Department of Agriculture) database and the literature, i.e. betaine, choline, myo-inositol, methionine, magnesium, niacin, pantothenic acid and folate contents. Choline and betaine densities were not significantly affected by processing while methionine and lipotropic micronutrient densities were significantly decreased, especially for magnesium, pantothenate and folates. Myo-inositol density decreases were insignificant due to lower product number resulting from limited literature data. Lipotropic micronutrient densities were more affected by processing than other densities. Fermentations increased betaine (median change of +32%) and choline (+34%) densities. Canning and boiling vegetables increased choline densities (+26%). Globally, processing significantly reduced LC by ∼20%, fermentations being less drastic (median change of -5%) than refining (-33%) and thermal treatments (-16%). More specifically, canning increased LC of beetroot (536 vs 390%) and common bean (40 vs 36%) as fermentation towards LC grape (14 vs 7% for wine). Results were then mainly discussed based on percentages of lipotrope content changes on a dry-weight basis. Results of this study also showed that the LC is quite a relevant index to estimate effect of processing on lipotropic potential of PBF. This journal is © The Royal Society of Chemistry 2011

Residual stress measurements via neutron diffraction of additive manufactured stainless steel 17-4 PH.

PubMed

Masoomi, Mohammad; Shamsaei, Nima; Winholtz, Robert A; Milner, Justin L; Gnäupel-Herold, Thomas; Elwany, Alaa; Mahmoudi, Mohamad; Thompson, Scott M

2017-08-01

Neutron diffraction was employed to measure internal residual stresses at various locations along stainless steel (SS) 17-4 PH specimens additively manufactured via laser-powder bed fusion (L-PBF). Of these specimens, two were rods (diameter=8 mm, length=80 mm) built vertically upward and one a parallelepiped (8×80×9 mm 3 ) built with its longest edge parallel to ground. One rod and the parallelepiped were left in their as-built condition, while the other rod was heat treated. Data presented provide insight into the microstructural characteristics of typical L-PBF SS 17-4 PH specimens and their dependence on build orientation and post-processing procedures such as heat treatment. Data have been deposited in the Data in Brief Dataverse repository (doi:10.7910/DVN/T41S3V).

Quantitative lung perfusion evaluation using Fourier decomposition perfusion MRI.

PubMed

Kjørstad, Åsmund; Corteville, Dominique M R; Fischer, Andre; Henzler, Thomas; Schmid-Bindert, Gerald; Zöllner, Frank G; Schad, Lothar R

2014-08-01

To quantitatively evaluate lung perfusion using Fourier decomposition perfusion MRI. The Fourier decomposition (FD) method is a noninvasive method for assessing ventilation- and perfusion-related information in the lungs, where the perfusion maps in particular have shown promise for clinical use. However, the perfusion maps are nonquantitative and dimensionless, making follow-ups and direct comparisons between patients difficult. We present an approach to obtain physically meaningful and quantifiable perfusion maps using the FD method. The standard FD perfusion images are quantified by comparing the partially blood-filled pixels in the lung parenchyma with the fully blood-filled pixels in the aorta. The percentage of blood in a pixel is then combined with the temporal information, yielding quantitative blood flow values. The values of 10 healthy volunteers are compared with SEEPAGE measurements which have shown high consistency with dynamic contrast enhanced-MRI. All pulmonary blood flow (PBF) values are within the expected range. The two methods are in good agreement (mean difference = 0.2 mL/min/100 mL, mean absolute difference = 11 mL/min/100 mL, mean PBF-FD = 150 mL/min/100 mL, mean PBF-SEEPAGE = 151 mL/min/100 mL). The Bland-Altman plot shows a good spread of values, indicating no systematic bias between the methods. Quantitative lung perfusion can be obtained using the Fourier Decomposition method combined with a small amount of postprocessing. Copyright © 2013 Wiley Periodicals, Inc.

Measurement and validation of measures for impulsive food choice across obese and healthy-weight individuals.

PubMed

Hendrickson, Kelsie L; Rasmussen, Erin B; Lawyer, Steven R

2015-07-01

The present study established a brief measure of delay discounting for food, the Food Choice Questionnaire (FCQ), and compared it to another more established measure of food discounting that uses the adjusting amount (AA) procedure. One hundred forty-four undergraduate participants completed either two measures of hypothetical food discounting (a computerized food AA procedure or the FCQ) or two measures of hypothetical money discounting [a computerized monetary AA procedure or the Monetary Choice questionnaire (MCQ)]. The money condition was used as a replication of previous work. Results indicated that the FCQ yielded consistent data that strongly correlated with the AA food discounting task. Moreover, a magnitude effect was found with the FCQ, such that smaller amounts of food were discounted more steeply than larger amounts. In addition, individuals with higher percent body fat (PBF) discounted food more steeply than individuals with lower PBF. The MCQ, which also produced a magnitude effect, and the monetary adjusting amount procedure yielded data that were orderly, consistent, and correlated strongly with one another, replicating previous literature. This study is the first to show that a novel measure of food discounting (the FCQ) yields consistent data strongly correlated with an established measure of food discounting and is sensitive to PBF. Moreover, the FCQ is easier and quicker to administer than the AA procedure, which may interest researchers who use discounting tasks in food-related research. Copyright © 2015 Elsevier Ltd. All rights reserved.

Structure and up-conversion luminescence in sol-gel derived Er 3+-Yb 3+ co-doped SiO 2:PbF 2 nano-glass-ceramics

NASA Astrophysics Data System (ADS)

del-Castillo, J.; Yanes, A. C.; Méndez-Ramos, J.; Tikhomirov, V. K.; Rodríguez, V. D.

2009-11-01

Transparent oxyfluoride nano-glass-ceramics 90(SiO 2)10(PbF 2) co-doped with 0.3 Yb 3+ and 0.1 Er 3+ (mol%) have been prepared by thermal treatment of precursor sol-gel glasses. X-ray diffraction and high resolution transmission electron microscopy analysis pointed out a precipitation of cubic β-PbF 2 nanocrystals of certain diameter in nano-glass-ceramics varying from 10 to 20 nm depending on heat treatment conditions. The incorporation of Yb 3+ and Er 3+ dopants in these nanocrystals has been confirmed by signatures of luminescence spectroscopy. Up-conversion luminescence pumped at 980 nm has been detected. Colour tuneability of up-conversion luminescence varying pump power has been analyzed in terms of standard chromaticity diagram. This tuneability opens applications for up-conversion phosphors and three-dimensional optical recording.

An analysis of estimation of pulmonary blood flow by the single-breath method

NASA Technical Reports Server (NTRS)

Srinivasan, R.

1986-01-01

The single-breath method represents a simple noninvasive technique for the assessment of capillary blood flow across the lung. However, this method has not gained widespread acceptance, because its accuracy is still being questioned. A rigorous procedure is described for estimating pulmonary blood flow (PBF) using data obtained with the aid of the single-breath method. Attention is given to the minimization of data-processing errors in the presence of measurement errors and to questions regarding a correction for possible loss of CO2 in the lung tissue. It is pointed out that the estimations are based on the exact solution of the underlying differential equations which describe the dynamics of gas exchange in the lung. The reported study demonstrates the feasibility of obtaining highly reliable estimates of PBF from expiratory data in the presence of random measurement errors.

Emergency braking is affected by the use of cruise control.

PubMed

Jammes, Yves; Behr, Michel; Llari, Maxime; Bonicel, Sarah; Weber, Jean Paul; Berdah, Stephane

2017-08-18

We compared the differences in the braking response to vehicle collision between an active human emergency braking (control condition) and cruise control (CC) or adaptive cruise control (ACC). In 11 male subjects, age 22 to 67 years, we measured the active emergency braking response during manual driving using the accelerator pedal (control condition) or in condition mimicking CC or ACC. In both conditions, we measured the brake reaction time (BRT), delay to produce the peak braking force (PBD), total emergency braking response (BRT + PBD), and peak braking force (PBF). Electromyograms of leg and thigh muscles were recorded during braking. The tonic vibratory response (TVR), Hoffman reflex (HR), and M-waves were recorded in leg muscles to explore the change in sensorimotor control. No difference in PBF, TVR amplitude, HR latency, and H max /M max ratio were found between the control and CC/ACC conditions. On the other hand, BRT and PBD were significantly lengthened in the CC/ACC condition (240 ± 13 ms and 704 ± 70 ms, respectively) compared to control (183 ± 7 ms and 568 ± 36 ms, respectively). BRT increased with the age of participants and the driving experience shortened PBD and increased PBF. In male subjects, driving in a CC/ACC condition significantly delays the active emergency braking response to vehicle collision. This could result from higher amplitude of leg motion in the CC/ACC condition and/or by the age-related changes in motor control. Car and truck drivers must take account of the significant increase in the braking distance in a CC/ACC condition.

Technological developments for strontium-90 determination using AMS

NASA Astrophysics Data System (ADS)

Satou, Yukihiko; Sueki, Keisuke; Sasa, Kimikazu; Matsunaka, Tetsuya; Takahashi, Tsutomu; Shibayama, Nao; Izumi, Daiki; Kinoshita, Norikazu; Matsuzaki, Hiroyuki

2015-10-01

Accelerator mass spectrometry (AMS) is one of method used for 90Sr determination. It would enable rapid 90Sr measurements from environmental samples such as water, soil, and milk. However, routine analysis of 90Sr using AMS has not yet been achieved because of difficulties associated with isobaric separation and production of intense negative ion beams characterized by currents from hundreds of nanoamperes to several microamperes. We have developed a rapid procedure for preparing samples with optimum compositions for use with AMS, which enables production of intense Sr beam currents from an ion source. Samples of SrF2 were prepared from a standard Sr solution and agricultural soil. The time required to prepare a SrF2 sample from a soil sample was 10 h. Negative 88SrF3- ions were successfully extracted at 500 nA from mixed samples of SrF2 and PbF2. In the present work, negative ions of 90Zr, included as an impurity, were accelerated with a tandem accelerator operated at a terminal voltage of 5 MV. Ions characterized by a charge state of 6+ were channeled into a gas counter. An atomic ratio of 90Zr/88Sr of 3 × 10-8 was estimated for the soil sample. No signal was detected from the assay of PbF2, which was pressed in an aluminum cathode, for a mass number of 90. PbF2 revealed good performance in the production of negative SrF3- molecular ion beams and detection of 90Sr with a gas counter.

Preliminary Investigation of Keyhole Phenomena during Single Layer Fabrication in Laser Additive Manufacturing of Stainless Steel

NASA Astrophysics Data System (ADS)

Matilainen, Ville-Pekka; Piili, Heidi; Salminen, Antti; Nyrhilä, Olli

Laser additive manufacturing (LAM) is a fabrication technology that enables production of complex parts from metallic materials with mechanical properties comparable to conventionally manufactured parts. In the LAM process, parts are manufactured by melting metallic powder layer-by-layer with a laser beam. This manufacturing technology is nowadays called powder bed fusion (PBF) according to the ASTM F2792-12a standard. This strategy involves several different independent and dependent thermal cycles, all of which have an influence on the final properties of the manufactured part. The quality of PBF parts depends strongly on the characteristics of each single laser-melted track and each single layer. This study consequently concentrates on investigating the effects of process parameters such as laser power on single track and layer formation and laser-material interaction phenomena occurring during the PBF process. Experimental tests were done with two different machines: a modified research machine based on an EOS EOSINT M-series system and an EOS EOSINT M280 system. The material used was EOS stainless steel 17-4 PH. Process monitoring was done with an active illuminated high speed camera system. After microscopy analysis, it was concluded that a keyhole can form during laser additive manufacturing of stainless steel. It was noted that heat input has an important effect on the likelihood of keyhole formation. The threshold intensity value for keyhole formation of 106 W/cm2 was exceeded in all manufactured single tracks. Laser interaction time was found to have an effect on penetration depth and keyhole formation, since the penetration depth increased with increased laser interaction time. It was also concluded that active illuminated high speed camera systems are suitable for monitoring of the manufacturing process and facilitate process control.

In vivo assessment of bone healing following Piezotome® ultrasonic instrumentation.

PubMed

Reside, Jonathan; Everett, Eric; Padilla, Ricardo; Arce, Roger; Miguez, Patricia; Brodala, Nadine; De Kok, Ingeborg; Nares, Salvador

2015-04-01

This pilot study evaluated the molecular, histologic, and radiographic healing of bone to instrumentation with piezoelectric or high speed rotary (R) devices over a 3-week healing period. Fourteen Sprague-Dawley rats (Charles River Laboratories International, Inc., Wilmington, MA, USA) underwent bilateral tibial osteotomies prepared in a randomized split-leg design using Piezotome® (P1) (Satelec Acteon, Merignac, France), Piezotome 2® (P2) (Satelec Acteon), High-speed R instrumentation, or sham surgery (S). At 1 week, an osteogenesis array was used to evaluate differences in gene expression while quantitative analysis assessed percentage bone fill (PBF) and bone mineral density (BMD) in the defect, peripheral, and distant regions at 3 weeks. Qualitative histologic evaluation of healing osteotomies was also performed at 3 weeks. At 1 week, expression of 11 and 18 genes involved in bone healing was significantly (p < .05) lower following P1 and P2 instrumentation, respectively, relative to S whereas 16 and 4 genes were lower relative to R. No differences in PBF or BMD were detected between groups within the osteotomy defect. However, significant differences in PBF (p = .020) and BMD (p = .008) were noted along the peripheral region between P2 and R groups, being R the group with the lowest values. Histologically, smooth osteotomy margins were present following instrumentation using P1 or P2 relative to R. Piezoelectric instrumentation favors preservation of bone adjacent to osteotomies while variations in gene expression suggest differences in healing rates due to surgical modality. Bone instrumented by piezoelectric surgery appears less detrimental to bone healing than high-speed R device. © 2013 Wiley Periodicals, Inc.

Effect of early exclusive breastfeeding on morbidity among infants born to HIV-negative mothers in Zimbabwe.

PubMed

Koyanagi, Ai; Humphrey, Jean H; Moulton, Lawrence H; Ntozini, Robert; Mutasa, Kuda; Iliff, Peter; Black, Robert E

2009-05-01

Early exclusive breastfeeding (EBF) is recommended by the World Health Organization, but EBF rates remain low throughout the world. For infants born to breastfeeding HIV-positive mothers, early EBF is associated with a lower risk of postnatal transmission than is feeding breast milk together with other liquids or foods. No studies conducted in Africa have reported any benefits of EBF for infants born to HIV-negative women. The objective was to compare the rate of sick clinic visits by infants aged 43-182 d according to breastfeeding exclusivity [EBF, predominant breastfeeding (PBF), and mixed breastfeeding (MBF)]. We compared rates of all-cause clinic visits and clinic visits related to diarrhea and lower respiratory tract infection (LRTI) among a cohort of 9207 infants of HIV-negative mothers during 2 age intervals: 43-91 and 92-182 d according to exclusivity of breastfeeding. Breastfeeding exclusivity was defined in 2 ways ("ever since birth" and "previous 7 d") and was assessed at 43 and 91 d. EBF between birth and 3 mo was significantly protective against diarrhea between 3 and 6 mo of age with the "ever since birth" definition [incidence rate ratios (IRRs) of 8.83 (95% CI: 1.07, 65.53) and 8.76 (95% CI: 1.13, 68.09) for PBF and MBF, respectively] and with the "previous 7 d" definition [2.04 (95% CI: 1.11, 3.77) and 2.05 (95% CI: 1.13, 3.72) for PBF and MBF, respectively]. The adverse effect of MBF on LRTI visits was weaker, reaching borderline significance only by the "ever since birth" definition during the 43-91-d interval (IRR: 1.91; 95% CI: 0.99, 3.67). Early EBF is associated with a significant reduction in sick clinic visits, especially those due to diarrhea.

Data reconstruction can improve abundance index estimation: An example using Taiwanese longline data for Pacific bluefin tuna

PubMed Central

Fukuda, Hiromu; Maunder, Mark N.

2017-01-01

Catch-per-unit-effort (CPUE) is often the main piece of information used in fisheries stock assessment; however, the catch and effort data that are traditionally compiled from commercial logbooks can be incomplete or unreliable due to many reasons. Pacific bluefin tuna (PBF) is a seasonal target species in the Taiwanese longline fishery. Since 2010, detailed catch information for each PBF has been made available through a catch documentation scheme. However, previously, only market landing data with a low coverage of logbooks were available. Therefore, several nontraditional procedures were performed to reconstruct catch and effort data from many alternative data sources not directly obtained from fishers for 2001–2015: (1) Estimating the catch number from the landing weight for 2001–2003, for which the catch number information was incomplete, based on Monte Carlo simulation; (2) deriving fishing days for 2007–2009 from voyage data recorder data, based on a newly developed algorithm; and (3) deriving fishing days for 2001–2006 from vessel trip information, based on linear relationships between fishing and at-sea days. Subsequently, generalized linear mixed models were developed with the delta-lognormal assumption for standardizing the CPUE calculated from the reconstructed data, and three-stage model evaluation was performed using (1) Akaike and Bayesian information criteria to determine the most favorable variable composition of standardization models, (2) overall R2 via cross-validation to compare fitting performance between area-separated and area-combined standardizations, and (3) system-based testing to explore the consistency of the standardized CPUEs with auxiliary data in the PBF stock assessment model. The last stage of evaluation revealed high consistency among the data, thus demonstrating improvements in data reconstruction for estimating the abundance index, and consequently the stock assessment. PMID:28968434

Which index best correlates with body fat mass: BAI, BMI, waist or WHR?

PubMed

Suchanek, Pavel; Kralova Lesna, Ivana; Mengerova, Olga; Mrazkova, Jolana; Lanska, Vera; Stavek, Petr

2012-01-01

The body mass index (BMI) has been the most commonly applied clinical measure to characterise body composition in individuals. However, the BMI has been criticised as being an inaccurate measure of body fatness. Recently, a new index reflecting body composition, the Body Adiposity Index (BAI) was proposed. The BAI was calculated using the equation BAI=((hip circumference)/ ((height)1.5) - 18). The aim of this study was to compare estimates of body fat content, i.e., body adiposity index (BAI), BMI, waist-hip ratio (WHR) and waist and hip circumferences, with respect to their ability to predict the percentage of body fat (PBF). To select an optimal surrogate for adiposity, we examined the correlation between body adiposity percentage as measured by BIA and several variables, including BAI, BMI and WHR. Correlations ranged from a high of 0.78 for BMI, 0.67 for BAI and 0.66 for waist circumference to a low value of 0.39 for the WHR index. The correlation between PBF and BAI (R=0.67, R2=0.45, p<0.001) and the correlation between PBF and BMI (R=0.78, R2=0.60, p<0.001) were of similar magnitude. Based on our results and those of other studies, we can say that the BAI index is not a universally valid index that could be used in the place of the BMI index in a Caucasian population; indeed, it would not accurately reflect body fat mass and thus could lead to an increased risk of obesity. Further, WHR index is not a suitable for an estimation of body fat.

Central and regional hemodynamics in prolonged space flights

NASA Astrophysics Data System (ADS)

Gazenko, O. G.; Shulzhenko, E. B.; Turchaninova, V. F.; Egorov, A. D.

This paper presents the results of measuring central and regional (head, forearm, calf) hemodynamics at rest and during provocative tests by the method of tetrapolar rheography in the course of Salyut-6-Soyuz and Salyut-7-Soyuz missions. The measurements were carried out during short-term (19 man-flights of 7 days in duration) and long-term (21 man-flights of 65-237 days in duration) manned missions. At rest, stroke volume (SV) and cardiac output (CO) as well as heart rate (HR) decreased insignificantly (in short-term flights) or remained essentially unchanged (in long-term flights). In prolonged flights CO increased significantly in response to exercise tests due to an increase in HR and the lack of changes in SV. After exercise tests SV and CO decreased as compared to the preflight level. During lower body negative pressure (LBNP) tests HR and CO were slightly higher than preflight. Changes in regional hemodynamics included a distinct decrease of pulse blood filling (PBF) of the calf, a reduction of the tone of large vessels of the calf and small vessels of the forearm. Head examination (in the region of the internal carotid artery) showed a decrease of PBF of the left hemisphere (during flight months 2-8) and a distinct decline of the tone of small vessels, mainly, in the right hemisphere. During LBNP tests the tone of pre- and postcapillary vessels of the brain returned to normal while PBF of the right and left hemisphere vessels declined. It has been shown that regional circulation variations depend on the area examined and are induced by a rearrangement of total hemodynamics of the human body in microgravity. This paper reviews the data concerning changes in central and regional circulation of men in space flights of different duration.

In Situ 3D Monitoring of Geometric Signatures in the Powder-Bed-Fusion Additive Manufacturing Process via Vision Sensing Methods.

PubMed

Li, Zhongwei; Liu, Xingjian; Wen, Shifeng; He, Piyao; Zhong, Kai; Wei, Qingsong; Shi, Yusheng; Liu, Sheng

2018-04-12

Lack of monitoring of the in situ process signatures is one of the challenges that has been restricting the improvement of Powder-Bed-Fusion Additive Manufacturing (PBF AM). Among various process signatures.

Effect of Laser Powder Bed Fusion Parameters on the Microstructure and Texture Development in Superelastic Ti-18Zr-14Nb Alloy

NASA Astrophysics Data System (ADS)

Kreitcberg, A.; Brailovski, V.; Sheremetyev, V.; Prokoshkin, S.

2017-12-01

The effect of different laser powder bed fusion (L-PBF) parameters on the phase composition, microstructure, and crystallographic texture of Ti-18Zr-14Nb alloy was studied. Two levels of laser power, scanning speed, and hatching space were used, while the layer thickness was kept constant. The resulting volume energy density was ranged from 20 to 60 J/mm3, and the build rate, from 12 to 36 cm3/h. The manufactured coupons were analyzed by X-ray diffractometry, transmission, and scanning electron microscopy. It was found that the greater influence observed on the microstructure and texture development was caused by the value of laser power, while the lowest, by that of hatching space. Based on the results obtained, the processing optimization strategy aimed at improving the density, superelastic, and fatigue properties of the L-PBF manufactured Ti-18Zr-14Nb alloy was proposed.

Soil health improvement in an organic orchard production system in Northwest Missouri

USDA-ARS?s Scientific Manuscript database

Prairie Birthday Farm (PBF), a diversified, organic enterprise on the loess hill landscape in northwestern Missouri, was previously managed as a conventional corn-soybean production system. Transition to organic farming began in 1995 and included soil organic matter restoration with native prairie e...

Performance-Based Funding in Public Schools.

ERIC Educational Resources Information Center

Foster, Charles A.; Marquart, Deanna J.

This report examines three performance-based funding (PBF) plans: (1) merit pay for teachers and/or administrators; (2) career ladders; and (3) formula-driven incentive payments to schools. The report contends that present-day problems in public schools result largely from the organizational structure of the educational enterprise. Being based on…

Ecologically-based management improves soil health in an organic orchard production system

USDA-ARS?s Scientific Manuscript database

Prairie Birthday Farm (PBF), a diversified, organic enterprise on the loess hill landscape in northwestern Missouri, was previously managed as a conventional corn-soybean production system. The soil (Sharpsburg silt loam; fine, montmorillonitic, mesic Typic Argiudolls) is mapped as an ‘eroded soil p...

Computer-Based Feedback and Goal Intervention: Learning Effects

ERIC Educational Resources Information Center

Valdez, Alfred

2012-01-01

This study investigated how a goal intervention influences the learning effects gained from feedback when acquiring concepts and rules pertaining to the topic of descriptive statistics. Three feedback conditions; knowledge of correct response feedback (KCRF), principle-based feedback (PBF), and no-feedback (NF), were crossed with two goal…

76 FR 36103 - Combined Notice of Filings #1

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-21

...-2077-005. Applicants: Delaware City Refining Company LLC, PBF Power Marketing LLC. Desciption: Delaware City Refining Company LLC, Triennial Market Power Analysis and Notice of Change in Status. Filed Date..., 2011. Docket Numbers: ER10-2074-001; ER10-2097-003. Applicants: Kansas City Power & Light Company, KCP...

Performance-Based Funding: State Policy Influences on Small Rural Community Colleges

ERIC Educational Resources Information Center

Thornton, Zoë Mercedes; Friedel, Janice Nahra

2016-01-01

Performance-based funding (PBF) models intend to increase efficiency and productivity of the institution, thereby influencing organizational change. This change may be structural, programmatic, or procedural, and it may affect institutional practice and/or policy. The purpose of this qualitative case study was to understand the organizational…

Behavior Management and Behavioral Change: How Can We Tell Them Apart?

ERIC Educational Resources Information Center

Olive, Edna

2010-01-01

Understanding the differences between behavior management and behavior change helps adults identify the differences between the two and teaches them what they can do to be effective in the use of both. This article introduces Positive Behavior Facilitation (PBF) Tool #3 which aims to support adults in understanding the differences between behavior…

Structural, morphological and optical investigations on electron-beam irradiated PbF2-TeO2-B2O3-Eu2O3 glasses

NASA Astrophysics Data System (ADS)

Wagh, Akshatha; Petwal, Vikash; Dwivedi, Jishnu; Upadhyaya, V.; Raviprakash, Y.; Kamath, Sudha D.

2016-09-01

Combined structural, optical and morphological studies were carried out on Eu2O3 doped PbF2-TeO2-B2O3 glass samples, before and after being subjected to electron beam of energy 7.5 MeV. XRD confirmed the amorphous nature of the glasses even after 150 kGy electron beam irradiation. Densities of the irradiated samples showed slightly greater values when compared to their respective values before irradiation, which proved the increase in the compaction of the network. The intensities of the three prominent bands; B-O-B linkages, BO4 units and BO3 units of FT-IR spectra, of the titled glasses, showed slight decrease after electron beam irradiation. The decrement in the values of energy band gap and shift in cut-off wavelength towards red edge, proved the formation of color centers in the glass network after irradiation. The change in Hunter L values, through color measurement was a proof for the Farbe/color/absorption centers created in the glass sites after irradiation.

The assisted bidirectional Glenn: a novel surgical approach for first-stage single-ventricle heart palliation.

PubMed

Esmaily-Moghadam, Mahdi; Hsia, Tain-Yen; Marsden, Alison L

2015-03-01

Outcomes after a modified Blalock-Taussig shunt (mBTS) in neonates with single-ventricle physiology remain unsatisfactory. However, initial palliation with a superior cavopulmonary connection, such as a bidirectional Glenn (BDG), is discouraged, owing to potential for inadequate pulmonary blood flow (PBF). We tested the feasibility of a novel surgical approach, adopting the engineering concept of an ejector pump, whereby the flow in the BDG is "assisted" by injection of a high-energy flow stream from the systemic circulation. Realistic 3-dimensional models of the neonatal mBTS and BDG circulations were created. The "assisted" bidirectional Glenn (ABG) consisted of a shunt between the right innominate artery and the superior vena cava (SVC), with a 1.5-mm clip near the SVC anastomosis to create a Venturi effect. The 3 models were coupled to a validated hydraulic circulation model, and 2 pulmonary vascular resistance (PVR) values (7 and 2.3 Wood units) were simulated. The ABG provided the highest systemic oxygen saturation and oxygen delivery at both PVR levels. In addition to achieving higher PBF than the BDG, the ABG produced a lower single-ventricular workload than mBTS. SVC pressure was highest in the ABG model (ABG: 15; Glenn: 11; mBTS: 3 mm Hg; PVR = 7 Wood units), but at low PVR, the SVC pressure was significantly lower (ABG: 8; Glenn: 6; mBTS: <3 mm Hg). Adopting the principle of an ejector pump, with additional flow directed into the SVC in a BDG, the ABG appears to increase PBF with a modest increase in SVC and pulmonary arterial pressure. Although multiscale modeling results demonstrate the conceptual feasibility of the ABG circulation, further technical refinement and investigations are necessary, especially in an appropriate animal model. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Emphysema on Thoracic CT and Exercise Ventilatory Inefficiency in Mild-to-Moderate COPD.

PubMed

Jones, Joshua H; Zelt, Joel T; Hirai, Daniel M; Diniz, Camilla V; Zaza, Aida; O'Donnell, Denis E; Neder, J Alberto

2017-04-01

There is growing evidence that emphysema on thoracic computed tomography (CT) is associated with poor exercise tolerance in COPD patients with only mild-to-moderate airflow obstruction. We hypothesized that an excessive ventilatory response to exercise (ventilatory inefficiency) would underlie these abnormalities. In a prospective study, 19 patients (FEV 1 = 82 ± 13%, 12 Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1) and 26 controls underwent an incremental exercise test. Ventilatory inefficiency was assessed by the ventilation ([Formula: see text]E)/CO 2 output ([Formula: see text]CO 2 ) nadir. Pulmonary blood flow (PBF) in a submaximal test was calculated by inert gas rebreathing. Emphysema was quantified as % of attenuation areas below 950 HU. Patients typically presented with centrilobular emphysema (76.8 ± 10.1% of total emphysema) in the upper lobes (upper/total lung ratio = 0.82 ± 0.04). They had lower peak oxygen uptake ([Formula: see text]O 2 ), higher [Formula: see text]E/[Formula: see text]CO 2 nadir, and greater dyspnea scores than controls (p < 0.05). Lower peak [Formula: see text]O 2 and worse dyspnea were found in patients with higher [Formula: see text]E/[Formula: see text]CO 2 nadirs (≥30). Patients had blunted increases in PBF from rest to iso-[Formula: see text]O 2 exercise (p < 0.05). Higher [Formula: see text]E/[Formula: see text]CO 2 nadir in COPD was associated with emphysema severity (r = 0.63) which, in turn, was related to reduced lung diffusing capacity (r = -0.72) and blunted changes in PBF from rest to exercise (r = -0.69) (p < 0.01). Ventilation "wasted" in emphysematous areas is associated with impaired exercise ventilatory efficiency in mild-to-moderate COPD. Exercise ventilatory inefficiency links structure (emphysema) and function (D L CO) to a key clinical outcome (poor exercise tolerance) in COPD patients with only modest spirometric abnormalities.

Risk-based decision making to manage water quality failures caused by combined sewer overflows

NASA Astrophysics Data System (ADS)

Sriwastava, A. K.; Torres-Matallana, J. A.; Tait, S.; Schellart, A.

2017-12-01

Regulatory authorities set certain environmental permit for water utilities such that the combined sewer overflows (CSO) managed by these companies conform to the regulations. These utility companies face the risk of paying penalty or negative publicity in case they breach the environmental permit. These risks can be addressed by designing appropriate solutions such as investing in additional infrastructure which improve the system capacity and reduce the impact of CSO spills. The performance of these solutions is often estimated using urban drainage models. Hence, any uncertainty in these models can have a significant effect on the decision making process. This study outlines a risk-based decision making approach to address water quality failure caused by CSO spills. A calibrated lumped urban drainage model is used to simulate CSO spill quality in Haute-Sûre catchment in Luxembourg. Uncertainty in rainfall and model parameters is propagated through Monte Carlo simulations to quantify uncertainty in the concentration of ammonia in the CSO spill. A combination of decision alternatives such as the construction of a storage tank at the CSO and the reduction in the flow contribution of catchment surfaces are selected as planning measures to avoid the water quality failure. Failure is defined as exceedance of a concentration-duration based threshold based on Austrian emission standards for ammonia (De Toffol, 2006) with a certain frequency. For each decision alternative, uncertainty quantification results into a probability distribution of the number of annual CSO spill events which exceed the threshold. For each alternative, a buffered failure probability as defined in Rockafellar & Royset (2010), is estimated. Buffered failure probability (pbf) is a conservative estimate of failure probability (pf), however, unlike failure probability, it includes information about the upper tail of the distribution. A pareto-optimal set of solutions is obtained by performing mean- pbf optimization. The effectiveness of using buffered failure probability compared to the failure probability is tested by comparing the solutions obtained by using mean-pbf and mean-pf optimizations.

Gene-by-environment interactions of the CLOCK, PEMT, and GHRELIN loci with average sleep duration in relation to obesity traits using a cohort of 643 New Zealand European children.

PubMed

Krishnan, Mohanraj; Shelling, Andrew N; Wall, Clare R; Mitchell, Edwin A; Murphy, Rinki; McCowan, Lesley M E; Thompson, John M D

2017-09-01

Modern technology may have desensitised the 'biological clock' to environmental cues, disrupting the appropriate co-ordination of metabolic processes. Susceptibility to misalignment of circadian rhythms may be partly genetically influenced and effects on sleep quality and duration could predispose to poorer health outcomes. Shorter sleep duration is associated with obesity traits, which are brought on by an increased opportunity to eat and/or a shift of hormonal profile promoting hunger. We hypothesised that increased sleep duration will offset susceptible genetic effects, resulting in reduced obesity risk. We recruited 643 (male: 338; female: 305) European children born to participants in the New Zealand centre of the International Screening for Pregnancy Endpoints sleep study. Ten genes directly involved in the circadian rhythm machinery and a further 20 genes hypothesised to be driven by cyclic oscillations were evaluated by Sequenom assay. Multivariable regression was performed to test the interaction between gene variants and average sleep length (derived from actigraphy), in relation to obesity traits (body mass index (BMI) z-scores and percentage body fat (PBF)). No association was found between average sleep length and BMI z-scores (p = 0.056) or PBF (p = 0.609). Uncorrected genotype associations were detected between STAT-rs8069645 (p = 0.0052) and ADIPOQ-rs266729 (p = 0.019) with differences in average sleep duration. Evidence for uncorrected gene-by-sleep interactions of the CLOCK-rs4864548 (p = 0.0039), PEMT-936108 (p = 0.016) and GHRELIN-rs696217 (p = 0.046) were found in relation to BMI z-scores but not for PBF. Our results indicate that children may have different genetic susceptibility to the effects of sleep duration on obesity. Further confirmatory studies are required in other population cohorts of different age groups. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of shielding parameters for heavy metal fluoride based tellurite-rich glasses for gamma ray shielding applications

NASA Astrophysics Data System (ADS)

Sayyed, M. I.; Lakshminarayana, G.; Kityk, I. V.; Mahdi, M. A.

2017-10-01

In this work, we have evaluated the γ-ray shielding parameters such as mass attenuation coefficient (μ/ρ), effective atomic number (Zeff), half value layer (HVL), mean free path (MFP) and exposure buildup factors (EBF) for heavy metal fluoride (PbF2) based tellurite-rich glasses. In addition, neutron total macroscopic cross sections (∑R) for these glasses were also calculated. The maximum value for μ/ρ, Zeff and ∑R was found for heavy metal (Bi2O3) oxide introduced glass. The results of the selected glasses have been compared, in terms of MFP with different glass systems. The shielding effectiveness of the selected glasses is found comparable or better than of common ones, which indicates that these glasses with suitable oxides could be developed for gamma ray shielding applications.

Shifting from Enrollment-to Performance-Based Funding in Higher Education: What Can We Learn from Washington's Experience?

ERIC Educational Resources Information Center

Kaikkonen, Darby

2016-01-01

Performance-based funding (PBF) in higher education has grown in recent years as a means of institutional accountability and incentive for improving student success. Although most states have successfully implemented their respective systems, research on early funding models suggests a difficult fiscal environment can introduce tension between…

Chemical and enzymatic catalytic routes to polyesters and oligopeptides biobased materials

NASA Astrophysics Data System (ADS)

Zhu, Jianhui

My Ph.D research focuses on the synthesis and property studies of different biobased materials, including polyesters, polyurethanes and oligopeptides. The first study describes the synthesis, crystal structure and physico-mechanical properties of a bio-based polyester prepared from 2,5-furandicarboxylic acid (FDCA) and 1,4-butanediol. Melt-polycondensation experiments were conducted by a two-stage polymerization using titanium tetraisopropoxide (Ti[OiPr] 4) as catalyst. Polymerization conditions (catalyst concentration, reaction time and 2nd stage reaction temperature) were varied to optimize poly(butylene furan dicarboxylate), PBF, molecular weight. A series of PBFs with different Mw were characterized by Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), Dynamic Mechanical Thermal Analysis (DMTA), X-Ray diffraction and tensile testing. Influence of molecular weight and melting/crystallization enthalpy on PBF material tensile properties was explored. Cold-drawing tensile tests at room temperature for PBF with Mw 16K to 27K showed a brittle-to-ductile transition. When Mw reaches 38K, the Young's Modulus of PBF remains above 900 MPa, and the elongation at break increases to above 1000%. The mechanical properties, thermal properties and crystal structures of PBF were similar to petroleum derived poly(butylenes terephthalate), PBT. Fiber diagrams of uniaxially stretched PBF films were collected, indexed, and the unit cell was determined as triclinic (a=4.78(3) A, b=6.03(5) A, c=12.3(1) A, alpha=110.1(2)°, beta=121.1(3)°, gamma=100.6(2)°). A crystal structure was derived from this data and final atomic coordinates are reported. We concluded that there is a close similarity of the PBF structure to PBT alpha- and beta-forms. In the second study, a biobased long chain polyester polyol (PC14-OH) was synthesized from o-hydroxytetradecanoic acid (o-HOC14) and 1,4-butanediol. The first section about polyester polyurethanes describes the synthesis and physico-mechanical properties for two series of linear polyurethane elastomers built from polyol polyesters which contain bio-based o-hydroxytetradecanoic acid (o-HOC14) repeat units. Varied quantities of o-HOC14 was converted by a condensation polymerization catalyzed by titanium tetraisopropoxide (Ti[OiPr]4) to polyester polyol with Mn around 2K. By end-cap the polyols with excess amount of 1,4-butanediol, low number of carbonyl end group can be achieved so that the polyols can be further used as soft segment of thermoplastic polyurethanes (TPU). We have studied the thermo-mechanical properties of two-series polyurethanes with different polyester polyols or polyester polyols mixtures. With increasing amount of o-HOC14 content in the soft segment polyols of polyurethanes, tensile strength of the polyurethanes kept increasing from 30MPa to 470MPa while at the same time their elongation ratio decreased from 900% to 300%. Their mechanical behavior shifted from elastomer to semi-crystalline plastic. In the second section about polyether polyurethanes, PC14-OH and poly(tetrahydrofuran) mixtures were used as soft segment in linear polyurethane elastomer synthesis. Similar thermal and mechanical property changing trends were observed with increasing amount of PC14-OH up to 30 wt% of total soft segments. In this study, the functions of PC14-OH in thermoplastic polyurethane elastomers were identified, and there are several benefits of incorporating this long chain fatty acid. In the third study, seven amphiphilic alternating oligopeptides were synthesized via chemo-enzymatic routes. Four proteases (papain, bromelain, alpha-chymotrypsin, and trypsin) were evaluated to determine their efficiency in synthesizing alternating peptides. The first series is hydrophobic-anionic alternating oligopeptides targeting for self assembly smart material design. So far, beta-sheet secondary structure of the anionic alternating oligopeptides was not observed very clearly at low pH comparing to the cationic alternating oligopeptides (KL)x, which is probably due to the short chain length of the oligopeptides. Combination of cationic and anionic alternating oligopeptides has been tested by (KL)x and (LD)x mixtures at 1:1 weight ratio, beta-sheet secondary structure started to appear at neutral pH. The preliminary CD results of the mixtures have shown the potential to manipulate self assembly behavior at different pHs. The second series is alternating oligo(Lys-Trp) targeting for antimicrobial agent design. The alternating (KW)x was successfully synthesized by alpha-chymotrypsin in mixed solvent medium. Chain length of (KW)x can be varied when using different mixed solvent medium. In order to increase the solubility of (KW)x-OEt, C-terminal ethyl ester moiety was modified by reaction with ethylene diamine. Antimicrobial activities of (KW)x with different chain lengths have been tested against E.coli and S. aureus. Our work utilizes a simplified synthetic method to prepare alternating peptides at the cost of chain length uniformity. However, (KW)x-OEt (n=3--6) alternating peptide mixtures still possesses quite good antimicrobial activity while the preparation method is much more easier and greener, which means this method is more economical and environmental friendly. Moreover, the adjustment of reaction conditions and proteases can successfully enhance the control over KW alternating peptide chain length to better achieve more antimicrobial active products. (Abstract shortened by UMI.).

75 FR 38813 - Granting of Request for Early Termination of the Waiting Period Under the Premerger Notification...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-06

... status Party name 26-APR-10 20100597 G PBF Energy Partners LP. G Valero Energy Corporation. G The Premcor.... G Armstrong World Industries, Inc. G Asbestos Personal Injury. G Armstrong World Industries, Inc. 20100605 G Brookfield Special Situations II L.P. G Ainsworth Lumber Co. Ltd. G Ainsworth Lumber Co. Ltd...

19 F(α,n) thick target yield from 3.5 to 10.0 MeV

DOE PAGES

Norman, E.B.; Chupp, T.E.; Lesko, K.T.; ...

2015-09-01

Using a target of PbF2, the thick-target yield from the 19F(α,n) reaction was measured from Eα=3.5–10 MeV. From these results, we infer the thick-target neutron yields from targets of F2 and UF6 over this same alpha-particle energy range.

Yb3+-Er3+-Tm3+ co-doped nano-glass-ceramics tuneable up-conversion phosphor

NASA Astrophysics Data System (ADS)

Méndez-Ramos, J.; Rodriguez, V. D.; Tikhomirov, V. K.; Del-Castillo, J.; Yanes, A. C.

2008-08-01

Transparent Yb3+-Er3+-Tm3+ co-doped nano-glass-ceramics have been prepared, 32(SiO{2}) 9(AlO{1.5}) 31.5(CdF{2}) 18.5(PbF{2}) 5.5(ZnF{2}): 3.5(Yb-Er-TmF{3}) mol%, where the co-dopants partition mostly to the fluoride PbF{2}-based nano-crystals. A comparative study of the up-conversion luminescence in nano-glass-ceramics and its precursor glass indicates that these materials can be used as blue/green/red tuneable up-conversion phosphor, in particular for white light generation. A ratio between blue, green and red emission bands of the Tm3+ and Er3+ can be widely varied with nano-ceramming of the precursor glass and with changing a pump power of luminescence. The change in the ratio between the blue, green and red emission bands is explained to be due to substantial lowering phonon energy and shortening of inter-dopant distances with nano-ceramming of the precursor glass and due to change in the ratio of 2- and 3-photon up-conversion processes with pump power.

Cardiovascular transition at birth: a physiological sequence.

PubMed

Hooper, Stuart B; Te Pas, Arjan B; Lang, Justin; van Vonderen, Jeroen J; Roehr, Charles Christoph; Kluckow, Martin; Gill, Andrew W; Wallace, Euan M; Polglase, Graeme R

2015-05-01

The transition to newborn life at birth involves major cardiovascular changes that are triggered by lung aeration. These include a large increase in pulmonary blood flow (PBF), which is required for pulmonary gas exchange and to replace umbilical venous return as the source of preload for the left heart. Clamping the umbilical cord before PBF increases reduces venous return and preload for the left heart and thereby reduces cardiac output. Thus, if ventilation onset is delayed following cord clamping, the infant is at risk of superimposing an ischemic insult, due to low cardiac output, on top of an asphyxic insult. Much debate has centered on the timing of cord clamping at birth, focusing mainly on the potential for a time-dependent placental to infant blood transfusion. This has prompted recommendations for delayed cord clamping for a set time after birth in infants not requiring resuscitation. However, recent evidence indicates that ventilation onset before cord clamping mitigates the adverse cardiovascular consequences caused by immediate cord clamping. This indicates that the timing of cord clamping should be based on the infant's physiology rather than an arbitrary period of time and that delayed cord clamping may be of greatest benefit to apneic infants.

Plasma-Based Mixing Actuation in Airflow, Quantitated by Probe Breakdown Fluorescence

NASA Astrophysics Data System (ADS)

Leonov, Sergey; Firsov, Alexander; Shurupov, Michail; Yarantsev, Dmitry; Ohio State University Team; JIHT RAS Team

2013-09-01

Effective mixing of fuel and oxidizer in air-breathing engine at compressible conditions is an essential problem of high-speed combustion due to short residence time of gas mixture in the combustor of limited length. The effect of the mixing actuation by plasma is observed because of the gasdynamic instability arisen after the long filamentary discharge of submicrosecond duration generated along the contact zone of two co-flown gases. The work is focused on detail consideration of the mechanism of gas instability, promoted by plasma, on effect of the discharge specific localization, and on diagnostics development for qualitative and quantitative estimation of the mixing efficiency. The dynamics of relative concentration of gas components is examined quantitatively by means of Probe Discharge Breakdown Fluorescence (PBF). In this method an optical emission spectra of weak filamentary high-voltage nanosecond probe discharge are collected from local zone of interest in airflow. The first measurements of the mixing efficiency in vicinity of wall-injected secondary gas are presented. It is shown that the method of PBF could deliver experimental data on state of the two-component medium with <1 mcs and <5 mm of time and spatial resolution, correspondingly. Funded by AFOSR under Dr Chiping Li supervision

Food prices and body fatness among youths.

PubMed

Grossman, Michael; Tekin, Erdal; Wada, Roy

2014-01-01

We examine the effect of food prices on clinical measures of obesity, including body mass index (BMI) and percentage body fat (PBF) measures derived from bioelectrical impedance analysis (BIA) and dual energy X-ray absorptiometry (DXA), among youths ages 12 through 18 in the National Health and Nutrition Examination Survey. This is the first study to consider clinically measured levels of body composition rather than BMI to investigate the effects of food prices on obesity outcomes among youths classified by gender and race/ethnicity. Our findings suggest that increases in the real price per calorie of food for home consumption and the real price of fast-food restaurant food lead to improvements in obesity outcomes among youths. We also find that a rise in the real price of fruits and vegetables leads to increased obesity. Finally, our results indicate that measures of PBF derived from BIA and DXA are no less sensitive and in some cases more sensitive to the prices just mentioned than BMI, and serve an important role in demonstrating that rising food prices (except fruit and vegetable prices) are indeed associated with reductions in obesity rather than with reductions in body size proportions alone. Copyright © 2013 Elsevier B.V. All rights reserved.

Demonstration of array eddy current technology for real-time monitoring of laser powder bed fusion additive manufacturing process

NASA Astrophysics Data System (ADS)

Todorov, Evgueni; Boulware, Paul; Gaah, Kingsley

2018-03-01

Nondestructive evaluation (NDE) at various fabrication stages is required to assure quality of feedstock and solid builds. Industry efforts are shifting towards solutions that can provide real-time monitoring of additive manufacturing (AM) fabrication process layer-by-layer while the component is being built to reduce or eliminate dependence on post-process inspection. Array eddy current (AEC), electromagnetic NDE technique was developed and implemented to directly scan the component without physical contact with the powder and fused layer surfaces at elevated temperatures inside a LPBF chamber. The technique can detect discontinuities, surface irregularities, and undesirable metallurgical phase transformations in magnetic and nonmagnetic conductive materials used for laser fusion. The AEC hardware and software were integrated with the L-PBF test bed. Two layer-by-layer tests of Inconel 625 coupons with AM built discontinuities and lack of fusion were conducted inside the L-PBF chamber. The AEC technology demonstrated excellent sensitivity to seeded, natural surface, and near-surface-embedded discontinuities, while also detecting surface topography. The data was acquired and imaged in a layer-by-layer sequence demonstrating the real-time monitoring capabilities of this new technology.

Finite Element Analysis of Interaction of Laser Beam with Material in Laser Metal Powder Bed Fusion Process.

PubMed

Fu, Guang; Zhang, David Z; He, Allen N; Mao, Zhongfa; Zhang, Kaifei

2018-05-10

A deep understanding of the laser-material interaction mechanism, characterized by laser absorption, is very important in simulating the laser metal powder bed fusion (PBF) process. This is because the laser absorption of material affects the temperature distribution, which influences the thermal stress development and the final quality of parts. In this paper, a three-dimensional finite element analysis model of heat transfer taking into account the effect of material state and phase changes on laser absorption is presented to gain insight into the absorption mechanism, and the evolution of instantaneous absorptance in the laser metal PBF process. The results showed that the instantaneous absorptance was significantly affected by the time of laser radiation, as well as process parameters, such as hatch space, scanning velocity, and laser power, which were consistent with the experiment-based findings. The applicability of this model to temperature simulation was demonstrated by a comparative study, wherein the peak temperature in fusion process was simulated in two scenarios, with and without considering the effect of material state and phase changes on laser absorption, and the simulated results in the two scenarios were then compared with experimental data respectively.

Meal ingestion markedly increases liver stiffness suggesting the need for liver stiffness determination in fasting conditions.

PubMed

Alvarez, Daniel; Orozco, Federico; Mella, José María; Anders, Maria; Antinucci, Florencia; Mastai, Ricardo

2015-01-01

The introduction of noninvasive liver stiffness (LS) determination has heralded a new stage in the diagnosis and treatment of liver fibrosis. We evaluated the effect of food intake on LS in patients with different degrees of liver disease. We evaluated 24 patients (F≤1, n=11 and F> 1, n=13). LS (Fibroscan®) and portal blood flow (PBF) (Doppler ultrasound) were studied before and 30min after ingestion of a standard liquid meal. Food intake increased PBF (51±10%, p<0.001). Splanchnic hyperemia was accompanied by a significant rise in LS (from 7.8±3.3 to 10.3±4.1kPa, p<0.001). These increases were similar in patients with minimal fibrosis(F≤1) and in those with more advanced fibrosis or cirrhosis (F>1). Hemodynamic and LS values returned to baseline pre-meal levels within 2hours. LS increases markedly after ingestion of a standard meal, irrespective of the degree of fibrosis. Our results strongly suggest that LS should be measured in fasting conditions. Copyright © 2015 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

Heat treatment versus properties studies associated with the Inconel 718 PBF acoustic filters

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

Smolik, G.R.; Reuter, W.G.

PBF acoustic filter Unit No. 1 cracked when heat treatment was attempted. The effects of prior thermal cycling, solution anneal temperature, and cooling rate from solution anneals were investigated. The investigations concerned influences of the above variables upon both 1400$sup 0$F stress rupture solution- annealed properties and room temperature age-hardened properties. 1400$sup 0$F stress rupture properties were of interest to assist the prevention of cracking during heat treatments. Room temperature age-hardened properties were needed to ensure that design requirement would be provided. Prior thermal cycling was investigated to determine if extra thermal cycles would be detrimental to the repaired filter.more » Slow furnace cools were considered as a means of reducing thermal stresses. Effects of solution annealing at 2000 and 1900$sup 0$F were also determined. Test results showed that slow cooling rates would not only reduce thermal stresses but also improve 1400$sup 0$F ductility. A modified aging treatment was established which provided the required 145 ksi room temperature yield strength for the slowly cooled material. Prior cooling did not degrade final age-hardened room temperature tensile or impact properties. (auth)« less

Process Evaluation of AISI 4340 Steel Manufactured by Laser Powder Bed Fusion

NASA Astrophysics Data System (ADS)

Jelis, Elias; Hespos, Michael R.; Ravindra, Nuggehalli M.

2018-01-01

Laser powder bed fusion (L-PBF) involves the consolidation of metal powder, layer by layer, through laser melting and solidification. In this study, process parameters are optimized for AISI 4340 steel to produce dense and homogeneous structures. The optimized process parameters produce mechanical properties at the center of the build plate that are comparable to wrought in the vertical and horizontal orientations after heat treatment and machining. Four subsequent builds are filled with specimens to evaluate the mechanical behavior as a function of location and orientation. Variations in the mechanical properties are likely due to recoater blade interactions with the powder and uneven gas flow. The results obtained in this study are analyzed to assess the reliability and reproducibility of the process. A different build evaluates the performance of near-net-shaped tensile specimens angled 35°-90° from the build plate surface (horizontal). Ductility measurements and surface roughness vary significantly as a function of the build angle. In the stress-relieved and as-built conditions, the mechanical behavior of vertically oriented specimens exhibits somewhat lower and more variable ductility than horizontally oriented specimens. Therefore, several process variables affect the mechanical properties of parts produced by the L-PBF process.

Parents' Perspective of the Impact of School Practices on the Functioning of Students with Special Educational Needs

ERIC Educational Resources Information Center

Lui, Ming; Yang, Lan; Sin, Kuen-Fung

2017-01-01

Students with special educational needs (SEN) are at an elevated risk of psychological and behavioural dysfunctions. In this study, we conducted a survey of parents of students with SEN in Hong Kong to examine the impact of two school practices--learning support and school climate--on the psychological and behavioural functioning (PBF) of students…

Fluoride glass compositions

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

El-Bayoumi, O.

1983-08-09

This invention relates to Fluoride-based glasses that exhibit a high degree of transparency throughout the near ultraviolet visible and mid infrared portions of the spectrum. The glasses are composed of MgF2 and ZnF2 as essential compositional ingredients together with at least two other metallic fluorides from the group of YbF3, ThF4, PbF2, A1F3 and MnF2.

Additive Manufacturing of Fuel Injectors

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

Sadek Tadros, Dr. Alber Alphonse; Ritter, Dr. George W.; Drews, Charles Donald

Additive manufacturing (AM), also known as 3D-printing, has been shifting from a novelty prototyping paradigm to a legitimate manufacturing tool capable of creating components for highly complex engineered products. An emerging AM technology for producing metal parts is the laser powder bed fusion (L-PBF) process; however, industry manufacturing specifications and component design practices for L-PBF have not yet been established. Solar Turbines Incorporated (Solar), an industrial gas turbine manufacturer, has been evaluating AM technology for development and production applications with the desire to enable accelerated product development cycle times, overall turbine efficiency improvements, and supply chain flexibility relative to conventionalmore » manufacturing processes (casting, brazing, welding). Accordingly, Solar teamed with EWI on a joint two-and-a-half-year project with the goal of developing a production L-PBF AM process capable of consistently producing high-nickel alloy material suitable for high temperature gas turbine engine fuel injector components. The project plan tasks were designed to understand the interaction of the process variables and their combined impact on the resultant AM material quality. The composition of the high-nickel alloy powders selected for this program met the conventional cast Hastelloy X compositional limits and were commercially available in different particle size distributions (PSD) from two suppliers. Solar produced all the test articles and both EWI and Solar shared responsibility for analyzing them. The effects of powder metal input stock, laser parameters, heat treatments, and post-finishing methods were evaluated. This process knowledge was then used to generate tensile, fatigue, and creep material properties data curves suitable for component design activities. The key process controls for ensuring consistent material properties were documented in AM powder and process specifications. The basic components of the project were: • Powder metal input stock: Powder characterization, dimensional accuracy, metallurgical characterization, and mechanical properties evaluation. • Process parameters: Laser parameter effects, post-printing heat-treatment development, mechanical properties evaluation, and post-finishing technique. • Material design curves: Room and elevated temperature tensiles, low cycle fatigue, and creep rupture properties curves generated. • AM specifications: Key metal powder characteristics, laser parameters, and heat-treatment controls identified.« less

Cytokine signalling in rat pulp interstitial fluid and transcapillary fluid exchange during lipopolysaccharide-induced acute inflammation

PubMed Central

Bletsa, Athanasia; Berggreen, Ellen; Fristad, Inge; Tenstad, Olav; Wiig, Helge

2006-01-01

The dental pulp consists of loose connective tissue encased in rigid dentinal walls. Because of its topography the tissue has low interstitial compliance and limited capacity to expand during fluid volume changes. Due to limitations regarding access to interstitial fluid, basic knowledge on transcapillary fluid transport parameters is lacking for this organ. The scope of this project was dual: first we aimed at establishing a method for isolation of pulp interstitial fluid (IF), and second we applied the method in rats subjected to lipopolysaccharide (LPS)-induced endotoxaemia. The aim was to measure colloid osmotic pressure (COP) and pro-inflammatory cytokines in the pulp IF during acute inflammation. Fluid volumes and pulpal blood flow (PBF) were measured to obtain more information about microcirculatory changes that take place in this pulpitis model. By centrifugation of incisor pulp at 239 g we were able to extract fluid representative for IF. Pulp IF had a relative high control COP (∼83% of plasma COP) and was similar to plasma COP 3 h after LPS challenge. The pulp exhibited a high content of IF (0.60 ± 0.03 ml (g wet weight)−1) and a vascular volume of 0.03 ± 0.01 ml (g w.w.)−1 No differences were observed in the distribution of fluid volumes after 1.5 and 3 h LPS exposure. PBF and systemic blood pressure dropped significantly after LPS administration. PBF remained low whereas systemic blood pressure was re-established during the 3-h period, implying organ dysfunction. There was a differential pattern of cytokine expression in pulp IF and serum with cytokines such as IL-1α, IL-1β and TNF-α locally produced, whereas others such as IFN-γ and IL-6 were produced systemically and probably spilled over to the pulp IF after LPS exposure. Our findings show that pulp IF can be isolated by centrifugation and that this method is useful when studying fluid balance and extracellular signalling mechanisms in the dental pulp in normal and pathological conditions. PMID:16527857

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.

Portal-drained viscera heat production in Iberian pigs fed betaine- and conjugated linoleic acid-supplemented diets.

PubMed

Rojas-Cano, María Luz; Lachica, Manuel; Lara, Luis; Haro, Ana; Fernández-Fígares, Ignacio

2017-01-01

Betaine and conjugated linoleic acid (CLA) may alter growth and body composition in pigs, although their mode of action is not well understood. Portal-drained viscera (PDV) have a disproportionate influence with respect to their masses, and this may affect the productivity of more profitable tissues. The objective of this study was to determine if the use of betaine and/or CLA in the diet affects PDV heat production. Postprandial portal blood flow (PBF) was greater (19.0%, P = 0.004) for control compared with the other three diets. The lowest (P < 0.001) value for postprandial PDV O 2 consumption corresponded to betaine + CLA followed by betaine and CLA diets (32.7, 25.4 and 17.7% respectively with respect to control diet). Postprandial PDV heat production was greater (26.4%, P < 0.001) for control with respect to the other three diets, with the minimum value corresponding to betaine + CLA (34.1% lower than control). Supplementation with betaine and/or CLA reduced the PBF, O 2 consumption and therefore PDV heat production with respect to control diet. This effect was more pronounced when betaine and CLA were supplemented together, potentially increasing the energy availability for other body tissues. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Process defects and in situ monitoring methods in metal powder bed fusion: a review

NASA Astrophysics Data System (ADS)

Grasso, Marco; Colosimo, Bianca Maria

2017-04-01

Despite continuous technological enhancements of metal Additive Manufacturing (AM) systems, the lack of process repeatability and stability still represents a barrier for the industrial breakthrough. The most relevant metal AM applications currently involve industrial sectors (e.g. aerospace and bio-medical) where defects avoidance is fundamental. Because of this, there is the need to develop novel in situ monitoring tools able to keep under control the stability of the process on a layer-by-layer basis, and to detect the onset of defects as soon as possible. On the one hand, AM systems must be equipped with in situ sensing devices able to measure relevant quantities during the process, a.k.a. process signatures. On the other hand, in-process data analytics and statistical monitoring techniques are required to detect and localize the defects in an automated way. This paper reviews the literature and the commercial tools for in situ monitoring of powder bed fusion (PBF) processes. It explores the different categories of defects and their main causes, the most relevant process signatures and the in situ sensing approaches proposed so far. Particular attention is devoted to the development of automated defect detection rules and the study of process control strategies, which represent two critical fields for the development of future smart PBF systems.

The calorimeter system of the new muon g-2 experiment at Fermilab

DOE PAGES

Alonzi, L. P.; Anastasi, A.; Bjorkquist, R.; ...

2015-12-02

The electromagnetic calorimeter for the new muon ( g–2) experiment at Fermilab will consist of arrays of PbF 2 Cerenkov crystals read out by large-area silicon photo-multiplier (SiPM) sensors. Here, we report here the requirements for this system, the achieved solution and the results obtained from a test beam using 2.0–4.5 GeV electrons with a 28-element prototype array.

Binding Site Turnover Produces Pervasive Quantitative Changes in Transcription Factor Binding between Closely Related Drosophila Species

PubMed Central

Trapnell, Cole; Davidson, Stuart; Pachter, Lior; Chu, Hou Cheng; Tonkin, Leath A.; Biggin, Mark D.; Eisen, Michael B.

2010-01-01

Changes in gene expression play an important role in evolution, yet the molecular mechanisms underlying regulatory evolution are poorly understood. Here we compare genome-wide binding of the six transcription factors that initiate segmentation along the anterior-posterior axis in embryos of two closely related species: Drosophila melanogaster and Drosophila yakuba. Where we observe binding by a factor in one species, we almost always observe binding by that factor to the orthologous sequence in the other species. Levels of binding, however, vary considerably. The magnitude and direction of the interspecies differences in binding levels of all six factors are strongly correlated, suggesting a role for chromatin or other factor-independent forces in mediating the divergence of transcription factor binding. Nonetheless, factor-specific quantitative variation in binding is common, and we show that it is driven to a large extent by the gain and loss of cognate recognition sequences for the given factor. We find only a weak correlation between binding variation and regulatory function. These data provide the first genome-wide picture of how modest levels of sequence divergence between highly morphologically similar species affect a system of coordinately acting transcription factors during animal development, and highlight the dominant role of quantitative variation in transcription factor binding over short evolutionary distances. PMID:20351773

Synthetic heparin-binding growth factor analogs

DOEpatents

Pena, Louis A.; Zamora, Paul; Lin, Xinhua; Glass, John D.

2007-01-23

The invention provides synthetic heparin-binding growth factor analogs having at least one peptide chain that binds a heparin-binding growth factor receptor, covalently bound to a hydrophobic linker, which is in turn covalently bound to a non-signaling peptide that includes a heparin-binding domain. The synthetic heparin-binding growth factor analogs are useful as soluble biologics or as surface coatings for medical devices.

America Makes: National Additive Manufacturing Innovation Institute (NAMII) Project 1: Nondestructive Evaluation (NDE) of Complex Metallic Additive Manufactured (AM) Structures

DTIC Science & Technology

2014-06-01

layer-by-layer manufacturing of a component by using PBF processes is accompanied by the establishment of a unidirectional heat transfer along the build...direction. Because grain growth during solidification preferably occurs in the opposite direction of heat transfer , the formation of elongated...development and deployment of phased array technology.[69] Phased array ultrasonic (PAUT) sensors use multiple elements instead of a single element

Performance evaluation of a dynamic telepathology system (Panoptiq™) in the morphologic assessment of peripheral blood film abnormalities.

PubMed

Goswami, R; Pi, D; Pal, J; Cheng, K; Hudoba De Badyn, M

2015-06-01

The study evaluated the performance of a dynamic imaging telepathology system (Panoptiq(™) ) as a diagnostic aid to the identification of peripheral blood film (PBF) abnormalities. The study assumed a laboratory personnel working in a clinical laboratory were operating the telepathology system to seek diagnostic opinion from an external consulting hematopathologist. The study examined 100 blood films, encompassing 23 different hematological diseases, reactive or normal cases. The study revealed that with real-time image transmission in live scanning mode of operation, the telepathology system was able to aid reviewers in achieving excellent accuracy, that is correct interpretation of morphologic abnormalities obtained in 83/84 of the hematologic diseases and 12/12 of the reactive/normal conditions (Sensitivity: 0.99; Specificity: 1.00). In contrast, when only saved static images in digital capture mode of operation were reviewed remotely, interpretative omissions occurred in 8/84 of the hematologic diseases and 0/12 of the reactive/normal conditions (Sensitivity: 0.91; Specificity: 1.00). It is hypothesized that real-time operator-reviewer communication during live scanning played an important role in the identification of key morphologic abnormalities for review. Our study showed the Panoptiq system can be adopted reliably as a dynamic telepathology tool in aiding community laboratories in the triage of PBF cases for external diagnostic consultation. © 2014 John Wiley & Sons Ltd.

Obesity and motor coordination ability in Taiwanese children with and without developmental coordination disorder.

PubMed

Zhu, Yi-Ching; Wu, Sheng K; Cairney, John

2011-01-01

The purpose of this study was to investigate the associations between obesity and motor coordination ability in Taiwanese children with and without developmental coordination disorder (DCD). 2029 children (1078 boys, 951 girls) aged nine to ten years were chosen randomly from 14 elementary schools across Taiwan. We used bioelectrical impedance analysis to measure percentage of body fat (PBF) and the Movement Assessment Battery for Children test (MABC test) to evaluate the motor coordination ability. Using cut-off points based on PBF from past studies, boys and girls were divided into obese, overweight and normal-weight groups, respectively. In boys, total impairment scores and scores on balance subtest in the MABC were significantly higher in the obese and overweight groups when compared against the normal-weight group. Girls in the obese and the overweight groups had higher balance impairment scores than those of the normal-weight group. Among boys, the prevalence of obesity was highest in the DCD group, when compared to the borderline DCD and TD boys. A higher percentage of DCD girls were overweight and obese than TD girls. Obesity may be associated with poor motor coordination ability among boys and girls, and particularly in relation to balance ability. Children with DCD may have a higher risk to be overweight or obese in Taiwan. Copyright © 2010 Elsevier Ltd. All rights reserved.

Developmental regulation of collagenase-3 mRNA in normal, differentiating osteoblasts through the activator protein-1 and the runt domain binding sites

NASA Technical Reports Server (NTRS)

Winchester, S. K.; Selvamurugan, N.; D'Alonzo, R. C.; Partridge, N. C.

2000-01-01

Collagenase-3 mRNA is initially detectable when osteoblasts cease proliferation, increasing during differentiation and mineralization. We showed that this developmental expression is due to an increase in collagenase-3 gene transcription. Mutation of either the activator protein-1 or the runt domain binding site decreased collagenase-3 promoter activity, demonstrating that these sites are responsible for collagenase-3 gene transcription. The activator protein-1 and runt domain binding sites bind members of the activator protein-1 and core-binding factor family of transcription factors, respectively. We identified core-binding factor a1 binding to the runt domain binding site and JunD in addition to a Fos-related antigen binding to the activator protein-1 site. Overexpression of both c-Fos and c-Jun in osteoblasts or core-binding factor a1 increased collagenase-3 promoter activity. Furthermore, overexpression of c-Fos, c-Jun, and core-binding factor a1 synergistically increased collagenase-3 promoter activity. Mutation of either the activator protein-1 or the runt domain binding site resulted in the inability of c-Fos and c-Jun or core-binding factor a1 to increase collagenase-3 promoter activity, suggesting that there is cooperative interaction between the sites and the proteins. Overexpression of Fra-2 and JunD repressed core-binding factor a1-induced collagenase-3 promoter activity. Our results suggest that members of the activator protein-1 and core-binding factor families, binding to the activator protein-1 and runt domain binding sites are responsible for the developmental regulation of collagenase-3 gene expression in osteoblasts.

Pyyromethene-BF2 Complexes as Laser Dyes

DTIC Science & Technology

1990-05-24

pyrromethene S1 state via exciplex formation, a pro- cess well known for polyamines [20], was not incompatible with the available information... exciplex formation [21]. Strong fluorescence in a bidentate BF 2 complex with nitrogen and/or oxygen atoms as ligand term’ini was afforded by P-BF2...M. Gordon and W. R. Ware, Eds., "The Exciplex ," Academic Press, New York, 1975. [21] M. E. Huston, K. W. Haider, and A. W. Czarnik, J. Amer. Chem. Soc

Oxide glass used as inorganic template for fluorescent fluoride nanoparticles synthesis

NASA Astrophysics Data System (ADS)

Mortier, Michel; Patriarche, Gilles

2006-09-01

We report an original way to synthesise single-crystal PbF 2 nanoparticles by selective chemical attack of a bulk nanocomposite oxyfluoride glass-ceramic. Free of impurities and homogeneously doped with Er 3+ ions, the particles are of narrow size dispersion around 15 nm and weakly aggregated. The nanocrystallites emit a very intense green and blue up conversion fluorescence after infrared excitation. The doping level and the size of the particles is finely driven through the precursor glass-ceramic synthesis and composition.

Growth of Ce+3 Doped Oxides by the Traveling Solvent Zone Technique.

DTIC Science & Technology

1983-06-01

ambient 1100 0.05 9 PbTiO3 PbF 2/PbO ambient 1075 0.05 9 In this program, we have evaluated several fluxes for growth of LaA10 3 , LaAll-xMxO3 (M = Sc+ 3...TABLE 2. X-RAY DIFFRACTIN PARAMETERS MEASURED FOR ARC FURNACE SYNTHESIZED LaAIO3 AND LaAl 0 .7Sc0 303 LaAIO3 LaAl 0 .7Sc .303 hkl d(A) d(A) 3.71 3.86

Functional interaction of the DNA-binding transcription factor Sp1 through its DNA-binding domain with the histone chaperone TAF-I.

PubMed

Suzuki, Toru; Muto, Shinsuke; Miyamoto, Saku; Aizawa, Kenichi; Horikoshi, Masami; Nagai, Ryozo

2003-08-01

Transcription involves molecular interactions between general and regulatory transcription factors with further regulation by protein-protein interactions (e.g. transcriptional cofactors). Here we describe functional interaction between DNA-binding transcription factor and histone chaperone. Affinity purification of factors interacting with the DNA-binding domain of the transcription factor Sp1 showed Sp1 to interact with the histone chaperone TAF-I, both alpha and beta isoforms. This interaction was specific as Sp1 did not interact with another histone chaperone CIA nor did other tested DNA-binding regulatory factors (MyoD, NFkappaB, p53) interact with TAF-I. Interaction of Sp1 and TAF-I occurs both in vitro and in vivo. Interaction with TAF-I results in inhibition of DNA-binding, and also likely as a result of such, inhibition of promoter activation by Sp1. Collectively, we describe interaction between DNA-binding transcription factor and histone chaperone which results in negative regulation of the former. This novel regulatory interaction advances our understanding of the mechanisms of eukaryotic transcription through DNA-binding regulatory transcription factors by protein-protein interactions, and also shows the DNA-binding domain to mediate important regulatory interactions.

Synthetic heparin-binding factor analogs

DOEpatents

Pena, Louis A [Poquott, NY; Zamora, Paul O [Gaithersburg, MD; Lin, Xinhua [Plainview, NY; Glass, John D [Shoreham, NY

2010-04-20

The invention provides synthetic heparin-binding growth factor analogs having at least one peptide chain, and preferably two peptide chains branched from a dipeptide branch moiety composed of two trifunctional amino acid residues, which peptide chain or chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a linker, which may be a hydrophobic linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

Supervised filters for EEG signal in naturally occurring epilepsy forecasting.

PubMed

Muñoz-Almaraz, Francisco Javier; Zamora-Martínez, Francisco; Botella-Rocamora, Paloma; Pardo, Juan

2017-01-01

Nearly 1% of the global population has Epilepsy. Forecasting epileptic seizures with an acceptable confidence level, could improve the disease treatment and thus the lifestyle of the people who suffer it. To do that the electroencephalogram (EEG) signal is usually studied through spectral power band filtering, but this paper proposes an alternative novel method of preprocessing the EEG signal based on supervised filters. Such filters have been employed in a machine learning algorithm, such as the K-Nearest Neighbor (KNN), to improve the prediction of seizures. The proposed solution extends with this novel approach an algorithm that was submitted to win the third prize of an international Data Science challenge promoted by Kaggle contest platform and the American Epilepsy Society, the Epilepsy Foundation, National Institutes of Health (NIH) and Mayo Clinic. A formal description of these preprocessing methods is presented and a detailed analysis in terms of Receiver Operating Characteristics (ROC) curve and Area Under ROC curve is performed. The obtained results show statistical significant improvements when compared with the spectral power band filtering (PBF) typical baseline. A trend between performance and the dataset size is observed, suggesting that the supervised filters bring better information, compared to the conventional PBF filters, as the dataset grows in terms of monitored variables (sensors) and time length. The paper demonstrates a better accuracy in forecasting when new filters are employed and its main contribution is in the field of machine learning algorithms to develop more accurate predictive systems.

Supervised filters for EEG signal in naturally occurring epilepsy forecasting

PubMed Central

2017-01-01

Nearly 1% of the global population has Epilepsy. Forecasting epileptic seizures with an acceptable confidence level, could improve the disease treatment and thus the lifestyle of the people who suffer it. To do that the electroencephalogram (EEG) signal is usually studied through spectral power band filtering, but this paper proposes an alternative novel method of preprocessing the EEG signal based on supervised filters. Such filters have been employed in a machine learning algorithm, such as the K-Nearest Neighbor (KNN), to improve the prediction of seizures. The proposed solution extends with this novel approach an algorithm that was submitted to win the third prize of an international Data Science challenge promoted by Kaggle contest platform and the American Epilepsy Society, the Epilepsy Foundation, National Institutes of Health (NIH) and Mayo Clinic. A formal description of these preprocessing methods is presented and a detailed analysis in terms of Receiver Operating Characteristics (ROC) curve and Area Under ROC curve is performed. The obtained results show statistical significant improvements when compared with the spectral power band filtering (PBF) typical baseline. A trend between performance and the dataset size is observed, suggesting that the supervised filters bring better information, compared to the conventional PBF filters, as the dataset grows in terms of monitored variables (sensors) and time length. The paper demonstrates a better accuracy in forecasting when new filters are employed and its main contribution is in the field of machine learning algorithms to develop more accurate predictive systems. PMID:28632737

CORE_TF: a user-friendly interface to identify evolutionary conserved transcription factor binding sites in sets of co-regulated genes

PubMed Central

Hestand, Matthew S; van Galen, Michiel; Villerius, Michel P; van Ommen, Gert-Jan B; den Dunnen, Johan T; 't Hoen, Peter AC

2008-01-01

Background The identification of transcription factor binding sites is difficult since they are only a small number of nucleotides in size, resulting in large numbers of false positives and false negatives in current approaches. Computational methods to reduce false positives are to look for over-representation of transcription factor binding sites in a set of similarly regulated promoters or to look for conservation in orthologous promoter alignments. Results We have developed a novel tool, "CORE_TF" (Conserved and Over-REpresented Transcription Factor binding sites) that identifies common transcription factor binding sites in promoters of co-regulated genes. To improve upon existing binding site predictions, the tool searches for position weight matrices from the TRANSFACR database that are over-represented in an experimental set compared to a random set of promoters and identifies cross-species conservation of the predicted transcription factor binding sites. The algorithm has been evaluated with expression and chromatin-immunoprecipitation on microarray data. We also implement and demonstrate the importance of matching the random set of promoters to the experimental promoters by GC content, which is a unique feature of our tool. Conclusion The program CORE_TF is accessible in a user friendly web interface at . It provides a table of over-represented transcription factor binding sites in the users input genes' promoters and a graphical view of evolutionary conserved transcription factor binding sites. In our test data sets it successfully predicts target transcription factors and their binding sites. PMID:19036135

Fibroblast growth factor regulates insulin-like growth factor-binding protein production by vascular smooth muscle cells.

PubMed

Ververis, J; Ku, L; Delafontaine, P

1994-02-01

Insulin-like growth factor I is an important mitogen for vascular smooth muscle cells, and its effects are regulated by several binding proteins. Western ligand blotting of conditioned medium from rat aortic smooth muscle cells detected a 24 kDa binding protein and a 28 kDa glycosylated variant of this protein, consistent with insulin-like growth factor binding protein-4 by size. Low amounts of a glycosylated 38 to 42 kDa doublet (consistent with binding protein-3) and a 31 kDa non-glycosylated protein also were present. Basic fibroblast growth factor markedly increased secretion of the 24 kDa binding protein and its 28 kDa glycosylated variant. This effect was dose- and time-dependent and was inhibited by co-incubation with cycloheximide. Crosslinking of [125I]-insulin-like growth factor I to cell monolayers revealed no surface-associated binding proteins, either basally or after agonist treatment. Induction of binding protein production by fibroblast growth factor at sites of vascular injury may be important in vascular proliferative responses in vivo.

PM trend study for the 1998 - 2012 period: Impact of Transport and Petroleum-based Fuels in Santiago Chile

NASA Astrophysics Data System (ADS)

Castillo, M. A.; Jhun, I.; Moreno, F.; Oyola, P.; Koutrakis, P.

2013-05-01

Santiago is the capital city of Chile and the combination of adverse climatic and geographical conditions, a continuously growing vehicle fleet, and an increasing number of industries, has made Santiago one of the most polluted cities in South America, and has been declared saturated zone for PM10 since 1996. Although there have been important reductions in the PM emissions due the implementation of the "Atmospheric Prevention and Decontamination Plan for the Metropolitan Region" (PPDA) however the efforts have not been enough to meet the actual standards. Currently is approved a standard for PM2.5, where the annual average is 20 μg/m3 and daily average 24 hr is 50 μg/m3. One of the PM2.5 sources are the traffic emission and one of the measures targeted in PPDA has been to regulate this source. In the last 20 years two of the main interventions have been the elimination of Lead in gasoline (2001) and the steadily reduced diesel sulfur content from 5,000 to 50 ppm. In this study we analyzed 14 years of PM2.5 mass and species concentration time's series, from April 1998 to August 2012, elemental chemical analysis was made for approximately 60% of samples using XRF technique at DRI Lab (USA). One of the objectives is evaluate the impact of fuel-related interventions and petroleum-based fuels (PBFs) sales. When was analyzed de lead concentration we found that is present in the environment despite of that was eliminated of gasoline 20 years ago. We analyzed the impact of diesel sulfur on ambient sulfur content, and was constructed a model to verify the relationship between ambient sulfur and diesel sulfur content after controlling for other covariates. The relation between ambient concentration and diesel content sulfur is linear, when the reduction of sulfur in diesel was from 1500 to 50 ppm the concentration decreased from 1.59 to 1.08 μg/m3. To determinate the impact of PBFs sales (gasoline, kerosene, petroleum) on PM2.5 concentration, we estimated PM2.5 regression model for PBF sales. In PM2.5 trend was observed an increase in 2005-2008 period ; when the PBF sales were included in the regression model, the concentration of PM2.5 was mitigated (2005-2008), this results indicates that if the PBF sales not had risen in this period the concentration of PM2.5 would not have increased as much.

Dual chain synthetic heparin-binding growth factor analogs

DOEpatents

Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY

2012-04-24

The invention provides synthetic heparin-binding growth factor analogs having two peptide chains each branched from a branch moiety, such as trifunctional amino acid residues, the branch moieties separated by a first linker of from 3 to about 20 backbone atoms, which peptide chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a second linker, which may be a hydrophobic second linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

Dual chain synthetic heparin-binding growth factor analogs

DOEpatents

Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY

2009-10-06

The invention provides synthetic heparin-binding growth factor analogs having two peptide chains each branched from a branch moiety, such as trifunctional amino acid residues, the branch moieties separated by a first linker of from 3 to about 20 backbone atoms, which peptide chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a second linker, which may be a hydrophobic second linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

Carboxyl‐terminal Heparin‐binding Fragments of Platelet Factor 4 Retain the Blocking Effect on the Receptor Binding of Basic Fibroblast Growth Factor

PubMed Central

Waki, Michinori; Ohno, Motonori; Kuwano, Michihiko; Sakata, Toshiie

1993-01-01

Platelet factor 4 (PF‐4) blocks the binding of basic fibroblast growth factor (bFGF) to its receptor. In the present study, we constructed carboxyl‐terminal fragments, which represent the heparin‐binding region of the PF‐4 molecule, and examined whether these synthetic peptides retain the blocking effects on the receptor binding of bFGF. Synthetic peptides inhibited the receptor binding of bFGF. Furthermore, they inhibited the migration and tube formation of bovine capillary endothelial cells in culture (these phenomena are dependent on endogenous bFGF). PMID:8320164

Inhibition by Siomycin and Thiostrepton of Both Aminoacyl-tRNA and Factor G Binding to Ribosomes

PubMed Central

Ll, Juan Modole; Cabrer, Bartolomé; Parmeggiani, Andrea; Azquez, David V

1971-01-01

Siomycin, a peptide antibiotic that interacts with the 50S ribosomal subunit and inhibits binding of factor G, is shown also to inhibit binding of aminoacyl-tRNA; however, it does not impair binding of fMet-tRNA and completion of the initiation complex. Moreover, unlike other inhibitors of aminoacyl-tRNA binding (tetracycline, sparsomycin, and streptogramin A), siomycin completely abolishes the GTPase activity associated with the binding of aminoacyl-tRNA catalyzed by factor Tu. A single-site interaction of siomycin appears to be responsible for its effect on both the binding of the aminoacyl-tRNA-Tu-GTP complex and that of factor G. PMID:4331558

An ensemble model of competitive multi-factor binding of the genome

PubMed Central

Wasson, Todd; Hartemink, Alexander J.

2009-01-01

Hundreds of different factors adorn the eukaryotic genome, binding to it in large number. These DNA binding factors (DBFs) include nucleosomes, transcription factors (TFs), and other proteins and protein complexes, such as the origin recognition complex (ORC). DBFs compete with one another for binding along the genome, yet many current models of genome binding do not consider different types of DBFs together simultaneously. Additionally, binding is a stochastic process that results in a continuum of binding probabilities at any position along the genome, but many current models tend to consider positions as being either binding sites or not. Here, we present a model that allows a multitude of DBFs, each at different concentrations, to compete with one another for binding sites along the genome. The result is an “occupancy profile,” a probabilistic description of the DNA occupancy of each factor at each position. We implement our model efficiently as the software package COMPETE. We demonstrate genome-wide and at specific loci how modeling nucleosome binding alters TF binding, and vice versa, and illustrate how factor concentration influences binding occupancy. Binding cooperativity between nearby TFs arises implicitly via mutual competition with nucleosomes. Our method applies not only to TFs, but also recapitulates known occupancy profiles of a well-studied replication origin with and without ORC binding. Importantly, the sequence preferences our model takes as input are derived from in vitro experiments. This ensures that the calculated occupancy profiles are the result of the forces of competition represented explicitly in our model and the inherent sequence affinities of the constituent DBFs. PMID:19720867

Endosomal receptor kinetics determine the stability of intracellular growth factor signalling complexes

PubMed Central

Tzafriri, A. Rami; Edelman, Elazer R.

2006-01-01

There is an emerging paradigm that growth factor signalling continues in the endosome and that cell response to a growth factor is defined by the integration of cell surface and endosomal events. As activated receptors in the endosome are exposed to a different set of binding partners, they probably elicit differential signals compared with when they are at the cell surface. As such, complete appreciation of growth factor signalling requires understanding of growth factor–receptor binding and trafficking kinetics both at the cell surface and in endosomes. Growth factor binding to surface receptors is well characterized, and endosomal binding is assumed to follow surface kinetics if one accounts for changes in pH. Yet, specific binding kinetics within the endosome has not been examined in detail. To parse the factors governing the binding state of endosomal receptors we analysed a whole-cell mathematical model of epidermal growth factor receptor trafficking and binding. We discovered that the stability of growth factor–receptor complexes within endosomes is governed by three primary independent factors: the endosomal dissociation constant, total endosomal volume and the number of endosomal receptors. These factors were combined into a single dimensionless parameter that determines the endosomal binding state of the growth factor–receptor complex and can distinguish different growth factors from each other and different cell states. Our findings indicate that growth factor binding within endosomal compartments cannot be appreciated solely on the basis of the pH-dependence of the dissociation constant and that the concentration of receptors in the endosomal compartment must also be considered. PMID:17117924

Binding efficiency of recombinant collagen-binding basic fibroblast growth factors (CBD-bFGFs) and their promotion for NIH-3T3 cell proliferation.

PubMed

Wu, Zhenxu; Zhou, Yulai; Chen, Li; Hu, Mingxin; Wang, Yu; Li, Linlong; Wang, Zongliang; Zhang, Peibiao

2018-03-01

The recombinant basic fibroblast growth factor (bFGF) containing collagen-binding domain (CBD) has been found to be a potential therapeutic factor in tissue regeneration. However, its binding efficiency and quantification remain uncertain. In this research, massive recombinant bFGFs with good bioactivity for enhancing the proliferation of NIH-3T3 cells were achieved. An ELISA-based quantitative method was set up to investigate the binding efficiency of CBD-bFGFs on collagen films. It indicated that the CBDs significantly increased the collagen-binding ability of bFGF (P < .05), with the optimum binding condition first determined to be in the pH range of 7.5-9.5 (P < .05). Then, the relevant equations to calculate the binding density of bFGF, C-bFGF, and V-bFGF were acquired. Analysis confirmed that the bioactivity of immobilized bFGFs was well correlated with the density of growth factor on collagen films. Based on this research, the density of growth factor is a logical and applicable dosage unit for quantification of binding efficiency of growth factors, rather than traditional concentration of soluble growth factors in tissue engineering applications. © 2018 Wiley Periodicals, Inc.

Luminescent hybrid materials based on (8-hydroxyquinoline)-substituted metal-organic complexes and lead-borate glasses

NASA Astrophysics Data System (ADS)

Petrova, Olga B.; Anurova, Maria O.; Akkuzina, Alina A.; Saifutyarov, Rasim R.; Ermolaeva, Ekaterina V.; Avetisov, Roman I.; Khomyakov, Andrew V.; Taydakov, Ilya V.; Avetissov, Igor Ch.

2017-07-01

Novel luminescent organic-inorganic hybrid materials based on 8-hydroxyquinoline metal complexes (Liq, Kq, Naq, Rbq, Mgq2, Srq2, Znq2, Scq3, Alq3, Gaq3, and Inq3) have been synthesized by a high temperature exchange reaction with 80PbF2-20B2O3 inorganic low-melting glass. The mechanical and optical properties, transmission spectra, emission an excitation photoluminescence, and luminescence kinetic of hybrid materials were studied. All hybrid materials showed a wide luminescence band in the range 400-700 nm.

Comparison of Insect Kinin Analogs With cis-Peptide Bond Motif 4-Aminopyroglutamate Identifies Optimal Stereochemistry for Diuretic Activity

DTIC Science & Technology

2006-01-01

Amino acid side-chain-protecting groups were Pbf for Arg and Boc for Trp. The coupling of Fmoc-4-amino- pyroglutamic acids (Fmoc-aPy-OH, Fmoc-apy-OH...Inc. Biopolymers (Pept Sci) 88:1–7, 2007. Keywords: 4-aminopyroglutamic acid ; cis-peptide bond; b-turn mimetic; constrained insect kinin analog...analogs containing three stereochemical var- iants of the (2S, 4S)-4-aminopyroglutamic acid (APy) com- ponent (see Figure 1), a mimic of the cis-peptide

Deletion of transcription factor binding motifs using the CRISPR/spCas9 system in the β-globin LCR.

PubMed

Kim, Yea Woon; Kim, AeRi

2017-07-20

Transcription factors play roles in gene transcription through direct binding to their motifs in genome, and inhibiting this binding provides an effective strategy for studying their roles. Here we applied the CRISPR/spCas9 system to mutate the binding motifs of transcription factors. Binding motifs for erythroid specific transcription factors were mutated in the locus control region hypersensitive sites of the human β-globin locus. Guide RNAs targeting binding motifs were cloned into lentiviral CRISPR vector containing the spCas9 gene, and transduced into MEL/ch11 cells carrying a human chromosome 11. DNA mutations in clonal cells were initially screened by quantitative PCR in genomic DNA and then clarified by sequencing. Mutations in binding motifs reduced occupancy by transcription factors in a chromatin environment. Characterization of mutations revealed that the CRISPR/spCas9 system mainly induced deletions in short regions of <20 bp and preferentially deleted nucleotides around the fifth nucleotide upstream of Protospacer adjacent motifs. These results indicate that the CRISPR/Cas9 system is suitable for mutating the binding motifs of transcription factors, and, consequently, would contribute to elucidate the direct roles of transcription factors. ©2017 The Author(s).

HMG I(Y) interferes with the DNA binding of NF-AT factors and the induction of the interleukin 4 promoter in T cells

PubMed Central

Klein-Hessling, Stefan; Schneider, Günter; Heinfling, Annette; Chuvpilo, Sergei; Serfling, Edgar

1996-01-01

HMG I(Y) proteins bind to double-stranded A+T oligonucleotides longer than three base pairs. Such motifs form part of numerous NF-AT-binding sites of lymphokine promoters, including the interleukin 4 (IL-4) promoter. NF-AT factors share short homologous peptide sequences in their DNA-binding domain with NF-κB factors and bind to certain NF-κB sites. It has been shown that HMG I(Y) proteins enhance NF-κB binding to the interferon β promoter and virus-mediated interferon β promoter induction. We show that HMG I(Y) proteins exert an opposite effect on the DNA binding of NF-AT factors and the induction of the IL-4 promoter in T lymphocytes. Introduction of mutations into a high-affinity HMG I(Y)-binding site of the IL-4 promoter, which decreased HMG I(Y)-binding to a NF-AT-binding sequence, the Pu-bB (or P) site, distinctly increased the induction of the IL-4 promoter in Jurkat T leukemia cells. High concentrations of HMG I(Y) proteins are able to displace NF-ATp from its binding to the Pu-bB site. High HMG I(Y) concentrations are typical for Jurkat cells and peripheral blood T lymphocytes, whereas El4 T lymphoma cells and certain T helper type 2 cell clones contain relatively low HMG I(Y) concentrations. Our results indicate that HMG I(Y) proteins do not cooperate, but instead compete with NF-AT factors for the binding to DNA even though NF-AT factors share some DNA-binding properties with NF-kB factors. This competition between HMG I(Y) and NF-AT proteins for DNA binding might be due to common contacts with minor groove nucleotides of DNA and may be one mechanism contributing to the selective IL-4 expression in certain T lymphocyte populations, such as T helper type 2 cells. PMID:8986808

A mammary cell-specific enhancer in mouse mammary tumor virus DNA is composed of multiple regulatory elements including binding sites for CTF/NFI and a novel transcription factor, mammary cell-activating factor.

PubMed Central

Mink, S; Härtig, E; Jennewein, P; Doppler, W; Cato, A C

1992-01-01

Mouse mammary tumor virus (MMTV) is a milk-transmitted retrovirus involved in the neoplastic transformation of mouse mammary gland cells. The expression of this virus is regulated by mammary cell type-specific factors, steroid hormones, and polypeptide growth factors. Sequences for mammary cell-specific expression are located in an enhancer element in the extreme 5' end of the long terminal repeat region of this virus. This enhancer, when cloned in front of the herpes simplex thymidine kinase promoter, endows the promoter with mammary cell-specific response. Using functional and DNA-protein-binding studies with constructs mutated in the MMTV long terminal repeat enhancer, we have identified two main regulatory elements necessary for the mammary cell-specific response. These elements consist of binding sites for a transcription factor in the family of CTF/NFI proteins and the transcription factor mammary cell-activating factor (MAF) that recognizes the sequence G Pu Pu G C/G A A G G/T. Combinations of CTF/NFI- and MAF-binding sites or multiple copies of either one of these binding sites but not solitary binding sites mediate mammary cell-specific expression. The functional activities of these two regulatory elements are enhanced by another factor that binds to the core sequence ACAAAG. Interdigitated binding sites for CTF/NFI, MAF, and/or the ACAAAG factor are also found in the 5' upstream regions of genes encoding whey milk proteins from different species. These findings suggest that mammary cell-specific regulation is achieved by a concerted action of factors binding to multiple regulatory sites. Images PMID:1328867

Blockade of renal medullary bradykinin B2 receptors increases tubular sodium reabsorption in rats fed a normal-salt diet

PubMed Central

Sivritas, Sema-Hayriye; Ploth, David W.; Fitzgibbon, Wayne R.

2008-01-01

The present study was performed to test the hypothesis that under normal physiological conditions and/or during augmentation of kinin levels, intrarenal kinins act on medullary bradykinin B2 (BKB2) receptors to acutely increase papillary blood flow (PBF) and therefore Na+ excretion. We determined the effect of acute inner medullary interstitial (IMI) BKB2 receptor blockade on renal hemodynamics and excretory function in rats fed either a normal (0.23%)- or a low (0.08%)-NaCl diet. For each NaCl diet, two groups of rats were studied. Baseline renal hemodynamic and excretory function were determined during IMI infusion of 0.9% NaCl into the left kidney. The infusion was then either changed to HOE-140 (100 μg·kg−1·h−1, treated group) or maintained with 0.9% NaCl (time control group), and the parameters were again determined. In rats fed a normal-salt diet, HOE-140 infusion decreased left kidney Na+ excretion (urinary Na+ extraction rate) and fractional Na+ excretion by 40 ± 5% and 40 ± 4%, respectively (P < 0.01), but did not alter glomerular filtration rate, inner medullary blood flow (PBF), or cortical blood flow. In rats fed a low-salt diet, HOE-140 infusion did not alter renal regional hemodynamics or excretory function. We conclude that in rats fed a normal-salt diet, kinins act tonically via medullary BKB2 receptors to increase Na+ excretion independent of changes in inner medullary blood flow. PMID:18632797

The Effective Hamiltonian for the Ground State of 207Pb19F and New Measurements of the Fine Structure Spectrum Near 1.2 μ m.

NASA Astrophysics Data System (ADS)

Mawhorter, Richard; Murphey, Benjamin; Baum, Alexander; Sears, Trevor J.; Yang, T. Zh.; Rupasinghe, P. M.; McRaven, C. P.; Shafer-Ray, N. E.; Alphei, Lukas D.; Grabow, Jens-Uwe.

2011-06-01

We have measured rotational transitions in the ground, X_1 ^2Π1/2, electronic state of naturally occuring isotopomers of PbF in a supersonic free jet Fourier transform microwave spectrometer. The data for 207Pb19F is particularly interesting because it is a candidate for a future experimental e-EDM measurement. To fit the data for this species to the measurement precision, the nuclear spin-spin dipolar interaction and a second term that can be equivalently viewed as a centrifugal distortion correction to the familiar Frosch and Foley hyperfine coupling terms, or an Ω- dependent correction to the nuclear spin-rotational coupling are required, in addition to the standard terms. To characterize the higher X_2 ^2Π3/2 component of the ground state of PbF, we are attempting a direct measurement of transitions between the two components in a slit jet-cooled sample using a frequency comb-referenced extended cavity diode laser. This spectrum was originally detected in a hot source by Fourier transform near-infrared spectroscopy, but low-J transitions were unresolved at that time. Acknowledgments: Work at Brookhaven National Laboratory was carried out under Contract No. DE-AC02-98CH10886 with the U.S. Department of Energy. Work by N. E. Shafer-Ray was performed with support from the National Science Foundatation award NSF-0855431. J.-U. Grabow ackonwledges funding from the Deutsche Forschungsgemeinschaft and the Land Niedersachsen. K. Ziebarth, K. Setzer, O. Shestakov and E. Fink J. Molec. Spectrosc. 191, 108 1998.

The Effect of Aerobic or Aerobic-Strength Exercise on Body Composition and Functional Capacity in Patients with BMI ≥35 after Bariatric Surgery: a Randomized Control Trial.

PubMed

Hassannejad, Alireza; Khalaj, Alireza; Mansournia, Mohammad Ali; Rajabian Tabesh, Mastaneh; Alizadeh, Zahra

2017-11-01

Although previous studies suggested that bariatric surgery is the most effective and sustainable treatment method for morbid obesity in long term, but without changing in lifestyle, maintaining optimal weight loss is almost impossible. Sixty morbid obese patients (BMI ≥ 35) were evaluated before and after 12 weeks of bariatric surgery in order to compare the impact of two different exercise programs on body composition and functional capacity outcomes. Participants were divided into three groups: aerobic (A), aerobic-strength (AS), and control (C) group. Aerobic capacity was assessed with 12-min walk-run test (12MWRT). One-repetition maximum (1RM) test was performed to evaluation upper limb muscle strength. Lower extremity functional capacity was assessed by sit-to-stand test. Weight, percent body fat (PBF), and fat mass (FM) reduced greater in the trial groups in comparison to the C group (P < 0.05). In the AS group, the reduction of fat-free mass (FFM) was significantly lower than that in the other groups. Mean changes in 12MWRT increased significantly in the intervention groups. The mean change in the sit-to-stand scores was not statistically significant between the three groups. Comparing the intervention groups showed that mean changes in 1RM variables increased in AS group (P = 0.03). The data suggests a positive effect of exercise on weight and PBF decrease after surgery, and it leads to significant improvement on aerobic capacity. Moreover, doing resisted exercise caused greater preserving of lean mass.

[Telephone support for breastfeeding by primary care: a randomised multicentre trial].

PubMed

Balaguer Martínez, Josep Vicent; Valcarce Pérez, Inmaculada; Esquivel Ojeda, Jessica Noelia; Hernández Gil, Alicia; Martín Jiménez, María Del Pilar; Bernad Albareda, Mercè

2018-03-22

To evaluate a telephone support programme for mothers who breastfeed for the first 6 months. A randomised unmasked clinical trial was conducted in 5 urban Primary Care centres that included mothers with healthy newborns who were breastfeeding exclusively (EBF) or partially (PBF). The control group received the usual care. The intervention group also received telephone support for breastfeeding on a weekly basis for the first 2months and then every 2weeks until the sixth month. The type of breastfeeding was recorded in the usual check-up visit (1, 2, 4 and 6 months). The study included 193 patients in the intervention group, and 187 in a control group. The greatest increase in the percentage of EBF was observed at 6 months: 21.4% in the control group compared to 30.1% in the intervention group. However, in the adjusted odds ratios analysis, confidence intervals did not show statistical significance. The odds ratio at 1 month, 2 months, 4 months, and 6 months for EBF were 1.45 (0.91-2.31), 1.35 (0.87-2.08), 1.21 (0.80-1.81), and 1.58 (0.99-2.53), respectively. The odds ratio in the same age groups for any type of breastfeeding (EBF + PBF) were 1.65 (0.39-7.00), 2.08 (0.94-4.61), 1.37 (0.79-2.38), and 1.60 (0.98-2.61), respectively. Telephone intervention was not effective enough to generalise it. Copyright © 2018. Publicado por Elsevier España, S.L.U.

Heterogeneity of pulmonary perfusion as a mechanistic image-based phenotype in emphysema susceptible smokers.

PubMed

Alford, Sara K; van Beek, Edwin J R; McLennan, Geoffrey; Hoffman, Eric A

2010-04-20

Recent evidence suggests that endothelial dysfunction and pathology of pulmonary vascular responses may serve as a precursor to smoking-associated emphysema. Although it is known that emphysematous destruction leads to vasculature changes, less is known about early regional vascular dysfunction which may contribute to and precede emphysematous changes. We sought to test the hypothesis, via multidetector row CT (MDCT) perfusion imaging, that smokers showing early signs of emphysema susceptibility have a greater heterogeneity in regional perfusion parameters than emphysema-free smokers and persons who had never smoked (NS). Assuming that all smokers have a consistent inflammatory response, increased perfusion heterogeneity in emphysema-susceptible smokers would be consistent with the notion that these subjects may have the inability to block hypoxic vasoconstriction in patchy, small regions of inflammation. Dynamic ECG-gated MDCT perfusion scans with a central bolus injection of contrast were acquired in 17 NS, 12 smokers with normal CT imaging studies (SNI), and 12 smokers with subtle CT findings of centrilobular emphysema (SCE). All subjects had normal spirometry. Quantitative image analysis determined regional perfusion parameters, pulmonary blood flow (PBF), and mean transit time (MTT). Mean and coefficient of variation were calculated, and statistical differences were assessed with one-way ANOVA. MDCT-based MTT and PBF measurements demonstrate globally increased heterogeneity in SCE subjects compared with NS and SNI subjects but demonstrate similarity between NS and SNI subjects. These findings demonstrate a functional lung-imaging measure that provides a more mechanistically oriented phenotype that differentiates smokers with and without evidence of emphysema susceptibility.

Effects of heparin-binding epidermal growth factor-like growth factor on cell repopulation and signal transduction in periodontal ligament cells after scratch wounding in vitro.

PubMed

Lee, J S; Kim, J M; Hong, E K; Kim, S-O; Yoo, Y-J; Cha, J-H

2009-02-01

A growing amount of attention has been placed on periodontal regeneration and wound healing for periodontal therapy. This study was conducted in an effort to determine the effects of heparin-binding epidermal growth factor-like growth factor on cell repopulation and signal transduction in periodontal ligament cells after scratch wounding in vitro. Human periodontal ligament cells were acquired from explant tissue of human healthy periodontal ligament. After the wounding of periodontal ligament cells, the change in expression of heparin-binding epidermal growth factor-like growth factor and epidermal growth factor receptors 1-4 mRNA was assessed. The effects of heparin-binding epidermal growth factor-like growth factor on periodontal ligament cell proliferation and repopulation were assessed in vitro via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and by photographing the injuries, respectively. Extracellular signal-regulated kinase (Erk)1/2, p38 and Akt phosphorylation was characterized via western blotting. Scratch wounding resulted in a significant up-regulation of heparin-binding epidermal growth factor-like growth factor mRNA expression, whereas wounding had no effect on the expression levels of epidermal growth factor receptors 1-4. Interestingly, no expression of epidermal growth factor receptors 2 and 4 was detectable prior to or after wounding. Heparin-binding epidermal growth factor-like growth factor treatment promoted the proliferation and repopulation of periodontal ligament cells. The scratch wounding also stimulated the phosphorylation of Erk1/2 and p38, but not of Akt, in periodontal ligament cells, and heparin-binding epidermal growth factor-like growth factor treatment applied after wounding amplified and extended the activations of Erk1/2 and p38, but not of Akt. Furthermore, Erk1/2 inhibition blocked the process of cell repopulation induced by heparin-binding epidermal growth factor-like growth factor, whereas the inhibition of p38 delayed the process. These results indicate that heparin-binding epidermal growth factor-like growth factor may constitute a critical factor in the wound healing of human periodontal ligament cells by a mechanism that requires the activation of Erk1/2 via specific interaction with epidermal growth factor receptor 1.

Modulation of DNA binding by gene-specific transcription factors.

PubMed

Schleif, Robert F

2013-10-01

The transcription of many genes, particularly in prokaryotes, is controlled by transcription factors whose activity can be modulated by controlling their DNA binding affinity. Understanding the molecular mechanisms by which DNA binding affinity is regulated is important, but because forming definitive conclusions usually requires detailed structural information in combination with data from extensive biophysical, biochemical, and sometimes genetic experiments, little is truly understood about this topic. This review describes the biological requirements placed upon DNA binding transcription factors and their consequent properties, particularly the ways that DNA binding affinity can be modulated and methods for its study. What is known and not known about the mechanisms modulating the DNA binding affinity of a number of prokaryotic transcription factors, including CAP and lac repressor, is provided.

Human corpus luteum: presence of epidermal growth factor receptors and binding characteristics

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

Ayyagari, R.R.; Khan-Dawood, F.S.

Epidermal growth factor receptors are present in many reproductive tissues but have not been demonstrated in the human corpus luteum. To determine the presence of epidermal growth factor receptors and its binding characteristics, we carried out studies on the plasma cell membrane fraction of seven human corpora lutea (days 16 to 25) of the menstrual cycle. Specific epidermal growth factor receptors were present in human corpus luteum. Insulin, nerve growth factor, and human chorionic gonadotropin did not competitively displace epidermal growth factor binding. The optimal conditions for corpus luteum-epidermal growth factor receptor binding were found to be incubation for 2more » hours at 4 degrees C with 500 micrograms plasma membrane protein and 140 femtomol /sup 125/I-epidermal growth factor per incubate. The number (mean +/- SEM) of epidermal growth factor binding sites was 12.34 +/- 2.99 X 10(-19) mol/micrograms protein; the dissociation constant was 2.26 +/- 0.56 X 10(-9) mol/L; the association constant was 0.59 +/- 0.12 X 10(9) L/mol. In two regressing corpora lutea obtained on days 2 and 3 of the menstrual cycle, there was no detectable specific epidermal growth factor receptor binding activity. Similarly no epidermal growth factor receptor binding activity could be detected in ovarian stromal tissue. Our findings demonstrate that specific receptors for epidermal growth factor are present in the human corpus luteum. The physiologic significance of epidermal growth factor receptors in human corpus luteum is unknown, but epidermal growth factor may be involved in intragonadal regulation of luteal function.« less

Naturally occurring mutations in the human 5-lipoxygenase gene promoter that modify transcription factor binding and reporter gene transcription.

PubMed Central

In, K H; Asano, K; Beier, D; Grobholz, J; Finn, P W; Silverman, E K; Silverman, E S; Collins, T; Fischer, A R; Keith, T P; Serino, K; Kim, S W; De Sanctis, G T; Yandava, C; Pillari, A; Rubin, P; Kemp, J; Israel, E; Busse, W; Ledford, D; Murray, J J; Segal, A; Tinkleman, D; Drazen, J M

1997-01-01

Five lipoxygenase (5-LO) is the first committed enzyme in the metabolic pathway leading to the synthesis of the leukotrienes. We examined genomic DNA isolated from 25 normal subjects and 31 patients with asthma (6 of whom had aspirin-sensitive asthma) for mutations in the known transcription factor binding regions and the protein encoding region of the 5-LO gene. A family of mutations in the G + C-rich transcription factor binding region was identified consisting of the deletion of one, deletion of two, or addition of one zinc finger (Sp1/Egr-1) binding sites in the region 176 to 147 bp upstream from the ATG translation start site where there are normally 5 Sp1 binding motifs in tandem. Reporter gene activity directed by any of the mutant forms of the transcription factor binding region was significantly (P < 0.05) less effective than the activity driven by the wild type transcription factor binding region. Electrophoretic mobility shift assays (EMSAs) demonstrated the capacity of wild type and mutant transcription factor binding regions to bind nuclear extracts from human umbilical vein endothelial cells (HUVECs). These data are consistent with a family of mutations in the 5-LO gene that can modify reporter gene transcription possibly through differences in Sp1 and Egr-1 transactivation. PMID:9062372

Naturally occurring mutations in the human 5-lipoxygenase gene promoter that modify transcription factor binding and reporter gene transcription.

PubMed

In, K H; Asano, K; Beier, D; Grobholz, J; Finn, P W; Silverman, E K; Silverman, E S; Collins, T; Fischer, A R; Keith, T P; Serino, K; Kim, S W; De Sanctis, G T; Yandava, C; Pillari, A; Rubin, P; Kemp, J; Israel, E; Busse, W; Ledford, D; Murray, J J; Segal, A; Tinkleman, D; Drazen, J M

1997-03-01

Five lipoxygenase (5-LO) is the first committed enzyme in the metabolic pathway leading to the synthesis of the leukotrienes. We examined genomic DNA isolated from 25 normal subjects and 31 patients with asthma (6 of whom had aspirin-sensitive asthma) for mutations in the known transcription factor binding regions and the protein encoding region of the 5-LO gene. A family of mutations in the G + C-rich transcription factor binding region was identified consisting of the deletion of one, deletion of two, or addition of one zinc finger (Sp1/Egr-1) binding sites in the region 176 to 147 bp upstream from the ATG translation start site where there are normally 5 Sp1 binding motifs in tandem. Reporter gene activity directed by any of the mutant forms of the transcription factor binding region was significantly (P < 0.05) less effective than the activity driven by the wild type transcription factor binding region. Electrophoretic mobility shift assays (EMSAs) demonstrated the capacity of wild type and mutant transcription factor binding regions to bind nuclear extracts from human umbilical vein endothelial cells (HUVECs). These data are consistent with a family of mutations in the 5-LO gene that can modify reporter gene transcription possibly through differences in Sp1 and Egr-1 transactivation.

Role of Fibroblast Growth Factor Binding Protein-1 in Mammary Development and Tumorigenesis

DTIC Science & Technology

2009-10-01

AD_________________ Award Number: W81XWH-06-1-0763 TITLE: Role of Fibroblast Growth Factor ...2009 4. TITLE AND SUBTITLE Role of Fibroblast Growth Factor Binding Protein-1 in Mammary Development 5a. CONTRACT NUMBER and Tumorigenesis...Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT 15. SUBJECT TERMS Fibroblast Growth Factor Binding Protein-1

Insights into the complex association of bovine factor Va with acidic-lipid-containing synthetic membranes.

PubMed Central

Cutsforth, G A; Koppaka, V; Krishnaswamy, S; Wu, J R; Mann, K G; Lentz, B R

1996-01-01

The mechanism of binding of blood coagulation cofactor factor Va to acidic-lipid-containing membranes has been addressed. Binding isotherms were generated at room temperature using the change in fluorescence anisotropy of pyrene-labeled bovine factor Va to detect binding to sonicated membrane vesicles containing either bovine brain phosphatidylserine (PS) or 1,2-dioleoyl-3-sn-phosphatidylglycerol (DOPG) in combination with 1-palmitoyl-2-oleoyl-3-sn-phosphatidylcholine (POPC). The composition of the membranes was varied from 0 to 40 mol% for PS/POPC and from 0 to 65 mol % for DOPG/POPC membranes. Fitting the data to a classical Langmuir adsorption model yielded estimates of the dissociation constant (Kd) and the stoichiometry of binding. The values of Kd defined in this way displayed a maximum at low acidic lipid content but were nearly constant at intermediate to high fractions of acidic lipid. Fitting the binding isotherms to a two-process binding model (nonspecific adsorption in addition to binding of acidic lipids to sites on the protein) suggested a significant acidic-lipid-independent binding affinity in addition to occupancy of three protein sites that bind PS in preference to DOPG. Both analyses indicated that interaction of factor Va with an acidic-lipid-containing membrane is much more complex than those of factor Xa or prothrombin. Furthermore, a change in the conformation of bound pyrene-labeled factor Va with surface concentration of acidic lipid was implied by variation of both the saturating fluorescence anisotropy and the binding parameters with the acidic lipid content of the membrane. Finally, the results cannot support the contention that binding occurs through nonspecific adsorption to a patch or domain of acidic lipids in the membrane. Factor Va is suggested to associate with membranes by a complex process that includes both acidic-lipid-specific and acidic-lipid-independent sites and a protein structure change induced by occupancy of acidic-lipid-specific sites on the factor Va molecule. Images FIGURE 5 PMID:8744332

Computer-Based Methods for Thermodynamic Analysis of Materials Processing.

DTIC Science & Technology

1983-11-30

metallic alloys (12,13), silicides (14),and oxynitride * . systems (15). - . 2. Thermochemical System Employed to Characterize Binary Ill-V Phase Diagrams The...reference to Figure I shows that the stable form of RbF is the sodium chloride S form. Table I shows that OGH -oS -RFRFLS-RFRFLM-12866-.381T J/g.at. (5...KF, BF=(I/3)8aF LF-(I/4)LaF3V PF-(113)PbF 2 S- Sodium Chloride Structures Stable form of NF, KE, RE and (;F L-Liquid, M-Stable form of ZF, KeStable form

Development of magnetic resonance technology for noninvasive boron quantification

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

Bradshaw, K.M.

1990-11-01

Boron magnetic resonance imaging (MRI) and spectroscopy (MRS) were developed in support of the noninvasive boron quantification task of the Idaho National Engineering Laboratory (INEL) Power Burst Facility/Boron Neutron Capture Therapy (PBF/BNCT) program. The hardware and software described in this report are modifications specific to a GE Signa{trademark} MRI system, release 3.X and are necessary for boron magnetic resonance operation. The technology developed in this task has been applied to obtaining animal pharmacokinetic data of boron compounds (drug time response) and the in-vivo localization of boron in animal tissue noninvasively. 9 refs., 21 figs.

Distal Insertions of the Biceps Femoris

PubMed Central

Branch, Eric A.; Anz, Adam W.

2015-01-01

Background: Avulsion of the biceps femoris from the fibula and proximal tibia is encountered in clinical practice. While the anatomy of the primary posterolateral corner structures has been qualitatively and quantitatively described, a quantitative analysis regarding the insertions of the biceps femoris on the fibula and proximal tibia is lacking. Purpose: To quantitatively assess the insertions of the biceps femoris, fibular collateral ligament (FCL), and anterolateral ligament (ALL) on the fibula and proximal tibia as well as establish relationships among these structures and to pertinent surgical anatomy. Study Design: Descriptive laboratory study. Methods: Dissections were performed on 12 nonpaired, fresh-frozen cadaveric specimens identifying the biceps femoris, FCL, and ALL, and their insertions on the proximal tibia and fibula. The footprint areas, orientations, and distances from relevant osseous landmarks were measured using a 3-dimensional coordinate measurement device. Results: Dissection produced 6 easily identifiable and reproducible anatomic footprints. Tibial footprints included the insertion of the ALL and an insertion of the biceps femoris (TBF). Fibular footprints included the insertion of the FCL, a distal insertion of the biceps femoris (DBF), a medial footprint of the biceps femoris (MBF), and a proximal footprint of the biceps femoris (PBF). The mean area of these footprints (95% CI) was as follows: ALL, 53.0 mm2 (38.4-67.6); TBF, 93.9 mm2 (72.0-115.8); FCL, 86.8 mm2 (72.3-101.2); DBF, 119 mm2 (91.1-146.9); MBF, 46.8 mm2 (29.0-64.5); and PBF, 215 mm2 (192.4-237.5). The mean distance (95% CI) from the Gerdy tubercle to the center of the ALL footprint was 24.3 mm (21.6-27.0) and to the center of the TBF was 22.5 mm (21.0-24.0). The center of the DBF was 8.68 mm (7.0-10.3) from the anterior border of the fibula, the center of the FCL was 14.6 mm (12.5-16.7) from the anterior border of the fibula and 20.7 mm (19.0-22.4) from the tip of the fibular styloid, and the center of the PBF was 8.96 mm (8.2-9.7) from the tip of the fibular styloid. Conclusion: A tibial footprint, distal fibular footprint, medial fibular footprint, and proximal fibular footprint were all consistent components of the insertion of the biceps femoris. Consistent relationships existed between the biceps femoris and insertions of the ALL and FCL. Clinical Relevance: The size of these footprints and distances from pertinent surgical landmarks will guide repairs of biceps femoris avulsion injuries. PMID:26535398

Arterial-to-end-tidal carbon dioxide tension difference in children with congenital heart disease.

PubMed

Choudhury, Minati; Kiran, Usha; Choudhary, Shiv Kumar; Airan, Balram

2006-04-01

This study estimated the arterial-to-end-tidal carbon dioxide tension difference (deltaPaCO2-PE'CO2) in children with congenital heart disease; evaluated whether hyperventilation can reduce this difference; and analyzed the relationship between the difference and the oxygen saturation (SaO2) and hemoglobin level. Prospective clinical study. Tertiary health care center. One hundred patients scheduled for correction of their underlying cardiac defect with either right-to-left or left-to-right intracardiac shunts were divided into 4 groups (n = 25 each): (1) N1, cyanotic with severe pulmonary artery hypertension; (2) N2, cyanotic with normal or decreased pulmonary artery pressure (PAP); (3) N3, acyanotic with normal or mild increases in PAP and severe increases in pulmonary blood flow (PBF); and (4) N4, acyanotic with normal PAP and normal or mild increase in PBF. All the patients received the same anesthetic regimen. The initial settings for tidal volume, respiratory rate, and inspiratory-to-expiratory (I:E) ratio were 10 mL/kg, 15 to 30 breath/min, and inspired time 40% of the total respiratory period with a 10% end-inspiratory pause. After the measurement of oxygen saturation, PO2, Hb, and deltaPaCO2-PE'CO2, all the children were hyperventilated (tidal volume: 14-15 mL/kg, respiratory rate: 5-6 breaths/min more than the initial rate, I:E ratio: same) to observe its effects on the deltaPaCO2-PE'CO2. The deltaPaCO2-PE'CO2, when predicted from the oxygen saturation, hemoglobin concentration, and PaO2, was found to be greater than the observed value in the first 3 groups (p < 0.001); whereas in group N4 these 2 values were comparable. It was also found that the gradient was higher when there was a decrease in SaO2 and an increase in the hemoglobin level. After hyperventilation, in groups N1 and N3, deltaPaCO2-PE'CO2 was decreased when compared with their baseline values; this reduction was not as much as predicted (p = 0.363 and 0.236, respectively). However, in groups N2 and N4 posthyperventilation, the deltaPaCO2-PE'27 CO2 was decreased significantly below their baseline measurements. These decreases were as much predicted. The deltaPaCO2-end-tidal carbon dioxide (PE'CO2) can be increased both in cyanotic and acyanotic children. Increased PAP is as important as increased PBF or right-to-left shunting in producing disorders in carbon dioxide homeostasis. Hyperventilation is of little use in reducing deltaPaCO2-PE'CO2 in children with high PAPs and pulmonary hyperperfusion.

Cherenkov radiation-based three-dimensional position-sensitive PET detector: A Monte Carlo study.

PubMed

Ota, Ryosuke; Yamada, Ryoko; Moriya, Takahiro; Hasegawa, Tomoyuki

2018-05-01

Cherenkov radiation has recently received attention due to its prompt emission phenomenon, which has the potential to improve the timing performance of radiation detectors dedicated to positron emission tomography (PET). In this study, a Cherenkov-based three-dimensional (3D) position-sensitive radiation detector was proposed, which is composed of a monolithic lead fluoride (PbF 2 ) crystal and a photodetector array of which the signals can be readout independently. Monte Carlo simulations were performed to estimate the performance of the proposed detector. The position- and time resolution were evaluated under various practical conditions. The radiator size and various properties of the photodetector, e.g., readout pitch and single photon timing resolution (SPTR), were parameterized. The single photon time response of the photodetector was assumed to be a single Gaussian for the simplification. The photo detection efficiency of the photodetector was ideally 100% for all wavelengths. Compton scattering was included in simulations, but partly analyzed. To estimate the position at which a γ-ray interacted in the Cherenkov radiator, the center-of-gravity (COG) method was employed. In addition, to estimate the depth-of-interaction (DOI) principal component analysis (PCA), which is a multivariate analysis method and has been used to identify the patterns in data, was employed. The time-space distribution of Cherenkov photons was quantified to perform PCA. To evaluate coincidence time resolution (CTR), the time difference of two independent γ-ray events was calculated. The detection time was defined as the first photon time after the SPTR of the photodetector was taken into account. The position resolution on the photodetector plane could be estimated with high accuracy, by using a small number of Cherenkov photons. Moreover, PCA showed an ability to estimate the DOI. The position resolution heavily depends on the pitch of the photodetector array and the radiator thickness. If the readout pitch were ideally 0 and practically 3 mm, a full-width at half-maximum (FWHM) of 0.348 and 1.92 mm was achievable with a 10-mm-thick PbF 2 crystal, respectively. Furthermore, first-order correlation could be observed between the primary principal component and the true DOI. To obtain a coincidence timing resolution better than 100-ps FWHM with a 20-mm-thick PbF 2 crystal, a photodetector with SPTR of better than σ = 30 ps was necessary. From these results, the improvement of SPTR allows us to achieve CTR better than 100-ps FWHM, even in the case where a 20-mm-thick radiator is used. Our proposed detector has the potential to estimate the 3D interaction position of γ-rays in the radiator, using only time and space information of Cherenkov photons. © 2018 American Association of Physicists in Medicine.

Architecture of the human regulatory network derived from ENCODE data.

PubMed

Gerstein, Mark B; Kundaje, Anshul; Hariharan, Manoj; Landt, Stephen G; Yan, Koon-Kiu; Cheng, Chao; Mu, Xinmeng Jasmine; Khurana, Ekta; Rozowsky, Joel; Alexander, Roger; Min, Renqiang; Alves, Pedro; Abyzov, Alexej; Addleman, Nick; Bhardwaj, Nitin; Boyle, Alan P; Cayting, Philip; Charos, Alexandra; Chen, David Z; Cheng, Yong; Clarke, Declan; Eastman, Catharine; Euskirchen, Ghia; Frietze, Seth; Fu, Yao; Gertz, Jason; Grubert, Fabian; Harmanci, Arif; Jain, Preti; Kasowski, Maya; Lacroute, Phil; Leng, Jing Jane; Lian, Jin; Monahan, Hannah; O'Geen, Henriette; Ouyang, Zhengqing; Partridge, E Christopher; Patacsil, Dorrelyn; Pauli, Florencia; Raha, Debasish; Ramirez, Lucia; Reddy, Timothy E; Reed, Brian; Shi, Minyi; Slifer, Teri; Wang, Jing; Wu, Linfeng; Yang, Xinqiong; Yip, Kevin Y; Zilberman-Schapira, Gili; Batzoglou, Serafim; Sidow, Arend; Farnham, Peggy J; Myers, Richard M; Weissman, Sherman M; Snyder, Michael

2012-09-06

Transcription factors bind in a combinatorial fashion to specify the on-and-off states of genes; the ensemble of these binding events forms a regulatory network, constituting the wiring diagram for a cell. To examine the principles of the human transcriptional regulatory network, we determined the genomic binding information of 119 transcription-related factors in over 450 distinct experiments. We found the combinatorial, co-association of transcription factors to be highly context specific: distinct combinations of factors bind at specific genomic locations. In particular, there are significant differences in the binding proximal and distal to genes. We organized all the transcription factor binding into a hierarchy and integrated it with other genomic information (for example, microRNA regulation), forming a dense meta-network. Factors at different levels have different properties; for instance, top-level transcription factors more strongly influence expression and middle-level ones co-regulate targets to mitigate information-flow bottlenecks. Moreover, these co-regulations give rise to many enriched network motifs (for example, noise-buffering feed-forward loops). Finally, more connected network components are under stronger selection and exhibit a greater degree of allele-specific activity (that is, differential binding to the two parental alleles). The regulatory information obtained in this study will be crucial for interpreting personal genome sequences and understanding basic principles of human biology and disease.

ABFs, a family of ABA-responsive element binding factors.

PubMed

Choi, H; Hong, J; Ha, J; Kang, J; Kim, S Y

2000-01-21

Abscisic acid (ABA) plays an important role in environmental stress responses of higher plants during vegetative growth. One of the ABA-mediated responses is the induced expression of a large number of genes, which is mediated by cis-regulatory elements known as abscisic acid-responsive elements (ABREs). Although a number of ABRE binding transcription factors have been known, they are not specifically from vegetative tissues under induced conditions. Considering the tissue specificity of ABA signaling pathways, factors mediating ABA-dependent stress responses during vegetative growth phase may thus have been unidentified so far. Here, we report a family of ABRE binding factors isolated from young Arabidopsis plants under stress conditions. The factors, isolated by a yeast one-hybrid system using a prototypical ABRE and named as ABFs (ABRE binding factors) belong to a distinct subfamily of bZIP proteins. Binding site selection assay performed with one ABF showed that its preferred binding site is the strong ABRE, CACGTGGC. ABFs can transactivate an ABRE-containing reporter gene in yeast. Expression of ABFs is induced by ABA and various stress treatments, whereas their induction patterns are different from one another. Thus, a new family of ABRE binding factors indeed exists that have the potential to activate a large number of ABA/stress-responsive genes in Arabidopsis.

Platelet binding sites for factor VIII in relation to fibrin and phosphatidylserine

PubMed Central

Novakovic, Valerie A.; Shi, Jialan; Rasmussen, Jan; Pipe, Steven W.

2015-01-01

Thrombin-stimulated platelets expose very little phosphatidylserine (PS) but express binding sites for factor VIII (fVIII), casting doubt on the role of exposed PS as the determinant of binding sites. We previously reported that fVIII binding sites are increased three- to sixfold when soluble fibrin (SF) binds the αIIbβ3 integrin. This study focuses on the hypothesis that platelet-bound SF is the major source of fVIII binding sites. Less than 10% of fVIII was displaced from thrombin-stimulated platelets by lactadherin, a PS-binding protein, and an fVIII mutant defective in PS-dependent binding retained platelet affinity. Therefore, PS is not the determinant of most binding sites. FVIII bound immobilized SF and paralleled platelet binding in affinity, dependence on separation from von Willebrand factor, and mediation by the C2 domain. SF also enhanced activity of fVIII in the factor Xase complex by two- to fourfold. Monoclonal antibody (mAb) ESH8, against the fVIII C2 domain, inhibited binding of fVIII to SF and platelets but not to PS-containing vesicles. Similarly, mAb ESH4 against the C2 domain, inhibited >90% of platelet-dependent fVIII activity vs 35% of vesicle-supported activity. These results imply that platelet-bound SF is a component of functional fVIII binding sites. PMID:26162408

A Single Rainbow Trout Cobalamin-binding Protein Stands in for Three Human Binders

PubMed Central

Greibe, Eva; Fedosov, Sergey; Sorensen, Boe S.; Højrup, Peter; Poulsen, Steen S.; Nexo, Ebba

2012-01-01

Cobalamin uptake and transport in mammals are mediated by three cobalamin-binding proteins: haptocorrin, intrinsic factor, and transcobalamin. The nature of cobalamin-binding proteins in lower vertebrates remains to be elucidated. The aim of this study was to characterize the cobalamin-binding proteins of the rainbow trout (Oncorhynchus mykiss) and to compare their properties with those of the three human cobalamin-binding proteins. High cobalamin-binding capacity was found in trout stomach (210 pmol/g), roe (400 pmol/g), roe fluid (390 nmol/liter), and plasma (2500 nmol/liter). In all cases, it appeared to be the same protein based on analysis of partial sequences and immunological responses. The trout cobalamin-binding protein was purified from roe fluid, sequenced, and further characterized. Like haptocorrin, the trout cobalamin-binding protein was stable at low pH and had a high binding affinity for the cobalamin analog cobinamide. Like haptocorrin and transcobalamin, the trout cobalamin-binding protein was present in plasma and recognized ligands with altered nucleotide moiety. Like intrinsic factors, the trout cobalamin-binding protein was present in the stomach and resisted degradation by trypsin and chymotrypsin. It also resembled intrinsic factor in the composition of conserved residues in the primary cobalamin-binding site in the C terminus. The trout cobalamin-binding protein was glycosylated and displayed spectral properties comparable with those of haptocorrin and intrinsic factor. In conclusion, only one soluble cobalamin-binding protein was identified in the rainbow trout, a protein that structurally behaves like an intermediate between the three human cobalamin-binding proteins. PMID:22872637

MONKEY: Identifying conserved transcription-factor binding sitesin multiple alignments using a binding site-specific evolutionarymodel

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

Moses, Alan M.; Chiang, Derek Y.; Pollard, Daniel A.

2004-10-28

We introduce a method (MONKEY) to identify conserved transcription-factor binding sites in multispecies alignments. MONKEY employs probabilistic models of factor specificity and binding site evolution, on which basis we compute the likelihood that putative sites are conserved and assign statistical significance to each hit. Using genomes from the genus Saccharomyces, we illustrate how the significance of real sites increases with evolutionary distance and explore the relationship between conservation and function.

Discovery and information-theoretic characterization of transcription factor binding sites that act cooperatively.

PubMed

Clifford, Jacob; Adami, Christoph

2015-09-02

Transcription factor binding to the surface of DNA regulatory regions is one of the primary causes of regulating gene expression levels. A probabilistic approach to model protein-DNA interactions at the sequence level is through position weight matrices (PWMs) that estimate the joint probability of a DNA binding site sequence by assuming positional independence within the DNA sequence. Here we construct conditional PWMs that depend on the motif signatures in the flanking DNA sequence, by conditioning known binding site loci on the presence or absence of additional binding sites in the flanking sequence of each site's locus. Pooling known sites with similar flanking sequence patterns allows for the estimation of the conditional distribution function over the binding site sequences. We apply our model to the Dorsal transcription factor binding sites active in patterning the Dorsal-Ventral axis of Drosophila development. We find that those binding sites that cooperate with nearby Twist sites on average contain about 0.5 bits of information about the presence of Twist transcription factor binding sites in the flanking sequence. We also find that Dorsal binding site detectors conditioned on flanking sequence information make better predictions about what is a Dorsal site relative to background DNA than detection without information about flanking sequence features.

HOCOMOCO: towards a complete collection of transcription factor binding models for human and mouse via large-scale ChIP-Seq analysis.

PubMed

Kulakovskiy, Ivan V; Vorontsov, Ilya E; Yevshin, Ivan S; Sharipov, Ruslan N; Fedorova, Alla D; Rumynskiy, Eugene I; Medvedeva, Yulia A; Magana-Mora, Arturo; Bajic, Vladimir B; Papatsenko, Dmitry A; Kolpakov, Fedor A; Makeev, Vsevolod J

2018-01-04

We present a major update of the HOCOMOCO collection that consists of patterns describing DNA binding specificities for human and mouse transcription factors. In this release, we profited from a nearly doubled volume of published in vivo experiments on transcription factor (TF) binding to expand the repertoire of binding models, replace low-quality models previously based on in vitro data only and cover more than a hundred TFs with previously unknown binding specificities. This was achieved by systematic motif discovery from more than five thousand ChIP-Seq experiments uniformly processed within the BioUML framework with several ChIP-Seq peak calling tools and aggregated in the GTRD database. HOCOMOCO v11 contains binding models for 453 mouse and 680 human transcription factors and includes 1302 mononucleotide and 576 dinucleotide position weight matrices, which describe primary binding preferences of each transcription factor and reliable alternative binding specificities. An interactive interface and bulk downloads are available on the web: http://hocomoco.autosome.ru and http://www.cbrc.kaust.edu.sa/hocomoco11. In this release, we complement HOCOMOCO by MoLoTool (Motif Location Toolbox, http://molotool.autosome.ru) that applies HOCOMOCO models for visualization of binding sites in short DNA sequences. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Developmental roles of 21 Drosophila transcription factors are determined by quantitative differences in binding to an overlapping set of thousands of genomic regions

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

MacArthur, Stewart; Li, Xiao-Yong; Li, Jingyi

2009-05-15

BACKGROUND: We previously established that six sequence-specific transcription factors that initiate anterior/posterior patterning in Drosophila bind to overlapping sets of thousands of genomic regions in blastoderm embryos. While regions bound at high levels include known and probable functional targets, more poorly bound regions are preferentially associated with housekeeping genes and/or genes not transcribed in the blastoderm, and are frequently found in protein coding sequences or in less conserved non-coding DNA, suggesting that many are likely non-functional. RESULTS: Here we show that an additional 15 transcription factors that regulate other aspects of embryo patterning show a similar quantitative continuum of functionmore » and binding to thousands of genomic regions in vivo. Collectively, the 21 regulators show a surprisingly high overlap in the regions they bind given that they belong to 11 DNA binding domain families, specify distinct developmental fates, and can act via different cis-regulatory modules. We demonstrate, however, that quantitative differences in relative levels of binding to shared targets correlate with the known biological and transcriptional regulatory specificities of these factors. CONCLUSIONS: It is likely that the overlap in binding of biochemically and functionally unrelated transcription factors arises from the high concentrations of these proteins in nuclei, which, coupled with their broad DNA binding specificities, directs them to regions of open chromatin. We suggest that most animal transcription factors will be found to show a similar broad overlapping pattern of binding in vivo, with specificity achieved by modulating the amount, rather than the identity, of bound factor.« less

Modular Evolution of DNA-Binding Preference of a Tbrain Transcription Factor Provides a Mechanism for Modifying Gene Regulatory Networks

PubMed Central

Cheatle Jarvela, Alys M.; Brubaker, Lisa; Vedenko, Anastasia; Gupta, Anisha; Armitage, Bruce A.; Bulyk, Martha L.; Hinman, Veronica F.

2014-01-01

Gene regulatory networks (GRNs) describe the progression of transcriptional states that take a single-celled zygote to a multicellular organism. It is well documented that GRNs can evolve extensively through mutations to cis-regulatory modules (CRMs). Transcription factor proteins that bind these CRMs may also evolve to produce novelty. Coding changes are considered to be rarer, however, because transcription factors are multifunctional and hence are more constrained to evolve in ways that will not produce widespread detrimental effects. Recent technological advances have unearthed a surprising variation in DNA-binding abilities, such that individual transcription factors may recognize both a preferred primary motif and an additional secondary motif. This provides a source of modularity in function. Here, we demonstrate that orthologous transcription factors can also evolve a changed preference for a secondary binding motif, thereby offering an unexplored mechanism for GRN evolution. Using protein-binding microarray, surface plasmon resonance, and in vivo reporter assays, we demonstrate an important difference in DNA-binding preference between Tbrain protein orthologs in two species of echinoderms, the sea star, Patiria miniata, and the sea urchin, Strongylocentrotus purpuratus. Although both orthologs recognize the same primary motif, only the sea star Tbr also has a secondary binding motif. Our in vivo assays demonstrate that this difference may allow for greater evolutionary change in timing of regulatory control. This uncovers a layer of transcription factor binding divergence that could exist for many pairs of orthologs. We hypothesize that this divergence provides modularity that allows orthologous transcription factors to evolve novel roles in GRNs through modification of binding to secondary sites. PMID:25016582

Chromatin-Specific Regulation of Mammalian rDNA Transcription by Clustered TTF-I Binding Sites

PubMed Central

Diermeier, Sarah D.; Németh, Attila; Rehli, Michael; Grummt, Ingrid; Längst, Gernot

2013-01-01

Enhancers and promoters often contain multiple binding sites for the same transcription factor, suggesting that homotypic clustering of binding sites may serve a role in transcription regulation. Here we show that clustering of binding sites for the transcription termination factor TTF-I downstream of the pre-rRNA coding region specifies transcription termination, increases the efficiency of transcription initiation and affects the three-dimensional structure of rRNA genes. On chromatin templates, but not on free rDNA, clustered binding sites promote cooperative binding of TTF-I, loading TTF-I to the downstream terminators before it binds to the rDNA promoter. Interaction of TTF-I with target sites upstream and downstream of the rDNA transcription unit connects these distal DNA elements by forming a chromatin loop between the rDNA promoter and the terminators. The results imply that clustered binding sites increase the binding affinity of transcription factors in chromatin, thus influencing the timing and strength of DNA-dependent processes. PMID:24068958

Feasibility of quantification of the distribution of blood flow in the normal human fetal circulation using CMR: a cross-sectional study.

PubMed

Seed, Mike; van Amerom, Joshua F P; Yoo, Shi-Joon; Al Nafisi, Bahiyah; Grosse-Wortmann, Lars; Jaeggi, Edgar; Jansz, Michael S; Macgowan, Christopher K

2012-11-26

We present the first phase contrast (PC) cardiovascular magnetic resonance (CMR) measurements of the distribution of blood flow in twelve late gestation human fetuses. These were obtained using a retrospective gating technique known as metric optimised gating (MOG). A validation experiment was performed in five adult volunteers where conventional cardiac gating was compared with MOG. Linear regression and Bland Altman plots were used to compare MOG with the gold standard of conventional gating. Measurements using MOG were then made in twelve normal fetuses at a median gestational age of 37 weeks (range 30-39 weeks). Flow was measured in the major fetal vessels and indexed to the fetal weight. There was good correlation between the conventional gated and MOG measurements in the adult validation experiment (R=0.96). Mean flows in ml/min/kg with standard deviations in the major fetal vessels were as follows: combined ventricular output (CVO) 540 ± 101, main pulmonary artery (MPA) 327 ± 68, ascending aorta (AAo) 198 ± 38, superior vena cava (SVC) 147 ± 46, ductus arteriosus (DA) 220 ± 39,pulmonary blood flow (PBF) 106 ± 59,descending aorta (DAo) 273 ± 85, umbilical vein (UV) 160 ± 62, foramen ovale (FO)107 ± 54. Results expressed as mean percentages of the CVO with standard deviations were as follows: MPA 60 ± 4, AAo37 ± 4, SVC 28 ± 7, DA 41 ± 8, PBF 19 ± 10, DAo50 ± 12, UV 30 ± 9, FO 21 ± 12. This study demonstrates how PC CMR with MOG is a feasible technique for measuring the distribution of the normal human fetal circulation in late pregnancy. Our preliminary results are in keeping with findings from previous experimental work in fetal lambs.

Using an Alternate Reality Game to Increase Physical Activity and Decrease Obesity Risk of College Students

PubMed Central

Johnston, Jeanne D.; Massey, Anne P.; Marker-Hoffman, Rickie Lee

2012-01-01

Background This quasi-experimental study investigated a game intervention—specifically, an alternate reality game (ARG)—as a means to influence college students’ physical activity (PA). An ARG is an interactive narrative that takes place in the real world and uses multiple media to reveal a story. Method Three sections of a college health course (n = 115 freshman students) were assigned either to a game group that played the ARG or to a comparison group that learned how to use exercise equipment in weekly laboratory sessions. Pre- and post-intervention measures included weight, waist circumference, body mass index (BMI), percentage body fat (PBF), and self-reported moderate physical activity (MPA) and vigorous physical activity (VPA), and PA (steps/week). Results A significant group x time interaction (p = .001) was detected for PA, with a significant increase in PA for the game (p < .001) versus a significant decrease (p = .001) for the comparison group. Significant within-group increases for weight (p = .001), BMI (p = .001), and PBF (p = .001) were detected. A significant group x time interaction (p = .001) was detected when analyzing self-reported VPA, with both groups reporting decreases in VPA over time; however, the decrease was only significant for the comparison group (p < .001). No significant group differences were found for MPA. Conclusions It is important that any intervention meet the needs and interests of its target population. Here, the ARG was designed in light of the learning preferences of today’s college students—collaborative and social, experiential and media-rich. Our results provide preliminary evidence that a game intervention can positively influence PA within the college student population. PMID:22920809

Open lung approach vs acute respiratory distress syndrome network ventilation in experimental acute lung injury.

PubMed

Spieth, P M; Güldner, A; Carvalho, A R; Kasper, M; Pelosi, P; Uhlig, S; Koch, T; Gama de Abreu, M

2011-09-01

Setting and strategies of mechanical ventilation with positive end-expiratory pressure (PEEP) in acute lung injury (ALI) remains controversial. This study compares the effects between lung-protective mechanical ventilation according to the Acute Respiratory Distress Syndrome Network recommendations (ARDSnet) and the open lung approach (OLA) on pulmonary function and inflammatory response. Eighteen juvenile pigs were anaesthetized, mechanically ventilated, and instrumented. ALI was induced by surfactant washout. Animals were randomly assigned to mechanical ventilation according to the ARDSnet protocol or the OLA (n=9 per group). Gas exchange, haemodynamics, pulmonary blood flow (PBF) distribution, and respiratory mechanics were measured at intervals and the lungs were removed after 6 h of mechanical ventilation for further analysis. PEEP and mean airway pressure were higher in the OLA than in the ARDSnet group [15 cmH(2)O, range 14-18 cmH(2)O, compared with 12 cmH(2)O; 20.5 (sd 2.3) compared with 18 (1.4) cmH(2)O by the end of the experiment, respectively], and OLA was associated with improved oxygenation compared with the ARDSnet group after 6 h. OLA showed more alveolar overdistension, especially in gravitationally non-dependent regions, while the ARDSnet group was associated with more intra-alveolar haemorrhage. Inflammatory mediators and markers of lung parenchymal stress did not differ significantly between groups. The PBF shifted from ventral to dorsal during OLA compared with ARDSnet protocol [-0.02 (-0.09 to -0.01) compared with -0.08 (-0.12 to -0.06), dorsal-ventral gradients after 6 h, respectively]. According to the OLA, mechanical ventilation improved oxygenation and redistributed pulmonary perfusion when compared with the ARDSnet protocol, without differences in lung inflammatory response.

Effects of parents' employment status on changes in body mass index and percent body fat in adolescent girls.

PubMed

Lee, Sunmin; Young, Deborah Rohm; Pratt, Charlotte A; Jobe, Jared B; Chae, Soo Eun; McMurray, Robert G; Johnson, Carolyn C; Going, Scott B; Elder, John P; Stevens, June

2012-12-01

Parents' employment status is frequently cited as a possible predictor of child weight status. Despite the importance of the topic, only a few studies have been conducted. No longitudinal studies have been conducted in the United States. A cohort of 1201 girls from the Trial of Activity for Adolescent Girls was used. Height, weight, and percent body fat (PBF) were measured at the 6th and 8th grades. Parents' employment status (measured at 6th grade) was categorized into working full time (reference), part time, unemployed, working or staying at home, and don't know. Mixed-model regression was used to reflect the hierarchical design of our study and adjusted for age, race, parents' education level, free or reduced-price school lunch status, and living arrangement. Girls whose mothers worked part time or stayed at home had a decreased risk of excess weight gain [relative risk (RR) = 0.94, 95% confidence interval (CI) 0.88, 1.00; RR = 0.89, 95% CI 0.79, 1.00, respectively] compared to girls whose mothers worked full time. Girls whose fathers were unemployed had a moderately increased risk of excess weight gain (RR = 1.13, 95% CI 1.00, 1.26) compared to girls whose fathers worked full time. Having an unemployed mother or part-time or stay-at-home father was not associated with excess weight gain. Parents' employment status was not associated with excess PBF gain. Our findings suggest that the availability of the mother has a greater influence on the weight of the daughter than the availability of the father. There is a need for a better understanding of how parents' employment status influences excess weight gain in adolescent girls.

Endothelin-1 stimulates catalase activity through the PKCδ mediated phosphorylation of Serine 167

PubMed Central

Rafikov, Ruslan; Kumar, Sanjiv; Aggarwal, Saurabh; Hou, Yali; Kangath, Archana; Pardo, Daniel; Fineman, Jeffrey R.; Black, Stephen M.

2013-01-01

Our previous studies have shown that endothelin-1 (ET-1) stimulates catalase activity in endothelial cells and lambs with acute increases in pulmonary blood flow (PBF), without altering gene expression. The purpose of this study was to investigate the molecular mechanism by which this occurs. Exposing pulmonary arterial endothelial cells (PAEC) to ET-1 increased catalase activity and decreased cellular hydrogen peroxide (H2O2) levels. These changes correlated with an increase in serine phosphorylated catalase. Using the inhibitory peptide δV1.1, this phosphorylation was shown to be PKCδ dependent. Mass spectrometry identified serine167 as the phosphorylation site. Site-directed mutagenesis was used to generate a phospho-mimic (S167D) catalase. Activity assays using recombinant protein purified from E.coli or transiently transfected COS-7 cells, demonstrated that S167D-catalase had an increased ability to degrade H2O2 compared to the wildtype enzyme. Using a phospho-specific antibody, we were able to verify that pS167 catalase levels are modulated in lambs with acute increases in PBF in the presence and absence of the ET receptor antagonist, tezosentan. S167 is being located on the dimeric interface suggesting it could be involved in regulating the formation of catalase tetramers. To evaluate this possibility we utilized analytical gel-filtration to examine the multimeric structure of recombinant wildtype- and S167D-catalase. We found that recombinant wildtype catalase was present as a mixture of monomers and dimers while S167D catalase was primarily tetrameric. Further, the incubation of wildtype catalase with PKCδ was sufficient to convert wildtype catalase into a tetrameric structure. In conclusion, this is the first report indicating that the phosphorylation of catalase regulates its multimeric structure and activity. PMID:24211614

Effects of Parents' Employment Status on Changes in Body Mass Index and Percent Body Fat in Adolescent Girls

PubMed Central

Young, Deborah Rohm; Pratt, Charlotte A.; Jobe, Jared B.; Chae, Soo Eun; McMurray, Robert G.; Johnson, Carolyn C.; Going, Scott B.; Elder, John P.; Stevens, June

2012-01-01

Abstract Background Parents' employment status is frequently cited as a possible predictor of child weight status. Despite the importance of the topic, only a few studies have been conducted. No longitudinal studies have been conducted in the United States. Methods A cohort of 1201 girls from the Trial of Activity for Adolescent Girls was used. Height, weight, and percent body fat (PBF) were measured at the 6th and 8th grades. Parents' employment status (measured at 6th grade) was categorized into working full time (reference), part time, unemployed, working or staying at home, and don't know. Mixed-model regression was used to reflect the hierarchical design of our study and adjusted for age, race, parents' education level, free or reduced-price school lunch status, and living arrangement. Results Girls whose mothers worked part time or stayed at home had a decreased risk of excess weight gain [relative risk (RR)=0.94, 95% confidence interval (CI) 0.88, 1.00; RR=0.89, 95% CI 0.79, 1.00, respectively] compared to girls whose mothers worked full time. Girls whose fathers were unemployed had a moderately increased risk of excess weight gain (RR=1.13, 95% CI 1.00, 1.26) compared to girls whose fathers worked full time. Having an unemployed mother or part-time or stay-at-home father was not associated with excess weight gain. Parents' employment status was not associated with excess PBF gain. Conclusions Our findings suggest that the availability of the mother has a greater influence on the weight of the daughter than the availability of the father. There is a need for a better understanding of how parents' employment status influences excess weight gain in adolescent girls. PMID:23181918

Using an alternate reality game to increase physical activity and decrease obesity risk of college students.

PubMed

Johnston, Jeanne D; Massey, Anne P; Marker-Hoffman, Rickie Lee

2012-07-01

This quasi-experimental study investigated a game intervention--specifically, an alternate reality game (ARG)--as a means to influence college students' physical activity (PA). An ARG is an interactive narrative that takes place in the real world and uses multiple media to reveal a story. Three sections of a college health course (n = 115 freshman students) were assigned either to a game group that played the ARG or to a comparison group that learned how to use exercise equipment in weekly laboratory sessions. Pre- and post-intervention measures included weight, waist circumference, body mass index (BMI), percentage body fat (PBF), and self-reported moderate physical activity (MPA) and vigorous physical activity (VPA), and PA (steps/week). A significant group x time interaction (p = .001) was detected for PA, with a significant increase in PA for the game (p < .001) versus a significant decrease (p = .001) for the comparison group. Significant within-group increases for weight (p = .001), BMI (p = .001), and PBF (p = .001) were detected. A significant group x time interaction (p = .001) was detected when analyzing self-reported VPA, with both groups reporting decreases in VPA over time; however, the decrease was only significant for the comparison group (p < .001). No significant group differences were found for MPA. It is important that any intervention meet the needs and interests of its target population. Here, the ARG was designed in light of the learning preferences of today's college students--collaborative and social, experiential and media-rich. Our results provide preliminary evidence that a game intervention can positively influence PA within the college student population. © 2012 Diabetes Technology Society.

Cenozoic intraplate tectonics in Central Patagonia: Record of main Andean phases in a weak upper plate

NASA Astrophysics Data System (ADS)

Gianni, G. M.; Echaurren, A.; Folguera, A.; Likerman, J.; Encinas, A.; García, H. P. A.; Dal Molin, C.; Valencia, V. A.

2017-11-01

Contraction in intraplate areas is still poorly understood relative to similar deformation at plate margins. In order to contribute to its comprehension, we study the Patagonian broken foreland (PBF) in South America whose evolution remains controversial. Time constraints of tectonic events and structural characterization of this belt are limited. Also, major causes of strain location in this orogen far from the plate margin are enigmatic. To unravel tectonic events, we studied the Cenozoic sedimentary record of the central sector of the Patagonian broken foreland (San Bernardo fold and thrust belt, 44°30‧S-46°S) and the Andes (Meseta de Chalia, 46°S) following an approach involving growth-strata detection, U-Pb geochronology and structural modeling. Additionally, we elaborate a high resolution analysis of the effective elastic thickness (Te) to examine the relation between intraplate contraction location and variations in lithospheric strength. The occurrence of Eocene growth-strata ( 44-40 Ma) suggests that contraction in the Andes and the Patagonian broken foreland was linked to the Incaic phase. Detection of synextensional deposits suggests that the broken foreland collapsed partially during Oligocene to early Miocene. During middle Miocene times, the Quechua contractional phase produced folding of Neogene volcanic rocks and olistostrome deposition at 17 Ma. Finally, the presented Te map shows that intraplate contraction related to Andean phases localized preferentially along weak lithospheric zones (Te < 15 km). Hence, the observed strain distribution in the PBF appears to be controlled by lateral variations in the lithospheric strength. Variations in this parameter could be related to thermo-mechanical weakening produced by intraplate rifting in Paleozoic-Mesozoic times.

Household costs and time to seek care for pregnancy related complications: The role of results-based financing.

PubMed

Chinkhumba, Jobiba; De Allegri, Manuela; Mazalale, Jacob; Brenner, Stephan; Mathanga, Don; Muula, Adamson S; Robberstad, Bjarne

2017-01-01

Results-based financing (RBF) schemes-including performance based financing (PBF) and conditional cash transfers (CCT)-are increasingly being used to encourage use and improve quality of institutional health care for pregnant women in order to reduce maternal and neonatal mortality in low-income countries. While there is emerging evidence that RBF can increase service use and quality, little is known on the impact of RBF on costs and time to seek care for obstetric complications, although the two represent important dimensions of access. We conducted this study to fill the existing gap in knowledge by investigating the impact of RBF (PBF+CCT) on household costs and time to seek care for obstetric complications in four districts in Malawi. The analysis included data on 2,219 women with obstetric complications from three waves of a population-based survey conducted at baseline in 2013 and repeated in 2014(midline) and 2015(endline). Using a before and after approach with controls, we applied generalized linear models to study the association between RBF and household costs and time to seek care. Results indicated that receipt of RBF was associated with a significant reduction in the expected mean time to seek care for women experiencing an obstetric complication. Relative to non-RBF, time to seek care in RBF areas decreased by 27.3% (95%CI: 28.4-25.9) at midline and 34.2% (95%CI: 37.8-30.4) at endline. No substantial change in household costs was observed. We conclude that the reduced time to seek care is a manifestation of RBF induced quality improvements, prompting faster decisions on care seeking at household level. Our results suggest RBF may contribute to timely emergency care seeking and thus ultimately reduce maternal and neonatal mortality in beneficiary populations.

Studies on DNA-binding selectivity of WRKY transcription factors lend structural clues into WRKY-domain function.

PubMed

Ciolkowski, Ingo; Wanke, Dierk; Birkenbihl, Rainer P; Somssich, Imre E

2008-09-01

WRKY transcription factors have been shown to play a major role in regulating, both positively and negatively, the plant defense transcriptome. Nearly all studied WRKY factors appear to have a stereotypic binding preference to one DNA element termed the W-box. How specificity for certain promoters is accomplished therefore remains completely unknown. In this study, we tested five distinct Arabidopsis WRKY transcription factor subfamily members for their DNA binding selectivity towards variants of the W-box embedded in neighboring DNA sequences. These studies revealed for the first time differences in their binding site preferences, which are partly dependent on additional adjacent DNA sequences outside of the TTGACY-core motif. A consensus WRKY binding site derived from these studies was used for in silico analysis to identify potential target genes within the Arabidopsis genome. Furthermore, we show that even subtle amino acid substitutions within the DNA binding region of AtWRKY11 strongly impinge on its binding activity. Additionally, all five factors were found localized exclusively to the plant cell nucleus and to be capable of trans-activating expression of a reporter gene construct in vivo.

msCentipede: Modeling Heterogeneity across Genomic Sites and Replicates Improves Accuracy in the Inference of Transcription Factor Binding

PubMed Central

Gilad, Yoav; Pritchard, Jonathan K.; Stephens, Matthew

2015-01-01

Understanding global gene regulation depends critically on accurate annotation of regulatory elements that are functional in a given cell type. CENTIPEDE, a powerful, probabilistic framework for identifying transcription factor binding sites from tissue-specific DNase I cleavage patterns and genomic sequence content, leverages the hypersensitivity of factor-bound chromatin and the information in the DNase I spatial cleavage profile characteristic of each DNA binding protein to accurately infer functional factor binding sites. However, the model for the spatial profile in this framework fails to account for the substantial variation in the DNase I cleavage profiles across different binding sites. Neither does it account for variation in the profiles at the same binding site across multiple replicate DNase I experiments, which are increasingly available. In this work, we introduce new methods, based on multi-scale models for inhomogeneous Poisson processes, to account for such variation in DNase I cleavage patterns both within and across binding sites. These models account for the spatial structure in the heterogeneity in DNase I cleavage patterns for each factor. Using DNase-seq measurements assayed in a lymphoblastoid cell line, we demonstrate the improved performance of this model for several transcription factors by comparing against the Chip-seq peaks for those factors. Finally, we explore the effects of DNase I sequence bias on inference of factor binding using a simple extension to our framework that allows for a more flexible background model. The proposed model can also be easily applied to paired-end ATAC-seq and DNase-seq data. msCentipede, a Python implementation of our algorithm, is available at http://rajanil.github.io/msCentipede. PMID:26406244

msCentipede: Modeling Heterogeneity across Genomic Sites and Replicates Improves Accuracy in the Inference of Transcription Factor Binding.

PubMed

Raj, Anil; Shim, Heejung; Gilad, Yoav; Pritchard, Jonathan K; Stephens, Matthew

2015-01-01

Understanding global gene regulation depends critically on accurate annotation of regulatory elements that are functional in a given cell type. CENTIPEDE, a powerful, probabilistic framework for identifying transcription factor binding sites from tissue-specific DNase I cleavage patterns and genomic sequence content, leverages the hypersensitivity of factor-bound chromatin and the information in the DNase I spatial cleavage profile characteristic of each DNA binding protein to accurately infer functional factor binding sites. However, the model for the spatial profile in this framework fails to account for the substantial variation in the DNase I cleavage profiles across different binding sites. Neither does it account for variation in the profiles at the same binding site across multiple replicate DNase I experiments, which are increasingly available. In this work, we introduce new methods, based on multi-scale models for inhomogeneous Poisson processes, to account for such variation in DNase I cleavage patterns both within and across binding sites. These models account for the spatial structure in the heterogeneity in DNase I cleavage patterns for each factor. Using DNase-seq measurements assayed in a lymphoblastoid cell line, we demonstrate the improved performance of this model for several transcription factors by comparing against the Chip-seq peaks for those factors. Finally, we explore the effects of DNase I sequence bias on inference of factor binding using a simple extension to our framework that allows for a more flexible background model. The proposed model can also be easily applied to paired-end ATAC-seq and DNase-seq data. msCentipede, a Python implementation of our algorithm, is available at http://rajanil.github.io/msCentipede.

Quantifying the Effect of DNA Packaging on Gene Expression Level

NASA Astrophysics Data System (ADS)

Kim, Harold

2010-10-01

Gene expression, the process by which the genetic code comes alive in the form of proteins, is one of the most important biological processes in living cells, and begins when transcription factors bind to specific DNA sequences in the promoter region upstream of a gene. The relationship between gene expression output and transcription factor input which is termed the gene regulation function is specific to each promoter, and predicting this gene regulation function from the locations of transcription factor binding sites is one of the challenges in biology. In eukaryotic organisms (for example, animals, plants, fungi etc), DNA is highly compacted into nucleosomes, 147-bp segments of DNA tightly wrapped around histone protein core, and therefore, the accessibility of transcription factor binding sites depends on their locations with respect to nucleosomes - sites inside nucleosomes are less accessible than those outside nucleosomes. To understand how transcription factor binding sites contribute to gene expression in a quantitative manner, we obtain gene regulation functions of promoters with various configurations of transcription factor binding sites by using fluorescent protein reporters to measure transcription factor input and gene expression output in single yeast cells. In this talk, I will show that the affinity of a transcription factor binding site inside and outside the nucleosome controls different aspects of the gene regulation function, and explain this finding based on a mass-action kinetic model that includes competition between nucleosomes and transcription factors.

Position specific variation in the rate of evolution in transcription factor binding sites

PubMed Central

Moses, Alan M; Chiang, Derek Y; Kellis, Manolis; Lander, Eric S; Eisen, Michael B

2003-01-01

Background The binding sites of sequence specific transcription factors are an important and relatively well-understood class of functional non-coding DNAs. Although a wide variety of experimental and computational methods have been developed to characterize transcription factor binding sites, they remain difficult to identify. Comparison of non-coding DNA from related species has shown considerable promise in identifying these functional non-coding sequences, even though relatively little is known about their evolution. Results Here we analyse the genome sequences of the budding yeasts Saccharomyces cerevisiae, S. bayanus, S. paradoxus and S. mikatae to study the evolution of transcription factor binding sites. As expected, we find that both experimentally characterized and computationally predicted binding sites evolve slower than surrounding sequence, consistent with the hypothesis that they are under purifying selection. We also observe position-specific variation in the rate of evolution within binding sites. We find that the position-specific rate of evolution is positively correlated with degeneracy among binding sites within S. cerevisiae. We test theoretical predictions for the rate of evolution at positions where the base frequencies deviate from background due to purifying selection and find reasonable agreement with the observed rates of evolution. Finally, we show how the evolutionary characteristics of real binding motifs can be used to distinguish them from artefacts of computational motif finding algorithms. Conclusion As has been observed for protein sequences, the rate of evolution in transcription factor binding sites varies with position, suggesting that some regions are under stronger functional constraint than others. This variation likely reflects the varying importance of different positions in the formation of the protein-DNA complex. The characterization of the pattern of evolution in known binding sites will likely contribute to the effective use of comparative sequence data in the identification of transcription factor binding sites and is an important step toward understanding the evolution of functional non-coding DNA. PMID:12946282

Binding Sites Analyser (BiSA): Software for Genomic Binding Sites Archiving and Overlap Analysis

PubMed Central

Khushi, Matloob; Liddle, Christopher; Clarke, Christine L.; Graham, J. Dinny

2014-01-01

Genome-wide mapping of transcription factor binding and histone modification reveals complex patterns of interactions. Identifying overlaps in binding patterns by different factors is a major objective of genomic studies, but existing methods to archive large numbers of datasets in a personalised database lack sophistication and utility. Therefore we have developed transcription factor DNA binding site analyser software (BiSA), for archiving of binding regions and easy identification of overlap with or proximity to other regions of interest. Analysis results can be restricted by chromosome or base pair overlap between regions or maximum distance between binding peaks. BiSA is capable of reporting overlapping regions that share common base pairs; regions that are nearby; regions that are not overlapping; and average region sizes. BiSA can identify genes located near binding regions of interest, genomic features near a gene or locus of interest and statistical significance of overlapping regions can also be reported. Overlapping results can be visualized as Venn diagrams. A major strength of BiSA is that it is supported by a comprehensive database of publicly available transcription factor binding sites and histone modifications, which can be directly compared to user data. The documentation and source code are available on http://bisa.sourceforge.net PMID:24533055

Factor h and properdin recognize different epitopes on renal tubular epithelial heparan sulfate.

PubMed

Zaferani, Azadeh; Vivès, Romain R; van der Pol, Pieter; Navis, Gerjan J; Daha, Mohamed R; van Kooten, Cees; Lortat-Jacob, Hugues; Seelen, Marc A; van den Born, Jacob

2012-09-07

During proteinuria, renal tubular epithelial cells become exposed to ultrafiltrate-derived serum proteins, including complement factors. Recently, we showed that properdin binds to tubular heparan sulfates (HS). We now document that factor H also binds to tubular HS, although to a different epitope than properdin. Factor H was present on the urinary side of renal tubular cells in proteinuric, but not in normal renal tissues and colocalized with properdin in proteinuric kidneys. Factor H dose-dependently bound to proximal tubular epithelial cells (PTEC) in vitro. Preincubation of factor H with exogenous heparin and pretreatment of PTECs with heparitinase abolished the binding to PTECs. Surface plasmon resonance experiments showed high affinity of factor H for heparin and HS (K(D) values of 32 and 93 nm, respectively). Using a library of HS-like polysaccharides, we showed that chain length and high sulfation density are the most important determinants for glycosaminoglycan-factor H interaction and clearly differ from properdin-heparinoid interaction. Coincubation of properdin and factor H did not hamper HS/heparin binding of one another, indicating recognition of different nonoverlapping epitopes on HS/heparin by factor H and properdin. Finally we showed that certain low anticoagulant heparinoids can inhibit properdin binding to tubular HS, with a minor effect on factor H binding to tubular HS. As a result, these heparinoids can control the alternative complement pathway. In conclusion, factor H and properdin interact with different HS epitopes of PTECs. These interactions can be manipulated with some low anticoagulant heparinoids, which can be important for preventing complement-derived tubular injury in proteinuric renal diseases.

Factor VII and protein C are phosphatidic acid-binding proteins.

PubMed

Tavoosi, Narjes; Smith, Stephanie A; Davis-Harrison, Rebecca L; Morrissey, James H

2013-08-20

Seven proteins in the human blood clotting cascade bind, via their GLA (γ-carboxyglutamate-rich) domains, to membranes containing exposed phosphatidylserine (PS), although with membrane binding affinities that vary by 3 orders of magnitude. Here we employed nanodiscs of defined phospholipid composition to quantify the phospholipid binding specificities of these seven clotting proteins. All bound preferentially to nanobilayers in which PS headgroups contained l-serine versus d-serine. Surprisingly, however, nanobilayers containing phosphatidic acid (PA) bound substantially more of two of these proteins, factor VIIa and activated protein C, than did equivalent bilayers containing PS. Consistent with this finding, liposomes containing PA supported higher proteolytic activity by factor VIIa and activated protein C toward their natural substrates (factors X and Va, respectively) than did PS-containing liposomes. Moreover, treating activated human platelets with phospholipase D enhanced the rates of factor X activation by factor VIIa in the presence of soluble tissue factor. We hypothesize that factor VII and protein C bind preferentially to the monoester phosphate of PA because of its accessibility and higher negative charge compared with the diester phosphates of most other phospholipids. We further found that phosphatidylinositol 4-phosphate, which contains a monoester phosphate attached to its myo-inositol headgroup, also supported enhanced enzymatic activity of factor VIIa and activated protein C. We conclude that factor VII and protein C bind preferentially to monoester phosphates, which may have implications for the function of these proteases in vivo.

ChIP-nexus: a novel ChIP-exo protocol for improved detection of in vivo transcription factor binding footprints

PubMed Central

He, Qiye; Johnston, Jeff; Zeitlinger, Julia

2014-01-01

Understanding how eukaryotic enhancers are bound and regulated by specific combinations of transcription factors is still a major challenge. To better map transcription factor binding genome-wide at nucleotide resolution in vivo, we have developed a robust ChIP-exo protocol called ChIP experiments with nucleotide resolution through exonuclease, unique barcode and single ligation (ChIP-nexus), which utilizes an efficient DNA self-circularization step during library preparation. Application of ChIP-nexus to four proteins—human TBP and Drosophila NFkB, Twist and Max— demonstrates that it outperforms existing ChIP protocols in resolution and specificity, pinpoints relevant binding sites within enhancers containing multiple binding motifs and allows the analysis of in vivo binding specificities. Notably, we show that Max frequently interacts with DNA sequences next to its motif, and that this binding pattern correlates with local DNA sequence features such as DNA shape. ChIP-nexus will be broadly applicable to studying in vivo transcription factor binding specificity and its relationship to cis-regulatory changes in humans and model organisms. PMID:25751057

From carpet bombing to cruise missiles: the 'second-order' mechanisms used by transcription factors to ensure specific DNA binding in vivo.

PubMed

Kodadek, T

1995-05-01

Transcription factors generally have only modest specificity for their target sites, yet must find them in a sea of non-specific DNA. Some transcription factors are expressed at very high levels, to ensure that, despite losses to non-specific binding, the promoter is still occupied (the carpet-bombing strategy). Others increase their binding specificity by collaborating with other factors in a variety of ways.

The Iron-Dependent Regulation of the Candida albicans Oxidative Stress Response by the CCAAT-Binding Factor

PubMed Central

Chakravarti, Ananya; Camp, Kyle; McNabb, David S.

2017-01-01

Candida albicans is the most frequently encountered fungal pathogen in humans, capable of causing mucocutaneous and systemic infections in immunocompromised individuals. C. albicans virulence is influenced by multiple factors. Importantly, iron acquisition and avoidance of the immune oxidative burst are two critical barriers for survival in the host. Prior studies using whole genome microarray expression data indicated that the CCAAT-binding factor is involved in the regulation of iron uptake/utilization and the oxidative stress response. This study examines directly the role of the CCAAT-binding factor in regulating the expression of oxidative stress genes in response to iron availability. The CCAAT-binding factor is a heterooligomeric transcription factor previously shown to regulate genes involved in respiration and iron uptake/utilization in C. albicans. Since these pathways directly influence the level of free radicals, it seemed plausible the CCAAT-binding factor regulates genes necessary for the oxidative stress response. In this study, we show the CCAAT-binding factor is involved in regulating some oxidative stress genes in response to iron availability, including CAT1, SOD4, GRX5, and TRX1. We also show that CAT1 expression and catalase activity correlate with the survival of C. albicans to oxidative stress, providing a connection between iron obtainability and the oxidative stress response. We further explore the role of the various CCAAT-binding factor subunits in the formation of distinct protein complexes that modulate the transcription of CAT1 in response to iron. We find that Hap31 and Hap32 can compensate for each other in the formation of an active transcriptional complex; however, they play distinct roles in the oxidative stress response during iron limitation. Moreover, Hap43 was found to be solely responsible for the repression observed under iron deprivation. PMID:28122000

The electrostatic role of the Zn-Cys2His2 complex in binding of operator DNA with transcription factors: mouse EGR-1 from the Cys2His2 family.

PubMed

Chirgadze, Y N; Boshkova, E A; Polozov, R V; Sivozhelezov, V S; Dzyabchenko, A V; Kuzminsky, M B; Stepanenko, V A; Ivanov, V V

2018-01-07

The mouse factor Zif268, known also as early growth response protein EGR-1, is a classical representative for the Cys2His2 transcription factor family. It is required for binding the RNA polymerase with operator dsDNA to initialize the transcription process. We have shown that only in this family of total six Zn-finger protein families the Zn complex plays a significant role in the protein-DNA binding. Electrostatic feature of this complex in the binding of factor Zif268 from Mus musculus with operator DNA has been considered. The factor consists of three similar Zn-finger units which bind with triplets of coding DNA. Essential contacts of the factor with the DNA phosphates are formed by three conservative His residues, one in each finger. We describe here the results of calculations of the electrostatic potentials for the Zn-Cys2His2 complex, Zn-finger unit 1, and the whole transcription factor. The potential of Zif268 has a positive area on the factor surface, and it corresponds exactly to the binding sites of each of Zn-finger units. The main part of these areas is determined by conservative His residues, which form contacts with the DNA phosphate groups. Our result shows that the electrostatic positive potential of this histidine residue is enhanced due to the Zn complex. The other contacts of the Zn-finger with DNA are related to nucleotide bases, and they are responsible for the sequence-specific binding with DNA. This result may be extended to all other members of the Cys2His2 transcription factor family.

Understanding Transcription Factor Regulation by Integrating Gene Expression and DNase I Hypersensitive Sites.

PubMed

Wang, Guohua; Wang, Fang; Huang, Qian; Li, Yu; Liu, Yunlong; Wang, Yadong

2015-01-01

Transcription factors are proteins that bind to DNA sequences to regulate gene transcription. The transcription factor binding sites are short DNA sequences (5-20 bp long) specifically bound by one or more transcription factors. The identification of transcription factor binding sites and prediction of their function continue to be challenging problems in computational biology. In this study, by integrating the DNase I hypersensitive sites with known position weight matrices in the TRANSFAC database, the transcription factor binding sites in gene regulatory region are identified. Based on the global gene expression patterns in cervical cancer HeLaS3 cell and HelaS3-ifnα4h cell (interferon treatment on HeLaS3 cell for 4 hours), we present a model-based computational approach to predict a set of transcription factors that potentially cause such differential gene expression. Significantly, 6 out 10 predicted functional factors, including IRF, IRF-2, IRF-9, IRF-1 and IRF-3, ICSBP, belong to interferon regulatory factor family and upregulate the gene expression levels responding to the interferon treatment. Another factor, ISGF-3, is also a transcriptional activator induced by interferon alpha. Using the different transcription factor binding sites selected criteria, the prediction result of our model is consistent. Our model demonstrated the potential to computationally identify the functional transcription factors in gene regulation.

Accurate Prediction of Inducible Transcription Factor Binding Intensities In Vivo

PubMed Central

Siepel, Adam; Lis, John T.

2012-01-01

DNA sequence and local chromatin landscape act jointly to determine transcription factor (TF) binding intensity profiles. To disentangle these influences, we developed an experimental approach, called protein/DNA binding followed by high-throughput sequencing (PB–seq), that allows the binding energy landscape to be characterized genome-wide in the absence of chromatin. We applied our methods to the Drosophila Heat Shock Factor (HSF), which inducibly binds a target DNA sequence element (HSE) following heat shock stress. PB–seq involves incubating sheared naked genomic DNA with recombinant HSF, partitioning the HSF–bound and HSF–free DNA, and then detecting HSF–bound DNA by high-throughput sequencing. We compared PB–seq binding profiles with ones observed in vivo by ChIP–seq and developed statistical models to predict the observed departures from idealized binding patterns based on covariates describing the local chromatin environment. We found that DNase I hypersensitivity and tetra-acetylation of H4 were the most influential covariates in predicting changes in HSF binding affinity. We also investigated the extent to which DNA accessibility, as measured by digital DNase I footprinting data, could be predicted from MNase–seq data and the ChIP–chip profiles for many histone modifications and TFs, and found GAGA element associated factor (GAF), tetra-acetylation of H4, and H4K16 acetylation to be the most predictive covariates. Lastly, we generated an unbiased model of HSF binding sequences, which revealed distinct biophysical properties of the HSF/HSE interaction and a previously unrecognized substructure within the HSE. These findings provide new insights into the interplay between the genomic sequence and the chromatin landscape in determining transcription factor binding intensity. PMID:22479205

Ternary Complex Factors and Cofactors Are Essential for Human T-Cell Leukemia Virus Type 1 Tax Transactivation of the Serum Response Element

PubMed Central

Shuh, Maureen; Derse, David

2000-01-01

The human T-cell leukemia virus type 1 Tax protein activates the expression of cellular immediate early genes controlled by the serum response element (SRE), which contains both the serum response factor (SRF) binding element (CArG box) and the ternary complex factor (TCF) binding element (Ets box). We show that TCF binding is necessary for Tax activation of the SRE and that Tax directly interacts with TCFs in vitro. In addition, Tax interactions with CREB binding protein (CBP) and p300- and CBP-associated factor were found to be essential for Tax activation of SRF-mediated transcription. PMID:11070040

[Interaction of human factor X with thromboplastin].

PubMed

Kiselev, S V; Zubairov, D M; Timarbaev, V N

2003-01-01

The binding of 125I-labeled human factor X to native and papaine-treated tissue tromboplastin in the presence of CaCl2 or EDTA was studied. The Scatchard analysis suggests the existence of high (Kd=l,8 x10(-9) M) and low affinity binding sites on the thromboplastin surface. The removal of Ca2+ reduced affinity of factor X to the high affinity sites. This was accompanied by some increase of their number. Proteolysis by papaine decreased affinity of high affinity sites and caused the increase of their number in the presence of Ca2+. In the absence of Ca2+ the affinity remained unchanged, but the number of sites decreased. At low concentrations of factor X positive cooperativity for high affinity binding sites was observed. It did not depend on the presence of Ca2+. The results indirectly confirm the role of hydrophobic interactons in Ca2+ dependent binding of factor X to thromboplastin and the fact that heterogeneity of this binding is determined by mesophase structure of the thromboplastin phospholipids.

Transforming growth factor (TGF. beta. ) decreases the proliferation of human bone marrow fibroblasts by inhibiting the platelet-derived growth factor (PDGF) binding

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

Bryckaert, M.C.; Tobelem, G.; Lindroth, M.

1988-12-01

Human bone marrow fibroblasts were cultivated and characterized by immunofluorescent staining and electron microscopy. Their interactions with PDGF and TGF{beta} were studied. While a positive intracellular antifibronectin staining was observed, the cultured cells were not labeled with specific antibodies toward factor VIII von Willebrand factor (F VIII/vWF), desmin, and macrophage antigen. The binding of pure human PDGF to the cultured bone marrow fibroblasts was investigated. Addition of an excess of unlabeled PDGF decreased the binding to 75 and 80%, which means that the nonspecific binding represented 20-25% of total binding, whereas epidermal growth factor (EGF) had no effect. Two classesmore » of sites were detected by Scatchard analysis. The stimulation of DNA synthesis of PDGF was quantified by ({sup 3}H)thymidine incorporation. The results suggested that PDGF and TGF{beta} could modulate the growth of bone marrow fibroblasts.« less

Searching for transcription factor binding sites in vector spaces

PubMed Central

2012-01-01

Background Computational approaches to transcription factor binding site identification have been actively researched in the past decade. Learning from known binding sites, new binding sites of a transcription factor in unannotated sequences can be identified. A number of search methods have been introduced over the years. However, one can rarely find one single method that performs the best on all the transcription factors. Instead, to identify the best method for a particular transcription factor, one usually has to compare a handful of methods. Hence, it is highly desirable for a method to perform automatic optimization for individual transcription factors. Results We proposed to search for transcription factor binding sites in vector spaces. This framework allows us to identify the best method for each individual transcription factor. We further introduced two novel methods, the negative-to-positive vector (NPV) and optimal discriminating vector (ODV) methods, to construct query vectors to search for binding sites in vector spaces. Extensive cross-validation experiments showed that the proposed methods significantly outperformed the ungapped likelihood under positional background method, a state-of-the-art method, and the widely-used position-specific scoring matrix method. We further demonstrated that motif subtypes of a TF can be readily identified in this framework and two variants called the k NPV and k ODV methods benefited significantly from motif subtype identification. Finally, independent validation on ChIP-seq data showed that the ODV and NPV methods significantly outperformed the other compared methods. Conclusions We conclude that the proposed framework is highly flexible. It enables the two novel methods to automatically identify a TF-specific subspace to search for binding sites. Implementations are available as source code at: http://biogrid.engr.uconn.edu/tfbs_search/. PMID:23244338

Dense Bicoid hubs accentuate binding along the morphogen gradient

PubMed Central

Mir, Mustafa; Reimer, Armando; Haines, Jenna E.; Li, Xiao-Yong; Stadler, Michael; Garcia, Hernan

2017-01-01

Morphogen gradients direct the spatial patterning of developing embryos; however, the mechanisms by which these gradients are interpreted remain elusive. Here we used lattice light-sheet microscopy to perform in vivo single-molecule imaging in early Drosophila melanogaster embryos of the transcription factor Bicoid that forms a gradient and initiates patterning along the anteroposterior axis. In contrast to canonical models, we observed that Bicoid binds to DNA with a rapid off rate throughout the embryo such that its average occupancy at target loci is on-rate-dependent. We further observed Bicoid forming transient “hubs” of locally high density that facilitate binding as factor levels drop, including in the posterior, where we observed Bicoid binding despite vanishingly low protein levels. We propose that localized modulation of transcription factor on rates via clustering provides a general mechanism to facilitate binding to low-affinity targets and that this may be a prevalent feature of other developmental transcription factors. PMID:28982761

The fundamental ribosomal RNA transcription initiation factor-IB (TIF-IB, SL1, factor D) binds to the rRNA core promoter primarily by minor groove contacts.

PubMed

Geiss, G K; Radebaugh, C A; Paule, M R

1997-11-14

Acanthamoeba castellanii transcription initiation factor-IB (TIF-IB) is the TATA-binding protein-containing transcription factor that binds the rRNA promoter to form the committed complex. Minor groove-specific drugs inhibit TIF-IB binding, with higher concentrations needed to disrupt preformed complexes because of drug exclusion by bound TIF-IB. TIF-IB/DNA interactions were mapped by hydroxyl radical and uranyl nitrate footprinting. TIF-IB contacts four minor grooves in its binding site. TIF-IB and DNA wrap around each other in a right-handed superhelix of high pitch, so the upstream and downstream contacts are on opposite faces of the helix. Dimethyl sulfate protection assays revealed limited contact with a few guanines in the major groove. This detailed analysis suggests significant DNA conformation dependence of the interaction.

Acanthamoeba castellanii contains a ribosomal RNA enhancer binding protein which stimulates TIF-IB binding and transcription under stringent conditions.

PubMed

Yang, Q; Radebaugh, C A; Kubaska, W; Geiss, G K; Paule, M R

1995-11-11

The intergenic spacer (IGS) of Acanthamoeba castellanii rRNA genes contains repeated elements which are weak enhancers for transcription by RNA polymerase I. A protein, EBF, was identified and partially purified which binds to the enhancers and to several other sequences within the IGS, but not to other DNA fragments, including the rRNA core promoter. No consensus binding sequence could be discerned in these fragments and bound factor is in rapid equilibrium with unbound. EBF has functional characteristics similar to vertebrate upstream binding factors (UBF). Not only does it bind to the enhancer and other IGS elements, but it also stimulates binding of TIF-IB, the fundamental transcription initiation factor, to the core promoter and stimulates transcription from the promoter. Attempts to identify polypeptides with epitopes similar to rat or Xenopus laevis UBF suggest that structurally the protein from A.castellanii is not closely related to vertebrate UBF.

Acanthamoeba castellanii contains a ribosomal RNA enhancer binding protein which stimulates TIF-IB binding and transcription under stringent conditions.

PubMed Central

Yang, Q; Radebaugh, C A; Kubaska, W; Geiss, G K; Paule, M R

1995-01-01

The intergenic spacer (IGS) of Acanthamoeba castellanii rRNA genes contains repeated elements which are weak enhancers for transcription by RNA polymerase I. A protein, EBF, was identified and partially purified which binds to the enhancers and to several other sequences within the IGS, but not to other DNA fragments, including the rRNA core promoter. No consensus binding sequence could be discerned in these fragments and bound factor is in rapid equilibrium with unbound. EBF has functional characteristics similar to vertebrate upstream binding factors (UBF). Not only does it bind to the enhancer and other IGS elements, but it also stimulates binding of TIF-IB, the fundamental transcription initiation factor, to the core promoter and stimulates transcription from the promoter. Attempts to identify polypeptides with epitopes similar to rat or Xenopus laevis UBF suggest that structurally the protein from A.castellanii is not closely related to vertebrate UBF. Images PMID:7501455

Selective inhibition of c-Myc/Max dimerization and DNA binding by small molecules.

PubMed

Kiessling, Anke; Sperl, Bianca; Hollis, Angela; Eick, Dirk; Berg, Thorsten

2006-07-01

bZip and bHLHZip protein family members comprise a large fraction of eukaryotic transcription factors and need to bind DNA in order to exert most of their fundamental biological roles. Their binding to DNA requires homo- or heterodimerization via alpha-helical domains, which generally do not contain obvious binding sites for small molecules. We have identified two small molecules, dubbed Mycro1 and Mycro2, which inhibit the protein-protein interactions between the bHLHZip proteins c-Myc and Max. Mycros are the first inhibitors of c-Myc/Max dimerization, which have been demonstrated to inhibit DNA binding of c-Myc with preference over other dimeric transcription factors in vitro. Mycros inhibit c-Myc-dependent proliferation, gene transcription, and oncogenic transformation in the low micromolar concentration range. Our data support the idea that dimeric transcription factors can be druggable even in the absence of obvious small-molecule binding pockets.

Energetic factors determining the binding of type I inhibitors to c-Met kinase: experimental studies and quantum mechanical calculations.

PubMed

Yu, Zhe; Ma, Yu-chi; Ai, Jing; Chen, Dan-qi; Zhao, Dong-mei; Wang, Xin; Chen, Yue-lei; Geng, Mei-yu; Xiong, Bing; Cheng, Mao-sheng; Shen, Jing-Kang

2013-11-01

To decipher the molecular interactions between c-Met and its type I inhibitors and to facilitate the design of novel c-Met inhibitors. Based on the prototype model inhibitor 1, four ligands with subtle differences in the fused aromatic rings were synthesized. Quantum chemistry was employed to calculate the binding free energy for each ligand. Symmetry-adapted perturbation theory (SAPT) was used to decompose the binding energy into several fundamental forces to elucidate the determinant factors. Binding free energies calculated from quantum chemistry were correlated well with experimental data. SAPT calculations showed that the predominant driving force for binding was derived from a sandwich π-π interaction with Tyr-1230. Arg-1208 was the differentiating factor, interacting with the 6-position of the fused aromatic ring system through the backbone carbonyl with a force pattern similar to hydrogen bonding. Therefore, a hydrogen atom must be attached at the 6-position, and changing the carbon atom to nitrogen caused unfavorable electrostatic interactions. The theoretical studies have elucidated the determinant factors involved in the binding of type I inhibitors to c-Met.

Investigation of arc repressor DNA-binding specificity by comparative molecular dynamics simulations.

PubMed

Song, Wei; Guo, Jun-Tao

2015-01-01

Transcription factors regulate gene expression through binding to specific DNA sequences. How transcription factors achieve high binding specificity is still not well understood. In this paper, we investigated the role of protein flexibility in protein-DNA-binding specificity by comparative molecular dynamics (MD) simulations. Protein flexibility has been considered as a key factor in molecular recognition, which is intrinsically a dynamic process involving fine structural fitting between binding components. In this study, we performed comparative MD simulations on wild-type and F10V mutant P22 Arc repressor in both free and complex conformations. The F10V mutant has lower DNA-binding specificity though both the bound and unbound main-chain structures between the wild-type and F10V mutant Arc are highly similar. We found that the DNA-binding motif of wild-type Arc is structurally more flexible than the F10V mutant in the unbound state, especially for the six DNA base-contacting residues in each dimer. We demonstrated that the flexible side chains of wild-type Arc lead to a higher DNA-binding specificity through forming more hydrogen bonds with DNA bases upon binding. Our simulations also showed a possible conformational selection mechanism for Arc-DNA binding. These results indicate the important roles of protein flexibility and dynamic properties in protein-DNA-binding specificity.

Zinc Finger Independent Genome-Wide Binding of Sp2 Potentiates Recruitment of Histone-Fold Protein Nf-y Distinguishing It from Sp1 and Sp3

PubMed Central

Finkernagel, Florian; Stiewe, Thorsten; Nist, Andrea; Suske, Guntram

2015-01-01

Transcription factors are grouped into families based on sequence similarity within functional domains, particularly DNA-binding domains. The Specificity proteins Sp1, Sp2 and Sp3 are paradigmatic of closely related transcription factors. They share amino-terminal glutamine-rich regions and a conserved carboxy-terminal zinc finger domain that can bind to GC rich motifs in vitro. All three Sp proteins are ubiquitously expressed; yet they carry out unique functions in vivo raising the question of how specificity is achieved. Crucially, it is unknown whether they bind to distinct genomic sites and, if so, how binding site selection is accomplished. In this study, we have examined the genomic binding patterns of Sp1, Sp2 and Sp3 in mouse embryonic fibroblasts by ChIP-seq. Sp1 and Sp3 essentially occupy the same promoters and localize to GC boxes. The genomic binding pattern of Sp2 is different; Sp2 primarily localizes at CCAAT motifs. Consistently, re-expression of Sp2 and Sp3 mutants in corresponding knockout MEFs revealed strikingly different modes of genomic binding site selection. Most significantly, while the zinc fingers dictate genomic binding of Sp3, they are completely dispensable for binding of Sp2. Instead, the glutamine-rich amino-terminal region is sufficient for recruitment of Sp2 to its target promoters in vivo. We have identified the trimeric histone-fold CCAAT box binding transcription factor Nf-y as the major partner for Sp2-chromatin interaction. Nf-y is critical for recruitment of Sp2 to co-occupied regulatory elements. Equally, Sp2 potentiates binding of Nf-y to shared sites indicating the existence of an extensive Sp2-Nf-y interaction network. Our results unveil strikingly different recruitment mechanisms of Sp1/Sp2/Sp3 transcription factor members uncovering an unexpected layer of complexity in their binding to chromatin in vivo. PMID:25793500

Nuclear factors that bind to the enhancer region of nondefective Friend murine leukemia virus.

PubMed Central

Manley, N R; O'Connell, M A; Sharp, P A; Hopkins, N

1989-01-01

Nondefective Friend murine leukemia virus (MuLV) causes erythroleukemia when injected into newborn NFS mice, while Moloney MuLV causes T-cell lymphoma. Exchange of the Friend virus enhancer region, a sequence of about 180 nucleotides including the direct repeat and a short 3'-adjacent segment, for the corresponding region in Moloney MuLV confers the ability to cause erythroid disease on Moloney MuLV. We have used the electrophoretic mobility shift assay and methylation interference analysis to identify cellular factors which bind to the Friend virus enhancer region and compared these with factors, previously identified, that bind to the Moloney virus direct repeat (N. A. Speck and D. Baltimore, Mol. Cell. Biol. 7:1101-1110, 1987). We identified five binding sites for sequence-specific DNA-binding proteins in the Friend virus enhancer region. While some binding sites are present in both the Moloney and Friend virus enhancers, both viruses contain unique sites not present in the other. Although none of the factors identified in this report which bind to these unique sites are present exclusively in T cells or erythroid cells, they bind to three regions of the enhancer shown by genetic analysis to encode disease specificity and thus are candidates to mediate the tissue-specific expression and distinct disease specificities encoded by these virus enhancer elements. Images PMID:2778872

In silico evolution of the Drosophila gap gene regulatory sequence under elevated mutational pressure.

PubMed

Chertkova, Aleksandra A; Schiffman, Joshua S; Nuzhdin, Sergey V; Kozlov, Konstantin N; Samsonova, Maria G; Gursky, Vitaly V

2017-02-07

Cis-regulatory sequences are often composed of many low-affinity transcription factor binding sites (TFBSs). Determining the evolutionary and functional importance of regulatory sequence composition is impeded without a detailed knowledge of the genotype-phenotype map. We simulate the evolution of regulatory sequences involved in Drosophila melanogaster embryo segmentation during early development. Natural selection evaluates gene expression dynamics produced by a computational model of the developmental network. We observe a dramatic decrease in the total number of transcription factor binding sites through the course of evolution. Despite a decrease in average sequence binding energies through time, the regulatory sequences tend towards organisations containing increased high affinity transcription factor binding sites. Additionally, the binding energies of separate sequence segments demonstrate ubiquitous mutual correlations through time. Fewer than 10% of initial TFBSs are maintained throughout the entire simulation, deemed 'core' sites. These sites have increased functional importance as assessed under wild-type conditions and their binding energy distributions are highly conserved. Furthermore, TFBSs within close proximity of core sites exhibit increased longevity, reflecting functional regulatory interactions with core sites. In response to elevated mutational pressure, evolution tends to sample regulatory sequence organisations with fewer, albeit on average, stronger functional transcription factor binding sites. These organisations are also shaped by the regulatory interactions among core binding sites with sites in their local vicinity.

Stable Binding of the Conserved Transcription Factor Grainy Head to its Target Genes Throughout Drosophila melanogaster Development

PubMed Central

Nevil, Markus; Bondra, Eliana R.; Schulz, Katharine N.; Kaplan, Tommy; Harrison, Melissa M.

2017-01-01

It has been suggested that transcription factor binding is temporally dynamic, and that changes in binding determine transcriptional output. Nonetheless, this model is based on relatively few examples in which transcription factor binding has been assayed at multiple developmental stages. The essential transcription factor Grainy head (Grh) is conserved from fungi to humans, and controls epithelial development and barrier formation in numerous tissues. Drosophila melanogaster, which possess a single grainy head (grh) gene, provide an excellent system to study this conserved factor. To determine whether temporally distinct binding events allow Grh to control cell fate specification in different tissue types, we used a combination of ChIP-seq and RNA-seq to elucidate the gene regulatory network controlled by Grh during four stages of embryonic development (spanning stages 5–17) and in larval tissue. Contrary to expectations, we discovered that Grh remains bound to at least 1146 genomic loci over days of development. In contrast to this stable DNA occupancy, the subset of genes whose expression is regulated by Grh varies. Grh transitions from functioning primarily as a transcriptional repressor early in development to functioning predominantly as an activator later. Our data reveal that Grh binds to target genes well before the Grh-dependent transcriptional program commences, suggesting it sets the stage for subsequent recruitment of additional factors that execute stage-specific Grh functions. PMID:28007888

Hormone induces binding of receptors and transcription factors to a rearranged nucleosome on the MMTV promoter in vivo.

PubMed Central

Truss, M; Bartsch, J; Schelbert, A; Haché, R J; Beato, M

1995-01-01

Hormonal induction of the mouse mammary tumour virus (MMTV) promoter is mediated by interactions between hormone receptors and other transcription factors bound to a complex array of sites. Previous results suggested that access to these sites is modulated by their precise organization into a positioned regulatory nucleosome. Using genomic footprinting, we show that MMTV promoter DNA is rotationally phased in intact cells containing either episomal or chromosomally integrated proviral fragments. Prior to induction there is no evidence for factors bound to the promoter. Following progesterone induction of cells with high levels of receptor, genomic footprinting detects simultaneous protection over the binding sites for hormone receptors, NF-I and the octamer binding proteins. Glucocorticoid or progestin induction leads to a characteristic chromatin remodelling that is independent of ongoing transcription. The centre of the regulatory nucleosome becomes more accessible to DNase I and restriction enzymes, but the limits of the nucleosome are unchanged and the 145 bp core region remains protected against micrococcal nuclease digestion. Thus, the nucleosome covering the MMTV promoter is neither removed nor shifted upon hormone induction, and all relevant transcription factors bind to the surface of the rearranged nucleosome. Since these factors cannot bind simultaneously to free DNA, maintainance of the nucleosome may be required for binding of factors to contiguous sites. Images PMID:7737125

DNA binding by the ribosomal DNA transcription factor rrn3 is essential for ribosomal DNA transcription.

PubMed

Stepanchick, Ann; Zhi, Huijun; Cavanaugh, Alice H; Rothblum, Katrina; Schneider, David A; Rothblum, Lawrence I

2013-03-29

The human homologue of yeast Rrn3 is an RNA polymerase I-associated transcription factor that is essential for ribosomal DNA (rDNA) transcription. The generally accepted model is that Rrn3 functions as a bridge between RNA polymerase I and the transcription factors bound to the committed template. In this model Rrn3 would mediate an interaction between the mammalian Rrn3-polymerase I complex and SL1, the rDNA transcription factor that binds to the core promoter element of the rDNA. In the course of studying the role of Rrn3 in recruitment, we found that Rrn3 was in fact a DNA-binding protein. Analysis of the sequence of Rrn3 identified a domain with sequence similarity to the DNA binding domain of heat shock transcription factor 2. Randomization, or deletion, of the amino acids in this region in Rrn3, amino acids 382-400, abrogated its ability to bind DNA, indicating that this domain was an important contributor to DNA binding by Rrn3. Control experiments demonstrated that these mutant Rrn3 constructs were capable of interacting with both rpa43 and SL1, two other activities demonstrated to be essential for Rrn3 function. However, neither of these Rrn3 mutants was capable of functioning in transcription in vitro. Moreover, although wild-type human Rrn3 complemented a yeast rrn3-ts mutant, the DNA-binding site mutant did not. These results demonstrate that DNA binding by Rrn3 is essential for transcription by RNA polymerase I.

DNA Binding by the Ribosomal DNA Transcription Factor Rrn3 Is Essential for Ribosomal DNA Transcription*

PubMed Central

Stepanchick, Ann; Zhi, Huijun; Cavanaugh, Alice H.; Rothblum, Katrina; Schneider, David A.; Rothblum, Lawrence I.

2013-01-01

The human homologue of yeast Rrn3 is an RNA polymerase I-associated transcription factor that is essential for ribosomal DNA (rDNA) transcription. The generally accepted model is that Rrn3 functions as a bridge between RNA polymerase I and the transcription factors bound to the committed template. In this model Rrn3 would mediate an interaction between the mammalian Rrn3-polymerase I complex and SL1, the rDNA transcription factor that binds to the core promoter element of the rDNA. In the course of studying the role of Rrn3 in recruitment, we found that Rrn3 was in fact a DNA-binding protein. Analysis of the sequence of Rrn3 identified a domain with sequence similarity to the DNA binding domain of heat shock transcription factor 2. Randomization, or deletion, of the amino acids in this region in Rrn3, amino acids 382–400, abrogated its ability to bind DNA, indicating that this domain was an important contributor to DNA binding by Rrn3. Control experiments demonstrated that these mutant Rrn3 constructs were capable of interacting with both rpa43 and SL1, two other activities demonstrated to be essential for Rrn3 function. However, neither of these Rrn3 mutants was capable of functioning in transcription in vitro. Moreover, although wild-type human Rrn3 complemented a yeast rrn3-ts mutant, the DNA-binding site mutant did not. These results demonstrate that DNA binding by Rrn3 is essential for transcription by RNA polymerase I. PMID:23393135

SP transcription factor paralogs and DNA-binding sites coevolve and adaptively converge in mammals and birds.

PubMed

Yokoyama, Ken Daigoro; Pollock, David D

2012-01-01

Functional modification of regulatory proteins can affect hundreds of genes throughout the genome, and is therefore thought to be almost universally deleterious. This belief, however, has recently been challenged. A potential example comes from transcription factor SP1, for which statistical evidence indicates that motif preferences were altered in eutherian mammals. Here, we set out to discover possible structural and theoretical explanations, evaluate the role of selection in SP1 evolution, and discover effects on coregulatory proteins. We show that SP1 motif preferences were convergently altered in birds as well as mammals, inducing coevolutionary changes in over 800 regulatory regions. Structural and phylogenic evidence implicates a single causative amino acid replacement at the same SP1 position along both lineages. Furthermore, paralogs SP3 and SP4, which coregulate SP1 target genes through competitive binding to the same sites, have accumulated convergent replacements at the homologous position multiple times during eutherian and bird evolution, presumably to preserve competitive binding. To determine plausibility, we developed and implemented a simple model of transcription factor and binding site coevolution. This model predicts that, in contrast to prevailing beliefs, even small selective benefits per locus can drive concurrent fixation of transcription factor and binding site mutants under a broad range of conditions. Novel binding sites tend to arise de novo, rather than by mutation from ancestral sites, a prediction substantiated by SP1-binding site alignments. Thus, multiple lines of evidence indicate that selection has driven convergent evolution of transcription factors along with their binding sites and coregulatory proteins.

SP Transcription Factor Paralogs and DNA-Binding Sites Coevolve and Adaptively Converge in Mammals and Birds

PubMed Central

Yokoyama, Ken Daigoro; Pollock, David D.

2012-01-01

Functional modification of regulatory proteins can affect hundreds of genes throughout the genome, and is therefore thought to be almost universally deleterious. This belief, however, has recently been challenged. A potential example comes from transcription factor SP1, for which statistical evidence indicates that motif preferences were altered in eutherian mammals. Here, we set out to discover possible structural and theoretical explanations, evaluate the role of selection in SP1 evolution, and discover effects on coregulatory proteins. We show that SP1 motif preferences were convergently altered in birds as well as mammals, inducing coevolutionary changes in over 800 regulatory regions. Structural and phylogenic evidence implicates a single causative amino acid replacement at the same SP1 position along both lineages. Furthermore, paralogs SP3 and SP4, which coregulate SP1 target genes through competitive binding to the same sites, have accumulated convergent replacements at the homologous position multiple times during eutherian and bird evolution, presumably to preserve competitive binding. To determine plausibility, we developed and implemented a simple model of transcription factor and binding site coevolution. This model predicts that, in contrast to prevailing beliefs, even small selective benefits per locus can drive concurrent fixation of transcription factor and binding site mutants under a broad range of conditions. Novel binding sites tend to arise de novo, rather than by mutation from ancestral sites, a prediction substantiated by SP1-binding site alignments. Thus, multiple lines of evidence indicate that selection has driven convergent evolution of transcription factors along with their binding sites and coregulatory proteins. PMID:23019068

Direct inhibition of the DNA-binding activity of POU transcription factors Pit-1 and Brn-3 by selective binding of a phenyl-furan-benzimidazole dication.

PubMed

Peixoto, Paul; Liu, Yang; Depauw, Sabine; Hildebrand, Marie-Paule; Boykin, David W; Bailly, Christian; Wilson, W David; David-Cordonnier, Marie-Hélène

2008-06-01

The development of small molecules to control gene expression could be the spearhead of future-targeted therapeutic approaches in multiple pathologies. Among heterocyclic dications developed with this aim, a phenyl-furan-benzimidazole dication DB293 binds AT-rich sites as a monomer and 5'-ATGA sequence as a stacked dimer, both in the minor groove. Here, we used a protein/DNA array approach to evaluate the ability of DB293 to specifically inhibit transcription factors DNA-binding in a single-step, competitive mode. DB293 inhibits two POU-domain transcription factors Pit-1 and Brn-3 but not IRF-1, despite the presence of an ATGA and AT-rich sites within all three consensus sequences. EMSA, DNase I footprinting and surface-plasmon-resonance experiments determined the precise binding site, affinity and stoichiometry of DB293 interaction to the consensus targets. Binding of DB293 occurred as a cooperative dimer on the ATGA part of Brn-3 site but as two monomers on AT-rich sites of IRF-1 sequence. For Pit-1 site, ATGA or AT-rich mutated sequences identified the contribution of both sites for DB293 recognition. In conclusion, DB293 is a strong inhibitor of two POU-domain transcription factors through a cooperative binding to ATGA. These findings are the first to show that heterocyclic dications can inhibit major groove transcription factors and they open the door to the control of transcription factors activity by those compounds.

Selective Activation of Transcription by a Novel CCAAT Binding Factor

NASA Astrophysics Data System (ADS)

Maity, Sankar N.; Golumbek, Paul T.; Karsenty, Gerard; de Crombrugghe, Benoit

1988-07-01

A novel CCAAT binding factor (CBF) composed of two different subunits has been extensively purified from rat liver. Both subunits are needed for specific binding to DNA. Addition of this purified protein to nuclear extracts of NIH 3T3 fibroblasts stimulates transcription from several promoters including the α 2(I) collagen, the α 1(I) collagen, the Rous sarcoma virus long terminal repeat (RSV-LTR), and the adenovirus major late promoter. Point mutations in the CCAAT motif that show either no binding or a decreased binding of CBF likewise abolish or reduce activation of transcription by CBF. Activation of transcription requires, therefore, the specific binding of CBF to its recognition sites.

DNA residence time is a regulatory factor of transcription repression

PubMed Central

Clauß, Karen; Popp, Achim P.; Schulze, Lena; Hettich, Johannes; Reisser, Matthias; Escoter Torres, Laura; Uhlenhaut, N. Henriette

2017-01-01

Abstract Transcription comprises a highly regulated sequence of intrinsically stochastic processes, resulting in bursts of transcription intermitted by quiescence. In transcription activation or repression, a transcription factor binds dynamically to DNA, with a residence time unique to each factor. Whether the DNA residence time is important in the transcription process is unclear. Here, we designed a series of transcription repressors differing in their DNA residence time by utilizing the modular DNA binding domain of transcription activator-like effectors (TALEs) and varying the number of nucleotide-recognizing repeat domains. We characterized the DNA residence times of our repressors in living cells using single molecule tracking. The residence times depended non-linearly on the number of repeat domains and differed by more than a factor of six. The factors provoked a residence time-dependent decrease in transcript level of the glucocorticoid receptor-activated gene SGK1. Down regulation of transcription was due to a lower burst frequency in the presence of long binding repressors and is in accordance with a model of competitive inhibition of endogenous activator binding. Our single molecule experiments reveal transcription factor DNA residence time as a regulatory factor controlling transcription repression and establish TALE-DNA binding domains as tools for the temporal dissection of transcription regulation. PMID:28977492

Genome-Wide Identification of Binding Sites Defines Distinct Functions for Caenorhabditis elegans PHA-4/FOXA in Development and Environmental Response

PubMed Central

Zhong, Mei; Niu, Wei; Lu, Zhi John; Sarov, Mihail; Murray, John I.; Janette, Judith; Raha, Debasish; Sheaffer, Karyn L.; Lam, Hugo Y. K.; Preston, Elicia; Slightham, Cindie; Hillier, LaDeana W.; Brock, Trisha; Agarwal, Ashish; Auerbach, Raymond; Hyman, Anthony A.; Gerstein, Mark; Mango, Susan E.; Kim, Stuart K.; Waterston, Robert H.; Reinke, Valerie; Snyder, Michael

2010-01-01

Transcription factors are key components of regulatory networks that control development, as well as the response to environmental stimuli. We have established an experimental pipeline in Caenorhabditis elegans that permits global identification of the binding sites for transcription factors using chromatin immunoprecipitation and deep sequencing. We describe and validate this strategy, and apply it to the transcription factor PHA-4, which plays critical roles in organ development and other cellular processes. We identified thousands of binding sites for PHA-4 during formation of the embryonic pharynx, and also found a role for this factor during the starvation response. Many binding sites were found to shift dramatically between embryos and starved larvae, from developmentally regulated genes to genes involved in metabolism. These results indicate distinct roles for this regulator in two different biological processes and demonstrate the versatility of transcription factors in mediating diverse biological roles. PMID:20174564

Measurements of nonlinear Hall-driven reconnection in the reversed field pinch

NASA Astrophysics Data System (ADS)

Tharp, Timothy D.

Complex organisms are able to develop because of the complex regulatory systems that control their gene expression. The first step in this regulation, transcription initiation, is controlled by transcription factors. Transcription factors are modular proteins composed of two distinct domains, the DNA binding domain and the regulatory domain. These molecules are involved in a plethora of important biological processes including embryogenesis, development, cell health, and cancer. Tissue enriched transcription factors Nkx-2.5 and Gata4 are involved in cardiac development and cardiac health. In this thesis the DNA binding specificity of Nkx-2.5 will be analyzed using a high throughput double stranded DNA platform called Cognate Site Identifier (CSI) arrays (Chapter 2). The full DNA binding specificity of Nkx-2.5 and Nkx-2.5 mutants will be visualized using Sequence Specificity Landscapes (SSLs). In Chapter 3, the definition of binding specificity will be investigated by evaluating a number of different DNA binding folds by CSI and SSLs. CSI and SSLs will also be used to evaluate different pyrrole/imidazole hairpin polyamides in order to better characterize these small molecule DNA binding domains. CSI and SSL data will be applied to the genome in order to explain the biological function an artificial transcription factor. Chapter 4 will discuss the mechanism of nonspecific DNA binding. The historical means of predicting DNA binding will be challenged by utilizing high throughput experiments. The effect of salt concentration on both specific and nonspecific binding will also be investigated. Finally, in Chapter 5, a generation of Protein DNA Dimerizer will be discussed. A PDD that regulates transcription on genomic DNA by binding cooperatively with the heart IF Gata4 will be characterized. These studies provide understanding of, and a means to control, how transcription factors sample the endless sea of DNA in the genome in order to regulate gene expression with such wonderful specificity.

JASPAR 2016: a major expansion and update of the open-access database of transcription factor binding profiles

PubMed Central

Mathelier, Anthony; Fornes, Oriol; Arenillas, David J.; Chen, Chih-yu; Denay, Grégoire; Lee, Jessica; Shi, Wenqiang; Shyr, Casper; Tan, Ge; Worsley-Hunt, Rebecca; Zhang, Allen W.; Parcy, François; Lenhard, Boris; Sandelin, Albin; Wasserman, Wyeth W.

2016-01-01

JASPAR (http://jaspar.genereg.net) is an open-access database storing curated, non-redundant transcription factor (TF) binding profiles representing transcription factor binding preferences as position frequency matrices for multiple species in six taxonomic groups. For this 2016 release, we expanded the JASPAR CORE collection with 494 new TF binding profiles (315 in vertebrates, 11 in nematodes, 3 in insects, 1 in fungi and 164 in plants) and updated 59 profiles (58 in vertebrates and 1 in fungi). The introduced profiles represent an 83% expansion and 10% update when compared to the previous release. We updated the structural annotation of the TF DNA binding domains (DBDs) following a published hierarchical structural classification. In addition, we introduced 130 transcription factor flexible models trained on ChIP-seq data for vertebrates, which capture dinucleotide dependencies within TF binding sites. This new JASPAR release is accompanied by a new web tool to infer JASPAR TF binding profiles recognized by a given TF protein sequence. Moreover, we provide the users with a Ruby module complementing the JASPAR API to ease programmatic access and use of the JASPAR collection of profiles. Finally, we provide the JASPAR2016 R/Bioconductor data package with the data of this release. PMID:26531826

Correlation Functions and Glass Structure

NASA Astrophysics Data System (ADS)

Chergui, Y.; Nehaoua, N.; Telghemti, B.; Guemid, S.; Deraddji, N. E.; Belkhir, H.; Mekki, D. E.

2011-04-01

This work presents the use of molecular dynamics (MD) and the code of Dl Poly, in order to study the structure of fluoride glass after melting and quenching. We are realized the processing phase liquid-phase, simulating rapid quenching at different speeds to see the effect of quenching rate on the operation of the devitrification. This technique of simulation has become a powerful tool for investigating the microscopic behaviour of matter as well as for calculating macroscopic observable quantities. As basic results, we calculated the interatomic distance, angles and statistics, which help us to know the geometric form and the structure of PbF2. These results are in experimental agreement to those reported in literature.

Crystal structure of the Escherichia coli regulator of sigma70, Rsd, in complex with sigma70 domain 4.

PubMed

Patikoglou, Georgia A; Westblade, Lars F; Campbell, Elizabeth A; Lamour, Valérie; Lane, William J; Darst, Seth A

2007-09-21

The Escherichia coli Rsd protein binds tightly and specifically to the RNA polymerase (RNAP) sigma(70) factor. Rsd plays a role in alternative sigma factor-dependent transcription by biasing the competition between sigma(70) and alternative sigma factors for the available core RNAP. Here, we determined the 2.6 A-resolution X-ray crystal structure of Rsd bound to sigma(70) domain 4 (sigma(70)(4)), the primary determinant for Rsd binding within sigma(70). The structure reveals that Rsd binding interferes with the two primary functions of sigma(70)(4), core RNAP binding and promoter -35 element binding. Interestingly, the most highly conserved Rsd residues form a network of interactions through the middle of the Rsd structure that connect the sigma(70)(4)-binding surface with three cavities exposed on distant surfaces of Rsd, suggesting functional coupling between sigma(70)(4) binding and other binding surfaces of Rsd, either for other proteins or for as yet unknown small molecule effectors. These results provide a structural basis for understanding the role of Rsd, as well as its ortholog, AlgQ, a positive regulator of Pseudomonas aeruginosa virulence, in transcription regulation.

Crystal structure of the Escherichia coli regulator of σ70, Rsd, in complex with σ70 domain 4

PubMed Central

Patikoglou, Georgia A.; Westblade, Lars F.; Campbell, Elizabeth A.; Lamour, Valérie; Lane, William J.; Darst, Seth A.

2007-01-01

Summary The Escherichia coli Rsd protein binds tightly and specifically to the RNA polymerase (RNAP) σ70 factor. Rsd plays a role in alternative σ factor-dependent transcription by biasing the competition between σ70 and alternative σ factors for the available core RNAP. Here, we determined the 2.6 Å-resolution X-ray crystal structure of Rsd bound to σ70 domain 4 (σ704), the primary determinant for Rsd binding within σ70. The structure reveals that Rsd binding interferes with the two primary functions of σ704, core RNAP binding and promoter –35 element binding. Interestingly, the most highly conserved Rsd residues form a network of interactions through the middle of the Rsd structure that connect the σ704-binding surface with three cavities exposed on distant surfaces of Rsd, suggesting functional coupling between σ704 binding and other binding surfaces of Rsd, either for other proteins or for as yet unknown small molecule effectors. These results provide a structural basis for understanding the role of Rsd, as well as its ortholog, AlgQ, a positive regulator of Pseudomonas aeruginosa virulence, in transcription regulation. PMID:17681541

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

Patikoglou,G.; Westblade, L.; Campbell, E.

The Escherichia coli Rsd protein binds tightly and specifically to the RNA polymerase (RNAP) {sigma}{sup 70} factor. Rsd plays a role in alternative {sigma} factor-dependent transcription by biasing the competition between {sigma}{sup 70} and alternative {sigma} factors for the available core RNAP. Here, we determined the 2.6 {angstrom}-resolution X-ray crystal structure of Rsd bound to {sigma}{sup 70} domain 4 ({sigma}{sup 70}{sub 4}), the primary determinant for Rsd binding within {sigma}{sup 70}. The structure reveals that Rsd binding interferes with the two primary functions of {sigma}{sup 70}{sub 4}, core RNAP binding and promoter -35 element binding. Interestingly, the most highly conservedmore » Rsd residues form a network of interactions through the middle of the Rsd structure that connect the {sigma}{sup 70}{sub 4}-binding surface with three cavities exposed on distant surfaces of Rsd, suggesting functional coupling between {sigma}{sup 70}{sub 4} binding and other binding surfaces of Rsd, either for other proteins or for as yet unknown small molecule effectors. These results provide a structural basis for understanding the role of Rsd, as well as its ortholog, AlgQ, a positive regulator of Pseudomonas aeruginosa virulence, in transcription regulation.« less

Ligand binding and dynamics of the monomeric epidermal growth factor receptor ectodomain

PubMed Central

Loeffler, Hannes H; Winn, Martyn D

2013-01-01

The ectodomain of the human epidermal growth factor receptor (hEGFR) controls input to several cell signalling networks via binding with extracellular growth factors. To gain insight into the dynamics and ligand binding of the ectodomain, the hEGFR monomer was subjected to molecular dynamics simulation. The monomer was found to be substantially more flexible than the ectodomain dimer studied previously. Simulations where the endogeneous ligand EGF binds to either Subdomain I or Subdomain III, or where hEGFR is unbound, show significant differences in dynamics. The molecular mechanics Poisson–Boltzmann surface area method has been used to derive relative free energies of ligand binding, and we find that the ligand is capable of binding either subdomain with a slight preference for III. Alanine-scanning calculations for the effect of selected ligand mutants on binding reproduce the trends of affinity measurements. Taken together, these results emphasize the possible role of the ectodomain monomer in the initial step of ligand binding, and add details to the static picture obtained from crystal structures. Proteins 2013; 81:1931–1943. © 2013 The Authors. Proteins published by Wiley Periodicals, Inc. PMID:23760854

Identification of Specific DNA Binding Residues in the TCP Family of Transcription Factors in Arabidopsis[W

PubMed Central

Aggarwal, Pooja; Das Gupta, Mainak; Joseph, Agnel Praveen; Chatterjee, Nirmalya; Srinivasan, N.; Nath, Utpal

2010-01-01

The TCP transcription factors control multiple developmental traits in diverse plant species. Members of this family share an ∼60-residue-long TCP domain that binds to DNA. The TCP domain is predicted to form a basic helix-loop-helix (bHLH) structure but shares little sequence similarity with canonical bHLH domain. This classifies the TCP domain as a novel class of DNA binding domain specific to the plant kingdom. Little is known about how the TCP domain interacts with its target DNA. We report biochemical characterization and DNA binding properties of a TCP member in Arabidopsis thaliana, TCP4. We have shown that the 58-residue domain of TCP4 is essential and sufficient for binding to DNA and possesses DNA binding parameters comparable to canonical bHLH proteins. Using a yeast-based random mutagenesis screen and site-directed mutants, we identified the residues important for DNA binding and dimer formation. Mutants defective in binding and dimerization failed to rescue the phenotype of an Arabidopsis line lacking the endogenous TCP4 activity. By combining structure prediction, functional characterization of the mutants, and molecular modeling, we suggest a possible DNA binding mechanism for this class of transcription factors. PMID:20363772

Competition between histone and transcription factor binding regulates the onset of transcription in zebrafish embryos

PubMed Central

Joseph, Shai R; Pálfy, Máté; Hilbert, Lennart; Kumar, Mukesh; Karschau, Jens; Zaburdaev, Vasily; Shevchenko, Andrej; Vastenhouw, Nadine L

2017-01-01

Upon fertilization, the genome of animal embryos remains transcriptionally inactive until the maternal-to-zygotic transition. At this time, the embryo takes control of its development and transcription begins. How the onset of zygotic transcription is regulated remains unclear. Here, we show that a dynamic competition for DNA binding between nucleosome-forming histones and transcription factors regulates zebrafish genome activation. Taking a quantitative approach, we found that the concentration of non-DNA-bound core histones sets the time for the onset of transcription. The reduction in nuclear histone concentration that coincides with genome activation does not affect nucleosome density on DNA, but allows transcription factors to compete successfully for DNA binding. In agreement with this, transcription factor binding is sensitive to histone levels and the concentration of transcription factors also affects the time of transcription. Our results demonstrate that the relative levels of histones and transcription factors regulate the onset of transcription in the embryo. DOI: http://dx.doi.org/10.7554/eLife.23326.001 PMID:28425915

Competition between histone and transcription factor binding regulates the onset of transcription in zebrafish embryos.

PubMed

Joseph, Shai R; Pálfy, Máté; Hilbert, Lennart; Kumar, Mukesh; Karschau, Jens; Zaburdaev, Vasily; Shevchenko, Andrej; Vastenhouw, Nadine L

2017-04-20

Upon fertilization, the genome of animal embryos remains transcriptionally inactive until the maternal-to-zygotic transition. At this time, the embryo takes control of its development and transcription begins. How the onset of zygotic transcription is regulated remains unclear. Here, we show that a dynamic competition for DNA binding between nucleosome-forming histones and transcription factors regulates zebrafish genome activation. Taking a quantitative approach, we found that the concentration of non-DNA-bound core histones sets the time for the onset of transcription. The reduction in nuclear histone concentration that coincides with genome activation does not affect nucleosome density on DNA, but allows transcription factors to compete successfully for DNA binding. In agreement with this, transcription factor binding is sensitive to histone levels and the concentration of transcription factors also affects the time of transcription. Our results demonstrate that the relative levels of histones and transcription factors regulate the onset of transcription in the embryo.

Synergistic binding of transcription factors to cell-specific enhancers programs motor neuron identity

PubMed Central

Mazzoni, Esteban O; Mahony, Shaun; Closser, Michael; Morrison, Carolyn A; Nedelec, Stephane; Williams, Damian J; An, Disi; Gifford, David K; Wichterle, Hynek

2013-01-01

Efficient transcriptional programming promises to open new frontiers in regenerative medicine. However, mechanisms by which programming factors transform cell fate are unknown, preventing more rational selection of factors to generate desirable cell types. Three transcription factors, Ngn2, Isl1 and Lhx3, were sufficient to program rapidly and efficiently spinal motor neuron identity when expressed in differentiating mouse embryonic stem cells. Replacement of Lhx3 by Phox2a led to specification of cranial, rather than spinal, motor neurons. Chromatin immunoprecipitation–sequencing analysis of Isl1, Lhx3 and Phox2a binding sites revealed that the two cell fates were programmed by the recruitment of Isl1-Lhx3 and Isl1-Phox2a complexes to distinct genomic locations characterized by a unique grammar of homeodomain binding motifs. Our findings suggest that synergistic interactions among transcription factors determine the specificity of their recruitment to cell type–specific binding sites and illustrate how a single transcription factor can be repurposed to program different cell types. PMID:23872598

Structural Determination of Functional Domains in Early B-cell Factor (EBF) Family of Transcription Factors Reveals Similarities to Rel DNA-binding Proteins and a Novel Dimerization Motif*

PubMed Central

Siponen, Marina I.; Wisniewska, Magdalena; Lehtiö, Lari; Johansson, Ida; Svensson, Linda; Raszewski, Grzegorz; Nilsson, Lennart; Sigvardsson, Mikael; Berglund, Helena

2010-01-01

The early B-cell factor (EBF) transcription factors are central regulators of development in several organs and tissues. This protein family shows low sequence similarity to other protein families, which is why structural information for the functional domains of these proteins is crucial to understand their biochemical features. We have used a modular approach to determine the crystal structures of the structured domains in the EBF family. The DNA binding domain reveals a striking resemblance to the DNA binding domains of the Rel homology superfamily of transcription factors but contains a unique zinc binding structure, termed zinc knuckle. Further the EBF proteins contain an IPT/TIG domain and an atypical helix-loop-helix domain with a novel type of dimerization motif. The data presented here provide insights into unique structural features of the EBF proteins and open possibilities for detailed molecular investigations of this important transcription factor family. PMID:20592035

Genetic variation in the MITF promoter affects skin colour and transcriptional activity in black-boned chickens.

PubMed

Wang, G; Liao, J; Tang, M; Yu, S

2018-02-01

1. Microphthalmia-associated transcription factor (MITF) plays a pivotal role in melanocyte development by regulating the transcription of major pigmentation enzymes (e.g. TYR, TYRP1 and DCT). A single-nucleotide polymorphism (SNP), c.-638T>C, was identified in the MITF promoter, and genotyping of a population (n = 426) revealed that SNP c.-638T>C was associated with skin colour in black-boned chickens. 2. Individuals with genotypes CC and TC exhibited greater MTIF expression than those with genotype TT. Luciferase assays also revealed that genotype CC and TC promoters had higher activity levels than genotype TT. Expression of melanogenesis-related gene (TYR) was higher in the skin of chickens with the CC and CT genotype compared to TT chickens (P < 0.05). 3. Transcription factor-binding site analyses showed that the c.-638C allele contains a putative binding site for transcription factor sterol regulatory element-binding transcription factor 2, aryl hydrocarbon receptor nuclear translocator, transcription factor binding to IGHM enhancer 3 and upstream transcription factor 2. In contrast, the c.-638T allele contains binding sites for Sp3 transcription factor and Krüppel-like factor 1. 4. It was concluded that MITF promoter polymorphisms affected chicken skin colour. SNP c.-638T>C could be used for the marker-assisted selection of skin colour in black-boned chicken breeding.

Sequestration of cAMP response element-binding proteins by transcription factor decoys causes collateral elaboration of regenerating Aplysia motor neuron axons.

PubMed

Dash, P K; Tian, L M; Moore, A N

1998-07-07

Axonal injury increases intracellular Ca2+ and cAMP and has been shown to induce gene expression, which is thought to be a key event for regeneration. Increases in intracellular Ca2+ and/or cAMP can alter gene expression via activation of a family of transcription factors that bind to and modulate the expression of CRE (Ca2+/cAMP response element) sequence-containing genes. We have used Aplysia motor neurons to examine the role of CRE-binding proteins in axonal regeneration after injury. We report that axonal injury increases the binding of proteins to a CRE sequence-containing probe. In addition, Western blot analysis revealed that the level of ApCREB2, a CRE sequence-binding repressor, was enhanced as a result of axonal injury. The sequestration of CRE-binding proteins by microinjection of CRE sequence-containing plasmids enhanced axon collateral formation (both number and length) as compared with control plasmid injections. These findings show that Ca2+/cAMP-mediated gene expression via CRE-binding transcription factors participates in the regeneration of motor neuron axons.

USF-related transcription factor, HIV-TF1, stimulates transcription of human immunodeficiency virus-1.

PubMed

Maekawa, T; Sudo, T; Kurimoto, M; Ishii, S

1991-09-11

The transcription factor HIV-TF1, which binds to a region about 60 bp upstream from the enhancer of the human immunodeficiency virus-1 (HIV-1), was purified from human B cells. HIV-TF1 had a molecular weight of 39,000. Binding of HIV-TF1 to the HIV long terminal repeat (LTR) activated transcription from the HIV promoter in vitro. The HIV-TF1-binding site in HIV LTR was similar to the site recognized by upstream stimulatory factor (USF) in the adenovirus major late promoter. DNA-binding properties of HIV-TF1 suggested that HIV-TF1 might be identical or related to USF. Interestingly, treatment of purified HIV-TF1 by phosphatase greatly reduced its DNA-binding activity, suggesting that phosphorylation of HIV-TF1 was essential for DNA binding. The disruption of HIV-TF1-binding site induced a 60% decrease in the level of transcription from the HIV promoter in vivo. These results suggest that HIV-TF1 is involved in transcriptional regulation of HIV-1.

Two signaling molecules share a phosphotyrosine-containing binding site in the platelet-derived growth factor receptor.

PubMed

Nishimura, R; Li, W; Kashishian, A; Mondino, A; Zhou, M; Cooper, J; Schlessinger, J

1993-11-01

Autophosphorylation sites of growth factor receptors with tyrosine kinase activity function as specific binding sites for Src homology 2 (SH2) domains of signaling molecules. This interaction appears to be a crucial step in a mechanism by which receptor tyrosine kinases relay signals to downstream signaling pathways. Nck is a widely expressed protein consisting exclusively of SH2 and SH3 domains, the overexpression of which causes cell transformation. It has been shown that various growth factors stimulate the phosphorylation of Nck and its association with autophosphorylated growth factor receptors. A panel of platelet-derived growth factor (PDGF) receptor mutations at tyrosine residues has been used to identify the Nck binding site. Here we show that mutation at Tyr-751 of the PDGF beta-receptor eliminates Nck binding both in vitro and in living cells. Moreover, the Y751F PDGF receptor mutant failed to mediate PDGF-stimulated phosphorylation of Nck in intact cells. A phosphorylated Tyr-751 is also required for binding of phosphatidylinositol-3 kinase to the PDGF receptor. Hence, the SH2 domains of p85 and Nck share a binding site in the PDGF receptor. Competition experiments with different phosphopeptides derived from the PDGF receptor suggest that binding of Nck and p85 is influenced by different residues around Tyr-751. Thus, a single tyrosine autophosphorylation site is able to link the PDGF receptor to two distinct SH2 domain-containing signaling molecules.

Enhanced protective antibody to a mutant meningococcal factor H-binding protein with low-factor H binding

PubMed Central

Granoff, Dan M.; Giuntini, Serena; Gowans, Flor A.; Lujan, Eduardo; Sharkey, Kelsey; Beernink, Peter T.

2016-01-01

Meningococcal factor H-binding protein (FHbp) is an antigen in 2 serogroup B meningococcal vaccines. FHbp specifically binds human and some nonhuman primate complement FH. To investigate the effect of binding of FH to FHbp on protective antibody responses, we immunized infant rhesus macaques with either a control recombinant FHbp antigen that bound macaque FH or a mutant antigen with 2 amino acid substitutions and >250-fold lower affinity for FH. The mutant antigen elicited 3-fold higher serum IgG anti-FHbp titers and up to 15-fold higher serum bactericidal titers than the control FHbp vaccine. When comparing sera with similar IgG anti-FHbp titers, the antibodies elicited by the mutant antigen gave greater deposition of complement component C4b on live meningococci (classical complement pathway) and inhibited binding of FH, while the anti-FHbp antibodies elicited by the control vaccine enhanced FH binding. Thus, the mutant FHbp vaccine elicited an anti-FHbp antibody repertoire directed at FHbp epitopes within the FH binding site, which resulted in greater protective activity than the antibodies elicited by the control vaccine, which targeted FHbp epitopes outside of the FH combining site. Binding of a host protein to a vaccine antigen impairs protective antibody responses, which can be overcome with low-binding mutant antigens. PMID:27668287

Complement-mediated bactericidal activity of anti-factor H binding protein monoclonal antibodies against the meningococcus relies upon blocking factor H binding.

PubMed

Giuntini, Serena; Reason, Donald C; Granoff, Dan M

2011-09-01

Binding of the complement-downregulating protein factor H (fH) to the surface of the meningococcus is important for survival of the organism in human serum. The meningococcal vaccine candidate factor H binding protein (fHbp) is an important ligand for human fH. While some fHbp-specific monoclonal antibodies (MAbs) block binding of fH to fHbp, the stoichiometry of blocking in the presence of high serum concentrations of fH and its effect on complement-mediated bactericidal activity are unknown. To investigate this question, we constructed chimeric antibodies in which the human IgG1 constant region was paired with three murine fHbp-specific binding domains designated JAR 3, JAR 5, and MAb502. By surface plasmon resonance, the association rates for binding of all three MAbs to immobilized fHbp were >50-fold higher than that for binding of fH to fHbp, and the MAb dissociation rates were >500-fold lower than that for fH. While all three MAbs elicited similar C1q-dependent C4b deposition on live bacteria (classical complement pathway), only those antibodies that inhibited binding of fH to fHbp (JAR 3 and JAR 5) had bactericidal activity with human complement. MAb502, which did not inhibit fH binding, had complement-mediated bactericidal activity only when tested with fH-depleted human complement. When an IgG1 anti-fHbp MAb binds to sparsely exposed fHbp on the bacterial surface, there appears to be insufficient complement activation for bacteriolysis unless fH binding also is inhibited. The ability of fHbp vaccines to elicit protective antibodies, therefore, is likely to be enhanced if the antibody repertoire is of high avidity and includes fH-blocking activity.

Dual DNA binding property of ABA insensitive 3 like factors targeted to promoters responsive to ABA and auxin.

PubMed

Nag, Ronita; Maity, Manas Kanti; Dasgupta, Maitrayee

2005-11-01

The ABA responsive ABI3 and the auxin responsive ARF family of transcription factors bind the CATGCATG (Sph) and TGTCTC core motifs in ABA and auxin response elements (ABRE and AuxRE), respectively. Several evidences indicate ABI3s to act downstream to auxin too. Because DNA binding domain of ABI3s shows significant overlap with ARFs we enquired whether auxin responsiveness through ABI3s could be mediated by their binding to canonical AuxREs. Investigations were undertaken through in vitro gel mobility shift assays (GMSA) using the DNA binding domain B3 of PvAlf (Phaseolus vulgaris ABI3 like factor) and upstream regions of auxin responsive gene GH3 (-267 to -141) and ABA responsive gene Em (-316 to -146) harboring AuxRE and ABRE, respectively. We demonstrate that B3 domain of PvAlf could bind AuxRE only when B3 was associated with its flanking domain B2 (B2B3). Such strict requirement of B2 domain was not observed with ABRE, where B3 could bind with or without being associated with B2. This dual specificity in DNA binding of ABI3s was also demonstrated with nuclear extracts of cultured cells of Arachis hypogea. Supershift analysis of ABRE and AuxRE bound nuclear proteins with antibodies raised against B2B3 domains of PvAlf revealed that ABI3 associated complexes were detectable in association with both cis elements. Competition GMSA confirmed the same complexes to bind ABRE and AuxRE. This dual specificity of ABI3 like factors in DNA binding targeted to natural promoters responsive to ABA and auxin suggests them to have a potential role in conferring crosstalk between these two phytohormones.

Evaluation of Novel Design Strategies for Developing Zinc Finger Nucleases Tools for Treating Human Diseases

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

Bach, Christian; Sherman, William; Pallis, Jani

Zinc finger nucleases (ZFNs) are associated with cell death and apoptosis by binding at countless undesired locations. This cytotoxicity is associated with the binding ability of engineered zinc finger domains to bind dissimilar DNA sequences with high affinity. In general, binding preferences of transcription factors are associated with significant degenerated diversity and complexity which convolutes the design and engineering of precise DNA binding domains. Evolutionary success of natural zinc finger proteins, however, evinces that nature created specific evolutionary traits and strategies, such as modularity and rank-specific recognition to cope with binding complexity that are critical for creating clinical viable toolsmore » to precisely modify the human genome. Our findings indicate preservation of general modularity and significant alteration of the rank-specific binding preferences of the three-finger binding domain of transcription factor SP1 when exchanging amino acids in the 2nd finger.« less

Effects of nucleoside analog incorporation on DNA binding to the DNA binding domain of the GATA-1 erythroid transcription factor.

PubMed

Foti, M; Omichinski, J G; Stahl, S; Maloney, D; West, J; Schweitzer, B I

1999-02-05

We investigate here the effects of the incorporation of the nucleoside analogs araC (1-beta-D-arabinofuranosylcytosine) and ganciclovir (9-[(1,3-dihydroxy-2-propoxy)methyl] guanine) into the DNA binding recognition sequence for the GATA-1 erythroid transcription factor. A 10-fold decrease in binding affinity was observed for the ganciclovir-substituted DNA complex in comparison to an unmodified DNA of the same sequence composition. AraC substitution did not result in any changes in binding affinity. 1H-15N HSQC and NOESY NMR experiments revealed a number of chemical shift changes in both DNA and protein in the ganciclovir-modified DNA-protein complex when compared to the unmodified DNA-protein complex. These changes in chemical shift and binding affinity suggest a change in the binding mode of the complex when ganciclovir is incorporated into the GATA DNA binding site.

Evaluation of Novel Design Strategies for Developing Zinc Finger Nucleases Tools for Treating Human Diseases

DOE PAGES

Bach, Christian; Sherman, William; Pallis, Jani; ...

2014-01-01

Zinc finger nucleases (ZFNs) are associated with cell death and apoptosis by binding at countless undesired locations. This cytotoxicity is associated with the binding ability of engineered zinc finger domains to bind dissimilar DNA sequences with high affinity. In general, binding preferences of transcription factors are associated with significant degenerated diversity and complexity which convolutes the design and engineering of precise DNA binding domains. Evolutionary success of natural zinc finger proteins, however, evinces that nature created specific evolutionary traits and strategies, such as modularity and rank-specific recognition to cope with binding complexity that are critical for creating clinical viable toolsmore » to precisely modify the human genome. Our findings indicate preservation of general modularity and significant alteration of the rank-specific binding preferences of the three-finger binding domain of transcription factor SP1 when exchanging amino acids in the 2nd finger.« less

[Insulin-like growth factor-binding protein-1: a new biochemical marker of nonalcoholic fatty liver disease?].

PubMed

Graffigna, Mabel Nora; Belli, Susana H; de Larrañaga, Gabriela; Fainboim, Hugo; Estepo, Claudio; Peres, Silvia; García, Natalia; Levalle, Oscar

2009-03-01

to assess the presence of nonalcoholic fatty liver disease in patients with risk factors for this pathology (obesity, dyslipidemia, metabolic syndrome and diabetes type 2) and to determine the role of insulin, HOMA index, insulin-like growth factor-binding protein-1, sex hormone-binding globulin and plasminogen activator inhibitor type 1, as biochemical markers. Ninety-one patients with risk factors for nonalcoholic fatty liver disease were evaluated. Serum transaminases, insulin, sex hormone-binding globulin, insulin-like growth factor-binding protein-1 and plasminogen activator inhibitor type 1 were measured. The diagnosis of fatty liver was performed by ultrasonography and liver biopsies were performed to 31 subjects who had steatosis by ultrasonography and high alanine aminotransferase. Nonalcoholic fatty liver disease was present in 65 out of 91 patients (71,4%). Liver biopsy performed to 31 subjects confirmed nonalcoholic steatohepatitis. Twenty-five patients had different degrees of fibrosis. Those individuals with fatty liver had higher waist circumference, serum levels of triglycerides, insulin and HOMA index, and lower serum insulin-like growth factor-binding protein-1 concentration. The degree ofhepatic steatosis by ultrasonography was positively correlated to waist circumference, triglycerides, insulin and HOMA index (p<0,003; p<0,003; p<0,002 and p<0,001, respectively), and was negatively correlated to HDL-cholesterol and insulin-like growth factor-binding protein-1 (p<0,025 and p<0,018, respectively). We found a high prevalence of NAFLD in patients with risk factors, most of them overweight or obese. Although SHBG and PAI-1 have a closely relationship to insulin resistance, they did not show to be markers of NAFLD. Regardless of low IGFBP-1 levels associated with NAFLD, serum IGFBP-1 measure is less accessible than insulin and triglycerides levels, HOMA index and waist circumference. Moreover, it is not a better marker for NAFLD than the above mentioned.

MGMT DNA repair gene promoter/enhancer haplotypes alter transcription factor binding and gene expression.

PubMed

Xu, Meixiang; Cross, Courtney E; Speidel, Jordan T; Abdel-Rahman, Sherif Z

2016-10-01

The O 6 -methylguanine-DNA methyltransferase (MGMT) protein removes O 6 -alkyl-guanine adducts from DNA. MGMT expression can thus alter the sensitivity of cells and tissues to environmental and chemotherapeutic alkylating agents. Previously, we defined the haplotype structure encompassing single nucleotide polymorphisms (SNPs) in the MGMT promoter/enhancer (P/E) region and found that haplotypes, rather than individual SNPs, alter MGMT promoter activity. The exact mechanism(s) by which these haplotypes exert their effect on MGMT promoter activity is currently unknown, but we noted that many of the SNPs comprising the MGMT P/E haplotypes are located within or in close proximity to putative transcription factor binding sites. Thus, these haplotypes could potentially affect transcription factor binding and, subsequently, alter MGMT promoter activity. In this study, we test the hypothesis that MGMT P/E haplotypes affect MGMT promoter activity by altering transcription factor (TF) binding to the P/E region. We used a promoter binding TF profiling array and a reporter assay to evaluate the effect of different P/E haplotypes on TF binding and MGMT expression, respectively. Our data revealed a significant difference in TF binding profiles between the different haplotypes evaluated. We identified TFs that consistently showed significant haplotype-dependent binding alterations (p ≤ 0.01) and revealed their role in regulating MGMT expression using siRNAs and a dual-luciferase reporter assay system. The data generated support our hypothesis that promoter haplotypes alter the binding of TFs to the MGMT P/E and, subsequently, affect their regulatory function on MGMT promoter activity and expression level.

CHEMOSENSITIZATION BY A NON-APOPTOGENIC HEAT SHOCK PROTEIN 70-BINDING APOPTOSIS INDUCING FACTOR MUTANT

EPA Science Inventory

Chemosensitization by a non-apoptogenic heat shock protein 70-binding apoptosis inducing factor mutant

Abstract
HSP70 inhibits apoptosis by neutralizing the caspase activator Apaf-1 and by interacting with apoptosis inducing factor (AIF), a mitochondrial flavoprotein wh...

Energetic factors determining the binding of type I inhibitors to c-Met kinase: experimental studies and quantum mechanical calculations

PubMed Central

Yu, Zhe; Ma, Yu-chi; Ai, Jing; Chen, Dan-qi; Zhao, Dong-mei; Wang, Xin; Chen, Yue-lei; Geng, Mei-yu; Xiong, Bing; Cheng, Mao-sheng; Shen, Jing-kang

2013-01-01

Aim: To decipher the molecular interactions between c-Met and its type I inhibitors and to facilitate the design of novel c-Met inhibitors. Methods: Based on the prototype model inhibitor 1, four ligands with subtle differences in the fused aromatic rings were synthesized. Quantum chemistry was employed to calculate the binding free energy for each ligand. Symmetry-adapted perturbation theory (SAPT) was used to decompose the binding energy into several fundamental forces to elucidate the determinant factors. Results: Binding free energies calculated from quantum chemistry were correlated well with experimental data. SAPT calculations showed that the predominant driving force for binding was derived from a sandwich π–π interaction with Tyr-1230. Arg-1208 was the differentiating factor, interacting with the 6-position of the fused aromatic ring system through the backbone carbonyl with a force pattern similar to hydrogen bonding. Therefore, a hydrogen atom must be attached at the 6-position, and changing the carbon atom to nitrogen caused unfavorable electrostatic interactions. Conclusion: The theoretical studies have elucidated the determinant factors involved in the binding of type I inhibitors to c-Met. PMID:24056705

Controlling gene networks and cell fate with precision-targeted DNA-binding proteins and small-molecule-based genome readers

PubMed Central

Eguchi, Asuka; Lee, Garrett O.; Wan, Fang; Erwin, Graham S.; Ansari, Aseem Z.

2014-01-01

Transcription factors control the fate of a cell by regulating the expression of genes and regulatory networks. Recent successes in inducing pluripotency in terminally differentiated cells as well as directing differentiation with natural transcription factors has lent credence to the efforts that aim to direct cell fate with rationally designed transcription factors. Because DNA-binding factors are modular in design, they can be engineered to target specific genomic sequences and perform pre-programmed regulatory functions upon binding. Such precision-tailored factors can serve as molecular tools to reprogramme or differentiate cells in a targeted manner. Using different types of engineered DNA binders, both regulatory transcriptional controls of gene networks, as well as permanent alteration of genomic content, can be implemented to study cell fate decisions. In the present review, we describe the current state of the art in artificial transcription factor design and the exciting prospect of employing artificial DNA-binding factors to manipulate the transcriptional networks as well as epigenetic landscapes that govern cell fate. PMID:25145439

Two DNA-binding factors recognize specific sequences at silencers, upstream activating sequences, autonomously replicating sequences, and telomeres in Saccharomyces cerevisiae

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

Buchman, A.R.; Kimmerly, W.J.; Rine, J.

1988-01-01

Two DNA-binding factors from Saccharomyces cerevisiae have been characterized, GRFI (general regulatory factor I) and ABFI (ARS-binding factor I), that recognize specific sequences within diverse genetic elements. GRFI bound to sequences at the negative regulatory elements (silencers) of the silent mating type loci HML E and HMR E and to the upstream activating sequence (UAS) required for transcription of the MAT ..cap alpha.. genes. A putative conserved UAS located at genes involved in translation (RPG box) was also recognized by GRFI. In addition, GRFI bound with high affinity to sequences within the (C/sub 1-3/A)-repeat region at yeast telomeres. Binding sitesmore » for GRFI with the highest affinity appeared to be of the form 5'-(A/G)(A/C)ACCCAN NCA(T/C)(T/C)-3', where N is any nucleotide. ABFI-binding sites were located next to autonomously replicating sequences (ARSs) at controlling elements of the silent mating type loci HMR E, HMR I, and HML I and were associated with ARS1, ARS2, and the 2..mu..m plasmid ARS. Two tandem ABFI binding sites were found between the HIS3 and DED1 genes, several kilobase pairs from any ARS, indicating that ABFI-binding sites are not restricted to ARSs. The sequences recognized by AFBI showed partial dyad-symmetry and appeared to be variations of the consensus 5'-TATCATTNNNNACGA-3'. GRFI and ABFI were both abundant DNA-binding factors and did not appear to be encoded by the SIR genes, whose product are required for repression of the silent mating type loci. Together, these results indicate that both GRFI and ABFI play multiple roles within the cell.« less

Effect of antemortem and postmortem factors on ( sup 3 H)MK-801 binding in the human brain: Transient elevation during early childhood

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

Kornhuber, J.; Mack-Burkhardt, F.; Konradi, C.

1989-01-01

The effect of a number of antemortem and postmortem factors on ({sup 3}H)MK-801 binding was investigated under equilibrium conditions in the frontal cortex of human brains of 38 controls. Binding values transiently increased during the early postnatal period reaching a maximum at the age of about 2 years. After age 10 years ({sup 3}H)MK-801 binding sites disappeared at 5.7% per decade. The storage time of brain tissue had a reducing effect on these binding sites. There was no effect of gender, brain weight or postmortem time interval and the binding sites were bilaterally symmetrically distributed in the frontal cortex.

Novel Family of Insect Salivary Inhibitors Blocks Contact Pathway Activation by Binding to Polyphosphate, Heparin, and Dextran Sulfate

PubMed Central

Alvarenga, Patricia H.; Xu, Xueqing; Oliveira, Fabiano; Chagas, Andrezza C.; Nascimento, Clarissa R.; Francischetti, Ivo M.B.; Juliano, Maria A.; Juliano, Luiz; Scharfstein, Julio; Valenzuela, Jesus G.; Ribeiro, José M.C.; Andersen, John F.

2014-01-01

Objective Polyphosphate and heparin are anionic polymers released by activated mast cells and platelets that are known to stimulate the contact pathway of coagulation. These polymers promote both the autoactivation of factor XII and the assembly of complexes containing factor XI, prekallikrein, and high-molecular-weight kininogen. We are searching for salivary proteins from blood-feeding insects that counteract the effect of procoagulant and proinflammatory factors in the host, including elements of the contact pathway. Approach and Results Here, we evaluate the ability of the sand fly salivary proteins, PdSP15a and PdSP15b, to inhibit the contact pathway by disrupting binding of its components to anionic polymers. We attempt to demonstrate binding of the proteins to polyphosphate, heparin, and dextran sulfate. We also evaluate the effect of this binding on contact pathway reactions. We also set out to determine the x-ray crystal structure of PdSP15b and examine the determinants of relevant molecular interactions. Both proteins bind polyphosphate, heparin, and dextran sulfate with high affinity. Through this mechanism they inhibit the autoactivation of factor XII and factor XI, the reciprocal activation of factor XII and prekallikrein, the activation of factor XI by thrombin and factor XIIa, the cleavage of high-molecular-weight kininogen in plasma, and plasma extravasation induced by polyphosphate. The crystal structure of PdSP15b contains an amphipathic helix studded with basic side chains that forms the likely interaction surface. Conclusions The results of these studies indicate that the binding of anionic polymers by salivary proteins is used by blood feeders as an antihemostatic/anti-inflammatory mechanism. PMID:24092749

Yeast one-hybrid system used to identify the binding proteins for rat glutathione S-transferase P enhancer I.

PubMed

Liao, Ming-Xiang; Liu, Dong-Yuan; Zuo, Jin; Fang, Fu-De

2002-03-01

To detect the trans-factors specifically binding to the strong enhancer element (GPEI) in the upstream of rat glutathione S-transferase P (GST-P) gene. Yeast one-hybrid system was used to screen rat lung MATCHMAKER cDNA library to identify potential trans-factors that can interact with core sequence of GPEI(cGPEI). Electrophoresis mobility shift assay (EMSA) was used to analyze the binding of transfactors to cGPEI. cDNA fragments coding for the C-terminal part of the transcription factor c-Jun and rat adenine nucleotide translocator (ANT) were isolated. The binding of c-Jun and ANT to GPEI core sequence were confirmed. Rat c-jun transcriptional factor and ANT may interact with cGPEI. They could play an important role in the induced expression of GST-P gene.

Mechanisms of extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor signal transduction pathway in depressive disorder☆

PubMed Central

Wang, Hongyan; Zhang, Yingquan; Qiao, Mingqi

2013-01-01

The extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor signal transduction pathway plays an important role in the mechanism of action of antidepressant drugs and has dominated recent studies on the pathogenesis of depression. In the present review we summarize the known roles of extracellular signal-regulated kinase, cAMP response element-binding protein and brain-derived neurotrophic factor in the pathogenesis of depression and in the mechanism of action of antidepressant medicines. The extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor pathway has potential to be used as a biological index to help diagnose depression, and as such it is considered as an important new target in the treatment of depression. PMID:25206732

Connecting RNA Processing to Abiotic Environmental Response in Arabidopsis: the role of a polyadenylation factor

NASA Astrophysics Data System (ADS)

Li, Q. Q.; Xu, R.; Hunt, A. G.; Falcone, D. L.

Plants are constantly challenged by numerous environmental stresses both biotic and abiotic It is clear that plants have evolved to counter these stresses using all but limited means We recently discovered the potential role of a messenger RNA processing factor namely the Arabidopsis cleavage and polyadenylation specificity factor 30 kDa subunit AtCPSF30 when a mutant deficient in this factor displayed altered responses to an array of abiotic stresses This AtCPSF30 mutant named oxt6 exhibited an elevated tolerance to oxidative stress Microarray experiments of oxt6 and its complemented lines revealed an altered gene expression profile among which were antioxidative defense genes Interestingly the same gene encoding AtCPSF30 can also be transcribed into a large transcript that codes for a potential splicing factor Both protein products have a domain for RNA binding and a calmodulin binding domain activities of which have been confirmed by biochemical assays Surprisingly binding of AtCPSF30 to calmodulin inhibits the RNA-binding activity of the protein Mutational analysis shows that a small part of the protein is responsible for calmodulin binding and point mutations in this region abolished both RNA binding activity and the inhibition of this activity by calmodulin Analyses of the potential splicing factor are on going and the results will be presented The interesting possibilities for both the interplay between splicing and polyadenylation and the regulation of these processes by stimuli that act through

Basic Fibroblast Growth Factor Activates Serum Response Factor Gene Expression by Multiple Distinct Signaling Mechanisms

PubMed Central

Spencer, Jeffrey A.; Major, Michael L.; Misra, Ravi P.

1999-01-01

Serum response factor (SRF) plays a central role in the transcriptional response of mammalian cells to a variety of extracellular signals. It is a key regulator of many cellular early response genes which are believed to be involved in cell growth and differentiation. The mechanism by which SRF activates transcription in response to mitogenic agents has been extensively studied; however, significantly less is known about regulation of the SRF gene itself. Previously, we identified distinct regulatory elements in the SRF promoter that play a role in activation, including a consensus ETS domain binding site, a consensus overlapping Sp/Egr-1 binding site, and two SRF binding sites. We further showed that serum induces SRF by a mechanism that requires an intact SRF binding site, also termed a CArG box. In the present study we demonstrate that in response to stimulation of cells by a purified growth factor, basic fibroblast growth factor (bFGF), the SRF promoter is upregulated by a complex pathway that involves at least two independent mechanisms: a CArG box-independent mechanism that is mediated by an ETS binding site, and a novel CArG box-dependent mechanism that requires both an Sp factor binding site and the CArG motifs for maximal stimulation. Our analysis indicates that the CArG/Sp element activation mechanism is mediated by distinct signaling pathways. The CArG box-dependent component is targeted by a Rho-mediated pathway, and the Sp binding site-dependent component is targeted by a Ras-mediated pathway. Both SRF and bFGF have been implicated in playing an important role in mediating cardiogenesis during development. The implications of our findings for SRF expression during development are discussed. PMID:10330138

Structure of the human factor VIII C2 domain in complex with the 3E6 inhibitory antibody

DOE PAGES

Wuerth, Michelle E.; Cragerud, Rebecca K.; Spiegel, P. Clint

2015-11-24

Blood coagulation factor VIII is a glycoprotein cofactor that is essential for the intrinsic pathway of the blood coagulation cascade. Inhibitory antibodies arise either spontaneously or in response to therapeutic infusion of functional factor VIII into hemophilia A patients, many of which are specific to the factor VIII C2 domain. The immune response is largely parsed into “classical” and “non-classical” inhibitory antibodies, which bind to opposing faces cooperatively. In this study, the 2.61 Å resolution structure of the C2 domain in complex with the antigen-binding fragment of the 3E6 classical inhibitory antibody is reported. The binding interface is largely conservedmore » when aligned with the previously determined structure of the C2 domain in complex with two antibodies simultaneously. Further inspection of the B factors for the C2 domain in various X-ray crystal structures indicates that 3E6 antibody binding decreases the thermal motion behavior of surface loops in the C2 domain on the opposing face, thereby suggesting that cooperative antibody binding is a dynamic effect. Furthermore, understanding the structural nature of the immune response to factor VIII following hemophilia A treatment will help lead to the development of better therapeutic reagents.« less

Smad2-dependent glycosaminoglycan elongation in aortic valve interstitial cells enhances binding of LDL to proteoglycans.

PubMed

Osman, Narin; Grande-Allen, K Jane; Ballinger, Mandy L; Getachew, Robel; Marasco, Silvana; O'Brien, Kevin D; Little, Peter J

2013-01-01

Calcific aortic valve disease is a progressive condition that shares some common pathogenic features with atherosclerosis. Transforming growth factor-β1 is a recognized mediator of atherosclerosis and is expressed in aortic valve lesions. Transforming growth factorβ1 stimulates glycosaminoglycan elongation of proteoglycans that is associated with increased lipid binding. We investigated the presence of transforming growth factor-β1 and downstream signaling intermediates in diseased human aortic valves and the effects of activated transforming growth factor-β1 receptor signaling on aortic valve interstitial cell proteoglycan synthesis and lipid binding as a possible mechanism for the initiation of the early lesion of calcific aortic valve disease. Diseased human aortic valve leaflets demonstrated strong immunohistochemical staining for transforming growth factor-β1 and phosphorylated Smad2/3. In primary porcine aortic valve interstitial cells, Western blots showed that transforming growth factor-β1 stimulated phosphorylation in both the carboxy and linker regions of Smad2/3, which was inhibited by the transforming growth factor-β1 receptor inhibitor SB431542. Gel electrophoresis and size exclusion chromatography demonstrated that SB431542 decreased transforming growth factor-β1-mediated [(35)S]-sulfate incorporation into proteoglycans in a dose-dependent manner. Further, in proteoglycans derived from transforming growth factor-β1-treated valve interstitial cells, gel mobility shift assays demonstrated that inhibition of transforming growth factor-β1 receptor signaling resulted in decreased lipid binding. Classic transforming growth factor-β1 signaling is present in human aortic valves in vivo and contributes to the modification of proteoglycans expressed by valve interstitial cells in vitro. These findings suggest that transforming growth factor-β1 may promote increased low-density lipoprotein binding in the early phases of calcific aortic valve disease. Copyright © 2013 Elsevier Inc. All rights reserved.

A Novel RNA Polymerase I Transcription Initiation Factor, TIF-IE, Commits rRNA Genes by Interaction with TIF-IB, Not by DNA Binding

PubMed Central

Al-Khouri, Anna Maria; Paule, Marvin R.

2002-01-01

In the small, free-living amoeba Acanthamoeba castellanii, rRNA transcription requires, in addition to RNA polymerase I, a single DNA-binding factor, transcription initiation factor IB (TIF-IB). TIF-IB is a multimeric protein that contains TATA-binding protein (TBP) and four TBP-associated factors that are specific for polymerase I transcription. TIF-IB is required for accurate and promoter-specific initiation of rRNA transcription, recruiting and positioning the polymerase on the start site by protein-protein interaction. In A. castellanii, partially purified TIF-IB can form a persistent complex with the ribosomal DNA (rDNA) promoter while homogeneous TIF-IB cannot. An additional factor, TIF-IE, is required along with homogeneous TIF-IB for the formation of a stable complex on the rDNA core promoter. We show that TIF-IE by itself, however, does not bind to the rDNA promoter and thus differs in its mechanism from the upstream binding factor and upstream activating factor, which carry out similar complex-stabilizing functions in vertebrates and yeast, respectively. In addition to its presence in impure TIF-IB, TIF-IE is found in highly purified fractions of polymerase I, with which it associates. Renaturation of polypeptides excised from sodium dodecyl sulfate-polyacrylamide gels showed that a 141-kDa polypeptide possesses all the known activities of TIF-IE. PMID:11784852

A novel RNA polymerase I transcription initiation factor, TIF-IE, commits rRNA genes by interaction with TIF-IB, not by DNA binding.

PubMed

Al-Khouri, Anna Maria; Paule, Marvin R

2002-02-01

In the small, free-living amoeba Acanthamoeba castellanii, rRNA transcription requires, in addition to RNA polymerase I, a single DNA-binding factor, transcription initiation factor IB (TIF-IB). TIF-IB is a multimeric protein that contains TATA-binding protein (TBP) and four TBP-associated factors that are specific for polymerase I transcription. TIF-IB is required for accurate and promoter-specific initiation of rRNA transcription, recruiting and positioning the polymerase on the start site by protein-protein interaction. In A. castellanii, partially purified TIF-IB can form a persistent complex with the ribosomal DNA (rDNA) promoter while homogeneous TIF-IB cannot. An additional factor, TIF-IE, is required along with homogeneous TIF-IB for the formation of a stable complex on the rDNA core promoter. We show that TIF-IE by itself, however, does not bind to the rDNA promoter and thus differs in its mechanism from the upstream binding factor and upstream activating factor, which carry out similar complex-stabilizing functions in vertebrates and yeast, respectively. In addition to its presence in impure TIF-IB, TIF-IE is found in highly purified fractions of polymerase I, with which it associates. Renaturation of polypeptides excised from sodium dodecyl sulfate-polyacrylamide gels showed that a 141-kDa polypeptide possesses all the known activities of TIF-IE.

Mismatch repair factor MSH2-MSH3 binds and alters the conformation of branched DNA structures predicted to form during genetic recombination.

PubMed

Surtees, Jennifer A; Alani, Eric

2006-07-14

Genetic studies in Saccharomyces cerevisiae predict that the mismatch repair (MMR) factor MSH2-MSH3 binds and stabilizes branched recombination intermediates that form during single strand annealing and gene conversion. To test this model, we constructed a series of DNA substrates that are predicted to form during these recombination events. We show in an electrophoretic mobility shift assay that S. cerevisiae MSH2-MSH3 specifically binds branched DNA substrates containing 3' single-stranded DNA and that ATP stimulates its release from these substrates. Chemical footprinting analyses indicate that MSH2-MSH3 specifically binds at the double-strand/single-strand junction of branched substrates, alters its conformation and opens up the junction. Therefore, MSH2-MSH3 binding to its substrates creates a unique nucleoprotein structure that may signal downstream steps in repair that include interactions with MMR and nucleotide excision repair factors.

DNA-binding activity of TNF-{alpha} inducing protein from Helicobacter pylori

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

Kuzuhara, T.; Suganuma, M.; Oka, K.

2007-11-03

Tumor necrosis factor-{alpha} (TNF-{alpha}) inducing protein (Tip{alpha}) is a carcinogenic factor secreted from Helicobacter pylori (H. pylori), mediated through both enhanced expression of TNF-{alpha} and chemokine genes and activation of nuclear factor-{kappa}B. Since Tip{alpha} enters gastric cancer cells, the Tip{alpha} binding molecules in the cells should be investigated. The direct DNA-binding activity of Tip{alpha} was observed by pull down assay using single- and double-stranded genomic DNA cellulose. The surface plasmon resonance assay, indicating an association between Tip{alpha} and DNA, revealed that the affinity of Tip{alpha} for (dGdC)10 is 2400 times stronger than that of del-Tip{alpha}, an inactive Tip{alpha}. This suggestsmore » a strong correlation between DNA-binding activity and carcinogenic activity of Tip{alpha}. And the DNA-binding activity of Tip{alpha} was first demonstrated with a molecule secreted from H. pylori.« less

Retinoblastoma-binding Protein 4-regulated Classical Nuclear Transport Is Involved in Cellular Senescence*

PubMed Central

Tsujii, Akira; Miyamoto, Yoichi; Moriyama, Tetsuji; Tsuchiya, Yuko; Obuse, Chikashi; Mizuguchi, Kenji; Oka, Masahiro; Yoneda, Yoshihiro

2015-01-01

Nucleocytoplasmic trafficking is a fundamental cellular process in eukaryotic cells. Here, we demonstrated that retinoblastoma-binding protein 4 (RBBP4) functions as a novel regulatory factor to increase the efficiency of importin α/β-mediated nuclear import. RBBP4 accelerates the release of importin β1 from importin α via competitive binding to the importin β-binding domain of importin α in the presence of RanGTP. Therefore, it facilitates importin α/β-mediated nuclear import. We showed that the importin α/β pathway is down-regulated in replicative senescent cells, concomitant with a decrease in RBBP4 level. Knockdown of RBBP4 caused both suppression of nuclear transport and induction of cellular senescence. This is the first report to identify a factor that competes with importin β1 to bind to importin α, and it demonstrates that the loss of this factor can trigger cellular senescence. PMID:26491019

JASPAR 2016: a major expansion and update of the open-access database of transcription factor binding profiles.

PubMed

Mathelier, Anthony; Fornes, Oriol; Arenillas, David J; Chen, Chih-Yu; Denay, Grégoire; Lee, Jessica; Shi, Wenqiang; Shyr, Casper; Tan, Ge; Worsley-Hunt, Rebecca; Zhang, Allen W; Parcy, François; Lenhard, Boris; Sandelin, Albin; Wasserman, Wyeth W

2016-01-04

JASPAR (http://jaspar.genereg.net) is an open-access database storing curated, non-redundant transcription factor (TF) binding profiles representing transcription factor binding preferences as position frequency matrices for multiple species in six taxonomic groups. For this 2016 release, we expanded the JASPAR CORE collection with 494 new TF binding profiles (315 in vertebrates, 11 in nematodes, 3 in insects, 1 in fungi and 164 in plants) and updated 59 profiles (58 in vertebrates and 1 in fungi). The introduced profiles represent an 83% expansion and 10% update when compared to the previous release. We updated the structural annotation of the TF DNA binding domains (DBDs) following a published hierarchical structural classification. In addition, we introduced 130 transcription factor flexible models trained on ChIP-seq data for vertebrates, which capture dinucleotide dependencies within TF binding sites. This new JASPAR release is accompanied by a new web tool to infer JASPAR TF binding profiles recognized by a given TF protein sequence. Moreover, we provide the users with a Ruby module complementing the JASPAR API to ease programmatic access and use of the JASPAR collection of profiles. Finally, we provide the JASPAR2016 R/Bioconductor data package with the data of this release. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Let's get specific: the relationship between specificity and affinity.

PubMed

Eaton, B E; Gold, L; Zichi, D A

1995-10-01

The factors that lead to high-affinity binding are a good fit between the surfaces of the two molecules in their ground state and charge complementarity. Exactly the same factors give high specificity for a target. We argue that selection for high-affinity binding automatically leads to highly specific binding. This principle can be used to simplify screening approaches aimed at generating useful drugs.

Nitric oxide alterations following acute ductal constriction in the fetal lamb: a role for superoxide

PubMed Central

Hsu, Jong-Hau; Oishi, Peter; Wiseman, Dean A.; Hou, Yali; Chikovani, Omar; Datar, Sanjeev; Sajti, Eniko; Johengen, Michael J.; Harmon, Cynthia; Black, Stephen M.

2010-01-01

Acute partial compression of the fetal ductus arteriosus (DA) results in an initial abrupt increase in pulmonary blood flow (PBF), which is followed by a significant reduction in PBF to baseline values over the ensuing 2–4 h. We have previously demonstrated that this potent vasoconstricting response is due, in part, to an endothelin-1 (ET-1)-mediated decrease in nitric oxide synthase (NOS) activity. In addition, in vitro data demonstrate that ET-1 increases superoxide levels in pulmonary arterial smooth muscle cells and that oxidative stress alters NOS activity. Therefore, the objectives of this study were to determine the potential role of superoxide in the alterations of hemodynamics and NOS activity following acute ductal constriction in the late-gestation fetal lamb. Eighteen anesthetized near-term fetal lambs were instrumented, and a lung biopsy was performed. After a 48-h recovery, acute constriction of the DA was performed by inflating a vascular occluder. Polyethylene glycol-superoxide dismutase (PEG-SOD; 1,000–1,500 units/kg, n = 7) or PEG-alone (vehicle control group, n = 5) was injected into the pulmonary artery before ductal constriction. Six animals had a sham operation. In PEG-alone-treated lambs, acute ductal constriction rapidly decreased pulmonary vascular resistance (PVR) by 88%. However, by 4 h, PVR returned to preconstriction baseline. This vasoconstriction was associated with an increase in lung superoxide levels (82%), a decrease in total NOS activity (50%), and an increase in P-eNOS-Thr495 (52%) (P < 0.05). PEG-SOD prevented the increase of superoxide after ductal constriction, attenuated the vasoconstriction, preserved NOS activity, and increased P-eNOS Ser1177 (307%, P < 0.05). Sham procedure induced no changes. These data suggest that an acute decrease in NOS activity that is mediated, in part, by increased superoxide levels, and alterations in the phosphorylation status of the endothelial NOS isoform, underlie the pulmonary vascular response to acute ductal constriction. PMID:20363848

Tracking urban carbon footprints from production and consumption perspectives

NASA Astrophysics Data System (ADS)

Lin, Jianyi; Hu, Yuanchao; Cui, Shenghui; Kang, Jiefeng; Ramaswami, Anu

2015-05-01

Cities are hotspots of socio-economic activities and greenhouse gas emissions. The aim of this study was to extend the research range of the urban carbon footprint (CF) to cover emissions embodied in products traded among regions and intra-city sectors. Using Xiamen City as a study case, the total urban-related emissions were evaluated, and the carbon flows among regions and intra-city sectors were tracked. Then five urban CF accountings were evaluated, including purely geographic accounting (PGA), community-wide infrastructure footprint (CIF), and consumption-based footprint (CBF) methods, as well as the newly defined production-based footprint (PBF) and purely production footprint (PPF). Research results show that the total urban-related emissions of Xiamen City in 2010 were 55.2 Mt CO2e/y, of which total carbon flow among regions or intra-city sectors accounted for 53.7 Mt CO2e/y. Within the total carbon flow, import and export respectively accounted for 59 and 65%, highlighting the importance of emissions embodied in trade. By regional trade balance, North America and Europe were the largest net carbon exported-to regions, and Mainland China and Taiwan the largest net carbon imported-from regions. Among intra-sector carbon flows, manufacturing was the largest emission-consuming sector of the total urban carbon flow, accounting for 77.4, and 98% of carbon export was through industrial products trade. By the PBF, PPF, CIF, PGA and CBF methods, the urban CFs were respectively 53.7 Mt CO2e/y, 44.8 Mt CO2e/y, 28.4 Mt CO2e/y, 23.7 Mt CO2e/y, and 19.0 Mt CO2e/y, so all of the other four CFs were higher than the CBF. All of these results indicate that urban carbon mitigation must consider the supply chain management of imported goods, the production efficiency within the city, the consumption patterns of urban consumers, and the responsibility of the ultimate consumers outside the city.

Household costs and time to seek care for pregnancy related complications: The role of results-based financing

PubMed Central

Chinkhumba, Jobiba; De Allegri, Manuela; Mazalale, Jacob; Brenner, Stephan; Mathanga, Don; Muula, Adamson S.; Robberstad, Bjarne

2017-01-01

Results-based financing (RBF) schemes–including performance based financing (PBF) and conditional cash transfers (CCT)-are increasingly being used to encourage use and improve quality of institutional health care for pregnant women in order to reduce maternal and neonatal mortality in low-income countries. While there is emerging evidence that RBF can increase service use and quality, little is known on the impact of RBF on costs and time to seek care for obstetric complications, although the two represent important dimensions of access. We conducted this study to fill the existing gap in knowledge by investigating the impact of RBF (PBF+CCT) on household costs and time to seek care for obstetric complications in four districts in Malawi. The analysis included data on 2,219 women with obstetric complications from three waves of a population-based survey conducted at baseline in 2013 and repeated in 2014(midline) and 2015(endline). Using a before and after approach with controls, we applied generalized linear models to study the association between RBF and household costs and time to seek care. Results indicated that receipt of RBF was associated with a significant reduction in the expected mean time to seek care for women experiencing an obstetric complication. Relative to non-RBF, time to seek care in RBF areas decreased by 27.3% (95%CI: 28.4–25.9) at midline and 34.2% (95%CI: 37.8–30.4) at endline. No substantial change in household costs was observed. We conclude that the reduced time to seek care is a manifestation of RBF induced quality improvements, prompting faster decisions on care seeking at household level. Our results suggest RBF may contribute to timely emergency care seeking and thus ultimately reduce maternal and neonatal mortality in beneficiary populations. PMID:28934320

Heparin-binding epidermal growth factor-like growth factor promotes neuroblastoma differentiation.

PubMed

Gaviglio, Angela L; Knelson, Erik H; Blobe, Gerard C

2017-05-01

High-risk neuroblastoma is characterized by undifferentiated neuroblasts and low schwannian stroma content. The tumor stroma contributes to the suppression of tumor growth by releasing soluble factors that promote neuroblast differentiation. Here we identify heparin-binding epidermal growth factor-like growth factor (HBEGF) as a potent prodifferentiating factor in neuroblastoma. HBEGF mRNA expression is decreased in human neuroblastoma tumors compared with benign tumors, with loss correlating with decreased survival. HBEGF protein is expressed only in stromal compartments of human neuroblastoma specimens, with tissue from high-stage disease containing very little stroma or HBEGF expression. In 3 human neuroblastoma cell lines (SK-N-AS, SK-N-BE2, and SH-SY5Y), soluble HBEGF is sufficient to promote neuroblast differentiation and decrease proliferation. Heparan sulfate proteoglycans and heparin derivatives further enhance HBEGF-induced differentiation by forming a complex with the epidermal growth factor receptor, leading to activation of the ERK1/2 and STAT3 pathways and up-regulation of the inhibitor of DNA binding transcription factor. These data support a role for loss of HBEGF in the neuroblastoma tumor microenvironment in neuroblastoma pathogenesis.-Gaviglio, A. L., Knelson, E. H., Blobe, G. C. Heparin-binding epidermal growth factor-like growth factor promotes neuroblastoma differentiation. © FASEB.

Prediction of Binding Energy of Keap1 Interaction Motifs in the Nrf2 Antioxidant Pathway and Design of Potential High-Affinity Peptides.

PubMed

Karttunen, Mikko; Choy, Wing-Yiu; Cino, Elio A

2018-06-07

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor and principal regulator of the antioxidant pathway. The Kelch domain of Kelch-like ECH-associated protein 1 (Keap1) binds to motifs in the N-terminal region of Nrf2, promoting its degradation. There is interest in developing ligands that can compete with Nrf2 for binding to Kelch, thereby activating its transcriptional activities and increasing antioxidant levels. Using experimental Δ G bind values of Kelch-binding motifs determined previously, a revised hydrophobicity-based model was developed for estimating Δ G bind from amino acid sequence and applied to rank potential uncharacterized Kelch-binding motifs identified from interaction databases and BLAST searches. Model predictions and molecular dynamics (MD) simulations suggested that full-length MAD2A binds Kelch more favorably than a high-affinity 20-mer Nrf2 E78P peptide, but that the motif in isolation is not a particularly strong binder. Endeavoring to develop shorter peptides for activating Nrf2, new designs were created based on the E78P peptide, some of which showed considerable propensity to form binding-competent structures in MD, and were predicted to interact with Kelch more favorably than the E78P peptide. The peptides could be promising new ligands for enhancing the oxidative stress response.

TFBSshape: a motif database for DNA shape features of transcription factor binding sites.

PubMed

Yang, Lin; Zhou, Tianyin; Dror, Iris; Mathelier, Anthony; Wasserman, Wyeth W; Gordân, Raluca; Rohs, Remo

2014-01-01

Transcription factor binding sites (TFBSs) are most commonly characterized by the nucleotide preferences at each position of the DNA target. Whereas these sequence motifs are quite accurate descriptions of DNA binding specificities of transcription factors (TFs), proteins recognize DNA as a three-dimensional object. DNA structural features refine the description of TF binding specificities and provide mechanistic insights into protein-DNA recognition. Existing motif databases contain extensive nucleotide sequences identified in binding experiments based on their selection by a TF. To utilize DNA shape information when analysing the DNA binding specificities of TFs, we developed a new tool, the TFBSshape database (available at http://rohslab.cmb.usc.edu/TFBSshape/), for calculating DNA structural features from nucleotide sequences provided by motif databases. The TFBSshape database can be used to generate heat maps and quantitative data for DNA structural features (i.e., minor groove width, roll, propeller twist and helix twist) for 739 TF datasets from 23 different species derived from the motif databases JASPAR and UniPROBE. As demonstrated for the basic helix-loop-helix and homeodomain TF families, our TFBSshape database can be used to compare, qualitatively and quantitatively, the DNA binding specificities of closely related TFs and, thus, uncover differential DNA binding specificities that are not apparent from nucleotide sequence alone.

TFBSshape: a motif database for DNA shape features of transcription factor binding sites

PubMed Central

Yang, Lin; Zhou, Tianyin; Dror, Iris; Mathelier, Anthony; Wasserman, Wyeth W.; Gordân, Raluca; Rohs, Remo

2014-01-01

Transcription factor binding sites (TFBSs) are most commonly characterized by the nucleotide preferences at each position of the DNA target. Whereas these sequence motifs are quite accurate descriptions of DNA binding specificities of transcription factors (TFs), proteins recognize DNA as a three-dimensional object. DNA structural features refine the description of TF binding specificities and provide mechanistic insights into protein–DNA recognition. Existing motif databases contain extensive nucleotide sequences identified in binding experiments based on their selection by a TF. To utilize DNA shape information when analysing the DNA binding specificities of TFs, we developed a new tool, the TFBSshape database (available at http://rohslab.cmb.usc.edu/TFBSshape/), for calculating DNA structural features from nucleotide sequences provided by motif databases. The TFBSshape database can be used to generate heat maps and quantitative data for DNA structural features (i.e., minor groove width, roll, propeller twist and helix twist) for 739 TF datasets from 23 different species derived from the motif databases JASPAR and UniPROBE. As demonstrated for the basic helix-loop-helix and homeodomain TF families, our TFBSshape database can be used to compare, qualitatively and quantitatively, the DNA binding specificities of closely related TFs and, thus, uncover differential DNA binding specificities that are not apparent from nucleotide sequence alone. PMID:24214955

Localized frustration and binding-induced conformational change in recognition of 5S RNA by TFIIIA zinc finger.

PubMed

Tan, Cheng; Li, Wenfei; Wang, Wei

2013-12-19

Protein TFIIIA is composed of nine tandemly arranged Cys2His2 zinc fingers. It can bind either to the 5S RNA gene as a transcription factor or to the 5S RNA transcript as a chaperone. Although structural and biochemical data provided valuable information on the recognition between the TFIIIIA and the 5S DNA/RNA, the involved conformational motions and energetic factors contributing to the binding affinity and specificity remain unclear. In this work, we conducted MD simulations and MM/GBSA calculations to investigate the binding-induced conformational changes in the recognition of the 5S RNA by the central three zinc fingers of TFIIIA and the energetic factors that influence the binding affinity and specificity at an atomistic level. Our results revealed drastic interdomain conformational changes between these three zinc fingers, involving the exposure/burial of several crucial DNA/RNA binding residues, which can be related to the competition between DNA and RNA for the binding of TFIIIA. We also showed that the specific recognition between finger 4/finger 6 and the 5S RNA introduces frustrations to the nonspecific interactions between finger 5 and the 5S RNA, which may be important to achieve optimal binding affinity and specificity.

The basic leucine zipper domain of c-Jun functions in transcriptional activation through interaction with the N terminus of human TATA-binding protein-associated factor-1 (human TAF(II)250).

PubMed

Lively, Tricia N; Nguyen, Tuan N; Galasinski, Shelly K; Goodrich, James A

2004-06-18

We previously reported that c-Jun binds directly to the N-terminal 163 amino acids of Homo sapiens TATA-binding protein-associated factor-1 (hsTAF1), causing a derepression of transcription factor IID (TFIID)-driven transcription (Lively, T. N., Ferguson, H. A., Galasinski, S. K., Seto, A. G., and Goodrich, J. A. (2001) J. Biol. Chem. 276, 25582-25588). This region of hsTAF1 binds TATA-binding protein to repress TFIID DNA binding and transcription. Here we show that the basic leucine zipper domain of c-Jun, which allows for DNA binding and homodimerization, is necessary and sufficient for interaction with hsTAF1. Interestingly, the isolated basic leucine zipper domain of c-Jun was able to derepress TFIID-directed basal transcription in vitro. Moreover, when the N-terminal region of hsTAF1 was added to in vitro transcription reactions and overexpressed in cells, it blocked c-Jun activation. c-Fos, another basic leucine zipper protein, did not interact with hsTAF1, but c-Fos/c-Jun heterodimers did bind the N terminus of hsTAF1. Our studies show that, in addition to dimerization and DNA binding, the well characterized basic leucine zipper domain of c-Jun functions in transcriptional activation by binding to the N terminus of hsTAF1 to derepress transcription.

The VBP and a1/EBP leucine zipper factors bind overlapping subsets of avian retroviral long terminal repeat CCAAT/enhancer elements.

PubMed

Smith, C D; Baglia, L A; Curristin, S M; Ruddell, A

1994-10-01

Two long terminal repeat (LTR) enhancer-binding proteins which may regulate high rates of avian leukosis virus (ALV) LTR-enhanced c-myc transcription during bursal lymphomagenesis have been identified (A. Ruddell, M. Linial, and M. Groudine, Mol. Cell. Biol. 9:5660-5668, 1989). The genes encoding the a1/EBP and a3/EBP binding factors were cloned by expression screening of a lambda gt11 cDNA library from chicken bursal lymphoma cells. The a1/EBP cDNA encodes a novel leucine zipper transcription factor (W. Bowers and A. Ruddell, J. Virol. 66:6578-6586, 1992). The partial a3/EBP cDNA clone encodes amino acids 84 to 313 of vitellogenin gene-binding protein (VBP), a leucine zipper factor that binds the avian vitellogenin II gene promoter (S. Iyer, D. Davis, and J. Burch, Mol. Cell. Biol. 11:4863-4875, 1991). Multiple VBP mRNAs are expressed in B cells in a pattern identical to that previously observed for VBP in other cell types. The LTR-binding activities of VBP, a1/EBP, and B-cell nuclear extract protein were compared and mapped by gel shift, DNase I footprinting, and methylation interference assays. The purified VBP and a1/EBP bacterial fusion proteins bind overlapping but distinct subsets of CCAAT/enhancer elements in the closely related ALV and Rous sarcoma virus (RSV) LTR enhancers. Protein binding to these CCAAT/enhancer elements accounts for most of the labile LTR enhancer-binding activity observed in B-cell nuclear extracts. VBP and a1/EBP could mediate the high rates of ALV and RSV LTR-enhanced transcription in bursal lymphoma cells and many other cell types.

Exploring the utility of organo-polyoxometalate hybrids to inhibit SOX transcription factors

PubMed Central

2014-01-01

Background SOX transcription factors constitute an attractive target class for intervention with small molecules as they play a prominent role in the field of regenerative biomedicine and cancer biology. However, rationally engineering specific inhibitors that interfere with transcription factor DNA interfaces continues to be a monumental challenge in the field of transcription factor chemical biology. Polyoxometalates (POMs) are inorganic compounds that were previously shown to target the high-mobility group (HMG) of SOX proteins at nanomolar concentrations. In continuation of this work, we carried out an assessment of the selectivity of a panel of newly synthesized organo-polyoxometalate hybrids in targeting different transcription factor families to enable the usage of polyoxometalates as specific SOX transcription factor drugs. Results The residual DNA-binding activities of 15 different transcription factors were measured after treatment with a panel of diverse polyoxometalates. Polyoxometalates belonging to the Dawson structural class were found to be more potent inhibitors than the Keggin class. Further, organically modified Dawson polyoxometalates were found to be the most potent in inhibiting transcription factor DNA binding activity. The size of the polyoxometalates and its derivitization were found to be the key determinants of their potency. Conclusion Polyoxometalates are highly potent, nanomolar range inhibitors of the DNA binding activity of the Sox-HMG family. However, binding assays involving a limited subset of structurally diverse polyoxometalates revealed a low selectivity profile against different transcription factor families. Further progress in achieving selectivity and deciphering structure-activity relationship of POMs require the identification of POM binding sites on transcription factors using elaborate approaches like X-ray crystallography and multidimensional NMR. In summary, our report reaffirms that transcription factors are challenging molecular architectures and that future polyoxometalate chemistry must consider further modification strategies, to address the substantial challenges involved in achieving target selectivity. PMID:25678957

Molecular coevolution of mammalian ribosomal gene terminator sequences and the transcription termination factor TTF-I.

PubMed Central

Evers, R; Grummt, I

1995-01-01

Both the DNA elements and the nuclear factors that direct termination of ribosomal gene transcription exhibit species-specific differences. Even between mammals--e.g., human and mouse--the termination signals are not identical and the respective transcription termination factors (TTFs) which bind to the terminator sequence are not fully interchangeable. To elucidate the molecular basis for this species-specificity, we have cloned TTF-I from human and mouse cells and compared their structural and functional properties. Recombinant TTF-I exhibits species-specific DNA binding and terminates transcription both in cell-free transcription assays and in transfection experiments. Chimeric constructs of mouse TTF-I and human TTF-I reveal that the major determinant for species-specific DNA binding resides within the C terminus of TTF-I. Replacing 31 C-terminal amino acids of mouse TTF-I with the homologous human sequences relaxes the DNA-binding specificity and, as a consequence, allows the chimeric factor to bind the human terminator sequence and to specifically stop rDNA transcription. Images Fig. 2 Fig. 3 Fig. 4 PMID:7597036

Nuclear factor ETF specifically stimulates transcription from promoters without a TATA box.

PubMed

Kageyama, R; Merlino, G T; Pastan, I

1989-09-15

Transcription factor ETF stimulates the expression of the epidermal growth factor receptor (EGFR) gene which does not have a TATA box in the promoter region. Here, we show that ETF recognizes various GC-rich sequences including stretches of deoxycytidine or deoxyguanosine residues and GC boxes with similar affinities. ETF also binds to TATA boxes but with a lower affinity. ETF stimulated in vitro transcription from several promoters without TATA boxes but had little or no effect on TATA box-containing promoters even though they had strong ETF-binding sites. These inactive ETF-binding sites became functional when placed upstream of the EGFR promoter whose own ETF-binding sites were removed. Furthermore, when a TATA box was introduced into the EGFR promoter, the responsiveness to ETF was abolished. These results indicate that ETF is a specific transcription factor for promoters which do not contain TATA elements.

Heparin-binding epidermal growth factor-like growth factor promotes neuroblastoma differentiation

PubMed Central

Gaviglio, Angela L.; Knelson, Erik H.; Blobe, Gerard C.

2017-01-01

High-risk neuroblastoma is characterized by undifferentiated neuroblasts and low schwannian stroma content. The tumor stroma contributes to the suppression of tumor growth by releasing soluble factors that promote neuroblast differentiation. Here we identify heparin-binding epidermal growth factor–like growth factor (HBEGF) as a potent prodifferentiating factor in neuroblastoma. HBEGF mRNA expression is decreased in human neuroblastoma tumors compared with benign tumors, with loss correlating with decreased survival. HBEGF protein is expressed only in stromal compartments of human neuroblastoma specimens, with tissue from high-stage disease containing very little stroma or HBEGF expression. In 3 human neuroblastoma cell lines (SK-N-AS, SK-N-BE2, and SH-SY5Y), soluble HBEGF is sufficient to promote neuroblast differentiation and decrease proliferation. Heparan sulfate proteoglycans and heparin derivatives further enhance HBEGF-induced differentiation by forming a complex with the epidermal growth factor receptor, leading to activation of the ERK1/2 and STAT3 pathways and up-regulation of the inhibitor of DNA binding transcription factor. These data support a role for loss of HBEGF in the neuroblastoma tumor microenvironment in neuroblastoma pathogenesis.—Gaviglio, A. L., Knelson, E. H., Blobe, G. C. Heparin-binding epidermal growth factor-like growth factor promotes neuroblastoma differentiation. PMID:28174207

Role of Fibroblast Growth Factor Binding Protein-1 in Mammary Development and Tumorigenesis

DTIC Science & Technology

2008-10-01

AD_________________ AWARD NUMBER: W81XWH-06-1-0763 TITLE: Role of Fibroblast Growth Factor ...Role of Fibroblast Growth Factor Binding Protein-1 in Mammary Development and Tumorigenesis 5b. GRANT NUMBER W81XWH-06-1-0763 5c. PROGRAM...Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Fibroblast growth factors (FGFs) are vital modulators of development as well as

EBP1 is a novel E2F target gene regulated by transforming growth factor-β.

PubMed

Judah, David; Chang, Wing Y; Dagnino, Lina

2010-11-10

Regulation of gene expression requires transcription factor binding to specific DNA elements, and a large body of work has focused on the identification of such sequences. However, it is becoming increasingly clear that eukaryotic transcription factors can exhibit widespread, nonfunctional binding to genomic DNA sites. Conversely, some of these proteins, such as E2F, can also modulate gene expression by binding to non-consensus elements. E2F comprises a family of transcription factors that play key roles in a wide variety of cellular functions, including survival, differentiation, activation during tissue regeneration, metabolism, and proliferation. E2F factors bind to the Erb3-binding protein 1 (EBP1) promoter in live cells. We now show that E2F binding to the EBP1 promoter occurs through two tandem DNA elements that do not conform to typical consensus E2F motifs. Exogenously expressed E2F1 activates EBP1 reporters lacking one, but not both sites, suggesting a degree of redundancy under certain conditions. E2F1 increases the levels of endogenous EBP1 mRNA in breast carcinoma and other transformed cell lines. In contrast, in non-transformed primary epidermal keratinocytes, E2F, together with the retinoblastoma family of proteins, appears to be involved in decreasing EBP1 mRNA abundance in response to growth inhibition by transforming growth factor-β1. Thus, E2F is likely a central coordinator of multiple responses that culminate in regulation of EBP1 gene expression, and which may vary depending on cell type and context.

Comparing anterior and posterior Hox complex formation reveals guidelines for predicting cis-regulatory elements

PubMed Central

Uhl, Juli D.; Cook, Tiffany A.; Gebelein, Brian

2010-01-01

Hox transcription factors specify numerous cell fates along the anterior-posterior axis by regulating the expression of downstream target genes. While expression analysis has uncovered large numbers of de-regulated genes in cells with altered Hox activity, determining which are direct versus indirect targets has remained a significant challenge. Here, we characterize the DNA binding activity of Hox transcription factor complexes on eight experimentally verified cis-regulatory elements. Hox factors regulate the activity of each element by forming protein complexes with two cofactor proteins, Extradenticle (Exd) and Homothorax (Hth). Using comparative DNA binding assays, we found that a number of flexible arrangements of Hox, Exd, and Hth binding sites mediate cooperative transcription factor complexes. Moreover, analysis of a Distal-less regulatory element (DMXR) that is repressed by abdominal Hox factors revealed that suboptimal binding sites can be combined to form high affinity transcription complexes. Lastly, we determined that the anterior Hox factors are more dependent upon Exd and Hth for complex formation than posterior Hox factors. Based upon these findings, we suggest a general set of guidelines to serve as a basis for designing bioinformatics algorithms aimed at identifying Hox regulatory elements using the wealth of recently sequenced genomes. PMID:20398649

A gravimetric analysis of protein-oligosaccharide interactions.

PubMed

Rudd, T; Gallagher, J T; Ron, D; Nichols, R J; Fernig, D G

2003-04-01

Interactions between an immobilized, heparin-derived octasaccharide and growth factors have been observed using a quartz crystal microbalance-dissipation (QCM-D). This device can measure the amount of growth factors binding to the octasaccharide surface and also the change of dissipation of the surface. Dissipation is a measure of how the adhered material 'damps' the surface vibrations. The octasaccharides were anchored through their reducing ends by the intermediary of the alkanethiol molecule, which covalently binds to the crystal surface through the thiol group. As expected, heparin sulphate binding growth factors bound to the octasaccharide, but the change in mass of growth factor bound per unit change in dissipation is different for the different growth factors. Suggesting that the structures of the various growth factor-octasaccharide complexes are different, therefore, indicates that the change in dissipation can give insights into the structure, orientation and packing of the oligosaccharide-growth factor complexes.

Downstream promoter interactions of TFIID TAFs facilitate transcription reinitiation

PubMed Central

Joo, Yoo Jin; Ficarro, Scott B.; Soares, Luis M.; Chun, Yujin; Marto, Jarrod A.; Buratowski, Stephen

2017-01-01

TFIID binds promoter DNA to recruit RNA polymerase II and other basal factors for transcription. Although the TATA-binding protein (TBP) subunit of TFIID is necessary and sufficient for in vitro transcription, the TBP-associated factor (TAF) subunits recognize downstream promoter elements, act as coactivators, and interact with nucleosomes. In yeast nuclear extracts, transcription induces stable TAF binding to downstream promoter DNA, promoting subsequent activator-independent transcription reinitiation. In vivo, promoter responses to TAF mutations correlate with the level of downstream, rather than overall, Taf1 cross-linking. We propose a new model in which TAFs function as reinitiation factors, accounting for the differential responses of promoters to various transcription factor mutations. PMID:29203645

Characterization of diverse subvariants of the meningococcal factor H (fH) binding protein for their ability to bind fH, to mediate serum resistance, and to induce bactericidal antibodies.

PubMed

Seib, Kate L; Brunelli, Brunella; Brogioni, Barbara; Palumbo, Emmanuelle; Bambini, Stefania; Muzzi, Alessandro; DiMarcello, Federica; Marchi, Sara; van der Ende, Arie; Aricó, Beatrice; Savino, Silvana; Scarselli, Maria; Comanducci, Maurizio; Rappuoli, Rino; Giuliani, Marzia M; Pizza, Mariagrazia

2011-02-01

Neisseria meningitidis is a commensal of the human nasopharynx but is also a major cause of septicemia and meningitis. The meningococcal factor H binding protein (fHbp) binds human factor H (fH), enabling downregulation of complement activation on the bacterial surface. fHbp is a component of two serogroup B meningococcal vaccines currently in clinical development. Here we characterize 12 fHbp subvariants for their level of surface exposure and ability to bind fH, to mediate serum resistance, and to induce bactericidal antibodies. Flow cytometry and Western analysis revealed that all strains examined expressed fHbp on their surface to different extents and bound fH in an fHbp-dependent manner. However, differences in fH binding did not always correlate with the level of fHbp expression, indicating that this is not the only factor affecting the amount of fH bound. To overcome the issue of strain variability in fHbp expression, the MC58ΔfHbp strain was genetically engineered to express different subvariants from a constitutive heterologous promoter. These recombinant strains were characterized for fH binding, and the data confirmed that each subvariant binds different levels of fH. Surface plasmon resonance revealed differences in the stability of the fHbp-fH complexes that ranged over 2 orders of magnitude, indicating that differences in residues between and within variant groups can influence fH binding. Interestingly, the level of survival in human sera of recombinant MC58 strains expressing diverse subvariants did not correlate with the level of fH binding, suggesting that the interaction of fHbp with fH is not the only function of fHbp that influences serum resistance. Furthermore, cross-reactive bactericidal activity was seen within each variant group, although the degree of activity varied, suggesting that amino acid differences within each variant group influence the bactericidal antibody response.

Legume receptors perceive the rhizobial lipochitin oligosaccharide signal molecules by direct binding

PubMed Central

Broghammer, Angelique; Krusell, Lene; Blaise, Mickaël; Sauer, Jørgen; Sullivan, John T.; Maolanon, Nicolai; Vinther, Maria; Lorentzen, Andrea; Madsen, Esben B.; Jensen, Knud J.; Roepstorff, Peter; Thirup, Søren; Ronson, Clive W.; Thygesen, Mikkel B.; Stougaard, Jens

2012-01-01

Lipochitin oligosaccharides called Nod factors function as primary rhizobial signal molecules triggering legumes to develop new plant organs: root nodules that host the bacteria as nitrogen-fixing bacteroids. Here, we show that the Lotus japonicus Nod factor receptor 5 (NFR5) and Nod factor receptor 1 (NFR1) bind Nod factor directly at high-affinity binding sites. Both receptor proteins were posttranslationally processed when expressed as fusion proteins and extracted from purified membrane fractions of Nicotiana benthamiana or Arabidopsis thaliana. The N-terminal signal peptides were cleaved, and NFR1 protein retained its in vitro kinase activity. Processing of NFR5 protein was characterized by determining the N-glycosylation patterns of the ectodomain. Two different glycan structures with identical composition, Man3XylFucGlcNAc4, were identified by mass spectrometry and located at amino acid positions N68 and N198. Receptor–ligand interaction was measured by using ligands that were labeled or immobilized by application of chemoselective chemistry at the anomeric center. High-affinity ligand binding was demonstrated with both solid-phase and free solution techniques. The Kd values obtained for Nod factor binding were in the nanomolar range and comparable to the concentration range sufficient for biological activity. Structure-dependent ligand specificity was shown by using chitin oligosaccharides. Taken together, our results suggest that ligand recognition through direct ligand binding is a key step in the receptor-mediated activation mechanism leading to root nodule development in legumes. PMID:22859506

[Multiply upconversion emission in oxyfluoride ceramics].

PubMed

Xiao, Si-guo; Yang, Xiao-liang; Liu, Zhen-wei

2003-02-01

Oxyfluoride ceramics with the host composition of SiO2 and PbF2 have been prepared. X-ray diffraction analysis of the ceramics revealed that fluoride type beta-PbF2 solid solution regions are precipitated in the glass matrix. Rare earth ions in the beta-PbF2 solid solution show highly efficient upconversion performance due to the very small multi-phonon relaxation rates. Eight upconversion emission bands whose central wavelength are 846, 803, 665, 549, 523, 487, 456 and 411 nm have been observed when the sample was excited with 930 nm diode light. Four possible energy transfer processes between Er3+ and Yb3+ cause the electronic population of high energy level of Er3+ and realize the abound upconversion luminescence bands.

Cryptic MCAT enhancer regulation in fibroblasts and smooth muscle cells. Suppression of TEF-1 mediated activation by the single-stranded DNA-binding proteins, Pur alpha, Pur beta, and MSY1.

PubMed

Carlini, Leslie E; Getz, Michael J; Strauch, Arthur R; Kelm, Robert J

2002-03-08

An asymmetric polypurine-polypyrimidine cis-element located in the 5' region of the mouse vascular smooth muscle alpha-actin gene serves as a binding site for multiple proteins with specific affinity for either single- or double-stranded DNA. Here, we test the hypothesis that single-stranded DNA-binding proteins are responsible for preventing a cryptic MCAT enhancer centered within this element from cooperating with a nearby serum response factor-interacting CArG motif to trans-activate the minimal promoter in fibroblasts and smooth muscle cells. DNA binding studies revealed that the core MCAT sequence mediates binding of transcription enhancer factor-1 to the double-stranded polypurine-polypyrimidine element while flanking nucleotides account for interaction of Pur alpha and Pur beta with the purine-rich strand and MSY1 with the complementary pyrimidine-rich strand. Mutations that selectively impaired high affinity single-stranded DNA binding by fibroblast or smooth muscle cell-derived Pur alpha, Pur beta, and MSY1 in vitro, released the cryptic MCAT enhancer from repression in transfected cells. Additional experiments indicated that Pur alpha, Pur beta, and MSY1 also interact specifically, albeit weakly, with double-stranded DNA and with transcription enhancer factor-1. These results are consistent with two plausible models of cryptic MCAT enhancer regulation by Pur alpha, Pur beta, and MSY1 involving either competitive single-stranded DNA binding or masking of MCAT-bound transcription enhancer factor-1.

A resource for characterizing genome-wide binding and putative target genes of transcription factors expressed during secondary growth and wood formation in Populus

Treesearch

Lijun Liu; Trevor Ramsay; Matthew S. Zinkgraf; David Sundell; Nathaniel Robert Street; Vladimir Filkov; Andrew Groover

2015-01-01

Identifying transcription factor target genes is essential for modeling the transcriptional networks underlying developmental processes. Here we report a chromatin immunoprecipitation sequencing (ChIP-seq) resource consisting of genome-wide binding regions and associated putative target genes for four Populus homeodomain transcription factors...

FGF growth factor analogs

DOEpatents

Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY; Takahashi, Kazuyuki [Germantown, MD

2012-07-24

The present invention provides a fibroblast growth factor heparin-binding analog of the formula: ##STR00001## where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, X, Y and Z are as defined, pharmaceutical compositions, coating compositions and medical devices including the fibroblast growth factor heparin-binding analog of the foregoing formula, and methods and uses thereof.

Direct interaction of SRY-related protein SOX9 and steroidogenic factor 1 regulates transcription of the human anti-Müllerian hormone gene.

PubMed

De Santa Barbara, P; Bonneaud, N; Boizet, B; Desclozeaux, M; Moniot, B; Sudbeck, P; Scherer, G; Poulat, F; Berta, P

1998-11-01

For proper male sexual differentiation, anti-Müllerian hormone (AMH) must be tightly regulated during embryonic development to promote regression of the Müllerian duct. However, the molecular mechanisms specifying the onset of AMH in male mammals are not yet clearly defined. A DNA-binding element for the steroidogenic factor 1 (SF-1), a member of the orphan nuclear receptor family, located in the AMH proximal promoter has recently been characterized and demonstrated as being essential for AMH gene activation. However, the requirement for a specific promoter environment for SF-1 activation as well as the presence of conserved cis DNA-binding elements in the AMH promoter suggest that SF-1 is a member of a combinatorial protein-protein and protein-DNA complex. In this study, we demonstrate that the canonical SOX-binding site within the human AMH proximal promoter can bind the transcription factor SOX9, a Sertoli cell factor closely associated with Sertoli cell differentiation and AMH expression. Transfection studies with COS-7 cells revealed that SOX9 can cooperate with SF-1 in this activation process. In vitro and in vivo protein-binding studies indicate that SOX9 and SF-1 interact directly via the SOX9 DNA-binding domain and the SF-1 C-terminal region, respectively. We propose that the two transcription factors SOX9 and SF-1 could both be involved in the expression of the AMH gene, in part as a result of their respective binding to the AMH promoter and in part because of their ability to interact with each other. Our work thus identifies SOX9 as an interaction partner of SF-1 that could be involved in the Sertoli cell-specific expression of AMH during embryogenesis.

Direct Interaction of SRY-Related Protein SOX9 and Steroidogenic Factor 1 Regulates Transcription of the Human Anti-Müllerian Hormone Gene

PubMed Central

De Santa Barbara, Pascal; Bonneaud, Nathalie; Boizet, Brigitte; Desclozeaux, Marion; Moniot, Brigitte; Sudbeck, Peter; Scherer, Gerd; Poulat, Francis; Berta, Philippe

1998-01-01

For proper male sexual differentiation, anti-Müllerian hormone (AMH) must be tightly regulated during embryonic development to promote regression of the Müllerian duct. However, the molecular mechanisms specifying the onset of AMH in male mammals are not yet clearly defined. A DNA-binding element for the steroidogenic factor 1 (SF-1), a member of the orphan nuclear receptor family, located in the AMH proximal promoter has recently been characterized and demonstrated as being essential for AMH gene activation. However, the requirement for a specific promoter environment for SF-1 activation as well as the presence of conserved cis DNA-binding elements in the AMH promoter suggest that SF-1 is a member of a combinatorial protein-protein and protein-DNA complex. In this study, we demonstrate that the canonical SOX-binding site within the human AMH proximal promoter can bind the transcription factor SOX9, a Sertoli cell factor closely associated with Sertoli cell differentiation and AMH expression. Transfection studies with COS-7 cells revealed that SOX9 can cooperate with SF-1 in this activation process. In vitro and in vivo protein-binding studies indicate that SOX9 and SF-1 interact directly via the SOX9 DNA-binding domain and the SF-1 C-terminal region, respectively. We propose that the two transcription factors SOX9 and SF-1 could both be involved in the expression of the AMH gene, in part as a result of their respective binding to the AMH promoter and in part because of their ability to interact with each other. Our work thus identifies SOX9 as an interaction partner of SF-1 that could be involved in the Sertoli cell-specific expression of AMH during embryogenesis. PMID:9774680

Differential mechanisms of binding of anti-sigma factors Escherichia coli Rsd and bacteriophage T4 AsiA to E. coli RNA polymerase lead to diverse physiological consequences.

PubMed

Sharma, Umender K; Chatterji, Dipankar

2008-05-01

Anti-sigma factors Escherichia coli Rsd and bacteriophage T4 AsiA bind to the essential housekeeping sigma factor, sigma(70), of E. coli. Though both factors are known to interact with the C-terminal region of sigma(70), the physiological consequences of these interactions are very different. This study was undertaken for the purpose of deciphering the mechanisms by which E. coli Rsd and bacteriophage T4 AsiA inhibit or modulate the activity of E. coli RNA polymerase, which leads to the inhibition of E. coli cell growth to different amounts. It was found that AsiA is the more potent inhibitor of in vivo transcription and thus causes higher inhibition of E. coli cell growth. Measurements of affinity constants by surface plasmon resonance experiments showed that Rsd and AsiA bind to sigma(70) with similar affinity. Data obtained from in vivo and in vitro binding experiments clearly demonstrated that the major difference between AsiA and Rsd is the ability of AsiA to form a stable ternary complex with RNA polymerase. The binding patterns of AsiA and Rsd with sigma(70) studied by using the yeast two-hybrid system revealed that region 4 of sigma(70) is involved in binding to both of these anti-sigma factors; however, Rsd interacts with other regions of sigma(70) as well. Taken together, these results suggest that the higher inhibition of E. coli growth by AsiA expression is probably due to the ability of the AsiA protein to trap the holoenzyme RNA polymerase rather than its higher binding affinity to sigma(70).

Differential Mechanisms of Binding of Anti-Sigma Factors Escherichia coli Rsd and Bacteriophage T4 AsiA to E. coli RNA Polymerase Lead to Diverse Physiological Consequences▿

PubMed Central

Sharma, Umender K.; Chatterji, Dipankar

2008-01-01

Anti-sigma factors Escherichia coli Rsd and bacteriophage T4 AsiA bind to the essential housekeeping sigma factor, σ70, of E. coli. Though both factors are known to interact with the C-terminal region of σ70, the physiological consequences of these interactions are very different. This study was undertaken for the purpose of deciphering the mechanisms by which E. coli Rsd and bacteriophage T4 AsiA inhibit or modulate the activity of E. coli RNA polymerase, which leads to the inhibition of E. coli cell growth to different amounts. It was found that AsiA is the more potent inhibitor of in vivo transcription and thus causes higher inhibition of E. coli cell growth. Measurements of affinity constants by surface plasmon resonance experiments showed that Rsd and AsiA bind to σ70 with similar affinity. Data obtained from in vivo and in vitro binding experiments clearly demonstrated that the major difference between AsiA and Rsd is the ability of AsiA to form a stable ternary complex with RNA polymerase. The binding patterns of AsiA and Rsd with σ70 studied by using the yeast two-hybrid system revealed that region 4 of σ70 is involved in binding to both of these anti-sigma factors; however, Rsd interacts with other regions of σ70 as well. Taken together, these results suggest that the higher inhibition of E. coli growth by AsiA expression is probably due to the ability of the AsiA protein to trap the holoenzyme RNA polymerase rather than its higher binding affinity to σ70. PMID:18359804

Binding of serum response factor to cystic fibrosis transmembrane conductance regulator CArG-like elements, as a new potential CFTR transcriptional regulation pathway

PubMed Central

René, Céline; Taulan, Magali; Iral, Florence; Doudement, Julien; L'Honoré, Aurore; Gerbon, Catherine; Demaille, Jacques; Claustres, Mireille; Romey, Marie-Catherine

2005-01-01

CFTR expression is tightly controlled by a complex network of ubiquitous and tissue-specific cis-elements and trans-factors. To better understand mechanisms that regulate transcription of CFTR, we examined transcription factors that specifically bind a CFTR CArG-like motif we have previously shown to modulate CFTR expression. Gel mobility shift assays and chromatin immunoprecipitation analyses demonstrated the CFTR CArG-like motif binds serum response factor both in vitro and in vivo. Transient co-transfections with various SRF expression vector, including dominant-negative forms and small interfering RNA, demonstrated that SRF significantly increases CFTR transcriptional activity in bronchial epithelial cells. Mutagenesis studies suggested that in addition to SRF other co-factors, such as Yin Yang 1 (YY1) previously shown to bind the CFTR promoter, are potentially involved in the CFTR regulation. Here, we show that functional interplay between SRF and YY1 might provide interesting perspectives to further characterize the underlying molecular mechanism of the basal CFTR transcriptional activity. Furthermore, the identification of multiple CArG binding sites in highly conserved CFTR untranslated regions, which form specific SRF complexes, provides direct evidence for a considerable role of SRF in the CFTR transcriptional regulation into specialized epithelial lung cells. PMID:16170155

PRISM offers a comprehensive genomic approach to transcription factor function prediction

PubMed Central

Wenger, Aaron M.; Clarke, Shoa L.; Guturu, Harendra; Chen, Jenny; Schaar, Bruce T.; McLean, Cory Y.; Bejerano, Gill

2013-01-01

The human genome encodes 1500–2000 different transcription factors (TFs). ChIP-seq is revealing the global binding profiles of a fraction of TFs in a fraction of their biological contexts. These data show that the majority of TFs bind directly next to a large number of context-relevant target genes, that most binding is distal, and that binding is context specific. Because of the effort and cost involved, ChIP-seq is seldom used in search of novel TF function. Such exploration is instead done using expression perturbation and genetic screens. Here we propose a comprehensive computational framework for transcription factor function prediction. We curate 332 high-quality nonredundant TF binding motifs that represent all major DNA binding domains, and improve cross-species conserved binding site prediction to obtain 3.3 million conserved, mostly distal, binding site predictions. We combine these with 2.4 million facts about all human and mouse gene functions, in a novel statistical framework, in search of enrichments of particular motifs next to groups of target genes of particular functions. Rigorous parameter tuning and a harsh null are used to minimize false positives. Our novel PRISM (predicting regulatory information from single motifs) approach obtains 2543 TF function predictions in a large variety of contexts, at a false discovery rate of 16%. The predictions are highly enriched for validated TF roles, and 45 of 67 (67%) tested binding site regions in five different contexts act as enhancers in functionally matched cells. PMID:23382538

Selective binding and oligomerization of the murine granulocyte colony-stimulating factor receptor by a low molecular weight, nonpeptidyl ligand.

PubMed

Doyle, Michael L; Tian, Shin-Shay; Miller, Stephen G; Kessler, Linda; Baker, Audrey E; Brigham-Burke, Michael R; Dillon, Susan B; Duffy, Kevin J; Keenan, Richard M; Lehr, Ruth; Rosen, Jon; Schneeweis, Lumelle A; Trill, John; Young, Peter R; Luengo, Juan I; Lamb, Peter

2003-03-14

Granulocyte colony-stimulating factor regulates neutrophil production by binding to a specific receptor, the granulocyte colony-stimulating factor receptor, expressed on cells of the granulocytic lineage. Recombinant forms of granulocyte colony-stimulating factor are used clinically to treat neutropenias. As part of an effort to develop granulocyte colony-stimulating factor mimics with the potential for oral bioavailability, we previously identified a nonpeptidyl small molecule (SB-247464) that selectively activates murine granulocyte colony-stimulating factor signal transduction pathways and promotes neutrophil formation in vivo. To elucidate the mechanism of action of SB-247464, a series of cell-based and biochemical assays were performed. The activity of SB-247464 is strictly dependent on the presence of zinc ions. Titration microcalorimetry experiments using a soluble murine granulocyte colony-stimulating factor receptor construct show that SB-247464 binds to the extracellular domain of the receptor in a zinc ion-dependent manner. Analytical ultracentrifugation studies demonstrate that SB-247464 induces self-association of the N-terminal three-domain fragment in a manner that is consistent with dimerization. SB-247464 induces internalization of granulocyte colony-stimulating factor receptor on intact cells, consistent with a mechanism involving receptor oligomerization. These data show that small nonpeptidyl compounds are capable of selectively binding and inducing productive oligomerization of cytokine receptors.

The Fn14 cytoplasmic tail binds tumour-necrosis-factor-receptor-associated factors 1, 2, 3 and 5 and mediates nuclear factor-kappaB activation.

PubMed Central

Brown, Sharron A N; Richards, Christine M; Hanscom, Heather N; Feng, Sheau-Line Y; Winkles, Jeffrey A

2003-01-01

Fn14 is a growth-factor-inducible immediate-early-response gene encoding a 102-amino-acid type I transmembrane protein. The human Fn14 protein was recently identified as a cell-surface receptor for the tumour necrosis factor (TNF) superfamily member named TWEAK (TNF-like weak inducer of apoptosis). In the present paper, we report that the human TWEAK extracellular domain can also bind the murine Fn14 protein. Furthermore, site-specific mutagenesis and directed yeast two-hybrid interaction assays revealed that the TNFR-associated factor (TRAF) 1, 2, 3 and 5 adaptor molecules bind the murine Fn14 cytoplasmic tail at an overlapping, but non-identical, amino acid sequence motif. We also found that TWEAK treatment of quiescent NIH 3T3 cells stimulates inhibitory kappaBalpha phosphorylation and transcriptional activation of a nuclear factor-kappaB (NF-kappaB) enhancer/luciferase reporter construct. Fn14 overexpression in transiently transfected NIH 3T3 cells also promotes NF-kappaB activation, and this cellular response requires an intact TRAF binding site. These results indicate that Fn14 is a functional TWEAK receptor that can associate with four distinct TRAF family members and stimulate the NF-kappaB transcription factor signalling pathway. PMID:12529173

Comprehensive meta-analysis of Signal Transducers and Activators of Transcription (STAT) genomic binding patterns discerns cell-specific cis-regulatory modules

PubMed Central

2013-01-01

Background Cytokine-activated transcription factors from the STAT (Signal Transducers and Activators of Transcription) family control common and context-specific genetic programs. It is not clear to what extent cell-specific features determine the binding capacity of seven STAT members and to what degree they share genetic targets. Molecular insight into the biology of STATs was gained from a meta-analysis of 29 available ChIP-seq data sets covering genome-wide occupancy of STATs 1, 3, 4, 5A, 5B and 6 in several cell types. Results We determined that the genomic binding capacity of STATs is primarily defined by the cell type and to a lesser extent by individual family members. For example, the overlap of shared binding sites between STATs 3 and 5 in T cells is greater than that between STAT5 in T cells and non-T cells. Even for the top 1,000 highly enriched STAT binding sites, ~15% of STAT5 binding sites in mouse female liver are shared by other STATs in different cell types while in T cells ~90% of STAT5 binding sites are co-occupied by STAT3, STAT4 and STAT6. In addition, we identified 116 cis-regulatory modules (CRM), which are recognized by all STAT members across cell types defining a common JAK-STAT signature. Lastly, in liver STAT5 binding significantly coincides with binding of the cell-specific transcription factors HNF4A, FOXA1 and FOXA2 and is associated with cell-type specific gene transcription. Conclusions Our results suggest that genomic binding of STATs is primarily determined by the cell type and further specificity is achieved in part by juxtaposed binding of cell-specific transcription factors. PMID:23324445

Mutant protein of recombinant human granulocyte colony-stimulating factor for receptor binding assay.

PubMed

Watanabe, M; Fukamachi, H; Uzumaki, H; Kabaya, K; Tsumura, H; Ishikawa, M; Matsuki, S; Kusaka, M

1991-05-15

A new mutant protein of recombinant human granulocyte colony-stimulating factor (rhG-CSF) was produced for the studies on receptors for human G-CSF. The mutant protein [(Tyr1, Tyr3]rhG-CSF), the biological activity of which was almost equal to that of rhG-CSF, was prepared by the replacement of threonine-1 and leucine-3 of rhG-CSF with tyrosine. The radioiodinated preparation of the mutant protein showed high specific radioactivity and retained full biological activity for at least 3 weeks. The binding capacity of the radioiodinated ligand was compared with that of [35S]rhG-CSF. Both radiolabeled ligands showed specific binding to murine bone marrow cells. Unlabeled rhG-CSF and human G-CSF purified from the culture supernatant of the human bladder carcinoma cell line 5637 equally competed for the binding of labeled rhG-CSFs in a dose-dependent manner, demonstrating that the sugar moiety of human G-CSF made no contribution to the binding of human G-CSF to target cells. In contrast, all other colony-stimulating factors and lymphokines examined did not affect the binding. Scatchard analysis of the specific binding of both labeled ligands revealed a single class of binding site with an apparent dissociation constant (Kd) of 20-30 pM and 100-200 maximal binding sites per cell. These data indicate that the radioiodinated preparation of the mutant protein binds the same specific receptor with the same affinity as [35S]rhG-CSF. The labeled mutant protein also showed specific binding to human circulating neutrophils.(ABSTRACT TRUNCATED AT 250 WORDS)

RNA binding specificity of Ebola virus transcription factor VP30.

PubMed

Schlereth, Julia; Grünweller, Arnold; Biedenkopf, Nadine; Becker, Stephan; Hartmann, Roland K

2016-09-01

The transcription factor VP30 of the non-segmented RNA negative strand Ebola virus balances viral transcription and replication. Here, we comprehensively studied RNA binding by VP30. Using a novel VP30:RNA electrophoretic mobility shift assay, we tested truncated variants of 2 potential natural RNA substrates of VP30 - the genomic Ebola viral 3'-leader region and its complementary antigenomic counterpart (each ∼155 nt in length) - and a series of other non-viral RNAs. Based on oligonucleotide interference, the major VP30 binding region on the genomic 3'-leader substrate was assigned to the internal expanded single-stranded region (∼ nt 125-80). Best binding to VP30 was obtained with ssRNAs of optimally ∼ 40 nt and mixed base composition; underrepresentation of purines or pyrimidines was tolerated, but homopolymeric sequences impaired binding. A stem-loop structure, particularly at the 3'-end or positioned internally, supports stable binding to VP30. In contrast, dsRNA or RNAs exposing large internal loops flanked by entirely helical arms on both sides are not bound. Introduction of a 5´-Cap(0) structure impaired VP30 binding. Also, ssDNAs bind substantially weaker than isosequential ssRNAs and heparin competes with RNA for binding to VP30, indicating that ribose 2'-hydroxyls and electrostatic contacts of the phosphate groups contribute to the formation of VP30:RNA complexes. Our results indicate a rather relaxed RNA binding specificity of filoviral VP30, which largely differs from that of the functionally related transcription factor of the Paramyxoviridae which binds to ssRNAs as short as 13 nt with a preference for oligo(A) sequences.

Characterization of insulin-like growth factor I receptor on human erythrocytes.

PubMed

Hizuka, N; Takano, K; Tanaka, I; Honda, N; Tsushima, T; Shizume, K

1985-12-01

[125I]Insulin-like growth factor I (IGF-I) specifically bound to erythrocytes; the binding was saturable, and time and temperature dependent. Steady state binding was reached at 16 h at 4 C, and specific binding averaged 14.3 +/- 0.7% (+/- SEM) at a concentration of 3.6 X 10(9) cells/ml in seven normal subjects. [125I]IGF-I binding to the cells was displaced by unlabeled IGF-I in a dose-dependent manner. Scatchard analysis indicated a linear plot, and Ka and number of binding sites/cell were 1.43 +/- 0.07 X 10(9) M-1 and 20.7 +/- 2.2, respectively. Compared to IGF-I, the relative potencies of multiplication-stimulating activity and insulin for displacing [125I]IGF-I binding were 20% and 1%, respectively. [125I]IGF-I binding to erythrocytes from patients with acromegaly was lower than binding to cells from pituitary dwarfs. An inverse correlation between plasma IGF-I level and the number of IGF-I-binding sites per cell was found (r = -0.75; P less than 0.005). These results demonstrate that [125I]IGF-I binding to erythrocytes can be used for clinical measurement of the IGF-I receptor.

Crystal structure of the Rasputin NTF2-like domain from Drosophila melanogaster

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

Vognsen, Tina, E-mail: tv@farma.ku.dk; Kristensen, Ole, E-mail: ok@farma.ku.dk

2012-03-30

Highlights: Black-Right-Pointing-Pointer The crystal structure of the NTF2-like domain of Rasputin protein is presented. Black-Right-Pointing-Pointer Differences to known ligand binding sites of nuclear transport factor 2 are discussed. Black-Right-Pointing-Pointer A new ligand binding site for the Rasputin and G3BP proteins is proposed. -- Abstract: The crystal structure of the NTF2-like domain of the Drosophila homolog of Ras GTPase SH3 Binding Protein (G3BP), Rasputin, was determined at 2.7 A resolution. The overall structure is highly similar to nuclear transport factor 2: It is a homodimer comprised of a {beta}-sheet and three {alpha}-helices forming a cone-like shape. However, known binding sites formore » RanGDP and FxFG containing peptides show electrostatic and steric differences compared to nuclear transport factor 2. A HEPES molecule bound in the structure suggests a new, and possibly physiologically relevant, ligand binding site.« less

T-lymphoid, megakaryocyte, and granulocyte development are sensitive to decreases in CBFβ dosage.

PubMed Central

Talebian, Laleh; Li, Zhe; Guo, Yalin; Gaudet, Justin; Speck, Maren E.; Sugiyama, Daisuke; Kaur, Prabhjot; Pear, Warren S.; Maillard, Ivan; Speck, Nancy A.

2007-01-01

The family of core-binding factors includes the DNA-binding subunits Runx1-3 and their common non–DNA-binding partner CBFβ. We examined the collective role of core-binding factors in hematopoiesis with a hypomorphic Cbfb allelic series. Reducing CBFβ levels by 3- or 6-fold caused abnormalities in bone development, megakaryocytes, granulocytes, and T cells. T-cell development was very sensitive to an incremental reduction of CBFβ levels: mature thymocytes were decreased in number upon a 3-fold reduction in CBFβ levels, and were virtually absent when CBFβ levels were 6-fold lower. Partially penetrant consecutive differentiation blocks were found among early T-lineage progenitors within the CD4−CD8− double-negative 1 and downstream double-negative 2 thymocyte subsets. Our data define a critical CBFβ threshold for normal T-cell development, and situate an essential role for core-binding factors during the earliest stages of T-cell development. PMID:16940420

Genome-wide identification of novel expression signatures reveal distinct patterns and prevalence of binding motifs for p53, nuclear factor-κB and other signal transcription factors in head and neck squamous cell carcinoma

PubMed Central

Yan, Bin; Yang, Xinping; Lee, Tin-Lap; Friedman, Jay; Tang, Jun; Van Waes, Carter; Chen, Zhong

2007-01-01

Background Differentially expressed gene profiles have previously been observed among pathologically defined cancers by microarray technologies, including head and neck squamous cell carcinomas (HNSCCs). However, the molecular expression signatures and transcriptional regulatory controls that underlie the heterogeneity in HNSCCs are not well defined. Results Genome-wide cDNA microarray profiling of ten HNSCC cell lines revealed novel gene expression signatures that distinguished cancer cell subsets associated with p53 status. Three major clusters of over-expressed genes (A to C) were defined through hierarchical clustering, Gene Ontology, and statistical modeling. The promoters of genes in these clusters exhibited different patterns and prevalence of transcription factor binding sites for p53, nuclear factor-κB (NF-κB), activator protein (AP)-1, signal transducer and activator of transcription (STAT)3 and early growth response (EGR)1, as compared with the frequency in vertebrate promoters. Cluster A genes involved in chromatin structure and function exhibited enrichment for p53 and decreased AP-1 binding sites, whereas clusters B and C, containing cytokine and antiapoptotic genes, exhibited a significant increase in prevalence of NF-κB binding sites. An increase in STAT3 and EGR1 binding sites was distributed among the over-expressed clusters. Novel regulatory modules containing p53 or NF-κB concomitant with other transcription factor binding motifs were identified, and experimental data supported the predicted transcriptional regulation and binding activity. Conclusion The transcription factors p53, NF-κB, and AP-1 may be important determinants of the heterogeneous pattern of gene expression, whereas STAT3 and EGR1 may broadly enhance gene expression in HNSCCs. Defining these novel gene signatures and regulatory mechanisms will be important for establishing new molecular classifications and subtyping, which in turn will promote development of targeted therapeutics for HNSCC. PMID:17498291

Effect of PDGF-B aptamer on PDGFRβ/PDGF-B interaction: Molecular dynamics study.

PubMed

Vu, Cong Quang; Rotkrua, Pichayanoot; Soontornworajit, Boonchoy; Tantirungrotechai, Yuthana

2018-06-01

PDGFRβ/PDGF-B interaction plays a role in angiogenesis, and is mandatory in wound healing and cancer treatment. It has been reported that the PDGF-B aptamer was able to bind to PDGF-B, thus regulating the angiogenesis. However, the binding interaction between the aptamer and the growth factor, including the binding sites, has not been well investigated. This study applied a molecular dynamics (MD) simulation to investigate the aptamer-growth factor interaction in the presence or absence of a receptor (PDGFRβ). Characterization of the structure of an aptamer-growth factor complex revealed binding sites from each section in the complex. Upon the complex formation, PDGF-B and its aptamer exhibited less flexibility in their molecular movement, as indicated by the minimum values of RMSD, RMSF, loop-to-loop distance, and the summation of PCA eigenvalues. Our study of residue pairwise interaction demonstrated that the binding interaction was mainly contributed by electrostatic interaction between the positively-charged amino acid and the negatively-charged phosphate backbone. The role of the PDGF-B aptamer in PDGFRβ/PDGF-B interaction was also investigated. We demonstrated that the stability of the Apt-PDGF-B complex could prevent the presence of a competitor, of PDGFRβ, interrupting the binding process. Because the aptamer was capable of binding with PDGF-B, and blocking the growth factor from the PDGFRβ, it could down regulate the consequent signaling pathway. We provide evidence that the PDGF-BB aptamer is a promising molecule for regulation of angiogenesis. The MD study provides a molecular understanding to modification of the aptamer binding interaction, which could be used in a number of medical applications. Copyright © 2018 Elsevier Inc. All rights reserved.

p48 Activates a UV-Damaged-DNA Binding Factor and Is Defective in Xeroderma Pigmentosum Group E Cells That Lack Binding Activity

PubMed Central

Hwang, Byung Joon; Toering, Stephanie; Francke, Uta; Chu, Gilbert

1998-01-01

A subset of xeroderma pigmentosum (XP) group E cells lack a factor that binds to DNA damaged by UV radiation. This factor can be purified to homogeneity as p125, a 125-kDa polypeptide. However, when cDNA encoding p125 is translated in vitro, only a small fraction binds to UV-damaged DNA, suggesting that a second factor is required for the activation of p125. We discovered that most hamster cell lines expressed inactive p125, which was activated in somatic cell hybrids containing human chromosome region 11p11.2-11cen. This region excluded p125 but included p48, which encodes a 48-kDa polypeptide known to copurify with p125 under some conditions. Expression of human p48 activated p125 binding in hamster cells and increased p125 binding in human cells. No such effects were observed from expression of p48 containing single amino acid substitutions from XP group E cells that lacked binding activity, demonstrating that the p48 gene is defective in those cells. Activation of p125 occurred by a “hit-and-run” mechanism, since the presence of p48 was not required for subsequent binding. Nevertheless, p48 was capable of forming a complex with p125 either bound to UV-damaged DNA or in free solution. It is notable that hamster cells fail to efficiently repair cyclobutane pyrimidine dimers in nontranscribed DNA and fail to express p48, which contains a WD motif with homology to proteins that reorganize chromatin. We propose that p48 plays a role in repairing lesions that would otherwise remain inaccessible in nontranscribed chromatin. PMID:9632823

Differences in DNA Binding Specificity of Floral Homeotic Protein Complexes Predict Organ-Specific Target Genes.

PubMed

Smaczniak, Cezary; Muiño, Jose M; Chen, Dijun; Angenent, Gerco C; Kaufmann, Kerstin

2017-08-01

Floral organ identities in plants are specified by the combinatorial action of homeotic master regulatory transcription factors. However, how these factors achieve their regulatory specificities is still largely unclear. Genome-wide in vivo DNA binding data show that homeotic MADS domain proteins recognize partly distinct genomic regions, suggesting that DNA binding specificity contributes to functional differences of homeotic protein complexes. We used in vitro systematic evolution of ligands by exponential enrichment followed by high-throughput DNA sequencing (SELEX-seq) on several floral MADS domain protein homo- and heterodimers to measure their DNA binding specificities. We show that specification of reproductive organs is associated with distinct binding preferences of a complex formed by SEPALLATA3 and AGAMOUS. Binding specificity is further modulated by different binding site spacing preferences. Combination of SELEX-seq and genome-wide DNA binding data allows differentiation between targets in specification of reproductive versus perianth organs in the flower. We validate the importance of DNA binding specificity for organ-specific gene regulation by modulating promoter activity through targeted mutagenesis. Our study shows that intrafamily protein interactions affect DNA binding specificity of floral MADS domain proteins. Differential DNA binding of MADS domain protein complexes plays a role in the specificity of target gene regulation. © 2017 American Society of Plant Biologists. All rights reserved.

Dehydration responsive element binding transcription factors and their applications for the engineering of stress tolerance.

PubMed

Agarwal, Pradeep K; Gupta, Kapil; Lopato, Sergiy; Agarwal, Parinita

2017-04-01

Dehydration responsive element binding (DREB) factors or CRT element binding factors (CBFs) are members of the AP2/ERF family, which comprises a large number of stress-responsive regulatory genes. This review traverses almost two decades of research, from the discovery of DREB/CBF factors to their optimization for application in plant biotechnology. In this review, we describe (i) the discovery, classification, structure, and evolution of DREB genes and proteins; (ii) induction of DREB genes by abiotic stresses and involvement of their products in stress responses; (iii) protein structure and DNA binding selectivity of different groups of DREB proteins; (iv) post-transcriptional and post-translational mechanisms of DREB transcription factor (TF) regulation; and (v) physical and/or functional interaction of DREB TFs with other proteins during plant stress responses. We also discuss existing issues in applications of DREB TFs for engineering of enhanced stress tolerance and improved performance under stress of transgenic crop plants. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

A small-molecule inhibitor of the aberrant transcription factor CBFβ-SMMHC delays leukemia in mice

PubMed Central

Illendula, Anuradha; Pulikkan, John A.; Zong, Hongliang; Grembecka, Jolanta; Xue, Liting; Sen, Siddhartha; Zhou, Yunpeng; Boulton, Adam; Kuntimaddi, Aravinda; Gao, Yan; Rajewski, Roger A.; Guzman, Monica L.; Castilla, Lucio H.; Bushweller, John H.

2015-01-01

Acute myeloid leukemia (AML) is the most common form of adult leukemia. The transcription factor fusion CBFβ-SMMHC (core binding factor β and the smooth-muscle myosin heavy chain), expressed in AML with the chromosome inversion inv(16)(p13q22), outcompetes wild-type CBFβ for binding to the transcription factor RUNX1, deregulates RUNX1 activity in hematopoiesis, and induces AML. Current inv(16) AML treatment with nonselective cytotoxic chemotherapy results in a good initial response but limited long-term survival. Here, we report the development of a protein-protein interaction inhibitor, AI-10-49, that selectively binds to CBFβ-SMMHC and disrupts its binding to RUNX1. AI-10-49 restores RUNX1 transcriptional activity, displays favorable pharmacokinetics, and delays leukemia progression in mice. Treatment of primary inv(16) AML patient blasts with AI-10-49 triggers selective cell death. These data suggest that direct inhibition of the oncogenic CBFβ-SMMHC fusion protein may be an effective therapeutic approach for inv(16) AML, and they provide support for transcription factor targeted therapy in other cancers. PMID:25678665

Depletion of elongation initiation factor 4E binding proteins by CRISPR/Cas9 genome editing enhances antiviral response in porcine cells

USDA-ARS?s Scientific Manuscript database

Type I interferons (IFN) are key mediators of the innate antiviral response in mammalian cells. Elongation initiation factor 4E binding proteins (4E-BPs) are translational controllers of interferon regulatory factor 7 (IRF7), the master regulator of IFN transcription. The role of 4EBPs in the negat...

Modulation of gene expression via overlapping binding sites exerted by ZNF143, Notch1 and THAP11

PubMed Central

Ngondo-Mbongo, Richard Patryk; Myslinski, Evelyne; Aster, Jon C.; Carbon, Philippe

2013-01-01

ZNF143 is a zinc-finger protein involved in the transcriptional regulation of both coding and non-coding genes from polymerase II and III promoters. Our study deciphers the genome-wide regulatory role of ZNF143 in relation with the two previously unrelated transcription factors Notch1/ICN1 and thanatos-associated protein 11 (THAP11) in several human and murine cells. We show that two distinct motifs, SBS1 and SBS2, are associated to ZNF143-binding events in promoters of >3000 genes. Without co-occupation, these sites are also bound by Notch1/ICN1 in T-lymphoblastic leukaemia cells as well as by THAP11, a factor involved in self-renewal of embryonic stem cells. We present evidence that ICN1 binding overlaps with ZNF143 binding events at the SBS1 and SBS2 motifs, whereas the overlap occurs only at SBS2 for THAP11. We demonstrate that the three factors modulate expression of common target genes through the mutually exclusive occupation of overlapping binding sites. The model we propose predicts that the binding competition between the three factors controls biological processes such as rapid cell growth of both neoplastic and stem cells. Overall, our study establishes a novel relationship between ZNF143, THAP11 and ICN1 and reveals important insights into ZNF143-mediated gene regulation. PMID:23408857

Structure and Biophysics of CBFβ/RUNX and Its Translocation Products.

PubMed

Tahirov, Tahir H; Bushweller, John

2017-01-01

The core binding factor (CBF) transcription factor is somewhat unique in that it is composed of a DNA binding RUNX subunit (RUNX1, 2, or 3) and a non-DNA binding CBFβ subunit, which modulates RUNX protein activity by modulating the auto-inhibition of the RUNX subunits. Since the discovery of this fascinating transcription factor more than 20 years ago, there has been a robust effort to characterize the structure as well as the biochemical properties of CBF. More recently, these efforts have also extended to the fusion proteins that arise from the subunits of CBF in leukemia. This chapter highlights the work of numerous labs which has provided a detailed understanding of the structure and function of this transcription factor and its fusion proteins.

Cooperative DNA binding and sequence discrimination by the Opaque2 bZIP factor.

PubMed Central

Yunes, J A; Vettore, A L; da Silva, M J; Leite, A; Arruda, P

1998-01-01

The maize Opaque2 (O2) protein is a basic leucine zipper transcription factor that controls the expression of distinct classes of endosperm genes through the recognition of different cis-acting elements in their promoters. The O2 target region in the promoter of the alpha-coixin gene was analyzed in detail and shown to comprise two closely adjacent binding sites, named O2u and O2d, which are related in sequence to the GCN4 binding site. Quantitative DNase footprint analysis indicated that O2 binding to alpha-coixin target sites is best described by a cooperative model. Transient expression assays showed that the two adjacent sites act synergistically. This synergy is mediated in part by cooperative DNA binding. In tobacco protoplasts, O2 binding at the O2u site is more important for enhancer activity than is binding at the O2d site, suggesting that the architecture of the O2-DNA complex is important for interaction with the transcriptional machinery. PMID:9811800

Cooperative DNA binding and sequence discrimination by the Opaque2 bZIP factor.

PubMed

Yunes, J A; Vettore, A L; da Silva, M J; Leite, A; Arruda, P

1998-11-01

The maize Opaque2 (O2) protein is a basic leucine zipper transcription factor that controls the expression of distinct classes of endosperm genes through the recognition of different cis-acting elements in their promoters. The O2 target region in the promoter of the alpha-coixin gene was analyzed in detail and shown to comprise two closely adjacent binding sites, named O2u and O2d, which are related in sequence to the GCN4 binding site. Quantitative DNase footprint analysis indicated that O2 binding to alpha-coixin target sites is best described by a cooperative model. Transient expression assays showed that the two adjacent sites act synergistically. This synergy is mediated in part by cooperative DNA binding. In tobacco protoplasts, O2 binding at the O2u site is more important for enhancer activity than is binding at the O2d site, suggesting that the architecture of the O2-DNA complex is important for interaction with the transcriptional machinery.

Binding and Translocation of Termination Factor Rho Studied at the Single-Molecule Level

PubMed Central

Koslover, Daniel J.; Fazal, Furqan M.; Mooney, Rachel A.; Landick, Robert; Block, Steven M.

2012-01-01

Rho termination factor is an essential hexameric helicase responsible for terminating 20–50% of all mRNA synthesis in E. coli. We used single- molecule force spectroscopy to investigate Rho-RNA binding interactions at the Rho- utilization (rut) site of the ? tR1 terminator. Our results are consistent with Rho complexes adopting two states, one that binds 57 ±2 nucleotides of RNA across all six of the Rho primary binding sites, and another that binds 85 ±2 nucleotides at the six primary sites plus a single secondary site situated at the center of the hexamer. The single-molecule data serve to establish that Rho translocates 5′-to-3′ towards RNA polymerase (RNAP) by a tethered-tracking mechanism, looping out the intervening RNA between the rut site and RNAP. These findings lead to a general model for Rho binding and translocation, and establish a novel experimental approach that should facilitate additional single- molecule studies of RNA-binding proteins. PMID:22885804

Clinical relevance of drug binding to plasma proteins

NASA Astrophysics Data System (ADS)

Ascenzi, Paolo; Fanali, Gabriella; Fasano, Mauro; Pallottini, Valentina; Trezza, Viviana

2014-12-01

Binding to plasma proteins highly influences drug efficacy, distribution, and disposition. Serum albumin, the most abundant protein in plasma, is a monomeric multi-domain macromolecule that displays an extraordinary ligand binding capacity, providing a depot and carrier for many endogenous and exogenous compounds, such as fatty acids and most acidic drugs. α-1-Acid glycoprotein, the second main plasma protein, is a glycoprotein physiologically involved in the acute phase reaction and is the main carrier for basic and neutral drugs. High- and low-density lipoproteins play a limited role in drug binding and are natural drug delivery system only for few lipophilic drugs or lipid-based formulations. Several factors influence drug binding to plasma proteins, such as pathological conditions, concurrent administration of drugs, sex, and age. Any of these factors, in turn, influences drug efficacy and toxicity. Here, biochemical, biomedical, and biotechnological aspects of drug binding to plasma proteins are reviewed.

Receptor binding sites for atrial natriuretic factor are expressed by brown adipose tissue

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

Bacay, A.C.; Mantyh, C.R.; Vigna, S.R.

1988-09-01

To explore the possibility that atrial natriuretic factor (ANF) is involved in thermoregulation we used quantitative receptor autoradiography and homogenate receptor binding assays to identify ANF bindings sites in neonatal rat and sheep brown adipose tissue, respectively. Using quantitative receptor autoradiography were were able to localize high levels of specific binding sites for {sup 125}I-rat ANF in neonatal rat brown adipose tissue. Homogenate binding assays on sheep brown fat demonstrated that the radioligand was binding to the membrane fraction and that the specific binding was not due to a lipophilic interaction between {sup 125}I-rat ANF and brown fat. Specific bindingmore » of {sup 125}I-rat ANF to the membranes of brown fat cells was inhibited by unlabeled rat ANF with a Ki of 8.0 x 10(-9) M, but not by unrelated peptides. These studies demonstrate that brown fat cells express high levels of ANF receptor binding sites in neonatal rat and sheep and suggest that ANF may play a role in thermoregulation.« less

Large-scale turnover of functional transcription factor bindingsites in Drosophila

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

Moses, Alan M.; Pollard, Daniel A.; Nix, David A.

2006-07-14

The gain and loss of functional transcription-factor bindingsites has been proposed as a major source of evolutionary change incis-regulatory DNA and gene expression. We have developed an evolutionarymodel to study binding site turnover that uses multiple sequencealignments to assess the evolutionary constraint on individual bindingsites, and to map gain and loss events along a phylogenetic tree. Weapply this model to study the evolutionary dynamics of binding sites ofthe Drosophila melanogaster transcription factor Zeste, using genome-widein vivo (ChIP-chip) binding data to identify functional Zeste bindingsites, and the genome sequences of D. melanogaster, D. simulans, D.erecta and D. yakuba to study theirmore » evolution. We estimate that more than5 percent of functional Zeste binding sites in D. melanogaster weregained along the D. melanogaster lineage or lost along one of the otherlineages. We find that Zeste bound regions have a reduced rate of bindingsite loss and an increased rate of binding site gain relative to flankingsequences. Finally, we show that binding site gains and losses areasymmetrically distributed with respect to D. melanogaster, consistentwith lineage-specific acquisition and loss of Zeste-responsive regulatoryelements.« less

Interaction of AIM with insulin-like growth factor-binding protein-4

PubMed Central

YOU, QIANG; WU, YAN; YAO, NANNAN; SHEN, GUANNAN; ZHANG, YING; XU, LIANGGUO; LI, GUIYING; JU, CYNTHIA

2015-01-01

Apoptosis inhibitor of macrophages (AIM/cluster of differentiation 5 antigen-like/soluble protein α) has been shown to inhibit cellular apoptosis; however, the underlying molecular mechanism has not been elucidated. Using yeast two-hybrid screening, the present study uncovered that AIM binds to insulin-like growth factor binding protein-4 (IGFBP-4). AIM interaction with IGFBP-4, as well as IGFBP-2 and -3, but not with IGFBP-1, -5 and -6, was further confirmed by co-immunoprecipitation (co-IP) using 293 cells. The binding activity and affinity between AIM and IGFBP-4 in vitro were analyzed by co-IP and biolayer interferometry. Serum depletion-induced cellular apoptosis was attenuated by insulin-like growth factor-I (IGF-I), and this effect was abrogated by IGFBP-4. Of note, in the presence of AIM, the inhibitory effect of IGFBP-4 on the anti-apoptosis function of IGF-I was attenuated, possibly through binding of AIM with IGFBP-4. In conclusion, to the best of our knowledge, the present study provides the first evidence that AIM binds to IGFBP-2, -3 and -4. The data suggest that this interaction may contribute to the mechanism of AIM-mediated anti-apoptosis function. PMID:26135353

Identification of a domain within human TAF(I)48, a subunit of Selectivity Factor 1, that interacts with helix 2 of TBP.

PubMed

Xu, Shuping; Hori, Roderick T

2004-09-01

RNA polymerase I transcription in human cells requires Selectivity Factor 1, a multisubunit complex composed of the TATA-box-binding protein (TBP) and three TBP-associated factors (TAFs) called TAF(I)48, TAF(I)63 and TAF(I)110. Each of the Selectivity Factor 1 subunits binds directly to the other three components, but these interactions have not been characterized. This study is the initial identification and analysis of a TBP-binding domain within a Selectivity Factor 1 TAF. The interaction between human TBP and human TAF(I)48 was initially examined using the yeast two-hybrid assay, and a TBP-binding domain was identified in the carboxyl-terminus of human (h)TAF(I)48. Consistent with this result, the hTAF(I)48 carboxyl-terminus was able to bind directly to TBP in protein-protein interaction assays. When mutations were introduced into the hTAF(I)48 carboxyl-terminus, we identified changes in uncharged and positive residues that affect its interaction with TBP. By examining TBP mutants, residues within and adjacent to helix 2 of TBP, previously demonstrated to interact with subunits of other TBP-containing complexes [Transcription Factor IID (TFIID) and TFIIIB] were also found to diminish its affinity for the carboxyl-terminus of hTAF(I)48. The regions of hTAF(I)48 and TBP that interact are compared to those identified within other complexes containing TBP.

A resource for characterizing genome-wide binding and putative target genes of transcription factors expressed during secondary growth and wood formation in Populus.

PubMed

Liu, Lijun; Ramsay, Trevor; Zinkgraf, Matthew; Sundell, David; Street, Nathaniel Robert; Filkov, Vladimir; Groover, Andrew

2015-06-01

Identifying transcription factor target genes is essential for modeling the transcriptional networks underlying developmental processes. Here we report a chromatin immunoprecipitation sequencing (ChIP-seq) resource consisting of genome-wide binding regions and associated putative target genes for four Populus homeodomain transcription factors expressed during secondary growth and wood formation. Software code (programs and scripts) for processing the Populus ChIP-seq data are provided within a publically available iPlant image, including tools for ChIP-seq data quality control and evaluation adapted from the human Encyclopedia of DNA Elements (ENCODE) project. Basic information for each transcription factor (including members of Class I KNOX, Class III HD ZIP, BEL1-like families) binding are summarized, including the number and location of binding regions, distribution of binding regions relative to gene features, associated putative target genes, and enriched functional categories of putative target genes. These ChIP-seq data have been integrated within the Populus Genome Integrative Explorer (PopGenIE) where they can be analyzed using a variety of web-based tools. We present an example analysis that shows preferential binding of transcription factor ARBORKNOX1 to the nearest neighbor genes in a pre-calculated co-expression network module, and enrichment for meristem-related genes within this module including multiple orthologs of Arabidopsis KNOTTED-like Arabidopsis 2/6. © 2015 Society for Experimental Biology and John Wiley & Sons Ltd This article has been contributed to by US Government employees and their work is in the public domain in the USA.

An ABA-responsive DRE-binding protein gene from Setaria italica, SiARDP, the target gene of SiAREB, plays a critical role under drought stress.

PubMed

Li, Cong; Yue, Jing; Wu, Xiaowei; Xu, Cong; Yu, Jingjuan

2014-10-01

The DREB (dehydration-responsive element binding)-type transcription factors regulate the expression of stress-inducible genes by binding the DRE/CRT cis-elements in promoter regions. The upstream transcription factors that regulate the transcription of DREB transcription factors have not been clearly defined, although the function of DREB transcription factors in abiotic stress is known. In this study, an abscisic acid (ABA)-responsive DREB-binding protein gene (SiARDP) was cloned from foxtail millet (Setaria italica). The transcript level of SiARDP increased not only after drought, high salt, and low temperature stresses, but also after an ABA treatment in foxtail millet seedlings. Two ABA-responsive elements (ABRE1: ACGTGTC; ABRE2: ACGTGGC) exist in the promoter of SiARDP. Further analyses showed that two ABA-responsive element binding (AREB)-type transcription factors, SiAREB1 and SiAREB2, could physically bind to the ABRE core element in vitro and in vivo. The constitutive expression of SiARDP in Arabidopsis thaliana enhanced drought and salt tolerance during seed germination and seedling development, and overexpression of SiARDP in foxtail millet improved drought tolerance. The expression levels of target genes of SiARDP were upregulated in transgenic Arabidopsis and foxtail millet. These results reveal that SiARDP, one of the target genes of SiAREB, is involved in ABA-dependent signal pathways and plays a critical role in the abiotic stress response in plants. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.