Improvements in fitness are not obligatory for exercise training-induced improvements in CV risk factors.

PubMed

Hartman, Yvonne A W; Hopman, Maria T E; Schreuder, Tim H; Verheggen, Rebecca J H M; Scholten, Ralph R; Oudegeest-Sander, Madelijn H; Poelkens, Fleur; Maiorana, Andrew J; Naylor, Louise H; Willems, Peter H; Tack, Cees J; Thijssen, Dick H J; Green, Daniel J

2018-02-01

The purpose of this study was to assess whether changes in physical fitness relate to changes in cardiovascular risk factors following standardized, center-based and supervised exercise training programs in subjects with increased cardiovascular risk. We pooled data from exercise training studies of subjects with increased cardiovascular risk (n = 166) who underwent 8-52 weeks endurance training. We determined fitness (i.e., peak oxygen uptake) and traditional cardiovascular risk factors (body mass index, blood pressure, total cholesterol, high-density lipoprotein cholesterol), before and after training. We divided subjects into quartiles based on improvement in fitness, and examined whether these groups differed in terms of risk factors. Associations between changes in fitness and in cardiovascular risk factors were further tested using Pearson correlations. Significant heterogeneity was apparent in the improvement of fitness and individual risk factors, with nonresponder rates of 17% for fitness, 44% for body mass index, 33% for mean arterial pressure, 49% for total cholesterol, and 49% for high-density lipoprotein cholesterol. Neither the number, nor the magnitude, of change in cardiovascular risk factors differed significantly between quartiles of fitness change. Changes in fitness were not correlated with changes in cardiovascular risk factors (all P > 0.05). Our data suggest that significant heterogeneity exists in changes in peak oxygen uptake after training, while improvement in fitness did not relate to improvement in cardiovascular risk factors. In subjects with increased cardiovascular risk, improvements in fitness are not obligatory for training-induced improvements in cardiovascular risk factors. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Power factor improvement in three-phase networks with unbalanced inductive loads using the Roederstein ESTAmat RPR power factor controller

NASA Astrophysics Data System (ADS)

Diniş, C. M.; Cunţan, C. D.; Rob, R. O. S.; Popa, G. N.

2018-01-01

The paper presents the analysis of a power factor with capacitors banks, without series coils, used for improving power factor for a three-phase and single-phase inductive loads. In the experimental measurements, to improve the power factor, the Roederstein ESTAmat RPR power factor controller can command up to twelve capacitors banks, while experimenting using only six capacitors banks. Six delta capacitors banks with approximately equal reactive powers were used for experimentation. The experimental measurements were carried out with a three-phase power quality analyser which worked in three cases: a case without a controller with all capacitors banks permanently parallel connected with network, and two other cases with power factor controller (one with setting power factor at 0.92 and the other one at 1). When performing experiments with the power factor controller, a current transformer was used to measure the current on one phase (at a more charged or less loaded phase).

Risk factors associated with recurrent hemorrhage after the initial improvement of colonic diverticular bleeding.

PubMed

Nishikawa, Hiroki; Maruo, Takanori; Tsumura, Takehiko; Sekikawa, Akira; Kanesaka, Takashi; Osaki, Yukio

2013-03-01

We elucidated risk factors contributing to recurrent hemorrhage after initial improvement of colonic diverticular bleeding. 172 consecutive hospitalized patients diagnosed with colonic diverticular bleeding were analyzed. Recurrent hemorrhage after initial improvement of colonic diverticular bleeding is main outcome measure. We analyzed factors contributing to recurrent hemorrhage risk in univariate and multivariate analyses. The length of the observation period after improvement of colonic diverticular bleeding was 26.4 +/- 14.6 months (range, 1-79 months). The cumulative recurrent hemorrhage rate in all patients at 1 and 2 years was 34.8% and 41.8%, respectively. By univariate analysis, age > 70 years (P = 0.021), BMI > 25 kg/m2 (P = 0.013), the use of anticoagulant drugs (P = 0.034), the use of NSAIDs (P = 0.040), history of hypertension (P = 0.011), history of smoking (P = 0.030) and serum creatinine level > 1.5 mg/dL (P < 0.001) were found to be significant risk factors for recurrent colonic diverticular bleeding. By multivariate analysis, age > 70 years (Hazard ratio (HR), 1.905, 95% confidence interval (CI), 1.067-3.403, P = 0.029), history of hypertension (HR, 0.493, 95% CI, 0.245-0.993, P = 0.048) and serum creatinine level > 1.5 mg/dL (HR, 95% CI, 0.288-0.964, P = 0.044) were shown to be significant independent risk factors. Close observation after the initial improvement of colonic diverticular bleeding is needed, especially in elderly patients or patients with history of hypertension or renal deficiency.

Three success factors for continual improvement in healthcare: an analysis of the reports of improvement team members.

PubMed

Brandrud, Aleidis Skard; Schreiner, Ada; Hjortdahl, Per; Helljesen, Gro Sævil; Nyen, Bjørnar; Nelson, Eugene C

2011-03-01

The objectives of the Breakthrough Series Collaborative are to close the gap between what we know and what we do, and to contribute to continuous quality improvement (CQI) of healthcare through collaborative learning. The improvement efforts are guided by a systematic approach, combining professional and improvement knowledge. To explore what the improvement teams have learnt from participating in the collaborative and from dealing with promoting and inhibiting factors encountered. Qualitative interviews with 19 team members were conducted in four focus groups, using the Critical Incident Technique. A critical incident is one that makes significant contributions, either positively or negatively, to an activity. The elements of a culture of improvement are revealed by the critical incidents, and reflect the eight domains of knowledge, as a product of collaborative learning. The improvement knowledge and skills of individuals are important elements, but not enough to achieve sustainable changes. 90% of the material reflects the need for a system of CQI to solve the problems that organisations experience in trying to make lasting improvements. A pattern of three success factors for CQI emerges: (1) continuous and reliable information, including measurement, about best and current practice; (2) engagement of everybody in all phases of the improvement work: the patient and family, the leadership, the professional environment and the staff; and (3) an infrastructure based on improvement knowledge, with multidisciplinary teams, available coaching, learning systems and sustainability systems.

Characterization of an improved 1-3 piezoelectric composite by simulation and experiment.

PubMed

Zhong, Chao; Wang, Likun; Qin, Lei; Zhang, Yanjun

2017-06-16

To increase electromechanical coupling factor of 1-3 piezoelectric composite and reduce its bending deformation under external stress, an improved 1-3 piezoelectric composite is developed. In the improved structure, both epoxy resin and silicone rubber are used as polymer material. The simulation model of the improved 1-3 piezoelectric composite was established using the finite element software ANSYS. The relationship of the performance of the improved composite to the volume percentage of silicone rubber was determined by harmonic response analysis and the bending deformation under external stress was simulated by static analysis. The improved composite samples were prepared by cutting and filling methods, and the performance was tested. The feasibility of the improved structure was verified by finite element simulation and experiment. The electromechanical coupling factor of the improved composite can reach 0.67 and meanwhile the characteristic impedance can decline to 13 MRayl. The electromechanical coupling factor of the improved composite is higher than that of the composite with only epoxy resin as the polymer and the improved composite can reduce bending deformation. Comparison of simulation and experiment, the results of the experiment are in general agreement with those from the simulation. However, most experimental values were higher than the simulation results, and the abnormality of the test results was also more obvious than that of the simulation. These findings may be attributed to slight difference in the material parameters of simulation and experiment.

The Impact of Soft Factors on Quality Improvement in Manufacturing Industry

NASA Astrophysics Data System (ADS)

Chan, Shiau Wei; Fauzi Ahmad, Md; Kong, Mei Wan

2017-08-01

Nowadays, soft factors have become the key factors of success in quality improvement of an organisation. Many organisations have neglected the importance of soft factors, this may influence the organisational performance. Hence, the purpose of this research is to examine the impact of soft factors on quality improvement in manufacturing industries. Six hypotheses were examined while considering six dimensions of soft factors including management commitment, customer focus, supplier relationship, employee involvement, training and education, and reward and recognition that have a positive impact on quality improvement. In this study, eighty one managers from the quality department were randomly selected in the manufacturing industry in Batu Pahat, Johor. The questionnaires were distributed to them. The researcher analysed the quantitatively collected data using descriptive analysis and correlation analysis. The findings of this study revealed that all soft factors are correlated to the quality improvement in an organisation with a high significant value but the regression analysis shows that the supplier relationship and employee involvement has more significant impact on quality improvement as compared to other soft factors which contributes of this study.

An improved gravity model for Mars: Goddard Mars Model-1 (GMM-1)

NASA Technical Reports Server (NTRS)

Smith, D. E.; Lerch, F. J.; Nerem, R. S.; Zuber, M. T.; Patel, G. B.; Fricke, S. K.; Lemoine, F. G.

1993-01-01

Doppler tracking data of three orbiting spacecraft have been reanalyzed to develop a new gravitational field model for the planet Mars, GMM-1 (Goddard Mars Model-1). This model employs nearly all available data, consisting of approximately 1100 days of S-bank tracking data collected by NASA's Deep Space Network from the Mariner 9, and Viking 1 and Viking 2 spacecraft, in seven different orbits, between 1971 and 1979. GMM-1 is complete to spherical harmonic degree and order 50, which corresponds to a half-wavelength spatial resolution of 200-300 km where the data permit. GMM-1 represents satellite orbits with considerably better accuracy than previous Mars gravity models and shows greater resolution of identifiable geological structures. The notable improvement in GMM-1 over previous models is a consequence of several factors: improved computational capabilities, the use of optimum weighting and least-squares collocation solution techniques which stabilized the behavior of the solution at high degree and order, and the use of longer satellite arcs than employed in previous solutions that were made possible by improved force and measurement models. The inclusion of X-band tracking data from the 379-km altitude, near-polar orbiting Mars Observer spacecraft should provide a significant improvement over GMM-1, particularly at high latitudes where current data poorly resolves the gravitational signature of the planet.

National plan to enhance aviation safety through human factors improvements

NASA Technical Reports Server (NTRS)

Foushee, Clay

1990-01-01

The purpose of this section of the plan is to establish a development and implementation strategy plan for improving safety and efficiency in the Air Traffic Control (ATC) system. These improvements will be achieved through the proper applications of human factors considerations to the present and future systems. The program will have four basic goals: (1) prepare for the future system through proper hiring and training; (2) develop a controller work station team concept (managing human errors); (3) understand and address the human factors implications of negative system results; and (4) define the proper division of responsibilities and interactions between the human and the machine in ATC systems. This plan addresses six program elements which together address the overall purpose. The six program elements are: (1) determine principles of human-centered automation that will enhance aviation safety and the efficiency of the air traffic controller; (2) provide new and/or enhanced methods and techniques to measure, assess, and improve human performance in the ATC environment; (3) determine system needs and methods for information transfer between and within controller teams and between controller teams and the cockpit; (4) determine how new controller work station technology can optimally be applied and integrated to enhance safety and efficiency; (5) assess training needs and develop improved techniques and strategies for selection, training, and evaluation of controllers; and (6) develop standards, methods, and procedures for the certification and validation of human engineering in the design, testing, and implementation of any hardware or software system element which affects information flow to or from the human.

Contextual Factors and Effective School Improvement

ERIC Educational Resources Information Center

Sun, Hechuan; Creemers, Bert P. M.; de Jong, Rob

2007-01-01

This research provides policy-makers, researchers, and educators at all levels with a glimpse of the contextual influence on effective school improvement (ESI) in 8 European countries. What are the factors at the contextual level, particularly at the national level, which influence ESI? Are there any similarities or differences between the…

Thioredoxin-1 (Trx1) engineered mesenchymal stem cell therapy increased pro-angiogenic factors, reduced fibrosis and improved heart function in the infarcted rat myocardium.

PubMed

Suresh, Sumanth C; Selvaraju, Vaithinathan; Thirunavukkarasu, Mahesh; Goldman, Joshua W; Husain, Aaftab; Alexander Palesty, J; Sanchez, Juan A; McFadden, David W; Maulik, Nilanjana

2015-12-15

Engraftment of mesenchymal stem cells (MSCs) has emerged as a powerful candidate for mediating myocardial repair. In this study, we genetically modified MSCs with an adenovector encoding thioredoxin-1 (Ad.Trx1). Trx1 has been described as a growth regulator, a transcription factor regulator, a cofactor, and a powerful antioxidant. We explored whether engineered MSCs, when transplanted, are capable of improving cardiac function and angiogenesis in a rat model of myocardial infarction (MI). Rat MSCs were cultured and divided into MSC, MSC+Ad.LacZ, and MSC+Ad.Trx1 groups. The cells were assayed for proliferation, and differentiation potential. In addition, rats were divided into control-sham (CS), control-MI (CMI), MSC+Ad.LacZ-MI (MLZMI), and MSC+Ad.Trx1-MI (MTrxMI) groups. MI was induced by left anterior descending coronary artery (LAD) ligation, and MSCs preconditioned with either Ad.LacZ or Ad.Trx1 were immediately administered to four sites in the peri-infarct zone. The MSC+Ad.Trx1 cells increased the proliferation capacity and maintained pluripotency, allowing them to divide into cardiomyocytes, smooth muscle, and endothelial cells. Western blot analysis, 4 days after treatment showed increased vascular endothelial growth factor (VEGF), heme oxygenase-1 (HO-1), and C-X-C chemokine receptor type 4 (CXCR4). Also capillary density along with myocardial function as examined by echocardiography was found to be increased. Fibrosis was reduced in the MTrxMI group compared to MLZMI and CMI. Visualization of Connexin-43 by immunohistochemistry confirmed increased intercellular connections in the MTrxMI rats compared to MLZMI. Engineering MSCs to express Trx1 may prove to be a strategic therapeutic modality in the treatment of cardiac failure. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Factors Associated With Worsened or Improved Mental Health in the Great East Japan Earthquake Survivors.

PubMed

Yamanouchi, Tomoko; Hiroshima, Mayo; Takeuchi, Yumiko; Sawada, Yumiko; Takahashi, Makiko; Amagai, Manami

2018-02-01

The aim of this study was to identify factors contributing to the worsening or improved mental health of long-term evacuees over three years following the Great East Japan Earthquake. The Japanese version of the K6 questionnaire was used as a measure of mental health. The first- and third-year survey results were compared and differences in mental health status calculated. Respondents were then divided into two groups according to worsening or improved mental health status. Differences in stress factors, stress relief methods, and demographics were compared between the two groups. Factors associated with exacerbation of poor mental health were the stress factors "Uncertainty about future" (p=0.048) and "Loss of purpose in life" (p=0.023). Multivariable analysis identified two factors associated with improved mental health, the stress relief methods "Accepting myself" (odds ratio (OR): 2.15, 95% confidence interval (CI): 1.02-4.51) and "Interactions with others" (OR: 3.34, 95% CI: 1.43-7.79). While motivation and hope of livelihood reconstruction have gradually risen in the three years since the disaster, anxieties about an uncertain future, loss of purpose in life, and disruption of social networks continue adversely to affect the mental health of survivors. Copyright © 2017 Elsevier Inc. All rights reserved.

Utilizing a Human Factors Nursing Worksystem Improvement Framework to Increase Nurses' Time at the Bedside and Enhance Safety.

PubMed

Probst, C Adam; Carter, Megan; Cadigan, Caton; Dalcour, Cortney; Cassity, Cindy; Quinn, Penny; Williams, Tiana; Montgomery, Donna Cook; Wilder, Claudia; Xiao, Yan

2017-02-01

The aim of this study is to increase nurses' time for direct patient care and improve safety via a novel human factors framework for nursing worksystem improvement. Time available for direct patient care influences outcomes, yet worksystem barriers prevent nurses adequate time at the bedside. A novel human factors framework was developed for worksystem improvement in 3 units at 2 facilities. Objectives included improving nurse efficiency as measured by time-and-motion studies, reducing missing medications and subsequent trips to medication rooms and improving medication safety. Worksystem improvement resulted in time savings of 16% to 32% per nurse per 12-hour shift. Requests for missing medications dropped from 3.2 to 1.3 per day. Nurse medication room trips were reduced by 30% and nurse-reported medication errors fell from a range of 1.2 to 0.8 and 6.3 to 4.0 per month. An innovative human factors framework for nursing worksystem improvement provided practical and high priority targets for interventions that significantly improved the nursing worksystem.

Effect of improved fitness beyond weight loss on cardiovascular risk factors in individuals with type 2 diabetes in the Look AHEAD study.

PubMed

Gibbs, Bethany Barone; Brancati, Frederick L; Chen, Haiying; Coday, Mace; Jakicic, John M; Lewis, Cora E; Stewart, Kerry J; Clark, Jeanne M

2014-05-01

Because lifestyle-induced improvements in cardiovascular risk factors vary substantially across individuals with type 2 diabetes, we investigated the extent to which increases in fitness explain cardiovascular risk factor improvements independent of weight loss in a lifestyle intervention. We studied 1-year changes in Look AHEAD, a randomized trial comparing an intensive lifestyle intervention (ILI) to a diabetes support and education (DSE) control group in adults with type 2 diabetes. Assessments included weight, fitness, blood pressure (BP), glucose, HbA1c, and lipids. We evaluated the effects of changes in weight and fitness on changes in cardiovascular risk factors by study arm, using R (2) from multiple linear regression. Analyses included participants with fitness data at baseline and 1-year (n = 4408; 41% male, 36% non-white; mean age 58.7 ± 6.8 years). Weight change alone improved R (2) for explaining changes in risk factors up to 8.2% in ILI and 1.7% in DSE. Fitness change alone improved R (2) up to 3.9% in ILI and 0.8% in DSE. After adjusting for weight change, fitness was independently associated (p < 0.05) with improvements in R (2) for glucose (+0.7%), HbA1c (+1.1%), high-density lipoprotein (HDL) cholesterol (+0.4%), and triglycerides (+0.2%) in ILI and diastolic BP (+0.3%), glucose (+0.3%), HbA1c (+0.4%), and triglycerides (+0.1%) in DSE. Taken together, weight and fitness changes explained from 0.1-9.3% of the variability in cardiovascular risk factor changes. Increased fitness explained statistically significant but small improvements in several cardiovascular risk factors beyond weight loss. Further research identifying other factors that explain cardiovascular risk factor change is needed.

Uncaria rhynchophylla and rhynchophylline improved kainic acid-induced epileptic seizures via IL-1β and brain-derived neurotrophic factor.

PubMed

Ho, Tin-Yun; Tang, Nou-Ying; Hsiang, Chien-Yun; Hsieh, Ching-Liang

2014-05-15

Uncaria rhynchophylla (UR) has been used for the treatment of convulsions and epilepsy in traditional Chinese medicine. This study reported the major anti-convulsive signaling pathways and effective targets of UR and rhynchophylline (RP) using genomic and immunohistochemical studies. Epileptic seizure model was established by intraperitoneal injection of kainic acid (KA) in rats. Electroencephalogram and electromyogram recordings indicated that UR and RP improved KA-induced epileptic seizures. Toll-like receptor (TLR) and neurotrophin signaling pathways were regulated by UR in both cortex and hippocampus of KA-treated rats. KA upregulated the expression levels of interleukin-1β (IL-1β) and brain-derived neurotrophin factor (BDNF), which were involved in TLR and neurotrophin signaling pathways, respectively. However, UR and RP downregulated the KA-induced IL-1β and BDNF gene expressions. Our findings suggested that UR and RP exhibited anti-convulsive effects in KA-induced rats via the regulation of TLR and neurotrophin signaling pathways, and the subsequent inhibition of IL-1β and BDNF gene expressions. Copyright © 2014 Elsevier GmbH. All rights reserved.

Kelch-like ECH-associated Protein 1-dependent Nuclear Factor-E2-related Factor 2 Activation in Relation to Antioxidation Induced by Sevoflurane Preconditioning.

PubMed

Cai, Min; Tong, Li; Dong, Beibei; Hou, Wugang; Shi, Likai; Dong, Hailong

2017-03-01

-like ECH-associated protein 1 overexpression reversed nuclear factor-E2-related factor 2 up-regulation and abolished the neuroprotection induced by sevoflurane preconditioning. Kelch-like ECH-associated protein 1 small interfering RNA administration improved nuclear factor-E2-related factor 2 expression and the outcome of mice subjected to ischemia/reperfusion injury. Kelch-like ECH-associated protein 1 down-regulation-dependent nuclear factor-E2-related factor 2 activation underlies the ability of sevoflurane preconditioning to activate the endogenous antioxidant response, which elicits its neuroprotection.

Optimization of Light-Harvesting Pigment Improves Photosynthetic Efficiency1[OPEN

PubMed Central

Jin, Honglei; Li, Mengshu; Duan, Sujuan; Fu, Mei; Dong, Xiaoxiao; Feng, Dongru; Wang, Jinfa

2016-01-01

Maximizing light capture by light-harvesting pigment optimization represents an attractive but challenging strategy to improve photosynthetic efficiency. Here, we report that loss of a previously uncharacterized gene, HIGH PHOTOSYNTHETIC EFFICIENCY1 (HPE1), optimizes light-harvesting pigments, leading to improved photosynthetic efficiency and biomass production. Arabidopsis (Arabidopsis thaliana) hpe1 mutants show faster electron transport and increased contents of carbohydrates. HPE1 encodes a chloroplast protein containing an RNA recognition motif that directly associates with and regulates the splicing of target RNAs of plastid genes. HPE1 also interacts with other plastid RNA-splicing factors, including CAF1 and OTP51, which share common targets with HPE1. Deficiency of HPE1 alters the expression of nucleus-encoded chlorophyll-related genes, probably through plastid-to-nucleus signaling, causing decreased total content of chlorophyll (a+b) in a limited range but increased chlorophyll a/b ratio. Interestingly, this adjustment of light-harvesting pigment reduces antenna size, improves light capture, decreases energy loss, mitigates photodamage, and enhances photosynthetic quantum yield during photosynthesis. Our findings suggest a novel strategy to optimize light-harvesting pigments that improves photosynthetic efficiency and biomass production in higher plants. PMID:27609860

Improvement in circulation and in cardiovascular risk factors with a proprietary isotonic bioflavonoid formula OPC-3.

PubMed

Cesarone, Maria R; Di Renzo, Andrea; Errichi, Silvia; Schönlau, Frank; Wilmer, James L; Blumenfeld, Julian

2008-01-01

This study investigated the efficacy of isotonic bioflavonoid supplementation, OPC-3 on 61 individuals presenting with risk factors meeting the criteria for metabolic syndrome. Subjects were supplemented with a proprietary isotonic bioflavonoid OPC-3 or placebo over 2 months. Plasma oxidative stress status was significantly lowered by 10.1% with OPC-3. All major cardiovascular risk factors were improved with blood pressure, total cholesterol, and fasting blood glucose lowered. OPC-3 significantly improved endothelial function as evaluated by increased vasorelaxation in reactive hyperemia and enhanced diastolic carotid artery flow. Cardiac ultrasound scanning revealed a significant increase of left ventricular ejection fraction. Skin microcirculation was enhanced, and better tissue perfusion led to significantly increased transcutaneous oxygen partial pressure and decreased pCO(2). With OPC-3 a dramatic and significant plasma C-reactive protein decrease by 52.1% occurred. Individuals may improve key cardiovascular risk factors by daily supplementation with the bioflavonoid OPC-3 as an important part of a healthier lifestyle.

Perceived Factors Associated with Sustained Improvement Following Participation in a Multicenter Quality Improvement Collaborative.

PubMed

Stone, Sohini; Lee, Henry C; Sharek, Paul J

2016-07-01

The California Perinatal Quality Care Collaborative led the Breastmilk Nutrition Quality Improvement Collaborative from October 2009 to September 2010 to increase the percentage of very low birth weight infants receiving breast milk at discharge in 11 collaborative neonatal ICUs (NICUs). Observed increases in breast milk feeding and decreases in necrotizing enterocolitis persisted for 6 months after the collaborative ended. Eighteen to 24 months after the end of the collaborative, some sites maintained or further increased their gains, while others trended back toward baseline. A study was conducted to assess the qualitative factors that affect sustained improvement following participation. Collaborative leaders at each of the 11 NICUs that participated in the Breastmilk Nutrition Quality Improvement Collaborative were invited to participate in a site-specific one-hour phone interview. Interviews were recorded and transcribed and then analyzed using qualitative research analysis software to identify themes associated with sustained improvement. Eight of 11 invited centers agreed to participate in the interviews. Thematic saturation was achieved by the sixth interview, so further interviews were not pursued. Factors contributing to sustainability included physician involvement within the multidisciplinary teams, continuous education, incorporation of interventions into the daily work flow, and integration of a data-driven feedback system. Early consideration by site leaders of how to integrate best-practice interventions into the daily work flow, and ensuring physician commitment and ongoing education based in continuous data review, should enhance the likelihood of sustaining improvements. To maximize sustained success, future collaborative design should consider proactively identifying and supporting these factors at participating sites.

Sustained IGF-1 Secretion by Adipose-Derived Stem Cells Improves Infarcted Heart Function.

PubMed

Bagno, Luiza L; Carvalho, Deivid; Mesquita, Fernanda; Louzada, Ruy A; Andrade, Bruno; Kasai-Brunswick, Taís H; Lago, Vivian M; Suhet, Grazielle; Cipitelli, Debora; Werneck-de-Castro, João Pedro; Campos-de-Carvalho, Antonio C

2016-01-01

The mechanism by which stem cell-based therapy improves heart function is still unknown, but paracrine mechanisms seem to be involved. Adipose-derived stem cells (ADSCs) secrete several factors, including insulin-like growth factor-1 (IGF-1), which may contribute to myocardial regeneration. Our aim was to investigate whether the overexpression of IGF-1 in ADSCs (IGF-1-ADSCs) improves treatment of chronically infarcted rat hearts. ADSCs were transduced with a lentiviral vector to induce IGF-1 overexpression. IGF-1-ADSCs transcribe100- to 200-fold more IGF-1 mRNA levels compared to nontransduced ADSCs. IGF-1 transduction did not alter ADSC immunophenotypic characteristics even under hypoxic conditions. However, IGF-1-ADSCs proliferate at higher rates and release greater amounts of growth factors such as IGF-1, vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) under normoxic and hypoxic conditions. Importantly, IGF-1 secreted by IGF-1-ADSCs is functional given that Akt-1 phosphorylation was remarkably induced in neonatal cardiomyocytes cocultured with IGF-1-ADSCs, and this increase was prevented with phosphatidylinositol 3-kinase (PI3K) inhibitor treatment. Next, we tested IGF-1-ADSCs in a rat myocardial infarction (MI) model. MI was performed by coronary ligation, and 4 weeks after MI, animals received intramyocardial injections of either ADSCs (n = 7), IGF-1-ADSCs (n = 7), or vehicle (n = 7) into the infarcted border zone. Left ventricular function was evaluated by echocardiography before and after 6 weeks of treatment, and left ventricular hemodynamics were assessed 7 weeks after cell injection. Notably, IGF-1-ADSCs improved left ventricular ejection fraction and cardiac contractility index, but did not reduce scar size when compared to the ADSC-treated group. In summary, transplantation of ADSCs transduced with IGF-1 is a superior therapeutic approach to treat MI compared to nontransduced ADSCs, suggesting that gene and cell

Cryptanalysis and improvement of an improved two factor authentication protocol for telecare medical information systems.

PubMed

Chaudhry, Shehzad Ashraf; Naqvi, Husnain; Shon, Taeshik; Sher, Muhammad; Farash, Mohammad Sabzinejad

2015-06-01

Telecare medical information systems (TMIS) provides rapid and convenient health care services remotely. Efficient authentication is a prerequisite to guarantee the security and privacy of patients in TMIS. Authentication is used to verify the legality of the patients and TMIS server during remote access. Very recently Islam et al. (J. Med. Syst. 38(10):135, 2014) proposed a two factor authentication protocol for TMIS using elliptic curve cryptography (ECC) to improve Xu et al.'s (J. Med. Syst. 38(1):9994, 2014) protocol. They claimed their improved protocol to be efficient and provides all security requirements. However our analysis reveals that Islam et al.'s protocol suffers from user impersonation and server impersonation attacks. Furthermore we proposed an enhanced protocol. The proposed protocol while delivering all the virtues of Islam et al.'s protocol resists all known attacks.

Insulin-like growth factor 1: common mediator of multiple enterotrophic hormones and growth factors.

PubMed

Bortvedt, Sarah F; Lund, P Kay

2012-03-01

To summarize the recent evidence that insulin-like growth factor 1 (IGF1) mediates growth effects of multiple trophic factors and discuss clinical relevance. Recent reviews and original reports indicate benefits of growth hormone (GH) and long-acting glucagon-like peptide 2 (GLP2) analogs in short bowel syndrome and Crohn's disease. This review highlights the evidence that biomarkers of sustained small intestinal growth or mucosal healing and evaluation of intestinal epithelial stem cell biomarkers may improve clinical measures of intestinal growth or response to trophic hormones. Compelling evidence that IGF1 mediates growth effects of GH and GLP2 on intestine or linear growth in preclinical models of resection or Crohn's disease is presented, along with a concept that these hormones or IGF1 may enhance sustained growth if given early after bowel resection. Evidence that suppressor of cytokine signaling protein induction by GH or GLP2 in normal or inflamed intestine may limit IGF1-induced growth, but protect against risk of dysplasia or fibrosis, is reviewed. Whether IGF1 receptor mediates IGF1 action and potential roles of insulin receptors are addressed. IGF1 has a central role in mediating trophic hormone action in small intestine. Better understanding of benefits and risks of IGF1, receptors that mediate IGF1 action, and factors that limit undesirable growth are needed.

Chapter 7. Assessing soil factors in wildland improvement programs

Treesearch

Arthur R. Tiedemann; Carlos F. Lopez

2004-01-01

Soil factors are an important consideration for successful wildland range development or improvement programs. Even though many soil improvement and amelioration practices are not realistic for wildlands, their evaluation is an important step in selection of adapted plant materials for revegetation. This chapter presents information for wildland managers on: the...

Regulation of Memory Formation by the Transcription Factor XBP1.

PubMed

Martínez, Gabriela; Vidal, René L; Mardones, Pablo; Serrano, Felipe G; Ardiles, Alvaro O; Wirth, Craig; Valdés, Pamela; Thielen, Peter; Schneider, Bernard L; Kerr, Bredford; Valdés, Jose L; Palacios, Adrian G; Inestrosa, Nibaldo C; Glimcher, Laurie H; Hetz, Claudio

2016-02-16

Contextual memory formation relies on the induction of new genes in the hippocampus. A polymorphism in the promoter of the transcription factor XBP1 was identified as a risk factor for Alzheimer's disease and bipolar disorders. XBP1 is a major regulator of the unfolded protein response (UPR), mediating adaptation to endoplasmic reticulum (ER) stress. Using a phenotypic screen, we uncovered an unexpected function of XBP1 in cognition and behavior. Mice lacking XBP1 in the nervous system showed specific impairment of contextual memory formation and long-term potentiation (LTP), whereas neuronal XBP1s overexpression improved performance in memory tasks. Gene expression analysis revealed that XBP1 regulates a group of memory-related genes, highlighting brain-derived neurotrophic factor (BDNF), a key component in memory consolidation. Overexpression of BDNF in the hippocampus reversed the XBP1-deficient phenotype. Our study revealed an unanticipated function of XBP1 in cognitive processes that is apparently unrelated to its role in ER stress. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Expression of the Maize Dof1 Transcription Factor in Wheat and Sorghum

PubMed Central

Peña, Pamela A.; Quach, Truyen; Sato, Shirley; Ge, Zhengxiang; Nersesian, Natalya; Changa, Taity; Dweikat, Ismail; Soundararajan, Madhavan; Clemente, Tom E.

2017-01-01

Nitrogen is essential for plant growth and development. Improving the ability of plants to acquire and assimilate nitrogen more efficiently is a key agronomic parameter that will augment sustainability in agriculture. A transcription factor approach was pursued to address improvement of nitrogen use efficiency in two major commodity crops. To this end, the Zea mays Dof1 (ZmDof1) transcription factor was expressed in both wheat (Triticum aestivum) and sorghum (Sorghum bicolor) either constitutively, UBI4 promoter from sugarcane, or in a tissue specific fashion via the maize rbcS1 promoter. The primary transcription activation target of ZmDof1, phosphoenolpyruvate carboxylase (PEPC), is observed in transgenic wheat events. Expression ZmDof1 under control of the rbcs1 promoter translates to increase in biomass and yield components in wheat. However, constitutive expression of ZmDof1 led to the down-regulation of genes involved in photosynthesis and the functional apparatus of chloroplasts, and an outcome that negatively impacts photosynthesis, height, and biomass in wheat. Similar patterns were also observed in sorghum transgenic events harboring the constitutive expression cassette of ZmDof1. These results indicate that transcription factor strategies to boost agronomic phenotypic outcomes in crops need to consider expression patterns of the genetic elements to be introduced. PMID:28424717

Interactome analysis of transcriptional coactivator multiprotein bridging factor 1 unveils a yeast AP-1-like transcription factor involved in oxidation tolerance of mycopathogen Beauveria bassiana.

PubMed

Chu, Xin-Ling; Dong, Wei-Xia; Ding, Jin-Li; Feng, Ming-Guang; Ying, Sheng-Hua

2018-02-01

Oxidation tolerance is an important determinant to predict the virulence and biocontrol potential of Beauveria bassiana, a well-known entomopathogenic fungus. As a transcriptional coactivator, multiprotein bridging factor 1 mediates the activity of transcription factor in diverse physiological processes, and its homolog in B. bassiana (BbMBF1) contributes to fungal oxidation tolerance. In this study, the BbMBF1-interactomes under oxidative stress and normal growth condition were deciphered by mass spectrometry integrated with the immunoprecipitation. BbMBF1p factor has a broad interaction with proteins that are involved in various cellular processes, and this interaction is dynamically regulated by oxidative stress. Importantly, a B. bassiana homolog of yeast AP-1-like transcription factor (BbAP-1) was specifically associated with the BbMBF1-interactome under oxidation and significantly contributed to fungal oxidation tolerance. In addition, qPCR analysis revealed that several antioxidant genes are jointly controlled by BbAP-1 and BbMBF1. Conclusively, it is proposed that BbMBF1p protein mediates BbAP-1p factor to transcribe the downstream antioxidant genes in B. bassiana under oxidative stress. This study demonstrates for the first time a proteomic view of the MBF1-interactome in fungi, and presents an initial framework to probe the transcriptional mechanism involved in fungal response to oxidation, which will provide a new strategy to improve the biocontrol efficacy of B. bassiana.

A Systematic Review and Meta-Analysis on Self-Management for Improving Risk Factor Control in Stroke Patients.

PubMed

Sakakibara, Brodie M; Kim, Amy J; Eng, Janice J

2017-02-01

The aims of this review were to describe the self-management interventions used to improve risk factor control in stroke patients and quantitatively assess their effects on the following: 1) overall risk factor control from lifestyle behaviour (i.e. physical activity, diet and nutrition, stress management, smoking, alcohol, and medication adherence), and medical risk factors (i.e. blood pressure, cholesterol, blood glucose) and (2) individual risk factors. We systematically searched the PubMed, PsycINFO, CINAHL and Cochrane Database of Systematic Reviews databases to September 2015 to identify relevant randomized controlled trials investigating self-management to improve stroke risk factors. The self-management interventions were qualitatively described, and the data included in meta-analyses. Fourteen studies were included for review. The model estimating an effect averaged across all stroke risk factors was not significant, but became significant when four low-quality studies were removed (SMD = 0.10 [95 % CI = 0.02 to 0.17], I 2  = 0 %, p = 0.01). Subgroup analyses revealed a significant effect of self-management interventions on lifestyle behaviour risk factors (SMD = 0.15 [95 % CI = 0.04 to 0.25], I 2  = 0 %, p = 0.007) but not medical risk factors. Medication adherence was the only individual risk factor that self-management interventions significantly improved (SMD = 0.31 [95 % CI = 0.07 to 0.56], I 2  = 0 %, p = 0.01). Self-management interventions appear to be effective at improving overall risk factor control; however, more high-quality research is needed to corroborate this observation. Self-management has a greater effect on lifestyle behaviour risk factors than medical risk factors, with the largest effect at improving medication adherence.

An improved gravity model for Mars: Goddard Mars Model 1

NASA Technical Reports Server (NTRS)

Smith, D. E.; Lerch, F. J.; Nerem, R. S.; Zuber, M. T.; Patel, G. B.; Fricke, S. K.; Lemoine, F. G.

1993-01-01

Doppler tracking data of three orbiting spacecraft have been reanalyzed to develop a new gravitational field model for the planet Mars, Goddard Mars Model 1 (GMM-1). This model employs nearly all available data, consisting of approximately 1100 days of S band tracking data collected by NASA's Deep Space Network from the Mariner 9 and Viking 1 and Viking 2 spacecraft, in seven different orbits, between 1971 and 1979. GMM-1 is complete to spherical harmonic degree and order 50, which corresponds to a half-wavelength spatial resolution of 200-300 km where the data permit. GMM-1 represents satellite orbits with considerably better accuracy than previous Mars gravity models and shows greater resolution of identifiable geological structures. The notable improvement in GMM-1 over previous models is a consequence of several factors: improved computational capabilities, the use of otpimum weighting and least squares collocation solution techniques which stabilized the behavior of the solution at high degree and order, and the use of longer satellite arcs than employed in previous solutions that were made possible by improved force and measurement models. The inclusion of X band tracking data from the 379-km altitude, nnear-polar orbiting Mars Observer spacecraft should provide a significant improvement over GMM-1, particularly at high latitudes where current data poorly resolve the gravitational signature of the planet.

[Factors associated with perception of improvement by users of Centers for Psychosocial Care in the South of Brazil].

PubMed

Franzmann, Uiasser Thomas; Kantorski, Luciane Prado; Jardim, Vanda Maria da Rosa; Treichel, Carlos Alberto Dos Santos; Oliveira, Michele Mandagará de; Pavani, Fabiane Machado

2017-08-07

This study aimed to investigate factors associated with perceived improvement among users of Centers for Psychosocial Care. This was a cross-sectional study of 1,493 users of Centers for Psychosocial Care in the South of Brazil. Users' perceived improvement was assessed by Perceived Change Scale - Patients (PCS-Patients). Associated factors were investigated using logistic regression guided by a hierarchical model, with statistical significance set at p < 0.05. Factors associated with the outcome were: state where the Center for Psychosocial Care was located, paid work, diagnosis of schizophrenia, age at diagnosis < 18 years, longer time attending the center, ease of access, and involvement in the evaluation. The factors that actually involve improvement in users include those pertaining to characteristics of the illness and aspects related to services in the implementation of mental health policies and their organization.

Improving In Vitro Generated Cartilage-Carrier-Constructs by Optimizing Growth Factor Combination

PubMed Central

Wiegandt, Katharina; Goepfert, Christiane; Pörtner, Ralf

2007-01-01

The presented study is focused on the generation of osteochondral implants for cartilage repair, which consist of bone substitutes covered with in vitro engineered cartilage. Re-differentiation of expanded porcine cells was performed in alginate gel followed by cartilage formation in high-density cell cultures. In this work, different combinations of growth factors for the stimulation of re-differentiation and cartilage formation have been tested to improve the quality of osteochondral implants. It has been demonstrated that supplementation of the medium with growth factors has significant effects on the properties of the matrix. The addition of the growth factors IGF-I (100 ng/mL) and TGF-β1 (10 ng/mL) during the alginate culture and the absence of any growth factors during the high-density cell culture led to significantly higher GAG to DNA ratios and Young’s Moduli of the constructs compared to other combinations. The histological sections showed homogenous tissue and intensive staining for collagen type II. PMID:19662133

Sivelestat sodium hydrate improves post-traumatic knee osteoarthritis through nuclear factor-κB in a rat model.

PubMed

Yu, Xiaofeng; Zhao, Lijun; Yu, Zhiping; Yu, Changzheng; Bi, Jianfei; Sun, Binglong; Cong, Haibo

2017-08-01

As a specific inhibitor of neutrophil elastase, sivelestat sodium hydrate has primarily been used in the treatment of acute lung injury caused by various factors since its approval in 2002. Sivelestat sodium hydrate also improves post-traumatic knee osteoarthritis (KOA), although its underlying mechanisms of action have yet to be elucidated. The aim of the current study was to determine if sivelestat sodium hydrate improves post-traumatic KOA through nuclear factor (NF)-κB in a rat model. Treatment with sivelestat sodium hydrate significantly inhibited the induction of structural changes and significantly increased the vertical episode count and ipsilateral static weight bearing of the joint in KOA rats (all P<0.01). Sivelestat sodium hydrate significantly inhibited tumor necrosis factor-α and interleukin-6 production, serum nitrite levels, inducible nitric oxide synthase protein expression and high mobility group box 1 (HMGB1) secretion in KOA rats compared with the model group (all P<0.01). Sivelestat sodium hydrate also significantly suppressed p50/p65 DNA binding activity and NF-κB and phosphorylated inhibitor of κB protein expression in the joints of KOA rats compared with the model group (all P<0.01). These results suggest that sivelestat sodium hydrate improves post-traumatic KOA through HMGB1 and NF-κB in rats.

Losartan improves cerebrovascular function in a mouse model of Alzheimer's disease with combined overproduction of amyloid-β and transforming growth factor-β1.

PubMed

Papadopoulos, Panayiota; Tong, Xin-Kang; Imboden, Hans; Hamel, Edith

2017-06-01

Alterations of the renin-angiotensin system have been implicated in the pathogenesis of Alzheimer's disease. We tested the efficacy of losartan (10 mg/kg/day for three months), a selective angiotensin II type 1 receptor antagonist, in alleviating cerebrovascular and cognitive deficits in double-transgenic mice (six months at endpoint) that overexpress a mutated form of the human amyloid precursor protein (APP Swe,Ind ) and a constitutively active form of the transforming growth factor-β1, thereafter named A/T mice. Losartan rescued cerebrovascular reactivity, particularly the dilatory responses, but failed to attenuate astroglial activation and to normalize the neurovascular uncoupling response to sensory stimulation. The cognitive deficits of A/T mice were not restored by losartan nor were the increased brain levels of soluble and insoluble Aβ 1-40 and Aβ 1-42 peptides normalized. Our results are the first to demonstrate the capacity of losartan to improve cerebrovascular reactivity in an Alzheimer's disease mouse model of combined Aβ-induced vascular oxidative stress and transforming growth factor-β1-mediated vascular fibrosis. These data suggest that losartan may be promising for restoring cerebrovascular function in patients with vascular diseases at risk for vascular dementia or Alzheimer's disease. However, a combined therapy may be warranted for rescuing both vascular and cognitive deficits in a multifaceted pathology like Alzheimer's disease.

An encapsulated juice powder concentrate improves markers of pulmonary function and cardiovascular risk factors in heavy smokers.

PubMed

Bamonti, Fabrizia; Pellegatta, Marco; Novembrino, Cristina; Vigna, Luisella; De Giuseppe, Rachele; de Liso, Federica; Gregori, Dario; Noce, Cinzia Della; Patrini, Lorenzo; Schiraldi, Gianfranco; Bonara, Paola; Calvelli, Laura; Maiavacca, Rita; Cighetti, Giuliana

2013-01-01

Cigarette smoking is associated with reduced pulmonary function and increased risk factors for cardiovascular disease. This randomized placebo-controlled double-blind study evaluated the effects of two different combinations of mixed fruit and vegetable juice powder concentrate (Juice Plus+, NSA, Collierville, TN) on heavy smokers. At baseline (T 0) and after 3 months' supplementation (T 1), pulmonary function parameters and cardiovascular risk factors-that is, plasma total homocysteine (tHcy) with related B vitamins and cysteine (tCys) concentrations-were assessed in 75 apparently healthy smokers (aged 49.2 ± 10.6 years, >20 cigarettes/d, duration ≥10 years) randomized into 3 groups: placebo (P), fruit/vegetable (FV) and fruit/vegetable/berry (FVB). T 0: most smokers showed abnormalities in tHcy and tCys concentrations. T 1: respiratory function was unchanged in P and slightly, but not significantly, improved in FV, whereas FVB showed a significant improvement in forced expiratory flow at 25% (FEF25; p < 0.0001 vs P and FV) and significant improvement in CO diffusion lung/alveolar volume (DLCO/VA). FV and FVB (50%) showed significant reduction in tHcy and tCys compared to T 0 ( p < 0.0001) and P ( p < 0.0001). At T 1, both supplemented groups, but to a greater extent the FVB group, showed improvements in some pulmonary parameters, cardiovascular risk factors, and folate status. The beneficial effects of Juice Plus+ supplementation could potentially help smokers, even if smoking cessation is advisable.

Opportunities to improve the conversion of food waste to lactate: Fine-tuning secondary factors.

PubMed

RedCorn, Raymond; Engelberth, Abigail S

2017-11-01

Extensive research has demonstrated the potential for bioconversion of food waste to lactate, with major emphasis on adjusting temperature, pH, and loading rate of the fermentation. Each of these factors has a significant effect on lactate production; however, additional secondary factors have received little attention. Here we investigate three additional factors where opportunities exist for process improvement: freezing of samples during storage, discontinuous pH control, and holdover of fermentation broth between fermentations. Freezing samples prior to fermentation was shown to reduce the production rate of lactate by 8%, indicating freeze-thaw should be avoided in experiments. Prior work indicated a trade-off in pH control strategies, where discontinuous pH control correlated with higher lactate accumulation while continuous pH control correlated with higher production rate. Here we demonstrate that continuous pH control can achieve both higher lactate accumulation and higher production rate. Finally, holding over fermentation broth was shown to be a simple method to improve production rate (by 18%) at high food waste loading rates (>140 g volatile solids L -1 ) but resulted in lower lactate accumulation (by 17%). The results inform continued process improvements within the waste treatment of food waste through fermentation to lactic acid.

Overexpression of OsTF1L, a rice HD-Zip transcription factor, promotes lignin biosynthesis and stomatal closure that improves drought tolerance.

PubMed

Bang, Seung Woon; Lee, Dong-Keun; Jung, Harin; Chung, Pil Joong; Kim, Youn Shic; Choi, Yang Do; Suh, Joo-Won; Kim, Ju-Kon

2018-05-21

Drought stress seriously impacts on plant development and productivity. Improvement of drought tolerance without yield penalty is a great challenge in crop biotechnology. Here, we report that the rice (Oryza sativa) homeodomain-leucine zipper transcription factor gene, OsTF1L (Oryza sativa transcription factor 1-like), is a key regulator of drought tolerance mechanisms. Overexpression of the OsTF1L in rice significantly increased drought tolerance at the vegetative stages of growth and promoted both effective photosynthesis and a reduction in the water loss rate under drought conditions. Importantly, the OsTF1L overexpressing plants showed a higher drought tolerance at the reproductive stage of growth with a higher grain yield than non-transgenic controls under field-drought conditions. Genome-wide analysis of OsTF1L overexpression plants revealed up-regulation of drought-inducible, stomatal movement and lignin biosynthetic genes. Overexpression of OsTF1L promoted accumulation of lignin in shoots, whereas the RNAi lines showed opposite patterns of lignin accumulation. OsTF1L is mainly expressed in outer cell layers including the epidermis, and the vasculature of the shoots, which coincides with areas of lignification. In addition, OsTF1L overexpression enhances stomatal closure under drought conditions resulted in drought tolerance. More importantly, OsTF1L directly bound to the promoters of lignin biosynthesis and drought-related genes involving poxN/PRX38, Nodulin protein, DHHC4, CASPL5B1 and AAA-type ATPase. Collectively, our results provide a new insight into the role of OsTF1L in enhancing drought tolerance through lignin biosynthesis and stomatal closure in rice. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Extracellular Matrix and Growth Factors Improve the Efficacy of Intramuscular Islet Transplantation.

PubMed

Tsuchiya, Haruyuki; Sakata, Naoaki; Yoshimatsu, Gumpei; Fukase, Masahiko; Aoki, Takeshi; Ishida, Masaharu; Katayose, Yu; Egawa, Shinichi; Unno, Michiaki

2015-01-01

The efficacy of intramuscular islet transplantation is poor despite being technically simple, safe, and associated with reduced rates of severe complications. We evaluated the efficacy of combined treatment with extracellular matrix (ECM) and growth factors in intramuscular islet transplantation. Male BALB/C mice were used for the in vitro and transplantation studies. The following three groups were evaluated: islets without treatment (islets-only group), islets embedded in ECM with growth factors (Matrigel group), and islets embedded in ECM without growth factors [growth factor-reduced (GFR) Matrigel group]. The viability and insulin-releasing function of islets cultured for 96 h were significantly improved in Matrigel and GFR Matrigel groups compared with the islets-only group. Blood glucose and serum insulin levels immediately following transplantation were significantly improved in the Matrigel and GFR Matrigel groups and remained significantly improved in the Matrigel group at postoperative day (POD) 28. On histological examination, significantly decreased numbers of TdT-mediated deoxyuridine triphosphate-biotin nick end labeling-positive islet cells and significantly increased numbers of Ki67-positive cells were observed in the Matrigel and GFR Matrigel groups at POD 3. Peri-islet revascularization was most prominent in the Matrigel group at POD 14. The efficacy of intramuscular islet transplantation was improved by combination treatment with ECM and growth factors through the inhibition of apoptosis, increased proliferation of islet cells, and promotion of revascularization.

Improving the Quality and Scientific Understanding of Trophic Magnification Factors (TMFs)

EPA Science Inventory

This short 1000 word report presents a series of research needs for improving the measurement and understanding of trophic magnification factors (TMFs). TMFs are useful measures of trophic magnification and represent the diet-weighted average biomagnification factor (BMF) of che...

Polymer-free carbon nanotube thermoelectrics with improved charge carrier transport and power factor

DOE PAGES

Norton-Baker, Brenna; Ihly, Rachelle; Gould, Isaac E.; ...

2016-11-17

Here, semiconducting single-walled carbon nanotubes (s-SWCNTs) have recently attracted attention for their promise as active components in a variety of optical and electronic applications, including thermoelectricity generation. Here we demonstrate that removing the wrapping polymer from the highly enriched s-SWCNT network leads to substantial improvements in charge carrier transport and thermoelectric power factor. These improvements arise primarily from an increase in charge carrier mobility within the s-SWCNT networks because of removal of the insulating polymer and control of the level of nanotube bundling in the network, which enables higher thin-film conductivity for a given carrier density. Ultimately, these studies demonstratemore » that highly enriched s-SWCNT thin films, in the complete absence of any accompanying semiconducting polymer, can attain thermoelectric power factors in the range of approximately 400 μW m -1K -2, which is on par with that of some of the best single-component organic thermoelectrics demonstrated to date.« less

Improved vascularization of planar membrane diffusion devices following continuous infusion of vascular endothelial growth factor.

PubMed

Trivedi, N; Steil, G M; Colton, C K; Bonner-Weir, S; Weir, G C

2000-01-01

Improving blood vessel formation around an immunobarrier device should improve the survival of the encapsulated tissue. In the present study we investigated the formation of new blood vessels around a planar membrane diffusion device (the Baxter Theracyte System) undergoing a continuous infusion of vascular endothelial growth factor through the membranes and into the surrounding tissue. Each device (20 microl) had both an inner immunoisolation membrane and an outer vascularizing membrane. Human recombinant vascular endothelial growth factor-165 was infused at 100 ng/day (low dose: n = 6) and 500 ng/day (high dose: n = 7) for 10 days into devices implanted s.c. in Sprague-Dawley rats; noninfused devices transplanted for an identical period were used as controls (n = 5). Two days following the termination of VEGF infusion, devices were loaded with 20 microl of Lispro insulin (1 U/kg) and the kinetics of insulin release from the lumen of the device was assessed. Devices were then explanted and the number of blood vessels (capillary and noncapillary) was quantified using morphometry. High-dose vascular endothelial growth factor infusion resulted in two- to threefold more blood vessels around the device than that obtained with the noninfused devices and devices infused with low-dose vascular endothelial growth factor. This increase in the number of blood vessels was accompanied by a modest increase in insulin diffusion from the device in the high-dose vascular endothelial growth factor infusion group. We conclude that vascular endothelial growth factor can be used to improve blood vessel formation adjacent to planar membrane diffusion devices.

47 CFR 73.35 - Calculation of improvement factors.

Code of Federal Regulations, 2014 CFR

2014-10-01

... for an allotment (See § 73.30) in the 1605-1705 kHz band filed by an existing fulltime AM station licensed in the 535-1605 kHz band will be ranked according to the station's calculated improvement factor... calculations excluding the subject station. The cumulative gain in the above service area is the numerator of...

47 CFR 73.35 - Calculation of improvement factors.

Code of Federal Regulations, 2013 CFR

2013-10-01

... for an allotment (See § 73.30) in the 1605-1705 kHz band filed by an existing fulltime AM station licensed in the 535-1605 kHz band will be ranked according to the station's calculated improvement factor... calculations excluding the subject station. The cumulative gain in the above service area is the numerator of...

47 CFR 73.35 - Calculation of improvement factors.

Code of Federal Regulations, 2011 CFR

2011-10-01

... for an allotment (See § 73.30) in the 1605-1705 kHz band filed by an existing fulltime AM station licensed in the 535-1605 kHz band will be ranked according to the station's calculated improvement factor... calculations excluding the subject station. The cumulative gain in the above service area is the numerator of...

47 CFR 73.35 - Calculation of improvement factors.

Code of Federal Regulations, 2010 CFR

2010-10-01

... for an allotment (See § 73.30) in the 1605-1705 kHz band filed by an existing fulltime AM station licensed in the 535-1605 kHz band will be ranked according to the station's calculated improvement factor... calculations excluding the subject station. The cumulative gain in the above service area is the numerator of...

47 CFR 73.35 - Calculation of improvement factors.

Code of Federal Regulations, 2012 CFR

2012-10-01

... for an allotment (See § 73.30) in the 1605-1705 kHz band filed by an existing fulltime AM station licensed in the 535-1605 kHz band will be ranked according to the station's calculated improvement factor... calculations excluding the subject station. The cumulative gain in the above service area is the numerator of...

Localisation of stem cell factor, stanniocalcin-1, connective tissue growth factor and heparin-binding epidermal growth factor in the bovine uterus at the time of blastocyst formation.

PubMed

Muñoz, M; Martin, D; Carrocera, S; Alonso-Guervos, M; Mora, M I; Corrales, F J; Peynot, N; Giraud-Delville, C; Duranthon, V; Sandra, O; Gómez, E

2017-10-01

Early embryonic losses before implantation account for the highest rates of reproductive failure in mammals, in particular when in vitro-produced embryos are transferred. In the present study, we used molecular biology techniques (real-time quantitative polymerase chain reaction), classical immunohistochemical staining coupled with confocal microscopy and proteomic analysis (multiple reaction monitoring and western blot analysis) to investigate the role of four growth factors in embryo-uterine interactions during blastocyst development. Supported by a validated embryo transfer model, the study investigated: (1) the expression of stem cell factor (SCF), stanniocalcin-1 (STC1), connective tissue growth factor (CTGF) and heparin-binding epidermal growth factor-like growth factor (HB-EGF) in bovine uterine fluid; (2) the presence of SCF, STC1, CTGF and HB-EGF mRNA and protein in the bovine endometrium and embryos; and (3) the existence of reciprocal regulation between endometrial and embryonic expression of SCF, STC1, CTGF and HB-EGF. The results suggest that these growth factors most likely play an important role during preimplantation embryo development in cattle. The information obtained from the present study can contribute to improving the performance of in vitro culture technology in cattle and other species.

Double overexpression of DREB and PIF transcription factors improves drought stress tolerance and cell elongation in transgenic plants.

PubMed

Kudo, Madoka; Kidokoro, Satoshi; Yoshida, Takuya; Mizoi, Junya; Todaka, Daisuke; Fernie, Alisdair R; Shinozaki, Kazuo; Yamaguchi-Shinozaki, Kazuko

2017-04-01

Although a variety of transgenic plants that are tolerant to drought stress have been generated, many of these plants show growth retardation. To improve drought tolerance and plant growth, we applied a gene-stacking approach using two transcription factor genes: DEHYDRATION-RESPONSIVE ELEMENT-BINDING 1A (DREB1A) and rice PHYTOCHROME-INTERACTING FACTOR-LIKE 1 (OsPIL1). The overexpression of DREB1A has been reported to improve drought stress tolerance in various crops, although it also causes a severe dwarf phenotype. OsPIL1 is a rice homologue of Arabidopsis PHYTOCHROME-INTERACTING FACTOR 4 (PIF4), and it enhances cell elongation by activating cell wall-related gene expression. We found that the OsPIL1 protein was more stable than PIF4 under light conditions in Arabidopsis protoplasts. Transactivation analyses revealed that DREB1A and OsPIL1 did not negatively affect each other's transcriptional activities. The transgenic plants overexpressing both OsPIL1 and DREB1A showed the improved drought stress tolerance similar to that of DREB1A overexpressors. Furthermore, double overexpressors showed the enhanced hypocotyl elongation and floral induction compared with the DREB1A overexpressors. Metabolome analyses indicated that compatible solutes, such as sugars and amino acids, accumulated in the double overexpressors, which was similar to the observations of the DREB1A overexpressors. Transcriptome analyses showed an increased expression of abiotic stress-inducible DREB1A downstream genes and cell elongation-related OsPIL1 downstream genes in the double overexpressors, which suggests that these two transcription factors function independently in the transgenic plants despite the trade-offs required to balance plant growth and stress tolerance. Our study provides a basis for plant genetic engineering designed to overcome growth retardation in drought-tolerant transgenic plants. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology

Interleukin-1, tumor necrosis factor-alpha, and transforming growth factor-beta 1 and integrative meniscal repair: influences on meniscal cell proliferation and migration

PubMed Central

2011-01-01

Introduction Interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) are up-regulated in injured and osteoarthritic knee joints. IL-1 and TNF-α inhibit integrative meniscal repair; however, the mechanisms by which this inhibition occurs are not fully understood. Transforming growth factor-β1 (TGF-β1) increases meniscal cell proliferation and accumulation, and enhances integrative meniscal repair. An improved understanding of the mechanisms modulating meniscal cell proliferation and migration will help to improve approaches for enhancing intrinsic or tissue-engineered repair of the meniscus. The goal of this study was to examine the hypothesis that IL-1 and TNF-α suppress, while TGF-β1 enhances, cellular proliferation and migration in cell and tissue models of meniscal repair. Methods A micro-wound assay was used to assess meniscal cell migration and proliferation in response to the following treatments for 0, 24, or 48 hours: 0 to 10 ng/mL IL-1, TNF-α, or TGF-β1, in the presence or absence of 10% serum. Proliferated and total cells were fluorescently labeled and imaged using confocal laser scanning microscopy and the number of proliferated, migrated, and total cells was determined in the micro-wound and edges of each image. Meniscal cell proliferation was also assessed throughout meniscal repair model explants treated with 0 or 10 ng/mL IL-1, TNF-α, or TGF-β1 for 14 days. At the end of the culture period, biomechanical testing and histological analyses were also performed. Statistical differences were assessed using an ANOVA and Newman-Keuls post hoc test. Results IL-1 and TNF-α decreased cell proliferation in both cell and tissue models of meniscal repair. In the presence of serum, TGF-β1 increased outer zone cell proliferation in the micro-wound and in the cross section of meniscal repair model explants. Both IL-1 and TNF-α decreased the integrative shear strength of repair and extracellular matrix deposition in the meniscal repair model system

Sivelestat sodium hydrate improves post-traumatic knee osteoarthritis through nuclear factor-κB in a rat model

PubMed Central

Yu, Xiaofeng; Zhao, Lijun; Yu, Zhiping; Yu, Changzheng; Bi, Jianfei; Sun, Binglong; Cong, Haibo

2017-01-01

As a specific inhibitor of neutrophil elastase, sivelestat sodium hydrate has primarily been used in the treatment of acute lung injury caused by various factors since its approval in 2002. Sivelestat sodium hydrate also improves post-traumatic knee osteoarthritis (KOA), although its underlying mechanisms of action have yet to be elucidated. The aim of the current study was to determine if sivelestat sodium hydrate improves post-traumatic KOA through nuclear factor (NF)-κB in a rat model. Treatment with sivelestat sodium hydrate significantly inhibited the induction of structural changes and significantly increased the vertical episode count and ipsilateral static weight bearing of the joint in KOA rats (all P<0.01). Sivelestat sodium hydrate significantly inhibited tumor necrosis factor-α and interleukin-6 production, serum nitrite levels, inducible nitric oxide synthase protein expression and high mobility group box 1 (HMGB1) secretion in KOA rats compared with the model group (all P<0.01). Sivelestat sodium hydrate also significantly suppressed p50/p65 DNA binding activity and NF-κB and phosphorylated inhibitor of κB protein expression in the joints of KOA rats compared with the model group (all P<0.01). These results suggest that sivelestat sodium hydrate improves post-traumatic KOA through HMGB1 and NF-κB in rats. PMID:28810618

Factors driving diabetes care improvement in a large medical group: ten years of progress.

PubMed

Sperl-Hillen, JoAnn M; O'Connor, Patrick J

2005-08-01

The purpose of this study was to document trends in diabetes quality of care and coinciding strategies for quality improvement over 10 years in a large medical group. Adults with diagnosed diabetes mellitus were identified each year from 1994 (N = 5610) to 2003 (N = 7650), and internal medical group data quantified improvement trends. Multivariate analysis was used to identify factors that did and did not contribute to improvement trends. Median glycosylated hemoglobin A1C (A1C) levels improved from 8.3% in 1994 to 6.9% in 2003 (P <.001). Mean low-density lipoprotein (LDL) cholesterol measurements improved from 132 mg/dL in 1995 to 97 mg/dL in 2003 (P <.001). Both A1C (P <.01) and LDL improvement (P <.0001) were driven by drug intensification, leadership commitment to diabetes improvement, greater continuity of primary care, participation in local and national diabetes care improvement initiatives, and allocation of multidisciplinary resources at the clinic level to improve diabetes care. Resources were spent on nurse and dietitian educators, active outreach to high-risk patients facilitated by registries, physician opinion leader activities including clinic-based training programs, and financial incentives to primary care clinics. Use of endocrinology referrals was stable throughout the period at about 10% of patients per year, and there were no disease management contracts to outside vendors over the study period. Electronic medical records did not favorably affect glycemic control or lipid control in this setting. This primary care-based system achieved A1C and LDL reductions sufficient to reduce macrovascular and microvascular risk by about 50% according to landmark studies; further risk reduction should be attainable through better blood pressure control. Strategies for diabetes improvement need to be customized to address documented gaps in quality of care, provider prescribing behaviors, and patient characteristics.

Identification and overexpression of a knotted1-like transcription factor in switchgrass ( Panicum virgatum L.) for lignocellulosic feedstock improvement

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

Wuddineh, Wegi A.; Mazarei, Mitra; Zhang, Ji -Yi

High biomass production and wide adaptation has made switchgrass ( Panicum virgatum L.) an important candidate lignocellulosic bioenergy crop. One major limitation of this and other lignocellulosic feedstocks is the recalcitrance of complex carbohydrates to hydrolysis for conversion to biofuels. Lignin is the major contributor to recalcitrance as it limits the accessibility of cell wall carbohydrates to enzymatic breakdown into fermentable sugars. Therefore, genetic manipulation of the lignin biosynthesis pathway is one strategy to reduce recalcitrance. Here, we identified a switchgrass Knotted1 transcription factor, PvKN1, with the aim of genetically engineering switchgrass for reduced biomass recalcitrance for biofuel production. Genemore » expression of the endogenous PvKN1 gene was observed to be highest in young inflorescences and stems. Ectopic overexpression of PvKN1 in switchgrass altered growth, especially in early developmental stages. Transgenic lines had reduced expression of most lignin biosynthetic genes accompanied by a reduction in lignin content suggesting the involvement of PvKN1 in the broad regulation of the lignin biosynthesis pathway. Moreover, the reduced expression of the Gibberellin 20-oxidase (GA20ox) gene in tandem with the increased expression of Gibberellin 2-oxidase (GA2ox) genes in transgenic PvKN1 lines suggest that PvKN1 may exert regulatory effects via modulation of GA signaling. Furthermore, overexpression of PvKN1 altered the expression of cellulose and hemicellulose biosynthetic genes and increased sugar release efficiency in transgenic lines. Our findings demonstrated that switchgrass PvKN1 is a putative ortholog of maize KN1 that is linked to plant lignification and cell wall and development traits as a major regulatory gene. Therefore, targeted overexpression of PvKN1 in bioenergy feedstocks may provide one feasible strategy for reducing biomass recalcitrance and simultaneously improving plant growth characteristics.« less

Identification and overexpression of a knotted1-like transcription factor in switchgrass ( Panicum virgatum L.) for lignocellulosic feedstock improvement

DOE PAGES

Wuddineh, Wegi A.; Mazarei, Mitra; Zhang, Ji -Yi; ...

2016-04-28

High biomass production and wide adaptation has made switchgrass ( Panicum virgatum L.) an important candidate lignocellulosic bioenergy crop. One major limitation of this and other lignocellulosic feedstocks is the recalcitrance of complex carbohydrates to hydrolysis for conversion to biofuels. Lignin is the major contributor to recalcitrance as it limits the accessibility of cell wall carbohydrates to enzymatic breakdown into fermentable sugars. Therefore, genetic manipulation of the lignin biosynthesis pathway is one strategy to reduce recalcitrance. Here, we identified a switchgrass Knotted1 transcription factor, PvKN1, with the aim of genetically engineering switchgrass for reduced biomass recalcitrance for biofuel production. Genemore » expression of the endogenous PvKN1 gene was observed to be highest in young inflorescences and stems. Ectopic overexpression of PvKN1 in switchgrass altered growth, especially in early developmental stages. Transgenic lines had reduced expression of most lignin biosynthetic genes accompanied by a reduction in lignin content suggesting the involvement of PvKN1 in the broad regulation of the lignin biosynthesis pathway. Moreover, the reduced expression of the Gibberellin 20-oxidase (GA20ox) gene in tandem with the increased expression of Gibberellin 2-oxidase (GA2ox) genes in transgenic PvKN1 lines suggest that PvKN1 may exert regulatory effects via modulation of GA signaling. Furthermore, overexpression of PvKN1 altered the expression of cellulose and hemicellulose biosynthetic genes and increased sugar release efficiency in transgenic lines. Our findings demonstrated that switchgrass PvKN1 is a putative ortholog of maize KN1 that is linked to plant lignification and cell wall and development traits as a major regulatory gene. Therefore, targeted overexpression of PvKN1 in bioenergy feedstocks may provide one feasible strategy for reducing biomass recalcitrance and simultaneously improving plant growth characteristics.« less

NRG1-Fc improves metabolic health via dual hepatic and central action.

PubMed

Zhang, Peng; Kuang, Henry; He, Yanlin; Idiga, Sharon O; Li, Siming; Chen, Zhimin; Yang, Zhao; Cai, Xing; Zhang, Kezhong; Potthoff, Matthew J; Xu, Yong; Lin, Jiandie D

2018-03-08

Neuregulins (NRGs) are emerging as an important family of signaling ligands that regulate glucose and lipid homeostasis. NRG1 lowers blood glucose levels in obese mice, whereas the brown fat-enriched secreted factor NRG4 protects mice from high-fat diet-induced insulin resistance and hepatic steatosis. However, the therapeutic potential of NRGs remains elusive, given the poor plasma half-life of the native ligands. Here, we engineered a fusion protein using human NRG1 and the Fc domain of human IgG1 (NRG1-Fc) that exhibited extended half-life in circulation and improved potency in receptor signaling. We evaluated its efficacy in improving metabolic parameters and dissected the mechanisms of action. NRG1-Fc treatment triggered potent AKT activation in the liver, lowered blood glucose, improved insulin sensitivity, and suppressed food intake in obese mice. NRG1-Fc acted as a potent secretagogue for the metabolic hormone FGF21; however, the latter was largely dispensable for its metabolic effects. NRG1-Fc directly targeted the hypothalamic POMC neurons to promote membrane depolarization and increase firing rate. Together, NRG1-Fc exhibits improved pharmacokinetic properties and exerts metabolic benefits through dual inhibition of hepatic gluconeogenesis and caloric intake.

NRG1-Fc improves metabolic health via dual hepatic and central action

PubMed Central

Kuang, Henry; Idiga, Sharon O.; Li, Siming; Chen, Zhimin; Cai, Xing; Zhang, Kezhong; Potthoff, Matthew J.; Xu, Yong; Lin, Jiandie D.

2018-01-01

Neuregulins (NRGs) are emerging as an important family of signaling ligands that regulate glucose and lipid homeostasis. NRG1 lowers blood glucose levels in obese mice, whereas the brown fat–enriched secreted factor NRG4 protects mice from high-fat diet–induced insulin resistance and hepatic steatosis. However, the therapeutic potential of NRGs remains elusive, given the poor plasma half-life of the native ligands. Here, we engineered a fusion protein using human NRG1 and the Fc domain of human IgG1 (NRG1-Fc) that exhibited extended half-life in circulation and improved potency in receptor signaling. We evaluated its efficacy in improving metabolic parameters and dissected the mechanisms of action. NRG1-Fc treatment triggered potent AKT activation in the liver, lowered blood glucose, improved insulin sensitivity, and suppressed food intake in obese mice. NRG1-Fc acted as a potent secretagogue for the metabolic hormone FGF21; however, the latter was largely dispensable for its metabolic effects. NRG1-Fc directly targeted the hypothalamic POMC neurons to promote membrane depolarization and increase firing rate. Together, NRG1-Fc exhibits improved pharmacokinetic properties and exerts metabolic benefits through dual inhibition of hepatic gluconeogenesis and caloric intake. PMID:29515030

Transplant of insulin-like growth factor-1 expressing bone marrow stem cells improves functional regeneration of injured rat uterus by NF-κB pathway.

PubMed

Wang, Lei; Yang, Mengnan; Jin, Minfei; Wu, Yuelin; Zheng, Tao; Gu, Shengyi; Hua, Xiaolin

2018-05-01

To investigate the potential beneficial effect of insulin-like growth factor-1 (IGF-1) in BMSC transplantation therapy of uterus injury and the underlying molecular mechanisms, rat BMSCs were isolated and cultured. The relative expressions of IGF-1 and IL-10 were determined by RT-PCR and immunoblotting. The secretory IL-10 and released E2 were measured using ELISA kits. The relative vWF and α-SMA expressions were determined by immunohistochemistry. The direct binding of NF-κB subunit p50 with IL-10 promoter was analysed by chromatin immunoprecipitation assay. The regulation of IL-10 expression by p50 was interrogated by luciferase reporter assay. Our data demonstrated that IGF-1 expression in BMSCs induced IL-10 expression and secretion, which was further enhanced by E2-PLGA. IGF-1 overexpression improved BMSCs transplantation therapy in rat uterus injury. We further demonstrated that both inhibition and knockdown of p50 abolished IGF-1-induced expression and secretion of IL-10 in BMSCs, which consequently compromised the IGF-1 conferred therapeutic benefits against uterus injury. Furthermore, we elucidated that p50 regulated IL-10 expression via direct association with its promoter. Our data suggested that transplantation of IGF-1 overexpressing BMSCs improved functional regeneration of injured uterus by inducing IL-10 expression and secretion via activation of NF-κB signalling. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Optimization of factors to obtain cassava starch films with improved mechanical properties

NASA Astrophysics Data System (ADS)

Monteiro, Mayra; Oliveira, Victor; Santos, Francisco; Barros Neto, Eduardo; Silva, Karyn; Silva, Rayane; Henrique, João; Chibério, Abimaelle

2017-08-01

In this study, was investigated the optimization of the factors that significantly influenced the mechanical property improvement of cassava starch films through complete factorial design 23. The factors to be analyzed were cassava starch, glycerol and modified clay contents. A regression model was proposed by the factorial analysis, aiming to estimate the condition of the individual factors investigated in the optimum state of the mechanical properties of the biofilm, using the following statistical tool: desirability function and response surface. The response variable that delimits the improvement of the mechanical property of the biofilm is the tensile strength, such improvement is obtained by maximizing the response variable. The factorial analysis showed that the best combination of factor configurations to reach the best response was found to be: with 5g of cassava starch, 10% of glycerol and 5% of modified clay, both percentages in relation to the dry mass of starch used. In addition, the starch biofilm showing the lowest response contained 2g of cassava starch, 0% of modified clay and 30% of glycerol, and was consequently considered the worst biofilm.

Combined treatment with a transforming growth factor beta inhibitor (1D11) and bortezomib improves bone architecture in a mouse model of myeloma-induced bone disease

PubMed Central

Nyman, Jeffry S.; Merkel, Alyssa R.; Uppuganti, Sasidhar; Nayak, Bijaya; Rowland, Barbara; Makowski, Alexander J.; Oyajobi, Babatunde O.; Sterling, Julie A.

2016-01-01

Multiplemyeloma (MM) patients frequently develop tumor-induced bone destruction, yet no therapy completely eliminates the tumor or fully reverses bone loss. Transforming growth factor-β (TGF-β) activity often contributes to tumor-induced bone disease, and pre-clinical studies have indicated that TGF-β inhibition improves bone volume and reduces tumor growth in bone metastatic breast cancer. We hypothesized that inhibition of TGF-β signaling also reduces tumor growth, increases bone volume, and improves vertebral body strength in MM-bearing mice. We treated myeloma tumor-bearing (immunocompetent KaLwRij and immunocompromised Rag2 −/−) mice with a TGF-β inhibitory (1D11) or control (13C4) antibody, with or without the anti-myeloma drug bortezomib, for 4 weeks after inoculation of murine 5TGM1 MM cells. TGF-β inhibition increased trabecular bone volume, improved trabecular architecture, increased tissue mineral density of the trabeculae as assessed by ex vivo micro-computed tomography, and was associated with significantly greater vertebral body strength in biomechanical compression tests. Serum monoclonal paraprotein titers and spleen weights showed that 1D11 monotherapy did not reduce overall MM tumor burden. Combination therapy with 1D11 and bortezomib increased vertebral body strength, reduced tumor burden, and reduced cortical lesions in the femoral metaphysis, although it did not significantly improve cortical bone strength in three-point bending tests of the mid-shaft femur. Overall, our data provides rationale for evaluating inhibition of TGF-β signaling in combination with existing anti-myeloma agents as a potential therapeutic strategy to improve outcomes in patients with myeloma bone disease. PMID:27423464

Combined treatment with a transforming growth factor beta inhibitor (1D11) and bortezomib improves bone architecture in a mouse model of myeloma-induced bone disease.

PubMed

Nyman, Jeffry S; Merkel, Alyssa R; Uppuganti, Sasidhar; Nayak, Bijaya; Rowland, Barbara; Makowski, Alexander J; Oyajobi, Babatunde O; Sterling, Julie A

2016-10-01

Multiple myeloma (MM) patients frequently develop tumor-induced bone destruction, yet no therapy completely eliminates the tumor or fully reverses bone loss. Transforming growth factor-β (TGF-β) activity often contributes to tumor-induced bone disease, and pre-clinical studies have indicated that TGF-β inhibition improves bone volume and reduces tumor growth in bone metastatic breast cancer. We hypothesized that inhibition of TGF-β signaling also reduces tumor growth, increases bone volume, and improves vertebral body strength in MM-bearing mice. We treated myeloma tumor-bearing (immunocompetent KaLwRij and immunocompromised Rag2-/-) mice with a TGF-β inhibitory (1D11) or control (13C4) antibody, with or without the anti-myeloma drug bortezomib, for 4weeks after inoculation of murine 5TGM1 MM cells. TGF-β inhibition increased trabecular bone volume, improved trabecular architecture, increased tissue mineral density of the trabeculae as assessed by ex vivo micro-computed tomography, and was associated with significantly greater vertebral body strength in biomechanical compression tests. Serum monoclonal paraprotein titers and spleen weights showed that 1D11 monotherapy did not reduce overall MM tumor burden. Combination therapy with 1D11 and bortezomib increased vertebral body strength, reduced tumor burden, and reduced cortical lesions in the femoral metaphysis, although it did not significantly improve cortical bone strength in three-point bending tests of the mid-shaft femur. Overall, our data provides rationale for evaluating inhibition of TGF-β signaling in combination with existing anti-myeloma agents as a potential therapeutic strategy to improve outcomes in patients with myeloma bone disease. Published by Elsevier Inc.

Improving English Speaking Fluency: The Role of Six Factors

ERIC Educational Resources Information Center

Shahini, Gholamhossein; Shahamirian, Fatemeh

2017-01-01

This qualitative study, using an open interview, set out to investigate the roles six factors, including age, university education, teachers of English Language institutes, teaching English, dictionary, and note-taking, played in improving English speaking fluency of seventeen fluent Iranian EFL speakers. The participants were chosen purposefully…

Enhanced mesenchymal cell engraftment by IGF-1 improves left ventricular function in rats undergoing myocardial infarction.

PubMed

Enoki, Chiharu; Otani, Hajime; Sato, Daisuke; Okada, Takayuki; Hattori, Reiji; Imamura, Hiroji

2010-01-07

We hypothesized that enhanced mesenchymal cell (MC) engraftment with insulin-like growth factor-1 (IGF-1) improves left ventricular (LV) function and survival. IGF-1 (10 microg/ml) increased adhesion and inhibited apoptosis under hypoxia in vitro through activation of phosphatidylinositol 3-kinase (PI3K) in bone marrow-derived MCs obtained from transgenic rats expressing green fluorescence protein. Myocardial infarction (MI) in rats was produced by ligature of the left coronary artery. One month after MI, rat hearts were injected with MCs in the presence or absence of 10 microg/ml IGF-1 with or without PI3K inhibitor, 5 microM LY294002. IGF-1 significantly increased engraftment of MCs between 6 h and 3 days after transplantation associated with the increase in stromal cell-derived factor-1alpha in the infracted LV. The transplanted MCs had disappeared 1 month after transplantation in all groups. MC transplantation with IGF-1 significantly increased neovascularization and inhibited cardiomyocyte apoptosis 3 days and 1 month after MC transplantation. This was associated with improved LV function 1 month after MC transplantation and eventually survival. LY294002 abrogated all of the beneficial effects of MC transplantation with IGF-1. IGF-1 alone had no effect on neovascularization and did not improve LV function and/or survival. These results suggest that IGF-1 improves engraftment of MCs at the time of transplantation via activation of PI3K and this improved engraftment of MCs may be attributed to an increased neovascularization and inhibition of cardiomyocyte death, leading to improvement of LV function and prolongation of survival despite the eventual loss of the transplanted MCs.

Interventions for improving modifiable risk factor control in the secondary prevention of stroke.

PubMed

Lager, Kate E; Mistri, Amit K; Khunti, Kamlesh; Haunton, Victoria J; Sett, Aung K; Wilson, Andrew D

2014-05-02

interval (CI) -5.46 to 0.31), mean diastolic blood pressure (MD -0.90 mmHg; 95% CI -2.49 to 0.68), blood pressure target achievement (OR 1.24; 95% CI 0.94 to 1.64) and mean body mass index (MD -0.68 kg/m(2); 95% CI -1.46 to 0.11). There were no significant effects of organisational interventions on lipid profile, HbA1c, medication adherence or recurrent cardiovascular events. Educational and behavioural interventions were not generally associated with clear differences in any of the review outcomes, with only two exceptions. Pooled results indicated that educational interventions were not associated with clear differences in any of the review outcomes. The estimated effects of organisational interventions were compatible with improvements and no differences in several modifiable risk factors. We identified a large number of ongoing studies, suggesting that research in this area is increasing. The use of standardised outcome measures would facilitate the synthesis of future research findings.

[Factors influencing research activity of Andalusian nurses and improvement strategies].

PubMed

López Alonso, Sergio R; Gálvez González, María; Amezcua, Manuel

2013-04-01

To identify factors influencing research activity of Andalusian nurses and to find improvement strategies. Qualitative research using SWOT analysis (weaknesses, threats, strengths, opportunities). Nurses were selected deliberately in eight groups according to predetermined criteria. Analysis included categorization and relationship of factors and strategies. 81 participants were included in groups of 7-12 range. 45 categories were identified with 212 factors: 12 weaknesses (50 factors), 10 strengths (44 factors), 12 threats (68 factors) and 11 opportunities (50 factors). In addition, 32 categories were identified with 53 strategies: 14 categories of W-T strategies (42 strategies), 3 categories of S-T strategies (11 strategies), 5 categories of W-O strategies (13 strategies) and 10 categories of S-O strategies (41 strategies). Nurses identified numerous factors, mainly threats. The strategies are focused on W-T but they also suggest many but weak 5-0 strategies due to the low potential of the opportunities and strengths perceived.

Reactivation of Latent HIV-1 Expression by Engineered TALE Transcription Factors.

PubMed

Perdigão, Pedro; Gaj, Thomas; Santa-Marta, Mariana; Barbas, Carlos F; Goncalves, Joao

2016-01-01

The presence of replication-competent HIV-1 -which resides mainly in resting CD4+ T cells--is a major hurdle to its eradication. While pharmacological approaches have been useful for inducing the expression of this latent population of virus, they have been unable to purge HIV-1 from all its reservoirs. Additionally, many of these strategies have been associated with adverse effects, underscoring the need for alternative approaches capable of reactivating viral expression. Here we show that engineered transcriptional modulators based on customizable transcription activator-like effector (TALE) proteins can induce gene expression from the HIV-1 long terminal repeat promoter, and that combinations of TALE transcription factors can synergistically reactivate latent viral expression in cell line models of HIV-1 latency. We further show that complementing TALE transcription factors with Vorinostat, a histone deacetylase inhibitor, enhances HIV-1 expression in latency models. Collectively, these findings demonstrate that TALE transcription factors are a potentially effective alternative to current pharmacological routes for reactivating latent virus and that combining synthetic transcriptional activators with histone deacetylase inhibitors could lead to the development of improved therapies for latent HIV-1 infection.

Reactivation of Latent HIV-1 Expression by Engineered TALE Transcription Factors

PubMed Central

Perdigão, Pedro; Gaj, Thomas; Santa-Marta, Mariana; Goncalves, Joao

2016-01-01

The presence of replication-competent HIV-1 –which resides mainly in resting CD4+ T cells–is a major hurdle to its eradication. While pharmacological approaches have been useful for inducing the expression of this latent population of virus, they have been unable to purge HIV-1 from all its reservoirs. Additionally, many of these strategies have been associated with adverse effects, underscoring the need for alternative approaches capable of reactivating viral expression. Here we show that engineered transcriptional modulators based on customizable transcription activator-like effector (TALE) proteins can induce gene expression from the HIV-1 long terminal repeat promoter, and that combinations of TALE transcription factors can synergistically reactivate latent viral expression in cell line models of HIV-1 latency. We further show that complementing TALE transcription factors with Vorinostat, a histone deacetylase inhibitor, enhances HIV-1 expression in latency models. Collectively, these findings demonstrate that TALE transcription factors are a potentially effective alternative to current pharmacological routes for reactivating latent virus and that combining synthetic transcriptional activators with histone deacetylase inhibitors could lead to the development of improved therapies for latent HIV-1 infection. PMID:26933881

Effects of controlled whole-body vibration training in improving fall risk factors among individuals with multiple sclerosis: A pilot study.

PubMed

Yang, Feng; Finlayson, Marcia; Bethoux, Francois; Su, Xiaogang; Dillon, Loretta; Maldonado, Hector M

2018-03-01

The purpose of this study was to systematically examine the effect of an 8-week controlled whole-body vibration training on improving fall risk factors and the bone mineral density among people with multiple sclerosis (PwMS). This study adopted a single group pre-test-post-test design. Twenty-five PwMS (50.3 years SD 14.1) received vibration training on a side-alternating vibration platform. Each training session was repeated three times every week for 8 weeks. Prior to and following the 8-week training course, a battery of fall risk factors were evaluated: the body balance, functional mobility, muscle strength, range of motion, and fear of falling. Bone density at both calcanei was also assessed. Twenty-two participants completed the study. Compared with pre-test, almost all fall risk factors and the bone density measurement were significantly improved at post-test, with moderate to large effect sizes varying between 0.571 and 1.007. The 8-week vibration training was well accepted by PwMS and improved their fall risk factors. The important findings of this study were that vibration training may increase the range of motion of ankle joints on the sagittal plane, lower the fear of falling, and improve bone density. IMPLICATIONS FOR REHABILITATION An 8-week vibration training course could be well-accepted by people with multiple sclerosis (MS). Vibration training improves the risk factors of falls in people living with MS. Vibration training could be a promising rehabilitation intervention in individuals with MS.

Reverse shoulder arthroplasty for massive rotator cuff tear: risk factors for poor functional improvement.

PubMed

Hartzler, Robert U; Steen, Brandon M; Hussey, Michael M; Cusick, Michael C; Cottrell, Benjamin J; Clark, Rachel E; Frankle, Mark A

2015-11-01

Some patients unexpectedly have poor functional improvement after reverse shoulder arthroplasty (RSA) for massive rotator cuff tear without glenohumeral arthritis. Our aim was to identify risk factors for this outcome. We also assessed the value of RSA for cases with poor functional improvement vs. The study was a retrospective case-control analysis for primary RSA performed for massive rotator cuff tear without glenohumeral arthritis with minimum 2-year follow-up. Cases were defined as Simple Shoulder Test (SST) score improvement of ≤1, whereas controls improved SST score ≥2. Risk factors were chosen on the basis of previous association with poor outcomes after shoulder arthroplasty. Latissimus dorsi tendon transfer results were analyzed as a subgroup. Value was defined as improvement in American Shoulder and Elbow Surgeons (ASES) score per $10,000 hospital cost. In a multivariate binomial logistic regression analysis, neurologic dysfunction (P = .006), age <60 years (P = .02), and high preoperative SST score (P = .03) were independently associated with poor functional improvement. Latissimus dorsi tendon transfer patients significantly improved in active external rotation (-0.3° to 38.7°; P < .01). The value of RSA (ΔASES/$10,000 cost) for cases was 0.8 compared with 17.5 for controls (P < .0001). Young age, high preoperative function, and neurologic dysfunction were associated with poor functional improvement. Surgeons should consider these associations in counseling and selection of patients. Concurrent latissimus dorsi transfer was successful in restoring active external rotation in a subgroup of patients. The critical economic importance of improved patient selection is emphasized by the very low value of the procedure in the case group. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Two weeks of high-intensity interval training improves novel but not traditional cardiovascular disease risk factors in adolescents.

PubMed

Bond, Bert; Cockcroft, Emma J; Williams, Craig A; Harris, Sam; Gates, Phillip E; Jackman, Sarah R; Armstrong, Neil; Barker, Alan R

2015-09-15

High-intensity interval training (HIIT) improves traditional cardiovascular disease (CVD) risk factors in adolescents, but no study has identified the influence of HIIT on endothelial and autonomic function in this group. Thirteen 13- to 14-yr-old adolescents (6 girls) completed six HIIT sessions over 2 wk. Each training session consisted of eight to ten 1-min repetitions of cycling at 90% peak power interspersed with 75 s of unloaded cycling. Traditional (triglycerides, cholesterol, glucose, insulin, and blood pressure) and novel [flow-mediated dilation (FMD), heart rate variability (HRV)] CVD risk factors were assessed in a fasted and postprandial state before (PRE), 1 day after (POST-1D), and 3 days after (POST-3D) training. Aerobic fitness was determined PRE and POST-3D. Two weeks of HIIT had no effect on aerobic fitness or traditional CVD risk factors determined in the fasted or postprandial state (P > 0.15). Compared with PRE, fasted FMD was improved POST-1D [P = 0.003, effect size (ES) = 0.70] but not POST-3D (P = 0.32, ES = 0.22). Fasted FMD was greater POST-1D compared with POST-3D (P = 0.04, ES = 0.48). Compared with PRE, postprandial FMD was greater POST-1D (P < 0.001, ES = 1.01) and POST-3D (P = 0.01, ES = 0.60). Fasted HRV was greater POST-1D (P = 0.001, ES = 0.71) and POST-3D (P = 0.02, ES = 0.44). The test meal lowered HRV in all laboratory visits (P < 0.001, ES = 0.59), but there were no differences in postprandial HRV between visits (P > 0.32 for all). Two weeks of HIIT enhanced endothelial function and HRV without improvements in traditional CVD risk factors. However, most of this favorable adaptation was lost POST-3D, suggesting that regularly performing high-intensity exercise is needed to maintain these benefits. Copyright © 2015 the American Physiological Society.

Transcription Factor Arabidopsis Activating Factor1 Integrates Carbon Starvation Responses with Trehalose Metabolism1[OPEN

PubMed Central

Garapati, Prashanth; Feil, Regina; Lunn, John Edward; Van Dijck, Patrick; Balazadeh, Salma; Mueller-Roeber, Bernd

2015-01-01

Plants respond to low carbon supply by massive reprogramming of the transcriptome and metabolome. We show here that the carbon starvation-induced NAC (for NO APICAL MERISTEM/ARABIDOPSIS TRANSCRIPTION ACTIVATION FACTOR/CUP-SHAPED COTYLEDON) transcription factor Arabidopsis (Arabidopsis thaliana) Transcription Activation Factor1 (ATAF1) plays an important role in this physiological process. We identified TREHALASE1, the only trehalase-encoding gene in Arabidopsis, as a direct downstream target of ATAF1. Overexpression of ATAF1 activates TREHALASE1 expression and leads to reduced trehalose-6-phosphate levels and a sugar starvation metabolome. In accordance with changes in expression of starch biosynthesis- and breakdown-related genes, starch levels are generally reduced in ATAF1 overexpressors but elevated in ataf1 knockout plants. At the global transcriptome level, genes affected by ATAF1 are broadly associated with energy and carbon starvation responses. Furthermore, transcriptional responses triggered by ATAF1 largely overlap with expression patterns observed in plants starved for carbon or energy supply. Collectively, our data highlight the existence of a positively acting feedforward loop between ATAF1 expression, which is induced by carbon starvation, and the depletion of cellular carbon/energy pools that is triggered by the transcriptional regulation of downstream gene regulatory networks by ATAF1. PMID:26149570

Ecological factors associated with pandemic influenza A (H1N1) hospitalization rates in California, USA: a geospatial analysis.

PubMed

Maliszewski, Paul J; Wei, Ran

2011-11-01

The 2009 H1N1 influenza A virus subtype (H1N1) pandemic had a large impact in the United States of America (USA), causing an estimated 192,000 to 398,000 hospitalizations and 8,720 to 18,050 deaths between April 2009 and mid-March 2010. Recent research on the 2009 H1N1 pandemic has largely focused on individual, non-spatial demographic characterizations (e.g. age and race/ethnicity) associated with H1N1 hospitalizations. Broader ecological factors such as transportation use, land use and other socioeconomic factors are important aspects of influenza studies that have not been empirically examined. This research explores and identifies ecological factors associated with 2009 H1N1 pandemic hospitalization rates. We conducted a spatial regression analysis of county level hospitalization rates from 3 April to 15 September, 2009 obtained via the California Department of Public Health. Hospitalization rates were found to be spatially dependent. Public transportation usage rates and agricultural land use proportions were significant environmental factors positively related to hospitalization rates. Consistent with public health official's assumptions and existing evidence, county percentages of persons less than 18 years of age were positively associated with hospitalization. These findings help to clarify the limited consensus and dubious evidence on the role of broader ecological factors associated with pandemic influenza. A better understanding of the ecological risk factors associated with hospitalizations should also benefit public health officials with respect to their work aiming at improving emergency supply allocation and non-pharmaceutical intervention strategies in the context of an influenza pandemic.

Pyridostigmine ameliorates cardiac remodeling induced by myocardial infarction via inhibition of the transforming growth factor-β1/TGF-β1-activated kinase pathway.

PubMed

Lu, Yi; Liu, Jin-Jun; Bi, Xue-Yuan; Yu, Xiao-Jiang; Kong, Shan-Shan; Qin, Fang-Fang; Zhou, Jun; Zang, Wei-Jin

2014-05-01

Autonomic imbalance characterized by sympathetic predominance coinciding with diminished vagal activity is an independent risk factor in cardiovascular diseases. Several studies show that vagus nerve stimulation exerted beneficial effects on cardiac function and survival. In this study, we investigated the vagomimetic effect of pyridostigmine on left ventricular (LV) remodeling in rats after myocardial infarction. After myocardial infarction, surviving rats were treated with or without pyridostigmine (31 mg·kg⁻¹·d⁻¹) for 2 weeks, and hemodynamic parameters were measured. LV tissue was used to assess infarct size and interstitial fibrosis by Masson's trichrome and 0.1% picrosirius red staining. Protein expression of heart tissues was used to assess the efficacy of the treatment. Pyridostigmine markedly reduced myocardial infarct size and improved cardiac diastolic function. These improvements were accompanied with a significant decrease in matrix metalloproteinase-2 expression and collagen deposition. Additionally, pyridostigmine inhibited both transforming growth factor-β1 (TGF-β1) and TGF-β1-activated kinase expression in hearts postmyocardial infarction. Thus, pyridostigmine reduces collagen deposition, attenuates cardiac fibrosis, and improves LV diastolic function after myocardial infarction via TGF-β1/TGF-β1-activated kinase pathway inhibition.

Improving Factor Score Estimation Through the Use of Observed Background Characteristics

PubMed Central

Curran, Patrick J.; Cole, Veronica; Bauer, Daniel J.; Hussong, Andrea M.; Gottfredson, Nisha

2016-01-01

A challenge facing nearly all studies in the psychological sciences is how to best combine multiple items into a valid and reliable score to be used in subsequent modelling. The most ubiquitous method is to compute a mean of items, but more contemporary approaches use various forms of latent score estimation. Regardless of approach, outside of large-scale testing applications, scoring models rarely include background characteristics to improve score quality. The current paper used a Monte Carlo simulation design to study score quality for different psychometric models that did and did not include covariates across levels of sample size, number of items, and degree of measurement invariance. The inclusion of covariates improved score quality for nearly all design factors, and in no case did the covariates degrade score quality relative to not considering the influences at all. Results suggest that the inclusion of observed covariates can improve factor score estimation. PMID:28757790

An improved technique for the 2H/1H analysis of urines from diabetic volunteers

USGS Publications Warehouse

Coplen, T.B.; Harper, I.T.

1994-01-01

The H2-H2O ambient-temperature equilibration technique for the determination of 2H/1H ratios in urinary waters from diabetic subjects provides improved accuracy over the conventional Zn reduction technique. The standard deviation, ~ 1-2???, is at least a factor of three better than that of the Zn reduction technique on urinary waters from diabetic volunteers. Experiments with pure water and solutions containing glucose, urea and albumen indicate that there is no measurable bias in the hydrogen equilibration technique.The H2-H2O ambient-temperature equilibration technique for the determination of 2H/1H ratios in urinary waters from diabetic subjects provides improved accuracy over the conventional Zn reduction technique. The standard deviation, approximately 1-2%, is at least a factor of three better than that of the Zn reduction technique on urinary waters from diabetic volunteers. Experiments with pure water and solutions containing glucose, urea and albumen indicate that there is no measurable bias in the hydrogen equilibration technique.

Growth Factor Stimulation Improves the Structure and Properties of Scaffold-Free Engineered Auricular Cartilage Constructs

PubMed Central

Rosa, Renata G.; Joazeiro, Paulo P.; Bianco, Juares; Kunz, Manuela; Weber, Joanna F.; Waldman, Stephen D.

2014-01-01

The reconstruction of the external ear to correct congenital deformities or repair following trauma remains a significant challenge in reconstructive surgery. Previously, we have developed a novel approach to create scaffold-free, tissue engineering elastic cartilage constructs directly from a small population of donor cells. Although the developed constructs appeared to adopt the structural appearance of native auricular cartilage, the constructs displayed limited expression and poor localization of elastin. In the present study, the effect of growth factor supplementation (insulin, IGF-1, or TGF-β1) was investigated to stimulate elastogenesis as well as to improve overall tissue formation. Using rabbit auricular chondrocytes, bioreactor-cultivated constructs supplemented with either insulin or IGF-1 displayed increased deposition of cartilaginous ECM, improved mechanical properties, and thicknesses comparable to native auricular cartilage after 4 weeks of growth. Similarly, growth factor supplementation resulted in increased expression and improved localization of elastin, primarily restricted within the cartilaginous region of the tissue construct. Additional studies were conducted to determine whether scaffold-free engineered auricular cartilage constructs could be developed in the 3D shape of the external ear. Isolated auricular chondrocytes were grown in rapid-prototyped tissue culture molds with additional insulin or IGF-1 supplementation during bioreactor cultivation. Using this approach, the developed tissue constructs were flexible and had a 3D shape in very good agreement to the culture mold (average error <400 µm). While scaffold-free, engineered auricular cartilage constructs can be created with both the appropriate tissue structure and 3D shape of the external ear, future studies will be aimed assessing potential changes in construct shape and properties after subcutaneous implantation. PMID:25126941

The use of patient factors to improve the prediction of operative duration using laparoscopic cholecystectomy.

PubMed

Thiels, Cornelius A; Yu, Denny; Abdelrahman, Amro M; Habermann, Elizabeth B; Hallbeck, Susan; Pasupathy, Kalyan S; Bingener, Juliane

2017-01-01

Reliable prediction of operative duration is essential for improving patient and care team satisfaction, optimizing resource utilization and reducing cost. Current operative scheduling systems are unreliable and contribute to costly over- and underestimation of operative time. We hypothesized that the inclusion of patient-specific factors would improve the accuracy in predicting operative duration. We reviewed all elective laparoscopic cholecystectomies performed at a single institution between 01/2007 and 06/2013. Concurrent procedures were excluded. Univariate analysis evaluated the effect of age, gender, BMI, ASA, laboratory values, smoking, and comorbidities on operative duration. Multivariable linear regression models were constructed using the significant factors (p < 0.05). The patient factors model was compared to the traditional surgical scheduling system estimates, which uses historical surgeon-specific and procedure-specific operative duration. External validation was done using the ACS-NSQIP database (n = 11,842). A total of 1801 laparoscopic cholecystectomy patients met inclusion criteria. Female sex was associated with reduced operative duration (-7.5 min, p < 0.001 vs. male sex) while increasing BMI (+5.1 min BMI 25-29.9, +6.9 min BMI 30-34.9, +10.4 min BMI 35-39.9, +17.0 min BMI 40 + , all p < 0.05 vs. normal BMI), increasing ASA (+7.4 min ASA III, +38.3 min ASA IV, all p < 0.01 vs. ASA I), and elevated liver function tests (+7.9 min, p < 0.01 vs. normal) were predictive of increased operative duration on univariate analysis. A model was then constructed using these predictive factors. The traditional surgical scheduling system was poorly predictive of actual operative duration (R 2  = 0.001) compared to the patient factors model (R 2  = 0.08). The model remained predictive on external validation (R 2  = 0.14).The addition of surgeon as a variable in the institutional model further improved predictive ability of the model

Alpha-lipoic acid improves high-fat diet-induced hepatic steatosis by modulating the transcription factors SREBP-1, FoxO1 and Nrf2 via the SIRT1/LKB1/AMPK pathway.

PubMed

Yang, Yi; Li, Wang; Liu, Yang; Sun, Yuning; Li, Yan; Yao, Qing; Li, Jianning; Zhang, Qian; Gao, Yujing; Gao, Ling; Zhao, Jiajun

2014-11-01

Understanding the mechanism by which alpha-lipoic acid supplementation has a protective effect upon nonalcoholic fatty liver disease in vivo and in vitro may lead to targets for preventing hepatic steatosis. Male C57BL/6J mice were fed a normal diet, high-fat diet or high-fat diet supplemented with alpha-lipoic acid for 24 weeks. HepG2 cells were incubated with normal medium, palmitate or alpha-lipoic acid. The lipid-lowering effects were measured. The protein expression and distribution were analyzed by Western blot, immunoprecipitation and immunofluorescence, respectively. We found that alpha-lipoic acid enhanced sirtuin 1 deacetylase activity through liver kinase B1 and stimulated AMP-activated protein kinase. By activating the sirtuin 1/liver kinase B1/AMP-activated protein kinase pathway, the translocation of sterol regulatory element-binding protein-1 into the nucleus and forkhead box O1 into the cytoplasm was prevented. Alpha-lipoic acid increased adipose triacylglycerol lipase expression and decreased fatty acid synthase abundance. In in vivo and in vitro studies, alpha-lipoic acid also increased nuclear NF-E2-related factor 2 levels and downstream target amounts via the sirtuin 1 pathway. Alpha-lipoic acid eventually reduced intrahepatic and serum triglyceride content. The protective effects of alpha-lipoic acid on hepatic steatosis appear to be associated with the transcription factors sterol regulatory element-binding protein-1, forkhead box O1 and NF-E2-related factor 2. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Analysis of Academic Administrators' Attitudes: Annual Evaluations and Factors That Improve Teaching

ERIC Educational Resources Information Center

Cherry, Brian D.; Grasse, Nathan; Kapla, Dale; Hamel, Brad

2017-01-01

This article examines academic administrators' attitudes towards the academic evaluation process in the US and those factors that are utilised to improve teaching. We use path regressions to examine satisfaction with evaluation procedures, as well as the direct and indirect effects of these factors on perceptions of whether the evaluation process…

Characterization of Transcription Factor Gene OsDRAP1 Conferring Drought Tolerance in Rice

PubMed Central

Huang, Liyu; Wang, Yinxiao; Wang, Wensheng; Zhao, Xiuqin; Qin, Qiao; Sun, Fan; Hu, Fengyi; Zhao, Yan; Li, Zichao; Fu, Binying; Li, Zhikang

2018-01-01

HIGHLIGHTS Overexpressing and RNA interfering OsDRAP1 transgenic rice plants exhibited significantly improved and reduced drought tolerance, but accompanied with negative effects on development and yield. The dehydration responsive element binding (DREBs) genes are important transcription factors which play a crucial role in plant abiotic stress tolerances. In this study, we functionally characterized a DREB2-like gene, OsDRAP1 conferring drought tolerance (DT) in rice. OsDRAP1, containing many cis-elements in its promoter region, was expressed in all organs (mainly expressed in vascular tissues) of rice, and induced by a variety of environmental stresses and plant hormones. Overexpressing OsDRAP1 transgenic plants exhibited significantly improved DT; while OsDRAP1 RNA interfering plants exhibited significantly reduced DT which also accompanied with significant negative effects on development and yield. Overexpression of OsDRAP1 has a positive impact on maintaining water balance, redox homeostasis and vascular development in transgenic rice plants under drought stress. OsDRAP1 interacted with many genes/proteins and could activate many downstream DT related genes, including important transcription factors such as OsCBSX3 to response drought stress, indicating the OsDRAP1-mediated pathways for DT involve complex genes networks. All these results provide a basis for further complete understanding of the OsDRAP1 mediated gene networks and their related phenotypic effects. PMID:29449862

Endurance Factors Improve Hippocampal Neurogenesis and Spatial Memory in Mice

ERIC Educational Resources Information Center

Kobilo, Tali; Yuan, Chunyan; van Praag, Henriette

2011-01-01

Physical activity improves learning and hippocampal neurogenesis. It is unknown whether compounds that increase endurance in muscle also enhance cognition. We investigated the effects of endurance factors, peroxisome proliferator-activated receptor [delta] agonist GW501516 and AICAR, activator of AMP-activated protein kinase on memory and…

Improved Sleep Quality is Associated with Reductions in Depression and PTSD Arousal Symptoms and Increases in IGF-1 Concentrations

PubMed Central

Rusch, Heather L.; Guardado, Pedro; Baxter, Tristin; Mysliwiec, Vincent; Gill, Jessica M.

2015-01-01

Study Objectives: One-third of deployed military personnel will be diagnosed with insomnia, placing them at high risk for comorbid depression, posttraumatic stress disorder (PTSD), and medical conditions. The disruption of trophic factors has been implicated in these comorbid conditions, which can impede postdeployment recovery. This study determined if improved sleep quality is associated with (1) reductions in depression and posttraumatic symptoms, as well as enrichments in health-related quality of life (HRQOL), and (2) changes in plasma concentrations of brain derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1). Methods: Forty-four military personnel diagnosed with insomnia underwent clinical evaluations and blood draws at pretreatment and at posttreatment following cognitive behavioral therapy for insomnia and automatic positive airway pressure treatment. Participants were classified as sleep improved (n = 28) or sleep declined (n = 16) based on their change in pretreatment to posttreatment Pittsburgh Sleep Quality Index (PSQI) score. Both groups were compared on outcomes of depression, PTSD, HRQOL, BDNF, and IGF-1. Results: Paired t-tests of the sleep improved group revealed significant declines in depression (p = 0.005) and posttraumatic arousal (p = 0.006) symptoms, and a significant increase in concentrations of IGF-1 (p = 0.009). The sleep declined group had no relevant change in psychiatric symptoms or trophic factors, and had further declines on five of eight dimensions of HRQOL. Between-group change score differences were significant at p < 0.05. Conclusions: These findings suggest that interventions, which successfully improve sleep quality, are an effective means to reduce the depression and posttraumatic arousal symptoms common to military personnel, as well as increase protective trophic factors implicated in these conditions. Citation: Rusch HL, Guardado P, Baxter T, Mysliwiec V, Gill JM. Improved sleep quality is

Using human factors engineering to improve the effectiveness of infection prevention and control.

PubMed

Anderson, Judith; Gosbee, Laura Lin; Bessesen, Mary; Williams, Linda

2010-08-01

Human factors engineering is a discipline that studies the capabilities and limitations of humans and the design of devices and systems for improved performance. The principles of human factors engineering can be applied to infection prevention and control to study the interaction between the healthcare worker and the system that he or she is working with, including the use of devices, the built environment, and the demands and complexities of patient care. Some key challenges in infection prevention, such as delayed feedback to healthcare workers, high cognitive workload, and poor ergonomic design, are explained, as is how human factors engineering can be used for improvement and increased compliance with practices to prevent hospital-acquired infections.

Loss of cIAP1 attenuates soleus muscle pathology and improves diaphragm function in mdx mice

PubMed Central

Enwere, Emeka K.; Boudreault, Louise; Holbrook, Janelle; Timusk, Kristen; Earl, Nathalie; LaCasse, Eric; Renaud, Jean-Marc; Korneluk, Robert G.

2013-01-01

The cellular inhibitor of apoptosis 1 (cIAP1) protein is an essential regulator of canonical and noncanonical nuclear factor κB (NF-κB) signaling pathways. NF-κB signaling is known to play important roles in myogenesis and degenerative muscle disorders such as Duchenne muscular dystrophy (DMD), but the involvement of cIAP1 in muscle disease has not been studied directly. Here, we asked whether the loss of cIAP1 would influence the pathology of skeletal muscle in the mdx mouse model of DMD. Double-mutant cIAP1−/−;mdx mice exhibited reduced muscle damage and decreased fiber centronucleation in the soleus, compared with single-mutant cIAP1+/+;mdx mice. This improvement in pathology was associated with a reduction in muscle infiltration by macrophages and diminished expression of inflammatory cytokines such as IL-6 and tumor necrosis factor-α. Furthermore, the cIAP1−/−;mdx mice exhibited reduced serum creatine kinase, and improved exercise endurance associated with improved exercise resilience by the diaphragm. Mechanistically, the loss of cIAP1 was sufficient to drive constitutive activation of the noncanonical NF-κB pathway, which led to increased myoblast fusion in vitro and in vivo. Collectively, these results show that the loss of cIAP1 protects skeletal muscle from the degenerative pathology resulting from systemic loss of dystrophin. PMID:23184147

Central insulin-like growth factor-1 (IGF-1) restores whole-body insulin action in a model of age-related insulin resistance and IGF-1 decline.

PubMed

Huffman, Derek M; Farias Quipildor, Gabriela; Mao, Kai; Zhang, Xueying; Wan, Junxiang; Apontes, Pasha; Cohen, Pinchas; Barzilai, Nir

2016-02-01

Low insulin-like growth factor-1 (IGF-1) signaling is associated with improved longevity, but is paradoxically linked with several age-related diseases in humans. Insulin-like growth factor-1 has proven to be particularly beneficial to the brain, where it confers protection against features of neuronal and cognitive decline. While aging is characterized by central insulin resistance in the face of hyperinsulinemia, the somatotropic axis markedly declines in older humans. Thus, we hypothesized that increasing IGF-1 in the brain may prove to be a novel therapeutic alternative to overcome central insulin resistance and restore whole-body insulin action in aging. Utilizing hyperinsulinemic-euglycemic clamps, we show that old insulin-resistant rats with age-related declines in IGF-1 level demonstrate markedly improved whole-body insulin action, when treated with central IGF-1, as compared to central vehicle or insulin (P < 0.05). Furthermore, central IGF-1, but not insulin, suppressed hepatic glucose production and increased glucose disposal rates in aging rats (P < 0.05). Taken together, IGF-1 action in the brain and periphery provides a 'balance' between its beneficial and detrimental actions. Therefore, we propose that strategies aimed at 'tipping the balance' of IGF-1 action centrally are the optimal approach to achieve healthy aging and longevity in humans. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Structure of a highly stable mutant of human fibroblast growth factor 1.

PubMed

Szlachcic, Anna; Zakrzewska, Małgorzata; Krowarsch, Daniel; Os, Vibeke; Helland, Ronny; Smalås, Arne O; Otlewski, Jacek

2009-01-01

Fibroblast growth factors (FGFs) are involved in diverse cellular processes such as cell migration, angiogenesis, osteogenesis, wound healing and embryonic and foetal development. Human acidic fibroblast growth factor (FGF-1) is the only member of the FGF family that binds with high affinity to all four FGF receptors and thus is considered to be the human mitogen with the broadest specificity. However, pharmacological applications of FGF-1 are limited owing to its low stability. It has previously been reported that the introduction of single mutations can significantly improve the stability of FGF-1 and its resistance to proteolytic degradation. Here, the structure of the Q40P/S47I/H93G triple mutant of FGF-1, which exhibits much higher stability, a prolonged half-life and enhanced mitogenic activity, is presented. Compared with the wild-type structure, three localized conformational changes in the stable triple mutant were observed, which is in agreement with the perfect energetic additivity of the single mutations described in a previous study. The huge change in FGF-1 stability (the denaturation temperature increased by 21.5 K, equivalent to DeltaDeltaG(den) = 24.3 kJ mol(-1)) seems to result from the formation of a short 3(10)-helix (position 40), an improvement in the propensity of amino acids to form beta-sheets (position 47) and the rearrangement of a local hydrogen-bond network (positions 47 and 93).

Improved RF Measurements of SRF Cavity Quality Factors

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

Holzbauer, J. P.; Contreras, C.; Pischalnikov, Y.

SRF cavity quality factors can be accurately measured using RF-power based techniques only when the cavity is very close to critically coupled. This limitation is from systematic errors driven by non-ideal RF components. When the cavity is not close to critically coupled, these systematic effects limit the accuracy of the measurements. The combination of the complex base-band envelopes of the cavity RF signals in combination with a trombone in the circuit allow the relative calibration of the RF signals to be extracted from the data and systematic effects to be characterized and suppressed. The improved calibration allows accurate measurements tomore » be made over a much wider range of couplings. Demonstration of these techniques during testing of a single-spoke resonator with a coupling factor of near 7 will be presented, along with recommendations for application of these techniques.« less

A low carbohydrate Mediterranean diet improves cardiovascular risk factors and diabetes control among overweight patients with type 2 diabetes mellitus: a 1-year prospective randomized intervention study.

PubMed

Elhayany, A; Lustman, A; Abel, R; Attal-Singer, J; Vinker, S

2010-03-01

The appropriate dietary intervention for overweight persons with type 2 diabetes mellitus (DM2) is unclear. Trials comparing the effectiveness of diets are frequently limited by short follow-up times and high dropout rates. The effects of a low carbohydrate Mediterranean (LCM), a traditional Mediterranean (TM), and the 2003 American Diabetic Association (ADA) diet were compared, on health parameters during a 12-month period. In this 12-month trial, 259 overweight diabetic patients (mean age 55 years, mean body mass index 31.4 kg/m(2)) were randomly assigned to one of the three diets. The primary end-points were reduction of fasting plasma glucose, HbA1c and triglyceride (TG) levels. 194 patients out of 259 (74.9%) completed follow-up. After 12 months, the mean weight loss for all patients was 8.3 kg: 7.7 kg for ADA, 7.4 kg for TM and 10.1 kg for LCM diets. The reduction in HbA1c was significantly greater in the LCM diet than in the ADA diet (-2.0 and -1.6%, respectively, p < 0.022). HDL cholesterol increased (0.1 mmol/l +/- 0.02) only on the LCM (p < 0.002). The reduction in serum TG was greater in the LCM (-1.3 mmol/l) and TM (-1.5 mmol/l) than in the ADA (-0.7 mmol/l), p = 0.001. An intensive 12-month dietary intervention in a community-based setting was effective in improving most modifiable cardiovascular risk factors in all the dietary groups. Only the LCM improved HDL levels and was superior to both the ADA and TM in improving glycaemic control.

Serum insulin-like growth factor-1 (IGF-1) during CF pulmonary exacerbation: trends and biomarker correlations.

PubMed

Gifford, A H; Nymon, A B; Ashare, A

2014-04-01

Cystic fibrosis (CF) is characterized by low circulating levels of insulin-like growth factor-1 (IGF-1), a hormone produced by the liver that governs anabolism and influences immune cell function. Because treatment of CF pulmonary exacerbation (CFPE) often improves body weight and lung function, we questioned whether serum IGF-1 trends were emblematic of these responses. Initially, we compared serum levels between healthy adults with CF and controls of similar age. We then measured serum IGF-1 throughout the CFPE cycle. We also investigated correlations among IGF-1 and other serum biomarkers during CFPE. Anthopometric, spirometric, and demographic data were collected. Serum IGF-1 concentrations were measured by ELISA. CF subjects in their usual state of health had lower serum IGF-1 levels than controls. Serum IGF-1 concentrations fell significantly from baseline at the beginning of CFPE. Treatment with intravenous antibiotics was associated with significant improvement in serum IGF-1 levels, body mass index (BMI), and percent-predicted forced expiratory volume in 1 sec (FEV1 %). At early and late CFPE, serum IGF-1 was directly correlated with FEV1 %, serum iron, hemoglobin concentration, and transferrin saturation (TSAT) and indirectly correlated with alpha-1-antitrypsin. This study not only supports the paradigm that CF is characterized by IGF-1 deficiency but also that trends in lung function, nutritional status, and serum IGF-1 are related. Improvements in all three parameters after antibiotics for CFPE likely highlight the connection between lung function and nutritional status in CF. Close correlations among IGF-1 and iron-related hematologic parameters suggest that IGF-1 may participate in CF iron homeostasis, another process that is known to be influenced by CFPE. © 2013 Wiley Periodicals, Inc.

Recent Advances of Colony-Stimulating Factor-1 Receptor (CSF-1R) Kinase and Its Inhibitors.

PubMed

El-Gamal, Mohammed I; Al-Ameen, Shahad K; Al-Koumi, Dania M; Hamad, Mawadda G; Jalal, Nouran A; Oh, Chang-Hyun

2018-01-17

Colony stimulation factor-1 receptor (CSF-1R), which is also known as FMS kinase, plays an important role in initiating inflammatory, cancer, and bone disorders when it is overstimulated by its ligand, CSF-1. Innate immunity, as well as macrophage differentiation and survival, are regulated by the stimulation of the CSF-1R. Another ligand, interlukin-34 (IL-34), was recently reported to activate the CSF-1R receptor in a different manner. The relationship between CSF-1R and microglia has been reviewed. Both CSF-1 antibodies and small molecule CSF-1R kinase inhibitors have now been tested in animal models and in humans. In this Perspective, we discuss the role of CSF-1 and IL-34 in producing cancer, bone disorders, and inflammation. We also review the newly discovered and improved small molecule kinase inhibitors and monoclonal antibodies that have shown potent activity toward CSF-1R, reported from 2012 until 2017.

Epigenetic and genetic variants in the HTR1B gene and clinical improvement in children and adolescents treated with fluoxetine.

PubMed

Gassó, Patricia; Rodríguez, Natalia; Blázquez, Ana; Monteagudo, Ana; Boloc, Daniel; Plana, Maria Teresa; Lafuente, Amalia; Lázaro, Luisa; Arnaiz, Joan Albert; Mas, Sergi

2017-04-03

The serotonin 1B receptor (5-HT 1B ) is important to both the pathogenesis of major depressive disorder and the antidepressant effects of selective serotonin reuptake inhibitors. Although fluoxetine has been shown to be effective and safe in children and adolescents, not all patients experience a proper clinical response, which has led to further study into the main factors involved in this inter-individual variability. Our aim was to study the effect of epigenetic and genetic factors that could affect 5-hydroxytryptamine receptor 1B (HTR1B) gene expression, and thereby response to fluoxetine. A total of 83 children and adolescents were clinically assessed 12weeks after of initiating an antidepressant treatment with fluoxetine for the first time. We evaluated the influence of single nucleotide polymorphisms (SNPs) specifically located in transcription factor binding sites (TFBSs) on their clinical improvement. A combined genetic analysis considering the significant SNPs together with the functional variant rs130058 previously associated in our population was also performed. Moreover, we assessed, for the first time in the literature, whether methylation levels of the HTR1B promoter region could be associated with the pharmacological response. Two, rs9361233 and rs9361235, were significantly associated with clinical improvement after treatment with fluoxetine. The heterozygous genotype combination analysis showed a negative correlation with clinical improvement. The lowest improvement was experienced by patients who were heterozygous for all three SNPs. Moreover, a negative correlation was found between clinical improvement and the average methylation level of the HTR1B promoter. These results give new evidence for the role of epigenetic and genetic factors which could modulate HTR1B expression in the pharmacological response to antidepressants. Copyright © 2016 Elsevier Inc. All rights reserved.

Hypoxia inducible factor 1 (HIF-1) and cardioprotection

PubMed Central

Tekin, Demet; Dursun, Ali D; Xi, Lei

2010-01-01

Since its discovery in early 1990s, hypoxia inducible factor 1 (HIF-1) has been increasingly recognized for its key role in transcriptional control of more than a hundred genes that regulate a wide-spectrum of cellular functional events, including angiogenesis, vasomotor control, glucose and energy metabolism, erythropoiesis, iron homeostasis, pH regulation, cell proliferation and viability. Evidence accumulated during the past 7 years suggests a critical role for HIF-1α in mediating cardioprotection. The purpose of our present article is to provide an updated overview on this important regulator of gene expression in the cellular stress-responsive and adaptive process. We have particularly emphasized the involvement of HIF-1 in the induction of cardioprotective molecules, such as inducible nitric oxide synthase (iNOS), hemeoxygenase 1 (HO-1), and erythropoietin (EPO), which in turn alleviate myocardial damages caused by harmful events such as ischemia-reperfusion injury. Despite these advances, further in-depth studies are needed to elucidate the possible coordination or interaction between HIF-1α and other key transcription factors in regulating protein expression that leads to cardioprotection. PMID:20711226

Longitudinal Household Trends in Access to Improved Water Sources and Sanitation in Chi Linh Town, Hai Duong Province, Viet Nam and Associated Factors.

PubMed

Tuyet-Hanh, Tran Thi; Long, Tran Khanh; Van Minh, Hoang; Huong, Le Thi Thanh

2016-01-01

This study aims to characterize household trends in access to improved water sources and sanitaton in Chi Linh Town, Hai Duong Province, Vietnam, and to identify factors affecting those trends. Data were extracted from the Chi Linh Health and Demographic Surveillance System (CHILILAB HDSS) database from 2004-2014, which included household access to improved water sources, household access to improved sanitation, and household demographic data. Descriptive statistical analysis and multinominal logistic regression were used. The results showed that over a 10-year period (2004-2014), the proportion of households with access to improved water and improved sanitation increased by 3.7% and 28.3%, respectively. As such, the 2015 Millennium Development Goal targets for safe drinking water and basic sanitation were met. However, 13.5% of households still had unimproved water and sanitation. People who are retired, work in trade or services, or other occupations were 1.49, 1.97, and 1.34 times more likely to have access to improved water and sanitation facilities than farming households, respectively ( p < 0.001). Households living in urban areas were 1.84 times more likely than those living in rural areas to have access to improved water sources and improved sanitation facilities (OR =1.84; 95% CI = 1.73-1.96). Non-poor households were 2.12 times more likely to have access to improved water sources and improved sanitation facilities compared to the poor group (OR = 2.12; 95% CI = 2.00-2.25). More efforts are required to increase household access to both improved water and sanitation in Chi Linh Town, focusing on the 13.5% of households currently without access. Similar to situations observed elsewhere in Vietnam and other low- and middle- income countries, there is a need to address socio-economic factors that are associated with inadequate access to improved water sources and sanitation facilities.

Human Factors Research Under Ground-Based and Space Conditions. Part 1

NASA Technical Reports Server (NTRS)

1997-01-01

Session TP2 includes short reports concerning: (1) Human Factors Engineering of the International space Station Human Research Facility; (2) Structured Methods for Identifying and Correcting Potential Human Errors in Space operation; (3) An Improved Procedure for Selecting Astronauts for Extended Space Missions; (4) The NASA Performance Assessment Workstation: Cognitive Performance During Head-Down Bedrest; (5) Cognitive Performance Aboard the Life and Microgravity Spacelab; and (6) Psychophysiological Reactivity Under MIR-Simulation and Real Micro-G.

Fifteen years of GH replacement improves body composition and cardiovascular risk factors.

PubMed

Elbornsson, Mariam; Götherström, Galina; Bosæus, Ingvar; Bengtsson, Bengt-Åke; Johannsson, Gudmundur; Svensson, Johan

2013-05-01

Few studies have determined the effects of more than 5-10 years of GH replacement in adults on body composition and cardiovascular risk factors. In this prospective, single-center, open-label study, the effects of 15 years of GH replacement on body composition and cardiovascular risk factors were determined in 156 hypopituitary adults (93 men) with adult-onset GH deficiency (GHD). Mean age was 50.5 (range 22-74) years at study start. Body composition was measured using dual-energy X-ray absorptiometry. The mean initial GH dose of 0.55 (S.E.M. 0.03) mg/day was gradually lowered to 0.40 (0.01) mg/day after 15 years. The mean serum IGF1 SDS increased from -1.53 (0.10) at baseline to 0.74 (0.13) at study end (P<0.001 vs baseline). Lean soft tissue (LST) increased to 3% above the baseline level at study end (P<0.001). After a 9% decrease during the first year of treatment (P<0.001 vs baseline), body fat (BF) started to increase and had returned to the baseline level after 15 years. Serum levels of total cholesterol and LDL-cholesterol decreased and serum HDL-cholesterol level increased. Fasting plasma glucose increased from 4.4 (0.1) at baseline to 4.8 (0.1) mmol/l at study end (P<0.001). However, blood HbA1c decreased from 5.0 (0.1) to 4.6 (0.1) % (P<0.001). Fifteen-year GH replacement in GHD adults induced a transient decrease in BF and sustained improvements of LST and serum lipid profile. Fasting plasma glucose increased whereas blood HbA1c was reduced.

Endurance factors improve hippocampal neurogenesis and spatial memory in mice

PubMed Central

Kobilo, Tali; Yuan, Chunyan; van Praag, Henriette

2011-01-01

Physical activity improves learning and hippocampal neurogenesis. It is unknown whether compounds that increase endurance in muscle also enhance cognition. We investigated the effects of endurance factors, peroxisome proliferator-activated receptor δ agonist GW501516 and AICAR, activator of AMP-activated protein kinase on memory and neurogenesis. Mice were injected with GW for 7 d or AICAR for 7 or 14 d. Two weeks thereafter mice were tested in the Morris water maze. AICAR (7 d) and GW improved spatial memory. Moreover, AICAR significantly, and GW modestly, elevated dentate gyrus neurogenesis. Thus, pharmacological activation of skeletal muscle may mediate cognitive effects. PMID:21245211

Improving furfural tolerance of Zymomonas mobilis by rewiring a sigma factor RpoD protein.

PubMed

Tan, Fu-Rong; Dai, Li-Chun; Wu, Bo; Qin, Han; Shui, Zong-Xia; Wang, Jing-Li; Zhu, Qi-Li; Hu, Qi-Chun; Ruan, Zhi-Yong; He, Ming-Xiong

2015-06-01

Furfural from lignocellulosic hydrolysates is the key inhibitor for bio-ethanol fermentation. In this study, we report a strategy of improving the furfural tolerance in Zymomonas mobilis on the transcriptional level by engineering its global transcription sigma factor (σ(70), RpoD) protein. Three furfural tolerance RpoD mutants (ZM4-MF1, ZM4-MF2, and ZM4-MF3) were identified from error-prone PCR libraries. The best furfural-tolerance strain ZM4-MF2 reached to the maximal cell density (OD600) about 2.0 after approximately 30 h, while control strain ZM4-rpoD reached its highest cell density of about 1.3 under the same conditions. ZM4-MF2 also consumed glucose faster and yield higher ethanol; expression levels and key Entner-Doudoroff (ED) pathway enzymatic activities were also compared to control strain under furfural stress condition. Our results suggest that global transcription machinery engineering could potentially be used to improve stress tolerance and ethanol production in Z. mobilis.

Overexpression of the TaSHN1 transcription factor in bread wheat leads to leaf surface modifications, improved drought tolerance and no yield penalty under controlled growth conditions.

PubMed

Bi, Huihui; Shi, Jianxin; Kovalchuk, Natalia; Luang, Sukanya; Bazanova, Natalia; Chirkova, Larissa; Zhang, Dabing; Shavrukov, Yuri; Stepanenko, Anton; Tricker, Penny; Langridge, Peter; Hrmova, Maria; Lopato, Sergiy; Borisjuk, Nikolai

2018-05-14

Transcription factors regulate multiple networks, mediating the responses of organisms to stresses, including drought. Here we investigated the role of the wheat transcription factor TaSHN1 in crop growth and drought tolerance. TaSHN1, isolated from bread wheat, was characterised for molecular interactions and functionality. The overexpression of TaSHN1 in wheat was followed by the evaluation of T 2 and T 3 transgenic lines for drought tolerance, growth and yield components. Leaf surface changes were analysed by light microscopy, SEM, TEM and GC-MS/GC-FID. TaSHN1 behaves as a transcriptional activator in a yeast transactivation assay and binds stress-related DNA cis-elements, determinants of which were revealed using 3D molecular modelling. The overexpression of TaSHN1 in transgenic wheat did not result in a yield penalty under the controlled plant growth conditions of a glasshouse. Transgenic lines had significantly lower stomatal density and leaf water loss, and exhibited improved recovery after severe drought, compared to control plants. The comparative analysis of cuticular waxes revealed an increased accumulation of alkanes in leaves of transgenic lines. Our data demonstrate that TaSHN1 may operate as a positive modulator of drought stress tolerance. Positive attributes could be mediated through an enhanced accumulation of alkanes and reduced stomatal density. This article is protected by copyright. All rights reserved.

Lifestyle intervention reduces body weight and improves cardiometabolic risk factors in worksites.

PubMed

Salinardi, Taylor C; Batra, Payal; Roberts, Susan B; Urban, Lorien E; Robinson, Lisa M; Pittas, Anastassios G; Lichtenstein, Alice H; Deckersbach, Thilo; Saltzman, Edward; Das, Sai Krupa

2013-04-01

Worksites are potentially effective locations for obesity control because they provide opportunities for group intervention and social support. Studies are needed to identify effective interventions in these settings. We examined the effects of a multicomponent lifestyle intervention on weight loss and prevention of regain in 4 worksites (2 intervention and 2 control sites). Overweight and obese employees (n = 133) enrolled in this pilot worksite-randomized controlled trial with a 0-6-mo weight-loss phase and a 6-12-mo structured weight-maintenance phase. The intervention combined recommendations to consume a reduced-energy, low-glycemic load, high-fiber diet with behavioral change education. Outcome measurements included changes in body weight and cardiometabolic risk factors. The mean ± SEM weight loss was substantial in intervention participants, whereas control subjects gained weight (-8.0 ± 0.7 compared with +0.9 ± 0.5 kg, respectively; P < 0.001), and 89% of participants completed the weight-loss phase. Intervention effects were not significant at the 0.05 level but would have been at the 0.10 level (P = 0.08) in a mixed model in which the worksite nested within group was a random factor. There were also significant improvements in cardiometabolic risk factors in intervention compared with control subjects regarding fasting total cholesterol, glucose, systolic blood pressure, and diastolic blood pressure (P ≤ 0.02 for each). No significant weight regain was observed in participants who enrolled in the structured weight-maintenance program (0.5 ± 0.7 kg; P = 0.65), and overweight and obese employees in intervention worksites who were not enrolled in the weight-loss program lost weight compared with subjects in control worksites (-1.3 ± 0.5 compared with +0.7 ± 0.2 kg, respectively; P = 0.02). Worksites can be effective for achieving clinically important reductions in body weight and improved cardiometabolic risk factors. This trial was registered at

Host factors that influence mother-to-child transmission of HIV-1: genetics, coinfections, behavior and nutrition.

PubMed

Ellington, Sascha R; King, Caroline C; Kourtis, Athena P

2011-01-01

Mother-to-child transmission (MTCT) is the most important mode of HIV-1 acquisition among infants and children and it can occur in utero , intrapartum and postnatally through breastfeeding. Great progress has been made in preventing MTCT through use of antiretroviral regimens during gestation, labor/delivery and breastfeeding. The mechanisms of MTCT, however, are multifactorial and remain incompletely understood. This review focuses on select host factors affecting MTCT, in particular genetic factors, coexisting infections, behavioral factors and nutrition. Whereas much emphasis has been placed on decreasing maternal HIV-1 viral load, an important determinant of MTCT, through use of antiretroviral agents, complementary focus on overall maternal health is often neglected. By addressing coinfections in mothers and infants, improving the mother's nutritional status and modifying risky behaviors and practices, not only is maternal and child health improved, but a direct benefit in reducing MTCT can be derived. The study of genetic variations in susceptibility to HIV-1 infection is rapidly evolving, and the future is likely to bring revolutionary changes in HIV-1 prevention by enhancing natural resistance to infection and by individually tailoring pharmacologic regimens.

Host factors that influence mother-to-child transmission of HIV-1: genetics, coinfections, behavior and nutrition

PubMed Central

Ellington, Sascha R; King, Caroline C; Kourtis, Athena P

2017-01-01

Mother-to-child transmission (MTCT) is the most important mode of HIV-1 acquisition among infants and children and it can occur in utero, intrapartum and postnatally through breastfeeding. Great progress has been made in preventing MTCT through use of antiretroviral regimens during gestation, labor/delivery and breastfeeding. The mechanisms of MTCT, however, are multifactorial and remain incompletely understood. This review focuses on select host factors affecting MTCT, in particular genetic factors, coexisting infections, behavioral factors and nutrition. Whereas much emphasis has been placed on decreasing maternal HIV-1 viral load, an important determinant of MTCT, through use of antiretroviral agents, complementary focus on overall maternal health is often neglected. By addressing coinfections in mothers and infants, improving the mother’s nutritional status and modifying risky behaviors and practices, not only is maternal and child health improved, but a direct benefit in reducing MTCT can be derived. The study of genetic variations in susceptibility to HIV-1 infection is rapidly evolving, and the future is likely to bring revolutionary changes in HIV-1 prevention by enhancing natural resistance to infection and by individually tailoring pharmacologic regimens. PMID:29348780

Predictive Factors of Headache Resolution After Chiari Type 1 Malformation Surgery.

PubMed

Grangeon, Lou; Puy, Laurent; Gilard, Vianney; Hebant, Benjamin; Langlois, Olivier; Derrey, Stephane; Gerardin, Emmanuel; Maltete, David; Guegan-Massardier, Evelyne; Magne, Nicolas

2018-02-01

Headache is the main and often isolated symptom of patients with Chiari type 1 malformation (CM1). Classically described as occipital and exacerbated by cough, headaches may be poorly characterized, making it difficult to establish CM1 as the underlying cause. Current guidelines for surgical posterior fossa decompression are undefined. The challenge is to distinguish headaches related to CM1 from headaches coincidentally coexisting with CM1. We aimed to determine predictive factors of headache resolution after surgery and applied to our cohort the Chiari Severity Index, a recently developed predictive prognostic score. This retrospective study enrolled 49 patients with CM1 and preoperative headache. Standardized telephone interviews regarding headaches before and after surgery were conducted by the same neurologist; magnetic resonance imaging morphometric analyses were performed by an independent neuroradiologist. Headache resolution was defined as ≥50% reduction in frequency of headache days. Preoperative factors of headache resolution after multivariate analysis were attack duration <5 minutes (P = 0.001), triggering by Valsalva maneuvers (P = 0.003), severe intensity of attack (P = 0.05), occipital location (P = 0.05), and greater number of headache days per month (P = 0.04). These characteristics are part of International Headache Society diagnostic criteria for headache attributed to CM1. No radiologic predictive factor was demonstrated. Postoperative improvement was inversely correlated with Chiari Severity Index. This study confirms the relevance of International Headache Society criteria to identify headaches related to CM1. We propose their systematic use in a preoperative questionnaire. Copyright © 2017 Elsevier Inc. All rights reserved.

Prognostic value of insulin-like growth factor 1 and insulin-like growth factor binding protein 3 blood levels in breast cancer.

PubMed

Hartog, H; Boezen, H M; de Jong, M M; Schaapveld, M; Wesseling, J; van der Graaf, W T A

2013-12-01

High circulating insulin-like growth factor 1 (IGF-1) levels are firmly established as a risk factor for developing breast cancer, especially estrogen positive tumors. The effect of circulating IGF-1 on prognosis once a tumor is established is unknown. The authors explored the effect of IGF-1 blood levels and of it's main binding protein, IGFBP-3, on overall survival and occurrence of second primary breast tumors in breast cancer patients, as well as reproductive and lifestyle factors that could modify this risk. Patients were accrued from six hospitals in the Netherlands between 1998 and 2003. Total IGF-1 and IGFBP-3 were measured in 582 plasma samples. No significant association between IGF-1 and IGFBP-3 plasma levels and overall survival was found. However, in a multivariate Cox regression model including standard prognostic variables high IGF-1 levels were related to worse overall survival in patients receiving endocrine therapy (HR = 1.37, 95% CI: 1.11, 1.69, P 0.004). These data at least indicate that higher IGF-1 levels, and as a consequence most likely IGF-1-induced signaling, are related to a less favorable overall survival in breast cancer patients treated with endocrine therapy. Interventions aimed at reducing circulating levels of IGF-1 in hormone receptor positive breast cancer may improve survival. Copyright © 2013 Elsevier Ltd. All rights reserved.

Clindamycin Affects Group A Streptococcus Virulence Factors and Improves Clinical Outcome.

PubMed

Andreoni, Federica; Zürcher, Claudia; Tarnutzer, Andrea; Schilcher, Katrin; Neff, Andrina; Keller, Nadia; Marques Maggio, Ewerton; Poyart, Claire; Schuepbach, Reto A; Zinkernagel, Annelies S

2017-01-15

Group A Streptococcus (GAS) has acquired an arsenal of virulence factors, promoting life-threatening invasive infections such as necrotizing fasciitis. Current therapeutic regimens for necrotizing fasciitis include surgical debridement and treatment with cell wall-active antibiotics. Addition of clindamycin (CLI) is recommended, although clinical evidence is lacking. Reflecting the current clinical dilemma, an observational study showed that only 63% of the patients with severe invasive GAS infection received CLI. This work thus aimed to address whether CLI improves necrotizing fasciitis outcome by modulating virulence factors of CLI-susceptible and CLI-resistant GAS in vitro and in vivo. Treatment with CLI reduced extracellular DNase Sda1 and streptolysin O (SLO) activity in vivo, whereas subinhibitory CLI concentrations induced expression and activity of SLO, DNase, and Streptococcus pyogenes cell envelope protease in vitro. Our in vivo results suggest that CLI should be administered as soon as possible to patients with necrotizing fasciitis, while our in vitro studies emphasize that a high dosage of CLI is essential. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Suppression of a NAC-Like Transcription Factor Gene Improves Boron-Toxicity Tolerance in Rice1

PubMed Central

Ochiai, Kumiko; Shimizu, Akifumi; Okumoto, Yutaka; Fujiwara, Toru; Matoh, Toru

2011-01-01

We identified a gene responsible for tolerance to boron (B) toxicity in rice (Oryza sativa), named BORON EXCESS TOLERANT1. Using recombinant inbred lines derived from the B-toxicity-sensitive indica-ecotype cultivar IR36 and the tolerant japonica-ecotype cultivar Nekken 1, the region responsible for tolerance to B toxicity was narrowed to 49 kb on chromosome 4. Eight genes are annotated in this region. The DNA sequence in this region was compared between the B-toxicity-sensitive japonica cultivar Wataribune and the B-toxicity-tolerant japonica cultivar Nipponbare by eco-TILLING analysis and revealed a one-base insertion mutation in the open reading frame sequence of the gene Os04g0477300. The gene encodes a NAC (NAM, ATAF, and CUC)-like transcription factor and the function of the transcript is abolished in B-toxicity-tolerant cultivars. Transgenic plants in which the expression of Os04g0477300 is abolished by RNA interference gain tolerance to B toxicity. PMID:21543724

Deep NPM1 Sequencing Following Allogeneic Hematopoietic Cell Transplantation Improves Risk Assessment in Adults with NPM1-Mutated AML.

PubMed

Zhou, Yi; Othus, Megan; Walter, Roland B; Estey, Elihu H; Wu, David; Wood, Brent L

2018-04-21

Relapse is the major cause of death in patients with acute myeloid leukemia (AML) after allogeneic hematopoietic cell transplantation (HCT). Measurable residual disease (MRD) detected by multiparameter flow cytometry (MFC) before and after HCT is a strong, independent risk factor for relapse. As next-generation sequencing (NGS) is increasingly applied in AML MRD detection, it remains to be determined if NGS can improve prediction of post-HCT relapse. Herein, we investigated pre-HCT MRD detected by MFC and NGS in 59 adult patients with NPM1-mutated AML in morphologic remission; 45 of the 59 had post-HCT MRD determined by MFC and NGS around day 28. Before HCT, MRD detected by MFC was the most significant risk factor for relapse (hazard ratio [HR], 4.63; P < .001), whereas MRD detected only by NGS was not. After HCT, MRD detected by either MFC or NGS was significant risk factor for relapse (HR, 4.96, P = .004 and HR, 4.36, P = .002, respectively). Combining pre- and post-HCT MRD provided the best prediction for relapse (HR, 5.25; P < .001), with a sensitivity at 83%. We conclude that NGS testing of mutated NPM1 post-HCT improves the risk assessment for relapse, whereas pre-HCT MFC testing identifies a subset of high-risk patients in whom additional therapy should be tested. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

The transcription factor Prep1 controls hepatic insulin sensitivity and gluconeogenesis by targeting nuclear localization of FOXO1.

PubMed

Kulebyakin, Konstantin; Penkov, Dmitry; Blasi, Francesco; Akopyan, Zhanna; Tkachuk, Vsevolod

2016-12-02

Liver plays a key role in controlling body carbohydrate homeostasis by switching between accumulation and production of glucose and this way maintaining constant level of glucose in blood. Increased blood glucose level triggers release of insulin from pancreatic β-cells. Insulin represses hepatic glucose production and increases glucose accumulation. Insulin resistance is the main cause of type 2 diabetes and hyperglycemia. Currently thiazolidinediones (TZDs) targeting transcriptional factor PPARγ are used as insulin sensitizers for treating patients with type 2 diabetes. However, TZDs are reported to be associated with cardiovascular and liver problems and stimulate obesity. Thus, it is necessary to search new approaches to improve insulin sensitivity. A promising candidate is transcriptional factor Prep1, as it was shown earlier it could affect insulin sensitivity in variety of insulin-sensitive tissues. The aim of the present study was to evaluate a possible involvement of transcriptional factor Prep1 in control of hepatic glucose accumulation and production. We created mice with liver-specific Prep1 knockout and discovered that hepatocytes derived from these mice are much more sensitive to insulin, comparing to their WT littermates. Incubation of these cells with 100 nM insulin results in almost complete inhibition of gluconeogenesis, while in WT cells this repression is only partial. However, Prep1 doesn't affect gluconeogenesis in the absence of insulin. Also, we observed that nuclear content of gluconeogenic transcription factor FOXO1 was greatly reduced in Prep1 knockout hepatocytes. These findings suggest that Prep1 may control hepatic insulin sensitivity by targeting FOXO1 nuclear stability. Copyright © 2016 Elsevier Inc. All rights reserved.

Greater flavonoid intake is associated with improved CVD risk factors in US adults.

PubMed

Kim, Kijoon; Vance, Terrence M; Chun, Ock K

2016-04-01

Epidemiological studies have reported that diets high in flavonoids are associated with a reduced risk of CVD. However, evidence on the association of dietary flavonoid intake with CVD risk factors is still scarce. The present study aimed to investigate the association of dietary flavonoid intake with CVD risk factors among US adults in the National Health and Nutrition Examination Survey (NHANES) 2007-2012. A total of 4042 US adults aged 19 years and older from the NHANES 2007-2012 participated in this cross-sectional, population-based study. Intakes of total and individual flavonoids were estimated from 2-d 24-h diet recall data by matching with the expanded US Department of Agriculture flavonoid, isoflavone and proanthocyanidin databases. After adjusting for covariates, increased HDL-cholesterol was associated with higher total flavonoid intake (0·54 % change). TAG and TAG:HDL-cholesterol ratio were inversely associated with anthocyanidin (-1·25 % change for TAG; -1·60 % change for TAG:HDL-cholesterol ratio) and total flavonoid intakes (-1·31 % change for TAG; -1·83 % change for TAG:HDL-cholesterol ratio), respectively. Insulin and homoeostasis model assessment for insulin resistance (HOMA-IR) were inversely associated with flavone (for insulin, -3·18 % change; 95 % CI -5·85, -0·44; for HOMA-IR, -3·10 % change; 95 % CI -5·93, -0·19) and isoflavone intakes (for insulin, -3·11 % change; 95 % CI -5·46, -0·70; for HOMA-IR, -4·01 % change; 95 % CI -6·67, -1·27). BMI was negatively associated with anthocyanidin intake (-0·60 % change). This study showed that higher flavonoid intake was associated with improved CVD risk factors. Further research is warranted to confirm the findings from this study as these associations were moderate in strength.

Deletion of JJJ1 improves acetic acid tolerance and bioethanol fermentation performance of Saccharomyces cerevisiae strains.

PubMed

Wu, Xuechang; Zhang, Lijie; Jin, Xinna; Fang, Yahong; Zhang, Ke; Qi, Lei; Zheng, Daoqiong

2016-07-01

To improve tolerance to acetic acid that is present in lignocellulosic hydrolysates and affects bioethanol production by Saccharomyces cerevisiae. Saccharomyces cerevisiae strains with improved tolerance to acetic acid were obtained through deletion of the JJJ1 gene. The lag phase of the JJJ1 deletion mutant BYΔJJJ1 was ~16 h shorter than that of the parent strain, BY4741, when the fermentation medium contained 4.5 g acetic acid/l. Additionally, the specific ethanol production rate of BYΔJJJ1 was increased (0.057 g/g h) compared to that of the parent strain (0.051 g/g h). Comparative transcription and physiological analyses revealed higher long chain fatty acid, trehalose, and catalase contents might be critical factors responsible for the acetic acid resistance of JJJ1 knockout strains. JJJ1 deletion improves acetic acid tolerance and ethanol fermentation performance of S. cerevisiae.

Steroidogenic Factor-1 and Human Disease

PubMed Central

El-Khairi, Ranna; Achermann, John C.

2016-01-01

Steroidogenic factor-1 (SF-1) (Ad4BP, NR5A1) is a nuclear receptor that plays a key role in adrenal and reproductive development and function. Deletion of the gene encoding Sf-1 (Nr5a1) in mice results in severe developmental defects of the adrenal gland and gonad. Consequently, initial work on the potential effects of SF-1 disruption in humans focused on individuals with primary adrenal failure, a 46,XY karyotype, complete gonadal dysgenesis, and Müllerian structures. This is a rare phenotype, but has been reported on two occasions, because of alterations that affect key DNA-binding domains of SF-1. Attention then turned to a potential wider role of SF-1 in human adrenal and reproductive disorders. Although changes in SF-1 only very rarely cause isolated adrenal failure, it is emerging that variations in SF-1 are a surprisingly frequent cause of reproductive dysfunction in humans. In 46,XY disorders of sex development, a spectrum of phenotypes has been reported including severe and partial forms of gonadal (testicular) dysgenesis, hypospadias, anorchia with microphallus, and even male factor infertility. In 46,XX females, alterations in SF-1 are associated with primary ovarian insufficiency. Thus, SF-1 seems be a more significant factor in human reproductive health than was first envisioned, with implications for adults as well as children. PMID:23044873

Improving poor fill factors for solar cells via light-induced plating

NASA Astrophysics Data System (ADS)

Zhao, Xing; Rui, Jia; Wuchang, Ding; Yanlong, Meng; Zhi, Jin; Xinyu, Liu

2012-09-01

Silicon solar cells are prepared following the conventional fabrication processes, except for the metallization firing process. The cells are divided into two groups with higher and lower fill factors, respectively. After light-induced plating (LIP), the fill factors of the solar cells in both groups with different initial values reach the same level. Scanning electron microscope (SEM) images are taken under the bulk silver electrodes, which prove that the improvement for cells with a poor factor after LIP should benefit from sufficient exploitation of the high density silver crystals formed during the firing process. Moreover, the application of LIP to cells with poor electrode contact performance, such as nanowire cells and radial junction solar cells, is proposed.

Improved neovascularization and wound repair by targeting human basic fibroblast growth factor (bFGF) to fibrin.

PubMed

Zhao, Wenxue; Han, Qianqian; Lin, Hang; Gao, Yuan; Sun, Wenjie; Zhao, Yannan; Wang, Bin; Chen, Bing; Xiao, Zhifeng; Dai, Jianwu

2008-10-01

Targeted therapy is a new generation of therapeutics, where two critical factors are involved. One is the particular molecular target, and the other is the specific target-binding drug. In this work, the fibrin, a main component of plasma clot at wound sites, was used as the target for human bFGF, aiming to improve therapeutic neovascularization and wound repair. To endow bFGF with fibrin-targeting ability, a fibrin-binding peptide Kringle1 (K1), derived from human plasminogen, was fused to human bFGF. The recombinant K1bFGF showed high fibrin and plasma-clot-binding ability. When applied to the wound sites with plasma clots, K1bFGF induced robust neovascularization and improved wound healing. To extend the application of K1bFGF to other cases where no plasma clots exist, we developed a fibrin-scaffold/K1bFGF system. This system could induce localized neovascularization by delivery of K1bFGF in a sustained and site-targeting manner, and provide a microenvironment promoting cell growth and tissue regeneration. In summary, we successfully used the pathologic environment fibrin clot as the target for bFGF, and based on which bFGF was designed into a targeting agent by introduction of a fibrin-binding peptide. This provides a potential approach to improve therapeutic neovascularization and wound repair.

Can insulin-like growth factor 1 (IGF-1), IGF-1 receptor connective tissue growth factor and Ki-67 labelling index have a prognostic role in pulmonary carcinoids?

PubMed

Kanakis, Georgios A; Grimelius, Lars; Papaioannou, Dimitrios; Kaltsas, Gregory; Tsolakis, Apostolos V

2018-04-27

Altered expression of Insulin-like Growth Factor-1 (IGF-1), its receptor (IGF-1R), Connective Tissue Growth Factor (CTGF) and Hypoxia Inducible Factor-1 (HIF-1), has been implicated in tumorigenesis. So far, these factors have not been studied systematically in Pulmonary Carcinoids (PCs). To examine IGF-1, IGF-1R, CTGF and HIF-1 expression in PCs, and assess their prognostic value over established factors. Retrospective study of 121 PCs (104 Typical and 17 Atypical). The expression of growth factors was studied immunohistochemically and tumors were considered positive if immunoreactivity appeared in >50% of cells. All studied parameters were expressed in the majority of tumors (IGF-1, IGF-1R, CTGF and HIF-1, in 78.5%, 67%, 72% and 78%, respectively). Their expression tended to be more frequent in TCs and in tumors with Ki-67≤2% (significant only for HIF-1; 82 vs. 53%; p=0.023 and 83 vs. 63%; p=0.025 respectively). CTGF was the only factor correlated with more extensive disease (larger size; presence of lymph node and distant metastases). According to logistic regression analysis, only advanced age, Ki-67≥3.4% and lymph node involvement could predict the development of distant metastases. IGF-1, IGF-1R, CTGF and HIF-1 are avidly expressed in PCs; however, their presence did not appear to be of statistically significant value over established prognostic factors.

Transforming growth factor β-activated kinase 1 negatively regulates interleukin-1α-induced stromal-derived factor-1 expression in vascular smooth muscle cells

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

Yang, Bin; Li, Wei; Zheng, Qichang

Stromal-derived Factor-1 (SDF-1) derived from vascular smooth muscle cells (VSMCs) contributes to vascular repair and remodeling in various vascular diseases. In this study, the mechanism underlying regulation of SDF-1 expression by interleukin-1α (IL-1α) was investigated in primary rat VSMCs. We found IL-1α promotes SDF-1 expression by up-regulating CCAAT-enhancer-binding protein β (C/EBPβ) in an IκB kinase β (IKKβ) signaling-dependent manner. Moreover, IL-1α-induced expression of C/EBPβ and SDF-1 was significantly potentiated by knockdown of transforming growth factor β-activated kinase 1 (TAK1), an upstream activator of IKKβ signaling. In addition, we also demonstrated that TAK1/p38 mitogen-activated protein kinase (p38 MAPK) signaling exerted negativemore » effect on IL-1α-induced expression of C/EBPβ and SDF-1 through counteracting ROS-dependent up-regulation of nuclear factor erythroid 2-related factor 2 (NRF2). In conclusion, TAK1 acts as an important regulator of IL-1α-induced SDF-1 expression in VSMCs, and modulating activity of TAK1 may serve as a potential strategy for modulating vascular repair and remodeling. - Highlights: • IL-1α induces IKKβ signaling-dependent SDF-1 expression by up-regulating C/EBPβ. • Activation of TAK1 by IL-1α negatively regulates C/EBPβ-dependent SDF-1 expression. • IL-1α-induced TAK1/p38 MAPK signaling counteracts ROS-dependent SDF-1 expression. • TAK1 counteracts IL-1α-induced SDF-1 expression by attenuating NRF2 up-regulation.« less

Catheter-based Intramyocardial Injection of FGF1 or NRG1-loaded MPs Improves Cardiac Function in a Preclinical Model of Ischemia-Reperfusion

PubMed Central

Garbayo, Elisa; Gavira, Juan José; de Yebenes, Manuel Garcia; Pelacho, Beatriz; Abizanda, Gloria; Lana, Hugo; Blanco-Prieto, María José; Prosper, Felipe

2016-01-01

Cardiovascular protein therapeutics such as neuregulin (NRG1) and acidic-fibroblast growth factor (FGF1) requires new formulation strategies that allow for sustained bioavailability of the drug in the infarcted myocardium. However, there is no FDA-approved injectable protein delivery platform due to translational concerns about biomaterial administration through cardiac catheters. We therefore sought to evaluate the efficacy of percutaneous intramyocardial injection of poly(lactic-co-glycolic acid) microparticles (MPs) loaded with NRG1 and FGF1 using the NOGA MYOSTAR injection catheter in a porcine model of ischemia-reperfusion. NRG1- and FGF1-loaded MPs were prepared using a multiple emulsion solvent-evaporation technique. Infarcted pigs were treated one week after ischemia-reperfusion with MPs containing NRG1, FGF1 or non-loaded MPs delivered via clinically-translatable percutaneous transendocardial-injection. Three months post-treatment, echocardiography indicated a significant improvement in systolic and diastolic cardiac function. Moreover, improvement in bipolar voltage and decrease in transmural infarct progression was demonstrated by electromechanical NOGA-mapping. Functional benefit was associated with an increase in myocardial vascularization and remodeling. These findings in a large animal model of ischemia-reperfusion demonstrate the feasibility and efficacy of using MPs as a delivery system for growth factors and provide strong evidence to move forward with clinical studies using therapeutic proteins combined with catheter-compatible biomaterials. PMID:27184924

Catheter-based Intramyocardial Injection of FGF1 or NRG1-loaded MPs Improves Cardiac Function in a Preclinical Model of Ischemia-Reperfusion

NASA Astrophysics Data System (ADS)

Garbayo, Elisa; Gavira, Juan José; de Yebenes, Manuel Garcia; Pelacho, Beatriz; Abizanda, Gloria; Lana, Hugo; Blanco-Prieto, María José; Prosper, Felipe

2016-05-01

Cardiovascular protein therapeutics such as neuregulin (NRG1) and acidic-fibroblast growth factor (FGF1) requires new formulation strategies that allow for sustained bioavailability of the drug in the infarcted myocardium. However, there is no FDA-approved injectable protein delivery platform due to translational concerns about biomaterial administration through cardiac catheters. We therefore sought to evaluate the efficacy of percutaneous intramyocardial injection of poly(lactic-co-glycolic acid) microparticles (MPs) loaded with NRG1 and FGF1 using the NOGA MYOSTAR injection catheter in a porcine model of ischemia-reperfusion. NRG1- and FGF1-loaded MPs were prepared using a multiple emulsion solvent-evaporation technique. Infarcted pigs were treated one week after ischemia-reperfusion with MPs containing NRG1, FGF1 or non-loaded MPs delivered via clinically-translatable percutaneous transendocardial-injection. Three months post-treatment, echocardiography indicated a significant improvement in systolic and diastolic cardiac function. Moreover, improvement in bipolar voltage and decrease in transmural infarct progression was demonstrated by electromechanical NOGA-mapping. Functional benefit was associated with an increase in myocardial vascularization and remodeling. These findings in a large animal model of ischemia-reperfusion demonstrate the feasibility and efficacy of using MPs as a delivery system for growth factors and provide strong evidence to move forward with clinical studies using therapeutic proteins combined with catheter-compatible biomaterials.

Manipulation of a Senescence-Associated Gene Improves Fleshy Fruit Yield1[OPEN

PubMed Central

Gramegna, Giovanna; Trench, Bruna A.; Alves, Frederico R.R.; Silva, Eder M.; Silva, Geraldo F.F.; Thirumalaikumar, Venkatesh P.; Lupi, Alessandra C.D.; Demarco, Diego; Nogueira, Fabio T.S.; Freschi, Luciano

2017-01-01

Senescence is the process that marks the end of a leaf’s lifespan. As it progresses, the massive macromolecular catabolism dismantles the chloroplasts and, consequently, decreases the photosynthetic capacity of these organs. Thus, senescence manipulation is a strategy to improve plant yield by extending the leaf’s photosynthetically active window of time. However, it remains to be addressed if this approach can improve fleshy fruit production and nutritional quality. One way to delay senescence initiation is by regulating key transcription factors (TFs) involved in triggering this process, such as the NAC TF ORESARA1 (ORE1). Here, three senescence-related NAC TFs from tomato (Solanum lycopersicum) were identified, namely SlORE1S02, SlORE1S03, and SlORE1S06. All three genes were shown to be responsive to senescence-inducing stimuli and posttranscriptionally regulated by the microRNA miR164. Moreover, the encoded proteins interacted physically with the chloroplast maintenance-related TF SlGLKs. This characterization led to the selection of a putative tomato ORE1 as target gene for RNA interference knockdown. Transgenic lines showed delayed senescence and enhanced carbon assimilation that, ultimately, increased the number of fruits and their total soluble solid content. Additionally, the fruit nutraceutical composition was enhanced. In conclusion, these data provide robust evidence that the manipulation of leaf senescence is an effective strategy for yield improvement in fleshy fruit-bearing species. PMID:28710129

Factors influencing householders' access to improved water in low-income urban areas of Accra, Ghana.

PubMed

Mahama, Ayisha Matuamo; Anaman, Kwabena Asomanin; Osei-Akoto, Isaac

2014-06-01

We analysed householders' access to improved water for drinking and other domestic uses in five selected low-income urban areas of Accra, Ghana using a survey of 1,500 households. Our definitions of improved water were different from those suggested by the World Health Organization (WHO). The results revealed that only 4.4% of the respondents had access to improved drinking water compared to 40.7% using the WHO definition. However, 88.7% of respondents had access to improved water for domestic uses compared to 98.3% using the WHO definition. Using logistic regression analysis, we established that the significant determinant of householders' access to improved drinking water was income. However, for access to improved water for other domestic uses, the significant factors were education, income and location of the household. Compared to migrants, indigenous people and people from mixed areas were less likely to have access to improved water for other domestic purposes. For the analysis using the WHO definitions, most of the independent variables were not statistically significant in determining householders' access, and those variables that were significant generated parameter estimates inconsistent with evidence from the literature and anecdotal evidence from officials of public health and water supply companies in Ghana.

Transgenic Overexpression of the Transcription Factor Nkx6.1 in β-Cells of Mice Does Not Increase β-Cell Proliferation, β-Cell Mass, or Improve Glucose Clearance

PubMed Central

Schaffer, Ashleigh E.; Yang, Almira J.; Thorel, Fabrizio; Herrera, Pedro L.

2011-01-01

The loss or dysfunction of the pancreatic endocrine β-cell results in diabetes. Recent innovative therapeutic approaches for diabetes aim to induce β-cell proliferation in vivo by pharmacological intervention. Based on the finding that overexpression of the transcription factor Nkx6.1 in islets in vitro increases β-cell proliferation while maintaining β-cell function, Nkx6.1 has been proposed as a potential target for diabetes therapy. However, it is unknown whether elevated Nkx6.1 levels in β-cells in vivo have similar effects as observed in isolated islets. To this end, we sought to investigate whether overexpression of Nkx6.1 in β-cells in vivo could increase β-cell mass and/or improve β-cell function in normal or β-cell-depleted mice. Using a bigenic inducible Cre-recombinase-based transgenic model, we analyzed the effects of Nkx6.1 overexpression on β-cell proliferation, β-cell mass, and glucose metabolism. We found that mice overexpressing Nkx6.1 in β-cells displayed similar β-cell proliferation rates and β-cell mass as control mice. Furthermore, after partial β-cell ablation, Nkx6.1 overexpression was not sufficient to induce β-cell regeneration under either nondiabetic or diabetic conditions. Together these results demonstrate that sustained Nkx6.1 overexpression in vivo does not stimulate β-cell proliferation, expand β-cell mass, or improve glucose metabolism in either normal or β-cell-depleted pancreata. Thus, raising cellular Nkx6.1 levels in β-cells in vivo is unlikely to have a positive impact on type 2 diabetes. PMID:21964593

Targeting placental growth factor/neuropilin 1 pathway inhibits growth and spread of medulloblastoma

PubMed Central

Snuderl, Matija; Batista, Ana; Kirkpatrick, Nathaniel D.; de Almodovar, Carmen Ruiz; Riedemann, Lars; Walsh, Elisa C.; Anolik, Rachel; Huang, Yuhui; Martin, John D.; Kamoun, Walid; Knevels, Ellen; Schmidt, Thomas; Farrar, Christian T.; Vakoc, Benjamin J.; Mohan, Nishant; Chung, Euiheon; Roberge, Sylvie; Peterson, Teresa; Bais, Carlos; Zhelyazkova, Boryana H.; Yip, Stephen; Hasselblatt, Martin; Rossig, Claudia; Niemeyer, Elisabeth; Ferrara, Napoleone; Klagsbrun, Michael; Duda, Dan G.; Fukumura, Dai; Xu, Lei; Carmeliet, Peter; Jain, Rakesh K.

2013-01-01

SUMMARY Medulloblastoma is the most common pediatric malignant brain tumor. Although current therapies improve survival, these regimens are highly toxic and associated with significant morbidity. Here, we report that placental growth factor (PlGF) is expressed in the majority of medulloblastomas independent of their subtype. Moreover, high expression of PlGF receptor neuropilin 1 (Nrp1) correlates with poor overall survival in patients. We demonstrate that PlGF and Nrp1 are required for the growth and spread of medulloblastoma: PlGF/Nrp1 blockade results in direct antitumor effects in vivo, resulting in medulloblastoma regression, decreased metastases, and increased mouse survival. We reveal that PlGF is produced in the cerebellar stroma via tumor-derived Sonic hedgehog (Shh) and show that PlGF acts through Nrp1—and not vascular endothelial growth factor receptor 1 (VEGFR1)—to promote tumor cell survival. This critical tumor-stroma interaction—mediated by Shh, PlGF, and Nrp1 across medulloblastoma subtypes—supports the development of therapies targeting PlGF/Nrp1 pathway. PMID:23452854

Factors influencing the long-term sustainment of quality improvements made in addiction treatment facilities: a qualitative study.

PubMed

Stumbo, Scott P; Ford, James H; Green, Carla A

2017-11-01

A greater understanding of the factors that influence long-term sustainment of quality improvement (QI) initiatives is needed to promote organizational ability to sustain QI practices over time, help improve future interventions, and increase the value of QI investments. We approached 83 of 201 executive sponsors or change leaders at addiction treatment organizations that participated in the 2007-2009 NIATx200 QI intervention. We completed semi-structured interviews with 33 individuals between November 2015 and April 2016. NIATx200 goals were to decrease wait time, increase admissions and improve retention in treatment. Interviews sought to understand factors that either facilitated or impeded long-term sustainment of organizational QI practices made during the intervention. We used thematic analysis to organize the data and group patterns of responses. We assessed available quantitative outcome data and intervention engagement data to corroborate qualitative results. We used narrative analysis to group four important themes related to long-term sustainment of QI practices: (1) finding alignment between business- and client-centered practices; (2) staff engagement early in QI process added legitimacy which facilitated sustainment; (3) commitment to integrating data into monitoring practices and the identification of a data champion; and (4) adequate organizational human resources devoted to sustainment. We found four corollary factors among agencies which did not sustain practices: (1) lack of evidence of impact on business practices led to discontinuation; (2) disengaged staff and lack of organizational capacity during implementation period led to lack of sustainment; (3) no data integration into overall business practices and no identified data champion; and (4) high staff turnover. In addition, we found that many agencies' current use of NIATx methods and tools suggested a legacy effect that might improve quality elsewhere, even absent overall sustainment of

Brain-derived neurotrophic factor mediates cognitive improvements following acute exercise.

PubMed

Borror, Andrew

2017-09-01

The mechanisms causing improved cognition following acute exercise are poorly understood. This article proposes that brain-derived neurotrophic factor (BDNF) is the main factor contributing to improved cognition following exercise. Additionally, it argues that cerebral blood flow (CBF) and oxidative stress explain the release of BDNF from cerebral endothelial cells. One way to test these hypotheses is to block endothelial function and measure the effect on BDNF levels and cognitive performance. The CBF and oxidative stress can also be examined in relationship to BDNF using a multiple linear regression. If these hypotheses are true, there would be a linear relationship between CBF+oxidative stress and BDNF levels as well as between BDNF levels and cognitive performance. The novelty of these hypotheses comes from the emphasis on the cerebral endothelium and the interplay between BDNF, CBF, and oxidative stress. If found to be valid, these hypotheses would draw attention to the cerebral endothelium and provide direction for future research regarding methods to optimize BDNF release and enhance cognition. Elucidating these mechanisms would provide direction for expediting recovery in clinical populations, such as stroke, and maintaining quality of life in the elderly. Copyright © 2017 Elsevier Ltd. All rights reserved.

Liposomal gene transfer of keratinocyte growth factor improves wound healing by altering growth factor and collagen expression.

PubMed

Pereira, Clifford T; Herndon, David N; Rocker, Roland; Jeschke, Marc G

2007-05-15

Growth factors affect the complex cascade of wound healing; however, interaction between different growth factors during dermal and epidermal regeneration are still not entirely defined. In the present study, we thought to determine the interaction between keratinocyte growth factor (KGF) administered as liposomal cDNA with other dermal and epidermal growth factors and collagen synthesis in an acute wound. Rats received an acute wound and were divided into two groups to receive weekly subcutaneous injections of liposomes plus the Lac-Z gene (0.22 microg, vehicle), or liposomes plus the KGF cDNA (2.2 microg) and Lac-Z gene (0.22 microg). Histological and immunohistochemical techniques were used to determine growth factor, collagen expression, and dermal and epidermal structure. KGF cDNA increased insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3), and fibroblast growth factor (FGF), decreased transforming growth factor-beta (TGF-beta), while it had no effect on platelet-derived growth factor (PDGF) levels in the wound. KGF cDNA significantly increased collagen Type IV at both the wound edge as well as the wound bed, while it had no effect on collagen Type I and III. KGF cDNA increased re-epithelialization, improved dermal regeneration, and increased neovascularization. Exogenous administered KGF cDNA causes increases in IGF-I, IGF-BP3, FGF, and collagen IV and decreases TGF-beta concentration. KGF gene transfer accelerates wound healing without causing an increase in collagen I or III.

Targeting DMPK with Antisense Oligonucleotide Improves Muscle Strength in Myotonic Dystrophy Type 1 Mice.

PubMed

Jauvin, Dominic; Chrétien, Jessina; Pandey, Sanjay K; Martineau, Laurie; Revillod, Lucille; Bassez, Guillaume; Lachon, Aline; MacLeod, A Robert; Gourdon, Geneviève; Wheeler, Thurman M; Thornton, Charles A; Bennett, C Frank; Puymirat, Jack

2017-06-16

Myotonic dystrophy type 1 (DM1), a dominant hereditary muscular dystrophy, is caused by an abnormal expansion of a (CTG) n trinucleotide repeat in the 3' UTR of the human dystrophia myotonica protein kinase (DMPK) gene. As a consequence, mutant transcripts containing expanded CUG repeats are retained in nuclear foci and alter the function of splicing regulatory factors members of the MBNL and CELF families, resulting in alternative splicing misregulation of specific transcripts in affected DM1 tissues. In the present study, we treated DMSXL mice systemically with a 2'-4'-constrained, ethyl-modified (ISIS 486178) antisense oligonucleotide (ASO) targeted to the 3' UTR of the DMPK gene, which led to a 70% reduction in CUG exp RNA abundance and foci in different skeletal muscles and a 30% reduction in the heart. Furthermore, treatment with ISIS 486178 ASO improved body weight, muscle strength, and muscle histology, whereas no overt toxicity was detected. This is evidence that the reduction of CUG exp RNA improves muscle strength in DM1, suggesting that muscle weakness in DM1 patients may be improved following elimination of toxic RNAs. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Human factors opportunities to improve Ohio's transportation system : final report, June 2005.

DOT National Transportation Integrated Search

2005-06-01

The aim of this study was to identify opportunities to apply human factors principles and research to improve : Ohios transportation system. The Office of Traffic Engineering assigned thirteen topic areas to provide information : and the study was...

Bicycling to school improves the cardiometabolic risk factor profile: a randomised controlled trial

PubMed Central

Østergaard, Lars; Børrestad, Line A B; Tarp, Jakob; Andersen, Lars Bo

2012-01-01

Objectives To investigate whether bicycling to school improves cardiometabolic risk factor profile and cardiorespiratory fitness among children. Design Prospective, blinded, randomised controlled trial. Setting Single centre study in Odense, Denmark Participants 43 children previously not bicycling to school were randomly allocated to control group (n=20) (ie, no change in lifestyle) or intervention group (ie, bicycling to school) (n=23). Primary and secondary outcome measures Change in cardiometabolic risk factor score and change in cardiorespiratory fitness. Results All participants measured at baseline returned at follow-up. Based upon intention-to-treat (ITT) analyses, clustering of cardiometabolic risk factors was lowered by 0.58 SD (95% CI −1.03 to −0.14, p=0.012) in the bicycling group compared to the control group. Cardiorespiratory fitness (l O2/min) per se did not increase significantly more in the intervention than in the control group (β=0.0337, 95% CI −0.06 to 0.12, p=0.458). Conclusions Bicycling to school counteracted a clustering of cardiometabolic risk factors and should thus be recognised as potential prevention of type 2 diabetes mellitus and cardiovascular disease (CVD). The intervention did, however, not elicit a larger increase in cardiorespiratory fitness in the intervention group as compared with the control group. Trial registration Registered at http://www.clinicaltrials.gov (NCT01236222). PMID:23117560

Improvement of vibration energy harvesters mechanical Q-factor through high density proof mass integration

NASA Astrophysics Data System (ADS)

Dompierre, A.; Fréchette, L. G.

2016-11-01

This paper reports on improvement of the mechanical Q-factor of resonant energy harvesters at ambient pressure via the use of tungsten proof masses by evaluating the impact of the mass size and density on the squeeze film damping. To this end, a simplified model is first proposed to evaluate cantilever beams deflection and the resulting fluid pressure build up between the mass and a near surface. The model, which accounts for simultaneous transverse and rotational motion of very long tip masses as well as for 2D fluid flow in the gap, is used to extract a scaling law for the device fluidic Q-factor Qf. This law states that Qf can be improved by either increasing the linear mass density of the tip mass or by reducing the side lengths compared to the gap height. The first approach is validated experimentally by adding a tungsten proof mass on a silicon based device and observing an improvement of the Q-factor by 103%, going from 430 to 871, while the resonance frequency drops from 457 to 127 Hz. In terms of fluidic Q-factor, this represents an increase from 562 to 1673. These results successfully demonstrate the benefits of integrating a tungsten mass to reduce the fluid losses while potentially reducing the device footprint.

Scaffold attachment factor B suppresses HIV-1 infection of CD4+ cells by preventing binding of RNA polymerase II to HIV-1's long terminal repeat.

PubMed

Ma, Li; Sun, Li; Jin, Xia; Xiong, Si-Dong; Wang, Jian-Hua

2018-06-10

The 5' end of HIV-1 long terminal repeat (LTR) promoter plays an essential role in driving viral transcription and productive infection. Multiple host and viral factors regulate LTR activity and modulate HIV-1 latency. Manipulation of the HIV-1 LTR provides a potential therapeutic strategy for combating HIV-1 persistence. In this study, we identified an RNA-/DNA-binding protein, Scaffold Attachment Factor B (SAFB1) as a host-cell factor that represses HIV-1 transcription. We found that SAFB1 bound to HIV-1 5`-LTR and significantly repressed 5`-LTR-driven-viral transcription and HIV-1 infection of CD4 + T cells. Mechanistically, SAFB1-mediated repression of HIV-1 transcription and infection was independent of its RNA- and DNA-binding capacities, instead, by binding to phosphorylated RNA polymerase II (RNA pol II), SAFB1 blocked its recruitment to the HIV-1 LTR. Of note, the SAFB1-mediated repression of HIV-1 transcription from proviral DNA maintained HIV-1 latency in CD4 + T cells. In summary, our findings reveal that SAFB1 binds to HIV-1-LTR and physically interacts with phosphorylated RNA pol II, repressing HIV-1 transcription initiation and elongation. Our findings improve the understanding of host modulation of HIV-1 transcription and latency and provide a new host-cell target for improved anti-HIV-1 therapies. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Identification of key factors in consumers' adoption behavior of intelligent medical terminals based on a hybrid modified MADM model for product improvement.

PubMed

Liu, Yupeng; Chen, Yifei; Tzeng, Gwo-Hshiung

2017-09-01

As a new application technology of the Internet of Things (IoT), intelligent medical treatment has attracted the attention of both nations and industries through its promotion of medical informatisation, modernisation, and intelligentisation. Faced with a wide variety of intelligent medical terminals, consumers may be affected by various factors when making purchase decisions. To examine and evaluate the key influential factors (and their interrelationships) of consumer adoption behavior for improving and promoting intelligent medical terminals toward achieving set aspiration level in each dimension and criterion. A hybrid modified Multiple Attribute Decision-Making (MADM) model was used for this study, based on three components: (1) the Decision-Making Trial and Evaluation Laboratory (DEMATEL) technique, to build an influential network relationship map (INRM) at both 'dimensions' and 'criteria' levels; (2) the DEMATEL-based analytic network process (DANP) method, to determine the interrelationships and influential weights among the criteria and identify the source-influential factors; and (3) the modified Vlse Kriterijumska Optimizacija I Kompromisno Resenje (VIKOR) method, to evaluate and improve for reducing the performance gaps to meet the consumers' needs for continuous improvement and sustainable products-development. First, a consensus on the influential factors affecting consumers' adoption of intelligent medical terminals was collected from experts' opinion in practical experience. Next, the interrelationships and influential weights of DANP among dimensions/criteria based on the DEMATEL technique were determined. Finally, two intelligent medicine bottles (AdhereTech, A 1 alternative; and Audio/Visual Alerting Pillbox, A 2 alternative) were reviewed as the terminal devices to verify the accuracy of the MADM model and evaluate its performance on each criterion for improving the total certification gaps by systematics according to the modified VIKOR method

The transcription factor Prep1 controls hepatic insulin sensitivity and gluconeogenesis by targeting nuclear localization of FOXO1

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

Kulebyakin, Konstantin; Penkov, Dmitry; IFOM – the FIRC Institute of Molecular Oncology, Via Adamello 16, Milan, 20139

Liver plays a key role in controlling body carbohydrate homeostasis by switching between accumulation and production of glucose and this way maintaining constant level of glucose in blood. Increased blood glucose level triggers release of insulin from pancreatic β-cells. Insulin represses hepatic glucose production and increases glucose accumulation. Insulin resistance is the main cause of type 2 diabetes and hyperglycemia. Currently thiazolidinediones (TZDs) targeting transcriptional factor PPARγ are used as insulin sensitizers for treating patients with type 2 diabetes. However, TZDs are reported to be associated with cardiovascular and liver problems and stimulate obesity. Thus, it is necessary to searchmore » new approaches to improve insulin sensitivity. A promising candidate is transcriptional factor Prep1, as it was shown earlier it could affect insulin sensitivity in variety of insulin-sensitive tissues. The aim of the present study was to evaluate a possible involvement of transcriptional factor Prep1 in control of hepatic glucose accumulation and production. We created mice with liver-specific Prep1 knockout and discovered that hepatocytes derived from these mice are much more sensitive to insulin, comparing to their WT littermates. Incubation of these cells with 100 nM insulin results in almost complete inhibition of gluconeogenesis, while in WT cells this repression is only partial. However, Prep1 doesn't affect gluconeogenesis in the absence of insulin. Also, we observed that nuclear content of gluconeogenic transcription factor FOXO1 was greatly reduced in Prep1 knockout hepatocytes. These findings suggest that Prep1 may control hepatic insulin sensitivity by targeting FOXO1 nuclear stability. - Highlights: • A novel model of liver-specific Prep1 knockout is established. • Ablation of Prep1 in hepatocytes increases insulin sensitivity. • Prep1 controls hepatic insulin sensitivity by regulating localization of FOXO1. • Prep1 regulates

Initial management of pneumonia and sepsis: factors associated with improved outcome.

PubMed

Menéndez, R; Torres, A; Reyes, S; Zalacain, R; Capelastegui, A; Aspa, J; Borderías, L; Martín-Villasclaras, J J; Bello, S; Alfageme, I; de Castro, F R; Rello, J; Molinos, L; Ruiz-Manzano, J

2012-01-01

Processes of care and adherence to guidelines have been associated with improved survival in community-acquired pneumonia (CAP). In sepsis, bundles of processes of care have also increased survival. We aimed to audit compliance with guideline-recommended processes of care and its impact on outcome in hospitalised CAP patients with sepsis. We prospectively studied 4,137 patients hospitalised with CAP in 13 hospitals. The processes of care evaluated were adherence to antibiotic prescription guidelines, first dose within 6 h and oxygen assessment. Outcome measures were mortality and length of stay (LOS). Oxygen assessment was measured in 3,745 (90.5%) patients; 3,024 (73.1%) patients received antibiotics according to guidelines and 3,053 (73.8%) received antibiotics within 6 h. In CAP patients with sepsis, the strongest independent factor for survival was antibiotic adherence (OR 0.4). In severe sepsis, only compliance to antibiotic adherence plus first dose within 6 h was associated with lower mortality (OR 0.60), adjusted for fine prognostic scale and hospital. Antibiotic adherence was related to shorter hospital stay. In sepsis, antibiotic adherence is the strongest protective factor of care associated with survival and LOS. In severe sepsis, combined antibiotic adherence and first dose within 6 h may reduce mortality.

Improving risk assessment in schizophrenia: epidemiological investigation of criminal history factors

PubMed Central

Witt, Katrina; Lichtenstein, Paul; Fazel, Seena

2015-01-01

Background Violence risk assessment in schizophrenia relies heavily on criminal history factors. Aims To investigate which criminal history factors are most strongly associated with violent crime in schizophrenia. Method A total of 13 806 individuals (8891 men and 4915 women) with two or more hospital admissions for schizophrenia were followed up for violent convictions. Multivariate hazard ratios for 15 criminal history factors included in different risk assessment tools were calculated. The incremental predictive validity of these factors was estimated using tests of discrimination, calibration and reclassification. Results Over a mean follow-up of 12.0 years, 17.3% of men (n = 1535) and 5.7% of women (n = 281) were convicted of a violent offence. Criminal history factors most strongly associated with subsequent violence for both men and women were a previous conviction for a violent offence; for assault, illegal threats and/or intimidation; and imprisonment. However, only a previous conviction for a violent offence was associated with incremental predictive validity in both genders following adjustment for young age and comorbid substance use disorder. Conclusions Clinical and actuarial approaches to assess violence risk can be improved if included risk factors are tested using multiple measures of performance. PMID:25657352

Improving risk assessment in schizophrenia: epidemiological investigation of criminal history factors.

PubMed

Witt, Katrina; Lichtenstein, Paul; Fazel, Seena

2015-05-01

Violence risk assessment in schizophrenia relies heavily on criminal history factors. To investigate which criminal history factors are most strongly associated with violent crime in schizophrenia. A total of 13 806 individuals (8891 men and 4915 women) with two or more hospital admissions for schizophrenia were followed up for violent convictions. Multivariate hazard ratios for 15 criminal history factors included in different risk assessment tools were calculated. The incremental predictive validity of these factors was estimated using tests of discrimination, calibration and reclassification. Over a mean follow-up of 12.0 years, 17.3% of men (n = 1535) and 5.7% of women (n = 281) were convicted of a violent offence. Criminal history factors most strongly associated with subsequent violence for both men and women were a previous conviction for a violent offence; for assault, illegal threats and/or intimidation; and imprisonment. However, only a previous conviction for a violent offence was associated with incremental predictive validity in both genders following adjustment for young age and comorbid substance use disorder. Clinical and actuarial approaches to assess violence risk can be improved if included risk factors are tested using multiple measures of performance. © The Royal College of Psychiatrists 2015.

Steroidogenic factor-1 (SF-1, NR5A1) and human disease

PubMed Central

Ferraz-de-Souza, Bruno; Lin, Lin; Achermann, John C.

2011-01-01

Steroidogenic factor-1 (SF-1, Ad4BP, encoded by NR5A1) is a key regulator of adrenal and reproductive development and function. Based upon the features found in Nr5a1 null mice, initial attempts to identify SF-1 changes in humans focused on those rare individuals with primary adrenal failure, a 46,XY karyotype, complete gonadal dysgenesis and Müllerian structures. Although alterations affecting DNA-binding of SF-1 were found in two such cases, disruption of SF-1 is not commonly found in patients with adrenal failure. In contrast, it is emerging that variations in SF-1 can be found in association with a range of human reproductive phenotypes such as 46,XY disorders of sex development (DSD), hypospadias, anorchia, male factor infertility, or primary ovarian insufficiency in women. Overexpression or overactivity of SF-1 is also reported in some adrenal tumors or endometriosis. Therefore, the clinical spectrum of phenotypes associated with variations in SF-1 is expanding and the importance of this nuclear receptor in human endocrine disease is now firmly established. PMID:21078366

Factorization and resummation: A new paradigm to improve gravitational wave amplitudes

NASA Astrophysics Data System (ADS)

Nagar, Alessandro; Shah, Abhay

2016-11-01

We introduce a new resummed analytical form of the post-Newtonian (PN), factorized, multipolar amplitude corrections fℓm of the effective-one-body (EOB) gravitational waveform of spinning, nonprecessing, circularized, coalescing black hole binaries (BBHs). This stems from the following two-step paradigm: (i) the factorization of the orbital (spin-independent) terms in fℓm; (ii) the resummation of the residual spin (or orbital) factors. We find that resumming the residual spin factor by taking its inverse resummed (iResum) is an efficient way to obtain amplitudes that are more accurate in the strong-field, fast-velocity regime. The performance of the method is illustrated on the ℓ=2 and m =(1 ,2 ) waveform multipoles, both for a test mass orbiting around a Kerr black hole and for comparable-mass BBHs. In the first case, the iResum fℓm's are much closer to the corresponding "exact" functions (obtained by numerically solving the Teukolsky equation) up to the light ring than the nonresummed ones, especially when the black-hole spin is nearly extremal. The iResum paradigm is also more efficient than including higher post-Newtonian terms (up to 20PN order): the resummed 5PN information yields per se a rather good numerical or analytical agreement at the last stable orbit and a well-controlled behavior up to the light ring. For comparable mass binaries (including the highest PN-order information available, 3.5PN), comparing EOB with numerical relativity (NR) data shows that the EOB/NR fractional disagreement at merger, without NR calibration of the EOB waveform, is generically reduced by iResum, from 40% of the usual approach to just a few percent. This suggests that EOBNR waveform models for coalescing BBHs may be improved by using iResum amplitudes.

Improved method estimating bioconcentration/bioaccumulation factor from octanol/water partition coefficient

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

Meylan, W.M.; Howard, P.H.; Aronson, D.

1999-04-01

A compound`s bioconcentration factor (BDF) is the most commonly used indicator of its tendency to accumulate in aquatic organisms from the surrounding medium. Because it is expensive to measure, the BCF is generally estimated from the octanol/water partition coefficient (K{sub ow}), but currently used regression equations were developed from small data sets that do not adequately represent the wide range of chemical substances now subject to review. To develop and improved method, the authors collected BCF data in a file that contained information on measured BCFs and other key experimental details for 694 chemicals. Log BCF was then regressed againstmore » log K{sub ow} and chemicals with significant deviations from the line of best fit were analyzed by chemical structure. The resulting algorithm classifies a substance as either nonionic or ionic, the latter group including carboxylic acids, sulfonic acids and their salts, and quaternary N compounds. Log BCF for nonionics is estimated from log K{sub ow} and a series of correction factors if applicable; different equations apply for log K{sub ow} 1.0 to 7.0 and >7.0. For ionics, chemicals are categorized by log K{sub ow} and a log BCF in the range 0.5 to 1.75 is assigned. Organometallics, nonionics with long alkyl chains, and aromatic azo compounds receive special treatment. The correlation coefficient and mean error for log BCF indicate that the new method is a significantly better fit to existing data than other methods.« less

E2F1 transcription factor and its impact on growth factor and cytokine signaling.

PubMed

Ertosun, Mustafa Gokhan; Hapil, Fatma Zehra; Osman Nidai, Ozes

2016-10-01

E2F1 is a transcription factor involved in cell cycle regulation and apoptosis. The transactivation capacity of E2F1 is regulated by pRb. In its hypophosphorylated form, pRb binds and inactivates DNA binding and transactivating functions of E2F1. The growth factor stimulation of cells leads to activation of CDKs (cyclin dependent kinases), which in turn phosphorylate Rb and hyperphosphorylated Rb is released from E2F1 or E2F1/DP complex, and free E2F1 can induce transcription of several genes involved in cell cycle entry, induction or inhibition of apoptosis. Thus, growth factors and cytokines generally utilize E2F1 to direct cells to either fate. Furthermore, E2F1 regulates expressions of various cytokines and growth factor receptors, establishing positive or negative feedback mechanisms. This review focuses on the relationship between E2F1 transcription factor and cytokines (IL-1, IL-2, IL-3, IL-6, TGF-beta, G-CSF, LIF), growth factors (EGF, KGF, VEGF, IGF, FGF, PDGF, HGF, NGF), and interferons (IFN-α, IFN-β and IFN-γ). Copyright © 2016 Elsevier Ltd. All rights reserved.

Improving Ascertainment of Risk Factors for HIV Infection: Results of a Group-Randomized Evaluation

ERIC Educational Resources Information Center

Harrison, Kathleen McDavid; Pals, Sherri L.; Sajak, Tammy; Chase, Jennifer; Kajese, Tebitha

2010-01-01

To allow appropriate allocation of prevention and care funding, HIV/AIDS surveillance data must include risk factor information, currently available for less than 70% of cases reported in the United States. The authors evaluated an intervention consisting of provider training and materials to improve risk factor reporting. Facilities were matched…

Q-factor improvement of degenerate four-wave-mixing regenerators for ASE degraded signals

NASA Astrophysics Data System (ADS)

Lu, Hang; Wu, Bao-jian; Geng, Yong; Zhou, Xing-yu; Sun, Fan

2017-11-01

All-optical regenerators can be used to suppress amplified spontaneous emission (ASE) noise introduced by cascaded erbium doped fiber amplifiers (EDFAs) in optical fiber communication systems and lead to the improvement of optical receiver sensitivity. By introducing the Q-factor transfer function (QTF), we evaluate the Q-factor performance of degenerate four-wave mixing (DFWM) regenerators with clock pump and reveal the differences between the optimal input powers determined from the static and dynamic power tranfer function (PTF) and the QTF curves. Our simulation shows that the clock-pump regnerator is capable of improving the Q-facor and receiver sensitivity for 40 Gbit/s ASE-degraded return-to-zero on-off keying (RZ-OOK) signal by 2.58 dB and 4.2 dB, respectively.

Plant nuclear factor Y (NF-Y) B subunits confer drought tolerance and lead to improved corn yields on water-limited acres.

PubMed

Nelson, Donald E; Repetti, Peter P; Adams, Tom R; Creelman, Robert A; Wu, Jingrui; Warner, David C; Anstrom, Don C; Bensen, Robert J; Castiglioni, Paolo P; Donnarummo, Meghan G; Hinchey, Brendan S; Kumimoto, Roderick W; Maszle, Don R; Canales, Roger D; Krolikowski, Katherine A; Dotson, Stanton B; Gutterson, Neal; Ratcliffe, Oliver J; Heard, Jacqueline E

2007-10-16

Commercially improved crop performance under drought conditions has been challenging because of the complexity of the trait and the multitude of factors that influence yield. Here we report the results of a functional genomics approach that identified a transcription factor from the nuclear factor Y (NF-Y) family, AtNF-YB1, which acts through a previously undescribed mechanism to confer improved performance in Arabidopsis under drought conditions. An orthologous maize transcription factor, ZmNF-YB2, is shown to have an equivalent activity. Under water-limited conditions, transgenic maize plants with increased ZmNF-YB2 expression show tolerance to drought based on the responses of a number of stress-related parameters, including chlorophyll content, stomatal conductance, leaf temperature, reduced wilting, and maintenance of photosynthesis. These stress adaptations contribute to a grain yield advantage to maize under water-limited environments. The application of this technology has the potential to significantly impact maize production systems that experience drought.

Plant nuclear factor Y (NF-Y) B subunits confer drought tolerance and lead to improved corn yields on water-limited acres

PubMed Central

Nelson, Donald E.; Repetti, Peter P.; Adams, Tom R.; Creelman, Robert A.; Wu, Jingrui; Warner, David C.; Anstrom, Don C.; Bensen, Robert J.; Castiglioni, Paolo P.; Donnarummo, Meghan G.; Hinchey, Brendan S.; Kumimoto, Roderick W.; Maszle, Don R.; Canales, Roger D.; Krolikowski, Katherine A.; Dotson, Stanton B.; Gutterson, Neal; Ratcliffe, Oliver J.; Heard, Jacqueline E.

2007-01-01

Commercially improved crop performance under drought conditions has been challenging because of the complexity of the trait and the multitude of factors that influence yield. Here we report the results of a functional genomics approach that identified a transcription factor from the nuclear factor Y (NF-Y) family, AtNF-YB1, which acts through a previously undescribed mechanism to confer improved performance in Arabidopsis under drought conditions. An orthologous maize transcription factor, ZmNF-YB2, is shown to have an equivalent activity. Under water-limited conditions, transgenic maize plants with increased ZmNF-YB2 expression show tolerance to drought based on the responses of a number of stress-related parameters, including chlorophyll content, stomatal conductance, leaf temperature, reduced wilting, and maintenance of photosynthesis. These stress adaptations contribute to a grain yield advantage to maize under water-limited environments. The application of this technology has the potential to significantly impact maize production systems that experience drought. PMID:17923671

Epidermal growth factor treatment decreases mortality and is associated with improved gut integrity in sepsis.

PubMed

Clark, Jessica A; Clark, Andrew T; Hotchkiss, Richard S; Buchman, Timothy G; Coopersmith, Craig M

2008-07-01

Epidermal growth factor (EGF) is a cytoprotective peptide that has healing effects on the intestinal mucosa. We sought to determine whether systemic administration of EGF after the onset of sepsis improved intestinal integrity and decreased mortality. FVB/N mice were subjected to either sham laparotomy or 2 x 23 cecal ligation and puncture (CLP). Septic mice were further randomized to receive injection of either 150 microg kg(-1) d(-1) (i.p.) EGF or 0.9% saline (i.p.). Circulating EGF levels were decreased after CLP compared with sham animals but were unaffected by giving exogenous EGF treatment. In contrast, intestinal EGF levels increased after CLP and were further augmented by exogenous EGF treatment. Intestinal EGF receptor was increased after CLP, whether assayed by immunohistochemistry, real-time polymerase chain reaction, or Western blot, and exogenous EGF treatment decreased intestinal EGF receptor. Villus length decreased 2-fold between sham and septic animals, and EGF treatment resulted in near total restitution of villus length. Sepsis decreased intestinal proliferation and increased intestinal apoptosis. This was accompanied by increased expression of the proapoptotic proteins Bid and Fas-associated death domain, as well as the cyclin-dependent kinase inhibitor p21 cip1/waf Epidermal growth factor treatment after the onset of sepsis restored both proliferation and apoptosis to levels seen in sham animals and normalized expression of Bid, Fas-associated death domain, and p21 cip1/waf . To determine whether improvements in gut homeostasis were associated with a decrease in sepsis-induced mortality, septic mice with or without EGF treatment after CLP were followed 7 days for survival. Mortality decreased from 60% to 30% in mice treated with EGF after the onset of sepsis (P < 0.05). Thus, EGF may be a potential therapeutic agent for the treatment of sepsis in part due to its ability to protect intestinal integrity.

26 CFR 1.846-1 - Application of discount factors.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (CONTINUED) INCOME TAXES (CONTINUED) Other Insurance Companies § 1.846-1 Application of discount factors. (a... losses based on their annual statement classification prior to the change. (2) Title insurance company reserves. A title insurance company may only take into account case reserves (relating to claims which have...

26 CFR 1.846-1 - Application of discount factors.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) INCOME TAXES Other Insurance Companies § 1.846-1 Application of discount factors. (a) In general... losses based on their annual statement classification prior to the change. (2) Title insurance company reserves. A title insurance company may only take into account case reserves (relating to claims which have...

Factors influencing improved attendance in the UK fire service

PubMed Central

Hinckley, P.

2016-01-01

Background Sickness absence rates in the UK continue to exceed those in much of the developed world, with an annual cost to employers of £29 billion. Rates of sickness absence in the public sector are higher than those in the private sector, with the exception of the fire service where they are consistently lower. Aims To understand the influences that increase attendance among operational firefighters. Methods A series of semi-structured interviews undertaken with operational staff to explore their attitudes to sickness absence. Results Review and analysis of participant responses identified a number of key themes, namely employee well-being, including physical fitness and mental health; employee engagement with the fire service as manifested by culture, experience, nature of the job and leadership; organizational factors including the staffing model and relationship with occupational health services and policy, which describes both refinements to and implementation of targeted policies. Conclusions Previously observed factors such as improved fitness and the distinct firefighter culture play a role, yet other factors emerged that could explain the differences. These include the greater work–life balance offered by their shift patterns, the terms and conditions of employment and perhaps most importantly the evolution of precisely targeted policies that understand the unique nature of the operational fire service. PMID:27810889

[Human factors and crisis resource management: improving patient safety].

PubMed

Rall, M; Oberfrank, S

2013-10-01

A continuing high number of patients suffer harm from medical treatment. In 60-70% of the cases the sources of harm can be attributed to the field of human factors (HFs) and teamwork; nevertheless, those topics are still neither part of medical education nor of basic and advanced training even though it has been known for many years and it has meanwhile also been demonstrated for surgical specialties that training in human factors and teamwork considerably reduces surgical mortality.Besides the medical field, the concept of crisis resource management (CRM) has already proven its worth in many other industries by improving teamwork and reducing errors in the domain of human factors. One of the best ways to learn about CRM and HFs is realistic simulation team training with well-trained instructors in CRM and HF. The educational concept of the HOTT (hand over team training) courses for trauma room training offered by the DGU integrates these elements based on the current state of science. It is time to establish such training for all medical teams in emergency medicine and operative care. Accompanying safety measures, such as the development of a positive culture of safety in every department and the use of effective critical incident reporting systems (CIRs) should be pursued.

Is insulin growth factor-1 the future for treating autism spectrum disorder and/or schizophrenia?

PubMed

Bou Khalil, Rami

2017-02-01

To date, no curative psychopharmacologic treatment exists for the core symptoms of autism spectrum disorder (ASD) as well as for schizophrenia. Bumatenide is a specific antagonist of the first isoform of the Na-K-Cl cotransporter (NKCC1). It is usually used as a diuretic but may also promote a decrease in intraneuronal chloride ion concentration leading to hyperpolarization in neuronal membrane and subsequent decrease in neuronal hyperexcitability. This physiologic effect has been considered to be behind the relative efficacy of bumetanide in improving symptoms of ASD and, to a lesser extent, schizophrenia. However, insulin growth factor-1 (IGF-1) shows the same physiologic effect. In addition, it may improve brain network dysconnectivity which is known to be an important neurobiological feature in ASD and schizophrenia. IGF-1 has started to prove its efficacy in improving symptoms of children with Rett syndrome, a genetic disorder that shares several clinical similarities with ASD. IGF-1 may also improve oxytocin secretion through the enhancement of the transient potential receptor V2 channel function. Accordingly, IGF-1 should be studied as a potential treatment of ASD and other mental disorders characterized with brain dysconnectivity such as schizophrenia. Copyright © 2016 Elsevier Ltd. All rights reserved.

The scalar and electromagnetic form factors of the nucleon in dispersively improved Chiral EFT

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

Alarcon, Jose Manuel

We present a method for calculating the nucleon form factors of G-parity-even operators. This method combines chiral effective field theory (χEFT) and dispersion theory. Through unitarity we factorize the imaginary part of the form factors into a perturbative part, calculable with χEFT, and a non-perturbative part, obtained through other methods. We consider the scalar and electromagnetic (EM) form factors of the nucleon. The results show an important improvement compared to standard chiral calculations, and can be used in analysis of the low-energy properties of the nucleon.

Improving the Optical Quality Factor of the WGM Resonator

NASA Technical Reports Server (NTRS)

Savchenkov, Anatoliy; Matsko, Andrey; Iltchenko, Vladimir

2008-01-01

Resonators usually are characterized with two partially dependent values: finesse (F) and quality factor (Q). The finesse of an empty Fabry-Perot (FP) resonator is defined solely by the quality of its mirrors and is calculated as F=piR(exp 1/2)/(1-R). The maximum up-to-date value of reflectivity R approximately equal to 1 - 1.6 x 10(exp -6) is achieved with dielectric mirrors. An FP resonator made with the mirrors has finesse F=1.9 x 10(exp 6). Further practical increase of the finesse of FP resonators is problematic because of the absorption and the scattering of light in the mirror material through fundamental limit on the reflection losses given by the internal material losses and by thermodynamic density fluctuations on the order of parts in 109. The quality factor of a resonator depends on both its finesse and its geometrical size. A one-dimensional FP resonator has Q=2 F L/lambda, where L is the distance between the mirrors and lambda is the wavelength. It is easy to see that the quality factor of the resonator is unlimited because L is unlimited. F and Q are equally important. In some cases, finesse is technically more valuable than the quality factor. For instance, buildup of the optical power inside the resonator, as well as the Purcell factor, is proportional to finesse. Sometimes, however, the quality factor is more valuable. For example, inverse threshold power of intracavity hyperparametric oscillation is proportional to Q(exp 2) and efficiency of parametric frequency mixing is proportional to Q(exp 3). Therefore, it is important to know both the maximally achievable finesse and quality factor values of a resonator. Whispering gallery mode (WGM) resonators are capable of achieving larger finesse compared to FP resonators. For instance, fused silica resonators with finesse 2.3 x 10(exp 6) and 2.8 x 10(exp 6) have been demonstrated. Crystalline WGM resonators reveal even larger finesse values, F=6.3 x 10(exp 6), because of low attenuation of light in the

Impact of Performance Improvement Continuing Medical Education on Cardiometabolic Risk Factor Control: The COSEHC Initiative

PubMed Central

Joyner, JaNae; Moore, Michael A.; Simmons, Debra R.; Forrest, Brian; Yu-Isenberg, Kristina; Piccione, Ron; Caton, Kirt; Lackland, Daniel T.; Ferrario, Carlos M.

2016-01-01

Introduction The Consortium for Southeastern Hypertension Control (COSEHC) implemented a study to assess benefits of a performance improvement continuing medical education (PI CME) activity focused on cardiometabolic risk factor management in primary care patients. Methods Using the plan-do-study-act (PDSA) model as the foundation, this PI CME activity aimed at improving practice gaps by integrating evidence-based clinical interventions, physician-patient education, processes of care, performance metrics, and patient outcomes. The PI CME intervention was implemented in a group of South Carolina physician practices, while a comparable physician practice group served as a control. Performance outcomes at 6 months included changes in patients’ cardiometabolic risk factor values and control rates from baseline. We also compared changes in diabetic, African American, the elderly (> 65 years), and female patient subpopulations and in patients with uncontrolled risk factors at baseline. Results Only women receiving health care by intervention physicians showed a statistical improvement in their cardiometabolic risk factors as evidenced by a −3.0 mg/dL and a −3.5 mg/dL decrease in mean LDL cholesterol and non-HDL cholesterol, respectively, and a −7.0 mg/dL decrease in LDL cholesterol among females with uncontrolled baseline LDL cholesterol values. No other statistical differences were found. Discussion These data demonstrate that our PI CME activity is a useful strategy in assisting physicians to improve their management of cardiometabolic control rates in female patients with abnormal cholesterol control. Other studies that extend across longer PI CME PDSA periods may be needed to demonstrate statistical improvements in overall cardiometabolic treatment goals in men, women, and various subpopulations. PMID:24648361

Significance of the interleukin-1 receptor antagonist/interleukin-1 beta ratio as a prognostic factor in patients with pulmonary sarcoidosis.

PubMed

Mikuniya, T; Nagai, S; Takeuchi, M; Mio, T; Hoshino, Y; Miki, H; Shigematsu, M; Hamada, K; Izumi, T

2000-01-01

Various factors such as serum angiotensin-converting enzyme (sACE) activity, bronchoalveolar lavage (BAL) fluid lymphocyte percent, CD4/CD8 ratio, and shadows on chest radiograph have been identified as indexes of disease activity in patients with sarcoidosis. However, it remains to be confirmed whether these factors can predict clinical outcomes. To examine whether the interleukin-1 receptor antagonist (IL-1ra)/IL-1 beta ratio can predict the clinical course, we prospectively followed the clinical courses of 30 patients with pulmonary sarcoidosis 4 years after measurement of immunoreactive amounts of IL-1ra or IL-1 beta in the culture supernatants obtained from BAL fluid macrophages. Immunoreactive amounts of IL-1ra or IL-1 beta were measured using ELISA. Changes in pulmonary function, sACE activity, and shadows on chest radiographs during observation periods were evaluated as markers of changes in disease activity. We found that the patients whose shadows on chest radiographs showed improvement had a higher molar IL-1ra/IL-1 beta ratio than the patients whose shadows persistently remained 4 years after BAL examination (p < 0.05). The molar ratio was found to be positively correlated with improvement of percent vital capacity (p < 0.05) and negatively correlated with the ratio of sACE activity at the time of the last observation to sACE activity at the time of BAL (sACE(LAST)/sACE(BAL), p < 0.01). The sACE(LAST)/sACE(BAL) ratio was significantly lower in patients whose shadows on chest radiographs decreased than in those whose shadows remained unchanged (p < 0.005). The IL-1ra/IL-1 beta ratio in the BAL fluid macrophage culture supernatants in patients with pulmonary sarcoidosis could be a useful marker in predicting the persistence of granulomatous lesions (chronicity). Copyright 2000 S. Karger AG, Basel

Rifaximin, but not growth factor 1, reduces brain edema in cirrhotic rats

PubMed Central

Òdena, Gemma; Miquel, Mireia; Serafín, Anna; Galan, Amparo; Morillas, Rosa; Planas, Ramon; Bartolí, Ramon

2012-01-01

AIM: To compare rifaximin and insulin-like growth factor (IGF)-1 treatment of hyperammonemia and brain edema in cirrhotic rats with portal occlusion. METHODS: Rats with CCl4-induced cirrhosis with ascites plus portal vein occlusion and controls were randomized into six groups: Cirrhosis; Cirrhosis + IGF-1; Cirrhosis + rifaximin; Controls; Controls + IGF-1; and Controls + rifaximin. An oral glutamine-challenge test was performed, and plasma and cerebral ammonia, glucose, bilirubin, transaminases, endotoxemia, brain water content and ileocecal cultures were measured and liver histology was assessed. RESULTS: Rifaximin treatment significantly reduced bacterial overgrowth and endotoxemia compared with cirrhosis groups, and improved some liver function parameters (bilirubin, alanine aminotransferase and aspartate aminotransferase). These effects were associated with a significant reduction in cerebral water content. Blood and cerebral ammonia levels, and area-under-the-curve values for oral glutamine-challenge tests were similar in rifaximin-treated cirrhotic rats and control group animals. By contrast, IGF-1 administration failed to improve most alterations observed in cirrhosis. CONCLUSION: By reducing gut bacterial overgrowth, only rifaximin was capable of normalizing plasma and brain ammonia and thereby abolishing low-grade brain edema, alterations associated with hepatic encephalopathy. PMID:22563196

49 CFR 325.75 - Ground surface correction factors. 1

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 5 2010-10-01 2010-10-01 false Ground surface correction factors. 1 325.75... MOTOR CARRIER NOISE EMISSION STANDARDS Correction Factors § 325.75 Ground surface correction factors. 1... account both the distance correction factors contained in § 325.73 and the ground surface correction...

49 CFR 325.75 - Ground surface correction factors. 1

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 5 2011-10-01 2011-10-01 false Ground surface correction factors. 1 325.75... MOTOR CARRIER NOISE EMISSION STANDARDS Correction Factors § 325.75 Ground surface correction factors. 1... account both the distance correction factors contained in § 325.73 and the ground surface correction...

Physiological and Therapeutic Vascular Remodeling Mediated by Hypoxia-Inducible Factor 1

NASA Astrophysics Data System (ADS)

Sarkar, Kakali; Semenza, Gregg L.

Angiogenesis along with arteriogenesis and vasculogenesis is a fundamental process in ischemic repair in adult animals including humans. Hypoxia-inducible factor 1 (HIF-1) plays a central role in mediating adaptive responses to hypoxia/ischemia by expressing angiogenic cytokines/growth factors and their cognate receptors. Angiogenic growth factors are the homing signal for circulating angiogenic cells (CACs), which are mobilized to peripheral blood from bone marrow, recruited to target tissues, and promote vascularization. Impairment of HIF-1-mediated gene transcription contributes to the impaired vascular responses in peripheral vascular disease that are associated with aging and diabetes. Promoting neovascularization in ischemic tissues is a promising strategy for the treatment of peripheral vascular disease when surgical or catheter-based revascularization is not possible. Intramuscular injection of an adenovirus encoding a constitutively active form of HIF-1α (AdCA5), into the ischemic limb of diabetic mice increases the recovery of limb perfusion and function, rescues the diabetes-associated impairment of CACs, and increases vascularization. Administration of AdCA5 overcomes the effect of aging on recovery of blood flow in middle-aged mice following femoral artery ligation in a mouse model of age-dependent critical limb ischemia. Intramuscular injection of AdCA5 along with intravenous injection of bone-marrow-derived angiogenic cells cultured in the presence of prolyl-4-hydroxylase inhibitor dimethyloxalylglycine, increases blood flow and limb salvage in old mice following femoral artery ligation. HIF-1α gene therapy increases homing of bone-marrow-derived cells, whereas induction of HIF-1 in these cells increases their retention in the ischemic tissue by increasing their adhesion to endothelium leading to synergistic effects of combined therapy on improving blood flow.

Proceedings of the human factors workshop : improving railroad safety through understanding close calls.

DOT National Transportation Integrated Search

2004-05-01

On April 23 and 24, 2003, the Federal Railroad Administrations Office of Research and Development held a Human Factors Workshop: Improving Railroad Safety Through Understanding Close Calls in Baltimore, Maryland. The purpose of the workshop ...

Edaravone Improves Septic Cardiac Function by Inducing an HIF-1α/HO-1 Pathway

PubMed Central

He, Chao; Zhang, Wei; Li, Suobei; Ruan, Wei; Xu, Junmei

2018-01-01

Septic myocardial dysfunction remains prevalent and raises mortality rate in patients with sepsis. During sepsis, tissues undergo tremendous oxidative stress which contributes critically to organ dysfunction. Edaravone, a potent radical scavenger, has been proved beneficial in ischemic injuries involving hypoxia-inducible factor- (HIF-) 1, a key regulator of a prominent antioxidative protein heme oxygenase- (HO-) 1. However, its effect in septic myocardial dysfunction remains unclarified. We hypothesized that edaravone may prevent septic myocardial dysfunction by inducing the HIF-1/HO-1 pathway. Rats were subjected to cecal ligation and puncture (CLP) with or without edaravone infusion at three doses (50, 100, or 200 mg/kg, resp.) before CLP and intraperitoneal injection of the HIF-1α antagonist, ME (15 mg/kg), after CLP. After CLP, rats had cardiac dysfunction, which was associated with deformed myocardium, augmented lipid peroxidation, and increased myocardial apoptosis and inflammation, along with decreased activities of catalase, HIF-1α, and HO-1 in the myocardium. Edaravone pretreatment dose-dependently reversed the changes, of which high dose most effectively improved cardiac function and survival rate of septic rats. However, inhibition of HIF-1α by ME demolished the beneficial effects of edaravone at high dose, reducing the survival rate of the septic rats without treatments. Taken together, edaravone, by inducing the HIF-1α/HO-1 pathway, suppressed oxidative stress and protected the heart against septic myocardial injury and dysfunction. PMID:29765498

Dexamethasone impairs hypoxia-inducible factor-1 function

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

Wagner, A.E.; Huck, G.; Stiehl, D.P.

2008-07-25

Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription-factor composed of {alpha}- and {beta}-subunits. HIF-1 is not only necessary for the cellular adaptation to hypoxia, but it is also involved in inflammatory processes and wound healing. Glucocorticoids (GC) are therapeutically used to suppress inflammatory responses. Herein, we investigated whether GC modulate HIF-1 function using GC receptor (GR) possessing (HepG2) and GR deficient (Hep3B) human hepatoma cell cultures as model systems. Dexamethasone (DEX) treatment increased HIF-1{alpha} levels in the cytosol of HepG2 cells, while nuclear HIF-1{alpha} levels and HIF-1 DNA-binding was reduced. In addition, DEX dose-dependently lowered the hypoxia-induced luciferase activity in amore » reporter gene system. DEX suppressed the hypoxic stimulation of the expression of the HIF-1 target gene VEGF (vascular endothelial growth factor) in HepG2 cultures. DEX did not reduce hypoxically induced luciferase activity in HRB5 cells, a Hep3B derivative lacking GR. Transient expression of the GR in HRB5 cells restored the susceptibility to DEX. Our study discloses the inhibitory action of GC on HIF-1 dependent gene expression, which may be important with respect to the impaired wound healing in DEX-treated patients.« less

Resveratrol Improved the Progression of Chronic Prostatitis via the Downregulation of c-kit/SCF by Activating Sirt1.

PubMed

He, Yi; Zeng, Huizhi; Yu, Yang; Zhang, Jiashu; Zeng, Xiaona; Gong, Fengtao; Duan, Xingping; Liu, Qi; Yang, Bo

2017-07-19

The regulation mechanism of inflammation inducing prostate carcinogenesis remains largely unknown. Therefore, we investigated the role of the c-kit/SCF pathway, which has been associated with the control of prostate carcinogenesis, in chronic prostatitis (CP) rats and evaluated the anti-prostatitis effect of resveratrol. We performed hemolysin and eosin staining to evaluate the histopathological changes in prostates. Multiple approaches evaluated the expression levels of c-kit, stem cell factor (SCF), Sirt1, and carcinogenesis-associated proteins. The CP group exhibited severe diffuse chronic inflammation. Meanwhile, the prostate cells appeared atypia; the activity of c-kit/SCF was upregulated, and carcinogenesis-associated proteins are dysregulated significantly in CP rats. Resveratrol treatment significantly improved these factors by Sirt1 activation. In summary, CP could further cause prostate carcinogenesis, which may be associated with activated c-kit/SCF signaling. Resveratrol treatment could improve the progression of CP via the downregulation of c-kit/SCF by activating Sirt1.

Novel host restriction factors implicated in HIV-1 replication.

PubMed

Ghimire, Dibya; Rai, Madhu; Gaur, Ritu

2018-04-01

Human immunodeficiency virus-1 (HIV-1) is known to interact with multiple host cellular proteins during its replication in the target cell. While many of these host cellular proteins facilitate viral replication, a number of them are reported to inhibit HIV-1 replication at various stages of its life cycle. These host cellular proteins, which are known as restriction factors, constitute an integral part of the host's first line of defence against the viral pathogen. Since the discovery of apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G) as an HIV-1 restriction factor, several human proteins have been identified that exhibit anti-HIV-1 restriction. While each restriction factor employs a distinct mechanism of inhibition, the HIV-1 virus has equally evolved complex counter strategies to neutralize their inhibitory effect. APOBEC3G, tetherin, sterile alpha motif and histidine-aspartate domain 1 (SAMHD1), and trim-5α are some of the best known HIV-1 restriction factors that have been studied in great detail. Recently, six novel restriction factors were discovered that exhibit significant antiviral activity: endoplasmic reticulum α1,2-mannosidase I (ERManI), translocator protein (TSPO), guanylate-binding protein 5 (GBP5), serine incorporator (SERINC3/5) and zinc-finger antiviral protein (ZAP). The focus of this review is to discuss the antiviral mechanism of action of these six restriction factors and provide insights into the probable counter-evasion strategies employed by the HIV-1 virus. The recent discovery of new restriction factors substantiates the complex host-pathogen interactions occurring during HIV-1 pathogenesis and makes it imperative that further investigations are conducted to elucidate the molecular basis of HIV-1 replication.

Factors influencing improved attendance in the UK fire service.

PubMed

Litchfield, I; Hinckley, P

2016-12-01

Sickness absence rates in the UK continue to exceed those in much of the developed world, with an annual cost to employers of £29 billion. Rates of sickness absence in the public sector are higher than those in the private sector, with the exception of the fire service where they are consistently lower. To understand the influences that increase attendance among operational firefighters. A series of semi-structured interviews undertaken with operational staff to explore their attitudes to sickness absence. Review and analysis of participant responses identified a number of key themes, namely employee well-being, including physical fitness and mental health; employee engagement with the fire service as manifested by culture, experience, nature of the job and leadership; organizational factors including the staffing model and relationship with occupational health services and policy, which describes both refinements to and implementation of targeted policies. Previously observed factors such as improved fitness and the distinct firefighter culture play a role, yet other factors emerged that could explain the differences. These include the greater work-life balance offered by their shift patterns, the terms and conditions of employment and perhaps most importantly the evolution of precisely targeted policies that understand the unique nature of the operational fire service. © The Author 2016. Published by Oxford University Press on behalf of the Society of Occupational Medicine.

Factors associated with the impact of quality improvement collaboratives in mental healthcare: An exploratory study

PubMed Central

2012-01-01

Background Quality improvement collaboratives (QICs) bring together groups of healthcare professionals to work in a structured manner to improve the quality of healthcare delivery within particular domains. We explored which characteristics of the composition, participation, functioning, and organization of these collaboratives related to changes in the healthcare for patients with anxiety disorders, dual diagnosis, or schizophrenia. Methods We studied three QICs involving 29 quality improvement (QI) teams representing a number of mental healthcare organizations in the Netherlands. The aims of the three QICs were the implementation of multidisciplinary practice guidelines in the domains of anxiety disorders, dual diagnosis, and schizophrenia, respectively. We used eight performance indicators to assess the impact of the QI teams on self-reported patient outcomes and process of care outcomes for 1,346 patients. The QI team members completed a questionnaire on the characteristics of the composition, participation in a national program, functioning, and organizational context for their teams. It was expected that an association would be found between these team characteristics and the quality of care for patients with anxiety disorders, dual diagnosis, and schizophrenia. Results No consistent patterns of association emerged. Theory-based factors did not perform better than practice-based factors. However, QI teams that received support from their management and both active and inspirational team leadership showed better results. Rather surprisingly, a lower average level of education among the team members was associated with better results, although less consistently than the management and leadership characteristics. Team views with regard to the QI goals of the team and attitudes towards multidisciplinary practice guidelines did not correlate with team success. Conclusions No general conclusions about the impact of the characteristics of QI teams on the quality of

Predictive factors for a one-year improvement in nontuberculous mycobacterial pulmonary disease: An 11-year retrospective and multicenter study.

PubMed

Cadelis, Gilbert; Ducrot, Rodolphe; Bourdin, Arnaud; Rastogi, Nalin

2017-08-01

Nontuberculous mycobacterial pulmonary disease (NTM-PD) has become an emerging infectious disease and is responsible for more deaths than tuberculosis in industrialized countries. NTM-PD mortality remains high in some series reportedly ranging from 25% to 40% at five years and often due to unfavorable evolution of NTM-PD despite established treatment. The purpose of our study was to search for early factors that could predict the favorable or unfavorable evolution of NTM-PD at the first year of treatment. In this retrospective and multicenter study, we selected 119 patients based on clinical, radiological and microbiological data from 2002 to 2012 from three French university hospitals (Guadeloupe, Martinique, Montpellier) with definite (meeting the criteria of the American Thoracic Society and the Infectious Disease Society of America in 2007; ATS/IDSA) or probable (one positive sputum culture) NTM-PD. We compared two patient groups: those who improved at one year (clinical symptoms, radiological lesions and microbiology data) and those who did not improve at one year. The data were analyzed for all patients as well as for subgroups by gender, HIV-positive patients, and Mycobacterium avium complex (MAC) infection. The average patient age was 50 years ± 19.4; 58% had respiratory comorbidities, 24% were HIV positive and 19% had cystic fibrosis. Coughing concerned 66% of patients and bronchiectasis concerned 45%. The most frequently isolated NTM were MAC (46%). 57% (n = 68) of patients met the ATS criteria and improved status concerned 38.6% (n = 46). The improvement factors at one year of NTM-PD were associated with the duration of ethambutol treatment: (Odds ratio adjusted [ORa]: 2.24, 95% Confidence interval [CI]; 2.11-3.41), HIV-positive status: (ORa: 3.23, 95% CI; 1.27-8.45), and male gender: (ORa: 2.34, 95% CI; 1.26-8.16). For the group with NTM-PD due to MAC, improvement was associated with the duration of macrolide treatment (ORa: 3.27, 95% CI; 1

Predictive factors for a one-year improvement in nontuberculous mycobacterial pulmonary disease: An 11-year retrospective and multicenter study

PubMed Central

Ducrot, Rodolphe; Bourdin, Arnaud; Rastogi, Nalin

2017-01-01

Background Nontuberculous mycobacterial pulmonary disease (NTM-PD) has become an emerging infectious disease and is responsible for more deaths than tuberculosis in industrialized countries. NTM-PD mortality remains high in some series reportedly ranging from 25% to 40% at five years and often due to unfavorable evolution of NTM-PD despite established treatment. The purpose of our study was to search for early factors that could predict the favorable or unfavorable evolution of NTM-PD at the first year of treatment. Methods In this retrospective and multicenter study, we selected 119 patients based on clinical, radiological and microbiological data from 2002 to 2012 from three French university hospitals (Guadeloupe, Martinique, Montpellier) with definite (meeting the criteria of the American Thoracic Society and the Infectious Disease Society of America in 2007; ATS/IDSA) or probable (one positive sputum culture) NTM-PD. We compared two patient groups: those who improved at one year (clinical symptoms, radiological lesions and microbiology data) and those who did not improve at one year. The data were analyzed for all patients as well as for subgroups by gender, HIV-positive patients, and Mycobacterium avium complex (MAC) infection. Results The average patient age was 50 years ± 19.4; 58% had respiratory comorbidities, 24% were HIV positive and 19% had cystic fibrosis. Coughing concerned 66% of patients and bronchiectasis concerned 45%. The most frequently isolated NTM were MAC (46%). 57% (n = 68) of patients met the ATS criteria and improved status concerned 38.6% (n = 46). The improvement factors at one year of NTM-PD were associated with the duration of ethambutol treatment: (Odds ratio adjusted [ORa]: 2.24, 95% Confidence interval [CI]; 2.11–3.41), HIV-positive status: (ORa: 3.23, 95% CI; 1.27–8.45), and male gender: (ORa: 2.34, 95% CI; 1.26–8.16). For the group with NTM-PD due to MAC, improvement was associated with the duration of macrolide treatment

Environmental Factors Associated with Type 1 Diabetes Development: A Case Control Study in Egypt.

PubMed

Awadalla, Nabil J; Hegazy, Amal A; Abd El-Salam, Manal; Elhady, Marwa

2017-06-07

Uncertainty still exists regarding the role of some environmental risk in the development of type 1 diabetes mellitus (T1DM) both globally and in Egypt. The objective here was to explore the potential environmental risk factors associated with the development of T1DM among children in Egypt. A case-controlled study of 204 T1DM children and an equal number of age and sex-matched controls was conducted in Assiut, Egypt. Data regarding the parental, gestational, neonatal, and childhood possible risk factors for T1DM were evaluated. The final sex adjusted multivariable logistic regression model revealed that the risk for T1DM was significantly higher among rural residents (aOR = 2.03, 95% CI: 1.30-4.25), those with parental history of T1DM (aOR = 9.03, 95% CI: 1.02-83.32), birth through cesarean section (aOR = 2.13, 95% CI: 1.09-5.03), and having history of early introduction of cow milk in the first year of life (aOR = 19.49, 95% CI: 8.73-45.53). On the other hand, a protective effect was observed between at least six months' breastfeeding, vitamin D supplementation in the first year of life, high physical activity, and the development of T1DM. Educational programs should be adopted to improve awareness and knowledge of the parents to avoid the increased risk factors and encourage protective practices.

Lentivirus-ABCG1 instillation reduces lipid accumulation and improves lung compliance in GM-CSF knock-out mice

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

Malur, Anagha; Huizar, Isham; Wells, Greg

2011-11-18

Highlights: Black-Right-Pointing-Pointer Lentivirus-ABCG1 reduces lipid accumulation in lungs of GM-CSF knock-out mice. Black-Right-Pointing-Pointer Up-regulation of ABCG1 improves lung function. Black-Right-Pointing-Pointer Upregulation of ABCG1 improves surfactant metabolism. -- Abstract: We have shown decreased expression of the nuclear transcription factor, peroxisome proliferator-activated receptor-gamma (PPAR{gamma}) and the PPAR{gamma}-regulated ATP-binding cassette transporter G1 (ABCG1) in alveolar macrophages from patients with pulmonary alveolar proteinosis (PAP). PAP patients also exhibit neutralizing antibodies to granulocyte-macrophage colony stimulating factor (GM-CSF), an upregulator of PPAR{gamma}. In association with functional GM-CSF deficiency, PAP lung is characterized by surfactant-filled alveolar spaces and lipid-filled alveolar macrophages. Similar pathology characterizes GM-CSF knock-out (KO)more » mice. We reported previously that intratracheal instillation of a lentivirus (lenti)-PPAR{gamma} plasmid into GM-CSF KO animals elevated ABCG1 and reduced alveolar macrophage lipid accumulation. Here, we hypothesized that instillation of lenti-ABCG1 might be sufficient to decrease lipid accumulation and improve pulmonary function in GM-CSF KO mice. Animals received intratracheal instillation of lenti-ABCG1 or control lenti-enhanced Green Fluorescent Protein (eGFP) plasmids and alveolar macrophages were harvested 10 days later. Alveolar macrophage transduction efficiency was 79% as shown by lenti-eGFP fluorescence. Quantitative PCR analyses indicated a threefold (p = 0.0005) increase in ABCG1 expression with no change of PPAR{gamma} or ABCA1 in alveolar macrophages of lenti-ABCG1 treated mice. ABCG1 was unchanged in control lenti-eGFP and PBS-instilled groups. Oil Red O staining detected reduced intracellular neutral lipid in alveolar macrophages from lenti-ABCG1 treated mice. Extracellular cholesterol and phospholipids were also decreased as

Targeting the UPR transcription factor XBP1 protects against Huntington's disease through the regulation of FoxO1 and autophagy

PubMed Central

Vidal, Rene L.; Figueroa, Alicia; Court, Felipe A.; Thielen, Peter; Molina, Claudia; Wirth, Craig; Caballero, Benjamin; Kiffin, Roberta; Segura-Aguilar, Juan; Cuervo, Ana Maria; Glimcher, Laurie H.; Hetz, Claudio

2012-01-01

Mutations leading to expansion of a poly-glutamine track in Huntingtin (Htt) cause Huntington's disease (HD). Signs of endoplasmic reticulum (ER) stress have been recently reported in animal models of HD, associated with the activation of the unfolded protein response (UPR). Here we have investigated the functional contribution of ER stress to HD by targeting the expression of two main UPR transcription factors, XBP1 and ATF4 (activating transcription factor 4), in full-length mutant Huntingtin (mHtt) transgenic mice. XBP1-deficient mice were more resistant to developing disease features, associated with improved neuronal survival and motor performance, and a drastic decrease in mHtt levels. The protective effects of XBP1 deficiency were associated with enhanced macroautophagy in both cellular and animal models of HD. In contrast, ATF4 deficiency did not alter mHtt levels. Although, XBP1 mRNA splicing was observed in the striatum of HD transgenic brains, no changes in the levels of classical ER stress markers were detected in symptomatic animals. At the mechanistic level, we observed that XBP1 deficiency led to augmented expression of Forkhead box O1 (FoxO1), a key transcription factor regulating autophagy in neurons. In agreement with this finding, ectopic expression of FoxO1 enhanced autophagy and mHtt clearance in vitro. Our results provide strong evidence supporting an involvement of XBP1 in HD pathogenesis probably due to an ER stress-independent mechanism involving the control of FoxO1 and autophagy levels. PMID:22337954

Glycogen synthase kinase 3 regulates expression of nuclear factor-erythroid-2 related transcription factor-1 (Nrf1) and inhibits pro-survival function of Nrf1

PubMed Central

Biswas, Madhurima; Kwong, Erick K.; Park, Eujean; Nagra, Parminder; Chan, Jefferson Y.

2013-01-01

Nuclear factor E2-related factor-1 (Nrf1) is a basic leucine zipper transcription factor that is known to regulate antioxidant and cytoprotective gene expression. It was recently shown that Nrf1 is regulated by SCF-Fbw7 ubiquitin ligase. However our knowledge of upstream signals that targets Nrf1 for degradation by the UPS is not known. We report here that Nrf1 expression is negatively regulated by glycogen synthase kinase 3 (GSK3) in Fbw7-dependent manner. We show that GSK3 interacts with Nrf1 and phosphorylates the Cdc4 phosphodegron domain (CPD) in Nrf1. Mutation of serine residue in the CPD of Nrf1 to alanine (S350A), blocks Nrf1 from phosphorylation by GSK3, and stabilizes Nrf1. Knockdown of Nrf1 and expression of a constitutively active form of GSK3 results in increased apoptosis in neuronal cells in response to ER stress, while expression of the GSK3 phosphorylation resistant S350A–Nrfl attenuates apoptotic cell death. Together these data suggest that GSK3 regulates Nrf1 expression and cell survival function in response to stress activation. PMID:23623971

B → Dℓν form factors at nonzero recoil and |V cb| from 2+1-flavor lattice QCD

DOE PAGES

Bailey, Jon A.

2015-08-10

We present the first unquenched lattice-QCD calculation of the hadronic form factors for the exclusive decay B¯→Dℓν¯ at nonzero recoil. We carry out numerical simulations on 14 ensembles of gauge-field configurations generated with 2+1 flavors of asqtad-improved staggered sea quarks. The ensembles encompass a wide range of lattice spacings (approximately 0.045 to 0.12 fm) and ratios of light (up and down) to strange sea-quark masses ranging from 0.05 to 0.4. For the b and c valence quarks we use improved Wilson fermions with the Fermilab interpretation, while for the light valence quarks we use asqtad-improved staggered fermions. We extrapolate ourmore » results to the physical point using rooted staggered heavy-light meson chiral perturbation theory. We then parametrize the form factors and extend them to the full kinematic range using model-independent functions based on analyticity and unitarity. We present our final results for f +(q 2) and f 0(q 2), including statistical and systematic errors, as coefficients of a series in the variable z and the covariance matrix between these coefficients. We then fit the lattice form-factor data jointly with the experimentally measured differential decay rate from BABAR to determine the CKM matrix element, |V cb|=(39.6 ± 1.7 QCD+exp ± 0.2 QED) × 10 –3. As a byproduct of the joint fit we obtain the form factors with improved precision at large recoil. In conclusion, we use them to update our calculation of the ratio R(D) in the Standard Model, which yields R(D)=0.299(11).« less

Human Factors Analysis to Improve the Processing of Ares-1 Launch Vehicle

NASA Technical Reports Server (NTRS)

Dippolito, Gregory M.; Stambolian, Damon B.

2011-01-01

The Constellation Program (CxP) is composed of an array of vehicles used to go to the Moon and Mars. The Ares vehicle one of the components of CxP, goes through several stages of processing before it is launched at the Kennedy Space Center. In order to have efficient and effective ground processing inside and outside the vehicle, all of the ground processing activities should be analyzed. The analysis for this program was performed, by engineers, technicians, and human factors experts with spacecraft processing experience. The procedure used to gather data was accomplished by observing human activities within physical mockups. The paper will focus on the procedures, analysis and results from these observations.

The Metastasis Efficiency Modifier Ribosomal RNA Processing 1 Homolog B (RRP1B) Is a Chromatin-associated Factor*

PubMed Central

Crawford, Nigel P. S.; Yang, Hailiu; Mattaini, Katherine R.; Hunter, Kent W.

2009-01-01

There is accumulating evidence for a role of germ line variation in breast cancer metastasis. We have recently identified a novel metastasis susceptibility gene, Rrp1b (ribosomal RNA processing 1 homolog B). Overexpression of Rrp1b in a mouse mammary tumor cell line induces a gene expression signature that predicts survival in breast cancer. Here we extend the analysis of RRP1B function by demonstrating that the Rrp1b activation gene expression signature accurately predicted the outcome in three of four publicly available breast carcinoma gene expression data sets. In addition, we provide insights into the mechanism of RRP1B. Tandem affinity purification demonstrated that RRP1B physically interacts with many nucleosome binding factors, including histone H1X, poly(ADP-ribose) polymerase 1, TRIM28 (tripartite motif-containing 28), and CSDA (cold shock domain protein A). Co-immunofluorescence and co-immunoprecipitation confirmed these interactions and also interactions with heterochromatin protein-1α and acetyl-histone H4 lysine 5. Finally, we investigated the effects of ectopic expression of an RRP1B allelic variant previously associated with improved survival in breast cancer. Gene expression analyses demonstrate that, compared with ectopic expression of wild type RRP1B in HeLa cells, the variant RRP1B differentially modulates various transcription factors controlled by TRIM28 and CSDA. These data suggest that RRP1B, a tumor progression and metastasis susceptibility candidate gene, is potentially a dynamic modulator of transcription and chromatin structure. PMID:19710015

Delayed treatment with recombinant human tissue factor pathway inhibitor improves survival in rabbits with gram-negative peritonitis.

PubMed

Camerota, A J; Creasey, A A; Patla, V; Larkin, V A; Fink, M P

1998-03-01

To determine whether treatment with recombinant human tissue factor pathway inhibitor (TFPI), an inhibitor of the extrinsic coagulation pathway, can improve survival in a clinically relevant model of gram-negative sepsis, rabbits were given an intraperitoneal inoculation of a suspension containing hemoglobin (40 microg/mL), porcine mucin (150 microg/mL), and viable Escherichia coli O18:K1 (1.0 +/- 0.5 x 10(5) cfu/kg). Treatment with gentamicin (5 mg/kg every 12 h for five doses) was instituted 4 h after induction of peritonitis. At the same time point, rabbits were randomized to receive a 24-h infusion of vehicle or one of three different doses of TFPI. Treatment groups, 7-day survival rates, and significance versus control were as follows: control, 1 of 20; TFPI(LOW DOSE) (0.1 mg/kg, then 1 microg/kg/min), 3 of 12 (P = .14); TFPI(MID DOSE), (0.5 mg/kg, then 5 microg/kg/min), 7 of 12 (P = .002); TFPI(HIGH DOSE) (10 mg/kg, then 10 microg/kg/min), 4 of 13 (P = .04). Thus, delayed treatment with TFPI improves survival in septic rabbits.

Improvement of force factor of magnetostrictive vibration power generator for high efficiency

NASA Astrophysics Data System (ADS)

Kita, Shota; Ueno, Toshiyuki; Yamada, Sotoshi

2015-05-01

We develop high power magnetostrictive vibration power generator for battery-free wireless electronics. The generator is based on a cantilever of parallel beam structure consisting of coil-wound Galfenol and stainless plates with permanent magnet for bias. Oscillating force exerted on the tip bends the cantilever in vibration yields stress variation of Galfenol plate, which causes flux variation and generates voltage on coil due to the law of induction. This generator has advantages over conventional, such as piezoelectric or moving magnet types, in the point of high efficiency, highly robust, and low electrical impedance. Our concern is the improvement of energy conversion efficiency dependent on the dimension. Especially, force factor, the conversion ratio of the electromotive force (voltage) on the tip velocity in vibration, has an important role in energy conversion process. First, the theoretical value of the force factor is formulated and then the validity was verified by experiments, where we compare four types of prototype with parameters of the dimension using 7.0 × 1.5 × 50 mm beams of Galfenol with 1606-turn wound coil. In addition, the energy conversion efficiency of the prototypes depending on load resistance was measured. The most efficient prototype exhibits the maximum instantaneous power of 0.73 W and energy of 4.7 mJ at a free vibration of frequency of 202 Hz in the case of applied force is 25 N. Further, it was found that energy conversion efficiency depends not only on the force factor but also on the damping (mechanical loss) of the vibration.

Improvement of long-term outcomes in pancreatic cancer and its associated factors within the gemcitabine era: a collaborative retrospective multicenter clinical review of 1,082 patients.

PubMed

Kuroda, Taira; Kumagi, Teru; Yokota, Tomoyuki; Seike, Hirotaka; Nishiyama, Mari; Imai, Yusuke; Inada, Nobu; Shibata, Naozumi; Imamine, Satoshi; Okada, Shin-ichi; Koizumi, Mitsuhito; Yamanishi, Hirofumi; Azemoto, Nobuaki; Miyaike, Jiro; Tanaka, Yoshinori; Tatsukawa, Haruka; Utsunomiya, Hiroki; Ohno, Yoshinori; Miyake, Teruki; Hirooka, Masashi; Furukawa, Shinya; Abe, Masanori; Ikeda, Yoshiou; Matsuura, Bunzo; Hiasa, Yoichi; Onji, Morikazu

2013-08-31

Although the outcomes of pancreatic cancer have been improved by gemcitabine, the changes in its characteristics and long-term outcomes within the gemcitabine era remain unclear. This study was conducted to identify clinical characteristics of pancreatic cancer patients within the gemcitabine era. A retrospective chart review was performed at 10 centers for 1,248 consecutive patients who were ever considered to have a diagnosis of pancreatic cancer between 2001 and 2010. Data collected included demographics, diagnosis date, clinical stage, treatment, and outcome 1,082 patients met the inclusion criteria and were analyzed further. The chi-square test, Student's t-test, and Mann-Whitney U-test were used for statistical analysis. Outcomes were analyzed using the Kaplan-Meier method and Cox proportional hazards regression. Differences in survival analyses were determined using the log-rank test. The distribution of clinical stages was: I, 2.2% II, 3.4% III, 13% IVa, 27% and IVb, 55%. Chemotherapy alone was administered to 42% of patients and 17% underwent resection. The 1-, 3-, and 5-year survival rates were 39%, 13%, and 6.9%, respectively. The median survival time was 257 days, but differed considerably among treatments and clinical stages. Demographics, distribution of clinical stage, and cause of death did not differ between groups A (2001-2005, n=406) and B (2006-2010, n=676). However, group B included more patients who underwent chemotherapy (P<0.0001) and fewer treated with best supportive care (P=0.0004), mirroring improvements in this group's long-term outcomes (P=0.0063). Finally, factors associated with long-term outcomes derived from multivariate analysis were clinical stage (P<0.0001), location of the tumor (P=0.0294) and treatments (surgery, chemotherapy) (<0.0001). Long-term outcomes in pancreatic cancer has improved even within the gemcitabine era, suggesting the importance of offering chemotherapy to patients previously only considered for best

Epidermal Growth Factor Improves Intestinal Integrity and Survival in Murine Sepsis Following Chronic Alcohol Ingestion.

PubMed

Klingensmith, Nathan J; Yoseph, Benyam P; Liang, Zhe; Lyons, John D; Burd, Eileen M; Margoles, Lindsay M; Koval, Michael; Ford, Mandy L; Coopersmith, Craig M

2017-02-01

Epidermal growth factor (EGF) is a cytoprotective protein that improves survival in preclinical models of sepsis through its beneficial effects on intestinal integrity. Alcohol use disorder worsens intestinal integrity and is associated with increased morbidity and mortality in critical illness. We sought to determine whether chronic alcohol ingestion alters the host response to systemic administration of EGF in sepsis. Six-week-old FVB/N mice were randomized to receive 20% alcohol or water for 12 weeks. All mice then underwent cecal ligation and puncture to induce polymicrobial sepsis. Mice were then randomized to receive either intraperitoneal injection of EGF (150 μg/kg/day) or normal saline. Water-fed mice given EGF had decreased 7-day mortality compared with water-fed mice (18% vs. 55%). Alcohol-fed mice given EGF also had decreased 7-day mortality compared with alcohol-fed mice (48% vs. 79%). Notably, while systemic EGF improved absolute survival to a similar degree in both water-fed and alcohol-fed mice, mortality was significantly higher in alcohol+EGF mice compared with water+EGF mice. Compared with water-fed septic mice, alcohol-fed septic mice had worsened intestinal integrity with intestinal hyperpermeability, increased intestinal epithelial apoptosis, decreased proliferation and shorter villus length. Systemic administration of EGF to septic alcohol-fed mice decreased intestinal permeability compared with septic alcohol-fed mice given vehicle, with increased levels of the tight junction mediators claudin-5 and JAM-A. Systemic administration of EGF to septic alcohol-fed mice also decreased intestinal apoptosis with an improvement in the Bax/Bcl-2 ratio. EGF also improved both crypt proliferation and villus length in septic alcohol-fed mice. EGF administration resulted in lower levels of both pro- and anti-inflammatory cytokines monocyte chemoattractant protein-1, tumor necrosis factor, and interleukin 10 in alcohol-fed mice. EGF is therefore

Factors associated with timing of early neurological improvement after thrombolysis for ischaemic stroke.

PubMed

Guettier, S; Cogez, J; Bonnet, A-L; Dean, P; Apoil, M; Tchoumi, T; Dubuc, L; Arzur, J; de la Sayette, V; Kouassi, L-K; Viader, F; Touzé, E

2016-03-01

Early neurological improvement (ENI) after fibrinolysis for ischaemic stroke is strongly associated with recanalization and favourable outcome. However, it remains unknown why some patients recover within the first hour after treatment (very ENI, VENI) whereas others recover later within 24 h. The factors associated with the timing of ENI were assessed. Consecutive stroke patients treated with intravenous recombinant tissue plasminogen activator (rt-PA) within 4.5 h after onset in four stroke centres of our geographical area were retrospectively studied. VENI assessed at 1 h and ENI assessed at 24 h post-treatment were defined by National Institutes of Health Stroke Scale (NIHSS) improvement by 40% from baseline. Of 421 patients, 65 (15%) had VENI and 110 (26%) had ENI. Patients with VENI had significantly lower serum creatinine level than patients with ENI (79 ± 19 vs. 91 ± 35 μmol/l; P = 0.01). After adjustment for age, sex, baseline NIHSS, hypertension and blood glucose level, patients with low serum creatinine level were more likely to have VENI (lowest tertile, odds ratio 3.8, 95% confidence interval 1.5-9.7; intermediate tertile, odds ratio 1.8, 95% confidence interval 0.8-4.3; P for trend <0.01). VENI patients were as likely as ENI patients to have a modified Rankin scale score ≤2 at 3 months. Low serum creatinine levels are associated with VENI, suggesting that swiftness of the efficacy of rt-PA or of neurological recovery may depend on renal function. © 2016 EAN.

The role of IL-1 gene polymorphisms (IL1A, IL1B, and IL1RN) as a risk factor in unsuccessful implants retaining overdentures.

PubMed

Sampaio Fernandes, Margarida; Vaz, Paula; Braga, Ana Cristina; Sampaio Fernandes, João Carlos; Figueiral, Maria Helena

2017-10-01

Implant-supported overdentures are an alternative predictable rehabilitation method that has a high impact on improving the patient's quality of life. However, some biological complications may interfere with the maintenance and survival of these overdenture implants. The goal of this article was to assess the factors that affect peri-implant success, through a hypothetical prediction model for biological complications of implant overdentures. A retrospective observational, prevalence study was conducted in 58 edentulous Caucasian patients rehabilitated with implant overdentures. A total of 229 implants were included in the study. Anamnestic, clinical, and implant-related parameters were collected and recorded in a single database. "Patient" was chosen as the unit of analysis, and a complete screening protocol was established. The data analytical study included assessing the odds ratio, concerning the presence or absence of a particular risk factor, by using binary logistic regression modeling. Probability values (p values) inferior to 0.05 were considered as representing statistically significant evidence. The performed prediction model included the following variables: mean probing depth, metal exposure, IL1B_allele2, maxillary edentulousness, and Fusobacterium nucleatum. The F. nucleatum showed significant association with the outcome. Introducing a negative coefficient appeared to prevent complications or even boost the biological defense when associated with other factors. The prediction model developed in this study could serve as a basis for further improved models that would assist clinicians in the daily diagnosis and treatment planning practice of oral rehabilitation with implant overdentures. Copyright © 2017 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

Thermoelectric Power Factor Limit of a 1D Nanowire

NASA Astrophysics Data System (ADS)

Chen, I.-Ju; Burke, Adam; Svilans, Artis; Linke, Heiner; Thelander, Claes

2018-04-01

In the past decade, there has been significant interest in the potentially advantageous thermoelectric properties of one-dimensional (1D) nanowires, but it has been challenging to find high thermoelectric power factors based on 1D effects in practice. Here we point out that there is an upper limit to the thermoelectric power factor of nonballistic 1D nanowires, as a consequence of the recently established quantum bound of thermoelectric power output. We experimentally test this limit in quasiballistic InAs nanowires by extracting the maximum power factor of the first 1D subband through I -V characterization, finding that the measured maximum power factors conform to the theoretical limit. The established limit allows the prediction of the achievable power factor of a specific nanowire material system with 1D electronic transport based on the nanowire dimension and mean free path. The power factor of state-of-the-art semiconductor nanowires with small cross section and high crystal quality can be expected to be highly competitive (on the order of mW /m K2 ) at low temperatures. However, they have no clear advantage over bulk materials at, or above, room temperature.

Thermoelectric Power Factor Limit of a 1D Nanowire.

PubMed

Chen, I-Ju; Burke, Adam; Svilans, Artis; Linke, Heiner; Thelander, Claes

2018-04-27

In the past decade, there has been significant interest in the potentially advantageous thermoelectric properties of one-dimensional (1D) nanowires, but it has been challenging to find high thermoelectric power factors based on 1D effects in practice. Here we point out that there is an upper limit to the thermoelectric power factor of nonballistic 1D nanowires, as a consequence of the recently established quantum bound of thermoelectric power output. We experimentally test this limit in quasiballistic InAs nanowires by extracting the maximum power factor of the first 1D subband through I-V characterization, finding that the measured maximum power factors conform to the theoretical limit. The established limit allows the prediction of the achievable power factor of a specific nanowire material system with 1D electronic transport based on the nanowire dimension and mean free path. The power factor of state-of-the-art semiconductor nanowires with small cross section and high crystal quality can be expected to be highly competitive (on the order of mW/m K^{2}) at low temperatures. However, they have no clear advantage over bulk materials at, or above, room temperature.

Improvements in Cardiometabolic Risk Factors Among Overweight and Obese Employees Participating in a University Worksite Wellness Program.

PubMed

Radler, Diane Rigassio; Marcus, Andrea Fleisch; Griehs, Rachel; Touger-Decker, Riva

2015-11-01

To determine immediate changes in weight and cardiometabolic risk of participants in a university worksite wellness program (WWP). It was hypothesized that there would be significant improvements in weight and waist circumference after 12 weeks. Employees volunteered for enrollment in a 12-week WWP that provided educational sessions in-person or online. At baseline and after 12 weeks, participants had one-on-one appointments with the study registered dietitian who measured clinical outcome markers (cardiometabolic risk factors) and provided individualized counseling. Among 79 participants who returned for 12-week appointments, there were statistically significant improvements in weight (p < .0001), waist circumference (p < .0001), and other cardiometabolic risk factors from baseline to 12-weeks. Improvements in cardiometabolic risk factors may be observed in a relatively short period of time among those who enrolled in a WWP. © 2014 Society for Public Health Education.

Formononetin accelerates wound repair by the regulation of early growth response factor-1 transcription factor through the phosphorylation of the ERK and p38 MAPK pathways.

PubMed

Huh, Jeong-Eun; Nam, Dong-Woo; Baek, Young-Hyun; Kang, Jung Won; Park, Dong-Suk; Choi, Do-Young; Lee, Jae-Dong

2011-01-01

Formononetin, a phytoestrogen from the root of Astragalus membranaceus, is used as a blood enhancer and to improve blood microcirculation in complementary and alternative medicine. The present study investigated the influence of formononetin on the expression of early growth response factor-1 (Egr-1) and growth factors contributing to wound healing. Formononetin significantly increased growth factors such as transforming growth factor-beta 1 (TGF-β1), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) in human umbilical vein endothelial cells (HUVECs). Formononetin also increased the expression of Egr-1 transcription factor by 3.2- and 10.5-fold, compared with recombinant VEGF(125) in HUVECs. The formononetin-mediated 12%-43% increase induced endothelial cell proliferation and recovered the migration of wounded HUVECs. In an ex vivo angiogenesis assay, formononetin produced a larger capillary sprouting area than produced using recombinant VEGF(125). Cell proliferation and migration of HUVECs were also greater in the presence of formonectin than VEGF(125). Western blot analysis of scratch-wounded confluent HUVECs showed that formononetin induced the phosphorylation of extracellular signal-regulated kinase (ERK) and slightly inhibited the phosphorylation of p38 mitogen-activated protein kinase (MAPK). The formononetin-mediated sustained activation of Egr-1 was suppressed by the ERK inhibitor PD98059 and the p38 inhibitor SB203580. PD98059 inhibited the formononetin-induced endothelial proliferation and repair in scratch-wounded HUVECs, SB203580 increased the cell proliferation and wound healing. Formononetin accelerate wound closure rate as early as day 3 after surgery and consistently observed until day 10 after in wound animal model. These data suggest that formononetin promotes endothelial repair and wound healing in a process involving the over-expression of Egr-1 transcription factor

Effect of basic fibroblast growth factor and transforming growth factor β1 on the healing of reconstructed dura by carbon dioxide laser soldering in minipigs.

PubMed

Zhong, Hong-liang; Wang, Zhen-min; Yang, Zhi-jun; Zhao, Fu; Wang, Bo; Wang, Zhong-cheng; Liu, Pi-nan

2012-02-01

Carbon dioxide (CO2) laser soldering is an alternative technique for tissue bonding. Basic fibroblast growth factor (bFGF) and transforming growth factor β(1) (TGFβ(1)) are two key factors for wound healing. This study was performed to demonstrate the efficacy of CO2 laser soldering for dural reconstruction and the effect of bFGF and TGFβ(1) on healing. In Part I, 10 minipigs were randomized into two equal groups. Dural defects were reconstructed by conventional fibrin glue bonding (group I(a)) or CO2 laser soldering (group I(b)). The reconstructed dura was subjected to burst pressure (BP) measurement and immunohistochemical staining after 1 week. In Part II, 36 minipigs were randomized into three equal groups. Dural reconstruction was achieved by CO2 laser soldering. Exogenous bFGF (group II(b)) or TGFβ(1) (group II(c)) was administered while group II(a) served as a control group. The specimens were subjected to BP measurement after 1, 2, 3, and 4 weeks, respectively. In Part I, the dura specimens displayed positive staining of only bFGF in group I(a) and of both bFGF and TGFβ(1) in group I(b). Group I(b) showed higher BP than group I(a) ((98.00 ± 21.41) mmHg vs. (70.80 ± 15.09) mmHg, respectively; P < 0.05). In Part II, BP of group II(c) was significantly higher than that of group II(a) (P < 0.01). The BP of group II(a) trended toward stabilization after 3 weeks of growth, while that of groups II(b) and II(c) trended toward stabilization after 2 weeks of growth. CO2 laser soldering is a reliable technique for dural reconstruction. The superior healing of dural reconstruction by CO2 laser soldering may be related to higher expression of bFGF and TGFβ(1), and CO2 lasers may stimulate their secretion. Exogenous bFGF or TGFβ(1) may improve healing by shortening the wound healing time, and exogenous TGFβ(1) may improve the tensile strength.

The effects of improved metabolic risk factors on bone turnover markers after 12 weeks of simvastatin treatment with or without exercise.

PubMed

Jiang, Jun; Boyle, Leryn J; Mikus, Catherine R; Oberlin, Douglas J; Fletcher, Justin A; Thyfault, John P; Hinton, Pamela S

2014-11-01

Emerging evidence supports an association between metabolic risk factors and bone turnover. Statins and exercise independently improve metabolic risk factors; however whether improvements in metabolic risk factor affects bone turnover is unknown. The purpose of the present study was to: 1) evaluate the relationship between metabolic risk factors and bone turnover; and 2) determine if improvements in metabolic risk factors after 12 weeks of statin treatment, exercise or the combination affect bone turnover. Fifty participants with ≥2 metabolic syndrome defining characteristics were randomly assigned to one of three groups: statin (STAT: simvastatin, 40 mg/day), exercise (EX: brisk walking and/or slow jogging, 45 minutes/day, 5 days/week), or the combination (STAT+EX). Body composition and whole body bone mineral density were measured with dual energy X-ray absorptiometry. Serum markers of bone formation (bone specific alkaline phosphatase, BAP; osteocalcin, OC), resorption (C-terminal peptide of type I collagen, CTX) and metabolic risk factors were determined. Two-factor (time, group) repeated-measures ANCOVA was used to examine changes of metabolic risk factors and bone turnover. General linear models were used to determine the effect of pre-treatment metabolic risk factors on post-treatment bone turnover marker outcomes. Participants with ≥4 metabolic syndrome defining characteristics had lower pre-treatment OC than those with 3 or fewer. OC was negatively correlated with glucose, and CTX was positively correlated with cholesterol. STAT or STAT+EX lowered total and LDL cholesterol. The OC to CTX ratio decreased in all groups with no other significant changes in bone turnover. Higher pre-treatment insulin or body fat predicted a greater CTX reduction and a greater BAP/CTX increase. Metabolic risk factors were negatively associated with bone turnover markers. Short-term statin treatment with or without exercise lowered cholesterol and all treatments had a small

Characteristics of adipose tissue macrophages and macrophage-derived insulin-like growth factor-1 in virus-induced obesity.

PubMed

Park, S; Park, H-L; Lee, S-Y; Nam, J-H

2016-03-01

Various pathogens are implicated in the induction of obesity. Previous studies have confirmed that human adenovirus 36 (Ad36) is associated with increased adiposity, improved glycemic control and induction of inflammation. The Ad36-induced inflammation is reflected in the infiltration of macrophages into adipose tissue. However, the characteristics and role of adipose tissue macrophages (ATMs) and macrophage-secreted factors in virus-induced obesity (VIO) are unclear. Although insulin-like growth factor-1 (IGF-1) is involved in obesity metabolism, the contribution of IGF secreted by macrophages in VIO has not been studied. Four-week-old male mice were studied 1 week and 12 weeks after Ad36 infection for determining the characteristics of ATMs in VIO and diet-induced obesity (DIO). In addition, macrophage-specific IGF-1-deficient (MIKO) mice were used to study the involvement of IGF-1 in VIO. In the early stage of VIO (1 week after Ad36 infection), the M1 ATM sub-population increased, which increased the M1/M2 ratio, whereas DIO did not cause this change. In the late stage of VIO (12 weeks after Ad36 infection), the M1/M2 ratio did not change because the M1 and M2 ATM sub-populations increased to a similar extent, despite an increase in adiposity. By contrast, DIO increased the M1/M2 ratio. In addition, VIO in wild-type mice upregulated angiogenesis in adipose tissue and improved glycemic control. However, MIKO mice showed no increase in adiposity, angiogenesis, infiltration of macrophages into adipose tissue, or improvement in glycemic control after Ad36 infection. These data suggest that IGF-1 secreted by macrophages may contribute to hyperplasia and hypertrophy in adipose tissue by increasing angiogenesis, which helps to maintain the 'adipose tissue robustness'.

Glycogen synthase kinase 3 regulates expression of nuclear factor-erythroid-2 related transcription factor-1 (Nrf1) and inhibits pro-survival function of Nrf1

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

Biswas, Madhurima; Kwong, Erick K.; Park, Eujean

2013-08-01

Nuclear factor E2-related factor-1 (Nrf1) is a basic leucine zipper transcription factor that is known to regulate antioxidant and cytoprotective gene expression. It was recently shown that Nrf1 is regulated by SCF–Fbw7 ubiquitin ligase. However our knowledge of upstream signals that targets Nrf1 for degradation by the UPS is not known. We report here that Nrf1 expression is negatively regulated by glycogen synthase kinase 3 (GSK3) in Fbw7-dependent manner. We show that GSK3 interacts with Nrf1 and phosphorylates the Cdc4 phosphodegron domain (CPD) in Nrf1. Mutation of serine residue in the CPD of Nrf1 to alanine (S350A), blocks Nrf1 frommore » phosphorylation by GSK3, and stabilizes Nrf1. Knockdown of Nrf1 and expression of a constitutively active form of GSK3 results in increased apoptosis in neuronal cells in response to ER stress, while expression of the GSK3 phosphorylation resistant S350A–Nrf1 attenuates apoptotic cell death. Together these data suggest that GSK3 regulates Nrf1 expression and cell survival function in response to stress activation. Highlights: • The effect of GSK3 on Nrf1 expression was examined. • GSK3 destabilizes Nrf1 protein via Fbw7 ubiquitin ligase. • GSK3 binds and phosphorylates Nrf1. • Protection from stress-induced apoptosis by Nrf1 is inhibited by GSK3.« less

Treatment With Recombinant Human Insulin-Like Growth Factor-1 Improves Growth in Patients With PAPP-A2 Deficiency

PubMed Central

Muñoz-Calvo, María T.; Barrios, Vicente; Pozo, Jesús; Chowen, Julie A.; Martos-Moreno, Gabriel Á.; Hawkins, Federico; Dauber, Andrew; Domené, Horacio M.; Yakar, Shoshana; Rosenfeld, Ron G.; Pérez-Jurado, Luis A.; Oxvig, Claus; Frystyk, Jan

2016-01-01

Context: Pregnancy-associated plasma protein-A2 (PAPP-A2) is a metalloproteinase that specifically cleaves IGFBP-3 and IGFBP-5. Mutations in the PAPP-A2 gene have recently been shown to cause postnatal growth failure in humans, with specific skeletal features, due to the resulting decrease in IGF-1 bioavailability. However, a pharmacological treatment of this entity is yet to be established. Case Description: A 10.5-year-old girl and a 6-year-old boy, siblings from a Spanish family, with short stature due to a homozygous loss-of-function mutation in the PAPP-A2 gene (p.D643fs25*) and undetectable PAPP-A2 activity, were treated with progressive doses (40, 80, 100, and 120 μg/kg) of recombinant human IGF-1 (rhIGF-1) twice daily for 1 year. There was a clear increase in growth velocity and height in both siblings. Bioactive IGF-1 was increased, and spontaneous GH secretion was diminished after acute administration of rhIGF-1, whereas serum total IGF-1 and IGFBP-3 levels remained elevated. No episodes of hypoglycemia or any other secondary effects were observed during treatment. Conclusion: Short-term treatment with rhIGF-1 improves growth in patients with PAPP-A2 deficiency. PMID:27648969

Environmental Risk Factors for Type 1 Diabetes Mellitus Development.

PubMed

Antonela, Boljat; Ivana, Gunjača; Ivan, Konstantinović; Nikolina, Vidan; Vesna, Boraska Perica; Marina, Pehlić; Veselin, Škrabić; Tatijana, Zemunik

2017-09-01

Background Although environmental factors induce development of type 1 diabetes mellitus (T1DM) in genetically susceptible individuals, many of those factors have been uncovered. Therefore, the aim of the present study was to analyze associations of T1DM with a wide range of environmental factors. Material and Methods A case-control study was conducted on 249 diabetic and 255 healthy individuals from the Dalmatian region of South Croatia. Data regarding risk factors during pregnancy and early life period of the child were evaluated. Results History of antihypertensive intake ( p =0.04) and frequency of stressful life events during pregnancy ( p =0.01) were associated with higher risk of T1DM, while hypertension was associated with lower risk of T1DM ( p =0.01). Maternal age<25 years at delivery was associated with a higher risk of T1DM ( p =0.01).Diabetic patients had a positive family history of T1DM or T2DM ( p =0.002) more frequently than controls, while history of infectious diseases was inversely associated with the risk of T1DM ( p =0.03). A higher risk of T1DM was significantly associated with earlier introduction of cow's milk ( p =0.001), higher number of meals consumed per day ( p =0.02), higher frequency of carbohydrate ( p =0.001) and meat ( p =0.01) consumption and stressful life events during childhood ( p =0.02) while earlier introduction of fruit was associated with a lower risk of T1DM ( p =0.03) Conclusion This case-control study confirmed associations of a large number of environmental factors with development of T1DM with emphasis on the association of mother's antihypertensive intake during pregnancy, which extends our knowledge about environmental factors related with development of T1DM. © Georg Thieme Verlag KG Stuttgart · New York.

Hypoxia-inducible factor 1α is a critical downstream mediator for hypoxia-induced mitogenic factor (FIZZ1/RELMα)-induced pulmonary hypertension

PubMed Central

Johns, Roger A.; Takimoto, Eiki; Meuchel, Lucas W.; Elsaigh, Esra; Zhang, Ailan; Heller, Nicola M.; Semenza, Gregg L.; Yamaji-Kegan, Kazuyo

2017-01-01

Objective Pulmonary hypertension (PH) is characterized by progressive elevation of pulmonary vascular resistance, right ventricular failure, and ultimately death. We have shown that in rodents, hypoxia-induced mitogenic factor (HIMF; also known as FIZZ1 or RELMα) causes PH by initiating lung vascular inflammation. We hypothesized that hypoxia-inducible factor-1 (HIF-1) is a critical downstream signal mediator of HIMF during PH development. Approach and Results In this study, we compared the degree of HIMF-induced pulmonary vascular remodeling and PH development in wild-type (HIF-1α+/+) and HIF-1α heterozygous null (HIF-1α+/−) mice. HIMF-induced PH was significantly diminished in HIF-1α+/− mice and was accompanied by a dysregulated VEGF-A–VEGF receptor 2 pathway. HIF-1α was critical for bone marrow-derived cell migration and vascular tube formation in response to HIMF. Furthermore, HIMF and its human homolog, resistin-like molecule-β (RELMβ), significantly increased IL-6 in macrophages and lung resident cells through a mechanism dependent on HIF-1α and, at least to some extent, on nuclear factor κB. Conclusions Our results suggest that HIF-1α is a critical downstream transcription factor for HIMF-induced pulmonary vascular remodeling and PH development. Importantly, both HIMF and human RELMβ significantly increased IL-6 in lung resident cells and increased perivascular accumulation of IL-6–expressing macrophages in the lungs of mice. These data suggest that HIMF can induce HIF-1, VEGF-A, and interleukin-6, which are critical mediators of both hypoxic inflammation and PH pathophysiology. PMID:26586659

The Ethylene Responsive Factor Required for Nodulation 1 (ERN1) Transcription Factor Is Required for Infection-Thread Formation in Lotus japonicus.

PubMed

Kawaharada, Yasuyuki; James, Euan K; Kelly, Simon; Sandal, Niels; Stougaard, Jens

2017-03-01

Several hundred genes are transcriptionally regulated during infection-thread formation and development of nitrogen-fixing root nodules. We have characterized a set of Lotus japonicus mutants impaired in root-nodule formation and found that the causative gene, Ern1, encodes a protein with a characteristic APETALA2/Ethylene Responsive Factor (AP2/ERF) transcription-factor domain. Phenotypic characterization of four ern1 alleles shows that infection pockets are formed but root-hair infection threads are absent. Formation of root-nodule primordia is delayed and no normal transcellular infection threads are found in the infected nodules. Corroborating the role of ERN1 (ERF Required for Nodulation1) in nodule organogenesis, spontaneous nodulation induced by an autoactive CCaMK and cytokinin-induced nodule primordia were not observed in ern1 mutants. Expression of Ern1 is induced in the susceptible zone by Nod factor treatment or rhizobial inoculation. At the cellular level, the pErn1:GUS reporter is highly expressed in root epidermal cells of the susceptible zone and in the cortical cells that form nodule primordia. The genetic regulation of this cellular expression pattern was further investigated in symbiotic mutants. Nod factor induction of Ern1 in epidermal cells was found to depend on Nfr1, Cyclops, and Nsp2 but was independent of Nin and Nf-ya1. These results suggest that ERN1 functions as a transcriptional regulator involved in the formation of infection threads and development of nodule primordia and may coordinate these two processes.

Risk Factors for 30-Day Complications After Thumb CMC Joint Arthroplasty: An American College of Surgeons National Surgery Quality Improvement Program Study.

PubMed

Shah, Kalpit N; Defroda, Steven F; Wang, Bo; Weiss, Arnold-Peter C

2017-12-01

The first carpometacarpal (CMC) joint is a common site of osteoarthritis, with arthroplasty being a common procedure to provide pain relief and improve function with low complications. However, little is known about risk factors that may predispose a patient for postoperative complications. All CMC joint arthroplasty from 2005 to 2015 in the prospectively collected American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database were identified. Bivariate testing and multiple logistic regressions were performed to determine which patient demographics, surgical variables and medical comorbidities were significant predictors for complications. These included wound related, cardiopulmonary, neurological and renal complications, return to the operating room (OR) and readmission. A total of 3344 patients were identified from the database. Of those, 45 patients (1.3%) experienced a complication including wound issues (0.66%), return to the OR (0.15%) and readmission (0.27%) amongst others. When performing bivariate analysis, age over 65, American Society of Anesthesiologists (ASA) Class, diabetes and renal dialysis were significant risk factors. Multiple logistic regression after adjusting for confounding factors demonstrated that insulin-dependent diabetes and ASA Class 4 had a strong trend while renal dialysis was a significant risk factor. CMC arthroplasty has a very low overall complication rate of 1.3% and wound complication rate of 0.66%. Diabetes requiring insulin and ASA Class 4 trended towards significance while renal dialysis was found to be a significant risk factors in logistic regression. This information may be useful for preoperative counseling and discussion with patients who have these risk factors.

Factors and values of willingness to pay for improved construction waste management--a perspective of Malaysian contractors.

PubMed

Begum, Rawshan Ara; Siwar, Chamhuri; Pereira, Joy Jacqueline; Jaafar, Abdul Hamid

2007-01-01

Malaysia is facing an increase in the generation of waste and of accompanying problems with the disposal of this waste. In the last two decades, extensive building and infrastructure development projects have led to an increase in the generation of construction waste material. The construction industry has a substantial impact on the environment, and its environmental effects are in direct relation to the quality and quantity of the waste it generates. This paper discusses general characteristics of the construction contractors, the contractors' willingness to pay (WTP) for improved construction waste management, determining factors which affect the amount of their willingness to pay, and suggestions and policy implications in the perspective of construction waste management in Malaysia. The data in this study is based on contractors registered with the construction industry development board (CIDB) of Malaysia. Employing the open ended contingent valuation method, the study assessed the contractors' average maximum WTP for improved construction waste management to be RM69.88 (1US$=3.6 RM) per tonne of waste. The result shows that the average maximum WTP is higher for large contractors than for medium and small contractors. The highest average maximum WTP value is RM88.00 for Group A (large contractors) RM78.25 for Group B (medium-size contractors) and RM55.80 for Group C (small contractors). One of the contributions of this study is to highlight the difference of CIDB registration grade in the WTP for improved construction waste management. It is found that contractors' WTP for improved waste collection and disposal services increases with the increase in contractors' current paid up capital. The identified factors and determinants of the WTP will assist the formulation of appropriate policies in addressing the construction waste problem in Malaysia and indirectly improve the quality of construction in the country.

An Improved Multi-Sensor Fusion Navigation Algorithm Based on the Factor Graph.

PubMed

Zeng, Qinghua; Chen, Weina; Liu, Jianye; Wang, Huizhe

2017-03-21

An integrated navigation system coupled with additional sensors can be used in the Micro Unmanned Aerial Vehicle (MUAV) applications because the multi-sensor information is redundant and complementary, which can markedly improve the system accuracy. How to deal with the information gathered from different sensors efficiently is an important problem. The fact that different sensors provide measurements asynchronously may complicate the processing of these measurements. In addition, the output signals of some sensors appear to have a non-linear character. In order to incorporate these measurements and calculate a navigation solution in real time, the multi-sensor fusion algorithm based on factor graph is proposed. The global optimum solution is factorized according to the chain structure of the factor graph, which allows for a more general form of the conditional probability density. It can convert the fusion matter into connecting factors defined by these measurements to the graph without considering the relationship between the sensor update frequency and the fusion period. An experimental MUAV system has been built and some experiments have been performed to prove the effectiveness of the proposed method.

TIAM1 variants improve clinical outcome in neuroblastoma.

PubMed

Sanmartín, Elena; Yáñez, Yania; Fornés-Ferrer, Victoria; Zugaza, José L; Cañete, Adela; Castel, Victoria; Font de Mora, Jaime

2017-07-11

Identification of tumor driver mutations is crucial for improving clinical outcome using a personalized approach to the treatment of cancer. Neuroblastoma is a tumor of the peripheral sympathetic nervous system for which only a few driver alterations have been described including MYCN amplification and ALK mutations. We assessed 106 primary neuroblastoma tumors by next generation sequencing using a customized amplicon-based gene panel. Our results reveal that genetic variants in TIAM1 gene associate with better clinical outcome, suggesting a role for these TIAM1 variants in preventing progression of this disease. The detected variants are located within the different domains of TIAM1 that signal to the upstream regulator RAS and downstream effector molecules MYC and RAC, which are all implicated in neuroblastoma etiology and progression. Clinical outcome was improved in tumors where a TIAM1 variant was present concomitantly with either ALK mutation or MYCN amplification. Given the function of these signaling molecules in cell survival, proliferation, differentiation and neurite outgrowth, our data suggest that the TIAM1-mediated network is essential to neuroblastoma and thus, inhibiting TIAM1 reflects a rational strategy for improving therapy efficacy in neuroblastoma.

Cholangiocyte Endothelin 1 and Transforming Growth Factor β1 Production in Rat Experimental Hepatopulmonary Syndrome

PubMed Central

LUO, BAO; TANG, LIPING; WANG, ZHISHAN; ZHANG, JUNLAN; LING, YIQUN; FENG, WENGUANG; SUN, JU-ZHONG; STOCKARD, CECIL R.; FROST, ANDRA R.; CHEN, YIU-FAI; GRIZZLE, WILLIAM E.; FALLON, MICHAEL B.

2010-01-01

Background & Aims Hepatic production and release of endothelin 1 plays a central role in experimental hepatopulmonary syndrome after common bile duct ligation by stimulating pulmonary endothelial nitric oxide production. In thioacetamide-induced nonbiliary cirrhosis, hepatic endothelin 1 production and release do not occur, and hepatopulmonary syndrome does not develop. However, the source and regulation of hepatic endothelin 1 after common bile duct ligation are not fully characterized. We evaluated the sources of hepatic endothelin 1 production after common bile duct ligation in relation to thioacetamide cirrhosis and assessed whether transforming growth factor β1 regulates endothelin 1 production. Methods Hepatopulmonary syndrome and hepatic and plasma endothelin 1 levels were evaluated after common bile duct ligation or thioacetamide administration. Cellular sources of endothelin 1 were assessed by immunohistochemistry and laser capture microdissection of cholangiocytes. Transforming growth factor β1 expression and signaling were assessed by using immunohistochemistry and Western blotting and by evaluating normal rat cholangiocytes. Results Hepatic and plasma endothelin 1 levels increased and hepatopulmonary syndrome developed only after common bile duct ligation. Hepatic endothelin 1 and transforming growth factor β1 levels increased over a similar time frame, and cholangiocytes were a major source of each peptide. Transforming growth factor β1 signaling in cholangiocytes in vivo was evident by increased phosphorylation and nuclear localization of Smad2, and hepatic endothelin 1 levels correlated directly with liver transforming growth factor β1 and phosphorylated Smad2 levels. Transforming growth factor β1 also stimulated endothelin 1 promoter activity, expression, and production in normal rat cholangiocytes. Conclusions Cholangiocytes are a major source of hepatic endothelin 1 production during the development of hepatopulmonary syndrome after common

Osthole improves acute lung injury in mice by up-regulating Nrf-2/thioredoxin 1.

PubMed

Chen, Xiang-Jun; Zhang, Bo; Hou, Shao-Jie; Shi, Yun; Xu, Dun-Quan; Wang, Yan-Xia; Liu, Man-Ling; Dong, Hai-Ying; Sun, Ri-He; Bao, Nan-Di; Jin, Fa-Guang; Li, Zhi-Chao

2013-08-15

Inhibiting reactive oxygen species (ROS) has been viewed as a therapeutic target for the treatment of acute lung injury (ALI). Osthole, an active component in Chinese herbal medicine, has drawn increasing attention because of its various pharmacological functions, including anti-inflammatory and anti-oxidative activities. The aim of the present study was to examine the effects of osthole on ALI induced by lipopolysaccharide (LPS) through intratracheal instillation. The mRNA and protein expression levels of thioredoxin 1 (Trx1) and the nuclear factor erythroid-2 related factor 2 (Nrf2) were detected by real-time PCR, reverse transcription PCR (RT-PCR) and Western blot, respectively. ROS production was measured by flow cytometry. Our results showed that osthole treatment improved the mice survival rates in the middle and high dosage groups, compared with the untreated LPS group. Moreover, osthole treatment significantly improved LPS-induced lung pathological damage, and it decreased the lung injury scores, lung wet/dry ratios and the total protein level in Bronchoalveolar lavage fluid (BALF). Osthole treatment dramatically reduced the H2O2, MDA and OH levels in the lung homogenates. LDH and ROS were markedly reduced in the osthole+LPS group in vitro. Furthermore, osthole increased Nrf2 and Trx1 expression in terms of mRNA and protein in vivo and in vitro. Nrf2 siRNA (siNrf2) could suppress the beneficial effects of osthole on ALI. In conclusion, the current study demonstrates that osthole exerted protective effects on LPS-induced ALI by up-regulating the Nrf-2/Trx-1 pathway. Copyright © 2013 Elsevier B.V. All rights reserved.

78 FR 21879 - Improving 9-1-1 Reliability; Reliability and Continuity of Communications Networks, Including...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-12

... maps? What are the public safety and homeland security implications of public disclosure of key network... 13-33] Improving 9-1-1 Reliability; Reliability and Continuity of Communications Networks, Including... improve the reliability and resiliency of the Nation's 9-1-1 networks. The Notice of Proposed Rulemaking...

Efficacy of caesarean scar defect repair in improving postmenstrual bleeding and factors associated with poor effect.

PubMed

Xu, He-Yang; Yang, Meng-Yi; Zhang, Xuyin; Wang, Qing; Yi, Xiao-Fang; Ding, Jing-Xin; Hua, Ke-Qin

2017-11-01

Caesarean scar defect (CSD) can cause postmenstrual bleeding. Defect repair is an effective technique to improve this symptom, but there are still a few patients getting little improvement. This retrospective study evaluates the efficacy of scar repair and explores the factors associated with poor effect. In total, 123 patients were involved in the final analysis. All of them complained about menstruation period >7 days due to postmenstrual bleeding. Before surgery, 87.8% of patients had a menstruation period more than 10 days and 20.3% had a period more than 15 days. After surgery, a normal menstruation period (< =7 days) was achieved in 46.3% (95%CI 37.3%-55.6%) of patients and a menstruation period lasting no more than 10 days was achieved in 74.8% (95%CI 66.2%-82.2%). Through multivariate logistic analysis, four factors were found dependently associated with poor effect (defined as menstruation period >10 days after surgery): repeated caesarean section (OR 9.75, 95%CI 2.30-41.36, 0.002) was a risk factor, while defect volume >600 mm 3 (OR 0.14, 95%CI 0.03-0.56, 0.006), interval from caesarean section to symptom emerging >3 months (OR 0.25, 95%CI 0.07-0.94, 0.041) and straight or retroflexed uterus (OR 0.19, 95%CI 0.05-0.79, 0.022) were protective factors. Impact statement What is already known on this subject? Caesarean scar defect can cause postmenstrual bleeding. Defect repair can improve this symptom, but there are still a few patients getting little improvement after surgery. What do the results of this study add? Defect volume >600 mm 3 , interval from caesarean section to symptom emerging >3 months and straight or retroflexed uterus are protective factors of poor effect (defined as menstruation period >10 days after surgery), and repeated caesarean section is a risk factor. What are the implications of these findings for clinical practice and/or further research? These findings may help in counselling the patients and in medical

Combined administration of mesenchymal stem cells overexpressing IGF-1 and HGF enhances neovascularization but moderately improves cardiac regeneration in a porcine model.

PubMed

Gómez-Mauricio, Guadalupe; Moscoso, Isabel; Martín-Cancho, María-Fernanda; Crisóstomo, Verónica; Prat-Vidal, Cristina; Báez-Díaz, Claudia; Sánchez-Margallo, Francisco M; Bernad, Antonio

2016-07-16

Insulin-like growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) are among the most promising growth factors for promoting cardiorepair. Here, we evaluated the combination of cell- and gene-based therapy using mesenchymal stem cells (MSC) genetically modified to overexpress IGF-1 or HGF to treat acute myocardial infarction (AMI) in a porcine model. Pig MSC from adipose tissue (paMSC) were genetically modified for evaluation of different therapeutic strategies to improve AMI treatment. Three groups of infarcted Large White pigs were compared (I, control, non-transplanted; II, transplanted with paMSC-GFP (green fluorescent protein); III, transplanted with paMSC-IGF-1/HGF). Cardiac function was evaluated non-invasively using magnetic resonance imaging (MRI) for 1 month. After euthanasia and sampling of the animal, infarcted areas were studied by histology and immunohistochemistry. Intramyocardial transplant in a porcine infarct model demonstrated the safety of paMSC in short-term treatments. Treatment with paMSC-IGF-1/HGF (1:1) compared with the other groups showed a clear reduction in inflammation in some sections analyzed and promoted angiogenic processes in ischemic tissue. Although cardiac function parameters were not significantly improved, cell retention and IGF-1 overexpression was confirmed within the myocardium. The simultaneous administration of IGF-1- and HGF-overexpressing paMSC appears not to promote a synergistic effect or effective repair. The combined enhancement of neovascularization and fibrosis in paMSC-IGF-1/HGF-treated animals nonetheless suggests that sustained exposure to high IGF-1 + HGF levels promotes beneficial as well as deleterious effects that do not improve overall cardiac regeneration.

Colony stimulating factor 1 receptor blockade improves the efficacy of chemotherapy against human neuroblastoma in the absence of T lymphocytes.

PubMed

Webb, Matthew W; Sun, Jianping; Sheard, Michael A; Liu, Wei-Yao; Wu, Hong-Wei; Jackson, Jeremy R; Malvar, Jemily; Sposto, Richard; Daniel, Dylan; Seeger, Robert C

2018-04-17

Tumor-associated macrophages can promote growth of cancers. In neuroblastoma, tumor-associated macrophages have greater frequency in metastatic versus loco-regional tumors, and higher expression of genes associated with macrophages helps to predict poor prognosis in the 60% of high-risk patients who have MYCN-non-amplified disease. The contribution of cytotoxic T-lymphocytes to anti-neuroblastoma immune responses may be limited by low MHC class I expression and low exonic mutation frequency. Therefore, we modelled human neuroblastoma in T-cell deficient mice to examine whether depletion of monocytes/macrophages from the neuroblastoma microenvironment by blockade of CSF-1R can improve the response to chemotherapy. In vitro, CSF-1 was released by neuroblastoma cells, and topotecan increased this release. In vivo, neuroblastomas formed by subcutaneous co-injection of human neuroblastoma cells and human monocytes into immunodeficient NOD/SCID mice had fewer human CD14 + and CD163 + cells and mouse F4/80 + cells after CSF-1R blockade. In subcutaneous or intra-renal models in immunodeficient NSG or NOD/SCID mice, CSF-1R blockade alone did not affect tumor growth or mouse survival. However, when combined with cyclophosphamide plus topotecan, the CSF-1R inhibitor BLZ945, either without or with anti-human and anti-mouse CSF-1 mAbs, inhibited neuroblastoma growth and synergistically improved mouse survival. These findings indicate that depletion of tumor-associated macrophages from neuroblastomas can be associated with increased chemotherapeutic efficacy without requiring a contribution from T-lymphocytes, suggesting the possibility that combination of CSF-1R blockade with chemotherapy might be effective in patients who have limited anti-tumor T-cell responses. © 2018 UICC.

Improvement in skin wrinkles using a preparation containing human growth factors and hyaluronic acid serum.

PubMed

Lee, Do Hyun; Oh, In Young; Koo, Kyo Tan; Suk, Jang Mi; Jung, Sang Wook; Park, Jin Oh; Kim, Beom Joon; Choi, Yoo Mi

2015-02-01

Skin aging is accompanied by wrinkle formation. At some sites, such as the periorbital skin, this is a relatively early phenomenon. We evaluated the anti-wrinkle effect of a preparation containing human growth factor and hyaluronic acid serum on periorbital wrinkles (crow's feet). In total, 23 Korean women (age range: 39-59 years), who were not pregnant, nursing, or undergoing any concurrent therapy, were enrolled in this study. All the patients completed an 8-week trial of twice-daily application of human growth factor and hyaluronic acid serum on the entire face. Efficacy was based on a global photodamage score, photographs, and image analysis using replicas and visiometer analysis every 4 weeks. The standard wrinkle and roughness parameters used in assessing skin by visiometer were calculated and statistically analyzed. Periorbital wrinkles were significantly improved after treatment, with improvements noted both by physician's assessment and visiometer analysis. Topical application of human growth factor and hyaluronic acid was beneficial in reducing periorbital wrinkles.

Isolation and molecular characterization of a novel WIN1/SHN1 ethylene-responsive transcription factor TdSHN1 from durum wheat (Triticum turgidum. L. subsp. durum).

PubMed

Djemal, Rania; Khoudi, Habib

2015-11-01

Over the last decade, APETALA2/Ethylene Responsive Factor (AP2/ERF) proteins have become the subject of intensive research activity due to their involvement in a variety of biological processes. This research led to the identification of AP2/ERF genes in many species; however, little is known about these genes in durum wheat, one of the most important cereal crops in the world. In this study, a new member of the AP2/ERF transcription factor family, designated TdSHN1, was isolated from durum wheat using thermal asymetric interlaced PCR (TAIL-PCR) method. Protein sequence analysis showed that TdSHN1 contained an AP2/ERF domain of 63 amino acids and a putative nuclear localization signal (NLS). Phylogenetic analysis showed that TdSHN1 belongs to a group Va protein in the ERF subfamily which contains the Arabidopsis ERF proteins (SHN1, SHN2, and SHN3). Expression of TdSHN1 was strongly induced by salt, drought, abscisic acid (ABA), and cold. In planta, TdSHN1 protein was able to activate the transcription of GUS reporter gene driven by the GCC box and DRE element sequences. In addition, TdSHN1 was targeted to the nucleus when transiently expressed in tobacco epidermal cells. In transgenic yeast, overexpression of TdSHN1 increased tolerance to multiple abiotic stresses. Taken together, the results showed that TdSHN1 encodes an abiotic stress-inducible, transcription factor which confers abiotic stress tolerance in yeast. TdSHN1 is therefore a promising candidate for improvement of biotic and abiotic stress tolerance in wheat as well as other crops.

The toothless osteopetrotic rat has a normal vitamin D-binding protein-macrophage activating factor (DBP-MAF) cascade and chondrodysplasia resistant to treatments with colony stimulating factor-1 (CSF-1) and/or DBP-MAF.

PubMed

Odgren, P R; Popoff, S N; Safadi, F F; MacKay, C A; Mason-Savas, A; Seifert, M F; Marks, S C

1999-08-01

The osteopetrotic rat mutation toothless (tl) is characterized by little or no bone resorption, few osteoclasts and macrophages, and chondrodysplasia at the growth plates. Short-term treatment of tl rats with colony-stimulating factor-1 (CSF-1) has been shown to increase the number of osteoclasts and macrophages, producing dramatic resolution of skeletal sclerosis at some, but not all, sites. Defects in production of vitamin D-binding protein-macrophage activating factor (DBP-MAF) have been identified in two other independent osteopetrotic mutations of the rat (op and ia), and two in the mouse (op and mi), in which macrophages and osteoclasts can be activated by the administration of exogenous DBP-MAF. The present studies were undertaken to examine the histology and residual growth defects in tl rats following longer CSF-1 treatments, to investigate the possibility that exogenous DBP-MAF might act synergistically with CSF-1 to improve the tl phenotype, and to assess the integrity of the endogenous DBP-MAF pathway in this mutation. CSF-1 treatment-with or without DBP-MAF-induced resorption of metaphyseal bone to the growth plate on the marrow side, improved slightly but did not normalize long bone growth, and caused no improvement in the abnormal histology of the growth plate. Injections of lysophosphatidylcholine (lyso-Pc) to prime macrophage activation via the DBP-MAF pathway raised superoxide production to similar levels in peritoneal macrophages from both normal and mutant animals, indicating no defect in the DBP-MAF pathway in tl rats. Interestingly, pretreatments with CSF-1 alone also increased superoxide production, although the mechanism for this remains unknown. In summary, we find that, unlike other osteopetrotic mutations investigated to date, the DBP-MAF pathway does not appear to be defective in the tl rat; that additional DBP-MAF does not augment the beneficial skeletal effects seen with CSF-1 alone; and that the growth plate chondrodystrophy seen in

Granulocyte colony-stimulating factor improves host defense to resuscitated shock and polymicrobial sepsis without provoking generalized neutrophil-mediated damage.

PubMed

Patton, J H; Lyden, S P; Ragsdale, D N; Croce, M A; Fabian, T C; Proctor, K G

1998-05-01

Granulocyte colony-stimulating factor (G-CSF) increases production and release of neutrophil precursors and activates multiple functions of circulating polymorphonuclear neutrophils (PMNs). G-CSF has therapeutic effects in many experimental models of sepsis; its actions with superimposed reperfusion insults are unknown. In traumatic conditions, G-CSF could exacerbate unregulated, PMN-dependent injury to otherwise normal host tissue or, it could partially reverse trauma-induced immune suppression, which may improve long-term outcome. This study tested whether stimulating PMN proliferation and function with G-CSF during recovery from trauma+sepsis potentiated reperfusion injury or whether it improved host defense. Anesthetized swine were subjected to cecal ligation and incision, 35% hemorrhage, and 1 hr of hypotension. Resuscitation consisted of intravenous G-CSF (5 microg/kg) or placebo followed by shed blood and 40 mL/kg of lactated Ringer's solution. The control group received laparotomy only. G-CSF or placebo was given daily. Animals were killed at 4 days. Observers, blind to the protocol, graded autopsy samples for localization of infection and quality of abscess wall formation. Data included complete blood count, granulocyte oxidative burst after phorbol myristate acetate stimulation in vitro (GO2B), bronchoalveolar lavage (BAL) cell count, BAL noncellular protein, lipopolysaccharide-stimulated tumor necrosis factor production in whole blood in vitro (lipopolysaccharide-tumor necrosis factor), and lung tissue myeloperoxidase (MPO). Neutrophilia and localization of infection, were significantly improved by G-CSF. Variables altered by G-CSF, though not significantly, showed GO2B potential increased by 50%, lipopolysaccharide-tumor necrosis factor decreased by 50%, and improved survival versus placebo (100% vs. 70%). G-CSF did not increase lung MPO, BAL cell count, or BAL protein. Both arterial and venous O2 saturations were unaltered. Our data show that G

Soluble Flt-1 improves the repair of ankle joint injury in rats

PubMed Central

Tian, Jing; Xie, Bing; Xiang, Liangbi; Zhao, Yong; Zhou, Dapeng

2016-01-01

The ankle injuries create great pain to a great number of patients worldwide. Past studies have focused on the development of practical treatments to relieve pain and improve recovery, but the molecular mechanisms underlying the ankle injuries, especially the local inflammation in the damaged ankle joint, have been rarely studied. Moreover, although reduction of production and secretion of pro-inflammatory cytokines may reduce the pain and promote the recovery, a practical approach is currently lacking. Here, we detected significantly higher levels of placental growth factor (PLGF) and pro-inflammatory cytokines in the joint fluid from the patients of acute ankle joint injury (AAJI). Interestingly, the levels of PLGF and pro-inflammatory cytokines in the joint fluid strongly correlated. In order to examine whether PLGF may regulate the production and secretion of pro-inflammatory cytokines in the injured joint, we used a rat carrageenan-induced ankle injury model for AAJI in humans. We injected soluble Flt-1 (sFlt-1) into the articular cavity of the injured ankle joint to block PLGF signaling and found that injection of sFlt-1 significantly improved the rat behavior in activity wheels test, which appeared to result from reduced secretion of the pro-inflammatory cytokines in the ankle joint. Thus, our study suggests that blocking PLGF signaling may be a novel therapeutic approach for treating AAJI in humans. PMID:27904694

Factors associated with falling in early, treated Parkinson's disease: The NET-PD LS1 cohort.

PubMed

Chou, Kelvin L; Elm, Jordan J; Wielinski, Catherine L; Simon, David K; Aminoff, Michael J; Christine, Chadwick W; Liang, Grace S; Hauser, Robert A; Sudarsky, Lewis; Umeh, Chizoba C; Voss, Tiffini; Juncos, Jorge; Fang, John Y; Boyd, James T; Bodis-Wollner, Ivan; Mari, Zoltan; Morgan, John C; Wills, Anne-Marie; Lee, Stephen L; Parashos, Sotirios A

2017-06-15

Recognizing the factors associated with falling in Parkinson's disease (PD) would improve identification of at-risk individuals. To examine frequency of falling and baseline characteristics associated with falling in PD using the National Institute of Neurological Disorders and Stroke (NINDS) Exploratory Trials in PD Long-term Study-1 (NET-PD LS-1) dataset. The LS-1 database included 1741 early treated PD subjects (median 4year follow-up). Baseline characteristics were tested for a univariate association with post-baseline falling during the trial. Significant variables were included in a multivariable logistic regression model. A separate analysis using a negative binomial model investigated baseline factors on fall rate. 728 subjects (42%) fell during the trial, including at baseline. A baseline history of falls was the factor most associated with post-baseline falling. Men had lower odds of post-baseline falling compared to women, but for men, the probability of a post-baseline fall increased with age such that after age 70, men and women had similar odds of falling. Other baseline factors associated with a post-baseline fall and increased fall rate included the Unified PD Rating Scale (UPDRS) Activities of Daily Living (ADL) score, total functional capacity (TFC), baseline ambulatory capacity score and dopamine agonist monotherapy. Falls are common in early treated PD. The biggest risk factor for falls in PD remains a history of falling. Measures of functional ability (UPDRS ADL, TFC) and ambulatory capacity are novel clinical risk factors needing further study. A significant age by sex interaction may help to explain why age has been an inconsistent risk factor for falls in PD. Copyright © 2017 Elsevier B.V. All rights reserved.

43 CFR 3863.1-2 - Proof of improvements for patent.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Proof of improvements for patent. 3863.1-2... MANAGEMENT, DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) MINERAL PATENT APPLICATIONS Placer Mining Claim Patent Applications § 3863.1-2 Proof of improvements for patent. The proof of improvements must...

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Code of Federal Regulations, 2012 CFR

2012-10-01

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43 CFR 3863.1-2 - Proof of improvements for patent.

Code of Federal Regulations, 2014 CFR

2014-10-01

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43 CFR 3863.1-2 - Proof of improvements for patent.

Code of Federal Regulations, 2011 CFR

2011-10-01

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Job embeddedness factors and retention of nurses with 1 to 3 years of experience.

PubMed

Halfer, Diana

2011-10-01

An aging work force, predictions of job growth in health care, and an eventual economic recovery suggest that the current reprieve from the national nursing shortage is temporary. New graduate nurses are an important part of the work force and are needed to replace nurses who will retire in the next decade. Organizational leaders can address the forecasted work force demand by proactively investing in programs for workplace development and retention. Recent literature reports an increased focus on understanding the work experience and career support needed for new graduate nurses. Several studies report improvements in job satisfaction and retention after implementation of structured mentoring programs for new graduate nurses. However, despite successful transition programs, turnover for these same nurses after 1 to 3 years of organizational tenure remains high. Studying factors that contribute to retention and supporting careers beyond the first year of practice may have a significant effect on improving retention and will contribute new knowledge to the nursing literature. This study, undertaken at a Midwestern pediatric academic medical center, examined job factors and career development support that lead to retention of nurses with 1 to 3 years of experience. Understanding these issues may guide nursing leaders and staff development educators in investing in focused retention and career development plans during an economic recession. Copyright 2011, SLACK Incorporated.

Screening for Behavioral Risk Factors Is Not Enough to Improve Preventive Services Delivery.

PubMed

Drouin, Olivier; Winickoff, Jonathan P

Unhealthy behaviors are a major cause of chronic disease. Preappointment screening has been suggested as one way to improve preventive care delivery related to these behaviors by specifying risks to be addressed. We aimed to determine whether screening for health-related behaviors before the clinical encounter will lead to higher counseling rate and service delivery by clinicians. We used a pre/post design in one practice with a control practice to evaluate the effects of preappointment screening for 3 behavioral risk factors (tobacco smoke exposure, no recent dental care visit, and consumption of sugar-sweetened beverages). After their clinic visit, we asked English-speaking parents whose child had one or more risk factor whether they had received counseling or services from their pediatrician to address them. We recruited 264 parents in the pre phase and 242 in the post phase. Among 215 parents whose child had one or more risk factors, parents in the post phase were as likely to report receiving counseling than parents in the pre phase for each of the risk factors: smoking odds ratio 6.75 (95% confidence interval, 0.51, 88.88), dental health odds ratio 1.44 (95% confidence interval, 0.47, 4.41), and sugar-sweetened beverage consumption odds ratio 0.34 (95% confidence interval, 0.23, 5.18). Service delivery and reported behavior change were also similar in both phases. Counseling rates for tobacco, dental health, or sugar-sweetened beverage consumption were low in pediatric primary care, and preappointment screening did not significantly affect clinician counseling. Future efforts will require a more robust approach to effect change in counseling, provision of service, and family behavior. Copyright © 2018 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

[Utilization of dental services for children: a review of the influencing factors and the possible improvements].

PubMed

Cheng, M L; Si, Y

2017-05-09

It has been reported that children's oral health conditions are correlated with their attendance to dental health services. Evaluating the influencing factors of utilization of dental services for children may give ways to improve the services per se, and furtherly the children's oral health. The present review retrieved and summarized domestic and foreign studies on the utilization of oral health services for children based on the Andersen behavior model. It was concluded that the utilization of dental services for children was affected by demographic characteristics, social structure, health belief, family factors, community factors and perceived/evaluated needs. To improve the utilization of dental services for children, effort should be made by means of changing caregivers' health belief, developing oral health insurance system, setting up regular oral health resources and increasing the financial support for oral health services by government.

Induction of Epstein-Barr Virus Oncoprotein LMP1 by Transcription Factors AP-2 and Early B Cell Factor

PubMed Central

Noda, Chieko; Narita, Yohei; Watanabe, Takahiro; Yoshida, Masahiro; Ashio, Keiji; Sato, Yoshitaka; Goshima, Fumi; Kanda, Teru; Yoshiyama, Hironori; Tsurumi, Tatsuya; Kimura, Hiroshi

2016-01-01

ABSTRACT Latent membrane protein 1 (LMP1) is a major oncogene essential for primary B cell transformation by Epstein-Barr virus (EBV). Previous studies suggested that some transcription factors, such as PU.1, RBP-Jκ, NF-κB, and STAT, are involved in this expression, but the underlying mechanism is unclear. Here, we identified binding sites for PAX5, AP-2, and EBF in the proximal LMP1 promoter (ED-L1p). We first confirmed the significance of PU.1 and POU domain transcription factor binding for activation of the promoter in latency III. We then focused on the transcription factors AP-2 and early B cell factor (EBF). Interestingly, among the three AP-2-binding sites in the LMP1 promoter, two motifs were also bound by EBF. Overexpression, knockdown, and mutagenesis in the context of the viral genome indicated that AP-2 plays an important role in LMP1 expression in latency II in epithelial cells. In latency III B cells, on the other hand, the B cell-specific transcription factor EBF binds to the ED-L1p and activates LMP1 transcription from the promoter. IMPORTANCE Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) is crucial for B cell transformation and oncogenesis of other EBV-related malignancies, such as nasopharyngeal carcinoma and T/NK lymphoma. Its expression is largely dependent on the cell type or condition, and some transcription factors have been implicated in its regulation. However, these previous reports evaluated the significance of specific factors mostly by reporter assay. In this study, we prepared point-mutated EBV at the binding sites of such transcription factors and confirmed the importance of AP-2, EBF, PU.1, and POU domain factors. Our results will provide insight into the transcriptional regulation of the major oncogene LMP1. PMID:26819314

The bHLH transcription factor GmPIB1 facilitates resistance to Phytophthora sojae in Glycine max

PubMed Central

Cheng, Qun; Dong, Lidong; Gao, Tianjiao; Liu, Tengfei; Li, Ninghui; Wang, Le; Chang, Xin; Wu, Junjiang; Xu, Pengfei

2018-01-01

Abstract Phytophthora sojae Kaufmann and Gerdemann causes Phytophthora root rot, a destructive soybean disease worldwide. A basic helix–loop–helix (bHLH) transcription factor is thought to be involved in the response to P. sojae infection in soybean, as revealed by RNA sequencing (RNA-seq). However, the molecular mechanism underlying this response is currently unclear. Here, we explored the function and underlying mechanisms of a bHLH transcription factor in soybean, designated GmPIB1 (P. sojae-inducible bHLH transcription factor), during host responses to P. sojae. GmPIB1 was significantly induced by P. sojae in the resistant soybean cultivar ‘L77-1863’. Analysis of transgenic soybean hairy roots with elevated or reduced expression of GmPIB1 demonstrated that GmPIB1 enhances resistance to P. sojae and reduces reactive oxygen species (ROS) accumulation. Quantitative reverse transcription PCR and chromatin immunoprecipitation–quantitative PCR assays revealed that GmPIB1 binds directly to the promoter of GmSPOD1 and represses its expression; this gene encodes a key enzyme in ROS production. Moreover, transgenic soybean hairy roots with GmSPOD1 silencing through RNA interference exhibited improved resistance to P. sojae and reduced ROS generation. These findings suggest that GmPIB1 enhances resistance to P. sojae by repressing the expression of GmSPOD1. PMID:29579245

Optimization of 1H-indazol-3-amine derivatives as potent fibroblast growth factor receptor inhibitors.

PubMed

Cui, Jing; Peng, Xia; Gao, Dingding; Dai, Yang; Ai, Jing; Li, Yingxia

2017-08-15

Fibroblast growth factor receptor (FGFR) is a potential target for cancer therapy because of its critical role in promoting cancer formation and progression. In a continuing effort to improve the cellular activity of hit compound 7r bearing an indazole scaffold, which was previously discovered by our group, several compounds harnessing fluorine substituents were designed, synthesized and biological evaluated. Besides, the region extended out to the ATP binding pocket toward solvent was also explored. Among them, compound 2a containing 2,6-difluoro-3-methoxyphenyl residue exhibited the most potent activities (FGFR1: less than 4.1nM, FGFR2: 2.0±0.8nM). More importantly, compound 2a showed an improved antiproliferative effect against KG1 cell lines and SNU16 cell lines with IC 50 values of 25.3±4.6nM and 77.4±6.2nM respectively. Copyright © 2017. Published by Elsevier Ltd.

A randomized trial of a primary care-based disease management program to improve cardiovascular risk factors and glycated hemoglobin levels in patients with diabetes.

PubMed

Rothman, Russell L; Malone, Robb; Bryant, Betsy; Shintani, Ayumi K; Crigler, Britton; Dewalt, Darren A; Dittus, Robert S; Weinberger, Morris; Pignone, Michael P

2005-03-01

To assess the efficacy of a pharmacist-led, primary care-based, disease management program to improve cardiovascular risk factors and glycated hemoglobin (A(1C)) levels in vulnerable patients with poorly controlled diabetes. A randomized controlled trial of 217 patients with type 2 diabetes and poor glycemic control (A(1C) level >or=8.0%) was conducted at an academic general medicine practice from February 2001 to April 2003. Intervention patients received intensive management from clinical pharmacists, as well as from a diabetes care coordinator who provided diabetes education, applied algorithms for managing glucose control and decreasing cardiovascular risk factors, and addressed barriers to care. Control patients received a one-time management session from a pharmacist followed by usual care from their primary care provider. Outcomes were recorded at baseline and at 6 and 12 months. Primary outcomes included blood pressure, A(1C) level, cholesterol level, and aspirin use. Secondary outcomes included diabetes knowledge, satisfaction, use of clinical services, and adverse events. For the 194 patients (89%) with 12-month data, the intervention group had significantly greater improvement than did the control group for systolic blood pressure (-9 mm Hg; 95% confidence interval [CI]: -16 to -3 mm Hg) and A(1C) level (-0.8%; 95% CI: -1.7% to 0%). Change in total cholesterol level was not significant. At 12 months, aspirin use was 91% in the intervention group versus 58% among controls (P <0.0001). Intervention patients had greater improvements in diabetes knowledge and satisfaction than did control patients. There were no significant differences in use of clinical services or adverse events. Our comprehensive disease management program reduced cardiovascular risk factors and A(1C) levels among vulnerable patients with type 2 diabetes and poor glycemic control.

Quantitative phosphoproteomics analysis reveals a key role of insulin growth factor 1 receptor (IGF1R) tyrosine kinase in human sperm capacitation.

PubMed

Wang, Jing; Qi, Lin; Huang, Shaoping; Zhou, Tao; Guo, Yueshuai; Wang, Gaigai; Guo, Xuejiang; Zhou, Zuomin; Sha, Jiahao

2015-04-01

One of the most important changes during sperm capacitation is the enhancement of tyrosine phosphorylation. However, the mechanisms of protein tyrosine phosphorylation during sperm capacitation are not well studied. We used label-free quantitative phosphoproteomics to investigate the overall phosphorylation events during sperm capacitation in humans and identified 231 sites with increased phosphorylation levels. Motif analysis using the NetworKIN algorithm revealed that the activity of tyrosine phosphorylation kinases insulin growth factor 1 receptor (IGF1R)/insulin receptor is significantly enriched among the up-regulated phosphorylation substrates during capacitation. Western blotting further confirmed inhibition of IGF1R with inhibitors GSK1904529A and NVP-AEW541, which inhibited the increase in tyrosine phosphorylation levels during sperm capacitation. Additionally, sperm hyperactivated motility was also inhibited by GSK1904529A and NVP-AEW541 but could be up-regulated by insulin growth factor 1, the ligand of IGF1R. Thus, the IGF1R-mediated tyrosine phosphorylation pathway may play important roles in the regulation of sperm capacitation in humans and could be a target for improvement in sperm functions in infertile men. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

O-GlcNAc Transferase/Host Cell Factor C1 Complex Regulates Gluconeogenesis by Modulating PGC-1α Stability

PubMed Central

Ruan, Hai-Bin; Han, Xuemei; Li, Min-Dian; Singh, Jay Prakash; Qian, Kevin; Azarhoush, Sascha; Zhao, Lin; Bennett, Anton M.; Samuel, Varman T.; Wu, Jing; Yates, John R.; Yang, Xiaoyong

2012-01-01

SUMMARY A major cause of hyperglycemia in diabetic patients is inappropriate hepatic gluconeogenesis. PGC-1α is a master regulator of gluconeogenesis, and its activity is controlled by various post-translational modifications. A small portion of glucose metabolizes through the hexosamine biosynthetic pathway, which leads to O-linked β-N-acetylglucosamine (O-GlcNAc) modification of cytoplasmic and nuclear proteins. Using a proteomic approach, we identified a broad variety of proteins associated with O-GlcNAc transferase (OGT), among which host cell factor C1 (HCF-1) is highly abundant. HCF-1 recruits OGT to O-GlcNAcylate PGC-1α and O-GlcNAcylation facilitates the binding of the deubiquitinase BAP1, thus protecting PGC-1α from degradation and promoting gluconeogenesis. Glucose availability modulates gluconeogenesis through the regulation of PGC-1α O-GlcNAcylation and stability by the OGT/HCF1 complex. Hepatic knockdown of OGT and HCF-1 improves glucose homeostasis in diabetic mice. These findings define the OGT/HCF-1 complex as a glucose sensor and key regulator of gluconeogenesis, shedding light on new strategies for treating diabetes. PMID:22883232

Improving nuclear envelope dynamics by EBV BFRF1 facilitates intranuclear component clearance through autophagy.

PubMed

Liu, Guan-Ting; Kung, Hsiu-Ni; Chen, Chung-Kuan; Huang, Cheng; Wang, Yung-Li; Yu, Cheng-Pu; Lee, Chung-Pei

2018-02-26

Although a vesicular nucleocytoplasmic transport system is believed to exist in eukaryotic cells, the features of this pathway are mostly unknown. Here, we report that the BFRF1 protein of the Epstein-Barr virus improves vesicular transport of nuclear envelope (NE) to facilitate the translocation and clearance of nuclear components. BFRF1 expression induces vesicles that selectively transport nuclear components to the cytoplasm. With the use of aggregation-prone proteins as tools, we found that aggregated nuclear proteins are dispersed when these BFRF1-induced vesicles are formed. BFRF1-containing vesicles engulf the NE-associated aggregates, exit through from the NE, and putatively fuse with autophagic vacuoles. Chemical treatment and genetic ablation of autophagy-related factors indicate that autophagosome formation and autophagy-linked FYVE protein-mediated autophagic proteolysis are involved in this selective clearance of nuclear proteins. Remarkably, vesicular transport, elicited by BFRF1, also attenuated nuclear aggregates accumulated in neuroblastoma cells. Accordingly, induction of NE-derived vesicles by BFRF1 facilitates nuclear protein translocation and clearance, suggesting that autophagy-coupled transport of nucleus-derived vesicles can be elicited for nuclear component catabolism in mammalian cells.-Liu, G.-T., Kung, H.-N., Chen, C.-K., Huang, C., Wang, Y.-L., Yu, C.-P., Lee, C.-P. Improving nuclear envelope dynamics by EBV BFRF1 facilitates intranuclear component clearance through autophagy.

The AP-1 transcription factor FOSL1 causes melanocyte reprogramming and transformation.

PubMed

Maurus, K; Hufnagel, A; Geiger, F; Graf, S; Berking, C; Heinemann, A; Paschen, A; Kneitz, S; Stigloher, C; Geissinger, E; Otto, C; Bosserhoff, A; Schartl, M; Meierjohann, S

2017-09-07

The MAPK pathway is activated in the majority of melanomas and is the target of therapeutic approaches. Under normal conditions, it initiates the so-called immediate early response, which encompasses the transient transcription of several genes belonging to the AP-1 transcription factor family. Under pathological conditions, such as continuous MAPK pathway overactivation due to oncogenic alterations occurring in melanoma, these genes are constitutively expressed. The consequences of a permanent expression of these genes are largely unknown. Here, we show that FOSL1 is the main immediate early AP-1 member induced by melanoma oncogenes. We first examined its role in established melanoma cells. We found that FOSL1 is involved in melanoma cell migration as well as cell proliferation and anoikis-independent growth, which is mediated by the gene product of its target gene HMGA1, encoding a multipotent chromatin modifier. As FOSL1 expression is increased in patient melanoma samples compared to nevi, we investigated the effect of enhanced FOSL1 expression on melanocytes. Intriguingly, we found that FOSL1 acts oncogenic and transforms melanocytes, enabling subcutaneous tumor growth in vivo. During the process of transformation, FOSL1 reprogrammed the melanocytes and downregulated MITF in a HMGA1-dependent manner. At the same time, AXL was upregulated, leading to a shift in the MITF/AXL balance. Furthermore, FOSL1 re-enforced pro-tumorigenic transcription factors MYC, E2F3 and AP-1. Together, this led to the enhancement of several growth-promoting processes, such as ribosome biogenesis, cellular detachment and pyrimidine metabolism. Overall, we demonstrate that FOSL1 is a novel reprogramming factor for melanocytes with potent tumor transformation potential.

An Improved Multi-Sensor Fusion Navigation Algorithm Based on the Factor Graph

PubMed Central

Zeng, Qinghua; Chen, Weina; Liu, Jianye; Wang, Huizhe

2017-01-01

An integrated navigation system coupled with additional sensors can be used in the Micro Unmanned Aerial Vehicle (MUAV) applications because the multi-sensor information is redundant and complementary, which can markedly improve the system accuracy. How to deal with the information gathered from different sensors efficiently is an important problem. The fact that different sensors provide measurements asynchronously may complicate the processing of these measurements. In addition, the output signals of some sensors appear to have a non-linear character. In order to incorporate these measurements and calculate a navigation solution in real time, the multi-sensor fusion algorithm based on factor graph is proposed. The global optimum solution is factorized according to the chain structure of the factor graph, which allows for a more general form of the conditional probability density. It can convert the fusion matter into connecting factors defined by these measurements to the graph without considering the relationship between the sensor update frequency and the fusion period. An experimental MUAV system has been built and some experiments have been performed to prove the effectiveness of the proposed method. PMID:28335570

Inhibition of CSF1 Receptor Improves the Anti-tumor Efficacy of Adoptive Cell Transfer Immunotherapy

PubMed Central

Tsui, Christopher; Xu, Jingying; Robert, Lídia; Wu, Lily; Graeber, Thomas; West, Brian L.; Bollag, Gideon; Ribas, Antoni

2013-01-01

Colony stimulating factor-1 (CSF-1) recruits tumor-infiltrating myeloid cells (TIMs) that suppress tumor immunity, including M2 macrophages and myeloid derived suppressor cells (MDSC). The CSF-1 receptor (CSF-1R) is a tyrosine kinase that is targetable by small molecule inhibitors such as PLX3397. In this study, we used a syngeneic mouse model of BRAFV600E-driven melanoma to evaluate the ability of PLX3397 to improve the efficacy of adoptive T-cell therapy (ACT). In this model, we found that combined treatment produced superior anti-tumor responses compared with single treatments. In mice receiving the combined treatment, a dramatic reduction of TIMs and a skewing of MHCIIlow to MHCIIhi macrophages was observed. Further, mice receiving the combined treatment exhibited an increase in tumor-infiltrating lymphocytes (TILs) and T cells, as revealed by real-time imaging in vivo. In support of these observations, TILs from these mice released higher levels of IFN-γ. In conclusion, CSF-1R blockade with PLX3397 improved the efficacy of ACT immunotherapy by inhibiting the intratumoral accumulation of immune suppressive macrophages. PMID:24247719

The Forkhead Transcription Factor Hcm1 Promotes Mitochondrial Biogenesis and Stress Resistance in Yeast*

PubMed Central

Rodriguez-Colman, Maria José; Reverter-Branchat, Gemma; Sorolla, M. Alba; Tamarit, Jordi; Ros, Joaquim; Cabiscol, Elisa

2010-01-01

In Saccharomyces cerevisiae, the forkhead transcription factor Hcm1 is involved in chromosome segregation, spindle pole dynamics, and budding. We found that Hcm1 interacts with the histone deacetylase Sir2 and shifts from cytoplasm to the nucleus in the G1/S phase or in response to oxidative stress stimuli. The nuclear localization of Hcm1 depends on the activity of Sir2 as revealed by activators and inhibitors of the sirtuins and the Δsir2 mutant. Hcm1-overexpressing cells display more mitochondria that can be attributed to increased amounts of Abf2, a protein involved in mitochondrial biogenesis. These cells also show higher rates of oxygen consumption and improved resistance to oxidative stress that would be explained by increased catalase and Sod2 activities and molecular chaperones such as Hsp26, Hsp30, and members of Hsp70 family. Microarray analyses also reveal increased expression of genes involved in mitochondrial energy pathways and those allowing the transition from the exponential to the stationary phase. Taken together, these results describe a new and relevant role of Hcm1 for mitochondrial functions, suggesting that this transcription factor would participate in the adaptation of cells from fermentative to respiratory metabolism. PMID:20847055

Insulin-Like Growth Factor 1 (IGF-1) in Parkinson's Disease: Potential as Trait-, Progression- and Prediction Marker and Confounding Factors.

PubMed

Bernhard, Felix P; Heinzel, Sebastian; Binder, Gerhard; Weber, Karin; Apel, Anja; Roeben, Benjamin; Deuschle, Christian; Maechtel, Mirjam; Heger, Tanja; Nussbaum, Susanne; Gasser, Thomas; Maetzler, Walter; Berg, Daniela

2016-01-01

Biomarkers indicating trait, progression and prediction of pathology and symptoms in Parkinson's disease (PD) often lack specificity or reliability. Investigating biomarker variance between individuals and over time and the effect of confounding factors is essential for the evaluation of biomarkers in PD, such as insulin-like growth factor 1 (IGF-1). IGF-1 serum levels were investigated in up to 8 biannual visits in 37 PD patients and 22 healthy controls (HC) in the longitudinal MODEP study. IGF-1 baseline levels and annual changes in IGF-1 were compared between PD patients and HC while accounting for baseline disease duration (19 early stage: ≤3.5 years; 18 moderate stage: >4 years), age, sex, body mass index (BMI) and common medical factors putatively modulating IGF-1. In addition, associations of baseline IGF-1 with annual changes of motor, cognitive and depressive symptoms and medication dose were investigated. PD patients in moderate (130±26 ng/mL; p = .004), but not early stages (115±19, p>.1), showed significantly increased baseline IGF-1 levels compared with HC (106±24 ng/mL; p = .017). Age had a significant negative correlation with IGF-1 levels in HC (r = -.47, p = .028) and no correlation in PD patients (r = -.06, p>.1). BMI was negatively correlated in the overall group (r = -.28, p = .034). The annual changes in IGF-1 did not differ significantly between groups and were not correlated with disease duration. Baseline IGF-1 levels were not associated with annual changes of clinical parameters. Elevated IGF-1 in serum might differentiate between patients in moderate PD stages and HC. However, the value of serum IGF-1 as a trait-, progression- and prediction marker in PD is limited as IGF-1 showed large inter- and intraindividual variability and may be modulated by several confounders.

HIF-1α and HIF-2α induce angiogenesis and improve muscle energy recovery.

PubMed

Niemi, Henna; Honkonen, Krista; Korpisalo, Petra; Huusko, Jenni; Kansanen, Emilia; Merentie, Mari; Rissanen, Tuomas T; André, Helder; Pereira, Teresa; Poellinger, Lorenz; Alitalo, Kari; Ylä-Herttuala, Seppo

2014-10-01

Cardiovascular patients suffer from reduced blood flow leading to ischaemia and impaired tissue metabolism. Unfortunately, an increasing group of elderly patients cannot be treated with current revascularization methods. Thus, new treatment strategies are urgently needed. Hypoxia-inducible factors (HIFs) upregulate the expression of angiogenic mediators together with genes involved in energy metabolism and recovery of ischaemic tissues. Especially, HIF-2α is a novel factor, and only limited information is available about its therapeutic potential. Gene transfers with adenoviral HIF-1α and HIF-2α were performed into the mouse heart and rabbit ischaemic hindlimbs. Angiogenesis was evaluated by histology. Left ventricle function was analysed with echocardiography. Perfusion in rabbit skeletal muscles and energy recovery after electrical stimulation-induced exercise were measured with ultrasound and (31)P-magnetic resonance spectroscopy ((31)P-MRS), respectively. HIF-1α and HIF-2α gene transfers increased capillary size up to fivefold in myocardium and ischaemic skeletal muscles. Perfusion in skeletal muscles was increased by fourfold without oedema. Especially, AdHIF-1α enhanced the recovery of ischaemic muscles from electrical stimulation-induced energy depletion. Special characteristic of HIF-2α gene transfer was a strong capillary growth in muscle connective tissue and that HIF-2α gene transfer maintained left ventricle function. We conclude that both AdHIF-1α and AdHIF-2α gene transfers induced beneficial angiogenesis in vivo. Transient moderate increases in angiogenesis improved energy recovery after exercise in ischaemic muscles. This study shows for the first time that a moderate increase in angiogenesis is enough to improve tissue energy metabolism, which is potentially a very useful feature for cardiovascular gene therapy. © 2014 Stichting European Society for Clinical Investigation Journal Foundation.

Improving the Performance of a 1-D Ultrasound Transducer Array by Subdicing.

PubMed

Janjic, Jovana; Shabanimotlagh, Maysam; van Soest, Gijs; van der Steen, Antonius F W; de Jong, Nico; Verweij, Martin D

2016-08-01

In medical ultrasound transducer design, the geometry of the individual elements is crucial since it affects the vibration mode of each element and its radiation impedance. For a fixed frequency, optimal vibration (i.e., uniform surface motion) can be achieved by designing elements with very small width-to-thickness ratios. However, for optimal radiation impedance (i.e., highest radiated power), the width should be as large as possible. This leads to a contradiction that can be solved by subdicing wide elements. To systematically examine the effect of subdicing on the performance of a 1-D ultrasound transducer array, we applied finite-element simulations. We investigated the influence of subdicing on the radiation impedance, on the time and frequency response, and on the directivity of linear arrays with variable element widths. We also studied the effect of varying the depth of the subdicing cut. The results show that, for elements having a width greater than 0.6 times the wavelength, subdicing improves the performance compared with that of nonsubdiced elements: the emitted pressure may be increased up to a factor of three, the ringing time may be reduced by up to 50%, the bandwidth increased by up to 77%, and the sidelobes reduced by up to 13 dB. Moreover, this simulation study shows that all these improvements can already be achieved by subdicing the elements to a depth of 70% of the total element thickness. Thus, subdicing can improve important transducer parameters and, therefore, help in achieving images with improved signal-to-noise ratio and improved resolution.

Human Factors Operability Timeline Analysis to Improve the Processing Flow of the Orion Spacecraft

NASA Technical Reports Server (NTRS)

Stambolian, Damon B.; Schlierf, Roland; Miller, Darcy; Posada, Juan; Haddock, Mike; Haddad, Mike; Tran, Donald; Henderon, Gena; Barth, Tim

2011-01-01

This slide presentation reviews the use of Human factors and timeline analysis to have a more efficient and effective processing flow. The solution involved developing a written timeline of events that included each activity within each functional flow block. Each activity had computer animation videos and pictures of the people involved and the hardware. The Human Factors Engineering Analysis Tool (HFEAT) was improved by modifying it to include the timeline of events. The HFEAT was used to define the human factors requirements and design solutions were developed for these requirements. An example of a functional flow block diagram is shown, and a view from one of the animations (i.e., short stack pallet) is shown and explained.

Growth factor deprivation induces cytosolic translocation of SIRT1

NASA Astrophysics Data System (ADS)

Meng, Chengbo; Xing, Da; Wu, Shengnan; Huang, Lei

2010-02-01

Sirtuin type 1 (SIRT1), a NAD+-dependent histone deacetylases, plays a critical role in cellular senescence, aging and longevity. In general, SIRT1 is localized in nucleus and is believed as a nuclear protein. Though overexpression of SIRT1 delays senescence, SIRT1-protein levels decline naturally in thymus and heart during aging. In the present studies, we investigated the subcellular localization of SIRT1 in response to growth factor deprivation in African green monkey SV40-transformed kidney fibroblast cells (COS-7). Using SIRT1-EGFP fluorescence reporter, we found that SIRT1 localized to nucleus in physiological conditions. We devised a model enabling cell senescence via growth factor deprivation, and we found that SIRT1 partially translocated to cytosol under the treatment, suggesting a reduced level of SIRT1's activity. We found PI3K/Akt pathway was involved in the inhibition of SIRT1's cytosolic translocation, because inhibition of these kinases significantly decreased the amount of SIRT1 maintained in nucleus. Taken together, we demonstrated that growth factor deprivation induces cytosolic translocation of SIRT1, which suggesting a possible connection between cytoplasm-localized SIRT1 and the aging process.

Nfatc1 Is a Functional Transcriptional Factor Mediating Nell-1-Induced Runx3 Upregulation in Chondrocytes.

PubMed

Li, Chenshuang; Zheng, Zhong; Zhang, Xinli; Asatrian, Greg; Chen, Eric; Song, Richard; Culiat, Cymbeline; Ting, Kang; Soo, Chia

2018-01-06

Neural EGFL like 1 (Nell-1) is essential for chondrogenic differentiation, maturation, and regeneration. Our previous studies have demonstrated that Nell-1's pro-chondrogenic activities are predominantly reliant upon runt-related transcription factor 3 (Runx3)-mediated Indian hedgehog (Ihh) signaling. Here, we identify the nuclear factor of activated T-cells 1 (Nfatc1) as the key transcriptional factor mediating the Nell-1 → Runx3 signal transduction in chondrocytes. Using chromatin immunoprecipitation assay, we were able to determine that Nfatc1 binds to the -833--810 region of the Runx3 -promoter in response to Nell-1 treatment. By revealing the Nell-1 → Nfatc1 → Runx3 → Ihh cascade, we demonstrate the involvement of Nfatc1, a nuclear factor of activated T-cells, in chondrogenesis, while providing innovative insights into developing a novel therapeutic strategy for cartilage regeneration and other chondrogenesis-related conditions.

Factorization and resummation: A new paradigm to improve gravitational wave amplitudes. II. The higher multipolar modes

NASA Astrophysics Data System (ADS)

Messina, Francesco; Maldarella, Alberto; Nagar, Alessandro

2018-04-01

The factorization and resummation approach of Nagar and Shah [Phys. Rev. D 94, 104017 (2016), 10.1103/PhysRevD.94.104017], designed to improve the strong-field behavior of the post-Newtonian (PN) residual waveform amplitudes fℓm's entering the effective-one-body, circularized, gravitational waveform for spinning coalescing binaries, is improved and generalized here to all multipoles up to ℓ=6 . For a test particle orbiting a Kerr black hole, each multipolar amplitude is truncated at relative 6 PN order, both for the orbital (nonspinning) and spin factors. By taking a certain Padé approximant (typically the P24 one) of the orbital factor in conjunction with the inverse Taylor (iResum) representation of the spin factor, it is possible to push the analytical/numerical agreement of the energy flux at the level of 5% at the last-stable orbit for a quasimaximally spinning black hole with dimensionless spin parameter +0.99 . When the procedure is generalized to comparable-mass binaries, each orbital factor is kept at relative 3+3 PN order; i.e., the globally 3 PN-accurate comparable-mass terms are hybridized with higher-PN test-particle terms up to 6 PN relative order in each mode. The same Padé resummation is used for continuity. By contrast, the spin factor is only kept at the highest comparable-mass PN order currently available. We illustrate that the consistency between different truncations in the spin content of the waveform amplitudes is more marked in the resummed case than when using the standard Taylor-expanded form of Pan et al. [Phys. Rev. D 83, 064003 (2011), 10.1103/PhysRevD.83.064003]. We finally introduce a method to consistently hybridize comparable-mass and test-particle information also in the presence of spin (including the spin of the particle), discussing it explicitly for the ℓ=m =2 spin-orbit and spin-square terms. The improved, factorized and resummed, multipolar waveform amplitudes presented here are expected to set a new standard for

Statistical analysis of the factors that influenced the mechanical properties improvement of cassava starch films

NASA Astrophysics Data System (ADS)

Monteiro, Mayra; Oliveira, Victor; Santos, Francisco; Barros Neto, Eduardo; Silva, Karyn; Silva, Rayane; Henrique, João; Chibério, Abimaelle

2017-08-01

In order to obtain cassava starch films with improved mechanical properties in relation to the synthetic polymer in the packaging production, a complete factorial design 23 was carried out in order to investigate which factor significantly influences the tensile strength of the biofilm. The factors to be investigated were cassava starch, glycerol and modified clay contents. Modified bentonite clay was used as a filling material of the biofilm. Glycerol was the plasticizer used to thermoplastify cassava starch. The factorial analysis suggested a regression model capable of predicting the optimal mechanical property of the cassava starch film from the maximization of the tensile strength. The reliability of the regression model was tested by the correlation established with the experimental data through the following statistical analyse: Pareto graph. The modified clay was the factor of greater statistical significance on the observed response variable, being the factor that contributed most to the improvement of the mechanical property of the starch film. The factorial experiments showed that the interaction of glycerol with both modified clay and cassava starch was significant for the reduction of biofilm ductility. Modified clay and cassava starch contributed to the maximization of biofilm ductility, while glycerol contributed to the minimization.

Achieving high power factor and output power density in p-type half-Heuslers Nb1-xTixFeSb.

PubMed

He, Ran; Kraemer, Daniel; Mao, Jun; Zeng, Lingping; Jie, Qing; Lan, Yucheng; Li, Chunhua; Shuai, Jing; Kim, Hee Seok; Liu, Yuan; Broido, David; Chu, Ching-Wu; Chen, Gang; Ren, Zhifeng

2016-11-29

Improvements in thermoelectric material performance over the past two decades have largely been based on decreasing the phonon thermal conductivity. Enhancing the power factor has been less successful in comparison. In this work, a peak power factor of ∼106 μW⋅cm -1 ⋅K -2 is achieved by increasing the hot pressing temperature up to 1,373 K in the p-type half-Heusler Nb 0.95 Ti 0.05 FeSb. The high power factor subsequently yields a record output power density of ∼22 W⋅cm -2 based on a single-leg device operating at between 293 K and 868 K. Such a high-output power density can be beneficial for large-scale power generation applications.

Achieving high power factor and output power density in p-type half-Heuslers Nb1-xTixFeSb

PubMed Central

He, Ran; Kraemer, Daniel; Mao, Jun; Zeng, Lingping; Jie, Qing; Lan, Yucheng; Li, Chunhua; Shuai, Jing; Kim, Hee Seok; Liu, Yuan; Broido, David; Chu, Ching-Wu; Chen, Gang; Ren, Zhifeng

2016-01-01

Improvements in thermoelectric material performance over the past two decades have largely been based on decreasing the phonon thermal conductivity. Enhancing the power factor has been less successful in comparison. In this work, a peak power factor of ∼106 μW⋅cm−1⋅K−2 is achieved by increasing the hot pressing temperature up to 1,373 K in the p-type half-Heusler Nb0.95Ti0.05FeSb. The high power factor subsequently yields a record output power density of ∼22 W⋅cm−2 based on a single-leg device operating at between 293 K and 868 K. Such a high-output power density can be beneficial for large-scale power generation applications. PMID:27856743

Heat shock factor 1 suppresses the HIV-induced inflammatory response by inhibiting nuclear factor-κB.

PubMed

Pan, Xiaoyan; Lin, Jian; Zeng, Xiaoyun; Li, Wenjuan; Wu, Wenjiao; Lu, Wan Zhen; Liu, Jing; Liu, Shuwen

2018-05-01

The persistent inflammation aggravated by a disordered immune response is considered to be the major cause of CD4 + T cell depletion in lymphoid tissue, which impels the progression of AIDS. Here, we report that heat shock factor 1 (HSF1) works as an innate repressor of HIV-induced inflammation. The activation of HSF1 was found to accompany inflammation during HIV infection. Further research uncovered that HSF1 activation inhibited HIV-induced inflammation. In addition, HSF1 overexpression suppressed the inflammatory response induced by HIV, while HSF1 deficiency exacerbated that inflammation. Mechanistically, HSF1 was found to compete with nuclear factor-κB (NF-κB) in the nucleus. Generally, our report highlights that HSF1 is an important host factor in regulating HIV-induced inflammation and may work as a potential target for curing AIDS. Copyright © 2018 Elsevier Inc. All rights reserved.

Fibroblast growth factor homologous factor 1 interacts with NEMO to regulate NF-κB signaling in neurons.

PubMed

König, Hans-Georg; Fenner, Beau J; Byrne, Jennifer C; Schwamborn, Robert F; Bernas, Tytus; Jefferies, Caroline A; Prehn, Jochen H M

2012-12-15

Neuronal survival and plasticity critically depend on constitutive activity of the transcription factor nuclear factor-κB (NF-κB). We here describe a role for a small intracellular fibroblast growth factor homologue, the fibroblast growth factor homologous factor 1 (FHF1/FGF12), in the regulation of NF-κB activity in mature neurons. FHFs have previously been described to control neuronal excitability, and mutations in FHF isoforms give rise to a form of progressive spinocerebellar ataxia. Using a protein-array approach, we identified FHF1b as a novel interactor of the canonical NF-κB modulator IKKγ/NEMO. Co-immunoprecipitation, pull-down and GAL4-reporter experiments, as well as proximity ligation assays, confirmed the interaction of FHF1 and NEMO and demonstrated that a major site of interaction occurred within the axon initial segment. Fhf1 gene silencing strongly activated neuronal NF-κB activity and increased neurite lengths, branching patterns and spine counts in mature cortical neurons. The effects of FHF1 on neuronal NF-κB activity and morphology required the presence of NEMO. Our results imply that FHF1 negatively regulates the constitutive NF-κB activity in neurons.

Novel vascular endothelial growth factor blocker improves cellular viability and reduces hypobaric hypoxia-induced vascular leakage and oedema in rat brain.

PubMed

Saraswat, Deepika; Nehra, Sarita; Chaudhary, Kamal; CVS, Siva Prasad

2015-05-01

Vascular endothelial growth factor (VEGF) is an important cerebral angiogenic and permeability factor under hypoxia. There is a need to find effective molecules that may ameliorate hypoxia-induced cerebral oedema. In silico identification of novel candidate molecules that block VEGF-A site were identified and validated with a Ramachandran plot. The active site residues of VEGF-A were detected by Pocketfinder, CASTp, and DogSiteScorer. Based on in silico data, three VEGF-A blocker (VAB) candidate molecules (VAB1, VAB2, and VAB3) were checked for improvement in cellular viability and regulation of VEGF levels in N2a cells under hypoxia (0.5% O2 ). Additionally, the best candidate molecule's efficacy was assessed in male Sprague-Dawley rats for its ameliorative effect on cerebral oedema and vascular leakage under hypobaric hypoxia 7260 m. All experimental results were compared with the commercially available VEGF blocker sunitinib. Vascular endothelial growth factor-A blocker 1 was found most effective in increasing cellular viability and maintaining normal VEGF levels under hypoxia (0.5% oxygen) in N2a cells. Vascular endothelial growth factor-A blocker 1 effectively restored VEGF levels, decreased cerebral oedema, and reduced vascular leakage under hypobaric hypoxia when compared to sunitinib-treated rats. Vascular endothelial growth factor-A blocker 1 may be a promising candidate molecule for ameliorating hypobaric hypoxia-induced vasogenic oedema by regulating VEGF levels. © 2015 Wiley Publishing Asia Pty Ltd.

Factors influencing variation in physician adenoma detection rates: a theory-based approach for performance improvement.

PubMed

Atkins, Louise; Hunkeler, Enid M; Jensen, Christopher D; Michie, Susan; Lee, Jeffrey K; Doubeni, Chyke A; Zauber, Ann G; Levin, Theodore R; Quinn, Virginia P; Corley, Douglas A

2016-03-01

Interventions to improve physician adenoma detection rates for colonoscopy have generally not been successful, and there are little data on the factors contributing to variation that may be appropriate targets for intervention. We sought to identify factors that may influence variation in detection rates by using theory-based tools for understanding behavior. We separately studied gastroenterologists and endoscopy nurses at 3 Kaiser Permanente Northern California medical centers to identify potentially modifiable factors relevant to physician adenoma detection rate variability by using structured group interviews (focus groups) and theory-based tools for understanding behavior and eliciting behavior change: the Capability, Opportunity, and Motivation behavior model; the Theoretical Domains Framework; and the Behavior Change Wheel. Nine factors potentially associated with adenoma detection rate variability were identified, including 6 related to capability (uncertainty about which types of polyps to remove, style of endoscopy team leadership, compromised ability to focus during an examination due to distractions, examination technique during withdrawal, difficulty detecting certain types of adenomas, and examiner fatigue and pain), 2 related to opportunity (perceived pressure due to the number of examinations expected per shift and social pressure to finish examinations before scheduled breaks or the end of a shift), and 1 related to motivation (valuing a meticulous examination as the top priority). Examples of potential intervention strategies are provided. By using theory-based tools, this study identified several novel and potentially modifiable factors relating to capability, opportunity, and motivation that may contribute to adenoma detection rate variability and be appropriate targets for future intervention trials. Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Insulin-like growth factor I (IGF-1) Ec/Mechano Growth factor--a splice variant of IGF-1 within the growth plate.

PubMed

Schlegel, Werner; Raimann, Adalbert; Halbauer, Daniel; Scharmer, Daniela; Sagmeister, Susanne; Wessner, Barbara; Helmreich, Magdalena; Haeusler, Gabriele; Egerbacher, Monika

2013-01-01

Human insulin-like growth factor 1 Ec (IGF-1Ec), also called mechano growth factor (MGF), is a splice variant of insulin-like growth factor 1 (IGF-1), which has been shown in vitro as well as in vivo to induce growth and hypertrophy in mechanically stimulated or damaged muscle. Growth, hypertrophy and responses to mechanical stimulation are important reactions of cartilaginous tissues, especially those in growth plates. Therefore, we wanted to ascertain if MGF is expressed in growth plate cartilage and if it influences proliferation of chondrocytes, as it does in musculoskeletal tissues. MGF expression was analyzed in growth plate and control tissue samples from piglets aged 3 to 6 weeks. Furthermore, growth plate chondrocyte cell culture was used to evaluate the effects of the MGF peptide on proliferation. We showed that MGF is expressed in considerable amounts in the tissues evaluated. We found the MGF peptide to be primarily located in the cytoplasm, and in some instances, it was also found in the nucleus of the cells. Addition of MGF peptides was not associated with growth plate chondrocyte proliferation.

Macrophage Colony-Stimulating Factor Improves Cardiac Function after Ischemic Injury by Inducing Vascular Endothelial Growth Factor Production and Survival of Cardiomyocytes

PubMed Central

Okazaki, Tatsuma; Ebihara, Satoru; Asada, Masanori; Yamanda, Shinsuke; Saijo, Yoshifumi; Shiraishi, Yasuyuki; Ebihara, Takae; Niu, Kaijun; Mei, He; Arai, Hiroyuki; Yambe, Tomoyuki

2007-01-01

Macrophage colony-stimulating factor (M-CSF), known as a hematopoietic growth factor, induces vascular endothelial growth factor (VEGF) production from skeletal muscles. However, the effects of M-CSF on cardiomyocytes have not been reported. Here, we show M-CSF increases VEGF production from cardiomyocytes, protects cardiomyocytes and myotubes from cell death, and improves cardiac function after ischemic injury. In mice, M-CSF increased VEGF production in hearts and in freshly isolated cardiomyocytes, which showed M-CSF receptor expression. In rat cell line H9c2 cardiomyocytes and myotubes, M-CSF induced VEGF production via the Akt signaling pathway, and M-CSF pretreatment protected these cells from H2O2-induced cell death. M-CSF activated Akt and extracellular signal-regulated kinase signaling pathways and up-regulated downstream anti-apoptotic Bcl-xL expression in these cells. Using goats as a large animal model of myocardial infarction, we found that M-CSF treatment after the onset of myocardial infarction by permanent coronary artery ligation promoted angiogenesis in ischemic hearts but did not reduce the infarct area. M-CSF pretreatment of the goat myocardial infarction model by coronary artery occlusion-reperfusion improved cardiac function, as assessed by hemodynamic parameters and echocardiography. These results suggest M-CSF might be a novel therapeutic agent for ischemic heart disease. PMID:17717142

Effective treatment of steatosis and steatohepatitis by fibroblast growth factor 1 in mouse models of nonalcoholic fatty liver disease.

PubMed

Liu, Weilin; Struik, Dicky; Nies, Vera J M; Jurdzinski, Angelika; Harkema, Liesbeth; de Bruin, Alain; Verkade, Henkjan J; Downes, Michael; Evans, Ronald M; van Zutphen, Tim; Jonker, Johan W

2016-02-23

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder and is strongly associated with obesity and type 2 diabetes. Currently, there is no approved pharmacological treatment for this disease, but improvement of insulin resistance using peroxisome proliferator-activated receptor-γ (PPARγ) agonists, such as thiazolidinediones (TZDs), has been shown to reduce steatosis and steatohepatitis effectively and to improve liver function in patients with obesity-related NAFLD. However, this approach is limited by adverse effects of TZDs. Recently, we have identified fibroblast growth factor 1 (FGF1) as a target of nuclear receptor PPARγ in visceral adipose tissue and as a critical factor in adipose remodeling. Because FGF1 is situated downstream of PPARγ, it is likely that therapeutic targeting of the FGF1 pathway will eliminate some of the serious adverse effects associated with TZDs. Here we show that pharmacological administration of recombinant FGF1 (rFGF1) effectively improves hepatic inflammation and damage in leptin-deficient ob/ob mice and in choline-deficient mice, two etiologically different models of NAFLD. Hepatic steatosis was effectively reduced only in ob/ob mice, suggesting that rFGF1 stimulates hepatic lipid catabolism. Potentially adverse effects such as fibrosis or proliferation were not observed in these models. Because the anti-inflammatory effects were observed in both the presence and absence of the antisteatotic effects, our findings further suggest that the anti-inflammatory property of rFGF1 is independent of its effect on lipid catabolism. Our current findings indicate that, in addition to its potent glucose-lowering and insulin-sensitizing effects, rFGF1 could be therapeutically effective in the treatment of NAFLD.

Beyond Framingham risk factors and coronary calcification: does aortic valve calcification improve risk prediction? The Heinz Nixdorf Recall Study.

PubMed

Kälsch, Hagen; Lehmann, Nils; Mahabadi, Amir A; Bauer, Marcus; Kara, Kaffer; Hüppe, Patricia; Moebus, Susanne; Möhlenkamp, Stefan; Dragano, Nico; Schmermund, Axel; Stang, Andreas; Jöckel, Karl-Heinz; Erbel, Raimund

2014-06-01

Aortic valve calcification (AVC) is considered a manifestation of atherosclerosis. In this study, we investigated whether AVC adds to cardiovascular risk prediction beyond Framingham risk factors and coronary artery calcification (CAC). A total of 3944 subjects from the population based Heinz Nixdorf Recall Study (59.3±7.7 years; 53% females) were evaluated for coronary events, stroke, and cardiovascular disease (CVD) events (including all plus CV death) over 9.1±1.9 years. CT scans were performed to quantify AVC. Cox proportional hazards regressions and Harrell's C were used to examine AVC as event predictor in addition to risk factors and CAC. During follow-up, 138 (3.5%) subjects experienced coronary events, 101 (2.6%) had a stroke, and 257 (6.5%) experienced CVD events. In subjects with AVC>0 versus AVC=0 the incidence of coronary events was 8.0% versus 3.0% (p<0.001) and the incidence of CVD events was 13.0% versus 5.7% (p<0.001). The frequency of events increased significantly with increasing AVC scores (p<0.001). After adjustment for Framingham risk factors, high AVC scores (3rd tertile) remained independently associated with coronary events (HR 2.21, 95% CI 1.28 to 3.81) and CVD events (HR 1.67, 95% CI 1.08 to 2.58). After further adjustment for CAC score, HRs were attenuated (coronary events 1.55, 95% CI 0.89 to 2.69; CVD events 1.29, 95% CI 0.83 to 2.00). When adding AVC to the model containing traditional risk factors and CAC, Harrell's C indices did not increase for coronary events (from 0.744 to 0.744) or CVD events (from 0.759 to 0.759). AVC is associated with incident coronary and CVD events independent of Framingham risk factors. However, AVC fails to improve cardiovascular event prediction over Framingham risk factors and CAC. 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.

Volume Bragg grating improves characteristic of resonantly diode-pumped Er:YAG, 1.65-μm DPSSL

NASA Astrophysics Data System (ADS)

Kudryashov, Igor; Garbuzov, Dmitri; Dubinskii, Mark

2007-02-01

Significant performance improvement of the Er(0.5%):YAG diode pumped solid state laser (DPSSL) has been achieved by pump diode spectral narrowing via implementation of external volumetric Bragg grating (VBG). Without spectral narrowing, with a pump path length of 15 mm, only 37% of 1532 nm pump was absorbed. After the VBG spectral narrowing, the absorption of the pumping radiation increased to 62%. As a result, the incident power threshold was reduced by a factor of 2.5; the efficiency increased by a factor of 1.7, resulting in a slope efficiency of ~23%. A maximum of 51 W of CW power was obtained versus 31 W without the pump spectrum narrowing.

Mortality after percutaneous coronary revascularization: Prior cardiovascular risk factor control and improved outcomes in patients with diabetes mellitus.

PubMed

Noman, Awsan; Balasubramaniam, Karthik; Alhous, M Hafez A; Lee, Kelvin; Jesudason, Peter; Rashid, Muhammad; Mamas, Mamas A; Zaman, Azfar G

2017-06-01

To assess the mortality in patients with diabetes mellitus (DM) following percutaneous coronary intervention (PCI) according to their insulin requirement and PCI setting (elective, urgent, and emergency). DM is a major risk factor to develop coronary artery disease (CAD). It is unclear if meticulous glycemic control and aggressive risk factor management in patients with DM has improved outcomes following PCI. Retrospective analysis of prospectively collected data on 9,224 patients treated with PCI at a regional tertiary center between 2008 and 2011. About 7,652 patients were nondiabetics (non-DM), 1,116 had non-insulin treated diabetes mellitus (NITDM) and 456 had ITDM. Multi-vessel coronary artery disease, renal impairment and non-coronary vascular disease were more prevalent in DM patients. Overall 30-day mortality rate was 2.4%. In a logistic regression model, the adjusted odds ratios (95% confidence intervals [CI]) for 30-day mortality were 1.28 (0.81-2.03, P = 0.34) in NITDM and 2.82 (1.61-4.94, P < 0.001) in ITDM compared with non-DM. During a median follow-up period of 641 days, longer-term post-30 day mortality rate was 5.3%. In the Cox's proportional hazard model, the hazard ratios (95% CI) for longer-term mortality were 1.15 (0.88-1.49, P = 0.31) in NITDM and 1.88 (1.38-2.55, P < 0.001) in ITDM compared with non-DM group. Similar result was observed in all three different PCI settings. In the modern era of aggressive cardiovascular risk factor control in diabetes, this study reveals higher mortality only in insulin-treated diabetic patients following PCI for stable coronary artery disease and acute coronary syndrome. Importantly, diabetic patients with good risk factor control and managed on diet or oral hypoglycemics have similar outcomes to the non-diabetic population. © 2016 The Authors Catheterization and Cardiovascular Interventions Published by Wiley Periodicals, Inc. © 2016 The Authors Catheterization and Cardiovascular

Improved graft mesenchymal stem cell survival in ischemic heart with a hypoxia-regulated heme oxygenase-1 vector.

PubMed

Tang, Yao Liang; Tang, Yi; Zhang, Y Clare; Qian, Keping; Shen, Leping; Phillips, M Ian

2005-10-04

The goal of this study was to modify mesenchymal stem cells (MSCs) cells with a hypoxia-regulated heme oxygenase-1 (HO-1) plasmid to enhance the survival of MSCs in acute myocardial infarction (MI) heart. Although stem cells are being tested clinically for cardiac repair, graft cells die in the ischemic heart because of the effects of hypoxia/reoxygenation, inflammatory cytokines, and proapoptotic factors. Heme oxygenase-1 is a key component in inhibiting most of these factors. Mesenchymal stem cells from bone marrow were transfected with either HO-1 or LacZ plasmids. Cell apoptosis was assayed in vitro after hypoxia-reoxygen treatment. In vivo, 1 x 10(6) of male MSC(HO-1), MSC(LacZ), MSCs, or medium was injected into mouse hearts 1 h after MI (n = 16/group). Cell survival was assessed in a gender-mismatched transplantation model. Apoptosis, left ventricular remodeling, and cardiac function were tested in a gender-matched model. In the ischemic myocardium, the MSC(HO-1) group had greater expression of HO-1 and a 2-fold reduction in the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate in situ nick end labeling-positive cells compared with the MSC(LacZ) group. At seven days after implantation, the survival MSC(HO-1) was five-fold greater than the MSC(LacZ) group; MSC(HO-1) also attenuated left ventricular remodeling and enhanced the functional recovery of infarcted hearts two weeks after MI. A hypoxia-regulated HO-1 vector modification of MSCs enhances the tolerance of engrafted MSCs to hypoxia-reoxygen injury in vitro and improves their viability in ischemic hearts. This demonstration is the first showing that a physiologically inducible vector expressing of HO-1 genes improves the survival of stem cells in myocardial ischemia.

Development of Inhibitors Targeting Hypoxia-Inducible Factor 1 and 2 for Cancer Therapy

PubMed Central

Yu, Tianchi

2017-01-01

Hypoxia is frequently observed in solid tumors and also one of the major obstacles for effective cancer therapies. Cancer cells take advantage of their ability to adapt hypoxia to initiate a special transcriptional program that renders them more aggressive biological behaviors. Hypoxia-inducible factors (HIFs) are the key factors that control hypoxia-inducible pathways by regulating the expression of a vast array of genes involved in cancer progression and treatment resistance. HIFs, mainly HIF-1 and -2, have become potential targets for developing novel cancer therapeutics. This article reviews the updated information in tumor HIF pathways, particularly recent advances in the development of HIF inhibitors. These inhibitors interfere with mRNA expression, protein synthesis, protein degradation and dimerization, DNA binding and transcriptional activity of HIF-1 and -2, or both. Despite efforts in the past two decades, no agents directly inhibiting HIFs have been approved for treating cancer patients. By analyzing results of the published reports, we put the perspectives at the end of the article. The therapeutic efficacy of HIF inhibitors may be improved if more efforts are devoted on developing agents that are able to simultaneously target HIF-1 and -2, increasing the penetrating capacity of HIF inhibitors, and selecting suitable patient subpopulations for clinical trials. PMID:28332352

Improved characterization of the TRAPPIST-1 planets

NASA Astrophysics Data System (ADS)

Delrez, Laetitia; Triaud, Amaury; Gillon, Michael; Demory, Brice-Olivier; Ingalls, Jim; Carey, Sean; Bolmont, Emeline; Queloz, Didier; Jehin, Emmanuel; de, Julien; Kilpatrick, Brian

2017-07-01

The aim of this DDT is to improve the characterization of the TRAPPIST-1 planets by using Spitzer to gather further high-precision infrared photometric time-series. The AORs for this program are in program ID 13067.

Insulin-Like Growth Factor 1 (IGF-1) in Parkinson's Disease: Potential as Trait-, Progression- and Prediction Marker and Confounding Factors

PubMed Central

Binder, Gerhard; Weber, Karin; Apel, Anja; Roeben, Benjamin; Deuschle, Christian; Maechtel, Mirjam; Heger, Tanja; Nussbaum, Susanne; Gasser, Thomas; Maetzler, Walter; Berg, Daniela

2016-01-01

Introduction Biomarkers indicating trait, progression and prediction of pathology and symptoms in Parkinson's disease (PD) often lack specificity or reliability. Investigating biomarker variance between individuals and over time and the effect of confounding factors is essential for the evaluation of biomarkers in PD, such as insulin-like growth factor 1 (IGF-1). Materials and Methods IGF-1 serum levels were investigated in up to 8 biannual visits in 37 PD patients and 22 healthy controls (HC) in the longitudinal MODEP study. IGF-1 baseline levels and annual changes in IGF-1 were compared between PD patients and HC while accounting for baseline disease duration (19 early stage: ≤3.5 years; 18 moderate stage: >4 years), age, sex, body mass index (BMI) and common medical factors putatively modulating IGF-1. In addition, associations of baseline IGF-1 with annual changes of motor, cognitive and depressive symptoms and medication dose were investigated. Results PD patients in moderate (130±26 ng/mL; p = .004), but not early stages (115±19, p>.1), showed significantly increased baseline IGF-1 levels compared with HC (106±24 ng/mL; p = .017). Age had a significant negative correlation with IGF-1 levels in HC (r = -.47, p = .028) and no correlation in PD patients (r = -.06, p>.1). BMI was negatively correlated in the overall group (r = -.28, p = .034). The annual changes in IGF-1 did not differ significantly between groups and were not correlated with disease duration. Baseline IGF-1 levels were not associated with annual changes of clinical parameters. Discussion Elevated IGF-1 in serum might differentiate between patients in moderate PD stages and HC. However, the value of serum IGF-1 as a trait-, progression- and prediction marker in PD is limited as IGF-1 showed large inter- and intraindividual variability and may be modulated by several confounders. PMID:26967642

Disruption of hypoxia-inducible transcription factor-prolyl hydroxylase domain-1 (PHD-1-/-) attenuates ex vivo myocardial ischemia/reperfusion injury through hypoxia-inducible factor-1α transcription factor and its target genes in mice.

PubMed

Adluri, Ram Sudheer; Thirunavukkarasu, Mahesh; Dunna, Nageswara Rao; Zhan, Lijun; Oriowo, Babatunde; Takeda, Kotaro; Sanchez, Juan A; Otani, Hajime; Maulik, Gautam; Fong, Guo-Hua; Maulik, Nilanjana

2011-10-01

Hypoxia-inducible transcription factor (HIF)-prolyl hydroxylases domain (PHD-1-3) are oxygen sensors that regulate the stability of the HIFs in an oxygen-dependent manner. Suppression of PHD enzymes leads to stabilization of HIFs and offers a potential treatment option for many ischemic disorders, such as peripheral artery occlusive disease, myocardial infarction, and stroke. Here, we show that homozygous disruption of PHD-1 (PHD-1(-/-)) could facilitate HIF-1α-mediated cardioprotection in ischemia/reperfused (I/R) myocardium. Wild-type (WT) and PHD-1(-/-) mice were randomized into WT time-matched control (TMC), PHD-1(-/-) TMC (PHD1TMC), WT I/R, and PHD-1(-/-) I/R (PHD1IR). Isolated hearts from each group were subjected to 30 min of global ischemia followed by 2 h of reperfusion. TMC hearts were perfused for 2 h 30 min without ischemia. Decreased infarct size (35%±0.6% vs. 49%±0.4%) and apoptotic cardiomyocytes (106±13 vs. 233±21 counts/100 high-power field) were observed in PHD1IR compared to wild-type ischemia/reperfusion (WTIR). Protein expression of HIF-1α was significantly increased in PHD1IR compared to WTIR. mRNA expression of β-catenin (1.9-fold), endothelial nitric oxide synthase (1.9-fold), p65 (1.9-fold), and Bcl-2 (2.7-fold) were upregulated in the PHD1IR compared with WTIR, which was studied by real-time quantitative polymerase chain reaction. Further, gel-shift analysis showed increased DNA binding activity of HIF-1α and nuclear factor-kappaB in PHD1IR compared to WTIR. In addition, nuclear translocation of β-catenin was increased in PHD1IR compared with WTIR. These findings indicated that silencing of PHD-1 attenuates myocardial I/R injury probably by enhancing HIF-1α/β-catenin/endothelial nitric oxide synthase/nuclear factor-kappaB and Bcl-2 signaling pathway.

The nuclear matrix protein NMP-1 is the transcription factor YY1.

PubMed Central

Guo, B; Odgren, P R; van Wijnen, A J; Last, T J; Nickerson, J; Penman, S; Lian, J B; Stein, J L; Stein, G S

1995-01-01

NMP-1 was initially identified as a nuclear matrix-associated DNA-binding factor that exhibits sequence-specific recognition for the site IV regulatory element of a histone H4 gene. This distal promoter domain is a nuclear matrix interaction site. In the present study, we show that NMP-1 is the multifunctional transcription factor YY1. Gel-shift and Western blot analyses demonstrate that NMP-1 is immunoreactive with YY1 antibody. Furthermore, purified YY1 protein specifically recognizes site IV and reconstitutes the NMP-1 complex. Western blot and gel-shift analyses indicate that YY1 is present within the nuclear matrix. In situ immunofluorescence studies show that a significant fraction of YY1 is localized in the nuclear matrix, principally but not exclusively associated with residual nucleoli. Our results confirm that NMP-1/YY1 is a ubiquitous protein that is present in both human cells and in rat osteosarcoma ROS 17/2.8 cells. The finding that NMP-1 is identical to YY1 suggests that this transcriptional regulator may mediate gene-matrix interactions. Our results are consistent with the concept that the nuclear matrix may functionally compartmentalize the eukaryotic nucleus to support regulation of gene expression. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:7479833

An Improvement of Cardiovascular Risk Factors by Omega-3 Polyunsaturated Fatty Acids.

PubMed

Yanai, Hidekatsu; Masui, Yoshinori; Katsuyama, Hisayuki; Adachi, Hiroki; Kawaguchi, Akiko; Hakoshima, Mariko; Waragai, Yoko; Harigae, Tadanao; Sako, Akahito

2018-04-01

An epidemiological survey in the Northwest Greenland reported that the Greenlanders have a lower frequency of acute myocardial infarction and diabetes mellitus. The very low incidence of ischemic heart disease in the Greenlanders was explained by consumption of a diet rich in omega-3 polyunsaturated fatty acids (PUFAs). Possible anti-atherothrombotic effects of omega-3 PUFA include an improvement of lipid metabolism such as a reduction of triglyceride and an increase of high-density lipoprotein-cholesterol (HDL-C), and glucose metabolism, anti-platelet activity, anti-inflammatory effects, an improvement of endothelial function and stabilization of atherosclerotic plaque. The present study reviews an improvement of cardiovascular risk factors such as dyslipidemia and diabetes due to consumption of omega-3 PUFA. A sufficient number of studies suggest that omega-3 PUFA supplementation reduces serum triglyceride and increases HDL-cholesterol. The mechanisms for omega-3 PUFA-mediated improvements of lipid metabolism have been partially elucidated. The studies using experimental animals, part of trials in humans, have shown the beneficial effects of omega-3 PUFA on glucose metabolism and insulin sensitivity. The meta-analysis showed that omega-3 PUFA might prevent development of diabetes in part of population. Further studies should be performed to elucidate the association of omega-3 PUFA supplementation with diabetes, in the future.

Cryptanalysis and security improvements of 'two-factor user authentication in wireless sensor networks'.

PubMed

Khan, Muhammad Khurram; Alghathbar, Khaled

2010-01-01

User authentication in wireless sensor networks (WSN) is a critical security issue due to their unattended and hostile deployment in the field. Since sensor nodes are equipped with limited computing power, storage, and communication modules; authenticating remote users in such resource-constrained environments is a paramount security concern. Recently, M.L. Das proposed a two-factor user authentication scheme in WSNs and claimed that his scheme is secure against different kinds of attack. However, in this paper, we show that the M.L. Das-scheme has some critical security pitfalls and cannot be recommended for real applications. We point out that in his scheme: users cannot change/update their passwords, it does not provide mutual authentication between gateway node and sensor node, and is vulnerable to gateway node bypassing attack and privileged-insider attack. To overcome the inherent security weaknesses of the M.L. Das-scheme, we propose improvements and security patches that attempt to fix the susceptibilities of his scheme. The proposed security improvements can be incorporated in the M.L. Das-scheme for achieving a more secure and robust two-factor user authentication in WSNs.

Disclosure of Personalized Rheumatoid Arthritis Risk Using Genetics, Biomarkers, and Lifestyle Factors to Motivate Health Behavior Improvements: A Randomized Controlled Trial.

PubMed

Sparks, Jeffrey A; Iversen, Maura D; Yu, Zhi; Triedman, Nellie A; Prado, Maria G; Miller Kroouze, Rachel; Kalia, Sarah S; Atkinson, Michael L; Mody, Elinor A; Helfgott, Simon M; Todd, Derrick J; Dellaripa, Paul F; Bermas, Bonnie L; Costenbader, Karen H; Deane, Kevin D; Lu, Bing; Green, Robert C; Karlson, Elizabeth W

2018-06-01

To determine the effect of disclosure of rheumatoid arthritis (RA) risk personalized with genetics, biomarkers, and lifestyle factors on health behavior intentions. We performed a randomized controlled trial among first-degree relatives without RA. Subjects assigned to the Personalized Risk Estimator for Rheumatoid Arthritis (PRE-RA) group received the web-based PRE-RA tool for RA risk factor education and disclosure of personalized RA risk estimates, including genotype/autoantibody results and behaviors (n = 158). Subjects assigned to the comparison arm received standard RA education (n = 80). The primary outcome was readiness for change based on the trans-theoretical model, using validated contemplation ladder scales. Increased motivation to improve RA risk-related behaviors (smoking, diet, exercise, or dental hygiene) was defined as an increase in any ladder score compared to baseline, assessed immediately, 6 weeks, and 6 months post-intervention. Subjects reported behavior change at each visit. We performed intent-to-treat analyses using generalized estimating equations for the binary outcome. Subjects randomized to PRE-RA were more likely to increase ladder scores over post-intervention assessments (relative risk 1.23, 95% confidence interval [95% CI] 1.01, 1.51) than those randomized to nonpersonalized education. At 6 months, 63.9% of PRE-RA subjects and 50.0% of comparison subjects increased motivation to improve behaviors (age-adjusted difference 15.8%; 95% CI 2.8%, 28.8%). Compared to nonpersonalized education, more PRE-RA subjects increased fish intake (45.0% versus 22.1%; P = 0.005), brushed more frequently (40.7% versus 22.9%; P = 0.01), flossed more frequently (55.7% versus 34.8%; P = 0.004), and quit smoking (62.5% versus 0.0% among 11 smokers; P = 0.18). Disclosure of RA risk personalized with genotype/biomarker results and behaviors increased motivation to improve RA risk-related behaviors. Personalized medicine approaches may motivate health

Phthalimide neovascular factor 1 (PNF1) modulates MT1-MMP activity in human microvascular endothelial cells

PubMed Central

Wieghaus, Kristen A.; Gianchandani, Erwin P.; Neal, Rebekah A.; Paige, Mikell A.; Brown, Milton L.; Papin, Jason A.; Botchwey, Edward A.

2009-01-01

We are creating synthetic pharmaceuticals with angiogenic activity and potential to promote vascular invasion. We previously demonstrated that one of these molecules, phthalimide neovascular factor 1 (PNF1), significantly expands microvascular networks in vivo following sustained release from poly(lactic-co-glycolic acid) (PLAGA) films. In addition, to probe PNF1 mode-of-action, we recently applied a novel pathway-based compendium analysis to a multi-timepoint, controlled microarray dataset of PNF1-treated (versus control) human microvascular endothelial cells (HMVECs), and we identified induction of tumor necrosis factor-alpha (TNF-α) and, subsequently, transforming growth factor-beta (TGF-β) signaling networks by PNF1. Here we validate this microarray data-set with quantitative real-time polymerase chain reaction (RT-PCR) analysis. Subsequently, we probe this dataset and identify three specific TGF-β-induced genes with regulation by PNF1 conserved over multiple timepoints—amyloid beta (A4) precursor protein (APP), early growth response 1 (EGR-1), and matrix metalloproteinase 14 (MMP14 or MT1-MMP)—that are also implicated in angiogenesis. We further focus on MMP14 given its unique role in angiogenesis, and we validate MT1-MMP modulation by PNF1 with an in vitro fluorescence assay that demonstrates the direct effects that PNF1 exerts on functional metalloproteinase activity. We also utilize endothelial cord formation in collagen gels to show that PNF1-induced stimulation of endothelial cord network formation in vitro is in some way MT1-MMP-dependent. Ultimately, this new network analysis of our transcriptional footprint characterizing PNF1 activity 1–48 h post-supplementation in HMVECs coupled with corresponding validating experiments suggests a key set of a few specific targets that are involved in PNF1 mode-of-action and important for successful promotion of the neovascularization that we have observed by the drug in vivo. PMID:19326468

Phthalimide neovascular factor 1 (PNF1) modulates MT1-MMP activity in human microvascular endothelial cells.

PubMed

Wieghaus, Kristen A; Gianchandani, Erwin P; Neal, Rebekah A; Paige, Mikell A; Brown, Milton L; Papin, Jason A; Botchwey, Edward A

2009-07-01

We are creating synthetic pharmaceuticals with angiogenic activity and potential to promote vascular invasion. We previously demonstrated that one of these molecules, phthalimide neovascular factor 1 (PNF1), significantly expands microvascular networks in vivo following sustained release from poly(lactic-co-glycolic acid) (PLAGA) films. In addition, to probe PNF1 mode of action, we recently applied a novel pathway-based compendium analysis to a multi-timepoint, controlled microarray data set of PNF1-treated (vs. control) human microvascular endothelial cells (HMVECs), and we identified induction of tumor necrosis factor-alpha (TNF-alpha) and, subsequently, transforming growth factor-beta (TGF-beta) signaling networks by PNF1. Here we validate this microarray data set with quantitative real-time polymerase chain reaction (RT-PCR) analysis. Subsequently, we probe this data set and identify three specific TGF-beta-induced genes with regulation by PNF1 conserved over multiple timepoints-amyloid beta (A4) precursor protein (APP), early growth response 1 (EGR-1), and matrix metalloproteinase 14 (MMP14 or MT1-MMP)-that are also implicated in angiogenesis. We further focus on MMP14 given its unique role in angiogenesis, and we validate MT1-MMP modulation by PNF1 with an in vitro fluorescence assay that demonstrates the direct effects that PNF1 exerts on functional metalloproteinase activity. We also utilize endothelial cord formation in collagen gels to show that PNF1-induced stimulation of endothelial cord network formation in vitro is in some way MT1-MMP-dependent. Ultimately, this new network analysis of our transcriptional footprint characterizing PNF1 activity 1-48 h post-supplementation in HMVECs coupled with corresponding validating experiments suggests a key set of a few specific targets that are involved in PNF1 mode of action and important for successful promotion of the neovascularization that we have observed by the drug in vivo.

Saxagliptin Induces β-Cell Proliferation through Increasing Stromal Cell-Derived Factor-1α In Vivo and In Vitro.

PubMed

Li, Chun-Jun; Sun, Bei; Fang, Qian-Hua; Ding, Min; Xing, Yun-Zhi; Chen, Li-Ming; Yu, De-Min

2017-01-01

Dipeptidyl peptidase-4 inhibitors, such as saxagliptin, have been reported to have beneficial effects on β-cell function, but the specific underlying mechanism remains unclear. Stromal cell-derived factor-1α (SDF-1α), a chemokine produced in multiple organs, has been considered as a crucial regulator in promoting β-cell survival. Here, we speculate that SDF-1α might mediate the effect of saxagliptin on improving β-cell function. After 12-week saxagliptin treatment in high-fat diet/streptozotocin-induced diabetic rats, significant improvement in pancreas insulin secretion capacity evaluated by hyperglycemia clamp and increased β-cell to α-cell areas ratio were observed. Saxagliptin significantly induced β-cell proliferation and upregulated the expression of proliferation-related factors including c-myc and cyclind D1 determined with western blotting from the isolated islets. The expression/activity of DPP-4 was significantly reduced and paralleled with the restoration of SDF-1α levels in the saxagliptin-treated diabetic rats, subsequently the key WNT-signaling regulators, β-catenin, and AKT were activated. However, the effect of saxagliptin inducing β-cell proliferation was attenuated when we silenced the SDF-1α receptor (CXCR4) with RNAi in INS cell lines. Collectively, our data indicate that SDF-1α mediates the protective effect of saxagliptin on β-cell proliferation, suggesting that DPP-4 inhibitors have the potential role on delaying β-cell failure and SDF-1α could be a therapeutic target of β-cell regeneration.

Saxagliptin Induces β-Cell Proliferation through Increasing Stromal Cell-Derived Factor-1α In Vivo and In Vitro

PubMed Central

Li, Chun-Jun; Sun, Bei; Fang, Qian-Hua; Ding, Min; Xing, Yun-Zhi; Chen, Li-Ming; Yu, De-Min

2017-01-01

Dipeptidyl peptidase-4 inhibitors, such as saxagliptin, have been reported to have beneficial effects on β-cell function, but the specific underlying mechanism remains unclear. Stromal cell-derived factor-1α (SDF-1α), a chemokine produced in multiple organs, has been considered as a crucial regulator in promoting β-cell survival. Here, we speculate that SDF-1α might mediate the effect of saxagliptin on improving β-cell function. After 12-week saxagliptin treatment in high-fat diet/streptozotocin-induced diabetic rats, significant improvement in pancreas insulin secretion capacity evaluated by hyperglycemia clamp and increased β-cell to α-cell areas ratio were observed. Saxagliptin significantly induced β-cell proliferation and upregulated the expression of proliferation-related factors including c-myc and cyclind D1 determined with western blotting from the isolated islets. The expression/activity of DPP-4 was significantly reduced and paralleled with the restoration of SDF-1α levels in the saxagliptin-treated diabetic rats, subsequently the key WNT-signaling regulators, β-catenin, and AKT were activated. However, the effect of saxagliptin inducing β-cell proliferation was attenuated when we silenced the SDF-1α receptor (CXCR4) with RNAi in INS cell lines. Collectively, our data indicate that SDF-1α mediates the protective effect of saxagliptin on β-cell proliferation, suggesting that DPP-4 inhibitors have the potential role on delaying β-cell failure and SDF-1α could be a therapeutic target of β-cell regeneration. PMID:29230196

Purification and characterization of human mitochondrial transcription factor 1.

PubMed Central

Fisher, R P; Clayton, D A

1988-01-01

We purified to near homogeneity a transcription factor from human KB cell mitochondria. This factor, designated mitochondrial transcription factor 1 (mtTF1), is required for the in vitro recognition of both major promoters of human mitochondrial DNA by the homologous mitochondrial RNA polymerase. Furthermore, it has been shown to bind upstream regulatory elements of the two major promoters. After separation from RNA polymerase by phosphocellulose chromatography, mtTF1 was chromatographed on a MonoQ anion-exchange fast-performance liquid chromatography column. Analysis of mtTF1-containing fractions by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a single major polypeptide with an Mr of approximately 25,000. Centrifugation in analytical glycerol gradients indicated a sedimentation coefficient of approximately 2.5 S, consistent with a monomeric 25-kilodalton protein. Finally, when the 25-kilodalton polypeptide was excised from a stained sodium dodecyl sulfate-polyacrylamide gel and allowed to renature, it regained DNA-binding and transcriptional stimulatory activities at both promoters. Although mtTF1 is the only mitochondrial DNA-binding transcription factor to be purified and characterized, its properties, such as a high affinity for random DNA and a weak specificity for one of its target sequences, may typify this class of regulatory proteins. Images PMID:3211148

Prosurvival Factors Improve Functional Engraftment of Myogenically Converted Dermal Cells into Dystrophic Skeletal Muscle

PubMed Central

Muir, Lindsey A.; Murry, Charles E.

2016-01-01

In Duchenne muscular dystrophy (DMD) and other muscle wasting disorders, cell therapies are a promising route for promoting muscle regeneration by supplying a functional copy of the missing dystrophin gene and contributing new muscle fibers. The clinical application of cell-based therapies is resource intensive, and it will therefore be necessary to address key limitations that reduce cell engraftment into muscle tissue. A pressing issue is poor donor cell survival following transplantation, which in preclinical studies limits the ability to effectively test the impact of cell-based therapy on whole muscle function. We, therefore, sought to improve engraftment and the functional impact of in vivo myogenically converted dermal fibroblasts (dFbs) using a prosurvival cocktail (PSC) that includes heat shock followed by treatment with insulin-like growth factor-1, a caspase inhibitor, a Bcl-XL peptide, a KATP channel opener, basic fibroblast growth factor, Matrigel, and cyclosporine A. Advantages of dFbs include compatibility with the autologous setting, ease of isolation, and greater proliferative potential than DMD satellite cells. dFbs expressed tamoxifen-inducible MyoD and carried a mini-dystrophin gene driven by a muscle-specific promoter. After transplantation into muscles of mdx mice, a 70% reduction in donor cells was observed by day 5, and a 94% reduction by day 28. However, treatment with PSC gave a nearly three-fold increase in donor cells in early engraftment, and greatly increased the number of donor-contributed muscle fibers and total engrafted area in transplanted muscles. Furthermore, dystrophic muscles that received dFbs with PSC displayed reduced injury with eccentric contractions and an increase in maximum isometric force. Thus, enhancing survival of myogenic cells increases engraftment and improves structure and function of dystrophic muscle. PMID:27503462

Human Hepatocyte Growth Factor (hHGF)-Modified Hepatic Oval Cells Improve Liver Transplant Survival

PubMed Central

Li, Li; Ran, Jiang-Hua; Li, Xue-Hua; Liu, Zhi-Heng; Liu, Gui-Jie; Gao, Yan-Chao; Zhang, Xue-Li; Sun, Hiu-Dong

2012-01-01

Despite progress in the field of immunosuppression, acute rejection is still a common postoperative complication following liver transplantation. This study aims to investigate the capacity of the human hepatocyte growth factor (hHGF) in modifying hepatic oval cells (HOCs) administered simultaneously with orthotopic liver transplantation as a means of improving graft survival. HOCs were activated and isolated using a modified 2-acetylaminofluorene/partial hepatectomy (2-AAF/PH) model in male Lewis rats. A HOC line stably expressing the HGF gene was established following stable transfection of the pBLAST2-hHGF plasmid. Our results demonstrated that hHGF-modified HOCs could efficiently differentiate into hepatocytes and bile duct epithelial cells in vitro. Administration of HOCs at the time of liver transplantation induced a wider distribution of SRY-positive donor cells in liver tissues. Administration of hHGF-HOC at the time of transplantation remarkably prolonged the median survival time and improved liver function for recipients compared to these parameters in the other treatment groups (P<0.05). Moreover, hHGF-HOC administration at the time of liver transplantation significantly suppressed elevation of interleukin-2 (IL-2), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) levels while increasing the production of IL-10 and TGF-β1 (P<0.05). HOC or hHGF-HOC administration promoted cell proliferation, reduced cell apoptosis, and decreased liver allograft rejection rates. Furthermore, hHGF-modified HOCs more efficiently reduced acute allograft rejection (P<0.05 versus HOC transplantation only). Our results indicate that the combination of hHGF-modified HOCs with liver transplantation decreased host anti-graft immune responses resulting in a reduction of allograft rejection rates and prolonging graft survival in recipient rats. This suggests that HOC-based cell transplantation therapies can be developed as a means of treating severe liver injuries. PMID

Prosurvival Factors Improve Functional Engraftment of Myogenically Converted Dermal Cells into Dystrophic Skeletal Muscle.

PubMed

Muir, Lindsey A; Murry, Charles E; Chamberlain, Jeffrey S

2016-09-07

In Duchenne muscular dystrophy (DMD) and other muscle wasting disorders, cell therapies are a promising route for promoting muscle regeneration by supplying a functional copy of the missing dystrophin gene and contributing new muscle fibers. The clinical application of cell-based therapies is resource intensive, and it will therefore be necessary to address key limitations that reduce cell engraftment into muscle tissue. A pressing issue is poor donor cell survival following transplantation, which in preclinical studies limits the ability to effectively test the impact of cell-based therapy on whole muscle function. We, therefore, sought to improve engraftment and the functional impact of in vivo myogenically converted dermal fibroblasts (dFbs) using a prosurvival cocktail (PSC) that includes heat shock followed by treatment with insulin-like growth factor-1, a caspase inhibitor, a Bcl-XL peptide, a K ATP channel opener, basic fibroblast growth factor, Matrigel, and cyclosporine A. Advantages of dFbs include compatibility with the autologous setting, ease of isolation, and greater proliferative potential than DMD satellite cells. dFbs expressed tamoxifen-inducible MyoD and carried a mini-dystrophin gene driven by a muscle-specific promoter. After transplantation into muscles of mdx mice, a 70% reduction in donor cells was observed by day 5, and a 94% reduction by day 28. However, treatment with PSC gave a nearly three-fold increase in donor cells in early engraftment, and greatly increased the number of donor-contributed muscle fibers and total engrafted area in transplanted muscles. Furthermore, dystrophic muscles that received dFbs with PSC displayed reduced injury with eccentric contractions and an increase in maximum isometric force. Thus, enhancing survival of myogenic cells increases engraftment and improves structure and function of dystrophic muscle.

Prediction of response factors for gas chromatography with flame ionization detection: Algorithm improvement, extension to silylated compounds, and application to the quantification of metabolites

PubMed Central

de Saint Laumer, Jean‐Yves; Leocata, Sabine; Tissot, Emeline; Baroux, Lucie; Kampf, David M.; Merle, Philippe; Boschung, Alain; Seyfried, Markus

2015-01-01

We previously showed that the relative response factors of volatile compounds were predictable from either combustion enthalpies or their molecular formulae only 1. We now extend this prediction to silylated derivatives by adding an increment in the ab initio calculation of combustion enthalpies. The accuracy of the experimental relative response factors database was also improved and its population increased to 490 values. In particular, more brominated compounds were measured, and their prediction accuracy was improved by adding a correction factor in the algorithm. The correlation coefficient between predicted and measured values increased from 0.936 to 0.972, leading to a mean prediction accuracy of ± 6%. Thus, 93% of the relative response factors values were predicted with an accuracy of better than ± 10%. The capabilities of the extended algorithm are exemplified by (i) the quick and accurate quantification of hydroxylated metabolites resulting from a biodegradation test after silylation and prediction of their relative response factors, without having the reference substances available; and (ii) the rapid purity determinations of volatile compounds. This study confirms that Gas chromatography with a flame ionization detector and using predicted relative response factors is one of the few techniques that enables quantification of volatile compounds without calibrating the instrument with the pure reference substance. PMID:26179324

Improvement of acetic acid tolerance of Saccharomyces cerevisiae using a zinc-finger-based artificial transcription factor and identification of novel genes involved in acetic acid tolerance.

PubMed

Ma, Cui; Wei, Xiaowen; Sun, Cuihuan; Zhang, Fei; Xu, Jianren; Zhao, Xinqing; Bai, Fengwu

2015-03-01

Acetic acid is present in cellulosic hydrolysate as a potent inhibitor, and the superior acetic acid tolerance of Saccharomyces cerevisiae ensures good cell viability and efficient ethanol production when cellulosic raw materials are used as substrates. In this study, a mutant strain of S. cerevisiae ATCC4126 (Sc4126-M01) with improved acetic acid tolerance was obtained through screening strains transformed with an artificial zinc finger protein transcription factor (ZFP-TF) library. Further analysis indicated that improved acetic acid tolerance was associated with improved catalase (CAT) activity. The ZFP coding sequence associated with the improved phenotype was identified, and real-time RT-PCR analysis revealed that three of the possible genes involved in the enhanced acetic acid tolerance regulated by this ZFP-TF, namely YFL040W, QDR3, and IKS1, showed decreased transcription levels in Sc4126-M01 in the presence of acetic acid, compared to those in the control strain. Sc4126-M01 mutants having QDR3 and IKS1 deletion (ΔQDR3 and ΔIKS1) exhibited higher acetic acid tolerance than the wild-type strain under acetic acid treatment. Glucose consumption rate and ethanol productivity in the presence of 5 g/L acetic acid were improved in the ΔQDR3 mutant compared to the wild-type strain. Our studies demonstrated that the synthetic ZFP-TF library can be used to improve acetic acid tolerance of S. cerevisiae and that the employment of an artificial transcription factor can facilitate the exploration of novel functional genes involved in stress tolerance of S. cerevisiae.

Exon Specific U1 snRNAs improve ELP1 exon 20 definition and rescue ELP1 protein expression in a Familial Dysautonomia mouse model.

PubMed

Donadon, Irving; Pinotti, Mirko; Rajkowska, Katarzyna; Pianigiani, Giulia; Barbon, Elena; Morini, Elisabetta; Motaln, Helena; Rogelj, Boris; Mingozzi, Federico; Slaugenhaupt, Susan A; Pagani, Franco

2018-04-25

Familial dysautonomia (FD) is a rare genetic disease with no treatment, caused by an intronic point mutation (c.2204 + 6T>C) that negatively affects the definition of exon 20 in the Elongator complex protein 1 gene (ELP1 also known as IKBKAP). This substitution modifies the 5' splice site and, in combination with regulatory splicing factors, induces different levels of exon 20 skipping, in various tissues. Here, we evaluated the therapeutic potential of a novel class of U1 snRNA molecules, Exon-Specific U1s (ExSpeU1s), in correcting ELP1 exon 20 recognition. Lentivirus-mediated expression of ELP1-ExSpeU1 in FD fibroblasts improved ELP1 splicing and protein levels. We next focused on a transgenic mouse model that recapitulates the same tissue-specific mis-splicing seen in FD patients. Intraperitoneal delivery of ELP1-ExSpeU1s-adeno-associated virus particles successfully increased the production of full-length human ELP1 transcript and protein. This splice-switching class of molecules is the first to specifically correct the ELP1 exon 20 splicing defect. Our data provide proof of principle of ExSpeU1s-adeno-associated virus particles as a novel therapeutic strategy for FD.

Transcription factor EGR-1 suppresses the growth and transformation of human HT-1080 fibrosarcoma cells by induction of transforming growth factor beta 1.

PubMed Central

Liu, C; Adamson, E; Mercola, D

1996-01-01

The early growth response 1 (EGR-1) gene product is a transcription factor with role in differentiation and growth. We have previously shown that expression of exogenous EGR-1 in various human tumor cells unexpectedly and markedly reduces growth and tumorigenicity and, conversely, that suppression of endogenous Egr-1 expression by antisense RNA eliminates protein expression, enhances growth, and promotes phenotypic transformation. However, the mechanism of these effects remained unknown. The promoter of human transforming growth factor beta 1 (TGF-beta 1) contains two GC-rich EGR-1 binding sites. We show that expression of EGR-1 in human HT-1080 fibrosarcoma cells uses increased secretion of biologically active TGF-beta 1 in direct proportion (rPearson = 0.96) to the amount of EGR-1 expressed and addition of recombinant human TGF-beta 1 is strongly growth-suppressive for these cells. Addition of monoclonal anti-TGF-beta 1 antibodies to EGR-1-expressing HT-1080 cells completely reverses the growth inhibitory effects of EGR-1. Reporter constructs bearing the EGR-1 binding segment of the TGF-beta 1 promoter was activated 4- to 6-fold relative to a control reporter in either HT-1080 cells that stably expressed or parental cells cotransfected with an EGR-1 expression vector. Expression of delta EGR-1, a mutant that cannot interact with the corepressors, nerve growth factor-activated factor binding proteins NAB1 and NAB2, due to deletion of the repressor domain, exhibited enhanced transactivation of 2- to 3.5-fold over that of wild-type EGR-1 showing that the reporter construct reflected the appropriate in vivo regulatory context. The EGR-1-stimulated transactivation was inhibited by expression of the Wilms tumor suppressor, a known specific DNA-binding competitor. These results indicate that EGR-1 suppresses growth of human HT-1080 fibrosarcoma cells by induction of TGF-beta 1. Images Fig. 1 Fig. 5 PMID:8876223

Kruppel-like factor 2 inhibits hypoxia-inducible factor 1alpha expression and function in the endothelium.

PubMed

Kawanami, Daiji; Mahabeleshwar, Ganapati H; Lin, Zhiyong; Atkins, G Brandon; Hamik, Anne; Haldar, Saptarsi M; Maemura, Koji; Lamanna, Joseph C; Jain, Mukesh K

2009-07-31

Hypoxia-inducible factor 1 (HIF-1) is a central regulator of the hypoxic response in many cell types. In endothelial cells, HIF-1 induces the expression of key proangiogenic factors to promote angiogenesis. Recent studies have identified Kruppel-like factor 2 (KLF2) as a potent inhibitor of angiogenesis. However, the role of KLF2 in regulating HIF-1 expression and function has not been evaluated. KLF2 expression was induced acutely by hypoxia in endothelial cells. Adenoviral overexpression of KLF2 inhibited hypoxia-induced expression of HIF-1alpha and its target genes such as interleukin 8, angiopoietin-2, and vascular endothelial growth factor in endothelial cells. Conversely, knockdown of KLF2 increased expression of HIF-1alpha and its targets. Furthermore, KLF2 inhibited hypoxia-induced endothelial tube formation, whereas endothelial cells from mice with haploinsufficiency of KLF2 showed increased tube formation in response to hypoxia. Consistent with this ex vivo observation, KLF2 heterozygous mice showed increased microvessel density in the brain. Mechanistically, KLF2 promoted HIF-1alpha degradation in a von Hippel-Lindau protein-independent but proteasome-dependent manner. Finally, KLF2 disrupted the interaction between HIF-1alpha and its chaperone Hsp90, suggesting that KLF2 promotes degradation of HIF-1alpha by affecting its folding and maturation. These observations identify KLF2 as a novel inhibitor of HIF-1alpha expression and function. Therefore, KLF2 may be a target for modulating the angiogenic response in disease states.

26 CFR 1.1019-1 - Property on which lessee has made improvements.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Basis Rules of General Application § 1.1019-1... value of such property attributable to such buildings or improvements, the basis of each portion of such... building would have a depreciated value of $50,000, which value the lessor elected to report (beginning in...

26 CFR 1.1019-1 - Property on which lessee has made improvements.

Code of Federal Regulations, 2014 CFR

2014-04-01

... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Basis Rules of General Application § 1.1019-1... value of such property attributable to such buildings or improvements, the basis of each portion of such... building would have a depreciated value of $50,000, which value the lessor elected to report (beginning in...

26 CFR 1.1019-1 - Property on which lessee has made improvements.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Basis Rules of General Application § 1.1019-1... value of such property attributable to such buildings or improvements, the basis of each portion of such... building would have a depreciated value of $50,000, which value the lessor elected to report (beginning in...

26 CFR 1.1019-1 - Property on which lessee has made improvements.

Code of Federal Regulations, 2012 CFR

2012-04-01

... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Basis Rules of General Application § 1.1019-1... value of such property attributable to such buildings or improvements, the basis of each portion of such... building would have a depreciated value of $50,000, which value the lessor elected to report (beginning in...

Human Factors Operability Timeline Analysis to Improve the Processing Flow of the Orion Spacecraft

NASA Technical Reports Server (NTRS)

Schlierf, Roland; Stambolian, Damon B.; Miller, Darcy; Posanda, Juan; Haddock, Mike; Haddad, Mike; Tran, Donald; Henderson, Gena; Barth, Tim

2010-01-01

The Constellation Program (CxP) Orion vehicle goes through several areas and stages of processing before its launched at the Kennedy Space Center. In order to have efficient and effective processing, all of the activities need to be analyzed. This was accomplished by first developing a timeline of events that included each activity, and then each activity was analyzed by operability experts and human factors experts with spacecraft processing experience. This papers focus is to explain the results and the process for developing this human factors operability timeline analysis to improve the processing flow of Orion.

TabHLH1, a bHLH-type transcription factor gene in wheat, improves plant tolerance to Pi and N deprivation via regulation of nutrient transporter gene transcription and ROS homeostasis.

PubMed

Yang, Tongren; Hao, Lin; Yao, Sufei; Zhao, Yuanyuan; Lu, Wenjing; Xiao, Kai

2016-07-01

Basic helix-loop-helix (bHLH) transcription factors (TFs) comprise a large TF family and act as crucial regulators in various biological processes in plants. Here, we report the functional characterization of TabHLH1, a bHLH TF member in wheat (Triticum aestivum). TabHLH1 shares conserved bHLH domain and targets to nucleus with transactivation activity. Upon Pi and N deprivation, the expression of TabHLH1 was up-regulated in roots and leaves, showing a pattern to be gradually increased within 23-h treatment regimes. The lines with overexpression of TabHLH1 exhibited drastically improved tolerance to Pi and N deprivation, showing larger plant phenotype, more biomass, higher concentration and more accumulation of P and N than wild type (WT) upon the Pi- and N-starvation stresses. NtPT1 and NtNRT2.2, the genes encoding phosphate transporter (PT) and nitrate transporter (NRT) in tobacco, respectively, showed up-regulated expression in TabHLH1-overexpressing plants; knockdown expression of them led to deteriorated growth feature, lowered biomass, and decreased nutrient accumulation of plants under Pi- and N-deficient conditions. Compared with WT, the TabHLH1-overexpressing plants also showed lowered reactive oxygen species (ROS) accumulation and improved antioxidant enzyme (AE) activities, such as those of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD). NtSOD1, NtCAT1, and NtPOD1;6 that encode SOD, CAT, and POD, respectively, were up-regulated in TabHLH1-overexpressing plants. Further knockdown of these AE gene expression caused reduced antioxidant enzymatic activities, indicative of their crucial roles in mediating cellular ROS homeostasis in Pi- and N-starvation conditions. Together, TabHLH1 plays an important role in mediating adaptation to the Pi- and N-starvation stresses through transcriptional regulation of a set of genes encoding PT, NRT and AEs that mediate the taken up of Pi and N and the cellular homeostasis of ROS initiated by the nutrient

Effects of Nuclear Factor-E2-related factor 2/Heme Oxygenase 1 on splanchnic hemodynamics in experimental cirrhosis with portal hypertension.

PubMed

Qin, Jun; He, Yue; Duan, Ming; Luo, Meng

2017-05-01

We explored the effects of Nuclear Factor-E2-related factor 2 (Nrf2) and Heme Oxygenase 1 (HO-1) on splanchnic hemodynamics in portal hypertensive rats. Experimental cirrhosis with portal hypertension was induced by intraperitoneal injection of carbon tetrachloride. The expression of proteins was examined by immunoblotting. Hemodynamic studies were performed by radioactive microspheres. The vascular perfusion system was used to measure the contractile response of mesentery arterioles in rats. Nrf2 expression in the nucleus and HO-1 expression in cytoplasm was significantly enhanced in portal hypertensive rats. Portal pressure, as well as regional blood flow, increased significantly in portal hypertension and can be blocked by tin protoporphyrin IX. The expression of endogenous nitric oxide synthase and vascular endothelial growth factors increased significantly compared to normal rats, while HO-1 inhibition decreased the expression of these proteins significantly. The contractile response of mesenteric arteries decreased in portal hypertension, but can be partially recovered through tin protoporphyrin IX treatment. The expression of Nrf2/HO-1 increased in mesenteric arteries of portal hypertensive rats, which was related to oxidative stress. HO-1was involved in increased portal pressure and anomaly splanchnic hemodynamics in portal hypertensive rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Role of Insulinlike Growth Factor 1 in Fetal Development and in the Early Postnatal Life of Premature Infants

PubMed Central

Hellström, Ann; Ley, David; Hansen-Pupp, Ingrid; Hallberg, Boubou; Ramenghi, Luca A.; Löfqvist, Chatarina; Smith, Lois E. H.; Hård, Anna-Lena

2018-01-01

The neonatal period of very preterm infants is often characterized by a difficult adjustment to extrauterine life, with an inadequate nutrient supply and insufficient levels of growth factors, resulting in poor growth and a high morbidity rate. Long-term multisystem complications include cognitive, behavioral, and motor dysfunction as a result of brain damage as well as visual and hearing deficits and metabolic disorders that persist into adulthood. Insulinlike growth factor 1 (IGF-1) is a major regulator of fetal growth and development of most organs especially the central nervous system including the retina. Glucose metabolism in the developing brain is controlled by IGF-1 which also stimulates differentiation and prevents apoptosis. Serum concentrations of IGF-1 decrease to very low levels after very preterm birth and remain low for most of the perinatal development. Strong correlations have been found between low neonatal serum concentrations of IGF-1 and poor brain and retinal growth as well as poor general growth with multiorgan morbidities, such as intraventricular hemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, and necrotizing enterocolitis. Experimental and clinical studies indicate that early supplementation with IGF-1 can improve growth in catabolic states and reduce brain injury after hypoxic/ischemic events. A multicenter phase II study is currently underway to determine whether intravenous replacement of human recombinant IGF-1 up to normal intrauterine serum concentrations can improve growth and development and reduce prematurity-associated morbidities. PMID:27603537

Herbal formula menoprogen alters insulin-like growth factor-1 and insulin-like growth factor binding protein-1 levels in the serum and ovaries of an aged female rat model of menopause.

PubMed

Wei, Min; Zheng, Sheng Z; Lu, Ye; Liu, Daniel; Ma, Hong; Mahady, Gail B

2015-10-01

Menoprogen (MPG), a traditional Chinese medicine formula for menopause, improves menopausal symptoms; however, its mechanism remains unknown. Previous studies have shown that MPG is not directly estrogenic; thus, the goal of this study was to investigate the effects of MPG on insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-1 (IGFBP-1) levels in an aged female rat model of menopause. In a six-arm study, 14-month-old female Sprague-Dawley rats (n = 8 per arm) were randomly divided into the following groups: untreated aged, 17β-estradiol-treated aged (estradiol [E2]), and three arms with increasing doses of MPG (162, 324, or 648 mg/kg/d). The sixth arm contained 4-month-old female Sprague-Dawley rats as a normal comparison group. Four weeks after MPG or E2 administration, animals were killed after blood draws, and ovarian tissues were excised. Levels of E2 and progesterone (P4) were determined by radioimmunoassay. Serum and ovarian tissue levels of IGF-1, IGFBP-1, and IGF-1 receptor were determined by enzyme-linked immunosorbent assay. Compared with the normal group, aged rats had significantly reduced serum levels of E2, P4, and IGF-1, and increased serum and ovarian tissue levels of IGFBP-1. MPG restored serum IGF-1 and IGFBP-1 levels and down-regulated ovarian levels of IGFBP-1, which were closely related to increases in E2 and P4 levels in aged rats. No significant differences in either IGF-1 or IGFBP-1 were observed between the three doses of MPG. MPG exerts a direct in vivo effect on aged female rats by positively regulating serum and ovarian IGF-1 and IGFBP-1 levels.

26 CFR 1.1019-1 - Property on which lessee has made improvements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Basis Rules of General Application § 1.1019-1 Property on... value of such property attributable to such buildings or improvements, the basis of each portion of such... building would have a depreciated value of $50,000, which value the lessor elected to report (beginning in...

Evolutionary pattern of improved 1-mile running performance.

PubMed

Foster, Carl; de Koning, Jos J; Thiel, Christian

2014-07-01

The official world records (WR) for the 1-mile run for men (3:43.13) and for women (4:12.58) have improved 12.2% and 32.3%, respectively, since the first WR recognized by the International Association of Athletics Federations. Previous observations have suggested that the pacing pattern for successive laps is characteristically faster-slower-slowest-faster. However, modeling studies have suggested that uneven energy-output distribution, particularly a high velocity at the end of the race, is essentially wasted kinetic energy that could have been used to finish sooner. Here the authors report that further analysis of the pacing pattern in 32 men's WR races is characterized by a progressive reduction in the within-lap variation of pace, suggesting that improving the WR in the 1-mile run is as much about how energetic resources are managed as about the capacity of the athletes performing the race. In the women's WR races, the pattern of lap times has changed little, probably secondary to a lack of depth in the women's fields. Contemporary WR performances have been achieved a coefficient of variation of lap times on the order of 1.5-3.0%. Reasonable projection suggests that the WR is overdue for improving and may require lap times with a coefficient of variation of ~1%.

Dark chocolate consumption improves leukocyte adhesion factors and vascular function in overweight men.

PubMed

Esser, Diederik; Mars, Monica; Oosterink, Els; Stalmach, Angelique; Müller, Michael; Afman, Lydia A

2014-03-01

Flavanol-enriched chocolate consumption increases endothelium-dependent vasodilation. Most research so far has focused on flow-mediated dilation (FMD) only; the effects on other factors relevant to endothelial health, such as inflammation and leukocyte adhesion, have hardly been addressed. We investigated whether consumption of regular dark chocolate also affects other markers of endothelial health, and whether chocolate enrichment with flavanols has additional benefits. In a randomized double-blind crossover study, the effects of acute and of 4 wk daily consumption of high flavanol chocolate (HFC) and normal flavanol chocolate (NFC) on FMD, augmentation index (AIX), leukocyte count, plasma cytokines, and leukocyte cell surface molecules in overweight men (age 45-70 yr) were investigated. Sensory profiles and motivation scores to eat chocolate were also collected. Findings showed that a 4 wk chocolate intake increased FMD by 1%, which was paralleled by a decreased AIX of 1%, decreased leukocyte cell count, decreased plasma sICAM1 and sICAM3, and decreased leukocyte adhesion marker expression (P<0.05 for time effect), with no difference between HFC and NFC consumption. Flavanol enrichment did affect taste and negatively affected motivation to consume chocolate. This study provides new insights on how chocolate affects endothelial health by demonstrating that chocolate consumption, besides improving vascular function, also lowers the adherence capacity of leukocytes in the circulation.

[Effects of a non-face-to-face behavioral intervention on poor sleepers and factors affecting improvement of sleep].

PubMed

Amamoto, Yuko; Adachi, Yoshiko; Kunituka, Kouko; Kumagai, Shuzo

2010-03-01

The purposes of this study were 1) to re-examine effects obtained from previous research of a non-face-to-face behavioral intervention in poorer sleepers and 2) to examine the factors impacting on improvement of sleep. The subjects were 178 poor sleepers who participated in an intervention for sleep improvement. The educational procedures comprised a minimal behavioral self-help package for one month that featured self- learning and self- monitoring of practical target habits for change. It was non face-to-face program conducted by only one member of staff. Subjects were asked to answer a questionnaire before and after the intervention. To reexamine the effects of this program found in our previous research, 9 sleep indices, sleep quality, and sleep-related behaviors were compared between before and after intervention. The sleep indices were total sleep time, sleep onset latency, sleep efficiency etc. Subjects were divided into an improvement group (n = 63) and a non-improvement group (n = 115) using a cutoff value for average change in sleep onset latency and sleep efficiency. After comparison of sleep and behavior between the two groups, logistic regression analysis was conducted to select parameters affecting improvement with this program. Total sleep time was significantly increased from 5.7 h to 6.1 h, sleep onset time decreased 18 minutes, and sleep efficiency improved 5.6 points. With 8 of 9 sleep-related behaviors, the proportion of subjects having an undesirable habit significantly decreased. The mean total number of desirable habit' changes was 2.63 in the improvement group and significantly higher than the 2.06 in the non-improvement group. Logistic regression analysis demonstrated that large sleep onset latency at baseline and beginning of regular exercise significantly affected the improvement of sleep in the subjects, after adjusting for all other parameters. The effects revealed by our previous research were reconfirmed. It is suggested that this

Insulin-Like Growth Factor I (IGF-1) Ec/Mechano Growth Factor – A Splice Variant of IGF-1 within the Growth Plate

PubMed Central

Schlegel, Werner; Raimann, Adalbert; Halbauer, Daniel; Scharmer, Daniela; Sagmeister, Susanne; Wessner, Barbara; Helmreich, Magdalena; Haeusler, Gabriele; Egerbacher, Monika

2013-01-01

Human insulin-like growth factor 1 Ec (IGF-1Ec), also called mechano growth factor (MGF), is a splice variant of insulin-like growth factor 1 (IGF-1), which has been shown in vitro as well as in vivo to induce growth and hypertrophy in mechanically stimulated or damaged muscle. Growth, hypertrophy and responses to mechanical stimulation are important reactions of cartilaginous tissues, especially those in growth plates. Therefore, we wanted to ascertain if MGF is expressed in growth plate cartilage and if it influences proliferation of chondrocytes, as it does in musculoskeletal tissues. MGF expression was analyzed in growth plate and control tissue samples from piglets aged 3 to 6 weeks. Furthermore, growth plate chondrocyte cell culture was used to evaluate the effects of the MGF peptide on proliferation. We showed that MGF is expressed in considerable amounts in the tissues evaluated. We found the MGF peptide to be primarily located in the cytoplasm, and in some instances, it was also found in the nucleus of the cells. Addition of MGF peptides was not associated with growth plate chondrocyte proliferation. PMID:24146828

26 CFR 1.167(i)-1 - Depreciation of improvements in the case of mines, etc.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Depreciation of improvements in the case of... and Corporations § 1.167(i)-1 Depreciation of improvements in the case of mines, etc. Property used in... depreciation provided in section 611 shall be treated for all purposes of the Code as if it were property...

How to Improve Teaching Practices: The Role of Teacher Motivation, Organizational Factors, and Leadership Practices

ERIC Educational Resources Information Center

Thoonen, Erik E. J.; Sleegers, Peter J. C.; Oort, Frans J.; Peetsma, Thea T. D.; Geijsel, Femke P.

2011-01-01

Purpose: Although it is expected that building schoolwide capacity for teacher learning will improve teaching practices, there is little systematic evidence to support this claim. This study aimed to examine the relative impact of transformational leadership practices, school organizational conditions, teacher motivational factors, and teacher…

Iranian staff nurses' views of their productivity and human resource factors improving and impeding it: a qualitative study

PubMed Central

Nayeri, Nahid Dehghan; Nazari, Ali Akbar; Salsali, Mahvash; Ahmadi, Fazlollah

2005-01-01

Background Nurses, as the largest human resource element of health care systems, have a major role in providing ongoing, high-quality care to patients. Productivity is a significant indicator of professional development within any professional group, including nurses. The human resource element has been identified as the most important factor affecting productivity. This research aimed to explore nurses' perceptions and experiences of productivity and human resource factors improving or impeding it. Method A qualitative approach was used to obtain rich data; open, semi-structured interviews were also conducted. The sampling was based on the maximum variant approach; data analysis was carried out by content analysis, with the constant comparative method. Results Participants indicated that human resources issues are the most important factor in promoting or impeding their productivity. They suggested that the factors influencing effectiveness of human resource elements include: systematic evaluation of staff numbers; a sound selection process based on verifiable criteria; provision of an adequate staffing level throughout the year; full involvement of the ward sister in the process of admitting patients; and sound communication within the care team. Paying attention to these factors creates a suitable background for improved productivity and decreases negative impacts of human resource shortages, whereas ignoring or interfering with them would result in lowering of nurses' productivity. Conclusion Participants maintained that satisfactory human resources can improve nurses' productivity and the quality of care they provide; thereby fulfilling the core objective of the health care system. PMID:16212672

Factors affecting the use of patient survey data for quality improvement in the Veterans Health Administration

PubMed Central

2011-01-01

Background Little is known about how to use patient feedback to improve experiences of health care. The Veterans Health Administration (VA) conducts regular patient surveys that have indicated improved care experiences over the past decade. The goal of this study was to assess factors that were barriers to, or promoters of, efforts to improve care experiences in VA facilities. Methods We conducted case studies at two VA facilities, one with stable high scores on inpatient reports of emotional support between 2002 and 2006, and one with stable low scores over the same period. A semi-structured interview was used to gather information from staff who worked with patient survey data at the study facilities. Data were analyzed using a previously developed qualitative framework describing organizational, professional and data-related barriers and promoters to data use. Results Respondents reported more promoters than barriers to using survey data, and particularly support for improvement efforts. Themes included developing patient-centered cultures, quality improvement structures such as regular data review, and training staff in patient-centered behaviors. The influence of incentives, the role of nursing leadership, and triangulating survey data with other data on patients' views also emerged as important. It was easier to collect data on current organization and practice than those in the past and this made it difficult to deduce which factors might influence differing facility performance. Conclusions Interviews with VA staff provided promising examples of how systematic processes for using survey data can be implemented as part of wider quality improvement efforts. However, prospective studies are needed to identify the most effective strategies for using patient feedback to improve specific aspects of patient-centered care. PMID:22151714

Improved 1-year mortality in elderly patients with a hip fracture following integrated orthogeriatric treatment.

PubMed

Folbert, E C; Hegeman, J H; Vermeer, M; Regtuijt, E M; van der Velde, D; Ten Duis, H J; Slaets, J P

2017-01-01

To improve the quality of care and reduce the healthcare costs of elderly patients with a hip fracture, surgeons and geriatricians collaborated intensively due to the special needs of these patients. After treatment at the Centre for Geriatric Traumatology (CvGT), we found a significant decrease in the 1-year mortality rate in frail elderly patients compared to the historical control patients who were treated with standard care. The study aimed to evaluate the effect of an orthogeriatric treatment model on elderly patients with a hip fracture on the 1-year mortality rate and identify associated risk factors. This study included patients, aged 70 years and older, who were admitted with a hip fracture and treated in accordance with the integrated orthogeriatric treatment model of the CvGT at the Hospital Group Twente (ZGT) between April 2008 and October 2013. Data registration was carried out by several disciplines using the clinical pathways of the CvGT database. A multivariate logistic regression analysis was used to identify independent risk factors for 1-year mortality. The outcome measures for the 850 patients were compared with those of 535 historical control patients who were managed under standard care between October 2002 and March 2008. The analysis demonstrated that the 1-year mortality rate was 23.2 % (n = 197) in the CvGT group compared to 35.1 % (n = 188) in the historical control group (p < 0.001). Independent risk factors for 1-year mortality were male gender (odds ratio (OR) 1.68), increasing age (OR 1.06), higher American Society of Anesthesiologists (ASA) score (ASA 3 OR 2.43, ASA 4-5 OR 7.05), higher Charlson Comorbidity Index (CCI) (CCI 1-2 OR 1.46, CCI 3-4 OR 1.59, CCI 5 OR 2.71), malnutrition (OR 2.01), physical limitations in activities of daily living (OR 2.35), and decreasing Barthel Index (BI) (OR 0.96). After integrated orthogeriatric treatment, a significant decrease was seen in the 1-year mortality rate in the frail

Bone marrow-derived monocyte infusion improves hepatic fibrosis by decreasing osteopontin, TGF-β1, IL-13 and oxidative stress.

PubMed

de Souza, Veruska Cintia Alexandrino; Pereira, Thiago Almeida; Teixeira, Valéria Wanderley; Carvalho, Helotonio; de Castro, Maria Carolina Accioly Brelaz; D'assunção, Carolline Guimarães; de Barros, Andréia Ferreira; Carvalho, Camila Lima; de Lorena, Virgínia Maria Barros; Costa, Vláudia Maria Assis; Teixeira, Álvaro Aguiar Coelho; Figueiredo, Regina Celia Bressan Queiroz; de Oliveira, Sheilla Andrade

2017-07-28

To evaluate the therapeutic effects of bone marrow-derived CD11b + CD14 + monocytes in a murine model of chronic liver damage. Chronic liver damage was induced in C57BL/6 mice by administration of carbon tetrachloride and ethanol for 6 mo. Bone marrow-derived monocytes isolated by immunomagnetic separation were used for therapy. The cell transplantation effects were evaluated by morphometry, biochemical assessment, immunohistochemistry and enzyme-linked immunosorbent assay. CD11b + CD14 + monocyte therapy significantly reduced liver fibrosis and increased hepatic glutathione levels. Levels of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-6 and IL-1β, in addition to pro-fibrotic factors, such as IL-13, transforming growth factor-β1 and tissue inhibitor of metalloproteinase-1 also decreased, while IL-10 and matrix metalloproteinase-9 increased in the monocyte-treated group. CD11b + CD14 + monocyte transplantation caused significant changes in the hepatic expression of α-smooth muscle actin and osteopontin. Monocyte therapy is capable of bringing about improvement of liver fibrosis by reducing oxidative stress and inflammation, as well as increasing anti-fibrogenic factors.

Rufinamide, an antiepileptic drug, improves cognition and increases neurogenesis in the aged gerbil hippocampal dentate gyrus via increasing expressions of IGF-1, IGF-1R and p-CREB.

PubMed

Chen, Bai Hui; Ahn, Ji Hyeon; Park, Joon Ha; Song, Minah; Kim, Hyunjung; Lee, Tae-Kyeong; Lee, Jae Chul; Kim, Young-Myeong; Hwang, In Koo; Kim, Dae Won; Lee, Choong-Hyun; Yan, Bing Chun; Kang, Il Jun; Won, Moo-Ho

2018-04-25

Rufinamide is a novel antiepileptic drug and commonly used in the treatment of Lennox-Gastaut syndrome. In the present study, we investigated effects of rufinamide on cognitive function using passive avoidance test and neurogenesis in the hippocampal dentate gyrus using Ki-67 (a marker for cell proliferation), doublecortin (DCX, a marker for neuroblast) and BrdU/NeuN (markers for newly generated mature neurons) immunohistochemistry in aged gerbils. Aged gerbils (24-month old) were treated with 1 mg/kg and 3 mg/kg rufinamide for 4 weeks. Treatment with 3 mg/kg rufinamide, not 1 mg/kg rufinamide, significantly improved cognitive function and increased neurogenesis, showing that proliferating cells (Ki-67-immunoreactive cells), differentiating neuroblasts (DCX-immunoreactive neuroblasts) and mature neurons (BrdU/NeuN-immunoreactive cells) in the aged dentate gyrus compared with those in the control group. When we examined its mechanisms, rufinamide significantly increased immunoreactivities of insulin-like growth factor-1 (IGF-1), its receptor (IGF-1R), and phosphorylated cAMP response element binding protein (p-CREB). However, rufinamide did not show any increase in immunoreactivities of brain-derived neurotrophic factor and its receptor. Therefore, our results indicate that rufinamide can improve cognitive function and increase neurogenesis in the hippocampus of the aged gerbil via increasing expressions of IGF-1, IGF-1R and p-CREB. Copyright © 2018 Elsevier B.V. All rights reserved.

Improvement of Biodesulfurization Rate of Alginate Immobilized Rhodococcus erythropolis R1.

PubMed

Derikvand, Peyman; Etemadifar, Zahra

2014-03-01

Sulfur oxides released from the burning of oil causes severe environmental pollution. The sulfur can be removed via the 4S pathway in biodesulfurization (BDS). Immobilization approaches have been developed to prevent cell contamination of oil during the BDS process. The encapsulation of Rhodococcus erythropolis R1 in calcium alginate beads was studied in order to enhance conversion of dibenzothiophene (DBT) to 2-hydroxy biphenyl (2-HBP) as the final product. Also the effect of different factors on the BDS process was investigated. Calcium alginate capsules were prepared using peristaltic pumps with different needle sizes to control the beads sizes. Scanning electron microscopy and flow cytometry methods were used to study the distribution and viability of encapsulated cells, respectively. Two non-ionic surfactants and also nano Ƴ-Al2O3were used with the ratio of 0.5% (v/v) and 1:5 (v/v) respectively to investigate their BDS efficiency. In addition, the effect of different bead sizes and different concentrations of sodium alginate in BDS activity was studied. The 2% (w/v) sodium alginate beads with 1.5mm size were found to be the optimum for beads stability and efficient 2-HBP production. The viability of encapsulated cells decreased by 12% after 20 h of desulfurization, compared to free cells. Adding the non-ionic surfactants markedly enhanced the rate of BDS, because of increasing mass transfer of DBT to the gel matrix. In addition, Span 80 was more effective than Tween 80. The nanoƳ-Al2O3 particles could increase BDS rate by up to two-folds greater than that of the control beads. The nano Ƴ-Al2O3 can improve the immobilized biocatalyst for excellent efficiency of DBT desulfurization. Also the BDS activity can be enhanced by setting the other explained factors at optimum levels.

Ginsenoside Rb1 improves spatial learning and memory by regulation of cell genesis in the hippocampal subregions of rats.

PubMed

Liu, Lei; Hoang-Gia, Trinh; Wu, Hui; Lee, Mi-Ra; Gu, Lijuan; Wang, Chunyan; Yun, Beom-Sik; Wang, Qijun; Ye, Shengquan; Sung, Chang-Keun

2011-03-25

Ginsenoside Rb1 (Rb1) is known to improve learning and memory in hippocampus-dependent tasks. However, the cellular mechanism remains unknown. Cell genesis in hippocampus is involved in spatial learning and memory. In the present study, Rb1 was orally administrated to adult rats for 30days. The behavioral training tests indicated that Rb1 improved spatial cognitive performance of rats in Morris water maze (MWM). Furthermore, we investigated the effects of Rb1 on cell genesis in adult rats' hippocampus, using thymidine analog bromodeoxyuridine (BrdU) as a marker for dividing cells. It has been shown that hippocampal cell genesis can be influenced by several factors such as learning and exercise. In order to avoid the effects of the interfering factors, only the rats treated with Rb1 without training in MWM were used to investigate cell genesis in hippocampus. When BrdU was given to the rats 30days prior to being killed, it was shown that oral administration of Rb1 significantly increased cell survival in dentate gyrus and hippocampal subregion CA3. However, when BrdU was injected 2h prior to sacrifice, the results indicated that Rb1 had no significant influence on cell proliferation in the hippocampal subregions. Thus, an increase of cell survival in hippocampus stimulated by Rb1 may be one of the mechanisms by which ginseng facilitates spatial learning and memory. Our study also indicates that Rb1 may be developed as a therapeutic agent for patients with memory impairment. Copyright © 2011 Elsevier B.V. All rights reserved.

Factors influencing the uptake of a mass media intervention to improve child feeding in Bangladesh.

PubMed

Kim, Sunny S; Roopnaraine, Terry; Nguyen, Phuong H; Saha, Kuntal K; Bhuiyan, Mahbubul I; Menon, Purnima

2018-04-11

Mass media are increasingly used to deliver health messages to promote social and behaviour change, but there has been little evidence of mass media use for improving a set of child feeding practices, other than campaigns to promote breastfeeding. This study aimed to examine the factors influencing the uptake of infant and young child feeding messages promoted in TV spots that were launched and aired nationwide in Bangladesh. We conducted a mixed-methods study, using household surveys (n = 2,000) and semistructured interviews (n = 251) with mothers of children 0-23.9 months and other household members. Factors associated with TV spot viewing and comprehension were analysed using multivariable logistic regression models, and interview transcripts were analysed by systematic coding and iterative summaries. Exposure ranged from 36% to 62% across 6 TV spots, with comprehension ranging from 33% to 96% among those who viewed the spots. Factors associated with comprehension of TV spot messages included younger maternal age and receipt of home visits by frontline health workers. Three direct narrative spots showed correct message recall and strong believability, identification, and feasibility of practicing the recommended behaviours. Two spots that used a metaphorical and indirect narrative style were not well understood by respondents. Understanding the differences in the uptake factors may help to explain variability of impacts and ways to improve the design and implementation of mass media strategies. © 2018 The Authors. Maternal and Child Nutrition Published by John Wiley & Sons, Ltd.

Improving Patient Safety: Improving Communication.

PubMed

Bittner-Fagan, Heather; Davis, Joshua; Savoy, Margot

2017-12-01

Communication among physicians, staff, and patients is a critical element in patient safety. Effective communication skills can be taught and improved through training and awareness. The practice of family medicine allows for long-term relationships with patients, which affords opportunities for ongoing, high-quality communication. There are many barriers to effective communication, including patient factors, clinician factors, and system factors, but tools and strategies exist to address these barriers, improve communication, and engage patients in their care. Use of universal precautions for health literacy, appropriate medical interpreters, and shared decision-making are evidence-based tools that improve communication and increase patient safety. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

26 CFR 1.611-5 - Depreciation of improvements.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (CONTINUED) INCOME TAXES (CONTINUED) Natural Resources § 1.611-5 Depreciation of improvements. (a) In general. Section 611 provides in the case of mines, oil and gas wells, other natural deposits, and timber that...). (b) Special rules for mines, oil and gas wells, other natural deposits and timber. (1) For principles...

Growth factor independence-1 antagonizes a p53-induced DNA damage response pathway in lymphoblastic leukemia

PubMed Central

Khandanpour, Cyrus; Phelan, James D.; Vassen, Lothar; Schütte, Judith; Chen, Riyan; Horman, Shane R.; Gaudreau, Marie-Claude; Krongold, Joseph; Zhu, Jinfang; Paul, William E.; Dührsen, Ulrich; Göttgens, Bertie; Grimes, H. Leighton; Möröy, Tarik

2013-01-01

Summary Most patients with acute lymphoblastic leukemia (ALL) fail current treatments highlighting the need for better therapies. Since oncogenic signaling activates a p53-dependent DNA-damage response and apoptosis, leukemic cells must devise appropriate countermeasures. We show here that growth factor independence 1 (Gfi1) can serve such a function, since Gfi1 ablation exacerbates p53 responses, and lowers the threshold for p53-induced cell death. Specifically, Gfi1 restricts p53 activity and expression of pro-apoptotic p53 targets such as Bax, Noxa (Pmaip1) and Puma (Bbc3). Subsequently, Gfi1 ablation cures mice from leukemia and limits the expansion of primary human T-ALL xenografts in mice. This suggests that targeting Gfi1 could improve the prognosis of patients with T-ALL or other lymphoid leukemias. PMID:23410974

Paracrine Engineering of Human Explant-Derived Cardiac Stem Cells to Over-Express Stromal-Cell Derived Factor 1α Enhances Myocardial Repair.

PubMed

Tilokee, Everad L; Latham, Nicholas; Jackson, Robyn; Mayfield, Audrey E; Ye, Bin; Mount, Seth; Lam, Buu-Khanh; Suuronen, Erik J; Ruel, Marc; Stewart, Duncan J; Davis, Darryl R

2016-07-01

First generation cardiac stem cell products provide indirect cardiac repair but variably produce key cardioprotective cytokines, such as stromal-cell derived factor 1α, which opens the prospect of maximizing up-front paracrine-mediated repair. The mesenchymal subpopulation within explant derived human cardiac stem cells underwent lentiviral mediated gene transfer of stromal-cell derived factor 1α. Unlike previous unsuccessful attempts to increase efficacy by boosting the paracrine signature of cardiac stem cells, cytokine profiling revealed that stromal-cell derived factor 1α over-expression prevented lv-mediated "loss of cytokines" through autocrine stimulation of CXCR4+ cardiac stem cells. Stromal-cell derived factor 1α enhanced angiogenesis and stem cell recruitment while priming cardiac stem cells to readily adopt a cardiac identity. As compared to injection with unmodified cardiac stem cells, transplant of stromal-cell derived factor 1α enhanced cells into immunodeficient mice improved myocardial function and angiogenesis while reducing scarring. Increases in myocardial stromal-cell derived factor 1α content paralleled reductions in myocyte apoptosis but did not influence long-term engraftment or the fate of transplanted cells. Transplantation of stromal-cell derived factor 1α transduced cardiac stem cells increased the generation of new myocytes, recruitment of bone marrow cells, new myocyte/vessel formation and the salvage of reversibly damaged myocardium to enhance cardiac repair after experimental infarction. Stem Cells 2016;34:1826-1835. © 2016 AlphaMed Press.

Improving the Factor Structure of Psychological Scales

PubMed Central

Zhang, Xijuan; Savalei, Victoria

2015-01-01

Many psychological scales written in the Likert format include reverse worded (RW) items in order to control acquiescence bias. However, studies have shown that RW items often contaminate the factor structure of the scale by creating one or more method factors. The present study examines an alternative scale format, called the Expanded format, which replaces each response option in the Likert scale with a full sentence. We hypothesized that this format would result in a cleaner factor structure as compared with the Likert format. We tested this hypothesis on three popular psychological scales: the Rosenberg Self-Esteem scale, the Conscientiousness subscale of the Big Five Inventory, and the Beck Depression Inventory II. Scales in both formats showed comparable reliabilities. However, scales in the Expanded format had better (i.e., lower and more theoretically defensible) dimensionalities than scales in the Likert format, as assessed by both exploratory factor analyses and confirmatory factor analyses. We encourage further study and wider use of the Expanded format, particularly when a scale’s dimensionality is of theoretical interest. PMID:27182074

Regulation of the mammalian heat shock factor 1.

PubMed

Dayalan Naidu, Sharadha; Dinkova-Kostova, Albena T

2017-06-01

Living organisms are endowed with the capability to tackle various forms of cellular stress due to the presence of molecular chaperone machinery complexes that are ubiquitous throughout the cell. During conditions of proteotoxic stress, the transcription factor heat shock factor 1 (HSF1) mediates the elevation of heat shock proteins, which are crucial components of the chaperone complex machinery and function to ameliorate protein misfolding and aggregation and restore protein homeostasis. In addition, HSF1 orchestrates a versatile transcriptional programme that includes genes involved in repair and clearance of damaged macromolecules and maintenance of cell structure and metabolism, and provides protection against a broad range of cellular stress mediators, beyond heat shock. Here, we discuss the structure and function of the mammalian HSF1 and its regulation by post-translational modifications (phosphorylation, sumoylation and acetylation), proteasomal degradation, and small-molecule activators and inhibitors. © 2017 Federation of European Biochemical Societies.

Systemic pretreatment with dimethyloxalylglycine increases myocardial HIF-1α and VEGF production and improves functional recovery after acute ischemia/reperfusion.

PubMed

Poynter, Jeffrey A; Manukyan, Mariuxi C; Wang, Yue; Brewster, Benjamin D; Herrmann, Jeremy L; Weil, Brent R; Abarbanell, Aaron M; Meldrum, Daniel R

2011-08-01

Stem cells protect the heart from ischemic damage in part by the release of cytoprotective growth factors, particularly vascular endothelial growth factor (VEGF). Production of VEGF is regulated in part by levels of the transcription factor hypoxia inducible factor 1-α (HIF-1α). Dimethyloxalylglycine (DMOG) prevents the deactivation of HIF-1α and increases VEGF production. However, the effects of systemic DMOG treatment on myocardial tolerance for ischemia are unknown. We hypothesized that systemic pretreatment with DMOG would improve myocardial ischemic tolerance. To study this hypothesis, adult male rats were randomly given an intraperitoneal injection of DMOG (40 mg/kg in 1 mL saline, n = 5) or saline (1 mL, n = 6) 24 h before cardiectomy and isolated heart perfusion. All hearts were subjected to 15 min equilibration, 25 min ischemia and 40 min reperfusion. Myocardial function was continuously monitored. Following reperfusion, myocardial homogenates were analyzed for HIF-1α and VEGF production. We observed that hearts in the DMOG group exhibited greater recovery of left ventricular developed pressure LVDP, +dP/dt and -dP/dt. Myocardial HIF-1α and VEGF levels were increased by DMOG therapy. In conclusion, systemic pretreatment with DMOG augments post-ischemic myocardial functional recovery through increased HIF-1α levels and greater VEGF production. Copyright © 2011 Mosby, Inc. All rights reserved.

Functional outcome and prognostic factors in anti-Jo1 patients with antisynthetase syndrome.

PubMed

Marie, Isabelle; Hatron, Pierre-Yves; Cherin, Patrick; Hachulla, Eric; Diot, Elisabeth; Vittecoq, Olivier; Menard, Jean-François; Jouen, Fabienne; Dominique, Stéphane

2013-10-08

The aims of this present study were firstly to assess the outcome, including functional course, in anti-Jo1 positive patients with antisynthetase syndrome (ASS), and secondly to determine predictive parameters of poor outcome in these patients. The medical records of 86 consecutive anti-Jo1 patients with ASS were reviewed in 4 academic centers. 13 patients (15.1%) achieved remission of ASS, whereas 55 (63.9%) improved and 18 (20.9%) deteriorated in their clinical status. Both steroid and cytotoxic drugs could be discontinued in only 4.7% of patients. ASS was associated with decreased quality of life at long-term follow-up: only 69.2% of patients considered to be in remission experienced a return to previous normal activities; and 24.7% of other patients with non-remitting ASS still had a marked reduction of activities (as shown by the disability scale of the Health Assessment Questionnaire). Decreased quality of life was further due to calcinosis cutis (8.1%) and adverse effects of steroid therapy (36%). Factors associated with ASS deterioration were older age, pulmonary and esophageal involvement, calcinosis cutis and cancer. Higher anti-Jo1 levels were further associated with disease severity in ASS patients. The present study shows high morbidity related to ASS. Furthermore, we suggest that patients with predictive factors of ASS deterioration may require more aggressive therapy. Our findings also suggest that in anti-Jo1 patients with severe esophageal manifestations, combined high dose steroids and intravenous immunoglobulins might be proposed as the first line therapy. Finally, as cancer occurred in 14% of anti-Jo1 patients, our findings underscore that the search for cancer should be performed in these patients.

Cloning and expression of porcine Colony Stimulating Factor-1 (CSF-1) and Colony Stimulating Factor-1 Receptor (CSF-1R) and analysis of the species specificity of stimulation by CSF-1 and Interleukin 34

PubMed Central

Gow, Deborah J.; Garceau, Valerie; Kapetanovic, Ronan; Sester, David P.; Fici, Greg J.; Shelly, John A.; Wilson, Thomas L.; Hume, David A.

2012-01-01

Macrophage Colony Stimulating Factor (CSF-1) controls the survival, differentiation and proliferation of cells of the mononuclear phagocyte system. A second ligand for the CSF-1R, Interleukin 34 (IL-34), has been described, but its physiological role is not yet known. The domestic pig provides an alternative to traditional rodent models for evaluating potential therapeutic applications of CSF-1R agonists and antagonists. To enable such studies, we cloned and expressed active pig CSF-1. To provide a bioassay, pig CSF-1R was expressed in the factor-dependent Ba/F3 cell line. On this transfected cell line, recombinant porcine CSF-1 and human CSF-1 had identical activity. Mouse CSF-1 does not interact with the human CSF-1 receptor but was active on pig. By contrast, porcine CSF-1 was active on mouse, human, cat and dog cells. IL-34 was previously shown to be species-specific, with mouse and human proteins demonstrating limited cross-species activity. The pig CSF-1R was equally responsive to both mouse and human IL-34. Based upon the published crystal structures of CSF-1/CSF-1R and IL34/CSF-1R complexes, we discuss the molecular basis for the species specificity. PMID:22974529

Low levels of ApoA1 improve risk prediction of type 2 diabetes mellitus.

PubMed

Wu, Xing; Yu, Zhexin; Su, Wen; Isquith, Daniel A; Neradilek, Moni B; Lu, Ning; Gu, Fusheng; Li, Hongwei; Zhao, Xue-Qiao

Type 2 diabetes mellitus (T2DM) has reported to be a major public health crisis in China. We examined the incidence of new T2DM over 4 years for association of clinical factors and lipids with development of T2DM in a community-based population. We included 923 Chinese subjects who participated in community-organized health checkout in both 2009 and 2013. Health history was collected; physical examination was performed; biochemistry, lipids, and glucose were measured. Of 923, 819 were confirmed without T2DM in 2009 and included in the analysis. Unadjusted and adjusted logistic regression models were used to estimate the effects of clinical factors and biomarkers on the risk of new T2DM. Of 819 subjects without T2DM in 2009, 65 were identified as T2DM in 2013, 8% over 4 years. These 65 subjects, compared with those 754 without new T2DM, were older, more likely to be male and smokers. They had higher body mass index (BMI), fasting glucose, blood pressure and triglycerides, and lower levels of high-density lipoprotein-cholesterol and apolipoprotein A1 (ApoA1). Multivariate logistic regression identified larger BMI (odds ratio [OR] = 1.7; 95% confidence interval [CI], 1.22-2.39, P = .002), higher fasting glucose levels (OR = 4.2, 95% CI, 2.90-6.19, P < .001), and low levels of ApoA1 (OR = 0.51, 95% CI 0.33-0.76, P = .002) were independently associated with new T2DM. Furthermore, receiver operating characteristics curves for multivariate models for new T2DM showed that area under the curve improved from 0.87 to 0.89 when adding ApoA1 to the Framingham Diabetes Risk Scoring Model and from 0.85 to 0.89 when adding ApoA1 to a 4-variable (age, BMI, glucose, and triglycerides) Chinese model. There is a high incidence of new T2DM at 8% over 4 years among Chinese. Larger BMI, higher glucose levels, and lower levels of ApoA1 are significantly and independently associated with new T2DM. Lower ApoA1 improves the risk prediction of new type 2 diabetes when it was

Improved detectivity of pyroelectric detectors

NASA Technical Reports Server (NTRS)

Marshall, D. E.; Gelpey, J. C.; Marciniec, J. W.; Chiang, A. M.; Maciolek, R. B.

1978-01-01

High detectivity single-element SBN pyroelectric detectors were fabricated. The theory and technology developments related to improved detector performance were identified and formulated. Improved methods of material characterization, thinning, mounting, blackening and amplifier matching are discussed. Detectors with detectivities of 1.3 x 10 to the 9th power square root of Hz/watt at 1 Hz are reported. Factors limiting performance and recommendations for future work are discussed.

Modeling and roles of meteorological factors in outbreaks of highly pathogenic avian influenza H5N1.

PubMed

Biswas, Paritosh K; Islam, Md Zohorul; Debnath, Nitish C; Yamage, Mat

2014-01-01

The highly pathogenic avian influenza A virus subtype H5N1 (HPAI H5N1) is a deadly zoonotic pathogen. Its persistence in poultry in several countries is a potential threat: a mutant or genetically reassorted progenitor might cause a human pandemic. Its world-wide eradication from poultry is important to protect public health. The global trend of outbreaks of influenza attributable to HPAI H5N1 shows a clear seasonality. Meteorological factors might be associated with such trend but have not been studied. For the first time, we analyze the role of meteorological factors in the occurrences of HPAI outbreaks in Bangladesh. We employed autoregressive integrated moving average (ARIMA) and multiplicative seasonal autoregressive integrated moving average (SARIMA) to assess the roles of different meteorological factors in outbreaks of HPAI. Outbreaks were modeled best when multiplicative seasonality was incorporated. Incorporation of any meteorological variable(s) as inputs did not improve the performance of any multivariable models, but relative humidity (RH) was a significant covariate in several ARIMA and SARIMA models with different autoregressive and moving average orders. The variable cloud cover was also a significant covariate in two SARIMA models, but air temperature along with RH might be a predictor when moving average (MA) order at lag 1 month is considered.

Chronic Inhibition of ERK1/2 Signaling Improves Disordered Bone and Mineral Metabolism in Hypophosphatemic (Hyp) Mice

PubMed Central

Zhang, Martin Y. H.; Ranch, Daniel; Pereira, Renata C.; Armbrecht, Harvey J.; Portale, Anthony A.

2012-01-01

The X-linked hypophosphatemic (Hyp) mouse carries a loss-of-function mutation in the phex gene and is characterized by hypophosphatemia due to renal phosphate (Pi) wasting, inappropriately suppressed 1,25-dihydroxyvitamin D [1,25(OH)2D] production, and rachitic bone disease. Increased serum fibroblast growth factor-23 concentration is responsible for the disordered metabolism of Pi and 1,25(OH)2D. In the present study, we tested the hypothesis that chronic inhibition of fibroblast growth factor-23-induced activation of MAPK signaling in Hyp mice can reverse their metabolic derangements and rachitic bone disease. Hyp mice were administered the MAPK inhibitor, PD0325901 orally for 4 wk. PD0325901 induced a 15-fold and 2-fold increase in renal 1α-hydroxylase mRNA and protein abundance, respectively, and thereby higher serum 1,25(OH)2D concentrations (115 ± 13 vs. 70 ± 16 pg/ml, P < 0.05), compared with values in vehicle-treated Hyp mice. With PD0325901, serum Pi levels were higher (5.1 ± 0.5 vs. 3 ± 0.2 mg/dl, P < 0.05), and the protein abundance of sodium-dependent phosphate cotransporter Npt2a, was greater than in vehicle-treated mice. The rachitic bone disease in Hyp mice is characterized by abundant unmineralized osteoid bone volume, widened epiphyses, and disorganized growth plates. In PD0325901-treated Hyp mice, mineralization of cortical and trabecular bone increased significantly, accompanied by a decrease in unmineralized osteoid volume and thickness, as determined by histomorphometric analysis. The improvement in mineralization in PD0325901-treated Hyp mice was confirmed by microcomputed tomography analysis, which showed an increase in cortical bone volume and thickness. These findings provide evidence that in Hyp mice, chronic MAPK inhibition improves disordered Pi and 1,25(OH)2D metabolism and bone mineralization. PMID:22334725

Chronic inhibition of ERK1/2 signaling improves disordered bone and mineral metabolism in hypophosphatemic (Hyp) mice.

PubMed

Zhang, Martin Y H; Ranch, Daniel; Pereira, Renata C; Armbrecht, Harvey J; Portale, Anthony A; Perwad, Farzana

2012-04-01

The X-linked hypophosphatemic (Hyp) mouse carries a loss-of-function mutation in the phex gene and is characterized by hypophosphatemia due to renal phosphate (Pi) wasting, inappropriately suppressed 1,25-dihydroxyvitamin D [1,25(OH)₂D] production, and rachitic bone disease. Increased serum fibroblast growth factor-23 concentration is responsible for the disordered metabolism of Pi and 1,25(OH)₂D. In the present study, we tested the hypothesis that chronic inhibition of fibroblast growth factor-23-induced activation of MAPK signaling in Hyp mice can reverse their metabolic derangements and rachitic bone disease. Hyp mice were administered the MAPK inhibitor, PD0325901 orally for 4 wk. PD0325901 induced a 15-fold and 2-fold increase in renal 1α-hydroxylase mRNA and protein abundance, respectively, and thereby higher serum 1,25(OH)₂D concentrations (115 ± 13 vs. 70 ± 16 pg/ml, P < 0.05), compared with values in vehicle-treated Hyp mice. With PD0325901, serum Pi levels were higher (5.1 ± 0.5 vs. 3 ± 0.2 mg/dl, P < 0.05), and the protein abundance of sodium-dependent phosphate cotransporter Npt2a, was greater than in vehicle-treated mice. The rachitic bone disease in Hyp mice is characterized by abundant unmineralized osteoid bone volume, widened epiphyses, and disorganized growth plates. In PD0325901-treated Hyp mice, mineralization of cortical and trabecular bone increased significantly, accompanied by a decrease in unmineralized osteoid volume and thickness, as determined by histomorphometric analysis. The improvement in mineralization in PD0325901-treated Hyp mice was confirmed by microcomputed tomography analysis, which showed an increase in cortical bone volume and thickness. These findings provide evidence that in Hyp mice, chronic MAPK inhibition improves disordered Pi and 1,25(OH)₂D metabolism and bone mineralization.

Work improvement factors for the amelioration of work ability, with a focus on individual capacity to deal with stress in an IT company.

PubMed

Ohta, Masanori; Higuchi, Yoshiyuki; Kumashiro, Masaharu; Yamato, Hiroshi; Sugimura, Hisamichi

2015-03-01

The aim of this study was to explore factors that ameliorate work ability by focusing on workers' capacity to deal with stress.The subjects were 1,330 workers from the Japanese information technology (IT) sector. Each subject completed questionnaires in 2011 and 2012 that consisted of the work ability index (WAI), the three-item sense of coherence (SOC), and the Mental Health Improvement and Reinforcement Research of Recognition (MIRROR). The results of the WAI were also obtained in 2013. The median SOC score in 2011 was used to divide the subjects into two groups, the Low SOC group and the High SOC group, then we verified the factors that contributed to improved work ability in both of these groups over a two-year period. Results indicate that an improvement in work ability in the Low SOC group could be predicted by giving workers opportunities for education or training, by making efforts to reduce the stress of commuting, by clarifying their assignments, and by establishing support systems when troubles occur. For the High SOC group, such improvements could be predicted by giving workers job control, by giving education or training for the promotion of their abilities, and by establishing a system for assuming responsibility. In conclusion, improvements in the work environment can increase the work ability of Japanese IT workers in conformity with their capacity to deal with stress.

Indirect comparisons of efficacy and weekly factor consumption during continuous prophylaxis with recombinant factor VIII Fc fusion protein and conventional recombinant factor VIII products.

PubMed

Iorio, A; Krishnan, S; Myrén, K J; Lethagen, S; McCormick, N; Yermakov, S; Karner, P

2017-05-01

Recombinant factor VIII (rFVIII) products with extended half-lives have the potential to improve adherence and outcomes in haemophilia beyond the results obtained with conventional rFVIII products. In the absence of head-to-head comparisons, annualized bleed rates (ABRs) and weekly factor consumption with rFVIII Fc fusion protein (rFVIIIFc) and conventional rFVIII products were indirectly compared using studies of continuous prophylaxis. A systematic literature review was conducted to identify studies of rFVIII products for comparison with rFVIIIFc in the continuous prophylactic treatment of previously treated adolescents and adults with moderate and severe haemophilia A. Mean ABRs were compared between rFVIIIFc and individual rFVIII studies and between rFVIIIFc and a pooled measure for rFVIII estimated by meta-analysis. Comparisons of factor consumption were based on mean or median weekly factor consumption. Results from seven studies of conventional rFVIII products (injections 2-4 times week -1 ) were compared with rFVIIIFc (injections 1.4-2.4 times week -1 ). The pooled mean ABR for rFVIII products was significantly higher compared with rFVIIIFc (difference = 2.0; P = 0.007). Compared with most rFVIII studies, the reported weekly factor consumption was lower with rFVIIIFc [mean differences = 15.5-21.8 IU kg -1 week -1 (17-26%); median differences = 12.7-29.8 IU kg -1 week -1 (16-37%)]. In one comparison, mean weekly factor consumption with rFVIII was significantly lower but mean ABR was significantly higher than rFVIIIFc. Prophylaxis with rFVIIIFc may be associated with improved bleeding rates and lower weekly factor consumption than more frequently injected rFVIII products. Relative to rFVIII products with similar bleeding rates, results indicate that rFVIIIFc is associated with reduced weekly factor consumption while requiring fewer prescribed injections. © 2017 John Wiley & Sons Ltd.

Somatomedin-1 binding protein-3: insulin-like growth factor-1 binding protein-3, insulin-like growth factor-1 carrier protein.

PubMed

2003-01-01

Somatomedin-1 binding protein-3 [insulin-like growth factor-1 binding protein-3, SomatoKine] is a recombinant complex of insulin-like growth factor-1 (rhIGF-1) and binding protein-3 (IGFBP-3), which is the major circulating somatomedin (insulin-like growth factor) binding protein; binding protein-3 regulates the delivery of somatomedin-1 to target tissues. Somatomedin-1 binding protein-3 has potential as replacement therapy for somatomedin-1 which may become depleted in indications such as major surgery, organ damage/failure and traumatic injury, resulting in catabolism. It also has potential for the treatment of osteoporosis; diseases associated with protein wasting including chronic renal failure, cachexia and severe trauma; and to attenuate cardiac dysfunction in a variety of disease states, including after severe burn trauma. Combined therapy with somatomedin-1 and somatomedin-1 binding protein-3 would prolong the duration of action of somatomedin-1 and would reduce or eliminate some of the undesirable effects associated with somatomedin-1 monotherapy. Somatomedin-1 is usually linked to binding protein-3 in the normal state of the body, and particular proteases clip them apart in response to stresses and release somatomedin-1 as needed. Therefore, somatomedin-1 binding protein-3 is a self-dosing system and SomatoKine would augment the natural supply of these linked compounds. Somatomedin-1 binding protein-3 was developed by Celtrix using its proprietary recombinant protein production technology. Subsequently, Celtrix was acquired by Insmed Pharmaceuticals on June 1 2000. Insmed and Avecia, UK, have signed an agreement for the manufacturing of SomatoKine and its components, IGF-1 and binding protein-3. CGMP clinical production of SomatoKine and its components will be done in Avecia's Advanced Biologics Centre, Billingham, UK, which manufactures recombinant-based medicines and vaccines with a capacity of up to 1000 litres. In 2003, manufacturing of SomatoKine is

Factors Associated with Post-Seasonal Serological Titer and Risk Factors for Infection with the Pandemic A/H1N1 Virus in the French General Population

PubMed Central

Lapidus, Nathanael; de Lamballerie, Xavier; Salez, Nicolas; Setbon, Michel; Delabre, Rosemary M.; Ferrari, Pascal; Moyen, Nanikaly; Gougeon, Marie-Lise; Vely, Frédéric; Leruez-Ville, Marianne; Andreoletti, Laurent; Cauchemez, Simon; Boëlle, Pierre-Yves; Vivier, Éric; Abel, Laurent; Schwarzinger, Michaël; Legeas, Michèle; Le Cann, Pierre; Flahault, Antoine; Carrat, Fabrice

2013-01-01

The CoPanFlu-France cohort of households was set up in 2009 to study the risk factors for infection by the pandemic influenza virus (H1N1pdm) in the French general population. The authors developed an integrative data-driven approach to identify individual, collective and environmental factors associated with the post-seasonal serological H1N1pdm geometric mean titer, and derived a nested case-control analysis to identify risk factors for infection during the first season. This analysis included 1377 subjects (601 households). The GMT for the general population was 47.1 (95% confidence interval (CI): 45.1, 49.2). According to a multivariable analysis, pandemic vaccination, seasonal vaccination in 2009, recent history of influenza-like illness, asthma, chronic obstructive pulmonary disease, social contacts at school and use of public transports by the local population were associated with a higher GMT, whereas history of smoking was associated with a lower GMT. Additionally, young age at inclusion and risk perception of exposure to the virus at work were identified as possible risk factors, whereas presence of an air humidifier in the living room was a possible protective factor. These findings will be interpreted in light of the longitudinal analyses of this ongoing cohort. PMID:23613718

Improved localization accuracy in stochastic super-resolution fluorescence microscopy by K-factor image deshadowing

PubMed Central

Ilovitsh, Tali; Meiri, Amihai; Ebeling, Carl G.; Menon, Rajesh; Gerton, Jordan M.; Jorgensen, Erik M.; Zalevsky, Zeev

2013-01-01

Localization of a single fluorescent particle with sub-diffraction-limit accuracy is a key merit in localization microscopy. Existing methods such as photoactivated localization microscopy (PALM) and stochastic optical reconstruction microscopy (STORM) achieve localization accuracies of single emitters that can reach an order of magnitude lower than the conventional resolving capabilities of optical microscopy. However, these techniques require a sparse distribution of simultaneously activated fluorophores in the field of view, resulting in larger time needed for the construction of the full image. In this paper we present the use of a nonlinear image decomposition algorithm termed K-factor, which reduces an image into a nonlinear set of contrast-ordered decompositions whose joint product reassembles the original image. The K-factor technique, when implemented on raw data prior to localization, can improve the localization accuracy of standard existing methods, and also enable the localization of overlapping particles, allowing the use of increased fluorophore activation density, and thereby increased data collection speed. Numerical simulations of fluorescence data with random probe positions, and especially at high densities of activated fluorophores, demonstrate an improvement of up to 85% in the localization precision compared to single fitting techniques. Implementing the proposed concept on experimental data of cellular structures yielded a 37% improvement in resolution for the same super-resolution image acquisition time, and a decrease of 42% in the collection time of super-resolution data with the same resolution. PMID:24466491

Household trends in access to improved water sources and sanitation facilities in Vietnam and associated factors: findings from the Multiple Indicator Cluster Surveys, 2000-2011.

PubMed

Tuyet-Hanh, Tran Thi; Lee, Jong-Koo; Oh, Juhwan; Van Minh, Hoang; Ou Lee, Chul; Hoan, Le Thi; Nam, You-Seon; Long, Tran Khanh

2016-01-01

Despite progress made by the Millennium Development Goal (MDG) number 7.C, Vietnam still faces challenges with regard to the provision of access to safe drinking water and basic sanitation. This paper describes household trends in access to improved water sources and sanitation facilities separately, and analyses factors associated with access to improved water sources and sanitation facilities in combination. Secondary data from the Vietnam Multiple Indicator Cluster Survey in 2000, 2006, and 2011 were analyzed. Descriptive statistics and tests of significance describe trends over time in access to water and sanitation by location, demographic and socio-economic factors. Binary logistic regressions (2000, 2006, and 2011) describe associations between access to water and sanitation, and geographic, demographic, and socio-economic factors. There have been some outstanding developments in access to improved water sources and sanitation facilities from 2000 to 2011. In 2011, the proportion of households with access to improved water sources and sanitation facilities reached 90% and 77%, respectively, meeting the 2015 MDG targets for safe drinking water and basic sanitation set at 88% and 75%, respectively. However, despite these achievements, in 2011, only 74% of households overall had access to combined improved drinking water and sanitation facilities. There were also stark differences between regions. In 2011, only 47% of households had access to both improved water and sanitation facilities in the Mekong River Delta compared with 94% in the Red River Delta. In 2011, households in urban compared to rural areas were more than twice as likely (odds ratio [OR]: 2.2; 95% confidence interval [CI]: 1.9-2.5) to have access to improved water and sanitation facilities in combination, and households in the highest compared with the lowest wealth quintile were over 40 times more likely (OR: 42.3; 95% CI: 29.8-60.0). More efforts are required to increase household access to

LRP1 protects the vasculature by regulating levels of connective tissue growth factor and HtrA1.

PubMed

Muratoglu, Selen C; Belgrave, Shani; Hampton, Brian; Migliorini, Mary; Coksaygan, Turhan; Chen, Ling; Mikhailenko, Irina; Strickland, Dudley K

2013-09-01

Low-density lipoprotein receptor-related protein 1 (LRP1) is a large endocytic and signaling receptor that is abundant in vascular smooth muscle cells. Mice in which the lrp1 gene is deleted in smooth muscle cells (smLRP1(-/-)) on a low-density lipoprotein receptor-deficient background display excessive platelet derived growth factor-signaling, smooth muscle cell proliferation, aneurysm formation, and increased susceptibility to atherosclerosis. The objectives of the current study were to examine the potential of LRP1 to modulate vascular physiology under nonatherogenic conditions. We found smLRP1(-/-) mice to have extensive in vivo aortic dilatation accompanied by disorganized and degraded elastic lamina along with medial thickening of the arterial vessels resulting from excess matrix deposition. Surprisingly, this was not attributable to excessive platelet derived growth factor-signaling. Rather, quantitative differential proteomic analysis revealed that smLRP1(-/-) vessels contain a 4-fold increase in protein levels of high-temperature requirement factor A1 (HtrA1), which is a secreted serine protease that is known to degrade matrix components and to impair elastogenesis, resulting in fragmentation of elastic fibers. Importantly, our study discovered that HtrA1 is a novel LRP1 ligand. Proteomics analysis also identified excessive accumulation of connective tissue growth factor, an LRP1 ligand and a key mediator of fibrosis. Our findings suggest a critical role for LRP1 in maintaining the integrity of vessels by regulating protease activity as well as matrix deposition by modulating HtrA1 and connective tissue growth factor protein levels. This study highlights 2 new molecules, connective tissue growth factor and HtrA1, which contribute to detrimental changes in the vasculature and, therefore, represent new target molecules for potential therapeutic intervention to maintain vessel wall homeostasis.

The yeast Hot1 transcription factor is critical for activating a single target gene, STL1

PubMed Central

Bai, Chen; Tesker, Masha; Engelberg, David

2015-01-01

Transcription factors are commonly activated by signal transduction cascades and induce expression of many genes. They therefore play critical roles in determining the cell's fate. The yeast Hog1 MAP kinase pathway is believed to control the transcription of hundreds of genes via several transcription factors. To identify the bona fide target genes of Hog1, we inducibly expressed the spontaneously active variant Hog1D170A+F318L in cells lacking the Hog1 activator Pbs2. This system allowed monitoring the effects of Hog1 by itself. Expression of Hog1D170A+F318L in pbs2∆ cells imposed induction of just 105 and suppression of only 26 transcripts by at least twofold. We looked for the Hog1-responsive element within the promoter of the most highly induced gene, STL1 (88-fold). A novel Hog1 responsive element (HoRE) was identified and shown to be the direct target of the transcription factor Hot1. Unexpectedly, we could not find this HoRE in any other yeast promoter. In addition, the only gene whose expression was abolished in hot1∆ cells was STL1. Thus Hot1 is essential for transcription of just one gene, STL1. Hot1 may represent a class of transcription factors that are essential for transcription of a very few genes or even just one. PMID:25904326

Exposure Factors Handbook Chapter 1

EPA Pesticide Factsheets

Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

Combined caveolin-1 and epidermal growth factor receptor expression as a prognostic marker for breast cancer.

PubMed

Liang, Ya-Nan; Liu, Yu; Wang, Letian; Yao, Guodong; Li, Xiaobo; Meng, Xiangning; Wang, Fan; Li, Ming; Tong, Dandan; Geng, Jingshu

2018-06-01

Previous studies have indicated that caveolin-1 (Cav-1) is able to bind the signal transduction factor epidermal growth factor receptor (EGFR) to regulate its tyrosine kinase activity. The aim of the present study was to evaluate the clinical significance of Cav-1 gene expression in association with the expression of EGFR in patients with breast cancer. Primary breast cancer samples from 306 patients were analyzed for Cav-1 and EGFR expression using immunohistochemistry, and clinical significance was assessed using multivariate Cox regression analysis, Kaplan-Meier estimator curves and the log-rank test. Stromal Cav-1 was downregulated in 38.56% (118/306) of tumor tissues, whereas cytoplasmic EGFR and Cav-1 were overexpressed in 53.92% (165/306) and 44.12% (135/306) of breast cancer tissues, respectively. EGFR expression was positively associated with cytoplasmic Cav-1 and not associated with stromal Cav-1 expression in breast cancer samples; however, low expression of stromal Cav-1 was negatively associated with cytoplasmic Cav-1 expression in total tumor tissues, and analogous results were identified in the chemotherapy group. Multivariate Cox's proportional hazards model analysis revealed that, for patients in the estrogen receptor (ER)(+) group, the expression of stromal Cav-1 alone was a significant prognostic marker of breast cancer. However, in the chemotherapy, human epidermal growth factor receptor 2 (HER-2)(-), HER-2(+) and ER(-) groups, the use of combined markers was more effective prognostic marker. Stromal Cav-1 has a tumor suppressor function, and the combined marker stromal Cav-1/EGFR expression was identified as an improved prognostic marker in the diagnosis of breast cancer. Parenchymal expression of Cav-1 is able to promote EGFR signaling in breast cancer, potentially being required for EGFR-mediated initiation of mitosis.

Combination Growth Factor Therapy via Electrostatically Assembled Wound Dressings Improves Diabetic Ulcer Healing In Vivo.

PubMed

Almquist, Benjamin D; Castleberry, Steven A; Sun, Julia B; Lu, Alice Y; Hammond, Paula T

2015-10-01

Chronic skin ulcerations are a common complication of diabetes mellitus, affecting up to one in four diabetic individuals. Despite the prevalence of these wounds, current pharmacologic options for treating them remain limited. Growth factor-based therapies have displayed a mixed ability to drive successful healing, which may be due to nonoptimal delivery strategies. Here, a method for coating commercially available nylon dressings using the layer-by-layer process is described to enable both sustained release and independent control over the release kinetics of vascular endothelial growth factor 165 and platelet-derived growth factor BB. It is shown that the use of strategically spaced diffusion barriers formed spontaneously by disulfide bonds enables independent control over the release rates of incorporated growth factors, and that in vivo these dressings improve several aspects of wound healing in db/db mice. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Interleaved segment correction achieves higher improvement factors in using genetic algorithm to optimize light focusing through scattering media

NASA Astrophysics Data System (ADS)

Li, Runze; Peng, Tong; Liang, Yansheng; Yang, Yanlong; Yao, Baoli; Yu, Xianghua; Min, Junwei; Lei, Ming; Yan, Shaohui; Zhang, Chunmin; Ye, Tong

2017-10-01

Focusing and imaging through scattering media has been proved possible with high resolution wavefront shaping. A completely scrambled scattering field can be corrected by applying a correction phase mask on a phase only spatial light modulator (SLM) and thereby the focusing quality can be improved. The correction phase is often found by global searching algorithms, among which Genetic Algorithm (GA) stands out for its parallel optimization process and high performance in noisy environment. However, the convergence of GA slows down gradually with the progression of optimization, causing the improvement factor of optimization to reach a plateau eventually. In this report, we propose an interleaved segment correction (ISC) method that can significantly boost the improvement factor with the same number of iterations comparing with the conventional all segment correction method. In the ISC method, all the phase segments are divided into a number of interleaved groups; GA optimization procedures are performed individually and sequentially among each group of segments. The final correction phase mask is formed by applying correction phases of all interleaved groups together on the SLM. The ISC method has been proved significantly useful in practice because of its ability to achieve better improvement factors when noise is present in the system. We have also demonstrated that the imaging quality is improved as better correction phases are found and applied on the SLM. Additionally, the ISC method lowers the demand of dynamic ranges of detection devices. The proposed method holds potential in applications, such as high-resolution imaging in deep tissue.

Paracrine Engineering of Human Cardiac Stem Cells With Insulin-Like Growth Factor 1 Enhances Myocardial Repair.

PubMed

Jackson, Robyn; Tilokee, Everad L; Latham, Nicholas; Mount, Seth; Rafatian, Ghazaleh; Strydhorst, Jared; Ye, Bin; Boodhwani, Munir; Chan, Vincent; Ruel, Marc; Ruddy, Terrence D; Suuronen, Erik J; Stewart, Duncan J; Davis, Darryl R

2015-09-11

Insulin-like growth factor 1 (IGF-1) activates prosurvival pathways and improves postischemic cardiac function, but this key cytokine is not robustly expressed by cultured human cardiac stem cells. We explored the influence of an enhanced IGF-1 paracrine signature on explant-derived cardiac stem cell-mediated cardiac repair. Receptor profiling demonstrated that IGF-1 receptor expression was increased in the infarct border zones of experimentally infarcted mice by 1 week after myocardial infarction. Human explant-derived cells underwent somatic gene transfer to overexpress human IGF-1 or the green fluorescent protein reporter alone. After culture in hypoxic reduced-serum media, overexpression of IGF-1 enhanced proliferation and expression of prosurvival transcripts and prosurvival proteins and decreased expression of apoptotic markers in both explant-derived cells and cocultured neonatal rat ventricular cardiomyocytes. Transplant of explant-derived cells genetically engineered to overexpress IGF-1 into immunodeficient mice 1 week after infarction boosted IGF-1 content within infarcted tissue and long-term engraftment of transplanted cells while reducing apoptosis and long-term myocardial scarring. Paracrine engineering of explant-derived cells to overexpress IGF-1 provided a targeted means of improving cardiac stem cell-mediated repair by enhancing the long-term survival of transplanted cells and surrounding myocardium. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

High-intensity aerobic interval training improves aerobic fitness and HbA1c among persons diagnosed with type 2 diabetes.

PubMed

Støa, Eva Maria; Meling, Sondre; Nyhus, Lill-Katrin; Glenn Strømstad; Mangerud, Karl Magnus; Helgerud, Jan; Bratland-Sanda, Solfrid; Støren, Øyvind

2017-03-01

It remains to be established how high-intensity aerobic interval training (HAIT) affects risk factors associated with type 2 diabetes (TD2). This study investigated effects of HAIT on maximal oxygen uptake (VO 2max ), glycated Hemoglobin type A1C (HbA1c), insulin resistance (IR), fat oxidation (FatOx), body weight (BW), percent body fat (%BF), lactate threshold (LT), blood pressure (BP), and blood lipid profile (BLP) among persons with T2D. Results were compared to the effects after a moderate-intensity training (MIT) program. Thirty-eight individuals with T2D completed 12 weeks of supervised training. HAIT consisted of 4 × 4 min of walking or running uphill at 85-95% of maximal heart rate, and MIT consisted of continuous walking at 70-75% of maximal heart rate. A 21% increase in VO 2max (from 25.6 to 30.9 ml kg -1  min -1 , p < 0.001), and a reduction in HbA1c by -0.58% points (from 7.78 to 7.20%, p < 0.001) was found in HAIT. BW and body mass index (BMI) was reduced by 1.9% (p < 0.01). There was a tendency towards an improved FatOx at 60% VO 2max (14%, p = 0.065). These improvements were significant different from MIT. Both HAIT and MIT increased velocity at LT, and reduced %BF, waist circumference, hip circumference, and BP, with no significant differences between the two groups. Correlations were found between change in VO 2max and change in HbA1c when the two intervention groups were combined (R = -0.52, p < 0.01). HAIT is an effective exercise strategy to improve aerobic fitness and reduce risk factors associated with T2D.

Timing of CSF-1/CSF-1R signaling blockade is critical to improving responses to CTLA-4 based immunotherapy

PubMed Central

Holmgaard, Rikke B.; Brachfeld, Alexandra; Gasmi, Billel; Jones, David R.; Mattar, Marissa; Doman, Thompson; Murphy, Mary; Schaer, David; Wolchok, Jedd D.; Merghoub, Taha

2016-01-01

ABSTRACT Colony stimulating factor-1 (CSF-1) is produced by a variety of cancers and recruits myeloid cells that suppress antitumor immunity, including myeloid-derived suppressor cells (MDSCs.) Here, we show that both CSF-1 and its receptor (CSF-1R) are frequently expressed in tumors from cancer patients, and that this expression correlates with tumor-infiltration of MDSCs. Furthermore, we demonstrate that these tumor-infiltrating MDSCs are highly immunosuppressive but can be reprogrammed toward an antitumor phenotype in vitro upon CSF-1/CSF-1R signaling blockade. Supporting these findings, we show that inhibition of CSF-1/CSF-1R signaling using an anti-CSF-1R antibody can regulate both the number and the function of MDSCs in murine tumors in vivo. We further find that treatment with anti-CSF-1R antibody induces antitumor T-cell responses and tumor regression in multiple tumor models when combined with CTLA-4 blockade therapy. However, this occurs only when administered after or concurrent with CTLA-4 blockade, indicating that timing of each therapeutic intervention is critical for optimal antitumor responses. Importantly, MDSCs present within murine tumors after CTLA-4 blockade showed increased expression of CSF-1R and were capable of suppressing T cell proliferation, and CSF-1/CSF-1R expression in the human tumors was not reduced after treatment with CTLA-4 blockade immunotherapy. Taken together, our findings suggest that CSF-1R-expressing MDSCs can be targeted to modulate the tumor microenvironment and that timing of CSF-1/CSF-1R signaling blockade is critical to improving responses to checkpoint based immunotherapy. Significance: Infiltration by immunosuppressive myeloid cells contributes to tumor immune escape and can render patients resistant or less responsive to therapeutic intervention with checkpoint blocking antibodies. Our data demonstrate that blocking CSF-1/CSF-1R signaling using a monoclonal antibody directed to CSF-1R can regulate both the number

An open-label dose escalation study to evaluate the safety of administration of nonviral stromal cell-derived factor-1 plasmid to treat symptomatic ischemic heart failure.

PubMed

Penn, Marc S; Mendelsohn, Farrell O; Schaer, Gary L; Sherman, Warren; Farr, Maryjane; Pastore, Joseph; Rouy, Didier; Clemens, Ruth; Aras, Rahul; Losordo, Douglas W

2013-03-01

Preclinical studies indicate that adult stem cells induce tissue repair by activating endogenous stem cells through the stromal cell-derived factor-1:chemokine receptor type 4 axis. JVS-100 is a DNA plasmid encoding human stromal cell-derived factor-1. We tested in a phase 1, open-label, dose-escalation study with 12 months of follow-up in subjects with ischemic cardiomyopathy to see if JVS-100 improves clinical parameters. Seventeen subjects with ischemic cardiomyopathy, New York Heart Association class III heart failure, with an ejection fraction ≤40% on stable medical therapy, were enrolled to receive 5, 15, or 30 mg of JVS-100 via endomyocardial injection. The primary end points for safety and efficacy were at 1 and 4 months, respectively. The primary safety end point was a major adverse cardiac event. Efficacy end points were change in quality of life, New York Heart Association class, 6-minute walk distance, single photon emission computed tomography, N-terminal pro-brain natruretic peptide, and echocardiography at 4 and 12 months. The primary safety end point was met. At 4 months, all of the cohorts demonstrated improvements in 6-minute walk distance, quality of life, and New York Heart Association class. Subjects in the 15- and 30-mg dose groups exhibited improvements in 6-minute walk distance (15 mg: median [range]: 41 minutes [3-61 minutes]; 30 mg: 31 minutes [22-74 minutes]) and quality of life (15 mg: -16 points [+1 to -32 points]; 30 mg: -24 points [+17 to -38 points]) over baseline. At 12 months, improvements in symptoms were maintained. These data highlight the importance of defining the molecular mechanisms of stem cell-based tissue repair and suggest that overexpression of stromal cell-derived factor-1 via gene therapy is a strategy for improving heart failure symptoms in patients with ischemic cardiomyopathy.

Factors influencing trust in doctors: a community segmentation strategy for quality improvement in healthcare

PubMed Central

Gopichandran, Vijayaprasad; Chetlapalli, Satish Kumar

2013-01-01

Background Trust is a forward-looking covenant between the patient and the doctor where the patient optimistically accepts his/her vulnerability. Trust is known to improve the clinical outcomes. Objectives To explore the factors that determine patients’ trust in doctors and to segment the community based on factors which drive their trust. Setting Resource-poor urban and rural settings in Tamil Nadu, a state in southern India. Participants A questionnaire was administered to a sample of 625 adult community-dwelling respondents from four districts of Tamil Nadu, India, chosen by multistage sampling strategy. Outcome measures The outcomes were to understand the main domains of factors influencing trust in doctors and to segment the community based on which of these domains predominantly influenced their trust. Results Factor analysis revealed five main categories, namely, comfort with the doctor, doctor with personal involvement with the patient, behaviourally competent doctor, doctor with a simple appearance and culturally competent doctor, which explained 49.3% of the total variance. Using k-means cluster analysis the respondents were segmented into four groups, namely, those who have ‘comfort-based trust’, ‘emotionally assessed trust’, who were predominantly older and belonging to lower socioeconomic status, those who had ‘personal trust’, who were younger people from higher socioeconomic strata of the community and the group who had ‘objectively assessed trust’, who were younger women. Conclusions Trust in doctors seems to be influenced by the doctor's behaviuor, perceived comfort levels, personal involvement with the patient, and to a lesser extent by cultural competence and doctor's physical appearance. On the basis of these dimensions, the community can be segmented into distinct groups, and trust building can happen in a strategic manner which may lead to improvement in perceived quality of care. PMID:24302512

Aiming for the Insulin-like Growth Factor-1 system in breast cancer therapeutics.

PubMed

Christopoulos, Panagiotis F; Corthay, Alexandre; Koutsilieris, Michael

2018-02-01

Despite the major discoveries occurred in oncology the recent years, breast malignancies remain one of the most common causes of cancer-related deaths for women in developed countries. Development of HER2-targeting drugs has been considered a breakthrough in anti-cancer approaches and alluded to the potential of targeting growth factors in breast cancer (BrCa) therapeutics. More than twenty-five years have passed since the Insulin-like Growth Factor-1 (IGF-1) system was initially recognized as a potential target candidate in BrCa therapy. To date, a growing body of studies have implicated the IGF-1 signaling with the BrCa biology. Despite the promising experimental evidence, the impression from clinical trials is rather disappointing. Several reasons may account for this and the last word regarding the efficacy of this system as a target candidate in BrCa therapeutics is probably not written yet. Herein, we provide the theoretical basis, as well as, a comprehensive overview of the current literature, regarding the different strategies targeting the various components of the IGF-1/IGF-1R axis in several pathophysiological aspects of BrCa, including the tumor micro-environment and cancer stemness. In addition, we review the rationale for targeting the IGF-1 system in the different BrCa molecular subtypes and in treatment resistant breast tumors with a focus on both the molecular mechanisms and on the clinical perspectives of such approaches in specific population subgroups. We also discuss the future challenges, as well as, the development of novel molecules and strategies targeting the system and suggest potential improvements in the field. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dexras1 links glucocorticoids to insulin-like growth factor-1 signaling in adipogenesis

PubMed Central

Kim, Hyo Jung; Cha, Jiyoung Y.; Seok, Jo Woon; Choi, Yoonjeong; Yoon, Bo Kyung; Choi, Hyeonjin; Yu, Jung Hwan; Song, Su Jin; Kim, Ara; Lee, Hyemin; Kim, Daeun; Han, Ji Yoon; Kim, Jae-woo

2016-01-01

Glucocorticoids are associated with obesity, but the underlying mechanism by which they function remains poorly understood. Previously, we showed that small G protein Dexras1 is expressed by glucocorticoids and leads to adipocyte differentiation. In this study, we explored the mechanism by which Dexras1 mediates adipogenesis and show a link to the insulin-like growth factor-1 (IGF-1) signaling pathway. Without Dexras1, the activation of MAPK and subsequent phosphorylation of CCAAT/enhancer binding protein β (C/EBPβ) is abolished, thereby inhibiting mitotic clonal expansion and further adipocyte differentiation. Dexras1 translocates to the plasma membrane upon insulin or IGF-1 treatment, for which the unique C-terminal domain (amino acids 223–276) is essential. Dexras1-dependent MAPK activation is selectively involved in the IGF-1 signaling, because another Ras protein, H-ras localized to the plasma membrane independently of insulin treatment. Moreover, neither epidermal growth factor nor other cell types shows Dexras1-dependent MAPK activation, indicating the importance of Dexras1 in IGF-1 signaling in adipogenesis. Dexras1 interacts with Shc and Raf, indicating that Dexras1-induced activation of MAPK is largely dependent on the Shc-Grb2-Raf complex. These results suggest that Dexras1 is a critical mediator of the IGF-1 signal to activate MAPK, linking glucocorticoid signaling to IGF-1 signaling in adipogenesis. PMID:27345868

Study of motivational factors in doctors in respect of healthcare quality improvement.

PubMed

Smiianov, Vladyslav A; Smiianova, Olga I; Gruzieva, Tetiana S; Vygivska, Liudmyla; Rudenko, Lesia A

The article presents the results of a survey among doctors with different certification categories and experience who work at inpatient and outpatient departments of Sumy healthcare institutions, in respect of the main factors that motivate them to provide quality healthcare. The aim of the study is to identify the factors that may be used as motivators to improve healthcare quality in terms of medical staff in order to ensure system construction of motivational component of healthcare quality management ("incentive picture"). We conducted a survey among physicians working at inpatient and outpatient departments. A total of 167 respondents were interviewed. The obtained results were processed using OCA-program. We have found an association between the salary level and certification category of a physician. Despite heavy workload, most doctors were willing to work harder and better for some additional payment. Even though financial satisfaction was low, most doctors did not agree to change their profession for a more payable one. The study revealed that, in doctors' opinion, the introduction of incentive system in healthcare institutions was necessary to provide quality healthcare. Regardless of length of service and workplace, two of the main motivational factors for doctors were moral satisfaction from work and respect of people.

Oil palm EgCBF3 conferred stress tolerance in transgenic tomato plants through modulation of the ethylene signaling pathway.

PubMed

Ebrahimi, Mortaza; Abdullah, Siti Nor Akmar; Abdul Aziz, Maheran; Namasivayam, Parameswari

2016-09-01

CBF/DREB1 is a group of transcription factors that are mainly involved in abiotic stress tolerance in plants. They belong to the AP2/ERF superfamily of plant-specific transcription factors. A gene encoding a new member of this group was isolated from ripening oil palm fruit and designated as EgCBF3. The oil palm fruit demonstrates the characteristics of a climacteric fruit like tomato, in which ethylene has a major impact on the ripening process. A transgenic approach was used for functional characterization of the EgCBF3, using tomato as the model plant. The effects of ectopic expression of EgCBF3 were analyzed based on expression profiling of the ethylene biosynthesis-related genes, anti-freeze proteins (AFPs), abiotic stress tolerance and plant growth and development. The EgCBF3 tomatoes demonstrated altered phenotypes compared to the wild type tomatoes. Delayed leaf senescence and flowering, increased chlorophyll content and abnormal flowering were the consequences of overexpression of EgCBF3 in the transgenic tomatoes. The EgCBF3 tomatoes demonstrated enhanced abiotic stress tolerance under in vitro conditions. Further, transcript levels of ethylene biosynthesis-related genes, including three SlACSs and two SlACOs, were altered in the transgenic plants' leaves and roots compared to that in the wild type tomato plant. Among the eight AFPs studied in the wounded leaves of the EgCBF3 tomato plants, transcript levels of SlOSM-L, SlNP24, SlPR5L and SlTSRF1 decreased, while expression of the other four, SlCHI3, SlPR1, SlPR-P2 and SlLAP2, were up-regulated. These findings indicate the possible functions of EgCBF3 in plant growth and development as a regulator of ethylene biosynthesis-related and AFP genes, and as a stimulator of abiotic stress tolerance. Copyright © 2016 Elsevier GmbH. All rights reserved.

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.

Improved crystallization and diffraction of caffeine-induced death suppressor protein 1 (Cid1)

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

Yates, Luke A., E-mail: luke@strubi.ox.ac.uk; Durrant, Benjamin P.; Barber, Michael

The use of truncation and RNA-binding mutations of caffeine induced death suppressor protein 1 (Cid1) as a means to enhance crystallogenesis leading to an improvement of X-ray diffraction resolution by 1.5 Å is reported. The post-transcriptional addition of uridines to the 3′-end of RNAs is an important regulatory process that is critical for coding and noncoding RNA stability. In fission yeast and metazoans this untemplated 3′-uridylylation is catalysed by a single family of terminal uridylyltransferases (TUTs) whose members are adapted to specific RNA targets. In Schizosaccharomyces pombe the TUT Cid1 is responsible for the uridylylation of polyadenylated mRNAs, targeting themmore » for destruction. In metazoans, the Cid1 orthologues ZCCHC6 and ZCCHC11 uridylate histone mRNAs, targeting them for degradation, but also uridylate microRNAs, altering their maturation. Cid1 has been studied as a model TUT that has provided insights into the larger and more complex metazoan enzyme system. In this paper, two strategies are described that led to improvements both in the crystallogenesis of Cid1 and in the resolution of diffraction by ∼1.5 Å. These advances have allowed high-resolution crystallo@@graphic studies of this TUT system to be initiated.« less