Contextual factors and effective school improvement

NARCIS (Netherlands)

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

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

Stress-inducible expression of AtDREB1A transcription factor greatly improves drought stress tolerance in transgenic indica rice.

Science.gov (United States)

Ravikumar, G; Manimaran, P; Voleti, S R; Subrahmanyam, D; Sundaram, R M; Bansal, K C; Viraktamath, B C; Balachandran, S M

2014-06-01

The cultivation of rice (Oryza sativa L.), a major food crop, requires ample water (30 % of the fresh water available worldwide), and its productivity is greatly affected by drought, the most significant environmental factor. Much research has focussed on identifying quantitative trait loci, stress-regulated genes and transcription factors that will contribute towards the development of climate-resilient/tolerant crop plants in general and rice in particular. The transcription factor DREB1A, identified from the model plant Arabidopsis thaliana, has been reported to enhance stress tolerance against drought stress. We developed transgenic rice plants with AtDREB1A in the background of indica rice cultivar Samba Mahsuri through Agrobacterium-mediated transformation. The AtDREB1A gene was stably inherited and expressed in T1 and T2 plants and in subsequent generations, as indicated by the results of PCR, Southern blot and RT-PCR analyses. Expression of AtDREB1A was induced by drought stress in transgenic rice lines, which were highly tolerant to severe water deficit stress in both the vegetative and reproductive stages without affecting their morphological or agronomic traits. The physiological studies revealed that the expression of AtDREB1A was associated with an increased accumulation of the osmotic substance proline, maintenance of chlorophyll, increased relative water content and decreased ion leakage under drought stress. Most of the homozygous lines were highly tolerant to drought stress and showed significantly a higher grain yield and spikelet fertility relative to the nontransgenic control plants under both stressed and unstressed conditions. The improvement in drought stress tolerance in combination with agronomic traits is very essential in high premium indica rice cultivars, such as Samba Mahsuri, so that farmers can benefit in times of seasonal droughts and water scarcity.

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

Science.gov (United States)

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

Science.gov (United States)

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.

Volume 11 No. 1 February 2011 4527 ADOPTION OF IMPROVED ...

African Journals Online (AJOL)

user

2011-02-01

Feb 1, 2011 ... (innovations) in soyabean processing and utilization in Tafawa Balewa ... recommended level of protein intake of 0.6g/kg body weight [5]. ... Factors that may influence adoption of improved soyabean technologies include.

Organizational factors influencing improvements in safety

International Nuclear Information System (INIS)

Marcus, A.; Nichols, M.L.; Olson, J.; Osborn, R.; Thurber, J.

1991-01-01

Results of conceptual and empirical research conducted by this research team, and published in NUREG-CR 5437, suggested that processes of organizational problem solving and learning provide a promising area for understanding improvement in safety-related performance in nuclear power plants. In this paper the authors describe the way in which they have built upon that work and gone much further in empirically examining a range of potentially important organizational factors related to safety. The paper describes (1) overall trends in plant performance over time on the Nuclear Regulatory Commission performance indicators, (2) the major elements in the conceptual framework guiding the current work, which seeks among other things to explain those trends, (3) the specific variables used as measures of the central concepts, (4) the results to date of the quantitative empirical work and qualitative work in progress, and (5) conclusions from the research

Improvements to the Chebyshev expansion of attenuation correction factors for cylindrical samples

International Nuclear Information System (INIS)

Mildner, D.F.R.; Carpenter, J.M.

1990-01-01

The accuracy of the Chebyshev expansion coefficients used for the calculation of attenuation correction factors for cylinderical samples has been improved. An increased order of expansion allows the method to be useful over a greater range of attenuation. It is shown that many of these coefficients are exactly zero, others are rational numbers, and others are rational frations of π -1 . The assumptions of Sears in his asymptotic expression of the attenuation correction factor are also examined. (orig.)

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

Science.gov (United States)

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.

Predictive Factors for Subjective Improvement in Lumbar Spinal Stenosis Patients with Nonsurgical Treatment: A 3-Year Prospective Cohort Study.

Directory of Open Access Journals (Sweden)

Ko Matsudaira

Full Text Available To assess the predictive factors for subjective improvement with nonsurgical treatment in consecutive patients with lumbar spinal stenosis (LSS.Patients with LSS were enrolled from 17 medical centres in Japan. We followed up 274 patients (151 men; mean age, 71 ± 7.4 years for 3 years. A multivariable logistic regression model was used to assess the predictive factors for subjective symptom improvement with nonsurgical treatment.In 30% of patients, conservative treatment led to a subjective improvement in the symptoms; in 70% of patients, the symptoms remained unchanged, worsened, or required surgical treatment. The multivariable analysis of predictive factors for subjective improvement with nonsurgical treatment showed that the absence of cauda equina symptoms (only radicular symptoms had an odds ratio (OR of 3.31 (95% confidence interval [CI]: 1.50-7.31; absence of degenerative spondylolisthesis/scoliosis had an OR of 2.53 (95% CI: 1.13-5.65; <1-year duration of illness had an OR of 3.81 (95% CI: 1.46-9.98; and hypertension had an OR of 2.09 (95% CI: 0.92-4.78.The predictive factors for subjective symptom improvement with nonsurgical treatment in LSS patients were the presence of only radicular symptoms, absence of degenerative spondylolisthesis/scoliosis, and an illness duration of <1 year.

Factor analysis improves the selection of prescribing indicators

DEFF Research Database (Denmark)

Rasmussen, Hanne Marie Skyggedal; Søndergaard, Jens; Sokolowski, Ineta

2006-01-01

OBJECTIVE: To test a method for improving the selection of indicators of general practitioners' prescribing. METHODS: We conducted a prescription database study including all 180 general practices in the County of Funen, Denmark, approximately 472,000 inhabitants. Principal factor analysis was us...... appropriate and inappropriate prescribing, as revealed by the correlation of the indicators in the first factor. CONCLUSION: Correlation and factor analysis is a feasible method that assists the selection of indicators and gives better insight into prescribing patterns....

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

Science.gov (United States)

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.

Reversible dual inhibitor against G9a and DNMT1 improves human iPSC derivation enhancing MET and facilitating transcription factor engagement to the genome.

Directory of Open Access Journals (Sweden)

Juan Roberto Rodriguez-Madoz

Full Text Available The combination of defined factors with small molecules targeting epigenetic factors is a strategy that has been shown to enhance optimal derivation of iPSCs and could be used for disease modelling, high throughput screenings and/or regenerative medicine applications. In this study, we showed that a new first-in-class reversible dual G9a/DNMT1 inhibitor compound (CM272 improves the efficiency of human cell reprogramming and iPSC generation from primary cells of healthy donors and patient samples, using both integrative and non-integrative methods. Moreover, CM272 facilitates the generation of human iPSC with only two factors allowing the removal of the most potent oncogenic factor cMYC. Furthermore, we demonstrated that mechanistically, treatment with CM272 induces heterochromatin relaxation, facilitates the engagement of OCT4 and SOX2 transcription factors to OSKM refractory binding regions that are required for iPSC establishment, and enhances mesenchymal to epithelial transition during the early phase of cell reprogramming. Thus, the use of this new G9a/DNMT reversible dual inhibitor compound may represent an interesting alternative for improving cell reprogramming and human iPSC derivation for many different applications while providing interesting insights into reprogramming mechanisms.

Reversible dual inhibitor against G9a and DNMT1 improves human iPSC derivation enhancing MET and facilitating transcription factor engagement to the genome.

Science.gov (United States)

Rodriguez-Madoz, Juan Roberto; San Jose-Eneriz, Edurne; Rabal, Obdulia; Zapata-Linares, Natalia; Miranda, Estibaliz; Rodriguez, Saray; Porciuncula, Angelo; Vilas-Zornoza, Amaia; Garate, Leire; Segura, Victor; Guruceaga, Elizabeth; Agirre, Xabier; Oyarzabal, Julen; Prosper, Felipe

2017-01-01

The combination of defined factors with small molecules targeting epigenetic factors is a strategy that has been shown to enhance optimal derivation of iPSCs and could be used for disease modelling, high throughput screenings and/or regenerative medicine applications. In this study, we showed that a new first-in-class reversible dual G9a/DNMT1 inhibitor compound (CM272) improves the efficiency of human cell reprogramming and iPSC generation from primary cells of healthy donors and patient samples, using both integrative and non-integrative methods. Moreover, CM272 facilitates the generation of human iPSC with only two factors allowing the removal of the most potent oncogenic factor cMYC. Furthermore, we demonstrated that mechanistically, treatment with CM272 induces heterochromatin relaxation, facilitates the engagement of OCT4 and SOX2 transcription factors to OSKM refractory binding regions that are required for iPSC establishment, and enhances mesenchymal to epithelial transition during the early phase of cell reprogramming. Thus, the use of this new G9a/DNMT reversible dual inhibitor compound may represent an interesting alternative for improving cell reprogramming and human iPSC derivation for many different applications while providing interesting insights into reprogramming mechanisms.

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

Science.gov (United States)

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.

Science.gov (United States)

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

Regulation of Memory Formation by the Transcription Factor XBP1

Directory of Open Access Journals (Sweden)

Gabriela Martínez

2016-02-01

Full Text Available 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.

Improving surface smoothness and photoluminescence of CdTe(1 1 1)A on Si(1 1 1) substrates grown by molecular beam epitaxy using Mn atoms

International Nuclear Information System (INIS)

Wang, Jyh-Shyang; Tsai, Yu-Hsuan; Chen, Chang-Wei; Dai, Zi-Yuan; Tong, Shih-Chang; Yang, Chu-Shou; Wu, Chih-Hung; Yuan, Chi-Tsu; Shen, Ji-Lin

2014-01-01

Highlights: • CdTe(1 1 1)A epilayers were grown on Si(1 1 1) substrates by molecular beam epitaxy. • We report an enhanced growth using Mn atoms. • The significant improvements in surface quality and optical properties were found. - Abstract: This work demonstrates an improvement of the molecular beam epitaxial growth of CdTe(1 1 1)A epilayer on Si(1 1 1) substrates using Mn atoms. The reflection high-energy electron diffraction patterns show that the involvement of some Mn atoms in the growth of CdTe(1 1 1)A is even more effective than the use of a buffer layer with a smooth surface for forming good CdTe(1 1 1)A epilayers. 10 K Photoluminescence spectra show that the incorporation of only 2% Mn significantly reduced the intensity of defect-related emissions and considerably increased the integral intensity of exciton-related emissions by a large factor of about 400

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

Science.gov (United States)

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.

Pretransplant mobilization with granulocyte colony-stimulating factor improves B-cell reconstitution by lentiviral vector gene therapy in SCID-X1 mice.

Science.gov (United States)

Huston, Marshall W; Riegman, Adriaan R A; Yadak, Rana; van Helsdingen, Yvette; de Boer, Helen; van Til, Niek P; Wagemaker, Gerard

2014-10-01

Hematopoietic stem cell (HSC) gene therapy is a demonstrated effective treatment for X-linked severe combined immunodeficiency (SCID-X1), but B-cell reconstitution and function has been deficient in many of the gene therapy treated patients. Cytoreductive preconditioning is known to improve HSC engraftment, but in general it is not considered for SCID-X1 since the poor health of most of these patients at diagnosis and the risk of toxicity preclude the conditioning used in standard bone marrow stem cell transplantation. We hypothesized that mobilization of HSC by granulocyte colony-stimulating factor (G-CSF) should create temporary space in bone marrow niches to improve engraftment and thereby B-cell reconstitution. In the present pilot study supplementing our earlier preclinical evaluation (Huston et al., 2011), Il2rg(-/-) mice pretreated with G-CSF were transplanted with wild-type lineage negative (Lin(-)) cells or Il2rg(-/-) Lin(-) cells transduced with therapeutic IL2RG lentiviral vectors. Mice were monitored for reconstitution of lymphocyte populations, level of donor cell chimerism, and antibody responses as compared to 2 Gy total body irradiation (TBI), previously found effective in promoting B-cell reconstitution. The results demonstrate that G-CSF promotes B-cell reconstitution similar to low-dose TBI and provides proof of principle for an alternative approach to improve efficacy of gene therapy in SCID patients without adverse effects associated with cytoreductive conditioning.

Chapter 7. Assessing soil factors in wildland improvement programs

Science.gov (United States)

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...

Is exercise a therapeutic tool for improvement of cardiovascular risk factors in adolescents with type 1 diabetes mellitus? A randomised controlled trial

Directory of Open Access Journals (Sweden)

Salem Mona A

2010-07-01

Full Text Available Abstract Background Type 1 diabetes mellitus (T1DM is associated with a high risk for early atherosclerotic complications especially risk of coronary heart disease. Objective To evaluate the impact of six months exercise prgram on glycemic control, plasma lipids values, blood pressure, severity and frequency of hypoglycemia, anthropometric measurements and insulin dose in a sample of adolescents with T1DM. Research design and methods A total of 196 type 1 diabetic patients participated in the study. They were classified into three groups: Group (A did not join the exercise program(n = 48, group (B attended the exercise sessions once/week (n = 75, group (C attended the exercise sessions three times/week (n = 73. Studied parameters were evaluated before and six months after exercise programe. Results Exercise improved glycemic control by reducing HbA1c values in exercise groups (P = 0.03, P = 0.01 respectively and no change in those who were not physically active (P = 0.2. Higher levels of HbA1c were associated with higher levels of cholesterol, LDL-c, and triglycerides (P = 0.000 each. In both groups, B and C, frequent exercise improved dyslipidemia and reduced insulin requirements significantly (P = 0.00 both, as well as a reduction in BMI (P = 0.05, P = 0.00 respectively and waist circumference(P = 0.02, P = 0.00 respectively. The frequency of hypoglycemic attacks were not statistically different between the control group and both intervention groups (4.7 ± 3.56 and 4.82 ± 4.23, P = 0.888 respectively. Reduction of blood pressure was statistically insignificant apart from the diastolic blood presure in group C (P = 0.04. Conclusion Exercise is an indispensable component in the medical treatment of patients with T1DM as it improves glycemic control and decreases cardiovascular risk factors among them.

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.

Science.gov (United States)

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.

Organizational factors influencing improvements in safety

International Nuclear Information System (INIS)

Marcus, A.; Nichols, M.L.; Olson, J.; Osborn, R.; Thurber, J.

1992-01-01

Research reported here seeks to identify the key organizational factors that influence safety-related performance indicators in nuclear power plants over time. It builds upon organizational factors identified in NUREG/CR-5437, and begins to develop a theory of safety-related performance and performance improvement based on economic and behavioral theories of the firm. Central to the theory are concepts of past performance, problem recognition, resource availability, resource allocation, and business strategies that focus attention. Variables which reflect those concepts are combined in statistical models and tested for their ability to explain scrams, safety system actuations, significant events, safety system failures, radiation exposure, and critical hours. Results show the performance indicators differ with respect to the sets of variables which serve as the best predictors of future performance, and past performance is the most consistent predictor of future performance

Reluctance motor of new design with improved efficiency and power factor

Energy Technology Data Exchange (ETDEWEB)

Hansen-Goos, P; Pieper, W

1981-09-01

Improvement of operating conditions and efficiency by development of new configurations of lamination and production methods for reluctance motors. Investigations during the starting-up period and of the operating behaviour in connection with variable frequency. Reluctance motors are designed in the range from 0,6-4kW with 4-pole winding. They are due to the following identification: 1. The power of motors is in accordance with VDE 42673. 2. The volume of lamination is equal to asynchronous motors of the same IED size. 3. Synchronous pull-out torque is in compliance with VDE 0530: Msub(K)sub(S) > 1,35 Mn (nominal torque). As against standard reluctance motors the following improvements with the new ones have been realized: 4. Increase of nominal power by approx. 100%. 5. Increase of quality factor by approx. 50%. 6. The efficiency is equal to asynchronous motors of the same IEC size.

An improved gravity model for Mars: Goddard Mars Model 1

Science.gov (United States)

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.

Multiple Factors Related to the Secretion of Glucagon-Like Peptide-1

Directory of Open Access Journals (Sweden)

XingChun Wang

2015-01-01

Full Text Available The glucagon-like peptide-1 is secreted by intestinal L cells in response to nutrient ingestion. It regulates the secretion and sensitivity of insulin while suppressing glucagon secretion and decreasing postprandial glucose levels. It also improves beta-cell proliferation and prevents beta-cell apoptosis induced by cytotoxic agents. Additionally, glucagon-like peptide-1 delays gastric emptying and suppresses appetite. The impaired secretion of glucagon-like peptide-1 has negative influence on diabetes, hyperlipidemia, and insulin resistance related diseases. Thus, glucagon-like peptide-1-based therapies (glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors are now well accepted in the management of type 2 diabetes. The levels of glucagon-like peptide-1 are influenced by multiple factors including a variety of nutrients. The component of a meal acts as potent stimulants of glucagon-like peptide-1 secretion. The levels of its secretion change with the intake of different nutrients. Some drugs also have influence on GLP-1 secretion. Bariatric surgery may improve metabolism through the action on GLP-1 levels. In recent years, there has been a great interest in developing effective methods to regulate glucagon-like peptide-1 secretion. This review summarizes the literature on glucagon-like peptide-1 and related factors affecting its levels.

Supplier selection or collaboration? Determining factors of performance improvement when outsourcing manufacturing

OpenAIRE

Dabhilkar, Mandar; Bengtsson, Lars; Haartman, Robin von; Åhlström, Pär

2009-01-01

An empirical study was designed to determine factors of performance improvement when outsourcing manufacturing. Findings from a survey of 136 manufacturing plants in Sweden show that most of them achieve their outsourcing motives, but not without trade-offs. Factors of performance improvements such as economies of scale or operations in low-cost countries can improve one performance dimension, such as product cost, yet negatively impact volume flexibility, speed or product innovation. The res...

Preoperative psychosocial risk factors for poor outcomes at 1 and 5 years after total knee replacement.

Science.gov (United States)

Wylde, Vikki; Trela-Larsen, Lea; Whitehouse, Michael R; Blom, Ashley W

2017-10-01

Background and purpose - Psychosocial factors are important risk factors for poor outcomes in the first year after total knee replacement (TKR), however their impact on long-term outcomes is unclear. We aimed to identify preoperative psychosocial risk factors for poor outcomes at 1 year and 5 years after TKR. Patients and methods - 266 patients were recruited prior to TKR surgery. Knee pain and function were assessed preoperatively and at 1 and 5 years postoperative using the WOMAC Pain score, WOMAC Function score and American Knee Society Score (AKSS) Knee score. Preoperative depression, anxiety, catastrophizing, pain self-efficacy and social support were assessed. Statistical analyses involved multiple linear regression and mixed effect linear regression. Results - Higher anxiety was a risk factor for worse pain at 1 year postoperative. No psychosocial factors were associated with any outcomes at 5 years postoperative. Analysis of change over time found that patients with higher pain self-efficacy had lower preoperative pain and experienced less improvement in pain up to 1 year postoperative. Higher pain self-efficacy was associated with less improvement in the AKSS up to 1 year postoperative but more improvement between 1 and 5 years postoperative. Interpretation - Preoperative anxiety was found to influence pain at 1 year after TKR. However, none of the psychosocial variables were risk factors for a poor outcome at 5 years post-operative, suggesting that the negative effects of anxiety on outcome do not persist in the longer-term.

The Polymorphism of Pituitary Factor 1 (POU1F1 in Cattle

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Teodora Crina Carsai

2012-05-01

Full Text Available The development and function of mammary gland is mainly controlled by growth hormone and prolactin, twoprotein hormones secreted by the anterior pituitary gland. Their synthesis is under regulatory influence of pituitaryfactor 1 (PIT1 or POU1F1, a protein factor produced in hypothalamic nuclei. In cattle, it was shown that a HinfIpolymorphism located in exon 6 of PIT1 gene may have significant influence on milk quantity. In particular A allelewas associated with a higher milk yield and could be a valuable genetic marker for improving milk quantity in cattle.In an effort to better understand the possible influence of this polymorphism on mammary gland development andfunction in cattle, we have studied the frequency this polymorphism in Romanian Black and White breed, a highmilk production cattle breed versus Romanian Grey Steppe breed, a primitive breed with very low milk production.In both breeds the frequency of B allele is much higher as compared with the frequency of A allele. The study ofPIT1 polymorphism in Romanian cattle breeds is a part of a more complex study targeting several key genesinvolved in mammary gland function.

Effects of transforming growth factor-beta1 and vascular endothelial growth factor 165 gene transfer on Achilles tendon healing.

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Hou, Yu; Mao, ZeBin; Wei, XueLei; Lin, Lin; Chen, LianXu; Wang, HaiJun; Fu, Xin; Zhang, JiYing; Yu, Changlong

2009-07-01

Repaired Achilles tendons typically take weeks before they are strong enough to handle physiological loads. Gene therapy is a promising treatment for Achilles tendon defects. The aim of the present study was to evaluate the histological/biomechanical effects of Transforming growth factor-beta1 (TGF-beta1) and vascular endothelial growth factor 165 (VEGF(165)) gene transfer on Achilles tendon healing in rabbits. Bone Marrow-Derived Mesenchymal Stem Cells (BMSCs) were transduced with adenovirus carrying human TGF-beta1 cDNA (Ad-TGF-beta1), human VEGF(165) cDNA (Ad-VEGF(165)), or both (PIRES-TGF-beta1/VEGF(165)) Viruses, no cDNA (Ad-GFP), and the BMSCs without gene transfer and the intact tendon were used as control. BMSCs were surgically implanted into the experimentally injured Achilles tendons. TGF-beta1 distribution, cellularity, nuclear aspect ratio, nuclear orientation angle, vascular number, collagen synthesis, and biomechanical features were measured at 1, 2, 4, and 8 weeks after surgery. The TGF-beta1 and TGF beta 1/VEGF(165) co-expression groups exhibited improved parameters compared with other groups, while the VEGF(165) expression group had a negative impact. In the co-expression group, the angiogenesis effects of VEGF(165) were diminished by TGF-beta1, while the collagen synthesis effects of TGF-beta1 were unaltered by VEGF(165). Thus treatment with TGF-beta1 cDNA-transduced BMSCs grafts is a promising therapy for acceleration and improvement of tendon healing, leading to quicker recovery and improved biomechanical properties of Achilles tendons.

Strand transfer and elongation of HIV-1 reverse transcription is facilitated by cell factors in vitro.

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David Warrilow

Full Text Available Recent work suggests a role for multiple host factors in facilitating HIV-1 reverse transcription. Previously, we identified a cellular activity which increases the efficiency of HIV-1 reverse transcription in vitro. Here, we describe aspects of the activity which shed light on its function. The cellular factor did not affect synthesis of strong-stop DNA but did improve downstream DNA synthesis. The stimulatory activity was isolated by gel filtration in a single fraction of the exclusion volume. Velocity-gradient purified HIV-1, which was free of detectable RNase activity, showed poor reverse transcription efficiency but was strongly stimulated by partially purified cell proteins. Hence, the cell factor(s did not inactivate an RNase activity that might degrade the viral genomic RNA and block completion of reverse transcription. Instead, the cell factor(s enhanced first strand transfer and synthesis of late reverse transcription suggesting it stabilized the reverse transcription complex. The factor did not affect lysis of HIV-1 by Triton X-100 in the endogenous reverse transcription (ERT system, and ERT reactions with HIV-1 containing capsid mutations, which varied the biochemical stability of viral core structures and impeded reverse transcription in cells, showed no difference in the ability to be stimulated by the cell factor(s suggesting a lack of involvement of the capsid in the in vitro assay. In addition, reverse transcription products were found to be resistant to exogenous DNase I activity when the active fraction was present in the ERT assay. These results indicate that the cell factor(s may improve reverse transcription by facilitating DNA strand transfer and DNA synthesis. It also had a protective function for the reverse transcription products, but it is unclear if this is related to improved DNA synthesis.

Improved Balanced Incomplete Factorization

Czech Academy of Sciences Publication Activity Database

Bru, R.; Marín, J.; Mas, J.; Tůma, Miroslav

2010-01-01

Roč. 31, č. 5 (2010), s. 2431-2452 ISSN 0895-4798 R&D Projects: GA AV ČR IAA100300802 Grant - others:GA AV ČR(CZ) M100300902 Institutional research plan: CEZ:AV0Z10300504 Source of funding: I - inštitucionálna podpora na rozvoj VO Keywords : preconditioned iterative methods * sparse matrices * incomplete decompositions * approximate inverses * Sherman-Morrison formula * nonsymmetric matrices Subject RIV: BA - General Mathematics Impact factor: 1.725, year: 2010

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

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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.

Improving Your Exploratory Factor Analysis for Ordinal Data: A Demonstration Using FACTOR

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James Baglin

2014-06-01

Full Text Available Exploratory factor analysis (EFA methods are used extensively in the field of assessment and evaluation. Due to EFA's widespread use, common methods and practices have come under close scrutiny. A substantial body of literature has been compiled highlighting problems with many of the methods and practices used in EFA, and, in response, many guidelines have been proposed with the aim to improve application. Unfortunately, implementing recommended EFA practices has been restricted by the range of options available in commercial statistical packages and, perhaps, due to an absence of clear, practical - how-to' demonstrations. Consequently, this article describes the application of methods recommended to get the most out of your EFA. The article focuses on dealing with the common situation of analysing ordinal data as derived from Likert-type scales. These methods are demonstrated using the free, stand-alone, easy-to-use and powerful EFA package FACTOR (http://psico.fcep.urv.es/utilitats/factor/, Lorenzo-Seva & Ferrando, 2006. The demonstration applies the recommended techniques using an accompanying dataset, based on the Big 5 personality test. The outcomes obtained by the EFA using the recommended procedures through FACTOR are compared to the default techniques currently available in SPSS.

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

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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.

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

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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.

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

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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

Identification and overexpression of a Knotted1-like transcription factor in switchgrass (Panicum virgatum L. for lignocellulosic feedstock improvement

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Wegi eWuddineh

2016-04-01

Full Text Available 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. Gene 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 signalling. Furthermore, overexpression of PvKN1 altered the expression of cellulose and hemicellulose biosynthetic genes and increased sugar release efficiency in transgenic lines. Our results 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.

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

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

Haruyuki Tsuchiya

Full Text Available 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.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

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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].

Science.gov (United States)

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.

Science.gov (United States)

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.

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Pedro Perdigão

Full Text Available 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.

Improving human performance: Industry factors influencing the ability to perform

OpenAIRE

Güera Massyn Romo

2013-01-01

Learning interventions and new technologies that aim to improve human performance must take cognisance of industry factors inhibiting human performance. The dynamic and fast pace nature of the Information and Communication Technologies (ICT) and the engineering industries do not lend themselves to proper skills planning and management. These industries experience real skills gaps, to some of which they contribute by themselves. This study reports on these performance-inhibiting factors such a...

Inhibition of colony-stimulating factor 1 receptor early in disease ameliorates motor deficits in SCA1 mice.

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Qu, Wenhui; Johnson, Andrea; Kim, Joo Hyun; Lukowicz, Abigail; Svedberg, Daniel; Cvetanovic, Marija

2017-05-25

Polyglutamine (polyQ) expansion in the protein Ataxin-1 (ATXN1) causes spinocerebellar ataxia type 1 (SCA1), a fatal dominantly inherited neurodegenerative disease characterized by motor deficits, cerebellar neurodegeneration, and gliosis. Currently, there are no treatments available to delay or ameliorate SCA1. We have examined the effect of depleting microglia during the early stage of disease by using PLX, an inhibitor of colony-stimulating factor 1 receptor (CSFR1), on disease severity in a mouse model of SCA1. Transgenic mouse model of SCA1, ATXN1[82Q] mice, and wild-type littermate controls were treated with PLX from 3 weeks of age. The effects of PLX on microglial density, astrogliosis, motor behavior, atrophy, and gene expression of Purkinje neurons were examined at 3 months of age. PLX treatment resulted in the elimination of 70-80% of microglia from the cerebellum of both wild-type and ATXN1[82Q] mice. Importantly, PLX ameliorated motor deficits in SCA1 mice. While we have not observed significant improvement in the atrophy or disease-associated gene expression changes in Purkinje neurons upon PLX treatment, we have detected reduced expression of pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) and increase in the protein levels of wild-type ataxin-1 and post-synaptic density protein 95 (PSD95) that may help improve PN function. A decrease in the number of microglia during an early stage of disease resulted in the amelioration of motor deficits in SCA1 mice.

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

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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 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

CNF1 Improves Astrocytic Ability to Support Neuronal Growth and Differentiation In vitro

OpenAIRE

Malchiodi-Albedi, Fiorella; Paradisi, Silvia; Di Nottia, Michela; Simone, Daiana; Travaglione, Sara; Falzano, Loredana; Guidotti, Marco; Frank, Claudio; Cutarelli, Alessandro; Fabbri, Alessia; Fiorentini, Carla

2012-01-01

Modulation of cerebral Rho GTPases activity in mice brain by intracerebral administration of Cytotoxic Necrotizing Factor 1 (CNF1) leads to enhanced neurotransmission and synaptic plasticity and improves learning and memory. To gain more insight into the interactions between CNF1 and neuronal cells, we used primary neuronal and astrocytic cultures from rat embryonic brain to study CNF1 effects on neuronal differentiation, focusing on dendritic tree growth and synapse formation, which are stri...

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

Science.gov (United States)

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 (Plevel at study end (Pbody 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.

Postmastectomy radiotherapy improves disease-free survival of high risk of locoregional recurrence breast cancer patients with T1-2 and 1 to 3 positive nodes.

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Zhen-Yu He

Full Text Available The indications for post-mastectomy radiotherapy (PMRT with T1-2 breast cancer and 1-3 positive axillary lymph nodes is still controversial. The purpose of this study was to investigate the role of PMRT in T1-2 breast cancer with 1-3 positive axillary lymph node.We retrospectively reviewed the file records of 79 patients receiving PMRT and not receiving PMRT (618 patients.The median follow-up was 65 months. Multivariate analysis showed that PMRT was an independent prognostic factor of locoregional recurrence-free survival (LRFS (P = 0.010. Subgroup analysis of patients who did not undergo PMRT showed that pT stage, number of positive axillary lymph nodes, and molecular subtype were independent prognostic factors of LRFS. PMRT improved LRFS in the entire group (P = 0.005, but did not affect distant metastasis-free survival (DMFS (P = 0.494, disease-free survival (DFS (P = 0.215, and overall survival (OS (P = 0.645. For patients without PMRT, the 5-year LRFS of low-risk patients (0-1 risk factor for locoregional recurrence of 94.5% was significantly higher than that of high-risk patients (2-3 risk factors for locoregional recurrence (80.9%, P < 0.001. PMRT improved LRFS (P = 0.001 and DFS (P = 0.027 in high-risk patients, but did not improve LRFS, DMFS, DFS, and OS in low-risk patients.PMRT is beneficial in patients with high risk of locoregional recurrence breast cancer patients with T1-2 and 1 to 3 positive nodes.

Factors Affecting the Adoption of Improved Rice Varieties in Borno ...

African Journals Online (AJOL)

USER

The study investigated the factors that affect adoption of improved rice varieties in the ... give a good results and also a threat to food security. Keywords: ..... decision of the farmers, however, inappropriate chain of supply/distributing the input or ...

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

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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 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 (R 2  = 0.18). The use of routinely available pre-operative patient factors improves the prediction of operative

Growth factor stimulation improves the structure and properties of scaffold-free engineered auricular cartilage constructs.

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Renata G Rosa

Full Text Available 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.

Improvement of Power Flow Calculation with Optimization Factor Based on Current Injection Method

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Lei Wang

2014-01-01

Full Text Available This paper presents an improvement in power flow calculation based on current injection method by introducing optimization factor. In the method proposed by this paper, the PQ buses are represented by current mismatches while the PV buses are represented by power mismatches. It is different from the representations in conventional current injection power flow equations. By using the combined power and current injection mismatches method, the number of the equations required can be decreased to only one for each PV bus. The optimization factor is used to improve the iteration process and to ensure the effectiveness of the improved method proposed when the system is ill-conditioned. To verify the effectiveness of the method, the IEEE test systems are tested by conventional current injection method and the improved method proposed separately. Then the results are compared. The comparisons show that the optimization factor improves the convergence character effectively, especially that when the system is at high loading level and R/X ratio, the iteration number is one or two times less than the conventional current injection method. When the overloading condition of the system is serious, the iteration number in this paper appears 4 times less than the conventional current injection method.

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

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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…

Improved USLE-K factor prediction: A case study on water erosion areas in China

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Bin Wang

2016-09-01

Full Text Available Soil erodibility (K-factor is an essential factor in soil erosion prediction and conservation practises. The major obstacles to any accurate, large-scale soil erodibility estimation are the lack of necessary data on soil characteristics and the misuse of variable K-factor calculators. In this study, we assessed the performance of available erodibility estimators Universal Soil Loss Equation (USLE, Revised Universal Soil Loss Equation (RUSLE, Erosion Productivity Impact Calculator (EPIC and the Geometric Mean Diameter based (Dg model for different geographic regions based on the Chinese soil erodibility database (CSED. Results showed that previous estimators overestimated almost all K-values. Furthermore, only the USLE and Dg approaches could be directly and reliably applicable to black and loess soil regions. Based on the nonlinear best fitting techniques, we improved soil erodibility prediction by combining Dg and soil organic matter (SOM. The NSE, R2 and RE values were 0.94, 0.67 and 9.5% after calibrating the results independently; similar model performance was showed for the validation process. The results obtained via the proposed approach were more accurate that the former K-value predictions. Moreover, those improvements allowed us to effectively establish a regional soil erodibility map (1:250,000 scale of water erosion areas in China. The mean K-value of Chinese water erosion regions was 0.0321 (t ha h·(ha MJ mm−1 with a standard deviation of 0.0107 (t ha h·(ha MJ mm−1; K-values present a decreasing trend from North to South in water erosion areas in China. The yield soil erodibility dataset also satisfactorily corresponded to former K-values from different scales (local, regional, and national.

Endurance Factors Improve Hippocampal Neurogenesis and Spatial Memory in Mice

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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…

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

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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

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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

Improving classroom practices: the impact of leadership, school organizational conditions, and teacher factors

NARCIS (Netherlands)

Thoonen, E.E.J.

2012-01-01

Schools are challenged to improve classroom practices as they are expected to enhance students’ motivation. While leadership, school organizational conditions and teacher factors are considered essential for improving classroom practices, more should be known about the interplay between school

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.

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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 IGF-1, but not insulin, suppressed hepatic glucose production and increased glucose disposal rates in aging rats (P 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.

Worksite Opportunities for Wellness (WOW): effects on cardiovascular disease risk factors after 1 year.

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Racette, Susan B; Deusinger, Susan S; Inman, Cindi L; Burlis, Tamara L; Highstein, Gabrielle R; Buskirk, Trent D; Steger-May, Karen; Peterson, Linda R

2009-01-01

To evaluate the effectiveness of a worksite health promotion program on improving cardiovascular disease risk factors. In St Louis, Missouri from 2005 to 2006, 151 employees (134 F, 17 M, 81% overweight/obese) participated in a cohort-randomized trial comparing assessments + intervention (worksite A) with assessments only (worksite B) for 1 year. All participants received personal health reports containing their assessment results. The intervention was designed to promote physical activity and favorable dietary patterns using pedometers, healthy snack cart, WeightWatchers(R) meetings, group exercise classes, seminars, team competitions, and participation rewards. Outcomes included BMI, body composition, blood pressure, fitness, lipids, and Framingham 10-year coronary heart disease risk. 123 participants, aged 45+/-9 yr, with BMI 32.9+/-8.8 kg/m(2) completed 1 year. Improvements (P< or =0.05) were observed at both worksites for fitness, blood pressure, and total-, HDL-, and LDL-cholesterol. Additional improvements occurred at worksite A in BMI, fat mass, Framingham risk score, and prevalence of the metabolic syndrome; only the changes in BMI and fat mass were different between worksites. A multi-faceted worksite intervention promoted favorable changes in cardiovascular disease risk factors, but many of the improvements were achieved with worksite health assessments and personalized health reports in the absence of an intervention.

Hypoxia-inducible factor-1 alpha has a key role in hypoxic preconditioning.

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Taie, Satoshi; Ono, Junichiro; Iwanaga, Yasuyuki; Tomita, Shuhei; Asaga, Takehiko; Chujo, Kosuke; Ueki, Masaaki

2009-08-01

Sublethal hypoxia induces tolerance to subsequent hypoxic insults in a process known as hypoxic preconditioning (HP). Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is a key transcription protein involved in the mechanism of HP. In this study, we investigated the effects of HP on tissue oxygenation and expression of HIF-1 alpha gene targets in the brain using neural cell-specific HIF-1 alpha-deficient mice. The animals were exposed to 8% oxygen for 3 hours. Twenty-four hours later, the oxygen partial pressure (pO(2)) of brain tissue and gene expression were measured during hypoxia. HP improved the pO(2) of brain tissue during subsequent hypoxia with upregulated inducible nitric oxide synthase in wild-type mice, whereas HP had no detectable effect in the mutant mice. Our results indicate that the protective effects of HP may be partially mediated by improving tissue oxygenation via HIF-1 alpha and inducible nitric oxide synthase.

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

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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.

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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.

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

Science.gov (United States)

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.

Molecular Characterization and Expression Analysis of Insulin-like Growth Factor-1 and Insulin-like Growth Factor Binding Protein-1 Genes in Qinghai-Tibet Plateau and Lowland

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Ya-bing Chen

2015-01-01

Full Text Available Insulin-like growth factor-1 (IGF-1 and insulin-like growth factor binding protein-1 (IGFBP-1 play a pivotal role in regulating cellular hypoxic response. In this study, we cloned and characterized the genes encoding IGF-1 and IGFBP-1 to improve the current knowledge on their roles in highland Bos grunniens (Yak. We also compared their expression levels in the liver and kidney tissues between yaks and lowland cattle. We obtained full-length 465 bp IGF-1 and 792 bp IGFBP-1, encoding 154 amino acids (AA IGF-1, and 263 AA IGFBP-1 protein, respectively using reverse transcriptase-polyerase chain reaction (RT-PCR technology. Analysis of their corresponding amino acid sequences showed a high identity between B. grunniens and lowland mammals. Moreover, the two genes were proved to be widely distributed in the examined tissues through expression pattern analysis. Real-time PCR results revealed that IGF-1 expression was higher in the liver and kidney tissues in B. grunniens than in Bos taurus (p<0.05. The IGFBP-1 gene was expressed at a higher level in the liver (p<0.05 of B. taurus than B. grunniens, but it has a similar expression level in the kidneys of the two species. These results indicated that upregulated IGF-1 and downregulated IGFBP-1 are associated with hypoxia adaptive response in B. grunniens.

SPATIAL VARIETY AND DISTRIBUTION OF TRADITIONAL MARKETS IN SURAKARTA AS POTENTIAL FACTORS IN IMPROVING SPATIAL-BASED MANAGEMENT

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Istijabatul Aliyah

2017-02-01

Full Text Available Traditional markets function as trading place, socio-culture interaction, and recreation facility either in regional or urban scope. Distribution and variety of spatial condition influence traditional markets’ planning both physically and non-physically. Therefore, this research aimed to conduct a mapping of traditional markets’ spatial distribution and variety as potential factors to improve spatial-based management. Analysis methods including: (1 Mapping by employing Geographic Information System, (2 Category Based Analysis (CBA, and (3 Interactive Analysis were applied in Surakarta City as the research location. The result of this research signifies that spatial variety and distribution of traditional markets in Surakarta had similar pattern between one market to others; overlapping service function; specific commodity types in accordance with the market’s characteristics; diverse operating hours. Spatial variety and distribution could be potential factors to improve traditional market management as shopping service. This result was contrasted with Central Place Theory by Christaller and NÆss & Jensen’s research finding stating that distance became a key factor influencing accessibility to a number of activity facilities. Therefore, distance toward the service center is not considered as the main factor in traditional market management. The main factor in managing and controlling traditional markets’ development includes service function, commodity specification, and operating hour’s flexibility.

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

Science.gov (United States)

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.

Effects of liraglutide on cardiovascular risk factors in patients with type 1 diabetes

DEFF Research Database (Denmark)

Dejgaard, Thomas F; Johansen, Nanna B; Frandsen, Christian S

2016-01-01

We investigated the short-term effect of adding liraglutide 1.8 mg once daily to insulin treatment on cardiovascular risk factors in patients with type 1 diabetes. In total, 100 overweight (BMI ≥25 kg/m(2) ) adult patients (age ≥18 years) with type 1 diabetes and HbA1c ≥ 8% (64 mmol/mol) were....... In conclusion, in patients with long-standing type 1 diabetes, liraglutide as add-on to insulin increased heart rate and did not improve other cardiovascular risk factors after 24 weeks of treatment....... randomized to liraglutide 1.8 mg or placebo added to insulin treatment in a 24-week double-blinded, placebo-controlled trial. At baseline and after 24 weeks of treatment, 24-hour blood pressure and heart rate, pulse pressure, pulse wave velocity and carotid intima-media thickness were evaluated. Compared...

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.

Science.gov (United States)

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.

Immunohistochemical expression of Insulin-like growth factor-1, Transforming growth factor-beta1, and Vascular endothelial growth factor in parathyroid adenoma and hyperplasia

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Hamide Sayar

2014-01-01

Full Text Available Background: Insulin-like growth factor (IGF, transforming growth factor-beta1 (TGF-β1, and vascular endothelial growth factor (VEGF are commonly studied growth factors, but little data are available on the immunohistochemical expression of these factors in parathyroid lesions. Materials and Methods: Tissue specimens from 36 patients with primary hyperparathyroidism (P-HPT (26 adenomas and 10 primary hyperplasias were examined. Normal parathyroid tissue adjacent to the adenoma or area of hyperplasia was used as control tissue. Preoperative laboratory testing [serum Ca and P, creatinine and parathormone levels (PTH] which led to the diagnosis of P-HPT had been performed, the size and weight of the parathyroid glands measured, and postoperative serum PTH levels determined. Paraffin-embedded parathyroid tissue specimens were stained with antibodies to IGF-1, VEGF, and TGF-β1 using standard immunohistochemical procedures. Results: IGF-1 immunoreactivity was seen in 50% of hyperplasia and in 46% of adenoma samples, but in 87% of normal parathyroid tissue in the vicinity of the adenomas (P = 0.005. TGF-β1 immunoreactivity was observed in 90% of hyperplasia, in 92% of adenoma samples, and in 95% of normal tissues around adenomas. VEGF immunoreactivity was observed in 70% of hyperplastic and 65% of adenomatous tissues, as well as in 54% of normal tissues in the vicinity of the adenoma. No significant differences in the expression of IGF-1, TGF-β1, and VEGF were observed between primary adenomas compared to hyperplasia samples (P > 0.05. Conclusions: Parathyroid tissue is clearly a site for production of IGF-1, TGF-β1, and VEGF. IGF-1 receptor activity was higher in normal parathyroid tissue compared to hyperplastic and adenomatous tissue.

26 CFR 1.611-5 - Depreciation of improvements.

Science.gov (United States)

2010-04-01

... 26 Internal Revenue 7 2010-04-01 2010-04-01 true Depreciation of improvements. 1.611-5 Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Natural Resources § 1.611-5 Depreciation of improvements. (a) In general... there shall be allowed as a deduction a reasonable allowance for depreciation of improvements. Such...

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

International Nuclear Information System (INIS)

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

2016-01-01

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. - 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

Improvements on Cardiovascular Diseases Risk Factors in Obese Adolescents

DEFF Research Database (Denmark)

Gomes Silva, Humberto José; Andersen, Lars Bo; Lofrano-Prado, Mara Cristina

2015-01-01

BACKGROUND: It is unclear how different exercise intensities affect cardiovascular disease (CVD) risk factors in obese adolescents. The aim of this study was to compare the effects of high intensity (HIT) vs. low intensity (LIT) aerobic training on CVD risk factors in obese adolescents. METHODS......: Forty-three obese adolescents (age: 15.7±1.3y, BMI: 34.3±4.1kg/m2) participated this study either HIT (corresponding to ventilatory threshold-I, VT1; N=20) or LIT (20% below VT1; N=23) for 12 weeks (12W). All sessions were isocaloric (350 kcal). All participants received the same nutritional......, psychological and clinical counseling. Subjects were assessed in fatness, fitness, lipid profile and glucose at baseline and after 12W. The CVD risk factors assessed were waist circumference (WC), total cholesterol (TC), HDL, glucose and fitness, which were single and clustered analyzed (Z-scores sum). RESULTS...

Analysis on nuclear power plant control room system design and improvement based on human factor engineering

International Nuclear Information System (INIS)

Gao Feng; Liu Yanzi; Sun Yongbin

2014-01-01

The design of nuclear power plant control room system is a process of improvement with the implementation of human factor engineering theory and guidance. The method of implementation human factor engineering principles into the nuclear power plant control room system design and improvement was discussed in this paper. It is recommended that comprehensive address should be done from control room system function, human machine interface, digital procedure, control room layout and environment design based on the human factor engineering theory and experience. The main issues which should be paid more attention during the control room system design and improvement also were addressed in this paper, and then advices and notices for the design and improvement of the nuclear power plant control room system were afforded. (authors)

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

Science.gov (United States)

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.

Factor Structure of the Conflict Tactics Scale 1

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Kaori Baba

2017-07-01

Full Text Available Background: The Conflict Tactics Scale 1 (CTS1 is a widely used self-report measure of abusive attitudes of parents towards children. The factor structure of the CTS1 still remains to be clarified. The aim of this study was to examine the factor structure of the Japanese version of the CTS1 for postpartum women in community settings. Method: The data in this study came from the Okayama and Kumamoto’s study. These were part of a larger survey using longitudinal questionnaire studies conducted in Japan from 2001 to 2002 and in 2011, respectively. In both study sites, the participant mothers were asked to fill in the CTS1 one month after delivery when they attended for check-up at the out-patient clinic. Results: A total of 1,150 questionnaires were collected, excluding the participants with missing values in the CTS1. Finally, 1,078 were included in the statistical analyses. Data of 1,078 women were divided into two parts. In the first halved sample (n=578, an exploratory factor analysis was conducted for the CTS1 items after exluding nine items with extremely low prevalence. It revealed 2-factor or 3-factor models. Then, we conducted a model comparison with the second halved sample (n=500, using confirmatory factor analysis. In terms of goodness-of-fit indeces, the 2-factor model was superior. Its subscales were Reasoning and Psycholosical Aggression. Conclusion: The 2-factor model of the CTS1 consisting of Reasoning and Psychological Aggression was superior to the 3-factor model. This is not inconsistent with the original authors’ theoretical model.

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

Science.gov (United States)

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.

Transplantation of Rat Mesenchymal Stem Cells Overexpressing Hypoxia-Inducible Factor 2α Improves Blood Perfusion and Arteriogenesis in a Rat Hindlimb Ischemia Model

Directory of Open Access Journals (Sweden)

Weifeng Lu

2017-01-01

Full Text Available Mesenchymal stem cells (MSCs have been increasingly tested in cell-based therapy to treat numerous diseases. Genetic modification to improve MSC behavior may enhance posttransplantation outcome. This study aims to test the potential therapeutic benefits of rat bone marrow MSCs overexpressing hypoxia-inducible factor 2α (rMSCsHIF-2α in a rat hindlimb ischemia model. PBS, rMSCs, or rMSCsHIF-2α were injected into rat ischemic hindlimb. Compared with the injection of PBS or rMSCs, transplantation of rMSCsHIF-2α significantly improved blood perfusion, increased the number of vessel branches in the muscle of the ischemic hindlimb, and improved the foot mobility of the ischemic hindlimb (all P<0.05. rMSCHIF-2α transplantation also markedly increased the expression of proangiogenic factors VEGF, bFGF, and SDF1 and Notch signaling proteins including DII4, NICD, Hey1, and Hes1, whereas it reduced the expression of proapoptotic factor Bax in the muscle of the ischemic hindlimb. Overexpression of HIF-2α did not affect rMSC stemness and proliferation under normoxia but significantly increased rMSC migration and tube formation in matrigel under hypoxia (all P<0.05. RMSCsHIF-2α stimulated endothelial cell invasion under hypoxia significantly (P<0.05. Genetic modification of rMSCs via overexpression of HIF-2α improves posttransplantation outcomes in a rat hindlimb ischemia model possibly by stimulating proangiogenic growth factors and cytokines.

A novel method for improved accuracy of transcription factor binding site prediction

KAUST Repository

Khamis, Abdullah M.; Motwalli, Olaa Amin; Oliva, Romina; Jankovic, Boris R.; Medvedeva, Yulia; Ashoor, Haitham; Essack, Magbubah; Gao, Xin; Bajic, Vladimir B.

2018-01-01

Identifying transcription factor (TF) binding sites (TFBSs) is important in the computational inference of gene regulation. Widely used computational methods of TFBS prediction based on position weight matrices (PWMs) usually have high false positive rates. Moreover, computational studies of transcription regulation in eukaryotes frequently require numerous PWM models of TFBSs due to a large number of TFs involved. To overcome these problems we developed DRAF, a novel method for TFBS prediction that requires only 14 prediction models for 232 human TFs, while at the same time significantly improves prediction accuracy. DRAF models use more features than PWM models, as they combine information from TFBS sequences and physicochemical properties of TF DNA-binding domains into machine learning models. Evaluation of DRAF on 98 human ChIP-seq datasets shows on average 1.54-, 1.96- and 5.19-fold reduction of false positives at the same sensitivities compared to models from HOCOMOCO, TRANSFAC and DeepBind, respectively. This observation suggests that one can efficiently replace the PWM models for TFBS prediction by a small number of DRAF models that significantly improve prediction accuracy. The DRAF method is implemented in a web tool and in a stand-alone software freely available at http://cbrc.kaust.edu.sa/DRAF.

A novel method for improved accuracy of transcription factor binding site prediction

KAUST Repository

Khamis, Abdullah M.

2018-03-20

Identifying transcription factor (TF) binding sites (TFBSs) is important in the computational inference of gene regulation. Widely used computational methods of TFBS prediction based on position weight matrices (PWMs) usually have high false positive rates. Moreover, computational studies of transcription regulation in eukaryotes frequently require numerous PWM models of TFBSs due to a large number of TFs involved. To overcome these problems we developed DRAF, a novel method for TFBS prediction that requires only 14 prediction models for 232 human TFs, while at the same time significantly improves prediction accuracy. DRAF models use more features than PWM models, as they combine information from TFBS sequences and physicochemical properties of TF DNA-binding domains into machine learning models. Evaluation of DRAF on 98 human ChIP-seq datasets shows on average 1.54-, 1.96- and 5.19-fold reduction of false positives at the same sensitivities compared to models from HOCOMOCO, TRANSFAC and DeepBind, respectively. This observation suggests that one can efficiently replace the PWM models for TFBS prediction by a small number of DRAF models that significantly improve prediction accuracy. The DRAF method is implemented in a web tool and in a stand-alone software freely available at http://cbrc.kaust.edu.sa/DRAF.

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

Energy Technology Data Exchange (ETDEWEB)

Yang, Bin [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China); Li, Wei [Department of Gerontology, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China); Zheng, Qichang [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China); Qin, Tao [Department of Hepatobiliary Pancreatic Surgery, People' s Hospital of Zhengzhou University, School of Medicine, Zhengzhou University, Zhengzhou 450003 (China); Wang, Kun; Li, Jinjin; Guo, Bing; Yu, Qihong; Wu, Yuzhe; Gao, Yang; Cheng, Xiang; Hu, Shaobo; Kumar, Stanley Naveen [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China); Liu, Sanguang, E-mail: sanguang1998@sina.com [Department of Hepatobiliary Surgery, The Second Hospital, Hebei Medical University, Shijiazhuang 050000 (China); Song, Zifang, E-mail: zsong@hust.edu.cn [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China)

2015-07-17

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 negative 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.

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

International Nuclear Information System (INIS)

Yang, Bin; Li, Wei; Zheng, Qichang; Qin, Tao; Wang, Kun; Li, Jinjin; Guo, Bing; Yu, Qihong; Wu, Yuzhe; Gao, Yang; Cheng, Xiang; Hu, Shaobo; Kumar, Stanley Naveen; Liu, Sanguang; Song, Zifang

2015-01-01

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 negative 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

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

Science.gov (United States)

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

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

Science.gov (United States)

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.

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

International Nuclear Information System (INIS)

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

2012-01-01

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. (semiconductor devices)

An Empirical Study of Critical Soft Factors for Quality Improvement in The Electrical and Electronics Firms in Malaysia

Directory of Open Access Journals (Sweden)

Muhammad Madi Abdullah

2009-03-01

Full Text Available Soft factors are important aspect that sustains the organizations in their efforts towards continuous quality improvement (QI and customer satisfaction. The conventional wisdom states that quality improvement in organizations increases profits and productivity. Therefore, the aim of the paper is to examine the influence of critical soft factors (CSF on quality improvement (QI. For that purpose, this study examine: (i the relationship between the CSF and QI and (ii to what extent the six CSF explain QI. The study used survey data from 255 electrical and electronics (E&E firms in Malaysia. The individual managers representing the each firm made the unit of analysis of the study. The finding reveals that QI was significantly influenced by the following soft factors: management commitment, customer focus, employee involvement, training & education, and reward & recognition. Supplier relationship was not a significant predictor of quality improvement. Finally, this study has empirically shown that quality improvement will increase when the organizations emphasize more on soft factors.Keywords: Critical soft factors, quality improvement, Electrical and Electronics firms

Three-dimensional flow analysis and improvement of slip factor model for forward-curved blades centrifugal fan

International Nuclear Information System (INIS)

Guo, En Min; Kim, Kwang Yong

2004-01-01

This work developed improved slip factor model and correction method to predict flow through impeller in forward-curved centrifugal fan. Both steady and unsteady three-dimensional CFD analyses were performed to validate the slip factor model and the correction method. The results show that the improved slip factor model presented in this paper could provide more accurate predictions for forward-curved centrifugal impeller than the other slip factor models since the present model takes into account the effect of blade curvature. The correction method is provided to predict mass-averaged absolute circumferential velocity at the exit of impeller by taking account of blockage effects induced by the large-scale backflow near the front plate and flow separation within blade passage. The comparison with CFD results also shows that the improved slip factor model coupled with the present correction method provides accurate predictions for mass-averaged absolute circumferential velocity at the exit of impeller near and above the flow rate of peak total pressure coefficient

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

Directory of Open Access Journals (Sweden)

Tran Thi Tuyet-Hanh

2016-10-01

Full Text Available Objective: 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. Method: 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.

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

Science.gov (United States)

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

An improvement of the applicability of human factors guidelines for coping with human factors issues in nuclear power plants

International Nuclear Information System (INIS)

Lee, Y. H.; Lee, J. Y.

2003-01-01

Human factors have been well known as one of the key factors to the system effectiveness as well as the efficiency and safety of nuclear power plants(NPPs). Human factors engineering(HFE) are included in periodic safety review(PSR) on the existing NPPs and the formal safety assessment for the new ones. However, HFE for NPPs is still neither popular in practice nor concrete in methodology. Especially, the human factors guidelines, which are the most frequent form of human factors engineering in practice, reveal the limitations in their applications. We discuss the limitations and their casual factors found in human factors guidelines in order to lesson the workload of HFE practitioners and to improve the applicability of human factors guidelines. According to the purposes and the phases of HFE for NPPs, more selective items and specified criteria should be prepared carefully in the human factors guidelines for the each HFE applications in practice. These finding on the human factors guidelines can be transferred to the other HFE application field, such as military, aviation, telecommunication, HCI, and product safety

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

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

Dominic Jauvin

2017-06-01

Full Text Available Myotonic dystrophy type 1 (DM1, a dominant hereditary muscular dystrophy, is caused by an abnormal expansion of a (CTGn 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 CUGexp 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 CUGexp RNA improves muscle strength in DM1, suggesting that muscle weakness in DM1 patients may be improved following elimination of toxic RNAs.

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

Science.gov (United States)

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.

The strength of small: Improved targeting of Insulin-like Growth Factor-1 Receptor (IGF-1R) with F(ab')2-R1507 fragments in Ewing sarcomas

NARCIS (Netherlands)

Fleuren, Emmy D. G.; Versleijen-Jonkers, Yvonne M. H.; Heskamp, Sandra; Roeffen, Melissa H. S.; Bouwman, Wilbert H.; Molkenboer-Kuenen, Janneke D. M.; van Laarhoven, Hanneke W. M.; Oyen, Wim J. G.; Boerman, Otto C.; van der Graaf, Winette T. A.

2013-01-01

To investigate whether F(ab')2-fragments of the monoclonal Insulin-like Growth Factor-1 Receptor (IGF-1R) antibody R1507 (F(ab')2-R1507) can successfully target IGF-1R in Ewing sarcomas (ES). BALB/c nude mice were subcutaneously implanted with IGF-1R-expressing human ES xenografts (EW-5 and EW-8)

Stromal cell-derived factor 1α (SDF-1α)

DEFF Research Database (Denmark)

Li, Dana; Bjørnager, Louise; Langkilde, Anne

2016-01-01

OBJECTIVES: Stromal cell-derived factor 1a (SDF-1α), is a chemokine and is able to home hematopoietic progenitor cells to injured areas of heart tissue for structural repair. Previous studies have found increased levels of SDF-1α in several cardiac diseases, but only few studies have investigated...

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

Science.gov (United States)

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

Financial incentives improve recognition but not treatment of cardiovascular risk factors in severe mental illness.

Directory of Open Access Journals (Sweden)

Carol L Wilson

Full Text Available Severe mental illness (SMI is associated with premature cardiovascular disease, prompting the UK primary care payment-for-performance system (Quality and Outcomes Framework, QOF to incentivise annual physical health reviews. This study aimed to assess the QOF's impact on detection and treatment of cardiovascular risk factors in people with SMI.A retrospective open cohort study of UK general practice was conducted between 1996 and 2014, using segmented logistic regression with 2004 and 2011 as break points, reflecting the introduction of relevant QOF incentives in these years. 67239 SMI cases and 359951 randomly-selected unmatched controls were extracted from the Clinical Practice Research Datalink (CPRD.There was strong evidence (p≤0.015 the 2004 QOF indicator (general health resulted in an immediate increase in recording of elevated cholesterol (odds ratio 1.37 (95% confidence interval 1.24 to 1.51; obesity (OR 1.21 (1.06 to 1.38; and hypertension (OR 1.19 (1.04 to 1.38 in the SMI group compared with the control group, which was sustained in subsequent years. Similar findings were found for diabetes, although the evidence was weaker (p = 0.059; OR 1.21 (0.99 to 1.49. There was evidence (p<0.001 of a further, but unsustained, increase in recording of elevated cholesterol and obesity in the SMI group following the 2011 QOF indicator (cardiovascular specific. There was no clear evidence that the QOF indicators affected the prescribing of lipid modifying medications or anti-diabetic medications.Incentivising general physical health review for SMI improves identification of cardiovascular risk factors, although the additional value of specifically incentivising cardiovascular risk factor assessment is unclear. However, incentives do not affect pharmacological management of these risks.

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

Science.gov (United States)

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.

Science.gov (United States)

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.

Improved SVR Model for Multi-Layer Buildup Factor Calculation

International Nuclear Information System (INIS)

Trontl, K.; Pevec, D.; Smuc, T.

2006-01-01

The accuracy of point kernel method applied in gamma ray dose rate calculations in shielding design and radiation safety analysis is limited by the accuracy of buildup factors used in calculations. Although buildup factors for single-layer shields are well defined and understood, buildup factors for stratified shields represent a complex physical problem that is hard to express in mathematical terms. The traditional approach for expressing buildup factors of multi-layer shields is through semi-empirical formulas obtained by fitting the results of transport theory or Monte Carlo calculations. Such an approach requires an ad-hoc definition of the fitting function and often results with numerous and usually inadequately explained and defined correction factors added to the final empirical formula. Even more, finally obtained formulas are generally limited to a small number of predefined combinations of materials within relatively small range of gamma ray energies and shield thicknesses. Recently, a new approach has been suggested by the authors involving one of machine learning techniques called Support Vector Machines, i.e., Support Vector Regression (SVR). Preliminary investigations performed for double-layer shields revealed great potential of the method, but also pointed out some drawbacks of the developed model, mostly related to the selection of one of the parameters describing the problem (material atomic number), and the method in which the model was designed to evolve during the learning process. It is the aim of this paper to introduce a new parameter (single material buildup factor) that is to replace the existing material atomic number as an input parameter. The comparison of two models generated by different input parameters has been performed. The second goal is to improve the evolution process of learning, i.e., the experimental computational procedure that provides a framework for automated construction of complex regression models of predefined

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

International Nuclear Information System (INIS)

Malur, Anagha; Huizar, Isham; Wells, Greg; Barna, Barbara P.; Malur, Achut G.; Thomassen, Mary Jane

2011-01-01

Highlights: ► Lentivirus-ABCG1 reduces lipid accumulation in lungs of GM-CSF knock-out mice. ► Up-regulation of ABCG1 improves lung function. ► Upregulation of ABCG1 improves surfactant metabolism. -- Abstract: We have shown decreased expression of the nuclear transcription factor, peroxisome proliferator-activated receptor-gamma (PPARγ) and the PPARγ-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 PPARγ. 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) mice. We reported previously that intratracheal instillation of a lentivirus (lenti)-PPARγ 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 PPARγ 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 shown by analysis of bronchoalveolar lavage fluid. Lung compliance was diminished in untreated GMCSF KO mice

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

Science.gov (United States)

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.

Science.gov (United States)

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.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

Scott P. Stumbo

2017-11-01

Full Text Available Abstract Background 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. Methods 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. 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

A New V2G Control Strategy for Load Factor Improvement Using Smoothing Technique

Directory of Open Access Journals (Sweden)

CHANHOM, P.

2017-08-01

Full Text Available This paper proposes a new vehicle-to-grid (V2G control strategy for improving the load factor in the power network. To operate the proposed strategy, the available storage capacity of the PEVs’ batteries is considered as a battery energy storage system (BESS for charging and discharging an amount of power corresponding to the V2G power command. Due to the remarkable advantages of the technique so-called simple moving average, it is selected for applying in the proposed V2G control strategy. In this research, for investigating the load factor improvement, the essential data including the daily-load profiles with 7-day and 14-day periods are used for the 3 studied cases. These 3 studied cases present the power network with variation of the PEVs locations for describing the PEVs usage and charging or discharging behavior. The performance of the proposed strategy is simulated and verified by the MATPOWER software. The simulation results show that the load factors of the 3 studied cases are improved. Moreover, the encouragement of energy arbitrage for the PEVs owners is also discussed in this paper.

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

Energy Technology Data Exchange (ETDEWEB)

Alarcon, Jose Manuel [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States)

2018-04-01

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.

Improvements in a four factor formula recipe for educational purposes

International Nuclear Information System (INIS)

Oelgaard, P.L.

1995-05-01

In introductory reactor physics courses the four-factor-formula and two-group theory is normally used to demonstrate to students in a quantitative way the physics of nuclear reactors. However, the agreement obtained between lattice calculations with such simple recipes and measurements is not very good. This is in particular the case for light water reactors. To improve this situation it has been investigated whether it is possible by relative simple modifications of such a recipe to obtain better agreement between theory and measurements. The results obtained from this investigation are presented in this paper. It is seen from the results that significant improvements in the agreement between measurements and theory have been obtained. This report was presented to the meeting on Reactor Physics Calculations in the Nordic Countries, Helsinki, May 8-9, 1995. (au)

Improving the Optical Quality Factor of the WGM Resonator

Science.gov (United States)

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

Improving the quality factor of an RF spiral inductor with non-uniform metal width and non-uniform coil spacing

International Nuclear Information System (INIS)

Shen Pei; Zhang Wanrong; Huang Lu; Jin Dongyue; Xie Hongyun

2011-01-01

An improved inductor layout with non-uniform metal width and non-uniform spacing is proposed to increase the quality factor (Q factor). For this inductor layout, from outer coil to inner coil, the metal width is reduced by an arithmetic-progression step, while the metal spacing is increased by a geometric-progression step. An improved layout with variable width and changed spacing is of benefit to the Q factor of RF spiral inductor improvement (approximately 42.86%), mainly due to the suppression of eddy-current loss by weakening the current crowding effect in the center of the spiral inductor. In order to increase the Q factor further, for the novel inductor, a patterned ground shield is used with optimized layout together. The results indicate that, in the range of 0.5 to 16 GHz, the Q factor of the novel inductor is at an optimum, which improves by 67% more than conventional inductors with uniform geometry dimensions (equal width and equal spacing), is enhanced by nearly 23% more than a PGS inductor with uniform geometry dimensions, and improves by almost 20% more than an inductor with an improved layout. (semiconductor devices)

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

Science.gov (United States)

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 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.

Factors of Quality Improvement of the Foreign Language Teaching in Technical University

Directory of Open Access Journals (Sweden)

Ira R. Agasieva

2017-03-01

Full Text Available In the article the problem of quality of teaching and knowledge of the English language has been considered. The factors that influence the improvement of the quality of teaching and knowledge of the English language in a technical college, the use of various methods of enhancing the quality of teaching and knowledge of the English language has been analyzed. It has been distinguished the necessity of taking into account the factors such as emotional maturity of the student, the desire for success, student cognitive style, its consistency and independence.

Critical success factors simplified implementing the powerful drivers of dramatic business improvement

CERN Document Server

Howell, Marvin T

2010-01-01

Critical-to-success factors (CSFs) have become essential elements to strategic planning and no business can achieve consistent success without effectively adopting them. To take full advantage of CSFs, however, an organization must first understand what they are and how they can be used to drive organizational initiatives and processes. Critical Success Factors Simplified: Implementing the Powerful Drivers of Dramatic Business Improvement provides a concise manual on CSFs that will teach you how to identify and select the right CSFs, measure their impact, and adjust them as needed to reach your goals.

Glycerol and environmental factors: effects on 1,3-propanediol production and NAD(+) regeneration in Lactobacillus panis PM1.

Science.gov (United States)

Kang, T S; Korber, D R; Tanaka, T

2013-10-01

This study was conducted to understand the influences of fermentation factors in NADH recycling and mechanisms of 1,3-propanediol (1,3-PDO) production in Lactobacillus panis PM1. We conducted metabolite analyses, qRT-PCR of the glycerol reductive pathway [glycerol dehydratase (DhaB) and 1,3-PDO dehydrogenase (DhaT)] and DhaT activity assays at different pH, temperature and initial glycerol concentrations. The supplementation of 150 mmol l(-1) glycerol caused a shift in NADH flux from ethanol to 1,3-PDO production, whereas 300 mol l(-1) glycerol negatively affected the regeneration of NAD(+) via 1,3-PDO production. This retardation decreased transcription levels and specific activities of DhaT. The decreased DhaT activity eventually caused the shutdown of 1,3-PDO production. Temperature and pH did not significantly affect the specific activity of DhaT, whereas expression of genes for DhaB and DhaT was activated under acidic conditions. Moreover, fresh glucose addition after its depletion could not restart the glycerol reduction, but increased ethanol production. Those environmental factors affect 1,3-PDO production in different ways through changing the expression level of enzymes and shifting the NAD(+) regeneration pathways. Our findings elucidated a key element to optimize 1,3-PDO production by Lact. panis PM1, which potentially improves 1,3-PDO manufacturing efficiencies. © 2013 The Society for Applied Microbiology.

Ticagrelor Improves Endothelial Function by Decreasing Circulating Epidermal Growth Factor (EGF

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Francesco Vieceli Dalla Sega

2018-04-01

Full Text Available Ticagrelor is one of the most powerful P2Y12 inhibitor. We have recently reported that, in patients with concomitant Stable Coronary Artery Disease (SCAD and Chronic Obstructive Pulmonary Disease (COPD undergoing percutaneous coronary intervention (PCI, treatment with ticagrelor, as compared to clopidogrel, is associated with an improvement of the endothelial function (Clinical Trial NCT02519608. In the present study, we showed that, in the same population, after 1 month treatment with ticagrelor, but not with clopidogrel, there is a decrease of the circulating levels of epidermal growth factor (EGF and that these changes in circulating levels of EGF correlate with on-treatment platelet reactivity. Furthermore, in human umbilical vein endothelial cells (HUVEC incubated with sera of the patients treated with ticagrelor, but not with clopidogrel there is an increase of p-eNOS levels. Finally, analyzing the changes in EGF and p-eNOS levels after treatment, we observed an inverse correlation between p-eNOS and EGF changes only in the ticagrelor group. Causality between EGF and eNOS activation was assessed in vitro in HUVEC where we showed that EGF decreases eNOS activity in a dose dependent manner. Taken together our data indicate that ticagrelor improves endothelial function by lowering circulating EGF that results in the activation of eNOS in the vascular endothelium.

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

Directory of Open Access Journals (Sweden)

Chao He

2018-01-01

Full Text Available 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.

Dexamethasone impairs hypoxia-inducible factor-1 function

International Nuclear Information System (INIS)

Wagner, A.E.; Huck, G.; Stiehl, D.P.; Jelkmann, W.; Hellwig-Buergel, T.

2008-01-01

Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription-factor composed of α- and β-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-1α levels in the cytosol of HepG2 cells, while nuclear HIF-1α levels and HIF-1 DNA-binding was reduced. In addition, DEX dose-dependently lowered the hypoxia-induced luciferase activity in a 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

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

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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.

An Improved Reinforcement Learning System Using Affective Factors

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Takashi Kuremoto

2013-07-01

Full Text Available As a powerful and intelligent machine learning method, reinforcement learning (RL has been widely used in many fields such as game theory, adaptive control, multi-agent system, nonlinear forecasting, and so on. The main contribution of this technique is its exploration and exploitation approaches to find the optimal solution or semi-optimal solution of goal-directed problems. However, when RL is applied to multi-agent systems (MASs, problems such as “curse of dimension”, “perceptual aliasing problem”, and uncertainty of the environment constitute high hurdles to RL. Meanwhile, although RL is inspired by behavioral psychology and reward/punishment from the environment is used, higher mental factors such as affects, emotions, and motivations are rarely adopted in the learning procedure of RL. In this paper, to challenge agents learning in MASs, we propose a computational motivation function, which adopts two principle affective factors “Arousal” and “Pleasure” of Russell’s circumplex model of affects, to improve the learning performance of a conventional RL algorithm named Q-learning (QL. Compared with the conventional QL, computer simulations of pursuit problems with static and dynamic preys were carried out, and the results showed that the proposed method results in agents having a faster and more stable learning performance.

Novel host restriction factors implicated in HIV-1 replication.

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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.

Science.gov (United States)

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

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Versteeg Marleen H

2012-01-01

Full Text Available Abstract 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

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

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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.

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Gilbert Cadelis

2017-08-01

Full Text Available 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

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

Energy Technology Data Exchange (ETDEWEB)

Malur, Anagha; Huizar, Isham [Program in Lung Cell Biology and Translational Research, Division of Pulmonary, Critical Care and Sleep Medicine, East Carolina University, Greenville, NC (United States); Wells, Greg [Department of Microbiology and Immunology, East Carolina University, Greenville, NC (United States); Barna, Barbara P. [Program in Lung Cell Biology and Translational Research, Division of Pulmonary, Critical Care and Sleep Medicine, East Carolina University, Greenville, NC (United States); Malur, Achut G. [Department of Microbiology and Immunology, East Carolina University, Greenville, NC (United States); Thomassen, Mary Jane, E-mail: thomassenm@ecu.edu [Program in Lung Cell Biology and Translational Research, Division of Pulmonary, Critical Care and Sleep Medicine, East Carolina University, Greenville, NC (United States); Department of Microbiology and Immunology, East Carolina University, Greenville, NC (United States)

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) 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 shown by

O-GlcNAc inhibits interaction between Sp1 and Elf-1 transcription factors

International Nuclear Information System (INIS)

Lim, Kihong; Chang, Hyo-Ihl

2009-01-01

The novel protein modification, O-linked N-acetylglucosamine (O-GlcNAc), plays an important role in various aspects of cell regulation. Although most of nuclear transcription regulatory factors are modified by O-GlcNAc, O-GlcNAc effects on transcription remain largely undefined yet. In this study, we show that O-GlcNAc inhibits a physical interaction between Sp1 and Elf-1 transcription factors, and negatively regulates transcription of placenta and embryonic expression oncofetal protein gene (Pem). These findings suggest that O-GlcNAc inhibits Sp1-mediated gene transcription possibly by interrupting Sp1 interaction with its cooperative factor.

Association between Insulin Like Growth Factor-1 (IGF-1) gene ...

African Journals Online (AJOL)

The insulin-like growth factor-1 (IGF1) is a key regulator of muscle development and metabolism in birds and other vertebrate. Our objective was to determine the association between IGF1 gene polymorphism and carcass traits in FUNAAB Alpha chicken. Genomic DNA was extracted from the blood of 50 normal feathered ...

Fibroblast growth factor-1 improves cardiac functional recovery and enhances cell survival after ischemia and reperfusion: a fibroblast growth factor receptor, protein kinase C, and tyrosine kinase-dependent mechanism

NARCIS (Netherlands)

Palmen, Meindert; Daemen, Mat J. A. P.; de Windt, Leon J.; Willems, Jodil; Dassen, Willem R. M.; Heeneman, Sylvia; Zimmermann, Rene; van Bilsen, Marc; Doevendans, Pieter A.

2004-01-01

We sought to investigate the role of fibroblast growth factor (FGF)-1 during acute myocardial ischemia and reperfusion. The FGFs display cardioprotective effects during ischemia and reperfusion. We investigated FGF-1-induced cardioprotection during ischemia and reperfusion and the intracellular

Supplementation of Blackcurrant Anthocyanins Increased Cyclic Glycine-Proline in the Cerebrospinal Fluid of Parkinson Patients: Potential Treatment to Improve Insulin-Like Growth Factor-1 Function

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Dawei Fan

2018-06-01

Full Text Available Background: Insulin-like growth factor-1 (IGF-1 function is impaired in Parkinson disease. Cyclic glycine-proline (cGP, a metabolite of IGF-1, is neuroprotective through improving IGF-1 function. Parkinson disease patients score lower on Hospital-associated Anxiety and Depression Scale after supplementing blackcurrant anthocyanins (BCA, which may be associated with IGF-1 function. We evaluated the changes of cGP and IGF-1 before and after the supplementation. Methods: Plasma and cerebrospinal fluid (CSF were collected from 11 male patients before and after 28 day supplementation of BCA. The concentrations of IGF-1, IGF binding protein (IGFBP-3, and cGP were measured using ELISA and HPLC-MS assays. The presence of cGP in the BCA was evaluated. Results: cGP presented in the BCA. BCA supplementation increased the concentration of cGP (p < 0.01, but not IGF-1 and IGFBP-3 in the CSF. CSF concentration of cGP was correlated with plasma concentration of cGP (R = 0.68, p = 0.01 and cGP/IGF-1 molar ratio (R = 0.66, p = 0.01. The CSF/plasma ratio was high in cGP and low in IGF-1 and IGFBP-3. Conclusion: cGP is a natural nutrient to the BCA. The increased CSF cGP in Parkinson disease patients may result from the central uptake of plasma cGP. Given neurotrophic function, oral availability, and effective central uptake of cGP, the BCA has the potential to be developed to treat neurological conditions with IGF-1 deficiency.

Improving human performance: Industry factors influencing the ability to perform

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Güera Massyn Romo

2013-03-01

Full Text Available Learning interventions and new technologies that aim to improve human performance must take cognisance of industry factors inhibiting human performance. The dynamic and fast pace nature of the Information and Communication Technologies (ICT and the engineering industries do not lend themselves to proper skills planning and management. These industries experience real skills gaps, to some of which they contribute by themselves. This study reports on these performance-inhibiting factors such as the underutilisation of available skills, tolerance for individual preferences, and dynamically, and informally refining a role objective while an employee is occupying a certain role. The important professional skills required by individuals to cope with these real life factors are also explored in the skills gaps management context. Moreover, these industries need a profile they refer to as Special Forces, which denotes a high calibre of worker that possesses well-developed professional skills whilst having advanced technical expertise and sufficient experience. This resource profile is required largely due to the poor management of human resource processes in practice and the current reported lack of adequate skills. Furthermore, this study refers to the recent lack of a working definition for these Special Forces leading to the omitted active development of these profiles in industry today, which appears to become a key human performance inhibiting factor.

Kaon semileptonic decay form factors from Nf = 2 non-perturbatively O(a)-improved Wilson fermions

International Nuclear Information System (INIS)

Broemmel, D.; Nakamura, Y.; Pleiter, D.

2007-10-01

We present first results from the QCDSF collaboration for the kaon semileptonic decay form factors at zero momentum transfer, using two flavours of non-perturbatively O(a)-improved Wilson quarks. A lattice determination of these form factors is of particular interest to improve the accuracy on the CKM matrix element vertical stroke V us vertical stroke. Calculations are performed on lattices with lattice spacing of about 0.08 fm with different values of light and strange quark masses, which allows us to extrapolate to chiral limit. Employing double ratio techniques, we are able to get small statistical errors. (orig.)

Upregulation of vascular endothelial growth factor receptor-1 contributes to sevoflurane preconditioning–mediated cardioprotection

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Qian B

2018-04-01

Full Text Available Bin Qian,1 Yang Yang,2 Yusheng Yao,3 Yanling Liao,3 Ying Lin3 1Department of Anesthesiology, People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China; 2Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China; 3Department of Anesthesiology, The Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China Purpose: Sevoflurane preconditioning (SPC can provide myocardial protective effects similar to ischemic preconditioning. However, the exact mechanism of SPC remains unclear. Previous studies indicate that vascular endothelial growth factor receptor 1 (VEGFR-1 is involved in ischemic preconditioning-mediated cardioprotection. This study was designed to determine the significance of VEGFR-1 signaling in SPC-mediated cardioprotection.Materials and methods: Myocardial ischemia–reperfusion (I/R rat model was established using the Langendorff isolated heart perfusion apparatus. Additionally, after 15 min of baseline equilibration, the isolated hearts were pretreated with 2.5% sevoflurane, 2.5% sevoflurane+MF1 10 µmol/L, or 2.5% sevoflurane+placental growth factor 10 µmol/L, and then subjected to 30 min of global ischemia and 120 min of reperfusion. The changes in hemodynamic parameters, myocardial infarct size, and the levels of creatine kinase-MB, lactate dehydrogenase, cardiac troponin-I, tumor necrosis factor-α, and interleukin 6 in the myocardium were evaluated.Results: Compared to the I/R group, pretreatment with 2.5% sevoflurane significantly improved the cardiac function, limited myocardial infarct size, reduced cardiac enzyme release, upregulated VEGFR-1 expression, and decreased inflammation. In addition, the selective VEGFR-1 agonist, placental growth factor, did not enhance the cardioprotection and anti-inflammation effects of sevoflurane, while the specific VEGFR-1 inhibitor, MF1, completely reversed these effects

Transcription factors zeb1, twist and snai1 in breast carcinoma

International Nuclear Information System (INIS)

Soini, Ylermi; Tuhkanen, Hanna; Sironen, Reijo; Virtanen, Ismo; Kataja, Vesa; Auvinen, Päivi; Mannermaa, Arto; Kosma, Veli-Matti

2011-01-01

Epitheliomesenchymal transition (EMT) is the process where cancer cells attain fibroblastic features and are thus able to invade neighboring tissues. Transcriptional factors zeb1, snai1 and twist regulate EMT. We used immunohistochemistry to investigate the expression of zeb1, twist and snai1 in tumor and stromal compartments by in a large set of breast carcinomas. The results were compared with estrogen and progesterone receptor status, HER2 amplification, grade, histology, TNM status and survival of the patients. Nuclear expression for twist was seen in the epithelial tumor cell compartment in 3.6% and for snai1 in 3.1% of the cases while zeb1 was not detected at all in these areas. In contrast, the tumor stromal compartment showed nuclear zeb1 and twist expression in 75% and 52.4% of the cases, respectively. Although rare, nuclear expression of twist in the epithelial tumor cell compartment was associated with a poor outcome of the patients (p = 0.054 log rank, p = 0.013, Breslow, p = 0.025 Tarone-Ware). Expression of snai1, or expression of zeb1 or twist in the stromal compartment did not have any prognostic significance. Furthermore, none of these factors associated with the size of the tumors, nor with the presence of axillary or distant metastases. Expression of zeb1 and twist in the stromal compartment was positively associated with a positive estrogen or progesterone receptor status of the tumors. Stromal zeb1 expression was significantly lower in ductal in situ carcinomas than in invasive carcinomas (p = 0.020). Medullary carcinomas (p = 0.017) and mucinous carcinomas (p = 0.009) had a lower stromal expression of zeb1 than ductal carcinomas. Stromal twist expression was also lower in mucinous (p = 0.017) than in ductal carcinomas. Expression of transcriptional factors zeb1 and twist mainly occur in the stromal compartment of breast carcinomas, possibly representing two populations of cells; EMT transformed neoplastic cells and stromal fibroblastic cells

Factors Related to Significant Improvement of Estimated Glomerular Filtration Rates in Chronic Hepatitis B Patients Receiving Telbivudine Therapy

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Te-Fu Lin

2017-01-01

Full Text Available Background and Aim. The improvement of estimated glomerular filtration rates (eGFRs in chronic hepatitis B (CHB patients receiving telbivudine therapy is well known. The aim of this study was to clarify the kinetics of eGFRs and to identify the significant factors related to the improvement of eGFRs in telbivudine-treated CHB patients in a real-world setting. Methods. Serial eGFRs were calculated every 3 months using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI equation. The patients were classified as CKD-1, -2, or -3 according to a baseline eGFR of ≥90, 60–89, or <60 mL/min/1.73 m2, respectively. A significant improvement of eGFR was defined as a more than 10% increase from the baseline. Results. A total of 129 patients were enrolled, of whom 36% had significantly improved eGFRs. According to a multivariate analysis, diabetes mellitus (DM (p=0.028 and CKD-3 (p=0.043 were both significantly related to such improvement. The rates of significant improvement of eGFR were about 73% and 77% in patients with DM and CKD-3, respectively. Conclusions. Telbivudine is an alternative drug of choice for the treatment of hepatitis B patients for whom renal safety is a concern, especially patients with DM and CKD-3.

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

Science.gov (United States)

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

10-Year Associations Between Tumor Necrosis Factor Receptors 1 and 2 and Cardiovascular Events in Patients With Stable Coronary Heart Disease

DEFF Research Database (Denmark)

Carlsson, Axel C.; Ruge, Toralph; Kjøller, Erik

2018-01-01

mortality. Patients were followed up for 10 years; discovery sample, those assigned placebo (1204 events in n=1998); and replication sample, those assigned clarithromycin (1220 events in n=1979). We used Cox regression adjusted for C-reactive protein level, established cardiovascular risk factors, kidney.......08-1.24; P0.001 for TNFR2). The associations were similar in the replication sample. The associations with the composite outcome were mainly driven by acute myocardial infarction, cardiovascular mortality, and noncardiovascular mortality. The addition of TNFR1 and TNFR2 to established cardiovascular risk...... factors improved prediction only modestly (TNFR1 and TNFR2 were associated with increased risks of cardiovascular events and mortality in patients with stable coronary heart disease. Yet, the utility of measuring TNFR1 and TNFR2 to improve risk...

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

Science.gov (United States)

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

Science.gov (United States)

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.

Improved NN-GM(1,1 for Postgraduates’ Employment Confidence Index Forecasting

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Lu Wang

2014-01-01

Full Text Available Postgraduates’ employment confidence index (ECI forecasting can help the university to predict the future trend of postgraduates’ employment. However, the common forecast method based on the grey model (GM has unsatisfactory performance to a certain extent. In order to forecast postgraduates’ ECI efficiently, this paper discusses a novel hybrid forecast model using limited raw samples. Different from previous work, the residual modified GM(1,1 model is combined with the improved neural network (NN in this work. In particullar, the hybrid model reduces the residue of the standard GM(1,1 model as well as accelerating the convergence rate of the standard NN. After numerical studies, the illustrative results are provided to demonstrate the forecast performance of the proposed model. In addition, some strategies for improving the postgraduates’ employment confidence have been discussed.

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

Science.gov (United States)

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.

Science.gov (United States)

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

Energy Technology Data Exchange (ETDEWEB)

Biswas, Madhurima; Kwong, Erick K.; Park, Eujean; Nagra, Parminder; Chan, Jefferson Y., E-mail: jchan@uci.edu

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 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–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.

Magic-factor 1, a partial agonist of Met, induces muscle hypertrophy by protecting myogenic progenitors from apoptosis.

Directory of Open Access Journals (Sweden)

Marco Cassano

2008-09-01

Full Text Available Hepatocyte Growth Factor (HGF is a pleiotropic cytokine of mesenchymal origin that mediates a characteristic array of biological activities including cell proliferation, survival, motility and morphogenesis. Its high affinity receptor, the tyrosine kinase Met, is expressed by a wide range of tissues and can be activated by either paracrine or autocrine stimulation. Adult myogenic precursor cells, the so called satellite cells, express both HGF and Met. Following muscle injury, autocrine HGF-Met stimulation plays a key role in promoting activation and early division of satellite cells, but is shut off in a second phase to allow myogenic differentiation. In culture, HGF stimulation promotes proliferation of muscle precursors thereby inhibiting their differentiation.Magic-Factor 1 (Met-Activating Genetically Improved Chimeric Factor-1 or Magic-F1 is an HGF-derived, engineered protein that contains two Met-binding domains repeated in tandem. It has a reduced affinity for Met and, in contrast to HGF it elicits activation of the AKT but not the ERK signaling pathway. As a result, Magic-F1 is not mitogenic but conserves the ability to promote cell survival. Here we show that Magic-F1 protects myogenic precursors against apoptosis, thus increasing their fusion ability and enhancing muscular differentiation. Electrotransfer of Magic-F1 gene into adult mice promoted muscular hypertrophy and decreased myocyte apoptosis. Magic-F1 transgenic mice displayed constitutive muscular hypertrophy, improved running performance and accelerated muscle regeneration following injury. Crossing of Magic-F1 transgenic mice with alpha-sarcoglycan knock-out mice -a mouse model of muscular dystrophy- or adenovirus-mediated Magic-F1 gene delivery resulted in amelioration of the dystrophic phenotype as measured by both anatomical/histological analysis and functional tests.Because of these features Magic-F1 represents a novel molecular tool to counteract muscle wasting in major

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

Science.gov (United States)

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.

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

Science.gov (United States)

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% (pAVC scores (pAVC 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.

Fasxiator, a novel factor XIa inhibitor from snake venom, and its site-specific mutagenesis to improve potency and selectivity.

Science.gov (United States)

Chen, W; Carvalho, L P D; Chan, M Y; Kini, R M; Kang, T S

2015-02-01

Bleeding remains a major limitation of standard anticoagulant drugs that target the extrinsic and common coagulation pathways. Recently, intrinsic coagulation factors are increasingly being investigated as alternative targets for developing anticoagulant drugs with lower bleeding risk. Goals were to (i) identify novel anticoagulants selectively targeting intrinsic coagulation pathway and (ii) characterize and further improve the properties of the identified anticoagulants. We have isolated and sequenced a specific factor XIa (FXIa) inhibitor, henceforth named Fasxiator, from the venom of the banded krait snake, Bungarus fasciatus. It is a Kunitz-type protease inhibitor that prolonged activated partial thromboplastin time without significant effects on prothrombin time. Fasxiator was recombinantly expressed (rFasxiator), purified, and characterized to be a slow-type inhibitor of FXIa that exerts its anticoagulant activities (doubled activated partial thromboplastin time at ~ 3 μmol L(-1) ) by selectively inhibiting human FXIa in in vitro assays. A series of mutants were subsequently generated to improve the potency and selectivity of recombinant rFasxiator. rFasxiatorN17R,L19E showed the best balance between potency (IC50 ~ 1 nmol L(-1) ) and selectivity (> 100 times). rFasxiatorN17R,L19E is a competitive slow-type inhibitor of FXIa (Ki  = 0.86 nmol L(-1) ), possesses anticoagulant activity that is ~ 10 times stronger in human plasma than in murine plasma, and prolonged the occlusion time of mice carotid artery in FeCl3 -induced thrombosis models. We have isolated an exogenous FXIa specific inhibitor, engineered it to improve its potency by ~ 1000 times and demonstrated its in vitro and in vivo efficacy. These proof-of-principle data supported the further development of Fasxiator as a novel anticoagulant candidate. © 2014 International Society on Thrombosis and Haemostasis.

TIAM1 variants improve clinical outcome in neuroblastoma.

Science.gov (United States)

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.

Electronic mode of control to obtain increased torque and improved power factor from an asynchronous machine

NARCIS (Netherlands)

Wyk, van J.D.

1970-01-01

It is indicated that, by changing the electronic switching mode of the rotor current of an induction machine, it is possible to operate the machine at improved (capacitive) power factors and increased torque, or conversely at lower effective current and capacitive power factors at rated torque.

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

International Nuclear Information System (INIS)

Kita, Shota; Ueno, Toshiyuki; Yamada, Sotoshi

2015-01-01

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

Improving the Stability and Robustness of Incomplete Symmetric Indefinite Factorization Preconditioners

Czech Academy of Sciences Publication Activity Database

Scott, J.; Tůma, Miroslav

2017-01-01

Roč. 24, č. 5 (2017), č. článku e2099. ISSN 1070-5325 Grant - others:GA ČR(CZ) GC17-04150J; GA ČR(CZ) GC17-04150J; EPSRC(GB) EP/I013067/1 Institutional support: RVO:67985807 Keywords : incomplete factorizations * indefinite symmetric systems * iterative solvers * pivoting * preconditioning * sparse linear systems * sparse matrices Subject RIV: BA - General Mathematics OBOR OECD: Applied mathematics Impact factor: 1.303, year: 2016

10-Year Associations Between Tumor Necrosis Factor Receptors 1 and 2 and Cardiovascular Events in Patients With Stable Coronary Heart Disease

DEFF Research Database (Denmark)

Carlsson, Axel C; Ruge, Toralph; Kjøller, Erik

2018-01-01

BACKGROUND: We aimed to assess the associations and predictive powers between the soluble receptors for tumor necrosis factor (TNF)-α (TNFR1 and TNFR2) and cardiovascular outcomes in patients with stable coronary heart disease. METHODS AND RESULTS: CLARICOR (Effect of Clarithromycin on Mortality...... and Morbidity in Patients With Ischemic Heart Disease) is a randomized clinical trial comparing clarithromycin with placebo in patients with stable coronary heart disease. The primary outcome was a composite of nonfatal acute myocardial infarction, unstable angina pectoris, cerebrovascular disease, and all...... factors improved prediction only modestly (concentrations of circulating TNFR1 and TNFR2 were associated with increased risks of cardiovascular events and mortality in patients with stable coronary heart disease. Yet, the utility of measuring TNFR1 and TNFR2 to improve risk...

Hypoxic stress simultaneously stimulates vascular endothelial growth factor via hypoxia-inducible factor-1α and inhibits stromal cell-derived factor-1 in human endometrial stromal cells.

Science.gov (United States)

Tsuzuki, Tomoko; Okada, Hidetaka; Cho, Hisayuu; Tsuji, Shoko; Nishigaki, Akemi; Yasuda, Katsuhiko; Kanzaki, Hideharu

2012-02-01

Hypoxia of the human endometrium is a physiologic event occurring during the perimenstrual period and the local stimulus for angiogenesis. The aim of this study was to investigate the effects of hypoxic stress on the regulation of vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1 (SDF-1/CXCL12), and the potential role of hypoxia-inducible factor-1α (HIF-1α) in the endometrium. Human endometrial stromal cells (ESCs, n= 22 samples) were studied in vitro. ESCs were cultured under hypoxic and normoxic conditions and treated with cobalt chloride (CoCl₂; a hypoxia-mimicking agent) and/or echinomycin, a small-molecule inhibitor of HIF-1α activity. The mRNA levels and production of VEGF and SDF-1 were assessed by real-time PCR and ELISA, respectively. The HIF-1α protein levels were measured using western blot analysis. Hypoxia simultaneously induced the expression of mRNA and production of VEGF and attenuated the expression and production of SDF-1 from ESCs in a time-dependent manner. Similar changes were observed in the ESCs after stimulation with CoCl₂ in a dose-dependent manner. CoCl₂ significantly induced the expression of HIF-1α protein, and its highest expression was observed at 6 h. Echinomycin inhibited hypoxia-induced VEGF production without affecting the HIF-1α protein level and cell toxicity and had no effect on SDF-1 secretion (P hypoxic conditions that could influence angiogenesis in the human endometrium.

Regulation of hypoxia-inducible factor-1α (HIF-1α expression by interleukin-1β (IL-1 β, insulin-like growth factors I (IGF-I and II (IGF-II in human osteoarthritic chondrocytes

Directory of Open Access Journals (Sweden)

Angelica Rossi Sartori-Cintra

2012-01-01

Full Text Available OBJECTIVE: Hypoxia-inducible factor 1 alpha regulates genes related to cellular survival under hypoxia. This factor is present in osteroarthritic chondrocytes, and cytokines, such as interleukin-1 beta, participate in the pathogenesis of osteoarthritis, thereby increasing the activities of proteolytic enzymes, such as matrix metalloproteinases, and accelerating cartilage destruction. We hypothesize that Hypoxia Inducible Factor-1 alpha (HIF-1α can regulate cytokines (catabolic action and/or growth factors (anabolic action in osteoarthritis. The purpose of this study was to investigate the modulation of HIF-1α in human osteoarthritic chondrocytes by interleukin-1 beta (IL-1β and insulin-like growth factors I (IGF-I and II (IGF-II and to determine the involvement of the phosphatidylinositol-3kinase (PI-3K pathway in this process. METHODS: Human osteroarthritic chondrocytes were stimulated with IL-1β, IGF-I and IGF-II and LY294002, a specific inhibitor of PI-3K. Nuclear protein levels and gene expression were analyzed by western blot and quantitative reverse transcription-polymerase chain reaction analyses, respectively. RESULTS: HIF-1α expression was upregulated by IL-1β at the protein level but not at the gene level. IGF-I treatment resulted in increases in both the protein and mRNA levels of HIF-1α , whereas IGF-II had no effect on its expression. However, all of these stimuli exploited the PI-3K pathway. CONCLUSION: IL-1β upregulated the levels of HIF-1α protein post-transcriptionally, whereas IGF-I increased HIF-1α at the transcript level. In contrast, IGF-II did not affect the protein or gene expression levels of HIF-1α . Furthermore, all of the tested stimuli exploited the PI-3K pathway to some degree. Based on these findings, we are able to suggest that Hypoxia inducible Factor-1 exhibits protective activity in chondrocytes during osteoarthritis.

Antithyroid Therapy Improves Glycemic Control in Hyperthyroid Type 1 Diabetes Mellitus Patients

Directory of Open Access Journals (Sweden)

Vlad Mihaela

2015-12-01

Full Text Available Background and aims. Thyroid disorders are more frequently met in patients with diabetes mellitus than in general population. Thyroid hormones increase glycemia by several mechanisms, but the effect of antithyroid treatment on glucose control in type 1 diabetes mellitus (T1DM cases is not well studied. The aim of our work was to analyze the evolution of glycemic control of T1DM patients submitted to specific therapy when hyperthyroidism was diagnosed. Material and method. The study group comprised by 37 patients, 35 women (94.6% and 2 men (5.4%, known as having T1DM and diagnosed with hyperthyroidism during a 10-years interval. They were treated with antithyroid medication and reassessed after 6 months regarding thyroid function and glycemic control. Results. In the whole group, there was a significant decrease in mean HbA1c level (with 0.41% and a significant increase in the percentage of patients being in the glycemic target (from 10.8% to 35.1%. The better glycemic control was obtained with a lower mean insulin dose. Patients who became euthyroid had a better evolution regarding glucose control in comparison to those who remained hyperthyroid. Changes in other cardiovascular risk factors were noted: systolic blood pressure decreased; diastolic blood pressure, HDL cholesterol, LDL cholesterol, non-HDL cholesterol, triglycerides and body weight increased. TSH and HbA1c values were inversely correlated. Conclusions. The therapeutic control of excessive thyroid function significantly contributes to the improvement of glycemic control in patients with T1DM and induces changes in the cardiovascular risk factors profile.

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

Science.gov (United States)

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.

IMPROVING CONTROL ROOM DESIGN AND OPERATIONS BASED ON HUMAN FACTORS ANALYSES OR HOW MUCH HUMAN FACTORS UPGRADE IS ENOUGH ?

Energy Technology Data Exchange (ETDEWEB)

HIGGINS,J.C.; OHARA,J.M.; ALMEIDA,P.

2002-09-19

THE JOSE CABRERA NUCLEAR POWER PLANT IS A ONE LOOP WESTINGHOUSE PRESSURIZED WATER REACTOR. IN THE CONTROL ROOM, THE DISPLAYS AND CONTROLS USED BY OPERATORS FOR THE EMERGENCY OPERATING PROCEDURES ARE DISTRIBUTED ON FRONT AND BACK PANELS. THIS CONFIGURATION CONTRIBUTED TO RISK IN THE PROBABILISTIC SAFETY ASSESSMENT WHERE IMPORTANT OPERATOR ACTIONS ARE REQUIRED. THIS STUDY WAS UNDERTAKEN TO EVALUATE THE IMPACT OF THE DESIGN ON CREW PERFORMANCE AND PLANT SAFETY AND TO DEVELOP DESIGN IMPROVEMENTS.FIVE POTENTIAL EFFECTS WERE IDENTIFIED. THEN NUREG-0711 [1], PROGRAMMATIC, HUMAN FACTORS, ANALYSES WERE CONDUCTED TO SYSTEMATICALLY EVALUATE THE CR-LA YOUT TO DETERMINE IF THERE WAS EVIDENCE OF THE POTENTIAL EFFECTS. THESE ANALYSES INCLUDED OPERATING EXPERIENCE REVIEW, PSA REVIEW, TASK ANALYSES, AND WALKTHROUGH SIMULATIONS. BASED ON THE RESULTS OF THESE ANALYSES, A VARIETY OF CONTROL ROOM MODIFICATIONS WERE IDENTIFIED. FROM THE ALTERNATIVES, A SELECTION WAS MADE THAT PROVIDED A REASONABLEBALANCE BE TWEEN PERFORMANCE, RISK AND ECONOMICS, AND MODIFICATIONS WERE MADE TO THE PLANT.

Application of thermal sterilization regimes simulation for improvement of canned foods quality factors

Directory of Open Access Journals (Sweden)

Stolyanov A.V.

2015-03-01

Full Text Available Results of comparison of optimization methods of thermal sterilization temperature-time regimes have been described. It has been shown that due to simulation the final canned foods’ quality factors are significantly improved, sterilization process time is decreased and energy consumption is reduced without sacrificing actual final lethality value

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

Science.gov (United States)

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.

On the uniqueness of the injective III1 factor

DEFF Research Database (Denmark)

Haagerup, U.

2016-01-01

We give a new proof of a theorem due to Alain Connes, that an injective factor N of type III1 with separable predual and with trivial bicentralizer is isomorphic to the Araki-Woods type III1 factor R∞. This, combined with the author's solution to the bicentralizer problem for injective III1 facto...

A Dynamic Momentum Compaction Factor Lattice for Improvements to Stochastic Cooling in Storage Rings

Energy Technology Data Exchange (ETDEWEB)

Olivieri, David Nicholas [Massachusetts U., Amherst

1996-01-01

A dynamic momentum compaction factor, also referred to as a dynamic $\\Delta \\gamma \\tau$, lattice for the FNAL Antiproton Source Debuncher Storage Ring is studied, both theoretically and experimentally, for the purpose of improving stochastic precooling, and hence, improving the global antiproton production and stacking performance. A dynamic $\\Delta \\gamma \\tau$ lattice is proposed due to the competing requirements inherent within the Debuncher storage ring upon $\\gamma \\tau$· Specifically, the Debuncher storage ring performs two disparate functions, $(i)$ accepting and debunching a large number of $\\overline{p}$s/pulse at the outset of the production cycle, which would perform ideally with a large value of $\\gamma\\tau$, and $(ii)$ subsequently employing stochastic cooling throughout the remainder of the $\\overline{p}$ production cycle for improved transfer and stacking efficiency into the Accumulator, for which a small value $\\gamma \\tau$ is ideal in order to reduce the diffusive heating caused by the mixing factor. In the initial design of the Debuncher optical lattice, an intermediate value of $\\gamma \\tau$ was chosen as a compromise between the two functional requirements. The goal of the thesis is to improve stochastic precooling by changing $\\gamma \\tau$ between two desired values during each p production cycle. In particular, the dynamic $\\Delta \\gamma \\tau$ lattice accomplishes a reduction in $\\gamma \\tau$, and hence the mixing factor, through an uniform increase to the dispersion throughout the arc sections of the storage ring. Experimental measurements of cooling rates and system performance parameters, with the implementation of the dynamic $\\Delta \\gamma \\tau$ lattice, are in agreement with theoretical predictions based upon a detailed integration of the stochastic cooling Fokker Planck equations. Based upon the consistency between theory and experiment, predictions of cooling rates are presented for future operational

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

Science.gov (United States)

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.

Hypoxia inducible factor 1-alpha (HIF-1 alpha is induced during reperfusion after renal ischemia and is critical for proximal tubule cell survival.

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Elisa Conde

Full Text Available Acute tubular necrosis (ATN caused by ischemia/reperfusion (I/R during renal transplantation delays allograft function. Identification of factors that mediate protection and/or epithelium recovery could help to improve graft outcome. We studied the expression, regulation and role of hypoxia inducible factor 1-alpha (HIF-1 α, using in vitro and in vivo experimental models of I/R as well as human post-transplant renal biopsies. We found that HIF-1 α is stabilized in proximal tubule cells during ischemia and unexpectedly in late reperfusion, when oxygen tension is normal. Both inductions lead to gene expression in vitro and in vivo. In vitro interference of HIF-1 α promoted cell death and in vivo interference exacerbated tissue damage and renal dysfunction. In pos-transplant human biopsies, HIF-1 α was expressed only in proximal tubules which exhibited normal renal structure with a significant negative correlation with ATN grade. In summary, using experimental models and human biopsies, we identified a novel HIF-1 α induction during reperfusion with a potential critical role in renal transplant.

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

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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.

Differentiation-inducing factor-1 suppresses gene expression of cyclin D1 in tumor cells

International Nuclear Information System (INIS)

Yasmin, Tania; Takahashi-Yanaga, Fumi; Mori, Jun; Miwa, Yoshikazu; Hirata, Masato; Watanabe, Yutaka; Morimoto, Sachio; Sasaguri, Toshiyuki

2005-01-01

To determine the mechanism by which differentiation-inducing factor-1 (DIF-1), a morphogen of Dictyostelium discoideum, inhibits tumor cell proliferation, we examined the effect of DIF-1 on the gene expression of cyclin D1. DIF-1 strongly reduced the expression of cyclin D1 mRNA and correspondingly decreased the amount of β-catenin in HeLa cells and squamous cell carcinoma cells. DIF-1 activated glycogen synthase kinase-3β (GSK-3β) and inhibition of GSK-3β attenuated the DIF-1-induced β-catenin degradation, indicating the involvement of GSK-3β in this effect. Moreover, DIF-1 reduced the activities of T-cell factor (TCF)/lymphoid enhancer factor (LEF) reporter plasmid and a reporter gene driven by the human cyclin D1 promoter. Eliminating the TCF/LEF consensus site from the cyclin D1 promoter diminished the effect of DIF-1. These results suggest that DIF-1 inhibits Wnt/β-catenin signaling, resulting in the suppression of cyclin D1 promoter activity

Compound list: transforming growth factor beta 1 [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available transforming growth factor beta 1 TGFB1 00182 ftp://ftp.biosciencedbc.jp/archive/op...en-tggates/LATEST/Human/in_vitro/transforming_growth_factor_beta_1.Human.in_vitro.Liver.zip ...

Citation trend and suggestions for improvement of impact factor of Journal of Korean Therapeutic Radiology and Oncology

International Nuclear Information System (INIS)

Kim, Seong Hwan; Hwang, Seong Su; Ahn, Myeong Im; Jeong, So Na

2006-01-01

To analyze the recent citation trend and to find a way to improve impact factor (IF) of the Journal of Korean Therapeutic Radiology and Oncology (JKSTRO) by analysis of Korean Medical Citation index (KoMCI) citation data of JKSTRO and comparison with that of mean citation data of all journals enlisted on KoMCI (KoMCI journals) during 2000-2005. All citation data of entire journals enlisted on KoMCI and JKSTRO from 2000 to 2005 were obtained from KoMCI. The trend of total and annual number of published articles and reference citations, total citations and self-citations per paper, IF and impact factor excluding self-citations (ZIF) were described and compared on both KoMCI journals an JKSTRO. Annual number of published articles was decreased for 6 years on both KoMCI journals and JKSTRO (32% and 38% reduction rate). The number of Korean journal references per article is 1.6 papers of JKSTRO comparing to 2.0 papers on KoMCI journals. The percentage of Korean references/total references increased from 5.0% in 2000 to 7.7% in 2005 on JKSTRO and from 8.5% in 2000 to 10.1% on KoMCI journals. The number of total citations received/paper on JKSTRO (average 1.333) is smaller than that of KoMCI journals (average 1.694), there was an increased rate of 67% in 2005 comparing to 2000. The percentage of self-citations/total citations (average 72%) on JKSTRO is slightly higher than that of KoMCI journals (average 61%)/ IF of JKSTRO was gradually improved and 0.144, 0.125, 0.088, 0.107, 0.187 and 0.203 in 2000-2005 respectively. However, ZIF of JKSTRO is steadily decreased from 0.038 in 2000 to 0.013 in 2005 except 0.044 in 2004. IF of JKSTRO was slightly improved but had some innate problem of smaller number of citations received . To make JKSTRO as a highly cited journal, the awareness of academic status of JKSTRO and active participation of every member of JKSTRO including encouraging self-citations of papers published recent 2 years and submission of English written papers, and

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

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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

Opioid growth factor improves clinical benefit and survival in patients with advanced pancreatic cancer

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Jill P Smith

2010-03-01

Full Text Available Jill P Smith1, Sandra I Bingaman1, David T Mauger2, Harold H Harvey1, Laurence M Demers3, Ian S Zagon41Departments of Medicine, 2Public Health Sciences, 3Pathology, and 4Neurosciences and Anatomy, Pennsylvania State University, College of Medicine, Hershey Medical Center, Hershey, PA, USABackground: Advanced pancreatic cancer carries the poorest prognosis of all gastrointestinal malignancies. Once the tumor has spread beyond the margins of the pancreas, chemotherapy is the major treatment modality offered to patients; however, chemotherapy does not significantly improve survival.Objective: Opioid growth factor (OGF; [Met5]-enkephalin is a natural peptide that has been shown to inhibit growth of pancreatic cancer in cell culture and in nude mice. The purpose of this study was to evaluate the effects of OGF biotherapy on subjects with advanced pancreatic cancer who failed chemotherapy.Methods: In a prospective phase II open-labeled clinical trial, 24 subjects who failed standard chemotherapy for advanced pancreatic cancer were treated weekly with OGF 250 μg/kg intravenously. Outcomes measured included clinical benefit, tumor response by radiographic imaging, quality of life, and survival.Results: Clinical benefit response was experienced by 53% of OGF-treated patients compared to historical controls of 23.8% and 4.8% for gemcitabine and 5-fluorouracil (5-FU, respectively. Of the subjects surviving more than eight weeks, 62% showed either a decrease or stabilization in tumor size by computed tomography. The median survival time for OGF-treated patients was three times that of untreated patients (65.5 versus 21 days, p < 0.001. No adverse effects on hematologic or chemistry parameters were noted, and quality of life surveys suggested improvement with OGF. Limitations: Measurements other than survival were not allowed in control patients, and clinical benefit comparisons were made to historical controls.Conclusion: OGF biotherapy improves the

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

Science.gov (United States)

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.

Insulin-Like Growth Factor-1 and Neuroinflammation

OpenAIRE

Labandeira-Garcia, Jose L.; Costa-Besada, Maria A.; Labandeira, Carmen M.; Villar-Cheda, Begoña; Rodríguez-Perez, Ana I.

2017-01-01

Insulin-like growth factor-1 (IGF-1) effects on aging and neurodegeneration is still controversial. However, it is widely admitted that IGF-1 is involved in the neuroinflammatory response. In peripheral tissues, several studies showed that IGF-1 inhibited the expression of inflammatory markers, although other studies concluded that IGF-1 has proinflammatory functions. Furthermore, proinflammatory cytokines such as TNF-α impaired IGF-1 signaling. In the brain, there are controversial results o...

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

Science.gov (United States)

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.

[Factors affecting the ability of caffeine to improve the short-term memory in man].

Science.gov (United States)

Arushanian, E B; Baĭda, O A; Mastiagin, S S; Popova, A P; Shikina, I B

2003-01-01

Caffeine is known to improve both visual and aural memory in healthy humans. This caffeine effect correlates with the mental work capacity and depends on a number of variable factors. In particular, the effect is more pronounced in the evening and in females.

Improving medication safety and cardiovascular risk factor control to mitigate disparities in African-American kidney transplant recipients: Design and methods

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Andrew J. Cole

2018-03-01

Full Text Available There is a lack of data analyzing the influence of cardiovascular disease (CVD risk factor control on graft survival disparities in African-American kidney transplant recipients. Studies in the general population indicate that CVD risk factor control is poor in African-Americans, leading to higher rates of renal failure and major acute cardiovascular events. However, with the exception of hypertension, there is no data demonstrating similar results within transplant recipients. Recent analyses conducted by our investigator group indicate that CVD risk factors, especially diabetes, are poorly controlled in African-American recipients, which likely impacts graft loss. This study protocol describes a prospective interventional clinical trial with the goal of demonstrating improved medication safety and CVD risk factor control in adult solitary kidney transplant recipients at least one-year post-transplant with a functioning graft. This is a prospective, interventional, 6-month, pharmacist-led and technology enabled study in adult kidney transplant recipients with the goal of improving CVD risk factor outcomes by improving medication safety and patient self-efficacy. This papers describes the issues related to racial disparities in transplant, the details of this intervention and how we expect this intervention to improve CVD risk factor control in kidney transplant recipients, particularly within African-Americans.

The Sustainable Office. An exploration of the potential for factor 20 environmental improvement of office accommodation

OpenAIRE

Van den Dobbelsteen, A.A.J.F.

2004-01-01

Sustainable development is the goal of a balance between economy and the environment, whilst establishing a better spread prosperity across the world. In order to make this possible, the environmental load of our commodities needs to be reduced by a factor of 20. This factor 20 can also be translated to the office market. The PhD research presented in this thesis focussed on finding solutions effectively contributing to factor 20 environmental improvement of office accommodation. In order to ...

Mp1p Is a Virulence Factor in Talaromyces (Penicillium marneffei.

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Patrick C Y Woo

2016-08-01

Full Text Available Talaromyces marneffei is an opportunistic dimorphic fungus prevalent in Southeast Asia. We previously demonstrated that Mp1p is an immunogenic surface and secretory mannoprotein of T. marneffei. Since Mp1p is a surface protein that can generate protective immunity, we hypothesized that Mp1p and/or its homologs are virulence factors.We examined the pathogenic roles of Mp1p and its homologs in a mouse model. All mice died 21 and 30 days after challenge with wild-type T. marneffei PM1 and MP1 complemented mutant respectively. None of the mice died 60 days after challenge with MP1 knockout mutant (P<0.0001. Seventy percent of mice died 60 days after challenge with MP1 knockdown mutant (P<0.0001. All mice died after challenge with MPLP1 to MPLP13 knockdown mutants, suggesting that only Mp1p plays a significant role in virulence. The mean fungal loads of PM1 and MP1 complemented mutant in the liver, lung, kidney and spleen were significantly higher than those of the MP1 knockout mutant. Similarly, the mean load of PM1 in the liver, lung and spleen were significantly higher than that of the MP1 knockdown mutant. Histopathological studies showed an abundance of yeast in the kidney, spleen, liver and lung with more marked hepatic and splenic necrosis in mice challenged with PM1 compared to MP1 knockout and MP1 knockdown mutants. Likewise, a higher abundance of yeast was observed in the liver and spleen of mice challenged with MP1 complemented mutant compared to MP1 knockout mutant. PM1 and MP1 complemented mutant survived significantly better than MP1 knockout mutant in macrophages at 48 hours (P<0.01 post-infection. The mean fungal counts of Pichia pastoris GS115-MP1 in the liver (P<0.001 and spleen (P<0.05 of mice were significantly higher than those of GS115 at 24 hours post-challenge.Mp1p is a key virulence factor of T. marneffei. Mp1p mediates virulence by improving the survival of T. marneffei in macrophages.

Down-regulation of hypoxia-inducible factor-1 alpha and vascular endothelial growth factor by HEXIM1 attenuates myocardial angiogenesis in hypoxic mice.

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Yoshikawa, Noritada; Shimizu, Noriaki; Ojima, Hidenori; Kobayashi, Hiroshi; Hosono, Osamu; Tanaka, Hirotoshi

2014-10-24

Pulmonary hypertension (PH) sustains elevation of pulmonary vascular resistance and ultimately leads to right ventricular (RV) hypertrophy and failure and death. Recently, proangiogenic factors hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) have been known to promote left ventricular myocardial angiogenesis and lead to cardiac hypertrophy, and this would be involved in RV hypertrophy of PH patients. Previously, we revealed that overexpression of HEXIM1 prevents endothelin-1-induced cardiomyocyte hypertrophy and hypertrophic genes expression, and that cardiomyocyte-specific HEXIM1 transgenic mice ameliorates RV hypertrophy in hypoxia-induced PH model. Given these results, here we analyzed the effect of HEXIM1 on the expression of HIF-1α and VEGF and on myocardial angiogenesis of RV in PH. We revealed that overexpression of HEXIM1 prevented hypoxia-induced expression of HIF-1α protein and its target genes including VEGF in the cultured cardiac myocytes and fibroblasts, and that cardiomyocyte-specific HEXIM1 transgenic mice repressed RV myocardial angiogenesis in hypoxia-induced PH model. Thus, we conclude that HEXIM1 could prevent RV hypertrophy, at least in part, via suppression of myocardial angiogenesis through down-regulation of HIF-1α and VEGF in the myocardium under hypoxic condition. Copyright © 2014 Elsevier Inc. All rights reserved.

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

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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

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

Science.gov (United States)

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 (Peffect), 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.

Prediction of clinical factors associated with pandemic influenza A (H1N1 2009 in Pakistan.

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Nadia Nisar

Full Text Available BACKGROUND: Influenza is a viral infection that can lead to serious complications and death(s in vulnerable groups if not diagnosed and managed in a timely manner. This study was conducted to improve the accuracy of predicting influenza through various clinical and statistical models. METHODOLOGY: A retrospective cross sectional analysis was done on demographic and epidemiological data collected from March 2009 to March 2010. Patients were classified as ILI or SARI using WHO case definitions. Respiratory specimens were tested by RT-PCR. Clinical symptoms and co-morbid conditions were analyzed using binary logistic regression models. RESULTS: In the first approach, analysis compared children (≤12 and adults (>12. Of 1,243 cases, 262 (21% tested positive for A(H1N1pdm09 and the proportion of children (≤12 and adults (>12 were 27% and 73% respectively. Four symptoms predicted influenza in children: fever (OR 2.849, 95% CI 1.931-8.722, cough (OR 1.99, 95% CI 1.512-3.643, diarrhea (OR 2.100, 95% CI 2.040-3.25 and respiratory disease (OR 3.269, 95% CI 2.128-12.624. In adults, the strongest clinical predictor was fever (OR 2.80, 95% CI 1.025-3.135 followed by cough (OR 1.431, 95% CI 1.032-2.815. In the second instance, patients were separated into two groups: SARI 326 (26% and ILI 917 (74% cases. Male to female ratio was 1.41∶1.12 for SARI and 2∶1.5 for ILI cases. Chi-square test showed that fever, cough and sore throat were significant factors for A(H1N1pdm09 infections (p = 0.008. CONCLUSION: Studies in a primary care setting should be encouraged focused on patients with influenza-like illness to develop sensitive clinical case definition that will help to improve accuracy of detecting influenza infections. Formulation of a standard "one size fits all" case definition that best correlates with influenza infections can help guide decisions for additional diagnostic testing and also discourage unjustified antibiotic prescription and usage

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

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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.

A New Approach to Improve Accuracy of Grey Model GMC(1,n in Time Series Prediction

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Sompop Moonchai

2015-01-01

Full Text Available This paper presents a modified grey model GMC(1,n for use in systems that involve one dependent system behavior and n-1 relative factors. The proposed model was developed from the conventional GMC(1,n model in order to improve its prediction accuracy by modifying the formula for calculating the background value, the system of parameter estimation, and the model prediction equation. The modified GMC(1,n model was verified by two cases: the study of forecasting CO2 emission in Thailand and forecasting electricity consumption in Thailand. The results demonstrated that the modified GMC(1,n model was able to achieve higher fitting and prediction accuracy compared with the conventional GMC(1,n and D-GMC(1,n models.

Overexpression of GmDREB1 improves salt tolerance in transgenic wheat and leaf protein response to high salinity

OpenAIRE

Qiyan Jiang; Zheng Hu; Hui Zhang; Youzhi Ma

2014-01-01

The transcription factor dehydration-responsive element binding protein (DREB) is able to improve tolerance to abiotic stress in plants by regulating the expression of downstream genes involved in environmental stress resistance. The objectives of this study were to evaluate the salt tolerance of GmDREB1 transgenic wheat (Triticum aestivum L.) and to evaluate its physiological and protein responses to salt stress. Compared with the wild type, the transgenic lines overexpressing GmDREB1 showed...

Space Vector Modulation for an Indirect Matrix Converter with Improved Input Power Factor

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Nguyen Dinh Tuyen

2017-04-01

Full Text Available Pulse width modulation strategies have been developed for indirect matrix converters (IMCs in order to improve their performance. In indirect matrix converters, the LC input filter is used to remove input current harmonics and electromagnetic interference problems. Unfortunately, due to the existence of the input filter, the input power factor is diminished, especially during operation at low voltage outputs. In this paper, a new space vector modulation (SVM is proposed to compensate for the input power factor of the indirect matrix converter. Both computer simulation and experimental studies through hardware implementation were performed to verify the effectiveness of the proposed modulation strategy.

Transforming growth factor β1 inhibition protects from noise-induced hearing loss

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Silvia eMurillo-Cuesta

2015-03-01

Full Text Available Excessive exposure to noise damages the principal cochlear structures leading to hearing impairment. Inflammatory and immune responses are central mechanisms in cochlear defensive response to noise but, if unregulated, they contribute to inner ear damage and hearing loss. Transforming growth factor ß (TGF-ß is a key regulator of both responses and high levels of this factor have been associated with cochlear injury in hearing loss animal models. To evaluate the potential of targeting TGF-ß as a therapeutic strategy for preventing or ameliorating noise-induced hearing loss, we studied the auditory function, cochlear morphology, gene expression and oxidative stress markers in mice exposed to noise and treated with TGF-ß1 peptidic inhibitors P17 and P144, just before or immediately after noise insult. Our results indicate that systemic administration of both peptides significantly improved both the evolution of hearing thresholds and the degenerative changes induced by noise-exposure in lateral wall structures. Moreover, treatments ameliorated the inflammatory state and redox balance. These therapeutic effects were dose-dependent and more effective if the TGF-ß1 inhibitors were administered prior to inducing the injury. In conclusion, inhibition of TGF-ß1 actions with antagonistic peptides represents a new, promising therapeutic strategy for the prevention and repair of noise-induced cochlear damage.

Innate immune factors associated with HIV-1 transmission

NARCIS (Netherlands)

Pollakis, Georgios; Stax, Martijn J.; Paxton, William A.

2011-01-01

Relatively little is known with regards to the mechanisms of HIV-1 transmission across a mucosal surface and more specifically what effects host factors have on influencing infection and early viral dissemination. The purpose of this review is to summarize which factors of the innate immune response

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

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Chenshuang Li

2018-01-01

Full Text Available 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.

Recognition factors of Ricinus communis agglutinin 1 (RCA(1)).

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Wu, Albert M; Wu, June H; Singh, Tanuja; Lai, Li-Ju; Yang, Zhangung; Herp, Anthony

2006-04-01

Ricinus communis agglutinin (RCA1) is one of the most important applied lectins that has been widely used as a tool to study cell surfaces and to purify glycans. Although the carbohydrate specificity of RCA1 has been described, the information obtained was mainly focused on inhibition of simple Galbeta1-related oligosaccharides and simple clusters. Here, all possible recognition factors of RCA1 of glycan binding were examined by enzyme-linked lectinosorbent (ELLSA) and inhibition assays, using known mammalian Gal/GalNAc carbohydrate structural units and natural polyvalent glycans. Among the glycoproteins (gps) tested and expressed as 50% nanogram inhibition, the high-density polyvalent Galbeta1-4GlcNAc (II) glycotopes occurring in natural gps, such as Pneumococcus type 14 capsular polysaccharide which is composed of repeating poly II residues, resulted in 9.0 x 10(4), 1.5 x 10(5), 2.3 x 10(4) and 2.1 x 10(4)-fold higher affinities to RCA1 than the monomeric Gal, linear I/II and Tri-antennary-II (Tri-II). Of the ligands tested and expressed as nanomoles of 50% inhibition, Tri-II was the best, being about 2, 4, 25.6 and 33.3 times better inhibitor than Di-II, II, I (Galbeta1-3GlcNAc) and Gal, respectively. From the results of this study, it is concluded that: (a) Galbeta1-4GlcNAc and other Galbeta1-related oligosaccharides are essential for lectin binding and their polyvalent form in macromolecules should be the most important recognition factor for RCA1; (b) the combining site of RCA1 may be a groove type, recognizing Galbeta1-4GlcNAc (II) as the major binding site; (c) its combining size may be large enough to accommodate a tetrasaccharide of beta-anomeric Gal at the non-reducing end and most complementary to human blood group I Ma active trisaccharide (Galbeta1-4GlcNAcbeta1-6Gal) and lacto-N-neotetraose (Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glc); (d) RCA1 has a preference for the beta-anomer of Gal oligosaccharides with a Galbeta1-4 linkage > Galbeta1-6 > or = Galbeta

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

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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.

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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.

CNF1 improves astrocytic ability to support neuronal growth and differentiation in vitro.

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Fiorella Malchiodi-Albedi

Full Text Available Modulation of cerebral Rho GTPases activity in mice brain by intracerebral administration of Cytotoxic Necrotizing Factor 1 (CNF1 leads to enhanced neurotransmission and synaptic plasticity and improves learning and memory. To gain more insight into the interactions between CNF1 and neuronal cells, we used primary neuronal and astrocytic cultures from rat embryonic brain to study CNF1 effects on neuronal differentiation, focusing on dendritic tree growth and synapse formation, which are strictly modulated by Rho GTPases. CNF1 profoundly remodeled the cytoskeleton of hippocampal and cortical neurons, which showed philopodia-like, actin-positive projections, thickened and poorly branched dendrites, and a decrease in synapse number. CNF1 removal, however, restored dendritic tree development and synapse formation, suggesting that the toxin can reversibly block neuronal differentiation. On differentiated neurons, CNF1 had a similar effacing effect on synapses. Therefore, a direct interaction with CNF1 is apparently deleterious for neurons. Since astrocytes play a pivotal role in neuronal differentiation and synaptic regulation, we wondered if the beneficial in vivo effect could be mediated by astrocytes. Primary astrocytes from embryonic cortex were treated with CNF1 for 48 hours and used as a substrate for growing hippocampal neurons. Such neurons showed an increased development of neurites, in respect to age-matched controls, with a wider dendritic tree and a richer content in synapses. In CNF1-exposed astrocytes, the production of interleukin 1β, known to reduce dendrite development and complexity in neuronal cultures, was decreased. These results demonstrate that astrocytes, under the influence of CNF1, increase their supporting activity on neuronal growth and differentiation, possibly related to the diminished levels of interleukin 1β. These observations suggest that the enhanced synaptic plasticity and improved learning and memory described

CNF1 Improves Astrocytic Ability to Support Neuronal Growth and Differentiation In vitro

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Malchiodi-Albedi, Fiorella; Paradisi, Silvia; Di Nottia, Michela; Simone, Daiana; Travaglione, Sara; Falzano, Loredana; Guidotti, Marco; Frank, Claudio; Cutarelli, Alessandro; Fabbri, Alessia; Fiorentini, Carla

2012-01-01

Modulation of cerebral Rho GTPases activity in mice brain by intracerebral administration of Cytotoxic Necrotizing Factor 1 (CNF1) leads to enhanced neurotransmission and synaptic plasticity and improves learning and memory. To gain more insight into the interactions between CNF1 and neuronal cells, we used primary neuronal and astrocytic cultures from rat embryonic brain to study CNF1 effects on neuronal differentiation, focusing on dendritic tree growth and synapse formation, which are strictly modulated by Rho GTPases. CNF1 profoundly remodeled the cytoskeleton of hippocampal and cortical neurons, which showed philopodia-like, actin-positive projections, thickened and poorly branched dendrites, and a decrease in synapse number. CNF1 removal, however, restored dendritic tree development and synapse formation, suggesting that the toxin can reversibly block neuronal differentiation. On differentiated neurons, CNF1 had a similar effacing effect on synapses. Therefore, a direct interaction with CNF1 is apparently deleterious for neurons. Since astrocytes play a pivotal role in neuronal differentiation and synaptic regulation, we wondered if the beneficial in vivo effect could be mediated by astrocytes. Primary astrocytes from embryonic cortex were treated with CNF1 for 48 hours and used as a substrate for growing hippocampal neurons. Such neurons showed an increased development of neurites, in respect to age-matched controls, with a wider dendritic tree and a richer content in synapses. In CNF1-exposed astrocytes, the production of interleukin 1β, known to reduce dendrite development and complexity in neuronal cultures, was decreased. These results demonstrate that astrocytes, under the influence of CNF1, increase their supporting activity on neuronal growth and differentiation, possibly related to the diminished levels of interleukin 1β. These observations suggest that the enhanced synaptic plasticity and improved learning and memory described in CNF1-injected

An improved correlated sampling method for calculating correction factor of detector

International Nuclear Information System (INIS)

Wu Zhen; Li Junli; Cheng Jianping

2006-01-01

In the case of a small size detector lying inside a bulk of medium, there are two problems in the correction factors calculation of the detectors. One is that the detector is too small for the particles to arrive at and collide in; the other is that the ratio of two quantities is not accurate enough. The method discussed in this paper, which combines correlated sampling with modified particle collision auto-importance sampling, and has been realized on the MCNP-4C platform, can solve these two problems. Besides, other 3 variance reduction techniques are also combined with correlated sampling respectively to calculate a simple calculating model of the correction factors of detectors. The results prove that, although all the variance reduction techniques combined with correlated sampling can improve the calculating efficiency, the method combining the modified particle collision auto-importance sampling with the correlated sampling is the most efficient one. (authors)

Improving English Speaking Fluency: The Role of Six Factors

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Gholamhossein Shahini

2017-12-01

Full Text Available 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 based on the speaking scale of Common European Framework of Reference for Languages (CEFRL. The findings indicated that early age had a great impact on the participants’ speaking fluency. They mentioned that they could not pick up fluency if they had started learning English at older ages. Moreover, university education had no effect on enhancing their fluency. They stated that not having enough opportunities to speak English in classrooms, being exposed to wrong amounts of input from their classmates or even from some university instructors, having no access to English native speakers in English Language Departments, professors’ talking in native language out of classes, in their offices or even sometimes in classes all led to their losing motivation after entering the university. In contrast, teachers in English language institutes had a supportive role in increasing the participants’ English learning. Although two participants quit teaching English since it had a negative influence on their speaking, it had a positive impact on improving speaking ability of the rest. And finally, fruitful strategies were suggested on how to use dictionaries and note-takings.

Improved 1-Deoxynojirimycin (DNJ production in mulberry leaves fermented by microorganism

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Yun-Gang Jiang

2014-06-01

Full Text Available DNJ, an inhibitor of α-glucosidase, is used to suppress the elevation of postprandial hyperglycemia. In this study, we focus on screening an appropriate microorganism for performing fermentation to improve DNJ content in mulberry leaf. Results showed that Ganoderma lucidum was selected from 8 species and shown to be the most effective in improvement of DNJ production from mulberry leaves through fermentation. Based on single factor and three factor influence level tests by following the Plackett-Burman design, the optimum extraction yield was analyzed by response surface methodology (RSM. The extracted DNJ was determined by reverse-phase high performance liquid chromatograph equipped with fluorescence detector (HPLC-FD. The results of RSM showed that the optimal condition for mulberry fermentation was defined as pH 6.97, potassium nitrate content 0.81% and inoculums volume 2 mL. The extraction efficiency reached to 0.548% in maximum which is 2.74 fold of those in mulberry leaf.

CONCEPTUAL FRAMEWORK FOR IMPROVING BUSINESS PERFORMANCE WITH LEAN MANUFACTURING AND SUCCESSFUL HUMAN FACTORS INTERVENTIONS-A CASE STUD

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Rajiv Sharm

2012-09-01

Full Text Available Nowadays organizations compete between themselves in various categories such as faster delivery, price tags, state of art - technology and higher quality dimensio ns. A Conceptual framework with lean manufacturing and hum an factors interventions for improving business performance in terms of improved quality, reduced cost and faster de livery is presented and example s from literature are given to illustrate the desir ed situation in which ergonomics is considered as an integrated part of performance strategy . A case from an industry engaged in manufacturing shafts using lean manufacturing practices with successful ergonomic or human factors interventions is also inves tigated.

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

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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.

Improving performance of high risk organizations Spanish nuclear sector from the analysis of organizational culture factors

International Nuclear Information System (INIS)

La Salabarnada, E.; German, S.; Silla, I.; Navajas, J.

2012-01-01

This paper presents the research project funded by UNESA and conducted by the CISOT-CIEMAT that aims to contribute to improving the operating performance of the Spanish nuclear power plants. This paper aims to identify the factors and key organizational processes to improve efficiency, in order to advance knowledge about the influence of organizational culture on the safety of high reliability organizations.

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

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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

Vascular endothelial growth factor receptor-3 is a novel target to improve net ultrafiltration in methylglyoxal-induced peritoneal injury.

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Terabayashi, Takeshi; Ito, Yasuhiko; Mizuno, Masashi; Suzuki, Yasuhiro; Kinashi, Hiroshi; Sakata, Fumiko; Tomita, Takako; Iguchi, Daiki; Tawada, Mitsuhiro; Nishio, Ryosuke; Maruyama, Shoichi; Imai, Enyu; Matsuo, Seiichi; Takei, Yoshifumi

2015-09-01

Appropriate fluid balance is important for good clinical outcomes and survival in patients on peritoneal dialysis. We recently reported that lymphangiogenesis associated with fibrosis developed in the peritoneal cavity via the transforming growth factor-β1-vascular endothelial growth factor-C (VEGF-C) pathway. We investigated whether VEGF receptor-3 (VEGFR-3), the receptor for VEGF-C and -D, might be a new target to improve net ultrafiltration by using adenovirus-expressing soluble VEGFR-3 (Adeno-sVEGFR-3) in rodent models of peritoneal injury induced by methylglyoxal (MGO). We demonstrated that lymphangiogenesis developed in these MGO models, especially in the diaphragm, indicating that lymphangiogenesis is a common feature in the peritoneal cavity with inflammation and fibrosis. In MGO models, VEGF-D was significantly increased in the diaphragm; however, VEGF-C was not significantly upregulated. Adeno-sVEGFR-3, which was detected on day 50 after administration via tail vein injections, successfully suppressed lymphangiogenesis in the diaphragm and parietal peritoneum in mouse MGO models without significant effects on fibrosis, inflammation, or neoangiogenesis. Drained volume in the peritoneal equilibration test using a 7.5% icodextrin peritoneal dialysis solution (the 7.5% icodextrin peritoneal equilibration test) was improved by Adeno-sVEGFR-3 on day 22 (Ptarget to improve net ultrafiltration by suppressing lymphatic absorption and that the 7.5% icodextrin peritoneal equilibration test is useful for estimation of lymphatic absorption.

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

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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.

Influential Factors for the Improvement of Peer Education in Adolescents: A Narrative Review

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Marzieh Azizi

2016-09-01

Full Text Available Context Peer education is an effective strategy for improving adolescents’ health. It focuses on the improvement of knowledge, attitudes and beliefs among adolescents with regards to different healthcare issues and empowers them to make informed decisions. This review study aimed to determine factors that promote peer education among adolescents. Evidence Acquisition In this narrative review, electronic databases including Google Scholar, Science Direct, PubMed (including Medline, Web of Science, Scientific Information Database, and Scopus were searched. Articles published between 1991 and 2016 were retrieved and undergone abstract and full-text appraisal. Lastly, 53 articles were selected and used to write this review. Results The factors influencing the promotion of peer education among adolescents were classified as follow: ‘characteristics of peer educators’: personal, skills and communication characteristics; ‘characteristics of the educational program’: theoretical foundations, program transparency, program sustainability, adolescents’ comprehensive participation, and evaluation and monitoring; and ‘structural characteristics of the educational program’: supportive structure, and financial-official structure. Conclusions Taking into account the importance of adolescence and issues surrounding this period, the important role of peer education in the promotion of adolescents’ health should be emphasized.

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

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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.

Identifying factors to improve oral cancer screening uptake: a qualitative study.

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Fatemeh Vida Zohoori

Full Text Available To engage with high risk groups to identify knowledge and awareness of oral cancer signs and symptoms and the factors likely to contribute to improved screening uptake.Focus group discussions were undertaken with 18 males; 40+ years of age; smokers and/or drinkers (15+ cigarettes per day and/or 15+ units of alcohol per week, irregular dental attenders living in economically deprived areas of Teesside.There was a striking reported lack of knowledge and awareness of oral cancer and its signs and symptoms among the participants. When oral/mouth cancer leaflets produced by Cancer Research UK were presented to the participants, they claimed that they would seek help on noticing such a condition. There was a preference to seek help from their general practitioner rather than their dentist due to perceptions that a dentist is 'inaccessible' on a physical and psychological level, costly, a 'tooth specialist' not a 'mouth specialist', and also not able to prescribe medication and make referrals to specialists. Interestingly, none of the 18 participants who were offered a free oral cancer examination at a dental practice took up this offer.The uptake of oral cancer screening may be improved by increasing knowledge of the existence and signs and symptoms of oral cancer. Other factors that may increase uptake are increased awareness of the role of dentists in diagnosing oral cancer, promotion of oral cancer screening by health professionals during routine health checks, and the use of a "health" screening setting as opposed to a "dental" setting for such checks.

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

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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

2017-10-12

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

Low-Frequency Electroacupuncture Improves Insulin Sensitivity in Obese Diabetic Mice through Activation of SIRT1/PGC-1α in Skeletal Muscle

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Fengxia Liang

2011-01-01

Full Text Available Electroacupuncture (EA has been observed to reduce insulin resistance in obesity and diabetes. However, the biochemical mechanism underlying this effect remains unclear. This study investigated the effects of low-frequency EA on metabolic action in genetically obese and type 2 diabetic db/db mice. Nine-week-old db/m and db/db mice were randomly divided into four groups, namely, db/m, db/m + EA, db/db, and db/db + EA. db/m + EA and db/db + EA mice received 3-Hz electroacupuncture five times weekly for eight consecutive weeks. In db/db mice, EA tempered the increase in fasting blood glucose, food intake, and body mass and maintained insulin levels. In EA-treated db/db mice, improved insulin sensitivity was established through intraperitoneal insulin tolerance test. EA was likewise observed to decrease free fatty acid levels in db/db mice; it increased protein expression in skeletal muscle Sirtuin 1 (SIRT1 and induced gene expression of peroxisome proliferator-activated receptor coactivator (PGC-, nuclear respiratory factor 1 (NRF1, and acyl-CoA oxidase (ACOX. These results indicated that EA offers a beneficial effect on insulin resistance in obese and diabetic db/db mice, at least partly, via stimulation of SIRT1/PGC-, thus resulting in improved insulin signal.

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

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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.

Frequency-restrained structure-factor refinement. Pt. 1

International Nuclear Information System (INIS)

Lunin, V.Yu.; Skovoroda, T.P.

1991-01-01

An analysis of the frequencies of different values encountered in protein electron-density syntheses reveals characteristic shapes for their distributions (histograms). This property can be used to refine ill-defined phases (and, perhaps, some of the moduli) of structure factors, and thus to obtain more-interpretable electron-density maps. A simple empirical model is designed which can predict the histogram for a protein with an undetermined structure provided its unit-cell volume and charge are known. The parameters of the histogram model are derived from a set of proteins with known spatial structures. The application of the simulated histogram is illustrated by an improved electron-density map for the 'dry' form of the protein γ-crystallin IIIb. (orig.)

East African Journal of Sciences (2010) Volume 4 (1) 41-47 Factors ...

African Journals Online (AJOL)

Mahdi

Factors Influencing the Adoption of Improved Sorghum Varieties in Awbere District of. Somali Regional ... Descriptive statistics and logistic regression model were ... and have access to market information can be greater technology adopters.

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

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Werner Schlegel

Full Text Available 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.

Availability improvement factors at Taipower's nuclear power plant system

International Nuclear Information System (INIS)

Chen, J.H.

1985-01-01

Sufficient electricity to meet the needs of a growing industrial economy, is one of the most important factors in the total economic development of a nation. Currently, nuclear power is considered one of the most economical and available sources of energy. To keep pace with Taiwan's rapid economic development, while also observing our government's policy of diversifying the requirements for imported forms of energy, Taiwan Power Company has embarked upon an ambitious of nuclear power plant construction. This paper discusses the improvement of Taiwan's nuclear power plants. At the present time, Taipower has completed three nuclear power plants. Two of these are located in northern Taiwan, along the East China Sea, while the third is on the southern tip of Taiwan, bordering the South China Sea. These three plants, each with two nuclear generating units, comprise a total nuclear generating capacity of 5144 MWe

Effect of hypoxia-inducible factor 1-alpha (HIF-1α) on proliferation ...

African Journals Online (AJOL)

Jane

2011-07-25

Jul 25, 2011 ... Full Length Research Paper. Effect of hypoxia-inducible factor 1-alpha ... 1Department of Neurosurgery, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200025,. China. 2Department of Neurosurgery, Chaoyang Hospital, Huainan, Anhui, China. 3Department of Neurosurgery ...

Experimental data for insulin-like growth factor-1 (IGF-1) and basic fibroblast growth factor (bFGF) in prevention of radiation myelopathy; Experimentelle Daten zum Einsatz von Insulin-Like Growth Factor-1 (IGF-1) und Basic Fibroblast Growth Factor (bFGF) zur Praevention einer Strahlenmyelopathie

Energy Technology Data Exchange (ETDEWEB)

Nieder, C. [Technische Univ. Muenchen (Germany). Klinik und Poliklinik fuer Strahlentherapie und Radiologische Onkologie; Price, R.E.; Rivera, B. [The Univ. of Texas, M. D. Anderson Cancer Center, Houston, TX (United States). Dept. of Veterinary Medicine and Surgery; Andratschke, N.; Kian Ang, K. [The Univ. of Texas, M. D. Anderson Cancer Center, Houston, TX (United States). Dept. of Experimental Radiation Oncology

2002-03-01

Background: Current models of radiation myelopathy provide a rationale for growth factor-based prevention strategies. Thus, we tested whether insulin-like growth factor-1 (IGF-1) and basic fibroblast growth factor (bFGF) alone or in combination modulate radiation tolerance of the rat cervical spinal cord. Materials and Methods: The cervical spinal cord of 68 adult Fisher F344 rats received a total dose of 30-36 Gy, given as a single fraction of 16 Gy followed by a second radiation dose of 14-20 Gy. Continuous intrathecal infusion of bFGF (44 rats) or saline (24 rats) into the cisterna magna was given concomitantly. A further experiment included 14 additional rats which were treated with subcutaneous injection of IGF-1 parallel to irradiation with a total dose of 34 Gy or 36 Gy. 20 rats received combined treatment, i.e. intrathecal infusion of bFGF plus subcutaneous injection of IGF-1, starting 24 hours before irradiation (total dose 33 Gy or 36 Gy) for a total of 4 days. Animals were followed until myelopathy developed or for a maximum of 12 months. Histopathologic examinations were performed post mortem. Results: Treatment with bFGF alone or IGF-1 alone increased the median time to myelopathy significantly. In the 36-Gy group, after combination treatment a comparable prolongation of latency was seen. Moreover, rats treated with 33 Gy and combined bFGF plus IGF-1 showed a significantly reduced risk of myelopathy, too (p = 0.0015). (orig.) [German] Hintergrund: Aktuelle Modelle zur Pathogenese der Strahlenmyelopathie lassen den praeventiven Einsatz von Wachstumsfaktoren sinnvoll erscheinen. Daher sollte ueberprueft werden, ob Insulin-Like Growth Factor-1 (IGF-1) und Basic Fibroblast Growth Factor (bFGF) als Einzelsubstanzen oder in Kombination die Strahlentoleranz des zervikalen Rueckenmarks von Ratten beeinflussen. Material und Methoden: Das Zervikalmark von 68 erwachsenen Fisher-F344-Ratten wurde mit zwei Einzelfraktionen bis insgesamt 30-36 Gy bestrahlt (16 Gy

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

Science.gov (United States)

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.

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

Science.gov (United States)

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 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 Interventions Published by Wiley Periodicals, Inc.

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.

Science.gov (United States)

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.

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

Science.gov (United States)

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 sACE activity at the time of the last observation to sACE activity at the time of BAL (sACE(LAST)/sACE(BAL), p 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

CYP1B1 expression, a potential risk factor for breast cancer

Energy Technology Data Exchange (ETDEWEB)

Goth-Goldstein, Regine; Erdmann, Christine A.; Russell, Marion

2001-05-31

CYP1B1 expression in non-tumor breast tissue from breast cancer patients and cancer-free individuals was determined to test the hypothesis that high CYP1B1 expression is a risk factor for breast cancer. Large interindividual variations in CYP1B1 expression were found with CYP1B1 levels notably higher in breast cancer patients than cancer-free individuals. The results indicate that CYP1B1 might play a role in breast cancer either through increased PAH activation or through metabolism of endogenous estrogen to a carcinogenic derivative.

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

Science.gov (United States)

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...

47 CFR 1.3003 - Mandatory factors for evaluating conflicts of interest.

Science.gov (United States)

2010-10-01

... determinations, designated agency ethics officials shall consider the following factors: (a) Whether the benefits... 47 Telecommunication 1 2010-10-01 2010-10-01 false Mandatory factors for evaluating conflicts of... Unconditional Gifts, Donations and Bequests § 1.3003 Mandatory factors for evaluating conflicts of interest. No...

Improvement of level-1 PSA computer code package

Energy Technology Data Exchange (ETDEWEB)

Kim, Tae Woon; Park, C. K.; Kim, K. Y.; Han, S. H.; Jung, W. D.; Chang, S. C.; Yang, J. E.; Sung, T. Y.; Kang, D. I.; Park, J. H.; Lee, Y. H.; Kim, S. H.; Hwang, M. J.; Choi, S. Y.

1997-07-01

This year the fifth (final) year of the phase-I of the Government-sponsored Mid- and Long-term Nuclear Power Technology Development Project. The scope of this subproject titled on `The improvement of level-1 PSA Computer Codes` is divided into two main activities : (1) improvement of level-1 PSA methodology, (2) development of applications methodology of PSA techniques to operations and maintenance of nuclear power plant. Level-1 PSA code KIRAP is converted to PC-Windows environment. For the improvement of efficiency in performing PSA, the fast cutset generation algorithm and an analytical technique for handling logical loop in fault tree modeling are developed. Using about 30 foreign generic data sources, generic component reliability database (GDB) are developed considering dependency among source data. A computer program which handles dependency among data sources are also developed based on three stage bayesian updating technique. Common cause failure (CCF) analysis methods are reviewed and CCF database are established. Impact vectors can be estimated from this CCF database. A computer code, called MPRIDP, which handles CCF database are also developed. A CCF analysis reflecting plant-specific defensive strategy against CCF event is also performed. A risk monitor computer program, called Risk Monster, are being developed for the application to the operation and maintenance of nuclear power plant. The PSA application technique is applied to review the feasibility study of on-line maintenance and to the prioritization of in-service test (IST) of motor-operated valves (MOV). Finally, the root cause analysis (RCA) and reliability-centered maintenance (RCM) technologies are adopted and applied to the improvement of reliability of emergency diesel generators (EDG) of nuclear power plant. To help RCA and RCM analyses, two software programs are developed, which are EPIS and RAM Pro. (author). 129 refs., 20 tabs., 60 figs.

Improvement of level-1 PSA computer code package

International Nuclear Information System (INIS)

Kim, Tae Woon; Park, C. K.; Kim, K. Y.; Han, S. H.; Jung, W. D.; Chang, S. C.; Yang, J. E.; Sung, T. Y.; Kang, D. I.; Park, J. H.; Lee, Y. H.; Kim, S. H.; Hwang, M. J.; Choi, S. Y.

1997-07-01

This year the fifth (final) year of the phase-I of the Government-sponsored Mid- and Long-term Nuclear Power Technology Development Project. The scope of this subproject titled on 'The improvement of level-1 PSA Computer Codes' is divided into two main activities : 1) improvement of level-1 PSA methodology, 2) development of applications methodology of PSA techniques to operations and maintenance of nuclear power plant. Level-1 PSA code KIRAP is converted to PC-Windows environment. For the improvement of efficiency in performing PSA, the fast cutset generation algorithm and an analytical technique for handling logical loop in fault tree modeling are developed. Using about 30 foreign generic data sources, generic component reliability database (GDB) are developed considering dependency among source data. A computer program which handles dependency among data sources are also developed based on three stage bayesian updating technique. Common cause failure (CCF) analysis methods are reviewed and CCF database are established. Impact vectors can be estimated from this CCF database. A computer code, called MPRIDP, which handles CCF database are also developed. A CCF analysis reflecting plant-specific defensive strategy against CCF event is also performed. A risk monitor computer program, called Risk Monster, are being developed for the application to the operation and maintenance of nuclear power plant. The PSA application technique is applied to review the feasibility study of on-line maintenance and to the prioritization of in-service test (IST) of motor-operated valves (MOV). Finally, the root cause analysis (RCA) and reliability-centered maintenance (RCM) technologies are adopted and applied to the improvement of reliability of emergency diesel generators (EDG) of nuclear power plant. To help RCA and RCM analyses, two software programs are developed, which are EPIS and RAM Pro. (author). 129 refs., 20 tabs., 60 figs

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

Directory of Open Access Journals (Sweden)

Salsali Mahvash

2005-10-01

Full Text Available Abstract 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.

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

Directory of Open Access Journals (Sweden)

Davies Elizabeth A

2011-12-01

Full Text Available Abstract 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.

CORCON-MOD1 modelling improvements

International Nuclear Information System (INIS)

Corradini, M.L.; Gonzales, F.G.; Vandervort, C.L.

1986-01-01

Given the unlikely occurrence of a severe accident in a light water reactor (LWR), the core may melt and slump into the reactor cavity below the reactor vessel. The interaction of the molten core with exposed concrete (a molten-core-concrete-interaction, MCCI) causes copious gas production which influences further heat transfer and concrete attack and may threaten containment integrity. In this paper the authors focus on the low-temperature phase of the MCCI where the molten pool is partially solidified, but is still capable of attacking concrete. The authors have developed some improved phenomenological models for pool freezing and molten core-coolant heat transfer and have incorporated them into the CORCON-MOD1 computer program. In the paper the authors compare the UW-CORCON/MOD1 calculations to CORCON/MOD2 and WECHSL results as well as the BETA experiments which are being conducted in Germany

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.

Science.gov (United States)

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.

Science.gov (United States)

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.

Structure and role of neutrophil cytosol factor 1 (NCF1) gene in ...

African Journals Online (AJOL)

Yomi

2010-12-27

Dec 27, 2010 ... The neutrophil cytosol factor 1 (NCF1) gene consists of 11 exons and is found in two forms; one is wild ... granulomatous disease, multiple sclerosis, arthritis and parasitic infection. ... TCR, T cell receptor; AhR, aryl hydrocarbon receptor; RA, .... During malaria, ROS production can contribute to both.

B→π form factor with 2 flavours of O(a) improved Wilson quarks

International Nuclear Information System (INIS)

Bahr, Felix; Bernardoni, Fabio; Ramos, Alberto; Simma, Hubert; Sommer, Rainer; Bulava, John

2012-10-01

The determinations of vertical stroke V ub vertical stroke from the exclusive branching ratios of B→τν and B→πlν tend to show a tension at the level of 3σ. On the theoretical side they depend on the lattice computation of the hadronic matrix elements f B and the B →>π form factor f + (q 2 ). To understand the tension, improved precision and a careful analysis of the systematics involved are necessary. Working towards this goal, we present preliminary lattice results of the ALPHA collaboration for the B→ π form factor f + (q 2 ) with N f =2 flavours of O(a)-improved Wilson fermions. Our computation uses HQET in the static limit, pion masses ranging down to ∼250 MeV, large volumes with m π L>4, three lattice spacings, and non-perturbative renormalization. We describe the techniques adopted to reduce the statistical noise (stochastic all-to-all with full time dilution) and the contamination from excited states (smearing for the B and the pion). We estimate the size of the chiral and continuum extrapolations. We discuss the impact our result could have to clarify the above mentioned discrepancy in the determination of vertical stroke V ub vertical stroke.

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

Science.gov (United States)

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.

Science.gov (United States)

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.

Topical photodynamic therapy following excisional wounding of human skin increases production of transforming growth factor-β3 and matrix metalloproteinases 1 and 9, with associated improvement in dermal matrix organization.

Science.gov (United States)

Mills, S J; Farrar, M D; Ashcroft, G S; Griffiths, C E M; Hardman, M J; Rhodes, L E

2014-07-01

Animal studies report photodynamic therapy (PDT) to improve healing of excisional wounds; the mechanism is uncertain and equivalent human studies are lacking. To explore the impact of methyl aminolaevulinate (MAL)-PDT on clinical and microscopic parameters of human cutaneous excisional wound healing, examining potential modulation through production of transforming growth factor (TGF)-β isoforms. In 27 healthy older men (60-77 years), a 4-mm punch biopsy wound was created in skin of the upper inner arm and treated with MAL-PDT three times over 5 days. An identical control wound to the contralateral arm was untreated and both wounds left to heal by secondary intention. Wounds were re-excised during the inflammatory phase (7 days, n = 10), matrix remodelling (3 weeks, n = 8) and cosmetic outcome/dermal structure (9 months, n = 9). Production of TGF-β1, TGF-β3 and matrix metalloproteinases (MMPs) was assessed by immunohistochemistry alongside microscopic measurement of wound size/area and clinical assessment of wound appearance. MAL-PDT delayed re-epithelialization at 7 days, associated with increased inflammation. However, 3 weeks postwounding, treated wounds were smaller with higher production of MMP-1 (P = 0·01), MMP-9 (P = 0·04) and TGF-β3 (P = 0·03). TGF-β1 was lower than control at 7 days and higher at 3 weeks (both P = 0·03). At 9 months, MAL-PDT-treated wounds showed greater, more ordered deposition of collagen I, collagen III and elastin (all P < 0·05). MAL-PDT increases MMP-1, MMP-9 and TGF-β3 production during matrix remodelling, ultimately producing scars with improved dermal matrix architecture. © 2014 British Association of Dermatologists.

Furan- and Thiophene-2-Carbonyl Amino Acid Derivatives Activate Hypoxia-Inducible Factor via Inhibition of Factor Inhibiting Hypoxia-Inducible Factor-1

Directory of Open Access Journals (Sweden)

Shin-ichi Kawaguchi

2018-04-01

Full Text Available Induction of a series of anti-hypoxic proteins protects cells during exposure to hypoxic conditions. Hypoxia-inducible factor-α (HIF-α is a major transcription factor that orchestrates this protective effect. To activate HIF exogenously, without exposing cells to hypoxic conditions, many small-molecule inhibitors targeting prolyl hydroxylase domain-containing protein have been developed. In addition, suppression of factor inhibiting HIF-1 (FIH-1 has also been shown to have the potential to activate HIF-α. However, few small-molecule inhibitors of FIH-1 have been developed. In this study, we synthesized a series of furan- and thiophene-2-carbonyl amino acid derivatives having the potential to inhibit FIH-1. The inhibitory activities of these compounds were evaluated in SK-N-BE(2c cells by measuring HIF response element (HRE promoter activity. Several furan- and thiophene-2-carbonyl amino acid derivatives inhibited FIH-1 based on correlations among the docking score of the FIH-1 active site, the chemical structure of the compounds, and biological HIF-α/HRE transcriptional activity.

Increasing plasma fibrinogen, but unchanged levels of intraplatelet cyclic nucleotides, plasma endothelin-1, factor VII, and neopterin during cholesterol lowering with fluvastatin.

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Gottsäter, A; Anwaar, I; Lind, P; Mattiasson, I; Lindgärde, F

1999-04-01

Lipid-lowering statin treatment reduces cardiovascular morbidity and mortality and improves endothelial function in patients with hypercholesterolemia. The aim of the present study was to evaluate plasma levels of fibrinogen, factor VII, and the macrophage-derived inflammatory mediator neopterin during lipid lowering. In addition, the endothelial production of platelet antiaggregatory and vasodilatory factors such as nitric oxide and prostacyclin, and vasoconstrictive factors such as endothelin-1, was assessed. Plasma fibrinogen, factor VII, endothelin-1, and the neopterin and intraplatelet nitric oxide and prostacyclin mediators cyclic 3'-5'guanosine monophosphate (cGMP) and cyclic 3'-5'adenosine monophosphate (cAMP) were measured before and 6 months after the institution of treatment with fluvastatin in 17 patients (eight men and nine women, median age 60 years) with vascular disease and previously untreated hypercholesterolemia. After 6 months, a decrease of 1.62 mmol/l [1.26-2.18 (19%); P factor VII [from 1.14 IE/ml (0.58-1.38) to 1.22 IE/ml (0.96-1.46); NS], or plasma neopterin [from 8.6 nmol/l (7.1-11.5) to 8.7 nmol/l (7.9-11.3); NS]. In conclusion, during cholesterol-lowering treatment with fluvastatin, plasma levels of fibrinogen increased whereas intraplatelet cyclic nucleotide levels and plasma endothelin-1, factor VII and neopterin levels were unchanged.

49 CFR 325.73 - Microphone distance correction factors. 1

Science.gov (United States)

2010-10-01

... 49 Transportation 5 2010-10-01 2010-10-01 false Microphone distance correction factors. 1 325.73 Section 325.73 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL MOTOR... MOTOR CARRIER NOISE EMISSION STANDARDS Correction Factors § 325.73 Microphone distance correction...

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

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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

The balancing act of transcription factors C-1-1 and Runx2 in articular cartilage development

International Nuclear Information System (INIS)

Iwamoto, Masahiro; Koyama, Eiki; Enomoto-Iwamoto, Motomi; Pacifici, Maurizio

2005-01-01

In previous studies we found that the ets transcription factor C-1-1 is involved in articular chondrocyte development, and we and others found that the transcription factor Runx2 is required for growth plate chondrocyte maturation and ossification. We determined here whether the two factors exert reciprocal influences on their expression and function and in so doing, steer chondrocyte developmental paths. Virally driven Runx2 over-expression in cultured chick chondrocytes did indeed lead to decreased C-1-1 expression, accompanied by decreased expression of articular cartilage marker tenascin-C, decreased proliferation, and increased expression of maturation marker collagen X. In good agreement, over-expression of a dominant-negative Runx2 form had opposite phenotypic consequences. When C-1-1 itself was over-expressed in chondrocytes already undergoing maturation, maturation was halted and the cells became small, rich in tenascin-C, and mitotically quite active. To extend these observations, we misexpressed C-1-1 in mouse cartilage and found that it caused a severe inhibition of chondrocyte maturation and widespread tenascin-C expression. In sum, C-1-1 and Runx2 do influence their respective expression patterns. The factors are powerful chondrocyte regulators and their functional interrelationships may be important for steering the cells toward alternative developmental paths

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

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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.

Improved features of MARS 1.4 and verification

Energy Technology Data Exchange (ETDEWEB)

Lee, Won Jae; Chung, Bub Don; Jeong, Jae Jun; Ha, Kwi Seok [Korea Atomic Energy Research Institute, Taejon (Korea)

1999-09-01

MARS 1.4 code has been developed as a basic code frame for multi-dimensional thermal-hydraulic analysis of light water reactor transients. This report describes the newly improved features of MARS 1.4 and their verification results. The new features of MARS 1.4 include the implementation of point kinetics model in the 3D module, the coupled heat structure model, the extension of control functions and input check functions in the 3D module, the implementation of new features of RELAP5/MOD3.2.2 -version, the addition of automatic initialization function for fuel 3-D analysis and the unification of material properties and forcing functions, etc. These features have been implemented in the code in order to extend the code modeling capability and to enhance the user friendliness. Among these features, this report describes the implementation of new features of RELAP5/MOD3.3.3-version such as reflood model and critical heat flux models, etc., the automatic initialization function, the unification of material properties and forcing functions and the other code improvements and error corrections, which were not reported in the previous report. Through the verification calculations, the new features of MARS 1.4 have been verified well implemented in the code. In conclusion, MARS 1.4 code has been developed and verified as implemented in the code. In conclusion, MARS 1.4 code has been developed and verified as a multi-dimensional system thermal-hydraulic analysis tool. And, it can play its role as a basic code frame for the future development of a multi-purpose consolidated code, MARS 2.x, for coupled analysis of multi-dimensional system thermal hydraulics, 3D core kinetics, core CHF and containment as well as for further improvement of thermal-hydraulic and numerical models. 4 refs., 10 figs. (Author)

Factors associated with post-seasonal serological titer and risk factors for infection with the pandemic A/H1N1 virus in the French general population.

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Nathanael Lapidus

Full Text Available 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.

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.

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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

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

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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 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 elderly patients with a hip fracture compared to the historical control patients who were treated with standard care. The most important risk factors for 1-year mortality were male gender, increasing age, malnutrition, physical limitations, increasing BI, and medical conditions. Awareness of risk factors that

Mipu1, a novel direct target gene, is involved in hypoxia inducible factor 1-mediated cytoprotection.

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Kangkai Wang

Full Text Available Mipu1 (myocardial ischemic preconditioning up-regulated protein 1, recently identified in our lab, is a novel zinc-finger transcription factor which is up-regulated during ischemic preconditioning. However, it is not clear what transcription factor contributes to its inducible expression. In the present study, we reported that HIF-1 regulates the inducible expression of Mipu1 which is involved in the cytoprotection of HIF-1α against oxidative stress by inhibiting Bax expression. Our results showed that the inducible expression of Mipu1 was associated with the expression and activation of transcription factor HIF-1 as indicated by cobalt chloride (CoCl2 treatment, HIF-1α overexpression and knockdown assays. EMSA and luciferase reporter gene assays showed that HIF-1α bound to the hypoxia response element (HRE within Mipu1 promoter region and promoted its transcription. Moreover, our results revealed that Mipu1 inhibited the expression of Bax, an important pro-apoptosis protein associated with the intrinsic pathway of apoptosis, elevating the cytoprotection of HIF-1 against hydrogen peroxide (H2O2-mediated injury in H9C2 cells. Our findings implied that Bax may be a potential target gene of transcription factor Mipu1, and provided a novel insight for understanding the cytoprotection of HIF-1 and new clues for further elucidating the mechanisms by which Mipu1 protects cell against pathological stress.

Cow placenta extract promotes murine hair growth through enhancing the insulin - like growth factor-1

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Dongliang Zhang

2011-01-01

Full Text Available Background: Hair loss is seen as an irreversible process. Most research concentrates on how to elongate the anagen, reduce the negative factors of obstructing hair growth and improve the hair number and size. Aim: In our experiment, we tried to prove that the cow placenta extract can promote hair growth by elongating hair shaft and increasing hair follicle number. Materials and Methods: Cow placenta extract (CPE, water and minoxidil applied separately on the back of depilated B57CL/6 mice for the case, negative and positive control respectively. We checked the proliferation of cells which are resident in hair sheath, and the expression of a few growth factors which stimulate hair growth. Results: Result shows that placenta extract more efficiently accelerates cell division and growth factor expression, by raising the insulin-like growth factor (IGF-1 mRNA and protein level to increase HF size and hair length. Conclusions: The extract is not a purified product; so, it is less effective than minoxidil, which is approved by the US FDA for the treatment of male pattern baldness. If refinement is done, the placenta extract would be a good candidate medicine for hair loss.

Interleaved segment correction achieves higher improvement factors in using genetic algorithm to optimize light focusing through scattering media

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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.

Timing of CSF-1/CSF-1R signaling blockade is critical to improving responses to CTLA-4 based immunotherapy

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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.

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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.

Improved (0 0 1)-texture of FePt-C for heat-assisted magnetic recording media by insertion of Cr buffer layer

Energy Technology Data Exchange (ETDEWEB)

Shiroyama, T.; Wang, J.; Felicia, A.; Takahashi, Y.K.; Hono, K., E-mail: kazuhiro.hono@nims.go.jp

2017-06-15

Highlights: • Improvement of (0 0 1)-texture of prototype FePt-C granular films for heat heat assisted magnetic recording media. • Insertion of Cr buffer layer improves the crystallographic textures of the MgO underlayers, thereby reduces in-plane component in the FePt-C recording layer. • The growth in the grain size of the MgO underlayer as well as the (0 0 1)-texture of the MgO underlayer are the key factor in reducing the in-plane component in the FePt-C recording layer. - Abstract: FePt-C granular films deposited on MgO underlayers are the prototype media for heat-assisted magnetic recording. To reduce the in-plane magnetic component in the FePt-C media, we investigated the effect of Cr buffer layers on the crystallographic textures of the MgO underlayers and the resultant magnetic properties of the FePt-C layers. By growing a MgO underlayer on a Cr buffer layer, the (0 0 1) texture of the MgO underlayer is improved, on which the in-plane component of a FePt-C film is substantially reduced. We conclude that the growth in the grain size of the MgO underlayer is the key factor in reducing the in-plane component in the FePt-C recording layer.

Cryptanalysis and Security Improvements of ‘Two-Factor User Authentication in Wireless Sensor Networks’

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Muhammad Khurram Khan

2010-03-01

Full Text Available 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.

The influence of contextual factors on healthcare quality improvement initiatives: what works, for whom and in what setting? Protocol for a realist review.

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Coles, Emma; Wells, Mary; Maxwell, Margaret; Harris, Fiona M; Anderson, Julie; Gray, Nicola M; Milner, Gill; MacGillivray, Stephen

2017-08-23

Context shapes the effectiveness of knowledge implementation and influences health improvement. Successful healthcare quality improvement (QI) initiatives frequently fail to transfer to different settings, with local contextual factors often cited as the cause. Understanding and overcoming contextual barriers is therefore crucial to implementing effective improvement; yet context is still poorly understood. There is a paucity of information on the mechanisms underlying how and why QI projects succeed or fail in given settings. A realist review of empirical studies of healthcare QI initiatives will be undertaken to examine the influence and impact of contextual factors on quality improvement in healthcare settings and explore whether QI initiatives can work in all contexts. The review will explore which contextual factors are important, and how, why, when and for whom they are important, within varied settings. The dynamic nature of context and change over time will be explored by examining which aspects of context impact at key points in the improvement trajectory. The review will also consider the influence of context on improvement outcomes (provider- and patient-level), spread and sustainability. The review process will follow five iterative steps: (1) clarify scope, (2) search for evidence, (3) appraise primary studies and extract data, (4) synthesise evidence and draw conclusions and (5) disseminate findings. The reviewers will consult with experts and stakeholders in the early stages to focus the review and develop a programme theory consisting of explanatory 'context-mechanism-outcome' configurations. Searches for primary evidence will be conducted iteratively. Data will be extracted and tested against the programme theory. A review advisory group will oversee the review process. Review findings will follow RAMESES guidelines and will be disseminated via a report, presentations and peer-reviewed publications. The review will update and consolidate evidence

Factors associated with poor Hemoglobin A1c control in Patients with Type 2 Diabetes.

Science.gov (United States)

Alqudah, Salam; Jarab, Anan S; Alefishat, Eman A; Mayyas, Fadia; Khdour, Maher; Pinto, Sharrel

2018-05-10

Background The limited implementation of clinical pharmacy service programs and the lack of studies identifying barriers to achieve blood glucose control have all attributed to the increased proportion of type 2 diabetes patients who have poor glycemic control in Jordan. Objective To explore factors associated with higher HbA1c in patients with type 2 diabetes in Jordan. Method Variables including socio-demographics, disease and treatment factors were collected from171 patients with type2 diabetes at an outpatient diabetes clinic in Amman. Validated questionnaires were used to assess medication adherence, self-care activities, diabetes knowledge and health-related quality of life in addition to data collected from medical records. After the single-predictor analysis, stepwise linear regression was performed to develop a model with variables that best predicted hemoglobin A1c. Results Medication adherence was inversely associated with HbA1c values (β = -0.275; t = 2.666; P diabetes duration (β = 0.092; t = 1.339; P diabetes and those with multiple comorbid diseases should be strongly considered in future diabetes management programs implemented to improve glycemic control in patients with type 2 diabetes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Dexras1 links glucocorticoids to insulin-like growth factor-1 signaling in adipogenesis

Science.gov (United States)

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

Transforming Growth Factor β1 Could Influence Thyroid Nodule Elasticity and Also Improve Cervical Lymph Node Metastasis in Papillary Thyroid Carcinoma.

Science.gov (United States)

Li, Yi; Wang, Yan; Wu, Qiong; Hu, Bing

2015-11-01

Ultrasound elastography has been a very useful tool in predicting the risk of malignant thyroid tumor for several years. The objective of this study was to determine if there is a correlation between strain ratio (SR), collagen deposition and transforming growth factor β1 (TGF-β1) expression in different types of thyroid nodules and if TGF-β1 is related to cervical lymph node metastasis. 102 nodules from 81 patients who underwent thyroid resection surgery in our hospital were retrospectively studied. All of these patients had undergone ultrasound elastography scanning before surgery. Masson staining and immunohistochemical staining were used to evaluate the ratio of expression of collagen deposition and TGF-β1. There was a significant difference between benign and malignant thyroid nodules in SR (8.913 ± 11.021 vs. 1.732 ± 0.727, p = 0.000), collagen content (0.371 ± 0.125 vs. 0.208 ± 0.057, p = 0.000) and TGF-β1 expression (0.336 ± 0.093 vs. 0.178 ± 0.071, p = 0.000). A cutoff of 2.99 for SR measurement was selected for the highest Youden index for predicting malignant thyroid nodules, which yielded 87.88% sensitivity, 100% specificity, 100% positive predictive value, 83.72% negative predictive value and 92.15% accuracy. Expression of collagen and TGF-β1 was positively correlated with SR measurements (coefficient = 0.839 for collagen and 0.855 for TGF-β1, p = 0.000). Among 61 nodules with papillary thyroid carcinoma, the average SR for the metastasis group was higher than that for the non-metastasis group (10.955 ± 13.805 and 7.852 ± 7.931, respectively), but without statistical significance (p = 0.287). Collagen deposition was significantly higher in the metastasis group than in the non-metastasis group (0.421 ± 0.091 vs. 0.353 ± 0.118, p = 0.011). TGF-β1 expression was also significantly higher in the metastasis group than in the non-metastasis group (0.378 ± 0.0.69 vs. 0.328 ± 0.091, p = 0.016). To conclude, TGF-β1 may contribute to thyroid

Oil palm EgCBF3 conferred stress tolerance in transgenic tomato plants through modulation of the ethylene signaling pathway.

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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.

Improved crystallization and diffraction of caffeine-induced death suppressor protein 1 (Cid1)

Energy Technology Data Exchange (ETDEWEB)

Yates, Luke A., E-mail: luke@strubi.ox.ac.uk; Durrant, Benjamin P.; Barber, Michael; Harlos, Karl [University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Fleurdépine, Sophie; Norbury, Chris J. [University of Oxford, South Parks Road, Oxford OX1 3RE (United Kingdom); Gilbert, Robert J. C., E-mail: luke@strubi.ox.ac.uk [University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom)

2015-02-21

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 them 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.

Improved crystallization and diffraction of caffeine-induced death suppressor protein 1 (Cid1)

International Nuclear Information System (INIS)

Yates, Luke A.; Durrant, Benjamin P.; Barber, Michael; Harlos, Karl; Fleurdépine, Sophie; Norbury, Chris J.; Gilbert, Robert J. C.

2015-01-01

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 them 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

Overexpression of GmDREB1 improves salt tolerance in transgenic wheat and leaf protein response to high salinity

Directory of Open Access Journals (Sweden)

Qiyan Jiang

2014-04-01

Full Text Available The transcription factor dehydration-responsive element binding protein (DREB is able to improve tolerance to abiotic stress in plants by regulating the expression of downstream genes involved in environmental stress resistance. The objectives of this study were to evaluate the salt tolerance of GmDREB1 transgenic wheat (Triticum aestivum L. and to evaluate its physiological and protein responses to salt stress. Compared with the wild type, the transgenic lines overexpressing GmDREB1 showed longer coleoptiles and radicles and a greater radicle number at the germination stage, as well as greater root length, fresh weight, and tiller number per plant at the seedling stage. The yield-related traits of transgenic lines were also improved compared with the wild type, indicating enhanced salt tolerance in transgenic lines overexpressing GmDREB1. Proteomics analysis revealed that osmotic- and oxidative-stress-related proteins were up-regulated in transgenic wheat leaves under salt stress conditions. Transgenic wheat had higher levels of proline and betaine and lower levels of malondialdehyde and relative electrolyte leakage than the wild type. These results suggest that GmDREB1 regulates the expression of osmotic- and oxidative-stress-related proteins that reduce the occurrence of cell injury caused by high salinity, thus improving the salt tolerance of transgenic wheat.

Acute hyperglycemia produces transient improvement in glucose transporter type 1 deficiency.

Science.gov (United States)

Akman, Cigdem I; Engelstad, Kristin; Hinton, Veronica J; Ullner, Paivi; Koenigsberger, Dorcas; Leary, Linda; Wang, Dong; De Vivo, Darryl C

2010-01-01

Glucose transporter type 1 deficiency syndrome (Glut1-DS) is characterized clinically by acquired microcephaly, infantile-onset seizures, psychomotor retardation, choreoathetosis, dystonia, and ataxia. The laboratory signature is hypoglycorrhachia. The 5-hour oral glucose tolerance test (OGTT) was performed to assess cerebral function and systemic carbohydrate homeostasis during acute hyperglycemia, in the knowledge that GLUT1 is constitutively expressed ubiquitously and upregulated in the brain. Thirteen Glut1-DS patients completed a 5-hour OGTT. Six patients had prolonged electroencephalographic (EEG)/video monitoring, 10 patients had plasma glucose and serum insulin measurements, and 5 patients had repeated measures of attention, memory, fine motor coordination, and well-being. All patients had a full neuropsychological battery prior to OGTT. The glycemic profile and insulin response during the OGTT were normal. Following the glucose load, transient improvement of clinical seizures and EEG findings were observed, with the most significant improvement beginning within the first 30 minutes and continuing for 180 minutes. Thereafter, clinical seizures returned, and EEG findings worsened. Additionally, transient improvement in attention, fine motor coordination, and reported well-being were observed without any change in memory performance. This study documents transient neurological improvement in Glut1-DS patients following acute hyperglycemia, associated with improved fine motor coordination and attention. Also, systemic carbohydrate homeostasis was normal, despite GLUT1 haploinsufficiency, confirming the specific role of GLUT1 as the transporter of metabolic fuel across the blood-brain barrier. The transient improvement in brain function underscores the rate-limiting role of glucose transport and the critical minute-to-minute dependence of cerebral function on fuel availability for energy metabolism.

Some strategies to improve performance in school chemistry, based on two cognitive factors

Science.gov (United States)

Danili, Eleni; Reid, Norman

2004-02-01

The background to this study are the difficulties facing the majority of Greek pupils in understanding chemistry concepts and, therefore, performing well in the National Examinations. The aim was to explore the problems and to suggest ways in which the situation might be improved. Working with 105 Greek pupils aged 15 to 16, the first stage of the enquiry confirmed that both working memory space and extent of field dependency were two psychological factors affecting performance. This is at least part of the nature of the problem. In the second stage, an attempt was made to explore how the problems might be reduced. New teaching materials were constructed to minimize any limitations to learning caused by working memory space and problems associated with being field dependent. The use of the new materials was compared to the normal teaching process working with 210 Greek pupils aged 15 to16. It was found that there was a significant difference in the average improvement of the experimental group and the control group, in favour of the experimental group. This result was independent of the effect of the teacher, and of the interaction of teaching method and teacher. It is suggested that approaches to learning must take into account cognitive factors in the learners in the context of information processing understandings of learning. If this is done, learning is much more effective.

CMAQv5.1 with new dust IMPROVE site compare files

Data.gov (United States)

U.S. Environmental Protection Agency — CMAQv5.1 with a new dust module IMPROVE sitex files containing 24-hr (every 3rd day) paired model/ob data for the IMPROVE network. This dataset is associated with...

The metal-responsive transcription factor-1 contributes to HIF-1 activation during hypoxic stress

International Nuclear Information System (INIS)

Murphy, Brian J.; Sato, Barbara G.; Dalton, Timothy P.; Laderoute, Keith R.

2005-01-01

Hypoxia-inducible factor-1 (HIF-1), the major transcriptional regulator of the mammalian cellular response to low oxygen (hypoxia), is embedded within a complex network of signaling pathways. We have been investigating the importance of another stress-responsive transcription factor, MTF-1, for the adaptation of cells to hypoxia. This article reports that MTF-1 plays a central role in hypoxic cells by contributing to HIF-1 activity. Loss of MTF-1 in transformed Mtf1 null mouse embryonic fibroblasts (MEFs) results in an attenuation of nuclear HIF-1α protein accumulation, HIF-1 transcriptional activity, and expression of an established HIF-1 target gene, glucose transporter-1 (Glut1). Mtf1 null (Mtf1 KO) MEFs also have constitutively higher levels of both glutathione (GSH) and the rate-limiting enzyme involved in GSH synthesis-glutamate cysteine ligase catalytic subunit-than wild type cells. The altered cellular redox state arising from increased GSH may perturb oxygen-sensing mechanisms in hypoxic Mtf1 KO cells and decrease the accumulation of HIF-1α protein. Together, these novel findings define a role for MTF-1 in the regulation of HIF-1 activity

Evaluation of vitrification factors from DWPF's macro-batch 1

International Nuclear Information System (INIS)

Edwards, T.B.

2000-01-01

The Defense Waste Processing Facility (DWPF) is evaluating new sampling and analytical methods that may be used to support future Slurry Mix Evaporator (SME) batch acceptability decisions. This report uses data acquired during DWPF's processing of macro-batch 1 to determine a set of vitrification factors covering several SME and Melter Feed Tank (MFT) batches. Such values are needed for converting the cation measurements derived from the new methods to a ''glass'' basis. The available data from macro-batch 1 were used to examine the stability of these vitrification factors, to estimate their uncertainty over the course of a macro-batch, and to provide a recommendation on the use of a single factor for an entire macro-batch. The report is in response to Technical Task Request HLW/DWPF/TTR-980015

Inhibitors of nuclease and redox activity of apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1).

Science.gov (United States)

Laev, Sergey S; Salakhutdinov, Nariman F; Lavrik, Olga I

2017-05-01

Human apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1) is a multifunctional protein which is essential in the base excision repair (BER) pathway of DNA lesions caused by oxidation and alkylation. This protein hydrolyzes DNA adjacent to the 5'-end of an apurinic/apyrimidinic (AP) site to produce a nick with a 3'-hydroxyl group and a 5'-deoxyribose phosphate moiety or activates the DNA-binding activity of certain transcription factors through its redox function. Studies have indicated a role for APE1/Ref-1 in the pathogenesis of cancer and in resistance to DNA-interactive drugs. Thus, this protein has potential as a target in cancer treatment. As a result, major efforts have been directed to identify small molecule inhibitors against APE1/Ref-1 activities. These agents have the potential to become anticancer drugs. The aim of this review is to present recent progress in studies of all published small molecule APE1/Ref-1 inhibitors. The structures and activities of APE1/Ref-1 inhibitors, that target both DNA repair and redox activities, are presented and discussed. To date, there is an urgent need for further development of the design and synthesis of APE1/Ref-1 inhibitors due to high importance of this protein target. Copyright © 2017 Elsevier Ltd. All rights reserved.

Muscle-derived expression of the chemokine CXCL1 attenuates diet-induced obesity and improves fatty acid oxidation in the muscle

DEFF Research Database (Denmark)

Pedersen, Line; Holkmann Olsen, Caroline; Pedersen, Bente Klarlund

2012-01-01

Serum levels and muscle expression of the chemokine CXCL1 increase markedly in response to exercise in mice. Because several studies have established muscle-derived factors as important contributors of metabolic effects of exercise, this study aimed at investigating the effect of increased expres...... in muscle angiogenesis. In conclusion, our data show that overexpression of CXCL1 within a physiological range attenuates diet-induced obesity, likely mediated through a CXCL1-induced improvement of fatty acid oxidation and oxidative capacity in skeletal muscle tissue....

Quantifying surgical complexity with machine learning: looking beyond patient factors to improve surgical models.

Science.gov (United States)

Van Esbroeck, Alexander; Rubinfeld, Ilan; Hall, Bruce; Syed, Zeeshan

2014-11-01

To investigate the use of machine learning to empirically determine the risk of individual surgical procedures and to improve surgical models with this information. American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) data from 2005 to 2009 were used to train support vector machine (SVM) classifiers to learn the relationship between textual constructs in current procedural terminology (CPT) descriptions and mortality, morbidity, Clavien 4 complications, and surgical-site infections (SSI) within 30 days of surgery. The procedural risk scores produced by the SVM classifiers were validated on data from 2010 in univariate and multivariate analyses. The procedural risk scores produced by the SVM classifiers achieved moderate-to-high levels of discrimination in univariate analyses (area under receiver operating characteristic curve: 0.871 for mortality, 0.789 for morbidity, 0.791 for SSI, 0.845 for Clavien 4 complications). Addition of these scores also substantially improved multivariate models comprising patient factors and previously proposed correlates of procedural risk (net reclassification improvement and integrated discrimination improvement: 0.54 and 0.001 for mortality, 0.46 and 0.011 for morbidity, 0.68 and 0.022 for SSI, 0.44 and 0.001 for Clavien 4 complications; P risk for individual procedures. This information can be measured in an entirely data-driven manner and substantially improves multifactorial models to predict postoperative complications. Copyright © 2014 Elsevier Inc. All rights reserved.

Growth factors FGF8 and FGF2 and their receptor FGFR1, transcriptional factors Msx-1 and MSX-2, and apoptotic factors p19 and RIP5 participate in the early human limb development.

Science.gov (United States)

Becic, Tina; Kero, Darko; Vukojevic, Katarina; Mardesic, Snjezana; Saraga-Babic, Mirna

2018-04-01

The expression pattern of fibroblast growth factors FGF8 and FGF2 and their receptor FGFR1, transcription factors MSX-1 and MSX-2, as well as cell proliferation (Ki-67) and cell death associated caspase-3, p19 and RIP5 factors were analyzed in histological sections of eight 4th-9th-weeks developing human limbs by immunohistochemistry and semi-thin sectioning. Increasing expression of all analyzed factors (except FGF8) characterized both the multilayered human apical ectodermal ridge (AER), sub-ridge mesenchyme (progress zone) and chondrocytes in developing human limbs. While cytoplasmic co-expression of MSX-1 and MSX-2 was observed in both limb epithelium and mesenchyme, p19 displayed strong cytoplasmic expression in non-proliferating cells. Nuclear expression of Ki-67 proliferating cells, and partly of MSX-1 and MSX-2 was detected in the whole limb primordium. Strong expression of factors p19 and RIP5, both in the AER and mesenchyme of human developing limbs indicates their possible involvement in control of cell senescence and cell death. In contrast to animal studies, expression of FGFR1 in the surface ectoderm and p19 in the whole limb primordium might reflect interspecies differences in limb morphology. Expression of FGF2 and downstream RIP5 gene, and transcription factors Msx-1 and MSX-2 did not show human-specific changes in expression pattern. Based on their spatio-temporal expression during human limb development, our study indicates role of FGFs and Msx genes in stimulation of cell proliferation, limb outgrowth, digit elongation and separation, and additionally MSX-2 in control of vasculogenesis. The cascade of orchestrated gene expressions, including the analyzed developmental factors, jointly contribute to the complex human limb development. Copyright © 2018 Elsevier GmbH. All rights reserved.

Stability and the improved methods of "1"8F-FDG

International Nuclear Information System (INIS)

Zhang Jinming; Li Yungang; Liu Jian; Zhang Xiaojun; Tian Jiahe

2011-01-01

To study the stability of "1"8F-FDG with routinely synthesis at high radio-dose and high radioconcentration, "1"8F-FDG was added 0.1% ethanol or repurification by solid-phase extract ion for radiolytic "1"8F-FDG to improve its radiochemical purity (RCP). The results showed that the RCP declined from 99% to 95% within 4 h at 6 TBq/L for room temperature (RT). The radiolysis could be depressed with 0.1% ethanol, the RCP could be over 95% even if the radioactivity concentration was 7.4 TBq/L at RT for 6 h. The repurification method could improve the RCP of "1"8F-FDG from 80% to 99%. Micro PET/ CT imagings of normal rats showed that the vertebra had high uptake with radiolytic "1"8F-FDG because of impurity. There were no radioactivity uptaking in bone with repuification of "1"8F- FDG. It indicated that 0.1% ethanol could be used as stabilizers for "1"8F-FDG to improve the RCP when "1"8F-FDG had high radio-do se and high radioconcentrtion. The radiolytic 18 F-FDG could be repurified by so lid-phase extraction to remove the radio-impurity. The method of added 0.1% thanot could be combined with repurification method to assure the RCP of "1"8F-FDG for over 95% at any given time andradiodose or contcentrayion. (authors)

Education to a Healthy Lifestyle Improves Symptoms and Cardiovascular Risk Factors – AsuRiesgo Study

Directory of Open Access Journals (Sweden)

Graciela Chaves

2015-05-01

Full Text Available Background: Cardiovascular diseases are the current leading causes of death and disability globally. Objective: To assess the effects of a basic educational program for cardiovascular prevention in an unselected outpatient population. Methods: All participants received an educational program to change to a healthy lifestyle. Assessments were conducted at study enrollment and during follow-up. Symptoms, habits, ATP III parameters for metabolic syndrome, and American Heart Association’s 2020 parameters of cardiovascular health were assessed. Results: A total of 15,073 participants aged ≥ 18 years entered the study. Data analysis was conducted in 3,009 patients who completed a second assessment. An improvement in weight (from 76.6 ± 15.3 to 76.4 ± 15.3 kg, p = 0.002, dyspnea on exertion NYHA grade II (from 23.4% to 21.0% and grade III (from 15.8% to 14.0% and a decrease in the proportion of current active smokers (from 3.6% to 2.9%, p = 0.002 could be documented. The proportion of patients with levels of triglycerides > 150 mg/dL (from 46.3% to 42.4%, p 100 mg/dL (from 69.3% to 65.5%, p < 0.001 improved. A ≥ 20% improvement of AHA 2020 metrics at the level graded as poor was found for smoking (-21.1%, diet (-29.8%, and cholesterol level (-23.6%. A large dropout as a surrogate indicator for low patient adherence was documented throughout the first 5 visits, 80% between the first and second assessments, 55.6% between the second and third assessments, 43.6% between the third and fourth assessments, and 38% between the fourth and fifth assessments. Conclusion: A simple, basic educational program may improve symptoms and modifiable cardiovascular risk factors, but shows low patient adherence.

Human cellular restriction factors that target HIV-1 replication

Directory of Open Access Journals (Sweden)

Jeang Kuan-Teh

2009-09-01

Full Text Available Abstract Recent findings have highlighted roles played by innate cellular factors in restricting intracellular viral replication. In this review, we discuss in brief the activities of apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G, bone marrow stromal cell antigen 2 (BST-2, cyclophilin A, tripartite motif protein 5 alpha (Trim5α, and cellular microRNAs as examples of host restriction factors that target HIV-1. We point to countermeasures encoded by HIV-1 for moderating the potency of these cellular restriction functions.

Sodium sulfite pH-buffering effect for improved xylose-phenylalanine conversion to N-(1-deoxy-d-xylulos-1-yl)-phenylalanine during an aqueous Maillard reaction.

Science.gov (United States)

Cui, Heping; Duhoranimana, Emmanuel; Karangwa, Eric; Jia, Chengsheng; Zhang, Xiaoming

2018-04-25

The yield of the Maillard reaction intermediate (MRI), prepared in aqueous medium, is usually unsatisfactory. However, the addition of sodium sulfite could improve the conversion of xylose-phenylalanine (Xyl-Phe) to the MRI (N-(1-deoxy-d-xylulos-1-yl)-phenylalanine) in aqueous medium. Sodium sulfite (Na 2 SO 3 ) showed a significant pH-buffering effect during the Maillard reaction, which accounted for its facilitation of the N-(1-deoxy-d-xylulos-1-yl)-phenylalanine yield. The results revealed that the pH could be maintained at a relatively high level (above 7.0) for an optimized pH-buffering effect when Na 2 SO 3 (4.0%) was added before the reaction of Xyl-Phe. Thus, the conversion of Xyl-Phe to N-(1-deoxy-d-xylulos-1-yl)-phenylalanine increased from 47.23% to 74.86%. Furthermore, the addition moment of Na 2 SO 3 and corresponding solution pH were crucial factors in regulating the pH-buffering effect of Na 2 SO 3 on N-(1-deoxy-d-xylulos-1-yl)-phenylalanine yield. Based on the pH-buffering effect of Na 2 SO 3 and maintaining the optimal pH 7.4 relatively stable, the conversion of Xyl-Phe to N-(1-deoxy-d-xylulos-1-yl)-phenylalanine was successfully improved. Copyright © 2017 Elsevier Ltd. All rights reserved.

Epidermal growth factor receptor inhibition reduces angiogenesis via hypoxia-inducible factor-1α and Notch1 in head neck squamous cell carcinoma.

Directory of Open Access Journals (Sweden)

Wei-Ming Wang

Full Text Available Angiogenesis, a marker of cancer development, affects response to radiotherapy sensibility. This preclinical study aims to understand the receptor tyrosine kinase-mediated angiogenesis in head neck squamous cell carcinoma (HNSCC. The receptor tyrosine kinase activity in a transgenic mouse model of HNSCC was assessed. The anti-tumorigenetic and anti-angiogenetic effects of cetuximab-induced epidermal growth factor receptor (EGFR inhibition were investigated in xenograft and transgenic mouse models of HNSCC. The signaling transduction of Notch1 and hypoxia-inducible factor-1α (HIF-1α was also analyzed. EGFR was overexpressed and activated in the Tgfbr1/Pten deletion (2cKO mouse model of HNSCC. Cetuximab significantly delayed tumor onset by reducing tumor angiogenesis. This drug exerted similar effects on heterotopic xenograft tumors. In the human HNSCC tissue array, increased EGFR expression correlated with increased HIF-1α and micro vessel density. Cetuximab inhibited tumor-induced angiogenesis in vitro and in vivo by significantly downregulating HIF-1α and Notch1. EGFR is involved in the tumor angiogenesis of HNSCC via the HIF-1α and Notch1 pathways. Therefore, targeting EGFR by suppressing hypoxia- and Notch-induced angiogenesis may benefit HNSCC therapy.

fibroblast growth factor, MTDH/Astrocyte elevated gene-1

African Journals Online (AJOL)

2012-12-05

Dec 5, 2012 ... Expression of basic FGF, MTDH/AEG-1, APC, matrix metalloproteinase 9, and COX-2 markers in prostate carcinomas many genetic and epigenetic alterations have been detected in human PC.[1]. Basic fibroblast growth factor (bFGF), also known as. FGF2 is a member of the FGF family, a group of more.

Collaborative Improvement

DEFF Research Database (Denmark)

Kaltoft, Rasmus

-organisational continuous improvement of their performance, relative to that of other EMEs. Developing a collaborative improvement relationship between companies is a protracted and complex process and, according to some surveys, the failure rate is as low as one to three. This failure rate is affected by a whole range...... of factors. The research presented in this thesis was aimed at identifying these factors and investigating their interplay and influence on the progress and success of the development of the collaborative improvement. This thesis presents our findings regarding the factors found, their interplay...

Directions of improvement of account of factoring operations

Directory of Open Access Journals (Sweden)

V.I. Kuz

2015-06-01

Full Text Available With the height of competition on commodity markets the suppliers of commodities and services for bringing in of new and maintenance of present clients are forced to give certain privileges to them, including postponement or arranging on the installment system of payment. In these terms one of perspective instruments of financing of enterprises of the real sector is factoring. Factoring plays an important role in a market economy. He provides to the enterprises and organizations of height of volume of turnover means and acceleration of circulating of capital; assists more rapid redemption a debtor and creditor debts and as a result, height of rates of production and circulating of commodities, works or services; assists expansion of production. How a process of development of factoring operations is intensive enough, a necessity grows for the detailed consideration of methodology of record-keeping of factoring operations. Methodology of record-keeping of factoring operations offered in the article for a supplier, at a factor and debtor, on the basis of operating card of accounts can be used in practice of commercial organizations-participants of agreement of factoring.

Risk factors for death from pandemic (H1N1) 2009, southern Brazil.

Science.gov (United States)

Yokota, Renata T C; Skalinski, Lacita M; Igansi, Cristine N; de Souza, Libia R O; Iser, Betine P M; Reis, Priscilleyne O; Barros, Eliana N C; Macário, Eduardo M; Bercini, Marilina A; Ranieri, Tani M S; Araújo, Wildo N

2011-08-01

To identify risk factors for death from pandemic (H1N1) 2009, we obtained data for 157 hospitalized patients with confirmed cases of this disease. Multivariate analysis showed that diabetes and class III obesity were associated with death. These findings helped define priority vaccination groups in Brazil.

Critical roles of mucin-1 in sensitivity of lung cancer cells to tumor necrosis factor-alpha and dexamethasone.

Science.gov (United States)

Xu, Menglin; Wang, Xiangdong

2017-08-01

Lung cancer is the leading cause of death from cancer. Mucins are glycoproteins with high molecular weight, responsible for cell growth, differentiation, and signaling, and were proposed to be correlated with gene heterogeneity of lung cancer. Here, we report aberrant expression of mucin genes and tumor necrosis factor receptors in lung adenocarcinoma tissues compared with normal tissues in GEO datasets. Mucin-1 (MUC1) gene was selected and considered as the target gene; furthermore, the expression pattern of adenocarcinomic cells (A549, H1650, or H1299 cells) was validated under the stimulation with tumor necrosis factor-alpha (TNFα) or dexamethasone (DEX), separately. MUC1 gene interference was done to A549 cells to show its role in sensitivity of lung cancer cells to TNFα and DEX. Results of our experiments indicate that MUC1 may regulate the influence of inflammatory mediators in effects of glucocorticoids (GCs), as a regulatory target to improve therapeutics. It shows the potential effect of MUC1 and GCs in lung adenocarcinoma (LADC), which may help in LADC treatment in the future.

Perinatal factors and type 1 diabetes-associated dysbiosis in Mexican infants.

Science.gov (United States)

Mejía-León, María Esther; Calderón de la Barca, Ana María

Type 1 diabetes (T1D) is currently an autoimmune disease occurring more frequently and early in life. T1D development requires genetic predisposition and environmental factors, which influence the gut microbiota in early infancy and could increase the risk for T1D-associated autoimmunity. In Mexico there are no published microbiota studies in children <6 years old with T1D. We report two contrasting Mexican T1D cases of children <6 years of age and a third case of a healthy child prior to autoimmunity and T1D onset. Perinatal factors, feeding regimes in the first year of life and gut microbiota composition are discussed and related to the T1D onset. The three cases show a particular microbiota profile with decreased bacterial diversity as compared with healthy children, which could be related to environmental factors prior to the development of T1D and disease control. T1D infant cases presented a decreased bacterial diversity, which appeared before autoimmunity and T1D onset. Glycemic control could tend to correct the gut dysbiosis in T1D children. Prospective studies are needed to follow-up healthy children at high genetic risk to assess factors related to the microbiota structure. Copyright © 2015 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Improving the bioavailability and anticancer effect of the PCA-1/ALKBH3 inhibitor HUHS015 using sodium salt.

Science.gov (United States)

Mabuchi, Miyuki; Shimizu, Tadashi; Ueda, Masahiro; Sasakawa, Yuka; Nakao, Syuhei; Ueda, Yuko; Kawamura, Akio; Tsujikawa, Kazutake; Tanaka, Akito

2015-01-01

Prostate cancer antigen (PCA)-1/AlkB homologue 3 (ALKBH3) has been identified as a clinically significant factor and siRNA of PCA-1 inhibits DU145 proliferation both in vitro and in vivo. HUHS015 ( 1: ), a previous reported PCA-1 small-molecule inhibitor, was also effective without any obvious side-effects or toxicity. The potency of HUHS015, however, is not satisfying. We thought the reason is poor solubility of HUHS015 because insoluble material remained at the injection site after subcutaneous administration. To improve this inhibitor's solubility, we prepared various salts of HUHS015 and examined their solubility, which resulted in the selection of HUHS015 sodium salt ( 2: ) for further studies in vivo. Next, we compared the pharmacokinetics of 1: and 2: via several administration routes. We observed significant improvements in the pharmacokinetic parameters. For example, subcutaneous administration of 2: increased the area under the curve (AUC)0-24 by 8-fold compared to 1 and increased the suppressive effect on the proliferation of DU145 cells in a xenograft model. Copyright © 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

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

Science.gov (United States)

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

Background 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. Objective 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. Design 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. Results 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). Conclusions More

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

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Tran Thi Tuyet-Hanh

2016-02-01

Full Text Available Background: 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. Objective: 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. Design: 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. Results: 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

Factores predictivos de la microalbuminuria en pacientes pediátricos con diabetes mellitus tipo 1 (DMt1

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Paola Marianella Pinto Ibárcena

2012-10-01

Full Text Available La nefropatía constituye la complicación más grave de la diabetes mellitus tipo 1 (DMt1 siendo una de las manifestaciones iniciales la microalbuminuria. Objetivos: Determinar el comportamiento de los factores epidemiológicos, clínicos y bioquímicos en el desarrollo de microalbuminuria en pacientes con DMt1. Diseño: Estudio de casos y controles. Lugar: Servicio de Endocrinología del Instituto Nacional de Salud del Niño, Lima, Perú. Participantes: Pacientes diabéticos tipo 1 menores de 18 años. Intervenciones: Se estudió 64 pacientes portadores de DMt1, 22 con microalbuminuria y 42 sin esta manifestación, que constituyeron los casos y controles respectivamente. Se consignó como factores epidemiológicos la edad al diagnóstico, tiempo de evolución, género, antecedentes familiares de diabetes, nefropatía, dislipidemia, hipertensión arterial; como factores clínicos, el estado nutricional, desarrollo puberal (Tanner, presión arterial; y como factores bioquímicos, la hemoglobina glicosilada (HbA1c, microalbuminuria y perfil lipídico. Tanto los casos como los controles fueron seguidos durante un año. El análisis estadístico se hizo mediante pruebas de chi cuadrado, odds ratio y regresión logística, para establecer predominancia de factores. Principales medidas de resultados: Estadio puberal, perfil lipídico y HbA1c. Resultados: Los factores de riesgo hallados fueron la presión arterial diastólica elevada (p=0,037, la pubertad (p=0,008, HbA1c alta (p< 0,0001, hipertrigliceridemia (p= 0,007 y la hipercolesterolemia (p< 0,0001. Conclusiones: La HbA1c elevada, la hipercolesterolemia y la pubertad fueron los factores de riesgo de mayor preponderancia para el desarrollo de microalbuminuria. A fin de prevenir el desarrollo de microalbuminuria, se sugiere buen control metabólico y cuidadoso manejo de la dislipidemia, en especial en pacientes púberes.

Comparative analysis of the ternary complex factors Elk-1, SAP-1a and SAP-2 (ERP/NET).

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Price, M A; Rogers, A E; Treisman, R

1995-06-01

A transcription factor ternary complex composed of Serum Response Factor (SRF) and Ternary Complex Factor (TCF) mediates the response of the c-fos Serum Response Element (SRE) to growth factors and mitogens. Three Ets domain proteins, Elk-1, SAP-1 and ERP/NET, have been reported to have the properties of TCF. Here we compare Elk-1 and SAP-1a with the human ERP/NET homologue SAP-2. All three TCF RNAs are ubiquitously expressed at similar relative levels. All three proteins contain conserved regions that interact with SRF and the c-fos SRE with comparable efficiency, but in vitro complex formation by SAP-2 is strongly inhibited by its C-terminal sequences. Similarly, only Elk-1 and SAP-1a efficiently bind the c-fos SRE in vivo; ternary complex formation by SAP-2 is weak and is substantially unaffected by serum stimulation or v-ras co-expression. All three TCFs contain C-terminal transcriptional activation domains that are phosphorylated following growth factor stimulation. Activation requires conserved S/T-P motifs found in all the TCF family members. Each TCF activation domain can be phosphorylated in vitro by partially purified ERK2, and ERK activation in vivo is sufficient to potentiate transcriptional activation.

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

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Paritosh K Biswas

Full Text Available 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.

Locally expressed IGF1 propeptide improves mouse heart function in induced dilated cardiomyopathy by blocking myocardial fibrosis and SRF-dependent CTGF induction

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Melissa Touvron

2012-07-01

Cardiac fibrosis is critically involved in the adverse remodeling accompanying dilated cardiomyopathies (DCMs, which leads to cardiac dysfunction and heart failure (HF. Connective tissue growth factor (CTGF, a profibrotic cytokine, plays a key role in this deleterious process. Some beneficial effects of IGF1 on cardiomyopathy have been described, but its potential role in improving DCM is less well characterized. We investigated the consequences of expressing a cardiac-specific transgene encoding locally acting IGF1 propeptide (muscle-produced IGF1; mIGF1 on disease progression in a mouse model of DCM [cardiac-specific and inducible serum response factor (SRF gene disruption] that mimics some forms of human DCM. Cardiac-specific mIGF1 expression substantially extended the lifespan of SRF mutant mice, markedly improved cardiac functions, and delayed both DCM and HF. These protective effects were accompanied by an overall improvement in cardiomyocyte architecture and a massive reduction of myocardial fibrosis with a concomitant amelioration of inflammation. At least some of the beneficial effects of mIGF1 transgene expression were due to mIGF1 counteracting the strong increase in CTGF expression within cardiomyocytes caused by SRF deficiency, resulting in the blockade of fibroblast proliferation and related myocardial fibrosis. These findings demonstrate that SRF plays a key role in the modulation of cardiac fibrosis through repression of cardiomyocyte CTGF expression in a paracrine fashion. They also explain how impaired SRF function observed in human HF promotes fibrosis and adverse cardiac remodeling. Locally acting mIGF1 efficiently protects the myocardium from these adverse processes, and might thus represent a therapeutic avenue to counter DCM.

Lifelong exercise and locally produced insulin-like growth factor-1 (IGF-1) have a modest influence on reducing age-related muscle wasting in mice.

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McMahon, C D; Chai, R; Radley-Crabb, H G; Watson, T; Matthews, K G; Sheard, P W; Soffe, Z; Grounds, M D; Shavlakadze, T

2014-12-01

The age-related loss of skeletal muscle mass and function is termed sarcopenia and has been attributed to a decline in concentrations of insulin-like growth factor-1 (IGF-1). We hypothesized that constitutively expressed IGF-1 within skeletal muscles with or without exercise would prevent sarcopenia. Male transgenic mice that overexpress IGF-1 Ea in skeletal muscles were compared with wild-type littermates. Four-month-old mice were assigned to be sedentary, or had access to free-running wheels, until 18 or 28 months of age. In wild-type mice, the mass of the quadriceps muscles was reduced at 28 months and exercise prevented such loss, without affecting the diameter of myofibers. Conversely, increased IGF-1 alone was ineffective, whereas the combination of exercise and IGF-1 was additive in maintaining the diameter of myofibers in the quadriceps muscles. For other muscles, the combination of IGF-1 and exercise was variable and either increased or decreased the mass at 18 months of age, but was ineffective thereafter. Despite an increase in the diameter of myofibers, grip strength was not improved. In conclusion, our data show that exercise and IGF-1 have a modest effect on reducing aged-related wasting of skeletal muscle, but that there is no improvement in muscle function when assessed by grip strength. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Does strabismus surgery improve quality and mood, and what factors influence this?

Science.gov (United States)

McBain, H B; MacKenzie, K A; Hancox, J; Ezra, D G; Adams, G G W; Newman, S P

2016-05-01

AimsTo establish the impact of adult strabismus surgery on clinical and psychosocial well-being and determine who experiences the greatest benefit from surgery and how one could intervene to improve quality of life post-surgery.MethodsA longitudinal study, with measurements taken pre-surgery and at 3 and 6 months post-surgery. All participants completed the AS-20 a disease specific quality of life scale, along with measures of mood, strabismus and appearance-related beliefs and cognitions and perceived social support. Participants also underwent a full orthoptic assessment at their preoperative visit and again 3 months postoperatively. Clinical outcomes of surgery were classified as success, partial success or failure, using the largest angle of deviation, diplopia and requirement for further therapy.Results210 participants took part in the study. Strabismus surgery led to statistically significant improvements in psychosocial and functional quality of life. Those whose surgery was deemed a partial success did however experience a deterioration in quality of life. A combination of clinical variables, high expectations, and negative beliefs about the illness and appearance pre-surgery were significant predictors of change in quality of life from pre- to post-surgery.ConclusionsStrabismus surgery leads to significant improvements in quality of life up to 6 months postoperatively. There are however a group of patients who do not experience these benefits. A series of clinical and psychosocial factors have now been identified, which will enable clinicians to identify patients who may be vulnerable to poorer outcomes post-surgery and allow for the development of interventions to improve quality of life after surgery.

Plasma rich in growth factors (PRGF-Endoret) reduces neuropathologic hallmarks and improves cognitive functions in an Alzheimer's disease mouse model.

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Anitua, Eduardo; Pascual, Consuelo; Antequera, Desiree; Bolos, Marta; Padilla, Sabino; Orive, Gorka; Carro, Eva

2014-07-01

Impaired growth factor function is thought to drive many of the alterations observed in Alzheimer's disease (AD) patients. Endogenous regenerative technology, PRGF (plasma rich in growth factor)-Endoret, is designed for the delivery of a complex pool of patient's own active morphogens that may stimulate tissue regeneration. We obtained and characterized PRGF-Endoret preparations from human blood. We used, as experimental approach in vivo, APP/PS1 mice, characterized by age-dependent brain amyloid-β (Aβ) accumulation. Intranasal administration of PRGF-Endoret to APP/PS1 mice resulted in an important decrease in brain Aβ deposition and tau phosphorylation. PRGF-Endoret-treated APP/PS1 mice also showed decreased astrocyte reactivity, and prevented protein synaptic loss. In vitro approaches demonstrated that PRGF-Endoret treatment modulated astrocyte activation, reducing inflammatory responses, and promoted Aβ degradation. Furthermore, PRGF-Endoret stimulated global improvements in anxiety, learning, and memory behaviors. Our findings show that PRGF-Endoret exerts multifunctional and complementary effects that result in the reversal of the broad range of cognitive deficits in AD, suggesting that PRGF-Endoret may hold promise as an innovative therapy in AD. Copyright © 2014 Elsevier Inc. All rights reserved.

Canagliflozin improves risk factors of metabolic syndrome in patients with type 2 diabetes mellitus and metabolic syndrome

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Davies MJ

2017-01-01

Full Text Available Michael J Davies,1 Katherine W Merton,1 Ujjwala Vijapurkar,2 Dainius A Balis,2 Mehul Desai2 1Janssen Scientific Affairs, LLC, Titusville, NJ, USA; 2Janssen Research & Development, LLC, Raritan, NJ, USA Objective: Metabolic syndrome refers to a collection of risk factors associated with the development of cardiovascular disease and type 2 diabetes mellitus (T2DM. Canagliflozin, a sodium glucose co-transporter 2 inhibitor, improves glycemic control and reduces body weight and blood pressure (BP in a broad range of patients with T2DM. This post hoc analysis assessed the effects of canagliflozin on the components of metabolic syndrome in patients with T2DM and metabolic syndrome.Methods: This analysis was based on data from 2 head-to-head studies of canagliflozin in patients with T2DM on background metformin versus glimepiride (study 1 and background metformin plus sulfonylurea versus sitagliptin 100 mg (study 2. Changes from baseline in glycemic efficacy, anthropometric measures, BP, and lipids were evaluated with canagliflozin versus glimepiride and sitagliptin at week 52 in patients who met ≥2 of the criteria for metabolic syndrome (in addition to T2DM: triglycerides ≥1.7 mmol/L; high-density lipoprotein cholesterol (HDL-C <1.0 mmol/L (men or <1.3 mmol/L (women; waist circumference ≥102 cm (non-Asian men, ≥88 cm (non-Asian women, >90 cm (Asian men, or >80 cm (Asian women; diagnosis of hypertension or meeting BP-related criteria (systolic BP ≥130 mmHg or diastolic BP ≥85 mmHg. Safety was assessed based on adverse event reports.Results: In study 1, canagliflozin 100 and 300 mg provided similar and greater HbA1c reductions versus glimepiride, respectively. In study 2, canagliflozin 300 mg provided greater HbA1c lowering versus sitagliptin 100 mg. Canagliflozin also reduced fasting plasma glucose, body weight, body mass index, waist circumference, BP, and triglycerides, and increased HDL-C and low-density lipoprotein cholesterol versus

Enabling factors for the improvement of nitride-based LED efficiency

International Nuclear Information System (INIS)

Laubsch, Ansgar; Bergbauer, Werner; Sabathil, Matthias; Peter, Matthias; Meyer, Tobias; Bruederl, Georg; Linder, Norbert; Streubel, Klaus; Oberschmid, Raimund; Hahn, Berthold; Wagner, Joachim

2008-01-01

Recent progress in the epitaxial growth of LEDs with InGaN/GaN quantum-well heterostructures has led to a significant enhancement of output power. In this talk, we will discuss the mechanisms limiting the devices' internal efficiency and identify enabling factors for further improvements. We compare samples with different Indium content as well as different design of the active layer. Although heteroepitaxial growth of GaN on sapphire generates high defect densities, non-radiative defect-related Shockley-Read-Hall recombination does not seem to substantially limit the efficiency of standard InGaN/GaN LED structures. We rather discuss a supplemental Auger-like non-radiative path for carrier recombination that becomes dominant at quantum-well carrier densities typical for LED operation. Additionally, the piezo-field induced reduced overlap of electron and hole wavefunction in standard c-plane grown InGaN quantum wells reduces the radiative recombination rate

Combined blockade of vascular endothelial growth factor and programmed death 1 pathways in advanced kidney cancer.

Science.gov (United States)

Einstein, David J; McDermott, David F

2017-06-01

Targeted and immune-based therapies have improved outcomes in advanced kidney cancer, yet novel strategies are needed to extend the duration of these benefits and expand them to more patients. Combined inhibition of vascular endothelial growth factor (VEGF) and the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathways with therapeutic agents already in clinical use may offer such a strategy. Here, we describe the development and clinical evaluation of VEGF inhibitors and, separately, PD-1/PD-L1 inhibitors. We present preclinical evidence of interaction between these pathways and the rationale for combined blockade. Beyond well-known effects on pathologic angiogenesis, VEGF blockade also may decrease immune tolerance and enhance PD-1/PD-L1 blockade. We conclude with the results of several early trials of combined VEGF and PD-1/PD-L1 blockade, which demonstrate encouraging antitumor activity, and we pose questions for future study.

Reduction in cardiovascular risk factors and insulin dose, but no beta-cell regeneration 1 year after Roux-en-Y gastric bypass in an obese patient with type 1 diabetes

DEFF Research Database (Denmark)

Dirksen, Carsten; Jacobsen, Siv H; Bojsen-Møller, Kirstine N

2013-01-01

Experience with Roux-en-Y gastric bypass in patients with type 1 diabetes is very limited, despite an increasing prevalence of obesity also in this population. We describe changes in anthropometric measures, insulin dose, HbA1c, blood pressure, lipid status, and metabolic response to a liquid mixed...... meal throughout the first year after RYGB in an obese patient with type 1 diabetes. No change in HbA1c was observed, but a 48% reduction in weight-adjusted insulin dose and improvements in cardiovascular risk factors was seen 1 year after surgery. Exaggerated secretions of anorexigenic gut hormones...

Enterocyte-specific epidermal growth factor prevents barrier dysfunction and improves mortality in murine peritonitis.

Science.gov (United States)

Clark, Jessica A; Gan, Heng; Samocha, Alexandr J; Fox, Amy C; Buchman, Timothy G; Coopersmith, Craig M

2009-09-01

Systemic administration of epidermal growth factor (EGF) decreases mortality in a murine model of septic peritonitis. Although EGF can have direct healing effects on the intestinal mucosa, it is unknown whether the benefits of systemic EGF in peritonitis are mediated through the intestine. Here, we demonstrate that enterocyte-specific overexpression of EGF is sufficient to prevent intestinal barrier dysfunction and improve survival in peritonitis. Transgenic FVB/N mice that overexpress EGF exclusively in enterocytes (IFABP-EGF) and wild-type (WT) mice were subjected to either sham laparotomy or cecal ligation and puncture (CLP). Intestinal permeability, expression of the tight junction proteins claudins-1, -2, -3, -4, -5, -7, and -8, occludin, and zonula occludens-1; villus length; intestinal epithelial proliferation; and epithelial apoptosis were evaluated. A separate cohort of mice was followed for survival. Peritonitis induced a threefold increase in intestinal permeability in WT mice. This was associated with increased claudin-2 expression and a change in subcellular localization. Permeability decreased to basal levels in IFABP-EGF septic mice, and claudin-2 expression and localization were similar to those of sham animals. Claudin-4 expression was decreased following CLP but was not different between WT septic mice and IFABP-EGF septic mice. Peritonitis-induced decreases in villus length and proliferation and increases in apoptosis seen in WT septic mice did not occur in IFABP-EGF septic mice. IFABP-EGF mice had improved 7-day mortality compared with WT septic mice (6% vs. 64%). Since enterocyte-specific overexpression of EGF is sufficient to prevent peritonitis-induced intestinal barrier dysfunction and confers a survival advantage, the protective effects of systemic EGF in septic peritonitis appear to be mediated in an intestine-specific fashion.

Expression, biosynthesis and release of preadipocyte factor-1/ delta-like protein/fetal antigen-1 in pancreatic beta-cells

DEFF Research Database (Denmark)

Friedrichsen, B N; Carlsson, C; Møldrup, Annette

2003-01-01

Preadipocyte factor-1 (Pref-1)/delta-like protein/fetal antigen-1 (FA1) is a member of the epidermal growth factor-like family. It is widely expressed in embryonic tissues, whereas in adults it is confined to the adrenal gland, the anterior pituitary, the endocrine pancreas, the testis...

Research on the improvement of nuclear safety -Improvement of level 1 PSA computer code package-

International Nuclear Information System (INIS)

Park, Chang Kyoo; Kim, Tae Woon; Kim, Kil Yoo; Han, Sang Hoon; Jung, Won Dae; Jang, Seung Chul; Yang, Joon Un; Choi, Yung; Sung, Tae Yong; Son, Yung Suk; Park, Won Suk; Jung, Kwang Sub; Kang Dae Il; Park, Jin Heui; Hwang, Mi Jung; Hah, Jae Joo

1995-07-01

This year is the third year of the Government-sponsored mid- and long-term nuclear power technology development project. The scope of this sub project titled on 'The improvement of level-1 PSA computer codes' is divided into three main activities : (1) Methodology development on the underdeveloped fields such as risk assessment technology for plant shutdown and low power situations, (2) Computer code package development for level-1 PSA, (3) Applications of new technologies to reactor safety assessment. At first, in this area of shutdown risk assessment technology development, plant outage experiences of domestic plants are reviewed and plant operating states (POS) are decided. A sample core damage frequency is estimated for over draining event in RCS low water inventory i.e. mid-loop operation. Human reliability analysis and thermal hydraulic support analysis are identified to be needed to reduce uncertainty. Two design improvement alternatives are evaluated using PSA technique for mid-loop operation situation: one is use of containment spray system as backup of shutdown cooling system and the other is installation of two independent level indication system. Procedure change is identified more preferable option to hardware modification in the core damage frequency point of view. Next, level-1 PSA code KIRAP is converted to PC-windows environment. For the improvement of efficiency in performing PSA, the fast cutest generation algorithm and an analytical technique for handling logical loop in fault tree modeling are developed. 48 figs, 15 tabs, 59 refs. (Author)

Research on the improvement of nuclear safety -Improvement of level 1 PSA computer code package-

Energy Technology Data Exchange (ETDEWEB)

Park, Chang Kyoo; Kim, Tae Woon; Kim, Kil Yoo; Han, Sang Hoon; Jung, Won Dae; Jang, Seung Chul; Yang, Joon Un; Choi, Yung; Sung, Tae Yong; Son, Yung Suk; Park, Won Suk; Jung, Kwang Sub; Kang Dae Il; Park, Jin Heui; Hwang, Mi Jung; Hah, Jae Joo [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

1995-07-01

This year is the third year of the Government-sponsored mid- and long-term nuclear power technology development project. The scope of this sub project titled on `The improvement of level-1 PSA computer codes` is divided into three main activities : (1) Methodology development on the underdeveloped fields such as risk assessment technology for plant shutdown and low power situations, (2) Computer code package development for level-1 PSA, (3) Applications of new technologies to reactor safety assessment. At first, in this area of shutdown risk assessment technology development, plant outage experiences of domestic plants are reviewed and plant operating states (POS) are decided. A sample core damage frequency is estimated for over draining event in RCS low water inventory i.e. mid-loop operation. Human reliability analysis and thermal hydraulic support analysis are identified to be needed to reduce uncertainty. Two design improvement alternatives are evaluated using PSA technique for mid-loop operation situation: one is use of containment spray system as backup of shutdown cooling system and the other is installation of two independent level indication system. Procedure change is identified more preferable option to hardware modification in the core damage frequency point of view. Next, level-1 PSA code KIRAP is converted to PC-windows environment. For the improvement of efficiency in performing PSA, the fast cutest generation algorithm and an analytical technique for handling logical loop in fault tree modeling are developed. 48 figs, 15 tabs, 59 refs. (Author).

The growth hormone-insulin-like growth factor axis in glycogen storage disease type 1: evidence of different growth patterns and insulin-like growth factor levels in patients with glycogen storage disease type 1a and 1b.

Science.gov (United States)

Melis, Daniela; Pivonello, Rosario; Parenti, Giancarlo; Della Casa, Roberto; Salerno, Mariacarolina; Balivo, Francesca; Piccolo, Pasquale; Di Somma, Carolina; Colao, Annamaria; Andria, Generoso

2010-04-01

To investigate the growth hormone (GH)-insulin-like growth factor (IGF) system in patients with glycogen storage disease type 1 (GSD1). This was a prospective, case-control study. Ten patients with GSD1a and 7 patients with GSD1b who were given dietary treatment and 34 sex-, age-, body mass index-, and pubertal stage-matched control subjects entered the study. Auxological parameters were correlated with circulating GH, either at basal or after growth hormone releasing hormone plus arginine test, insulin-like growth factors (IGF-I and IGF-II), and anti-pituitary antibodies (APA). Short stature was detected in 10.0% of patients with GSD1a, 42.9% of patients with GSD1b (P = .02), and none of the control subjects. Serum IGF-I levels were lower in patients with GSD1b (P = .0001). An impaired GH secretion was found in 40% of patients with GSD1a (P = .008), 57.1% of patients with GSD1b (P = .006), and none of the control subjects. Short stature was demonstrated in 3 of 4 patients with GSD1b and GH deficiency. The prevalence of APA was significantly higher in patients with GSD1b than in patients with GSD1a (P = .02) and control subjects (P = .03). The GH response to the provocative test inversely correlated with the presence of APA (P = .003). Compared with levels in control subjects, serum IGF-II and insulin levels were higher in both groups of patients, in whom IGF-II levels directly correlated with height SD scores (P = .003). Patients with GSD1a have an impaired GH secretion associated with reference range serum IGF-I levels and normal stature, whereas in patients with GSD1b, the impaired GH secretion, probably because of the presence of APA, was associated with reduced IGF-I levels and increased prevalence of short stature. The increased IGF-II levels, probably caused by increased insulin levels, in patients with GSD1 are presumably responsible for the improved growth pattern observed in patients receiving strict dietary treatment. Copyright 2010 Mosby, Inc. All

Transplantation of MSCs in combination with netrin-1 improves neoangiogenesis in a rat model of hind limb ischemia.

Science.gov (United States)

Li, Qian; Yao, Dan; Ma, Jianhua; Zhu, Jian; Xu, Xianghong; Ren, Yunli; Ding, Xinsheng; Mao, Xiaoming

2011-03-01

Similar to the neural network, the vascular network is formed from central axial structures that send sprouts along predetermined trajectories to their distal destinations. Indeed, recent evidence indicates that neuronal guidance factors and their receptors function as angiogenic regulators. As neural guidance cues, netrin-1 is the most extensively studied gene in the field of angiogenesis. Despite achieving some advances in mesenchymal stem cell (MSC) therapy in angiogenesis, there are still a certain number of patients who fail to respond to cell therapy. Thus, a novel therapeutic strategy to enhance the angiogenic property of transplanted cells is desirable. This study examined the impact of combined netrin-1 protein and MSC implantation on therapeutic angiogenesis in a rat model of hind limb ischemia. Hind limb ischemic rats (n = 24) were divided randomly into four groups (six rats per group): control group (0.05 mL saline); netrin-1 group (1 μg netrin-1 dissolved in 0.05 mL saline); MSC group (1 × 10(6) MSCs); and netrin-1/MSCs group (1 μg netrin-1 combined with MSCs). Netrin-1 and/or MSCs were injected directly into the muscle of the ischemic limb. Gross appearance of ischemic limb, collateral vessel formation, and vascular endothelial growth factor (VEGF) level were assessed 28 d after treatment. The results showed that pretreatment of MSCs with a recombinant netrin-1 protein markedly augmented the angiographic score and capillary density, improved function of the ischemic limb, and increased levels of VEGF in the plasma and damaged tissues. Further studies assaying the cell migration and network formation suggested that netrin-1 promoted MSC migration and enhanced its ability to participate in tube formation. These results demonstrated that transplantation of MSCs pretreated with netrin-1 protein significantly improved the therapeutic effect of MSCs and, therefore, may provide a novel therapeutic approach for ischemic disease. Copyright © 2011 Elsevier

A two-factor method for appraising building renovation and energy efficiency improvement projects

International Nuclear Information System (INIS)

Martinaitis, Vytautas; Kazakevicius, Eduardas; Vitkauskas, Aloyzas

2007-01-01

The renovation of residential buildings usually involves a variety of measures aiming at reducing energy and building maintenance bills, increasing safety and market value, and improving comfort and aesthetics. A significant number of project appraisal methods in current use-such as calculations of payback time, net present value, internal rate of return or cost of conserved energy (CCE)-only quantify energy efficiency gains. These approaches are relatively easy to use, but offer a distorted view of complex modernization projects. On the other hand, various methods using multiple criteria take a much wider perspective but are usually time-consuming, based on sometimes uncertain assumptions and require sophisticated tools. A 'two-factor' appraisal method offers a compromise between these two approaches. The main idea of the method is to separate investments into those related to energy efficiency improvements, and those related to building renovation. Costs and benefits of complex measures, which both influence energy consumption and improve building constructions, are separated by using a building rehabilitation coefficient. The CCE is used for the appraisal of energy efficiency investments, while investments in building renovation are appraised using standard tools for the assessment of investments in maintenance, repair and rehabilitation

Improvement of Biodesulfurization Rate of Alginate Immobilized Rhodococcus erythropolis R1

Science.gov (United States)

Derikvand, Peyman; Etemadifar, Zahra

2014-01-01

Background: 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. Objectives: 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. Materials and Methods: 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. Results: 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. Conclusions: 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. PMID:25147685

Age as Risk Factor for Death from Pandemic (H1N1) 2009, Chile

Science.gov (United States)

Dabanch, Jeannette; Nájera, Manuel; González, Claudia; Guerrero, Andrea; Olea, Andrea; Fasce, Rodrigo; Morales, Cecilia; Vega, Jeanette

2011-01-01

Pandemic (H1N1) 2009 affected Chile during the winter of 2009. The hospitalization rate was 0.56% overall and 3.47% for persons >60 years of age at risk for severe disease and death independent of concurrent conditions. Age >60 years was the major risk factor for death from pandemic (H1N1) 2009. PMID:21762580

Improvements on the calculation of the epithermal disadvantage factor for thermal nuclear reactors

Energy Technology Data Exchange (ETDEWEB)

Aboustta, Mohamed A.; Martinez, Aquilino S. [Universidade Federal, Rio de Janeiro, RJ (Brazil). Coordenacao dos Programas de Pos-graduacao de Engenharia

1997-12-01

The disadvantage factor takes into account the neutron flux variation through the fuel cell. In the fuel the flux is depressed in relation to its level in the moderator region. In order to avoid detailed calculations for each different set of cell dimensions, which turns out necessary the development of problem-dependent neutron cross section libraries, a disadvantage factor based on a two-region equivalence theory was proposed for the EPRI-CELL code. However, it uses a rational approximation to the neutron escape probability to describe the neutron transport between cell regions. Such approximation allows the use of the equivalence principals but introduces a non negligible error which results in an underestimation of the cell neutron fluxes. A new proposed treatment, that will be presented in this work, remarkably improves the numerical calculation and reduces the error of the above mentioned method. (author). 4 refs., 2 figs.

Improvements on the calculation of the epithermal disadvantage factor for thermal nuclear reactors

International Nuclear Information System (INIS)

Aboustta, Mohamed A.; Martinez, Aquilino S.

1997-01-01

The disadvantage factor takes into account the neutron flux variation through the fuel cell. In the fuel the flux is depressed in relation to its level in the moderator region. In order to avoid detailed calculations for each different set of cell dimensions, which turns out necessary the development of problem-dependent neutron cross section libraries, a disadvantage factor based on a two-region equivalence theory was proposed for the EPRI-CELL code. However, it uses a rational approximation to the neutron escape probability to describe the neutron transport between cell regions. Such approximation allows the use of the equivalence principals but introduces a non negligible error which results in an underestimation of the cell neutron fluxes. A new proposed treatment, that will be presented in this work, remarkably improves the numerical calculation and reduces the error of the above mentioned method. (author). 4 refs., 2 figs

CNF1-like deamidase domains: common Lego bricks among cancer-promoting immunomodulatory bacterial virulence factors.

Science.gov (United States)

Ho, Mengfei; Mettouchi, Amel; Wilson, Brenda A; Lemichez, Emmanuel

2018-05-03

Alterations of the cellular proteome over time due to spontaneous or toxin-mediated enzymatic deamidation of glutamine (Gln) and asparagine (Asn) residues contribute to bacterial infection and might represent a source of aging-related diseases. Here, we put into perspective what is known about the mode of action of the CNF1 toxin from pathogenic E. coli, a paradigm of bacterial deamidases that activate Rho GTPases, to illustrate the importance of determining whether exposure to these factors are risk factors in the etiology age-related diseases, such as cancer. In particular, through in silico analysis of the distribution of the CNF1-like deamidase active site Gly-Cys-(Xaa)n-His sequence motif in bacterial genomes, we unveil the wide distribution of the super-family of CNF-like toxins and CNF-like deamidase domains among members of the enterobacteriacae and in association with a large variety of toxin delivery systems. We extent our discussion with recent findings concerning cellular systems that control activated Rac1 GTPase stability and provide protection against cancer. These findings point to the urgency for developing holistic approaches toward personalized medicine that include monitoring for asymptomatic carriage of pathogenic toxin-producing bacteria and that ultimately might lead to improved public health and increased lifespans.

The redox protein thioredoxin-1 (Trx-1) increases hypoxia-inducible factor 1alpha protein expression: Trx-1 overexpression results in increased vascular endothelial growth factor production and enhanced tumor angiogenesis.

Science.gov (United States)

Welsh, Sarah J; Bellamy, William T; Briehl, Margaret M; Powis, Garth

2002-09-01

Hypoxia-inducible factor 1 (HIF-1), a heterodimer of HIF-1alpha and HIF-1beta subunits, is a transcriptional activator central to the cellular response to low oxygen that includes metabolic adaptation, angiogenesis, metastasis, and inhibited apoptosis. Thioredoxin-1 (Trx-1) is a small redox protein overexpressed in a number of human primary tumors. We have examined the effects of Trx-1 on HIF activity and the activation of downstream genes. Stable transfection of human breast carcinoma MCF-7 cells with human Trx-1 caused a significant increase in HIF-1alpha protein levels under both normoxic (20% oxygen) and hypoxic (1% oxygen) conditions. Trx-1 increased hypoxia-induced HIF-1 transactivation activity measured using a luciferase reporter under the control of the hypoxia response element. Changes in HIF-1alpha mRNA levels did not account for the changes observed at the protein level, and HIF-1beta protein levels did not change. Trx-1 transfection also caused a significant increase in the protein products of hypoxia-responsive genes, including vascular endothelial growth factor (VEGF) and nitric oxide synthase 2 in a number of different cell lines (MCF-7 human breast and HT29 human colon carcinomas and WEHI7.2 mouse lymphoma cells) under both normoxic and hypoxic conditions. The pattern of expression of the different isoforms of VEGF was not changed by Trx-1. Transfection of a redox-inactive Trx-1 (C32S/C35S) markedly decreased levels of HIF-1alpha protein, HIF-1 transactivating activity, and VEGF protein in MCF-7 cells compared with empty vector controls. In vivo studies using WEHI7.2 cells transfected with Trx-1 showed significantly increased tumor VEGF and angiogenesis. The results suggest that Trx-1 increases HIF-1alpha protein levels in cancer cells and increases VEGF production and tumor angiogenesis.

A protocol improves GP recording of long-term sickness absence risk factors.

Science.gov (United States)

van Dijk, Paul; Hogervorst, Wouter; ter Riet, Gerben; van Dijk, Frank

2008-06-01

If general practitioners (GPs) were better informed about patients' risks of long-term sickness absence (LTSA), they could incorporate these risk assessments into their patient management plans and cooperate more with occupational physicians to prevent LTSA. To evaluate the effectiveness of a protocol helping GPs in recording risks of LTSA and in co-operating with occupational physicians (OPs). Twenty-six GPs (co-operating in four groups) in Amsterdam, The Netherlands, participated in a controlled intervention study. Fourteen GPs were the protocol-supported intervention group and twelve GPs were the reference group. Outcome measures were consultations containing work-related information, information about two risk factors for LTSA, referrals to OPs and contacts of OPs with GPs and patients. Outcomes were identified through an electronic search in the GPs' information systems. Entries containing information were independently scored by two investigators. The proportions of patients with consultations documenting LTSA-pertinent items were compared between the groups, accounting for differences at baseline. There was no increase in consultations containing work-related information. Recording of risk factor information increased in the intervention group; the difference was 4.5% [95% CI 1.5-7.6] and 1.8% (95% CI -0.8 to 4.4) for the two risk factors. The referral rate to the OP increased by 2.9% (95% CI 1.2-4.5). There was no effect on contacts of OPs with GPs or with patients. Protocol-supported consultations may lead to a modest increase in information regarding two risk factors for LTSA in GPs' electronic records and to more referrals to OPs.

Severe hypoglycaemia in type 1 diabetes: impact of the renin-angiotensin system and other risk factors

DEFF Research Database (Denmark)

Pedersen-Bjergaard, Ulrik

2009-01-01

this thesis was conducted to assess the significance of severe hypoglycaemia as a clinical problem in the type 1 diabetic population, to evaluate the impact of known risk factors on occurrence of severe hypoglycaemia, and to identify new markers that could contribute to improved prediction of, and inspire...... targets and thereby open for prevention of severe hypoglycaemia. Furthermore, subjects with elevated renin-angiotensin system activity and a high rate of severe hypoglycaemia might benefit from pharmacological blockade of the renin-angiotensin system by ACE inhibitors or angiotensin II receptor blockers...

HGF and BFGF Secretion by Human Adipose-Derived Stem Cells Improves Ovarian Function During Natural Aging via Activation of the SIRT1/FOXO1 Signaling Pathway.

Science.gov (United States)

Ding, Chenyue; Zou, Qinyan; Wang, Fuxin; Wu, Huihua; Wang, Wei; Li, Hong; Huang, Boxian

2018-01-01

Human adipose-derived stem cells (hADSCs) are a potential therapeutic option for clinical applications because of their ability to produce cytokines and their capacity for trilineage differentiation. To date, few researchers have investigated the effects of hADSCs on natural ovarian aging (NOA). An NOA mouse model and human ovarian granule cells (hGCs) collected from individuals with NOA were prepared to assess the therapeutic effects and illuminate the mechanism of hADSCs in curing NOA. Enzyme-linked immunosorbent assay was used to detect the serum levels of sex hormones and antioxidative enzymes. The proliferation rate and marker expression level of hGCs were measured by flow cytometry (FACS). Cytokines were measured by a protein antibody array methodology. Western blot assays were used to determine the protein expression levels of SIRT1 and FOXO1. Our results showed that hADSCs displayed therapeutic activity against ovarian function in an NOA mouse model, increasing the proliferation rate and marker expression level of hGCs. Furthermore, the yields of hADSC-secreted HGF and bFGF were higher than those of other growth factors. FACS showed that combination treatment with the growth factors HGF and bFGF more strongly promoted proliferation and inhibited apoptosis in hGCs than HGF or bFGF treatment alone. FACS and ELISA revealed that the combination treatment with both growth factors inhibited oxidative stress more forcefully than treatments with only one of these growth factors. In addition, protein assays demonstrated that combination treatment with both growth factors suppressed oxidative stress by up-regulating the expression of SIRT1 and FOXO1. These findings demonstrate for the first time the molecular cascade and related cell biology events involved in the mechanism by which HGF and bFGF derived from hADSCs improved ovarian function during natural aging via reduction of oxidative stress by activating the SIRT1/FOXO1 signaling pathway. © 2018 The Author

The porcine circovirus type 1 capsid gene promoter improves antigen expression and immunogenicity in a HIV-1 plasmid vaccine

Directory of Open Access Journals (Sweden)

Burger Marieta

2011-02-01

Full Text Available Abstract Background One of the promising avenues for development of vaccines against Human immunodeficiency virus type 1 (HIV-1 and other human pathogens is the use of plasmid-based DNA vaccines. However, relatively large doses of plasmid must be injected for a relatively weak response. We investigated whether genome elements from Porcine circovirus type 1 (PCV-1, an apathogenic small ssDNA-containing virus, had useful expression-enhancing properties that could allow dose-sparing in a plasmid vaccine. Results The linearised PCV-1 genome inserted 5' of the CMV promoter in the well-characterised HIV-1 plasmid vaccine pTHgrttnC increased expression of the polyantigen up to 2-fold, and elicited 3-fold higher CTL responses in mice at 10-fold lower doses than unmodified pTHgrttnC. The PCV-1 capsid gene promoter (Pcap alone was equally effective. Enhancing activity was traced to a putative composite host transcription factor binding site and a "Conserved Late Element" transcription-enhancing sequence previously unidentified in circoviruses. Conclusions We identified a novel PCV-1 genome-derived enhancer sequence that significantly increased antigen expression from plasmids in in vitro assays, and improved immunogenicity in mice of the HIV-1 subtype C vaccine plasmid, pTHgrttnC. This should allow significant dose sparing of, or increased responses to, this and other plasmid-based vaccines. We also report investigations of the potential of other circovirus-derived sequences to be similarly used.

Interaction of Sp1 zinc finger with transport factor in the nuclear localization of transcription factor Sp1

International Nuclear Information System (INIS)

Ito, Tatsuo; Kitamura, Haruka; Uwatoko, Chisana; Azumano, Makiko; Itoh, Kohji; Kuwahara, Jun

2010-01-01

Research highlights: → Sp1 zinc fingers themselves interact with importin α. → Sp1 zinc finger domains play an essential role as a nuclear localization signal. → Sp1 can be transported into the nucleus in an importin-dependent manner. -- Abstract: Transcription factor Sp1 is localized in the nucleus and regulates the expression of many cellular genes, but the nuclear transport mechanism of Sp1 is not well understood. In this study, we revealed that GST-fused Sp1 protein bound to endogenous importin α in HeLa cells via the Sp1 zinc finger domains, which comprise the DNA binding domain of Sp1. It was found that the Sp1 zinc finger domains directly interacted with a wide range of importin α including the armadillo (arm) repeat domain and the C-terminal acidic domain. Furthermore, it turned out that all three zinc fingers of Sp1 are essential for binding to importin α. Taken together, these results suggest that the Sp1 zinc finger domains play an essential role as a NLS and Sp1 can be transported into the nucleus in an importin-dependent manner even though it possesses no classical NLSs.

A combined continuous and interval aerobic training improves metabolic syndrome risk factors in men

Directory of Open Access Journals (Sweden)

Sari-Sarraf V

2015-05-01

Full Text Available Vahid Sari-Sarraf,1 Akbar Aliasgarzadeh,2 Mohammad-Mahdi Naderali,3 Hamid Esmaeili,1 Ebrahim K Naderali4 1Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, University of Tabriz, 2Bone Research Centre, Endocrine Unit, Department of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; 3The School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, 4Faculty of Science, Liverpool Hope University, Liverpool, UK Abstract: Individuals with metabolic syndrome have significantly higher risk of cardiovascular disease and type 2 diabetes leading to premature death mortality. Metabolic syndrome has a complex etiology; thus, it may require a combined and multi-targeted aerobic exercise regimen to improve risk factors associated with it. Therefore, the aim of this study was to evaluate the effect of combined continuous and interval aerobic training on patients with metabolic syndrome. Thirty adult male with metabolic syndrome (54±8 years were randomly divided into two groups: test training group (TTG; n=15 and control group (CG; n=15. Subjects in TTG performed combined continuous and interval aerobic training using a motorized treadmill three times per week for 16 weeks. Subjects in CG were advised to continue with their normal activities of life. Twenty-two men completed the study (eleven men in each group. At the end of the study, in TTG, there were significant (for all, P<0.05 reductions in total body weight (-3.2%, waist circumference (-3.43 cm, blood pressure (up to -12.7 mmHg, and plasma insulin, glucose, and triacylglyceride levels. Moreover, there were significant (for all, P<0.05 increases VO2max (-15.3% and isometric strength of thigh muscle (28.1% and high-density lipoprotein in TTG. None of the above indices were changed in CG at the end of 16-week study period. Our study suggests that adoption of a 16-week combined continuous and interval aerobic training regimen in men

Effect of maternal factors on nutritional status of 1-5-year-old children in urban slum population

Directory of Open Access Journals (Sweden)

Mittal A

2007-01-01

Full Text Available Objective: To study the effect of various maternal factors on the prevalence of underweight and stunting among 1-5-year-old children in urban slum population. Design: Cross-sectional study. Materials and Methods: The study was carried out in three urban slums of Tripuri Town, Patiala. All 1-5-year children living in these slums were included, whose mother′s demographic profile, weight and height were recorded. Results: Out of 482 children who participated in the study, 185 (38.38% had low weight for age whereas 222 (46.06% had low height for age. Both kinds of malnutrition were common in females than in males. Prevalence of malnutrition was more where mother′s age was less than 20 years. Children of educated mothers were better nourished as compared to illiterate ones. Conclusion: Maternal factors significantly affect a child′s nutritional status, thus encouraging the improvement in the social status of women so as to have healthy children and thereby a healthy future.

Modelling of safety barriers including human and organisational factors to improve process safety

DEFF Research Database (Denmark)

Markert, Frank; Duijm, Nijs Jan; Thommesen, Jacob

2013-01-01

It is believed that traditional safety management needs to be improved on the aspect of preparedness for coping with expected and unexpected deviations, avoiding an overly optimistic reliance on safety systems. Remembering recent major accidents, such as the Deep Water Horizon, the Texas City....... A valuable approach is the inclusion of human and organisational factors into the simulation of the reliability of the technical system using event trees and fault trees and the concept of safety barriers. This has been demonstrated e.g. in the former European research project ARAMIS (Accidental Risk...

Three Phase Six-Switch PWM Buck Rectifier with Power Factor Improvement

DEFF Research Database (Denmark)

Zafar Ullah Khan, M; Mohsin Naveed, M.; Hussain, Dil Muhammad Akbar

2013-01-01

Conventional Phase Controlled Rectifier injects low order current harmonics into the AC mains. Large size filtering components are required to attenuate these harmonics. In this paper, Three Phase Six-Switch PWM Buck Rectifier[1] is presented which operates at nearly unity power factor and provides...

Optical Molecular Imaging of Epidermal Growth Factor Receptor Expression to Improve Detection of Oral Neoplasia

Directory of Open Access Journals (Sweden)

Nitin Nitin

2009-06-01

Full Text Available Background: The development of noninvasive molecular imaging approaches has the potential to improve management of cancer. Methods: In this study, we demonstrate the potential of noninvasive topical delivery of an epidermal growth factor-Alexa 647 (EGF-Alexa 647 conjugate to image changes in epidermal growth factor receptor expression associated with oral neoplasia. We report a series of preclinical analyses to evaluate the optical contrast achieved after topical delivery of EGF-Alexa 647 in a variety of model systems, including cells, three-dimensional tissue cultures, and intact human tissue specimens using wide-field and high-resolution fluorescence imaging. Data were collected from 17 different oral cancer patients: eight pairs of normal and abnormal biopsies and nine resected tumors were examined. Results: The EGF-dye conjugate can be uniformly delivered throughout the oral epithelium with a penetration depth exceeding 500 µm and incubation time of less than 30 minutes. After EGF-Alexa 647 incubation, the presence of oral neoplasia is associated with a 1.5- to 6.9-fold increase in fluorescence contrast compared with grossly normal mucosa from the same patient with both wide-field and high-resolution fluorescence imaging. Conclusions: Results illustrate the potential of EGF-targeted fluorescent agents for in vivo molecular imaging, a technique that may aid in the diagnosis and characterization of oral neoplasia and allow real-time detection of tumor margins.

A stromal cell-derived factor-1 releasing matrix enhances the progenitor cell response and blood vessel growth in ischaemic skeletal muscle

Directory of Open Access Journals (Sweden)

D Kuraitis

2011-09-01

Full Text Available Although many regenerative cell therapies are being developed to replace or regenerate ischaemic muscle, the lack of vasculature and poor persistence of the therapeutic cells represent major limiting factors to successful tissue restoration. In response to ischaemia, stromal cell-derived factor-1 (SDF-1 is up-regulated by the affected tissue to stimulate stem cell-mediated regenerative responses. Therefore, we encapsulated SDF-1 into alginate microspheres and further incorporated these into an injectable collagen-based matrix in order to improve local delivery. Microsphere-matrix impregnation reduced the time for matrix thermogelation, and also increased the viscosity reached. This double-incorporation prolonged the release of SDF-1, which maintained adhesive and migratory bioactivity, attributed to chemotaxis in response to SDF-1. In vivo, treatment of ischaemic hindlimb muscle with microsphere-matrix led to increased mobilisation of bone marrow-derived progenitor cells, and also improved recruitment of angiogenic cells expressing the SDF-1 receptor (CXCR4 from bone marrow and local tissues. Both matrix and SDF-1-releasing matrix were successful at restoring perfusion, but SDF-1 treatment appeared to play an earlier role, as evidenced by arterioles that are phenotypically older and by increased angiogenic cytokine production, stimulating the generation of a qualitative microenvironment for a rapid and therefore more efficient regeneration. These results support the release of implanted SDF-1 as a promising method for enhancing progenitor cell responses and restoring perfusion to ischaemic tissues via neovascularisation.

Tissue localization of human trefoil factors 1, 2, and 3

DEFF Research Database (Denmark)

Madsen, Jens; Nielsen, Ole; Tornøe, Ida

2007-01-01

Trefoil factors (TTFs) are small, compact proteins coexpressed with mucins in the gastrointestinal tract. Three trefoil factors are known in mammals: TFF1, TFF2, and TFF3. They are implicated to play diverse roles in maintenance and repair of the gastrointestinal channel. We compared the expression...... pattern of the three trefoil factors analyzing mRNA from a panel of 20 human tissues by conventional reverse transcriptase (RT) PCR and, in addition, by real-time PCR. These findings were supported by immunohistochemical analysis of paraffin-embedded human tissues using rabbit polyclonal antibodies raised...... against these factors. TFF1 showed highest expression in the stomach and colon, whereas TFF2 and TFF3 showed highest expression in stomach and colon, respectively. All three TFFs were found in the ducts of pancreas. Whereas TFF2 was found to be restricted to these two tissues, the structurally more...

26 CFR 157.5891-1 - Imposition of excise tax on structured settlement factoring transactions.

Science.gov (United States)

2010-04-01

... settlement factoring transactions. 157.5891-1 Section 157.5891-1 Internal Revenue INTERNAL REVENUE SERVICE... SETTLEMENT FACTORING TRANSACTIONS Tax on Structured Settlement Factoring Transactions § 157.5891-1 Imposition of excise tax on structured settlement factoring transactions. (a) In general. Section 5891 imposes...

High serum soluble tumor necrosis factor receptor 1 predicts poor treatment response in acute-stage schizophrenia.

Science.gov (United States)

Nishimon, Shohei; Ohnuma, Tohru; Takebayashi, Yuto; Katsuta, Narimasa; Takeda, Mayu; Nakamura, Toru; Sannohe, Takahiro; Higashiyama, Ryoko; Kimoto, Ayako; Shibata, Nobuto; Gohda, Tomohito; Suzuki, Yusuke; Yamagishi, Sho-Ichi; Tomino, Yasuhiko; Arai, Heii

2017-06-02

Inflammation may be involved in the pathophysiology of schizophrenia. However, few cross-sectional or longitudinal studies have examined changes in biomarker expression to evaluate diagnostic and prognostic efficacy in acute-stage schizophrenia. We compared serum inflammatory biomarker concentrations in 87 patients with acute-stage schizophrenia on admission to 105 age-, sex-, and body mass index (BMI)-matched healthy controls. The measured biomarkers were soluble tumor necrosis factor receptor 1 (sTNFR1) and adiponectin, which are associated with inflammatory responses, and pigment epithelium-derived factor (PEDF), which has anti-inflammatory properties. We then investigated biomarker concentrations and associations with clinical factors in 213 patients (including 42 medication-free patients) and 110 unmatched healthy controls to model conditions typical of clinical practice. Clinical symptoms were assessed using the Brief Psychiatric Rating Scale and Global Assessment of Function. In 121 patients, biomarker levels and clinical status were evaluated at both admission and discharge. Serum sTNFR1 was significantly higher in patients with acute-stage schizophrenia compared to matched controls while no significant group differences were observed for the other markers. Serum sTNFR1 was also significantly higher in the 213 patients compared to unmatched controls. The 42 unmedicated patients had significantly lower PEDF levels compared to controls. Between admission and discharge, sTNFR1 levels decreased significantly; however, biomarker changes did not correlate with clinical symptoms. The discriminant accuracy of sTNFR1 was 93.2% between controls and patients, showing no symptom improvement during care. Inflammation and a low-level anti-inflammatory state may be involved in both schizophrenia pathogenesis and acute-stage onset. High serum sTNFR1 in the acute stage could be a useful prognostic biomarker for treatment response in clinical practice. Copyright © 2017

Prognostic Markers in Core-Binding Factor AML and Improved Survival with Multiple Consolidation Cycles of Intermediate/High-dose Cytarabine.

Science.gov (United States)

Prabahran, Ashvind; Tacey, Mark; Fleming, Shaun; Wei, Andrew; Tate, Courtney; Marlton, Paula; Wight, Joel; Grigg, Andrew; Tuckfield, Annabel; Szer, Jeff; Ritchie, David; Chee, Lynette

2018-05-02

Core-binding factor acute myeloid leukaemia (CBF AML) defined by t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22) has a favourable prognosis, however 30-40% of patients still relapse after chemotherapy. We sought to evaluate risk factors for relapse in a de novo CBF AML cohort. A retrospective review of patients from 4 Australian tertiary centres from 2001-2012, comprising 40 t(8;21) and 30 inv(16) AMLs. Multivariate analysis identified age (p=0.032) and WCC>40 (p=0.025) as significant predictors for inferior OS and relapse respectively. Relapse risk was higher in the inv(16) group vs the t(8;21) group (57% vs 18%, HR 4.31, 95% CI: 1.78-10.42, p=0.001). Induction therapy had no bearing on OS or relapse free survival (RFS) however, consolidation treatment with >3 cycles of intermediate/high dose cytarabine improved OS (p=0.035) and relapse-free survival (RFS) (p=0.063). 5 patients demonstrated post-treatment stable q PCR positivity without relapse. (1)>3 consolidation cycles of intermediate/ high-dose cytarabine improves patient outcomes. (2)Age and inv(16) CBF AML subtype are predictors of inferior OS and RFS respectively. (3)Stable low-level MRD by qPCR does not predict relapse. (4)Similar OS in the inv(16) cohort compared to the t(8;21) cohort, despite a higher relapse rate, confirms salvageability of relapsed disease. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Role of Insulin-Like Growth Factor-1 Signaling Pathway in Cisplatin-Resistant Lung Cancer Cells

International Nuclear Information System (INIS)

Sun Yunguang; Zheng Siyuan; Torossian, Artour; Speirs, Christina K.; Schleicher, Stephen; Giacalone, Nicholas J.; Carbone, David P.; Zhao Zhongming; Lu Bo

2012-01-01

Purpose: The development of drug-resistant phenotypes has been a major obstacle to cisplatin use in non–small-cell lung cancer. We aimed to identify some of the molecular mechanisms that underlie cisplatin resistance using microarray expression analysis. Methods and Materials: H460 cells were treated with cisplatin. The differences between cisplatin-resistant lung cancer cells and parental H460 cells were studied using Western blot, MTS, and clonogenic assays, in vivo tumor implantation, and microarray analysis. The cisplatin-R cells were treated with human recombinant insulin-like growth factor (IGF) binding protein-3 and siRNA targeting IGF-1 receptor. Results: Cisplatin-R cells illustrated greater expression of the markers CD133 and aldehyde dehydrogenase, more rapid in vivo tumor growth, more resistance to cisplatin- and etoposide-induced apoptosis, and greater survival after treatment with cisplatin or radiation than the parental H460 cells. Also, cisplatin-R demonstrated decreased expression of insulin-like growth factor binding protein-3 and increased activation of IGF-1 receptor signaling compared with parental H460 cells in the presence of IGF-1. Human recombinant IGF binding protein-3 reversed cisplatin resistance in cisplatin-R cells and targeting of IGF-1 receptor using siRNA resulted in sensitization of cisplatin-R-cells to cisplatin and radiation. Conclusions: The IGF-1 signaling pathway contributes to cisplatin-R to cisplatin and radiation. Thus, this pathway represents a potential target for improved lung cancer response to treatment.

Role of Insulin-Like Growth Factor-1 Signaling Pathway in Cisplatin-Resistant Lung Cancer Cells

Energy Technology Data Exchange (ETDEWEB)

Sun Yunguang [Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN (United States); Zheng Siyuan [Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN (United States); Torossian, Artour; Speirs, Christina K.; Schleicher, Stephen; Giacalone, Nicholas J. [Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN (United States); Carbone, David P. [Department of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, TN (United States); Zhao Zhongming, E-mail: zhongming.zhao@vanderbilt.edu [Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN (United States); Lu Bo, E-mail: bo.lu@vanderbilt.edu [Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN (United States)

2012-03-01

Purpose: The development of drug-resistant phenotypes has been a major obstacle to cisplatin use in non-small-cell lung cancer. We aimed to identify some of the molecular mechanisms that underlie cisplatin resistance using microarray expression analysis. Methods and Materials: H460 cells were treated with cisplatin. The differences between cisplatin-resistant lung cancer cells and parental H460 cells were studied using Western blot, MTS, and clonogenic assays, in vivo tumor implantation, and microarray analysis. The cisplatin-R cells were treated with human recombinant insulin-like growth factor (IGF) binding protein-3 and siRNA targeting IGF-1 receptor. Results: Cisplatin-R cells illustrated greater expression of the markers CD133 and aldehyde dehydrogenase, more rapid in vivo tumor growth, more resistance to cisplatin- and etoposide-induced apoptosis, and greater survival after treatment with cisplatin or radiation than the parental H460 cells. Also, cisplatin-R demonstrated decreased expression of insulin-like growth factor binding protein-3 and increased activation of IGF-1 receptor signaling compared with parental H460 cells in the presence of IGF-1. Human recombinant IGF binding protein-3 reversed cisplatin resistance in cisplatin-R cells and targeting of IGF-1 receptor using siRNA resulted in sensitization of cisplatin-R-cells to cisplatin and radiation. Conclusions: The IGF-1 signaling pathway contributes to cisplatin-R to cisplatin and radiation. Thus, this pathway represents a potential target for improved lung cancer response to treatment.

Evaluation of a multicomponent workplace health promotion program conducted in Japan for improving employees' cardiovascular disease risk factors.

Science.gov (United States)

Muto, T; Yamauchi, K

2001-12-01

The long-term effectiveness of multicomponent worksite health promotion programs targeting cardiovascular disease risk factors remains unclear in Japan. This study was conducted to evaluate the effectiveness of such a health promotion program consisting of a main program provided over 4 days and a follow-up program provided over 1 year. The subjects of this randomized controlled trial were male employees working for a building maintenance company in Japan. The intervention group (n = 152) and the control group (n = 150) consisted of employees having abnormal findings in at least one of the following items at baseline health examination: body mass index (BMI), systolic (SBP) or diastolic blood pressure, total cholesterol, HDL cholesterol, triglycerides, and fasting blood glucose. Evaluation was conducted at 18 months after the main program. BMI, SBP, total cholesterol, and triglycerides improved significantly in the intervention group compared with the control group (P < 0.05). When comparisons were limited to those who showed abnormality at baseline, BMI, total cholesterol, and triglycerides improved significantly in the intervention group (P < 0.05). The multicomponent health promotion program provided to employees was shown to be effective in improving obesity, high blood pressure, and hyperlipidemia when evaluated 18 months after the main intervention program. Copyright 2001 American Health Foundation and Elsevier Science.

Carbon Monoxide Releasing Molecule-A1 (CORM-A1) Improves Neurogenesis: Increase of Neuronal Differentiation Yield by Preventing Cell Death.

Science.gov (United States)

Almeida, Ana S; Soares, Nuno L; Vieira, Melissa; Gramsbergen, Jan Bert; Vieira, Helena L A

2016-01-01

Cerebral ischemia and neurodegenerative diseases lead to impairment or death of neurons in the central nervous system. Stem cell based therapies are promising strategies currently under investigation. Carbon monoxide (CO) is an endogenous product of heme degradation by heme oxygenase (HO) activity. Administration of CO at low concentrations produces several beneficial effects in distinct tissues, namely anti-apoptotic and anti-inflammatory. Herein the CO role on modulation of neuronal differentiation was assessed. Three different models with increasing complexity were used: human neuroblastoma SH-S5Y5 cell line, human teratocarcinoma NT2 cell line and organotypic hippocampal slice cultures (OHSC). Cell lines were differentiated into post-mitotic neurons by treatment with retinoic acid (RA) supplemented with CO-releasing molecule A1 (CORM-A1). CORM-A1 positively modulated neuronal differentiation, since it increased final neuronal production and enhanced the expression of specific neuronal genes: Nestin, Tuj1 and MAP2. Furthermore, during neuronal differentiation process, there was an increase in proliferative cell number (ki67 mRNA expressing cells) and a decrease in cell death (lower propidium iodide (PI) uptake, limitation of caspase-3 activation and higher Bcl-2 expressing cells). CO supplementation did not increase the expression of RA receptors. In the case of SH-S5Y5 model, small amounts of reactive oxygen species (ROS) generation emerges as important signaling molecules during CO-promoted neuronal differentiation. CO's improvement of neuronal differentiation yield was validated using OHSC as ex vivo model. CORM-A1 treatment of OHSC promoted higher levels of cells expressing the neuronal marker Tuj1. Still, CORM-A1 increased cell proliferation assessed by ki67 expression and also prevented cell death, which was followed by increased Bcl-2 expression, decreased levels of active caspase-3 and PI uptake. Likewise, ROS signaling emerged as key factors in CO

Theoretical study on new bias factor methods to effectively use critical experiments for improvement of prediction accuracy of neutronic characteristics

International Nuclear Information System (INIS)

Kugo, Teruhiko; Mori, Takamasa; Takeda, Toshikazu

2007-01-01

Extended bias factor methods are proposed with two new concepts, the LC method and the PE method, in order to effectively use critical experiments and to enhance the applicability of the bias factor method for the improvement of the prediction accuracy of neutronic characteristics of a target core. Both methods utilize a number of critical experimental results and produce a semifictitious experimental value with them. The LC and PE methods define the semifictitious experimental values by a linear combination of experimental values and the product of exponentiated experimental values, respectively, and the corresponding semifictitious calculation values by those of calculation values. A bias factor is defined by the ratio of the semifictitious experimental value to the semifictitious calculation value in both methods. We formulate how to determine weights for the LC method and exponents for the PE method in order to minimize the variance of the design prediction value obtained by multiplying the design calculation value by the bias factor. From a theoretical comparison of these new methods with the conventional method which utilizes a single experimental result and the generalized bias factor method which was previously proposed to utilize a number of experimental results, it is concluded that the PE method is the most useful method for improving the prediction accuracy. The main advantages of the PE method are summarized as follows. The prediction accuracy is necessarily improved compared with the design calculation value even when experimental results include large experimental errors. This is a special feature that the other methods do not have. The prediction accuracy is most effectively improved by utilizing all the experimental results. From these facts, it can be said that the PE method effectively utilizes all the experimental results and has a possibility to make a full-scale-mockup experiment unnecessary with the use of existing and future benchmark

Intramyocardial implantation of differentiated rat bone marrow mesenchymal stem cells enhanced by TGF-β1 improves cardiac function in heart failure rats

Energy Technology Data Exchange (ETDEWEB)

Lv, Y. [Department of Histology and Embryology, Hebei Medical University, Shijiazhuang, Hebei (China); Liu, B. [Department of Pathology, the First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei (China); Wang, H.P. [Department of Histology and Embryology, Hebei North University, Zhangjiakou, Hebei (China); Zhang, L. [Department of Histology and Embryology, Hebei Medical University, Shijiazhuang, Hebei (China)

2016-05-31

The present study tested the hypotheses that i) transforming growth factor beta 1 (TGF-β1) enhances differentiation of rat bone marrow mesenchymal stem cells (MSCs) towards the cardiomyogenic phenotype and ii) intramyocardial implantation of the TGF-β1-treated MSCs improves cardiac function in heart failure rats. MSCs were treated with different concentrations of TGF-β1 for 72 h, and then morphological characteristics, surface antigens and mRNA expression of several transcription factors were assessed. Intramyocardial implantation of these TGF-β1-treated MSCs to infarcted heart was also investigated. MSCs were initially spindle-shaped with irregular processes. On day 28 after TGF-β1 treatment, MSCs showed fusiform shape, orientating parallel with one another, and were connected with adjoining cells forming myotube-like structures. Immunofluorescence revealed the expression of cardiomyocyte-specific proteins, α-sarcomeric actin and troponin T, in these cells. The mRNA expression of GATA4 and Nkx2.5 genes was slightly increased on day 7, enhanced on day 14 and decreased on day 28 while α-MHC gene was not expressed on day 7, but expressed slightly on day 14 and enhanced on day 28. Transmission electron microscopy showed that the induced cells had myofilaments, z line-like substances, desmosomes, and gap junctions, in contrast with control cells. Furthermore, intramyocardial implantation of TGF-β1-treated MSCs to infarcted heart reduced scar area and increased the number of muscle cells. This structure regeneration was concomitant with the improvement of cardiac function, evidenced by decreased left ventricular end-diastolic pressure, increased left ventricular systolic pressure and increased maximal positive pressure development rate. Taken together, these results indicate that intramyocardial implantation of differentiated MSCs enhanced by TGF-β1 improved cardiac function in heart failure rats.

Intramyocardial implantation of differentiated rat bone marrow mesenchymal stem cells enhanced by TGF-β1 improves cardiac function in heart failure rats

International Nuclear Information System (INIS)

Lv, Y.; Liu, B.; Wang, H.P.; Zhang, L.

2016-01-01

The present study tested the hypotheses that i) transforming growth factor beta 1 (TGF-β1) enhances differentiation of rat bone marrow mesenchymal stem cells (MSCs) towards the cardiomyogenic phenotype and ii) intramyocardial implantation of the TGF-β1-treated MSCs improves cardiac function in heart failure rats. MSCs were treated with different concentrations of TGF-β1 for 72 h, and then morphological characteristics, surface antigens and mRNA expression of several transcription factors were assessed. Intramyocardial implantation of these TGF-β1-treated MSCs to infarcted heart was also investigated. MSCs were initially spindle-shaped with irregular processes. On day 28 after TGF-β1 treatment, MSCs showed fusiform shape, orientating parallel with one another, and were connected with adjoining cells forming myotube-like structures. Immunofluorescence revealed the expression of cardiomyocyte-specific proteins, α-sarcomeric actin and troponin T, in these cells. The mRNA expression of GATA4 and Nkx2.5 genes was slightly increased on day 7, enhanced on day 14 and decreased on day 28 while α-MHC gene was not expressed on day 7, but expressed slightly on day 14 and enhanced on day 28. Transmission electron microscopy showed that the induced cells had myofilaments, z line-like substances, desmosomes, and gap junctions, in contrast with control cells. Furthermore, intramyocardial implantation of TGF-β1-treated MSCs to infarcted heart reduced scar area and increased the number of muscle cells. This structure regeneration was concomitant with the improvement of cardiac function, evidenced by decreased left ventricular end-diastolic pressure, increased left ventricular systolic pressure and increased maximal positive pressure development rate. Taken together, these results indicate that intramyocardial implantation of differentiated MSCs enhanced by TGF-β1 improved cardiac function in heart failure rats

CF6 jet engine performance improvement program. Task 1: Feasibility analysis

Science.gov (United States)

Fasching, W. A.

1979-01-01

Technical and economic engine improvement concepts selected for subsequent development include: (1) fan improvement; (2) short core exhaust; (3) HP turbine aerodynamic improvement; (4) HP turbine roundness control; (5) HP turbine active clearance control; and (6) cabin air recirculation. The fuel savings for the selected engine modification concepts for the CF6 fleet are estimated.

Hypoxia-Inducible Factor-1α in carcinogenesis and progression of breast cancer

NARCIS (Netherlands)

Bos, R.

2004-01-01

This thesis is primarily focused on the previously hardly explored role of HIF-1 in breast cancer. HIF-1 is a transcription factor induced by hypoxia, but also by some oncogenes, tumor suppressor genes and growth factors. Activated HIF-1 can induce angiogenesis, glycolysis, erythropoiesis, and other

Bilirubin modulated cytokines, growth factors and angiogenesis to improve cutaneous wound healing process in diabetic rats.

Science.gov (United States)

Ram, Mahendra; Singh, Vishakha; Kumawat, Sanjay; Kant, Vinay; Tandan, Surendra Kumar; Kumar, Dinesh

2016-01-01

Bilirubin has shown cutaneous wound healing potential in some preliminary studies. Here we hypothesize that bilirubin facilitates wound healing in diabetic rats by modulating important healing factors/candidates and antioxidant parameters in a time-dependent manner. Diabetes was induced in male Wistar rats by streptozotocin. In all diabetic rats wounds were created under pentobarbitone anesthesia. All the rats were divided into two groups, of which one (control) was treated with ointment base and other with bilirubin ointment (0.3%). Wound closer measurement and tissue collection were done on days 3, 7, 14 and 19 post-wounding. The relative expressions of hypoxia inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 alpha (SDF-1α), transforming growth factor- beta1 (TGF-β1()), tumor necrosis factor-α (TNF-α) and interlukin-10 (IL-10) mRNA and proteins and the mRNA of interlukin-1 beta (IL-1β) and matrix metalloprteinase-9 (MMP-9) were determined in the wound tissues. CD-31 staining and collagen content were evaluated by immunohistochemistry and picrosirius red staining, respectively. Histopathological changes were assessed by H&E staining. The per cent wound closer was significantly higher from day 7 onwards in bilirubin-treated rats. HIF-1α, VEGF, SDF-1α, TGF-β1, IL-10 mRNA and protein levels were significantly higher on days 3, 7 and 14 in bilirubin-treated rats. The mRNA expression and protein level of TNF-α and the mRNA of IL-1β and MMP-9 were progressively and markedly reduced in bilirubin-treated rats. The collagen deposition and formation of blood vessels were greater in bilirubin-treated rats. Bilirubin markedly facilitated cutaneous wound healing in diabetic rats by modulating growth factors, cytokines, neovasculogenesis and collagen contents to the wound site. Topical application of bilirubin ointment might be of great use in cutaneous wound healing in diabetic patients. Copyright © 2015