14 CFR 1274.701 - Suspension or termination.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Agreement if the recipient is not making anticipated technical progress, if the recipient materially changes...) Similarly, the recipient may terminate the agreement if, for example, technical progress is not being made, if the commercial recipient shifts its technical emphasis, or if other technological advances have...

14 CFR 1274.701 - Suspension or termination.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Agreement if the recipient is not making anticipated technical progress, if the recipient materially changes...) Similarly, the recipient may terminate the agreement if, for example, technical progress is not being made, if the commercial recipient shifts its technical emphasis, or if other technological advances have...

Computational Methods to Assess the Production Potential of Bio-Based Chemicals.

PubMed

Campodonico, Miguel A; Sukumara, Sumesh; Feist, Adam M; Herrgård, Markus J

2018-01-01

Elevated costs and long implementation times of bio-based processes for producing chemicals represent a bottleneck for moving to a bio-based economy. A prospective analysis able to elucidate economically and technically feasible product targets at early research phases is mandatory. Computational tools can be implemented to explore the biological and technical spectrum of feasibility, while constraining the operational space for desired chemicals. In this chapter, two different computational tools for assessing potential for bio-based production of chemicals from different perspectives are described in detail. The first tool is GEM-Path: an algorithm to compute all structurally possible pathways from one target molecule to the host metabolome. The second tool is a framework for Modeling Sustainable Industrial Chemicals production (MuSIC), which integrates modeling approaches for cellular metabolism, bioreactor design, upstream/downstream processes, and economic impact assessment. Integrating GEM-Path and MuSIC will play a vital role in supporting early phases of research efforts and guide the policy makers with decisions, as we progress toward planning a sustainable chemical industry.

Progress in Scientific and Technical Communications, 1968 Annual Report.

ERIC Educational Resources Information Center

Federal Council for Science and Technology, Washington, DC. Committee on Scientific and Technical Information.

This sixth annual report describes progress achieved by the Federal Government in improving the communication of scientific and technical information to support and enhance national science and technology. Included in the report are details regarding the scientific and technical activities of individual Federal Agencies, such as the Atomic Energy…

Biofuels from food processing wastes.

PubMed

Zhang, Zhanying; O'Hara, Ian M; Mundree, Sagadevan; Gao, Baoyu; Ball, Andrew S; Zhu, Nanwen; Bai, Zhihui; Jin, Bo

2016-04-01

Food processing industry generates substantial high organic wastes along with high energy uses. The recovery of food processing wastes as renewable energy sources represents a sustainable option for the substitution of fossil energy, contributing to the transition of food sector towards a low-carbon economy. This article reviews the latest research progress on biofuel production using food processing wastes. While extensive work on laboratory and pilot-scale biosystems for energy production has been reported, this work presents a review of advances in metabolic pathways, key technical issues and bioengineering outcomes in biofuel production from food processing wastes. Research challenges and further prospects associated with the knowledge advances and technology development of biofuel production are discussed. Copyright © 2016. Published by Elsevier Ltd.

A Comparison of Physical and Technical Performance Profiles Between Successful and Less-Successful Professional Rugby League Teams.

PubMed

Kempton, Thomas; Sirotic, Anita C; Coutts, Aaron J

2017-04-01

To examine differences in physical and technical performance profiles using a large sample of match observations drawn from successful and less-successful professional rugby league teams. Match activity profiles were collected using global positioning satellite (GPS) technology from 29 players from a successful rugby league team during 24 games and 25 players from a less-successful team during 18 games throughout 2 separate competition seasons. Technical performance data were obtained from a commercial statistics provider. A progressive magnitude-based statistical approach was used to compare differences in physical and technical performance variables between the reference teams. There were no clear differences in playing time, absolute and relative total distances, or low-speed running distances between successful and less-successful teams. The successful team possibly to very likely had lower higher-speed running demands and likely had fewer physical collisions than the less-successful team, although they likely to most likely demonstrated more accelerations and decelerations and likely had higher average metabolic power. The successful team very likely gained more territory in attack, very likely had more possessions, and likely committed fewer errors. In contrast, the less-successful team was likely required to attempt more tackles, most likely missed more tackles, and very likely had a lower effective tackle percentage. In the current study, successful match performance was not contingent on higher match running outputs or more physical collisions; rather, proficiency in technical performance components better differentiated successful and less-successful teams.

48 CFR 2452.242-71 - Contract management system.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., concise summary of technical progress made and the costs incurred for each task during the reporting... technical progress made for each task during the reporting period; and (B) Identifies problems, or potential... and progress reporting as described herein. (b) The contract management system shall consist of two...

Integrating Transcriptomics with Metabolic Modeling Predicts Biomarkers and Drug Targets for Alzheimer's Disease

PubMed Central

Stempler, Shiri; Yizhak, Keren; Ruppin, Eytan

2014-01-01

Accumulating evidence links numerous abnormalities in cerebral metabolism with the progression of Alzheimer's disease (AD), beginning in its early stages. Here, we integrate transcriptomic data from AD patients with a genome-scale computational human metabolic model to characterize the altered metabolism in AD, and employ state-of-the-art metabolic modelling methods to predict metabolic biomarkers and drug targets in AD. The metabolic descriptions derived are first tested and validated on a large scale versus existing AD proteomics and metabolomics data. Our analysis shows a significant decrease in the activity of several key metabolic pathways, including the carnitine shuttle, folate metabolism and mitochondrial transport. We predict several metabolic biomarkers of AD progression in the blood and the CSF, including succinate and prostaglandin D2. Vitamin D and steroid metabolism pathways are enriched with predicted drug targets that could mitigate the metabolic alterations observed. Taken together, this study provides the first network wide view of the metabolic alterations associated with AD progression. Most importantly, it offers a cohort of new metabolic leads for the diagnosis of AD and its treatment. PMID:25127241

ANNUAL REPORT, JULY 1, 1957

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

None

1958-10-31

The progress and trends of research are presented along with a description of operational, service, end administrative activities. Some scientific and technical details are given on research programs in the physical sciences, life sciences, and engineering, however, more complete technical information is available in quarterly progress reports, BNL technical reports, and scientific and technical periodicals. A bibliography of these publications is appended. (For preceding period see BNL-426.) (D.E.B.)

20 CFR 411.180 - What is timely progress toward self-supporting employment?

Code of Federal Regulations, 2010 CFR

2010-04-01

... certificate or vocational or technical training that will enhance your ability to return to work. In addition...-secondary education requirement or vocational or technical training requirement in the applicable progress... this 12-month period; or (iv) You must have been enrolled in a vocational or technical training program...

The metabolic co-regulator PGC1α suppresses prostate cancer metastasis

PubMed Central

Cortazar, Ana Rosa; Liu, Xiaojing; Urosevic, Jelena; Castillo-Martin, Mireia; Fernández-Ruiz, Sonia; Morciano, Giampaolo; Caro-Maldonado, Alfredo; Guiu, Marc; Zúñiga-García, Patricia; Graupera, Mariona; Bellmunt, Anna; Pandya, Pahini; Lorente, Mar; Martín-Martín, Natalia; Sutherland, James David; Sanchez-Mosquera, Pilar; Bozal-Basterra, Laura; Zabala-Letona, Amaia; Arruabarrena-Aristorena, Amaia; Berenguer, Antonio; Embade, Nieves; Ugalde-Olano, Aitziber; Lacasa-Viscasillas, Isabel; Loizaga-Iriarte, Ana; Unda-Urzaiz, Miguel; Schultz, Nikolaus; Aransay, Ana Maria; Sanz-Moreno, Victoria; Barrio, Rosa; Velasco, Guillermo; Pinton, Paolo; Cordon-Cardo, Carlos; Carracedo, Arkaitz

2016-01-01

Cellular transformation and cancer progression is accompanied by changes in the metabolic landscape. Master co-regulators of metabolism orchestrate the modulation of multiple metabolic pathways through transcriptional programs, and hence constitute a probabilistically parsimonious mechanism for general metabolic rewiring. Here we show that the transcriptional co-activator PGC1α suppresses prostate cancer progression and metastasis. A metabolic co-regulator data mining analysis unveiled that PGC1α is down-regulated in prostate cancer and associated to disease progression. Using genetically engineered mouse models and xenografts, we demonstrated that PGC1α opposes prostate cancer progression and metastasis. Mechanistically, the use of integrative metabolomics and transcriptomics revealed that PGC1α activates an Oestrogen-related receptor alpha (ERRα)-dependent transcriptional program to elicit a catabolic state and metastasis suppression. Importantly, a signature based on the PGC1α-ERRα pathway exhibited prognostic potential in prostate cancer, thus uncovering the relevance of monitoring and manipulating this pathway for prostate cancer stratification and treatment. PMID:27214280

76 FR 57057 - International Cooperation on Harmonisation of Technical Requirements for Registration of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-15

... Drugs in Food-Producing Animals: Comparative Metabolism Studies in Laboratory Animals; Availability...: Comparative Metabolism Studies in Laboratory Animals'' (VICH GL47). This guidance has been developed for... Metabolism and Residue Kinetics of Veterinary Drugs in Food- Producing Animals: Comparative Metabolism...

The Changes They are A-Timed: Metabolism, Endogenous Clocks, and the Timing of Puberty

PubMed Central

Tolson, Kristen P.; Chappell, Patrick E.

2012-01-01

Childhood obesity has increased dramatically over the last several decades, particularly in industrialized countries, often accompanied by acceleration of pubertal progression and associated reproductive abnormalities (Biro et al., 2006; Rosenfield et al., 2009). The timing of pubertal initiation and progression in mammals is likely influenced by nutritional and metabolic state, leading to the hypothesis that deviations from normal metabolic rate, such as those seen in obesity, may contribute to observed alterations in the rate of pubertal progression. While several recent reviews have addressed the effects of metabolic disorders on reproductive function in general, this review will explore previous and current models of pubertal timing, outlining a potential role of endogenous timing mechanisms such as cellular circadian clocks in the initiation of puberty, and how these clocks might be altered by metabolic factors. Additionally, we will examine recently elucidated neuroendocrine regulators of pubertal progression such as kisspeptin, explore models detailing how the mammalian reproductive axis is silenced during the juvenile period and reactivated at appropriate developmental times, and emphasize how metabolic dysfunction such as childhood obesity may alter timing cues that advance or delay pubertal progression, resulting in diminished reproductive capacity. PMID:22645521

Serum metabolomics of slow vs. rapid motor progression Parkinson's disease: a pilot study.

PubMed

Roede, James R; Uppal, Karan; Park, Youngja; Lee, Kichun; Tran, Vilinh; Walker, Douglas; Strobel, Frederick H; Rhodes, Shannon L; Ritz, Beate; Jones, Dean P

2013-01-01

Progression of Parkinson's disease (PD) is highly variable, indicating that differences between slow and rapid progression forms could provide valuable information for improved early detection and management. Unfortunately, this represents a complex problem due to the heterogeneous nature of humans in regards to demographic characteristics, genetics, diet, environmental exposures and health behaviors. In this pilot study, we employed high resolution mass spectrometry-based metabolic profiling to investigate the metabolic signatures of slow versus rapidly progressing PD present in human serum. Archival serum samples from PD patients obtained within 3 years of disease onset were analyzed via dual chromatography-high resolution mass spectrometry, with data extraction by xMSanalyzer and used to predict rapid or slow motor progression of these patients during follow-up. Statistical analyses, such as false discovery rate analysis and partial least squares discriminant analysis, yielded a list of statistically significant metabolic features and further investigation revealed potential biomarkers. In particular, N8-acetyl spermidine was found to be significantly elevated in the rapid progressors compared to both control subjects and slow progressors. Our exploratory data indicate that a fast motor progression disease phenotype can be distinguished early in disease using high resolution mass spectrometry-based metabolic profiling and that altered polyamine metabolism may be a predictive marker of rapidly progressing PD.

Evaporation by mechanical vapor recompression. Technical progress report, September 1-December 31, 1979

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

Iverson, C.H.; Coury, G.E.

1979-01-01

Progress to date in the development of a study of the application of the technologies of mechanical vapor recompression and falling film evaporators as applied to the beet sugar industry is reported. Progress is reported in the following areas: technical literature search and plant visitations of existing applications of VR/FFE.

25 CFR 30.109 - Will the Secretary provide assistance in developing an alternative AYP definition?

Code of Federal Regulations, 2011 CFR

2011-04-01

... EDUCATION ADEQUATE YEARLY PROGRESS Defining Adequate Yearly Progress Technical Assistance § 30.109 Will the... Bureau, shall provide technical assistance either directly or through contract to the tribal governing...

25 CFR 30.109 - Will the Secretary provide assistance in developing an alternative AYP definition?

Code of Federal Regulations, 2010 CFR

2010-04-01

... EDUCATION ADEQUATE YEARLY PROGRESS Defining Adequate Yearly Progress Technical Assistance § 30.109 Will the... Bureau, shall provide technical assistance either directly or through contract to the tribal governing...

The fate of technical-grade chlordane in mice fed a high-fat diet and its roles as a candidate obesogen.

PubMed

Wang, Dezhen; Wang, Xinru; Zhang, Ping; Wang, Yao; Zhang, Renke; Yan, Jin; Zhou, Zhiqiang; Zhu, Wentao

2017-03-01

Epidemiological studies indicate that exposure to persistent organic pollutants is positively associated with the prevalence of obesity. To delineate the potential role of technical-grade chlordane in obesity development, chlordane metabolism and chlordane-induced metabolic changes were investigated in mice fed high-fat diet (HFD) over a 6-week period. Gas chromatography-electron capture detector analysis showed that HFD induced more accumulation of technical chlordane in the liver, muscle and adipose tissue. The enantioselectivities of oxychlordane in selected tissues were also influenced by HFD. 1 H NMR-based liver metabolome indicated that technical chlordane can enhance the metabolic alterations induced by HFD. Compared with the low-fat diet (LFD) group, no differences were observed in the LFD + chlordane group. However, as many as 16 metabolites were significantly different between the HFD group and HFD + chlordane group. Moreover, compared to the LFD + chlordane group, the abundances of 24 metabolites significantly increased or decreased in the HFD + chlordane group. Twenty metabolites were altered in the HFD group compared to the LFD group. Tryptophan profiling suggested that both chlordane and HFD can disturb tryptophan catabolism. These interactions between technical chlordane and HFD suggest that technical chlordane is a candidate obesogen. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Role of Central Metabolism in Prostate Cancer Progression

DTIC Science & Technology

2012-07-01

AD_________________ Award Number: W81XWH-08-1-0694 TITLE: The Role of Central Metabolism in Prostate...SUBTITLE The Role of Central Metabolism in Prostate Cancer Progression 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-08-1-0694 5c. PROGRAM...examine the excised prostate tissue for differences in tumor growth, proteomes and intermediates in polyunsaturated fatty acid (PUFA) metabolism . The

Building a Better Canine Warrior

DTIC Science & Technology

2017-10-12

without adversely affecting pe r formance and to develop technical methodology that would dissipate metabolic heat without the expense o f body water...technical methodology that would dissipate metabolic heat without the expense of body water. Neither an increase in dietary salt nor decrease in...from a methodological aspect as well as emerging regulatory issues related to research in working dogs. Data suggested that the effect of high

Metabolic abnormalities in pituitary adenoma patients: a novel therapeutic target and prognostic factor

PubMed Central

Zheng, Xin; Li, Song; Zhang, Wei-hua; Yang, Hui

2015-01-01

Metabolic abnormalities are common in cancers, and targeting metabolism is emerging as a novel therapeutic approach to cancer management. Pituitary adenoma (PA) is a type of benign tumor. Impairment of tumor cells’ metabolism in PA seems not to be as apparent as that of other malignant tumor cells; however, aberrant hormone secretion is conspicuous in most PAs. Hormones have direct impacts on systemic metabolism, which in turn, may affect the progression of PA. Nowadays, conventional therapeutic strategies for PA do not include modalities of adjusting whole-body metabolism, which is most likely due to the current consideration of the aberrant whole-body metabolism of PA patients as a passive associated symptom and not involved in PA progression. Because systemic metabolic abnormalities are presented by 22.3%–52.5% PA patients and are closely correlated with disease progression and prognosis, we propose that assessment of metabolic status should be emphasized during the treatment of PA and that control of metabolic abnormalities should be added into the current therapies for PA. PMID:26347444

Current Trends and Innovations in Bioanalytical Techniques of Metabolomics.

PubMed

Zhang, Tianlei; Zhang, Aihua; Qiu, Shi; Yang, Suqing; Wang, Xijun

2016-07-03

The advancement of omics technology has vigorously promoted the development of the life sciences; metabolomics in particular has emerged as a powerful tool that has a promising future in scientific research and clinical practice. As terminal products of complex biochemical networks, endogenous low-molecular-weight metabolites contain rich information about the physiological status of an individual or group of people. Also, this information has more practical significance in that we know "what happened" instead of "what might happen" to some degree. Rapid and accurate screening of metabolites on a large scale was beyond imagining in the past; however, benefiting from high-throughput technical means, the overall disturbance of metabolites induced by environmental stimulus or treatments can now be well analyzed. After appropriate bioinformatic analysis, clinically relevant biomarkers of a disease can be found, and an accurate and dynamic picture of metabolic disturbance that contributes to a phenotype of a certain organism can be constructed. Biomarkers can also reveal the general metabolic condition by pathways that correlate with disease progression, or even with the risk of certain diseases. Thus, as an indispensable part of the framework of systems biology, metabolomics has been widely used in, but not limited to, the fields of medical science, pharmaceuticals, botany, and microbiology. In this article, we focus on metabolomics' mainstream research content and technical innovations such as determination methods for biologically active compounds; further, we pay more attention to the future trends and various possibilities for metabolomics study.

Monitoring the Durability Performance of Concrete in Nuclear Waste Containment. Technical Progress Report No. 3

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

Ulm, Franz-Josef

2000-03-31

OAK-B135 Monitoring the Durability Performance of Concrete in Nuclear Waste Containment. Technical Progress Report No. 3(NOTE: Part II A item 1 indicates ''PAPER'', but a report is attached electronically)

Crosscutting Technology Development at the Center for Advanced Separation Technologies

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

Christopher E. Hull

2006-09-30

This Technical Progress Report describes progress made on the twenty nine subprojects awarded in the second year of Cooperative Agreement DE-FC26-02NT41607: Crosscutting Technology Development at the Center for Advanced Separation Technologies. This work is summarized in the body of the main report: the individual sub-project Technical Progress Reports are attached as Appendices.

CROSSCUTTING TECHNOLOGY DEVELOPMENT AT THE CENTER FOR ADVANCED SEPARATION TECHNOLOGIES

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

Christopher E. Hull

2006-05-15

This Technical Progress Report describes progress made on the twenty nine subprojects awarded in the second year of Cooperative Agreement DE-FC26-02NT41607: Crosscutting Technology Development at the Center for Advanced Separation Technologies. This work is summarized in the body of the main report: the individual sub-project Technical Progress Reports are attached as Appendices.

The Development and Technical Adequacy of Seventh-Grade Reading Comprehension Measures in a Progress Monitoring Assessment System. Technical Report #1102

ERIC Educational Resources Information Center

Park, Bitnara Jasmine; Alonzo, Julie; Tindal, Gerald

2011-01-01

This technical report describes the process of development and piloting of reading comprehension measures that are appropriate for seventh-grade students as part of an online progress screening and monitoring assessment system, http://easycbm.com. Each measure consists of an original fictional story of approximately 1,600 to 1,900 words with 20…

Generation and focusing of pulsed intense ion beams. Technical progress report, 1 October 1982 - 30 September, 1983

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

Hammer, D.A.; Kusse, B.R.; Sudan, R.N.

1983-07-01

The progress on this contract is described in three parts. The first deals with the technical operation of the LION accelerator. The second and third parts are concerned with the experimental results.

The Role of Central Metabolism in Prostate Cancer Progression

DTIC Science & Technology

2009-10-01

metabolites of dietary ω-3 and - 6 PUFAs directly affect PCa and the ability to do so depends on intake and metabolic enzyme expression. Omega -3 and - 6 ...The Role of Central Metabolism in Prostate Cancer Progression 5b. GRANT NUMBER W81XWH-08-1-0694 5c. PROGRAM ELEMENT NUMBER 6 . AUTHOR(S) Thomas...ABSTRACT We hypothesize that by enriching the diet with -3 PUFAs PCa tumor progression will be significantly reduced. Patients with localized PCa

[Regulation of terpene metabolism]. Annual progress report, March 15, 1988--March 14, 1989

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

Croteau, R.

1989-12-31

Progress in understanding of the metabolism of monoterpenes by peppermint and spearmint is recorded including the actions of two key enzymes, geranyl pyrophosphate:limonene cyclase and a UDP-glucose dependent glucosyl transferase; concerning the ultrastructure of oil gland senescence; enzyme subcellular localization; regulation of metabolism; and tissue culture systems.

The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Kindergarten. Technical Report # 0921

ERIC Educational Resources Information Center

Alonzo, Julie; Tindal, Gerald

2009-01-01

In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in kindergarten. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2008 and administered to approximately 2800 students from…

Assessment Program Technical Progress Report, 1996-1997.

ERIC Educational Resources Information Center

McCown, Laurie; Fanning, Erin; Eickmeyer, Barbara

Coconino Community College (CCC) annually assesses its institutional effectiveness to demonstrate its commitment to improving programs and services to students. The 1996-97 Assessment Program Technical Progress Report records the assessment and institutional activities enacted during the academic year, detailing the assessment model, timelines,…

The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 1. Technical Report # 0919

ERIC Educational Resources Information Center

Alonzo, Julie; Tindal, Gerald

2009-01-01

In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grade 1. These measures, available as part of easyCBM [TM], an online progress monitoring assessment system, were developed in 2008 and administered to approximately 2800 students from schools…

The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 3. Technical Report # 09-02

ERIC Educational Resources Information Center

Alonzo, Julie; Lai, Cheng Fei; Tindal, Gerald

2009-01-01

In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grades kindergarten through eighth grade. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2007 and 2008 and administered to…

The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 2. Technical Report # 0920

ERIC Educational Resources Information Center

Alonzo, Julie; Lai, Cheng Fei; Tindal, Gerald

2009-01-01

In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grades kindergarten through eighth grade. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2007 and 2008 and administered to…

The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 5. Technical Report # 09-01

ERIC Educational Resources Information Center

Lai, Cheng Fei; Alonzo, Julie; Tindal, Gerald

2009-01-01

In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grades kindergarten through eighth grade. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2007 and 2008 and administered to…

The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 4. Technical Report # 09-03

ERIC Educational Resources Information Center

Alonzo, Julie; Lai, Cheng Fei; Tindal, Gerald

2009-01-01

In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grades kindergarten through eighth grade. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2007 and 2008 and administered to…

The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 7. Technical Report 0908

ERIC Educational Resources Information Center

Lai, Cheng Fei; Alonzo, Julie; Tindal, Gerald

2009-01-01

In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grades kindergarten through eighth grade. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2007 and 2008 and administered to…

The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 8. Technical Report # 09-04

ERIC Educational Resources Information Center

Lai, Cheng Fei; Alonzo, Julie; Tindal, Gerald

2009-01-01

In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grades kindergarten through eighth grade. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2007 and 2008 and administered to…

[Research Progress on Metabolic Regulatory Mechanisms of Hematopoietic Stem Cells -Review].

PubMed

Zhang, Ya-Wen; Cheng, Hui; Cheng, Tao

2018-06-01

Hematopoietic stem cells (HSC) are a class of stem cells with self-renewal and multipotent differentiation into a variety of blood cells and are most thoroughly studied, maturely applied in the clinic adult stem cell. Function of HSC is closely associated with metabolic regulation. The metabolic state mainly maintains HSC living in hypoxic bone marrow microenvironment depending on glycolysis for energy metabolism, and keeping low reactive oxygen species (ROS) level. Proteins like Hif-1, FoxO3, ATM, PTPMT1 protect HSC from ROS injury, maintaining HSC in hypoxic state. In addition, glucose metabolism-related enzymes, glutamine, fatty acid oxidation, purine and amino acid metabolism also play important roles in metabolic regulation of HSC. In this review the research progress on metabolism regnlation mechanisms of HSC is summurized, focusing on the mechanisms releted with oxydation metabolism regulation, carbohydrate metabolism level, purine metabolism and aminoacide metabolism.

Metabolomic analysis reveals altered metabolic pathways in a rat model of gastric carcinogenesis.

PubMed

Gu, Jinping; Hu, Xiaomin; Shao, Wei; Ji, Tianhai; Yang, Wensheng; Zhuo, Huiqin; Jin, Zeyu; Huang, Huiying; Chen, Jiacheng; Huang, Caihua; Lin, Donghai

2016-09-13

Gastric cancer (GC) is one of the most malignant tumors with a poor prognosis. Alterations in metabolic pathways are inextricably linked to GC progression. However, the underlying molecular mechanisms remain elusive. We performed NMR-based metabolomic analysis of sera derived from a rat model of gastric carcinogenesis, revealed significantly altered metabolic pathways correlated with the progression of gastric carcinogenesis. Rats were histologically classified into four pathological groups (gastritis, GS; low-grade gastric dysplasia, LGD; high-grade gastric dysplasia, HGD; GC) and the normal control group (CON). The metabolic profiles of the five groups were clearly distinguished from each other. Furthermore, significant inter-metabolite correlations were extracted and used to reconstruct perturbed metabolic networks associated with the four pathological stages compared with the normal stage. Then, significantly altered metabolic pathways were identified by pathway analysis. Our results showed that oxidative stress-related metabolic pathways, choline phosphorylation and fatty acid degradation were continually disturbed during gastric carcinogenesis. Moreover, amino acid metabolism was perturbed dramatically in gastric dysplasia and GC. The GC stage showed more changed metabolite levels and more altered metabolic pathways. Two activated pathways (glycolysis; glycine, serine and threonine metabolism) substantially contributed to the metabolic alterations in GC. These results lay the basis for addressing the molecular mechanisms underlying gastric carcinogenesis and extend our understanding of GC progression.

Development and Validation of a Novel Scoring System for Predicting Technical Success of Chronic Total Occlusion Percutaneous Coronary Interventions: The PROGRESS CTO (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention) Score.

PubMed

Christopoulos, Georgios; Kandzari, David E; Yeh, Robert W; Jaffer, Farouc A; Karmpaliotis, Dimitri; Wyman, Michael R; Alaswad, Khaldoon; Lombardi, William; Grantham, J Aaron; Moses, Jeffrey; Christakopoulos, Georgios; Tarar, Muhammad Nauman J; Rangan, Bavana V; Lembo, Nicholas; Garcia, Santiago; Cipher, Daisha; Thompson, Craig A; Banerjee, Subhash; Brilakis, Emmanouil S

2016-01-11

This study sought to develop a novel parsimonious score for predicting technical success of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) performed using the hybrid approach. Predicting technical success of CTO PCI can facilitate clinical decision making and procedural planning. We analyzed clinical and angiographic parameters from 781 CTO PCIs included in PROGRESS CTO (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention) using a derivation and validation cohort (2:1 sampling ratio). Variables with strong association with technical success in multivariable analysis were assigned 1 point, and a 4-point score was developed from summing all points. The PROGRESS CTO score was subsequently compared with the J-CTO (Multicenter Chronic Total Occlusion Registry in Japan) score in the validation cohort. Technical success was 92.9%. On multivariable analysis, factors associated with technical success included proximal cap ambiguity (beta coefficient [b] = 0.88), moderate/severe tortuosity (b = 1.18), circumflex artery CTO (b = 0.99), and absence of "interventional" collaterals (b = 0.88). The resulting score demonstrated good calibration and discriminatory capacity in the derivation (Hosmer-Lemeshow chi-square = 2.633; p = 0.268, and receiver-operator characteristic [ROC] area = 0.778) and validation (Hosmer-Lemeshow chi-square = 5.333; p = 0.070, and ROC area = 0.720) subset. In the validation cohort, the PROGRESS CTO and J-CTO scores performed similarly in predicting technical success (ROC area 0.720 vs. 0.746, area under the curve difference = 0.026, 95% confidence interval = -0.093 to 0.144). The PROGRESS CTO score is a novel useful tool for estimating technical success in CTO PCI performed using the hybrid approach. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Current advances in transdermal delivery of drugs for Alzheimer's disease.

PubMed

Nguyen, Thuy Trang; Giau, Vo Van; Vo, Tuong Kha

2017-01-01

Alzheimer's disease (AD) is a common, progressive, fatal neurodegenerative disorder, which will play an increasingly important role both socially and financially in the aging populations. Treatments for AD show modest improvements in cognition and global functioning among patients. Furthermore, the oral administration of treating AD has had some drawbacks that decrease the medication adherence and efficacy of the therapy. Transdermal drugs are proposed as an alternative remedy to overcome the disadvantages of current pharmaceutical dosage options for this chronic disorder. They could have different strengths, such as offering a stable diffusion of active substance, avoiding the first pass metabolism, and reducing system adverse reactions. This article reviews the technical principles, novel techniques of transdermal delivery drug, and prospects for future development for the management of cognitive and behavioral dysfunctions in AD patients.

Solo Single-Incision Laparoscopic Resectional Roux-en-Y Gastric Bypass for Morbid Obesity with Metabolic Syndrome.

PubMed

Kang, So Hyun; Lee, Yoontaek; Park, Young Suk; Ahn, Sang-Hoon; Park, Do Joong; Kim, Hyung-Ho

2017-12-01

With the advancement of laparoscopic devices and surgical technology, the era of minimal invasive surgery has progressed to reduced-port surgery, and finally to single-incision laparoscopic surgery (SILS). Several reports show successful application of SILS to various types of bariatric surgery. Oftentimes, this requires a skilled and experienced scopist to perform the procedure. To overcome the technical difficulties of single-incision Roux-en-Y gastric bypass, a manual scope holder was used instead of an assistant scopist, greatly stabilizing the field of view. This allows the surgery to be performed at any time without being influenced by the need of a highly experienced scopist. In this report, we describe in detail the world's first solo single-incision laparoscopic resectional Roux-en-Y gastric bypass.

Final report : for the period of December 1999 through November 30, 2000 : Florida Transit Training Program (1999/2000) : Florida Technical Assistance Program (1999/2000)

DOT National Transportation Integrated Search

2000-01-01

The following progress report is intended to highlight the significant activities of the Florida Transit Training Program and Florida Technical Assistant Program. The following progress report is intended to highlight the significant activities of th...

Annual progress report : for the period of January 2001 through December 2001 : Florida Transit Training Program (2001) : Florida Technical Assistance Program (2001)

DOT National Transportation Integrated Search

2001-01-01

The following progress report is intended to highlight the significant activities of the Florida Transit Training Program and Florida Technical Assistant Program for the 2001 year. Activities of the Florida Statewide Transit Training Program are pres...

76 FR 64083 - Reliability Technical Conference; Notice of Technical Conference

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-17

... Technical Conference; Notice of Technical Conference Take notice that the Federal Energy Regulatory Commission will hold a Technical Conference on Tuesday, November 29, 2011, from 1 p.m. to 5 p.m. and... System. The conference will explore the progress made on the priorities for addressing risks to...

48 CFR 2052.211-70 - Preparation of technical reports.

Code of Federal Regulations, 2014 CFR

2014-10-01

....211-70 Preparation of technical reports. As prescribed at 2011.104-70(a), the contracting officer... Reports (JAN 1993) All technical reports required by Section C and all Technical Progress Reports required... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Preparation of technical...

48 CFR 2052.211-70 - Preparation of technical reports.

Code of Federal Regulations, 2012 CFR

2012-10-01

....211-70 Preparation of technical reports. As prescribed at 2011.104-70(a), the contracting officer... Reports (JAN 1993) All technical reports required by Section C and all Technical Progress Reports required... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Preparation of technical...

48 CFR 2052.211-70 - Preparation of technical reports.

Code of Federal Regulations, 2010 CFR

2010-10-01

....211-70 Preparation of technical reports. As prescribed at 2011.104-70(a), the contracting officer... Reports (JAN 1993) All technical reports required by Section C and all Technical Progress Reports required... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Preparation of technical...

48 CFR 2052.211-70 - Preparation of technical reports.

Code of Federal Regulations, 2013 CFR

2013-10-01

....211-70 Preparation of technical reports. As prescribed at 2011.104-70(a), the contracting officer... Reports (JAN 1993) All technical reports required by Section C and all Technical Progress Reports required... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Preparation of technical...

48 CFR 2052.211-70 - Preparation of technical reports.

Code of Federal Regulations, 2011 CFR

2011-10-01

....211-70 Preparation of technical reports. As prescribed at 2011.104-70(a), the contracting officer... Reports (JAN 1993) All technical reports required by Section C and all Technical Progress Reports required... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Preparation of technical...

The Role of Mitochondria in Cancer Induction, Progression and Changes in Metabolism.

PubMed

Rogalinska, Malgorzata

2016-01-01

Mitochondria play important roles as energetic centers. Mutations in mitochondrial DNA (mtDNA) were found in several diseases, including cancers. Studies on cytoplasmic hybrids (cybrids) confirm that directed mutation introduced into mtDNA could be a reason for cancer induction. Mitochondria could also be a factor linking cancer transformation and progression. The importance of mitochondria in cancer also confirms their involvement in the resistance to treatment. Resistance to treatment of cancer cells can frequently be a reason for glycolysis acceleration. It could be explained by cancer cells' high proliferation index and high energy request. The involvement of mitochondria in metabolic disturbances of several metabolic diseases, including cancers, was reported. These data confirm that cancer induction, as well as cancer progression, could have metabolic roots. The aberrant products observed in prostate cells involved in the Krebs cycle could promote cancer progression. These multiple relationships between alterations on a genetic level translated into disturbances in cellular metabolism and their potential relation with epigenetic control of gene expression make cancerogenesis more complicated and prognoses' success in studies on cancer etiology more distant in time.

[THE FACTORS OF THE PROGRESSION OF METABOLIC DISORDERS IN THE PANCREAS IN PATIENTS WITH ASSOCIATED CLINICAL VARIANTS OF THE CHRONIC PANCREATITIS AND TYPE 2 DIABETES MELLITUS].

PubMed

Zhuravlyova, L V; Shekhovtsova, Y O

2015-01-01

The purpose of the present study was to determine the causal factors of the progression of metabolic disorders in pancreatic tissue and their relationships in patients with assotiated clinical variants of chronic pancreatitis (CP) and type 2 diabetes mellitus (T2DM). The study involved of 76 patients with CP and T2DM. The causes of progression of metabolic disorders in the pancreas in patients with associated clinical variants of CP and T2DM has been analyzed. The most significant of them were insulin resistance and abdominal obesity, which promotes early formation of the metabolic syndrome and the activation of fibrogenesis and steatosis in the pancreas and is caused by dyslipidemia, impaired glucose metabolism and the development of systemic inflammation and imbalance of adipocytokines. The relationships between adipocytokines, body weight and individual components of the metabolic syndrome in patients with CP and T2DM suggests the involvement of these hormones of adipose tissue in the formation of the metabolic syndrome and its components.

75 FR 18507 - International Cooperation on Harmonisation of Technical Requirements for Registration of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-12

... Veterinary Drugs in Food-Producing Animals: Comparative Metabolism Studies in Laboratory Animals (VICH GL47... Food-Producing Animals: Comparative Metabolism Studies in Laboratory Animals,'' VICH GL47. This draft... Food-Producing Animals: Comparative Metabolism Studies in Laboratory Animals,'' VICH GL47. In recent...

Metabolic brain networks in aging and preclinical Alzheimer's disease.

PubMed

Arnemann, Katelyn L; Stöber, Franziska; Narayan, Sharada; Rabinovici, Gil D; Jagust, William J

2018-01-01

Metabolic brain networks can provide insight into the network processes underlying progression from healthy aging to Alzheimer's disease. We explore the effect of two Alzheimer's disease risk factors, amyloid-β and ApoE ε4 genotype, on metabolic brain networks in cognitively normal older adults (N = 64, ages 69-89) compared to young adults (N = 17, ages 20-30) and patients with Alzheimer's disease (N = 22, ages 69-89). Subjects underwent MRI and PET imaging of metabolism (FDG) and amyloid-β (PIB). Normal older adults were divided into four subgroups based on amyloid-β and ApoE genotype. Metabolic brain networks were constructed cross-sectionally by computing pairwise correlations of metabolism across subjects within each group for 80 regions of interest. We found widespread elevated metabolic correlations and desegregation of metabolic brain networks in normal aging compared to youth and Alzheimer's disease, suggesting that normal aging leads to widespread loss of independent metabolic function across the brain. Amyloid-β and the combination of ApoE ε4 led to less extensive elevated metabolic correlations compared to other normal older adults, as well as a metabolic brain network more similar to youth and Alzheimer's disease. This could reflect early progression towards Alzheimer's disease in these individuals. Altered metabolic brain networks of older adults and those at the highest risk for progression to Alzheimer's disease open up novel lines of inquiry into the metabolic and network processes that underlie normal aging and Alzheimer's disease.

REACTOR PHYSICS QUARTERLY REPORT JANUARY, FEBRUARY, MARCH 1970

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

Schmid, L. C.; Clayton, E. D.; Heineman, R. E.

1970-05-01

The objective of the Reactor Physics Quarterly Report is to inform the scientific community in a timely manner of the technical progress made on the many phases of reactor physics work within the laboratory. The report contains brief technical discussions of accomplishments in all areas where significant progress has been made during the quarter.

George A. Olah, Carbocation and Hydrocarbon Chemistry

Science.gov Websites

. Final Technical Report. [HF:BF{sub 2}/H{sub 2}] , DOE Technical Report, 1980 Superacid Catalyzed Coal Conversion Chemistry. 1st and 2nd Quarterly Technical Progress Reports, September 1, 1983-March 30, 1984 , DOE Technical Report, 1984 Superacid Catalyzed Coal Conversion Chemistry. Final Technical Report

HKHC Community Dashboard: design, development, and function of a Web-based performance monitoring system.

PubMed

Bors, Philip A; Kemner, Allison; Fulton, John; Stachecki, Jessica; Brennan, Laura K

2015-01-01

As part of Robert Wood Johnson Foundation's Healthy Kids, Healthy Communities (HKHC) national grant program, a technical assistance team designed the HKHC Community Dashboard, an online progress documentation and networking system. The Dashboard was central to HKHC's multimethod program evaluation and became a communication interface for grantees and technical assistance providers. The Dashboard was designed through an iterative process of identifying needs and priorities; designing the user experience, technical development, and usability testing; and applying visual design. The system was created with an open-source content management system and support for building an online community of users. The site developer trained technical assistance providers at the national program office and evaluators, who subsequently trained all 49 grantees. Evaluators provided support for Dashboard users and populated the site with the bulk of its uploaded tools and resource documents. The system tracked progress through an interactive work plan template, regular documentation by local staff and partners, and data coding and analysis by the evaluation team. Other features included the ability to broadcast information to Dashboard users via e-mail, event calendars, discussion forums, private messaging, a resource clearinghouse, a technical assistance diary, and real-time progress reports. The average number of Dashboard posts was 694 per grantee during the grant period. Technical assistance providers and grantees uploaded a total of 1304 resource documents. The Dashboard functions with the highest grantee satisfaction were its interfaces for sharing and progress documentation. A majority of Dashboard users (69%) indicated a preference for continued access to the Dashboard's uploaded resource documents. The Dashboard was a useful and innovative tool for participatory evaluation of a large national grant program. While progress documentation added some burden to local project staff, the system proved to be a useful resource-sharing technology.

Modeling the impacts of climate change and technical progress on the wheat yield in inland China: An autoregressive distributed lag approach.

PubMed

Zhai, Shiyan; Song, Genxin; Qin, Yaochen; Ye, Xinyue; Lee, Jay

2017-01-01

This study aims to evaluate the impacts of climate change and technical progress on the wheat yield per unit area from 1970 to 2014 in Henan, the largest agricultural province in China, using an autoregressive distributed lag approach. The bounded F-test for cointegration among the model variables yielded evidence of a long-run relationship among climate change, technical progress, and the wheat yield per unit area. In the long run, agricultural machinery and fertilizer use both had significantly positive impacts on the per unit area wheat yield. A 1% increase in the aggregate quantity of fertilizer use increased the wheat yield by 0.19%. Additionally, a 1% increase in machine use increased the wheat yield by 0.21%. In contrast, precipitation during the wheat growth period (from emergence to maturity, consisting of the period from last October to June) led to a decrease in the wheat yield per unit area. In the short run, the coefficient of the aggregate quantity of fertilizer used was negative. Land size had a significantly positive impact on the per unit area wheat yield in the short run. There was no significant short-run or long-run impact of temperature on the wheat yield per unit area in Henan Province. The results of our analysis suggest that climate change had a weak impact on the wheat yield, while technical progress played an important role in increasing the wheat yield per unit area. The results of this study have implications for national and local agriculture policies under climate change. To design well-targeted agriculture adaptation policies for the future and to reduce the adverse effects of climate change on the wheat yield, climate change and technical progress factors should be considered simultaneously. In addition, adaptive measures associated with technical progress should be given more attention.

Modeling the impacts of climate change and technical progress on the wheat yield in inland China: An autoregressive distributed lag approach

PubMed Central

Qin, Yaochen; Lee, Jay

2017-01-01

This study aims to evaluate the impacts of climate change and technical progress on the wheat yield per unit area from 1970 to 2014 in Henan, the largest agricultural province in China, using an autoregressive distributed lag approach. The bounded F-test for cointegration among the model variables yielded evidence of a long-run relationship among climate change, technical progress, and the wheat yield per unit area. In the long run, agricultural machinery and fertilizer use both had significantly positive impacts on the per unit area wheat yield. A 1% increase in the aggregate quantity of fertilizer use increased the wheat yield by 0.19%. Additionally, a 1% increase in machine use increased the wheat yield by 0.21%. In contrast, precipitation during the wheat growth period (from emergence to maturity, consisting of the period from last October to June) led to a decrease in the wheat yield per unit area. In the short run, the coefficient of the aggregate quantity of fertilizer used was negative. Land size had a significantly positive impact on the per unit area wheat yield in the short run. There was no significant short-run or long-run impact of temperature on the wheat yield per unit area in Henan Province. The results of our analysis suggest that climate change had a weak impact on the wheat yield, while technical progress played an important role in increasing the wheat yield per unit area. The results of this study have implications for national and local agriculture policies under climate change. To design well-targeted agriculture adaptation policies for the future and to reduce the adverse effects of climate change on the wheat yield, climate change and technical progress factors should be considered simultaneously. In addition, adaptive measures associated with technical progress should be given more attention. PMID:28950027

Supply Chain Sustainability Analysis of Whole Algae Hydrothermal Liquefaction and Upgrading

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

Pegallapati, Ambica Koushik; Dunn, Jennifer B.; Frank, Edward D.

2015-04-01

The Department of Energy's Bioenergy Technology Office (BETO) collaborates with a wide range of institutions towards the development and deployment of biofuels and bioproducts. To facilitate this effort, BETO and its partner national laboratories develop detailed techno-economic assessments (TEA) of biofuel production technologies as part of the development of design cases and state of technology (SOT) analyses. A design case is a TEA that outlines a target case for a particular biofuel pathway. It enables preliminary identification of data gaps and research and development needs and provides goals and targets against which technology progress is assessed. On the other hand,more » an SOT analysis assesses progress within and across relevant technology areas based on actual experimental results relative to technical targets and cost goals from design cases and includes technical, economic, and environmental criteria as available. (SOT) analyses. A design case is a TEA that outlines a target case for a particular biofuel pathway. It enables preliminary identification of data gaps and research and development needs and provides goals and targets against which technology progress is assessed. On the other hand, an SOT analysis assesses progress within and across relevant technology areas based on actual experimental results relative to technical targets and cost goals from design cases and includes technical, economic, and environmental criteria as available. (SOT) analyses. A design case is a TEA that outlines a target case for a particular biofuel pathway. It enables preliminary identification of data gaps and research and development needs and provides goals and targets against which technology progress is assessed. On the other hand, an SOT analysis assesses progress within and across relevant technology areas based on actual experimental results relative to technical targets and cost goals from design cases and includes technical, economic, and environmental criteria as available.« less

One-Carbon Metabolism in Prostate Cancer: The Role of Androgen Signaling

PubMed Central

Corbin, Joshua M.; Ruiz-Echevarría, Maria J.

2016-01-01

Cancer cell metabolism differs significantly from the metabolism of non-transformed cells. This altered metabolic reprogramming mediates changes in the uptake and use of nutrients that permit high rates of proliferation, growth, and survival. The androgen receptor (AR) plays an essential role in the establishment and progression of prostate cancer (PCa), and in the metabolic adaptation that takes place during this progression. In its role as a transcription factor, the AR directly affects the expression of several effectors and regulators of essential catabolic and biosynthetic pathways. Indirectly, as a modulator of the one-carbon metabolism, the AR can affect epigenetic processes, DNA metabolism, and redox balance, all of which are important factors in tumorigenesis. In this review, we focus on the role of AR-signaling on one-carbon metabolism in tumorigenesis. Clinical implications of one-carbon metabolism and AR-targeted therapies for PCa are discussed in this context. PMID:27472325

Obesity and Cancer Progression: Is There a Role of Fatty Acid Metabolism?

PubMed Central

Balaban, Seher; Lee, Lisa S.; Schreuder, Mark; Hoy, Andrew J.

2015-01-01

Currently, there is renewed interest in elucidating the metabolic characteristics of cancer and how these characteristics may be exploited as therapeutic targets. Much attention has centered on glucose, glutamine and de novo lipogenesis, yet the metabolism of fatty acids that arise from extracellular, as well as intracellular, stores as triacylglycerol has received much less attention. This review focuses on the key pathways of fatty acid metabolism, including uptake, esterification, lipolysis, and mitochondrial oxidation, and how the regulators of these pathways are altered in cancer. Additionally, we discuss the potential link that fatty acid metabolism may serve between obesity and changes in cancer progression. PMID:25866768

75 FR 18508 - International Cooperation on Harmonisation of Technical Requirements for Registration of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-12

... a framework for metabolism testing, it is important that the design of the studies remains flexible... Products (VICH); Draft Guidance for Industry on Studies to Evaluate the Metabolism and Residue Kinetics of Veterinary Drugs in Food-Producing Animals: Metabolism Study to Determine the Quantity and Identify the...

76 FR 57054 - International Cooperation on Harmonisation of Technical Requirements for Registration of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-15

... recommends a framework for metabolism testing, it is important that the design of the studies remains... Products; Guidance for Industry on Studies To Evaluate the Metabolism and Residue Kinetics of Veterinary Drugs in Food-Producing Animals: Metabolism Study To Determine the Quantity and Identify the Nature of...

Technical Adequacy of Growth Estimates from a Computer Adaptive Test: Implications for Progress Monitoring

ERIC Educational Resources Information Center

Van Norman, Ethan R.; Nelson, Peter M.; Parker, David C.

2017-01-01

Computer adaptive tests (CATs) hold promise to monitor student progress within multitiered systems of support. However, the relationship between how long and how often data are collected and the technical adequacy of growth estimates from CATs has not been explored. Given CAT administration times, it is important to identify optimal data…

Education, Industrialization and Technical Progress in Mexico. IIEP Research Report No. 6.

ERIC Educational Resources Information Center

Padua, Jorge

This report attempts to analyze the contributions of the educational system and job training programs to industrialization and technical progress in the Conubal zone of the Lower Balsas River of Mexico. The first of the study's three sections consists of two chapters that provide general background. Chapter 1, "Theories of Development and the…

Technical Adequacy and Acceptability of Curriculum-Based Measurement and the Measures of Academic Progress

ERIC Educational Resources Information Center

January, Stacy-Ann A.; Ardoin, Scott P.

2015-01-01

Curriculum-based measurement in reading (CBM-R) and the Measures of Academic Progress (MAP) are assessment tools widely employed for universal screening in schools. Although a large body of research supports the validity of CBM-R, limited empirical evidence exists supporting the technical adequacy of MAP or the acceptability of either measure for…

Annual Technical Progress Report for Emergency School Assistance Program, Title 45, 1970-71.

ERIC Educational Resources Information Center

Lindsey, Randall B.

This paper presents a technical progress report of two programs conducted with funds provided under the Emergency School Assistance Program. One, the Mobile Learning Unit, said to have been designed to measure changes in fourth and fifth grade students' self-concept in a reorganized desegregated school environment, focuses on whether a positive…

Third Progress and Information Report of the Vocational-Technical Education Consortium of States.

ERIC Educational Resources Information Center

Lee, Connie W.; And Others

This description of major activities and accomplishments of the Vocational-Technical Education Consortium of the States (V-TECS) since the second progress report of May, 1975, is designed to provide the reader with a basic understanding of the processes and procedures used by the consortium in achieving its major goal: The production of catalogs…

A PSFI-based analysis on the energy efficiency potential of China’s domestic passenger vehicles

NASA Astrophysics Data System (ADS)

Chen, Chuan; Ren, Huanhuan; Zhao, Dongchang

2017-01-01

In this article, China’s domestic passenger vehicles (excluding new energy vehicles) are categorized into two groups: local brand vehicles and vehicles manufactured by joint ventures. Performance-Size-Fuel economy Index (PSFI) will be applied to analyse the speed of technical progress and the future trends of these vehicles. In addition, a forecast on energy efficiency potential of domestic passenger vehicles from 2016 to 2020 will be made based on different Emphasis on Reducing Fuel Consumption (ERFC) scenarios. According to the study, if the process of technical progress continues at its current speed, domestic ICE passenger vehicles will hardly meet Phase IV requirements by 2020 even though companies contribute as much technical progress to fuel consumption reduction as possible.

Advanced Thermal Emission Imaging Systems Definition and Development

NASA Technical Reports Server (NTRS)

Blasius, Karl; Nava, David (Technical Monitor)

2002-01-01

Santa Barbara Remote Sensing (SBRS), Raytheon Company, is pleased to submit this quarterly progress report of the work performed in the third quarter of Year 2 of the Advanced THEMIS Project, July through September 2002. We review here progress in the proposed tasks. During July through September 2002 progress was made in two major tasks, Spectral Response Characterization and Flight Instrument Definition. Because of staffing problems and technical problems earlier in the program we have refocused the remaining time and budget on the key technical tasks. Current technical problems with a central piece of test equipment has lead us to request a 1 quarter extension to the period of performance. This request is being made through a separate letter independent of this report.

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

Stout, D.K.

Flaws are noted in equilibrium growth models which ignore the facts that labor is no longer homogeneous, national governments can no longer guarantee a managed demand, and technical progress is not an independent force. The pace of technical progress is the major variable and increases with competition and certainty in the growth of demand. The outlook for technical progress is examined in the context of productivity, using microprocessor development for illustration. The author takes an optimistic view of new developments in that they do not bring the self-destructive possibility of overpopulation, irreversible damage to the environment, or nuclear war anymore » closer, while having a positive chance to promote a more rewarding relationship between education, work, and life style. The opportunities for positive humanistic changes through microprocessing are confirmed. (DCK)« less

Current advances in transdermal delivery of drugs for Alzheimer's disease

PubMed Central

Nguyen, Thuy Trang; Giau, Vo Van; Vo, Tuong Kha

2017-01-01

Alzheimer's disease (AD) is a common, progressive, fatal neurodegenerative disorder, which will play an increasingly important role both socially and financially in the aging populations. Treatments for AD show modest improvements in cognition and global functioning among patients. Furthermore, the oral administration of treating AD has had some drawbacks that decrease the medication adherence and efficacy of the therapy. Transdermal drugs are proposed as an alternative remedy to overcome the disadvantages of current pharmaceutical dosage options for this chronic disorder. They could have different strengths, such as offering a stable diffusion of active substance, avoiding the first pass metabolism, and reducing system adverse reactions. This article reviews the technical principles, novel techniques of transdermal delivery drug, and prospects for future development for the management of cognitive and behavioral dysfunctions in AD patients. PMID:28706327

Peroxisomal β-oxidation regulates whole body metabolism, inflammatory vigor, and pathogenesis of nonalcoholic fatty liver disease

PubMed Central

Moreno-Fernandez, Maria E.; Giles, Daniel A.; Stankiewicz, Traci E.; Sheridan, Rachel; Karns, Rebekah; Cappelletti, Monica; Lampe, Kristin; Mukherjee, Rajib; Sina, Christian; Sallese, Anthony; Bridges, James P.; Hogan, Simon P.; Aronow, Bruce J.; Hoebe, Kasper

2018-01-01

Nonalcoholic fatty liver disease (NAFLD), a metabolic predisposition for development of hepatocellular carcinoma (HCC), represents a disease spectrum ranging from steatosis to steatohepatitis to cirrhosis. Acox1, a rate-limiting enzyme in peroxisomal fatty acid β-oxidation, regulates metabolism, spontaneous hepatic steatosis, and hepatocellular damage over time. However, it is unknown whether Acox1 modulates inflammation relevant to NAFLD pathogenesis or if Acox1-associated metabolic and inflammatory derangements uncover and accelerate potential for NAFLD progression. Here, we show that mice with a point mutation in Acox1 (Acox1Lampe1) exhibited altered cellular metabolism, modified T cell polarization, and exacerbated immune cell inflammatory potential. Further, in context of a brief obesogenic diet stress, NAFLD progression associated with Acox1 mutation resulted in significantly accelerated and exacerbated hepatocellular damage via induction of profound histological changes in hepatocytes, hepatic inflammation, and robust upregulation of gene expression associated with HCC development. Collectively, these data demonstrate that β-oxidation links metabolism and immune responsiveness and that a better understanding of peroxisomal β-oxidation may allow for discovery of mechanisms central for NAFLD progression. PMID:29563328

Index to Nuclear Safety. A technical progress review by chronology, permuted title, and author. Vol. 11, No. 1--Vol. 17, No. 6

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

Cottrell, W.B.; Klein, A.

1977-02-23

This index to Nuclear Safety covers articles in Nuclear Safety Vol. 11, No. 1 (Jan.-Feb. 1970), through Vol. 17, No. 6 (Nov.-Dec. 1976). The index includes a chronological list of articles (including abstract) followed by KWIC and Author Indexes. Nuclear Safety, a bimonthly technical progress review prepared by the Nuclear Safety Information Center, covers all safety aspects of nuclear power reactors and associated facilities. The index lists over 350 technical articles in the last six years of publication.

Metabolic pathways as possible therapeutic targets for progressive multiple sclerosis.

PubMed

Heidker, Rebecca M; Emerson, Mitchell R; LeVine, Steven M

2017-08-01

Unlike relapsing remitting multiple sclerosis, there are very few therapeutic options for patients with progressive forms of multiple sclerosis. While immune mechanisms are key participants in the pathogenesis of relapsing remitting multiple sclerosis, the mechanisms underlying the development of progressive multiple sclerosis are less well understood. Putative mechanisms behind progressive multiple sclerosis have been put forth: insufficient energy production via mitochondrial dysfunction, activated microglia, iron accumulation, oxidative stress, activated astrocytes, Wallerian degeneration, apoptosis, etc . Furthermore, repair processes such as remyelination are incomplete. Experimental therapies that strive to improve metabolism within neurons and glia, e.g. , oligodendrocytes, could act to counter inadequate energy supplies and/or support remyelination. Most experimental approaches have been examined as standalone interventions; however, it is apparent that the biochemical steps being targeted are part of larger pathways, which are further intertwined with other metabolic pathways. Thus, the potential benefits of a tested intervention, or of an established therapy, e.g. , ocrelizumab, could be undermined by constraints on upstream and/or downstream steps. If correct, then this argues for a more comprehensive, multifaceted approach to therapy. Here we review experimental approaches to support neuronal and glial metabolism, and/or promote remyelination, which may have potential to lessen or delay progressive multiple sclerosis.

Characterization of the Tumor Microenvironment and Tumor–Stroma Interaction by Non-invasive Preclinical Imaging

PubMed Central

Ramamonjisoa, Nirilanto; Ackerstaff, Ellen

2017-01-01

Tumors are often characterized by hypoxia, vascular abnormalities, low extracellular pH, increased interstitial fluid pressure, altered choline-phospholipid metabolism, and aerobic glycolysis (Warburg effect). The impact of these tumor characteristics has been investigated extensively in the context of tumor development, progression, and treatment response, resulting in a number of non-invasive imaging biomarkers. More recent evidence suggests that cancer cells undergo metabolic reprograming, beyond aerobic glycolysis, in the course of tumor development and progression. The resulting altered metabolic content in tumors has the ability to affect cell signaling and block cellular differentiation. Additional emerging evidence reveals that the interaction between tumor and stroma cells can alter tumor metabolism (leading to metabolic reprograming) as well as tumor growth and vascular features. This review will summarize previous and current preclinical, non-invasive, multimodal imaging efforts to characterize the tumor microenvironment, including its stromal components and understand tumor–stroma interaction in cancer development, progression, and treatment response. PMID:28197395

[Address Given at the Regional Junior College Recreation Education Institute, American River College, September 25, 1969.

ERIC Educational Resources Information Center

Lutzin, Sidney G.

The United States has made striking technical advances in recent years, but there has not been comparable progress in social services. Greater affluence and leisure for some have been one result of technical progress, but problems of poverty and urban development are more pressing. New developments to improve the condition of society can be…

THE DEVELOPMENT OF PRE-VOCATIONAL EDUCATION LITERACY COURSES FOR USE WITH COMPUTER ASSISTED INSTRUCTION OF DISADVANTAGED YOUTH AND ADULTS. TECHNICAL PROGRESS REPORT.

ERIC Educational Resources Information Center

HANKIN, EDWARD K.; AND OTHERS

THIS TECHNICAL PROGRESS REPORT COVERS THE FIRST THREE MONTHS OF A PROJECT TO DEVELOP COMPUTER ASSISTED PREVOCATIONAL READING AND ARITHMETIC COURSES FOR DISADVANTAGED YOUTHS AND ADULTS. DURING THE FIRST MONTH OF OPERATION, PROJECT PERSONNEL CONCENTRATED ON SUCH ADMINISTRATIVE MATTERS AS TRAINING STAFF AND PREPARING FACILITIES. AN ARITHMETIC PROGRAM…

Generation and focusing of pulsed intense ion beams. Technical progress report, 20 August 1981-30 September 1982

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

Hammer, D.A.; Kusse, B.R.; Sudan, R.N.

1983-07-01

The progress on this contract is described in two parts. The first deals with the technical operation of the LION accelerator which is the exact equivalent to one line of PBFA-I. The second part is concerned with the experimental results on the ion diode mounted at the front end of the LION accelerator.

Project LIFE--Language Improvement to Facilitate Education. (Technical Progress Report; Third Quarter; March 1, 1974-May 31, 1974).

ERIC Educational Resources Information Center

National Foundation for the Improvement of Education, Washington, DC.

Reported is the third quarter, fiscal year 1974 (March 1, 1974-May 31, 1974) technical progress of Project LIFE (Language Improvement to Facilitate Education), toward developing an instructional system in which filmstrips in the areas of perceptual training, perceptual thinking, and language/reading are used to assist hearing impaired children in…

Improved radioimmunotherapy of hematologic malignancies. Progress report, 1988--1991

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

Press, O.W.; Barofsky, D.F.

1991-12-31

This progress report describes accomplishments under four headings, namely: The study of the relative rates of metabolic degradation of radiolabeled monoclonal antibodies (MAb) targeting tumor associated antigens; Effects of lysosomotropic amines, carboxylic ionophores, and thioamides on the retention of radiolabeled MAbs by tumor cells; Subcellular site of radioimmunoconjugate degradation and the sizes of fragments generated by intracellular metabolism of radiolabeled antibodies; and Patterns of metabolic degradation of radioimmunoconjugates made with different techniques and with different radionuclides.

The impact of transcription on metabolism in prostate and breast cancers.

PubMed

Poulose, Ninu; Mills, Ian G; Steele, Rebecca E

2018-05-14

Metabolic dysregulation is regarded as an important driver in cancer development and progression. The impact of transcriptional changes on metabolism have been intensively studied in hormone-dependent cancers, and in particular in prostate and breast cancer. These cancers have strong similarities in the function of important transcriptional drivers, such as the estrogen and androgen receptor, at the level of dietary risk and epidemiology, genetics and therapeutically. In this review we will focus on the function of these nuclear hormone receptors and their downstream impact on metabolism, with a particular focus on lipid metabolism. We go on to discuss how lipid metabolism remains dysregulated as the cancers progress. We conclude by discussing the opportunities that this presents for drug repurposing, imaging and the development and testing of new therapeutics and treatment combinations.

Monitoring the Durability Performance of Concrete in Nuclear Waste Containment. Technical Progress Report No. 4

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

Ulm, Franz-Josef

2000-06-30

OAK-B135 Monitoring the Durability Performance of Concrete in Nuclear Waste Containment. Technical Progress Report No. 4. The analysis of the effect of cracks on the acceleration of the calcium leaching process of cement-based materials has been pursued. During the last period (Technical Progress Report No 3), we have introduced a modeling accounting for the high diffusivity of fractures in comparison with the weak solid material diffusivity. It has been shown through dimensional and asymptotic analysis that small fractures do not significantly accelerate the material aging process. This important result for the overall structural aging kinetics of containment structure has beenmore » developed in a paper submitted to the international journal ''Transport in Porous Media''.« less

Metabolic disorders causing childhood ataxia.

PubMed

Parker, Colette C; Evans, Owen B

2003-09-01

Ataxia is a common neurologic finding in many disease processes of the nervous system, and has classically been associated with numerous metabolic disorders. An error of metabolism should be considered when the ataxia is either intermittent or progressive. Acute exacerbation or worsening after high protein ingestion, concurrent febrile illness, or other physical stress is also suggestive. A positive family history can be an important diagnostic clue. Progressive molecular and biochemical techniques are revolutionizing this area of medicine, and there has been rapid advancement in understanding of the disease processes.

Cancer metabolism in space and time: Beyond the Warburg effect.

PubMed

Danhier, Pierre; Bański, Piotr; Payen, Valéry L; Grasso, Debora; Ippolito, Luigi; Sonveaux, Pierre; Porporato, Paolo E

2017-08-01

Altered metabolism in cancer cells is pivotal for tumor growth, most notably by providing energy, reducing equivalents and building blocks while several metabolites exert a signaling function promoting tumor growth and progression. A cancer tissue cannot be simply reduced to a bulk of proliferating cells. Tumors are indeed complex and dynamic structures where single cells can heterogeneously perform various biological activities with different metabolic requirements. Because tumors are composed of different types of cells with metabolic activities affected by different spatial and temporal contexts, it is important to address metabolism taking into account cellular and biological heterogeneity. In this review, we describe this heterogeneity also in metabolic fluxes, thus showing the relative contribution of different metabolic activities to tumor progression according to the cellular context. This article is part of a Special Issue entitled Mitochondria in Cancer, edited by Giuseppe Gasparre, Rodrigue Rossignol and Pierre Sonveaux. Copyright © 2017 Elsevier B.V. All rights reserved.

Department of Clinical Investigation Annual Research Progress Report, Fiscal Year 1984. Volume 1,

DTIC Science & Technology

1984-10-01

on a low dosage of medication . Technical Approach: None. Progress: The placebo has not been received from the company. Since the drug company...determine the effect of high dose Ar-C intensification therapy on the -. incidence of CNS relapse. - Technical Approach: All patients with a new...Enrolled to Date: 7 Date of Periodic Review Results Objective(s): To determine the incidence of

Region- and age-dependent alterations of glial-neuronal metabolic interactions correlate with CNS pathology in a mouse model of globoid cell leukodystrophy.

PubMed

Meisingset, Tore Wergeland; Ricca, Alessandra; Neri, Margherita; Sonnewald, Ursula; Gritti, Angela

2013-07-01

Globoid cell leukodystrophy (GLD) or Krabbe disease is a lysosomal storage disorder caused by genetic defects in the expression and activity of galactosylceramidase, a key enzyme in the catabolism of myelin-enriched sphingolipids. While there are several histologic, biochemical, and functional studies on GLD, correlations between morphologic and biochemical alterations in central nervous system (CNS) tissues during disease progression are lacking. Here, we combined immunohistochemistry and metabolic analysis using (1)H and (13)C magnetic resonance (MR) spectra of spinal cord, cerebellum, and forebrain to investigate glial-neuronal metabolic interactions and dysfunction in a GLD murine model that recapitulates the human pathology. In order to assess the temporal- and region-dependent disease progression and the potential metabolic correlates, we investigated CNS tissues at mildly symptomatic and fully symptomatic stages of the disease. When compared with age-matched controls, GLD mice showed glucose hypometabolism, alterations in neurotransmitter content, N-acetylaspartate, N-acetylaspartylglutamate, and osmolytes levels. Notably, age- and region-dependent patterns of metabolic disturbances were in close agreement with the progression of astrogliosis, microglia activation, apoptosis, and neurodegeneration. We suggest that MR spectroscopy could be used in vivo to monitor disease progression, as well as ex vivo and in vivo to provide criteria for the outcome of experimental therapies.

Current technical approaches to brain energy metabolism.

PubMed

Barros, L Felipe; Bolaños, Juan P; Bonvento, Gilles; Bouzier-Sore, Anne-Karine; Brown, Angus; Hirrlinger, Johannes; Kasparov, Sergey; Kirchhoff, Frank; Murphy, Anne N; Pellerin, Luc; Robinson, Michael B; Weber, Bruno

2018-06-01

Neuroscience is a technology-driven discipline and brain energy metabolism is no exception. Once satisfied with mapping metabolic pathways at organ level, we are now looking to learn what it is exactly that metabolic enzymes and transporters do and when, where do they reside, how are they regulated, and how do they relate to the specific functions of neurons, glial cells, and their subcellular domains and organelles, in different areas of the brain. Moreover, we aim to quantify the fluxes of metabolites within and between cells. Energy metabolism is not just a necessity for proper cell function and viability but plays specific roles in higher brain functions such as memory processing and behavior, whose mechanisms need to be understood at all hierarchical levels, from isolated proteins to whole subjects, in both health and disease. To this aim, the field takes advantage of diverse disciplines including anatomy, histology, physiology, biochemistry, bioenergetics, cellular biology, molecular biology, developmental biology, neurology, and mathematical modeling. This article presents a well-referenced synopsis of the technical side of brain energy metabolism research. Detail and jargon are avoided whenever possible and emphasis is given to comparative strengths, limitations, and weaknesses, information that is often not available in regular articles. © 2017 Wiley Periodicals, Inc.

Total Factor Productivity Growth, Technical Progress & Efficiency Change in Vietnam Coal Industry - Nonparametric Approach

NASA Astrophysics Data System (ADS)

Phuong, Vu Hung

2018-03-01

This research applies Data Envelopment Analysis (DEA) approach to analyze Total Factor Productivity (TFP) and efficiency changes in Vietnam coal mining industry from 2007 to 2013. The TFP of Vietnam coal mining companies decreased due to slow technological progress and unimproved efficiency. The decadence of technical efficiency in many enterprises proved that the coal mining industry has a large potential to increase productivity through technical efficiency improvement. Enhancing human resource training, technology and research & development investment could help the industry to improve efficiency and productivity in Vietnam coal mining industry.

Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity

PubMed Central

Henao-Mejia, Jorge; Elinav, Eran; Jin, Cheng-Cheng; Hao, Liming; Mehal, Wajahat Z.; Strowig, Till; Thaiss, Christoph A.; Kau, Andrew L.; Eisenbarth, Stephanie C.; Jurczak, Michael J.; Camporez, Joao-Paulo; Shulman, Gerald I.; Gordon, Jeffrey I.; Hoffman, Hal M.; Flavell, Richard A.

2012-01-01

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and the leading cause of chronic liver disease in the Western world. Twenty percent of NAFLD individuals develop chronic hepatic inflammation (non-alcoholic steatohepatitis, NASH) associated with cirrhosis, portal hypertension and hepatocellular carcinoma, yet causes of progression from NAFLD to NASH remain obscure. Here, we show that the NLRP6 and NLRP3 inflammasomes and the effector protein IL-18 negatively regulate NAFLD/NASH progression, as well as multiple aspects of metabolic syndrome via modulation of the gut microbiota. Different animal models reveal that inflammasome deficiency-associated changes in the configuration of the gut microbiota are associated with exacerbated hepatic steatosis and inflammation through influx of TLR4 and TLR9 agonists into the portal circulation, leading to enhanced hepatic TNF-α expression that drives NASH progression. Furthermore, co-housing of inflammasome-deficient animals to wild type mice results in exacerbation of hepatic steatosis, glucose intolerance, and obesity. Thus, altered interactions between the gut microbiota and the host, produced by defective NLRP3 and NLRP6 inflammasome sensing, may govern the rate of progression of multiple metabolic syndrome-associated abnormalities, highlighting the central role of the microbiota in the pathogenesis of heretofore seemingly unrelated systemic auto-inflammatory and metabolic disorders. PMID:22297845

KABAM Version 1.0 User's Guide and Technical Documentation - Appendix H - Methods for Estimating Metabolism Rate Constant

EPA Pesticide Factsheets

Appendix H of KABAM Version 1.0 documentation related to estimating the metabolism rate constant. KABAM is a simulation model used to predict pesticide concentrations in aquatic regions for use in exposure assessments.

48 CFR 2011.104-70 - NRC Clauses.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Technical Reports, when deliverables include a technical report. (b) The contracting officer shall insert the clause at 2052.211-71 Technical Progress Report, in all solicitations and contracts except— (1...) The contracting officer shall insert the clause at 2052.211-72 Financial Status Report, in applicable...

48 CFR 2011.104-70 - NRC Clauses.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Technical Reports, when deliverables include a technical report. (b) The contracting officer shall insert the clause at 2052.211-71 Technical Progress Report, in all solicitations and contracts except— (1...) The contracting officer shall insert the clause at 2052.211-72 Financial Status Report, in applicable...

48 CFR 2011.104-70 - NRC Clauses.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Technical Reports, when deliverables include a technical report. (b) The contracting officer shall insert the clause at 2052.211-71 Technical Progress Report, in all solicitations and contracts except— (1...) The contracting officer shall insert the clause at 2052.211-72 Financial Status Report, in applicable...

48 CFR 2011.104-70 - NRC Clauses.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Technical Reports, when deliverables include a technical report. (b) The contracting officer shall insert the clause at 2052.211-71 Technical Progress Report, in all solicitations and contracts except— (1...) The contracting officer shall insert the clause at 2052.211-72 Financial Status Report, in applicable...

48 CFR 2011.104-70 - NRC Clauses.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Technical Reports, when deliverables include a technical report. (b) The contracting officer shall insert the clause at 2052.211-71 Technical Progress Report, in all solicitations and contracts except— (1...) The contracting officer shall insert the clause at 2052.211-72 Financial Status Report, in applicable...

32 CFR 203.17 - Technical assistance provider reporting requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 2 2010-07-01 2010-07-01 false Technical assistance provider reporting requirements. 203.17 Section 203.17 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY... technical assistance provider shall submit progress reports, financial status reports, materials prepared...

32 CFR 203.17 - Technical assistance provider reporting requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 2 2014-07-01 2014-07-01 false Technical assistance provider reporting requirements. 203.17 Section 203.17 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY... technical assistance provider shall submit progress reports, financial status reports, materials prepared...

32 CFR 203.17 - Technical assistance provider reporting requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 2 2013-07-01 2013-07-01 false Technical assistance provider reporting requirements. 203.17 Section 203.17 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY... technical assistance provider shall submit progress reports, financial status reports, materials prepared...

32 CFR 203.17 - Technical assistance provider reporting requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 2 2011-07-01 2011-07-01 false Technical assistance provider reporting requirements. 203.17 Section 203.17 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY... technical assistance provider shall submit progress reports, financial status reports, materials prepared...

32 CFR 203.17 - Technical assistance provider reporting requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 2 2012-07-01 2012-07-01 false Technical assistance provider reporting requirements. 203.17 Section 203.17 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY... technical assistance provider shall submit progress reports, financial status reports, materials prepared...

ISABELLE: a progress report

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

Hahn, H

This paper discusses the ISABELLE project, which has the objective of constructing a high-energy proton colliding beam facility at Brookhaven National Laboratory. The major technical features of the intersecting storage accelerators with their projected performance are described. Application of over 1000 superconducting magnets in the two rings represents the salient characteristic of the machine. The status of the entire project, the technical progress made so far, and difficulties encountered are reviewed.

Final Technical Progress Report: Development of Low-Cost Suspension Heliostat; December 7, 2011 - December 6, 2012

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

Bender, W.

2013-01-01

Final technical progress report of SunShot Incubator Solaflect Energy. The project succeeded in demonstrating that the Solaflect Suspension Heliostat design is viable for large-scale CSP installations. Canting accuracy is acceptable and is continually improving as Solaflect improves its understanding of this design. Cost reduction initiatives were successful, and there are still many opportunities for further development and further cost reduction.

Measurement of solids motion in gas-fluidized beds. Technical progress report, 1 October 1982-31 December 1982

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

Chen, M.M.; Chao, B.T.

This technical progress report covers the progress made during the fifth quarter of the project entitled Measurements of Solids Motion in Gas Fluidized Beds under Grant No. DOE-F22-81PC40804 during the period 1 October through 31 December 1982. The research concerns the measurement of solids particle velocity distribution and residence time distribution using the Computer-Aided Particle Tracking Facility (CAPTF) at the University of Illinois at Urbana-Champaign. The experimental equipment and measuring methods used to determine particle size distribution and particle motion and the results obtained are presented.

The role of depressed metabolism in space biology: An overview

NASA Technical Reports Server (NTRS)

Saunders, J.

1973-01-01

Organization and research activities of the entire NASA Space Biology Program are outlined. Various technical approaches are reported to study depressed metabolism particularly in the situation of 100% oxygen and reduced ambient pressures. These include hibernation and hypothermia, thermal regulation, and diluent gases.

The 1996 NAEP Technical Report.

ERIC Educational Resources Information Center

Allen, Nancy L.; Carlson, James E.; Zelenak, Christine A.

This report documents the design, administration, and data analysis procedure of the National Assessment of Education Progress (NAEP) for 1996. It indicates the technical decisions that were made and the rationale behind them. Detailed substantive findings are not presented in this report. These chapters provide technical information about the…

Epigenetics and Cellular Metabolism

PubMed Central

Xu, Wenyi; Wang, Fengzhong; Yu, Zhongsheng; Xin, Fengjiao

2016-01-01

Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc.) is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the processing of epigenetic memory. Here, we summarize the recent research progress in the epigenetic regulation of cellular metabolism and discuss how the dysfunction of epigenetic machineries influences the development of metabolic disorders such as diabetes and obesity; then, we focus on discussing the notion that manipulating metabolites, the fuel of cell metabolism, can function as a strategy for interfering epigenetic machinery and its related disease progression as well. PMID:27695375

Lincoln County nuclear waste project. Quarterly progress report, October 1, 1991--December 31, 1991

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

NONE

1996-03-01

This document included the following three progress reports to the Yucca Mountain Project Office on radioactive waste storage in Lincoln County, Nevada: financial status report; federal cash transactions report; and technical progress report.

Lincoln County nuclear waste project. Quarterly progress report, January 1, 1992--March 31, 1992

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

NONE

1996-03-01

This document included the following three progress reports to the Yucca Mountain Project Office on radioactive waste storage in Lincoln County, Nevada: financial status report; federal cash transactions report; and technical progress report.

Lincoln County nuclear waste project quarterly progress report, April 1, 1992--June 30, 1992

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

NONE

1996-03-01

This document included the following three progress reports to the Yucca Mountain Project Office on radioactive waste storage in Lincoln County, Nevada: financial status report; federal cash transactions report; and technical progress report.

Index to Nuclear Safety: a technical progress review by chronology, permuted title, and author, Volume 18 (1) through Volume 22 (6)

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

Cottrell, W.B.; Passiakos, M.

This index to Nuclear Safety covers articles published in Nuclear Safety, Volume 18, Number 1 (January-February 1977) through Volume 22, Number 6 (November-December 1981). The index is divided into three section: a chronological list of articles (including abstracts), a permuted-title (KWIC) index, and an author index. Nuclear Safety, a bimonthly technical progress review prepared by the Nuclear Safety Information Center, covers all safety aspects of nuclear power reactors and associated facilities. Over 300 technical articles published in Nuclear Safety in the last 5 years are listed in this index.

ERRs and cancers: effects on metabolism and on proliferation and migration capacities.

PubMed

Bianco, Stéphanie; Sailland, Juliette; Vanacker, Jean-Marc

2012-07-01

ERRs are orphan members of the nuclear receptor superfamily which, at least for ERRα and ERRγ display important roles in the control of various metabolic processes. On other hand, correlations have been found between the expression of ERRα and γ and diverse parameters of tumor progression in human cancers. Whereas it is tempting to speculate that ERR receptors act in tumors through the regulation of metabolism, recent data have suggested that they also may directly regulate tumor proliferation and progression independently of their effects on metabolism. The two aspects of tumoral functions of ERR receptors are the purpose of the present review. Copyright © 2011 Elsevier Ltd. All rights reserved.

77 FR 16250 - Notice of Proposed Information Collection for Public Comment; Office of Native American Programs...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-20

... Information Collection for Public Comment; Office of Native American Programs (ONAP) Training and Technical... subject proposal. The data required by Office of Native American Programs Training and Technical... progress. The data identifies needs, outputs and outcomes of the training and technical assistance. DATES...

Social inequalities in the face of scientific and technological development: an antinomy or an historic problem?

PubMed

Delgado, Guilherme Costa

2017-07-01

This paper aims to conduct a conceptual analysis of the relationship between scientific and technical progress and social equality, or the reduction of inequalities. We examine this relationship by drawing on three theoretical perspectives: 1) ethical economics, championed by classical economic thinkers and centered on utilitarian self-interest, 2) Mainstream theories of economic development espousing the endogenous link between labor productivity growth and technical progress, 3) the critique of theories of economic development that emerged in the second half of the twentieth century, including Celso Furtado's critique of the theory of underdevelopment, emphasizing the prevalence of egalitarian tendencies, and ecological economics, which suggest alternative paths to those set by "classical" theories of development. The fundamental antinomy posed by the title of this article, characterized by an intrinsic contradiction between technical progress and social equality, strictly presupposes the ethical economics perspective, dominated by the social relations that constitute the "social order".

76 FR 57058 - International Cooperation on Harmonisation of Technical Requirements for Registration of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-15

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0165] International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products; Guidance for Industry on Studies To Evaluate the Metabolism and Residue Kinetics of Veterinary...

Targeting lipid metabolism of cancer cells: A promising therapeutic strategy for cancer.

PubMed

Liu, Qiuping; Luo, Qing; Halim, Alexander; Song, Guanbin

2017-08-10

One of the most important metabolic hallmarks of cancer cells is deregulation of lipid metabolism. In addition, enhancing de novo fatty acid (FA) synthesis, increasing lipid uptake and lipolysis have also been considered as means of FA acquisition in cancer cells. FAs are involved in various aspects of tumourigenesis and tumour progression. Therefore, targeting lipid metabolism is a promising therapeutic strategy for human cancer. Recent studies have shown that reprogramming lipid metabolism plays important roles in providing energy, macromolecules for membrane synthesis, and lipid signals during cancer progression. Moreover, accumulation of lipid droplets in cancer cells acts as a pivotal adaptive response to harmful conditions. Here, we provide a brief review of the crucial roles of FA metabolism in cancer development, and place emphasis on FA origin, utilization and storage in cancer cells. Understanding the regulation of lipid metabolism in cancer cells has important implications for exploring a new therapeutic strategy for management and treatment of cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Mass Spectrometry Strategies for Clinical Metabolomics and Lipidomics in Psychiatry, Neurology, and Neuro-Oncology

PubMed Central

Wood, Paul L

2014-01-01

Metabolomics research has the potential to provide biomarkers for the detection of disease, for subtyping complex disease populations, for monitoring disease progression and therapy, and for defining new molecular targets for therapeutic intervention. These potentials are far from being realized because of a number of technical, conceptual, financial, and bioinformatics issues. Mass spectrometry provides analytical platforms that address the technical barriers to success in metabolomics research; however, the limited commercial availability of analytical and stable isotope standards has created a bottleneck for the absolute quantitation of a number of metabolites. Conceptual and financial factors contribute to the generation of statistically under-powered clinical studies, whereas bioinformatics issues result in the publication of a large number of unidentified metabolites. The path forward in this field involves targeted metabolomics analyses of large control and patient populations to define both the normal range of a defined metabolite and the potential heterogeneity (eg, bimodal) in complex patient populations. This approach requires that metabolomics research groups, in addition to developing a number of analytical platforms, build sufficient chemistry resources to supply the analytical standards required for absolute metabolite quantitation. Examples of metabolomics evaluations of sulfur amino-acid metabolism in psychiatry, neurology, and neuro-oncology and of lipidomics in neurology will be reviewed. PMID:23842599

Mass spectrometry strategies for clinical metabolomics and lipidomics in psychiatry, neurology, and neuro-oncology.

PubMed

Wood, Paul L

2014-01-01

Metabolomics research has the potential to provide biomarkers for the detection of disease, for subtyping complex disease populations, for monitoring disease progression and therapy, and for defining new molecular targets for therapeutic intervention. These potentials are far from being realized because of a number of technical, conceptual, financial, and bioinformatics issues. Mass spectrometry provides analytical platforms that address the technical barriers to success in metabolomics research; however, the limited commercial availability of analytical and stable isotope standards has created a bottleneck for the absolute quantitation of a number of metabolites. Conceptual and financial factors contribute to the generation of statistically under-powered clinical studies, whereas bioinformatics issues result in the publication of a large number of unidentified metabolites. The path forward in this field involves targeted metabolomics analyses of large control and patient populations to define both the normal range of a defined metabolite and the potential heterogeneity (eg, bimodal) in complex patient populations. This approach requires that metabolomics research groups, in addition to developing a number of analytical platforms, build sufficient chemistry resources to supply the analytical standards required for absolute metabolite quantitation. Examples of metabolomics evaluations of sulfur amino-acid metabolism in psychiatry, neurology, and neuro-oncology and of lipidomics in neurology will be reviewed.

The Potential Biomarkers to Identify the Development of Steatosis in Hyperuricemia

PubMed Central

He, Xiaojuan; Lu, Cheng; He, Bing; Niu, Xuyan; Xiao, Cheng; Xu, Gang; Bian, Zhaoxiang; Zu, Xianpeng; Zhang, Ge; Zhang, Weidong; Lu, Aiping

2016-01-01

Hyperuricemia (HU) often progresses to combine with non-alcoholic fatty liver disease (NAFLD) in the clinical scenario, which further exacerbates metabolic disorders; early detection of biomarkers, if obtained during the HU progression, may be beneficial for preventing its combination with NAFLD. This study aimed to decipher the biomarkers and mechanisms of the development of steatosis in HU. Four groups of subjects undergoing health screening, including healthy subjects, subjects with HU, subjects with HU combined with NAFLD (HU+NAFLD) and subjects with HU initially and then with HU+NAFLD one year later (HU→HU+NAFLD), were recruited in this study. The metabolic profiles of all subjects’ serum were analyzed by liquid chromatography quadruple time-of-flight mass spectrometry. The metabolomic data from subjects with HU and HU+NAFLD were compared, and the biomarkers for the progression from HU to HU+NAFLD were predicted. The metabolomic data from HU→HU+NAFLD subjects were collected for further verification. The results showed that the progression was associated with disturbances of phospholipase metabolism, purine nucleotide degradation and Liver X receptor/retinoic X receptor activation as characterized by up-regulated phosphatidic acid, cholesterol ester (18:0) and down-regulated inosine. These metabolic alterations may be at least partially responsible for the development of steatosis in HU. This study provides a new paradigm for better understanding and further prevention of disease progression. PMID:26890003

Early and progressive impairment of spinal blood flow-glucose metabolism coupling in motor neuron degeneration of ALS model mice.

PubMed

Miyazaki, Kazunori; Masamoto, Kazuto; Morimoto, Nobutoshi; Kurata, Tomoko; Mimoto, Takahumi; Obata, Takayuki; Kanno, Iwao; Abe, Koji

2012-03-01

The exact mechanism of selective motor neuron death in amyotrophic lateral sclerosis (ALS) remains still unclear. In the present study, we performed in vivo capillary imaging, directly measured spinal blood flow (SBF) and glucose metabolism, and analyzed whether if a possible flow-metabolism coupling is disturbed in motor neuron degeneration of ALS model mice. In vivo capillary imaging showed progressive decrease of capillary diameter, capillary density, and red blood cell speed during the disease course. Spinal blood flow was progressively decreased in the anterior gray matter (GM) from presymptomatic stage to 0.80-fold of wild-type (WT) mice, 0.61 at early-symptomatic, and 0.49 at end stage of the disease. Local spinal glucose utilization (LSGU) was transiently increased to 1.19-fold in anterior GM at presymptomatic stage, which in turn progressively decreased to 0.84 and 0.60 at early-symptomatic and end stage of the disease. The LSGU/SBF ratio representing flow-metabolism uncoupling (FMU) preceded the sequential pathological changes in the spinal cord of ALS mice and was preferentially found in the affected region of ALS. The present study suggests that this early and progressive FMU could profoundly involve in the whole disease process as a vascular factor of ALS pathology, and could also be a potential target for therapeutic intervention of ALS.

Molecular profiling of dilated cardiomyopathy that progresses to heart failure

PubMed Central

Burke, Michael A.; Chang, Stephen; Wakimoto, Hiroko; Gorham, Joshua M.; Conner, David A.; Christodoulou, Danos C.; Parfenov, Michael G.; DePalma, Steve R.; Eminaga, Seda; Konno, Tetsuo; Seidman, Jonathan G.; Seidman, Christine E.

2016-01-01

Dilated cardiomyopathy (DCM) is defined by progressive functional and structural changes. We performed RNA-seq at different stages of disease to define molecular signaling in the progression from pre-DCM hearts to DCM and overt heart failure (HF) using a genetic model of DCM (phospholamban missense mutation, PLNR9C/+). Pre-DCM hearts were phenotypically normal yet displayed proliferation of nonmyocytes (59% relative increase vs. WT, P = 8 × 10–4) and activation of proinflammatory signaling with notable cardiomyocyte-specific induction of a subset of profibrotic cytokines including TGFβ2 and TGFβ3. These changes progressed through DCM and HF, resulting in substantial fibrosis (17.6% of left ventricle [LV] vs. WT, P = 6 × 10–33). Cardiomyocytes displayed a marked shift in metabolic gene transcription: downregulation of aerobic respiration and subsequent upregulation of glucose utilization, changes coincident with attenuated expression of PPARα and PPARγ coactivators -1α (PGC1α) and -1β, and increased expression of the metabolic regulator T-box transcription factor 15 (Tbx15). Comparing DCM transcriptional profiles with those in hypertrophic cardiomyopathy (HCM) revealed similar and distinct molecular mechanisms. Our data suggest that cardiomyocyte-specific cytokine expression, early fibroblast activation, and the shift in metabolic gene expression are hallmarks of cardiomyopathy progression. Notably, key components of these profibrotic and metabolic networks were disease specific and distinguish DCM from HCM. PMID:27239561

Targeting Hypoxia-Inducible Factor-1α/Pyruvate Dehydrogenase Kinase 1 Axis by Dichloroacetate Suppresses Bleomycin-induced Pulmonary Fibrosis.

PubMed

Goodwin, Justin; Choi, Hyunsung; Hsieh, Meng-Hsiung; Neugent, Michael L; Ahn, Jung-Mo; Hayenga, Heather N; Singh, Pankaj K; Shackelford, David B; Lee, In-Kyu; Shulaev, Vladimir; Dhar, Shanta; Takeda, Norihiko; Kim, Jung-Whan

2018-02-01

Hypoxia has long been implicated in the pathogenesis of fibrotic diseases. Aberrantly activated myofibroblasts are the primary pathological driver of fibrotic progression, yet how various microenvironmental influences, such as hypoxia, contribute to their sustained activation and differentiation is poorly understood. As a defining feature of hypoxia is its impact on cellular metabolism, we sought to investigate how hypoxia-induced metabolic reprogramming affects myofibroblast differentiation and fibrotic progression, and to test the preclinical efficacy of targeting glycolytic metabolism for the treatment of pulmonary fibrosis. Bleomycin-induced pulmonary fibrotic progression was evaluated in two independent, fibroblast-specific, promoter-driven, hypoxia-inducible factor (Hif) 1A knockout mouse models and in glycolytic inhibitor, dichloroacetate-treated mice. Genetic and pharmacological approaches were used to explicate the role of metabolic reprogramming in myofibroblast differentiation. Hypoxia significantly enhanced transforming growth factor-β-induced myofibroblast differentiation through HIF-1α, whereas overexpression of the critical HIF-1α-mediated glycolytic switch, pyruvate dehydrogenase kinase 1 (PDK1) was sufficient to activate glycolysis and potentiate myofibroblast differentiation, even in the absence of HIF-1α. Inhibition of the HIF-1α/PDK1 axis by genomic deletion of Hif1A or pharmacological inhibition of PDK1 significantly attenuated bleomycin-induced pulmonary fibrosis. Our findings suggest that HIF-1α/PDK1-mediated glycolytic reprogramming is a critical metabolic alteration that acts to promote myofibroblast differentiation and fibrotic progression, and demonstrate that targeting glycolytic metabolism may prove to be a potential therapeutic strategy for the treatment of pulmonary fibrosis.

Metabolic Dysfunctions in Amyotrophic Lateral Sclerosis Pathogenesis and Potential Metabolic Treatments

PubMed Central

Tefera, Tesfaye W.; Borges, Karin

2017-01-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease primarily characterized by loss of motor neurons in brain and spinal cord. The death of motor neurons leads to denervation of muscle which in turn causes muscle weakness and paralysis, decreased respiratory function and eventually death. Growing evidence indicates disturbances in energy metabolism in patients with ALS and animal models of ALS, which are likely to contribute to disease progression. Particularly, defects in glucose metabolism and mitochondrial dysfunction limit the availability of ATP to CNS tissues and muscle. Several metabolic approaches improving mitochondrial function have been investigated in vitro and in vivo and showed varying effects in ALS. The effects of metabolic approaches in ALS models encompass delays in onset of motor symptoms, protection of motor neurons and extension of survival, which signifies an important role of metabolism in the pathogenesis of the disease. There is now an urgent need to test metabolic approaches in controlled clinical trials. In addition, more detailed studies to better characterize the abnormalities in energy metabolism in patients with ALS and ALS models are necessary to develop metabolically targeted effective therapies that can slow the progression of the disease and prolong life for patients with ALS. PMID:28119559

Metabolic enzymes dysregulation in heart failure: the prospective therapy.

PubMed

Parihar, Priyanka; Parihar, Mordhwaj Singh

2017-01-01

The heart failure accounts for the highest mortality rate all over the world. The development of preventive therapeutic approaches is still in their infancy. Owing to the extremely high energy demand of the heart, the bioenergetics pathways need to respond efficiently based on substrate availability. The metabolic regulation of such heart bioenergetics is mediated by various rate limiting enzymes involved in energy metabolism. Although all the pertinent mechanisms are not clearly understood, the progressive decline in the activity of metabolic enzymes leading to diminished ATP production is known to cause progression of the heart failure. Therefore, metabolic therapy that can maintain the appropriate activities of metabolic enzymes can be a promising approach for the prevention and treatment of the heart failure. The flavonoids that constitute various human dietary ingredients also effectively offer a variety of health benefits. The flavonoids target a variety of metabolic enzymes and facilitate effective management of the equilibrium between production and utilization of energy in the heart. This review discusses the broad impact of metabolic enzymes in the heart functions and explains how the dysregulated enzyme activity causes the heart failure. In addition, the prospects of targeting dysregulated metabolic enzymes by developing flavonoid-based metabolic approaches are discussed.

In-Vivo Zinc Metabolism by Isotope Ratio Mass Spectrometry

USDA-ARS?s Scientific Manuscript database

The purpose of this chapter is to highlight some of the methodological and technical issues surrounding the in vivo use of stable isotopes and to provide examples of how such studies have advanced our knowledge of human zinc metabolism. The advantages and disadvantages of the currently available in...

Developments in Technical Education in the British Caribbean, 1940-60.

ERIC Educational Resources Information Center

Pemberton, S. Macpherson

The paper discusses developments in technical education in the British West Indies from 1940-1960 emphasizing the relation between education and economic development. The objective is to analyze the economic basis of progress in technical education. The document is presented in four chapters. Chapter I summarizes historical background prior to…

Programs of Study: Year 2 Joint Technical Report. Research Snapshot

ERIC Educational Resources Information Center

National Research Center for Career and Technical Education, 2010

2010-01-01

In January 2010, the National Research Center for Career and Technical Education (NRCCTE) issued a progress report on three studies being conducted by the Center that examine the implementation and outcomes of Programs of Study (POS), which were required in the 2006 reauthorization of the federal legislation for career and technical education…

The progression from a lower to a higher invasive stage of bladder cancer is associated with severe alterations in glucose and pyruvate metabolism

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

Conde, Vanessa R.; Oliveira, Pedro F.; Department of Microscopy, Laboratory of Cell Biology and Unit for Multidisciplinary Research in Biomedicine, Abel Salazar Institute of Biomedical Sciences, University of Porto – UMIB/ICBAS/UP

Cancer cells present a particular metabolic behavior. We hypothesized that the progression of bladder cancer could be accompanied by changes in cells glycolytic profile. We studied two human bladder cancer cells, RT4 and TCCSUP, in which the latter represents a more invasive stage. The levels of glucose, pyruvate, alanine and lactate in the extracellular media were measured by Proton Nuclear Magnetic Resonance. The protein expression levels of glucose transporters 1 (GLUT1) and 3 (GLUT3), monocarboxylate transporter 4 (MCT4), phosphofructokinase-1 (PFK1), glutamic-pyruvate transaminase (GPT) and lactate dehydrogenase (LDH) were determined. Our data showed that glucose consumption and GLUT3 levels were similarmore » in both cell lines, but TCCSUP cells displayed lower levels of GLUT1 and PFK expression. An increase in pyruvate consumption, concordant with the higher levels of lactate and alanine production, was also detected in TCCSUP cells. Moreover, TCCSUP cells presented lower protein expression levels of GPT and LDH. These results illustrate that bladder cancer progression is associated with alterations in cells glycolytic profile, namely the switch from glucose to pyruvate consumption in the more aggressive stage. This may be useful to develop new therapies and to identify biomarkers for cancer progression. - Highlights: • Metabolic phenotype of less and high invasive bladder cancer cells was studied. • Bladder cancer progression involves alterations in cells glycolytic profile. • More invasive bladder cancer cells switch from glucose to pyruvate consumption. • Our results may help to identify metabolic biomarkers of bladder cancer progression.« less

Gradual training of alpacas to the confinement of metabolism pens reduces stress when normal excretion behavior is accommodated.

PubMed

Lund, Kirrin E; Maloney, Shane K; Milton, John T B; Blache, Dominique

2012-01-01

Confinement in metabolism pens may provoke a stress response in alpacas that will reduce the welfare of the animal and jeopardize the validity of scientific results obtained in such pens. In this study, we tested a protocol designed to successfully train alpacas to be held in a specially designed metabolism pen so that the animals' confinement would not jeopardize their welfare. We hypothesized that the alpacas would show fewer behaviors associated with a response to stress as training gradually progressed, and that they would adapt to being in the confinement of the metabolism pen. The training protocol was successful at introducing alpacas to the metabolism pens, and it did reduce the incidence of behavioral responses to stress as the training progressed. The success of the training protocol may be attributed to the progressive nature of the training, the tailoring of the protocol to suit alpacas, and the use of positive reinforcement. This study demonstrated that both animal welfare and the validity of the scientific outcomes could be maximized by the gradual training of experimental animals, thereby minimizing the stress imposed on the animals during experimental procedures.

Nuclear localization of metabolic enzymes in immunity and metastasis.

PubMed

He, Yuchen; Gao, Menghui; Cao, Yiqu; Tang, Haosheng; Liu, Shuang; Tao, Yongguang

2017-12-01

Metabolism is essential to all living organisms that provide cells with energy, regulators, building blocks, enzyme cofactors and signaling molecules, and is in tune with nutritional conditions and the function of cells to make the appropriate developmental decisions or maintain homeostasis. As a fundamental biological process, metabolism state affects the production of multiple metabolites and the activation of various enzymes that participate in regulating gene expression, cell apoptosis, cancer progression and immunoreactions. Previous studies generally focus on the function played by the metabolic enzymes in the cytoplasm and mitochondrion. In this review, we conclude the role of them in the nucleus and their implications for cancer progression, immunity and metastasis. Copyright © 2017 Elsevier B.V. All rights reserved.

Proceedings: Computer Science and Data Systems Technical Symposium, volume 1

NASA Technical Reports Server (NTRS)

Larsen, Ronald L.; Wallgren, Kenneth

1985-01-01

Progress reports and technical updates of programs being performed by NASA centers are covered. Presentations in viewgraph form are included for topics in three categories: computer science, data systems and space station applications.

Cancer progression by reprogrammed BCAA metabolism in myeloid leukaemia.

PubMed

Hattori, Ayuna; Tsunoda, Makoto; Konuma, Takaaki; Kobayashi, Masayuki; Nagy, Tamas; Glushka, John; Tayyari, Fariba; McSkimming, Daniel; Kannan, Natarajan; Tojo, Arinobu; Edison, Arthur S; Ito, Takahiro

2017-05-25

Reprogrammed cellular metabolism is a common characteristic observed in various cancers. However, whether metabolic changes directly regulate cancer development and progression remains poorly understood. Here we show that BCAT1, a cytosolic aminotransferase for branched-chain amino acids (BCAAs), is aberrantly activated and functionally required for chronic myeloid leukaemia (CML) in humans and in mouse models of CML. BCAT1 is upregulated during progression of CML and promotes BCAA production in leukaemia cells by aminating the branched-chain keto acids. Blocking BCAT1 gene expression or enzymatic activity induces cellular differentiation and impairs the propagation of blast crisis CML both in vitro and in vivo. Stable-isotope tracer experiments combined with nuclear magnetic resonance-based metabolic analysis demonstrate the intracellular production of BCAAs by BCAT1. Direct supplementation with BCAAs ameliorates the defects caused by BCAT1 knockdown, indicating that BCAT1 exerts its oncogenic function through BCAA production in blast crisis CML cells. Importantly, BCAT1 expression not only is activated in human blast crisis CML and de novo acute myeloid leukaemia, but also predicts disease outcome in patients. As an upstream regulator of BCAT1 expression, we identified Musashi2 (MSI2), an oncogenic RNA binding protein that is required for blast crisis CML. MSI2 is physically associated with the BCAT1 transcript and positively regulates its protein expression in leukaemia. Taken together, this work reveals that altered BCAA metabolism activated through the MSI2-BCAT1 axis drives cancer progression in myeloid leukaemia.

Energy stress-induced lncRNA HAND2-AS1 represses HIF1α-mediated energy metabolism and inhibits osteosarcoma progression

PubMed Central

Kang, Yao; Zhu, Xiaojun; Xu, Yanyang; Tang, Qinglian; Huang, Zongwen; Zhao, Zhiqiang; Lu, Jinchang; Song, Guohui; Xu, Huaiyuan; Deng, Chuangzhong; Wang, Jin

2018-01-01

During recent years, long noncoding RNAs (lncRNAs) have been recognized as key regulators in the development and progression of human cancers, however, their roles in osteosarcoma metabolism are still not well understood. The present study aims to investigate the expression profiles and potential modulation of specific lncRNA(s) in osteosarcoma metabolism. The high-throughput Hiseq sequencing was performed to screen for abnormally expressed lncRNAs in osteosarcoma cells cultured under glucose starvation condition, and lncRNA HAND2-AS1 was eventually identified as one that was significantly up-regulated when compared with normal cultured cells. Mechanistic investigations indicated that knockdown of HAND2-AS1 abrogated the energy stress-induced effect on cell apoptosis and proliferation, and promoted osteosarcoma progression. Moreover, knockdown of HAND2-AS1 promoted glucose uptake, lactate production, and the expression level of a serious of enzymes that involved in energy metabolism. Subsequently, RNA pull-down and RNA immuneprecipitation revealed that, upon energy stress, HAND2-AS1 regulated osteosarcoma metabolism through sequestering FBP1 from binding to HIF1α, thereby releasing HIF1α expression and promoting the protein level. Taken together, our integrated approach reveals a regulatory mechanism by lncRNA HAND2-AS1 to control energy metabolism and tumor development in osteosarcoma. Thus, HAND2-AS1 may be a potential biomarker and therapeutic target for the repression of osteosarcoma metabolism. PMID:29637006

Liver Inflammation and Metabolic Signaling in ApcMin/+ Mice: The Role of Cachexia Progression

PubMed Central

Narsale, Aditi A.; Enos, Reilly T.; Puppa, Melissa J.; Chatterjee, Saurabh; Murphy, E. Angela; Fayad, Raja; Pena, Majorette O’; Durstine, J. Larry; Carson, James A.

2015-01-01

The ApcMin/+ mouse exhibits an intestinal tumor associated loss of muscle and fat that is accompanied by chronic inflammation, insulin resistance and hyperlipidemia. Since the liver governs systemic energy demands through regulation of glucose and lipid metabolism, it is likely that the liver is a pathological target of cachexia progression in the ApcMin/+ mouse. The purpose of this study was to determine if cancer and the progression of cachexia affected liver endoplasmic reticulum (ER)-stress, inflammation, metabolism, and protein synthesis signaling. The effect of cancer (without cachexia) was examined in wild-type and weight-stable ApcMin/+ mice. Cachexia progression was examined in weight-stable, pre-cachectic, and severely-cachectic ApcMin/+ mice. Livers were analyzed for morphology, glycogen content, ER-stress, inflammation, and metabolic changes. Cancer induced hepatic expression of ER-stress markers BiP (binding immunoglobulin protein), IRE-1α (endoplasmic reticulum to nucleus signaling 1), and inflammatory intermediate STAT-3 (signal transducer and activator of transcription 3). While gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression was suppressed by cancer, glycogen content or protein synthesis signaling remained unaffected. Cachexia progression depleted liver glycogen content and increased mRNA expression of glycolytic enzyme PFK (phosphofrucktokinase) and gluconeogenic enzyme PEPCK. Cachexia progression further increased pSTAT-3 but suppressed p-65 and JNK (c-Jun NH2-terminal kinase) activation. Interestingly, progression of cachexia suppressed upstream ER-stress markers BiP and IRE-1α, while inducing its downstream target CHOP (DNA-damage inducible transcript 3). Cachectic mice exhibited a dysregulation of protein synthesis signaling, with an induction of p-mTOR (mechanistic target of rapamycin), despite a suppression of Akt (thymoma viral proto-oncogene 1) and S6 (ribosomal protein S6) phosphorylation. Thus, cancer induced ER-stress markers in the liver, however cachexia progression further deteriorated liver ER-stress, disrupted protein synthesis regulation and caused a differential inflammatory response related to STAT-3 and NF-κB (Nuclear factor—κB) signaling. PMID:25789991

Technical progress in silicon sheet growth under DOE/JPL FSA program, 1975-1986

NASA Technical Reports Server (NTRS)

Kalejs, J. P.

1986-01-01

The technical progress made in the Silicon Sheet Growth Program during its 11 years was reviewed. At present, in 1986, only two of the original 9 techniques have survived to the start-up, pilot-plant stage in industry. These two techniques are the edge-defined, film-fed growth (EFG) technique that produces closed shape polygons, and the WEB dendritic technique that produces single ribbons. Both the status and future concerns of the EFG and WEB techniques were discussed.

Annual Progress Report (17th) and 1992-97 Renewal Proposal Interactive Graphics for Molecular Studies

DTIC Science & Technology

1991-01-24

Molecular Graphics, vol. 6, No. 4 (Dec. 1988), p. 223. Turk, Greg, "Interactive Collision Detection for Molecular Graphics," M.S. thesis , UNC-Chapel Hill...Problem," Master’s thesis , UNC Department of Computer Science Technical Report #TR87-013, May 1987. Pique, ME., "Technical Trends in Molecular Graphics...AD-A236 598 Seventeenth Annual Progress Report and 1992-97 Renewal Proposal Interactive Graphics for Molecular Studies TR91-020 January 24, 1991 red

Enhanced oil recovery utilizing high-angle wells in the Frontier Formation, Badger Basin Field, Park County, Wyoming. Quarterly technical progress report, 1 March 1993--30 June 1993

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

Fortmann, R.G.; Walker, J.P.

1993-07-10

Sierra Energy Company`s targeted goals during the third quarter of this Cooperative Agreement included the following objectives from the Statement of Work: in Phase 2A, completion of subtask 2.1.2--acquire best possible field data in the 3-D seismic program; and initiation of Subtask 2.1.3--process acquired 3-D seismic data. Technical progress is described for these tasks.

Regulation of vascular prostaglandin synthesis by metabolites of arachidonic acid in perfused rabbit aorta.

PubMed Central

Kent, R S; Diedrich, S L; Whorton, A R

1983-01-01

To address the hypothesis that metabolites of arachidonic acid are important regulators of prostaglandin (PG) synthesis in intact vascular tissue, we studied arachidonate metabolism in rabbit aortas in response to a continuous infusion of arachidonic acid, 10 micrograms/ml. Prostacyclin (PGI2; measured as 6-keto-PGF1 alpha) production rate accelerated during the first 2 min, reached peak velocity at 2 min, and then progressively decelerated. The velocity profile of PGI2 production was similar to that previously reported for cyclooxygenase holoenzyme assayed in vitro, and was consistent with progressive inactivation of the enzymes leading to PGI2 synthesis. We determined the specific inhibition of cyclooxygenase and prostacyclin synthetase by measuring PGI2 and PGE2 production rates and by infusing cyclic endoperoxides. Our results indicate preferential inactivation of cyclooxygenase during arachidonate metabolism, most likely due to cyclooxygenase-derived oxidative intermediates. This was a dose-dependent response and resulted in a progressive decrease in the 6-keto-PGF1 alpha/PGE2 ratio. Exogenously added 15-hydroperoxy eicosatetraenoic acid, on the other hand, actually stimulated cyclooxygenase activity at low doses, while markedly inhibiting prostacyclin synthetase. This finding, along with the accelerating nature of arachidonate metabolism, is consistent with the concept of "peroxide tone" as a mediator of cyclooxygenase activity in this system. These results demonstrate that arachidonate metabolites regulate PG synthesis in intact blood vessels. The progressive enzymatic inhibition intrinsic to arachidonate metabolism may be a model for similar changes occurring in states of enhanced lipid peroxidation. These metabolic alterations might greatly influence the numerous vascular functions known to involve arachidonic acid metabolism. PMID:6409932

[Evaluation of risk of progression of endometrial hyperplasia in patients with metabolic syndrome].

PubMed

Bochkareva, N V; Kolomiets, L A; Chernyshova, A L; Stukanov, S L; Savenkova, O V

2010-01-01

A mathematical model based on principles of multifactor analysis was developed to predict clinical outcome of endometrial hyperplasia (EH) in patients with metabolic syndrome (80). Seventy-seven factors--anthropometric, clinical, anamnestic, hormono-metabolic, immunohistochemical, etc.--were included. Evaluation of the most informative indices integrated with the discriminative model showed that anthropometric (waist and hip circumference, sagittal diameter, etc.) and clinico-anamnestic (age, age of secondary sexual characters appearance, body weight at birth, suckling pattern, etc.) ones are of similar significance. A profile of hormono-metabolic parameters (cholesterol-low density lipoprotein, leptin, testosterone, progesterone and fasting glucose levels) helped identify a wide range of EH-related disorders in patients with metabolic syndrome. Consistently with the literature data, level of PTEN expression pointed to the presence of this tumor's suppressor in most EH cases which was matched by absence of its expression in endometrial carcinoma. Our model provided high sensitivity (89%) and specificity (82%) in predicting risk of progression in patients with endometrial hyperplasia and metabolic syndrome.

10 CFR 603.1100 - Contracting officer's post-award responsibilities.

Code of Federal Regulations, 2011 CFR

2011-01-01

... technical progress, financial status, and future program plans. (b) Tracking and processing of reports... progress reports, and patent reports. (c) Handling payment requests and related matters. For a TIA using advance payments, that includes reviews of progress to verify that there is continued justification for...

7 CFR 3402.23 - Documentation of progress on funded projects.

Code of Federal Regulations, 2011 CFR

2011-01-01

... the academic program due to unsatisfactory academic progress; or voluntarily withdraws from the Fellowship or the academic program. If a Fellow has not completed all degree requirements at the end of the... database contains narrative project information, progress/impact statements, and final technical reports...

7 CFR 3402.23 - Documentation of progress on funded projects.

Code of Federal Regulations, 2014 CFR

2014-01-01

... the academic program due to unsatisfactory academic progress; or voluntarily withdraws from the Fellowship or the academic program. If a Fellow has not completed all degree requirements at the end of the... database contains narrative project information, progress/impact statements, and final technical reports...

7 CFR 3402.23 - Documentation of progress on funded projects.

Code of Federal Regulations, 2012 CFR

2012-01-01

... the academic program due to unsatisfactory academic progress; or voluntarily withdraws from the Fellowship or the academic program. If a Fellow has not completed all degree requirements at the end of the... database contains narrative project information, progress/impact statements, and final technical reports...

7 CFR 3402.23 - Documentation of progress on funded projects.

Code of Federal Regulations, 2013 CFR

2013-01-01

... the academic program due to unsatisfactory academic progress; or voluntarily withdraws from the Fellowship or the academic program. If a Fellow has not completed all degree requirements at the end of the... database contains narrative project information, progress/impact statements, and final technical reports...

Emerging Metabolic Therapies in Pulmonary Arterial Hypertension

PubMed Central

Harvey, Lloyd D.; Chan, Stephen Y.

2017-01-01

Pulmonary hypertension (PH) is an enigmatic vascular disorder characterized by pulmonary vascular remodeling and increased pulmonary vascular resistance, ultimately resulting in pressure overload, dysfunction, and failure of the right ventricle. Current medications for PH do not reverse or prevent disease progression, and current diagnostic strategies are suboptimal for detecting early-stage disease. Thus, there is a substantial need to develop new diagnostics and therapies that target the molecular origins of PH. Emerging investigations have defined metabolic aberrations as fundamental and early components of disease manifestation in both pulmonary vasculature and the right ventricle. As such, the elucidation of metabolic dysregulation in pulmonary hypertension allows for greater therapeutic insight into preventing, halting, or even reversing disease progression. This review will aim to discuss (1) the reprogramming and dysregulation of metabolic pathways in pulmonary hypertension; (2) the emerging therapeutic interventions targeting these metabolic pathways; and (3) further innovation needed to overcome barriers in the treatment of this devastating disease. PMID:28375184

Exosome-derived microRNAs in cancer metabolism: possible implications in cancer diagnostics and therapy.

PubMed

Tomasetti, Marco; Lee, Wan; Santarelli, Lory; Neuzil, Jiri

2017-01-20

Malignant progression is greatly affected by dynamic cross-talk between stromal and cancer cells. Exosomes are secreted nanovesicles that have key roles in cell-cell communication by transferring nucleic acids and proteins to target cells and tissues. Recently, MicroRNAs (miRs) and their delivery in exosomes have been implicated in physiological and pathological processes. Tumor-delivered miRs, interacting with stromal cells in the tumor microenvironment, modulate tumor progression, angiogenesis, metastasis and immune escape. Altered cell metabolism is one of the hallmarks of cancer. A number of different types of tumor rely on mitochondrial metabolism by triggering adaptive mechanisms to optimize their oxidative phosphorylation in relation to their substrate supply and energy demands. Exogenous exosomes can induce metabolic reprogramming by restoring the respiration of cancer cells and supress tumor growth. The exosomal miRs involved in the modulation of cancer metabolism may be potentially utilized for better diagnostics and therapy.

NAEP 1999 Long-Term Trend Technical Analysis Report: Three Decades of Student Performance. NCES 2005-484

ERIC Educational Resources Information Center

Allen, Nancy L.; McClellan, Catherine A.; Stoeckel, Joan J.

2005-01-01

This report provides an update to the technical analysis procedures documenting the 1996 National Assessment of Educational Progress (NAEP) as presented in "The NAEP 1996 Technical Report" (Allen, Carlson, and Zelenak, 1999). It describes how the 1999 long-term trend data were incorporated into the trend analyses. Since no national main…

Genetic alterations in fatty acid transport and metabolism genes are associated with metastatic progression and poor prognosis of human cancers

PubMed Central

Nath, Aritro; Chan, Christina

2016-01-01

Reprogramming of cellular metabolism is a hallmark feature of cancer cells. While a distinct set of processes drive metastasis when compared to tumorigenesis, it is yet unclear if genetic alterations in metabolic pathways are associated with metastatic progression of human cancers. Here, we analyzed the mutation, copy number variation and gene expression patterns of a literature-derived model of metabolic genes associated with glycolysis (Warburg effect), fatty acid metabolism (lipogenesis, oxidation, lipolysis, esterification) and fatty acid uptake in >9000 primary or metastatic tumor samples from the multi-cancer TCGA datasets. Our association analysis revealed a uniform pattern of Warburg effect mutations influencing prognosis across all tumor types, while copy number alterations in the electron transport chain gene SCO2, fatty acid uptake (CAV1, CD36) and lipogenesis (PPARA, PPARD, MLXIPL) genes were enriched in metastatic tumors. Using gene expression profiles, we established a gene-signature (CAV1, CD36, MLXIPL, CPT1C, CYP2E1) that strongly associated with epithelial-mesenchymal program across multiple cancers. Moreover, stratification of samples based on the copy number or expression profiles of the genes identified in our analysis revealed a significant effect on patient survival rates, thus confirming prominent roles of fatty acid uptake and metabolism in metastatic progression and poor prognosis of human cancers. PMID:26725848

Genetic alterations in fatty acid transport and metabolism genes are associated with metastatic progression and poor prognosis of human cancers.

PubMed

Nath, Aritro; Chan, Christina

2016-01-04

Reprogramming of cellular metabolism is a hallmark feature of cancer cells. While a distinct set of processes drive metastasis when compared to tumorigenesis, it is yet unclear if genetic alterations in metabolic pathways are associated with metastatic progression of human cancers. Here, we analyzed the mutation, copy number variation and gene expression patterns of a literature-derived model of metabolic genes associated with glycolysis (Warburg effect), fatty acid metabolism (lipogenesis, oxidation, lipolysis, esterification) and fatty acid uptake in >9000 primary or metastatic tumor samples from the multi-cancer TCGA datasets. Our association analysis revealed a uniform pattern of Warburg effect mutations influencing prognosis across all tumor types, while copy number alterations in the electron transport chain gene SCO2, fatty acid uptake (CAV1, CD36) and lipogenesis (PPARA, PPARD, MLXIPL) genes were enriched in metastatic tumors. Using gene expression profiles, we established a gene-signature (CAV1, CD36, MLXIPL, CPT1C, CYP2E1) that strongly associated with epithelial-mesenchymal program across multiple cancers. Moreover, stratification of samples based on the copy number or expression profiles of the genes identified in our analysis revealed a significant effect on patient survival rates, thus confirming prominent roles of fatty acid uptake and metabolism in metastatic progression and poor prognosis of human cancers.

The Pentose Phosphate Pathway as a Potential Target for Cancer Therapy

PubMed Central

Cho, Eunae Sandra; Cha, Yong Hoon; Kim, Hyun Sil; Kim, Nam Hee; Yook, Jong In

2018-01-01

During cancer progression, cancer cells are repeatedly exposed to metabolic stress conditions in a resource-limited environment which they must escape. Increasing evidence indicates the importance of nicotinamide adenine dinucleotide phosphate (NADPH) homeostasis in the survival of cancer cells under metabolic stress conditions, such as metabolic resource limitation and therapeutic intervention. NADPH is essential for scavenging of reactive oxygen species (ROS) mainly derived from oxidative phosphorylation required for ATP generation. Thus, metabolic reprogramming of NADPH homeostasis is an important step in cancer progression as well as in combinational therapeutic approaches. In mammalian, the pentose phosphate pathway (PPP) and one-carbon metabolism are major sources of NADPH production. In this review, we focus on the importance of glucose flux control towards PPP regulated by oncogenic pathways and the potential therein for metabolic targeting as a cancer therapy. We also summarize the role of Snail (Snai1), an important regulator of the epithelial mesenchymal transition (EMT), in controlling glucose flux towards PPP and thus potentiating cancer cell survival under oxidative and metabolic stress. PMID:29212304

xCT (SLC7A11)-mediated metabolic reprogramming promotes non-small cell lung cancer progression.

PubMed

Ji, Xiangming; Qian, Jun; Rahman, S M Jamshedur; Siska, Peter J; Zou, Yong; Harris, Bradford K; Hoeksema, Megan D; Trenary, Irina A; Heidi, Chen; Eisenberg, Rosana; Rathmell, Jeffrey C; Young, Jamey D; Massion, Pierre P

2018-05-23

Many tumors increase uptake and dependence on glucose, cystine or glutamine. These basic observations on cancer cell metabolism have opened multiple new diagnostic and therapeutic avenues in cancer research. Recent studies demonstrated that smoking could induce the expression of xCT (SLC7A11) in oral cancer cells, suggesting that overexpression of xCT may support lung tumor progression. We hypothesized that overexpression of xCT occurs in lung cancer cells to satisfy the metabolic requirements for growth and survival. Our results demonstrated that 1) xCT was highly expressed at the cytoplasmic membrane in non-small cell lung cancer (NSCLC), 2) the expression of xCT was correlated with advanced stage and predicted a worse 5-year survival, 3) targeting xCT transport activity in xCT overexpressing NSCLC cells with sulfasalazine decreased cell proliferation and invasion in vitro and in vivo and 4) increased dependence on glutamine was observed in xCT overexpressed normal airway epithelial cells. These results suggested that xCT regulate metabolic requirements during lung cancer progression and be a potential therapeutic target in NSCLC.

Suppression of mitochondrial respiration with auraptene inhibits the progression of renal cell carcinoma: involvement of HIF-1α degradation.

PubMed

Jang, Yunseon; Han, Jeongsu; Kim, Soo Jeong; Kim, Jungim; Lee, Min Joung; Jeong, Soyeon; Ryu, Min Jeong; Seo, Kang-Sik; Choi, Song-Yi; Shong, Minho; Lim, Kyu; Heo, Jun Young; Kweon, Gi Ryang

2015-11-10

Renal cell carcinoma (RCC) progression resulting from the uncontrolled migration and enhanced angiogenesis is an obstacle to effective therapeutic intervention. Tumor metabolism has distinctive feature called Warburg effect, which enhances the aerobic glycolysis rapidly supplying the energy for migration of tumor. To manipulate this metabolic change characteristic of aggressive tumors, we utilized the citrus extract, auraptene, known as a mitochondrial inhibitor, testing its anticancer effects against the RCC4 cell line. We found that auraptene impaired RCC4 cell motility through reduction of mitochondrial respiration and glycolytic pathway-related genes. It also strongly disrupted VEGF-induced angiogenesis in vitro and in vivo. Hypoxia-inducible factor 1a (HIF-1a), a key regulator of cancer metabolism, migration and angiogenesis that is stably expressed in RCCs by virtue of a genetic mutation in the von Hippel-Lindau (VHL) tumor-suppressor protein, was impeded by auraptene, which blocked HIF-1a translation initiation without causing cytotoxicity. We suggest that blockade HIF-1a and reforming energy metabolism with auraptene is an effective approach for suspension RCC progression.

Technologies for diagnosis and treatment of acute stroke

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

Fitch, J.P.

1998-02-09

From October 1994 to June 1997, a multidisciplinary team of scientists and engineers at Lawrence Livermore National Laboratory were funded through LDRD to develop and integrate technologies for diagnosis and treatment of acute stroke. The project was summarized in a Science and Technology Review article `Brain Attack` that appeared in June 1997 and again in the Center for Healthcare Technologies Report (UCRL-LR-124761). This article is the best overview of the project, epidemiology of stroke and technical progress. Most of the technical progress has been documented in conference papers and presentations and refereed journal articles. Additional technical publication can be expectedmore » as our remaining patent applications progress through the US Patent and Trademark Office. The purpose of this report is to provide an appropriate introduction and organization to the numerous publications so that interested readers can quickly find information. Because there is no documentation for the history of this project, this report provides a summary. It also provides the final status report for the LDRD funding.« less

Metabolic cooperation between cancer and non-cancerous stromal cells is pivotal in cancer progression.

PubMed

Lopes-Coelho, Filipa; Gouveia-Fernandes, Sofia; Serpa, Jacinta

2018-02-01

The way cancer cells adapt to microenvironment is crucial for the success of carcinogenesis, and metabolic fitness is essential for a cancer cell to survive and proliferate in a certain organ/tissue. The metabolic remodeling in a tumor niche is endured not only by cancer cells but also by non-cancerous cells that share the same microenvironment. For this reason, tumor cells and stromal cells constitute a complex network of signal and organic compound transfer that supports cellular viability and proliferation. The intensive dual-address cooperation of all components of a tumor sustains disease progression and metastasis. Herein, we will detail the role of cancer-associated fibroblasts, cancer-associated adipocytes, and inflammatory cells, mainly monocytes/macrophages (tumor-associated macrophages), in the remodeling and metabolic adaptation of tumors.

Albuminuria and Glomerular Filtration Rate in Individuals with Type 1 Diabetes Mellitus: Contribution of Metabolic Syndrome.

PubMed

Uribe-Wiechers, Ana Cecilia; Janka-Zires, Marcela; Almeda-Valdés, Paloma; López-Gutiérrez, Joel; Gómez-Pérez, Francisco J

2015-01-01

The development of metabolic syndrome has been described in patients with type 1 diabetes mellitus as the disease progresses over time. The purpose of this study is to assess the relationship between metabolic syndrome, albuminuria, and glomerular filtration rate, as well as to determine the prevalence of metabolic syndrome, in a group of Mexican patients with type 1 diabetes mellitus. We conducted a cross-sectional study that included patients with type 1 diabetes mellitus who were diagnosed over 10 years ago and who are seen at the Diabetes Intensive Control Clinic of the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran in Mexico City. The presence of metabolic syndrome was determined by using the National Cholesterol Education Program-Adult Treatment Panel III (ATP III) criteria. A total of 81 individuals were studied. The prevalence of metabolic syndrome was 18.5% (n = 15). A higher albuminuria was found in subjects with metabolic syndrome (34.9 mg/24 hours; 8.3-169.3) than in those without metabolic syndrome (9.0 mg/24 hours; 5.0-27.0; p = 0.02). Glomerular filtration rate was lower in patients with metabolic syndrome (95.3 ml/minute; [64.9-107.2] vs. 110.2 ml/minute [88.1-120.3]; p = 0.04). After classifying the population according to the number of metabolic syndrome criteria, a progressive increase in albuminuria and a progressive decrease in glomerular filtration rate were found with each additional metabolic syndrome criterion (p = 0.008 and p = 0.032, respectively). After adjusting for age, time from diagnosis, systolic blood pressure, triglycerides, HDL-cholesterol, and treatment with angiotensin receptor blockers or angiotensin converting enzyme inhibitors, we found that age, time from diagnosis, triglycerides, and HDL-cholesterol were independent factors associated with glomerular filtration rate (R2 = 0.286; p < 0.001). Metabolic syndrome was associated with a higher albuminuria and a reduction in glomerular filtration rate in patients with type 1 diabetes mellitus. Metabolic syndrome was present in 18.5% of this group of Mexican individuals with type 1 diabetes mellitus.

Proceedings: Computer Science and Data Systems Technical Symposium, volume 2

NASA Technical Reports Server (NTRS)

Larsen, Ronald L.; Wallgren, Kenneth

1985-01-01

Progress reports and technical updates of programs being performed by NASA centers are covered. Presentations in viewgraph form, along with abstracts, are included for topics in three catagories: computer science, data systems, and space station applications.

A study on operation efficiency evaluation based on firm's financial index and benchmark selection: take China Unicom as an example

NASA Astrophysics Data System (ADS)

Wu, Zu-guang; Tian, Zhan-jun; Liu, Hui; Huang, Rui; Zhu, Guo-hua

2009-07-01

Being the only listed telecom operators of A share market, China Unicom has always been attracted many institutional investors under the concept of 3G recent years,which itself is a great technical progress expectation.Do the institutional investors or the concept of technical progress have signficant effect on the improving of firm's operating efficiency?Though reviewing the documentary about operating efficiency we find that schoolars study this problem useing the regress analyzing based on traditional production function and data envelopment analysis(DEA) and financial index anayzing and marginal function and capital labor ratio coefficient etc. All the methods mainly based on macrodata. This paper we use the micro-data of company to evaluate the operating efficiency.Using factor analyzing based on financial index and comparing the factor score of three years from 2005 to 2007, we find that China Unicom's operating efficiency is under the averge level of benchmark corporates and has't improved under the concept of 3G from 2005 to 2007.In other words,institutional investor or the conception of technical progress expectation have faint effect on the changes of China Unicom's operating efficiency. Selecting benchmark corporates as post to evaluate the operating efficiency is a characteristic of this method ,which is basicallly sipmly and direct.This method is suit for the operation efficiency evaluation of agriculture listed companies because agriculture listed also face technical progress and marketing concept such as tax-free etc.

Decontamination Systems Information and Research Program. Quarterly technical progress report, January 1--March 31, 1994

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

Not Available

1994-05-01

West Virginia University (WVU) and the US DOE Morgantown Energy Technology Center (METC) entered into a Cooperative Agreement on August 29, 1992 entitled ``Decontamination Systems Information and Research Programs.`` Stipulated within the Agreement is the requirement that WVU submit to METC a series of Technical Progress Reports on a quarterly basis. This report comprises the first Quarterly Technical Progress Report for Year 2 of the Agreement. This report reflects the progress and/or efforts performed on the sixteen (16) technical projects encompassed by the Year 2 Agreement for the period of January 1 through March 31, 1994. In situ bioremediation ofmore » chlorinated organic solvents; Microbial enrichment for enhancing in-situ biodegradation of hazardous organic wastes; Treatment of volatile organic compounds (VOCs) using biofilters; Drain-enhanced soil flushing (DESF) for organic contaminants removal; Chemical destruction of chlorinated organic compounds; Remediation of hazardous sites with steam reforming; Soil decontamination with a packed flotation column; Use of granular activated carbon columns for the simultaneous removal of organics, heavy metals, and radionuclides; Monolayer and multilayer self-assembled polyion films for gas-phase chemical sensors; Compact mercuric iodide detector technology development; Evaluation of IR and mass spectrometric techniques for on-site monitoring of volatile organic compounds; A systematic database of the state of hazardous waste clean-up technologies; Dust control methods for insitu nuclear and hazardous waste handling; Winfield Lock and Dam remediation; and Socio-economic assessment of alternative environmental restoration technologies.« less

[Regulation of terpene metabolism]. [Mentha piperita, Mentha spicata

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

Croteau, R.

1989-01-01

Progress in understanding of the metabolism of monoterpenes by peppermint and spearmint is recorded including the actions of two key enzymes, geranyl pyrophosphate:limonene cyclase and a UDP-glucose dependent glucosyl transferase; concerning the ultrastructure of oil gland senescence; enzyme subcellular localization; regulation of metabolism; and tissue culture systems.

Regulation of Tumor Progression by Programmed Necrosis

PubMed Central

Jeon, Hyun Min; Jeong, Eui Kyong; Lee, Yig Ji; Kim, Cho Hee; Park, Hye Gyeong

2018-01-01

Rapidly growing malignant tumors frequently encounter hypoxia and nutrient (e.g., glucose) deprivation, which occurs because of insufficient blood supply. This results in necrotic cell death in the core region of solid tumors. Necrotic cells release their cellular cytoplasmic contents into the extracellular space, such as high mobility group box 1 (HMGB1), which is a nonhistone nuclear protein, but acts as a proinflammatory and tumor-promoting cytokine when released by necrotic cells. These released molecules recruit immune and inflammatory cells, which exert tumor-promoting activity by inducing angiogenesis, proliferation, and invasion. Development of a necrotic core in cancer patients is also associated with poor prognosis. Conventionally, necrosis has been thought of as an unregulated process, unlike programmed cell death processes like apoptosis and autophagy. Recently, necrosis has been recognized as a programmed cell death, encompassing processes such as oncosis, necroptosis, and others. Metabolic stress-induced necrosis and its regulatory mechanisms have been poorly investigated until recently. Snail and Dlx-2, EMT-inducing transcription factors, are responsible for metabolic stress-induced necrosis in tumors. Snail and Dlx-2 contribute to tumor progression by promoting necrosis and inducing EMT and oncogenic metabolism. Oncogenic metabolism has been shown to play a role(s) in initiating necrosis. Here, we discuss the molecular mechanisms underlying metabolic stress-induced programmed necrosis that promote tumor progression and aggressiveness. PMID:29636841

Seizing the Future: How Ohio's Career-Technical Education Programs Fuse Academic Rigor and Real-World Experiences to Prepare Students for College and Careers

ERIC Educational Resources Information Center

Guarino, Heidi; Yoder, Shaun

2015-01-01

"Seizing the Future: How Ohio's Career and Technical Education Programs Fuse Academic Rigor and Real-World Experiences to Prepare Students for College and Work," demonstrates Ohio's progress in developing strong policies for career and technical education (CTE) programs to promote rigor, including college- and career-ready graduation…

Case Study on Technical and Vocational Education in Japan. Case Studies on Technical and Vocational Education in Asia and the Pacific.

ERIC Educational Resources Information Center

Iwamoto, Muneharu

In the course of Japan's economic progress, remarkable changes have occurred in the structure of industry and employment. Workers are in extremely short supply in such occupations as mining, manufacturing and construction, services, transportation and communication, sales, and professional and technical. On the basis of recommendations of the…

25 CFR 30.104 - What is the Secretary's definition of AYP?

Code of Federal Regulations, 2011 CFR

2011-04-01

... PROGRESS Defining Adequate Yearly Progress § 30.104 What is the Secretary's definition of AYP? The... accepted by the Department of Education. The Secretary is committed to providing technical assistance to a...

25 CFR 30.104 - What is the Secretary's definition of AYP?

Code of Federal Regulations, 2010 CFR

2010-04-01

... PROGRESS Defining Adequate Yearly Progress § 30.104 What is the Secretary's definition of AYP? The... accepted by the Department of Education. The Secretary is committed to providing technical assistance to a...

Tumor Response and Survival Predicted by Post-Therapy FDG-PET/CT in Anal Cancer

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

Schwarz, Julie K.; Siegel, Barry A.; Dehdashti, Farrokh

2008-05-01

Purpose: To evaluate the response to therapy for anal carcinoma using post-therapy imaging with positron emission tomography (PET)/computed tomography and F-18 fluorodeoxyglucose (FDG) and to compare the metabolic response with patient outcome. Patients and Methods: This was a prospective cohort study of 53 consecutive patients with anal cancer. All patients underwent pre- and post-treatment whole-body FDG-PET/computed tomography. Patients had been treated with external beam radiotherapy and concurrent chemotherapy. Whole-body FDG-PET was performed 0.9-5.4 months (mean, 2.1) after therapy completion. Results: The post-therapy PET scan did not show any abnormal FDG uptake (complete metabolic response) in 44 patients. Persistent abnormal FDGmore » uptake (partial metabolic response) was found in the anal tumor in 9 patients. The 2-year cause-specific survival rate was 94% for patients with a complete vs. 39% for patients with a partial metabolic response in the anal tumor (p = 0.0008). The 2-year progression-free survival rate was 95% for patients with a complete vs. 22% for patients with a partial metabolic response in the anal tumor (p < 0.0001). A Cox proportional hazards model of survival outcome indicated that a complete metabolic response was the most significant predictor of progression-free survival in our patient population (p = 0.0003). Conclusions: A partial metabolic response in the anal tumor as determined by post-therapy FDG-PET is predictive of significantly decreased progression-free and cause-specific survival after chemoradiotherapy for anal cancer.« less

Second-harmonic generation and fluorescence lifetime imaging microscopy through a rodent mammary imaging window

NASA Astrophysics Data System (ADS)

Young, Pamela A.; Nazir, Muhammad; Szulczewski, Michael J.; Keely, Patricia J.; Eliceiri, Kevin W.

2012-03-01

Tumor-Associated Collagen Signatures (TACS) have been identified that manifest in specific ways during breast tumor progression and that correspond to patient outcome. There are also compelling metabolic changes associated with carcinoma invasion and progression. We have characterized the difference in the autofluorescent properties of metabolic co-factors, NADH and FAD, between normal and carcinoma breast cell lines. Also, we have shown in vitro that increased collagen density alters metabolic genes which are associated with glycolysis and leads to a more invasive phenotype. Establishing the relationship between collagen density, cellular metabolism, and metastasis in physiologically relevant cancer models is crucial for developing cancer therapies. To study cellular metabolism with respect to collagen density in vivo, we use multiphoton fluorescence excitation microscopy (MPM) in conjunction with a rodent mammary imaging window implanted in defined mouse cancer models. These models are ideal for the study of collagen changes in vivo, allowing determination of corresponding metabolic changes in breast cancer invasion and progression. To measure cellular metabolism, we collect fluorescence lifetime (FLIM) signatures of NADH and FAD, which are known to change based on the microenvironment of the cells. Additionally, MPM systems are capable of collecting second harmonic generation (SHG) signals which are a nonlinear optical property of collagen. Therefore, MPM, SHG, and FLIM are powerful tools with great potential for characterizing key features of breast carcinoma in vivo. Below we present the current efforts of our collaborative group to develop intravital approaches based on these imaging techniques to look at defined mouse mammary models.

Machine Learning Approach for Classifying Multiple Sclerosis Courses by Combining Clinical Data with Lesion Loads and Magnetic Resonance Metabolic Features.

PubMed

Ion-Mărgineanu, Adrian; Kocevar, Gabriel; Stamile, Claudio; Sima, Diana M; Durand-Dubief, Françoise; Van Huffel, Sabine; Sappey-Marinier, Dominique

2017-01-01

Purpose: The purpose of this study is classifying multiple sclerosis (MS) patients in the four clinical forms as defined by the McDonald criteria using machine learning algorithms trained on clinical data combined with lesion loads and magnetic resonance metabolic features. Materials and Methods: Eighty-seven MS patients [12 Clinically Isolated Syndrome (CIS), 30 Relapse Remitting (RR), 17 Primary Progressive (PP), and 28 Secondary Progressive (SP)] and 18 healthy controls were included in this study. Longitudinal data available for each MS patient included clinical (e.g., age, disease duration, Expanded Disability Status Scale), conventional magnetic resonance imaging and spectroscopic imaging. We extract N -acetyl-aspartate (NAA), Choline (Cho), and Creatine (Cre) concentrations, and we compute three features for each spectroscopic grid by averaging metabolite ratios (NAA/Cho, NAA/Cre, Cho/Cre) over good quality voxels. We built linear mixed-effects models to test for statistically significant differences between MS forms. We test nine binary classification tasks on clinical data, lesion loads, and metabolic features, using a leave-one-patient-out cross-validation method based on 100 random patient-based bootstrap selections. We compute F1-scores and BAR values after tuning Linear Discriminant Analysis (LDA), Support Vector Machines with gaussian kernel (SVM-rbf), and Random Forests. Results: Statistically significant differences were found between the disease starting points of each MS form using four different response variables: Lesion Load, NAA/Cre, NAA/Cho, and Cho/Cre ratios. Training SVM-rbf on clinical and lesion loads yields F1-scores of 71-72% for CIS vs. RR and CIS vs. RR+SP, respectively. For RR vs. PP we obtained good classification results (maximum F1-score of 85%) after training LDA on clinical and metabolic features, while for RR vs. SP we obtained slightly higher classification results (maximum F1-score of 87%) after training LDA and SVM-rbf on clinical, lesion loads and metabolic features. Conclusions: Our results suggest that metabolic features are better at differentiating between relapsing-remitting and primary progressive forms, while lesion loads are better at differentiating between relapsing-remitting and secondary progressive forms. Therefore, combining clinical data with magnetic resonance lesion loads and metabolic features can improve the discrimination between relapsing-remitting and progressive forms.

Metabolic Bone Diseases and Total Hip Arthroplasty: Preventing Complications.

PubMed

Moya-Angeler, Joaquin; Lane, Joseph M; Rodriguez, Jose A

2017-11-01

Metabolic bone diseases are a diverse group of conditions characterized by abnormalities in calcium metabolism and/or bone cell physiology. These unbalanced processes can eventually lead to bony deformities and altered joint biomechanics, resulting in degenerative joint disease. Not infrequently, patients with metabolic bone diseases have restricting hip joint pain that ultimately necessitates hip arthroplasty. To minimize complications, the surgeon must consider the particular characteristics of these patients. The surgical and medical management of patients with metabolic bone diseases undergoing hip arthroplasty requires appropriate preoperative diagnosis, careful attention to the technical challenges of surgery, and strategies to maximize the long-term results of the surgical intervention, such as the use of bone anabolic and anticatabolic agents.

ANNUAL REPORT, JULY 1, 1958

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

None

1959-02-01

This annual report of Brookhaven National Laboratory describes its program and activities for the fiscal year 1958. The progress and trends of the research program are presented along with a description of the operational, service, and administrative activities of the Laboratory. The scientific and technical details of the many research and development activities are covered more fully in scientific and technical periodicals and in the quarterly scientific progress reports and other scientiflc reports of the Laboratory. A list of all publications for July 1, 1957 to June 30, 1958, is given. Status and progress are given in fields of physics,more » accelerator development, instrumentation, applied mathematics, chemistry, nuclear engineering, biology, and medical research. (For preceding period see BNL-462.) (W.D.M.)« less

Towards a space-borne quantum gravity gradiometer: progress in laboratory demonstration

NASA Technical Reports Server (NTRS)

Yu, Nan; Kohel, James M.; Kellogg, James R.; Maleki, Lute

2005-01-01

This paper describes the working principles and technical benefits of atom-wave interferometer-based inertial sensors, and gives a progress report on the development of a quantum gravity gradiometer for space applications at JPL.

Technical Progress of the New Worlds Observer Mission

NASA Astrophysics Data System (ADS)

Lo, Amy; Noecker, C.; Cash, W.; NWO Study Team

2009-01-01

We report on the technical progress of the New Worlds Observer (NWO) mission concept. NWO is a two spacecraft mission that is capable of detecting and characterizing extra-solar, terrestrial planets and planetary systems. NWO consists of an external starshade and an UV-optical space telescope, flying in tandem. The starshade is a petal-shaped, opaque screen that creates an extremely dark shadow large enough to shade the telescope aperture from the target star. The NWO team has been addressing the top technology challenges of the concept, and report here our progress. We will present the current mission configuration best suited to address Terrestrial Planet Finding requirements, and highlight the technological breakthroughs that we have achieved this year. In particular, we will report on progress made in precision deployables for the large starshade, and the trajectory & alignment control system for NWO. We will also briefly highlight advances in understanding the starshade optical performance.

A disease-specific metabolic brain network associated with corticobasal degeneration

PubMed Central

Niethammer, Martin; Tang, Chris C.; Feigin, Andrew; Allen, Patricia J.; Heinen, Lisette; Hellwig, Sabine; Amtage, Florian; Hanspal, Era; Vonsattel, Jean Paul; Poston, Kathleen L.; Meyer, Philipp T.; Leenders, Klaus L.

2014-01-01

Corticobasal degeneration is an uncommon parkinsonian variant condition that is diagnosed mainly on clinical examination. To facilitate the differential diagnosis of this disorder, we used metabolic brain imaging to characterize a specific network that can be used to discriminate corticobasal degeneration from other atypical parkinsonian syndromes. Ten non-demented patients (eight females/two males; age 73.9 ± 5.7 years) underwent metabolic brain imaging with 18F-fluorodeoxyglucose positron emission tomography for atypical parkinsonism. These individuals were diagnosed clinically with probable corticobasal degeneration. This diagnosis was confirmed in the three subjects who additionally underwent post-mortem examination. Ten age-matched healthy subjects (five females/five males; age 71.7 ± 6.7 years) served as controls for the imaging studies. Spatial covariance analysis was applied to scan data from the combined group to identify a significant corticobasal degeneration-related metabolic pattern that discriminated (P < 0.001) the patients from the healthy control group. This pattern was characterized by bilateral, asymmetric metabolic reductions involving frontal and parietal cortex, thalamus, and caudate nucleus. These pattern-related changes were greater in magnitude in the cerebral hemisphere opposite the more clinically affected body side. The presence of this corticobasal degeneration-related metabolic topography was confirmed in two independent testing sets of patient and control scans, with elevated pattern expression (P < 0.001) in both disease groups relative to corresponding normal values. We next determined whether prospectively computed expression values for this pattern accurately discriminated corticobasal degeneration from multiple system atrophy and progressive supranuclear palsy (the two most common atypical parkinsonian syndromes) on a single case basis. Based upon this measure, corticobasal degeneration was successfully distinguished from multiple system atrophy (P < 0.001) but not progressive supranuclear palsy, presumably because of the overlap (∼24%) that existed between the corticobasal degeneration- and the progressive supranuclear palsy-related metabolic topographies. Nonetheless, excellent discrimination between these disease entities was achieved by computing hemispheric asymmetry scores for the corticobasal degeneration-related pattern on a prospective single scan basis. Indeed, a logistic algorithm based on the asymmetry scores combined with separately computed expression values for a previously validated progressive supranuclear palsy-related pattern provided excellent specificity (corticobasal degeneration: 92.7%; progressive supranuclear palsy: 94.1%) in classifying 58 testing subjects. In conclusion, corticobasal degeneration is associated with a reproducible disease-related metabolic covariance pattern that may help to distinguish this disorder from other atypical parkinsonian syndromes. PMID:25208922

A disease-specific metabolic brain network associated with corticobasal degeneration.

PubMed

Niethammer, Martin; Tang, Chris C; Feigin, Andrew; Allen, Patricia J; Heinen, Lisette; Hellwig, Sabine; Amtage, Florian; Hanspal, Era; Vonsattel, Jean Paul; Poston, Kathleen L; Meyer, Philipp T; Leenders, Klaus L; Eidelberg, David

2014-11-01

Corticobasal degeneration is an uncommon parkinsonian variant condition that is diagnosed mainly on clinical examination. To facilitate the differential diagnosis of this disorder, we used metabolic brain imaging to characterize a specific network that can be used to discriminate corticobasal degeneration from other atypical parkinsonian syndromes. Ten non-demented patients (eight females/two males; age 73.9 ± 5.7 years) underwent metabolic brain imaging with (18)F-fluorodeoxyglucose positron emission tomography for atypical parkinsonism. These individuals were diagnosed clinically with probable corticobasal degeneration. This diagnosis was confirmed in the three subjects who additionally underwent post-mortem examination. Ten age-matched healthy subjects (five females/five males; age 71.7 ± 6.7 years) served as controls for the imaging studies. Spatial covariance analysis was applied to scan data from the combined group to identify a significant corticobasal degeneration-related metabolic pattern that discriminated (P < 0.001) the patients from the healthy control group. This pattern was characterized by bilateral, asymmetric metabolic reductions involving frontal and parietal cortex, thalamus, and caudate nucleus. These pattern-related changes were greater in magnitude in the cerebral hemisphere opposite the more clinically affected body side. The presence of this corticobasal degeneration-related metabolic topography was confirmed in two independent testing sets of patient and control scans, with elevated pattern expression (P < 0.001) in both disease groups relative to corresponding normal values. We next determined whether prospectively computed expression values for this pattern accurately discriminated corticobasal degeneration from multiple system atrophy and progressive supranuclear palsy (the two most common atypical parkinsonian syndromes) on a single case basis. Based upon this measure, corticobasal degeneration was successfully distinguished from multiple system atrophy (P < 0.001) but not progressive supranuclear palsy, presumably because of the overlap (∼ 24%) that existed between the corticobasal degeneration- and the progressive supranuclear palsy-related metabolic topographies. Nonetheless, excellent discrimination between these disease entities was achieved by computing hemispheric asymmetry scores for the corticobasal degeneration-related pattern on a prospective single scan basis. Indeed, a logistic algorithm based on the asymmetry scores combined with separately computed expression values for a previously validated progressive supranuclear palsy-related pattern provided excellent specificity (corticobasal degeneration: 92.7%; progressive supranuclear palsy: 94.1%) in classifying 58 testing subjects. In conclusion, corticobasal degeneration is associated with a reproducible disease-related metabolic covariance pattern that may help to distinguish this disorder from other atypical parkinsonian syndromes. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

Ghirardi, Maria L

The National Renewable Energy Laboratory (NREL), under the guidance of Drs. Michael Seibert (retired, Fellow Emeritus) and Maria Ghirardi (Fellow), led 15 years of research addressing the issue of algal H2 photoproduction. This project resulted in greatly increased rates and yields of algal hydrogen production; increased understanding of the H2 metabolism in the green alga, Chlamydomonas reinhardtii; expanded our knowledge of other physiological aspects relevant to sustained algal photosynthetic H2 production; led to the genetic identification, cloning and manipulation of algal hydrogenase genes; and contributed to a broader, fundamental understanding of the technical and scientific challenges to improving the conversionmore » efficiencies in order to reach the U.S. Department of Energy’s Fuel Cell Technologies Office’s targets. Some of the tangible results are: (i) 64 publications and 6 patents, (ii) international visibility to NREL, (iii) reinvigoration of national and international biohydrogen research, and (iv) research progress that helped stimulate new funding from other DOE and non-DOE programs, including the AFOSR and the DOE Office of Science.« less

Improvement of industrially important microbial strains by genome shuffling: Current status and future prospects.

PubMed

Magocha, Tinashe Archbold; Zabed, H; Yang, Miaomiao; Yun, Junhua; Zhang, Huanhuan; Qi, Xianghui

2018-06-01

The growing demand for biotechnological products against limited metabolic capacity of industrially used microorganisms has led to an increased interest on strain-improvement over the last several decades, which aimed to enhance metabolite yield, substrate uptake and tolerance of the strains. Among a few techniques of strain-improvement, genome shuffling is the most recent and promising approach used for rapid strain-improvement that can yield a new strain by combining whole genomes of multi-parental microorganisms using the principles of protoplast fusion. Genome shuffling has brought a major breakthrough in the strain-improvement concept as it is found to be effective and reliable for expressing complex phenotypes. This review will discuss the technical aspects and applications of genome shuffling for various industrial strains to present its current status and recent progress. In the concluding remarks, a summary will be presented focusing on the major challenges and future outlooks of this technology. Copyright © 2018 Elsevier Ltd. All rights reserved.

Murine CD103+ dendritic cells protect against steatosis progression towards steatohepatitis.

PubMed

Heier, Eva-Carina; Meier, Anna; Julich-Haertel, Henrike; Djudjaj, Sonja; Rau, Monica; Tschernig, Thomas; Geier, Andreas; Boor, Peter; Lammert, Frank; Lukacs-Kornek, Veronika

2017-06-01

Non-alcoholic fatty liver (NAFL) is the hepatic consequence of metabolic syndrome and can progress to non-alcoholic steatohepatitis (NASH). The identification of molecular and cellular factors that determine the progression of NASH and lead to irreversible hepatocellular damage are crucial. Dendritic cells (DCs) represent a heterogeneous cell population among which CD103 + DCs play a significant role in immunity and tolerance. We aimed to clarify the role of this DC subset in the pathomechanism of NASH. Steatosis progression towards steatohepatitis was analysed using multicolor FACS analyses, cytokine and qPCR array in high sucrose diet (HSD) and methionine and choline deficient diet (MCD) fed wild-type and basic leucine zipper transcription factor, ATF-Like-3 (Batf3) deficient animals, which lack CD103 + DCs (classical type-1 DC, cDC1s). Metabolic challenge of Batf3 -/- animals resulted in the progression of steatosis towards steatohepatitis, manifesting by an increased influx of inflammatory cells into the liver and elevated inflammatory cytokine production of myeloid cells upon innate stimuli. However, the lack of cDC1s did not affect cellular apoptosis and fibrosis progression but altered genes involved in lipid metabolism. The adoptive transfer of CD103 + cDC1s to Batf3 deficient animals reversed these observed changes and more importantly could attenuate cellular damage and inflammation in established murine steatohepatitis. Here, we have identified the murine CD103 + cDC1s as a protective DC subtype that influences the pro-anti-inflammatory balance and protects the liver from metabolic damage. As guardians of liver integrity, they play a key role in the inflammatory process during the development of steatohepatitis in mice. Non-alcoholic fatty liver (NAFL) is the hepatic consequence of metabolic syndrome and can lead to non-alcoholic steatohepatitis (NASH). The current study demonstrated that a specific murine dendritic cell subtype possesses a potent regulatory role to influence the inflammatory milieu of the liver in this process. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Inhibition of Pyruvate Dehydrogenase Kinase as a Therapeutic Strategy against Cancer.

PubMed

Sradhanjali, Swatishree; Reddy, Mamatha M

2018-05-22

Cancer cells alter their metabolism to support the uninterrupted supply of biosynthetic molecules required for continuous proliferation. Glucose metabolism is frequently reprogrammed in several tumors in addition to fatty acid, amino acid and glutamine metabolism. Pyruvate dehydrogenase kinase (PDK) is a gatekeeper enzyme involved in altered glucose metabolism in tumors. There are four isoforms of PDK (1 to 4) in humans. PDK phosphorylates E1α subunit of pyruvate dehydrogenase complex (PDC) and inactivates it. PDC decarboxylates pyruvate to acetyl CoA, which is further metabolized in mitochondria. Overexpression of PDK was observed in several tumors and is frequently associated with chemotherapy related drug resistance, invasion and metastasis. Elevated expression of PDK leads to a shift in glucose metabolism towards glycolysis instead of oxidative phosphorylation. This review summarizes recent literature related to the role of PDKs in cancer and their inhibition as a strategy. In particular, we discuss the role of PDK in tumor progression, metabolic reprogramming in stem cells, and their regulation by miRNAs and lncRNAs, oncogenes and tumor suppressors. Further, we review strategies aimed at targeting PDK to halt tumor growth and progression. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Glycans as Regulatory Elements of the Insulin/IGF System: Impact in Cancer Progression

PubMed Central

Andrade-da-Costa, Jéssica; Silva, Mariana Costa

2017-01-01

The insulin/insulin-like growth factor (IGF) system in mammals comprises a dynamic network of proteins that modulate several biological processes such as development, cell growth, metabolism, and aging. Dysregulation of the insulin/IGF system has major implications for several pathological conditions such as diabetes and cancer. Metabolic changes also culminate in aberrant glycosylation, which has been highlighted as a hallmark of cancer. Changes in glycosylation regulate every pathophysiological step of cancer progression including tumour cell-cell dissociation, cell migration, cell signaling and metastasis. This review discusses how the insulin/IGF system integrates with glycosylation alterations and impacts on cell behaviour, metabolism and drug resistance in cancer. PMID:28880250

Loss of ovarian function in the VCD mouse-model of menopause leads to insulin resistance and a rapid progression into the metabolic syndrome.

PubMed

Romero-Aleshire, Melissa J; Diamond-Stanic, Maggie K; Hasty, Alyssa H; Hoyer, Patricia B; Brooks, Heddwen L

2009-09-01

Factors comprising the metabolic syndrome occur with increased incidence in postmenopausal women. To investigate the effects of ovarian failure on the progression of the metabolic syndrome, female B(6)C(3)F(1) mice were treated with 4-vinylcyclohexene diepoxide (VCD) and fed a high-fat (HF) diet for 16 wk. VCD destroys preantral follicles, causing early ovarian failure and is a well-characterized model for the gradual onset of menopause. After 12 wk on a HF diet, VCD-treated mice had developed an impaired glucose tolerance, whereas cycling controls were unaffected [12 wk AUC HF mice 13,455 +/- 643 vs. HF/VCD 17,378 +/- 1140 mg/dl/min, P < 0.05]. After 16 wk on a HF diet, VCD-treated mice had significantly higher fasting insulin levels (HF 5.4 +/- 1.3 vs. HF/VCD 10.1 +/- 1.4 ng/ml, P < 0.05) and were significantly more insulin resistant (HOMA-IR) than cycling controls on a HF diet (HF 56.2 +/- 16.7 vs. HF/VCD 113.1 +/- 19.6 mg/dl x microU/ml, P < 0.05). All mice on a HF diet gained more weight than mice on a standard diet, and weight gain in HF/VCD mice was significantly increased compared with HF cycling controls. Interestingly, even without a HF diet, progression into VCD-induced menopause caused a significant increase in cholesterol and free fatty acids. Furthermore, in mice fed a standard diet (6% fat), insulin resistance developed 4 mo after VCD-induced ovarian failure. Insulin resistance following ovarian failure (menopause) was prevented by estrogen replacement. Studies here demonstrate that ovarian failure (menopause) accelerates progression into the metabolic syndrome and that estrogen replacement prevents the onset of insulin resistance in VCD-treated mice. Thus, the VCD model of menopause provides a physiologically relevant means of studying how sex hormones influence the progression of the metabolic syndrome.

Epidemiological-molecular evidence of metabolic reprogramming on proliferation, autophagy and cell signaling in pancreas cancer.

PubMed

Søreide, Kjetil; Sund, Malin

2015-01-28

Pancreatic cancer remains one of the deadliest human cancers with little progress made in survival over the past decades, and 5-year survival usually below 5%. Despite this dismal scenario, progresses have been made in understanding of the underlying tumor biology through among other definition of precursor lesions, delineation of molecular pathways, and advances in genome-wide technology. Further, exploring the relationship between epidemiological risk factors involving metabolic features to that of an altered cancer metabolism may provide the foundation for new therapies. Here we explore how nutrients and caloric intake may influence the KRAS-driven ductal carcinogenesis through mediators of metabolic stress, including autophagy in presence of TP53, advanced glycation end products (AGE) and the receptors (RAGE) and ligands (HMGB1), as well as glutamine pathways, among others. Effective understanding the cancer metabolism mechanisms in pancreatic cancer may propose new ways of prevention and treatment. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Metabolic remodeling of substrate utilization during heart failure progression.

PubMed

Chen, Liang; Song, Jiangping; Hu, Shengshou

2018-05-23

Heart failure (HF) is a clinical syndrome caused by a decline in cardiac systolic or diastolic function, which leaves the heart unable to pump enough blood to meet the normal physiological requirements of the human body. It is a serious disease burden worldwide affecting nearly 23 million patients. The concept that heart failure is "an engine out of fuel" has been generally accepted and metabolic remodeling has been recognized as an important aspect of this condition; it is characterized by defects in energy production and changes in metabolic pathways involved in the regulation of essential cellular functions such as the process of substrate utilization, the tricarboxylic acid cycle, oxidative phosphorylation, and high-energy phosphate metabolism. Advances in second-generation sequencing, proteomics, and metabolomics have made it possible to perform comprehensive tests on genes and metabolites that are crucial in the process of HF, thereby providing a clearer and comprehensive understanding of metabolic remodeling during HF. In recent years, new metabolic changes such as ketone bodies and branched-chain amino acids were demonstrated as alternative substrates in end-stage HF. This systematic review focuses on changes in metabolic substrate utilization during the progression of HF and the underlying regulatory mechanisms. Accordingly, the conventional concepts of metabolic remodeling characteristics are reviewed, and the latest developments, particularly multi-omics studies, are compiled.

Risk factors of diabetes in North Indians with metabolic syndrome.

PubMed

Pratyush, Daliparthy D; Tiwari, Shalbha; Singh, Saurabh; Singh, Surya K

2016-01-01

Metabolic syndrome progresses to diabetes and determinants of this progression like hyperinsulinemia, hypertriglyceridemia and genetic factors have been speculative. The present study was aimed at quantifying the insulin resistance and influence of family history of diabetes in subjects with metabolic syndrome developing prediabetes and diabetes. Consecutive subjects attending the endocrine clinic were evaluated for metabolic syndrome as per definition of International Diabetes Federation, 2005. The family history of diabetes in their first degree relatives was ascertained and Homeostasis model assessment of Insulin resistance (HOMA-IR), Homeostasis model assessment for beta cell function (HOMA-B) and Quantitative insulin sensitivity check index (QUICKI) were calculated in 163 subjects enrolled. HOMA-IR was higher (p<0.05) but HOMA-B and QUICKI were lower (p<0.0001) in subjects with metabolic syndrome+prediabetes or diabetes compared to metabolic syndrome with normal glucose tolerance. HOMA-B was lower and prevalence of prediabetes and diabetes was higher in metabolic syndrome subjects with family history of diabetes than in those without such family history (p<0.05). subjects with metabolic syndrome having prediabetes and diabetes had more severe insulin resistance than those with metabolic syndrome only. Beta cell dysfunction was remarkable and prevalence of prediabetes was high in metabolic syndrome subjects with family history of diabetes. Both the severity of the insulin resistance and family history of diabetes are therefore proposed to be determinants of diminished Beta cell function leading to diabetes in metabolic syndrome. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Amarillo National Resource Center for Plutonium. Quarterly technical progress report, May 1, 1997--July 31, 1997

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

NONE

Progress summaries are provided from the Amarillo National Center for Plutonium. Programs include the plutonium information resource center, environment, public health, and safety, education and training, nuclear and other material studies.

Urology technical and non-technical skills development: the emerging role of simulation.

PubMed

Rashid, Prem; Gianduzzo, Troy R J

2016-04-01

To review the emerging role of technical and non-technical simulation in urological education and training. A review was conducted to examine the current role of simulation in urology training. A PUBMED search of the terms 'urology training', 'urology simulation' and 'urology education' revealed 11,504 titles. Three hundred and fifty-seven abstracts were identified as English language, peer reviewed papers pertaining to the role of simulation in urology and related topics. Key papers were used to explore themes. Some cross-referenced papers were also included. There is an ongoing need to ensure that training time is efficiently utilised while ensuring that optimal technical and non-technical skills are achieved. Changing working conditions and the need to minimise patient harm by inadvertent errors must be taken into account. Simulation models for specific technical aspects have been the mainstay of graduated step-wise low and high fidelity training. Whole scenario environments as well as non-technical aspects can be slowly incorporated into the curriculum. Doing so should also help define what have been challenging competencies to teach and evaluate. Dedicated time, resources and trainer up-skilling are important. Concurrent studies are needed to help evaluate the effectiveness of introducing step-wise simulation for technical and non-technical competencies. Simulation based learning remains the best avenue of progressing surgical education. Technical and non-technical simulation could be used in the selection process. There are good economic, logistic and safety reasons to pursue the process of ongoing development of simulation co-curricula. While the role of simulation is assured, its progress will depend on a structured program that takes advantage of what can be delivered via this medium. Overall, simulation can be developed further for urological training programs to encompass technical and non-technical skill development at all stages, including recertification. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

A Portfolio Analysis Tool for Measuring NASAs Aeronautics Research Progress toward Planned Strategic Outcomes

NASA Technical Reports Server (NTRS)

Tahmasebi, Farhad; Pearce, Robert

2016-01-01

Description of a tool for portfolio analysis of NASA's Aeronautics research progress toward planned community strategic Outcomes is presented. The strategic planning process for determining the community Outcomes is also briefly described. Stakeholder buy-in, partnership performance, progress of supporting Technical Challenges, and enablement forecast are used as the criteria for evaluating progress toward Outcomes. A few illustrative examples are also presented.

An approach to knowledge structuring for advanced phases of the Technical and Management Information System (TMIS)

NASA Technical Reports Server (NTRS)

Goranson, H. T.

1986-01-01

The Technical and Management Information System (TMIS) must employ on enlightened approach to its object structure, but basic issues in conceptual structuring remain to be resolved. Sirius outlines the necessary agenda and reports on progress toward solutions.

48 CFR 752.7035 - Public notices.

Code of Federal Regulations, 2011 CFR

2011-10-01

... notices. The following clause is for use when the cognizant technical office determines that the contract... to time, to announce progress and accomplishments. Press releases or other public notices should... cognizant technical officer and to USAID's Legislative and Public Affairs (LPA) as far in advance of release...

14 CFR 1260.71 - Supplements and renewals.

Code of Federal Regulations, 2011 CFR

2011-01-01

..., continued research relevance, and progress made by the recipient. (2) To insure uninterrupted programs, the technical office should forward to the grant office a completed award package, including a funded procurement request, technical evaluation of the proposed budget, and other support documentation, at least 29...

[A technical modification of the use of Dwyer's equipment].

PubMed

Carlioz, H; Damsin, J P

1991-01-01

Dwyer's technique for correction and anterior fusion of the spine was improved by using lockers at the level of each screw. So, like with the Zielke's technic this procedure allowed a global progressive and controllable correction and a real derotation of the spine.

Probing the prostate tumour microenvironment II: Impact of hypoxia on a cell model of prostate cancer progression

PubMed Central

Tonry, Claire; Armstrong, John; Pennington, Stephen

2017-01-01

Approximately one in six men are diagnosed with Prostate Cancer every year in the Western world. Although it can be well managed and non-life threatening in the early stages, over time many patients cease to respond to treatment and develop castrate resistant prostate cancer (CRPC). CRPC represents a clinically challenging and lethal form of prostate cancer. Progression of CRPC is, in part, driven by the ability of cancer cells to alter their metabolic profile during the course of tumourgenesis and metastasis so that they can survive in oxygen and nutrient-poor environments and even withstand treatment. This work was carried out as a continuation of a study aimed towards gaining greater mechanistic understanding of how conditions within the tumour microenvironment impact on both androgen sensitive (LNCaP) and androgen independent (LNCaP-abl and LNCaP-abl-Hof) prostate cancer cell lines. Here we have applied technically robust and reproducible label-free liquid chromatography mass spectrometry analysis for comprehensive proteomic profiling of prostate cancer cell lines under hypoxic conditions. This led to the identification of over 4,000 proteins – one of the largest protein datasets for prostate cancer cell lines established to date. The biological and clinical significance of proteins showing a significant change in expression as result of hypoxic conditions was established. Novel, intuitive workflows were subsequently implemented to enable robust, reproducible and high throughput verification of selected proteins of interest. Overall, these data suggest that this strategy supports identification of protein biomarkers of prostate cancer progression and potential therapeutic targets for CRPC. PMID:28410543

A systematic assessment of the state of hazardous waste clean-up technologies. Quarterly technical progress report, April 1--June 30, 1993

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

Berg, M.T.; Reed, B.E.; Gabr, M.

1993-07-01

West Virginia University (WVU) and the US DOE Morgantown Energy Technology Center (METC) entered into a Cooperative Agreement on August 29, 1992 entitled ``Decontamination Systems Information and Research Programs.`` Stipulated within the Agreement is the requirement that WVU submit to METC a series of Technical Progress Report for Year 1 of the Agreement. This report reflects the progress and/or efforts performed on the following nine technical projects encompassed by the Year 1 Agreement for the period of April 1 through June 30, 1993: Systematic assessment of the state of hazardous waste clean-up technologies; site remediation technologies -- drain-enhanced soil flushingmore » (DESF) for organic contaminants removal; site remediation technologies -- in situ bioremediation of organic contaminants; excavation systems for hazardous waste sites; chemical destruction of polychlorinated biphenyls; development of organic sensors -- monolayer and multilayer self-assembled films for chemical sensors; Winfield lock and dam remediation; Assessments of Technologies for hazardous waste site remediation -- non-treatment technologies and pilot scale test facility implementation; and remediation of hazardous sites with stream reforming.« less

Expression profiling in progressive stages of fumarate-hydratase deficiency: the contribution of metabolic changes to tumorigenesis.

PubMed

Ashrafian, Houman; O'Flaherty, Linda; Adam, Julie; Steeples, Violetta; Chung, Yuen-Li; East, Phil; Vanharanta, Sakari; Lehtonen, Heli; Nye, Emma; Hatipoglu, Emine; Miranda, Melroy; Howarth, Kimberley; Shukla, Deepa; Troy, Helen; Griffiths, John; Spencer-Dene, Bradley; Yusuf, Mohammed; Volpi, Emanuela; Maxwell, Patrick H; Stamp, Gordon; Poulsom, Richard; Pugh, Christopher W; Costa, Barbara; Bardella, Chiara; Di Renzo, Maria Flavia; Kotlikoff, Michael I; Launonen, Virpi; Aaltonen, Lauri; El-Bahrawy, Mona; Tomlinson, Ian; Pollard, Patrick J

2010-11-15

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is caused by mutations in the Krebs cycle enzyme fumarate hydratase (FH). It has been proposed that "pseudohypoxic" stabilization of hypoxia-inducible factor-α (HIF-α) by fumarate accumulation contributes to tumorigenesis in HLRCC. We hypothesized that an additional direct consequence of FH deficiency is the establishment of a biosynthetic milieu. To investigate this hypothesis, we isolated primary mouse embryonic fibroblast (MEF) lines from Fh1-deficient mice. As predicted, these MEFs upregulated Hif-1α and HIF target genes directly as a result of FH deficiency. In addition, detailed metabolic assessment of these MEFs confirmed their dependence on glycolysis, and an elevated rate of lactate efflux, associated with the upregulation of glycolytic enzymes known to be associated with tumorigenesis. Correspondingly, Fh1-deficient benign murine renal cysts and an advanced human HLRCC-related renal cell carcinoma manifested a prominent and progressive increase in the expression of HIF-α target genes and in genes known to be relevant to tumorigenesis and metastasis. In accord with our hypothesis, in a variety of different FH-deficient tissues, including a novel murine model of Fh1-deficient smooth muscle, we show a striking and progressive upregulation of a tumorigenic metabolic profile, as manifested by increased PKM2 and LDHA protein. Based on the models assessed herein, we infer that that FH deficiency compels cells to adopt an early, reversible, and progressive protumorigenic metabolic milieu that is reminiscent of that driving the Warburg effect. Targets identified in these novel and diverse FH-deficient models represent excellent potential candidates for further mechanistic investigation and therapeutic metabolic manipulation in tumors. Copyright © 2010 AACR.

A link between lipid metabolism and epithelial-mesenchymal transition provides a target for colon cancer therapy

PubMed Central

Sánchez-Martínez, Ruth; Álvarez-Fernández, Mónica; Vargas, Teodoro; Molina, Susana; García, Belén; Herranz, Jesús; Moreno-Rubio, Juan; Reglero, Guillermo; Pérez-Moreno, Mirna; Feliu, Jaime; Malumbres, Marcos; de Molina, Ana Ramírez

2015-01-01

The alterations in carbohydrate metabolism that fuel tumor growth have been extensively studied. However, other metabolic pathways involved in malignant progression, demand further understanding. Here we describe a metabolic acyl-CoA synthetase/stearoyl-CoA desaturase ACSL/SCD network causing an epithelial-mesenchymal transition (EMT) program that promotes migration and invasion of colon cancer cells. The mesenchymal phenotype produced upon overexpression of these enzymes is reverted through reactivation of AMPK signaling. Furthermore, this network expression correlates with poorer clinical outcome of stage-II colon cancer patients. Finally, combined treatment with chemical inhibitors of ACSL/SCD selectively decreases cancer cell viability without reducing normal cells viability. Thus, ACSL/SCD network stimulates colon cancer progression through conferring increased energetic capacity and invasive and migratory properties to cancer cells, and might represent a new therapeutic opportunity for colon cancer treatment. PMID:26451612

Comprehensive Plasma Metabolomic Analyses of Atherosclerotic Progression Reveal Alterations in Glycerophospholipid and Sphingolipid Metabolism in Apolipoprotein E-deficient Mice

PubMed Central

Dang, Vi T.; Huang, Aric; Zhong, Lexy H.; Shi, Yuanyuan; Werstuck, Geoff H.

2016-01-01

Atherosclerosis is the major underlying cause of most cardiovascular diseases. Despite recent advances, the molecular mechanisms underlying the pathophysiology of atherogenesis are not clear. In this study, comprehensive plasma metabolomics were used to investigate early-stage atherosclerotic development and progression in chow-fed apolipoprotein E-deficient mice at 5, 10 and 15 weeks of age. Comprehensive plasma metabolomic profiles, based on 4365 detected metabolite features, differentiate atherosclerosis-prone from atherosclerosis-resistant models. Metabolites in the sphingomyelin pathway were significantly altered prior to detectable lesion formation and at all subsequent time-points. The cytidine diphosphate-diacylglycerol pathway was up-regulated during stage I of atherosclerosis, while metabolites in the phosphatidylethanolamine and glycosphingolipid pathways were augmented in mice with stage II lesions. These pathways, involving glycerophospholipid and sphingolipid metabolism, were also significantly affected during the course of atherosclerotic progression. Our findings suggest that distinct plasma metabolomic profiles can differentiate the different stages of atherosclerotic progression. This study reveals that alteration of specific, previously unreported pathways of glycerophospholipid and sphingolipid metabolism are associated with atherosclerosis. The clear difference in the level of several metabolites supports the use of plasma lipid profiling as a diagnostic tool of atherogenesis. PMID:27721472

Progress, innovation and regulatory science in drug development: the politics of international standard-setting.

PubMed

Abraham, John; Reed, Tim

2002-06-01

This paper examines international standard-setting in the toxicology of pharmaceuticals during the 1990s, which has involved both the pharmaceutical industry and regulatory agencies in an organization known as the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The analysis shows that the relationships between innovation, regulatory science and 'progress' may be more complex and controversial than is often assumed. An assessment of the ICH's claims about the implications of 'technical' harmonization of drug-testing standards for the maintenance of drug safety, via toxicological testing, and the delivery of therapeutic progress, via innovation, is presented. By demonstrating that there is not a technoscientific validity for these claims, it is argued that, within the ICH, a discourse of technological innovation and scientific progress has been used by regulatory agencies and prominent parts of the transnational pharmaceutical industry to legitimize the lowering and loosening of toxicological standards for drug testing. The mobilization and acceptance of this discourse are shown to be pivotal to the ICH's transformation of reductions in safety standards, which are apparently against the interests of patients and public health, into supposed therapeutic benefits derived from promises of greater access to more innovative drug products. The evidence suggests that it is highly implausible that these reductions in the standards of regulatory toxicology are consistent with therapeutic progress for patients, and highlights a worrying aspect embedded in the 'technical trajectories' of regulatory science.

Identification of the Consistently Altered Metabolic Targets in Human Hepatocellular Carcinoma.

PubMed

Nwosu, Zeribe Chike; Megger, Dominik Andre; Hammad, Seddik; Sitek, Barbara; Roessler, Stephanie; Ebert, Matthias Philip; Meyer, Christoph; Dooley, Steven

2017-09-01

Cancer cells rely on metabolic alterations to enhance proliferation and survival. Metabolic gene alterations that repeatedly occur in liver cancer are largely unknown. We aimed to identify metabolic genes that are consistently deregulated, and are of potential clinical significance in human hepatocellular carcinoma (HCC). We studied the expression of 2,761 metabolic genes in 8 microarray datasets comprising 521 human HCC tissues. Genes exclusively up-regulated or down-regulated in 6 or more datasets were defined as consistently deregulated. The consistent genes that correlated with tumor progression markers ( ECM2 and MMP9) (Pearson correlation P < .05) were used for Kaplan-Meier overall survival analysis in a patient cohort. We further compared proteomic expression of metabolic genes in 19 tumors vs adjacent normal liver tissues. We identified 634 consistent metabolic genes, ∼60% of which are not yet described in HCC. The down-regulated genes (n = 350) are mostly involved in physiologic hepatocyte metabolic functions (eg, xenobiotic, fatty acid, and amino acid metabolism). In contrast, among consistently up-regulated metabolic genes (n = 284) are those involved in glycolysis, pentose phosphate pathway, nucleotide biosynthesis, tricarboxylic acid cycle, oxidative phosphorylation, proton transport, membrane lipid, and glycan metabolism. Several metabolic genes (n = 434) correlated with progression markers, and of these, 201 predicted overall survival outcome in the patient cohort analyzed. Over 90% of the metabolic targets significantly altered at the protein level were similarly up- or down-regulated as in genomic profile. We provide the first exposition of the consistently altered metabolic genes in HCC and show that these genes are potentially relevant targets for onward studies in preclinical and clinical contexts.

7 CFR 1944.541 - Reporting requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

...) PROGRAM REGULATIONS (CONTINUED) HOUSING Technical and Supervisory Assistance Grants § 1944.541 Reporting... District Director to determine satisfactory progress. The District Director will work with the grantee to... five working days of receipt. (1) If the reports indicate satisfactory progress, the State Director...

The role of thioredoxin reductase 1 in melanoma metabolism and metastasis.

PubMed

Cassidy, Pamela B; Honeggar, Matthew; Poerschke, Robyn L; White, Karen; Florell, Scott R; Andtbacka, Robert H I; Tross, Joycelyn; Anderson, Madeleine; Leachman, Sancy A; Moos, Philip J

2015-11-01

Although significant progress has been made in targeted and immunologic therapeutics for melanoma, many tumors fail to respond, and most eventually progress when treated with the most efficacious targeted combination therapies thus far identified. Therefore, alternative approaches that exploit distinct melanoma phenotypes are necessary to develop new approaches for therapeutic intervention. Tissue microarrays containing human nevi and melanomas were used to evaluate levels of the antioxidant protein thioredoxin reductase 1 (TR1), which was found to increase as a function of disease progression. Melanoma cell lines revealed metabolic differences that correlated with TR1 levels. We used this new insight to design a model treatment strategy that creates a synthetic lethal interaction wherein targeting TR1 sensitizes melanoma to inhibition of glycolytic metabolism, resulting in a decrease in metastases in vivo. This approach holds the promise of a new clinical therapeutic strategy, distinct from oncoprotein inhibition. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The magnetohydrodynamics coal-fired flow facility

NASA Astrophysics Data System (ADS)

1995-01-01

In this quarterly technical progress report, UTSI reports on the status of a multitask contract to develop the technology for the steam bottoming portion of a MHD Steam Combined Cycle Power Plant. The report describes the facility maintenance and environmental work completed, status of completing technical reports and certain key administrative actions occurring during the quarter. With program resources at a minimum to closeout the MHD program, no further testing occurred during the quarter, but the DOE CFFF facility was maintained in a standby status with winterization, preventive maintenance and repairs accomplished as needed. Plans and preparations progressed for environmental actions needed at the site to investigate and characterize the groundwater and for removal/disposal of asbestos in the cooling tower. Work continued to progress on archiving the results of the MHD program.

METABOLISM OF RUTHENIUM IN THE RAT. Technical Documentary Report

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

Traynor, J.E.; Leeper, S.W.

1961-12-01

Seventeen Sprague-Dawley rats were injected intramuscularly and intraperitoneally with ruthenium-106. The amount of this isotope was determined daily for 5 weeks in the urine and feces. Animals were sacrificed at intervals and the various organs were analyzed for ruthenium. It was noted from this experiment that the pathways of absorption, metabolism, and excretion are dependent on the route of administration of ruthenium. (auth)

Ultrasound-guided direct delivery of 3-bromopyruvate blocks tumor progression in an orthotopic mouse model of human pancreatic cancer.

PubMed

Ota, Shinichi; Geschwind, Jean-Francois H; Buijs, Manon; Wijlemans, Joost W; Kwak, Byung Kook; Ganapathy-Kanniappan, Shanmugasundaram

2013-06-01

Studies in animal models of cancer have demonstrated that targeting tumor metabolism can be an effective anticancer strategy. Previously, we showed that inhibition of glucose metabolism by the pyruvate analog, 3-bromopyruvate (3-BrPA), induces anticancer effects both in vitro and in vivo. We have also documented that intratumoral delivery of 3-BrPA affects tumor growth in a subcutaneous tumor model of human liver cancer. However, the efficacy of such an approach in a clinically relevant orthotopic tumor model has not been reported. Here, we investigated the feasibility of ultrasound (US) image-guided delivery of 3-BrPA in an orthotopic mouse model of human pancreatic cancer and evaluated its therapeutic efficacy. In vitro, treatment of Panc-1 cells with 3-BrPA resulted in a dose-dependent decrease in cell viability. The loss of viability correlated with a dose-dependent decrease in the intracellular ATP level and lactate production confirming that disruption of energy metabolism underlies these 3-BrPA-mediated effects. In vivo, US-guided delivery of 3-BrPA was feasible and effective as demonstrated by a marked decrease in tumor size on imaging. Further, the antitumor effect was confirmed by (1) a decrease in the proliferative potential by Ki-67 immunohistochemical staining and (2) the induction of apoptosis by terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphospate nick end labeling staining. We therefore demonstrate the technical feasibility of US-guided intratumoral injection of 3-BrPA in a mouse model of human pancreatic cancer as well as its therapeutic efficacy. Our data suggest that this new therapeutic approach consisting of a direct intratumoral injection of antiglycolytic agents may represent an exciting opportunity to treat patients with pancreas cancer.

Tumor glycolysis as a target for cancer therapy: progress and prospects

PubMed Central

2013-01-01

Altered energy metabolism is a biochemical fingerprint of cancer cells that represents one of the “hallmarks of cancer”. This metabolic phenotype is characterized by preferential dependence on glycolysis (the process of conversion of glucose into pyruvate followed by lactate production) for energy production in an oxygen-independent manner. Although glycolysis is less efficient than oxidative phosphorylation in the net yield of adenosine triphosphate (ATP), cancer cells adapt to this mathematical disadvantage by increased glucose up-take, which in turn facilitates a higher rate of glycolysis. Apart from providing cellular energy, the metabolic intermediates of glycolysis also play a pivotal role in macromolecular biosynthesis, thus conferring selective advantage to cancer cells under diminished nutrient supply. Accumulating data also indicate that intracellular ATP is a critical determinant of chemoresistance. Under hypoxic conditions where glycolysis remains the predominant energy producing pathway sensitizing cancer cells would require intracellular depletion of ATP by inhibition of glycolysis. Together, the oncogenic regulation of glycolysis and multifaceted roles of glycolytic components underscore the biological significance of tumor glycolysis. Thus targeting glycolysis remains attractive for therapeutic intervention. Several preclinical investigations have indeed demonstrated the effectiveness of this therapeutic approach thereby supporting its scientific rationale. Recent reviews have provided a wealth of information on the biochemical targets of glycolysis and their inhibitors. The objective of this review is to present the most recent research on the cancer-specific role of glycolytic enzymes including their non-glycolytic functions in order to explore the potential for therapeutic opportunities. Further, we discuss the translational potential of emerging drug candidates in light of technical advances in treatment modalities such as image-guided targeted delivery of cancer therapeutics. PMID:24298908

GPHS-RTGs in support of the Cassini RTG Program

NASA Astrophysics Data System (ADS)

1995-04-01

The technical progress achieved during the period 26 Sep. 1994 - 2 Apr. 1995 on Contract DE-AC03-91SF-18852 Radioisotope Thermoelectric Generators and Ancillary Activities is described herein. Monthly technical activity for the period 27 Feb. - 2 Apr. 1995 is included in this progress report. The report addresses tasks, including: spacecraft integration and liaison; engineering support; safety; qualified unicouple production; ETG fabrication, assembly, and test; ground support equipment; RTG shipping and launch support; designs, reviews, and mission applications; project management, quality assurance, reliability, contract changes, CAGO acquisition (operating funds), and CAGO maintenance and repair; and CAGO acquisition (capital funds).

Reduced Renal Methylarginine Metabolism Protects against Progressive Kidney Damage

PubMed Central

Caplin, Ben; Boruc, Olga; Bruce-Cobbold, Claire; Cutillas, Pedro; Dormann, Dirk; Faull, Peter; Grossman, Rebecca C.; Khadayate, Sanjay; Mas, Valeria R.; Nitsch, Dorothea D.; Wang, Zhen; Norman, Jill T.; Wilcox, Christopher S.; Wheeler, David C.; Leiper, James

2015-01-01

Nitric oxide (NO) production is diminished in many patients with cardiovascular and renal disease. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthesis, and elevated plasma levels of ADMA are associated with poor outcomes. Dimethylarginine dimethylaminohydrolase-1 (DDAH1) is a methylarginine-metabolizing enzyme that reduces ADMA levels. We reported previously that a DDAH1 gene variant associated with increased renal DDAH1 mRNA transcription and lower plasma ADMA levels, but counterintuitively, a steeper rate of renal function decline. Here, we test the hypothesis that reduced renal-specific ADMA metabolism protects against progressive renal damage. Renal DDAH1 is expressed predominately within the proximal tubule. A novel proximal tubule–specific Ddah1 knockout (Ddah1PT−/−) mouse demonstrated tubular cell accumulation of ADMA and lower NO concentrations, but unaltered plasma ADMA concentrations. Ddah1PT−/− mice were protected from reduced kidney tissue mass, collagen deposition, and profibrotic cytokine expression in two independent renal injury models: folate nephropathy and unilateral ureteric obstruction. Furthermore, a study of two independent kidney transplant cohorts revealed higher levels of human renal allograft methylarginine-metabolizing enzyme gene expression associated with steeper function decline. We also report an association among DDAH1 expression, NO activity, and uromodulin expression supported by data from both animal and human studies, raising the possibility that kidney DDAH1 expression exacerbates renal injury through uromodulin-related mechanisms. Together, these data demonstrate that reduced renal tubular ADMA metabolism protects against progressive kidney function decline. Thus, circulating ADMA may be an imprecise marker of renal methylarginine metabolism, and therapeutic ADMA reduction may even be deleterious to kidney function. PMID:25855779

Characterisation of tissue-type metabolic content in secondary progressive multiple sclerosis: a magnetic resonance spectroscopic imaging study.

PubMed

Marshall, Ian; Thrippleton, Michael J; Bastin, Mark E; Mollison, Daisy; Dickie, David A; Chappell, Francesca M; Semple, Scott I K; Cooper, Annette; Pavitt, Sue; Giovannoni, Gavin; Wheeler-Kingshott, Claudia A M Gandini; Solanky, Bhavana S; Weir, Christopher J; Stallard, Nigel; Hawkins, Clive; Sharrack, Basil; Chataway, Jeremy; Connick, Peter; Chandran, Siddharthan

2018-05-30

Proton magnetic resonance spectroscopy yields metabolic information and has proved to be a useful addition to structural imaging in neurological diseases. We applied short-echo time Spectroscopic Imaging in a cohort of 42 patients with secondary progressive multiple sclerosis (SPMS). Linear modelling with respect to brain tissue type yielded metabolite levels that were significantly different in white matter lesions compared with normal-appearing white matter, suggestive of higher myelin turnover (higher choline), higher metabolic rate (higher creatine) and increased glial activity (higher myo-inositol) within the lesions. These findings suggest that the lesions have ongoing cellular activity that is not consistent with the usual assumption of 'chronic' lesions in SPMS, and may represent a target for repair therapies.

Kidney cancer progression linked to shifts in tumor metabolism

Cancer.gov

Investigators in The Cancer Genome Atlas Research Network have uncovered a connection between how tumor cells use energy from metabolic processes and the aggressiveness of the most common form of kidney cancer, clear cell renal cell carcinoma.

The Gap That Can't Go Away: The Catch-22 of Reclassification in Monitoring the Progress of English Learners

ERIC Educational Resources Information Center

Saunders, William M.; Marcelletti, David J.

2013-01-01

When English Learners (ELs) demonstrate English language proficiency, they are reclassified as Fluent English Proficient (RFEP). Subsequently they are often left out of the analysis of EL progress because they are, technically, no longer ELs. This article examines the effects of including and excluding RFEPs from the analysis of EL progress. Based…

Bone Conduction Communication: Research Progress and Directions

DTIC Science & Technology

2017-08-16

ARL-TR-8096 ● AUG 2017 US Army Research Laboratory Bone Conduction Communication: Research Progress and Directions by Maranda...this report when it is no longer needed. Do not return it to the originator. ARL-TR-8096 ● AUG 2017 US Army Research Laboratory...Bone Conduction Communication: Research Progress and Directions by Maranda McBride North Carolina Agricultural and Technical State University

25 CFR 30.123 - What is the Bureau's role in assisting Bureau-funded schools to make AYP?

Code of Federal Regulations, 2010 CFR

2010-04-01

... EDUCATION ADEQUATE YEARLY PROGRESS Failure To Make Adequate Yearly Progress § 30.123 What is the Bureau's...-funded schools to assist them in achieving AYP. This includes technical assistance and other forms of...

25 CFR 30.123 - What is the Bureau's role in assisting Bureau-funded schools to make AYP?

Code of Federal Regulations, 2011 CFR

2011-04-01

... EDUCATION ADEQUATE YEARLY PROGRESS Failure To Make Adequate Yearly Progress § 30.123 What is the Bureau's...-funded schools to assist them in achieving AYP. This includes technical assistance and other forms of...

Endothelial cell metabolism: A novel player in atherosclerosis? Basic principles and therapeutic opportunities.

PubMed

Pircher, Andreas; Treps, Lucas; Bodrug, Natalia; Carmeliet, Peter

2016-10-01

Atherosclerosis is a leading cause of morbidity and mortality in Western society. Despite improved insight into disease pathogenesis and therapeutic options, additional treatment strategies are required. Emerging evidence highlights the relevance of endothelial cell (EC) metabolism for angiogenesis, and indicates that EC metabolism is perturbed when ECs become dysfunctional to promote atherogenesis. In this review, we overview the latest insights on EC metabolism and discuss current knowledge on how atherosclerosis deregulates EC metabolism, and how maladaptation of deregulated EC metabolism can contribute to atherosclerosis progression. We will also highlight possible therapeutic avenues, based on targeting EC metabolism. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Black River Technical College, Exploring America's Communities. Progress Report.

ERIC Educational Resources Information Center

Black River Vocational-Technical School, Pocahontas, AR.

In 1996, Arkansas's Black River Technical College (BRTC) participated in the American Association of Community Colleges' Exploring America's Communities project, which worked to strengthen the teaching and learning of American history, literature, and culture at U.S. community colleges. The proposed centerpiece of BRTC's program is called the…

40 CFR 40.150 - Evaluation of applications.

Code of Federal Regulations, 2011 CFR

2011-07-01

.... Relevancy, coupled with the results of technical review, will provide the basis for funding recommendations... will be reviewed for technical merit by at least one reviewer within EPA and at least two reviewers.... Recommendations for continuation of funding will be based on progress toward the accomplishment of the goals set...

40 CFR 35.4235 - Are there specific provisions my group's contract(s) must contain?

Code of Federal Regulations, 2011 CFR

2011-07-01

... PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL ASSISTANCE Grants for Technical Assistance Procuring A Technical Advisor Or Other Contractor with Tag Funds § 35.4235 Are there specific... progress reports; (3) Expenditures; and (4) Commitments indicating their relationship to established costs...

Missouri local technical assistance program at Missouri University of Science and Technology (formerly University of Missouri--Rolla) : annual progress report January-December 2007.

DOT National Transportation Integrated Search

2009-02-01

This annual report is a summary of the activities during 2007 for the Missouri Local Technical Assistance Program (Missouri LTAP), which is located at Missouri University of Science and Technology. The report highlights Missouri LTAPs performance ...

Global Issues in Career and Technical Fields: Internationalizing the Community College Curriculum.

ERIC Educational Resources Information Center

Peck, Shirley S.

1991-01-01

Presents a rationale for incorporating international content in both general education and career/technical fields, providing a status report on progress to date. Describes four modules prepared by Catonsville Community College (Maryland) instructors for inclusion in criminal justice, air transportation, automotive service, and electronics…

Technical and Vocational Education in Cameroon and Critical Avenues for Development

ERIC Educational Resources Information Center

Che, S. Megan

2007-01-01

Technical and vocational education (TVE) can influence development and economic progress for post-colonial societies. Some newly independent sub-Saharan African countries attempted curricular transformation that might produce a skilled workforce through widespread access to versions of TVE. In Cameroon, no such post-colonial curricular revolution…

[The use of bemitil in patients with progressive muscular dystrophies].

PubMed

Lobzin, V S; Saĭkova, L A; Chukhlovina, M L; Pustozerov, V G

1992-04-01

Bemithyl treatment was carried out in 22 patients with neuromuscular diseases (progressive myodystrophy). The actoprotector bemithyl inhibited in these patients the processes of lipid peroxidation, activation of neoglucogenesis favours improvement of interorganic exchange of metabolites. Bemithyl is recommended in patients with progressive myodystrophy along with drugs normalizing the protein, energy and electrolyte metabolism.

Comprehensive analysis of serum metabolites in gestational diabetes mellitus by UPLC/Q-TOF-MS.

PubMed

Liu, Tianhu; Li, Jiaxun; Xu, Fengcheng; Wang, Mengni; Ding, Shijia; Xu, Hongbing; Dong, Fang

2016-02-01

Gestational diabetes mellitus (GDM) refers to the first sign or onset of diabetes mellitus during pregnancy rather than progestation. In recent decades, more and more research has focused on the etiology and pathogenesis of GDM in order to further understand GDM progress and recovery. Using an advanced metabolomics platform based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS), we explored the changes in serum metabolites between women with GDM and healthy controls during and after pregnancy. Some significant differences were discovered using multivariate analysis including partial least-squares discriminant analysis (PLS-DA) and orthogonal PLS-DA (OPLS-DA). The dysregulated metabolites were further compared and verified in several databases to understand how these compounds might function as potential biomarkers. Analyses of the metabolic pathways associated with these potential biomarkers were subsequently explored. A total of 35 metabolites were identified, contributing to GDM progress to some extent. The identified biomarkers were involved in some important metabolic pathways including glycine, serine, and threonine metabolism; steroid hormone biosynthesis; tyrosine metabolism; glycerophospholipid metabolism; and fatty acid metabolism. The above mentioned metabolic pathways mainly participate in three major metabolic cycles in humans, including lipid metabolism, carbohydrate metabolism, and amino acid metabolism. In this pilot study, the valuable comprehensive analysis gave us further insight into the etiology and pathophysiology of GDM, which might benefit the feasibility of a rapid, accurate diagnosis and reasonable treatment as soon as possible but also prevent GDM and its related short- and long-term complications.

Publications of the Jet Propulsion Laboratory, January through December 1974. [deep space network, Apollo project, information theory, and space exploration

NASA Technical Reports Server (NTRS)

1975-01-01

Formalized technical reporting is described and indexed, which resulted from scientific and engineering work performed, or managed, by the Jet Propulsion Laboratory. The five classes of publications included are technical reports, technical memorandums, articles from the bimonthly Deep Space Network Progress Report, special publications, and articles published in the open literature. The publications are indexed by author, subject, and publication type and number.

Glutamine activates STAT3 to control cancer cell proliferation independently of glutamine metabolism

PubMed Central

Vazeille, Thibaut; Sonveaux, Pierre

2016-01-01

Cancer cells can use a variety of metabolic substrates to fulfill the bioenergetic and biosynthetic needs of their oncogenic program. Besides bioenergetics, cancer cell metabolism also directly influences genetic, epigenetic and signaling events associated with tumor progression. Many cancer cells are addicted to glutamine, and this addiction is observed in oxidative as well as in glycolytic cells. While both oxidative and bioreductive glutamine metabolism can contribute to cancer progression and glutamine can further serve to generate peptides (including glutathione) and proteins, we report that glutamine promotes the proliferation of cancer cells independently of its use as a metabolic fuel or as a precursor of glutathione. Extracellular glutamine activates transcription factor STAT3, which is necessary and sufficient to mediate the proliferative effects of glutamine in glycolytic and in oxidative cancer cells. Glutamine also activates transcription factors HIF-1, mTOR and c-Myc, but these factors do not mediate the effects of glutamine on cancer cell proliferation. Our findings shed a new light on the anticancer effects of L-asparaginase that possesses glutaminase activity and converts glutamine into glutamate extracellularly. Conversely, cancer resistance to treatments that block glutamine metabolism could arise from glutamine-independent STAT3 re-activation. PMID:27748760

Obesity, metabolic syndrome and diabetic retinopathy: Beyond hyperglycemia

PubMed Central

Mbata, Osinakachukwu; Abo El-Magd, Nada Fawzy; El-Remessy, Azza Bahram

2017-01-01

Diabetic retinopathy (DR) is the most feared ocular manifestation of diabetes. DR is characterized by progressive retinal damage that may eventually result in blindness. Clinically, this blindness is caused by progressive damage to the retinal microvasculature, which leads to ischemia, retinal swelling, and neovascularization. Retinopathy is associated with both type 1 and type 2 diabetes, with DR being the leading cause of new onset blindness in United States adults. Despite this strong association with diabetes, it must be noted that the development of retinopathy lesions is multifactorial and may occur in individuals without an established history of diabetes. Metabolic syndrome is a multifactorial condition of central obesity, hypertriglyceridemia, dyslipidemia, hypertension, fasting hyperglycemia, and insulin resistance. Although several studies examined the individual components observed in the metabolic syndrome in relation to the development of DR, there is conflicting data as to the association of the metabolic syndrome with the development of retinopathy lesions in non-diabetic subjects. This review will summarize the current literature on the evidence of the metabolic syndrome on retinopathy in subjects with and without an established history of diabetes. This review will also discuss some of the mechanisms through which metabolic syndrome can contribute to the development of retinopathy. PMID:28751954

Metabolic enzymes: key modulators of functionality in cancer stem-like cells

PubMed Central

Dong, Bo-Wen; Qin, Guang-Ming; Luo, Yan; Mao, Jian-Shan

2017-01-01

Cancer Stem-like Cells (CSCs) are a subpopulation of cancer cells with self-renewal capacity and are important for the initiation, progression and recurrence of cancer diseases. The metabolic profile of CSCs is consistent with their stem-like properties. Studies have indicated that enzymes, the main regulators of cellular metabolism, dictate functionalities of CSCs in both catalysis-dependent and catalysis-independent manners. This paper reviews diverse studies of metabolic enzymes, and describes the effects of these enzymes on metabolic adaptation, gene transcription and signal transduction, in CSCs. PMID:28009990

Metabolic enzymes: key modulators of functionality in cancer stem-like cells.

PubMed

Dong, Bo-Wen; Qin, Guang-Ming; Luo, Yan; Mao, Jian-Shan

2017-02-21

Cancer Stem-like Cells (CSCs) are a subpopulation of cancer cells with self-renewal capacity and are important for the initiation, progression and recurrence of cancer diseases. The metabolic profile of CSCs is consistent with their stem-like properties. Studies have indicated that enzymes, the main regulators of cellular metabolism, dictate functionalities of CSCs in both catalysis-dependent and catalysis-independent manners. This paper reviews diverse studies of metabolic enzymes, and describes the effects of these enzymes on metabolic adaptation, gene transcription and signal transduction, in CSCs.

Defective lysosomal proteolysis and axonal transport are early pathogenic events that worsen with age leading to increased APP metabolism and synaptic Abeta in transgenic APP/PS1 hippocampus.

PubMed

Torres, Manuel; Jimenez, Sebastian; Sanchez-Varo, Raquel; Navarro, Victoria; Trujillo-Estrada, Laura; Sanchez-Mejias, Elisabeth; Carmona, Irene; Davila, Jose Carlos; Vizuete, Marisa; Gutierrez, Antonia; Vitorica, Javier

2012-11-22

Axonal pathology might constitute one of the earliest manifestations of Alzheimer disease. Axonal dystrophies were observed in Alzheimer's patients and transgenic models at early ages. These axonal dystrophies could reflect the disruption of axonal transport and the accumulation of multiple vesicles at local points. It has been also proposed that dystrophies might interfere with normal intracellular proteolysis. In this work, we have investigated the progression of the hippocampal pathology and the possible implication in Abeta production in young (6 months) and aged (18 months) PS1(M146L)/APP(751sl) transgenic mice. Our data demonstrated the existence of a progressive, age-dependent, formation of axonal dystrophies, mainly located in contact with congophilic Abeta deposition, which exhibited tau and neurofilament hyperphosphorylation. This progressive pathology was paralleled with decreased expression of the motor proteins kinesin and dynein. Furthermore, we also observed an early decrease in the activity of cathepsins B and D, progressing to a deep inhibition of these lysosomal proteases at late ages. This lysosomal impairment could be responsible for the accumulation of LC3-II and ubiquitinated proteins within axonal dystrophies. We have also investigated the repercussion of these deficiencies on the APP metabolism. Our data demonstrated the existence of an increase in the amyloidogenic pathway, which was reflected by the accumulation of hAPPfl, C99 fragment, intracellular Abeta in parallel with an increase in BACE and gamma-secretase activities. In vitro experiments, using APPswe transfected N2a cells, demonstrated that any imbalance on the proteolytic systems reproduced the in vivo alterations in APP metabolism. Finally, our data also demonstrated that Abeta peptides were preferentially accumulated in isolated synaptosomes. A progressive age-dependent cytoskeletal pathology along with a reduction of lysosomal and, in minor extent, proteasomal activity could be directly implicated in the progressive accumulation of APP derived fragments (and Abeta peptides) in parallel with the increase of BACE-1 and gamma-secretase activities. This retard in the APP metabolism seemed to be directly implicated in the synaptic Abeta accumulation and, in consequence, in the pathology progression between synaptically connected regions.

Cell cycle progression is an essential regulatory component of phospholipid metabolism and membrane homeostasis

PubMed Central

Sanchez-Alvarez, Miguel; Zhang, Qifeng; Finger, Fabian; Wakelam, Michael J. O.; Bakal, Chris

2015-01-01

We show that phospholipid anabolism does not occur uniformly during the metazoan cell cycle. Transition to S-phase is required for optimal mobilization of lipid precursors, synthesis of specific phospholipid species and endoplasmic reticulum (ER) homeostasis. Average changes observed in whole-cell phospholipid composition, and total ER lipid content, upon stimulation of cell growth can be explained by the cell cycle distribution of the population. TORC1 promotes phospholipid anabolism by slowing S/G2 progression. The cell cycle stage-specific nature of lipid biogenesis is dependent on p53. We propose that coupling lipid metabolism to cell cycle progression is a means by which cells have evolved to coordinate proliferation with cell and organelle growth. PMID:26333836

Cell cycle progression is an essential regulatory component of phospholipid metabolism and membrane homeostasis.

PubMed

Sanchez-Alvarez, Miguel; Zhang, Qifeng; Finger, Fabian; Wakelam, Michael J O; Bakal, Chris

2015-09-01

We show that phospholipid anabolism does not occur uniformly during the metazoan cell cycle. Transition to S-phase is required for optimal mobilization of lipid precursors, synthesis of specific phospholipid species and endoplasmic reticulum (ER) homeostasis. Average changes observed in whole-cell phospholipid composition, and total ER lipid content, upon stimulation of cell growth can be explained by the cell cycle distribution of the population. TORC1 promotes phospholipid anabolism by slowing S/G2 progression. The cell cycle stage-specific nature of lipid biogenesis is dependent on p53. We propose that coupling lipid metabolism to cell cycle progression is a means by which cells have evolved to coordinate proliferation with cell and organelle growth. © 2015 The Authors.

Technical adequacy of growth estimates from a computer adaptive test: Implications for progress monitoring.

PubMed

Van Norman, Ethan R; Nelson, Peter M; Parker, David C

2017-09-01

Computer adaptive tests (CATs) hold promise to monitor student progress within multitiered systems of support. However, the relationship between how long and how often data are collected and the technical adequacy of growth estimates from CATs has not been explored. Given CAT administration times, it is important to identify optimal data collection schedules to minimize missed instructional time. We used simulation methodology to investigate how the duration and frequency of data collection influenced the reliability, validity, and precision of growth estimates from a math CAT. A progress monitoring dataset of 746 Grade 4, 664 Grade 5, and 400 Grade 6 students from 40 schools in the upper Midwest was used to generate model parameters. Across grades, 53% of students were female and 53% were White. Grade level was not as influential as the duration and frequency of data collection on the technical adequacy of growth estimates. Low-stakes decisions were possible after 14-18 weeks when data were collected weekly (420-540 min of assessment), 20-24 weeks when collected every other week (300-360 min of assessment), and 20-28 weeks (150-210 min of assessment) when data were collected once a month, depending on student grade level. The validity and precision of growth estimates improved when the duration and frequency of progress monitoring increased. Given the amount of time required to obtain technically adequate growth estimates in the present study, results highlight the importance of weighing the potential costs of missed instructional time relative to other types of assessments, such as curriculum-based measures. Implications for practice, research, as well as future directions are also discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

24 CFR 1006.430 - Corrective and remedial action.

Code of Federal Regulations, 2011 CFR

2011-04-01

... plan; (3) Made substantial progress in carrying out its program and achieving its quantifiable goals as... to submit progress schedules for completing activities or complying with the requirements of the Act... appropriate technical assistance using existing grant funds or other available resources to overcome the...

Temporal fluxomics reveals oscillations in TCA cycle flux throughout the mammalian cell cycle.

PubMed

Ahn, Eunyong; Kumar, Praveen; Mukha, Dzmitry; Tzur, Amit; Shlomi, Tomer

2017-11-06

Cellular metabolic demands change throughout the cell cycle. Nevertheless, a characterization of how metabolic fluxes adapt to the changing demands throughout the cell cycle is lacking. Here, we developed a temporal-fluxomics approach to derive a comprehensive and quantitative view of alterations in metabolic fluxes throughout the mammalian cell cycle. This is achieved by combining pulse-chase LC-MS-based isotope tracing in synchronized cell populations with computational deconvolution and metabolic flux modeling. We find that TCA cycle fluxes are rewired as cells progress through the cell cycle with complementary oscillations of glucose versus glutamine-derived fluxes: Oxidation of glucose-derived flux peaks in late G1 phase, while oxidative and reductive glutamine metabolism dominates S phase. These complementary flux oscillations maintain a constant production rate of reducing equivalents and oxidative phosphorylation flux throughout the cell cycle. The shift from glucose to glutamine oxidation in S phase plays an important role in cell cycle progression and cell proliferation. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Physical fitness predicts technical-tactical and time-motion profile in simulated Judo and Brazilian Jiu-Jitsu matches.

PubMed

Coswig, Victor S; Gentil, Paulo; Bueno, João C A; Follmer, Bruno; Marques, Vitor A; Del Vecchio, Fabrício B

2018-01-01

Among combat sports, Judo and Brazilian Jiu-Jitsu (BJJ) present elevated physical fitness demands from the high-intensity intermittent efforts. However, information regarding how metabolic and neuromuscular physical fitness is associated with technical-tactical performance in Judo and BJJ fights is not available. This study aimed to relate indicators of physical fitness with combat performance variables in Judo and BJJ. The sample consisted of Judo ( n  = 16) and BJJ ( n  = 24) male athletes. At the first meeting, the physical tests were applied and, in the second, simulated fights were performed for later notational analysis. The main findings indicate: (i) high reproducibility of the proposed instrument and protocol used for notational analysis in a mobile device; (ii) differences in the technical-tactical and time-motion patterns between modalities; (iii) performance-related variables are different in Judo and BJJ; and (iv) regression models based on metabolic fitness variables may account for up to 53% of the variances in technical-tactical and/or time-motion variables in Judo and up to 31% in BJJ, whereas neuromuscular fitness models can reach values up to 44 and 73% of prediction in Judo and BJJ, respectively. When all components are combined, they can explain up to 90% of high intensity actions in Judo. In conclusion, performance prediction models in simulated combat indicate that anaerobic, aerobic and neuromuscular fitness variables contribute to explain time-motion variables associated with high intensity and technical-tactical variables in Judo and BJJ fights.

Identification of Metabolic Routes and Catabolic Enzymes Involved in Phytoremediation of the Nitro-Substituted Explosives TNT, RDX, and HMX

DTIC Science & Technology

2006-07-31

Identification of Metabolic Routes and Catabolic Enzymes Involved in Phytoremediation of the Nitro- Substituted Explosives TNT, RDX...Routes and Catabolic Enzymes Involved in Phytoremediation of the Nitro-Substituted Explosives TNT, RDX, and HMX Final Technical Report 5a. CONTRACT NUMBER... Phytoremediation has been shown to provide a cost-effective alternative to classical technologies for cleaning up nitro-substituted explosive

Hepatocyte transplantation for liver-based metabolic disorders.

PubMed

Dhawan, Anil; Mitry, Ragai R; Hughes, Robin D

2006-01-01

Hepatocyte transplantation is being investigated as an alternative to orthotopic liver transplantation in patients with liver-based metabolic disorders. The progress made in this field to date is reviewed. Protocols have been developed using collagenase perfusion to isolate human hepatocytes from unused donor liver tissue. Hepatocytes with a high viability can often be obtained and can be cryopreserved for later use, though with loss of function on thawing. For clinical use, hepatocytes must be prepared in clean GMP conditions with cells meeting criteria of function and lack of microbial contamination before patient use. Hepatocytes are infused intraportally into the patient's liver, where a proportion of cells will engraft and replace the deficient metabolic function without the need for major surgery. Twenty patients have now received hepatocyte transplantation, including eight children at King's College Hospital. There was a range of aetiologies of liver disease: familial hypercholesterolaemia, Crigler-Najjar syndrome type 1, urea cycle defects, infantile Refsum disease, glycogen storage disease type Ia, inherited factor VII deficiency and progressive familial intrahepatic cholestasis type 2. Clinical improvement and partial correction of the metabolic abnormality was observed in most cases. Considerable progress has been made in developing the technique, but hepatocyte transplantation is limited by the available supply of liver tissue. Hepatocytes derived from stem cells could provide alternative sources of cells in the future.

Progress and Prospect: A Report Submitted to the Governing Board of the Maricopa County Community College District.

ERIC Educational Resources Information Center

Maricopa Technical Community Coll., Phoenix, AZ.

This two-part report seeks to outline the progress made to date by Maricopa Technical Community College (MTCC) through its first eight years of operation, and to recommend specific actions which might be taken in the future by the college to insure its continued progress and response to community needs in light of constraints on funding and…

INTESTINAL METABOLISM OF ORGANOPHOSPHATE INSECTICIDES: POTENTIAL FIRST-PASS METABOLISM. (R828608)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Optical fiber sensors for materials and structures characterization

NASA Technical Reports Server (NTRS)

Lindner, D. K.; Claus, R. O.

1991-01-01

The final technical report on Optical Fiber Sensors for Materials and Structures Characterization, covering the period August 1990 through August 1991 is presented. Research programs in the following technical areas are described; sapphire optical fiber sensors; vibration analysis using two-mode elliptical core fibers and sensors; extrinsic Fabry-Perot interferometer development; and coatings for fluorescent-based sensor. Research progress in each of these areas was substantial, as evidenced by the technical publications which are included as appendices.

44 CFR 206.437 - State administrative plan.

Code of Federal Regulations, 2010 CFR

2010-10-01

... requests for advances of funds and reimbursement; (vii) Monitor and evaluate the progress and completion of... technical assistance as required to subgrantee(s); (xi) Comply with the administrative and audit requirements of 44 CFR parts 13 and 206; (xii) Provide quarterly progress reports to the Regional Administrator...

25 CFR 30.122 - Must the Bureau assist a school it identified for school improvement, corrective action, or...

Code of Federal Regulations, 2010 CFR

2010-04-01

..., DEPARTMENT OF THE INTERIOR EDUCATION ADEQUATE YEARLY PROGRESS Failure To Make Adequate Yearly Progress § 30... restructuring, the Bureau must provide technical or other assistance described in 20 U.S.C. 6316(b)(4) and 20 U...

44 CFR 206.437 - State administrative plan.

Code of Federal Regulations, 2011 CFR

2011-10-01

... requests for advances of funds and reimbursement; (vii) Monitor and evaluate the progress and completion of... technical assistance as required to subgrantee(s); (xi) Comply with the administrative and audit requirements of 44 CFR parts 13 and 206; (xii) Provide quarterly progress reports to the Regional Administrator...

25 CFR 30.122 - Must the Bureau assist a school it identified for school improvement, corrective action, or...

Code of Federal Regulations, 2011 CFR

2011-04-01

..., DEPARTMENT OF THE INTERIOR EDUCATION ADEQUATE YEARLY PROGRESS Failure To Make Adequate Yearly Progress § 30... restructuring, the Bureau must provide technical or other assistance described in 20 U.S.C. 6316(b)(4) and 20 U...

Assessment Program Technical Progress Report, 1997-1998.

ERIC Educational Resources Information Center

Eickmeyer, Barbara; Hill, Stephen

This Assessment Program Progress Report (APPR) records the institutional activities that have taken place at Coconino Community College (CCC) during the 1997-98 academic year. It presents models, timelines, accomplishments, and opportunities for improvement in the assessment practices at CCC. Implementation and outcomes information is included for…

Diagnostic Efficiency of easyCBM[R] Math: Oregon. Technical Report #1009

ERIC Educational Resources Information Center

Anderson, Daniel; Alonzo, Julie; Tindal, Gerald

2010-01-01

The easyCBM[R] assessment system is an online benchmark and progress monitoring assessment system designed for use within a response to intervention framework. Educators using easyCBM[R] are often interested in using the results to predict students' state test performance. In the following technical document, we report diagnostic efficiency…

Longitudinal Surveys of Australian Youth (LSAY) 2009 Cohort: Wave 2 (2010)-- Questionnaire. Technical Report 71A

ERIC Educational Resources Information Center

National Centre for Vocational Education Research (NCVER), 2012

2012-01-01

The Longitudinal Surveys of Australian Youth (LSAY) program studies the progress of several groups of young Australians as they move from school into post-secondary education and work. This technical paper contains the questionnaire for the LSAY 2009 cohort Wave 2 (2010) data set.

Longitudinal Surveys of Australian Youth (LSAY) 2009 Cohort: Wave 3 (2011)--Questionnaire. Technical Report 72A

ERIC Educational Resources Information Center

National Centre for Vocational Education Research (NCVER), 2012

2012-01-01

The Longitudinal Surveys of Australian Youth (LSAY) program studies the progress of several groups of young Australians as they move from school into post-secondary education and work. This technical paper contains the questionnaire for the LSAY 2009 cohort Wave 3 (2011) data set.

Educational Reform and the World of Work: Italy

ERIC Educational Resources Information Center

von Blumenthal, Viktor

1977-01-01

One of a four-issue series on educational reform and the world of work in Europe, this issue discusses educational planning and secondary school reform in Italy. Topics discussed include planning and research in vocational-technical education, and the relation between acquisition of specific skills and scientific and technical progress. (Author/DB)

Longitudinal Surveys of Australian Youth (LSAY) 2009 Cohort: Wave 2 (2010)--Frequency Tables. Technical Report 71B

ERIC Educational Resources Information Center

National Centre for Vocational Education Research (NCVER), 2012

2012-01-01

The Longitudinal Surveys of Australian Youth (LSAY) program studies the progress of several groups of young Australians as they move from school into post-secondary education and work. This technical paper contains the frequency tables for the LSAY 2009 cohort Wave 2 (2010) data set.

Higher Education in Kazakhstan and the Bologna Process

ERIC Educational Resources Information Center

Piven, G.; Pak, I.U.

2006-01-01

The constantly rising role of higher education in the twenty-first century goes hand in hand with scientific and technical progress and the global technologization of the developed countries of the world. A country's level of technical and technological development determines its economic condition, its national security, and its role in the world…

A State Response to Indian Vocational Education.

ERIC Educational Resources Information Center

McConnell, Bruce

In 1977 more than 500 Native Americans attended Wisconsin's vocational, technical and adult schools located in the state's 16 vocational-technical districts. While many problems still lack a clear identification and many new programs are needed to meet the needs of Native Americans, a great deal of progress has been made. A group of four Indians…

Analytical Chemistry Division. Annual progress report for period ending December 31, 1980

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

Lyon, W.S.

1981-05-01

This report is divided into: analytical methodology; mass and emission spectrometry; technical support; bio/organic analysis; nuclear and radiochemical analysis; quality assurance, safety, and tabulation of analyses; supplementary activities; and presentation of research results. Separate abstracts were prepared for the technical support, bio/organic analysis, and nuclear and radiochemical analysis. (DLC)

Scientific and Technical Information Transfer for Education (STITE). Research Report No. 2.

ERIC Educational Resources Information Center

Zunde, Pranas

STITE (Scientific and Technical Information Transfer for Education) is basically a system to interface between science information and the science learner. As such STITE acts as a link between STIC (Science and Technology Infromation Centers) and LIS (Learning Information Systems). In this second progress report the internal knowledge of STITE is…

Mathematics Technical Report: Exercise Volume. National Assessment of Educational Progress. Report No. 04-MA-20.

ERIC Educational Resources Information Center

Education Commission of the States, Denver, CO. National Assessment of Educational Progress.

Included in Chapter 1 of this report are background information on the 1972-73 mathematics assessment; details of the computational formulas used in reporting results; and explanations of the technical documentation, exercise presentation, documentation pages, scoring guides, and data tables for released and unreleased exercises. The remainder of…

Experimentation with Computer-Assisted Instruction in Technical Education. Semi-Annual Progress Report.

ERIC Educational Resources Information Center

Mitzel, Harold E.; Brandon, George L.

A series of five reports is presented which describes the activities carried out by the Pennsylvania State University group engaged in research in computer-assisted instruction (CAI) in vocational-technical education. The reports cover the period January 1968-June 1968 and deal with: 1) prior knowledge and individualized instruction; 2) numerical…

Do failures in non-technical skills contribute to fatal medical accidents in Japan? A review of the 2010–2013 national accident reports

PubMed Central

Uramatsu, Masashi; Fujisawa, Yoshikazu; Mizuno, Shinya; Souma, Takahiro; Komatsubara, Akinori; Miki, Tamotsu

2017-01-01

Objectives We sought to clarify how large a proportion of fatal medical accidents can be considered to be caused by poor non-technical skills, and to support development of a policy to reduce number of such accidents by making recommendations about possible training requirements. Design Summaries of reports of fatal medical accidents, published by the Japan Medical Safety Research Organization, were reviewed individually. Three experienced clinicians and one patient safety expert conducted the reviews to determine the cause of death. Views of the patient safety expert were given additional weight in the overall determination. Setting A total of 73 summary reports of fatal medical accidents were reviewed. These reports had been submitted by healthcare organisations across Japan to the Japan Medical Safety Research Organization between April 2010 and March 2013. Primary and secondary outcome measures The cause of death in fatal medical accidents, categorised into technical skills, non-technical skills and inevitable progress of disease were evaluated. Non-technical skills were further subdivided into situation awareness, decision making, communication, team working, leadership, managing stress and coping with fatigue. Results Overall, the cause of death was identified as non-technical skills in 34 cases (46.6%), disease progression in 33 cases (45.2%) and technical skills in two cases (5.5%). In two cases, no consensual determination could be achieved. Further categorisation of cases of non-technical skills were identified as 14 cases (41.2%) of problems with situation awareness, eight (23.5%) with team working and three (8.8%) with decision making. These three subcategories, or combinations of them, were identified as the cause of death in 33 cases (97.1%). Conclusions Poor non-technical skills were considered to be a significant cause of adverse events in nearly half of the fatal medical accidents examined. Improving non-technical skills may be effective for reducing accidents, and training in particular subcategories of non-technical skills may be especially relevant. PMID:28209605

Ivabradine and metoprolol differentially affect cardiac glucose metabolism despite similar heart rate reduction in a mouse model of dyslipidemia.

PubMed

Vaillant, Fanny; Lauzier, Benjamin; Ruiz, Matthieu; Shi, Yanfen; Lachance, Dominic; Rivard, Marie-Eve; Bolduc, Virginie; Thorin, Eric; Tardif, Jean-Claude; Des Rosiers, Christine

2016-10-01

While heart rate reduction (HRR) is a target for the management of patients with heart disease, contradictory results were reported using ivabradine, which selectively inhibits the pacemaker I f current, vs. β-blockers like metoprolol. This study aimed at testing whether similar HRR with ivabradine vs. metoprolol differentially modulates cardiac energy substrate metabolism, a factor determinant for cardiac function, in a mouse model of dyslipidemia (hApoB +/+ ;LDLR -/- ). Following a longitudinal study design, we used 3- and 6-mo-old mice, untreated or treated for 3 mo with ivabradine or metoprolol. Cardiac function was evaluated in vivo and ex vivo in working hearts perfused with 13 C-labeled substrates to assess substrate fluxes through energy metabolic pathways. Compared with 3-mo-old, 6-mo-old dyslipidemic mice had similar cardiac hemodynamics in vivo but impaired (P < 0.001) contractile function (aortic flow: -45%; cardiac output: -34%; stroke volume: -35%) and glycolysis (-24%) ex vivo. Despite inducing a similar 10% HRR, ivabradine-treated hearts displayed significantly higher stroke volume values and glycolysis vs. their metoprolol-treated counterparts ex vivo, values for the ivabradine group being often not significantly different from 3-mo-old mice. Further analyses highlighted additional significant cardiac alterations with disease progression, namely in the total tissue level of proteins modified by O-linked N-acetylglucosamine (O-GlcNAc), whose formation is governed by glucose metabolism via the hexosamine biosynthetic pathway, which showed a similar pattern with ivabradine vs. metoprolol treatment. Collectively, our results emphasize the implication of alterations in cardiac glucose metabolism and signaling linked to disease progression in our mouse model. Despite similar HRR, ivabradine, but not metoprolol, preserved cardiac function and glucose metabolism during disease progression. Copyright © 2016 the American Physiological Society.

Reduced Renal Methylarginine Metabolism Protects against Progressive Kidney Damage.

PubMed

Tomlinson, James A P; Caplin, Ben; Boruc, Olga; Bruce-Cobbold, Claire; Cutillas, Pedro; Dormann, Dirk; Faull, Peter; Grossman, Rebecca C; Khadayate, Sanjay; Mas, Valeria R; Nitsch, Dorothea D; Wang, Zhen; Norman, Jill T; Wilcox, Christopher S; Wheeler, David C; Leiper, James

2015-12-01

Nitric oxide (NO) production is diminished in many patients with cardiovascular and renal disease. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthesis, and elevated plasma levels of ADMA are associated with poor outcomes. Dimethylarginine dimethylaminohydrolase-1 (DDAH1) is a methylarginine-metabolizing enzyme that reduces ADMA levels. We reported previously that a DDAH1 gene variant associated with increased renal DDAH1 mRNA transcription and lower plasma ADMA levels, but counterintuitively, a steeper rate of renal function decline. Here, we test the hypothesis that reduced renal-specific ADMA metabolism protects against progressive renal damage. Renal DDAH1 is expressed predominately within the proximal tubule. A novel proximal tubule-specific Ddah1 knockout (Ddah1(PT-/-)) mouse demonstrated tubular cell accumulation of ADMA and lower NO concentrations, but unaltered plasma ADMA concentrations. Ddah1(PT-/-) mice were protected from reduced kidney tissue mass, collagen deposition, and profibrotic cytokine expression in two independent renal injury models: folate nephropathy and unilateral ureteric obstruction. Furthermore, a study of two independent kidney transplant cohorts revealed higher levels of human renal allograft methylarginine-metabolizing enzyme gene expression associated with steeper function decline. We also report an association among DDAH1 expression, NO activity, and uromodulin expression supported by data from both animal and human studies, raising the possibility that kidney DDAH1 expression exacerbates renal injury through uromodulin-related mechanisms. Together, these data demonstrate that reduced renal tubular ADMA metabolism protects against progressive kidney function decline. Thus, circulating ADMA may be an imprecise marker of renal methylarginine metabolism, and therapeutic ADMA reduction may even be deleterious to kidney function. Copyright © 2015 by the American Society of Nephrology.

Therapeutic possibilities and opportunities for comparative oncopathology.

PubMed

Kaiser, H E

1993-01-01

In reviewing abnormal growth, we may distinguish autonomous and nonautonomous growth processes. The highest diversification is reached in the autonomous non-self-limiting processes, the malignant neoplasms which, if not treated, are characterized by extensive growth and progression. In their development these processes exhibit autonomy on one hand and heterogeneity on the other. Neoplastic and related diseases are extremely complex. It is unacceptable to view them exclusively as genetic or metabolic diseases, or merely as the tumor itself, including its progressive stages, as evidenced in neoplastic metastasis. All these characteristics appear in the different types of neoplastic malignomas, e.g. genetic variations in the neoplastic cells from the normal cells of the parent tissue(s). Included here are tumor progression and cloning of the neoplastic cells, stagewise development of host metabolism and of tumor metabolism; neoplastic hereditary and endocrine-like syndromes as well as paraneoplastic syndromes and cachexia. Neoplastic progression, as observed in the metastatic cascade, derives from the cells of the primary tumor. In contrast, multiple primary tumors originate from different host tissues, whereas the syndromes themselves constitute a symptom complex developing in a neoplasm-bearing host and cannot be assigned to local or distant spread of neoplasms. The only possible explanation for these apparently contrasting processes lies in the interaction of tumor and host metabolism, which seemingly varies in tumor-bearing hosts and in those cases where the tumor has been surgical removed. Antigens and other compounds again show an increase with the usually ensuing secondary tumor spread, a course which provides the basis for most deaths from cancer.

Comparing urban solid waste recycling from the viewpoint of urban metabolism based on physical input-output model: A case of Suzhou in China

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

Liang Sai, E-mail: liangsai09@gmail.com; Zhang Tianzhu, E-mail: zhangtz@mail.tsinghua.edu.cn

Highlights: Black-Right-Pointing-Pointer Impacts of solid waste recycling on Suzhou's urban metabolism in 2015 are analyzed. Black-Right-Pointing-Pointer Sludge recycling for biogas is regarded as an accepted method. Black-Right-Pointing-Pointer Technical levels of reusing scrap tires and food wastes should be improved. Black-Right-Pointing-Pointer Other fly ash utilization methods should be exploited. Black-Right-Pointing-Pointer Secondary wastes from reusing food wastes and sludge should be concerned. - Abstract: Investigating impacts of urban solid waste recycling on urban metabolism contributes to sustainable urban solid waste management and urban sustainability. Using a physical input-output model and scenario analysis, urban metabolism of Suzhou in 2015 is predicted and impactsmore » of four categories of solid waste recycling on urban metabolism are illustrated: scrap tire recycling, food waste recycling, fly ash recycling and sludge recycling. Sludge recycling has positive effects on reducing all material flows. Thus, sludge recycling for biogas is regarded as an accepted method. Moreover, technical levels of scrap tire recycling and food waste recycling should be improved to produce positive effects on reducing more material flows. Fly ash recycling for cement production has negative effects on reducing all material flows except solid wastes. Thus, other fly ash utilization methods should be exploited. In addition, the utilization and treatment of secondary wastes from food waste recycling and sludge recycling should be concerned.« less

Whole Grains in Amelioration of Metabolic Derangements

PubMed Central

Develaraja, Samir; Reddy, Anup; Yadav, Mukesh; Jain, Shalini; Yadav, Hariom

2017-01-01

Daily diet influences whole body metabolism, and intricately linked to the prevention or progression of metabolic diseases including obesity, diabetes and cardiovascular diseases. Several epidemiological and large scale studies have shown that diets enriched with whole grains improves metabolic function and protect from the development of metabolic diseases. Direct impact of whole grain diet can be mediated on several levels of metabolic functions i.e. reduced glycemic index, improved fat oxidation potential, increased cholesterol clearance or decreased cholesterol biosynthesis and modulation of gut microbiome. In this article we reviewed several studies indicating the beneficial effects of whole grain diets on metabolic functions, as well as discussed the potential active phytochemicals present in these whole grain foods to contribute in modulation of metabolic function in our body. PMID:28944285

Cancer metabolism: fatty acid oxidation in the limelight

PubMed Central

Carracedo, Arkaitz; Cantley, Lewis C.; Pandolfi, Pier Paolo

2013-01-01

Warburg suggested that the alterations in metabolism that he observed in cancer cells were due to the malfunction of mitochondria. In the past decade, we have revisited this idea and reached a better understanding of the ‘metabolic switch’ in cancer cells, including the intimate and causal relationship between cancer genes and metabolic alterations, and their potential to be targeted for cancer treatment. However, the vast majority of the research into cancer metabolism has been limited to a handful of metabolic pathways, while other pathways have remained in the dark. This Progress article brings to light the important contribution of fatty acid oxidation to cancer cell function. PMID:23446547

HEPATOKIN1 is a biochemistry-based model of liver metabolism for applications in medicine and pharmacology.

PubMed

Berndt, Nikolaus; Bulik, Sascha; Wallach, Iwona; Wünsch, Tilo; König, Matthias; Stockmann, Martin; Meierhofer, David; Holzhütter, Hermann-Georg

2018-06-19

The epidemic increase of non-alcoholic fatty liver diseases (NAFLD) requires a deeper understanding of the regulatory circuits controlling the response of liver metabolism to nutritional challenges, medical drugs, and genetic enzyme variants. As in vivo studies of human liver metabolism are encumbered with serious ethical and technical issues, we developed a comprehensive biochemistry-based kinetic model of the central liver metabolism including the regulation of enzyme activities by their reactants, allosteric effectors, and hormone-dependent phosphorylation. The utility of the model for basic research and applications in medicine and pharmacology is illustrated by simulating diurnal variations of the metabolic state of the liver at various perturbations caused by nutritional challenges (alcohol), drugs (valproate), and inherited enzyme disorders (galactosemia). Using proteomics data to scale maximal enzyme activities, the model is used to highlight differences in the metabolic functions of normal hepatocytes and malignant liver cells (adenoma and hepatocellular carcinoma).

Prediction of Metabolism of Drugs using Artificial Intelligence: How far have we reached?

PubMed

Kumar, Rajnish; Sharma, Anju; Siddiqui, Mohammed Haris; Tiwari, Rajesh Kumar

2016-01-01

Information about drug metabolism is an essential component of drug development. Modeling the drug metabolism requires identification of the involved enzymes, rate and extent of metabolism, the sites of metabolism etc. There has been continuous attempts in the prediction of metabolism of drugs using artificial intelligence in effort to reduce the attrition rate of drug candidates entering to preclinical and clinical trials. Currently, there are number of predictive models available for metabolism using Support vector machines, Artificial neural networks, Bayesian classifiers etc. There is an urgent need to review their progress so far and address the existing challenges in prediction of metabolism. In this attempt, we are presenting the currently available literature models and some of the critical issues regarding prediction of drug metabolism.

The Interactions between Insulin and Androgens in Progression to Castrate-Resistant Prostate Cancer

PubMed Central

Gunter, Jennifer H.; Lubik, Amy A.; McKenzie, Ian; Pollak, Michael; Nelson, Colleen C.

2012-01-01

An association between the metabolic syndrome and reduced testosterone levels has been identified, and a specific inverse relationship between insulin and testosterone levels suggests that an important metabolic crosstalk exists between these two hormonal axes; however, the mechanisms by which insulin and androgens may be reciprocally regulated are not well described. Androgen-dependant gene pathways regulate the growth and maintenance of both normal and malignant prostate tissue, and androgen-deprivation therapy (ADT) in patients exploits this dependence when used to treat recurrent and metastatic prostate cancer resulting in tumour regression. A major systemic side effect of ADT includes induction of key features of the metabolic syndrome and the consistent feature of hyperinsulinaemia. Recent studies have specifically identified a correlation between elevated insulin and high-grade PCa and more rapid progression to castrate resistant disease. This paper examines the relationship between insulin and androgens in the context of prostate cancer progression. Prostate cancer patients present a promising cohort for the exploration of insulin stabilising agents as adjunct treatments for hormone deprivation or enhancers of chemosensitivity for treatment of advanced prostate cancer. PMID:22548055

Cytochrome P450 CYP1A1: wider roles in cancer progression and prevention

PubMed Central

2009-01-01

CYP1A1 is one of the main cytochrome P450 enzymes, examined extensively for its capacity to activate compounds with carcinogenic properties. Continuous exposure to inhalation chemicals and environmental carcinogens is thought to increase the level of CYP1A1 expression in extrahepatic tissues, through the aryl hydrocarbon receptor (AhR). Although the latter has long been recognized as a ligand-induced transcription factor, which is responsible for the xenobiotic activating pathway of several phase I and phase II metabolizing enzymes, recent evidence suggests that the AhR is involved in various cell signaling pathways critical to cell cycle regulation and normal homeostasis. Disregulation of these pathways is implicated in tumor progression. In addition, it is becoming increasingly evident that CYP1A1 plays an important role in the detoxication of environmental carcinogens, as well as in the metabolic activation of dietary compounds with cancer preventative activity. Ultimately the contribution of CYP1A1 to cancer progression or prevention may depend on the balance of procarcinogen activation/detoxication and dietary natural product extrahepatic metabolism. PMID:19531241

The Role of Central Metabolism in Prostate Cancer Progression

DTIC Science & Technology

2013-09-01

prostate tissue for differences in tumor growth, proteomes and intermediates in polyunsaturated fatty acid (PUFA) metabolism . The use of the... MRM -based targeted proteomics. She has also learned a great deal of techniques in molecular and cell biology. As her initial study, she transfected

The role of low-grade inflammation and metabolic flexibility in aging and nutritional modulation thereof: a systems biology approach.

PubMed

Calçada, Dulce; Vianello, Dario; Giampieri, Enrico; Sala, Claudia; Castellani, Gastone; de Graaf, Albert; Kremer, Bas; van Ommen, Ben; Feskens, Edith; Santoro, Aurelia; Franceschi, Claudio; Bouwman, Jildau

2014-01-01

Aging is a biological process characterized by the progressive functional decline of many interrelated physiological systems. In particular, aging is associated with the development of a systemic state of low-grade chronic inflammation (inflammaging), and with progressive deterioration of metabolic function. Systems biology has helped in identifying the mediators and pathways involved in these phenomena, mainly through the application of high-throughput screening methods, valued for their molecular comprehensiveness. Nevertheless, inflammation and metabolic regulation are dynamical processes whose behavior must be understood at multiple levels of biological organization (molecular, cellular, organ, and system levels) and on multiple time scales. Mathematical modeling of such behavior, with incorporation of mechanistic knowledge on interactions between inflammatory and metabolic mediators, may help in devising nutritional interventions capable of preventing, or ameliorating, the age-associated functional decline of the corresponding systems. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Metabolic reprogramming during TGFβ1-induced epithelial-to-mesenchymal transition

PubMed Central

Jiang, Lei; Xiao, Ling; Sugiura, Hidekazu; Huang, Xiumei; Ali, Aktar; Kuro-o, Makoto; Deberardinis, Ralph J.; Boothman, David A.

2014-01-01

Metastatic progression, including extravasation and micro-metastatic outgrowth, is the main cause of cancer patient death. Recent studies suggest that cancer cells reprogram their metabolism to support increased proliferation through increased glycolysis and biosynthetic activities, including lipogenesis pathways. However, metabolic changes during metastatic progression, including alterations in regulatory gene expression, remain undefined. We show that transforming growth factor beta 1 (TGFβ1) induced Epithelial-to-Mesenchymal Transition (EMT) is accompanied by coordinately reduced enzyme expression required to convert glucose into fatty acids, and concomitant enhanced respiration. Over-expressed Snail1, a transcription factor mediating TGFβ1-induced EMT, was sufficient to suppress carbohydrate-responsive-element-binding protein (ChREBP, a master lipogenic regulator), and fatty acid synthase (FASN), its effector lipogenic gene. Stable FASN knock-down was sufficient to induce EMT, stimulate migration and extravasation in vitro. FASN silencing enhanced lung metastasis and death in vivo. These data suggest that a metabolic transition that suppresses lipogenesis and favors energy production is an essential component of TGFβ1-induced EMT and metastasis. PMID:25284588

Long-Range Trends in the Development of Higher Education in Mining

ERIC Educational Resources Information Center

Pzhevskii, V. V.

1978-01-01

Reviews the relationship between scientific and technological progress, needs of the Soviet economy, and capacities of higher education institutions in terms of the future of the mining industry. Mining specialists will have to prepare for technical progress in the extracting industries, growth in production, complex mechanization, and automation…

Progress Monitoring in Middle School Mathematics: Options and Issues

ERIC Educational Resources Information Center

Foegen, Anne

2008-01-01

This study investigated the technical features of six potential progress-monitoring measures in mathematics appropriate for use at the middle school level, including two commercially available measures for sixth-grade mathematics, two measures used in previous middle school studies, and two new measures of numeracy concepts. Five hundred…

10 CFR 600.341 - Monitoring and reporting program and financial performance.

Code of Federal Regulations, 2012 CFR

2012-01-01

... will be taken to address the deviations. (2) A final technical report if the award is for research and... dates for reports. At a minimum, requirements must include: (1) Periodic progress reports (at least... follows: (i) The program portions of the reports must address progress toward achieving program...

10 CFR 600.341 - Monitoring and reporting program and financial performance.

Code of Federal Regulations, 2014 CFR

2014-01-01

... will be taken to address the deviations. (2) A final technical report if the award is for research and... dates for reports. At a minimum, requirements must include: (1) Periodic progress reports (at least... follows: (i) The program portions of the reports must address progress toward achieving program...

10 CFR 600.341 - Monitoring and reporting program and financial performance.

Code of Federal Regulations, 2013 CFR

2013-01-01

... will be taken to address the deviations. (2) A final technical report if the award is for research and... dates for reports. At a minimum, requirements must include: (1) Periodic progress reports (at least... follows: (i) The program portions of the reports must address progress toward achieving program...

10 CFR 600.341 - Monitoring and reporting program and financial performance.

Code of Federal Regulations, 2011 CFR

2011-01-01

... will be taken to address the deviations. (2) A final technical report if the award is for research and... dates for reports. At a minimum, requirements must include: (1) Periodic progress reports (at least... follows: (i) The program portions of the reports must address progress toward achieving program...

Nuclear waste management. Semiannual progress report, October 1982-March 1983

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

Chikalla, T.D.; Powell, J.A.

1983-06-01

This document is one of a series of technical progress reports designed to report radioactive waste management programs at the Pacific Northwest Laboratory. Accomplishments in the following programs are reported: waste stabilization; Materials Characterization Center; waste isolation; low-level waste management; remedial action; and supporting studies.

Advancing Stage 2 Research on Measures for Monitoring Kindergarten Reading Progress

ERIC Educational Resources Information Center

Clemens, Nathan H.; Soohoo, Michelle M.; Wiley, Colby P.; Hsiao, Yu-Yu; Estrella, Ivonne; Allee-Smith, Paula J.; Yoon, Myeongsun

2018-01-01

Although several measures exist for frequently monitoring early reading progress, little research has specifically investigated their technical properties when administered on a frequent basis with kindergarten students. In this study, kindergarten students (N = 137) of whom the majority was receiving supplemental intervention for reading skills…

Metabolic activity, experiment M171. [space flight effects on human metabolism

NASA Technical Reports Server (NTRS)

Michel, E. L.; Rummel, J. A.

1973-01-01

The Skylab metabolic activity experiment determines if man's metabolic effectiveness in doing mechanical work is progressively altered by a simulated Skylab environment, including environmental factors such as slightly increased pCO2. This test identified several hardware/procedural anomalies. The most important of these were: (1) the metabolic analyzer measured carbon dioxide production and expired water too high; (2) the ergometer load module failed under continuous high workload conditions; (3) a higher than desirable number of erroneous blood pressure measurements were recorded; (4) vital capacity measurements were unreliable; and (5) anticipated crew personal exercise needs to be more structured.

Temporal Changes in Technical and Physical Performances During a Small-Sided Game in Elite Youth Soccer Players

PubMed Central

Moreira, Alexandre; Saldanha Aoki, Marcelo; Carling, Chris; Alan Rodrigues Lopes, Rafael; Felipe Schultz de Arruda, Ademir; Lima, Marcelo; Cesar Correa, Umberto; Bradley, Paul S

2016-01-01

Background There have been claims that small-sided games (SSG) may generate an appropriate environment to develop youth players’ technical performance associated to game-related problem solving. However, the temporal change in technical performance parameters of youth players during SSG is still unknown. Objectives The aim of this study was to examine temporal changes in technical and physical performances during a small-sided game (SSG) in elite soccer players. Methods Sixty elite youth players (age 14.8 ± 0.2 yr; stature 177 ± 5 cm; body mass 66.2 ± 4.7 kg) completed a 5 v 5 SSG using two repetitions of 8 minutes interspersed by 3 minutes of passive recovery. To evaluate temporal changes in performance, the data were analysed across 4 minutes quarters. Physical performance parameters included the total distance covered (TDC), the frequency of sprints (>18 km•h-1), accelerations and decelerations (> 2.0 m•s-2 and - 2.0 m•s-2), metabolic power (W•kg-1), training impulse (TRIMP), TDC: TRIMP, number of impacts, and body load. Technical performance parameters included goal attempts, total number of tackles, tackles and interceptions, total number of passes, and passes effectiveness. Results All physical performance parameters decreased from the first to the last quarter with notable declines in TDC, metabolic power and the frequency of sprints, accelerations and decelerations (P < 0.05; moderate to very large ES: 1.08 - 3.30). However, technical performance parameters did not vary across quarters (P > 0.05; trivial ES for 1st v 4th quarters: 0.15 - 0.33). Conclusions The data demonstrate that technical performance is maintained despite substantial declines in physical performance during a SSG in elite youth players. This finding may have implications for designing SSG’s for elite youth players to ensure physical, technical and tactical capabilities are optimized. Modifications in player number, pitch dimensions, rules, coach encouragement, for instance, should be included taking into account the main aim of a given session and then focused on overloading physical or technical elements. PMID:28144411

Temporal Changes in Technical and Physical Performances During a Small-Sided Game in Elite Youth Soccer Players.

PubMed

Moreira, Alexandre; Saldanha Aoki, Marcelo; Carling, Chris; Alan Rodrigues Lopes, Rafael; Felipe Schultz de Arruda, Ademir; Lima, Marcelo; Cesar Correa, Umberto; Bradley, Paul S

2016-12-01

There have been claims that small-sided games (SSG) may generate an appropriate environment to develop youth players' technical performance associated to game-related problem solving. However, the temporal change in technical performance parameters of youth players during SSG is still unknown. The aim of this study was to examine temporal changes in technical and physical performances during a small-sided game (SSG) in elite soccer players. Sixty elite youth players (age 14.8 ± 0.2 yr; stature 177 ± 5 cm; body mass 66.2 ± 4.7 kg) completed a 5 v 5 SSG using two repetitions of 8 minutes interspersed by 3 minutes of passive recovery. To evaluate temporal changes in performance, the data were analysed across 4 minutes quarters. Physical performance parameters included the total distance covered (TDC), the frequency of sprints (>18 km•h -1 ), accelerations and decelerations (> 2.0 m•s -2 and - 2.0 m•s -2 ), metabolic power (W•kg -1 ), training impulse (TRIMP), TDC: TRIMP, number of impacts, and body load. Technical performance parameters included goal attempts, total number of tackles, tackles and interceptions, total number of passes, and passes effectiveness. All physical performance parameters decreased from the first to the last quarter with notable declines in TDC, metabolic power and the frequency of sprints, accelerations and decelerations (P < 0.05; moderate to very large ES: 1.08 - 3.30). However, technical performance parameters did not vary across quarters (P > 0.05; trivial ES for 1st v 4th quarters: 0.15 - 0.33). The data demonstrate that technical performance is maintained despite substantial declines in physical performance during a SSG in elite youth players. This finding may have implications for designing SSG's for elite youth players to ensure physical, technical and tactical capabilities are optimized. Modifications in player number, pitch dimensions, rules, coach encouragement, for instance, should be included taking into account the main aim of a given session and then focused on overloading physical or technical elements.

Progressive gait ataxia following deep brain stimulation for essential tremor: adverse effect or lack of efficacy?

PubMed

Reich, Martin M; Brumberg, Joachim; Pozzi, Nicolò G; Marotta, Giorgio; Roothans, Jonas; Åström, Mattias; Musacchio, Thomas; Lopiano, Leonardo; Lanotte, Michele; Lehrke, Ralph; Buck, Andreas K; Volkmann, Jens; Isaias, Ioannis U

2016-11-01

Thalamic deep brain stimulation is a mainstay treatment for severe and drug-refractory essential tremor, but postoperative management may be complicated in some patients by a progressive cerebellar syndrome including gait ataxia, dysmetria, worsening of intention tremor and dysarthria. Typically, this syndrome manifests several months after an initially effective therapy and necessitates frequent adjustments in stimulation parameters. There is an ongoing debate as to whether progressive ataxia reflects a delayed therapeutic failure due to disease progression or an adverse effect related to repeated increases of stimulation intensity. In this study we used a multimodal approach comparing clinical stimulation responses, modelling of volume of tissue activated and metabolic brain maps in essential tremor patients with and without progressive ataxia to disentangle a disease-related from a stimulation-induced aetiology. Ten subjects with stable and effective bilateral thalamic stimulation were stratified according to the presence (five subjects) of severe chronic-progressive gait ataxia. We quantified stimulated brain areas and identified the stimulation-induced brain metabolic changes by multiple 18 F-fluorodeoxyglucose positron emission tomography performed with and without active neurostimulation. Three days after deactivating thalamic stimulation and following an initial rebound of symptom severity, gait ataxia had dramatically improved in all affected patients, while tremor had worsened to the presurgical severity, thus indicating a stimulation rather than disease-related phenomenon. Models of the volume of tissue activated revealed a more ventrocaudal stimulation in the (sub)thalamic area of patients with progressive gait ataxia. Metabolic maps of both patient groups differed by an increased glucose uptake in the cerebellar nodule of patients with gait ataxia. Our data suggest that chronic progressive gait ataxia in essential tremor is a reversible cerebellar syndrome caused by a maladaptive response to neurostimulation of the (sub)thalamic area. The metabolic signature of progressive gait ataxia is an activation of the cerebellar nodule, which may be caused by inadvertent current spread and antidromic stimulation of a cerebellar outflow pathway originating in the vermis. An anatomical candidate could be the ascending limb of the uncinate tract in the subthalamic area. Adjustments in programming and precise placement of the electrode may prevent this adverse effect and help fine-tuning deep brain stimulation to ameliorate tremor without negative cerebellar signs. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

NONE

This report summarizes geothermal technical assistance, R&D, and technology transfer activities of the Geo-Heat Center. It describes 95 contacts with parties during this period related to technical assistance with goethermal direct heat projects. Areas dealt with include geothermal heat pumps, space heating, greenhouses, aquaculture, equipment, economics, and resources. Research activities are summarized on geothermal district heating system cost evaluation and silica waste utilization project. Outreach activities include publication of a geothermal direct use Bulletin, dissemination of information, goethermal library, technical papers and seminars, and progress monitor reports on geothermal resources and utilization.

Coevolution of metabolic networks and membranes: the scenario of progressive sequestration.

PubMed

Szathmáry, Eörs

2007-10-29

Many regard metabolism as one of the central phenomena (or criteria) of life. Yet, the earliest infrabiological systems may have been devoid of metabolism: such systems would have been extreme heterotrophs. We do not know what level of complexity is attainable for chemical systems without enzymatic aid. Lack of template-instructed enzymatic catalysis may put a ceiling on complexity owing to inevitable spontaneous decay and wear and tear of chemodynamical machines. Views on the origin of metabolism critically depend on the assumptions concerning the sites of synthesis and consumption of organic compounds. If these sites are different, non-enzymatic origin of autotrophy is excluded. Whether autotrophy is secondary or not, it seems that protocell boundaries may have become more selective with time, concurrent with the enzymatization of the metabolic network. Primary heterotrophy and autotrophy imply pathway innovation and retention, respectively. The idea of metabolism-membrane coevolution leads to a scenario of progressive sequestration of the emerging living system from its exterior milieu. Comparative data on current protein enzymes may shed some light on such a primeval process by analogy, since two main ideas about enzymatization (the retroevolution and the patchwork scenarios) may not necessarily be mutually exclusive and the earliest enzymatic system may have used ribozymes rather than proteins.

Alcohol extract of North American ginseng (Panax quinquefolius) reduces fatty liver, dyslipidemia, and other complications of metabolic syndrome in a mouse model.

PubMed

Singh, Ratnesh K; Lui, Edmund; Wright, David; Taylor, Adrian; Bakovic, Marica

2017-09-01

We investigated whether North American ginseng (Panax quinquefolius) could reduce development of the metabolic syndrome phenotype in a mouse model (ETKO) of the disease. Young ETKO mice have no disease but similar to humans start to develop the fatty liver, hypertriglyceridemia, obesity, and insulin resistance at 25-30 weeks of age, and the disease continues to progress with ageing. ETKO mice were orally given an ethanol extract of ginseng roots at 4 and 32 weeks of age. Treatments with ginseng eliminated the ETKO fatty liver, reduced hepatic and intestinal lipoprotein secretion, and reduced the level of circulating lipids. Improvements by ginseng treatments were manifested as a reduction in the expression of genes involved in the regulation of fatty acid and triglyceride (fat) synthesis and secretion by the lipoproteins on one hand, and the stimulation of fatty acid oxidation and triglyceride degradation by lipolysis on the other hand. These processes altogether improved glucose, fatty acid, and triglyceride metabolism, reduced liver fat load, and reversed the progression of metabolic syndrome. These data confirm that treatments with North American ginseng could alleviate metabolic syndrome through the maintenance of a better balance between glucose and fatty acid metabolism, lipoprotein secretion, and energy homeostasis in disease-prone states.

Stabilization of LKB1 and Akt by neddylation regulates energy metabolism in liver cancer

PubMed Central

Barbier-Torres, Lucía; Delgado, Teresa C.; García-Rodríguez, Juan L.; Zubiete-Franco, Imanol; Fernández-Ramos, David; Buqué, Xabier; Cano, Ainara; Juan, Virginia Gutiérrez-de; Fernández-Domínguez, Itziar; Lopitz-Otsoa, Fernando; Fernández-Tussy, Pablo; Boix, Loreto; Bruix, Jordi; Villa, Erica; Castro, Azucena; Lu, Shelly C.; Aspichueta, Patricia; Xirodimas, Dimitris; Varela-Rey, Marta; Mato, José M.; Beraza, Naiara; Martínez-Chantar, María L.

2015-01-01

The current view of cancer progression highlights that cancer cells must undergo through a post-translational regulation and metabolic reprogramming to progress in an unfriendly environment. In here, the importance of neddylation modification in liver cancer was investigated. We found that hepatic neddylation was specifically enriched in liver cancer patients with bad prognosis. In addition, the treatment with the neddylation inhibitor MLN4924 in Phb1-KO mice, an animal model of hepatocellular carcinoma showing elevated neddylation, reverted the malignant phenotype. Tumor cell death in vivo translating into liver tumor regression was associated with augmented phosphatidylcholine synthesis by the PEMT pathway, known as a liver-specific tumor suppressor, and restored mitochondrial function and TCA cycle flux. Otherwise, in protumoral hepatocytes, neddylation inhibition resulted in metabolic reprogramming rendering a decrease in oxidative phosphorylation and concomitant tumor cell apoptosis. Moreover, Akt and LKB1, hallmarks of proliferative metabolism, were altered in liver cancer being new targets of neddylation. Importantly, we show that neddylation-induced metabolic reprogramming and apoptosis were dependent on LKB1 and Akt stabilization. Overall, our results implicate neddylation/signaling/metabolism, partly mediated by LKB1 and Akt, in the development of liver cancer, paving the way for novel therapeutic approaches targeting neddylation in hepatocellular carcinoma. PMID:25650664

Advanced biotechnology: metabolically engineered cells for the bio-based production of chemicals and fuels, materials, and health-care products.

PubMed

Becker, Judith; Wittmann, Christoph

2015-03-09

Corynebacterium glutamicum, Escherichia coli, and Saccharomyces cerevisiae in particular, have become established as important industrial workhorses in biotechnology. Recent years have seen tremendous progress in their advance into tailor-made producers, driven by the upcoming demand for sustainable processes and renewable raw materials. Here, the diversity and complexity of nature is simultaneously a challenge and a benefit. Harnessing biodiversity in the right manner through synergistic progress in systems metabolic engineering and chemical synthesis promises a future innovative bio-economy. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The evolution of endovascular electroencephalography: historical perspective and future applications.

PubMed

Sefcik, Roberta K; Opie, Nicholas L; John, Sam E; Kellner, Christopher P; Mocco, J; Oxley, Thomas J

2016-05-01

Current standard practice requires an invasive approach to the recording of electroencephalography (EEG) for epilepsy surgery, deep brain stimulation (DBS), and brain-machine interfaces (BMIs). The development of endovascular techniques offers a minimally invasive route to recording EEG from deep brain structures. This historical perspective aims to describe the technical progress in endovascular EEG by reviewing the first endovascular recordings made using a wire electrode, which was followed by the development of nanowire and catheter recordings and, finally, the most recent progress in stent-electrode recordings. The technical progress in device technology over time and the development of the ability to record chronic intravenous EEG from electrode arrays is described. Future applications for the use of endovascular EEG in the preoperative and operative management of epilepsy surgery are then discussed, followed by the possibility of the technique's future application in minimally invasive operative approaches to DBS and BMI.

Systems metabolic engineering: the creation of microbial cell factories by rational metabolic design and evolution.

PubMed

Furusawa, Chikara; Horinouchi, Takaaki; Hirasawa, Takashi; Shimizu, Hiroshi

2013-01-01

It is widely acknowledged that in order to establish sustainable societies, production processes should shift from petrochemical-based processes to bioprocesses. Because bioconversion technologies, in which biomass resources are converted to valuable materials, are preferable to processes dependent on fossil resources, the former should be further developed. The following two approaches can be adopted to improve cellular properties and obtain high productivity and production yield of target products: (1) optimization of cellular metabolic pathways involved in various bioprocesses and (2) creation of stress-tolerant cells that can be active even under severe stress conditions in the bioprocesses. Recent progress in omics analyses has facilitated the analysis of microorganisms based on bioinformatics data for molecular breeding and bioprocess development. Systems metabolic engineering is a new area of study, and it has been defined as a methodology in which metabolic engineering and systems biology are integrated to upgrade the designability of industrially useful microorganisms. This chapter discusses multi-omics analyses and rational design methods for molecular breeding. The first is an example of the rational design of metabolic networks for target production by flux balance analysis using genome-scale metabolic models. Recent progress in the development of genome-scale metabolic models and the application of these models to the design of desirable metabolic networks is also described in this example. The second is an example of evolution engineering with omics analyses for the creation of stress-tolerant microorganisms. Long-term culture experiments to obtain the desired phenotypes and omics analyses to identify the phenotypic changes are described here.

Diagnosis and Treatment of Metabolic Acidosis in Patients with Chronic Kidney Disease - Position Statement of the Working Group of the Polish Society of Nephrology.

PubMed

Adamczak, Marcin; Masajtis-Zagajewska, Anna; Mazanowska, Oktawia; Madziarska, Katarzyna; Stompór, Tomasz; Więcek, Andrzej

2018-01-01

Metabolic acidosis is commonly found in patients with chronic kidney disease (CKD), and its causes are: impaired ammonia excretion, reduced tubular bicarbonate reabsorption and insufficient renal bicarbonate production in relation to the amount of acids synthesised by the body and ingested with food. As the consequence, numerous metabolic abnormalities develop, which may lead to dysfunction of several organs. In observational studies, it has been found that CKD patients with metabolic acidosis are characterised by faster progression of kidney disease towards end stage kidney failure, and by increased mortality. Results of interventional studies suggest that alkali therapy in CKD patients slows progression of kidney disease. In view of these facts, the members of "The Working Group of the Polish Society of Nephrology on Metabolic and Endocrine Abnormalities in Kidney Diseases" have prepared the following statement and guidelines for the diagnosis and treatment of metabolic acidosis in CKD patients. Measurement of bicarbonate concentration in venous plasma or venous blood to check for metabolic acidosis should be performed in all CKD patients and metabolic acidosis in these patients should be diagnosed when the venous plasma or venous blood bicarbonate concentration is lower than 22 mmol/l. In patients with metabolic acidosis and CKD, oral sodium bicarbonate administration is recommended. The goal of such a treatment is to achieve a plasma or blood bicarbonate concentration equal to or greater than 22 mmol/l. © 2018 The Author(s). Published by S. Karger AG, Basel.

The combination of four analytical methods to explore skeletal muscle metabolomics: Better coverage of metabolic pathways or a marketing argument?

PubMed

Bruno, C; Patin, F; Bocca, C; Nadal-Desbarats, L; Bonnier, F; Reynier, P; Emond, P; Vourc'h, P; Joseph-Delafont, K; Corcia, P; Andres, C R; Blasco, H

2018-01-30

Metabolomics is an emerging science based on diverse high throughput methods that are rapidly evolving to improve metabolic coverage of biological fluids and tissues. Technical progress has led researchers to combine several analytical methods without reporting the impact on metabolic coverage of such a strategy. The objective of our study was to develop and validate several analytical techniques (mass spectrometry coupled to gas or liquid chromatography and nuclear magnetic resonance) for the metabolomic analysis of small muscle samples and evaluate the impact of combining methods for more exhaustive metabolite covering. We evaluated the muscle metabolome from the same pool of mouse muscle samples after 2 metabolite extraction protocols. Four analytical methods were used: targeted flow injection analysis coupled with mass spectrometry (FIA-MS/MS), gas chromatography coupled with mass spectrometry (GC-MS), liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS), and nuclear magnetic resonance (NMR) analysis. We evaluated the global variability of each compound i.e., analytical (from quality controls) and extraction variability (from muscle extracts). We determined the best extraction method and we reported the common and distinct metabolites identified based on the number and identity of the compounds detected with low analytical variability (variation coefficient<30%) for each method. Finally, we assessed the coverage of muscle metabolic pathways obtained. Methanol/chloroform/water and water/methanol were the best extraction solvent for muscle metabolome analysis by NMR and MS, respectively. We identified 38 metabolites by nuclear magnetic resonance, 37 by FIA-MS/MS, 18 by GC-MS, and 80 by LC-HRMS. The combination led us to identify a total of 132 metabolites with low variability partitioned into 58 metabolic pathways, such as amino acid, nitrogen, purine, and pyrimidine metabolism, and the citric acid cycle. This combination also showed that the contribution of GC-MS was low when used in combination with other mass spectrometry methods and nuclear magnetic resonance to explore muscle samples. This study reports the validation of several analytical methods, based on nuclear magnetic resonance and several mass spectrometry methods, to explore the muscle metabolome from a small amount of tissue, comparable to that obtained during a clinical trial. The combination of several techniques may be relevant for the exploration of muscle metabolism, with acceptable analytical variability and overlap between methods However, the difficult and time-consuming data pre-processing, processing, and statistical analysis steps do not justify systematically combining analytical methods. Copyright © 2017 Elsevier B.V. All rights reserved.

THE DEVELOPMENT OF ACHIEVEMENT MEASURES FOR TRADE AND TECHNICAL EDUCATION. PROGRESS REPORT NUMBER THREE.

ERIC Educational Resources Information Center

BALDWIN, THOMAS S.

DURING THIS PERIOD FROM SEPTEMBER 1 THROUGH NOVEMBER 30, 1966, 35 FIELD CONSULTANTS COMPLETED ANALYSIS OF THEIR INDIVIDUAL TRADE AND TECHNICAL CURRICULUMS. THESE ANALYSES WERE DEVELOPED INTO AN OUTLINE TO SERVE AS A GUIDE FOR DEVELOPING ACHIEVEMENT TESTS. THE FINAL OUTLINE WAS DIVIDED INTO AS MANY DIFFERENT AREAS AS THE CONSULTANTS FELT NECESSARY…

25 CFR 547.7 - What are the minimum technical hardware standards applicable to Class II gaming systems?

Code of Federal Regulations, 2011 CFR

2011-04-01

... OF CLASS II GAMES § 547.7 What are the minimum technical hardware standards applicable to Class II... the game, and are specially manufactured or proprietary and not off-the-shelf, shall display a unique... outcome or integrity of any game, progressive award, financial instrument, cashless transaction, voucher...

25 CFR 547.7 - What are the minimum technical hardware standards applicable to Class II gaming systems?

Code of Federal Regulations, 2012 CFR

2012-04-01

... OF CLASS II GAMES § 547.7 What are the minimum technical hardware standards applicable to Class II... the game, and are specially manufactured or proprietary and not off-the-shelf, shall display a unique... outcome or integrity of any game, progressive award, financial instrument, cashless transaction, voucher...

25 CFR 547.7 - What are the minimum technical hardware standards applicable to Class II gaming systems?

Code of Federal Regulations, 2010 CFR

2010-04-01

... OF CLASS II GAMES § 547.7 What are the minimum technical hardware standards applicable to Class II... the game, and are specially manufactured or proprietary and not off-the-shelf, shall display a unique... outcome or integrity of any game, progressive award, financial instrument, cashless transaction, voucher...

Diagnostic Efficiency of easyCBM[R] Math: Washington State. Technical Report #1008

ERIC Educational Resources Information Center

Anderson, Daniel; Alonzo, Julie; Tindal, Gerald

2010-01-01

easyCBM[R] is an online benchmark and progress monitoring assessment system designed for use within a response to intervention framework. Educators using easyCBM[R] are often interested in using the results to predict students' state test performance. In the following technical document, we report diagnostic efficiency statistics using a sample…

U.S. TIMSS and PIRLS 2011 Technical Report and User's Guide. NCES 2013-046

ERIC Educational Resources Information Center

Kastberg, David; Roey, Stephen; Ferraro, David; Lemanski, Nita; Erberber, Ebru

2013-01-01

The "U.S. TIMSS and PIRLS 2011 Technical Report and User's Guide" provides an overview of the design and implementation of the Trends in International Mathematics and Science Study (TIMSS) 2011 and the Progress in International Reading Literacy Study (PIRLS) 2011 in the United States and the nine participating benchmarking states:…

Longitudinal Surveys of Australian Youth (LSAY) 1998 Cohort: Wave 12 (2009)--Questionnaire. Technical Report 58A

ERIC Educational Resources Information Center

National Centre for Vocational Education Research (NCVER), 2010

2010-01-01

The Longitudinal Surveys of Australian Youth (LSAY) program studies the progress of several groups of young Australians as they move from school into post-secondary education and work. This technical paper contains the questionnaire for the LSAY 1998 cohort Wave 12 (2009) data set. [For the accompanying frequency tables, "Longitudinal Surveys…

The Development of the easyCBM CCSS Reading Assessments: Grade 3. Technical Report #1221

ERIC Educational Resources Information Center

Alonzo, Julie; Park, Bitnara Jasmine; Tindal, Gerald

2012-01-01

In this technical report, we document the development and piloting of easyCBM reading measures aligned to the Common Core State Standards, designed for use in screening students at risk for reading difficulty and monitoring their progress as they develop reading skills. The measures, which assess students' ability to respond to…

Developing Technical Writing Skills in the Physical Chemistry Laboratory: A Progressive Approach Employing Peer Review

ERIC Educational Resources Information Center

Gragson, Derek E.; Hagen, John P.

2010-01-01

Writing formal "journal-style" lab reports is often one of the requirements chemistry and biochemistry students encounter in the physical chemistry laboratory. Helping students improve their technical writing skills is the primary reason this type of writing is a requirement in the physical chemistry laboratory. Developing these skills is an…

Quality and Quality Assurance in Technical and Vocational Education and Training. Thematic Studies

ERIC Educational Resources Information Center

Seyfried, Erwin

2008-01-01

In many countries in both the Mediterranean region and the European Union (EU), interest in the quality of, and improvements to, technical and vocational education and training (TVET) systems has increased progressively in recent years. The main reason underlying this interest is a growing awareness of the key role played by education and training…

The Development of CBM Vocabulary Measures: Grade 4. Technical Report #1211

ERIC Educational Resources Information Center

Alonzo, Julie; Anderson, Daniel; Park, Bitnara Jasmine; Tindal, Gerald

2012-01-01

In this technical report, we describe the development and piloting of a series of vocabulary assessments intended for use with students in grades two through eight. These measures, available as part of easyCBM[TM], an online progress monitoring and benchmark/screening assessment system, were developed in 2010 and administered to approximately 1200…

The Development of CBM Vocabulary Measures: Grade 7. Technical Report #1214

ERIC Educational Resources Information Center

Alonzo, Julie; Anderson, Daniel; Park, Bitnara Jasmine; Tindal, Gerald

2012-01-01

In this technical report, we describe the development and piloting of a series of vocabulary assessments intended for use with students in grades two through eight. These measures, available as part of easyCBM[TM], an online progress monitoring and benchmark/screening assessment system, were developed in 2010 and administered to approximately 1200…

The Development of CBM Vocabulary Measures: Grade 5. Technical Report #1212

ERIC Educational Resources Information Center

Alonzo, Julie; Anderson, Daniel; Park, Bitnara Jasmine; Tindal, Gerald

2012-01-01

In this technical report, we describe the development and piloting of a series of vocabulary assessments intended for use with students in grades two through eight. These measures, available as part of easyCBM[TM], an online progress monitoring and benchmark/screening assessment system, were developed in 2010 and administered to approximately 1200…

The Development of CBM Vocabulary Measures: Grade 8. Technical Report #1215

ERIC Educational Resources Information Center

Alonzo, Julie; Anderson, Daniel; Park, Bitnara Jasmine; Tindal, Gerald

2012-01-01

In this technical report, we describe the development and piloting of a series of vocabulary assessments intended for use with students in grades two through eight. These measures, available as part of easyCBM[TM], an online progress monitoring and benchmark/screening assessment system, were developed in 2010 and administered to approximately 1200…

The Development of CBM Vocabulary Measures: Grade 2. Technical Report #1209

ERIC Educational Resources Information Center

Alonzo, Julie; Anderson, Daniel; Park, Bitnara Jasmine; Tindal, Gerald

2012-01-01

In this technical report, we describe the development and piloting of a series of vocabulary assessments intended for use with students in grades two through eight. These measures, available as part of easyCBM[TM], an online progress monitoring and benchmark/screening assessment system, were developed in 2010 and administered to approximately 1200…

The Development of CBM Vocabulary Measures: Grade 3. Technical Report #1210

ERIC Educational Resources Information Center

Alonzo, Julie; Anderson, Daniel; Park, Bitnara Jasmine; Tindal, Gerald

2012-01-01

In this technical report, we describe the development and piloting of a series of vocabulary assessments intended for use with students in grades two through eight. These measures, available as part of easyCBM[TM], an online progress monitoring and benchmark/screening assessment system, were developed in 2010 and administered to approximately 1200…

The Development of CBM Vocabulary Measures: Grade 6. Technical Report # 1213

ERIC Educational Resources Information Center

Alonzo, Julie; Anderson, Daniel; Park, Bitnara Jasmine; Tindal, Gerald

2012-01-01

In this technical report, we describe the development and piloting of a series of vocabulary assessments intended for use with students in grades two through eight. These measures, available as part of easyCBM[TM], an online progress monitoring and benchmark/screening assessment system, were developed in 2010 and administered to approximately 1200…

Application of Communications Satellites to Educational Development. Final Technical Report, September 1, 1969-August 31, 1975.

ERIC Educational Resources Information Center

Morgan, Robert P.

Research is summarized in a brief final report built around a four-section bibliography. The first section lists periodic progress reports and articles which provide an overview of the program, including articles which pertain primarily to educational rather than technical aspects of satellite utilization. Theses carried out in the fields of…

Technical efficiency and productivity of Chinese county hospitals: an exploratory study in Henan province, China.

PubMed

Cheng, Zhaohui; Tao, Hongbing; Cai, Miao; Lin, Haifeng; Lin, Xiaojun; Shu, Qin; Zhang, Ru-Ning

2015-09-09

Chinese county hospitals have been excessively enlarging their scale during the healthcare reform since 2009. The purpose of this paper is to examine the technical efficiency and productivity of county hospitals during the reform process, and to determine whether, and how, efficiency is affected by various factors. 114 sample county hospitals were selected from Henan province, China, from 2010 to 2012. Data envelopment analysis was employed to estimate the technical and scale efficiency of sample hospitals. The Malmquist index was used to calculate productivity changes over time. Tobit regression was used to regress against 4 environmental factors and 5 institutional factors that affected the technical efficiency. (1) 112 (98.2%), 112 (98.2%) and 104 (91.2%) of the 114 sample hospitals ran inefficiently in 2010, 2011 and 2012, with average technical efficiency of 0.697, 0.748 and 0.790, respectively. (2) On average, during 2010-2012, productivity of sample county hospitals increased by 7.8%, which was produced by the progress in technical efficiency changes and technological changes of 0.9% and 6.8%, respectively. (3) Tobit regression analysis indicated that government subsidy, hospital size with above 618 beds and average length of stay assumed a negative sign with technical efficiency; bed occupancy rate, ratio of beds to nurses and ratio of nurses to physicians assumed a positive sign with technical efficiency. There was considerable space for technical efficiency improvement in Henan county hospitals. During 2010-2012, sample hospitals experienced productivity progress; however, the adverse change in pure technical efficiency should be emphasised. Moreover, according to the Tobit results, policy interventions that strictly supervise hospital bed scale, shorten the average length of stay and coordinate the proportion among physicians, nurses and beds, would benefit hospital efficiency. 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.

Technical efficiency and productivity of Chinese county hospitals: an exploratory study in Henan province, China

PubMed Central

Cheng, Zhaohui; Tao, Hongbing; Cai, Miao; Lin, Haifeng; Lin, Xiaojun; Shu, Qin; Zhang, Ru-ning

2015-01-01

Objectives Chinese county hospitals have been excessively enlarging their scale during the healthcare reform since 2009. The purpose of this paper is to examine the technical efficiency and productivity of county hospitals during the reform process, and to determine whether, and how, efficiency is affected by various factors. Setting and participants 114 sample county hospitals were selected from Henan province, China, from 2010 to 2012. Outcome measures Data envelopment analysis was employed to estimate the technical and scale efficiency of sample hospitals. The Malmquist index was used to calculate productivity changes over time. Tobit regression was used to regress against 4 environmental factors and 5 institutional factors that affected the technical efficiency. Results (1) 112 (98.2%), 112 (98.2%) and 104 (91.2%) of the 114 sample hospitals ran inefficiently in 2010, 2011 and 2012, with average technical efficiency of 0.697, 0.748 and 0.790, respectively. (2) On average, during 2010–2012, productivity of sample county hospitals increased by 7.8%, which was produced by the progress in technical efficiency changes and technological changes of 0.9% and 6.8%, respectively. (3) Tobit regression analysis indicated that government subsidy, hospital size with above 618 beds and average length of stay assumed a negative sign with technical efficiency; bed occupancy rate, ratio of beds to nurses and ratio of nurses to physicians assumed a positive sign with technical efficiency. Conclusions There was considerable space for technical efficiency improvement in Henan county hospitals. During 2010–2012, sample hospitals experienced productivity progress; however, the adverse change in pure technical efficiency should be emphasised. Moreover, according to the Tobit results, policy interventions that strictly supervise hospital bed scale, shorten the average length of stay and coordinate the proportion among physicians, nurses and beds, would benefit hospital efficiency. PMID:26353864

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

Gauglitz, Phillip A.; Bontha, Jagannadha R.; Daniel, Richard C.

The Hanford Waste Treatment and Immobilization Plant (WTP) is currently being designed and constructed to pretreat and vitrify a large portion of the waste in the 177 underground waste storage tanks at the Hanford Site. A number of technical issues related to the design of the pretreatment facility (PTF) of the WTP have been identified. These issues must be resolved prior to the U.S. Department of Energy (DOE) Office of River Protection (ORP) reaching a decision to proceed with engineering, procurement, and construction activities for the PTF. One of the issues is Technical Issue T1 - Hydrogen Gas Release frommore » Vessels (hereafter referred to as T1). The focus of T1 is identifying controls for hydrogen release and completing any testing required to close the technical issue. In advance of selecting specific controls for hydrogen gas safety, a number of preliminary technical studies were initiated to support anticipated future testing and to improve the understanding of hydrogen gas generation, retention, and release within PTF vessels. These activities supported the development of a plan defining an overall strategy and approach for addressing T1 and achieving technical endpoints identified for T1. Preliminary studies also supported the development of a test plan for conducting testing and analysis to support closing T1. Both of these plans were developed in advance of selecting specific controls, and in the course of working on T1 it was decided that the testing and analysis identified in the test plan were not immediately needed. However, planning activities and preliminary studies led to significant technical progress in a number of areas. This report summarizes the progress to date from the preliminary technical studies. The technical results in this report should not be used for WTP design or safety and hazards analyses and technical results are marked with the following statement: “Preliminary Technical Results for Planning – Not to be used for WTP Design or Safety Analyses.”« less

METHODS AND ANALYSES FOR IMPLEMENTING NATURAL ATTENUATION PROTOCOLS

EPA Science Inventory

Technical protocols for evaluating natural attenuation at petroleum hydrocarbon and chlorinated solvent contaminated sites specify the analysis of electron acceptors and metabolic by-products for identifying and quantifying natural attenuation processes. However, these protocols ...

Progressive Inhibition by Water Deficit of Cell Wall Extensibility and Growth along the Elongation Zone of Maize Roots Is Related to Increased Lignin Metabolism and Progressive Stelar Accumulation of Wall Phenolics1

PubMed Central

Fan, Ling; Linker, Raphael; Gepstein, Shimon; Tanimoto, Eiichi; Yamamoto, Ryoichi; Neumann, Peter M.

2006-01-01

Water deficit caused by addition of polyethylene glycol 6000 at −0.5 MPa water potential to well-aerated nutrient solution for 48 h inhibited the elongation of maize (Zea mays) seedling primary roots. Segmental growth rates in the root elongation zone were maintained 0 to 3 mm behind the tip, but in comparison with well-watered control roots, progressive growth inhibition was initiated by water deficit as expanding cells crossed the region 3 to 9 mm behind the tip. The mechanical extensibility of the cell walls was also progressively inhibited. We investigated the possible involvement in root growth inhibition by water deficit of alterations in metabolism and accumulation of wall-linked phenolic substances. Water deficit increased expression in the root elongation zone of transcripts of two genes involved in lignin biosynthesis, cinnamoyl-CoA reductase 1 and 2, after only 1 h, i.e. before decreases in wall extensibility. Further increases in transcript expression and increased lignin staining were detected after 48 h. Progressive stress-induced increases in wall-linked phenolics at 3 to 6 and 6 to 9 mm behind the root tip were detected by comparing Fourier transform infrared spectra and UV-fluorescence images of isolated cell walls from water deficit and control roots. Increased UV fluorescence and lignin staining colocated to vascular tissues in the stele. Longitudinal bisection of the elongation zone resulted in inward curvature, suggesting that inner, stelar tissues were also rate limiting for root growth. We suggest that spatially localized changes in wall-phenolic metabolism are involved in the progressive inhibition of wall extensibility and root growth and may facilitate root acclimation to drying environments. PMID:16384904

Geraniol modulates tongue and hepatic phase I and phase II conjugation activities and may contribute directly to the chemopreventive activity against experimental oral carcinogenesis.

PubMed

Madankumar, Arumugam; Jayakumar, Subramaniyan; Gokuladhas, Krishnan; Rajan, Balan; Raghunandhakumar, Subramanian; Asokkumar, Selvamani; Devaki, Thiruvengadam

2013-04-05

Xenobiotic metabolizing enzymes are chief determinants in both the susceptibility to mutagenic effect of chemical carcinogens and in the response of tumors to chemotherapy. The present study was aimed to analyze the effect of geraniol administration on the activity of phase I and phase II carcinogen metabolizing enzymes through the nuclear factor erythroid 2-related factor-2 (Nrf2) activation against 4-niroquinoline-1-oxide (4NQO) induced oral carcinogenesis. The well-known chemical carcinogen 4NQO (50 ppm) was used to induce oral carcinogenesis through drinking water for 4, 12, and 20 weeks. The degree of cancer progression at each stage was confirmed by histological examination. At the end of the experimental period, 100% tumor formation was observed in the oral cavity of 4NQO induced animals with significant (P<0.05) alteration in the status of tumor markers, tongue and liver phase I and phase II drug metabolizing enzymes indicating progression of disease. Oral administration of geraniol at the dose of 200 mg/kg b.wt., thrice a week to 4NQO induced animals was able to inhibit tumor formation and thereby delayed the progression of oral carcinogenesis by modulating tongue and liver phase I and phase II drug metabolizing enzymes, as substantiated further by the histological and transmission electron microscopic studies. Our results demonstrate that geraniol exerts its chemopreventive potential by altering activities of phases I and II drug metabolizing enzymes to achieve minimum bioactivation of carcinogen and maximum detoxification. Copyright © 2013 Elsevier B.V. All rights reserved.

Metabolic changes associated with tumor metastasis, part 2: Mitochondria, lipid and amino acid metabolism.

PubMed

Porporato, Paolo E; Payen, Valéry L; Baselet, Bjorn; Sonveaux, Pierre

2016-04-01

Metabolic alterations are a hallmark of cancer controlling tumor progression and metastasis. Among the various metabolic phenotypes encountered in tumors, this review focuses on the contributions of mitochondria, lipid and amino acid metabolism to the metastatic process. Tumor cells require functional mitochondria to grow, proliferate and metastasize, but shifts in mitochondrial activities confer pro-metastatic traits encompassing increased production of mitochondrial reactive oxygen species (mtROS), enhanced resistance to apoptosis and the increased or de novo production of metabolic intermediates of the TCA cycle behaving as oncometabolites, including succinate, fumarate, and D-2-hydroxyglutarate that control energy production, biosynthesis and the redox state. Lipid metabolism and the metabolism of amino acids, such as glutamine, glutamate and proline are also currently emerging as focal control points of cancer metastasis.

Physical fitness predicts technical-tactical and time-motion profile in simulated Judo and Brazilian Jiu-Jitsu matches

PubMed Central

Gentil, Paulo; Bueno, João C.A.; Follmer, Bruno; Marques, Vitor A.; Del Vecchio, Fabrício B.

2018-01-01

Background Among combat sports, Judo and Brazilian Jiu-Jitsu (BJJ) present elevated physical fitness demands from the high-intensity intermittent efforts. However, information regarding how metabolic and neuromuscular physical fitness is associated with technical-tactical performance in Judo and BJJ fights is not available. This study aimed to relate indicators of physical fitness with combat performance variables in Judo and BJJ. Methods The sample consisted of Judo (n = 16) and BJJ (n = 24) male athletes. At the first meeting, the physical tests were applied and, in the second, simulated fights were performed for later notational analysis. Results The main findings indicate: (i) high reproducibility of the proposed instrument and protocol used for notational analysis in a mobile device; (ii) differences in the technical-tactical and time-motion patterns between modalities; (iii) performance-related variables are different in Judo and BJJ; and (iv) regression models based on metabolic fitness variables may account for up to 53% of the variances in technical-tactical and/or time-motion variables in Judo and up to 31% in BJJ, whereas neuromuscular fitness models can reach values up to 44 and 73% of prediction in Judo and BJJ, respectively. When all components are combined, they can explain up to 90% of high intensity actions in Judo. Discussion In conclusion, performance prediction models in simulated combat indicate that anaerobic, aerobic and neuromuscular fitness variables contribute to explain time-motion variables associated with high intensity and technical-tactical variables in Judo and BJJ fights. PMID:29844991

Final Technical Report

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

Michael Laub

2008-12-29

Our team of investigators from MIT (Michael Laub) and Stanford (Harley McAdams and Lucy Shapiro) conducted a multi-faceted, systematic experimental analysis of the 106 Caulobacter two-component signal transduction system proteins (62 histidine kinases and 44 response regulators) to understand how they coordinate cell cycle progression, metabolism, and response to environmental changes. These two-component signaling proteins were characterized at the genetic, biochemical, and genomic levels. The results generated by our laboratories have provided numerous insights into how Caulobacter cells sense and respond to a myriad of signals. As nearly all bacteria use two-component signaling for cell regulation, the results from thismore » project help to deepen our general understanding of bacterial signal transduction. The tools and approaches developed can be applied to other bacteria. In particular, work from the Laub laboratory now enables the systematic, rational rewiring of two-component signaling proteins, a major advance that stands to impact synthetic biology and the development of biosensors and other designer molecular circuits. Results are summarized from our work. Each section lists publications and publicly-available resources which result from the work described.« less

Genetic Engineering Strategies for Enhanced Biodiesel Production.

PubMed

Hegde, Krishnamoorthy; Chandra, Niharika; Sarma, Saurabh Jyoti; Brar, Satinder Kaur; Veeranki, Venkata Dasu

2015-07-01

The focus on biodiesel research has shown a tremendous growth over the last few years. Several microbial and plant sources are being explored for the sustainable biodiesel production to replace the petroleum diesel. Conventional methods of biodiesel production have several limitations related to yield and quality, which led to development of new engineering strategies to improve the biodiesel production in plants, and microorganisms. Substantial progress in utilizing algae, yeast, and Escherichia coli for the renewable production of biodiesel feedstock via genetic engineering of fatty acid metabolic pathways has been reported in the past few years. However, in most of the cases, the successful commercialization of such engineering strategies for sustainable biodiesel production is yet to be seen. This paper systematically presents the drawbacks in the conventional methods for biodiesel production and an exhaustive review on the present status of research in genetic engineering strategies for production of biodiesel in plants, and microorganisms. Further, we summarize the technical challenges need to be tackled to make genetic engineering technology economically sustainable. Finally, the need and prospects of genetic engineering technology for the sustainable biodiesel production and the recommendations for the future research are discussed.

Abnormal metabolic brain networks in Parkinson's disease from blackboard to bedside.

PubMed

Tang, Chris C; Eidelberg, David

2010-01-01

Metabolic imaging in the rest state has provided valuable information concerning the abnormalities of regional brain function that underlie idiopathic Parkinson's disease (PD). Moreover, network modeling procedures, such as spatial covariance analysis, have further allowed for the quantification of these changes at the systems level. In recent years, we have utilized this strategy to identify and validate three discrete metabolic networks in PD associated with the motor and cognitive manifestations of the disease. In this chapter, we will review and compare the specific functional topographies underlying parkinsonian akinesia/rigidity, tremor, and cognitive disturbance. While network activity progressed over time, the rate of change for each pattern was distinctive and paralleled the development of the corresponding clinical symptoms in early-stage patients. This approach is already showing great promise in identifying individuals with prodromal manifestations of PD and in assessing the rate of progression before clinical onset. Network modulation was found to correlate with the clinical effects of dopaminergic treatment and surgical interventions, such as subthalamic nucleus (STN) deep brain stimulation (DBS) and gene therapy. Abnormal metabolic networks have also been identified for atypical parkinsonian syndromes, such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Using multiple disease-related networks for PD, MSA, and PSP, we have developed a novel, fully automated algorithm for accurate classification at the single-patient level, even at early disease stages. Copyright © 2010 Elsevier B.V. All rights reserved.

Potential use of metabolic breath tests to assess liver disease and prognosis: has the time arrived for routine use in the clinic?

PubMed

Stravitz, R Todd; Ilan, Yaron

2017-03-01

The progression of liver disease may be unique among organ system diseases in that progressive fibrosis compromises not only the sufficiency of hepatocyte mass but also impairs blood flow to the liver, resulting in porto-systemic shunting. Although liver biopsy as an assessment of fibrosis has become the key biomarker of and target for new therapies, it is invasive and subject to sampling error, and cannot quantify metabolic function or porto-systemic shunting. Measurement of the hepatic venous pressure gradient accommodates some of the deficiencies of biopsy but requires expertise not widely available and misses minor changes in hepatocellular mass and thereby information about metabolic function. Thus, an unmet need in clinical hepatology remains unfulfilled: a noninvasive biomarker which quantitates both the hepatocellular insufficiency and porto-systemic shunting inherent in progressive hepatic fibrosis. Ideally, such a biomarker should correlate with clinical endpoints including liver-related survival and cirrhotic complications, be performed at the point-of-care, and be affordable and easy to use. This review, an expert opinion, summarizes background and recent data suggesting that metabolic breath tests may now meet these requirements and have a valid place in clinical hepatology to supplant the time-honoured assessment of hepatic fibrosis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Regulatory T cells as suppressors of anti-tumor immunity: Role of metabolism.

PubMed

De Rosa, Veronica; Di Rella, Francesca; Di Giacomo, Antonio; Matarese, Giuseppe

2017-06-01

Novel concepts in immunometabolism support the hypothesis that glucose consumption is also used to modulate anti-tumor immune responses, favoring growth and expansion of specific cellular subsets defined in the past as suppressor T cells and currently reborn as regulatory T (Treg) cells. During the 1920s, Otto Warburg and colleagues observed that tumors consumed high amounts of glucose compared to normal tissues, even in the presence of oxygen and completely functioning mitochondria. However, the role of the Warburg Effect is still not completely understood, particularly in the context of an ongoing anti-tumor immune response. Current experimental evidence suggests that tumor-derived metabolic restrictions can drive T cell hyporesponsiveness and immune tolerance. For example, several glycolytic enzymes, deregulated in cancer, contribute to tumor progression independently from their canonical metabolic activity. Indeed, they can control apoptosis, gene expression and activation of specific intracellular pathways, thus suggesting a direct link between metabolic switches and pro-tumorigenic transcriptional programs. Focus of this review is to define the specific metabolic pathways controlling Treg cell immunobiology in the context of anti-tumor immunity and tumor progression. Copyright © 2017 Elsevier Ltd. All rights reserved.

Amino Acid Catabolism in Alzheimer's Disease Brain: Friend or Foe?

PubMed Central

2017-01-01

There is a dire need to discover new targets for Alzheimer's disease (AD) drug development. Decreased neuronal glucose metabolism that occurs in AD brain could play a central role in disease progression. Little is known about the compensatory neuronal changes that occur to attempt to maintain energy homeostasis. In this review using the PubMed literature database, we summarize evidence that amino acid oxidation can temporarily compensate for the decreased glucose metabolism, but eventually altered amino acid and amino acid catabolite levels likely lead to toxicities contributing to AD progression. Because amino acids are involved in so many cellular metabolic and signaling pathways, the effects of altered amino acid metabolism in AD brain are far-reaching. Possible pathological results from changes in the levels of several important amino acids are discussed. Urea cycle function may be induced in endothelial cells of AD patient brains, possibly to remove excess ammonia produced from increased amino acid catabolism. Studying AD from a metabolic perspective provides new insights into AD pathogenesis and may lead to the discovery of dietary metabolite supplements that can partially compensate for alterations of enzymatic function to delay AD or alleviate some of the suffering caused by the disease. PMID:28261376

11β-HSD1 inhibition ameliorates metabolic syndrome and prevents progression of atherosclerosis in mice

PubMed Central

Hermanowski-Vosatka, Anne; Balkovec, James M.; Cheng, Kang; Chen, Howard Y.; Hernandez, Melba; Koo, Gloria C.; Le Grand, Cheryl B.; Li, Zhihua; Metzger, Joseph M.; Mundt, Steven S.; Noonan, Heather; Nunes, Christian N.; Olson, Steven H.; Pikounis, Bill; Ren, Ning; Robertson, Nancy; Schaeffer, James M.; Shah, Kashmira; Springer, Martin S.; Strack, Alison M.; Strowski, Matthias; Wu, Kenneth; Wu, TsueiJu; Xiao, Jianying; Zhang, Bei B.; Wright, Samuel D.; Thieringer, Rolf

2005-01-01

The enzyme 11β–hydroxysteroid dehydrogenase (HSD) type 1 converts inactive cortisone into active cortisol in cells, thereby raising the effective glucocorticoid (GC) tone above serum levels. We report that pharmacologic inhibition of 11β-HSD1 has a therapeutic effect in mouse models of metabolic syndrome. Administration of a selective, potent 11β-HSD1 inhibitor lowered body weight, insulin, fasting glucose, triglycerides, and cholesterol in diet-induced obese mice and lowered fasting glucose, insulin, glucagon, triglycerides, and free fatty acids, as well as improved glucose tolerance, in a mouse model of type 2 diabetes. Most importantly, inhibition of 11β-HSD1 slowed plaque progression in a murine model of atherosclerosis, the key clinical sequela of metabolic syndrome. Mice with a targeted deletion of apolipoprotein E exhibited 84% less accumulation of aortic total cholesterol, as well as lower serum cholesterol and triglycerides, when treated with an 11β-HSD1 inhibitor. These data provide the first evidence that pharmacologic inhibition of intracellular GC activation can effectively treat atherosclerosis, the key clinical consequence of metabolic syndrome, in addition to its salutary effect on multiple aspects of the metabolic syndrome itself. PMID:16103409

Effects of a selenium-laden soil amendment on grapevine metabolism and progression of Pierce’s disease

USDA-ARS?s Scientific Manuscript database

Selenium containing soil amendments might be beneficial to growers as selenium may increase resistance to certain plant pathogens and pests. Therefore, grapevines growing in soil with different amounts of selenium-laden amendment were evaluated for metabolism and susceptibility to Pierce’s disease (...

Fundamentals of cancer metabolism

PubMed Central

DeBerardinis, Ralph J.; Chandel, Navdeep S.

2016-01-01

Tumors reprogram pathways of nutrient acquisition and metabolism to meet the bioenergetic, biosynthetic, and redox demands of malignant cells. These reprogrammed activities are now recognized as hallmarks of cancer, and recent work has uncovered remarkable flexibility in the specific pathways activated by tumor cells to support these key functions. In this perspective, we provide a conceptual framework to understand how and why metabolic reprogramming occurs in tumor cells, and the mechanisms linking altered metabolism to tumorigenesis and metastasis. Understanding these concepts will progressively support the development of new strategies to treat human cancer. PMID:27386546

VRML metabolic network visualizer.

PubMed

Rojdestvenski, Igor

2003-03-01

A successful date collection visualization should satisfy a set of many requirements: unification of diverse data formats, support for serendipity research, support of hierarchical structures, algorithmizability, vast information density, Internet-readiness, and other. Recently, virtual reality has made significant progress in engineering, architectural design, entertainment and communication. We experiment with the possibility of using the immersive abstract three-dimensional visualizations of the metabolic networks. We present the trial Metabolic Network Visualizer software, which produces graphical representation of a metabolic network as a VRML world from a formal description written in a simple SGML-type scripting language.

Defective lysosomal proteolysis and axonal transport are early pathogenic events that worsen with age leading to increased APP metabolism and synaptic Abeta in transgenic APP/PS1 hippocampus

PubMed Central

2012-01-01

Background Axonal pathology might constitute one of the earliest manifestations of Alzheimer disease. Axonal dystrophies were observed in Alzheimer’s patients and transgenic models at early ages. These axonal dystrophies could reflect the disruption of axonal transport and the accumulation of multiple vesicles at local points. It has been also proposed that dystrophies might interfere with normal intracellular proteolysis. In this work, we have investigated the progression of the hippocampal pathology and the possible implication in Abeta production in young (6 months) and aged (18 months) PS1(M146L)/APP(751sl) transgenic mice. Results Our data demonstrated the existence of a progressive, age-dependent, formation of axonal dystrophies, mainly located in contact with congophilic Abeta deposition, which exhibited tau and neurofilament hyperphosphorylation. This progressive pathology was paralleled with decreased expression of the motor proteins kinesin and dynein. Furthermore, we also observed an early decrease in the activity of cathepsins B and D, progressing to a deep inhibition of these lysosomal proteases at late ages. This lysosomal impairment could be responsible for the accumulation of LC3-II and ubiquitinated proteins within axonal dystrophies. We have also investigated the repercussion of these deficiencies on the APP metabolism. Our data demonstrated the existence of an increase in the amyloidogenic pathway, which was reflected by the accumulation of hAPPfl, C99 fragment, intracellular Abeta in parallel with an increase in BACE and gamma-secretase activities. In vitro experiments, using APPswe transfected N2a cells, demonstrated that any imbalance on the proteolytic systems reproduced the in vivo alterations in APP metabolism. Finally, our data also demonstrated that Abeta peptides were preferentially accumulated in isolated synaptosomes. Conclusion A progressive age-dependent cytoskeletal pathology along with a reduction of lysosomal and, in minor extent, proteasomal activity could be directly implicated in the progressive accumulation of APP derived fragments (and Abeta peptides) in parallel with the increase of BACE-1 and gamma-secretase activities. This retard in the APP metabolism seemed to be directly implicated in the synaptic Abeta accumulation and, in consequence, in the pathology progression between synaptically connected regions. PMID:23173743

Automotive Stirling engine development program

NASA Technical Reports Server (NTRS)

Ernst, W.; Richey, A.; Farrell, R.; Riecke, G.; Smith, G.; Howarth, R.; Cronin, M.; Simetkosky, M.; Meacher, J.

1986-01-01

This is the ninth Semiannual Technical Progress Report prepared under the Automotive Stirling Engine Development Program. It covers the twenty-eighth and twenty-ninth quarters of activity after award of the contract. Quarterly Technical Progress Reports related program activities from the first through the thirteenth quarters; thereafter, reporting was changed to a Semiannual format. This report summarizes the study of higher-power kinematic Stirling engines for transportation use, development testing of Mod I Stirling engines, and component development activities. Component development testing included successful conical fuel nozzle testing and functional checkout of Mod II controls and auxiliaries on Mod I engine test beds. Overall program philosophy is outlined and data and test results are presented.

Publications of the Jet Propulsion Laboratory, 1981

NASA Technical Reports Server (NTRS)

1982-01-01

Over 500 externally distributed technical reports released during 1981 that resulted from scientific and engineering work performed, or managed by Jet Propulsion Laboratory are listed by primary author. Of the total number of entries, 311 are from the bimonthly Deep Space Network Progress Report, and its successor, the Telecommunications and Data Acquisition Progress Report.

40 CFR 35.4170 - What kinds of reporting does EPA require?

Code of Federal Regulations, 2011 CFR

2011-07-01

... OTHER FEDERAL ASSISTANCE STATE AND LOCAL ASSISTANCE Grants for Technical Assistance Managing Your Tag... period which ends June 30 and December 31 of each year. (b) [Reserved] (c) Progress Report Full description in chart or narrative format of the progress your group made in relation to your approved schedule...

77 FR 75441 - Healthy Home and Lead Hazard Control Grant Programs Data Collection; Progress Reporting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-20

... DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT [Docket No. FR-5603-N-93] Healthy Home and Lead Hazard... collection is designed to provide HUD timely information on progress of Healthy Homes Demonstration Program, Healthy Homes Technical Studies Program, Lead Base paint Hazard Control program, Lead Hazard Reduction...

Measuring Student Progress in the Classroom: A Guide to Testing and Evaluating Progress of Students with Disabilities.

ERIC Educational Resources Information Center

Hartman, Rhona C.; Redden, Martha Ross

This fact sheet provides guidelines on adapting testing situations for disabled postsecondary students. Discussed in the first section are considerations in determining when testing adaptations are needed including disability verification procedures, policy consistency, and maintenance of academic and technical standards. Facts about disabilities…

Progress in the First Five Years: An Evaluation of Achieving the Dream Colleges in Washington State

ERIC Educational Resources Information Center

Jenkins, Davis; Wachen, John; Kerrigan, Monica Reid; Mayer, Alexander K.

2012-01-01

In 2006, six community and technical colleges in Washington State joined the innovative national reform initiative called Achieving the Dream (ATD). This report describes the progress each college made in implementing ATD's "culture of evidence" principles for institutional improvement, examines strategies implemented by the colleges to…

Effect of pulsed progressive fluoroscopy on reduction of radiation dose in the cardiac catheterization laboratory

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

Holmes, D.R. Jr.; Wondrow, M.A.; Gray, J.E.

1990-01-01

The increased application of therapeutic interventional cardiology procedures is associated with increased radiation exposure to physicians, patients and technical personnel. New advances in imaging techniques have the potential for reducing radiation exposure. A progressive scanning video system with a standard vascular phantom has been shown to decrease entrance radiation exposure. The effect of this system on reducing actual radiation exposure to physicians and technicians was assessed from 1984 through 1987. During this time, progressive fluoroscopy was added sequentially to all four adult catheterization laboratories; no changes in shielding procedures were made. During this time, the case load per physician increasedmore » by 63% and the number of percutaneous transluminal coronary angioplasty procedures (a high radiation procedure) increased by 244%. Despite these increases in both case load and higher radiation procedures, the average radiation exposure per physician declined by 37%. During the same time, the radiation exposure for technicians decreased by 35%. Pulsed progressive fluoroscopy is effective for reducing radiation exposure to catheterization laboratory physicians and technical staff.« less

Selection of Type I and Type II Methanotrophic Proteobacteria in a Fluidized Bed Reactor under Non-Sterile Conditions

DTIC Science & Technology

2011-08-01

2009). Polyhydroxyalkanoates (PHAs), which can be used as bioplastics (Reddy et al., 2003), are intracellular granules that accumulate in some bacteria...Dawes, E., 1990. Occurrence, metabolism, metabolic rate, and industrial uses of bacterial polyhydroxyalkanoates . Microbiol. Rev. 54, 450–472. Araki...bacteria? Progress and prospects for polyhydroxyalkanoate production in bacteria. TibTechnology 14, 431–438. Madison, L., Huisman, G., 1999. Metabolic

A Tool for Measuring NASA's Aeronautics Research Progress Toward Planned Strategic Community Outcomes

NASA Technical Reports Server (NTRS)

Tahmasebi, Farhad; Pearce, Robert

2016-01-01

Description of a tool for portfolio analysis of NASA's Aeronautics research progress toward planned community strategic Outcomes is presented. For efficiency and speed, the tool takes advantage of a function developed in Excels Visual Basic for Applications. The strategic planning process for determining the community Outcomes is also briefly discussed. Stakeholder buy-in, partnership performance, progress of supporting Technical Challenges, and enablement forecast are used as the criteria for evaluating progress toward Outcomes. A few illustrative examples of using the tool are also presented.

Metabolic genes in cancer: their roles in tumor progression and clinical implications

PubMed Central

Furuta, Eiji; Okuda, Hiroshi; Kobayashi, Aya; Watabe, Kounosuke

2010-01-01

Re-programming of metabolic pathways is a hallmark of physiological changes in cancer cells. The expression of certain genes that directly control the rate of key metabolic pathways including glycolysis, lipogenesis and nucleotide synthesis are drastically altered at different stages of tumor progression. These alterations are generally considered as an adaptation of tumor cells; however, they also contribute to the progression of tumor cells to become more aggressive phenotypes. This review summarizes the recent information about the mechanistic link of these genes to oncogenesis and their potential utility as diagnostic markers as well as for therapeutic targets. We particularly focus on three groups of genes; GLUT1, G6PD, TKTL1 and PGI/AMF in glycolytic pathway, ACLY, ACC1 and FAS in lipogenesis and RRM1, RRM2 and TYMS for nucleotide synthesis. All these genes are highly up-regulated in a variety of tumor cells in cancer patients, and they play active roles in tumor progression rather than expressing merely as a consequence of phenotypic change of the cancer cells. Molecular dissection of their orchestrated networks and understanding the exact mechanism of their expression will provide a window of opportunity to target these genes for specific cancer therapy. We also reviewed existing database of gene microarray to validate the utility of these genes for cancer diagnosis. PMID:20122995

Rationale for treating hepatitis C virus infection in patients with mild to moderate chronic kidney disease.

PubMed

Ridruejo, Ezequiel; Mendizabal, Manuel; Silva, Marcelo O

2018-04-01

Hepatitis C virus infection (HCV) is highly prevalent in patients with chronic kidney disease (CKD) and kidney transplant recipients. Little information exists on treatment in patients with CKD stages 2 to 3, where CKD progression might be slowed by HCV treatment. These patients are not considered a high priority for HCV treatment in most international guidelines. Although some recently published guidelines propose universal treatment, others are still recommending it only in high priority groups. In this review, we evaluate current evidence of HCV infection impact on CKD progression, on cardiovascular and metabolic risk, and the benefits of HCV infection treatment to improve cardiovascular and metabolic outcomes. We made special focus on the benefits of HCV infection treatment in patients with stages 2 to 3 CKD to avoid CKD progression. © 2018 International Society for Hemodialysis.

Choline metabolism in malignant transformation

PubMed Central

Glunde, Kristine; Bhujwalla, Zaver M.; Ronen, Sabrina M.

2015-01-01

Abnormal choline metabolism is emerging as a metabolic hallmark that is associated with oncogenesis and tumour progression. Following transformation, the modulation of enzymes that control anabolic and catabolic pathways causes increased levels of choline-containing precursors and breakdown products of membrane phospholipids. These increased levels are associated with proliferation, and recent studies emphasize the complex reciprocal interactions between oncogenic signalling and choline metabolism. Because choline-containing compounds are detected by non-invasive magnetic resonance spectroscopy (MRS), increased levels of these compounds provide a non-invasive biomarker of transformation, staging and response to therapy. Furthermore, enzymes of choline metabolism, such as choline kinase, present novel targets for image-guided cancer therapy. PMID:22089420

Recent advances in understanding Streptomyces

PubMed Central

Chater, Keith F.

2016-01-01

About 2,500 papers dated 2014–2016 were recovered by searching the PubMed database for Streptomyces, which are the richest known source of antibiotics. This review integrates around 100 of these papers in sections dealing with evolution, ecology, pathogenicity, growth and development, stress responses and secondary metabolism, gene expression, and technical advances. Genomic approaches have greatly accelerated progress. For example, it has been definitively shown that interspecies recombination of conserved genes has occurred during evolution, in addition to exchanges of some of the tens of thousands of non-conserved accessory genes. The closeness of the association of Streptomyces with plants, fungi, and insects has become clear and is reflected in the importance of regulators of cellulose and chitin utilisation in overall Streptomyces biology. Interestingly, endogenous cellulose-like glycans are also proving important in hyphal growth and in the clumping that affects industrial fermentations. Nucleotide secondary messengers, including cyclic di-GMP, have been shown to provide key input into developmental processes such as germination and reproductive growth, while late morphological changes during sporulation involve control by phosphorylation. The discovery that nitric oxide is produced endogenously puts a new face on speculative models in which regulatory Wbl proteins (peculiar to actinobacteria) respond to nitric oxide produced in stressful physiological transitions. Some dramatic insights have come from a new model system for Streptomyces developmental biology, Streptomyces venezuelae, including molecular evidence of very close interplay in each of two pairs of regulatory proteins. An extra dimension has been added to the many complexities of the regulation of secondary metabolism by findings of regulatory crosstalk within and between pathways, and even between species, mediated by end products. Among many outcomes from the application of chromosome immunoprecipitation sequencing (ChIP-seq) analysis and other methods based on “next-generation sequencing” has been the finding that 21% of Streptomyces mRNA species lack leader sequences and conventional ribosome binding sites. Further technical advances now emerging should lead to continued acceleration of knowledge, and more effective exploitation, of these astonishing and critically important organisms. PMID:27990276

Career and Technical Education and Academic Progress at the End of High School: Evidence from the Education Longitudinal Study of 2002

ERIC Educational Resources Information Center

Bozick, Robert; Dalton, Ben

2013-01-01

This report examines the role of career and technical education (CTE) for assessing students in learning mathematics and preventing students from dropping out of high school. CTE is a wide field of educational practice that includes occupational training and career preparation offered in formats ranging from individual courses to comprehensive…

easyCBM[R] Mathematics Criterion Related Validity Evidence: Oregon State Test. Technical Report #1011

ERIC Educational Resources Information Center

Anderson, Daniel; Alonzo, Julie; Tindal, Gerald

2010-01-01

In this technical report, we present the results of a study examining the relation between the math measures available on the easyCBM[R] online benchmark and progress monitoring assessment system and the Oregon statewide assessment of mathematics. Designed for use within a response to intervention (RTI) framework, easyCBM[R] is intended to help…

New York City School Survey 2008-2010: Assessing the Reliability and Validity of a Progress Report Measure. Technical Appendices

ERIC Educational Resources Information Center

Nathanson, Lori; Cole, Rachel; Kemple, James J.; Lent, Jessica; McCormick, Meghan; Segeritz, Micha

2013-01-01

The Research Alliance for New York City Schools examined Department of Education (DOE) School Survey data from 2008-2010 to better understand the richness and complexities of the information elicited by the Survey from parents, students, and teachers. This document provides the appendices to the technical report "New York City School Survey…

The 1992 Research/Technology report

NASA Technical Reports Server (NTRS)

1992-01-01

The 1992 Research & Technology report is organized so that a broad cross section of the community can readily use it. A short introductory paragraph begins each article and will prove to be an invaluable reference tool for the layperson. The approximately 200 articles summarize the progress made during the year in various technical areas and portray the technical and administrative support associated with Lewis technology programs.

Trends in Articulation Arrangements for Technical and Vocational Education in the South East Asian Region.

ERIC Educational Resources Information Center

Haas, Adrian R.

Trends in articulation arrangements for technical and vocational education (TVE) in the South East Asia region were studied. A key feature of articulation is the existence of pathways that allow graduates of one course of study to progress to other courses. Effective articulation opens up advancement for individuals and helps to create a flexible…

Longitudinal Surveys of Australian Youth (LSAY) 1998 Cohort: Wave 12 (2009)--Frequency Tables. Technical Report 58B

ERIC Educational Resources Information Center

National Centre for Vocational Education Research (NCVER), 2010

2010-01-01

The Longitudinal Surveys of Australian Youth (LSAY) program studies the progress of several groups of young Australians as they move from school into post-secondary education and work. This technical paper contains the frequency tables for the LSAY 1998 cohort Wave 12 (2009) data set. [For the accompanying questionnaire, "Longitudinal Surveys…

Longitudinal Surveys of Australian Youth (LSAY): 2003 Cohort Wave 7 (2009)--Frequency Tables. Technical Report 57B

ERIC Educational Resources Information Center

National Centre for Vocational Education Research (NCVER), 2010

2010-01-01

The Longitudinal Surveys of Australian Youth (LSAY) program studies the progress of several groups of young Australians as they move from school into post-secondary education and work. This technical paper contains the frequency tables for the LSAY 2003 cohort Wave 7 (2009) data set. [For the related questionnaire, see ED512164.

Longitudinal Surveys of Australian Youth (LSAY) 2009 Cohort: Wave 3 (2011)--Frequency Tables. Technical Report 72B

ERIC Educational Resources Information Center

National Centre for Vocational Education Research (NCVER), 2012

2012-01-01

The Longitudinal Surveys of Australian Youth (LSAY) program studies the progress of several groups of young Australians as they move from school into post-secondary education and work. This technical paper contains the frequency tables for the LSAY 2009 cohort Wave 3 (2011) data set. [For the related questionnaire, see ED536306.

Longitudinal Surveys of Australian Youth (LSAY) 2003 Cohort: Wave 7 (2009)--Questionnaire. Technical Report 57A

ERIC Educational Resources Information Center

National Centre for Vocational Education Research (NCVER), 2010

2010-01-01

The Longitudinal Surveys of Australian Youth (LSAY) program studies the progress of several groups of young Australians as they move from school into post-secondary education and work. This technical paper contains the questionnaire for the LSAY 2003 cohort Wave 7 (2009) data set. [For the related frequency tables, see ED512163.

Making the Good Even Better: Feedback from easyCBM Focus Groups, School Year 2009/2010. Technical Report # 1001

ERIC Educational Resources Information Center

Alonzo, Julie; Tindal, Gerald; Lai, Cheng-Fei

2010-01-01

This technical report provides a summary of feedback from teachers, administrators, and support personnel who used the easyCBM progress monitoring and benchmark assessment system during school year 2009/2010. Data were gathered from semi-structured focus groups conducted during the 2010 easyCBM August Institute at the University of Oregon. Results…

Longitudinal Surveys of Australian Youth (LSAY): 2006 Cohort Wave 4 (2009)--Frequency Tables. Technical Report 56B

ERIC Educational Resources Information Center

National Centre for Vocational Education Research (NCVER), 2010

2010-01-01

The Longitudinal Surveys of Australian Youth (LSAY) program studies the progress of several groups of young Australians as they move from school into post-secondary education and work. This technical paper contains the frequency tables for the LSAY 2006 cohort Wave 4 (2009) data set. [For the "Longitudinal Surveys of Australian Youth (LSAY):…

Longitudinal Surveys of Australian Youth (LSAY): 2006 Cohort Wave 4 (2009)--Questionnaire. Technical Report 56A

ERIC Educational Resources Information Center

National Centre for Vocational Education Research (NCVER), 2010

2010-01-01

The Longitudinal Surveys of Australian Youth (LSAY) program studies the progress of several groups of young Australians as they move from school into post-secondary education and work. This technical paper contains the questionnaire for the LSAY 2006 cohort Wave 4 (2009) data set. [For the "Longitudinal Surveys of Australian Youth (LSAY):…

Establishment of the Center for Advanced Separation Technologies

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

Christopher E. Hull

2006-09-30

This Final Technical Report covers the eight sub-projects awarded in the first year and the five projects awarded in the second year of Cooperative Agreement DE-FC26-01NT41091: Establishment of the Center for Advanced Separation Technologies. This work is summarized in the body of the main report: the individual sub-project Technical Progress Reports are attached as Appendices.

A Historical Introduction to Library Education: Problems and Progress to 1951.

ERIC Educational Resources Information Center

White, Carl M.

The growth of libraries and of technical education in the middle of the 19th century led to the organization of Melvil Dewey's School of Library Economy in 1887. The School offered a technical course to replace the apprenticeships then in favor. Its curriculum persisted as the model for library education through 1920. A break with the early form…

Progress Report on Reactivity Analyses (October-December Test Data). Beginning Teacher Evaluation Study. Technical Note Series. Technical Note III-5.

ERIC Educational Resources Information Center

Filby, Nikola N.

The development and refinement of the measures of student achievement in reading and mathematics for the Beginning Teacher Evaluation Study are described. The concept of reactivity to instruction is introduced: the tests used to evaluate instructional processes must be sensitive indicators of classroom learning overtime. Data collection activities…

First results of ground-based LWIR hyperspectral imaging remote gas detection

NASA Astrophysics Data System (ADS)

Zheng, Wei-jian; Lei, Zheng-gang; Yu, Chun-chao; Wang, Hai-yang; Fu, Yan-peng; Liao, Ning-fang; Su, Jun-hong

2014-11-01

The new progress of ground-based long-wave infrared remote sensing is presented. The LWIR hyperspectral imaging by using the windowing spatial and temporal modulation Fourier spectroscopy, and the results of outdoor ether gas detection, verify the features of LWIR hyperspectral imaging remote sensing and technical approach. It provides a new technical means for ground-based gas remote sensing.

Review of Web-Based Technical Documentation Processes. FY07 NAEP-QA Special Study Report. TR-08-17

ERIC Educational Resources Information Center

Gribben, Monica; Wise, Lauress; Becker, D. E.

2008-01-01

Beginning with the 2000 and 2001 National Assessment of Educational Progress (NAEP) assessments, the National Center for Education Statistics (NCES) has made technical documentation available on the worldwide web at http://nces.ed.gov/nationsreportcard/tdw/. The web-based documentation is designed to be less dense and more accessible than prior…

Technical considerations in continuous jugular venous oxygen saturation measurement.

PubMed

Dearden, N M; Midgley, S

1993-01-01

Fibreoptic reflection oximetry allows continuous in-vivo estimation of jugular venous oxygen saturation. In combination with pulse oximetry the oxygen extraction ratio SaO2-SjO2/SaO2 can be derived enabling identification of states of global luxury perfusion, normal coupling of global cerebral blood flow with global cerebral metabolism, global cerebral hypoperfusion and global cerebral ischemia. Several technical difficulties may arise affecting the accuracy of SjO2 recordings which must be recognised by the clinician before medical intervention is contemplated.

The Childhood Obesity Epidemic As a Result of Non-Genetic Evolution: the Maternal Resources Hypothesis

PubMed Central

Archer, Edward

2014-01-01

Over the past century, socio-environmental evolution (e.g., reduced pathogenic load, decreased physical activity [PA], improved nutrition) led to cumulative increments in maternal energy resources (i.e., body mass, adiposity) and decrements in energy expenditure and metabolic control. These decrements reduced the competition between maternal and fetal energy demands and increased the availability of energy substrates to the intrauterine milieu. This perturbation of mother-conceptus energy partitioning stimulated fetal pancreatic beta-cell and adipocyte hyperplasia, thereby inducing an enduring competitive advantage of adipocytes over other tissues in the acquisition and sequestering of nutrient-energy via intensified insulin secretion and hyperplastic adiposity. At menarche, the competitive dominance of adipocytes was further amplified via hormone-induced adipocyte hyperplasia and weight-induced decrements in PA. These metabolic and behavioral effects were propagated progressively when obese, inactive, metabolically compromised women produced progressively larger, more inactive and metabolically compromised children. Consequently, the evolution of human energy metabolism was significantly altered. This phenotypic evolution was exacerbated by increments in the use of Caesarian sections that allowed both the larger fetuses and the metabolically compromised mothers who produced them to survive and reproduce. Thus, natural selection was iatrogenically rendered artificial selection, and the frequency of obese, inactive, metabolically compromised phenotypes increased in the global population. By the late 20th century, a metabolic tipping point was reached in which the post-prandial insulin response was so intense, the relative number of adipocytes so magnified, and inactivity so pervasive that the competitive dominance of adipocytes in the sequestering of nutrient-energy was inevitable, and obesity was unavoidable. PMID:25440888

Role of abnormal lipid metabolism in development, progression, diagnosis and therapy of pancreatic cancer

PubMed Central

Swierczynski, Julian; Hebanowska, Areta; Sledzinski, Tomasz

2014-01-01

There is growing evidence that metabolic alterations play an important role in cancer development and progression. The metabolism of cancer cells is reprogrammed in order to support their rapid proliferation. Elevated fatty acid synthesis is one of the most important aberrations of cancer cell metabolism. An enhancement of fatty acids synthesis is required both for carcinogenesis and cancer cell survival, as inhibition of key lipogenic enzymes slows down the growth of tumor cells and impairs their survival. Based on the data that serum fatty acid synthase (FASN), also known as oncoantigen 519, is elevated in patients with certain types of cancer, its serum level was proposed as a marker of neoplasia. This review aims to demonstrate the changes in lipid metabolism and other metabolic processes associated with lipid metabolism in pancreatic ductal adenocarcinoma (PDAC), the most common pancreatic neoplasm, characterized by high mortality. We also addressed the influence of some oncogenic factors and tumor suppressors on pancreatic cancer cell metabolism. Additionally the review discusses the potential role of elevated lipid synthesis in diagnosis and treatment of pancreatic cancer. In particular, FASN is a viable candidate for indicator of pathologic state, marker of neoplasia, as well as, pharmacological treatment target in pancreatic cancer. Recent research showed that, in addition to lipogenesis, certain cancer cells can use fatty acids from circulation, derived from diet (chylomicrons), synthesized in liver, or released from adipose tissue for their growth. Thus, the interactions between de novo lipogenesis and uptake of fatty acids from circulation by PDAC cells require further investigation. PMID:24605027

Professional technical standards in colleges and schools of pharmacy.

PubMed

Berry, Tricia M; Chichester, Clinton O; Lundquist, Lisa M; Sanoski, Cynthia A; Woodward, Donald A; Worley, Marcia M; Early, Johnnie L

2011-04-11

To determine the prevalence, characteristics, and use of professional technical standards among colleges and schools of pharmacy accredited by the Accreditation Council for Pharmacy Education (ACPE). The Web site of every college and school of pharmacy accredited by ACPE was searched to identify information regarding the availability, content, and use of technical standards and to obtain demographic information. Information was obtained from all of the 114 colleges and schools of pharmacy and 67 (59%) had technical standards in place. Common themes for technical standards were: observation; communication; motor; intellectual, conceptual, integrative and quantitative abilities; and behavioral and social attributes. Of those colleges and schools with technical standards, 61 (91%) had standards that addressed all 5 of these themes and 34 (51%) specified that the technical standards were used in their admission, progression, and graduation procedures. More than half of the colleges and schools of pharmacy examined in this study have technical standards; however, 41% have yet to develop and implement them. Colleges and schools of pharmacy looking for guidance in technical standards development could use the technical standards themes identified in this study.

Professional Technical Standards in Colleges and Schools of Pharmacy

PubMed Central

Berry, Tricia M.; Chichester, Clinton O.; Sanoski, Cynthia A.; Woodward, Donald A.; Worley, Marcia M.; Early, Johnnie L.

2011-01-01

Objective To determine the prevalence, characteristics, and use of professional technical standards among colleges and schools of pharmacy accredited by the Accreditation Council for Pharmacy Education (ACPE). Methods The Web site of every college and school of pharmacy accredited by ACPE was searched to identify information regarding the availability, content, and use of technical standards and to obtain demographic information. Results Information was obtained from all of the 114 colleges and schools of pharmacy and 67 (59%) had technical standards in place. Common themes for technical standards were: observation; communication; motor; intellectual, conceptual, integrative and quantitative abilities; and behavioral and social attributes. Of those colleges and schools with technical standards, 61 (91%) had standards that addressed all 5 of these themes and 34 (51%) specified that the technical standards were used in their admission, progression, and graduation procedures. Conclusion More than half of the colleges and schools of pharmacy examined in this study have technical standards; however, 41% have yet to develop and implement them. Colleges and schools of pharmacy looking for guidance in technical standards development could use the technical standards themes identified in this study. PMID:21655404

Modularization of genetic elements promotes synthetic metabolic engineering.

PubMed

Qi, Hao; Li, Bing-Zhi; Zhang, Wen-Qian; Liu, Duo; Yuan, Ying-Jin

2015-11-15

In the context of emerging synthetic biology, metabolic engineering is moving to the next stage powered by new technologies. Systematical modularization of genetic elements makes it more convenient to engineer biological systems for chemical production or other desired purposes. In the past few years, progresses were made in engineering metabolic pathway using synthetic biology tools. Here, we spotlighted the topic of implementation of modularized genetic elements in metabolic engineering. First, we overviewed the principle developed for modularizing genetic elements and then discussed how the genetic modules advanced metabolic engineering studies. Next, we picked up some milestones of engineered metabolic pathway achieved in the past few years. Last, we discussed the rapid raised synthetic biology field of "building a genome" and the potential in metabolic engineering. Copyright © 2015 Elsevier Inc. All rights reserved.

Economic growth and decline in mortality in developing countries: an analysis of the World Bank development datasets.

PubMed

Renton, A; Wall, M; Lintott, J

2012-07-01

The 1999 World Bank report claimed that growth in gross domestic product (GDP) between 1960 and 1990 only accounted for 15% of concomitant growth in life expectancy in developing countries. These findings were used repeatedly by the World Health Organization (WHO) to support a policy shift away from promoting social and economic development, towards vertical technology-driven programmes. This paper updates the 1999 World Bank report using the World Bank's 2005 dataset, providing a new assessment of the relative contribution of economic growth. Time-series analysis. Cross-sectional time-series regression analysis using a random effect model of associations between GDP, education and technical progress and improved health outcomes. The proportion of improvement in health indicators between 1970 and 2000 associated with changes in GDP, education and technical progress was estimated. In 1970, a 1% difference in GDP between countries was associated with 6% difference in female (LEBF) and 5% male (LEBM) life expectancy at birth. By 2000, these values had increased to 14% and 12%, explaining most of the observed health gain. Excluding Europe and Central Asia, the proportion of the increase in LEBF and LEBM attributable to increased GDP was 31% and 33% in the present analysis, vs. 17% and 14%, respectively, estimated by the World Bank. In the poorest countries, higher GDPs were required in 2000 than in 1970 to achieve the same health outcomes. In the poorest countries, socio-economic change is likely to be a more important source of health improvement than technical progress. Technical progress, operating by increasing the size of the effect of a unit of GDP on health, is likely to benefit richer countries more than poorer countries, thereby increasing global health inequalities. Copyright © 2012 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Pheochromocytoma: The First Metabolic Endocrine Cancer

PubMed Central

Jochmanova, Ivana; Pacak, Karel

2016-01-01

Dysregulated metabolism is one of the key characteristics of cancer cells. The most prominent alterations are present during regulation of cell respiration, which leads to a switch from oxidative phosphorylation to aerobic glycolysis. This metabolic shift results in activation of numerous signaling and metabolic pathways supporting cell proliferation and survival. Recent progress in genetics and metabolomics allowed us to take a closer look at the metabolic changes present in pheochromocytomas and paragangliomas (PHEOs/PGLs). These neuroendocrine tumors often exhibit dysregulation of mitochondrial metabolism, which is driven by mutations in genes encoding Krebs cycle enzymes or by activation of hypoxia signaling. Present metabolic changes are involved in processes associated with tumorigenesis, invasiveness, metastasis, and resistance to various cancer therapies. In this review, we discuss the metabolic nature of PHEOs/PGLs and how unveiling the metabolic disturbances present in tumors could lead to identification of new biomarkers and personalized cancer therapies. PMID:27742786

Critical Review of Technical Questions Facing Low Impact Development and Green Infrastructure: A Perspective from the Great Plains.

PubMed

Vogel, Jason R; Moore, Trisha L; Coffman, Reid R; Rodie, Steven N; Hutchinson, Stacy L; McDonough, Kelsey R; McLemore, Alex J; McMaine, John T

2015-09-01

Since its inception, Low Impact Development (LID) has become part of urban stormwater management across the United States, marking progress in the gradual transition from centralized to distributed runoff management infrastructure. The ultimate goal of LID is full, cost-effective implementation to maximize watershed-scale ecosystem services and enhance resilience. To reach that goal in the Great Plains, the multi-disciplinary author team presents this critical review based on thirteen technical questions within the context of regional climate and socioeconomics across increasing complexities in scale and function. Although some progress has been made, much remains to be done including continued basic and applied research, development of local LID design specifications, local demonstrations, and identifying funding mechanisms for these solutions. Within the Great Plains and beyond, by addressing these technical questions within a local context, the goal of widespread acceptance of LID can be achieved, resulting in more effective and resilient stormwater management.

Cancer cachexia: mediators, signaling, and metabolic pathways.

PubMed

Fearon, Kenneth C H; Glass, David J; Guttridge, Denis C

2012-08-08

Cancer cachexia is characterized by a significant reduction in body weight resulting predominantly from loss of adipose tissue and skeletal muscle. Cachexia causes reduced cancer treatment tolerance and reduced quality and length of life, and remains an unmet medical need. Therapeutic progress has been impeded, in part, by the marked heterogeneity of mediators, signaling, and metabolic pathways both within and between model systems and the clinical syndrome. Recent progress in understanding conserved, molecular mechanisms of skeletal muscle atrophy/hypertrophy has provided a downstream platform for circumventing the variations and redundancy in upstream mediators and may ultimately translate into new targeted therapies. Copyright © 2012 Elsevier Inc. All rights reserved.

Bone Metabolism of the Patient with a Malignant Melanoma during the Entry Examination and the Check-up of Whole-body Bone Scintigraphy.

PubMed

Weissensteiner, Jaroslav; Babušíková, Eva

Malignant melanoma is a malignancy located predominantly in the skin and the incidence of melanoma increases. We compared the markers of bone metabolism - osteocalcin (OC), beta-carboxyterminal cross-linked telopeptide of type I collagen (β-CrossLaps, β-CTx) and tumour marker - human epididymis protein 4 (HE4) in the serum with finding during the entry examination and the check-up of whole-body bone scintigraphy of the patient with a malignant melanoma. Serum concentrations of OC, β-CTx, HE4 were determined in 1 patient (female, age 64 years) with malignant melanoma and correlated with the presence of equivocal bone metastases detected by whole-body bone scintigraphy (the entry examination and check-up after 6 months). Concentrations of bone metabolism markers decreased during six months and we observed progress in bone metastases. The change of the markers levels during the entry examination and the check-up of the whole-body bone scintigraphy with equivocal finding of bone metastases could be a sign of a possible initiating progression of malignant melanoma despite a clinically negative finding that does not prove the progression of the disease.

Mitochondrial fatty acid biosynthesis and muscle fiber plasticity in very long-chain acyl-CoA dehydrogenase-deficient mice.

PubMed

Tucci, Sara; Mingirulli, Nadja; Wehbe, Zeinab; Dumit, Verónica I; Kirschner, Janbernd; Spiekerkoetter, Ute

2018-01-01

The white skeletal muscle of very long-chain acyl-CoA-dehydrogenase-deficient (VLCAD -/- ) mice undergoes metabolic modification to compensate for defective β-oxidation in a progressive and time-dependent manner by upregulating glucose oxidation. This metabolic regulation seems to be accompanied by morphologic adaptation of muscle fibers toward the glycolytic fiber type II with the concomitant upregulation of mitochondrial fatty acid biosynthesis (mFASII) and lipoic acid biosynthesis. Dietary supplementation of VLCAD -/- mice with different medium-chain triglycerides over 1 year revealed that odd-chain species has no effect on muscle fiber switch, whereas even-chain species inhibit progressive metabolic adaptation. Our study shows that muscle may undergo adaptive mechanisms that are modulated by dietary supplementation. We describe for the first time a concomitant change of mFASII in this muscular adaptation process. © 2017 Federation of European Biochemical Societies.

Do failures in non-technical skills contribute to fatal medical accidents in Japan? A review of the 2010-2013 national accident reports.

PubMed

Uramatsu, Masashi; Fujisawa, Yoshikazu; Mizuno, Shinya; Souma, Takahiro; Komatsubara, Akinori; Miki, Tamotsu

2017-02-16

We sought to clarify how large a proportion of fatal medical accidents can be considered to be caused by poor non-technical skills, and to support development of a policy to reduce number of such accidents by making recommendations about possible training requirements. Summaries of reports of fatal medical accidents, published by the Japan Medical Safety Research Organization, were reviewed individually. Three experienced clinicians and one patient safety expert conducted the reviews to determine the cause of death. Views of the patient safety expert were given additional weight in the overall determination. A total of 73 summary reports of fatal medical accidents were reviewed. These reports had been submitted by healthcare organisations across Japan to the Japan Medical Safety Research Organization between April 2010 and March 2013. The cause of death in fatal medical accidents, categorised into technical skills, non-technical skills and inevitable progress of disease were evaluated. Non-technical skills were further subdivided into situation awareness, decision making, communication, team working, leadership, managing stress and coping with fatigue. Overall, the cause of death was identified as non-technical skills in 34 cases (46.6%), disease progression in 33 cases (45.2%) and technical skills in two cases (5.5%). In two cases, no consensual determination could be achieved. Further categorisation of cases of non-technical skills were identified as 14 cases (41.2%) of problems with situation awareness, eight (23.5%) with team working and three (8.8%) with decision making. These three subcategories, or combinations of them, were identified as the cause of death in 33 cases (97.1%). Poor non-technical skills were considered to be a significant cause of adverse events in nearly half of the fatal medical accidents examined. Improving non-technical skills may be effective for reducing accidents, and training in particular subcategories of non-technical skills may be especially relevant. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Next Generation Attenuation Relationships for the Eastern United States (NGA-East)

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

Mahin, Stephen; Bozorgnia, Yousef

2016-04-11

This is a progress report to DOE for project Next Generation Attenuation for Central & Eastern US (NGA-East).This progress report consists of numerous monthly progress segments starting June 1, 2010 until December 31, 2015. Please note: the December 2015 progress report was issued in January 2016 due to the final university financial reporting at the end of this project. For each month, there is a technical progress list, and an update on the financial progress of the project. As you know, this project is jointly funded by the DOE, US Nuclear Regulatory Commission (NRC) and Electric Power Research Institute (EPRI).more » Thus, each segment includes financial progress for these three funding agencies.« less

Technical Feasibility Aspects of the Geothermal Resource Reporting Methodology (GRRM)

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

Badgett, Alex; Young, Katherine R; Dobson, Patrick F.

This paper reviews the technical assessment of the Geothermal Research Reporting Methodology (GRRM, http://en.openei.org/wiki/GRRM) being developed for reporting geothermal resources and project progress. The goal of the methodology is to provide the U.S. Department of Energy's Geothermal Technologies Office (GTO) with a consistent and comprehensible means of evaluating the impacts of its funding programs. The GRRM is designed to provide uniform assessment criteria for geothermal resource grades and developmental phases of geothermal resource exploration and development. This resource grade system provides information on twelve attributes of geothermal resource locations (e.g., temperature, permeability, land access) to indicate potential for geothermal development.more » The GTO plans to use these Protocols to help quantitatively identify the greatest barriers to geothermal development, develop measureable program goals that will have the greatest impact to geothermal deployment, objectively evaluate proposals based (in part) on a project's ability to contribute to program goals, monitor project progress, and report on GTO portfolio performance. The GRRM assesses three areas of geothermal potential: geological, socio-economic, and technical. Previous work and publications have discussed the work done on the geological aspects of this methodology (Young et al. 2015c); this paper details the development of the technical assessment of the GRRM. Technical development attributes considered include: reservoir management, drilling, logistics, and power conversion.« less

Plasma metabolomic profiles reflective of glucose homeostasis in non-diabetic and Type 2 diabetic obese African-American women

USDA-ARS?s Scientific Manuscript database

Insulin resistance progressing to type 2 diabetes mellitus (T2DM) is marked by a broad perturbation of macronutrient intermediary metabolism. Understanding the biochemical networks that underlie metabolic homeostasis and how they associate with insulin action will help unravel diabetes etiology and...

Comparison of effects of cryopreservation diluents on the ability of Ram sperm to reduce resazurin dye

USDA-ARS?s Scientific Manuscript database

Resazurin dye is an effective way to test the metabolism of sperm. As sperm move, they create metabolic waste which is detected by the dye. Another way sperm are evaluated is by Computer-Assisted Sperm Analysis (CASA). CASA detects motility, progression, curvilinear velocity, lateral head amplitude,...

Dissection of the Mouse Pancreas for Histological Analysis and Metabolic Profiling.

PubMed

Veite-Schmahl, Michelle J; Regan, Daniel P; Rivers, Adam C; Nowatzke, Joseph F; Kennedy, Michael A

2017-08-19

We have been investigating the pancreas specific transcription factor, 1a cre-recombinase; lox-stop-lox- Kristen rat sarcoma, glycine to aspartic acid at the 12 codon (Ptf1a cre/+ ;LSL-Kras G12D/+ ) mouse strain as a model of human pancreatic cancer. The goal of our current studies is to identify novel metabolic biomarkers of pancreatic cancer progression. We have performed metabolic profiling of urine, feces, blood, and pancreas tissue extracts, as well as histological analyses of the pancreas to stage the cancer progression. The mouse pancreas is not a well-defined solid organ like in humans, but rather is a diffusely distributed soft tissue that is not easily identified by individuals unfamiliar with mouse internal anatomy or by individuals that have little or no experience performing mouse organ dissections. The purpose of this article is to provide a detailed step-wise visual demonstration to guide novices in the removal of the mouse pancreas by dissection. This article should be especially valuable to students and investigators new to research that requires harvesting of the mouse pancreas by dissection for metabolic profiling or histological analyses.

Gene-gene and gene-environment interactions defining lipid-related traits.

PubMed

Ordovás, José M; Robertson, Ruairi; Cléirigh, Ellen Ní

2011-04-01

Steps towards reducing chronic disease progression are continuously being taken through the form of genomic research. Studies over the last year have highlighted more and more polymorphisms, pathways and interactions responsible for metabolic disorders such as cardiovascular disease, obesity and dyslipidemia. Many of these chronic illnesses can be partially blamed by altered lipid metabolism, combined with individual genetic components. Critical evaluation and comparison of these recent studies is essential in order to comprehend the results, conclusions and future prospects in the field of genomics as a whole. Recent literature elucidates significant gene--diet and gene--environment interactions resulting in altered lipid metabolism, inflammation and other metabolic imbalances leading to cardiovascular disease and obesity. Epigenetic and epistatic interactions are now becoming more significantly associated with such disorders, as genomic research digs deeper into the complex nature of genetic individuality and heritability. The vast array of data collected from genome-wide association studies must now be empowered and explored through more complex interaction studies, using standardized methods and larger sample sizes. In doing so the etiology of chronic disease progression will be further understood.

The Dysregulation of Polyamine Metabolism in Colorectal Cancer Is Associated with Overexpression of c-Myc and C/EBPβ rather than Enterotoxigenic Bacteroides fragilis Infection.

PubMed

Snezhkina, Anastasiya V; Krasnov, George S; Lipatova, Anastasiya V; Sadritdinova, Asiya F; Kardymon, Olga L; Fedorova, Maria S; Melnikova, Nataliya V; Stepanov, Oleg A; Zaretsky, Andrew R; Kaprin, Andrey D; Alekseev, Boris Y; Dmitriev, Alexey A; Kudryavtseva, Anna V

2016-01-01

Colorectal cancer is one of the most common cancers in the world. It is well known that the chronic inflammation can promote the progression of colorectal cancer (CRC). Recently, a number of studies revealed a potential association between colorectal inflammation, cancer progression, and infection caused by enterotoxigenic Bacteroides fragilis (ETBF). Bacterial enterotoxin activates spermine oxidase (SMO), which produces spermidine and H2O2 as byproducts of polyamine catabolism, which, in turn, enhances inflammation and tissue injury. Using qPCR analysis, we estimated the expression of SMOX gene and ETBF colonization in CRC patients. We found no statistically significant associations between them. Then we selected genes involved in polyamine metabolism, metabolic reprogramming, and inflammation regulation and estimated their expression in CRC. We observed overexpression of SMOX, ODC1, SRM, SMS, MTAP, c-Myc, C/EBPβ (CREBP), and other genes. We found that two mediators of metabolic reprogramming, inflammation, and cell proliferation c-Myc and C/EBPβ may serve as regulators of polyamine metabolism genes (SMOX, AZIN1, MTAP, SRM, ODC1, AMD1, and AGMAT) as they are overexpressed in tumors, have binding site according to ENCODE ChIP-Seq data, and demonstrate strong coexpression with their targets. Thus, increased polyamine metabolism in CRC could be driven by c-Myc and C/EBPβ rather than ETBF infection.

The Dysregulation of Polyamine Metabolism in Colorectal Cancer Is Associated with Overexpression of c-Myc and C/EBPβ rather than Enterotoxigenic Bacteroides fragilis Infection

PubMed Central

Snezhkina, Anastasiya V.; Lipatova, Anastasiya V.; Sadritdinova, Asiya F.; Kardymon, Olga L.; Fedorova, Maria S.; Kaprin, Andrey D.

2016-01-01

Colorectal cancer is one of the most common cancers in the world. It is well known that the chronic inflammation can promote the progression of colorectal cancer (CRC). Recently, a number of studies revealed a potential association between colorectal inflammation, cancer progression, and infection caused by enterotoxigenic Bacteroides fragilis (ETBF). Bacterial enterotoxin activates spermine oxidase (SMO), which produces spermidine and H2O2 as byproducts of polyamine catabolism, which, in turn, enhances inflammation and tissue injury. Using qPCR analysis, we estimated the expression of SMOX gene and ETBF colonization in CRC patients. We found no statistically significant associations between them. Then we selected genes involved in polyamine metabolism, metabolic reprogramming, and inflammation regulation and estimated their expression in CRC. We observed overexpression of SMOX, ODC1, SRM, SMS, MTAP, c-Myc, C/EBPβ (CREBP), and other genes. We found that two mediators of metabolic reprogramming, inflammation, and cell proliferation c-Myc and C/EBPβ may serve as regulators of polyamine metabolism genes (SMOX, AZIN1, MTAP, SRM, ODC1, AMD1, and AGMAT) as they are overexpressed in tumors, have binding site according to ENCODE ChIP-Seq data, and demonstrate strong coexpression with their targets. Thus, increased polyamine metabolism in CRC could be driven by c-Myc and C/EBPβ rather than ETBF infection. PMID:27433286

Fetal Alcohol Syndrome, Chemo-Biology and OMICS: Ethanol Effects on Vitamin Metabolism During Neurodevelopment as Measured by Systems Biology Analysis

PubMed Central

Feltes, Bruno César; de Faria Poloni, Joice; Nunes, Itamar José Guimarães

2014-01-01

Abstract Fetal alcohol syndrome (FAS) is a prenatal disease characterized by fetal morphological and neurological abnormalities originating from exposure to alcohol. Although FAS is a well-described pathology, the molecular mechanisms underlying its progression are virtually unknown. Moreover, alcohol abuse can affect vitamin metabolism and absorption, although how alcohol impairs such biochemical pathways remains to be elucidated. We employed a variety of systems chemo-biology tools to understand the interplay between ethanol metabolism and vitamins during mouse neurodevelopment. For this purpose, we designed interactomes and employed transcriptomic data analysis approaches to study the neural tissue of Mus musculus exposed to ethanol prenatally and postnatally, simulating conditions that could lead to FAS development at different life stages. Our results showed that FAS can promote early changes in neurotransmitter release and glutamate equilibrium, as well as an abnormal calcium influx that can lead to neuroinflammation and impaired neurodifferentiation, both extensively connected with vitamin action and metabolism. Genes related to retinoic acid, niacin, vitamin D, and folate metabolism were underexpressed during neurodevelopment and appear to contribute to neuroinflammation progression and impaired synapsis. Our results also indicate that genes coding for tubulin, tubulin-associated proteins, synapse plasticity proteins, and proteins related to neurodifferentiation are extensively affected by ethanol exposure. Finally, we developed a molecular model of how ethanol can affect vitamin metabolism and impair neurodevelopment. PMID:24816220

Fetal alcohol syndrome, chemo-biology and OMICS: ethanol effects on vitamin metabolism during neurodevelopment as measured by systems biology analysis.

PubMed

Feltes, Bruno César; de Faria Poloni, Joice; Nunes, Itamar José Guimarães; Bonatto, Diego

2014-06-01

Fetal alcohol syndrome (FAS) is a prenatal disease characterized by fetal morphological and neurological abnormalities originating from exposure to alcohol. Although FAS is a well-described pathology, the molecular mechanisms underlying its progression are virtually unknown. Moreover, alcohol abuse can affect vitamin metabolism and absorption, although how alcohol impairs such biochemical pathways remains to be elucidated. We employed a variety of systems chemo-biology tools to understand the interplay between ethanol metabolism and vitamins during mouse neurodevelopment. For this purpose, we designed interactomes and employed transcriptomic data analysis approaches to study the neural tissue of Mus musculus exposed to ethanol prenatally and postnatally, simulating conditions that could lead to FAS development at different life stages. Our results showed that FAS can promote early changes in neurotransmitter release and glutamate equilibrium, as well as an abnormal calcium influx that can lead to neuroinflammation and impaired neurodifferentiation, both extensively connected with vitamin action and metabolism. Genes related to retinoic acid, niacin, vitamin D, and folate metabolism were underexpressed during neurodevelopment and appear to contribute to neuroinflammation progression and impaired synapsis. Our results also indicate that genes coding for tubulin, tubulin-associated proteins, synapse plasticity proteins, and proteins related to neurodifferentiation are extensively affected by ethanol exposure. Finally, we developed a molecular model of how ethanol can affect vitamin metabolism and impair neurodevelopment.

Potato tuber cytokinin oxidase/dehydrogenase genes: Biochemical properties, activity, and expression during tuber dormancy progression

USDA-ARS?s Scientific Manuscript database

The enzymatic and biochemical properties of the proteins encoded by five potato cytokinin oxidase/dehydrogenase (CKX)-like genes functionally expressed in yeast and the effects of tuber dormancy progression on StCKX expression and cytokinin metabolism were examined in meristems isolated from field-g...

Retinopathy predicts progression of fasting plasma glucose: An Early Diabetes Intervention Program (EDIP) Analysis

PubMed Central

Patel, Yash R.; Kirkman, M. Sue; Considine, Robert V; Hannon, Tamara S; Mather, Kieren J

2017-01-01

Background Retinopathy is increasingly recognized in prediabetic populations, and may herald increased risk of metabolic worsening. The Early Diabetes Intervention Program (EDIP) evaluated worsening of glycemia in screen-detected Type 2 diabetes, following participants for up to 5 years. Here we have evaluated whether the presence of retinopathy at the time of detection of diabetes was associated with accelerated progression of glycemia. Methods We prospectively studied 194 participants from EDIP with available baseline retinal photographs. Retinopathy was determined at baseline using 7-field fundus photography and defined as an Early Treatment of Diabetic Retinopathy Study Scale grading score of ≥20. Results At baseline, 12% of participants had classical retinal lesions indicating retinopathy. In univariate Cox proportional hazard analysis, the presence of retinopathy at baseline was associated with a doubled risk of progression of fasting plasma glucose (HR 2.02; 95% CI 1.05–3.89). The retinopathy effect was robust to individual adjustment for age and glucose, the most potent determinants of progression in EDIP. Conclusion Retinopathy was associated with increased risk of progression of fasting plasma glucose among adults with screen-detected, early diabetes. Early detection of retinopathy may help individualize more aggressive therapy to prevent progressive metabolic worsening in early diabetes. PMID:28003103

Preliminary Investigations of the Application of the Early Communication Indicator (ECI) for Infants and Toddlers

ERIC Educational Resources Information Center

Greenwood, Charles R.; Carta, Judith J.; Walker, Dale; Hughes, Kere; Weathers, Mary

2006-01-01

Early interventionists are accountable for the progress of children receiving their services. Technically adequate measures of the progress of individual children are needed. While the Early Communication Indicator (ECI) for infants and toddlers is one such measure, data to support its use are limited to a single research report. In this…

Curriculum-Based Measurement in Science Learning: Vocabulary-Matching as an Indicator of Performance and Progress

ERIC Educational Resources Information Center

Espin, Christine A.; Busch, Todd W.; Lembke, Erica S.; Hampton, David D.; Seo, Kyounghee; Zukowski, Beth A.

2013-01-01

The technical adequacy of curriculum-based measures in the form of short and simple vocabulary-matching probes to predict students' performance and progress in science at the secondary level was investigated. Participants were 198 seventh-grade students from 10 science classrooms. Curriculum-based measurements (CBM) were 5-min vocabulary-matching…

Technical Adequacy of Early Numeracy Curriculum-Based Progress Monitoring Measures for Kindergarten and First-Grade Students

ERIC Educational Resources Information Center

Hampton, David D.; Lembke, Erica S.; Lee, Young-Sun; Pappas, Sandra; Chiong, Cynthia; Ginsburg, Herbert P.

2012-01-01

The purpose of this study was to examine six early numeracy measures used to monitor the mathematics progress of kindergarten and first-grade students. Seventy-one kindergarten students and 75 first-grade students were administered the measures each week. Delayed-alternate form reliability was adequate for instructional decision making on some…

Jet Crackle

DTIC Science & Technology

2015-06-23

DISTRIBUTION/AVAILABILITY STATEMENT DISTRIBUTION A 13. SUPPLEMENTARY NOTES 14. ABSTRACT Fighter jets and other aircraft with high specific thrust engines...interim, memorandum, master’s thesis , progress, quarterly, research, special, group study, etc. 3. DATES COVERED. Indicate the time during which the...State the type of report, such as final, technical, interim, memorandum, master’s thesis , progress, quarterly, research, special, group study, etc

Reading Achievement in Disadvantaged Children as a Consequence of Non Verbal Perceptual Training. Final Technical Progress Report.

ERIC Educational Resources Information Center

Elkind, David; Deblinger, Jo Ann

The theoretical orientation based on perceptual development, proposed by Piaget in 1961, is the starting point of this investigation. According to Piaget, the perception of the young child is "centered" on dominant aspects of the field. With maturity, perception becomes "decentered" and progressively freed from the field. The…

Curriculum-Based Measurement of Reading Progress Monitoring: The Importance of Growth Magnitude and Goal Setting in Decision Making

ERIC Educational Resources Information Center

Van Norman, Ethan R.; Christ, Theodore J.; Newell, Kirsten W.

2017-01-01

Research regarding the technical adequacy of growth estimates from curriculum-based measurement of reading progress monitoring data suggests that current decision-making frameworks are likely to yield inaccurate recommendations unless data are collected for extensive periods of time. Instances where data may not need to be collected for long…

Monitoring Student Progress and Publicising the Results. Information Bank Number 1270.

ERIC Educational Resources Information Center

Jones, D. T. L.

Arguing that assessments of student progress describe the consequences of the interaction of the multitude of elements that make up the educational system, this paper examines the three-tiered assessment system used at Redhill Technical College (RTC), in Surrey, England, to fulfill diagnostic and motivational functions for the college as a whole.…

Mutant Kras copy number defines metabolic reprogramming and therapeutic susceptibilities

PubMed Central

Kerr, Emma; Gaude, Edoardo; Turrell, Frances; Frezza, Christian; Martins, Carla P

2016-01-01

Summary The RAS/MAPK-signalling pathway is frequently deregulated in non-small cell lung cancer (NSCLC), often through KRAS activating mutations1-3. A single endogenous mutant Kras allele is sufficient to promote lung tumour formation in mice but malignant progression requires additional genetic alterations4-7. We recently showed that advanced lung tumours from KrasG12D/+;p53-null mice frequently exhibit KrasG12D allelic enrichment (KrasG12D/Kraswild-type>1)7, implying that mutant Kras copy gains are positively selected during progression. Through a comprehensive analysis of mutant Kras homozygous and heterozygous MEFs and lung cancer cells we now show that these genotypes are phenotypically distinct. In particular, KrasG12D/G12D cells exhibit a glycolytic switch coupled to increased channelling of glucose-derived metabolites into the TCA cycle and glutathione biosynthesis, resulting in enhanced glutathione-mediated detoxification. This metabolic rewiring is recapitulated in mutant KRAS homozygous NSCLC cells and in vivo, in spontaneous advanced murine lung tumours (which display a high frequency of KrasG12D copy gain), but not in the corresponding early tumours (KrasG12D heterozygous). Finally, we demonstrate that mutant Kras copy gain creates unique metabolic dependences that can be exploited to selectively target these aggressive mutant Kras tumours. Our data demonstrate that mutant Kras lung tumours are not a single disease but rather a heterogeneous group comprised of two classes of tumours with distinct metabolic profiles, prognosis and therapeutic susceptibility, which can be discriminated based on their relative mutant allelic content. We also provide the first in vivo evidence of metabolic rewiring during lung cancer malignant progression. PMID:26909577

Differentiation in the microbial ecology and activity of suspended and attached bacteria in a nitritation-anammox process.

PubMed

Park, Hongkeun; Sundar, Suneethi; Ma, Yiwei; Chandran, Kartik

2015-02-01

A directed differentiation between the biofilm and suspension was observed in the molecular microbial ecology and gene expression of different bacteria in a biofilm nitritation-anammox process operated at varying hydraulic residence times (HRT) and nitrogen loading rates (NLR). The highest degree of enrichment observed in the biofilm was of anaerobic ammonia-oxidizing bacteria (AMX) followed by that of Nitrospira spp. related nitrite-oxidizing bacteria (NOB). For AMX, a major shift from Candidatus "Brocadia fulgida" to Candidatus "Kuenenia stuttgartiensis" in both suspension and biofilm was observed with progressively shorter HRT, using discriminatory biomarkers targeting the hydrazine synthase (hzsA) gene. In parallel, expression of the hydrazine oxidoreductase gene (hzo), a functional biomarker for AMX energy metabolism, became progressively prominent in the biofilm. A marginal but statistically significant enrichment in the biofilm was observed for Nitrosomonas europaea related ammonia-oxidizing bacteria (AOB). In direct contrast to AMX, the gene expression of ammonia monooxygenase subunit A (amoA), a functional biomarker for AOB energy metabolism, progressively increased in suspension. Using gene expression and biomass concentration measures in conjunction, it was determined that signatures of AOB metabolism were primarily present in the biofilm throughout the study. On the other hand, AMX metabolism gradually shifted from being uniformly distributed in both the biofilm and suspension to primarily the biofilm at shorter HRTs and higher NLRs. These results therefore highlight the complexity and key differences in the microbial ecology, gene expression and activity between the biofilm and suspension of a nitritation-anammox process and the biokinetic and metabolic drivers for such niche segregation. © 2014 Wiley Periodicals, Inc.

Nutritional and metabolic support in patients with amyotrophic lateral sclerosis.

PubMed

Muscaritoli, Maurizio; Kushta, Irma; Molfino, Alessio; Inghilleri, Maurizio; Sabatelli, Mario; Rossi Fanelli, Filippo

2012-10-01

Amyotrophic lateral sclerosis (ALS) is the most common form of progressive motor neuron disease and the most devastating neurodegenerative disorder. ALS is characterized by progressive paralysis and respiratory failure leading to death within 3 to 5 years after its onset. Protein-energy malnutrition is a frequent finding in ALS. The pathogenesis of protein-energy malnutrition in ALS is multifactorial. Muscle atrophy, hypophagia, dysphagia, and hypermetabolism play a role in determining the deterioration of nutritional status. A multidisciplinary approach is crucial to set an appropriate plan for metabolic and nutritional support in ALS. Nutritional management incorporates a continuous assessment and implementation of dietary modifications throughout the duration of the disease. The nutritional and metabolic approaches to ALS should start when the diagnosis of ALS is made and should become an integral part of the continuous care to the patient, including nutritional surveillance, dietary counseling, management of dysphagia, and enteral nutrition when needed. Parenteral nutrition is rarely indicated. Standard polymeric enteral formulas are routinely used, usually providing 25 to 30 kcal/kg and protein 0.8 to 1.2 g /kg per day. The use of fiber-enriched formulas may help prevent constipation. However, considering the complex metabolic abnormalities of ALS, standard and/or fiber-enriched formulas might not be sufficient to achieve optimal metabolic and nutritional support. Based on the most recent clinical and experimental evidence, it is tempting to hypothesize that personalized nutritional support including specific nutritional substrates could act on disease progression and improve the quality of life and the response to the few and yet scarcely effective, currently available pharmacologic therapies. Copyright © 2012 Elsevier Inc. All rights reserved.

In vivo and in silico dynamics of the development of Metabolic Syndrome.

PubMed

Rozendaal, Yvonne J W; Wang, Yanan; Paalvast, Yared; Tambyrajah, Lauren L; Li, Zhuang; Willems van Dijk, Ko; Rensen, Patrick C N; Kuivenhoven, Jan A; Groen, Albert K; Hilbers, Peter A J; van Riel, Natal A W

2018-06-01

The Metabolic Syndrome (MetS) is a complex, multifactorial disorder that develops slowly over time presenting itself with large differences among MetS patients. We applied a systems biology approach to describe and predict the onset and progressive development of MetS, in a study that combined in vivo and in silico models. A new data-driven, physiological model (MINGLeD: Model INtegrating Glucose and Lipid Dynamics) was developed, describing glucose, lipid and cholesterol metabolism. Since classic kinetic models cannot describe slowly progressing disorders, a simulation method (ADAPT) was used to describe longitudinal dynamics and to predict metabolic concentrations and fluxes. This approach yielded a novel model that can describe long-term MetS development and progression. This model was integrated with longitudinal in vivo data that was obtained from male APOE*3-Leiden.CETP mice fed a high-fat, high-cholesterol diet for three months and that developed MetS as reflected by classical symptoms including obesity and glucose intolerance. Two distinct subgroups were identified: those who developed dyslipidemia, and those who did not. The combination of MINGLeD with ADAPT could correctly predict both phenotypes, without making any prior assumptions about changes in kinetic rates or metabolic regulation. Modeling and flux trajectory analysis revealed that differences in liver fluxes and dietary cholesterol absorption could explain this occurrence of the two different phenotypes. In individual mice with dyslipidemia dietary cholesterol absorption and hepatic turnover of metabolites, including lipid fluxes, were higher compared to those without dyslipidemia. Predicted differences were also observed in gene expression data, and consistent with the emergence of insulin resistance and hepatic steatosis, two well-known MetS co-morbidities. Whereas MINGLeD specifically models the metabolic derangements underlying MetS, the simulation method ADAPT is generic and can be applied to other diseases where dynamic modeling and longitudinal data are available.

Role of acidosis-induced increases in calcium on PTH secretion in acute metabolic and respiratory acidosis in the dog.

PubMed

López, Ignacio; Aguilera-Tejero, Escolástico; Estepa, José Carlos; Rodríguez, Mariano; Felsenfeld, Arnold J

2004-05-01

Recently, we showed that both acute metabolic acidosis and respiratory acidosis stimulate parathyroid hormone (PTH) secretion in the dog. To evaluate the specific effect of acidosis, ionized calcium (iCa) was clamped at a normal value. Because iCa values normally increase during acute acidosis, we now have studied the PTH response to acute metabolic and respiratory acidosis in dogs in which the iCa concentration was allowed to increase (nonclamped) compared with dogs with a normal iCa concentration (clamped). Five groups of dogs were studied: control, metabolic (clamped and nonclamped), and respiratory (clamped and nonclamped) acidosis. Metabolic (HCl infusion) and respiratory (hypoventilation) acidosis was progressively induced during 60 min. In the two clamped groups, iCa was maintained at a normal value with an EDTA infusion. Both metabolic and respiratory acidosis increased (P < 0.05) iCa values in nonclamped groups. In metabolic acidosis, the increase in iCa was progressive and greater (P < 0.05) than in respiratory acidosis, in which iCa increased by 0.04 mM and then remained constant despite further pH reductions. The increase in PTH values was greater (P < 0.05) in clamped than in nonclamped groups (metabolic and respiratory acidosis). In the nonclamped metabolic acidosis group, PTH values first increased and then decreased from peak values when iCa increased by > 0.1 mM. In the nonclamped respiratory acidosis group, PTH values exceeded (P < 0.05) baseline values only after iCa values stopped increasing at a pH of 7.30. For the same increase in iCa in the nonclamped groups, PTH values increased more in metabolic acidosis. In conclusion, 1) both metabolic acidosis and respiratory acidosis stimulate PTH secretion; 2) the physiological increase in the iCa concentration during the induction of metabolic and respiratory acidosis reduces the magnitude of the PTH increase; 3) in metabolic acidosis, the increase in the iCa concentration can be of sufficient magnitude to reverse the increase in PTH values; and 4) for the same degree of acidosis-induced hypercalcemia, the increase in PTH values is greater in metabolic than in respiratory acidosis.

Magnetic Earth Ionosphere Resonant Frequencies

NASA Technical Reports Server (NTRS)

Spaniol, Craig

1994-01-01

The Community College Division is pleased to report progress of NASA funded research at West Virginia State College. During this reporting period, the project research group has continued with activities to develop instrumentation capability designed to monitor resonant cavity frequencies in the atmospheric region between the Earth's surface and the ionosphere. In addition, the project's principal investigator, Dr. Craig Spaniol, and NASA technical officer, Dr. John Sutton, have written and published technical papers intended to expand the scientific and technical framework needed for project research. This research continues to provide an excellent example of government and education working together to provide significant research in the college environment. This cooperative effort has provided many students with technical project work which compliments their education.

Kinetic activity, membrane mitochondrial potential, lipid peroxidation, intracellular pH and calcium of frozen/thawed bovine spermatozoa treated with metabolic enhancers.

PubMed

Boni, R; Gallo, A; Cecchini, S

2017-01-01

Owing to the progressive decline of sperm motility during storage there is a need to find substances capable of enhancing sperm energy metabolism and motility and/or preserving it from oxidative damage. The aim of this study was to evaluate in frozen/thawed bovine spermatozoa the effect of several compounds, such as myo-inositol, pentoxifylline, penicillamine + hypotaurine + epinephrine mixture (PHE), caffeine and coenzyme Q10+ zinc + d-aspartate mixture (CZA), on either kinetic or metabolic parameters. Sperm kinetics was evaluated by Sperm Class Analyser whereas specific fluorochromes were used to evaluated mitochondrial membrane potential (MMP), intracellular pH, intracellular calcium concentration and lipid peroxidation. Lipid peroxidation was also evaluated by TBARS analysis. Treatments significantly affected total and progressive motility with different dynamics in relation to the incubation time. After the first hour of incubation, CZA treatment produced the best performance in total and progressive sperm motility as well as in curvilinear velocity, average path velocity and amplitude of head displacement, whereas pentoxifylline stimulated the highest straight-line velocity. MMP showed higher values (p < 0.01) after treatment with pentoxifylline and PHE. Intracytoplasmic calcium concentration and lipid peroxidation were significantly (p < 0.05) affected by the incubation time rather than the treatments. Intracellular pH varied significantly (p < 0.01) in relation to either the incubation time or treatments. In particular, it showed a progressive increase throughout incubation with values in control group significantly higher than in myo-inositol, PHE, caffeine, pentoxifylline and CZA groups (7.37 ± 0.03 vs. 7.29 ± 0.03, 7.28 ± 0.03, 7.26 ± 0.03, 7.22 ± 0.03 and 7.00 ± 0.03, respectively; p < 0.01).; however, among treatments, CZA displayed the lowest values. Significant correlations were found between sperm kinetic and metabolic parameters. These findings provide new comparative information on the effects of putative metabolic enhancers on kinetics and metabolic activities of bovine spermatozoa. In this study, a rapid methodological approach for evaluating sperm quality is proposed. © 2016 American Society of Andrology and European Academy of Andrology.

48 CFR 742.1170-1 - General.

Code of Federal Regulations, 2013 CFR

2013-10-01

... MANAGEMENT CONTRACT ADMINISTRATION Production, Surveillance, and Reporting 742.1170-1 General. Performance... cognizant technical officer, to maintain adequate knowledge of the contractor's activities and progress in...

48 CFR 742.1170-1 - General.

Code of Federal Regulations, 2012 CFR

2012-10-01

... MANAGEMENT CONTRACT ADMINISTRATION Production, Surveillance, and Reporting 742.1170-1 General. Performance... cognizant technical officer, to maintain adequate knowledge of the contractor's activities and progress in...

48 CFR 742.1170-1 - General.

Code of Federal Regulations, 2014 CFR

2014-10-01

... MANAGEMENT CONTRACT ADMINISTRATION Production, Surveillance, and Reporting 742.1170-1 General. Performance... cognizant technical officer, to maintain adequate knowledge of the contractor's activities and progress in...

48 CFR 742.1170-1 - General.

Code of Federal Regulations, 2010 CFR

2010-10-01

... MANAGEMENT CONTRACT ADMINISTRATION Production, Surveillance, and Reporting 742.1170-1 General. Performance... cognizant technical officer, to maintain adequate knowledge of the contractor's activities and progress in...

Access and Success for System Goals for People of Color in Washington Community and Technical Colleges: Progress Report. Research Report No. 05-3

ERIC Educational Resources Information Center

Washington State Board for Community and Technical Colleges, 2005

2005-01-01

This report is designed to provide information for readers, promote discussion, and set the stage for future initiatives to address outcomes for people of color. The data provided speaks to the success that Washington's community and technical colleges have achieved in increasing higher education access and participation for students of color. It…

Internal Consistency of General Outcome Measures in Grades 1-8. Technical Report # 0915

ERIC Educational Resources Information Center

Anderson, Daniel; Tindal, Gerald; Alonzo, Julie

2009-01-01

We developed alternate forms of a math test for use in both screening students at risk of failure and monitoring their progress over time. In this technical report, we present results of the screener, used in the fall of 2009. The 48-item test was aligned to the National Council of Teachers of Mathematics (NCTM) Curriculum Focal Point Standards…

Career and Technical Education: States Aligning Programs to Meet Workforce Needs. The Progress of Education Reform. Volume 15, Number 2

ERIC Educational Resources Information Center

Zinth, Jennifer Dounay

2014-01-01

Across the 50 states, career and technical education (CTE) programs at the K-12 and postsecondary levels have seen enormous policy action - 2013 alone saw at least 78 substantive policy changes via legislation, state board rules and executive orders specific to CTE and workforce development. What are the drivers behind this sudden policymaker…

Progressive hypoxia decouples activity and aerobic performance of skate embryos

PubMed Central

Di Santo, Valentina; Tran, Anna H.; Svendsen, Jon C.

2016-01-01

Although fish population size is strongly affected by survival during embryonic stages, our understanding of physiological responses to environmental stressors is based primarily on studies of post-hatch fishes. Embryonic responses to acute exposure to changes in abiotic conditions, including increase in hypoxia, could be particularly important in species exhibiting long developmental time, as embryos are unable to select a different environment behaviourally. Given that oxygen is key to metabolic processes in fishes and aquatic hypoxia is becoming more severe and frequent worldwide, organisms are expected to reduce their aerobic performance. Here, we examined the metabolic and behavioural responses of embryos of a benthic elasmobranch fish, the little skate (Leucoraja erinacea), to acute progressive hypoxia, by measuring oxygen consumption and movement (tail-beat) rates inside the egg case. Oxygen consumption rates were not significantly affected by ambient oxygen levels until reaching 45% air saturation (critical oxygen saturation, Scrit). Below Scrit, oxygen consumption rates declined rapidly, revealing an oxygen conformity response. Surprisingly, we observed a decoupling of aerobic performance and activity, as tail-beat rates increased, rather than matching the declining metabolic rates, at air saturation levels of 55% and below. These results suggest a significantly divergent response at the physiological and behavioural levels. While skate embryos depressed their metabolic rates in response to progressive hypoxia, they increased water circulation inside the egg case, presumably to restore normoxic conditions, until activity ceased abruptly around 9.8% air saturation. PMID:27293746

Mitoferrin-1 is involved in the progression of alzheimer's disease through targeting mitochondrial iron metabolism in a caenorhabditis elegans model of alzheimers disease.

PubMed

Huang, Jiatao; Chen, Sixi; Hu, Li; Niu, Huan; Sun, Qianqian; Li, Wenna; Tan, Guoqian; Li, Jianghui; Jin, LongJin; Lyu, Jianxin; Zhou, Huaibin

2018-06-13

In mammals, mitoferrin-1and mitoferrin-2, two homologous proteins of the mitochondrial solute carrier family are required for iron delivery into mitochondria. However, there is only one kind, called W02B12 (mitoferrin-1 or mfn-1), in Caenorhabditis elegans and its regulatory mechanism is unknown. In this study, we used Caenorhabditis elegans strains CL2006 and GMC101 as models to investigate what role mitoferrin-1 played in Alzheimer's disease (AD). We found that knockdown of mitoferrin-1 by feeding-RNAi treatment extended lifespans of both strains of C. elegans. In addition, it reduced the paralysis rate in the GMC101 strain. These results suggest that mitoferrin-1 may be involved in the progression of Alzheimer's disease. Knockdown of mitoferrin-1 was seen to disturb mitochondrial morphology in the CB5600 strain. We tested whether knockdown of mitoferrin-1 could influence mitochondrial metabolism. Analysis of mitochondrial iron metabolism and mitochondrial ROS showed that knockdown of mitoferrin-1 could reduce mitochondrial iron content and reduce the level of mitochondrial ROS in the CL2006 and GMC101 strains. These results confirm that knockdown of mitoferrin-1 can slow the progress of disease in Alzheimer model of C. elegans and suggest that mitoferrin-1 plays a major role in mediating mitochondrial iron metabolism in this process. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Oxidative stress and mitochondrial adaptive shift during pituitary tumoral growth.

PubMed

Sabatino, Maria Eugenia; Grondona, Ezequiel; Sosa, Liliana D V; Mongi Bragato, Bethania; Carreño, Lucia; Juarez, Virginia; da Silva, Rodrigo A; Remor, Aline; de Bortoli, Lucila; de Paula Martins, Roberta; Pérez, Pablo A; Petiti, Juan Pablo; Gutiérrez, Silvina; Torres, Alicia I; Latini, Alexandra; De Paul, Ana L

2018-05-20

The cellular transformation of normal functional cells to neoplastic ones implies alterations in the cellular metabolism and mitochondrial function in order to provide the bioenergetics and growth requirements for tumour growth progression. Currently, the mitochondrial physiology and dynamic shift during pituitary tumour development are not well understood. Pituitary tumours present endocrine neoplastic benign growth which, in previous reports, we had shown that in addition to increased proliferation, these tumours were also characterized by cellular senescence signs with no indication of apoptosis. Here, we show clear evidence of oxidative stress in pituitary cells, accompanied by bigger and round mitochondria during tumour development, associated with augmented biogenesis and an increased fusion process. An activation of the Nrf2 stress response pathway together with the attenuation of the oxidative damage signs occurring during tumour development were also observed which will probably provide survival advantages to the pituitary cells. These neoplasms also presented a progressive increase in lactate production, suggesting a metabolic shift towards glycolysis metabolism. These findings might imply an oxidative stress state that could impact on the pathogenesis of pituitary tumours. These data may also reflect that pituitary cells can modulate their metabolism to adapt to different energy requirements and signalling events in a pathophysiological situation to obtain protection from damage and enhance their survival chances. Thus, we suggest that mitochondria function, oxidative stress or damage might play a critical role in pituitary tumour progression. Copyright © 2018 Elsevier Inc. All rights reserved.

Progressive hypoxia decouples activity and aerobic performance of skate embryos.

PubMed

Di Santo, Valentina; Tran, Anna H; Svendsen, Jon C

2016-01-01

Although fish population size is strongly affected by survival during embryonic stages, our understanding of physiological responses to environmental stressors is based primarily on studies of post-hatch fishes. Embryonic responses to acute exposure to changes in abiotic conditions, including increase in hypoxia, could be particularly important in species exhibiting long developmental time, as embryos are unable to select a different environment behaviourally. Given that oxygen is key to metabolic processes in fishes and aquatic hypoxia is becoming more severe and frequent worldwide, organisms are expected to reduce their aerobic performance. Here, we examined the metabolic and behavioural responses of embryos of a benthic elasmobranch fish, the little skate (Leucoraja erinacea), to acute progressive hypoxia, by measuring oxygen consumption and movement (tail-beat) rates inside the egg case. Oxygen consumption rates were not significantly affected by ambient oxygen levels until reaching 45% air saturation (critical oxygen saturation, S crit). Below S crit, oxygen consumption rates declined rapidly, revealing an oxygen conformity response. Surprisingly, we observed a decoupling of aerobic performance and activity, as tail-beat rates increased, rather than matching the declining metabolic rates, at air saturation levels of 55% and below. These results suggest a significantly divergent response at the physiological and behavioural levels. While skate embryos depressed their metabolic rates in response to progressive hypoxia, they increased water circulation inside the egg case, presumably to restore normoxic conditions, until activity ceased abruptly around 9.8% air saturation.

Chronic Trypanosoma cruzi infection potentiates adipose tissue macrophage polarization toward an anti-inflammatory M2 phenotype and contributes to diabetes progression in a diet-induced obesity model.

PubMed

Cabalén, María E; Cabral, María F; Sanmarco, Liliana M; Andrada, Marta C; Onofrio, Luisina I; Ponce, Nicolás E; Aoki, María P; Gea, Susana; Cano, Roxana C

2016-03-22

Chronic obesity and Chagas disease (caused by the protozoan Trypanosoma cruzi) represent serious public health concerns. The interrelation between parasite infection, adipose tissue, immune system and metabolism in an obesogenic context, has not been entirely explored. A novel diet-induced obesity model (DIO) was developed in C57BL/6 wild type mice to examine the effect of chronic infection (DIO+I) on metabolic parameters and on obesity-related disorders. Dyslipidemia, hyperleptinemia, and cardiac/hepatic steatosis were strongly developed in DIO mice. Strikingly, although these metabolic alterations were collectively improved by infection, plasmatic apoB100 levels remain significantly increased in DIO+I, suggesting the presence of pro-atherogenic small and dense LDL particles. Moreover, acute insulin resistance followed by chronic hyperglycemia with hypoinsulinemia was found, evidencing an infection-related-diabetes progression. These lipid and glucose metabolic changes seemed to be highly dependent on TLR4 expression since TLR4-/- mice were protected from obesity and its complications. Notably, chronic infection promoted a strong increase in MCP-1 producing macrophages with a M2 (F4/80+CD11c-CD206+) phenotype associated to oxidative stress in visceral adipose tissue of DIO+I mice. Importantly, infection reduced lipid content but intensified inflammatory infiltrates in target tissues. Thus, parasite persistence in an obesogenic environment and the resulting host immunometabolic dysregulation may contribute to diabetes/atherosclerosis progression.

Plac8 links oncogenic mutations to regulation of autophagy and is critical to pancreatic cancer progression

PubMed Central

Kinsey, Conan; Balakrishnan, Vijaya; O’Dell, Michael R.; Huang, Jing Li; Newman, Laurel; Whitney-Miller, Christa L.; Hezel, Aram F.; Land, Hartmut

2014-01-01

Summary Mutations in p53 and RAS potently cooperate in oncogenic transformation and correspondingly these genetic alterations frequently coexist in pancreatic ductal adenocarcinoma (PDA) and other human cancers. Previously we identified a set of genes synergistically activated by combined RAS and p53 mutations as frequent downstream mediators of tumorigenesis. Here, we show that the synergistically activated gene Plac8 is critical for pancreatic cancer growth. Silencing of Plac8 in cell lines suppresses tumor formation by blocking autophagy, a process essential for maintaining metabolic homeostasis in PDA, and genetic inactivation in an engineered mouse model inhibits PDA progression. We show that Plac8 is a critical regulator of the autophagic machinery, localizing to the lysosomal compartment and facilitating lysosome-autophagosome fusion. Plac8 thus provides a mechanistic link between primary oncogenic mutations and the induction of autophagy, a central mechanism of metabolic reprogramming, during PDA progression. PMID:24794439

Aerospace medicine and biology: A continuing bibliography with indexes, supplement 273

NASA Technical Reports Server (NTRS)

1985-01-01

This bibliography lists 265 reports, articles, and other documents introduced into the NASA scientific and technical information system in June 1985. Topics in aerospace medicine and biology, metabolism, human behavior, man machine systems, and injuries are included.

Transcript level coordination of carbon pathways during silicon starvation-induced lipid accumulation in the diatom Thalassiosira pseudonana

DOE PAGES

Smith, Sarah R.; Gle, Corine; Abbriano, Raffaela M.; ...

2016-02-04

Diatoms are one of the most productive and successful photosynthetic taxa on Earth and possess attributes such as rapid growth rates and production of lipids, making them candidate sources of renewable fuels. Despite their significance, few details of the mechanisms used to regulate growth and carbon metabolism are currently known, hindering metabolic engineering approaches to enhance productivity. To characterize the transcript level component of metabolic regulation, genome-wide changes in transcript abundance were documented in the model diatom Thalassiosira pseudonana on a time-course of silicon starvation. Growth, cell cycle progression, chloroplast replication, fatty acid composition, pigmentation, and photosynthetic parameters were characterizedmore » alongside lipid accumulation. Extensive coordination of large suites of genes was observed, highlighting the existence of clusters of coregulated genes as a key feature of global gene regulation in T. pseudonana. The identity of key enzymes for carbon metabolic pathway inputs (photosynthesis) and outputs (growth and storage) reveals these clusters are organized to synchronize these processes. Coordinated transcript level responses to silicon starvation are probably driven by signals linked to cell cycle progression and shifts in photophysiology. A mechanistic understanding of how this is accomplished will aid efforts to engineer metabolism for development of algal-derived biofuels.« less

Metabolic consequences of sleep and circadian disorders

PubMed Central

Depner, Christopher M.; Stothard, Ellen R.; Wright, Kenneth P.

2014-01-01

Sleep and circadian rhythms modulate or control daily physiological patterns with importance for normal metabolic health. Sleep deficiencies associated with insufficient sleep schedules, insomnia with short-sleep duration, sleep apnea, narcolepsy, circadian misalignment, shift work, night eating syndrome and sleep-related eating disorder may all contribute to metabolic dysregulation. Sleep deficiencies and circadian disruption associated with metabolic dysregulation may contribute to weight gain, obesity, and type 2 diabetes potentially by altering timing and amount of food intake, disrupting energy balance, inflammation, impairing glucose tolerance and insulin sensitivity. Given the rapidly increasing prevalence of metabolic diseases, it is important to recognize the role of sleep and circadian disruption in the development, progression, and morbidity of metabolic disease. Some findings indicate sleep treatments and countermeasures improve metabolic health, but future clinical research investigating prevention and treatment of chronic metabolic disorders through treatment of sleep and circadian disruption is needed. PMID:24816752

Lipid Metabolism and Lipid Droplets in Pancreatic Cancer and Stellate Cells

PubMed Central

Sunami, Yoshiaki; Rebelo, Artur; Kleeff, Jörg

2017-01-01

Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second deadliest cancer by 2030, and the overall 5-year survival rate is currently less than 7%. Cancer cells frequently exhibit reprogramming of their metabolic activity. It is increasingly recognized that aberrant de novo lipid synthesis and reprogrammed lipid metabolism are both associated with the development and progression of various cancers, including pancreatic cancer. In this review, the current knowledge about lipid metabolism and lipid droplets in pancreatic cancer is discussed. In the first part, molecular mechanisms of lipid metabolism and roles of enzymes involved in lipid metabolism which are relevant for pancreatic cancer research are presented. Further, preclinical studies and clinical trials with drugs/inhibitors targeting cancer metabolic systems in cancer are summarized. An increase of our knowledge in lipid metabolism in pancreatic cancer cells and in tumor stroma is important for developing novel strategies of future individualized therapies of pancreatic cancer. PMID:29295482

Metabolic consequences of sleep and circadian disorders.

PubMed

Depner, Christopher M; Stothard, Ellen R; Wright, Kenneth P

2014-07-01

Sleep and circadian rhythms modulate or control daily physiological patterns with importance for normal metabolic health. Sleep deficiencies associated with insufficient sleep schedules, insomnia with short-sleep duration, sleep apnea, narcolepsy, circadian misalignment, shift work, night eating syndrome, and sleep-related eating disorder may all contribute to metabolic dysregulation. Sleep deficiencies and circadian disruption associated with metabolic dysregulation may contribute to weight gain, obesity, and type 2 diabetes potentially by altering timing and amount of food intake, disrupting energy balance, inflammation, impairing glucose tolerance, and insulin sensitivity. Given the rapidly increasing prevalence of metabolic diseases, it is important to recognize the role of sleep and circadian disruption in the development, progression, and morbidity of metabolic disease. Some findings indicate sleep treatments and countermeasures improve metabolic health, but future clinical research investigating prevention and treatment of chronic metabolic disorders through treatment of sleep and circadian disruption is needed.

Nuclear Technology Division annual progress report for period ending June 30, 1972

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

None

1972-10-01

This document is a report of progress on technical programs of the Nuclear Technology,Division of Aerojet Nuclear Company for FY 72 ending June 30, 1972. It contains abstracts or expansions of abstracts of papers which have been published within the year. In these cases, preprints or reprints of the articles available. Results of work in progress are also reported; since this work is of a preliminary nature, the authors should be contacted before including any reference to these works in other publications.

Flux analysis and metabolomics for systematic metabolic engineering of microorganisms.

PubMed

Toya, Yoshihiro; Shimizu, Hiroshi

2013-11-01

Rational engineering of metabolism is important for bio-production using microorganisms. Metabolic design based on in silico simulations and experimental validation of the metabolic state in the engineered strain helps in accomplishing systematic metabolic engineering. Flux balance analysis (FBA) is a method for the prediction of metabolic phenotype, and many applications have been developed using FBA to design metabolic networks. Elementary mode analysis (EMA) and ensemble modeling techniques are also useful tools for in silico strain design. The metabolome and flux distribution of the metabolic pathways enable us to evaluate the metabolic state and provide useful clues to improve target productivity. Here, we reviewed several computational applications for metabolic engineering by using genome-scale metabolic models of microorganisms. We also discussed the recent progress made in the field of metabolomics and (13)C-metabolic flux analysis techniques, and reviewed these applications pertaining to bio-production development. Because these in silico or experimental approaches have their respective advantages and disadvantages, the combined usage of these methods is complementary and effective for metabolic engineering. Copyright © 2013 Elsevier Inc. All rights reserved.

CPS1 maintains pyrimidine pools and DNA synthesis in KRAS/LKB1-mutant lung cancer cells. | Office of Cancer Genomics

Cancer.gov

Metabolic reprogramming by oncogenic signals promotes cancer initiation and progression. The oncogene KRAS and tumor suppressor STK11, which encodes the kinase LKB1, regulate metabolism and are frequently mutated in non-small-cell lung cancer(NSCLC). Concurrent occurrence of oncogenic KRAS and loss of LKB1 (KL) in cells specifies aggressive oncological behavior. Here we show that human KL cells and tumors share metabolic signatures of perturbed nitrogen handling.

28 CFR 33.12 - Establishment of State Office.

Code of Federal Regulations, 2011 CFR

2011-07-01

... received from the Bureau of Justice Assistance, including receipt, review, processing, monitoring, progress and financial report review, technical assistance, grant adjustments, accounting, auditing, and fund...

28 CFR 33.12 - Establishment of State Office.

Code of Federal Regulations, 2010 CFR

2010-07-01

... received from the Bureau of Justice Assistance, including receipt, review, processing, monitoring, progress and financial report review, technical assistance, grant adjustments, accounting, auditing, and fund...

Metabolic Reprogramming in Thyroid Carcinoma

PubMed Central

Coelho, Raquel Guimaraes; Fortunato, Rodrigo S.; Carvalho, Denise P.

2018-01-01

Among all the adaptations of cancer cells, their ability to change metabolism from the oxidative to the glycolytic phenotype is a hallmark called the Warburg effect. Studies on tumor metabolism show that improved glycolysis and glutaminolysis are necessary to maintain rapid cell proliferation, tumor progression, and resistance to cell death. Thyroid neoplasms are common endocrine tumors that are more prevalent in women and elderly individuals. The incidence of thyroid cancer has increased in the Past decades, and recent findings describing the metabolic profiles of thyroid tumors have emerged. Currently, several drugs are in development or clinical trials that target the altered metabolic pathways of tumors are undergoing. We present a review of the metabolic reprogramming in cancerous thyroid tissues with a focus on the factors that promote enhanced glycolysis and the possible identification of promising metabolic targets in thyroid cancer. PMID:29629339

STOICHIOMETRIC MODEL FOR EVALUATING THE METABOLIC CAPABILITIES OF THE FACULTATIVE METHYLOTROPH METHYLOBACTERIUM EXTORQUENS AM1, WITH APPLICATION TO RECONSTRUCTION OF C(3) AND C(4) METABOLISM. (R826729)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

'Dual hit' metabolic modulator LDCA selectively kills cancer cells by efficient competitive inhibition of LDH-A.

PubMed

Ghosh, Monisankar; Saha, Suchandrima; Dutta, Samir Kumar

2016-02-07

Herein, we synthesize and elucidate the potential of a novel 'dual hit' molecule, LDCA, to constitutively block lactate dehydrogenase isoform-A (LDH-A) to selectively subvert apoptosis and rigorously attenuate breast tumor progression in a mouse model, comprehensively delineating the therapeutic prospectus of LDCA in the field of cancer metabolics.

Aldehydic load and aldehyde dehydrogenase 2 profile during the progression of post-myocardial infarction cardiomyopathy: benefits of Alda-1

PubMed Central

Gomes, Katia M.S.; Bechara, Luiz R.G.; Lima, Vanessa M.; Ribeiro, Márcio A.C.; Campos, Juliane C.; Dourado, Paulo M.; Kowaltowski, Alicia J.; Mochly-Rosen, Daria; Ferreira, Julio C.B.

2015-01-01

Background/Objectives We previously demonstrated that reducing cardiac aldehydic load by aldehyde dehydrogenase 2 (ALDH2), a mitochondrial enzyme responsible for metabolizing the major lipid peroxidation product, protects against acute ischemia/reperfusion injury and chronic heart failure. However, time-dependent changes in ALDH2 profile, aldehydic load and mitochondrial bioenergetics during progression of post-myocardial infarction (post-MI) cardiomyopathy is unknown and should be established to determine the optimal time window for drug treatment. Methods Here we characterized cardiac ALDH2 activity and expression, lipid peroxidation, 4-hydroxy-2-nonenal (4-HNE) adduct formation, glutathione pool and mitochondrial energy metabolism and H2O2 release during the 4 weeks after permanent left anterior descending (LAD) coronary artery occlusion in rats. Results We observed a sustained disruption of cardiac mitochondrial function during the progression of post-MI cardiomyopathy, characterized by >50% reduced mitochondrial respiratory control ratios and up to 2 fold increase in H2O2 release. Mitochondrial dysfunction was accompanied by accumulation of cardiac and circulating lipid peroxides and 4-HNE protein adducts and down-regulation of electron transport chain complexes I and V. Moreover, increased aldehydic load was associated with a 90% reduction in cardiac ALDH2 activity and increased glutathione pool. Further supporting an ALDH2 mechanism, sustained Alda-1 treatment (starting 24hrs after permanent LAD occlusion surgery) prevented aldehydic overload, mitochondrial dysfunction and improved ventricular function in post-MI cardiomyopathy rats. Conclusion Taken together, our findings demonstrate a disrupted mitochondrial metabolism along with an insufficient cardiac ALDH2-mediated aldehyde clearance during the progression of ventricular dysfunction, suggesting a potential therapeutic value of ALDH2 activators during the progression of post-myocardial infarction cardiomyopathy. PMID:25464432

Cardiovascular function in male and female JCR:LA-cp rats: effect of high-fat/high-sucrose diet.

PubMed

Hunter, Ian; Soler, Amanda; Joseph, Gregory; Hutcheson, Brenda; Bradford, Chastity; Zhang, Frank Fan; Potter, Barry; Proctor, Spencer; Rocic, Petra

2017-04-01

Thirty percent of the world population is diagnosed with metabolic syndrome. High-fat/high-sucrose (HF/HS) diet (Western diet) correlates with metabolic syndrome prevalence. We characterized effects of the HF/HS diet on vascular (arterial stiffness, vasoreactivity, and coronary collateral development) and cardiac (echocardiography) function, oxidative stress, and inflammation in a rat model of metabolic syndrome (JCR rats). Furthermore, we determined whether male versus female animals were affected differentially by the Western diet. Cardiovascular function in JCR male rats was impaired versus normal Sprague-Dawley (SD) rats. HF/HS diet compromised cardiovascular (dys)function in JCR but not SD male rats. In contrast, cardiovascular function was minimally impaired in JCR female rats on normal chow. However, cardiovascular function in JCR female rats on the HF/HS diet deteriorated to levels comparable to JCR male rats on the HF/HS diet. Similarly, oxidative stress was markedly increased in male but not female JCR rats on normal chow but was equally exacerbated by the HF/HS diet in male and female JCR rats. These results indicate that the Western diet enhances oxidative stress and cardiovascular dysfunction in metabolic syndrome and eliminates the protective effect of female sex on cardiovascular function, implying that both males and females with metabolic syndrome are at equal risk for cardiovascular disease. NEW & NOTEWORTHY Western diet abolished protective effect of sex against cardiovascular disease (CVD) development in premenopausal animals with metabolic syndrome. Western diet accelerates progression of CVD in male and female animals with preexisting metabolic syndrome but not normal animals. Exacerbation of baseline oxidative stress correlates with accelerated progression of CVD in metabolic syndrome animals on Western diet. Copyright © 2017 the American Physiological Society.

Cardiovascular function in male and female JCR:LA-cp rats: effect of high-fat/high-sucrose diet

PubMed Central

Hunter, Ian; Soler, Amanda; Joseph, Gregory; Hutcheson, Brenda; Bradford, Chastity; Zhang, Frank Fan; Potter, Barry; Proctor, Spencer

2017-01-01

Thirty percent of the world population is diagnosed with metabolic syndrome. High-fat/high-sucrose (HF/HS) diet (Western diet) correlates with metabolic syndrome prevalence. We characterized effects of the HF/HS diet on vascular (arterial stiffness, vasoreactivity, and coronary collateral development) and cardiac (echocardiography) function, oxidative stress, and inflammation in a rat model of metabolic syndrome (JCR rats). Furthermore, we determined whether male versus female animals were affected differentially by the Western diet. Cardiovascular function in JCR male rats was impaired versus normal Sprague-Dawley (SD) rats. HF/HS diet compromised cardiovascular (dys)function in JCR but not SD male rats. In contrast, cardiovascular function was minimally impaired in JCR female rats on normal chow. However, cardiovascular function in JCR female rats on the HF/HS diet deteriorated to levels comparable to JCR male rats on the HF/HS diet. Similarly, oxidative stress was markedly increased in male but not female JCR rats on normal chow but was equally exacerbated by the HF/HS diet in male and female JCR rats. These results indicate that the Western diet enhances oxidative stress and cardiovascular dysfunction in metabolic syndrome and eliminates the protective effect of female sex on cardiovascular function, implying that both males and females with metabolic syndrome are at equal risk for cardiovascular disease. NEW & NOTEWORTHY Western diet abolished protective effect of sex against cardiovascular disease (CVD) development in premenopausal animals with metabolic syndrome. Western diet accelerates progression of CVD in male and female animals with preexisting metabolic syndrome but not normal animals. Exacerbation of baseline oxidative stress correlates with accelerated progression of CVD in metabolic syndrome animals on Western diet. PMID:28087518

The childhood obesity epidemic as a result of nongenetic evolution: the maternal resources hypothesis.

PubMed

Archer, Edward

2015-01-01

Over the past century, socioenvironmental evolution (eg, reduced pathogenic load, decreased physical activity, and improved nutrition) led to cumulative increments in maternal energy resources (ie, body mass and adiposity) and decrements in energy expenditure and metabolic control. These decrements reduced the competition between maternal and fetal energy demands and increased the availability of energy substrates to the intrauterine milieu. This perturbation of mother-conceptus energy partitioning stimulated fetal pancreatic β-cell and adipocyte hyperplasia, thereby inducing an enduring competitive dominance of adipocytes over other tissues in the acquisition and sequestering of nutrient energy via intensified insulin secretion and hyperplastic adiposity. At menarche, the competitive dominance of adipocytes was further amplified via hormone-induced adipocyte hyperplasia and weight-induced decrements in physical activity. These metabolic and behavioral effects were propagated progressively when obese, inactive, metabolically compromised women produced progressively larger, more inactive, metabolically compromised children. Consequently, the evolution of human energy metabolism was markedly altered. This phenotypic evolution was exacerbated by increments in the use of cesarean sections, which allowed both the larger fetuses and the metabolically compromised mothers who produced them to survive and reproduce. Thus, natural selection was iatrogenically rendered artificial selection, and the frequency of obese, inactive, metabolically compromised phenotypes increased in the global population. By the late 20th century, a metabolic tipping point was reached at which the postprandial insulin response was so intense, the relative number of adipocytes so large, and inactivity so pervasive that the competitive dominance of adipocytes in the sequestering of nutrient energy was inevitable and obesity was unavoidable. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Apple Peel Supplemented Diet Reduces Parameters of Metabolic Syndrome and Atherogenic Progression in ApoE-/- Mice.

PubMed

Gonzalez, Jaime; Donoso, Wendy; Sandoval, Nathalie; Reyes, María; Gonzalez, Priscila; Gajardo, Monica; Morales, Erik; Neira, Amalia; Razmilic, Iván; Yuri, José A; Moore-Carrasco, Rodrigo

2015-01-01

Cardiovascular Diseases (CVD) represent about 30% of all causes of death worldwide. The development of CVD is related in many cases with the previous existence of metabolic syndrome (MS). It is known that apple consumption has a cardiovascular protecting effect, containing phenolic compounds with antioxidant effect, which are concentrated in the fruit peel. The objective of this study was to test the effect of apple peel consumption in a murine model of MS and apoE-/- mice. Apple supplemented diets reduced the biochemical parameters (glycaemia, total cholesterol, HDL-cholesterol, LDL-cholesterol, ureic nitrogen, triglycerides, insulin, and asymmetric dimethylarginine (ADMA)) of MS model in CF1 mice significantly. The model apoE-/- mouse was used to evaluate the capacity of the apple peel to revert the progression of the atherogenesis. FD with HAP reverts cholesterol significantly and slows down the progression of the plate diminishing the cholesterol accumulation area. With these results, it can be concluded that the consumption of apple peel reduces several MS parameters and the atherogenic progression in mice.

Oxidative stress, protein modification and Alzheimer disease.

PubMed

Tramutola, A; Lanzillotta, C; Perluigi, M; Butterfield, D Allan

2017-07-01

Alzheimer disease (AD) is a progressive neurodegenerative disease that affects the elderly population with complex etiology. Many hypotheses have been proposed to explain different causes of AD, but the exact mechanisms remain unclear. In this review, we focus attention on the oxidative-stress hypothesis of neurodegeneration and we discuss redox proteomics approaches to analyze post-mortem human brain from AD brain. Collectively, these studies have provided valuable insights into the molecular mechanisms involved both in the pathogenesis and progression of AD, demonstrating the impairment of numerous cellular processes such as energy production, cellular structure, signal transduction, synaptic function, mitochondrial function, cell cycle progression, and degradative systems. Each of these cellular functions normally contributes to maintain healthy neuronal homeostasis, so the deregulation of one or more of these functions could contribute to the pathology and clinical presentation of AD. In particular, we discuss the evidence demonstrating the oxidation/dysfunction of a number of enzymes specifically involved in energy metabolism that support the view that reduced glucose metabolism and loss of ATP are crucial events triggering neurodegeneration and progression of AD. Copyright © 2016 Elsevier Inc. All rights reserved.

Apple Peel Supplemented Diet Reduces Parameters of Metabolic Syndrome and Atherogenic Progression in ApoE−/− Mice

PubMed Central

Gonzalez, Jaime; Donoso, Wendy; Sandoval, Nathalie; Reyes, María; Gonzalez, Priscila; Gajardo, Monica; Morales, Erik; Neira, Amalia; Razmilic, Iván; Yuri, José A.

2015-01-01

Cardiovascular Diseases (CVD) represent about 30% of all causes of death worldwide. The development of CVD is related in many cases with the previous existence of metabolic syndrome (MS). It is known that apple consumption has a cardiovascular protecting effect, containing phenolic compounds with antioxidant effect, which are concentrated in the fruit peel. The objective of this study was to test the effect of apple peel consumption in a murine model of MS and apoE−/− mice. Apple supplemented diets reduced the biochemical parameters (glycaemia, total cholesterol, HDL-cholesterol, LDL-cholesterol, ureic nitrogen, triglycerides, insulin, and asymmetric dimethylarginine (ADMA)) of MS model in CF1 mice significantly. The model apoE−/− mouse was used to evaluate the capacity of the apple peel to revert the progression of the atherogenesis. FD with HAP reverts cholesterol significantly and slows down the progression of the plate diminishing the cholesterol accumulation area. With these results, it can be concluded that the consumption of apple peel reduces several MS parameters and the atherogenic progression in mice. PMID:26075004

41. Photocopy of progress photograph ca. 1974, photographer unknown. Original ...

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

41. Photocopy of progress photograph ca. 1974, photographer unknown. Original photograph Property of United States Air Force, 21" Space Command. This is the source for views 41 to 47. CAPE COD AIR STATION PAVE PAWS FACILITY - SHOWING BUILDING "RED IRON" STEEL STRUCTURE NEARING COMPLETION. - Cape Cod Air Station, Technical Facility-Scanner Building & Power Plant, Massachusetts Military Reservation, Sandwich, Barnstable County, MA

Center for Information Services Fourth Quarterly Progress Report, Phase IIB; Detailed Design and Prototype Development, 1 October 1971 to 31 December 1971.

ERIC Educational Resources Information Center

Kehl, W. B.; And Others

The administrative activity, including organization, staff, budget and external contacts, and the technical progress of IPS development, experimental service, workshops, documentation and related activities of the Center for Information Services (at the University of California, Los Angeles) are reported upon in this document. Pages 9 and 10 may…

Curriculum-Based Measurement: Developing a Computer-Based Assessment Instrument for Monitoring Student Reading Progress on Multiple Indicators

ERIC Educational Resources Information Center

Forster, Natalie; Souvignier, Elmar

2011-01-01

The purpose of this study was to examine the technical adequacy of a computer-based assessment instrument which is based on hierarchical models of text comprehension for monitoring student reading progress following the Curriculum-Based Measurement (CBM) approach. At intervals of two weeks, 120 third-grade students finished eight CBM tests. To…

Role of MicroRNAs in Obesity-Induced Metabolic Disorder and Immune Response.

PubMed

Zhong, Hong; Ma, Minjuan; Liang, Tingming; Guo, Li

2018-01-01

In all living organisms, metabolic homeostasis and the immune system are the most fundamental requirements for survival. Recently, obesity has become a global public health issue, which is the cardinal risk factor for metabolic disorder. Many diseases emanating from obesity-induced metabolic dysfunction are responsible for the activated immune system, including innate and adaptive responses. Of note, inflammation is the manifest accountant signal. Deeply studied microRNAs (miRNAs) have participated in many pathways involved in metabolism and immune responses to protect cells from multiple harmful stimulants, and they play an important role in determining the progress through targeting different inflammatory pathways. Thus, immune response and metabolic regulation are highly integrated with miRNAs. Collectively, miRNAs are the new targets for therapy in immune dysfunction.

Chemical Approaches to Probe Metabolic Networks

PubMed Central

Medina-Cleghorn, Daniel; Nomura, Daniel K.

2013-01-01

One of the more provocative realizations that have come out of the genome sequencing projects is that organisms possess a large number of uncharacterized or poorly characterized enzymes. This finding belies the commonly held notion that our knowledge of cell metabolism is nearly complete, underscoring the vast landscape of unannotated metabolic and signaling networks that operate under normal physiological conditions, let alone in disease states where metabolic networks may be rewired, dysregulated, or altered to drive disease progression. Consequently, the functional annotation of enzymatic pathways represents a grand challenge for researchers in the post-genomic era. This review will highlight the chemical technologies that have been successfully used to characterize metabolism, and put forth some of the challenges we face as we expand our map of metabolic pathways. PMID:23296751

Role of MicroRNAs in Obesity-Induced Metabolic Disorder and Immune Response

PubMed Central

Zhong, Hong; Ma, Minjuan

2018-01-01

In all living organisms, metabolic homeostasis and the immune system are the most fundamental requirements for survival. Recently, obesity has become a global public health issue, which is the cardinal risk factor for metabolic disorder. Many diseases emanating from obesity-induced metabolic dysfunction are responsible for the activated immune system, including innate and adaptive responses. Of note, inflammation is the manifest accountant signal. Deeply studied microRNAs (miRNAs) have participated in many pathways involved in metabolism and immune responses to protect cells from multiple harmful stimulants, and they play an important role in determining the progress through targeting different inflammatory pathways. Thus, immune response and metabolic regulation are highly integrated with miRNAs. Collectively, miRNAs are the new targets for therapy in immune dysfunction. PMID:29484304

Metabolic reconstruction, constraint-based analysis and game theory to probe genome-scale metabolic networks.

PubMed

Ruppin, Eytan; Papin, Jason A; de Figueiredo, Luis F; Schuster, Stefan

2010-08-01

With the advent of modern omics technologies, it has become feasible to reconstruct (quasi-) whole-cell metabolic networks and characterize them in more and more detail. Computer simulations of the dynamic behavior of such networks are difficult due to a lack of kinetic data and to computational limitations. In contrast, network analysis based on appropriate constraints such as the steady-state condition (constraint-based analysis) is feasible and allows one to derive conclusions about the system's metabolic capabilities. Here, we review methods for the reconstruction of metabolic networks, modeling techniques such as flux balance analysis and elementary flux modes and current progress in their development and applications. Game-theoretical methods for studying metabolic networks are discussed as well. Copyright © 2010 Elsevier Ltd. All rights reserved.

Impaired in vivo mitochondrial Krebs cycle activity after myocardial infarction assessed using hyperpolarized magnetic resonance spectroscopy.

PubMed

Dodd, Michael S; Atherton, Helen J; Carr, Carolyn A; Stuckey, Daniel J; West, James A; Griffin, Julian L; Radda, George K; Clarke, Kieran; Heather, Lisa C; Tyler, Damian J

2014-11-01

Myocardial infarction (MI) is one of the leading causes of heart failure. An increasing body of evidence links alterations in cardiac metabolism and mitochondrial function with the progression of heart disease. The aim of this work was to, therefore, follow the in vivo mitochondrial metabolic alterations caused by MI, thereby allowing a greater understanding of the interplay between metabolic and functional abnormalities. Using hyperpolarized carbon-13 ((13)C)-magnetic resonance spectroscopy, in vivo alterations in mitochondrial metabolism were assessed for 22 weeks after surgically induced MI with reperfusion in female Wister rats. One week after MI, there were no detectable alterations in in vivo cardiac mitochondrial metabolism over the range of ejection fractions observed (from 28% to 84%). At 6 weeks after MI, in vivo mitochondrial Krebs cycle activity was impaired, with decreased (13)C-label flux into citrate, glutamate, and acetylcarnitine, which correlated with the degree of cardiac dysfunction. These changes were independent of alterations in pyruvate dehydrogenase flux. By 22 weeks, alterations were also seen in pyruvate dehydrogenase flux, which decreased at lower ejection fractions. These results were confirmed using in vitro analysis of enzyme activities and metabolomic profiles of key intermediates. The in vivo decrease in Krebs cycle activity in the 6-week post-MI heart may represent an early maladaptive phase in the metabolic alterations after MI in which reductions in Krebs cycle activity precede a reduction in pyruvate dehydrogenase flux. Changes in mitochondrial metabolism in heart disease are progressive and proportional to the degree of cardiac impairment. © 2014 American Heart Association, Inc.

Impaired In Vivo Mitochondrial Krebs Cycle Activity After Myocardial Infarction Assessed Using Hyperpolarized Magnetic Resonance Spectroscopy

PubMed Central

Carr, Carolyn A.; Stuckey, Daniel J.; West, James A.; Griffin, Julian L.; Radda, George K.; Clarke, Kieran; Heather, Lisa C.; Tyler, Damian J.

2015-01-01

Background Myocardial infarction (MI) is one of the leading causes of heart failure. An increasing body of evidence links alterations in cardiac metabolism and mitochondrial function with the progression of heart disease. The aim of this work was to, therefore, follow the in vivo mitochondrial metabolic alterations caused by MI, thereby allowing a greater understanding of the interplay between metabolic and functional abnormalities. Methods and Results Using hyperpolarized carbon-13 (13C)-magnetic resonance spectroscopy, in vivo alterations in mitochondrial metabolism were assessed for 22 weeks after surgically induced MI with reperfusion in female Wister rats. One week after MI, there were no detectable alterations in in vivo cardiac mitochondrial metabolism over the range of ejection fractions observed (from 28% to 84%). At 6 weeks after MI, in vivo mitochondrial Krebs cycle activity was impaired, with decreased 13C-label flux into citrate, glutamate, and acetylcarnitine, which correlated with the degree of cardiac dysfunction. These changes were independent of alterations in pyruvate dehydrogenase flux. By 22 weeks, alterations were also seen in pyruvate dehydrogenase flux, which decreased at lower ejection fractions. These results were confirmed using in vitro analysis of enzyme activities and metabolomic profiles of key intermediates. Conclusions The in vivo decrease in Krebs cycle activity in the 6-week post-MI heart may represent an early maladaptive phase in the metabolic alterations after MI in which reductions in Krebs cycle activity precede a reduction in pyruvate dehydrogenase flux. Changes in mitochondrial metabolism in heart disease are progressive and proportional to the degree of cardiac impairment. PMID:25201905

Profile of Circulatory Metabolites in a Relapsing-remitting Animal Model of Multiple Sclerosis using Global Metabolomics

PubMed Central

Mangalam, AK; Poisson, LM; Nemutlu, E; Datta, I; Denic, A; Dzeja, P; Rodriguez, M; Rattan, R; Giri, S

2013-01-01

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the CNS. Although, MS is well characterized in terms of the role played by immune cells, cytokines and CNS pathology, nothing is known about the metabolic alterations that occur during the disease process in circulation. Recently, metabolic aberrations have been defined in various disease processes either as contributing to the disease, as potential biomarkers, or as therapeutic targets. Thus in an attempt to define the metabolic alterations that may be associated with MS disease progression, we profiled the plasma metabolites at the chronic phase of disease utilizing relapsing remitting-experimental autoimmune encephalomyelitis (RR-EAE) model in SJL mice. At the chronic phase of the disease (day 45), untargeted global metabolomic profiling of plasma collected from EAE diseased SJL and healthy mice was performed, using a combination of high-throughput liquid-and-gas chromatography with mass spectrometry. A total of 282 metabolites were identified, with significant changes observed in 44 metabolites (32 up-regulated and 12 down-regulated), that mapped to lipid, amino acid, nucleotide and xenobiotic metabolism and distinguished EAE from healthy group (p<0.05, false discovery rate (FDR)<0.23). Mapping the differential metabolite signature to their respective biochemical pathways using the Kyoto Encyclopedia of Genes and Genomics (KEGG) database, we found six major pathways that were significantly altered (containing concerted alterations) or impacted (containing alteration in key junctions). These included bile acid biosynthesis, taurine metabolism, tryptophan and histidine metabolism, linoleic acid and D-arginine metabolism pathways. Overall, this study identified a 44 metabolite signature drawn from various metabolic pathways which correlated well with severity of the EAE disease, suggesting that these metabolic changes could be exploited as (1) biomarkers for EAE/MS progression and (2) to design new treatment paradigms where metabolic interventions could be combined with present and experimental therapeutics to achieve better treatment of MS. PMID:24273690

Volatile science? Metabolic engineering of terpenoids in plants.

PubMed

Aharoni, Asaph; Jongsma, Maarten A; Bouwmeester, Harro J

2005-12-01

Terpenoids are important for plant survival and also possess biological properties that are beneficial to humans. Here, we describe the state of the art in terpenoid metabolic engineering, showing that significant progress has been made over the past few years. Subcellular targeting of enzymes has demonstrated that terpenoid precursors in subcellular compartments are not as strictly separated as previously thought and that multistep pathway engineering is feasible, even across cell compartments. These engineered plants show that insect behavior is influenced by terpenoids. In the future, we expect rapid progress in the engineering of terpenoid production in plants. In addition to commercial applications, such transgenic plants should increase our understanding of the biological relevance of these volatile secondary metabolites.

Preliminary technical results review of FY81 experiments. Volume 1: Fiscal year 1981/82 spring small grains pilot experiment. [Canada and the United States

NASA Technical Reports Server (NTRS)

1981-01-01

Technical progress made in the foreign commodity production forecasting for the advancement of spring small grains (SSG) area estimation is reported with emphasis on results achieved since the last AgRISTARS level semiannual review. Major objectives and accomplishments are reviewed and the experiment is described. The technical approach data assessment, and data systems used are considered. Results of the group approach comparison study are presented along with preliminary aggregation results for SSG processing procedures. The outlook for the future is assessed.

JPRS Report, Science & Technology, USSR: Science & Technology Policy.

DTIC Science & Technology

1987-07-07

fully reflect the end results of scientific and technical progress. The formation of the unified fund for the development of science and technology ...209058 JPRS-UST-87-009 7 JULY 1987 /ffifr FOREIGN BROADCAST INFORMATION SERVICE JPRS Repor Science & Technology USSR: Science... Technology Policy 19980715 121 REPRODUCED BY U.S. DEPARTMENTOF COMMERCE NATIONAL TECHNICAL •^ INFORMATIONSERVICE A rf *r*lQ ürjA T Tw» SPRINGFIELD, VA

Advances in optimal routing through computer networks

NASA Technical Reports Server (NTRS)

Paz, I. M.

1977-01-01

The optimal routing problem is defined. Progress in solving the problem during the previous decade is reviewed, with special emphasis on technical developments made during the last few years. The relationships between the routing, the throughput, and the switching technology used are discussed and their future trends are reviewed. Economic aspects are also briefly considered. Modern technical approaches for handling the routing problems and, more generally, the flow control problems are reviewed.

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

Rhinefrank, Kenneth; Lamb, Bradford; Prudell, Joseph

This Project aims to satisfy objectives of the DOE’s Water Power Program by completing a system detailed design (SDD) and other important activities in the first phase of a utility-scale grid-connected ocean wave energy demonstration. In early 2012, Columbia Power (CPwr) had determined that further cost and performance optimization was necessary in order to commercialize its StingRAY wave energy converter (WEC). CPwr’s progress toward commercialization, and the requisite technology development path, were focused on transitioning toward a commercial-scale demonstration. This path required significant investment to be successful, and the justification for this investment required improved annual energy production (AEP) andmore » lower capital costs. Engineering solutions were developed to address these technical and cost challenges, incorporated into a proposal to the US Department of Energy (DOE), and then adapted to form the technical content and statement of project objectives of the resulting Project (DE-EE0005930). Through Project cost-sharing and technical collaboration between DOE and CPwr, and technical collaboration with Oregon State University (OSU), National Renewable Energy Lab (NREL) and other Project partners, we have demonstrated experimentally that these conceptual improvements have merit and made significant progress towards a certified WEC system design at a selected and contracted deployment site at the Wave Energy Test Site (WETS) at the Marine Corps Base in Oahu, HI (MCBH).« less

Formation of toxic 2-nonyl-p-benzoquinones from α-tertiary 4-nonylphenol isomers during microbial metabolism of technical nonylphenol.

PubMed

Gabriel, Frédéric L P; Mora, Mauricio Arrieta; Kolvenbach, Boris A; Corvini, Philippe F X; Kohler, Hans-Peter E

2012-06-05

In many environmental compartments, microbial degradation of α-quaternary nonylphenols proceeds along an ipso-substitution pathway. It has been reported that technical nonylphenol contains, besides α-quaternary nonylphenols, minor amounts of various α-H, α-methyl substituted tertiary isomers. Here, we show that potentially toxic metabolites of such minor components are formed during ipso-degradation of technical nonylphenol by Sphingobium xenophagum Bayram, a strain isolated from activated sewage sludge. Small but significant amounts of nonylphenols were converted to the corresponding nonylhydroquinones, which in the presence of air oxygen oxidized to the corresponding nonyl-p-benzoquinones-yielding a complex mixture of potentially toxic metabolites. Through reduction with ascorbic acid and subsequent analysis by gas chromatography-mass spectrometry, we were able to characterize this unique metabolic fingerprint and to show that its components originated for the most part from α-tertiary nonylphenol isomers. Furthermore, our results indicate that the metabolites mixture also contained several α, β-dehydrogenated derivatives of nonyl-p-benzoquinones that originated by hydroxylation induced rearrangement, and subsequent ring and side chain oxidation from α-tertiary nonylphenol isomers. We predict that in nonylphenol polluted natural systems, in which microbial ipso-degradation is prominent, 2-alkylquinone metabolites will be produced and will contribute to the overall toxicity of the remaining material.

[Charles Darwin and the problem of evolutionary progress].

PubMed

Iordanskiĭ, N N

2010-01-01

According to Ch. Darwin's evolutionary theory, evolutionary progress (interpreted as morpho-physiological progress or arogenesis in recent terminology) is one of logical results of natural selection. At the same time, natural selection does not hold any factors especially promoting evolutionary progress. Darwin emphasized that the pattern of evolutionary changes depends on organism nature more than on the pattern of environment changes. Arogenesis specificity is determined by organization of rigorous biological systems - integral organisms. Onward progressive development is determined by fundamental features of living organisms: metabolism and homeostasis. The concept of social Darwinism differs fundamentally from Darwin's ideas about the most important role of social instincts in progress of mankind. Competition and selection play secondary role in socio-cultural progress of human society.

FDG-PET metabolic response predicts outcomes in anal cancer managed with chemoradiotherapy.

PubMed

Day, F L; Link, E; Ngan, S; Leong, T; Moodie, K; Lynch, C; Michael, M; Winton, E de; Hogg, A; Hicks, R J; Heriot, A

2011-08-09

The aim was to investigate the correlation between (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) metabolic response to chemoradiotherapy and clinical outcomes in squamous cell carcinoma (SCC) of the anus. A total of 48 patients with biopsy-proven anal SCC underwent FDG-PET scans at baseline and post chemoradiotherapy (54 Gy, concurrent 5-FU/mitomycin). Kaplan-Meier analysis was used to determine survival outcomes according to FDG-PET metabolic response. In all, 79% patients (n=38) had a complete metabolic response (CMR) at all sites of disease, 15% (n=7) had a CMR in regional nodes but only partial response in the primary tumour (overall partial metabolic response (PMR)) and 6% (n=3) had progressive distant disease despite CMR locoregionally (overall no response (NR)). The 2-year progression-free survival (PFS) was 95% for patients with a CMR, 71% for PMR and 0% for NR (P<0.0001). The 5-year overall survival (OS) was 88% in CMR, 69% in PMR and 0% in NR (P<0.0001). Cox proportional hazards regression analyses for PFS and OS found significant associations for incomplete (PMR+NR) vs complete FDG-PET response to treatment only, (HR 4.1 (95% CI: 1.5-11.5, P=0.013) and 6.7 (95% CI: 2.1-21.6, P=0.002), respectively). FDG-PET metabolic response to chemoradiotherapy in anal cancer is significantly associated with PFS and OS, and in this cohort incomplete FDG-PET response was a stronger predictor than T or N stage.

Cardiac Metabolism in Heart Failure - Implications beyond ATP production

PubMed Central

Doenst, Torsten; Nguyen, T. Dung; Abel, E. Dale

2013-01-01

The heart has a high rate of ATP production and turnover which is required to maintain its continuous mechanical work. Perturbations in ATP generating processes may therefore affect contractile function directly. Characterizing cardiac metabolism in heart failure revealed several metabolic alterations termed metabolic remodeling, ranging from changes in substrate utilization to mitochondrial dysfunction, ultimately resulting in ATP deficiency and impaired contractility. However, ATP depletion is not the only relevant consequence of metabolic remodeling during heart failure. By providing cellular building blocks and signaling molecules, metabolic pathways control essential processes such as cell growth and regeneration. Thus, alterations in cardiac metabolism may also affect the progression to heart failure by mechanisms beyond ATP supply. Our aim is therefore to highlight that metabolic remodeling in heart failure not only results in impaired cardiac energetics, but also induces other processes implicated in the development of heart failure such as structural remodeling and oxidative stress. Accordingly, modulating cardiac metabolism in heart failure may have significant therapeutic relevance that goes beyond the energetic aspect. PMID:23989714

Tissue-specific insulin signaling, metabolic syndrome and cardiovascular disease

PubMed Central

Rask-Madsen, Christian; Kahn, C. Ronald

2012-01-01

Summary Impaired insulin signaling is central to the development of the metabolic syndrome and can promote cardiovascular disease indirectly through development of abnormal glucose and lipid metabolism, hypertension and a proinflammatory state. However, insulin action directly on vascular endothelium, atherosclerotic plaque macrophages, and in the heart, kidney, and retina has now been described, and impaired insulin signaling in these locations can alter progression of cardiovascular disease in the metabolic syndrome and affect development of microvascular complications of diabetes. Recent advances in our understanding of the complex pathophysiology of insulin’s effects on vascular tissues offer new opportunities for preventing these cardiovascular disorders. PMID:22895666

Review of nonalcoholic fatty liver disease in women with polycystic ovary syndrome

PubMed Central

Kelley, Carly E; Brown, Ann J; Diehl, Anna Mae; Setji, Tracy L

2014-01-01

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-aged women. Women with PCOS frequently have metabolic complications including insulin resistance (IR), early diabetes, hypertension and dyslipidemia. Recent studies have demonstrated an association between PCOS and another metabolic complication: nonalcoholic fatty liver disease (NAFLD). NAFLD occurs as a result of abnormal lipid handling by the liver, which sensitizes the liver to injury and inflammation. It can progress to nonalcoholic steatohepatitis (NASH), which is characterized by hepatocyte injury and apoptosis. With time and further inflammation, NASH can progress to cirrhosis. Thus, given the young age at which NAFLD may occur in PCOS, these women may be at significant risk for progressive hepatic injury over the course of their lives. Many potential links between PCOS and NAFLD have been proposed, most notably IR and hyperandrogenemia. Further studies are needed to clarify the association between PCOS and NAFLD. In the interim, clinicians should be aware of this connection and consider screening for NAFLD in PCOS patients who have other metabolic risk factors. The optimal method of screening is unknown. However, measuring alanine aminotransferase and/or obtaining ultrasound on high-risk patients can be considered. First line treatment consists of lifestyle interventions and weight loss, with possible pharmacologic interventions in some cases. PMID:25339805

Molecular monitoring of epithelial-to-mesenchymal transition in breast cancer cells by means of Raman spectroscopy.

PubMed

Marro, M; Nieva, C; Sanz-Pamplona, R; Sierra, A

2014-09-01

In breast cancer the presence of cells undergoing the epithelial-to-mesenchymal transition is indicative of metastasis progression. Since metabolic features of breast tumour cells are critical in cancer progression and drug resistance, we hypothesized that the lipid content of malignant cells might be a useful indirect measure of cancer progression. In this study Multivariate Curve Resolution was applied to cellular Raman spectra to assess the metabolic composition of breast cancer cells undergoing the epithelial to mesenchymal transition. Multivariate Curve Resolution analysis led to the conclusion that this transition affects the lipid profile of cells, increasing tryptophan but maintaining a low fatty acid content in comparison with highly metastatic cells. Supporting those results, a Partial Least Square-Discriminant analysis was performed to test the ability of Raman spectroscopy to discriminate the initial steps of epithelial to mesenchymal transition in breast cancer cells. We achieved a high level of sensitivity and specificity, 94% and 100%, respectively. In conclusion, Raman microspectroscopy coupled with Multivariate Curve Resolution enables deconvolution and tracking of the molecular content of cancer cells during a biochemical process, being a powerful, rapid, reagent-free and non-invasive tool for identifying metabolic features of breast cancer cell aggressiveness at first stages of malignancy. Copyright © 2014 Elsevier B.V. All rights reserved.

Genetic Determinants of Cardio-Metabolic Risk: A Proposed Model for Phenotype Association and Interaction

PubMed Central

Blackett, Piers R; Sanghera, Dharambir K

2012-01-01

This review provides a translational and unifying summary of metabolic syndrome genetics and highlights evidence that genetic studies are starting to unravel and untangle origins of the complex and challenging cluster of disease phenotypes. The associated genes effectively express in the brain, liver, kidney, arterial endothelium, adipocytes, myocytes and β cells. Progression of syndrome traits has been associated with ectopic lipid accumulation in the arterial wall, visceral adipocytes, myocytes, and liver. Thus it follows that the genetics of dyslipidemia, obesity, and non-alcoholic fatty liver (NAFLD) disease are central in triggering progression of the syndrome to overt expression of disease traits, and have become a key focus of interest for early detection and for designing prevention and treatments. To support the “birds’ eye view” approach we provide a road-map depicting commonality and interrelationships between the traits and their genetic and environmental determinants based on known risk factors, metabolic pathways, pharmacological targets, treatment responses, gene networks, pleiotropy, and association with circadian rhythm. Although only a small portion of the known heritability is accounted for and there is insufficient support for clinical application of gene-based prediction models, there is direction and encouraging progress in a rapidly moving field that is beginning to show clinical relevance. PMID:23351585

Use of a Bacterial Luciferase Monitoring System To Estimate Real-Time Dynamics of Intracellular Metabolism in Escherichia coli.

PubMed

Shimada, Tomohiro; Tanaka, Kan

2016-10-01

Regulation of central carbon metabolism has long been an important research subject in every organism. While the dynamics of metabolic flows during changes in available carbon sources have been estimated based on changes in metabolism-related gene expression, as well as on changes in the metabolome, the flux change itself has scarcely been measured because of technical difficulty, which has made conclusions elusive in many cases. Here, we used a monitoring system employing Vibrio fischeri luciferase to probe the intracellular metabolic condition in Escherichia coli Using a batch culture provided with a limited amount of glucose, we performed a time course analysis, where the predominant carbon source shifts from glucose to acetate, and identified a series of sequential peaks in the luciferase activity (peaks 1 to 4). Two major peaks, peaks 1 and 3, were considered to correspond to the glucose and acetate consuming phases, respectively, based on the glucose, acetate, and dissolved oxygen concentrations in the medium. The pattern of these peaks was changed by the addition of a different carbon source or by an increasing concentration of glucose, which was consistent with the present model. Genetically, mutations involved in glycolysis or the tricarboxylic acid (TCA) cycle/gluconeogenesis specifically affected peak 1 or peak 3, respectively, as expected from the corresponding metabolic phase. Intriguingly, mutants for the acetate excretion pathway showed a phenotype of extended peak 2 and delayed transition to the TCA cycle/gluconeogenesis phase, which suggests that peak 2 represents the metabolic transition phase. These results indicate that the bacterial luciferase monitoring system is useful to understand the real-time dynamics of metabolism in living bacterial cells. Intracellular metabolic flows dynamically change during shifts in available carbon sources. However, because of technical difficulty, the flux change has scarcely been measured in living cells. Here, we used a Vibrio fischeri luciferase monitoring system to probe the intracellular metabolic condition in Escherichia coli Using a limited amount of glucose batch culture, a series of sequential peaks (peaks 1 to 4) in the luciferase activity was observed. Changes in the pattern of these peaks by the addition of extra carbon sources and in mutant strains involved in glycolysis or the TCA cycle/gluconeogenesis gene assigned the metabolic phase corresponding to peak 1 as the glycolysis phase and peak 3 as the TCA cycle/gluconeogenesis phase. Intriguingly, the acetate excretion pathway engaged in peak 2 represents the metabolic transition phase. These results indicate that the bacterial luciferase monitoring system is useful to understand the real-time dynamics of metabolism in living bacterial cells. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

[Improving industrial microbial stress resistance by metabolic engineering: a review].

PubMed

Fu, Ruiyan; Li, Yin

2010-09-01

Metabolic engineering is a technologic platform for industrial strain improvement and aims not only at modifying microbial metabolic fluxes, but also improving the physiological performance of industrial microbes. Microbes will meet multiple stresses in industrial processes. Consequently, elicited gene responses might result in a decrease in overall cell fitness and the efficiency of biotransformation. Thus, it is crucial to develop robust and productive microbial strains that can be integrated into industrial-scale bioprocesses. In this review, we focus on the progress of these novel methods and strategies for engineering stress-tolerance phenotypes referring to rational metabolic engineering and inverse metabolic engineering in recent years. In addition, we also address problems existing in this area and future research needs of microbial physiological functionality engineering.

Bridging the gap between fluxomics and industrial biotechnology.

PubMed

Feng, Xueyang; Page, Lawrence; Rubens, Jacob; Chircus, Lauren; Colletti, Peter; Pakrasi, Himadri B; Tang, Yinjie J

2010-01-01

Metabolic flux analysis is a vital tool used to determine the ultimate output of cellular metabolism and thus detect biotechnologically relevant bottlenecks in productivity. ¹³C-based metabolic flux analysis (¹³C-MFA) and flux balance analysis (FBA) have many potential applications in biotechnology. However, noteworthy hurdles in fluxomics study are still present. First, several technical difficulties in both ¹³C-MFA and FBA severely limit the scope of fluxomics findings and the applicability of obtained metabolic information. Second, the complexity of metabolic regulation poses a great challenge for precise prediction and analysis of metabolic networks, as there are gaps between fluxomics results and other omics studies. Third, despite identified metabolic bottlenecks or sources of host stress from product synthesis, it remains difficult to overcome inherent metabolic robustness or to efficiently import and express nonnative pathways. Fourth, product yields often decrease as the number of enzymatic steps increases. Such decrease in yield may not be caused by rate-limiting enzymes, but rather is accumulated through each enzymatic reaction. Fifth, a high-throughput fluxomics tool hasnot been developed for characterizing nonmodel microorganisms and maximizing their application in industrial biotechnology. Refining fluxomics tools and understanding these obstacles will improve our ability to engineer highly efficient metabolic pathways in microbial hosts.

40 CFR 57.605 - Consent.

Code of Federal Regulations, 2011 CFR

2011-07-01

... such agency determines are needed to evaluate the technical or economic merits of the program; (c... discussions of progress, interpretation of data and results, and any other similar purposes as deemed...

78 FR 14361 - Proposal Review; Notice of Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-05

... awards. The review and evaluation may also include assessment of the progress of awarded proposals. The... confidential nature, including technical information; financial data, such as salaries; and personal...

78 FR 54686 - Proposal Review; Notice of Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-05

... awards. The review and evaluation may also include assessment of the progress of awarded proposals. The... confidential nature, including technical information; financial data, such as salaries; and personal...

Engineering plant metabolism into microbes: from systems biology to synthetic biology.

PubMed

Xu, Peng; Bhan, Namita; Koffas, Mattheos A G

2013-04-01

Plant metabolism represents an enormous repository of compounds that are of pharmaceutical and biotechnological importance. Engineering plant metabolism into microbes will provide sustainable solutions to produce pharmaceutical and fuel molecules that could one day replace substantial portions of the current fossil-fuel based economy. Metabolic engineering entails targeted manipulation of biosynthetic pathways to maximize yields of desired products. Recent advances in Systems Biology and the emergence of Synthetic Biology have accelerated our ability to design, construct and optimize cell factories for metabolic engineering applications. Progress in predicting and modeling genome-scale metabolic networks, versatile gene assembly platforms and delicate synthetic pathway optimization strategies has provided us exciting opportunities to exploit the full potential of cell metabolism. In this review, we will discuss how systems and synthetic biology tools can be integrated to create tailor-made cell factories for efficient production of natural products and fuel molecules in microorganisms. Copyright © 2012 Elsevier Ltd. All rights reserved.

Personal Background Interview of Jim McBarron

NASA Technical Reports Server (NTRS)

McBarron, Jim; Wright, Rebecca

2012-01-01

Jim McBarron exhibits a wealth of knowledge gathered from more than 40 years of experience with NASA, EVA, and spacesuits. His biography, progression of work at NASA, impact on EVA and the U.S. spacesuit, and career accomplishments are of interest to many. Wright, from the JSC History Office, conducted a personal background interview with McBarron. This interview highlighted the influences and decision-making methods that impacted McBarron's technical and management contributions to the space program. Attendees gained insight on the external and internal NASA influences on career progression within the EVA and spacesuit, and the type of accomplishments and technical advances that committed individuals can make. He concluded the presentation with a question and answer period that included a brief discussion about close calls and Russian spacesuits.

Moses Lake Fishery Restoration Project; Factors Affecting the Recreational Fishery in Moses Lake Washington, Annual Report 2002-2003.

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

Burgess, Dave

2003-11-01

This annual report is a precursor to the final technical report we will be writing the next contract period. Consequently, this report, covering the period between September 27, 2002, and September 26, 2003, represents a progress report towards the final technical report we anticipate completing by September 26, 2004. Sample analysis and field work have progressed well and we anticipate no further delays. There are 4 objectives: (1) To quantify secondary production Moses Lake; (2) To quantify the influence of predation on target fishes in Moses Lake; (3) To quantify mortality of selected fished in Moses Lake; and (4) Tomore » assess effects of habitat changes from shoreline development and carp on the fish community in Moses Lake.« less

Yeast biotechnology: teaching the old dog new tricks.

PubMed

Mattanovich, Diethard; Sauer, Michael; Gasser, Brigitte

2014-03-06

Yeasts are regarded as the first microorganisms used by humans to process food and alcoholic beverages. The technology developed out of these ancient processes has been the basis for modern industrial biotechnology. Yeast biotechnology has gained great interest again in the last decades. Joining the potentials of genomics, metabolic engineering, systems and synthetic biology enables the production of numerous valuable products of primary and secondary metabolism, technical enzymes and biopharmaceutical proteins. An overview of emerging and established substrates and products of yeast biotechnology is provided and discussed in the light of the recent literature.

Resistance to diabetes-promoting lifestyle factors -- what is the mechanism?

PubMed

Kolb, Hubert

2012-08-01

Not all people exposed to diabetes-promoting lifestyle factors progress to overt type 2 diabetes. The emerging concept of hormesis provides an explanation for the resistance to metabolic stress. Hormesis requires limited stress or damage which elicits an adaptive repair and protective response which renders the organism resistant to further metabolic stress. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

PHENYLKETONURIA, A COMPREHENSIVE BIBLIOGRAPHY, 1964.

ERIC Educational Resources Information Center

Children's Bureau (DHEW), Washington, DC.

INTENDED AS AN AID TO PROFESSIONAL AND TECHNICAL PERSONS INTERESTED IN PHENYLKETONURIA (PKU), THE BIBLIOGRAPHY LISTS AND ANNOTATES 817 ITEMS. CONTENT DIVISIONS ARE (1) GENERAL--MONOGRAPHS AND ARTICLES, (2) BIOCHEMISTRY--METABOLISM, EXPERIMENTS, TESTS, AND CASES IN WHICH THE EMPHASIS IS ON BIOCHEMISTRY, (3) GENETICS--GENE STUDIES, HEREDITARY…

DISTRIBUTION OF PCB 84 ENANTIOMERS IN C57BL/6 MICE

EPA Science Inventory

Nineteen of the 209 possible PCB congeners exist as pairs of stable rotational isomers that are enantiomeric to each other. A racemic mixture of PCB atropisomers is present in technical PCB mixtures, thus raising concerns about enantioselective distribution, metabolism, and dispo...

Metabolic Context of the Competence-Induced Checkpoint for Cell Replication in Streptococcus suis.

PubMed

Zaccaria, Edoardo; Wells, Jerry M; van Baarlen, Peter

2016-01-01

Natural genetic transformation is a transient, rapidly progressing energy-consuming process characterized by expression of the transformasome and competence-associated regulatory genes. This transient state is tightly controlled to avoid potentially adverse effects of genetic recombination on genome integrity during cell division. We investigated the global response of Streptococcus suis to exposure to the SigX competence-inducing peptide (XIP), and thus to the activation of the competence machinery, using time series analysis together with PCA analysis, gene clustering followed by heatmap visualisation, and GO enrichment analysis. We explored the possible regulatory link between metabolism and competence, and predicted the physiological adaptation of S. suis during competence induction, progression and exit using transcriptome analysis. We showed that competence development is associated with a suppression of basal metabolism, which may have consequences for the microbe's resilience to fluctuations in the environment, as competence is costly in terms of use of energy and protein translation. Furthermore our data suggest that several basal metabolic pathways are incompatible with activation of competence in S. suis. This study also showed that targeting specific pathways during the development of competence, might render S. suis more vulnerable toward novel antibiotic therapies.

Metabolic Context of the Competence-Induced Checkpoint for Cell Replication in Streptococcus suis

PubMed Central

Zaccaria, Edoardo; Wells, Jerry M.

2016-01-01

Natural genetic transformation is a transient, rapidly progressing energy-consuming process characterized by expression of the transformasome and competence-associated regulatory genes. This transient state is tightly controlled to avoid potentially adverse effects of genetic recombination on genome integrity during cell division. We investigated the global response of Streptococcus suis to exposure to the SigX competence-inducing peptide (XIP), and thus to the activation of the competence machinery, using time series analysis together with PCA analysis, gene clustering followed by heatmap visualisation, and GO enrichment analysis. We explored the possible regulatory link between metabolism and competence, and predicted the physiological adaptation of S. suis during competence induction, progression and exit using transcriptome analysis. We showed that competence development is associated with a suppression of basal metabolism, which may have consequences for the microbe's resilience to fluctuations in the environment, as competence is costly in terms of use of energy and protein translation. Furthermore our data suggest that several basal metabolic pathways are incompatible with activation of competence in S. suis. This study also showed that targeting specific pathways during the development of competence, might render S. suis more vulnerable toward novel antibiotic therapies. PMID:27149631

Wild Blueberries (Vaccinium myrtillus) Alleviate Inflammation and Hypertension Associated with Developing Obesity in Mice Fed with a High-Fat Diet

PubMed Central

Mykkänen, Otto T.; Huotari, Anne; Herzig, Karl-Heinz; Dunlop, Thomas W.; Mykkänen, Hannu; Kirjavainen, Pirkka V.

2014-01-01

Background Low-grade metabolic inflammation and hypertension are primary mechanisms involved in obesity-associated adverse health effects. Berries, especially Nordic wild blueberries (hereafter referred to as bilberries), represent an important source of dietary anthocyanins, a group of polyphenols with potential beneficial effects to combat obesity-associated metabolic disturbances. Methods The effects of 5% or 10% (w/w) of whole bilberries (BB) were studied on the development of obesity and its metabolic disturbances in C57BL mice fed with a high-fat diet (HFD) for three months. Cytokines, inflammatory cells, systolic blood pressure, glucose tolerance, insulin sensitivity, weight gain, body fat, food consumption and energy metabolism were assessed. Results Bilberries ameliorated type 1 pro-inflammatory responsiveness induced by HFD. This was indicated by the altered cytokine profile and the reduced prevalence of interferon gamma -producing T-cells, in particular T helper type 1 cells. Bilberries also prevented the progression of obesity associated long term increase in systolic blood pressure in mice. Conclusions Bilberries reduce the development of systemic inflammation and prevent the progression of chronic hypertension, thus supporting their potential role in alleviating the adverse health effects associated with developing obesity. PMID:25501421

A metabolic switch toward lipid use in glycolytic muscle is an early pathologic event in a mouse model of amyotrophic lateral sclerosis

PubMed Central

Palamiuc, Lavinia; Schlagowski, Anna; Ngo, Shyuan T; Vernay, Aurelia; Dirrig-Grosch, Sylvie; Henriques, Alexandre; Boutillier, Anne-Laurence; Zoll, Joffrey; Echaniz-Laguna, Andoni; Loeffler, Jean-Philippe; René, Frédérique

2015-01-01

Amyotrophic lateral sclerosis (ALS) is the most common fatal motor neuron disease in adults. Numerous studies indicate that ALS is a systemic disease that affects whole body physiology and metabolic homeostasis. Using a mouse model of the disease (SOD1G86R), we investigated muscle physiology and motor behavior with respect to muscle metabolic capacity. We found that at 65 days of age, an age described as asymptomatic, SOD1G86R mice presented with improved endurance capacity associated with an early inhibition in the capacity for glycolytic muscle to use glucose as a source of energy and a switch in fuel preference toward lipids. Indeed, in glycolytic muscles we showed progressive induction of pyruvate dehydrogenase kinase 4 expression. Phosphofructokinase 1 was inhibited, and the expression of lipid handling molecules was increased. This mechanism represents a chronic pathologic alteration in muscle metabolism that is exacerbated with disease progression. Further, inhibition of pyruvate dehydrogenase kinase 4 activity with dichloroacetate delayed symptom onset while improving mitochondrial dysfunction and ameliorating muscle denervation. In this study, we provide the first molecular basis for the particular sensitivity of glycolytic muscles to ALS pathology. PMID:25820275

Progressive metabolic impairment underlies the novel nematicidal action of fluensulfone on the potato cyst nematode Globodera pallida.

PubMed

Kearn, James; Lilley, Catherine; Urwin, Peter; O'Connor, Vincent; Holden-Dye, Lindy

2017-10-01

Fluensulfone is a new nematicide with an excellent profile of selective toxicity against plant parasitic nematodes. Here, its effects on the physiology and biochemistry of the potato cyst nematode Globodera pallida have been investigated and comparisons made with its effect on the life-span of the free-living nematode Caenorhabditis elegans to provide insight into its mode of action and its selective toxicity. Fluensulfone exerts acute effects (≤1h; ≥100μM) on stylet thrusting and motility of hatched second stage G. pallida juveniles (J2s). Chronic exposure to lower concentrations of fluensulfone (≥3days; ≤30μM), reveals a slowly developing metabolic insult in which G. pallida J2s sequentially exhibit a reduction in motility, loss of a metabolic marker for cell viability, high lipid content and tissue degeneration prior to death. These effects are absent in adults and dauers of the model genetic nematode Caenorhabditis elegans. The nematicidal action of fluensulfone follows a time-course which progresses from an early impact on motility through to an accumulating metabolic impairment, an inability to access lipid stores and death. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Flat-plate solar array project. Volume 8: Project analysis and integration

NASA Technical Reports Server (NTRS)

Mcguire, P.; Henry, P.

1986-01-01

Project Analysis and Integration (PA&I) performed planning and integration activities to support management of the various Flat-Plate Solar Array (FSA) Project R&D activities. Technical and economic goals were established by PA&I for each R&D task within the project to coordinate the thrust toward the National Photovoltaic Program goals. A sophisticated computer modeling capability was developed to assess technical progress toward meeting the economic goals. These models included a manufacturing facility simulation, a photovoltaic power station simulation and a decision aid model incorporating uncertainty. This family of analysis tools was used to track the progress of the technology and to explore the effects of alternative technical paths. Numerous studies conducted by PA&I signaled the achievement of milestones or were the foundation of major FSA project and national program decisions. The most important PA&I activities during the project history are summarized. The PA&I planning function is discussed and how it relates to project direction and important analytical models developed by PA&I for its analytical and assessment activities are reviewed.

Ongoing Progress in Spacecraft Controls

NASA Technical Reports Server (NTRS)

Ghosh, Dave (Editor)

1992-01-01

This publication is a collection of papers presented at the Mars Mission Research Center workshop on Ongoing Progress in Spacecraft Controls. The technical program addressed additional Mars mission control problems that currently exist in robotic missions in addition to human missions. Topics include control systems design in the presence of large time delays, fuel-optimal propulsive control, and adaptive control to handle a variety of unknown conditions.

Xenon Feed System Progress

DTIC Science & Technology

2006-01-01

From - To) 13-06-2006 Technical Paper 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER F04611-00-C-0055 Xenon Feed System Progress (Preprint) 5b. GRANT...propulsion xenon feed system for a flight technology demonstration program. Major accomplishments include: 1) Utilization of the Moog...successfully fed xenon to a 200 watt Hall Effect Thruster in a Technology Demonstration Program. The feed system has demonstrated throttling of xenon

Gas-heat-pump development

NASA Astrophysics Data System (ADS)

Creswick, F. A.

Incentives for the development of gas heat pumps are discussed. Technical progress made on several promising technologies was reviewed. The status of development of gas-engine-driven heat pumps, the absorption cycle for the near- and long-term gas heat pump systems, the Stirling engine, the small Rankine-cycle engines, and gas-turbine-driven heat pump systems were briefly reviewed. Progress in the US, Japan, and Europe is noted.

Examining the Technical Adequacy of Progress Monitoring Using Early Writing Curriculum-Based Measures

ERIC Educational Resources Information Center

Hampton, David D.; Lembke, Erica S.

2016-01-01

The purpose of this study was to examine 4 early writing measures used to monitor the early writing progress of 1st-grade students. We administered the measures to 23 1st-grade students biweekly for a total of 16 weeks. We obtained 3-min samples and conducted analyses for each 1-min increment. We scored samples using 2 different methods: correct…

USAARL Annual Progress Report Fiscal Year 2012

DTIC Science & Technology

2013-04-01

analyzed. A technical report is currently in progress. A research project entitled “Clinical Assessment of the Noise Immune Stethoscope ” evaluated the...noise immune stethoscope (NIS), a dual mode electronic and Doppler device, at Madigan Army Medical Center. Insight from the evaluations, data...Immune Stethoscope aboard a U.S. Navy Carrier. (Report No. 2012-02). Fort Rucker, AL: U.S. Army Aeromedical Research Laboratory. Gordon, E., & Reeves

State Test Score Trends through 2007-08, Part 6: Has Progress Been Made in Raising Achievement for English Language Learners?

ERIC Educational Resources Information Center

Chudowsky, Naomi; Chudowsky, Victor

2010-01-01

This report by the Center on Education Policy (CEP), an independent nonprofit organization, examines progress in raising achievement for English language learners. It also describes the factors that make it difficult to accurately assess what ELLs know and can do. The data for this analysis were collected by CEP with technical support from the…

A "Fear" Studies Perspective and Critique: Analyzing English and Stengel's Progressive Study of Fear and Learning in "Education Theory." Technical Paper No. 37

ERIC Educational Resources Information Center

Fisher, R. Michael

2011-01-01

The author critiques the progressive approach of two contemporary educational philosophers (English and Stengel) on the topic of fear and learning. Using a postmodern integral approach, this article examines the tendency of reductionism, individualism, and psychologism as part of a hegemonic liberalism and modernism in discourses on fear and…

Quantum Manybody Physics with Rydberg Polaritons

DTIC Science & Technology

2016-06-22

report, such as final, technical, interim, memorandum, master’s thesis, progress, quarterly, research , special, group study, etc. 3. DATES COVERED...for public release. Over the course of this grant, we have seen tremendous progress, both theoretically and experimentally , in our control of photonic...shown in multiple stages of construction at left and below, spans three optical tables in two rooms: One for the experimental control system

Minireview: Epigenetics of Obesity and Diabetes in Humans

PubMed Central

Slomko, Howard; Heo, Hye J.

2012-01-01

Understanding the determinants of human health and disease is overwhelmingly complex, particularly for common, late-onset, chronic disorders, such as obesity and diabetes. Elucidating the genetic and environmental factors that influence susceptibility to disruptions in energy homeostasis and metabolic regulation remain a challenge, and progress will entail the integration of multiple assessments of temporally dynamic environmental exposures in the context of each individual's genotype. To meet this challenge, researchers are increasingly exploring the epigenome, which is the malleable interface of gene-environment interactions. Epigenetic variation, whether innate or induced, contributes to variation in gene expression, the range of potential individual responses to internal and external cues, and risk for metabolic disease. Ultimately, advancement in our understanding of chronic disease susceptibility in humans will depend on refinement of exposure assessment tools and systems biology approaches to interpretation. In this review, we present recent progress in epigenetics of human obesity and diabetes, existing challenges, and the potential for new approaches to unravel the complex biology of metabolic dysregulation. PMID:22253427

Constraint-based stoichiometric modelling from single organisms to microbial communities

PubMed Central

Olivier, Brett G.; Bruggeman, Frank J.; Teusink, Bas

2016-01-01

Microbial communities are ubiquitously found in Nature and have direct implications for the environment, human health and biotechnology. The species composition and overall function of microbial communities are largely shaped by metabolic interactions such as competition for resources and cross-feeding. Although considerable scientific progress has been made towards mapping and modelling species-level metabolism, elucidating the metabolic exchanges between microorganisms and steering the community dynamics remain an enormous scientific challenge. In view of the complexity, computational models of microbial communities are essential to obtain systems-level understanding of ecosystem functioning. This review discusses the applications and limitations of constraint-based stoichiometric modelling tools, and in particular flux balance analysis (FBA). We explain this approach from first principles and identify the challenges one faces when extending it to communities, and discuss the approaches used in the field in view of these challenges. We distinguish between steady-state and dynamic FBA approaches extended to communities. We conclude that much progress has been made, but many of the challenges are still open. PMID:28334697