Electric vehicle recycling 2020: Key component power electronics.

PubMed

Bulach, Winfried; Schüler, Doris; Sellin, Guido; Elwert, Tobias; Schmid, Dieter; Goldmann, Daniel; Buchert, Matthias; Kammer, Ulrich

2018-04-01

Electromobility will play a key role in order to reach the specified ambitious greenhouse gas reduction targets in the German transport sector of 42% between 1990 and 2030. Subsequently, a significant rise in the sale of electric vehicles (EVs) is to be anticipated in future. The amount of EVs to be recycled will rise correspondingly after a delay. This includes the recyclable power electronics modules which are incorporated in every EV as an important component for energy management. Current recycling methods using car shredders and subsequent post shredder technologies show high recycling rates for the bulk metals but are still associated with high losses of precious and strategic metals such as gold, silver, platinum, palladium and tantalum. For this reason, the project 'Electric vehicle recycling 2020 - key component power electronics' developed an optimised recycling route for recycling power electronics modules from EVs which is also practicable in series production and can be implemented using standardised technology. This 'WEEE recycling route' involves the disassembly of the power electronics from the vehicle and a subsequent recycling in an electronic end-of-life equipment recycling plant. The developed recycling process is economical under the current conditions and raw material prices, even though it involves considerably higher costs than recycling using the car shredder. The life cycle assessment shows basically good results, both for the traditional car shredder route and the developed WEEE recycling route: the latter provides additional benefits from some higher recovery rates and corresponding credits.

funRNA: a fungi-centered genomics platform for genes encoding key components of RNAi.

PubMed

Choi, Jaeyoung; Kim, Ki-Tae; Jeon, Jongbum; Wu, Jiayao; Song, Hyeunjeong; Asiegbu, Fred O; Lee, Yong-Hwan

2014-01-01

RNA interference (RNAi) is involved in genome defense as well as diverse cellular, developmental, and physiological processes. Key components of RNAi are Argonaute, Dicer, and RNA-dependent RNA polymerase (RdRP), which have been functionally characterized mainly in model organisms. The key components are believed to exist throughout eukaryotes; however, there is no systematic platform for archiving and dissecting these important gene families. In addition, few fungi have been studied to date, limiting our understanding of RNAi in fungi. Here we present funRNA http://funrna.riceblast.snu.ac.kr/, a fungal kingdom-wide comparative genomics platform for putative genes encoding Argonaute, Dicer, and RdRP. To identify and archive genes encoding the abovementioned key components, protein domain profiles were determined from reference sequences obtained from UniProtKB/SwissProt. The domain profiles were searched using fungal, metazoan, and plant genomes, as well as bacterial and archaeal genomes. 1,163, 442, and 678 genes encoding Argonaute, Dicer, and RdRP, respectively, were predicted. Based on the identification results, active site variation of Argonaute, diversification of Dicer, and sequence analysis of RdRP were discussed in a fungus-oriented manner. funRNA provides results from diverse bioinformatics programs and job submission forms for BLAST, BLASTMatrix, and ClustalW. Furthermore, sequence collections created in funRNA are synced with several gene family analysis portals and databases, offering further analysis opportunities. funRNA provides identification results from a broad taxonomic range and diverse analysis functions, and could be used in diverse comparative and evolutionary studies. It could serve as a versatile genomics workbench for key components of RNAi.

Homeland security challenges in nursing practice.

PubMed

Boatright, Connie; McGlown, K Joanne

2005-09-01

Nurses need a comprehensive knowledge of doctrine, laws, regulations,programs, and processes that build the operational framework for health care preparedness. Key components of this knowledge base reside in the areas of: evolution of homeland security: laws and mandates affecting health care and compliance and regulatory issues for health care organizations. This article addresses primary components in both of these areas, after first assessing the status of nursing's involvement (in homeland security), as portrayed in the professional literature.

Productive Mathematical Noticing: What It Is and Why It Matters

ERIC Educational Resources Information Center

Choy, Ban Heng

2013-01-01

Teacher mathematical noticing is a key component of mathematics teaching expertise and has been a focus of recent professional development efforts. In this paper, I propose and describe explicitly the notion of "productive" mathematical noticing, which surfaces from a case study involving a group of seven mathematics teachers who…

Resolving misassembled cattle immune gene clusters with hierarchical, long read sequencing

USDA-ARS?s Scientific Manuscript database

Animal health is a critical component of productivity; however, current genomic selection genotyping tools have a paucity of genetic markers within key immune gene clusters (IGC) involved in the cattle innate and adaptive immune systems. With diseases such as Bovine Tuberculosis and Johne’s disease ...

The Role of International Research Collaboration in Enhancing Global Presence of an Institution

ERIC Educational Resources Information Center

Ao, Fiona Ka Wa

2012-01-01

In recent decades, higher education institutions have steadily increased their international involvement in response to globalization. High-level research is generally a key component in efforts to increase international visibility (Armstrong, 2007). International research collaborations are perceived to be an important way to enhance global…

Communication Apprehension Levels of Student Governance Leaders

ERIC Educational Resources Information Center

Miller, Michael T.; Nadler, Daniel P.

2009-01-01

A major component of the college student experience is the engagement with out-of-class activities. This involvement has been linked to a variety of success indicators, including higher levels of academic achievement, high retention and matriculation, and overall collegiate satisfaction. One of the key areas for student engagement is college…

Development of an optimised key worker framework for people with dementia, their family and caring unit living in the community.

PubMed

Renehan, Emma; Goeman, Dianne; Koch, Susan

2017-07-20

In Australia, dementia is a national health priority. With the rising number of people living with dementia and shortage of formal and informal carers predicted in the near future, developing approaches to coordinating services in quality-focused ways is considered an urgent priority. Key worker support models are one approach that have been used to assist people living with dementia and their caring unit coordinate services and navigate service systems; however, there is limited literature outlining comprehensive frameworks for the implementation of community dementia key worker roles in practice. In this paper an optimised key worker framework for people with dementia, their family and caring unit living in the community is developed and presented. A number of processes were undertaken to inform the development of a co-designed optimised key worker framework: an expert working and reference group; a systematic review of the literature; and a qualitative evaluation of 14 dementia key worker models operating in Australia involving 14 interviews with organisation managers, 19 with key workers and 15 with people living with dementia and/or their caring unit. Data from the systematic review and evaluation of dementia key worker models were analysed by the researchers and the expert working and reference group using a constant comparative approach to define the essential components of the optimised framework. The developed framework consisted of four main components: overarching philosophies; organisational context; role definition; and key worker competencies. A number of more clearly defined sub-themes sat under each component. Reflected in the framework is the complexity of the dementia journey and the difficulty in trying to develop a 'one size fits all' approach. This co-designed study led to the development of an evidence based framework which outlines a comprehensive synthesis of components viewed as being essential to the implementation of a dementia key worker model of care in the community. The framework was informed and endorsed by people living with dementia and their caring unit, key workers, managers, Australian industry experts, policy makers and researchers. An evaluation of its effectiveness and relevance for practice within the dementia care space is required.

Strychnine inhibits inflammatory angiogenesis in mice via down regulation of VEGF, TNF-α and TGF-β.

PubMed

Saraswati, Sarita; Agarwal, S S

2013-05-01

Strychnine is known to possess anti-inflammatory and antitumour activity, but its roles in tumour angiogenesis, the key step involved in tumour growth and metastasis, and the involved molecular mechanism are still unknown. We aimed to investigate the effects of strychnine on key components of inflammatory angiogenesis in the murine cannulated sponge implant angiogenesis model. Polyester-polyurethane sponges, used as a framework for fibrovascular tissue growth, were implanted in Swiss albino mice and strychnine (0.25, and 0.5 mg/kg/day) was given through installed cannulas for 9 days. The implants collected at day 9 postimplantation were processed for the assessment of haemoglobin (Hb), myeloperoxidase (MPO), N-acetylglucosaminidase (NAG) and collagen used as indexes for angiogenesis, neutrophil and macrophage accumulation and extracellular matrix deposition, respectively. Relevant inflammatory, angiogenic and fibrogenic cytokines were also determined. Strychnine treatment attenuated the main components of the fibrovascular tissue, wet weight, vascularization (Hb content), macrophage recruitment (NAG activity), collagen deposition and the levels of vascular endothelial growth factor (VEGF), tumour necrosis factor (TNF)-α and transforming growth factor (TGF-β). A regulatory function of strychnine on multiple parameters of main components of inflammatory angiogenesis has been revealed giving insight into the potential therapeutic underlying the actions of strychnine. Copyright © 2013 Elsevier Inc. All rights reserved.

Unlocking Hidden Potential through Mentoring

ERIC Educational Resources Information Center

McCluskey, Ken W.; Noller, Ruth B.; Lamoureux, Kevin; McCluskey, Andrea L. A.

2004-01-01

One of the many legacies left to us through ancient Greek literature is the concept of mentoring. The ideal mentoring relationship involves three key components: (1) Continuing to carry out other duties while assuming the care-giving role; (2) Serving as a conduit for the wisdom of others; and (3) Developing a long-term connection. Mentoring can…

A Qualitative Examination of the Implementation of a Community-Academic Coalition

ERIC Educational Resources Information Center

Boydell, Katherine M.; Volpe, Tiziana

2004-01-01

Many recent grant initiatives have mandated coalition building as a key component of their health promotion efforts. Health service leaders are increasingly representing their organizations on coalitions and need to better understand the complexities involved in their creation and management. In this paper we focus on the implementation of a…

Accumulation of sphingoid bases and sphingoid base 1-phosphates: A possible mechanism for Fusarium verticillioides corn-seedling disease

USDA-ARS?s Scientific Manuscript database

Sphingolipids are important structural components of membranes involved in signaling pathways that regulate cell growth and death. Fumonisins (FB) are water soluble mycotoxins produced by F. verticillioides, which is parasitic to corn. FBs are inhibitors of ceramide synthase (CS), a key enzyme in sp...

THE ROLE OF ENDOCRINE DISRUPTORS IN CHILDHOOD OBESITY

EPA Science Inventory

We hypothesize that prenatal exposure to PAH and BPA (1) will be associated with higher weight gain trajectories from age 5 to 8-10, and at age 8-10 years with BMI z-score, fat mass and metabolic syndrome components and (2) will alter the methylation status of key genes involv...

La mala educación of tumor-associated macrophages: Diverse pathways and new players.

PubMed

Mantovani, Alberto

2010-02-17

Inflammation is a key component of the tumor microenvironment. Two reports published in this issue of Cancer Cell, Andreu et al. and Erez et al., shed new light on pathways and players involved in the orchestration of cancer-related inflammation. 2010 Elsevier Inc. All rights reserved.

Navigating Tensions between Conceptual and Metaconceptual Goals in the Use of Models

ERIC Educational Resources Information Center

Delgado, Cesar

2015-01-01

Science education involves learning about phenomena at three levels: concrete (facts and generalizations), conceptual (concepts and theories), and metaconceptual (epistemology) (Snir et al. in "J Sci Educ Technol" 2(2):373-388, 1993). Models are key components in science, can help build conceptual understanding, and may also build…

Affordable Development and Demonstrationof a Small NTR Engine and Stage: A Preliminary NASA, DOE and Industry Assessment

NASA Technical Reports Server (NTRS)

Borowski, Stanley K.; Sefcik, Robert J.; Qualls, A. L.; Schnitzler, B.G.; Joyner, C. R.

2014-01-01

Formulation of Affordable and Sustainable NTP Development Strategy is Underway Involving NASA, DOE and Industry. In FY11, Nuclear Thermal Propulsion (NTP) was identified as a key propulsion option under the Advanced In-Space Propulsion (AISP) component of NASA's Exploration Technology Development and Demonstration (ETDD) program.

Amygdala and Hippocampus Enlargement during Adolescence in Autism

ERIC Educational Resources Information Center

Groen, Wouter; Teluij, Michelle; Buitelaar, Jan; Tendolkar, Indira

2010-01-01

Objective: The amygdala and hippocampus are key components of the neural system mediating emotion perception and regulation and are thought to be involved in the pathophysiology of autism. Although some studies in children with autism suggest that there is an enlargement of amygdala and hippocampal volume, findings in adolescence are sparse.…

A plan analysis of pedophile sexual abusers' motivations for treatment: a qualitative pilot study.

PubMed

Drapeau, Martin; Körner, Annett; Granger, Luc; Brunet, Louis; Caspar, Franz

2005-06-01

Many authors have suggested adapting treatment programs to the specific needs of sexual abusers. However, little research has been conducted to understand what these patients seek in therapy or what elements play a key role in keeping them in treatment. In this pilot study, fifteen (N=15) pedophile sexual abusers from La Macaza clinic for sexual abusers were interviewed. Plan analysis was used to investigate the most prevalent components involved in staying in or leaving therapy. Results suggest that many components involved in the plans leading to doing and to avoiding treatment were similar. Differences were found in regards to the outcome of confrontations with the therapists, a tendency to isolate and overcomply, guilt related to the abuse, a need for a stable environment, and a need to be accepted. These results are discussed along with possible ways to improve the patients' involvement in treatment.

Biomarkers for diet and cancer prevention research: potentials and challenges.

PubMed

Davis, Cindy D; Milner, John A

2007-09-01

As cancer incidence is projected to increase for decades there is a need for effective preventive strategies. Fortunately, evidence continues to mount that altering dietary habits is an effective and cost-efficient approach for reducing cancer risk and for modifying the biological behavior of tumors. Predictive, validated and sensitive biomarkers, including those that reliably evaluate "intake" or exposure to a specific food or bioactive component, that assess one or more specific biological "effects" that are linked to cancer, and that effectively predict individual "susceptibility" as a function of nutrient-nutrient interactions and genetics, are fundamental to evaluating who will benefit most from dietary interventions. These biomarkers must be readily accessible, easily and reliably assayed, and predictive of a key process(es) involved in cancer. The response to a food is determined not only by the effective concentration of the bioactive food component(s) reaching the target tissue, but also by the amount of the target requiring modification. Thus, this threshold response to foods and their components will vary from individual to individual. The key to understanding a personalized response is a greater knowledge of nutrigenomics, proteomics and metabolomics.

Chronic stress induced disruption of the peri-infarct neurovascular unit following experimentally induced photothrombotic stroke.

PubMed

Zhao, Zidan; Ong, Lin Kooi; Johnson, Sarah; Nilsson, Michael; Walker, Frederick R

2017-12-01

How stress influences brain repair is an issue of considerable importance, as patients recovering from stroke are known to experience high and often unremitting levels of stress post-event. In the current study, we investigated how chronic stress modified the key cellular components of the neurovascular unit. Using an experimental model of focal cortical ischemia in male C57BL/6 mice, we examined how exposure to a persistently aversive environment, induced by the application of chronic restraint stress, altered the cortical remodeling post-stroke. We focused on systematically investigating changes in the key components of the neurovascular unit (i.e. neurons, microglia, astrocytes, and blood vessels) within the peri-infarct territories using both immunohistochemistry and Western blotting. The results from our study indicated that exposure to chronic stress exerted a significant suppressive effect on each of the key cellular components involved in neurovascular remodeling. Co-incident with these cellular changes, we observed that chronic stress was associated with an exacerbation of motor impairment 42 days post-event. Collectively, these results highlight the vulnerability of the peri-infarct neurovascular unit to the negative effects of chronic stress.

Active Rehabilitation-a community peer-based approach for persons with spinal cord injury: international utilisation of key elements.

PubMed

Divanoglou, A; Tasiemski, T; Augutis, M; Trok, K

2017-06-01

Active Rehabilitation (AR) is a community peer-based approach that started in Sweden in 1976. As a key component of the approach, AR training camps provide intensive, goal-oriented, intentional, group-based, customised training and peer-support opportunities in a community environment for individuals with spinal cord injury. Prospective cross-sectional study. To describe the profile of the organisations that use components of the AR approach, and to explore the characteristics and the international variations of the approach. Twenty-two organisations from 21 countries from Europe, Asia and Africa reported using components of the AR approach during the past 10 years. An electronic survey was developed and distributed through a personalised email. Sampling involved a prospective identification of organisations that met the inclusion criteria and snowball strategies. While there were many collaborating links between the organisations, RG Active Rehabilitation from Sweden and Motivation Charitable Trust from the United Kingdom were identified as key supporting organisations. The 10 key elements of the AR approach were found to be used uniformly across the participating organisations. Small variations were associated with variations in country income and key supporting organisation. This is the first study to describe the key elements and international variations of the AR approach. This will provide the basis for further studies exploring the effectiveness of the approach, it will likely facilitate international collaboration on research and operational aspects and it could potentially support higher integration in the health-care system and long-term funding of these programmes.

Neurotransmitter release mechanisms studied in Caenorhabditis elegans.

PubMed

Barclay, Jeff W; Morgan, Alan; Burgoyne, Robert D

2012-01-01

The process of regulated exocytosis has received considerable interest as a key component of synaptic transmission. Fusion of presynaptic vesicles and the subsequent release of their neurotransmitter contents is driven by a series of interactions between evolutionarily conserved proteins. Key insights into the molecular mechanisms of vesicle fusion have come from research using genetic model systems such as the nematode worm Caenorhabditis elegans. We review here the current knowledge regarding regulated exocytosis at the C. elegans synapse and future research directions involving this model organism. Copyright © 2012 Elsevier Ltd. All rights reserved.

Novel ways to explore surgical interventions in randomised controlled trials: applying case study methodology in the operating theatre.

PubMed

Blencowe, Natalie S; Blazeby, Jane M; Donovan, Jenny L; Mills, Nicola

2015-12-28

Multi-centre randomised controlled trials (RCTs) in surgery are challenging. It is particularly difficult to establish standards of surgery and ensure that interventions are delivered as intended. This study developed and tested methods for identifying the key components of surgical interventions and standardising interventions within RCTs. Qualitative case studies of surgical interventions were undertaken within the internal pilot phase of a surgical RCT for obesity (the By-Band study). Each case study involved video data capture and non-participant observation of gastric bypass surgery in the operating theatre and interviews with surgeons. Methods were developed to transcribe and synchronise data from video recordings with observational data to identify key intervention components, which were then explored in the interviews with surgeons. Eight qualitative case studies were undertaken. A novel combination of video data capture, observation and interview data identified variations in intervention delivery between surgeons and centres. Although surgeons agreed that the most critical intervention component was the size and shape of the gastric pouch, there was no consensus regarding other aspects of the procedure. They conceded that evidence about the 'best way' to perform bypass was lacking and, combined with the pragmatic nature of the By-Band study, agreed that strict standardisation of bypass might not be required. This study has developed and tested methods for understanding how surgical interventions are designed and delivered delivered in RCTs. Applying these methods more widely may help identify key components of interventions to be delivered by surgeons in trials, enabling monitoring of key components and adherence to the protocol. These methods are now being tested in the context of other surgical RCTs. Current Controlled Trials ISRCTN00786323 , 05/09/2011.

Supporting Bilingual Learners and Their Families: Key Understandings for Pre-Service Teachers and the Institutions That Prepare Them

ERIC Educational Resources Information Center

Commins, Nancy L.

2014-01-01

An essential component of successful schooling in linguistically and culturally diverse settings is the active involvement of parents and community members. This is made possible when teachers honor families' languages and cultural traditions and build upon them. Teacher preparation programs play a critical role in helping preservice teachers…

Between Counting and Multiplication: Low-Attaining Students' Spatial Structuring, Enumeration and Errors in Concretely-Presented 3D Array Tasks

ERIC Educational Resources Information Center

Finesilver, Carla

2017-01-01

The move from additive to multiplicative thinking requires significant change in children's comprehension and manipulation of numerical relationships, involves various conceptual components, and can be a slow, multistage process for some. Unit arrays are a key visuospatial representation for supporting learning, but most research focuses on 2D…

Preventing Conduct Problems and Improving School Readiness: Evaluation of the Incredible Years Teacher and Child Training Programs in High-Risk Schools

ERIC Educational Resources Information Center

Webster-Stratton, Carolyn; Reid, M. Jamila; Stoolmiller, Mike

2008-01-01

Background: School readiness, conceptualized as three components including emotional self-regulation, social competence, and family/school involvement, as well as absence of conduct problems play a key role in young children's future interpersonal adjustment and academic success. Unfortunately, exposure to multiple poverty-related risks increases…

Computational Thinking and Media & Information Literacy: An Integrated Approach to Teaching Twenty-First Century Skills

ERIC Educational Resources Information Center

Gretter, Sarah; Yadav, Aman

2016-01-01

Developing students' 21st century skills, including creativity, critical thinking, and problem solving, has been a prevailing concern in our globalized and hyper-connected society. One of the key components for students to accomplish this is to take part in today's participatory culture, which involves becoming creators of knowledge rather than…

San Diego Met High School: Personalization as a Foundation

ERIC Educational Resources Information Center

Principal Leadership, 2010

2010-01-01

The mission of San Diego Met High School is to prepare students for college and the workforce through active learning, academic rigor, and community involvement in a small school setting. Because personalization is a key component of the school culture, advisories of 20-25 students work with the same teachers for all four years. Advisers, parents,…

Learning Racial Hierarchies: Communication Skills Training in Transnational Customer Service Work

ERIC Educational Resources Information Center

Mirchandani, Kiran

2012-01-01

Purpose: This paper aims to focus on the communications skills training given to transnational call center workers in India whose jobs involve providing customer service to Western customers. Emotion work is a key component of customer service jobs, and this work is constructed as an important soft skill. Design/methodology/approach: Between 2002…

Getting to the Right Algebra: The Equity 2000 Initiative in Milwaukee Public Schools. MDRC Working Papers.

ERIC Educational Resources Information Center

Ham, Sandra; Walker, Erica

This paper describes the Milwaukee Public Schools' involvement in Equity 2000, a standards-based reform initiative to enhance mathematics education and achievement among students of color, thereby increasing their likelihood of college enrollment and completion. The study highlights efforts to support and sustain a key component of Equity 2000:…

Intentional Self-Regulation, Ecological Assets, and Thriving in Adolescence: A Developmental Systems Model

ERIC Educational Resources Information Center

Gestsdottir, Steinunn; Urban, Jennifer Brown; Bowers, Edmond P.; Lerner, Jacqueline V.; Lerner, Richard M.

2011-01-01

The positive youth development (PYD) perspective emphasizes that thriving occurs when individual [double arrow] context relations involve the alignment of adolescent strengths with the resources in their contexts. The authors propose that a key component of this relational process is the strength that youth possess in the form of self-regulatory…

Inspire: The Quest for a Coherent Curriculum through a Performing Arts-Focused Curriculum Integration Project

ERIC Educational Resources Information Center

Carlisle, Katie

2011-01-01

The author reports on the formation of a performing arts-focused curriculum integration project, in which key components of curriculum integration were employed within a project-focus involving the performing arts of music, theater, and dance. The project occurred within a curricular community partnership between a public school and nearby…

Building bridges with clinicians.

PubMed

Brady, Timothy S; Hankins, Robert W

2003-06-01

Clinical and ancillary staff need and welcome the opportunity to be involved in healthcare financial management. To provide them with the financial tools they need, a group of clinical and nonclinical professionals identified the key components of a curriculum that addressed financial, managerial, and cost accounting, along with training objectives that include understanding cost allocation, trend analysis, and variance analysis.

Analysis of Coupled Model Uncertainties in Source to Dose Modeling of Human Exposures to Ambient Air Pollution: a PM2.5 Case-Study

EPA Science Inventory

Quantitative assessment of human exposures and health effects due to air pollution involve detailed characterization of impacts of air quality on exposure and dose. A key challenge is to integrate these three components on a consistent spatial and temporal basis taking into acco...

Development and pretest of key visual imagery in a campaign for the prevention of child maltreatment.

PubMed

Charest, Émilie; Gagné, Marie-Hélène; Goulet, Julie

2017-08-01

This article discusses the development and pretesting of key visual imagery in a promotional campaign developed in Quebec, Canada. This campaign is the media-based component of a broader prevention strategy involving the use of the Triple P program (Sanders, 1999). The purpose was to pretest with parents the preliminary version of a poster that uses the campaign's key visual imagery prior to final production. In total, 26 parents from the regions of Quebec City and Montreal participated in four focus groups. Two general themes emerged from the focus groups: (i) emotions and reactions arising from the key visual imagery; and (ii) comprehension of the message being conveyed. Based on this information, recommendations were made to the marketing agency, which then modified the campaign's key visual imagery and proposed a final layout.

A homolog of Drosophila grainy head is essential for epidermal integrity in mice.

PubMed

Ting, Stephen B; Caddy, Jacinta; Hislop, Nikki; Wilanowski, Tomasz; Auden, Alana; Zhao, Lin-Lin; Ellis, Sarah; Kaur, Pritinder; Uchida, Yoshikazu; Holleran, Walter M; Elias, Peter M; Cunningham, John M; Jane, Stephen M

2005-04-15

The Drosophila cuticle is essential for maintaining the surface barrier defenses of the fly. Integral to cuticle resilience is the transcription factor grainy head, which regulates production of the enzyme required for covalent cross-linking of the cuticular structural components. We report that formation and maintenance of the epidermal barrier in mice are dependent on a mammalian homolog of grainy head, Grainy head-like 3. Mice lacking this factor display defective skin barrier function and deficient wound repair, accompanied by reduced expression of transglutaminase 1, the key enzyme involved in cross-linking the structural components of the superficial epidermis. These findings suggest that the functional mechanisms involving protein cross-linking that maintain the epidermal barrier and induce tissue repair are conserved across 700 million years of evolution.

Elements of impact assessment: a case study with cyber attacks

NASA Astrophysics Data System (ADS)

Yang, Shanchieh Jay; Holsopple, Jared; Liu, Daniel

2009-05-01

Extensive discussions have taken place in recent year regarding impact assessment - what is it and how can we do it? It is especially intriguing in this modern era where non-traditional warfare has caused either information overload or limited understanding of adversary doctrines. This work provides a methodical discussion of key elements for the broad definition of impact assessment (IA). The discussion will start with a process flow involving components related to IA. Two key functional components, impact estimation and threat projection, are compared and illustrated in detail. These details include a discussion of when to model red and blue knowledge. Algorithmic approaches will be discussed, augmented with lessons learned from our IA development for cyber situation awareness. This paper aims at providing the community with a systematic understanding of IA and its open issues with specific examples.

Evaluation of interventions on road traffic injuries in Peru: a qualitative approach

PubMed Central

2012-01-01

Background Evaluation of interventions on road traffic injuries (RTI) going beyond the assessment of impact to include factors underlying success or failure is an important complement to standard impact evaluations. We report here how we used a qualitative approach to assess current interventions implemented to reduce RTIs in Peru. Methods We performed in-depth interviews with policymakers and technical officers involved in the implementation of RTI interventions to get their insight on design, implementation and evaluation aspects. We then conducted a workshop with key stakeholders to analyze the results of in-depth interviews, and to further discuss and identify key programmatic considerations when designing and implementing RTI interventions. We finally performed brainstorming sessions to assess potential system-wide effects of a selected intervention (Zero Tolerance), and to identify adaptation and redesign needs for this intervention. Results Key programmatic components were consistently identified that should be considered when designing and implementing RTI interventions. They include effective and sustained political commitment and planning; sufficient and sustained budget allocation; training, supervision, monitoring and evaluation of implemented policies; multisectoral participation; and strong governance and accountability. Brainstorming sessions revealed major negative effects of the selected intervention on various system building blocks. Conclusions Our approach revealed substantial caveats in current RTI interventions in Peru, and fundamental negative effects on several components of the sectors and systems involved. It also highlighted programmatic issues that should be applied to guarantee an effective implementation and evaluation of these policies. The findings from this study were discussed with key stakeholders for consideration in further designing and planning RTI control interventions in Peru. PMID:22269578

Evaluation of interventions on road traffic injuries in Peru: a qualitative approach.

PubMed

Huicho, Luis; Adam, Taghreed; Rosales, Edmundo; Paca-Palao, Ada; López, Luis; Luna, Diego; Miranda, J Jaime

2012-01-23

Evaluation of interventions on road traffic injuries (RTI) going beyond the assessment of impact to include factors underlying success or failure is an important complement to standard impact evaluations. We report here how we used a qualitative approach to assess current interventions implemented to reduce RTIs in Peru. We performed in-depth interviews with policymakers and technical officers involved in the implementation of RTI interventions to get their insight on design, implementation and evaluation aspects. We then conducted a workshop with key stakeholders to analyze the results of in-depth interviews, and to further discuss and identify key programmatic considerations when designing and implementing RTI interventions. We finally performed brainstorming sessions to assess potential system-wide effects of a selected intervention (Zero Tolerance), and to identify adaptation and redesign needs for this intervention. Key programmatic components were consistently identified that should be considered when designing and implementing RTI interventions. They include effective and sustained political commitment and planning; sufficient and sustained budget allocation; training, supervision, monitoring and evaluation of implemented policies; multisectoral participation; and strong governance and accountability. Brainstorming sessions revealed major negative effects of the selected intervention on various system building blocks. Our approach revealed substantial caveats in current RTI interventions in Peru, and fundamental negative effects on several components of the sectors and systems involved. It also highlighted programmatic issues that should be applied to guarantee an effective implementation and evaluation of these policies. The findings from this study were discussed with key stakeholders for consideration in further designing and planning RTI control interventions in Peru.

Developing dimensions for a multicomponent multidisciplinary approach to obesity management: a qualitative study.

PubMed

Cochrane, Anita J; Dick, Bob; King, Neil A; Hills, Andrew P; Kavanagh, David J

2017-10-16

There have been consistent recommendations for multicomponent and multidisciplinary approaches for obesity management. However, there is no clear agreement on the components, disciplines or processes to be considered within such an approach. In this study, we explored multicomponent and multidisciplinary approaches through an examination of knowledge, skills, beliefs, and recommendations of stakeholders involved in obesity management. These stakeholders included researchers, practitioners, educators, and patients. We used qualitative action research methods, including convergent interviewing and observation, to assist the process of inquiry. The consensus was that a multicomponent and multidisciplinary approach should be based on four central meta-components (patient, practitioner, process, and environmental factors), and specific components of these factors were identified. Psychologists, dieticians, exercise physiologists and general practitioners were nominated as key practitioners to be included. A complex condition like obesity requires that multiple components be addressed, and that both patients and multiple disciplines are involved in developing solutions. Implementing cycles of continuous improvement to deal with complexity, instead of trying to control for it, offers an effective way to deal with complex, changing multisystem problems like obesity.

Street conflict mediation to prevent youth violence: conflict characteristics and outcomes.

PubMed

Whitehill, Jennifer M; Webster, Daniel W; Vernick, Jon S

2013-06-01

Mediation of potentially violent conflicts is a key component of CeaseFire, an effective gun violence-prevention programme. To describe conflicts mediated by outreach workers (OW) in Baltimore's CeaseFire replication, examine neighbourhood variation, and measure associations between conflict risk factors and successful nonviolent resolution. A cross-sectional study was conducted using records for 158 conflicts mediated between 2007 and 2009. Involvement of youth, gangs, retaliation, weapons and other risk factors were described. Principal component analysis (PCA) was used for data-reduction purposes before the relationship between conflict risk components and mediation success was assessed with multivariate logistic regression. Most conflicts involved 2-3 individuals. Youth, persons with a history of violence, gang members and weapons were commonly present. OWs reported immediate, nonviolent resolution for 65% of mediated conflicts; an additional 23% were at least temporarily resolved without violence. PCA identified four dimensions of conflict risk: the risk-level of individuals involved; whether the incident was related to retaliation; the number of people involved; and shooting likelihood. However, these factors were not related to the OW's ability to resolve the conflict. Neighbourhoods with programme-associated reductions in homicides mediated more gang-related conflicts; neighbourhoods without programme-related homicide reductions encountered more retaliatory conflicts and more weapons.

Resistance to Change and Relapse of Observing

PubMed Central

Thrailkill, Eric A; Shahan, Timothy A

2012-01-01

Four experiments examined relapse of extinguished observing behavior of pigeons using a two-component multiple schedule of observing-response procedures. In both components, unsignaled periods of variable-interval (VI) food reinforcement alternated with extinction and observing responses produced stimuli associated with the availability of the VI schedule (i.e., S+). The components differed in the rate of food arranged (Rich  = VI 30 s; Lean  =  VI 120 s). In Experiment 1, following baseline training, extinction of observing involved removal of both food and S+ deliveries, and reinstatement was examined by presenting either response-independent food or S+ deliveries. In Experiment 2, extinction involved removal of only food deliveries while observing responses continued to produce S+. Reinstatement was examined by delivering food contingent upon the first two food-key responses occurring in the presence of the S+. Experiment 3 assessed ABA renewal of observing by extinguishing food-key and observing responses in the presence of one contextual stimulus (i.e., B) and then returning to the original training context (i.e., A) during continued extinction. Experiment 4 examined resurgence by introducing food reinforcement for an alternative response during extinction, and subsequently removing that alternative source of food. Across experiments, relative resistance to extinction and relapse of observing tended to be greater in the component previously associated with the higher rate of primary reinforcement. Relapse of observing or attending to stimuli associated with primary reinforcement appears to be impacted by frequency of primary reinforcement in a manner similar to responding maintained directly by primary reinforcement. PMID:22693359

Factors Influencing Team Performance in a Continuous Quality Improvement Process in the Wisconsin Technical College System

ERIC Educational Resources Information Center

Pietz, Victoria Lynn

2014-01-01

Continuous Quality Improvement (CQI) programs are growing in popularity in higher education settings and a key component is the use of work groups, which require active employee involvement. The problem addressed in this research was the lack of employee engagement in the Quality Review Process (QRP), which is a statewide CQI model developed by…

Low-power cryptographic coprocessor for autonomous wireless sensor networks

NASA Astrophysics Data System (ADS)

Olszyna, Jakub; Winiecki, Wiesław

2013-10-01

The concept of autonomous wireless sensor networks involves energy harvesting, as well as effective management of system resources. Public-key cryptography (PKC) offers the advantage of elegant key agreement schemes with which a secret key can be securely established over unsecure channels. In addition to solving the key management problem, the other major application of PKC is digital signatures, with which non-repudiation of messages exchanges can be achieved. The motivation for studying low-power and area efficient modular arithmetic algorithms comes from enabling public-key security for low-power devices that can perform under constrained environment like autonomous wireless sensor networks. This paper presents a cryptographic coprocessor tailored to the autonomous wireless sensor networks constraints. Such hardware circuit is aimed to support the implementation of different public-key cryptosystems based on modular arithmetic in GF(p) and GF(2m). Key components of the coprocessor are described as GEZEL models and can be easily transformed to VHDL and implemented in hardware.

Could Notch signaling pathway be a potential therapeutic option in renal diseases?

PubMed

Marquez-Exposito, Laura; Cantero-Navarro, Elena; Lavoz, Carolina; Fierro-Fernández, Marta; Poveda, Jonay; Rayego-Mateos, Sandra; Rodrigues-Diez, Raúl R; Morgado-Pascual, José Luis; Orejudo, Macarena; Mezzano, Sergio; Ruiz-Ortega, Marta

2018-02-10

Notch pathway regulates key processes in the kidney, involved in embryonic development and tissue damage. In many human chronic renal diseases a local activation of Notch pathway has been described, suggesting that several components of Notch pathway could be considered as biomarkers of renal damage. Experimental studies by genetic modulation of Notch components or pharmacological approaches by γ-secretase inhibitors have demonstrated the role of this pathway in renal regeneration renal, podocyte apoptosis, proliferation and fibroblasts activation, and induction of epithelial to mesenchymal transition of tubular epithelial cells. Recent studies suggest an interaction between Notch and NF-κB pathway involved in the regulation of renal inflammatory process. On the other hand, there are some miRNAs that could regulate Notch components and down-stream responses. All these data suggest that Notch blockade could be a novel therapeutic option for renal diseases. Copyright © 2018 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Lysosomal enzymes and their receptors in invertebrates: an evolutionary perspective.

PubMed

Kumar, Nadimpalli Siva; Bhamidimarri, Poorna M

2015-01-01

Lysosomal biogenesis is an important process in eukaryotic cells to maintain cellular homeostasis. The key components that are involved in the biogenesis such as the lysosomal enzymes, their modifications and the mannose 6-phosphate receptors have been well studied and their evolutionary conservation across mammalian and non-mammalian vertebrates is clearly established. Invertebrate lysosomal biogenesis pathway on the other hand is not well studied. Although, details on mannose 6-phosphate receptors and enzymes involved in lysosomal enzyme modifications were reported earlier, a clear cut pathway has not been established. Recent research on the invertebrate species involving biogenesis of lysosomal enzymes suggests a possible conserved pathway in invertebrates. This review presents certain observations based on these processes that include biochemical, immunological and functional studies. Major conclusions include conservation of MPR-dependent pathway in higher invertebrates and recent evidence suggests that MPR-independent pathway might have been more prominent among lower invertebrates. The possible components of MPR-independent pathway that may play a role in lysosomal enzyme targeting are also discussed here.

Autophagy as a macrophage response to bacterial infection.

PubMed

Gong, Lan; Devenish, Rodney J; Prescott, Mark

2012-09-01

The macrophage is a key component of host defense mechanisms against pathogens. In addition to the phagocytosis of bacteria and secretion of proinflammatory mediators by macrophages, autophagy, a process involved in turnover of cellular material, is a recently identified component of the immune response to bacterial infection. Despite the bactericidal effect of autophagy, some species of intracellular bacteria are able to survive by using one or more strategies to avoid host autophagic attack. Here, we review the latest findings on the interactions between bacteria and autophagy in macrophages. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.

The Power of Plain Talk: Exploring One Program' Influence on the Adolescent Reproductive Health Field

ERIC Educational Resources Information Center

Summerville, Geri; Canova, Karen

2006-01-01

Launched by the Annie E. Casey Foundation in the early 1990s, Plain Talk is a community-based initiative that seeks to reduce the incidence of teen pregnancy and STDs by improving adult/teen communication about sex. A key component of the program is parental involvement--which was once seen by many in the adolescent reproductive health (ARH) field…

Multiple Integrated Navigation Sensors for Improved Occupancy Grid FastSLAM

DTIC Science & Technology

2011-03-01

to the Faculty Department of Electrical and Computer Engineering Graduate School of Engineering and Management Air Force Institute of Technology Air...autonomous vehicle exploration with applications to search and rescue. To current knowledge , this research presents the first SLAM solution to...solution is a key component of an autonomous vehicle, especially one whose mission involves gaining knowledge of unknown areas. It provides the ability

Transcriptional Activity of the MADS Box ARLEQUIN/TOMATO AGAMOUS-LIKE1 Gene Is Required for Cuticle Development of Tomato Fruit1

PubMed Central

Giménez, Estela; Dominguez, Eva; Pineda, Benito; Heredia, Antonio; Moreno, Vicente; Angosto, Trinidad

2015-01-01

Fruit development and ripening entail key biological and agronomic events, which ensure the appropriate formation and dispersal of seeds and determine productivity and yield quality traits. The MADS box gene ARLEQUIN/TOMATO AGAMOUS-LIKE1 (hereafter referred to as TAGL1) was reported as a key regulator of tomato (Solanum lycopersicum) reproductive development, mainly involved in flower development, early fruit development, and ripening. It is shown here that silencing of the TAGL1 gene (RNA interference lines) promotes significant changes affecting cuticle development, mainly a reduction of thickness and stiffness, as well as a significant decrease in the content of cuticle components (cutin, waxes, polysaccharides, and phenolic compounds). Accordingly, overexpression of TAGL1 significantly increased the amount of cuticle and most of its components while rendering a mechanically weak cuticle. Expression of the genes involved in cuticle biosynthesis agreed with the biochemical and biomechanical features of cuticles isolated from transgenic fruits; it also indicated that TAGL1 participates in the transcriptional control of cuticle development mediating the biosynthesis of cuticle components. Furthermore, cell morphology and the arrangement of epidermal cell layers, on whose activity cuticle formation depends, were altered when TAGL1 was either silenced or constitutively expressed, indicating that this transcription factor regulates cuticle development, probably through the biosynthetic activity of epidermal cells. Our results also support cuticle development as an integrated event in the fruit expansion and ripening processes that characterize fleshy-fruited species such as tomato. PMID:26019301

A qualitative study of DRG coding practice in hospitals under the Thai Universal Coverage scheme.

PubMed

Pongpirul, Krit; Walker, Damian G; Winch, Peter J; Robinson, Courtland

2011-04-08

In the Thai Universal Coverage health insurance scheme, hospital providers are paid for their inpatient care using Diagnosis Related Group-based retrospective payment, for which quality of the diagnosis and procedure codes is crucial. However, there has been limited understandings on which health care professions are involved and how the diagnosis and procedure coding is actually done within hospital settings. The objective of this study is to detail hospital coding structure and process, and to describe the roles of key hospital staff, and other related internal dynamics in Thai hospitals that affect quality of data submitted for inpatient care reimbursement. Research involved qualitative semi-structured interview with 43 participants at 10 hospitals chosen to represent a range of hospital sizes (small/medium/large), location (urban/rural), and type (public/private). Hospital Coding Practice has structural and process components. While the structural component includes human resources, hospital committee, and information technology infrastructure, the process component comprises all activities from patient discharge to submission of the diagnosis and procedure codes. At least eight health care professional disciplines are involved in the coding process which comprises seven major steps, each of which involves different hospital staff: 1) Discharge Summarization, 2) Completeness Checking, 3) Diagnosis and Procedure Coding, 4) Code Checking, 5) Relative Weight Challenging, 6) Coding Report, and 7) Internal Audit. The hospital coding practice can be affected by at least five main factors: 1) Internal Dynamics, 2) Management Context, 3) Financial Dependency, 4) Resource and Capacity, and 5) External Factors. Hospital coding practice comprises both structural and process components, involves many health care professional disciplines, and is greatly varied across hospitals as a result of five main factors.

A qualitative study of DRG coding practice in hospitals under the Thai Universal Coverage Scheme

PubMed Central

2011-01-01

Background In the Thai Universal Coverage health insurance scheme, hospital providers are paid for their inpatient care using Diagnosis Related Group-based retrospective payment, for which quality of the diagnosis and procedure codes is crucial. However, there has been limited understandings on which health care professions are involved and how the diagnosis and procedure coding is actually done within hospital settings. The objective of this study is to detail hospital coding structure and process, and to describe the roles of key hospital staff, and other related internal dynamics in Thai hospitals that affect quality of data submitted for inpatient care reimbursement. Methods Research involved qualitative semi-structured interview with 43 participants at 10 hospitals chosen to represent a range of hospital sizes (small/medium/large), location (urban/rural), and type (public/private). Results Hospital Coding Practice has structural and process components. While the structural component includes human resources, hospital committee, and information technology infrastructure, the process component comprises all activities from patient discharge to submission of the diagnosis and procedure codes. At least eight health care professional disciplines are involved in the coding process which comprises seven major steps, each of which involves different hospital staff: 1) Discharge Summarization, 2) Completeness Checking, 3) Diagnosis and Procedure Coding, 4) Code Checking, 5) Relative Weight Challenging, 6) Coding Report, and 7) Internal Audit. The hospital coding practice can be affected by at least five main factors: 1) Internal Dynamics, 2) Management Context, 3) Financial Dependency, 4) Resource and Capacity, and 5) External Factors. Conclusions Hospital coding practice comprises both structural and process components, involves many health care professional disciplines, and is greatly varied across hospitals as a result of five main factors. PMID:21477310

Comparative proteomics analysis of Bacillus amyloliquefaciens SQR9 revealed the key proteins involved in in situ root colonization.

PubMed

Qiu, Meihua; Xu, Zhihui; Li, Xingxing; Li, Qing; Zhang, Nan; Shen, Qirong; Zhang, Ruifu

2014-12-05

Bacillus Amyloliquefaciens SQR9 is a well-investigated plant growth-promoting rhizobacteria with strong root colonization capability. To identify the key proteins involved in in situ root colonization and biofilm formation, the proteomic profiles of planktonic and root colonized SQR9 cells were compared. A total of 755 proteins were identified, of which 78 and 95 proteins were significantly increased and deceased, respectively, when SQR9 was colonized on the root. The proteins that were closely affiliated with the root colonization belonged to the functional categories of biocontrol, detoxification, biofilm formation, cell motility and chemotaxis, transport, and degradation of plant polysaccharides. A two-component system protein ResE was increased 100-fold when compared to the planktonic status; impairment of the resE gene postponed the formation of cell biofilm and decreased the root colonization capability, which may be regulated through the spo0A-sinI-yqxM pathway. The SQR9 proteomic data provide valuable clues for screening key proteins in the plant-rhizobacteria interaction.

Classic fungal natural products in the genomic age: the molecular legacy of Harold Raistrick.

PubMed

Schor, Raissa; Cox, Russell

2018-03-01

Covering: 1893 to 2017Harold Raistrick was involved in the discovery of many of the most important classes of fungal metabolites during the 20th century. This review focusses on how these discoveries led to developments in isotopic labelling, biomimetic chemistry and the discovery, analysis and exploitation of biosynthetic gene clusters for major classes of fungal metabolites including: alternariol; geodin and metabolites of the emodin pathway; maleidrides; citrinin and the azaphilones; dehydrocurvularin; mycophenolic acid; and the tropolones. Key recent advances in the molecular understanding of these important pathways, including the discovery of biosynthetic gene clusters, the investigation of the molecular and chemical aspects of key biosynthetic steps, and the reengineering of key components of the pathways are reviewed and compared. Finally, discussion of key relationships between metabolites and pathways and the most important recent advances and opportunities for future research directions are given.

Second-order schedules: discrimination of components1

PubMed Central

Squires, Nancy; Norborg, James; Fantino, Edmund

1975-01-01

Pigeons were exposed to a series of second-order schedules in which the completion of a fixed number of fixed-interval components produced food. In Experiment 1, brief (2 sec) stimulus presentations occurred as each fixed-interval component was completed. During the brief-stimulus presentation terminating the last fixed-interval component, a response was required on a second key, the brief-stimulus key, to produce food. Responses on the brief-stimulus key before the last brief-stimulus presentation had no scheduled consequences, but served as a measure of the extent to which the final component was discriminated from preceding components. Whether there were one, two, four, or eight fixed-interval components, responses on the brief-stimulus key occurred during virtually every brief-stimulus presentation. In Experiment 2, an attempt was made to punish unnecessary responses on the brief-stimulus key, i.e., responses on the brief-stimulus key that occurred before the last component. None of the pigeons learned to withhold these responses, even though they produced a 15-sec timeout and loss of primary reinforcement. In Experiment 3, different key colors were associated with each component of a second-order schedule (a chain schedule). In contrast to Experiment 1, brief-stimulus key responses were confined to the last component. It was concluded that pigeons do not discriminate well between components of second-order schedules unless a unique exteroceptive cue is provided for each component. The relative discriminability of the components may account for the observed differences in initial-component response rates between comparable brief-stimulus, tandem, and chain schedules. PMID:16811868

A novel property of DNA - as a bioflotation reagent in mineral processing.

PubMed

Vasanthakumar, Balasubramanian; Ravishankar, Honnavar; Subramanian, Sankaran

2012-01-01

Environmental concerns regarding the use of certain chemicals in the froth flotation of minerals have led investigators to explore biological entities as potential substitutes for the reagents in vogue. Despite the fact that several microorganisms have been used for the separation of a variety of mineral systems, a detailed characterization of the biochemical molecules involved therein has not been reported so far. In this investigation, the selective flotation of sphalerite from a sphalerite-galena mineral mixture has been achieved using the cellular components of Bacillus species. The key constituent primarily responsible for the flotation of sphalerite has been identified as DNA, which functions as a bio-collector. Furthermore, using reconstitution studies, the obligatory need for the presence of non-DNA components as bio-depressants for galena has been demonstrated. A probable model involving these entities in the selective flotation of sphalerite from the mineral mixture has been discussed.

A Novel Property of DNA – As a Bioflotation Reagent in Mineral Processing

PubMed Central

Vasanthakumar, Balasubramanian; Ravishankar, Honnavar; Subramanian, Sankaran

2012-01-01

Environmental concerns regarding the use of certain chemicals in the froth flotation of minerals have led investigators to explore biological entities as potential substitutes for the reagents in vogue. Despite the fact that several microorganisms have been used for the separation of a variety of mineral systems, a detailed characterization of the biochemical molecules involved therein has not been reported so far. In this investigation, the selective flotation of sphalerite from a sphalerite-galena mineral mixture has been achieved using the cellular components of Bacillus species. The key constituent primarily responsible for the flotation of sphalerite has been identified as DNA, which functions as a bio-collector. Furthermore, using reconstitution studies, the obligatory need for the presence of non-DNA components as bio-depressants for galena has been demonstrated. A probable model involving these entities in the selective flotation of sphalerite from the mineral mixture has been discussed. PMID:22768298

Protein components of the microRNA pathway and human diseases

PubMed Central

Perron, Marjorie P.; Provost, Patrick

2010-01-01

Summary MicroRNAs (miRNAs) are key regulators of messenger RNA (mRNA) translation known to be involved in a wide variety of cellular processes. In fact, their individual importance is reflected in the diseases that may arise upon the loss, mutation or dysfunction of specific miRNAs. It has been appreciated only recently that diseases may also develop when the protein components of the miRNA machinery itself are affected. The core enzymes of the major protein complexes involved in miRNA biogenesis and function, such as the ribonucleases III (RNases III) Drosha and Dicer as well as Argonaute 2 (Ago2), appear to be essential. However, the accessory proteins of the miRNA pathway, such as the DiGeorge syndrome critical region gene 8 (DGCR8) protein, Exportin-5 (Exp-5), TAR RNA binding protein (TRBP) and Fragile X mental retardation protein (FMRP), are each related, in various ways, to specific genetic diseases. PMID:19301657

Graduate Teaching Assistants; Critical Colleagues or Casual Components in the Undergraduate Laboratory Learning? An Exploration of the Role of the Postgraduate Teacher in the Sciences

ERIC Educational Resources Information Center

Ryan, Barry J.

2014-01-01

Laboratory training is key to many science subjects and those that teach the practical laboratory skills maintain a pivotal role in undergraduate science training. Graduate Teaching Assistants (GTAs) are regularly used in higher education institutes to teach these practical lab skills. The GTA can be involved in both laboratory teaching and…

Evidence for the Induction of Key Components of the NOTCH Signaling Pathway via Deltamethrin and Azamethiphos Treatment in the Sea Louse Caligus rogercresseyi

PubMed Central

Boltaña, Sebastian; Chávez-Mardones, Jaqueline; Valenzuela-Muñoz, Valentina; Gallardo-Escárate, Cristian

2016-01-01

The extensive use of organophosphates and pyrethroids in the aquaculture industry has negatively impacted parasite sensitivity to the delousing effects of these antiparasitics, especially among sea lice species. The NOTCH signaling pathway is a positive regulator of ABC transporter subfamily C expression and plays a key role in the generation and modulation of pesticide resistance. However, little is known about the molecular mechanisms behind pesticide resistance, partly due to the lack of genomic and molecular information on the processes involved in the resistance mechanism of sea lice. Next-generation sequencing technologies provide an opportunity for rapid and cost-effective generation of genome-scale data. The present study, through RNA-seq analysis, determined that the sea louse Caligus rogercresseyi (C. rogercresseyi) specifically responds to the delousing drugs azamethiphos and deltamethrin at the transcriptomic level by differentially activating mRNA of the NOTCH signaling pathway and of ABC genes. These results suggest that frequent antiparasitic application may increase the activity of inhibitory mRNA components, thereby promoting inhibitory NOTCH output and conditions for increased resistance to delousing drugs. Moreover, data analysis underscored that key functions of NOTCH/ABC components were regulated during distinct phases of the drug response, thus indicating resistance modifications in C. rogercresseyi resulting from the frequent use of organophosphates and pyrethroids. PMID:27187362

Evidence for the Induction of Key Components of the NOTCH Signaling Pathway via Deltamethrin and Azamethiphos Treatment in the Sea Louse Caligus rogercresseyi.

PubMed

Boltaña, Sebastian; Chávez-Mardones, Jaqueline; Valenzuela-Muñoz, Valentina; Gallardo-Escárate, Cristian

2016-05-12

The extensive use of organophosphates and pyrethroids in the aquaculture industry has negatively impacted parasite sensitivity to the delousing effects of these antiparasitics, especially among sea lice species. The NOTCH signaling pathway is a positive regulator of ABC transporter subfamily C expression and plays a key role in the generation and modulation of pesticide resistance. However, little is known about the molecular mechanisms behind pesticide resistance, partly due to the lack of genomic and molecular information on the processes involved in the resistance mechanism of sea lice. Next-generation sequencing technologies provide an opportunity for rapid and cost-effective generation of genome-scale data. The present study, through RNA-seq analysis, determined that the sea louse Caligus rogercresseyi (C. rogercresseyi) specifically responds to the delousing drugs azamethiphos and deltamethrin at the transcriptomic level by differentially activating mRNA of the NOTCH signaling pathway and of ABC genes. These results suggest that frequent antiparasitic application may increase the activity of inhibitory mRNA components, thereby promoting inhibitory NOTCH output and conditions for increased resistance to delousing drugs. Moreover, data analysis underscored that key functions of NOTCH/ABC components were regulated during distinct phases of the drug response, thus indicating resistance modifications in C. rogercresseyi resulting from the frequent use of organophosphates and pyrethroids.

Concentrating Solar Power Central Receiver Panel Component Fabrication and Testing FINAL REPORT

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

McDowell, Michael W; Miner, Kris

The objective of this project is to complete a design of an advanced concentrated solar panel and demonstrate the manufacturability of key components. Then confirm the operation of the key components under prototypic solar flux conditions. This work is an important step in reducing the levelized cost of energy (LCOE) from a central receiver solar power plant. The key technical risk to building larger power towers is building the larger receiver systems. Therefore, this proposed technology project includes the design of an advanced molten salt prototypic sub-scale receiver panel that can be utilized into a large receiver system. Then completemore » the fabrication and testing of key components of the receive design that will be used to validate the design. This project shall have a significant impact on solar thermal power plant design. Receiver panels of suitable size for utility scale plants are a key element to a solar power tower plant. Many subtle and complex manufacturing processes are involved in producing a reliable, robust receiver panel. Given the substantial size difference between receiver panels manufactured in the past and those needed for large plant designs, the manufacture and demonstration on prototype receiver panel components with representative features of a full-sized panel will be important to improving the build process for commercial success. Given the thermal flux limitations of the test facility, the panel components cannot be rendered full size. Significance changes occurred in the projects technical strategies from project initiation to the accomplishments described herein. The initial strategy was to define cost improvements for the receiver, design and build a scale prototype receiver and test, on sun, with a molten salt heat transport system. DOE had committed to constructing a molten salt heat transport loop to support receiver testing at the top of the NSTTF tower. Because of funding constraints this did not happen. A subsequent plan to test scale prototype receiver, off sun but at temperature, at a molten salt loop at ground level adjacent to the tower also had to be abandoned. Thus, no test facility existed for a molten salt receiver test. As a result, PWR completed the prototype receiver design and then fabricated key components for testing instead of fabricating the complete prototype receiver. A number of innovative design ideas have been developed. Key features of the receiver panel have been identified. This evaluation includes input from Solar 2, personal experience of people working on these programs and meetings with Sandia. Key components of the receiver design and key processes used to fabricate a receiver have been selected for further evaluation. The Test Plan, Concentrated Solar Power Receiver In Cooperation with the Department of Energy and Sandia National Laboratory was written to define the scope of the testing to be completed as well as to provide details related to the hardware, instrumentation, and data acquisition. The document contains a list of test objectives, a test matrix, and an associated test box showing the operating points to be tested. Test Objectives: 1. Demonstrate low-cost manufacturability 2. Demonstrate robustness of two different tube base materials 3. Collect temperature data during on sun operation 4. Demonstrate long term repeated daily operation of heat shields 5. Complete pinhole tube weld repairs 6. Anchor thermal models This report discusses the tests performed, the results, and implications for design improvements and LCOE reduction.« less

Multiple Sclerosis: Molecular Mechanisms and Therapeutic Opportunities

PubMed Central

Miljković, Djordje; Spasojević, Ivan

2013-01-01

Abstract The pathophysiology of multiple sclerosis (MS) involves several components: redox, inflammatory/autoimmune, vascular, and neurodegenerative. All of them are supported by the intertwined lines of evidence, and none of them should be written off. However, the exact mechanisms of MS initiation, its development, and progression are still elusive, despite the impressive pace by which the data on MS are accumulating. In this review, we will try to integrate the current facts and concepts, focusing on the role of redox changes and various reactive species in MS. Knowing the schedule of initial changes in pathogenic factors and the key turning points, as well as understanding the redox processes involved in MS pathogenesis is the way to enable MS prevention, early treatment, and the development of therapies that target specific pathophysiological components of the heterogeneous mechanisms of MS, which could alleviate the symptoms and hopefully stop MS. Pertinent to this, we will outline (i) redox processes involved in MS initiation; (ii) the role of reactive species in inflammation; (iii) prooxidative changes responsible for neurodegeneration; and (iv) the potential of antioxidative therapy. Antioxid. Redox Signal. 19, 2286–2334. PMID:23473637

Ram locus is a key regulator to trigger multidrug resistance in Enterobacter aerogenes.

PubMed

Molitor, Alexander; James, Chloë E; Fanning, Séamus; Pagès, Jean-Marie; Davin-Regli, Anne

2018-02-01

Several genetic regulators belonging to AraC family are involved in the emergence of MDR isolates of E. aerogenes due to alterations in membrane permeability. Compared with the genetic regulator Mar, RamA may be more relevant towards the emergence of antibiotic resistance. Focusing on the global regulators, Mar and Ram, we compared the amino acid sequences of the Ram repressor in 59 clinical isolates and laboratory strains of E. aerogenes. Sequence types were associated with their corresponding multi-drug resistance phenotypes and membrane protein expression profiles using MIC and immunoblot assays. Quantitative gene expression analysis of the different regulators and their targets (porins and efflux pump components) were performed. In the majority of the MDR isolates tested, ramR and a region upstream of ramA were mutated but marR or marA were unchanged. Expression and cloning experiments highlighted the involvement of the ram locus in the modification of membrane permeability. Overexpression of RamA lead to decreased porin production and increased expression of efflux pump components, whereas overexpression of RamR had the opposite effects. Mutations or deletions in ramR, leading to the overexpression of RamA predominated in clinical MDR E. aerogenes isolates and were associated with a higher-level of expression of efflux pump components. It was hypothesised that mutations in ramR, and the self-regulating region proximal to ramA, probably altered the binding properties of the RamR repressor; thereby producing the MDR phenotype. Consequently, mutability of RamR may play a key role in predisposing E. aerogenes towards the emergence of a MDR phenotype.

Enhancing nurses' roles to improve quality and efficiency of non-medical cardiac stress tests.

PubMed

Bernhardt, Lizelle; Ross, Lisa; Greaves, Claire

Myocardial perfusion imaging (MPI) is a test that aids the diagnosis of coronary heart disease, of which pharmacological stress is a key component. An increase in demand had resulted in a 42 week waiting time for MPI in Leicester. This article looks at how implementing non-medically led stress tests reduced this waiting list. It discusses the obstacles involved and the measures needed to make the service a success.

A systematic review of the international published literature relating to quality of institutional care for people with longer term mental health problems

PubMed Central

Taylor, Tatiana L; Killaspy, Helen; Wright, Christine; Turton, Penny; White, Sarah; Kallert, Thomas W; Schuster, Mirjam; Cervilla, Jorge A; Brangier, Paulette; Raboch, Jiri; Kališová, Lucie; Onchev, Georgi; Dimitrov, Hristo; Mezzina, Roberto; Wolf, Kinou; Wiersma, Durk; Visser, Ellen; Kiejna, Andrzej; Piotrowski, Patryk; Ploumpidis, Dimitri; Gonidakis, Fragiskos; Caldas-de-Almeida, José; Cardoso, Graça; King, Michael B

2009-01-01

Background A proportion of people with mental health problems require longer term care in a psychiatric or social care institution. However, there are no internationally agreed quality standards for institutional care and no method to assess common care standards across countries. We aimed to identify the key components of institutional care for people with longer term mental health problems and the effectiveness of these components. Methods We undertook a systematic review of the literature using comprehensive search terms in 11 electronic databases and identified 12,182 titles. We viewed 550 abstracts, reviewed 223 papers and included 110 of these. A "critical interpretative synthesis" of the evidence was used to identify domains of institutional care that are key to service users' recovery. Results We identified eight domains of institutional care that were key to service users' recovery: living conditions; interventions for schizophrenia; physical health; restraint and seclusion; staff training and support; therapeutic relationship; autonomy and service user involvement; and clinical governance. Evidence was strongest for specific interventions for the treatment of schizophrenia (family psychoeducation, cognitive behavioural therapy (CBT) and vocational rehabilitation). Conclusion Institutions should, ideally, be community based, operate a flexible regime, maintain a low density of residents and maximise residents' privacy. For service users with a diagnosis of schizophrenia, specific interventions (CBT, family interventions involving psychoeducation, and supported employment) should be provided through integrated programmes. Restraint and seclusion should be avoided wherever possible and staff should have adequate training in de-escalation techniques. Regular staff supervision should be provided and this should support service user involvement in decision making and positive therapeutic relationships between staff and service users. There should be clear lines of clinical governance that ensure adherence to evidence-based guidelines and attention should be paid to service users' physical health through regular screening. PMID:19735562

A systematic review of the international published literature relating to quality of institutional care for people with longer term mental health problems.

PubMed

Taylor, Tatiana L; Killaspy, Helen; Wright, Christine; Turton, Penny; White, Sarah; Kallert, Thomas W; Schuster, Mirjam; Cervilla, Jorge A; Brangier, Paulette; Raboch, Jiri; Kalisová, Lucie; Onchev, Georgi; Dimitrov, Hristo; Mezzina, Roberto; Wolf, Kinou; Wiersma, Durk; Visser, Ellen; Kiejna, Andrzej; Piotrowski, Patryk; Ploumpidis, Dimitri; Gonidakis, Fragiskos; Caldas-de-Almeida, José; Cardoso, Graça; King, Michael B

2009-09-07

A proportion of people with mental health problems require longer term care in a psychiatric or social care institution. However, there are no internationally agreed quality standards for institutional care and no method to assess common care standards across countries. We aimed to identify the key components of institutional care for people with longer term mental health problems and the effectiveness of these components. We undertook a systematic review of the literature using comprehensive search terms in 11 electronic databases and identified 12,182 titles. We viewed 550 abstracts, reviewed 223 papers and included 110 of these. A "critical interpretative synthesis" of the evidence was used to identify domains of institutional care that are key to service users' recovery. We identified eight domains of institutional care that were key to service users' recovery: living conditions; interventions for schizophrenia; physical health; restraint and seclusion; staff training and support; therapeutic relationship; autonomy and service user involvement; and clinical governance. Evidence was strongest for specific interventions for the treatment of schizophrenia (family psychoeducation, cognitive behavioural therapy (CBT) and vocational rehabilitation). Institutions should, ideally, be community based, operate a flexible regime, maintain a low density of residents and maximise residents' privacy. For service users with a diagnosis of schizophrenia, specific interventions (CBT, family interventions involving psychoeducation, and supported employment) should be provided through integrated programmes. Restraint and seclusion should be avoided wherever possible and staff should have adequate training in de-escalation techniques. Regular staff supervision should be provided and this should support service user involvement in decision making and positive therapeutic relationships between staff and service users. There should be clear lines of clinical governance that ensure adherence to evidence-based guidelines and attention should be paid to service users' physical health through regular screening.

The emerging role of lysosomes in copper homeostasis.

PubMed

Polishchuk, Elena V; Polishchuk, Roman S

2016-09-01

The lysosomal system operates as a focal point where a number of important physiological processes such as endocytosis, autophagy and nutrient sensing converge. One of the key functions of lysosomes consists of regulating the metabolism/homeostasis of metals. Metal-containing components are carried to the lysosome through incoming membrane flows, while numerous transporters allow metal ions to move across the lysosome membrane. These properties enable lysosomes to direct metal fluxes to the sites where metal ions are either used by cellular components or sequestered. Copper belongs to a group of metals that are essential for the activity of vitally important enzymes, although it is toxic when in excess. Thus, copper uptake, supply and intracellular compartmentalization have to be tightly regulated. An increasing number of publications have indicated that these processes involve lysosomes. Here we review studies that reveal the expanding role of the lysosomal system as a hub for the control of Cu homeostasis and for the regulation of key Cu-dependent processes in health and disease.

Induced unconventional superconductivity on the surface states of Bi2Te3 topological insulator.

PubMed

Charpentier, Sophie; Galletti, Luca; Kunakova, Gunta; Arpaia, Riccardo; Song, Yuxin; Baghdadi, Reza; Wang, Shu Min; Kalaboukhov, Alexei; Olsson, Eva; Tafuri, Francesco; Golubev, Dmitry; Linder, Jacob; Bauch, Thilo; Lombardi, Floriana

2017-12-08

Topological superconductivity is central to a variety of novel phenomena involving the interplay between topologically ordered phases and broken-symmetry states. The key ingredient is an unconventional order parameter, with an orbital component containing a chiral p x  + ip y wave term. Here we present phase-sensitive measurements, based on the quantum interference in nanoscale Josephson junctions, realized by using Bi 2 Te 3 topological insulator. We demonstrate that the induced superconductivity is unconventional and consistent with a sign-changing order parameter, such as a chiral p x  + ip y component. The magnetic field pattern of the junctions shows a dip at zero externally applied magnetic field, which is an incontrovertible signature of the simultaneous existence of 0 and π coupling within the junction, inherent to a non trivial order parameter phase. The nano-textured morphology of the Bi 2 Te 3 flakes, and the dramatic role played by thermal strain are the surprising key factors for the display of an unconventional induced order parameter.

Visualizing Sound: Demonstrations to Teach Acoustic Concepts

NASA Astrophysics Data System (ADS)

Rennoll, Valerie

Interference, a phenomenon in which two sound waves superpose to form a resultant wave of greater or lower amplitude, is a key concept when learning about the physics of sound waves. Typical interference demonstrations involve students listening for changes in sound level as they move throughout a room. Here, new tools are developed to teach this concept that provide a visual component, allowing individuals to see changes in sound level on a light display. This is accomplished using a microcontroller that analyzes sound levels collected by a microphone and displays the sound level in real-time on an LED strip. The light display is placed on a sliding rail between two speakers to show the interference occurring between two sound waves. When a long-exposure photograph is taken of the light display being slid from one end of the rail to the other, a wave of the interference pattern can be captured. By providing a visual component, these tools will help students and the general public to better understand interference, a key concept in acoustics.

Reticular Formation and Pain: The Past and the Future

PubMed Central

Martins, Isabel; Tavares, Isaura

2017-01-01

The involvement of the reticular formation (RF) in the transmission and modulation of nociceptive information has been extensively studied. The brainstem RF contains several areas which are targeted by spinal cord afferents conveying nociceptive input. The arrival of nociceptive input to the RF may trigger alert reactions which generate a protective/defense reaction to pain. RF neurons located at the medulla oblongata and targeted by ascending nociceptive information are also involved in the control of vital functions that can be affected by pain, namely cardiovascular control. The RF contains centers that belong to the pain modulatory system, namely areas involved in bidirectional balance (decrease or enhancement) of pain responses. It is currently accepted that the imbalance of pain modulation towards pain facilitation accounts for chronic pain. The medullary RF has the peculiarity of harboring areas involved in bidirectional pain control namely by the existence of specific neuronal populations involved in antinociceptive or pronociceptive behavioral responses, namely at the rostroventromedial medulla (RVM) and the caudal ventrolateral medulla (VLM). Furthermore the dorsal reticular nucleus (also known as subnucleus reticularis dorsalis; DRt) may enhance nociceptive responses, through a reverberative circuit established with spinal lamina I neurons and inhibit wide-dynamic range (WDR) neurons of the deep dorsal horn. The components of the triad RVM-VLM-DRt are reciprocally connected and represent a key gateway for top-down pain modulation. The RVM-VLM-DRt triad also represents the neurobiological substrate for the emotional and cognitive modulation of pain, through pathways that involve the periaqueductal gray (PAG)-RVM connection. Collectively, we propose that the RVM-VLM-DRt triad represents a key component of the “dynamic pain connectome” with special features to provide integrated and rapid responses in situations which are life-threatening and involve pain. The new available techniques in neurobiological studies both in animal and human studies are producing new and fascinating data which allow to understand the complex role of the RF in pain modulation and its integration with several body functions and also how the RF accounts for chronic pain. PMID:28725185

Reticular Formation and Pain: The Past and the Future.

PubMed

Martins, Isabel; Tavares, Isaura

2017-01-01

The involvement of the reticular formation (RF) in the transmission and modulation of nociceptive information has been extensively studied. The brainstem RF contains several areas which are targeted by spinal cord afferents conveying nociceptive input. The arrival of nociceptive input to the RF may trigger alert reactions which generate a protective/defense reaction to pain. RF neurons located at the medulla oblongata and targeted by ascending nociceptive information are also involved in the control of vital functions that can be affected by pain, namely cardiovascular control. The RF contains centers that belong to the pain modulatory system, namely areas involved in bidirectional balance (decrease or enhancement) of pain responses. It is currently accepted that the imbalance of pain modulation towards pain facilitation accounts for chronic pain. The medullary RF has the peculiarity of harboring areas involved in bidirectional pain control namely by the existence of specific neuronal populations involved in antinociceptive or pronociceptive behavioral responses, namely at the rostroventromedial medulla (RVM) and the caudal ventrolateral medulla (VLM). Furthermore the dorsal reticular nucleus (also known as subnucleus reticularis dorsalis; DRt) may enhance nociceptive responses, through a reverberative circuit established with spinal lamina I neurons and inhibit wide-dynamic range (WDR) neurons of the deep dorsal horn. The components of the triad RVM-VLM-DRt are reciprocally connected and represent a key gateway for top-down pain modulation. The RVM-VLM-DRt triad also represents the neurobiological substrate for the emotional and cognitive modulation of pain, through pathways that involve the periaqueductal gray (PAG)-RVM connection. Collectively, we propose that the RVM-VLM-DRt triad represents a key component of the "dynamic pain connectome" with special features to provide integrated and rapid responses in situations which are life-threatening and involve pain. The new available techniques in neurobiological studies both in animal and human studies are producing new and fascinating data which allow to understand the complex role of the RF in pain modulation and its integration with several body functions and also how the RF accounts for chronic pain.

Motor learning.

PubMed

Wolpert, Daniel M; Flanagan, J Randall

2010-06-08

Although learning a motor skill, such as a tennis stroke, feels like a unitary experience, researchers who study motor control and learning break the processes involved into a number of interacting components. These components can be organized into four main groups. First, skilled performance requires the effective and efficient gathering of sensory information, such as deciding where and when to direct one's gaze around the court, and thus an important component of skill acquisition involves learning how best to extract task-relevant information. Second, the performer must learn key features of the task such as the geometry and mechanics of the tennis racket and ball, the properties of the court surface, and how the wind affects the ball's flight. Third, the player needs to set up different classes of control that include predictive and reactive control mechanisms that generate appropriate motor commands to achieve the task goals, as well as compliance control that specifies, for example, the stiffness with which the arm holds the racket. Finally, the successful performer can learn higher-level skills such as anticipating and countering the opponent's strategy and making effective decisions about shot selection. In this Primer we shall consider these components of motor learning using as an example how we learn to play tennis. 2010 Elsevier Ltd. All rights reserved.

Bovine somatotropin and lactation: from basic science to commercial application.

PubMed

Bauman, D E

1999-10-01

Bovine somatotropin (bST) results in increased milk yield and an unprecedented improvement in efficiency. Beginning in the 1930s to present day, investigations have examined animal-related factors such as nutrition, bioenergetics, metabolism, health and well being and consumer-related factors such as milk quality, manufacturing characteristics, and product safety. Overall, bST is a homeorhetic control involved in orchestrating many physiological processes. Direct effects involve adaptations in many tissues and the metabolism of all nutrient classes--carbohydrates, lipids, protein, and minerals. Mechanisms include alterations in key enzymes, intracellular signal transduction systems, and tissue response to homeostatic signals. Indirect effects involve the mammary gland and are thought to be mediated by the insulin-like growth factor (IGF) system. Specific changes include increased cellular rates of milk synthesis and enhanced maintenance of secretory cells. Indirect effects are modulated by environment and management factors, especially nutritional status. This modulation is a central component in allowing ST to play a key role in regulating nutrient utilization across a range of physiological situations. U.S. commercial use began in 1994, and adoption has been extensive. From a consumer perspective, bST was unique, and special interest groups loudly predicted dire consequences. However, introduction of bST had no impact on milk consumption, and milk labeled as recombinant bST-free occupies a minor niche market. From a producer perspective, commercial use verified scientific studies and enhanced net farm income. Overall, ST is a key homeorhetic control regulating nutrient partitioning, and the ST/IGF system plays a key role in animal performance and well being across a range of physiological situations.

NASA Integrated Model Centric Architecture (NIMA) Model Use and Re-Use

NASA Technical Reports Server (NTRS)

Conroy, Mike; Mazzone, Rebecca; Lin, Wei

2012-01-01

This whitepaper accepts the goals, needs and objectives of NASA's Integrated Model-centric Architecture (NIMA); adds experience and expertise from the Constellation program as well as NASA's architecture development efforts; and provides suggested concepts, practices and norms that nurture and enable model use and re-use across programs, projects and other complex endeavors. Key components include the ability to effectively move relevant information through a large community, process patterns that support model reuse and the identification of the necessary meta-information (ex. history, credibility, and provenance) to safely use and re-use that information. In order to successfully Use and Re-Use Models and Simulations we must define and meet key organizational and structural needs: 1. We must understand and acknowledge all the roles and players involved from the initial need identification through to the final product, as well as how they change across the lifecycle. 2. We must create the necessary structural elements to store and share NIMA-enabled information throughout the Program or Project lifecycle. 3. We must create the necessary organizational processes to stand up and execute a NIMA-enabled Program or Project throughout its lifecycle. NASA must meet all three of these needs to successfully use and re-use models. The ability to Reuse Models a key component of NIMA and the capabilities inherent in NIMA are key to accomplishing NASA's space exploration goals. 11

A Thyroid Hormone Challenge in Hypothyroid Rats Identifies T3 Regulated Genes in the Hypothalamus and in Models with Altered Energy Balance and Glucose Homeostasis

PubMed Central

Herwig, Annika; Campbell, Gill; Mayer, Claus-Dieter; Boelen, Anita; Anderson, Richard A.; Ross, Alexander W.; Mercer, Julian G.

2014-01-01

Background: The thyroid hormone triiodothyronine (T3) is known to affect energy balance. Recent evidence points to an action of T3 in the hypothalamus, a key area of the brain involved in energy homeostasis, but the components and mechanisms are far from understood. The aim of this study was to identify components in the hypothalamus that may be involved in the action of T3 on energy balance regulatory mechanisms. Methods: Sprague Dawley rats were made hypothyroid by giving 0.025% methimazole (MMI) in their drinking water for 22 days. On day 21, half the MMI-treated rats received a saline injection, whereas the others were injected with T3. Food intake and body weight measurements were taken daily. Body composition was determined by magnetic resonance imaging, gene expression was analyzed by in situ hybridization, and T3-induced gene expression was determined by microarray analysis of MMI-treated compared to MMI-T3-injected hypothalamic RNA. Results: Post mortem serum thyroid hormone levels showed that MMI treatment decreased circulating thyroid hormones and increased thyrotropin (TSH). MMI treatment decreased food intake and body weight. Body composition analysis revealed reduced lean and fat mass in thyroidectomized rats from day 14 of the experiment. MMI treatment caused a decrease in circulating triglyceride concentrations, an increase in nonesterified fatty acids, and decreased insulin levels. A glucose tolerance test showed impaired glucose clearance in the thyroidectomized animals. In the brain, in situ hybridization revealed marked changes in gene expression, including genes such as Mct8, a thyroid hormone transporter, and Agrp, a key component in energy balance regulation. Microarray analysis revealed 110 genes to be up- or downregulated with T3 treatment (±1.3-fold change, p<0.05). Three genes chosen from the differentially expressed genes were verified by in situ hybridization to be activated by T3 in cells located at or close to the hypothalamic ventricular ependymal layer and differentially expressed in animal models of long- and short-term body weight regulation. Conclusion: This study identified genes regulated by T3 in the hypothalamus, a key area of the brain involved in homeostasis and neuroendocrine functions. These include genes hitherto not known to be regulated by thyroid status. PMID:25087834

Key influences in the design and implementation of mental health information systems in Ghana and South Africa.

PubMed

Ahuja, S; Mirzoev, T; Lund, C; Ofori-Atta, A; Skeen, S; Kufuor, A

2016-01-01

Strengthening of mental health information systems (MHIS) is essential to monitor and evaluate mental health services in low and middle-income countries. While research exists assessing wider health management information systems, there is limited published evidence exploring the design and implementation of MHIS in these settings. This paper aims to identify and assess the key factors affecting the design and implementation of MHIS, as perceived by the key stakeholders in Ghana and South Africa. We report findings from the Mental Health and Poverty Project, a 5-year research programme implemented within four African countries. The MHIS strengthening in South Africa and Ghana included two related components: intervention and research. The intervention component aimed to strengthen MHIS in the two countries, and the research component aimed to document interventions in each country, including the key influences. Data were collected using semi structured interviews with key stakeholders and reviews of key documents and secondary data from the improved MHIS. We analyzed the qualitative data using a framework approach. Key components of the MHIS intervention involved the introduction of a redesigned patient registration form, entry into computers for analysis every 2 months by clinical managerial staff, and utilization of data in hospital management meetings in three psychiatric hospitals in Ghana; and the introduction of a new set of mental health indicators and related forms and tally sheets at primary care clinics and district hospitals in five districts in the KwaZulu-Natal and Northern Cape provinces in South Africa. Overall, the key stakeholders perceived the MHIS strengthening as an effective intervention in both countries with an enhanced set of indicators in South Africa and introduction of a computerized system in Ghana. Influences on the design and implementation of MHIS interventions in Ghana and South Africa relate to resources, working approaches (including degree of consultations during the design stage and communication during implementation stage) and the low priority of mental health. Although the influencing factors represent similar categories, more influences were identified on MHIS implementation, compared with the design stage. Different influences appear to be related within, and across, the MHIS design and implementation and may reinforce or negate each other thus leading to the multiplier or minimization effects. The wider context, similar to other studies, is important in ensuring the success of such interventions. Future MHIS strengthening interventions can consider three policy implications which emerged from our analysis and experience: enhancing consultations during the intervention design, better consideration of implementation challenges during design, and better recognition of relations between different influences.

Acetogenesis and the Wood-Ljungdahl Pathway of CO2 Fixation

PubMed Central

Ragsdale, Stephen W.; Pierce, Elizabeth

2008-01-01

I. Summary Conceptually, the simplest way to synthesize an organic molecule is to construct it one carbon at a time. The Wood-Ljungdahl pathway of CO2 fixation involves this type of stepwise process. The biochemical events that underlie the condensation of two one-carbon units to form the two-carbon compound, acetate, have intrigued chemists, biochemists, and microbiologists for many decades. We begin this review with a description of the biology of acetogenesis. Then, we provide a short history of the important discoveries that have led to the identification of the key components and steps of this usual mechanism of CO and CO2 fixation. In this historical perspective, we have included reflections that hopefully will sketch the landscape of the controversies, hypotheses, and opinions that led to the key experiments and discoveries. We then describe the properties of the genes and enzymes involved in the pathway and conclude with a section describing some major questions that remain unanswered. PMID:18801467

Tyrosine phosphorylation of WW proteins

PubMed Central

Reuven, Nina; Shanzer, Matan

2015-01-01

A number of key regulatory proteins contain one or two copies of the WW domain known to mediate protein–protein interaction via proline-rich motifs, such as PPxY. The Hippo pathway components take advantage of this module to transduce tumor suppressor signaling. It is becoming evident that tyrosine phosphorylation is a critical regulator of the WW proteins. Here, we review the current knowledge on the involved tyrosine kinases and their roles in regulating the WW proteins. PMID:25627656

TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis.

PubMed

Kabashi, Edor; Valdmanis, Paul N; Dion, Patrick; Spiegelman, Dan; McConkey, Brendan J; Vande Velde, Christine; Bouchard, Jean-Pierre; Lacomblez, Lucette; Pochigaeva, Ksenia; Salachas, Francois; Pradat, Pierre-Francois; Camu, William; Meininger, Vincent; Dupre, Nicolas; Rouleau, Guy A

2008-05-01

Recently, TDP-43 was identified as a key component of ubiquitinated aggregates in amyotrophic lateral sclerosis (ALS), an adult-onset neurological disorder that leads to the degeneration of motor neurons. Here we report eight missense mutations in nine individuals--six from individuals with sporadic ALS (SALS) and three from those with familial ALS (FALS)--and a concurring increase of a smaller TDP-43 product. These findings further corroborate that TDP-43 is involved in ALS pathogenesis.

Analysis of inflammasomes and antiviral sensing components reveals decreased expression of NLRX1 in HIV-positive patients assuming efficient antiretroviral therapy.

PubMed

Nasi, Milena; De Biasi, Sara; Bianchini, Elena; Digaetano, Margherita; Pinti, Marcello; Gibellini, Lara; Pecorini, Simone; Carnevale, Gianluca; Guaraldi, Giovanni; Borghi, Vanni; Mussini, Cristina; Cossarizza, Andrea

2015-09-24

Few studies have investigated the importance of different components of the inflammasome system and of innate mitochondrial sensing (IMS) pathways in HIV infection and its treatment. We analysed the expression of several components of the inflammasome and of the IMS in HIV-positive patients taking successful combination antiretroviral therapy (cART). We enrolled 20 HIV-positive patients under cART, who achieved viral suppression since at least 10 months and 20 age and sex-matched healthy donors. By RT-PCR, using peripheral blood mononuclear cells (PBMCs), we quantified the mRNA expression of 16 genes involved in inflammasome activation and regulation (AIM2, NAIP, PYCARD, CASP1, CASP5, NLRP6, NLRP1, NLRP3, TXNIP, BCL2, NLRC4, PANX1, P2RX7, IL-18, IL-1β, SUGT1) and eight genes involved in IMS (MFN2, MFN1, cGAS, RIG-I, MAVS, NLRX1, RAB32, STING). Compared with controls, HIV-positive patients showed significantly lower mRNA levels of the mitochondrial protein NLRX1, which plays a key role in regulating apoptotic cell death; main PBMC subpopulations behave in a similar manner. No differences were observed in the expression of inflammasome components, which however showed complex correlations. The decreased level of NLRX1 in HIV infection could suggest that the virus is able to downregulate mechanisms linked to triggering of cell death in several immune cell types. The fact that HIV-positive patients did not show altered expression of inflammasome components, nor of most genes involved in IMS, suggests that the infection and/or the chronic immune activation does not influence the transcriptional machinery of innate mechanisms able to trigger inflammation at different levels.

The National Heart, Lung, and Blood Institute Recipient Epidemiology and Donor Evaluation Study (REDS-III): A research program striving to improve blood donor and transfusion recipient outcomes

PubMed Central

Kleinman, Steven; Busch, Michael P; Murphy, Edward L; Shan, Hua; Ness, Paul; Glynn, Simone A.

2014-01-01

Background The Recipient Epidemiology and Donor Evaluation Study -III (REDS-III) is a 7-year multicenter transfusion safety research initiative launched in 2011 by the National Heart, Lung, and Blood Institute. Study design The domestic component involves 4 blood centers, 12 hospitals, a data coordinating center, and a central laboratory. The international component consists of distinct programs in Brazil, China, and South Africa which involve US and in-country investigators. Results REDS-III is using two major methods to address key research priorities in blood banking/transfusion medicine. First, there will be numerous analyses of large “core” databases; the international programs have each constructed a donor/donation database while the domestic program has established a detailed research database that links data from blood donors and their donations, the components made from these donations, and data extracts from the electronic medical records of the recipients of these components. Secondly, there are more than 25 focused research protocols involving transfusion recipients, blood donors, or both that are either in progress or scheduled to begin within the next 3 years. Areas of study include transfusion epidemiology and blood utilization; transfusion outcomes; non-infectious transfusion risks; HIV-related safety issues (particularly in the international programs); emerging infectious agents; blood component quality; donor health and safety; and other donor issues. Conclusions It is intended that REDS-III serve as an impetus for more widespread recipient and linked donor-recipient research in the US as well as to help assure a safe and available blood supply in the US and in international locations. PMID:24188564

Gene Network Polymorphism Illuminates Loss and Retention of Novel RNAi Silencing Components in the Cryptococcus Pathogenic Species Complex.

PubMed

Feretzaki, Marianna; Billmyre, R Blake; Clancey, Shelly Applen; Wang, Xuying; Heitman, Joseph

2016-03-01

RNAi is a ubiquitous pathway that serves central functions throughout eukaryotes, including maintenance of genome stability and repression of transposon expression and movement. However, a number of organisms have lost their RNAi pathways, including the model yeast Saccharomyces cerevisiae, the maize pathogen Ustilago maydis, the human pathogen Cryptococcus deuterogattii, and some human parasite pathogens, suggesting there may be adaptive benefits associated with both retention and loss of RNAi. By comparing the RNAi-deficient genome of the Pacific Northwest Outbreak C. deuterogattii strain R265 with the RNAi-proficient genomes of the Cryptococcus pathogenic species complex, we identified a set of conserved genes that were lost in R265 and all other C. deuterogattii isolates examined. Genetic and molecular analyses reveal several of these lost genes play roles in RNAi pathways. Four novel components were examined further. Znf3 (a zinc finger protein) and Qip1 (a homolog of N. crassa Qip) were found to be essential for RNAi, while Cpr2 (a constitutive pheromone receptor) and Fzc28 (a transcription factor) are involved in sex-induced but not mitosis-induced silencing. Our results demonstrate that the mitotic and sex-induced RNAi pathways rely on the same core components, but sex-induced silencing may be a more specific, highly induced variant that involves additional specialized or regulatory components. Our studies further illustrate how gene network polymorphisms involving known components of key cellular pathways can inform identification of novel elements and suggest that RNAi loss may have been a core event in the speciation of C. deuterogattii and possibly contributed to its pathogenic trajectory.

Design Considerations For Imaging Charge-Coupled Device (ICCD) Star Sensors

NASA Astrophysics Data System (ADS)

McAloon, K. J.

1981-04-01

A development program is currently underway to produce a precision star sensor using imaging charge coupled device (ICCD) technology. The effort is the critical component development phase for the Air Force Multi-Mission Attitude Determination and Autonomous Navigation System (MADAN). A number of unique considerations have evolved in designing an arcsecond accuracy sensor around an ICCD detector. Three tiers of performance criteria are involved: at the spacecraft attitude determination system level, at the star sensor level, and at the detector level. Optimum attitude determination system performance involves a tradeoff between Kalman filter iteration time and sensor ICCD integration time. The ICCD star sensor lends itself to the use of a new approach in the functional interface between the attitude determination system and the sensor. At the sensor level image data processing tradeoffs are important for optimum sensor performance. These tradeoffs involve the sensor optic configuration, the optical point spread function (PSF) size and shape, the PSF position locator, and the microprocessor locator algorithm. Performance modelling of the sensor mandates the use of computer simulation programs. Five key performance parameters at the ICCD detector level are defined. ICCD error characteristics have also been isolated to five key parameters.

Autism: reduced connectivity between cortical areas involved in face expression, theory of mind, and the sense of self.

PubMed

Cheng, Wei; Rolls, Edmund T; Gu, Huaguang; Zhang, Jie; Feng, Jianfeng

2015-05-01

Whole-brain voxel-based unbiased resting state functional connectivity was analysed in 418 subjects with autism and 509 matched typically developing individuals. We identified a key system in the middle temporal gyrus/superior temporal sulcus region that has reduced cortical functional connectivity (and increased with the medial thalamus), which is implicated in face expression processing involved in social behaviour. This system has reduced functional connectivity with the ventromedial prefrontal cortex, which is implicated in emotion and social communication. The middle temporal gyrus system is also implicated in theory of mind processing. We also identified in autism a second key system in the precuneus/superior parietal lobule region with reduced functional connectivity, which is implicated in spatial functions including of oneself, and of the spatial environment. It is proposed that these two types of functionality, face expression-related, and of one's self and the environment, are important components of the computations involved in theory of mind, whether of oneself or of others, and that reduced connectivity within and between these regions may make a major contribution to the symptoms of autism. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

Technology assessment in healthcare: a review and description of a "best practice" technology assessment process.

PubMed

Fernandez, A M; Schrogie, J J; Wilson, W W; Nash, D B

1997-01-01

Technology assessment has become a rapidly growing component of the healthcare system. It has assumed a functional role in operational settings and is rapidly impacting decisions involving purchasing, coverage, and reimbursement. This review is intended to assist the healthcare decision maker in considering the application of technology assessment in healthcare, so as to maximize the efficiency of future purchasing decisions. This "best practice" was synthesized after identifying key institutions performing technology assessment in healthcare and analyzing their working processes, including literature review, consensus panel discussions, and expert opinion. We describe this best practice on a reiterative loop that consists of five processes: awareness, strategic appropriateness, analysis versus need, acquisition and implementation, and reassessment. Typical barriers to adoption of technology assessment are also identified and discussed. This review suggests a common terminology for the core processes involved in technology assessment, thereby facilitating a more uniform understanding among the different components of the healthcare system (i.e., payer, provider, and society) while recognizing their different perspectives.

Food allergy phenotypes: The key to personalized therapy.

PubMed

Deschildre, A; Lejeune, S; Cap, M; Flammarion, S; Jouannic, L; Amat, F; Just, J

2017-09-01

Food allergies (FAs) are of increasing public health concern and are characterized by a large spectrum of diseases. Their diversity is well known for immunologic pathways (IgE, non-IgE-mediated FAs) and natural history. Many other factors and patient characteristics are involved including type of food, exposure route, allergic comorbidities, gender, racial and ethnic backgrounds, cofactors and health conditions. Food allergen components and sensitization profiles are also involved in FA phenotypes. A new approach to chronic disorders based on the identification of phenotypes through extensive knowledge of all the complex components is also applicable to FAs and could lead towards integrative care management. Diagnostic biomarkers for FAs are emerging which also contribute to better care modalities. The aim of this article was to highlight current knowledge regarding the phenotypic diversity of FA. This review will focus on IgE-mediated FAs and how identifying phenotypes may help to better understand the pathophysiological complexity, improve diagnosis and lead to personalized treatment strategies. © 2017 John Wiley & Sons Ltd.

Fast image interpolation for motion estimation using graphics hardware

NASA Astrophysics Data System (ADS)

Kelly, Francis; Kokaram, Anil

2004-05-01

Motion estimation and compensation is the key to high quality video coding. Block matching motion estimation is used in most video codecs, including MPEG-2, MPEG-4, H.263 and H.26L. Motion estimation is also a key component in the digital restoration of archived video and for post-production and special effects in the movie industry. Sub-pixel accurate motion vectors can improve the quality of the vector field and lead to more efficient video coding. However sub-pixel accuracy requires interpolation of the image data. Image interpolation is a key requirement of many image processing algorithms. Often interpolation can be a bottleneck in these applications, especially in motion estimation due to the large number pixels involved. In this paper we propose using commodity computer graphics hardware for fast image interpolation. We use the full search block matching algorithm to illustrate the problems and limitations of using graphics hardware in this way.

Mitochondrial transcription in mammalian cells

PubMed Central

Shokolenko, Inna N.; Alexeyev, Mikhail F.

2017-01-01

As a consequence of recent discoveries of intimate involvement of mitochondria with key cellular processes, there has been a resurgence of interest in all aspects of mitochondrial biology, including the intricate mechanisms of mitochondrial DNA maintenance and expression. Despite four decades of research, there remains a lot to be learned about the processes that enable transcription of genetic information from mitochondrial DNA to RNA, as well as their regulation. These processes are vitally important, as evidenced by the lethality of inactivating the central components of mitochondrial transcription machinery. Here, we review the current understanding of mitochondrial transcription and its regulation in mammalian cells. We also discuss key theories in the field and highlight controversial subjects and future directions as we see them. PMID:27814650

FRAMEWORK AND APPLICATION FOR MODELING CONTROL ROOM CREW PERFORMANCE AT NUCLEAR POWER PLANTS

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

Ronald L Boring; David I Gertman; Tuan Q Tran

2008-09-01

This paper summarizes an emerging project regarding the utilization of high-fidelity MIDAS simulations for visualizing and modeling control room crew performance at nuclear power plants. The key envisioned uses for MIDAS-based control room simulations are: (i) the estimation of human error associated with advanced control room equipment and configurations, (ii) the investigative determination of contributory cognitive factors for risk significant scenarios involving control room operating crews, and (iii) the certification of reduced staffing levels in advanced control rooms. It is proposed that MIDAS serves as a key component for the effective modeling of cognition, elements of situation awareness, and riskmore » associated with human performance in next generation control rooms.« less

miR-958 inhibits Toll signaling and Drosomycin expression via direct targeting of Toll and Dif in Drosophila melanogaster.

PubMed

Li, Shengjie; Li, Yao; Shen, Li; Jin, Ping; Chen, Liming; Ma, Fei

2017-02-01

Drosophila melanogaster is widely used as a model system to study innate immunity and signaling pathways related to innate immunity, including the Toll signaling pathway. Although this pathway is well studied, the precise mechanisms of posttranscriptional regulation of key components of the Toll signaling pathway by microRNAs (miRNAs) remain obscure. In this study, we used an in silico strategy in combination with the Gal80 ts -Gal4 driver system to identify microRNA-958 (miR-958) as a candidate Toll pathway regulating miRNA in Drosophila We report that overexpression of miR-958 significantly reduces the expression of Drosomycin, a key antimicrobial peptide involved in Toll signaling and the innate immune response. We further demonstrate in vitro and in vivo that miR-958 targets the Toll and Dif genes, key components of the Toll signaling pathway, to negatively regulate Drosomycin expression. In addition, a miR-958 sponge rescued the expression of Toll and Dif, resulting in increased expression of Drosomycin. These results, not only revealed a novel function and modulation pattern of miR-958, but also provided a new insight into the underlying molecular mechanisms of Toll signaling in regulation of innate immunity. Copyright © 2017 the American Physiological Society.

A National Evaluation of the Nighttime and Passenger Restriction Components of Graduated Driver Licensing

PubMed Central

Fell, James C.; Todd, Michael; Voas, Robert B.

2011-01-01

Introduction The high crash rate of youthful novice drivers has been recognized for half a century. Over the last decade, graduated driver licensing (GDL) systems, which extend the period of supervised driving and limit the novice’s exposure to higher-risk conditions (such as nighttime driving) has effectively reduced crash involvements of novice drivers. Method This study used data from the Fatality Analysis Reporting System (FARS) and the implementation dates of GDL laws in a state-by-year panel study to evaluate the effectiveness of two key elements of GDL laws: nighttime restrictions and passenger limitations. Results Nighttime restrictions were found to reduce 16- and 17-year-old driver involvements in nighttime fatal crashes by an estimated 10% and 16- and 17-year-old drinking drivers in nighttime fatal crashes by 13%. Passenger restrictions were found to reduce 16- and 17-year-old driver involvements in fatal crashes with teen passengers by an estimated 9%. Conclusions These results confirm the effectiveness of these provisions in GDL systems. Impact on Public Health The results of this study indicate that nighttime restrictions and passenger limitations are very important components of any GDL law. PMID:22017831

Intelligence, Dataveillance, and Information Privacy

NASA Astrophysics Data System (ADS)

Mace, Robyn R.

The extent and scope of intelligence activities are expanding in response to technological and economic transformations of the past decades. Intelligence efforts involving aggregated data from multiple public and private sources combined with past abuses of domestic intelligence functions have generated significant concerns among privacy advocates and citizens about the protection of individual civil liberties and information privacy from corporate and governmental misuse. In the information age, effective regulation and oversight are key components in the legitimacy and success of government domestic intelligence activities.

One-Pot Two-Step Multicomponent Process of Indole and Other Nitrogenous Heterocycles or Amines toward α-Oxo-acetamidines.

PubMed

Martinez-Ariza, Guillermo; McConnell, Nicholas; Hulme, Christopher

2016-04-15

A cesium carbonate promoted three-component reaction of N-H containing heterocycles, primary or secondary amines, arylglyoxaldehydes, and anilines is reported. The key step involves a tandem sequence of N-1 addition of a heterocycle or an amine to preformed α-iminoketones, followed by an air- or oxygen-mediated oxidation to form α-oxo-acetamidines. The scope of the reaction is enticingly broad, and this novel methodology is applied toward the synthesis of various polycyclic heterocycles.

Deciphering the ubiquitin-mediated pathway in apicomplexan parasites: a potential strategy to interfere with parasite virulence.

PubMed

Ponts, Nadia; Yang, Jianfeng; Chung, Duk-Won Doug; Prudhomme, Jacques; Girke, Thomas; Horrocks, Paul; Le Roch, Karine G

2008-06-11

Reversible modification of proteins through the attachment of ubiquitin or ubiquitin-like modifiers is an essential post-translational regulatory mechanism in eukaryotes. The conjugation of ubiquitin or ubiquitin-like proteins has been demonstrated to play roles in growth, adaptation and homeostasis in all eukaryotes, with perturbation of ubiquitin-mediated systems associated with the pathogenesis of many human diseases, including cancer and neurodegenerative disorders. Here we describe the use of an HMM search of functional Pfam domains found in the key components of the ubiquitin-mediated pathway necessary to activate and reversibly modify target proteins in eight apicomplexan parasitic protozoa for which complete or late-stage genome projects exist. In parallel, the same search was conducted on five model organisms, single-celled and metazoans, to generate data to validate both the search parameters employed and aid paralog classification in Apicomplexa. For each of the 13 species investigated, a set of proteins predicted to be involved in the ubiquitylation pathway has been identified and demonstrates increasing component members of the ubiquitylation pathway correlating with organism and genome complexity. Sequence homology and domain architecture analyses facilitated prediction of apicomplexan-specific protein function, particularly those involved in regulating cell division during these parasite's complex life cycles. This study provides a comprehensive analysis of proteins predicted to be involved in the apicomplexan ubiquitin-mediated pathway. Given the importance of such pathway in a wide variety of cellular processes, our data is a key step in elucidating the biological networks that, in part, direct the pathogenicity of these parasites resulting in a massive impact on global health. Moreover, apicomplexan-specific adaptations of the ubiquitylation pathway may represent new therapeutic targets for much needed drugs against apicomplexan parasites.

Finding a BETTER way: A qualitative study exploring the prevention practitioner intervention to improve chronic disease prevention and screening in family practice

PubMed Central

2014-01-01

Background Our randomized controlled trial (The BETTER Trial) found that training a clinician to become a Prevention Practitioner (PP) in family practices improved chronic disease prevention and screening (CDPS). PPs were trained on CDPS and provided prevention prescriptions tailored to participating patients. For this embedded qualitative study, we explored perceptions of this new role to understand the PP intervention. Methods We used grounded theory methodology and purposefully sampled participants involved in any capacity with the BETTER Trial. Two physicians and one coordinator in each of two cities (Toronto, Ontario and Edmonton, Alberta) conducted eight individual semi-structured interviews and seven focus groups. We used an interview guide and documented research activities through an audit trail, journals, field notes and memos. We analyzed the data using the constant comparative method throughout open coding followed by theoretical coding. Results A framework and process involving external and internal practice facilitation using the new role of PP was thought to impact CDPS. The PP facilitated CDPS through on-going relationships with patients and practice team members. Key components included: 1) approaching CDPS in a comprehensive manner, 2) an individualized and personalized approach at multiple levels, 3) integrated continuity that included linking the patients and practices to CPDS resources, and 4) adaptability to different practices and settings. Conclusions The BETTER framework and key components are described as impacting CDPS through a process that involved a new role, the PP. The introduction of a novel role of a clinician within the primary care practice with skills in CDPS could appropriately address gaps in prevention and screening. PMID:24720686

Using Separable Nonnegative Matrix Factorization Techniques for the Analysis of Time-Resolved Raman Spectra

NASA Astrophysics Data System (ADS)

Luce, R.; Hildebrandt, P.; Kuhlmann, U.; Liesen, J.

2016-09-01

The key challenge of time-resolved Raman spectroscopy is the identification of the constituent species and the analysis of the kinetics of the underlying reaction network. In this work we present an integral approach that allows for determining both the component spectra and the rate constants simultaneously from a series of vibrational spectra. It is based on an algorithm for non-negative matrix factorization which is applied to the experimental data set following a few pre-processing steps. As a prerequisite for physically unambiguous solutions, each component spectrum must include one vibrational band that does not significantly interfere with vibrational bands of other species. The approach is applied to synthetic "experimental" spectra derived from model systems comprising a set of species with component spectra differing with respect to their degree of spectral interferences and signal-to-noise ratios. In each case, the species involved are connected via monomolecular reaction pathways. The potential and limitations of the approach for recovering the respective rate constants and component spectra are discussed.

Sphingolipids role in the regulation of inflammatory response: From leukocyte biology to bacterial infection.

PubMed

Chiricozzi, Elena; Loberto, Nicoletta; Schiumarini, Domitilla; Samarani, Maura; Mancini, Giulia; Tamanini, Anna; Lippi, Giuseppe; Dechecchi, Maria Cristina; Bassi, Rosaria; Giussani, Paola; Aureli, Massimo

2018-03-01

Sphingolipids (SLs) are amphiphilic molecules mainly associated with the external leaflet of eukaryotic plasma membrane, and are structural membrane components with key signaling properties. Since the beginning of the last century, a large number of papers described the involvement of these molecules in several aspects of cell physiology and pathology. Several lines of evidence support the critical role of SLs in inflammatory diseases, by acting as anti- or pro-inflammatory mediators. They are involved in control of leukocyte activation and migration, and are recognized as essential players in host response to pathogenic infection. We propose here a critical overview of current knowledge on involvement of different classes of SLs in inflammation, focusing on the role of simple and complex SLs in pathogen-mediated inflammatory response. ©2018 Society for Leukocyte Biology.

Multidisciplinary, interdisciplinary, or dysfunctional? Team working in mixed-methods research.

PubMed

O'Cathain, Alicia; Murphy, Elizabeth; Nicholl, Jon

2008-11-01

Combining qualitative and quantitative methods in a single study-otherwise known as mixed-methods research-is common. In health research these projects can be delivered by research teams. A typical scenario, for example, involves medical sociologists delivering qualitative components and researchers from medicine or health economics delivering quantitative components. We undertook semistructured interviews with 20 researchers who had worked on mixed-methods studies in health services research to explore the facilitators of and barriers to exploiting the potential of this approach. Team working emerged as a key issue, with three models of team working apparent: multidisciplinary, interdisciplinary, and dysfunctional. Interdisciplinary research was associated with integration of data or findings from the qualitative and quantitative components in both the final reports and the peer-reviewed publications. Methodological respect between team members and a principal investigator who valued integration emerged as essential to achieving integrated research outcomes.

Selective attention impairments in Alzheimer's disease: evidence for dissociable components.

PubMed

Levinoff, Elise J; Li, Karen Z H; Murtha, Susan; Chertkow, Howard

2004-07-01

Tasks emphasizing 3 different aspects of selective attention-inhibition, visuospatial selective attention, and decision making-were administered to subjects with mild Alzheimer's disease (AD) and to healthy elderly control (HEC) subjects to determine which components of selective attention were impaired in AD subjects and whether selective attention could be dissociated into different components. The tasks were administered with easy versus hard levels of difficulty to assess proportional slowing as the key variable across tasks. The results indicated that the inhibitory and visual search tasks showed greater proportional slowing in subjects with AD than in HEC subjects, and that the task involving inhibition was significantly more affected in subjects with AD. Furthermore, there were no significant intertask correlations, and the results cannot be explained simply in terms of generalized cognitive slowing. These results provide evidence that inhibition is the most strikingly affected aspect of selective attention that is observed to be impaired in early stages of AD.

Kidneys: Key Modulators of HDL Levels and Function

PubMed Central

Yang, Haichun; Fogo, Agnes B.; Kon, Valentina

2016-01-01

Purpose of review This review will examine advances in our understanding of the role kidneys play in HDL metabolism and the effect on levels, composition, and function of HDL particles. Recent findings Components of the HDL particles can cross the glomerular filtration barrier. Some of these components, including apolipoproteins and enzymes involved in lipid metabolism, are taken up by the proximal tubule and degraded, modified, salvaged/returned to the circulation, or lost in the urine. Injury of the glomerular capillaries or tubules can affect these intrarenal processes and modify HDL. Changes in the plasma and urine levels of HDL may be novel markers of kidney damage and/or mechanism(s) of kidney disease. Summary The kidneys have a significant role in metabolism of individual HDL components, which in turn modulate HDL levels, composition and functionality of HDL particles. These intrarenal effects may be useful markers of kidney damage and have consequences on kidney-related perturbations in HDL. PMID:27008596

Improving human activity recognition and its application in early stroke diagnosis.

PubMed

Villar, José R; González, Silvia; Sedano, Javier; Chira, Camelia; Trejo-Gabriel-Galan, Jose M

2015-06-01

The development of efficient stroke-detection methods is of significant importance in today's society due to the effects and impact of stroke on health and economy worldwide. This study focuses on Human Activity Recognition (HAR), which is a key component in developing an early stroke-diagnosis tool. An overview of the proposed global approach able to discriminate normal resting from stroke-related paralysis is detailed. The main contributions include an extension of the Genetic Fuzzy Finite State Machine (GFFSM) method and a new hybrid feature selection (FS) algorithm involving Principal Component Analysis (PCA) and a voting scheme putting the cross-validation results together. Experimental results show that the proposed approach is a well-performing HAR tool that can be successfully embedded in devices.

Extreme-Scale De Novo Genome Assembly

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

Georganas, Evangelos; Hofmeyr, Steven; Egan, Rob

De novo whole genome assembly reconstructs genomic sequence from short, overlapping, and potentially erroneous DNA segments and is one of the most important computations in modern genomics. This work presents HipMER, a high-quality end-to-end de novo assembler designed for extreme scale analysis, via efficient parallelization of the Meraculous code. Genome assembly software has many components, each of which stresses different components of a computer system. This chapter explains the computational challenges involved in each step of the HipMer pipeline, the key distributed data structures, and communication costs in detail. We present performance results of assembling the human genome and themore » large hexaploid wheat genome on large supercomputers up to tens of thousands of cores.« less

Parallel Three-Dimensional Computation of Fluid Dynamics and Fluid-Structure Interactions of Ram-Air Parachutes

NASA Technical Reports Server (NTRS)

Tezduyar, Tayfun E.

1998-01-01

This is a final report as far as our work at University of Minnesota is concerned. The report describes our research progress and accomplishments in development of high performance computing methods and tools for 3D finite element computation of aerodynamic characteristics and fluid-structure interactions (FSI) arising in airdrop systems, namely ram-air parachutes and round parachutes. This class of simulations involves complex geometries, flexible structural components, deforming fluid domains, and unsteady flow patterns. The key components of our simulation toolkit are a stabilized finite element flow solver, a nonlinear structural dynamics solver, an automatic mesh moving scheme, and an interface between the fluid and structural solvers; all of these have been developed within a parallel message-passing paradigm.

Coordination between veterinary services and other relevant authorities: a key component of good public governance.

PubMed

Bellemain, V

2012-08-01

Coordination between Veterinary Services and other relevant authorities is a key component of good public governance, especially for effective action and optimal management of available resources. The importance of good coordination is reflected in the World Organisation for Animal Health'Tool forthe Evaluation of Performance of Veterinary Services', which includes a critical competency on coordination. Many partners from technical, administrative and legal fields are involved. The degree of formalisation of coordination tends to depend on a country's level of organisation and development. Contingency plans against avian influenza led to breakthroughs in many countries in the mid-2000s. While interpersonal relationships remain vital, not everything should hinge on them. Organisation and management are critical to operational efficiency. The distribution of responsibilities needs to be defined clearly, avoiding duplication and areas of conflict. Lead authorities should be designated according to subject (Veterinary Services in animal health areas) and endowed with the necessary legitimacy. Lead authorities will be responsible for coordinating the drafting and updating of the relevant documents: agreements between authorities, contingency plans, standard operating procedures, etc.

Failure Impact Analysis of Key Management in AMI Using Cybernomic Situational Assessment (CSA)

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

Abercrombie, Robert K; Sheldon, Frederick T; Hauser, Katie R

2013-01-01

In earlier work, we presented a computational framework for quantifying the security of a system in terms of the average loss a stakeholder stands to sustain as a result of threats to the system. We named this system, the Cyberspace Security Econometrics System (CSES). In this paper, we refine the framework and apply it to cryptographic key management within the Advanced Metering Infrastructure (AMI) as an example. The stakeholders, requirements, components, and threats are determined. We then populate the matrices with justified values by addressing the AMI at a higher level, rather than trying to consider every piece of hardwaremore » and software involved. We accomplish this task by leveraging the recently established NISTR 7628 guideline for smart grid security. This allowed us to choose the stakeholders, requirements, components, and threats realistically. We reviewed the literature and selected an industry technical working group to select three representative threats from a collection of 29 threats. From this subset, we populate the stakes, dependency, and impact matrices, and the threat vector with realistic numbers. Each Stakeholder s Mean Failure Cost is then computed.« less

Mobile Technology for Improved Family Planning (MOTIF): the development of a mobile phone-based (mHealth) intervention to support post-abortion family planning (PAFP) in Cambodia.

PubMed

Smith, Chris; Vannak, Uk; Sokhey, Ly; Ngo, Thoai D; Gold, Judy; Free, Caroline

2016-01-05

The objective of this paper is to outline the formative research process used to develop the MOTIF mobile phone-based (mHealth) intervention to support post-abortion family planning in Cambodia. The formative research process involved literature reviews, interviews and focus group discussions with clients, and consultation with clinicians and organisations implementing mHealth activities in Cambodia. This process led to the development of a conceptual framework and the intervention. Key findings from the formative research included identification of the main reasons for non-use of contraception and patterns of mobile phone use in Cambodia. We drew on components of existing interventions and behaviour change theory to develop a conceptual framework. A multi-faceted voice-based intervention was designed to address health concerns and other key determinants of contraception use. Formative research was essential in order to develop an appropriate mHealth intervention to support post-abortion contraception in Cambodia. Each component of the formative research contributed to the final intervention design.

Security of quantum key distribution with multiphoton components

PubMed Central

Yin, Hua-Lei; Fu, Yao; Mao, Yingqiu; Chen, Zeng-Bing

2016-01-01

Most qubit-based quantum key distribution (QKD) protocols extract the secure key merely from single-photon component of the attenuated lasers. However, with the Scarani-Acin-Ribordy-Gisin 2004 (SARG04) QKD protocol, the unconditionally secure key can be extracted from the two-photon component by modifying the classical post-processing procedure in the BB84 protocol. Employing the merits of SARG04 QKD protocol and six-state preparation, one can extract secure key from the components of single photon up to four photons. In this paper, we provide the exact relations between the secure key rate and the bit error rate in a six-state SARG04 protocol with single-photon, two-photon, three-photon, and four-photon sources. By restricting the mutual information between the phase error and bit error, we obtain a higher secure bit error rate threshold of the multiphoton components than previous works. Besides, we compare the performances of the six-state SARG04 with other prepare-and-measure QKD protocols using decoy states. PMID:27383014

Key components of financial-analysis education for clinical nurses.

PubMed

Lim, Ji Young; Noh, Wonjung

2015-09-01

In this study, we identified key components of financial-analysis education for clinical nurses. We used a literature review, focus group discussions, and a content validity index survey to develop key components of financial-analysis education. First, a wide range of references were reviewed, and 55 financial-analysis education components were gathered. Second, two focus group discussions were performed; the participants were 11 nurses who had worked for more than 3 years in a hospital, and nine components were agreed upon. Third, 12 professionals, including professors, nurse executive, nurse managers, and an accountant, participated in the content validity index. Finally, six key components of financial-analysis education were selected. These key components were as follows: understanding the need for financial analysis, introduction to financial analysis, reading and implementing balance sheets, reading and implementing income statements, understanding the concepts of financial ratios, and interpretation and practice of financial ratio analysis. The results of this study will be used to develop an education program to increase financial-management competency among clinical nurses. © 2015 Wiley Publishing Asia Pty Ltd.

A method for analyzing the business case for provider participation in the National Cancer Institute's Community Clinical Oncology Program and similar federally funded, provider-based research networks.

PubMed

Reiter, Kristin L; Song, Paula H; Minasian, Lori; Good, Marjorie; Weiner, Bryan J; McAlearney, Ann Scheck

2012-09-01

The Community Clinical Oncology Program (CCOP) plays an essential role in the efforts of the National Cancer Institute (NCI) to increase enrollment in clinical trials. Currently, there is little practical guidance in the literature to assist provider organizations in analyzing the return on investment (ROI), or business case, for establishing and operating a provider-based research network (PBRN) such as the CCOP. In this article, the authors present a conceptual model of the business case for PBRN participation, a spreadsheet-based tool and advice for evaluating the business case for provider participation in a CCOP organization. A comparative, case-study approach was used to identify key components of the business case for hospitals attempting to support a CCOP research infrastructure. Semistructured interviews were conducted with providers and administrators. Key themes were identified and used to develop the financial analysis tool. Key components of the business case included CCOP start-up costs, direct revenue from the NCI CCOP grant, direct expenses required to maintain the CCOP research infrastructure, and incidental benefits, most notably downstream revenues from CCOP patients. The authors recognized the value of incidental benefits as an important contributor to the business case for CCOP participation; however, currently, this component is not calculated. The current results indicated that providing a method for documenting the business case for CCOP or other PBRN involvement will contribute to the long-term sustainability and expansion of these programs by improving providers' understanding of the financial implications of participation. Copyright © 2011 American Cancer Society.

Profiling the role of mammalian target of rapamycin in the vascular smooth muscle metabolome in pulmonary arterial hypertension

PubMed Central

Kudryashova, Tatiana V.; Goncharov, Dmitry A.; Pena, Andressa; Ihida-Stansbury, Kaori; DeLisser, Horace; Kawut, Steven M.

2015-01-01

Abstract Increased proliferation and resistance to apoptosis of pulmonary arterial vascular smooth muscle cells (PAVSMCs), coupled with metabolic reprogramming, are key components of pulmonary vascular remodeling, a major and currently irreversible pathophysiological feature of pulmonary arterial hypertension (PAH). We recently reported that activation of mammalian target of rapamycin (mTOR) plays a key role in increased energy generation and maintenance of the proliferative, apoptosis-resistant PAVSMC phenotype in human PAH, but the downstream effects of mTOR activation on PAH PAVSMC metabolism are not clear. Using liquid and gas chromatography–based mass spectrometry, we performed pilot metabolomic profiling of human microvascular PAVSMCs from idiopathic-PAH subjects before and after treatment with the selective adenosine triphosphate–competitive mTOR inhibitor PP242 and from nondiseased lungs. We have shown that PAH PAVSMCs have a distinct metabolomic signature of altered metabolites—components of fatty acid synthesis, deficiency of sugars, amino sugars, and nucleotide sugars—intermediates of protein and lipid glycosylation, and downregulation of key biochemicals involved in glutathione and nicotinamide adenine dinucleotide (NAD) metabolism. We also report that mTOR inhibition attenuated or reversed the majority of the PAH-specific abnormalities in lipogenesis, glycosylation, glutathione, and NAD metabolism without affecting altered polyunsaturated fatty acid metabolism. Collectively, our data demonstrate a critical role of mTOR in major PAH PAVSMC metabolic abnormalities and suggest the existence of de novo lipid synthesis in PAVSMCs in human PAH that may represent a new, important component of disease pathogenesis worthy of future investigation. PMID:26697174

The involvement of heparan sulfate proteoglycans in stem cell differentiation and in malignant glioma

NASA Astrophysics Data System (ADS)

Kundu, Soumi; Xiong, Anqi; Forsberg-Nilsson, Karin

2016-04-01

Heparan sulfate (HS) proteoglycans (HSPG) are major components of the extracellular matrix. They interact with a plethora of macromolecules that are of physiological importance. The pattern of sulfation of the HS chain determines the specificity of these interactions. The enzymes that synthesize and degrade HS are thus key regulators of processes ranging from embryonic development to tissue homeostasis and tumor development. Formation of the nervous system is also critically dependent on appropriate HSPGs as shown by several studies on the role of HS in neural induction from embryonic stem cells. High-grade glioma is the most common primary malignant brain tumor among adults, and the prognosis is poor. Neural and glioma stem cells share several traits, including sustained proliferation and highly efficient migration in the brain. There are also similarities between the neurogenic niche where adult neural stem cells reside and the tumorigenic niche, including their interactions with components of the extracellular matrix (ECM). The levels of many of these components, for example HSPGs and enzymes involved in the biosynthesis and modification of HS are attenuated in gliomas. In this paper, HS regulation of pathways involved in neural differentiation and how these may be of importance for brain development are discussed. The literature suggesting that modifications of HS could regulate glioma growth and invasion is reviewed. Targeting the invasiveness of glioma cells by modulating HS may improve upon present therapeutic options, which only marginally enhance the survival of glioma patients.

Effects of "D"-Amphetamine and Ethanol on Variable and Repetitive Key-Peck Sequences in Pigeons

ERIC Educational Resources Information Center

Ward, Ryan D.; Bailey, Ericka M.; Odum, Amy L.

2006-01-01

This experiment assessed the effects of "d"-Amphetamine and ethanol on reinforced variable and repetitive key-peck sequences in pigeons. Pigeons responded on two keys under a multiple schedule of Repeat and Vary components. In the Repeat component, completion of a target sequence of right, right, left, left resulted in food. In the Vary component,…

A Natural Component-Based Oxygen Indicator with In-Pack Activation for Intelligent Food Packaging.

PubMed

Won, Keehoon; Jang, Nan Young; Jeon, Junsu

2016-12-28

Intelligent food packaging can provide consumers with reliable and correct information on the quality and safety of packaged foods. One of the key constituents in intelligent packaging is a colorimetric oxygen indicator, which is widely used to detect oxygen gas involved in food spoilage by means of a color change. Traditional oxygen indicators consisting of redox dyes and strong reducing agents have two major problems: they must be manufactured and stored under anaerobic conditions because air depletes the reductant, and their components are synthetic and toxic. To address both of these serious problems, we have developed a natural component-based oxygen indicator characterized by in-pack activation. The conventional oxygen indicator composed of synthetic and artificial components was redesigned using naturally occurring compounds (laccase, guaiacol, and cysteine). These natural components were physically separated into two compartments by a fragile barrier. Only when the barrier was broken were all of the components mixed and the function as an oxygen indicator was begun (i.e., in-pack activation). Depending on the component concentrations, the natural component-based oxygen indicator exhibited different response times and color differences. The rate of the color change was proportional to the oxygen concentration. This novel colorimetric oxygen indicator will contribute greatly to intelligent packaging for healthier and safer foods.

User Interaction Design for a Home-Based Telecare System

NASA Astrophysics Data System (ADS)

Raptis, Spyros; Tsiakoulis, Pirros; Chalamandaris, Aimilios; Karabetsos, Sotiris

This paper presents the design of the user-interaction component of a home-based telecare system for congestive heart failure patients. It provides a short overview of the overall system and offers details on the different interaction types supported by the system. Interacting with the user occurs either as part of a scheduled procedure or as a consequence of identifying or predicting a potentially hazardous deterioration of the patients' health state. The overall logic of the interaction is structured around event-scenario associations, where a scenario consists of concrete actions to be performed, some of which may involve the patient. A key objective in this type of interaction that it is very simple, intuitive and short, involving common everyday objects and familiar media such as speech.

Progress in Advanced Spray Combustion Code Integration

NASA Technical Reports Server (NTRS)

Liang, Pak-Yan

1993-01-01

A multiyear project to assemble a robust, muitiphase spray combustion code is now underway and gradually building up to full speed. The overall effort involves several university and government research teams as well as Rocketdyne. The first part of this paper will give an overview of the respective roles of the different participants involved, the master strategy, the evolutionary milestones, and an assessment of the state-of-the-art of various key components. The second half of this paper will highlight the progress made to date in extending the baseline Navier-Stokes solver to handle multiphase, multispecies, chemically reactive sub- to supersonic flows. The major hurdles to overcome in order to achieve significant speed ups are delineated and the approaches to overcoming them will be discussed.

I am going to make the most out of it! Italian university Credit Mobility Students' social representations of alcohol use during study abroad experiences.

PubMed

Aresi, Giovanni; Fattori, Francesco; Pozzi, Maura; Moore, Simon C

2016-09-01

The aim was to explore shared representations of alcohol use in students who were to travel abroad to study. Focus group data from Italian students ( N = 69) were collected. Analyses used Grounded Theory Methodology and were informed by the four key components of Social Representation Theory (cognition, emotion, attitude and behavioural intentions). The study abroad experience was described as one that would involve an increase in alcohol consumption compared to pre-departure levels. Reasons given included greater social and leisure opportunities involving alcohol, reduced social control and features of the host country environment. Opportunities to intervene and address risky alcohol use in this group are discussed.

Architecture of autonomous systems

NASA Technical Reports Server (NTRS)

Dikshit, Piyush; Guimaraes, Katia; Ramamurthy, Maya; Agrawala, Ashok; Larsen, Ronald L.

1986-01-01

Automation of Space Station functions and activities, particularly those involving robotic capabilities with interactive or supervisory human control, is a complex, multi-disciplinary systems design problem. A wide variety of applications using autonomous control can be found in the literature, but none of them seem to address the problem in general. All of them are designed with a specific application in mind. In this report, an abstract model is described which unifies the key concepts underlying the design of automated systems such as those studied by the aerospace contractors. The model has been kept as general as possible. The attempt is to capture all the key components of autonomous systems. With a little effort, it should be possible to map the functions of any specific autonomous system application to the model presented here.

Architecture of autonomous systems

NASA Technical Reports Server (NTRS)

Dikshit, Piyush; Guimaraes, Katia; Ramamurthy, Maya; Agrawala, Ashok; Larsen, Ronald L.

1989-01-01

Automation of Space Station functions and activities, particularly those involving robotic capabilities with interactive or supervisory human control, is a complex, multi-disciplinary systems design problem. A wide variety of applications using autonomous control can be found in the literature, but none of them seem to address the problem in general. All of them are designed with a specific application in mind. In this report, an abstract model is described which unifies the key concepts underlying the design of automated systems such as those studied by the aerospace contractors. The model has been kept as general as possible. The attempt is to capture all the key components of autonomous systems. With a little effort, it should be possible to map the functions of any specific autonomous system application to the model presented here.

Weight management in community pharmacy: what do the experts think?

PubMed

Um, Irene S; Armour, Carol; Krass, Ines; Gill, Timothy; Chaar, Betty B

2013-06-01

The increasing prevalence of obesity and overweight adults creates a significant public health burden and there is great potential for pharmacists to be involved in the provision of weight management services, other than the mundane supply of commercial products. In order to provide optimal services that can be integrated into the healthcare system, a best practice model for weight management services in community pharmacy should be in place. We sought experts' and key stakeholders' opinions on this matter. (1) To identify components of a best practice model of a weight management service feasible in Australian community pharmacy. (2) To identify the role of pharmacists and the training requirements to up-skill pharmacists to competently provide weight management services. (3) To elicit any practical suggestions that would contribute to successful implementation of weight management services in pharmacy. Australian primary care sector. Semi-structured interviews were conducted with a purposive sample of 12 participants including Australian experts in obesity and representatives of main Australian professional organisations in pharmacy. Interviews were digitally recorded, transcribed verbatim and thematically analysed using the framework approach. Recommended components of pharmacy-based weight management services and training requirements. Participants perceived two potential roles for pharmacists involved in weight management: health promotion and individualised service. Multi-component interventions targeting all three areas: diet, physical activity and behaviour change were emphasised. Physical assessment (e.g. weight, waist circumference measurements), goal setting, referral to allied healthcare professionals and on-going support for weight maintenance were also proposed. Participants suggested pharmacists should undergo formal training and identified various training topics to improve pharmacists' knowledge, attributes and skills to acquire competencies necessary for delivery of this service. Some physical and financial barriers in providing these services were also identified including infrastructure, pharmacists' time and cost-effectiveness. Pharmacists are well-positioned to promote healthy weight and/or implement weight management interventions. Furthering pharmacists' role would involve training and up-skilling; and addressing key practice change facilitators such as pharmacy layout and remuneration. This study provides some insight into the design and implementation of a best practice model for pharmacy-based weight management services in Australia.

Identification of key transcription factors in caerulein-induced pancreatitis through expression profiling data

PubMed Central

QI, DACHUAN; WU, BO; TONG, DANIAN; PAN, YE; CHEN, WEI

2015-01-01

The current study aimed to isolate key transcription factors (TFs) in caerulein-induced pancreatitis, and to identify the difference between wild type and Mist1 knockout (KO) mice, in order to elucidate the contribution of Mist1 to pancreatitis. The gene profile of GSE3644 was downloaded from the Gene Expression Omnibus database then analyzed using the t-test. The isolated differentially expressed genes (DEGs) were mapped into a transcriptional regulatory network derived from the Integrated Transcription Factor Platform database and in the network, the interaction pairs involving at least one DEG were screened. Fisher’s exact test was used to analyze the functional enrichment of the target genes. A total of 1,555 and 3,057 DEGs were identified in the wild type and Mist1KO mice treated with caerulein, respectively. DEGs screened in Mist1KO mice were predominantly enriched in apoptosis, mitogen-activated protein kinase signaling and other cancer-associated pathways. A total of 188 and 51 TFs associated with pathopoiesis were isolated in Mist1KO and wild type mice, respectively. Out of the top 10 TFs (ranked by P-value), 7 TFs, including S-phase kinase-associated protein 2 (Skp2); minichromosome maintenance complex component 3 (Mcm3); cell division cycle 6 (Cdc6); cyclin B1 (Ccnb1); mutS homolog 6 (Msh6); cyclin A2 (Ccna2); and cyclin B2 (Ccnb2), were expressed in the two types of mouse. These TFs were predominantly involved in phosphorylation, DNA replication, cell division and DNA mismatch repair. In addition, specific TFs, including minichromosome maintenance complex component 7 (Mcm7); lymphoid-specific helicase (Hells); and minichromosome maintenance complex component 6 (Mcm6), that function in the unwinding of DNA were identified to participate in Mist1KO pancreatitis. The DEGs, including Cdc6, Mcm6, Msh6 and Wdr1 are closely associated with the regulation of caerulein-induced pancreatitis. Furthermore, other identified TFs were also involved in this type of regulation. PMID:25975747

Leadership for ethical policy and practice (LEPP): participatory action project.

PubMed

Storch, Janet; Rodney, Patricia; Varcoe, Colleen; Pauly, Bernadette; Starzomski, Rosalie; Stevenson, Lynne; Best, Lynette; Mass, Heather; Fulton, Thomas Reilly; Mildon, Barbara; Bees, Fiona; Chisholm, Anne; MacDonald-Rencz, Sandra; McCutcheon, Amy Sanchez; Shamian, Judith; Thompson, Charlotte; Makaroff, Kara Schick; Newton, Lorelei

2009-01-01

Within Canada's fast-paced, ever-changing healthcare environment, providers are experiencing difficulty practising according to their professional ethical standards, leading many to experience moral or ethical distress. Limited attention has been paid to improvements in the ethical climate in healthcare settings in research focusing on nurses' workplaces. In this three-year study, we focused on how the ethical climate in healthcare delivery can be improved and how the use of participatory action research methods can lead to continued enhancements and lasting changes in services delivery. Together, we developed strategies for taking action, aimed at improving the quality of the work environment. This action involved both nurses in direct care and those in key leadership positions (CNOs or their equivalents). Through the active participation of those for whom the research-based change was intended, these strategies were tested in various sites across British Columbia and can be used as templates or designs for use in other settings. A key component of the success of the projects and action plans that were created was the integral involvement of nurse leaders through all phases.

Dissecting microRNA dysregulation in age-related macular degeneration: new targets for eye gene therapy.

PubMed

Askou, Anne Louise; Alsing, Sidsel; Holmgaard, Andreas; Bek, Toke; Corydon, Thomas J

2018-02-01

MicroRNAs (miRNAs) are key regulators of gene expression in humans. Overexpression or depletion of individual miRNAs is associated with human disease. Current knowledge suggests that the retina is influenced by miRNAs and that dysregulation of miRNAs as well as alterations in components of the miRNA biogenesis machinery are involved in retinal diseases, including age-related macular degeneration (AMD). Furthermore, recent studies have indicated that the vitreous has a specific panel of circulating miRNAs and that this panel varies according to the specific pathological stress experienced by the retinal cells. MicroRNA (miRNA) profiling indicates subtype-specific miRNA profiles for late-stage AMD highlighting the importance of proper miRNA regulation in AMD. This review will describe the function of important miRNAs involved in inflammation, oxidative stress and pathological neovascularization, the key molecular mechanisms leading to AMD, and focus on dysregulated miRNAs as potential therapeutic targets in AMD. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Key-peck durations under behavioral contrast and differential reinforcement

PubMed Central

Whipple, William R.; Fantino, Edmund

1980-01-01

Pigeons were maintained on a multiple schedule in which both components were variable-interval one-minute schedules. When they were switched to a condition in which one component was extinction, behavioral contrast was observed. The median durations of the key pecks in the unchanged component did not decrease in size. The results are incompatible with a theory of behavioral contrast which considers the added pecks to be short-duration responses. In a second experiment, pigeons were required to emit short-duration key pecks in one component of a multiple schedule, and long-duration pecks in the other. Two of three pigeons learned to emit responses appropriate to the requirements of the component in effect, suggesting that the duration of the key-peck response is sensitive to differential reinforcement. PMID:16812185

Function of ABA in Stomatal Defense against Biotic and Drought Stresses

PubMed Central

Lim, Chae Woo; Baek, Woonhee; Jung, Jangho; Kim, Jung-Hyun; Lee, Sung Chul

2015-01-01

The plant hormone abscisic acid (ABA) regulates many key processes involved in plant development and adaptation to biotic and abiotic stresses. Under stress conditions, plants synthesize ABA in various organs and initiate defense mechanisms, such as the regulation of stomatal aperture and expression of defense-related genes conferring resistance to environmental stresses. The regulation of stomatal opening and closure is important to pathogen defense and control of transpirational water loss. Recent studies using a combination of approaches, including genetics, physiology, and molecular biology, have contributed considerably to our understanding of ABA signal transduction. A number of proteins associated with ABA signaling and responses—especially ABA receptors—have been identified. ABA signal transduction initiates signal perception by ABA receptors and transfer via downstream proteins, including protein kinases and phosphatases. In the present review, we focus on the function of ABA in stomatal defense against biotic and abiotic stresses, through analysis of each ABA signal component and the relationships of these components in the complex network of interactions. In particular, two ABA signal pathway models in response to biotic and abiotic stress were proposed, from stress signaling to stomatal closure, involving the pyrabactin resistance (PYR)/PYR-like (PYL) or regulatory component of ABA receptor (RCAR) family proteins, 2C-type protein phosphatases, and SnRK2-type protein kinases. PMID:26154766

Religious involvement, beliefs about God, and the sense of mattering among older adults.

PubMed

Schieman, Scott; Bierman, Alex; Ellison, Christopher G

2010-01-01

Using data from a 2001–2002 sample of adults aged 65 and older living in the Washington, DC metropolitan area, we examine the associations among religious involvement (as measured by the frequency of attendance at religious services and praying), the belief in divine control, and the sense of mattering—a key component of the self-concept. We also assess the extent to which these patterns vary by gender, race, and education. Findings indicate indirect effects of religious attendance on mattering through divine control beliefs and the frequency of social contact. Praying increases mattering indirectly only through divine control beliefs. Moreover, divine control beliefs are more strongly associated with mattering among women, African Americans, and individuals with less education. We discuss the contribution of these findings for theory about the links between religious involvement, beliefs about God, and psychosocial resources, and the influence of core dimensions of social status and stratification.

Effector peptides of the renin-angiotensin system in the central mechanisms of acquired and innate behavior in thirst in rats.

PubMed

Vlasenko, R Ya; Kotov, A V

2007-03-01

We report here a comparative analysis of the involvement of a number of components of the renin-angiotensin system in the performance of simple and complex forms of drinking behavior and thirst-associated non-drinking types of behavior. On central (intracerebroventricular) microinjection, [des-Asp1]-angiotensin I at doses equieffective to those of angiotensins II and III was found to be involved only in the performance of simple (taking water from the bowl) and linked forms of activity (comfort behavior, stress grooming, orientational-investigative, and feeding behavior). Angiotensin II was involved in the central mechanisms of complex acquired drinking behavior, selectively modulating its key stages (initial, final), while angiotensin III was involved only in the mechanisms of reproduction of the complex skill. All three substances induced "innate patterns of behavior" specific for each compound, these occurring at fixed periods of time after intracerebral microinjection. The effects of these substances were selectively suppressed by the AT1 receptor blocker losartan potassium.

A combined qualitative-quantitative approach for the identification of highly co-creative technology-driven firms

NASA Astrophysics Data System (ADS)

Milyakov, Hristo; Tanev, Stoyan; Ruskov, Petko

2011-03-01

Value co-creation, is an emerging business and innovation paradigm, however, there is not enough clarity on the distinctive characteristics of value co-creation as compared to more traditional value creation approaches. The present paper summarizes the results from an empirically-derived research study focusing on the development of a systematic procedure for the identification of firms that are active in value co-creation. The study is based on a sample 273 firms that were selected for being representative of the breadth of their value co-creation activities. The results include: i) the identification of the key components of value co-creation based on a research methodology using web search and Principal Component Analysis techniques, and ii) the comparison of two different classification techniques identifying the firms with the highest degree of involvement in value co-creation practices. To the best of our knowledge this is the first study using sophisticated data collection techniques to provide a classification of firms according to the degree of their involvement in value co-creation.

The CasKR Two-Component System Is Required for the Growth of Mesophilic and Psychrotolerant Bacillus cereus Strains at Low Temperatures

PubMed Central

Diomandé, Sara Esther; Chamot, Stéphanie; Antolinos, Vera; Vasai, Florian; Guinebretière, Marie-Hélène; Bornard, Isabelle; Nguyen-the, Christophe; Broussolle, Véronique

2014-01-01

The different strains of Bacillus cereus can grow at temperatures covering a very diverse range. Some B. cereus strains can grow in chilled food and consequently cause food poisoning. We have identified a new sensor/regulator mechanism involved in low-temperature B. cereus growth. Construction of a mutant of this two-component system enabled us to show that this system, called CasKR, is required for growth at the minimal temperature (Tmin). CasKR was also involved in optimal cold growth above Tmin and in cell survival below Tmin. Microscopic observation showed that CasKR plays a key role in cell shape during cold growth. Introducing the casKR genes in a ΔcasKR mutant restored its ability to grow at Tmin. Although it was first identified in the ATCC 14579 model strain, this mechanism has been conserved in most strains of the B. cereus group. We show that the role of CasKR in cold growth is similar in other B. cereus sensu lato strains with different growth temperature ranges, including psychrotolerant strains. PMID:24509924

Programmable chemical reaction networks: emulating regulatory functions in living cells using a bottom-up approach.

PubMed

van Roekel, Hendrik W H; Rosier, Bas J H M; Meijer, Lenny H H; Hilbers, Peter A J; Markvoort, Albert J; Huck, Wilhelm T S; de Greef, Tom F A

2015-11-07

Living cells are able to produce a wide variety of biological responses when subjected to biochemical stimuli. It has become apparent that these biological responses are regulated by complex chemical reaction networks (CRNs). Unravelling the function of these circuits is a key topic of both systems biology and synthetic biology. Recent progress at the interface of chemistry and biology together with the realisation that current experimental tools are insufficient to quantitatively understand the molecular logic of pathways inside living cells has triggered renewed interest in the bottom-up development of CRNs. This builds upon earlier work of physical chemists who extensively studied inorganic CRNs and showed how a system of chemical reactions can give rise to complex spatiotemporal responses such as oscillations and pattern formation. Using purified biochemical components, in vitro synthetic biologists have started to engineer simplified model systems with the goal of mimicking biological responses of intracellular circuits. Emulation and reconstruction of system-level properties of intracellular networks using simplified circuits are able to reveal key design principles and molecular programs that underlie the biological function of interest. In this Tutorial Review, we present an accessible overview of this emerging field starting with key studies on inorganic CRNs followed by a discussion of recent work involving purified biochemical components. Finally, we review recent work showing the versatility of programmable biochemical reaction networks (BRNs) in analytical and diagnostic applications.

An Initial Multi-Domain Modeling of an Actively Cooled Structure

NASA Technical Reports Server (NTRS)

Steinthorsson, Erlendur

1997-01-01

A methodology for the simulation of turbine cooling flows is being developed. The methodology seeks to combine numerical techniques that optimize both accuracy and computational efficiency. Key components of the methodology include the use of multiblock grid systems for modeling complex geometries, and multigrid convergence acceleration for enhancing computational efficiency in highly resolved fluid flow simulations. The use of the methodology has been demonstrated in several turbo machinery flow and heat transfer studies. Ongoing and future work involves implementing additional turbulence models, improving computational efficiency, adding AMR.

A pediatrician's view. Skin manifestations of bioterrorism.

PubMed

Cross, J T; Altemeier, W A

2000-01-01

The physician must be in contact with the local public health infrastructure as soon as a potential biological agent is perceived as possible. Most states are now setting up contingency plans and means to address these issues in a systematic way. This involves using local health departments, police departments, fire departments, National Guard units, and federal agencies such as the CDC and the FBI. The key component, however, is actually identifying a biological agent in the community and then moving quickly to isolate those who may be at risk of spreading the infection.

Centralized Cryptographic Key Management and Critical Risk Assessment - CRADA Final Report For CRADA Number NFE-11-03562

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

Abercrombie, R. K.; Peters, Scott

The Department of Energy Office of Electricity Delivery and Energy Reliability (DOE-OE) Cyber Security for Energy Delivery Systems (CSEDS) industry led program (DE-FOA-0000359) entitled "Innovation for Increasing Cyber Security for Energy Delivery Systems (12CSEDS)," awarded a contract to Sypris Electronics LLC to develop a Cryptographic Key Management System for the smart grid (Scalable Key Management Solutions for Critical Infrastructure Protection). Oak Ridge National Laboratory (ORNL) and Sypris Electronics, LLC as a result of that award entered into a CRADA (NFE-11-03562) between ORNL and Sypris Electronics, LLC. ORNL provided its Cyber Security Econometrics System (CSES) as a tool to be modifiedmore » and used as a metric to address risks and vulnerabilities in the management of cryptographic keys within the Advanced Metering Infrastructure (AMI) domain of the electric sector. ORNL concentrated our analysis on the AMI domain of which the National Electric Sector Cyber security Organization Resource (NESCOR) Working Group 1 (WG1) has documented 29 failure scenarios. The computational infrastructure of this metric involves system stakeholders, security requirements, system components and security threats. To compute this metric, we estimated the stakes that each stakeholder associates with each security requirement, as well as stochastic matrices that represent the probability of a threat to cause a component failure and the probability of a component failure to cause a security requirement violation. We applied this model to estimate the security of the AMI, by leveraging the recently established National Institute of Standards and Technology Interagency Report (NISTIR) 7628 guidelines for smart grid security and the International Electrotechnical Commission (IEC) 63351, Part 9 to identify the life cycle for cryptographic key management, resulting in a vector that assigned to each stakeholder an estimate of their average loss in terms of dollars per day of system operation. To further address probabilities of threats, information security analysis can be performed using game theory implemented in dynamic Agent Based Game Theoretic (ABGT) simulations. Such simulations can be verified with the results from game theory analysis and further used to explore larger scale, real world scenarios involving multiple attackers, defenders, and information assets. The strategy for the game was developed by analyzing five electric sector representative failure scenarios contained in the AMI functional domain from NESCOR WG1. From these five selected scenarios, we characterized them into three specific threat categories affecting confidentiality, integrity and availability (CIA). The analysis using our ABGT simulation demonstrated how to model the AMI functional domain using a set of rationalized game theoretic rules decomposed from the failure scenarios in terms of how those scenarios might impact the AMI network with respect to CIA.« less

Cryptographic Key Management and Critical Risk Assessment

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

Abercrombie, Robert K

The Department of Energy Office of Electricity Delivery and Energy Reliability (DOE-OE) CyberSecurity for Energy Delivery Systems (CSEDS) industry led program (DE-FOA-0000359) entitled "Innovation for Increasing CyberSecurity for Energy Delivery Systems (12CSEDS)," awarded a contract to Sypris Electronics LLC to develop a Cryptographic Key Management System for the smart grid (Scalable Key Management Solutions for Critical Infrastructure Protection). Oak Ridge National Laboratory (ORNL) and Sypris Electronics, LLC as a result of that award entered into a CRADA (NFE-11-03562) between ORNL and Sypris Electronics, LLC. ORNL provided its Cyber Security Econometrics System (CSES) as a tool to be modified and usedmore » as a metric to address risks and vulnerabilities in the management of cryptographic keys within the Advanced Metering Infrastructure (AMI) domain of the electric sector. ORNL concentrated our analysis on the AMI domain of which the National Electric Sector Cyber security Organization Resource (NESCOR) Working Group 1 (WG1) has documented 29 failure scenarios. The computational infrastructure of this metric involves system stakeholders, security requirements, system components and security threats. To compute this metric, we estimated the stakes that each stakeholder associates with each security requirement, as well as stochastic matrices that represent the probability of a threat to cause a component failure and the probability of a component failure to cause a security requirement violation. We applied this model to estimate the security of the AMI, by leveraging the recently established National Institute of Standards and Technology Interagency Report (NISTIR) 7628 guidelines for smart grid security and the International Electrotechnical Commission (IEC) 63351, Part 9 to identify the life cycle for cryptographic key management, resulting in a vector that assigned to each stakeholder an estimate of their average loss in terms of dollars per day of system operation. To further address probabilities of threats, information security analysis can be performed using game theory implemented in dynamic Agent Based Game Theoretic (ABGT) simulations. Such simulations can be verified with the results from game theory analysis and further used to explore larger scale, real world scenarios involving multiple attackers, defenders, and information assets. The strategy for the game was developed by analyzing five electric sector representative failure scenarios contained in the AMI functional domain from NESCOR WG1. From these five selected scenarios, we characterized them into three specific threat categories affecting confidentiality, integrity and availability (CIA). The analysis using our ABGT simulation demonstrated how to model the AMI functional domain using a set of rationalized game theoretic rules decomposed from the failure scenarios in terms of how those scenarios might impact the AMI network with respect to CIA.« less

Advancing antimicrobial stewardship: Summary of the 2015 CIDSC Report.

PubMed

Khan, F; Arthur, J; Maidment, L; Blue, D

2016-11-03

Antimicrobial resistance (AMR) is recognized as an important global public health concern that has a cross-cutting impact on human health, animal health, food and agriculture and the environment. The Communicable and Infectious Disease Steering Committee (CIDSC) of the Pan-Canadian Public Health Network (PHN) created a Task Group on Antimicrobial Stewardship to look at this issue from a Canadian perspective. To summarize the key findings of the Task Group Report that identified core components of antimicrobial stewardship programs, best practices, key challenges, gaps and recommendations to advance stewardship across jurisdictions. Search strategies were developed to identify scientific literature, grey literature and relevant websites on antimicrobial stewardship. The information was reviewed and based on this evidence, expert opinion and consensus-building, the Task Group identified core components, best practices, key challenges and gaps and developed recommendations to advance stewardship in Canada. The four components of a promising antimicrobial stewardship initiative were: leadership, interventions, monitoring/evaluation and future research. Best practices include a multi-sectoral/multipronged approach involving a wide range of stakeholders at the national, provincial/territorial, local and health care organizational levels. Key challenges and gaps identified were: the success and sustainability of stewardship undertakings require appropriate and sustained resourcing and expertise; there is limited evidence about how to effectively implement treatment guidance; and there is a challenge in ensuring accessibility, standardization and consistency of use among professionals. ​: Recommendations to the CIDSC about how to advance stewardship across jurisdictions included the following: institute a national infrastructure; develop best practices to implement stewardship programs; develop education and promote awareness; establish consistent evidence-based guidance, resources, tools and training; mandate the incorporation of stewardship education; develop audit and feedback tools; establish benchmarks and performance targets for stewardship; and conduct timely evaluation of stewardship programs. Findings of this report will inform a more systematic approach to addressing antimicrobial stewardship Canada-wide.

Laser Additive Manufacturing of F/M Steels for Radiation Tolerant Nuclear Components

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

Lienert, Thomas J.; Maloy, Stuart Andrew

According to the Nuclear Energy R&D Roadmap Report submitted to Congress in 2010, one the key challenges facing the nuclear energy industry involves development of new reactor designs with reduced capital costs. Two related R&D objectives outlined in the report include: 1) Making improvements in the affordability of new reactors; and 2) Development of structural materials to withstand irradiation for longer periods. Laser additive manufacturing (LAM) is particularly well suited for more rapid and economical fabrication of reactor components relative to current fabrication methods. The proposed work involving LAM directly addresses the two R&D objectives outlined above relevant to themore » pertinent mission problems. The classical Materials Science approach involving development of Process/Structure/Property/Performance (P/S/P/P) relations was employed in this project. Processing included LAM and heat-treating. Thermal cycling during LAM is discussed here, and phase diagrams and continuous cooling transformation (CCT) diagrams are used to rationalize microstructural evolution. Structures were characterized including grain size & morphology, volume fraction, morphology, composition and location of carbides in as-deposited and heat-treated conditions. In the simplest sense, the goal was to control microstructures through process manipulation with a view toward optimizing properties and performance in service.« less

Pleomorphic copper coordination by Alzheimer's disease amyloid-beta peptide.

PubMed

Drew, Simon C; Noble, Christopher J; Masters, Colin L; Hanson, Graeme R; Barnham, Kevin J

2009-01-28

Numerous conflicting models have been proposed regarding the nature of the Cu(2+) coordination environment of the amyloid beta (Abeta) peptide, the causative agent of Alzheimer's disease. This study used multifrequency CW-EPR spectroscopy to directly resolve the superhyperfine interactions between Cu(2+) and the ligand nuclei of Abeta, thereby avoiding ambiguities associated with introducing point mutations. Using a library of Abeta16 analogues with site-specific (15)N-labeling at Asp1, His6, His13, and His14, numerical simulations of the superhyperfine resonances delineated two independent 3N1O Cu(2+) coordination modes, {N(a)(D1), O, N(epsilon)(H6), N(epsilon)(H13)} (component Ia) and {N(a)(D1), O, N(epsilon)(H6), N(epsilon)(H14)} (component Ib), between pH 6-7. A third coordination mode (component II) was identified at pH 8.0, and simulation of the superhyperfine resonances indicated a 3N1O coordination sphere involving nitrogen ligation by His6, His13, and His14. No differences were observed upon (17)O-labeling of the phenolic oxygen of Tyr10, confirming it is not a key oxygen ligand in the physiological pH range. Hyperfine sublevel correlation (HYSCORE) spectroscopy, in conjunction with site-specific (15)N-labeling, provided additional support for the common role of His6 in components Ia and Ib, and for the assignment of a {O, N(epsilon)(H6), N(epsilon)(H13), N(epsilon)(H14)} coordination sphere to component II. HYSCORE studies of a peptide analogue with selective (13)C-labeling of Asp1 revealed (13)C cross-peaks characteristic of equatorial coordination by the carboxylate oxygen of Asp1 in component Ia/b coordination. The direct resolution of Cu(2+) ligand interactions, together with the key finding that component I is composed of two distinct coordination modes, provides valuable insight into a range of conflicting ligand assignments and highlights the complexity of Cu(2+)/Abeta interactions.

Comparative Study of Human and Mouse Postsynaptic Proteomes Finds High Compositional Conservation and Abundance Differences for Key Synaptic Proteins

PubMed Central

Bayés, Àlex; Collins, Mark O.; Croning, Mike D. R.; van de Lagemaat, Louie N.; Choudhary, Jyoti S.; Grant, Seth G. N.

2012-01-01

Direct comparison of protein components from human and mouse excitatory synapses is important for determining the suitability of mice as models of human brain disease and to understand the evolution of the mammalian brain. The postsynaptic density is a highly complex set of proteins organized into molecular networks that play a central role in behavior and disease. We report the first direct comparison of the proteome of triplicate isolates of mouse and human cortical postsynaptic densities. The mouse postsynaptic density comprised 1556 proteins and the human one 1461. A large compositional overlap was observed; more than 70% of human postsynaptic density proteins were also observed in the mouse postsynaptic density. Quantitative analysis of postsynaptic density components in both species indicates a broadly similar profile of abundance but also shows that there is higher abundance variation between species than within species. Well known components of this synaptic structure are generally more abundant in the mouse postsynaptic density. Significant inter-species abundance differences exist in some families of key postsynaptic density proteins including glutamatergic neurotransmitter receptors and adaptor proteins. Furthermore, we have identified a closely interacting set of molecules enriched in the human postsynaptic density that could be involved in dendrite and spine structural plasticity. Understanding synapse proteome diversity within and between species will be important to further our understanding of brain complexity and disease. PMID:23071613

No evidence for induction of key components of the Notch signaling pathway (Notch-1, Jagged-1) by treatment with UV-B, 1,25(OH)(2)D(3), and/or epigenetic drugs (TSA, 5-Aza) in human keratinocytes in vitro.

PubMed

Reichrath, Sandra; Reichrath, Jörg

2012-01-01

Notch signaling is of high importance for growth and survival of various cell types. We now analyzed the protein expression of two key components of the Notch signaling pathway (Notch-1, Jagged-1) in spontaneously immortalized (HaCaT) and in malignant (SCL-1) human keratinocytes, using western analysis. We found that Notch-1 and its corresponding ligand Jagged-1 are expressed in both cell lines, with no marked change following UV-B treatment. Moreover, treatment of both cell lines before or after UV-B irradiation with 1,25-dihydroxyvitamin D(3), the biologically active form of vitamin D, and/or epigenetic modulating drugs (TSA; 5-Aza) did not result in a marked modulation of the protein expression of Notch-1 or Jagged-1. Under the experimental conditions of this study, treatment with 1,25(OH)(2)D(3) protected human keratinocytes in part against the antiproliferative effects of UV-B-radiation. In conclusion, our findings do not point at a differential expression of these two key components of Notch signaling in non-malignant as compared to malignant human keratinocytes, indicating that alterations in their expression are not of importance for the photocarcinogenesis of human squamous cell carcinomas. Moreover, our findings do not support the hypothesis that modulation of Notch signaling may be involved in the photoprotective effect of 1,25-dihydroxyvitamin D(3), that we and others reported previously. Additionally, we demonstrate that epigenetic modulating drugs (TSA, 5-Aza) do not markedly modulate the expression Notch-1 or Jagged-1 in UV-B-treated human keratinocytes in vitro.

Resistance to reinforcement change in multiple and concurrent schedules assessed in transition and at steady state.

PubMed

McLean, A P; Blampied, N M

1995-01-01

Behavioral momentum theory relates resistance to change of responding in a multiple-schedule component to the total reinforcement obtained in that component, regardless of how the reinforcers are produced. Four pigeons responded in a series of multiple-schedule conditions in which a variable-interval 40-s schedule arranged reinforcers for pecking in one component and a variable-interval 360-s schedule arranged them in the other. In addition, responses on a second key were reinforced according to variable-interval schedules that were equal in the two components. In different parts of the experiment, responding was disrupted by changing the rate of reinforcement on the second key or by delivering response-independent food during a blackout separating the two components. Consistent with momentum theory, responding on the first key in Part 1 changed more in the component with the lower reinforcement total when it was disrupted by changes in the rate of reinforcement on the second key. However, responding on the second key changed more in the component with the higher reinforcement total. In Parts 2 and 3, responding was disrupted with free food presented during intercomponent blackouts, with extinction (Part 2) or variable-interval 80-s reinforcement (Part 3) arranged on the second key. Here, resistance to change was greater for the component with greater overall reinforcement. Failures of momentum theory to predict short-term differences in resistance to change occurred with disruptors that caused greater change between steady states for the richer component. Consistency of effects across disruptors may yet be found if short-term effects of disruptors are assessed relative to the extent of change observed after prolonged exposure.

Data collection and analysis software development for rotor dynamics testing in spin laboratory

NASA Astrophysics Data System (ADS)

Abdul-Aziz, Ali; Arble, Daniel; Woike, Mark

2017-04-01

Gas turbine engine components undergo high rotational loading another complex environmental conditions. Such operating environment leads these components to experience damages and cracks that can cause catastrophic failure during flights. There are traditional crack detections and health monitoring methodologies currently being used which rely on periodic routine maintenances, nondestructive inspections that often times involve engine and components dis-assemblies. These methods do not also offer adequate information about the faults, especially, if these faults at subsurface or not clearly evident. At NASA Glenn research center, the rotor dynamics laboratory is presently involved in developing newer techniques that are highly dependent on sensor technology to enable health monitoring and prediction of damage and cracks in rotor disks. These approaches are noninvasive and relatively economical. Spin tests are performed using a subscale test article mimicking turbine rotor disk undergoing rotational load. Non-contact instruments such as capacitive and microwave sensors are used to measure the blade tip gap displacement and blade vibrations characteristics in an attempt develop a physics based model to assess/predict the faults in the rotor disk. Data collection is a major component in this experimental-analytical procedure and as a result, an upgrade to an older version of the data acquisition software which is based on LabVIEW program has been implemented to support efficiently running tests and analyze the results. Outcomes obtained from the tests data and related experimental and analytical rotor dynamics modeling including key features of the updated software are presented and discussed.

Injection drug users’ involvement in drug dealing in the downtown eastside of Vancouver: Social organization and systemic violence

PubMed Central

Small, Will; Maher, Lisa; Lawlor, Jeff; Wood, Evan; Shannon, Kate; Kerr, Thomas

2014-01-01

Background Illicit drug markets are a key component of the risk environment surrounding injection drug use. However, relatively few studies have explored how injection drug users’ (IDUs) involvement in drug dealing shapes their experiences of drug market-related harm. This exploratory qualitative study aims to understand IDUs’ dealing activities and roles, as well as the perceived benefits and risks related to participation in illicit drug markets, including experiences of drug market violence. Methods Ten IDUs with extensive involvement in drug dealing activities were recruited from the Vancouver Injection Drug User Study (VIDUS) and participated in semi-structured qualitative interviews, which elicited discussion of experiences dealing drugs, perceived benefits and hazards related to dealing, and understandings of drug market violence. Results Participant's involvement in drug market activities included corporate sales, freelance or independent sales, and opportunistic sales termed “middling” as well as drug market-related hustles entailing selling bogus drugs and robbing dealers. Participants primarily dealt drugs to support their own illicit drug use, and we found that arrest and criminal justice involvement, hazards stemming from drug debts, and drug market-related violence were key risks related to dealing activities. Conclusion The challenges of managing personal consumption while selling drugs exacerbates the hazards associated with drug dealing. Efforts to address drug dealing among IDUs should consider both drug dependency and the material conditions that propel drug users towards dealing activities. Interventions should explore the potential of combining enhanced drug treatment programs with low threshold employment and alternative income generation opportunities. PMID:23664788

Word-to-picture recognition is a function of motor components mappings at the stage of retrieval.

PubMed

Brouillet, Denis; Brouillet, Thibaut; Milhau, Audrey; Heurley, Loïc; Vagnot, Caroline; Brunel, Lionel

2016-10-01

Embodied approaches of cognition argue that retrieval involves the re-enactment of both sensory and motor components of the desired remembering. In this study, we investigated the effect of motor action performed to produce the response in a recognition task when this action is compatible with the affordance of the objects that have to be recognised. In our experiment, participants were first asked to learn a list of words referring to graspable objects, and then told to make recognition judgements on pictures. The pictures represented objects where the graspable part was either pointing to the same or to the opposite side of the "Yes" response key. Results show a robust effect of compatibility between objects affordance and response hand. Moreover, this compatibility improves participants' ability of discrimination, suggesting that motor components are relevant cue for memory judgement at the stage of retrieval in a recognition task. More broadly, our data highlight that memory judgements are a function of motor components mappings at the stage of retrieval. © 2015 International Union of Psychological Science.

Using Separable Nonnegative Matrix Factorization Techniques for the Analysis of Time-Resolved Raman Spectra.

PubMed

Luce, Robert; Hildebrandt, Peter; Kuhlmann, Uwe; Liesen, Jörg

2016-09-01

The key challenge of time-resolved Raman spectroscopy is the identification of the constituent species and the analysis of the kinetics of the underlying reaction network. In this work we present an integral approach that allows for determining both the component spectra and the rate constants simultaneously from a series of vibrational spectra. It is based on an algorithm for nonnegative matrix factorization that is applied to the experimental data set following a few pre-processing steps. As a prerequisite for physically unambiguous solutions, each component spectrum must include one vibrational band that does not significantly interfere with the vibrational bands of other species. The approach is applied to synthetic "experimental" spectra derived from model systems comprising a set of species with component spectra differing with respect to their degree of spectral interferences and signal-to-noise ratios. In each case, the species involved are connected via monomolecular reaction pathways. The potential and limitations of the approach for recovering the respective rate constants and component spectra are discussed. © The Author(s) 2016.

Establishing key components of yoga interventions for musculoskeletal conditions: a Delphi survey

PubMed Central

2014-01-01

Background Evidence suggests yoga is a safe and effective intervention for the management of physical and psychosocial symptoms associated with musculoskeletal conditions. However, heterogeneity in the components and reporting of clinical yoga trials impedes both the generalization of study results and the replication of study protocols. The aim of this Delphi survey was to address these issues of heterogeneity, by developing a list of recommendations of key components for the design and reporting of yoga interventions for musculoskeletal conditions. Methods Recognised experts involved in the design, conduct, and teaching of yoga for musculoskeletal conditions were identified from a systematic review, and invited to contribute to the Delphi survey. Forty-one of the 58 experts contacted, representing six countries, agreed to participate. A three-round Delphi was conducted via electronic surveys. Round 1 presented an open-ended question, allowing panellists to individually identify components they considered key to the design and reporting of yoga interventions for musculoskeletal conditions. Thematic analysis of Round 1 identified items for quantitative rating in Round 2; items not reaching consensus were forwarded to Round 3 for re-rating. Results Thirty-six panellists (36/41; 88%) completed the three rounds of the Delphi survey. Panellists provided 348 comments to the Round 1 question. These comments were reduced to 49 items, grouped under five themes, for rating in subsequent rounds. A priori group consensus of ≥80% was reached on 28 items related to five themes concerning defining the yoga intervention, types of yoga practices to include in an intervention, delivery of the yoga protocol, domains of outcome measures, and reporting of yoga interventions for musculoskeletal conditions. Additionally, a priori consensus of ≥50% was reached on five items relating to minimum values for intervention parameters. Conclusions Expert consensus has provided a non-prescriptive reference list for the design and reporting of yoga interventions for musculoskeletal conditions. It is anticipated future research incorporating the Delphi guidelines will facilitate high quality international research in this field, increase homogeneity of intervention components and parameters, and enhance the comparison and reproducibility of research into the use of yoga for the management of musculoskeletal conditions. PMID:24942270

Measuring the value of healthcare business assets.

PubMed

Evans, C J

2000-04-01

Healthcare organizations obtain valuations of business assets for many reasons, including to support decisions regarding potential mergers, sale of business components, or financing; for tax assessments; and for defense against law-suits. If compliance with regulations may be an issue, such as when a not-for-profit organization is involved in a transaction, healthcare organizations should seek an independent appraisal to ensure that applicable legal standards are met. Whether or not regulatory issues are involved, however, an accurate and useful valuation of business assets depends on many factors. Financial managers must understand the purpose and function of the valuation, choice of appropriate valuation techniques, proper assessment of intangible value, use of realistic growth rates, appropriate emphasis on key focus areas of the valuation (e.g., risk and future income streams), and an accounting of physician compensation.

A four-component synthetic attractant for Drosophila suzukii (Diptera: Drosophilidae) isolated from fermented bait headspace.

PubMed

Cha, Dong H; Adams, Todd; Werle, Christopher T; Sampson, Blair J; Adamczyk, John J; Rogg, Helmuth; Landolt, Peter J

2014-02-01

A mixture of wine and vinegar is more attractive than wine or vinegar to spotted wing drosophila, Drosophila suzukii (Matsumura) (Diptera: Drosophilidae), and ethanol and acetic acid are considered key to that attractiveness. In addition to ethanol and acetic acid, 13 other wine and vinegar volatiles are antennally active to D. suzukii and might be involved in food finding. Out of the 13 antennally active chemicals, acetoin, ethyl lactate and methionol increased fly response to a mixture of acetic acid and ethanol in field trapping experiments. A five-component blend of acetic acid, ethanol, acetoin, ethyl lactate and methionol was as attractive as the starting mixture of wine and vinegar in field tests conducted in the states of Oregon and Mississippi. Subtracting ethyl lactate from the five-component blend did not reduce the captures of flies in the trap. However, subtracting any other compound from the blend significantly reduced the numbers of flies captured. These results indicate that acetic acid, ethanol, acetoin and methionol are key olfactory cues for D. suzukii when attracted to wine and vinegar, which may be food-finding behavior leading flies to fermenting fruit in nature. It is anticipated that this four-component blend can be used as a highly attractive chemical lure for detection and management of D. suzukii. Published 2013. This article is a U.S. Government work and is in the public domain in the USA. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

Stakeholder engagement: a key component of integrating genomic information into electronic health records

PubMed Central

Hartzler, Andrea; McCarty, Catherine A.; Rasmussen, Luke V.; Williams, Marc S.; Brilliant, Murray; Bowton, Erica A.; Clayton, Ellen Wright; Faucett, William A.; Ferryman, Kadija; Field, Julie R.; Fullerton, Stephanie M.; Horowitz, Carol R.; Koenig, Barbara A.; McCormick, Jennifer B.; Ralston, James D.; Sanderson, Saskia C.; Smith, Maureen E.; Trinidad, Susan Brown

2014-01-01

Integrating genomic information into clinical care and the electronic health record can facilitate personalized medicine through genetically guided clinical decision support. Stakeholder involvement is critical to the success of these implementation efforts. Prior work on implementation of clinical information systems provides broad guidance to inform effective engagement strategies. We add to this evidence-based recommendations that are specific to issues at the intersection of genomics and the electronic health record. We describe stakeholder engagement strategies employed by the Electronic Medical Records and Genomics Network, a national consortium of US research institutions funded by the National Human Genome Research Institute to develop, disseminate, and apply approaches that combine genomic and electronic health record data. Through select examples drawn from sites of the Electronic Medical Records and Genomics Network, we illustrate a continuum of engagement strategies to inform genomic integration into commercial and homegrown electronic health records across a range of health-care settings. We frame engagement as activities to consult, involve, and partner with key stakeholder groups throughout specific phases of health information technology implementation. Our aim is to provide insights into engagement strategies to guide genomic integration based on our unique network experiences and lessons learned within the broader context of implementation research in biomedical informatics. On the basis of our collective experience, we describe key stakeholder practices, challenges, and considerations for successful genomic integration to support personalized medicine. PMID:24030437

The hedgehog system machinery controls transforming growth factor-β-dependent myofibroblastic differentiation in humans: involvement in idiopathic pulmonary fibrosis.

PubMed

Cigna, Natacha; Farrokhi Moshai, Elika; Brayer, Stéphanie; Marchal-Somme, Joëlle; Wémeau-Stervinou, Lidwine; Fabre, Aurélie; Mal, Hervé; Lesèche, Guy; Dehoux, Monique; Soler, Paul; Crestani, Bruno; Mailleux, Arnaud A

2012-12-01

Idiopathic pulmonary fibrosis (IPF) is a devastating disease of unknown cause. Key signaling developmental pathways are aberrantly expressed in IPF. The hedgehog pathway plays a key role during fetal lung development and may be involved in lung fibrogenesis. We determined the expression pattern of several Sonic hedgehog (SHH) pathway members in normal and IPF human lung biopsies and primary fibroblasts. The effect of hedgehog pathway inhibition was assayed by lung fibroblast proliferation and differentiation with and without transforming growth factor (TGF)-β1. We showed that the hedgehog pathway was reactivated in the IPF lung. Importantly, we deciphered the cross talk between the hedgehog and TGF-β pathway in human lung fibroblasts. TGF-β1 modulated the expression of key components of the hedgehog pathway independent of Smoothened, the obligatory signal transducer of the pathway. Smoothened was required for TGF-β1-induced myofibroblastic differentiation of control fibroblasts, but differentiation of IPF fibroblasts was partially resistant to Smoothened inhibition. Furthermore, functional hedgehog pathway machinery from the primary cilium, as well as GLI-dependent transcription in the nucleus, was required for the TGF-β1 effects on normal and IPF fibroblasts during myofibroblastic differentiation. These data identify the GLI transcription factors as potential therapeutic targets in lung fibrosis. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Epigenetic effects of the pregnancy Mediterranean diet adherence on the offspring metabolic syndrome markers.

PubMed

Lorite Mingot, David; Gesteiro, Eva; Bastida, Sara; Sánchez-Muniz, Francisco J

2017-11-01

Metabolic syndrome (MS) has a multifactorial and not yet fully clarified origin. Insulin resistance is a key element that connects all the accepted components of MS (obesity, dyslipemia, high blood pressure, and hyperglycemia). There is strong evidence that epigenetic changes during fetal development are key factors in the development of MS. These changes are induced by maternal nutrition, among different factors, affecting the intrauterine environment. The Mediterranean diet has been shown to be a healthy eating pattern that protects against the development of MS in adults. Similarly, the Mediterranean diet could have a similar action during pregnancy, protecting the fetus against the development of MS throughout life. This review assembles studies carried out, both in animals and humans, on the epigenetic modifications associated with the consumption, during pregnancy, of Mediterranean diet main components. The relationship between these modifications and the occurrence of factors involved in development of MS is also explained. In addition, the results of our group relating adherence to the Mediterranean diet with MS markers are discussed. The paper ends suggesting future actuation lines in order to increase knowledge on Mediterranean diet adherence as a prevention tool of MS development.

A national survey of cardiac rehabilitation services in New Zealand: 2015.

PubMed

Kira, Geoff; Doolan-Noble, Fiona; Humphreys, Grace; Williams, Gina; O'Shaughnessy, Helen; Devlin, Gerry

2016-05-27

Guidelines for cardiac rehabilitation (CR) programmes inform best practice. In Aotearoa NewZealand, little information exists about the structure and services provided by CR programmes and there is a poor understanding of how existing CR programmes are delivered with respect to evidence-based national guidelines. All 46 CR providers in New Zealand were invited to participate in a national survey in 2015. The survey sought information on the following: unit structure; referral processes; patient assessment; audit (including quality assurance activity); Phase 2 CR content; and support for special populations. Simple descriptive analysis of the responses was conducted, involving forming counts and percentages. Thirty-six distinct units completed the survey and 94% provided Phase 2. Assessment tools, Phase 2 educational components, and the methods of providing the exercise component varied. Most units audited their services, 25% audited their programme six-monthly or more frequently. Just over half of the units (56%) reported key performance indicators. The survey identified variations in delivery and content of CR in New Zealand, with poor understanding of the impact on patient outcomes. This is likely due to the absence of standardised audit practices and routine collection of key performance indicators on a national basis.

Statistical issues in quality control of proteomic analyses: good experimental design and planning.

PubMed

Cairns, David A

2011-03-01

Quality control is becoming increasingly important in proteomic investigations as experiments become more multivariate and quantitative. Quality control applies to all stages of an investigation and statistics can play a key role. In this review, the role of statistical ideas in the design and planning of an investigation is described. This involves the design of unbiased experiments using key concepts from statistical experimental design, the understanding of the biological and analytical variation in a system using variance components analysis and the determination of a required sample size to perform a statistically powerful investigation. These concepts are described through simple examples and an example data set from a 2-D DIGE pilot experiment. Each of these concepts can prove useful in producing better and more reproducible data. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The role of the opioid system in binge eating disorder.

PubMed

Giuliano, Chiara; Cottone, Pietro

2015-12-01

Binge eating disorder is characterized by excessive, uncontrollable consumption of palatable food within brief periods of time. Excessive intake of palatable food is thought to be driven by hedonic, rather than energy homeostatic, mechanisms. However, reward processing does not only comprise consummatory actions; a key component is represented by the anticipatory phase directed at procuring the reward. This phase is highly influenced by environmental food-associated stimuli, which can robustly enhance the desire to eat even in the absence of physiological needs. The opioid system (endogenous peptides and their receptors) has been strongly linked to the rewarding aspects of palatable food intake, and perhaps represents the key system involved in hedonic overeating. Here we review evidence suggesting that the opioid system can also be regarded as one of the systems that regulates the anticipatory incentive processes preceding binge eating hedonic episodes.

Modulation of intestinal sulfur assimilation metabolism regulates iron homeostasis

PubMed Central

Hudson, Benjamin H.; Hale, Andrew T.; Irving, Ryan P.; Li, Shenglan; York, John D.

2018-01-01

Sulfur assimilation is an evolutionarily conserved pathway that plays an essential role in cellular and metabolic processes, including sulfation, amino acid biosynthesis, and organismal development. We report that loss of a key enzymatic component of the pathway, bisphosphate 3′-nucleotidase (Bpnt1), in mice, both whole animal and intestine-specific, leads to iron-deficiency anemia. Analysis of mutant enterocytes demonstrates that modulation of their substrate 3′-phosphoadenosine 5′-phosphate (PAP) influences levels of key iron homeostasis factors involved in dietary iron reduction, import and transport, that in part mimic those reported for the loss of hypoxic-induced transcription factor, HIF-2α. Our studies define a genetic basis for iron-deficiency anemia, a molecular approach for rescuing loss of nucleotidase function, and an unanticipated link between nucleotide hydrolysis in the sulfur assimilation pathway and iron homeostasis. PMID:29507250

Neem components as potential agents for cancer prevention and treatment

PubMed Central

Hao, Fang; Kumar, Sandeep; Yadav, Neelu; Chandra, Dhyan

2016-01-01

Azadirachta indica, also known as neem, is commonly found in many semi-tropical and tropical countries including India, Pakistan, and Bangladesh. The components extracted from neem plant have been used in traditional medicine for the cure of multiple diseases including cancer for centuries. The extracts of seeds, leaves, flowers, and fruits of neem have consistently shown chemopreventive and antitumor effects in different types of cancer. Azadirachtin and nimbolide are among the few bioactive components in neem that have been studied extensively, but research on a great number of additional bioactive components is warranted. The key anticancer effects of neem components on malignant cells include inhibition of cell proliferation, induction of cell death, suppression of cancer angiogenesis, restoration of cellular reduction/oxidation (redox) balance, and enhancement of the host immune responses against tumor cells. While the underlying mechanisms of these effects are mostly unclear, the suppression of NF-κB signaling pathway is, at least partially, involved in the anticancer functions of neem components. Importantly, the anti-proliferative and apoptosis-inducing effects of neem components are tumor selective as the effects on normal cells are significantly weaker. In addition, neem extracts sensitize cancer cells to immunotherapy and radiotherapy, and enhance the efficacy of certain cancer chemotherapeutic agents. This review summarizes the current updates on the anticancer effects of neem components and their possible impact on managing cancer incidence and treatment. PMID:25016141

Orosensory-directed identification of astringent mouthfeel and bitter-tasting compounds in red wine.

PubMed

Hufnagel, Jan Carlos; Hofmann, Thomas

2008-02-27

Application of sequential solvent extraction, followed by HPLC combined with the taste dilution analysis, enabled the localization of the most intense velvety astringent, drying, and puckering astringent, as well as bitter-tasting, compounds in red wine, respectively. Isolation of the taste components involving gel adsorption chromatography, ultrafiltration, and synthesis revealed the identification of 26 sensory-active nonvolatiles, among which several hydroxybenzoic acids, hydroxycinnamic acids, flavon-3-ol glycosides, and dihydroflavon-3-ol rhamnosides as well as a structurally undefined polymeric fraction (>5 kDa) were identified as the key astringent components. In contradiction to literature suggestions, flavan-3-ols were found to be not of major importance for astringency and bitter taste, respectively. Surprisingly, a series of hydroxybenzoic acid ethyl esters and hydroxycinnamic acid ethyl esters were identified as bitter compounds in wine. Taste qualities and taste threshold concentrations of the individual wine components were determined by means of a three-alternative forced-choice test and the half-mouth test, respectively.

The role of probiotics on each component of the metabolic syndrome and other cardiovascular risks.

PubMed

Miglioranza Scavuzzi, Bruna; Miglioranza, Lucia Helena da Silva; Henrique, Fernanda Carla; Pitelli Paroschi, Thanise; Lozovoy, Marcell Alysson Batisti; Simão, Andréa Name Colado; Dichi, Isaias

2015-01-01

Probiotics are defined as live microorganisms that when administered in adequate amounts confer health benefits to the host. The consumption of probiotics has gained increasing recognition from the scientific community due to the promising effects on metabolic health through gut microbiota modulation. This article presents a review of scientific studies investigating probiotic species and their effects on different risk factors of the metabolic syndrome (MetS). This article also presents a summary of the major mechanisms involved with gut microbiota and the components of the MetS and raises the key issues to be considered by scientists in search of probiotics species for treatment of patients suffering from this metabolic disorder. Probiotics may confer numerous health benefits to the host through positive gut microbiota modulation. The strain selection is the most important factor for determining health effects. Further studies may consider gut microbiota as a novel target for prevention and management of MetS components and other cardiovascular risks.

Conveying endogenous and exogenous signals: MAPK cascades in plant growth and defense.

PubMed

Zhang, Mengmeng; Su, Jianbin; Zhang, Yan; Xu, Juan; Zhang, Shuqun

2018-05-09

Mitogen-activated protein kinase (MAPK) cascades are key signaling modules downstream of receptors/sensors that perceive endogenous and exogenous stimuli such as hormones, peptide ligands, and pathogen-derived patterns/effectors. In this review, we summarize recent advances in the establishment of MAPK cascades as unified signaling modules downstream of receptor-like kinases (RLKs) and receptor-like proteins (RLPs) in plant growth and defense, the identification of components connecting the RLK/RLP receptor complexes to the MAPK cascades, and the interactions between MAPK and hormone signaling pathways. We also propose a set of criteria for defining the physiological substrates of plant MAPKs. With only a limited number of MAPK components, multiple functional pathways often share the same MAPK cascade. As a result, understanding the signaling specificity, which requires detailed information about the spatiotemporal expression of the components involved, their complex formation, and the consequence of substrate phosphorylation, is central to our study of MAPK functions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Binding Properties of General Odorant Binding Proteins from the Oriental Fruit Moth, Grapholita molesta (Busck) (Lepidoptera: Tortricidae)

PubMed Central

Li, Guangwei; Chen, Xiulin; Li, Boliao; Zhang, Guohui; Li, Yiping; Wu, Junxiang

2016-01-01

Background The oriental fruit moth Grapholita molesta is a host-switching pest species. The adults highly depend on olfactory cues in locating optimal host plants and oviposition sites. Odorant binding proteins (OBPs) are thought to be responsible for recognizing and transporting hydrophobic odorants across the aqueous sensillum lymph to stimulate the odorant receptors (ORs) within the antennal sensilla and activate the olfactory signal transduction pathway. Exploring the physiological function of these OBPs could facilitate understanding insect chemical communications. Methodology/Principal Finding Two antennae-specific general OBPs (GOBPs) of G. molesta were expressed and purified in vitro. The binding affinities of G. molesta GOBP1 and 2 (GmolGOBP1 and 2) for sex pheromone components and host plant volatiles were measured by fluorescence ligand-binding assays. The distribution of GmolGOBP1 and 2 in the antennal sensillum were defined by whole mount fluorescence immunohistochemistry (WM-FIHC) experiments. The binding sites of GmolGOBP2 were predicted using homology modeling, molecular docking and site-directed mutagenesis. Both GmolGOBP1 and 2 are housing in sensilla basiconica and with no differences in male and female antennae. Recombinant GmolGOBP1 (rGmolGOBP1) exhibited broad binding properties towards host plant volatiles and sex pheromone components; rGmolGOBP2 could not effectively bind host plant volatiles but showed specific binding affinity with a minor sex pheromone component dodecanol. We chose GmolGOBP2 and dodecanol for further homology modeling, molecular docking, and site-directed mutagenesis. Binding affinities of mutants demonstrated that Thr9 was the key binding site and confirmed dodecanol bonding to protein involves a hydrogen bond. Combined with the pH effect on binding affinities of rGmolGOBP2, ligand binding and release of GmolGOBP2 were related to a pH-dependent conformational transition. Conclusion Two rGmolGOBPs exhibit different binding characteristics for tested ligands. rGmolGOBP1 has dual functions in recognition of host plant volatiles and sex pheromone components, while rGmolGOBP2 is mainly involved in minor sex pheromone component dodecanol perception. This study also provides empirical evidence for the predicted functions of key amino acids in recombinant protein ligand-binding characteristics. PMID:27152703

Salinity-induced inhibition of growth in the aquatic pteridophyte Azolla microphylla primarily involves inhibition of photosynthetic components and signaling molecules as revealed by proteome analysis.

PubMed

Thagela, Preeti; Yadav, Ravindra Kumar; Mishra, Vagish; Dahuja, Anil; Ahmad, Altaf; Singh, Pawan Kumar; Tiwari, Budhi Sagar; Abraham, Gerard

2017-01-01

Salinity stress causes adverse physiological and biochemical changes in the growth and productivity of a plant. Azolla, a symbiotic pteridophyte and potent candidate for biofertilizer due to its nitrogen fixation ability, shows reduced growth and nitrogen fixation during saline stress. To better understand regulatory components involved in salinity-induced physiological changes, in the present study, Azolla microphylla plants were exposed to NaCl (6.74 and 8.61 ds/m) and growth, photochemical reactions of photosynthesis, ion accumulation, and changes in cellular proteome were studied. Maximum dry weight was accumulated in control and untreated plant while a substantial decrease in dry weight was observed in the plants exposed to salinity. Exposure of the organism to different concentrations of salt in hydroponic conditions resulted in differential level of Na + and K + ion accumulation. Comparative analysis of salinity-induced proteome changes in A. microphylla revealed 58 salt responsive proteins which were differentially expressed during the salt exposure. Moreover, 42 % spots among differentially expressed proteins were involved in different signaling events. The identified proteins are involved in photosynthesis, energy metabolism, amino acid biosynthesis, protein synthesis, and defense. Downregulation of these key metabolic proteins appears to inhibit the growth of A. microphylla in response to salinity. Altogether, the study revealed that in Azolla, increased salinity primarily affected signaling and photosynthesis that in turn leads to reduced biomass.

A systematic review of the evidence on service user involvement in interpersonal skills training of mental health students.

PubMed

Perry, J; Watkins, M; Gilbert, A; Rawlinson, J

2013-08-01

Service user involvement has become a common feature of education programmes for mental health students. However, little is known about the effects of this type of education on the interpersonal skills of students taking part. This paper reports findings from a systematic review that formed part of a wider investigation into service user involvement in teaching interpersonal skills. The review aimed to locate and assess the quality of the published evidence relating to the effects of service user involvement on mental health students interpersonal skills and to synthesize results, using a definition of interpersonal skill that includes attitudes, empathy and skills as its key components. Results from this study indicate that the quality of evidence in this area is poor. However, sufficient synthesis of the evidence base was possible to allow conclusions and recommendations for both research and practice. Conclusions were that the involvement of service users in this area is both acceptable and valuable for students and had specific impacts on attitudes, empathy and skills. Some difficulties and reservations about the style of involvement are discussed. Recommendations for the conduct of future research are also made. © 2012 John Wiley & Sons Ltd.

Tailored combination prevention packages and PrEP for young key populations

PubMed Central

Pettifor, Audrey; Nguyen, Nadia L; Celum, Connie; Cowan, Frances M; Go, Vivian; Hightow-Weidman, Lisa

2015-01-01

Introduction Young key populations, defined in this article as men who have sex with men, transgender persons, people who sell sex and people who inject drugs, are at particularly high risk for HIV. Due to the often marginalized and sometimes criminalized status of young people who identify as members of key populations, there is a need for HIV prevention packages that account for the unique and challenging circumstances they face. Pre-exposure prophylaxis (PrEP) is likely to become an important element of combination prevention for many young key populations. Objective In this paper, we discuss important challenges to HIV prevention among young key populations, identify key components of a tailored combination prevention package for this population and examine the role of PrEP in these prevention packages. Methods We conducted a comprehensive review of the evidence to date on prevention strategies, challenges to prevention and combination prevention packages for young key populations. We focused specifically on the role of PrEP in these prevention packages and on young people under the age of 24, and 18 in particular. Results and discussion Combination prevention packages that include effective, acceptable and scalable behavioural, structural and biologic interventions are needed for all key populations to prevent new HIV infections. Interventions in these packages should meaningfully involve beneficiaries in the design and implementation of the intervention, and take into account the context in which the intervention is being delivered to thoughtfully address issues of stigma and discrimination. These interventions will likely be most effective if implemented in conjunction with strategies to facilitate an enabling environment, including increasing access to HIV testing and health services for PrEP and other prevention strategies, decriminalizing key populations’ practices, increasing access to prevention and care, reducing stigma and discrimination, and fostering community empowerment. PrEP could offer a highly effective, time-limited primary prevention for young key populations if it is implemented in combination with other programs to increase access to health services and encourage the reliable use of PrEP while at risk of HIV exposure. Conclusions Reductions in HIV incidence will only be achieved through the implementation of combinations of interventions that include biomedical and behavioural interventions, as well as components that address social, economic and other structural factors that influence HIV prevention and transmission. PMID:25724507

FUM2, a Cytosolic Fumarase, Is Essential for Acclimation to Low Temperature in Arabidopsis thaliana1[OPEN

PubMed Central

Dyson, Beth C.; Miller, Matthew A.E.; Feil, Regina; Rattray, Nicholas; Bowsher, Caroline G.

2016-01-01

Although cold acclimation is a key process in plants from temperate climates, the mechanisms sensing low temperature remain obscure. Here, we show that the accumulation of the organic acid fumaric acid, mediated by the cytosolic fumarase FUM2, is essential for cold acclimation of metabolism in the cold-tolerant model species Arabidopsis (Arabidopsis thaliana). A nontargeted metabolomic approach, using gas chromatography-mass spectrometry, identifies fumarate as a key component of the cold response in this species. Plants of T-DNA insertion mutants, lacking FUM2, show marked differences in their response to cold, with contrasting responses both in terms of metabolite concentrations and gene expression. The fum2 plants accumulated higher concentrations of phosphorylated sugar intermediates and of starch and malate. Transcripts for proteins involved in photosynthesis were markedly down-regulated in fum2.2 but not in wild-type Columbia-0. Plants of fum2 show a complete loss of the ability to acclimate photosynthesis to low temperature. We conclude that fumarate accumulation plays an essential role in low temperature sensing in Arabidopsis, either indirectly modulating metabolic or redox signals or possibly being itself directly involved in cold sensing. PMID:27440755

On the Evolution of the Cardiac Pacemaker

PubMed Central

Burkhard, Silja; van Eif, Vincent; Garric, Laurence; Christoffels, Vincent M.; Bakkers, Jeroen

2017-01-01

The rhythmic contraction of the heart is initiated and controlled by an intrinsic pacemaker system. Cardiac contractions commence at very early embryonic stages and coordination remains crucial for survival. The underlying molecular mechanisms of pacemaker cell development and function are still not fully understood. Heart form and function show high evolutionary conservation. Even in simple contractile cardiac tubes in primitive invertebrates, cardiac function is controlled by intrinsic, autonomous pacemaker cells. Understanding the evolutionary origin and development of cardiac pacemaker cells will help us outline the important pathways and factors involved. Key patterning factors, such as the homeodomain transcription factors Nkx2.5 and Shox2, and the LIM-homeodomain transcription factor Islet-1, components of the T-box (Tbx), and bone morphogenic protein (Bmp) families are well conserved. Here we compare the dominant pacemaking systems in various organisms with respect to the underlying molecular regulation. Comparative analysis of the pathways involved in patterning the pacemaker domain in an evolutionary context might help us outline a common fundamental pacemaker cell gene programme. Special focus is given to pacemaker development in zebrafish, an extensively used model for vertebrate development. Finally, we conclude with a summary of highly conserved key factors in pacemaker cell development and function. PMID:29367536

DGAT and triglyceride synthesis: a new target for obesity treatment?

PubMed

Chen, H C; Farese, R V

2000-07-01

Because triglycerides are considered essential for survival and their synthesis has been thought to occur through a single mechanism, inhibiting triglyceride synthesis has been largely unexplored as a possible target for obesity treatment. However, recent studies indicate that mice lacking acyl CoA:diacylglycerol acyltransferase (DGAT), a key enzyme in triglyceride synthesis, are viable and resistant to diet-induced obesity. Unexpectedly, this resistance is caused by a mechanism involving increased energy expenditure. These findings suggest that inhibiting specific components of triglyceride synthesis, such as DGAT, is feasible and may represent a novel approach to treating obesity.

Insight into the SEA amide thioester equilibrium. Application to the synthesis of thioesters at neutral pH.

PubMed

Pira, S L; El Mahdi, O; Raibaut, L; Drobecq, H; Dheur, J; Boll, E; Melnyk, O

2016-07-26

The bis(2-sulfanylethyl)amide (SEA) N,S-acyl shift thioester surrogate has found a variety of useful applications in the field of protein total synthesis. Here we present novel insights into the SEA amide/thioester equilibrium in water which is an essential step in any reaction involving the thioester surrogate properties of the SEA group. We also show that the SEA amide thioester equilibrium can be efficiently displaced at neutral pH for accessing peptide alkylthioesters, i.e. the key components of the native chemical ligation (NCL) reaction.

Multifunctional 2D- Materials: Selenides and Halides

NASA Technical Reports Server (NTRS)

Singh, N. B.; Su, Ching Hua; Arnold, Brad; Choa, Fow-Sen; Bohorfous, Sara

2016-01-01

Material is the key component and controls the performance of the detectors, devices and sensors. The materials design, processing, growth and fabrication of bulk and nanocrystals and fabrication into devices and sensors involve multidisciplinary team of experts. This places a large burden on the cost of the novel materials development. Due to this reason there is a big thrust for the prediction of multifunctionality of materials before design and development. Up to some extent design can achieve certain properties. In multinary materials processing is also a big factor. In this presentation, examples of two classes of industrially important materials will be described.

Tuning the developing brain to social signals of emotions

PubMed Central

Leppänen, Jukka M.; Nelson, Charles A.

2010-01-01

PREFACE Humans in diverse cultures develop a similar capacity to recognize the emotional signals of different facial expressions. This capacity is mediated by a brain network that involves emotion-related brain circuits and higher-level visual representation areas. Recent studies suggest that the key components of this network begin to emerge early in life. The studies also suggest that initial biases in emotion-related brain circuits and the early coupling of these circuits and cortical perceptual areas provides a foundation for a rapid acquisition of representations of those facial features that denote specific emotions. PMID:19050711

Forensic aspects and assessment of school bullying.

PubMed

Freeman, Bradley W; Thompson, Christopher; Jaques, Cory

2012-12-01

This article describes school's obligations related to bullying behavior, the assessment of bullying students and their victims, the evaluation of claimed damages due to bullying, and potential interventions for both individuals and school systems to reduce the frequency of bullying behavior. This article assists evaluators when assessing youth who are involved in bullying behavior, either as victims or perpetrators. Key areas highlighted include an overview of bullying behaviors, legal issues related to a school's responsibility in preventing or curtailing bullying behaviors, important components of a bullying assessment, and proposed interventions to minimize bullying. Copyright © 2012 Elsevier Inc. All rights reserved.

Integrated Distributed Directory Service for KSC

NASA Technical Reports Server (NTRS)

Ghansah, Isaac

1997-01-01

This paper describes an integrated distributed directory services (DDS) architecture as a fundamental component of KSC distributed computing systems. Specifically, an architecture for an integrated directory service based on DNS and X.500/LDAP has been suggested. The architecture supports using DNS in its traditional role as a name service and X.500 for other services. Specific designs were made in the integration of X.500 DDS for Public Key Certificates, Kerberos Security Services, Network-wide Login, Electronic Mail, WWW URLS, Servers, and other diverse network objects. Issues involved in incorporating the emerging Microsoft Active Directory Service MADS in KSC's X.500 were discussed.

Comparative Analysis of Wolbachia Genomes Reveals Streamlining and Divergence of Minimalist Two-Component Systems

PubMed Central

Christensen, Steen; Serbus, Laura Renee

2015-01-01

Two-component regulatory systems are commonly used by bacteria to coordinate intracellular responses with environmental cues. These systems are composed of functional protein pairs consisting of a sensor histidine kinase and cognate response regulator. In contrast to the well-studied Caulobacter crescentus system, which carries dozens of these pairs, the streamlined bacterial endosymbiont Wolbachia pipientis encodes only two pairs: CckA/CtrA and PleC/PleD. Here, we used bioinformatic tools to compare characterized two-component system relays from C. crescentus, the related Anaplasmataceae species Anaplasma phagocytophilum and Ehrlichia chaffeensis, and 12 sequenced Wolbachia strains. We found the core protein pairs and a subset of interacting partners to be highly conserved within Wolbachia and these other Anaplasmataceae. Genes involved in two-component signaling were positioned differently within the various Wolbachia genomes, whereas the local context of each gene was conserved. Unlike Anaplasma and Ehrlichia, Wolbachia two-component genes were more consistently found clustered with metabolic genes. The domain architecture and key functional residues standard for two-component system proteins were well-conserved in Wolbachia, although residues that specify cognate pairing diverged substantially from other Anaplasmataceae. These findings indicate that Wolbachia two-component signaling pairs share considerable functional overlap with other α-proteobacterial systems, whereas their divergence suggests the potential for regulatory differences and cross-talk. PMID:25809075

Strategies for investigating nuclear-cytoplasmic tRNA dynamics in yeast and mammalian cells.

PubMed

Pierce, Jacqueline B; Chafe, Shawn C; Eswara, Manoja B K; van der Merwe, George; Mangroo, Dev

2014-01-01

Nuclear-cytoplasmic tRNA transport involves multiple pathways that are segregated by the involvement of distinct proteins. The tRNA export process begins in the nucleolus, where the functionality of newly produced tRNAs are tested by aminoacylation, and ends with the delivery of the exported aminoacyl tRNAs to the eukaryotic elongation factor eEF-1A for utilization in protein synthesis in the cytoplasm. Recent studies have identified a number of proteins that participate in nuclear tRNA export in both yeast and mammals. However, genetic and biochemical evidence suggest that additional components, which have yet to be identified, also participate in nuclear-cytoplasmic tRNA trafficking. Here we review key strategies that have led to the identification and characterization of proteins that are involved in the nuclear tRNA export process in yeasts and mammals. The approaches described will greatly facilitate the identification and delineation of the roles of new proteins involved in nuclear export of tRNAs to the cytoplasm. Copyright © 2014 Elsevier Inc. All rights reserved.

Kdo2-lipid A: structural diversity and impact on immunopharmacology

PubMed Central

Wang, Xiaoyuan; Quinn, Peter J; Yan, Aixin

2015-01-01

3-deoxy-d-manno-octulosonic acid-lipid A (Kdo2-lipid A) is the essential component of lipopolysaccharide in most Gram-negative bacteria and the minimal structural component to sustain bacterial viability. It serves as the active component of lipopolysaccharide to stimulate potent host immune responses through the complex of Toll-like-receptor 4 (TLR4) and myeloid differentiation protein 2. The entire biosynthetic pathway of Escherichia coli Kdo2-lipid A has been elucidated and the nine enzymes of the pathway are shared by most Gram-negative bacteria, indicating conserved Kdo2-lipid A structure across different species. Yet many bacteria can modify the structure of their Kdo2-lipid A which serves as a strategy to modulate bacterial virulence and adapt to different growth environments as well as to avoid recognition by the mammalian innate immune systems. Key enzymes and receptors involved in Kdo2-lipid A biosynthesis, structural modification and its interaction with the TLR4 pathway represent a clear opportunity for immunopharmacological exploitation. These include the development of novel antibiotics targeting key biosynthetic enzymes and utilization of structurally modified Kdo2-lipid A or correspondingly engineered live bacteria as vaccines and adjuvants. Kdo2-lipid A/TLR4 antagonists can also be applied in anti-inflammatory interventions. This review summarizes recent knowledge on both the fundamental processes of Kdo2-lipid A biosynthesis, structural modification and immune stimulation, and applied research on pharmacological exploitations of these processes for therapeutic development. PMID:24838025

HemR is an OmpR/PhoB-like response regulator from Leptospira, which simultaneously effects transcriptional activation and repression of key haem metabolism genes.

PubMed

Morero, Natalia R; Botti, Horacio; Nitta, Kazuhiro R; Carrión, Federico; Obal, Gonzalo; Picardeau, Mathieu; Buschiazzo, Alejandro

2014-10-01

Several Leptospira species cause leptospirosis, the most extended zoonosis worldwide. In bacteria, two-component systems constitute key signalling pathways, some of which are involved in pathogenesis. The physiological roles of two-component systems in Leptospira are largely unknown, despite identifying several dozens within their genomes. Biochemical confirmation of an operative phosphorelaying two-component system has been obtained so far only for the Hklep/Rrlep pair. It is known that hklep/rrlep knockout strains of Leptospira biflexa result in haem auxotrophy, although their de novo biosynthesis machinery remains fully functional. Haem is essential for Leptospira, but information about Hklep/Rrlep effector function(s) and target(s) is still lacking. We are now reporting a thorough molecular characterization of this system, which we rename HemK/HemR. The DNA HemR-binding motif was determined, and found within the genomes of saprophyte and pathogenic Leptospira. In this way, putative HemR-regulated genes were pinpointed, including haem catabolism-related (hmuO - haem oxygenase) and biosynthesis-related (the hemA/C/D/B/L/E/N/G operon). Specific HemR binding to these two promoters was quantified, and a dual function was observed in vivo, inversely repressing the hmuO, while activating the hemA operon transcription. The crystal structure of HemR receiver domain was determined, leading to a mechanistic model for its dual regulatory role. © 2014 John Wiley & Sons Ltd.

Key Components in eHealth Interventions Combining Self-Tracking and Persuasive eCoaching to Promote a Healthier Lifestyle: A Scoping Review

PubMed Central

Oldenhuis, Hilbrand KE; de Groot, Martijn; Polstra, Louis; Velthuijsen, Hugo; van Gemert-Pijnen, Julia EWC

2017-01-01

Background The combination of self-tracking and persuasive eCoaching in automated interventions is a new and promising approach for healthy lifestyle management. Objective The aim of this study was to identify key components of self-tracking and persuasive eCoaching in automated healthy lifestyle interventions that contribute to their effectiveness on health outcomes, usability, and adherence. A secondary aim was to identify the way in which these key components should be designed to contribute to improved health outcomes, usability, and adherence. Methods The scoping review methodology proposed by Arskey and O’Malley was applied. Scopus, EMBASE, PsycINFO, and PubMed were searched for publications dated from January 1, 2013 to January 31, 2016 that included (1) self-tracking, (2) persuasive eCoaching, and (3) healthy lifestyle intervention. Results The search resulted in 32 publications, 17 of which provided results regarding the effect on health outcomes, 27 of which provided results regarding usability, and 13 of which provided results regarding adherence. Among the 32 publications, 27 described an intervention. The most commonly applied persuasive eCoaching components in the described interventions were personalization (n=24), suggestion (n=19), goal-setting (n=17), simulation (n=17), and reminders (n=15). As for self-tracking components, most interventions utilized an accelerometer to measure steps (n=11). Furthermore, the medium through which the user could access the intervention was usually a mobile phone (n=10). The following key components and their specific design seem to influence both health outcomes and usability in a positive way: reduction by setting short-term goals to eventually reach long-term goals, personalization of goals, praise messages, reminders to input self-tracking data into the technology, use of validity-tested devices, integration of self-tracking and persuasive eCoaching, and provision of face-to-face instructions during implementation. In addition, health outcomes or usability were not negatively affected when more effort was requested from participants to input data into the technology. The data extracted from the included publications provided limited ability to identify key components for adherence. However, one key component was identified for both usability and adherence, namely the provision of personalized content. Conclusions This scoping review provides a first overview of the key components in automated healthy lifestyle interventions combining self-tracking and persuasive eCoaching that can be utilized during the development of such interventions. Future studies should focus on the identification of key components for effects on adherence, as adherence is a prerequisite for an intervention to be effective. PMID:28765103

A review on interleukins: The key manipulators in rheumatoid arthritis.

PubMed

Sharma, Jatin; Bhar, Sutonuka; Devi, C Subathra

2017-09-01

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease associated with weakening of bones and joint pain. It primarily involves autoimmunity, matrix destruction, osteoclastogenesis, inflammation, and angiogenesis. Numerous cellular and humoral components of the immune system are involved in the etiology of diseases; however, the cardinal part is played by the inter-cellular signaling messengers called cytokines. Interleukins is a vaguely defined sub-class of cytokines that are abundantly found in the RA patients. The multifariousness and diversity in the function of the interleukins make them very likely to be associated with the pathogenesis in multiple ways. Nonetheless, the variety in opinions of researchers globally has led to contentious inferences. Ergo, in this review we have amalgamated the views of researchers from the past two decades till date to provide a comprehensive report about the role of interleukins in rheumatoid arthritis.

Diet-dependent gene expression in honey bees: honey vs. sucrose or high fructose corn syrup.

PubMed

Wheeler, Marsha M; Robinson, Gene E

2014-07-17

Severe declines in honey bee populations have made it imperative to understand key factors impacting honey bee health. Of major concern is nutrition, as malnutrition in honey bees is associated with immune system impairment and increased pesticide susceptibility. Beekeepers often feed high fructose corn syrup (HFCS) or sucrose after harvesting honey or during periods of nectar dearth. We report that, relative to honey, chronic feeding of either of these two alternative carbohydrate sources elicited hundreds of differences in gene expression in the fat body, a peripheral nutrient-sensing tissue analogous to vertebrate liver and adipose tissues. These expression differences included genes involved in protein metabolism and oxidation-reduction, including some involved in tyrosine and phenylalanine metabolism. Differences between HFCS and sucrose diets were much more subtle and included a few genes involved in carbohydrate and lipid metabolism. Our results suggest that bees receive nutritional components from honey that are not provided by alternative food sources widely used in apiculture.

Diet-dependent gene expression in honey bees: honey vs. sucrose or high fructose corn syrup

PubMed Central

Wheeler, Marsha M.; Robinson, Gene E.

2014-01-01

Severe declines in honey bee populations have made it imperative to understand key factors impacting honey bee health. Of major concern is nutrition, as malnutrition in honey bees is associated with immune system impairment and increased pesticide susceptibility. Beekeepers often feed high fructose corn syrup (HFCS) or sucrose after harvesting honey or during periods of nectar dearth. We report that, relative to honey, chronic feeding of either of these two alternative carbohydrate sources elicited hundreds of differences in gene expression in the fat body, a peripheral nutrient-sensing tissue analogous to vertebrate liver and adipose tissues. These expression differences included genes involved in protein metabolism and oxidation-reduction, including some involved in tyrosine and phenylalanine metabolism. Differences between HFCS and sucrose diets were much more subtle and included a few genes involved in carbohydrate and lipid metabolism. Our results suggest that bees receive nutritional components from honey that are not provided by alternative food sources widely used in apiculture. PMID:25034029

Antimetabolic Effects of Polyphenols in Breast Cancer Cells: Focus on Glucose Uptake and Metabolism.

PubMed

Keating, Elisa; Martel, Fátima

2018-01-01

In the last years, metabolic reprogramming became a new key hallmark of tumor cells. One of its components is a deviant energetic metabolism, known as Warburg effect-an aerobic lactatogenesis- characterized by elevated rates of glucose uptake and consumption with high-lactate production even in the presence of oxygen. Because many cancer cells display a greater sensitivity to glucose deprivation-induced cytotoxicity than normal cells, inhibitors of glucose cellular uptake (facilitative glucose transporter 1 inhibitors) and oxidative metabolism (glycolysis inhibitors) are potential therapeutic targets in cancer treatment. Polyphenols, abundantly contained in fruits and vegetables, are dietary components with an established protective role against cancer. Several molecular mechanisms are involved in the anticancer effect of polyphenols, including effects on apoptosis, cell cycle regulation, plasma membrane receptors, signaling pathways, and epigenetic mechanisms. Additionally, inhibition of glucose cellular uptake and metabolism in cancer cell lines has been described for several polyphenols, and this effect was shown to be associated with their anticarcinogenic effect. This work will review data showing an antimetabolic effect of polyphenols and its involvement in the chemopreventive/chemotherapeutic potential of these dietary compounds, in relation to breast cancer.

Creativity and executive function across manic, mixed and depressive episodes in bipolar I disorder.

PubMed

Soeiro-de-Souza, Márcio Gerhardt; Dias, Vasco Videira; Bio, Danielle Soares; Post, Robert M; Moreno, Ricardo A

2011-12-01

Creativity is a complex construct involving affective and cognitive components. Bipolar Disorder (BD) has been associated with creativity and is characterized by a wide range of affective and cognitive symptoms. Although studies of creativity in BD have tended to focus on creativity as a trait variable in medicated euthymic patients, it probably fluctuates during symptomatic states of BD. Since creativity is known to involve key affective and cognitive components, it is plausible to speculate that cognitive deficits and symptoms present in symptomatic BD could interfere with creativity. Sixty-seven BD type I patients medication free, age 18-35 years and experiencing a maniac, mixed, or depressive episodes, were assessed for creativity, executive functioning, and intelligence. Manic and mixed state patients had higher creativity scores than depressive individuals. Creativity was influenced by executive function measures only in manic patients. Intelligence did not influence creativity for any of the mood episode types. We propose that creativity in BD might be linked to the putative hyperdopaminergic state of mania and be dependent on intact executive function. Future studies should further explore the role of dopaminergic mechanisms in creativity in BD. Copyright © 2011 Elsevier B.V. All rights reserved.

UV fatigue investigations with non-destructive tools in silica

NASA Astrophysics Data System (ADS)

Natoli, Jean-Yves; Beaudier, Alexandre; Wagner, Frank R.

2017-08-01

A fatigue effect is often observed under multiple laser irradiations, overall in UV. This decrease of LIDT, is a critical parameter for laser sources with high repetition rates and with a need of long-term life, as in spatial applications at 355nm. A challenge is also to replace excimer lasers by solid laser sources, this challenge requires to improve drastically the lifetime of optical materials at 266nm. Main applications of these sources are devoted to material surface nanostructuration, spectroscopy and medical surgeries. In this work we focus on the understanding of the laser matter interaction at 266nm in silica in order to predict the lifetime of components and study parameters links to these lifetimes to give keys of improvement for material suppliers. In order to study the mechanism involved in the case of multiple irradiations, an interesting approach is to involve the evolution of fluorescence, in order to observe the first stages of material changes just before breakdown. We will show that it is sometime possible to estimate the lifetime of component only with the fluorescence measurement, saving time and materials. Moreover, the data from the diagnostics give relevant informations to highlight "defects" induced by multiple laser irradiations.

Strategies for manipulation of oxygen utilization by the electron transfer chain in microbes for metabolic engineering purposes.

PubMed

Bennett, George N; San, Ka-Yiu

2017-05-01

Microaerobic growth is of importance in ecological niches, pathogenic infections and industrial production of chemicals. The use of low levels of oxygen enables the cell to gain energy and grow more robustly in the presence of a carbon source that can be oxidized and provide electrons to the respiratory chain in the membrane. A considerable amount of information is available on the genes and proteins involved in respiratory growth and the regulation of genes involved in aerobic and anaerobic metabolism. The dependence of regulation on sensing systems that respond to reduced quinones (e.g. ArcB) or oxygen levels that affect labile redox components of transcription regulators (Fnr) are key in understanding the regulation. Manipulation of the amount of respiration can be difficult to control in dense cultures or inadequately mixed reactors leading to inhomogeneous cultures that may have lower than optimal performance. Efforts to control respiration through genetic means have been reported and address mutations affecting components of the electron transport chain. In a recent report completion for intermediates of the ubiquinone biosynthetic pathway was used to dial the level of respiration vs lactate formation in an aerobically grown E. coli culture.

Modelling and scale-up of chemical flooding: Second annual report for the period October 1986--September 1987

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

Pope, G.A.; Lake, L.W.; Sepehrnoori, K.

1988-11-01

The objective of this research is to develop, validate, and apply a comprehensive chemical flooding simulator for chemical recovery processes involving surfactants, polymers, and alkaline chemicals in various combinations. This integrated program includes components of laboratory experiments, physical property modelling, scale-up theory, and numerical analysis as necessary and integral components of the simulation activity. Developing, testing and applying flooding simulator (UTCHEM) to a wide variety of laboratory and reservoir problems involving tracers, polymers, polymer gels, surfactants, and alkaline agent has been continued. Improvements in both the physical-chemical and numerical aspects of UTCHEM have been made which enhance its versatility, accuracymore » and speed. Supporting experimental studies during the past year include relative permeability and trapping of microemulsion, tracer flow studies oil recovery in cores using alcohol free surfactant slugs, and microemulsion viscosity measurements. These have enabled model improvement simulator testing. Another code called PROPACK has also been developed which is used as a preprocessor for UTCHEM. Specifically, it is used to evaluate input to UTCHEM by computing and plotting key physical properties such as phase behavior interfacial tension.« less

Around and beyond 53BP1 Nuclear Bodies.

PubMed

Fernandez-Vidal, Anne; Vignard, Julien; Mirey, Gladys

2017-12-05

Within the nucleus, sub-nuclear domains define territories where specific functions occur. Nuclear bodies (NBs) are dynamic structures that concentrate nuclear factors and that can be observed microscopically. Recently, NBs containing the p53 binding protein 1 (53BP1), a key component of the DNA damage response, were defined. Interestingly, 53BP1 NBs are visualized during G1 phase, in daughter cells, while DNA damage was generated in mother cells and not properly processed. Unlike most NBs involved in transcriptional processes, replication has proven to be key for 53BP1 NBs, with replication stress leading to the formation of these large chromatin domains in daughter cells. In this review, we expose the composition and organization of 53BP1 NBs and focus on recent findings regarding their regulation and dynamics. We then concentrate on the importance of the replication stress, examine the relation of 53BP1 NBs with DNA damage and discuss their dysfunction.

Exploring safety systems for dispensing in community pharmacies: focusing on how staff relate to organizational components.

PubMed

Harvey, Jasmine; Avery, Anthony J; Ashcroft, Darren; Boyd, Matthew; Phipps, Denham L; Barber, Nicholas

2015-01-01

Identifying risk is an important facet of a safety practice in an organization. To identify risk, all components within a system of operation should be considered. In clinical safety practice, a team of people, technologies, procedures and protocols, management structure and environment have been identified as key components in a system of operation. To explore risks in relation to prescription dispensing in community pharmacies by taking into account relationships between key components that relate to the dispensing process. Fifteen community pharmacies in England with varied characteristics were identified, and data were collected using non-participant observations, shadowing and interviews. Approximately 360 hours of observations and 38 interviews were conducted by the team. Observation field notes from each pharmacy were written into case studies. Overall, 52,500 words from 15 case studies and interview transcripts were analyzed using thematic and line-by-line analyses. Validation techniques included multiple data collectors co-authoring each case study for consensus, review of case studies by members of the wider team including academic and practicing community pharmacists, and patient safety experts and two presentations (internally and externally) to review and discuss findings. Risks identified were related to relationships between people and other key components in dispensing. This included how different levels of staff communicated internally and externally, followed procedures, interacted with technical systems, worked with management, and engaged with the environment. In a dispensing journey, the following categories were identified which show how risks are inextricably linked through relationships between human components and other key components: 1) dispensing with divided attention; 2) dispensing under pressure; 3) dispensing in a restricted space or environment; and, 4) managing external influences. To identify and evaluate risks effectively, an approach that includes understanding relationships between key components in dispensing is required. Since teams of people in community pharmacies are a key dispensing component, and therefore part of the operational process, it is important to note how they relate to other components in the environment within which they operate. Pharmacies can take the opportunity to reflect on the organization of their systems and review in particular how they can improve on the four key categories identified. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Evolving Systems: An Outcome of Fondest Hopes and Wildest Dreams

NASA Technical Reports Server (NTRS)

Frost, Susan A.; Balas, Mark J.

2012-01-01

New theory is presented for evolving systems, which are autonomously controlled subsystems that self-assemble into a new evolved system with a higher purpose. Evolving systems of aerospace structures often require additional control when assembling to maintain stability during the entire evolution process. This is the concept of Adaptive Key Component Control that operates through one specific component to maintain stability during the evolution. In addition, this control must often overcome persistent disturbances that occur while the evolution is in progress. Theoretical results will be presented for Adaptive Key Component control for persistent disturbance rejection. An illustrative example will demonstrate the Adaptive Key Component controller on a system composed of rigid body and flexible body modes.

Exploring the role of community engagement in improving the health of disadvantaged populations: a systematic review

PubMed Central

Cyril, Sheila; Smith, Ben J.; Possamai-Inesedy, Alphia; Renzaho, Andre M. N.

2015-01-01

Background Although community engagement (CE) is widely used in health promotion, components of CE models associated with improved health are poorly understood. This study aimed to examine the magnitude of the impact of CE on health and health inequalities among disadvantaged populations, which methodological approaches maximise the effectiveness of CE, and components of CE that are acceptable, feasible, and effective when used among disadvantaged populations. Design The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We carried out methodological assessments of the included studies using rating scales. The analysis focussed on model synthesis to identify the key CE components linked to positive study outcomes and comparative analysis between positive study outcomes, processes, and quality indicators of CE. Results Out of 24 studies that met our inclusion criteria, 21 (87.5%) had positively impacted health behaviours, public health planning, health service access, health literacy, and a range of health outcomes. More than half of the studies (58%) were of good quality, whereas 71% and 42% of studies showed good community involvement in research and achieved high levels of CE, respectively. Key CE components that affected health outcomes included real power-sharing, collaborative partnerships, bidirectional learning, incorporating the voice and agency of beneficiary communities in research protocol, and using bicultural health workers for intervention delivery. Conclusions The findings suggest that CE models can lead to improved health and health behaviours among disadvantaged populations if designed properly and implemented through effective community consultation and participation. We also found several gaps in the current measurement of CE in health intervention studies, which suggests the importance of developing innovative approaches to measure CE impact on health outcomes in a more rigorous way. PMID:26689460

The pink gene encodes the Drosophila orthologue of the human Hermansky-Pudlak syndrome 5 (HPS5) gene.

PubMed

Syrzycka, Monika; McEachern, Lori A; Kinneard, Jennifer; Prabhu, Kristel; Fitzpatrick, Kathleen; Schulze, Sandra; Rawls, John M; Lloyd, Vett K; Sinclair, Donald A R; Honda, Barry M

2007-06-01

Hermansky-Pudlak syndrome (HPS) consists of a set of human autosomal recessive disorders, with symptoms resulting from defects in genes required for protein trafficking in lysosome-related organelles such as melanosomes and platelet dense granules. A number of human HPS genes and rodent orthologues have been identified whose protein products are key components of 1 of 4 different protein complexes (AP-3 or BLOC-1, -2, and -3) that are key participants in the process. Drosophila melanogaster has been a key model organism in demonstrating the in vivo significance of many genes involved in protein trafficking pathways; for example, mutations in the "granule group" genes lead to changes in eye colour arising from improper protein trafficking to pigment granules in the developing eye. An examination of the chromosomal positioning of Drosophila HPS gene orthologues suggested that CG9770, the Drosophila HPS5 orthologue, might correspond to the pink locus. Here we confirm this gene assignment, making pink the first eye colour gene in flies to be identified as a BLOC complex gene.

Validating emotional attention regulation as a component of emotional intelligence: A Stroop approach to individual differences in tuning in to and out of nonverbal cues.

PubMed

Elfenbein, Hillary Anger; Jang, Daisung; Sharma, Sudeep; Sanchez-Burks, Jeffrey

2017-03-01

Emotional intelligence (EI) has captivated researchers and the public alike, but it has been challenging to establish its components as objective abilities. Self-report scales lack divergent validity from personality traits, and few ability tests have objectively correct answers. We adapt the Stroop task to introduce a new facet of EI called emotional attention regulation (EAR), which involves focusing emotion-related attention for the sake of information processing rather than for the sake of regulating one's own internal state. EAR includes 2 distinct components. First, tuning in to nonverbal cues involves identifying nonverbal cues while ignoring alternate content, that is, emotion recognition under conditions of distraction by competing stimuli. Second, tuning out of nonverbal cues involves ignoring nonverbal cues while identifying alternate content, that is, the ability to interrupt emotion recognition when needed to focus attention elsewhere. An auditory test of valence included positive and negative words spoken in positive and negative vocal tones. A visual test of approach-avoidance included green- and red-colored facial expressions depicting happiness and anger. The error rates for incongruent trials met the key criteria for establishing the validity of an EI test, in that the measure demonstrated test-retest reliability, convergent validity with other EI measures, divergent validity from factors such as general processing speed and mostly personality, and predictive validity in this case for well-being. By demonstrating that facets of EI can be validly theorized and empirically assessed, results also speak to the validity of EI more generally. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

CSN5/JAB1 Interacts with the Centromeric Components CENP-T and CENP-W and Regulates Their Proteasome-mediated Degradation*

PubMed Central

Chun, Younghwa; Lee, Miae; Park, Byoungwoo; Lee, Soojin

2013-01-01

The CENP-T·CENP-W complex is a recently identified inner centromere component that plays crucial roles in the formation of a functional kinetochore involved in cell division during mitosis. Using yeast two-hybrid screening, we identified an interaction between CENP-T and CSN5, the fifth component of the COP9 signalosome and a key modulator of the cell cycle and cancer. Co-immunoprecipitation revealed that CSN5 directly interacts with both CENP-T and CENP-W. Ectopically expressed CSN5 promoted the ubiquitin- and proteasome-dependent degradation of CENP-T·CENP-W. The formation of a CENP-T·CENP-W complex greatly enhanced the stabilities of the respective proteins, possibly by blocking CSN5-mediated degradation. Furthermore, dysregulation of CSN5 induced severe defects in the recruitment of CENP-T·CENP-W to the kinetochore during the prophase stage of mitosis. Thus, our results indicate that CSN5 regulates the stability of the inner kinetochore components CENP-T and CENP-W, providing the first direct link between CSN5 and the mitotic apparatus, highlighting the role of CSN5 as a multifunctional cell cycle regulator. PMID:23926101

Deciphering the molecular mechanisms underlying sea urchin reversible adhesion: A quantitative proteomics approach.

PubMed

Lebesgue, Nicolas; da Costa, Gonçalo; Ribeiro, Raquel Mesquita; Ribeiro-Silva, Cristina; Martins, Gabriel G; Matranga, Valeria; Scholten, Arjen; Cordeiro, Carlos; Heck, Albert J R; Santos, Romana

2016-04-14

Marine bioadhesives have unmatched performances in wet environments, being an inspiration for biomedical applications. In sea urchins specialized adhesive organs, tube feet, mediate reversible adhesion, being composed by a disc, producing adhesive and de-adhesive secretions, and a motile stem. After tube foot detachment, the secreted adhesive remains bound to the substratum as a footprint. Sea urchin adhesive is composed by proteins and sugars, but so far only one protein, Nectin, was shown to be over-expressed as a transcript in tube feet discs, suggesting its involvement in sea urchin adhesion. Here we use high-resolution quantitative mass-spectrometry to perform the first study combining the analysis of the differential proteome of an adhesive organ, with the proteome of its secreted adhesive. This strategy allowed us to identify 163 highly over-expressed disc proteins, specifically involved in sea urchin reversible adhesion; to find that 70% of the secreted adhesive components fall within five protein groups, involved in exocytosis and microbial protection; and to provide evidences that Nectin is not only highly expressed in tube feet discs but is an actual component of the adhesive. These results give an unprecedented insight into the molecular mechanisms underlying sea urchin adhesion, and opening new doors to develop wet-reliable, reversible, and ecological biomimetic adhesives. Sea urchins attach strongly but in a reversible manner to substratum, being a valuable source of inspiration for industrial and biomedical applications. Yet, the molecular mechanisms governing reversible adhesion are still poorly studied delaying the engineering of biomimetic adhesives. We used the latest mass spectrometry techniques to analyze the differential proteome of an adhesive organ and the proteome of its secreted adhesive, allowing us to uncover the key players in sea urchin reversible adhesion. We demonstrate, that Nectin, a protein previously pointed out as potentially involved in sea urchin adhesion, is not only highly expressed in tube feet discs, but is a genuine component of the secreted adhesive. Copyright © 2016 Elsevier B.V. All rights reserved.

Interoceptive Awareness Skills for Emotion Regulation: Theory and Approach of Mindful Awareness in Body-Oriented Therapy (MABT).

PubMed

Price, Cynthia J; Hooven, Carole

2018-01-01

Emotion regulation involves a coherent relationship with the self, specifically effective communication between body, mind, and feelings. Effective emotion regulation involves the ability to accurately detect and evaluate cues related to physiological reactions to stressful events, accompanied by appropriate regulation strategies that temper and influence the emotional response. There is compelling evidence demonstrating links between poor or disrupted awareness of sensory information, or interoceptive awareness, and difficulties with emotion regulation. This paper presents a framework, based on psychological and neurobiological research, for understanding how interoceptive awareness facilitates regulation and an integrated sense of self, and thus contributes to health and well-being. A mind-body therapeutic approach called mindful awareness in body-oriented therapy (MABT), uniquely designed to teach fundamental skills of interoceptive awareness, is described. MABT develops the distinct interoceptive awareness capacities of identifying, accessing, and appraising internal bodily signals that are identified in physiological models as the critical components of interoception for emotion regulation. The explanatory model is that the development of these key interoceptive capacities improves sensory (physical and emotional) awareness, reduces distress, and improves regulation. Strategies for teaching and learning interoceptive awareness are not well-developed in mindfulness or psychotherapeutic approaches, particularly important for people who may have difficulty attending to interoceptive awareness due to stress, chronic pain or trauma. To address this issue, MABT provides an individualized protocol for scaffolding interoceptive awareness through a combination of psychoeducation and somatic approaches explicitly addressing difficulties with interoceptive processing. Clinical vignettes are included to provide exemplars of this approach and to highlight key components of the therapeutic process. Results from research are also included to highlight the acceptability, safety, health outcomes, and possible mechanisms underlying the MABT approach.

Sphingolipids from the human fungal pathogen Aspergillus fumigatus.

PubMed

Fontaine, Thierry

2017-10-01

Sphingolipids (SPLs) are key components of the plasma membrane in yeast and filamentous fungi. These molecules are involved in a number of cellular processes, and particularly, SGLs are essential components of the highly polarized fungal growth where they are required for the formation of the polarisome organization at the hyphal apex. Aspergillus fumigatus, a human fungal pathogen, produce SGLs that are discriminated into neutral cerebrosides, glycosylinositolphosphoceramides (GIPCs) and glycosylphosphatidylinositol (GPI) anchors. In addition to complex hydrophilic head groups of GIPCs, A. fumigatus is, to date, the sole fungus that produces a GPI-anchored polysaccharide. These SPLs follow three different biosynthetic pathways. Genetics blockage leading to the inhibition of any SPL biosynthesis or to the alteration of the structure of SPL induces growth and virulence defects. The complete lipid moiety of SPLs is essential for the lipid microdomain organization and their biosynthetic pathways are potential antifungal targets but remains understudied. Copyright © 2017. Published by Elsevier B.V.

Links between the police response and women's psychological outcomes following intimate partner violence.

PubMed

Srinivas, Tejaswinhi; DePrince, Anne P

2015-01-01

Virtually no research considers the psychological impact of institutional support for survivors of intimate partner violence (IPV). This study sought to fill this gap by examining associations between one component of institutional support--the police response--and posttraumatic stress disorder (PTSD) symptom severity and posttrauma appraisals (i.e., anger, fear, and self-blame) in a diverse sample of female IPV survivors (N = 236). Results indicated that a more negative police response, as operationalized by women's unmet expectations in relation to the police, was significantly associated with greater PTSD symptom severity in a very conservative test that involved controlling for personal resources and social support. Police response was not significantly associated with the tested posttrauma appraisals. Implications for policy and practice will be discussed. This study advances understanding of the psychological impact of the police response--one key component of institutional support.

Wind Turbine Contingency Control Through Generator De-Rating

NASA Technical Reports Server (NTRS)

Frost, Susan; Goebel, Kai; Balas, Mark

2013-01-01

Maximizing turbine up-time and reducing maintenance costs are key technology drivers for wind turbine operators. Components within wind turbines are subject to considerable stresses due to unpredictable environmental conditions resulting from rapidly changing local dynamics. In that context, systems health management has the aim to assess the state-of-health of components within a wind turbine, to estimate remaining life, and to aid in autonomous decision-making to minimize damage to the turbine. Advanced contingency control is one way to enable autonomous decision-making by providing the mechanism to enable safe and efficient turbine operation. The work reported herein explores the integration of condition monitoring of wind turbines with contingency control to balance the trade-offs between maintaining system health and energy capture. The contingency control involves de-rating the generator operating point to achieve reduced loads on the wind turbine. Results are demonstrated using a high fidelity simulator of a utility-scale wind turbine.

The role of proton shuttling mechanisms in solvent-free and catalyst-free acetalization reactions of imines.

PubMed

Lillo, Victor J; Mansilla, Javier; Saá, José M

2018-06-06

Proton transfer is central to the understanding of chemical processes. More so in addition reactions of the type NuH + E → Nu-EH taking place under solvent-free and catalyst-free conditions. Herein we show that the addition of alcohols or amines (the NuH component) to imine derivatives (the E component), in 1 : 1 ratio, under solvent-free and catalyst-free conditions, are efficient methods to access N,O and N,N-acetal derivatives. In addition, computational studies reveal that they are catalyzed reactions involving two or even three NuH molecules operating in a cooperative manner as H-bonded NuH(NuH)nNuH associates (many body effects) in the transition state through a concerted proton shuttling mechanism (addition of alcohols) or stepwise proton shuttling mechanism (addition of amines), thereby facilitating the key proton transfer step.

Physiology of ageing of the musculoskeletal system.

PubMed

Boros, Katalin; Freemont, Tony

2017-04-01

This review aims to provide a summary of current concepts of ageing in relation to the musculoskeletal system, highlighting recent advances in the understanding of the mechanisms involved in the development of age-related changes in bone, skeletal muscle, chondroid and fibrous tissues. The key components of the musculoskeletal system and their functions are introduced together with a general overview of the molecular hallmarks of ageing. A brief description of the normal architecture of each of these tissue types is followed by a summary of established and developing concepts of mechanisms contributing to the age-related alterations in each. Extensive detailed description of these changes is beyond the scope of this review; instead, we aim to highlight some of the most significant processes and, where possible, the molecular changes underlying these and refer the reader to in-depth, subspecialist reviews of the individual components for further details. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Supportive supervision and constructive relationships with healthcare workers support CHW performance: Use of a qualitative framework to evaluate CHW programming in Uganda.

PubMed

Ludwick, Teralynn; Turyakira, Eleanor; Kyomuhangi, Teddy; Manalili, Kimberly; Robinson, Sheila; Brenner, Jennifer L

2018-02-13

While evidence supports community health worker (CHW) capacity to improve maternal and newborn health in less-resourced countries, key implementation gaps remain. Tools for assessing CHW performance and evidence on what programmatic components affect performance are lacking. This study developed and tested a qualitative evaluative framework and tool to assess CHW team performance in a district program in rural Uganda. A new assessment framework was developed to collect and analyze qualitative evidence based on CHW perspectives on seven program components associated with effectiveness (selection; training; community embeddedness; peer support; supportive supervision; relationship with other healthcare workers; retention and incentive structures). Focus groups were conducted with four high/medium-performing CHW teams and four low-performing CHW teams selected through random, stratified sampling. Content analysis involved organizing focus group transcripts according to the seven program effectiveness components, and assigning scores to each component per focus group. Four components, 'supportive supervision', 'good relationships with other healthcare workers', 'peer support', and 'retention and incentive structures' received the lowest overall scores. Variances in scores between 'high'/'medium'- and 'low'-performing CHW teams were largest for 'supportive supervision' and 'good relationships with other healthcare workers.' Our analysis suggests that in the Bushenyi intervention context, CHW team performance is highly correlated with the quality of supervision and relationships with other healthcare workers. CHWs identified key performance-related issues of absentee supervisors, referral system challenges, and lack of engagement/respect by health workers. Other less-correlated program components warrant further study and may have been impacted by relatively consistent program implementation within our limited study area. Applying process-oriented measurement tools are needed to better understand CHW performance-related factors and build a supportive environment for CHW program effectiveness and sustainability. Findings from a qualitative, multi-component tool developed and applied in this study suggest that factors related to (1) supportive supervision and (2) relationships with other healthcare workers may be strongly associated with variances in performance outcomes within a program. Careful consideration of supervisory structure and health worker orientation during program implementation are among strategies proposed to increase CHW performance.

Mouse Models for Unraveling the Importance of Diet in Colon Cancer Prevention

PubMed Central

Tammariello, Alexandra E.; Milner, John A.

2010-01-01

Diet and genetics are both considered important risk determinants for colorectal cancer, a leading cause of death worldwide. Several genetically engineered mouse models have been created, including the ApcMin mouse, to aid in the identification of key cancer related processes and to assist with the characterization of environmental factors, including the diet, which influence risk. Current research using these models provides evidence that several bioactive food components can inhibit genetically predisposed colorectal cancer, while others increase risk. Specifically, calorie restriction or increased exposure to n-3 fatty acids, sulforaphane, chafuroside, curcumin, and dibenzoylmethane were reported protective. Total fat, calories and all-trans retinoic acid are associated with an increased risk. Unraveling the importance of specific dietary components in these models is complicated by the basal diet used, the quantity of test components provided, and interactions among food components. Newer models are increasingly available to evaluate fundamental cellular processes, including DNA mismatch repair, immune function and inflammation as markers for colon cancer risk. Unfortunately, these models have been used infrequently to examine the influence of specific dietary components. The enhanced use of these models can shed mechanistic insights about the involvement of specific bioactive food and components and energy as determinants of colon cancer risk. However, the use of available mouse models to exactly represent processes important to human gastrointestinal cancers will remain a continued scientific challenge. PMID:20122631

Profiling Taste and Aroma Compound Metabolism during Apricot Fruit Development and Ripening

PubMed Central

Xi, Wanpeng; Zheng, Huiwen; Zhang, Qiuyun; Li, Wenhui

2016-01-01

Sugars, organic acids and volatiles of apricot were determined by HPLC and GC-MS during fruit development and ripening, and the key taste and aroma components were identified by integrating flavor compound contents with consumers’ evaluation. Sucrose and glucose were the major sugars in apricot fruit. The contents of all sugars increased rapidly, and the accumulation pattern of sugars converted from glucose-predominated to sucrose-predominated during fruit development and ripening. Sucrose synthase (SS), sorbitol oxidase (SO) and sorbitol dehydrogenase (SDH) are under tight developmental control and they might play important roles in sugar accumulation. Almost all organic acids identified increased during early development and then decrease rapidly. During early development, fruit mainly accumulated quinate and malate, with the increase of citrate after maturation, and quinate, malate and citrate were the predominant organic acids at the ripening stage. The odor activity values (OAV) of aroma volatiles showed that 18 aroma compounds were the characteristic components of apricot fruit. Aldehydes and terpenes decreased significantly during the whole development period, whereas lactones and apocarotenoids significantly increased with fruit ripening. The partial least squares regression (PLSR) results revealed that β-ionone, γ-decalactone, sucrose and citrate are the key characteristic flavor factors contributing to consumer acceptance. Carotenoid cleavage dioxygenases (CCD) may be involved in β-ionone formation in apricot fruit. PMID:27347931

Neural foundations to moral reasoning and antisocial behavior

PubMed Central

Yang, Yaling

2006-01-01

A common feature of the antisocial, rule-breaking behavior that is central to criminal, violent and psychopathic individuals is the failure to follow moral guidelines. This review summarizes key findings from brain imaging research on both antisocial behavior and moral reasoning, and integrates these findings into a neural moral model of antisocial behavior. Key areas found to be functionally or structurally impaired in antisocial populations include dorsal and ventral regions of the prefrontal cortex (PFC), amygdala, hippocampus, angular gyrus, anterior cingulate and temporal cortex. Regions most commonly activated in moral judgment tasks consist of the polar/medial and ventral PFC, amygdala, angular gyrus and posterior cingulate. It is hypothesized that the rule-breaking behavior common to antisocial, violent and psychopathic individuals is in part due to impairments in some of the structures (dorsal and ventral PFC, amygdala and angular gyrus) subserving moral cognition and emotion. Impairments to the emotional component that comprises the feeling of what is moral is viewed as the primary deficit in antisocials, although some disruption to the cognitive and cognitive-emotional components of morality (particularly self-referential thinking and emotion regulation) cannot be ruled out. While this neurobiological predisposition is likely only one of several biosocial processes involved in the etiology of antisocial behavior, it raises significant moral issues for the legal system and neuroethics. PMID:18985107

WE-E-217A-02: Methodologies for Evaluation of Standalone CAD System Performance.

PubMed

Sahiner, B

2012-06-01

Standalone performance evaluation of a CAD system provides information about the abnormality detection or classification performance of the computerized system alone. Although the performance of the reader with CAD is the final step in CAD system assessment, standalone performance evaluation is an important component for several reasons: First, standalone evaluation informs the reader about the performance level of the CAD system and may have an impact on how the reader uses the system. Second, it provides essential information to the system designer for algorithm optimization during system development. Third, standalone evaluation can provide a detailed description of algorithm performance (e.g., on subgroups of the population) because a larger data set with more samples from different subgroups can be included in standalone studies compared to reader studies. Proper standalone evaluation of a CAD system involves a number of key components, some of which are shared with the assessment of reader performance with CAD. These include (1) selection of a test data set that allows performance assessment with little or no bias and acceptable uncertainty; (2) a reference standard that indicates disease status as well as the location and extent of disease; (3) a clearly defined method for labeling each CAD mark as a true-positive or false-positive; and (4) a properly selected set of metrics to summarize the accuracy of the computer marks and their corresponding scores. In this lecture, we will discuss various approaches for the key components of standalone CAD performance evaluation listed above, and present some of the recommendations and opinions from the AAPM CAD subcommittee on these issues. Learning Objectives 1. Identify basic components and metrics in the assessment of standalone CAD systems 2. Understand how each component may affect the assessed performance 3. Learn about AAPM CAD subcommittee's opinions and recommendations on factors and metrics related to the evaluation of standalone CAD system performance. © 2012 American Association of Physicists in Medicine.

When 1+1 can be >2: Uncertainties compound when simulating climate, fisheries and marine ecosystems

NASA Astrophysics Data System (ADS)

Evans, Karen; Brown, Jaclyn N.; Sen Gupta, Alex; Nicol, Simon J.; Hoyle, Simon; Matear, Richard; Arrizabalaga, Haritz

2015-03-01

Multi-disciplinary approaches that combine oceanographic, biogeochemical, ecosystem, fisheries population and socio-economic models are vital tools for modelling whole ecosystems. Interpreting the outputs from such complex models requires an appreciation of the many different types of modelling frameworks being used and their associated limitations and uncertainties. Both users and developers of particular model components will often have little involvement or understanding of other components within such modelling frameworks. Failure to recognise limitations and uncertainties associated with components and how these uncertainties might propagate throughout modelling frameworks can potentially result in poor advice for resource management. Unfortunately, many of the current integrative frameworks do not propagate the uncertainties of their constituent parts. In this review, we outline the major components of a generic whole of ecosystem modelling framework incorporating the external pressures of climate and fishing. We discuss the limitations and uncertainties associated with each component of such a modelling system, along with key research gaps. Major uncertainties in modelling frameworks are broadly categorised into those associated with (i) deficient knowledge in the interactions of climate and ocean dynamics with marine organisms and ecosystems; (ii) lack of observations to assess and advance modelling efforts and (iii) an inability to predict with confidence natural ecosystem variability and longer term changes as a result of external drivers (e.g. greenhouse gases, fishing effort) and the consequences for marine ecosystems. As a result of these uncertainties and intrinsic differences in the structure and parameterisation of models, users are faced with considerable challenges associated with making appropriate choices on which models to use. We suggest research directions required to address these uncertainties, and caution against overconfident predictions. Understanding the full impact of uncertainty makes it clear that full comprehension and robust certainty about the systems themselves are not feasible. A key research direction is the development of management systems that are robust to this unavoidable uncertainty.

A network analysis of the Chinese medicine Lianhua-Qingwen formula to identify its main effective components.

PubMed

Wang, Chun-Hua; Zhong, Yi; Zhang, Yan; Liu, Jin-Ping; Wang, Yue-Fei; Jia, Wei-Na; Wang, Guo-Cai; Li, Zheng; Zhu, Yan; Gao, Xiu-Mei

2016-02-01

Chinese medicine is known to treat complex diseases with multiple components and multiple targets. However, the main effective components and their related key targets and functions remain to be identified. Herein, a network analysis method was developed to identify the main effective components and key targets of a Chinese medicine, Lianhua-Qingwen Formula (LQF). The LQF is commonly used for the prevention and treatment of viral influenza in China. It is composed of 11 herbs, gypsum and menthol with 61 compounds being identified in our previous work. In this paper, these 61 candidate compounds were used to find their related targets and construct the predicted-target (PT) network. An influenza-related protein-protein interaction (PPI) network was constructed and integrated with the PT network. Then the compound-effective target (CET) network and compound-ineffective target network (CIT) were extracted, respectively. A novel approach was developed to identify effective components by comparing CET and CIT networks. As a result, 15 main effective components were identified along with 61 corresponding targets. 7 of these main effective components were further experimentally validated to have antivirus efficacy in vitro. The main effective component-target (MECT) network was further constructed with main effective components and their key targets. Gene Ontology (GO) analysis of the MECT network predicted key functions such as NO production being modulated by the LQF. Interestingly, five effective components were experimentally tested and exhibited inhibitory effects on NO production in the LPS induced RAW 264.7 cell. In summary, we have developed a novel approach to identify the main effective components in a Chinese medicine LQF and experimentally validated some of the predictions.

Cycling operation of fossil plants

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

Bhatnagar, U.S.; Weiss, M.D.; White, W.H.

1991-05-01

This report presents a methodology for examining the economic feasibility of converting fossil power plants from baseload to cycling service. It employs this approach to examine a proposed change of Pepco's Potomac River units 3, 4, and 5 from baseload operation of two-shift cycling. The project team first reviewed all components and listed potential cycling effects involved in the conversion of Potomac River units 3, 4, and 5. They developed general cycling plant screening criteria including the number of hot, warm, or cold restart per year and desired load ramp rates. In addition, they evaluated specific limitations on the boiler,more » turbine, and the balance of plant. They estimated the remaining life of the facility through component evaluation and boiler testing and also identified and prioritized potential component deficiencies by their impact on key operational factors: safety, heat rate, turn down, startup/shutdown time, and plant availability. They developed solutions to these problems; and, since many solutions mitigate more than one problem, they combined and reprioritized these synergistic solutions. Economic assessments were performed on all solutions. 13 figs., 20 tabs.« less

Targeting and assembly of components of the TOC protein import complex at the chloroplast outer envelope membrane

PubMed Central

Richardson, Lynn G. L.; Paila, Yamuna D.; Siman, Steven R.; Chen, Yi; Smith, Matthew D.; Schnell, Danny J.

2014-01-01

The translocon at the outer envelope membrane of chloroplasts (TOC) initiates the import of thousands of nuclear encoded preproteins required for chloroplast biogenesis and function. The multimeric TOC complex contains two GTP-regulated receptors, Toc34 and Toc159, which recognize the transit peptides of preproteins and initiate protein import through a β–barrel membrane channel, Toc75. Different isoforms of Toc34 and Toc159 assemble with Toc75 to form structurally and functionally diverse translocons, and the composition and levels of TOC translocons is required for the import of specific subsets of coordinately expressed proteins during plant growth and development. Consequently, the proper assembly of the TOC complexes is key to ensuring organelle homeostasis. This review will focus on our current knowledge of the targeting and assembly of TOC components to form functional translocons at the outer membrane. Our analyses reveal that the targeting of TOC components involves elements common to the targeting of other outer membrane proteins, but also include unique features that appear to have evolved to specifically facilitate assembly of the import apparatus. PMID:24966864

Targeting and assembly of components of the TOC protein import complex at the chloroplast outer envelope membrane.

PubMed

Richardson, Lynn G L; Paila, Yamuna D; Siman, Steven R; Chen, Yi; Smith, Matthew D; Schnell, Danny J

2014-01-01

The translocon at the outer envelope membrane of chloroplasts (TOC) initiates the import of thousands of nuclear encoded preproteins required for chloroplast biogenesis and function. The multimeric TOC complex contains two GTP-regulated receptors, Toc34 and Toc159, which recognize the transit peptides of preproteins and initiate protein import through a β-barrel membrane channel, Toc75. Different isoforms of Toc34 and Toc159 assemble with Toc75 to form structurally and functionally diverse translocons, and the composition and levels of TOC translocons is required for the import of specific subsets of coordinately expressed proteins during plant growth and development. Consequently, the proper assembly of the TOC complexes is key to ensuring organelle homeostasis. This review will focus on our current knowledge of the targeting and assembly of TOC components to form functional translocons at the outer membrane. Our analyses reveal that the targeting of TOC components involves elements common to the targeting of other outer membrane proteins, but also include unique features that appear to have evolved to specifically facilitate assembly of the import apparatus.

Eosinophils Regulate Interferon Alpha Production in Plasmacytoid Dendritic Cells Stimulated with Components of Neutrophil Extracellular Traps.

PubMed

Skrzeczynska-Moncznik, Joanna; Zabieglo, Katarzyna; Bossowski, Jozef P; Osiecka, Oktawia; Wlodarczyk, Agnieszka; Kapinska-Mrowiecka, Monika; Kwitniewski, Mateusz; Majewski, Pawel; Dubin, Adam; Cichy, Joanna

2017-03-01

Eosinophils constitute an important component of helminth immunity and are not only associated with various allergies but are also linked to autoinflammatory disorders, including the skin disease psoriasis. Here we demonstrate the functional relationship between eosinophils and plasmacytoid dendritic cells (pDCs) as related to skin diseases. We previously showed that pDCs colocalize with neutrophil extracellular traps (NETs) in psoriatic skin. Here we demonstrate that eosinophils are found in psoriatic skin near neutrophils and NETs, suggesting that pDC responses can be regulated by eosinophils. Eosinophils inhibited pDC function in vitro through a mechanism that did not involve cell contact but depended on soluble factors. In pDCs stimulated by specific NET components, eosinophil-conditioned media attenuated the production of interferon α (IFNα) but did not affect the maturation of pDCs as evidenced by the unaltered expression of the costimulatory molecules CD80 and CD86. As pDCs and IFNα play a key role in autoimmune skin inflammation, these data suggest that eosinophils may influence autoinflammatory responses through their impact on the production of IFNα by pDCs.

Plasma facing components: a conceptual design strategy for the first wall in FAST tokamak

NASA Astrophysics Data System (ADS)

Labate, C.; Di Gironimo, G.; Renno, F.

2015-09-01

Satellite tokamaks are conceived with the main purpose of developing new or alternative ITER- and DEMO-relevant technologies, able to contribute in resolving the pending issues about plasma operation. In particular, a high criticality needs to be associated to the design of plasma facing components, i.e. first wall (FW) and divertor, due to physical, topological and thermo-structural reasons. In such a context, the design of the FW in FAST fusion plant, whose operational range is close to ITER’s one, takes place. According to the mission of experimental satellites, the FW design strategy, which is presented in this paper relies on a series of innovative design choices and proposals with a particular attention to the typical key points of plasma facing components design. Such an approach, taking into account a series of involved physical constraints and functional requirements to be fulfilled, marks a clear borderline with the FW solution adopted in ITER, in terms of basic ideas, manufacturing aspects, remote maintenance procedure, manifolds management, cooling cycle and support system configuration.

The plant cell nucleus: a true arena for the fight between plants and pathogens.

PubMed

Deslandes, Laurent; Rivas, Susana

2011-01-01

Communication between the cytoplasm and the nucleus is a fundamental feature shared by both plant and animal cells. Cellular factors involved in the transport of macromolecules through the nuclear envelope, including nucleoporins, importins and Ran-GTP related components, are conserved among a variety of eukaryotic systems. Interestingly, mutations in these nuclear components compromise resistance signalling, illustrating the importance of nucleocytoplasmic trafficking in plant innate immunity. Indeed, spatial restriction of defence regulators by the nuclear envelope and stimulus-induced nuclear translocation constitute an important level of defence-associated gene regulation in plants. A significant number of effectors from different microbial pathogens are targeted to the plant cell nucleus. In addition, key host factors, including resistance proteins, immunity components, transcription factors and transcriptional regulators shuttle between the cytoplasm and the nucleus, and their level of nuclear accumulation determines the output of the defence response, further confirming the crucial role played by the nucleus during the interaction between plants and pathogens. Here, we discuss recent findings that situate the nucleus at the frontline of the mutual recognition between plants and invading microbes.

Key Components in eHealth Interventions Combining Self-Tracking and Persuasive eCoaching to Promote a Healthier Lifestyle: A Scoping Review.

PubMed

Lentferink, Aniek J; Oldenhuis, Hilbrand Ke; de Groot, Martijn; Polstra, Louis; Velthuijsen, Hugo; van Gemert-Pijnen, Julia Ewc

2017-08-01

The combination of self-tracking and persuasive eCoaching in automated interventions is a new and promising approach for healthy lifestyle management. The aim of this study was to identify key components of self-tracking and persuasive eCoaching in automated healthy lifestyle interventions that contribute to their effectiveness on health outcomes, usability, and adherence. A secondary aim was to identify the way in which these key components should be designed to contribute to improved health outcomes, usability, and adherence. The scoping review methodology proposed by Arskey and O'Malley was applied. Scopus, EMBASE, PsycINFO, and PubMed were searched for publications dated from January 1, 2013 to January 31, 2016 that included (1) self-tracking, (2) persuasive eCoaching, and (3) healthy lifestyle intervention. The search resulted in 32 publications, 17 of which provided results regarding the effect on health outcomes, 27 of which provided results regarding usability, and 13 of which provided results regarding adherence. Among the 32 publications, 27 described an intervention. The most commonly applied persuasive eCoaching components in the described interventions were personalization (n=24), suggestion (n=19), goal-setting (n=17), simulation (n=17), and reminders (n=15). As for self-tracking components, most interventions utilized an accelerometer to measure steps (n=11). Furthermore, the medium through which the user could access the intervention was usually a mobile phone (n=10). The following key components and their specific design seem to influence both health outcomes and usability in a positive way: reduction by setting short-term goals to eventually reach long-term goals, personalization of goals, praise messages, reminders to input self-tracking data into the technology, use of validity-tested devices, integration of self-tracking and persuasive eCoaching, and provision of face-to-face instructions during implementation. In addition, health outcomes or usability were not negatively affected when more effort was requested from participants to input data into the technology. The data extracted from the included publications provided limited ability to identify key components for adherence. However, one key component was identified for both usability and adherence, namely the provision of personalized content. This scoping review provides a first overview of the key components in automated healthy lifestyle interventions combining self-tracking and persuasive eCoaching that can be utilized during the development of such interventions. Future studies should focus on the identification of key components for effects on adherence, as adherence is a prerequisite for an intervention to be effective. ©Aniek J Lentferink, Hilbrand KE Oldenhuis, Martijn de Groot, Louis Polstra, Hugo Velthuijsen, Julia EWC van Gemert-Pijnen. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 01.08.2017.

Evolutionary analysis and lateral gene transfer of two-component regulatory systems associated with heavy-metal tolerance in bacteria.

PubMed

Bouzat, Juan L; Hoostal, Matthew J

2013-05-01

Microorganisms have adapted intricate signal transduction mechanisms to coordinate tolerance to toxic levels of metals, including two-component regulatory systems (TCRS). In particular, both cop and czc operons are regulated by TCRS; the cop operon plays a key role in bacterial tolerance to copper, whereas the czc operon is involved in the efflux of cadmium, zinc, and cobalt from the cell. Although the molecular physiology of heavy metal tolerance genes has been extensively studied, their evolutionary relationships are not well-understood. Phylogenetic relationships among heavy-metal efflux proteins and their corresponding two-component regulatory proteins revealed orthologous and paralogous relationships from species divergences and ancient gene duplications. The presence of heavy metal tolerance genes on bacterial plasmids suggests these genes may be prone to spread through horizontal gene transfer. Phylogenetic inferences revealed nine potential examples of lateral gene transfer associated with metal efflux proteins and two examples for regulatory proteins. Notably, four of the examples suggest lateral transfer across major evolutionary domains. In most cases, differences in GC content in metal tolerance genes and their corresponding host genomes confirmed lateral gene transfer events. Three-dimensional protein structures predicted for the response regulators encoded by cop and czc operons showed a high degree of structural similarity with other known proteins involved in TCRS signal transduction, which suggests common evolutionary origins of functional phenotypes and similar mechanisms of action for these response regulators.

Health risk behaviors and depressive symptoms among Hispanic adolescents: Examining acculturation discrepancies and family functioning.

PubMed

Cano, Miguel Ángel; Schwartz, Seth J; Castillo, Linda G; Unger, Jennifer B; Huang, Shi; Zamboanga, Byron L; Romero, Andrea J; Lorenzo-Blanco, Elma I; Córdova, David; Des Rosiers, Sabrina E; Lizzi, Karina M; Baezconde-Garbanati, Lourdes; Soto, Daniel W; Villamar, Juan Andres; Pattarroyo, Monica; Szapocznik, José

2016-03-01

Drawing from a theory of bicultural family functioning 2 models were tested to examine the longitudinal effects of acculturation-related variables on adolescent health risk behaviors and depressive symptoms (HRB/DS) mediated by caregiver and adolescent reports of family functioning. One model examined the effects of caregiver-adolescent acculturation discrepancies in relation to family functioning and HRB/DS. A second model examined the individual effects of caregiver and adolescent acculturation components in relation to family functioning and HRB/DS. A sample of 302 recently immigrated Hispanic caregiver-child dyads completed measures of Hispanic and U.S. cultural practices, values, and identities at baseline (predictors); measures of family cohesion, family communications, and family involvement 6 months postbaseline (mediators); and only adolescents completed measures of smoking, binge drinking, inconsistent condom use, and depressive symptoms 1 year postbaseline (outcomes). Measures of family cohesion, family communications, and family involvement were used to conduct a confirmatory factor analysis to estimate the fit of a latent construct for family functioning. Key findings indicate that (a) adolescent acculturation components drove the effect of caregiver-adolescent acculturation discrepancies in relation to family functioning; (b) higher levels of adolescent family functioning were associated with less HRB/DS, whereas higher levels of caregiver family functioning were associated with more adolescent HRB/DS; (c) and only adolescent reports of family functioning mediated the effects of acculturation components and caregiver-adolescent acculturation discrepancies on HRB/DS. (c) 2016 APA, all rights reserved).

Health Risk Behaviors and Depressive Symptoms among Hispanic Adolescents: Examining Acculturation Discrepancies and Family Functioning

PubMed Central

Cano, Miguel Ángel; Schwartz, Seth J.; Castillo, Linda G.; Unger, Jennifer B.; Huang, Shi; Zamboanga, Byron L.; Romero, Andrea J.; Lorenzo-Blanco, Elma I.; Córdova, David; Des Rosiers, Sabrina E.; Lizzi, Karina M.; Baezconde-Garbanati, Lourdes; Soto, Daniel W.; Villamar, Juan Andres; Pattarroyo, Monica; Szapocznik, José

2015-01-01

Drawing from a theory of bicultural family functioning two models were tested to examine the longitudinal effects of acculturation-related variables on adolescent health risk behaviors and depressive symptoms (HRB/DS) mediated by caregiver and adolescent reports of family functioning. One model examined the effects of caregiver-adolescent acculturation discrepancies in relation to family functioning and HRB/DS. A second model examined the individual effects of caregiver and adolescent acculturation components in relation to family functioning and HRB/DS. A sample of 302 recently immigrated Hispanic caregiver-child dyads completed measures of Hispanic and U.S. cultural practices, values, and identities at baseline (predictors); measures of family cohesion, family communications, and family involvement six months post-baseline (mediators); and only adolescents completed measures of smoking, binge drinking, inconsistent condom use, and depressive symptoms one year post-baseline (outcomes). Measures of family cohesion, family communications, and family involvement were used to conduct a confirmatory factor analysis to estimate the fit of a latent construct for family functioning. Key findings indicate that (a) adolescent acculturation components drove the effect of caregiver-adolescent acculturation discrepancies in relation to family functioning, (b) higher levels of adolescent family functioning were associated with less HRB/DS, whereas higher levels of caregiver family functioning were associated with more adolescent HRB/DS, (c) and only adolescent reports of family functioning mediated the effects of acculturation components and caregiver-adolescent acculturation discrepancies on HRB/DS. PMID:26301514

Pathophysiogenesis of Mesial Temporal Lobe Epilepsy: Is Prevention of Damage Antiepileptogenic?

PubMed Central

Curia, G.; Lucchi, C.; Vinet, J.; Gualtieri, F.; Marinelli, C.; Torsello, A.; Costantino, L.; Biagini*,, G.

2014-01-01

Temporal lobe epilepsy (TLE) is frequently associated with hippocampal sclerosis, possibly caused by a primary brain injury that occurred a long time before the appearance of neurological symptoms. This type of epilepsy is characterized by refractoriness to drug treatment, so to require surgical resection of mesial temporal regions involved in seizure onset. Even this last therapeutic approach may fail in giving relief to patients. Although prevention of hippocampal damage and epileptogenesis after a primary event could be a key innovative approach to TLE, the lack of clear data on the pathophysiological mechanisms leading to TLE does not allow any rational therapy. Here we address the current knowledge on mechanisms supposed to be involved in epileptogenesis, as well as on the possible innovative treatments that may lead to a preventive approach. Besides loss of principal neurons and of specific interneurons, network rearrangement caused by axonal sprouting and neurogenesis are well known phenomena that are integrated by changes in receptor and channel functioning and modifications in other cellular components. In particular, a growing body of evidence from the study of animal models suggests that disruption of vascular and astrocytic components of the blood-brain barrier takes place in injured brain regions such as the hippocampus and piriform cortex. These events may be counteracted by drugs able to prevent damage to the vascular component, as in the case of the growth hormone secretagogue ghrelin and its analogues. A thoroughly investigation on these new pharmacological tools may lead to design effective preventive therapies. PMID:24251566

WRKY Transcription Factors: Key Components in Abscisic Acid Signaling

DTIC Science & Technology

2011-01-01

Review article WRKY transcription factors : key components in abscisic acid signalling Deena L. Rushton1, Prateek Tripathi1, Roel C. Rabara1, Jun Lin1...May 2011. *Correspondence (Tel +605 688 5749; fax +605 688 5624; email paul.rushton@sdstate.edu) Keywords: abscisic acid, WRKY transcription factor ...seed germination, drought, abiotic stress. Summary WRKY transcription factors (TFs) are key regulators of many plant processes, including the responses

Intracellular pH in sperm physiology.

PubMed

Nishigaki, Takuya; José, Omar; González-Cota, Ana Laura; Romero, Francisco; Treviño, Claudia L; Darszon, Alberto

2014-08-01

Intracellular pH (pHi) regulation is essential for cell function. Notably, several unique sperm ion transporters and enzymes whose elimination causes infertility are either pHi dependent or somehow related to pHi regulation. Amongst them are: CatSper, a Ca(2+) channel; Slo3, a K(+) channel; the sperm-specific Na(+)/H(+) exchanger and the soluble adenylyl cyclase. It is thus clear that pHi regulation is of the utmost importance for sperm physiology. This review briefly summarizes the key components involved in pHi regulation, their characteristics and participation in fundamental sperm functions such as motility, maturation and the acrosome reaction. Copyright © 2014 Elsevier Inc. All rights reserved.

[Interactions of food and drug metabolism].

PubMed

Delzenne, N M; Verbeeck, R K

2001-01-01

The nutritional state, and/or the ingestion of specific nutrients, is/are able to modify drug disposition, by interfering with drug absorption, distribution, storage, and metabolism. Recent data report that nutrients interfere with drug metabolism either by modifying key enzymes of phase I (cytochromeP450 dependent mixed function oxidase) and II (glucuronosyl, sulfonyl- ... transferases), or by modulating coenzymes availability (NADPH, UDPglucuronic acid...). Food components involved in drug metabolism modifications are either macro-nutrients (carbohydrates, lipids, proteins, ethanol), micronutriments (vitamins, minerals), or phytochemicals. Drug-nutrients interactions may be beneficials, and thus could constitute, i.e. a way to improve drug therapeutic index, or generate adverse effects.

Anticancer Activity of Curcumin and Its Analogues: Preclinical and Clinical Studies.

PubMed

Allegra, Alessandro; Innao, Vanessa; Russo, Sabina; Gerace, Demetrio; Alonci, Andrea; Musolino, Caterina

2017-01-02

Curcumin has been shown to have a wide variety of therapeutic effects, ranging from anti-inflammatory, chemopreventive, anti-proliferative, and anti-metastatic. This review provides an overview of the recent research conducted to overcome the problems with the bioavailability of curcumin, and of the preclinical and clinical studies that have reported success in combinatorial strategies coupling curcumin with other treatments. Research on the signaling pathways that curcumin treatment targets shows that it potently acts on major intracellular components involved in key processes such as genomic modulations, cell invasion and cell death pathways. Curcumin is a promising molecule for the prevention and treatment of cancer.

DNS and Embedded DNS as Tools for Investigating Unsteady Heat Transfer Phenomena in Turbines

NASA Technical Reports Server (NTRS)

vonTerzi, Dominic; Bauer, H.-J.

2010-01-01

DNS is a powerful tool with high potential for investigating unsteady heat transfer and fluid flow phenomena, in particular for cases involving transition to turbulence and/or large coherent structures. - DNS of idealized configurations related to turbomachinery components is already possible. - For more realistic configurations and the inclusion of more effects, reduction of computational cost is key issue (e.g., hybrid methods). - Approach pursued here: Embedded DNS ( segregated coupling of DNS with LES and/or RANS). - Embedded DNS is an enabling technology for many studies. - Pre-transitional heat transfer and trailing-edge cutback film-cooling are good candidates for (embedded) DNS studies.

Role of Intermediate Filaments in Vesicular Traffic.

PubMed

Margiotta, Azzurra; Bucci, Cecilia

2016-04-25

Intermediate filaments are an important component of the cellular cytoskeleton. The first established role attributed to intermediate filaments was the mechanical support to cells. However, it is now clear that intermediate filaments have many different roles affecting a variety of other biological functions, such as the organization of microtubules and microfilaments, the regulation of nuclear structure and activity, the control of cell cycle and the regulation of signal transduction pathways. Furthermore, a number of intermediate filament proteins have been involved in the acquisition of tumorigenic properties. Over the last years, a strong involvement of intermediate filament proteins in the regulation of several aspects of intracellular trafficking has strongly emerged. Here, we review the functions of intermediate filaments proteins focusing mainly on the recent knowledge gained from the discovery that intermediate filaments associate with key proteins of the vesicular membrane transport machinery. In particular, we analyze the current understanding of the contribution of intermediate filaments to the endocytic pathway.

Aquaporins and plant transpiration.

PubMed

Maurel, Christophe; Verdoucq, Lionel; Rodrigues, Olivier

2016-11-01

Although transpiration and aquaporins have long been identified as two key components influencing plant water status, it is only recently that their relations have been investigated in detail. The present review first examines the various facets of aquaporin function in stomatal guard cells and shows that it involves transport of water but also of other molecules such as carbon dioxide and hydrogen peroxide. At the whole plant level, changes in tissue hydraulics mediated by root and shoot aquaporins can indirectly impact plant transpiration. Recent studies also point to a feedback effect of transpiration on aquaporin function. These mechanisms may contribute to the difference between isohydric and anisohydric stomatal regulation of leaf water status. The contribution of aquaporins to transpiration control goes far beyond the issue of water transport during stomatal movements and involves emerging cellular and long-distance signalling mechanisms which ultimately act on plant growth. © 2016 John Wiley & Sons Ltd.

Changes of the nucleolus architecture in absence of the nuclear factor CTCF.

PubMed

Hernández-Hernández, A; Soto-Reyes, E; Ortiz, R; Arriaga-Canon, C; Echeverría-Martinez, O M; Vázquez-Nin, G H; Recillas-Targa, F

2012-01-01

CTCF is a multifunctional nuclear factor involved in many cellular processes like gene regulation, chromatin insulation and genomic organization. Recently, CTCF has been shown to be involved in the transcriptional regulation of ribosomal genes and nucleolar organization in Drosophila cells and different murine cell types, including embryonic stem cells. Moreover, it has been suggested that CTCF could be associated to the nucleolus of human erythroleukemic K562 cells. In the present work, we took advantage of efficient small hairpin RNA interference against human CTCF to analyze nucleolar organization in HeLa cells. We have found that key components of the nucleolar architecture are altered. As a consequence of such alterations, an upregulation of ribosomal gene transcription was observed. We propose that CTCF contributes to the structural organization of the nucleolus and, through epigenetic mechanisms, to the regulation of the ribosomal gene expression. Copyright © 2012 S. Karger AG, Basel.

Mechanism and Substrate Recognition of Human Holo ACP Synthase

PubMed Central

Bunkoczi, Gabor; Pasta, Saloni; Joshi, Anil; Wu, Xiaoqiu; Kavanagh, Kathryn L.; Smith, Stuart; Oppermann, Udo

2007-01-01

Summary Mammals utilize a single phosphopantetheinyl transferase for the posttranslational modification of at least three different apoproteins: the carrier protein components of cytosolic and mitochondrial fatty acid synthases and the aminoadipate semialdehyde reductase involved in lysine degradation. We determined the crystal structure of the human phosphopantetheinyl transferase, a eukaryotic phosphopantetheinyl transferase characterized, complexed with CoA and Mg2+, and in ternary complex with CoA and ACP. The involvement of key residues in ligand binding and catalysis was confirmed by mutagenesis and kinetic analysis. Human phosphopantetheinyl transferase exhibits an α/β fold and 2-fold pseudosymmetry similar to the Sfp phosphopantetheinyl transferase from Bacillus subtilis. Although the bound ACP exhibits a typical four-helix structure, its binding is unusual in that it is facilitated predominantly by hydrophobic interactions. A detailed mechanism is proposed describing the substrate binding and catalytic process. PMID:18022563

Identification of the main venom protein components of Aphidius ervi, a parasitoid wasp of the aphid model Acyrthosiphon pisum.

PubMed

Colinet, Dominique; Anselme, Caroline; Deleury, Emeline; Mancini, Donato; Poulain, Julie; Azéma-Dossat, Carole; Belghazi, Maya; Tares, Sophie; Pennacchio, Francesco; Poirié, Marylène; Gatti, Jean-Luc

2014-05-06

Endoparasitoid wasps are important natural enemies of the widely distributed aphid pests and are mainly used as biological control agents. However, despite the increased interest on aphid interaction networks, only sparse information is available on the factors used by parasitoids to modulate the aphid physiology. Our aim was here to identify the major protein components of the venom injected at oviposition by Aphidius ervi to ensure successful development in its aphid host, Acyrthosiphon pisum. A combined large-scale transcriptomic and proteomic approach allowed us to identify 16 putative venom proteins among which three γ-glutamyl transpeptidases (γ-GTs) were by far the most abundant. Two of the γ-GTs most likely correspond to alleles of the same gene, with one of these alleles previously described as involved in host castration. The third γ-GT was only distantly related to the others and may not be functional owing to the presence of mutations in the active site. Among the other abundant proteins in the venom, several were unique to A. ervi such as the molecular chaperone endoplasmin possibly involved in protecting proteins during their secretion and transport in the host. Abundant transcripts encoding three secreted cystein-rich toxin-like peptides whose function remains to be explored were also identified. Our data further support the role of γ-GTs as key players in A. ervi success on aphid hosts. However, they also evidence that this wasp venom is a complex fluid that contains diverse, more or less specific, protein components. Their characterization will undoubtedly help deciphering parasitoid-aphid and parasitoid-aphid-symbiont interactions. Finally, this study also shed light on the quick evolution of venom components through processes such as duplication and convergent recruitment of virulence factors between unrelated organisms.

Does the context of reinforcement affect resistance to change?

PubMed

Nevin, J A; Grace, R C

1999-04-01

Eight pigeons were trained on multiple schedules of reinforcement where pairs of components alternated in blocks on different keys to define 2 local contexts. On 1 key, components arranged 160 and 40 reinforcers/hr; on the other, components arranged 40 and 10 reinforcers/hr. Response rates in the 40/hr component were higher in the latter pair. Within pairs, resistance to prefeeding and resistance to extinction were generally greater in the richer component. The two 40/hr components did not differ in resistance to prefeeding, but the 40/hr component that alternated with 10/hr was more resistant to extinction. This discrepancy was interpreted by an algebraic model relating response strength to component reinforcer rate, including generalization decrement. According to this model, strength is independent of context, consistent with research on schedule preference.

Notes from the field: the economic value chain in disease management organizations.

PubMed

Fetterolf, Donald

2006-12-01

The disease management (DM) "value chain" is composed of a linear series of steps that include operational milestones in the development of knowledge, each stage evolving from the preceding one. As an adaptation of Michael Porter's "value chain" model, the process flow in DM moves along the following path: (1) data/information technology, (2) information generation, (3) analysis, (4) assessment/recommendations, (5) actionable customer plan, and (6) program assessment/reassessment. Each of these stages is managed as a major line of product operations within a DM company or health plan. Metrics around each of the key production variables create benchmark milestones, ongoing management insight into program effectiveness, and potential drivers for activity-based cost accounting pricing models. The value chain process must remain robust from early entry of data and information into the system, through the final presentation and recommendations for our clients if the program is to be effective. For individuals involved in the evaluation or review of DM programs, this framework is an excellent method to visualize the key components and sequence in the process. The value chain model is an excellent way to establish the value of a formal DM program and to create a consultancy relationship with a client involved in purchasing these complex services.

Cardiac-specific overexpression of catalase prevents diabetes-induced pathological changes by inhibiting NF-κB signaling activation in the heart.

PubMed

Cong, Weitao; Ruan, Dandan; Xuan, Yuanhu; Niu, Chao; Tao, Youli; Wang, Yang; Zhan, Kungao; Cai, Lu; Jin, Litai; Tan, Yi

2015-12-01

Catalase is an antioxidant enzyme that specifically catabolizes hydrogen peroxide (H2O2). Overexpression of catalase via a heart-specific promoter (CAT-TG) was reported to reduce diabetes-induced accumulation of reactive oxygen species (ROS) and further prevent diabetes-induced pathological abnormalities, including cardiac structural derangement and left ventricular abnormity in mice. However, the mechanism by which catalase overexpression protects heart function remains unclear. This study found that activation of a ROS-dependent NF-κB signaling pathway was downregulated in hearts of diabetic mice overexpressing catalase. In addition, catalase overexpression inhibited the significant increase in nitration levels of key enzymes involved in energy metabolism, including α-oxoglutarate dehydrogenase E1 component (α-KGD) and ATP synthase α and β subunits (ATP-α and ATP-β). To assess the effects of the NF-κB pathway activation on heart function, Bay11-7082, an inhibitor of the NF-κB signaling pathway, was injected into diabetic mice, protecting mice against the development of cardiac damage and increased nitrative modifications of key enzymes involved in energy metabolism. In conclusion, these findings demonstrated that catalase protects mouse hearts against diabetic cardiomyopathy, partially by suppressing NF-κB-dependent inflammatory responses and associated protein nitration. Copyright © 2015 Elsevier Ltd. All rights reserved.

Macrophages under pressure: the role of macrophage polarization in hypertension.

PubMed

Harwani, Sailesh C

2018-01-01

Hypertension is a multifactorial disease involving the nervous, renal, and cardiovascular systems. Macrophages are the most abundant and ubiquitous immune cells, placing them in a unique position to serve as key mediators between these components. The polarization of macrophages confers vast phenotypic and functional plasticity, allowing them to act as proinflammatory, homeostatic, and anti-inflammatory agents. Key differences between the M1 and M2 phenotypes, the 2 subsets at the extremes of this polarization spectrum, place macrophages at a juncture to mediate many mechanisms involved in the pathogenesis of hypertension. Neuronal and non-neuronal regulation of the immune system, that is, the "neuroimmuno" axis, plays an integral role in the polarization of macrophages. In hypertension, the neuroimmuno axis results in synchronization of macrophage mobilization from immune cell reservoirs and their chemotaxis, via increased expression of chemoattractants, to end organs critical in the development of hypertension. This complicated system is largely coordinated by the dichotomous actions of the autonomic neuronal and non-neuronal activation of cholinergic, adrenergic, and neurohormonal receptors on macrophages, leading to their ability to "switch" between phenotypes at sites of active inflammation. Data from experimental models and human studies are in concordance with each other and support a central role for macrophage polarization in the pathogenesis of hypertension. Copyright © 2017 Elsevier Inc. All rights reserved.

The clinical role of lecturers in nursing in Ireland: perceptions from key stakeholder groups in nurse education on the role.

PubMed

Meskell, Pauline; Murphy, Kathleen; Shaw, David

2009-10-01

The clinical role of lecturers in nursing has been a focus of debate since the integration of nurse education into higher education institutions. The purpose of this paper is to report the findings from the preliminary phase of a study, undertaken to investigate the perceptions of key stakeholder groups in nurse education, regarding the current clinical role of nurse lecturers in Ireland. A descriptive exploratory design was used involving focus group and individual interviews, soliciting views of purposefully selected educationalists, clinicians, policy formulators and students. The issue was examined from a policy perspective, aiming to collectively represent views of all participant groups. This approach facilitated a more complete picture of perceptions of the role to emerge, to better inform future decision making. Twenty two focus group interviews and twenty one individual interviews were conducted. Content analysis was used to identify themes. All groups were in agreement that role definition was urgently required to dispel ambiguities surrounding what the clinical role should involve. Conflicting views were evident among groups regarding lecturers' clinical credibility, visibility and teaching effectiveness. Findings highlight the essential nature of nurse lecturers engaging with clinical areas to maintain their skills, demonstrate a value for the practice component of the role and provide a link between education and practice.

Patient-Centered Imaging: Shared Decision Making for Cardiac Imaging Procedures with Exposure to Ionizing Radiation

PubMed Central

Einstein, Andrew J.; Berman, Daniel S.; Min, James K.; Hendel, Robert C.; Gerber, Thomas C.; Carr, J. Jeffrey; Cerqueira, Manuel D.; Cullom, S. James; DeKemp, Robert; Dickert, Neal; Dorbala, Sharmila; Garcia, Ernest V.; Gibbons, Raymond J.; Halliburton, Sandra S.; Hausleiter, Jörg; Heller, Gary V.; Jerome, Scott; Lesser, John R.; Fazel, Reza; Raff, Gilbert L.; Tilkemeier, Peter; Williams, Kim A.; Shaw, Leslee J.

2014-01-01

Objective To identify key components of a radiation accountability framework fostering patient-centered imaging and shared decision-making in cardiac imaging. Background An NIH-NHLBI/NCI-sponsored symposium was held in November 2012 to address these issues. Methods Symposium participants, working in three tracks, identified key components of a framework to target critical radiation safety issues for the patient, the laboratory, and the larger population of patients with known or suspected cardiovascular disease. Results Use of ionizing radiation during an imaging procedure should be disclosed to all patients by the ordering provider at the time of ordering, and reinforced by the performing provider team. An imaging protocol with effective dose ≤3mSv is considered very low risk, not warranting extensive discussion or written consent. However, a protocol effective dose <20mSv was proposed as a level requiring particular attention in terms of shared decision-making and either formal discussion or written informed consent. Laboratory reporting of radiation dosimetry is a critical component of creating a quality laboratory fostering a patient-centered environment with transparent procedural methodology. Efforts should be directed to avoiding testing involving radiation, in patients with inappropriate indications. Standardized reporting and diagnostic reference levels for computed tomography and nuclear cardiology are important for the goal of public reporting of laboratory radiation dose levels in conjunction with diagnostic performance. Conclusions The development of cardiac imaging technologies revolutionized cardiology practice by allowing routine, noninvasive assessment of myocardial perfusion and anatomy. It is now incumbent upon the imaging community to create an accountability framework to safely drive appropriate imaging utilization. PMID:24530677

Localization and Functionality of the Inflammasome in Neutrophils*

PubMed Central

Bakele, Martina; Joos, Melanie; Burdi, Sofia; Allgaier, Nicolas; Pöschel, Simone; Fehrenbacher, Birgit; Schaller, Martin; Marcos, Veronica; Kümmerle-Deschner, Jasmin; Rieber, Nikolaus; Borregaard, Niels; Yazdi, Amir; Hector, Andreas; Hartl, Dominik

2014-01-01

Neutrophils represent the major fraction of circulating immune cells and are rapidly recruited to sites of infection and inflammation. The inflammasome is a multiprotein complex that regulates the generation of IL-1 family proteins. The precise subcellular localization and functionality of the inflammasome in human neutrophils are poorly defined. Here we demonstrate that highly purified human neutrophils express key components of the NOD-like receptor family, pyrin domain containing 3 (NLRP3), and absent in melanoma 2 (AIM2) inflammasomes, particularly apoptosis-associated speck-like protein containing a CARD (ASC), AIM2, and caspase-1. Subcellular fractionation and microscopic analyses further showed that inflammasome components were localized in the cytoplasm and also noncanonically in secretory vesicle and tertiary granule compartments. Whereas IL-1β and IL-18 were expressed at the mRNA level and released as protein, highly purified neutrophils neither expressed nor released IL-1α at baseline or upon stimulation. Upon inflammasome activation, highly purified neutrophils released substantially lower levels of IL-1β protein compared with partially purified neutrophils. Serine proteases and caspases were differentially involved in IL-1β release, depending on the stimulus. Spontaneous activation of the NLRP3 inflammasome in neutrophils in vivo affected IL-1β, but not IL-18 release. In summary, these studies show that human neutrophils express key components of the inflammasome machinery in distinct intracellular compartments and release IL-1β and IL-18, but not IL-1α or IL-33 protein. Targeting the neutrophil inflammasome may represent a future therapeutic strategy to modulate neutrophilic inflammatory diseases, such as cystic fibrosis, rheumatoid arthritis, or sepsis. PMID:24398679

Physical exercise increases involvement of motor networks as a compensatory mechanism during a cognitively challenging task.

PubMed

Ji, Lanxin; Pearlson, Godfrey D; Zhang, Xue; Steffens, David C; Ji, Xiaoqing; Guo, Hua; Wang, Lihong

2018-05-31

Neuroimaging studies suggest that older adults may compensate for declines in cognitive function through neural compensation and reorganization of neural resources. While neural compensation as a key component of cognitive reserve is an important factor that mediates cognitive decline, the field lacks a quantitative measure of neural compensatory ability, and little is known about factors that may modify compensation, such as physical exercise. Twenty-five healthy older adults participated in a 6-week dance training exercise program. Gait speed, cognitive function, and functional magnetic resonance imaging during a challenging memory task were measured before and after the exercise program. In this study, we used a newly proposed data-driven independent component analysis approach to measure neural compensatory ability and tested the effect of physical exercise on neural compensation through a longitudinal study. After the exercise program, participants showed significantly improved memory performance in Logical Memory Test (WMS(LM)) (P < .001) and Rey Auditory Verbal Learning Test (P = .001) and increased gait speed measured by the 6-minute walking test (P = .01). Among all identified neural networks, only the motor cortices and cerebellum showed greater involvement during the memory task after exercise. Importantly, subjects who activated the motor network only after exercise (but not before exercise) showed WMS(LM) increases. We conclude that physical exercise improved gait speed, cognitive function, and compensatory ability through increased involvement of motor-related networks. Copyright © 2018 John Wiley & Sons, Ltd.

In situ analysis of Bacillus licheniformis biofilms: amyloid-like polymers and eDNA are involved in the adherence and aggregation of the extracellular matrix.

PubMed

Randrianjatovo-Gbalou, I; Rouquette, P; Lefebvre, D; Girbal-Neuhauser, E; Marcato-Romain, C-E

2017-05-01

This study attempts to determine which of the exopolymeric substances are involved in the adherence and aggregation of a Bacillus licheniformis biofilm. The involvement of extracellular proteins and eDNA were particularly investigated using DNase and proteinase K treatment. The permeability of the biofilms increased fivefold after DNase I treatment. The quantification of the matrix components showed that, irrespective to the enzyme tested, eDNA and amyloid-like polymers were removed simultaneously. Size-exclusion chromatography analyses supported these observations and revealed the presence of associated nucleic acid and protein complexes in the biofilm lysates. These data suggest that some extracellular DNA and amyloid-like proteins were closely interlaced within the matrix. Finally, confocal laser scanning microscopy imaging gave supplementary clues about the 3D organization of the biofilms, confirming that eDNA and exoproteins were essentially layered under and around the bacterial cells, whereas the amyloid-like fractions were homogeneously distributed within the matrix. These results confirm that some DNA-amyloid complexes play a key role in the modulation of the mechanical resistance of B. licheniformis biofilms. The study highlights the need to consider the whole structure of biofilms and to target the interactions between matrix components. A better understanding of B. licheniformis biofilm physiology and the structural organization of the matrix will strengthen strategies of biofilm control. © 2017 The Society for Applied Microbiology.

Thermoelectric-Driven Sustainable Sensing and Actuation Systems for Fault-Tolerant Nuclear Incidents

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

Longtin, Jon

2016-02-08

The Fukushima Daiichi nuclear incident in March 2011 represented an unprecedented stress test on the safety and backup systems of a nuclear power plant. The lack of reliable information from key components due to station blackout was a serious setback, leaving sensing, actuation, and reporting systems unable to communicate, and safety was compromised. Although there were several independent backup power sources for required safety function on site, ultimately the batteries were drained and the systems stopped working. If, however, key system components were instrumented with self-powered sensing and actuation packages that could report indefinitely on the status of the system,more » then critical system information could be obtained while providing core actuation and control during off-normal status for as long as needed. This research project focused on the development of such a self-powered sensing and actuation system. The electrical power is derived from intrinsic heat in the reactor components, which is both reliable and plentiful. The key concept was based around using thermoelectric generators that can be integrated directly onto key nuclear components, including pipes, pump housings, heat exchangers, reactor vessels, and shielding structures, as well as secondary-side components. Thermoelectric generators are solid-state devices capable of converting heat directly into electricity. They are commercially available technology. They are compact, have no moving parts, are silent, and have excellent reliability. The key components to the sensor package include a thermoelectric generator (TEG), microcontroller, signal processing, and a wireless radio package, environmental hardening to survive radiation, flooding, vibration, mechanical shock (explosions), corrosion, and excessive temperature. The energy harvested from the intrinsic heat of reactor components can be then made available to power sensors, provide bi-directional communication, recharge batteries for other safety systems, etc. Such an approach is intrinsically fault tolerant: in the event that system temperatures increase, the amount of available energy will increase, which will make more power available for applications. The system can also be used during normal conditions to provide enhanced monitoring of key system components.« less

Integrated agriculture programs to address malnutrition in northern Malawi.

PubMed

Kerr, Rachel Bezner; Chilanga, Emmanuel; Nyantakyi-Frimpong, Hanson; Luginaah, Isaac; Lupafya, Esther

2016-11-28

In countries where the majority of undernourished people are smallholder farmers, there has been interest in agricultural interventions to improve nutritional outcomes. Addressing gender inequality, however, is a key mechanism by which agriculture can improve nutrition, since women often play a crucial role in farming, food processing and child care, but have limited decision-making and control over agricultural resources. This study examines the approaches by which gender equity in agrarian, resource-poor settings can be improved using a case study in Malawi. A quasi-experimental design with qualitative methods was used to examine the effects of a participatory intervention on gender relations. Thirty married couple households in 19 villages with children under the age of 5 years were interviewed before and then after the intervention. An additional 7 interviews were conducted with key informants, and participant observation was carried out before, during the intervention and afterwards in the communities. The interviews were recorded and transcribed, and analysed qualitatively for key themes, concepts and contradictions. Several barriers were identified that undermine the quality of child care practices, many linked to gender constructions and norms. The dominant concepts of masculinity created shame and embarrassment if men deviated from these norms, by cooking or caring for their children. The study provided evidence that participatory education supported new masculinities through public performances that encouraged men to take on these new roles. Invoking men's family responsibilities, encouraging new social norms alongside providing new information about different healthy recipes were all pathways by which men developed new 'emergent' masculinities in which they were more involved in cooking and child care. The transformational approach, intergenerational and intra-gendered events, a focus on agriculture and food security, alongside involving male leaders were some of the reasons that respondents named for changed gender norms. Participatory education that explicitly addresses hegemonic masculinities related to child nutrition, such as women's roles in child care, can begin to change dominant gender norms. Involving male leaders, participatory methods and integrating agriculture and food security concerns with nutrition appear to be key components in the context of agrarian communities.

The development and evaluation of written medicines information for type 2 diabetes.

PubMed

Lee, D Y L; Armour, C; Krass, I

2007-12-01

Written Medicines Information (WMI) is regarded as a key component in diabetes consumer education. In Australia, there is a paucity of WMI that specifically tailors to the extensive array of medicines used for the lifelong management of Type 2 diabetes. This research project aimed to employ a novel framework, the 'Consumer Involvement Cycle', to investigate consumer perspectives and needs of medicines information for Type 2 diabetes and develop appropriate WMI for the Type 2 diabetes population. The Consumer Involvement Cycle involved people with Type 2 diabetes and health professionals (HPs) working in partnership to design a series of WMI, incorporating a range of consumer-conceived ideas and concepts with professional evaluation from an expert panel of reviewing HPs. A total of 12 leaflets were developed. The Flesch-Kincaid Grade Level Score for the leaflets was approximately 8.0, which is considered to be 'fairly easy', in other words easily understood by a large proportion of the general public. The Consumer Involvement Cycle was validated as a useful framework in developing and evaluating appropriate consumer information. Consumer perspectives should be sought and well incorporated throughout the process of designing and assessing educational materials intended for consumer use.

Cultural competency training in psychiatry.

PubMed

Qureshi, A; Collazos, F; Ramos, M; Casas, M

2008-01-01

Recent reports indicate that the quality of care provided to immigrant and ethnic minority patients is not at the same level as that provided to majority group patients. Although the European Board of Medical Specialists recognizes awareness of cultural issues as a core component of the psychiatry specialization, few medical schools provide training in cultural issues. Cultural competence represents a comprehensive response to the mental health care needs of immigrant and ethnic minority patients. Cultural competence training involves the development of knowledge, skills, and attitudes that can improve the effectiveness of psychiatric treatment. Cognitive cultural competence involves awareness of the various ways in which culture, immigration status, and race impact psychosocial development, psychopathology, and therapeutic transactions. Technical cultural competence involves the application of cognitive cultural competence, and requires proficiency in intercultural communication, the capacity to develop a therapeutic relationship with a culturally different patient, and the ability to adapt diagnosis and treatment in response to cultural difference. Perhaps the greatest challenge in cultural competence training involves the development of attitudinal competence inasmuch as it requires exploration of cultural and racial preconceptions. Although research is in its infancy, there are increasing indications that cultural competence can improve key aspects of the psychiatric treatment of immigrant and minority group patients.

Special Education Law: Illustrative Basics and Nuances of Key IDEA Components

ERIC Educational Resources Information Center

Zirkel, Perry A.

2015-01-01

Intended as professional development for both new and experienced special educators, this article provides both the basic requirements and nuanced issues for foundational, successive, and overlapping key components under the Individuals With Disabilities Education Act (IDEA): (a) child find, (b) eligibility, and (c) free appropriate public…

Childhood Immunization: A Key Component of Early Childhood Development

ERIC Educational Resources Information Center

Messonnier, Nancy

2017-01-01

Physical health is a key component of early childhood development and school readiness. By keeping children healthy and decreasing the chances of disease outbreaks, immunizations help early childhood programs create a safe environment for children. While overall vaccination rates are high nationally for most vaccines routinely recommended for…

A Connected History of Health and Education: Learning Together toward a Better City

ERIC Educational Resources Information Center

Howard, Joanne; Howard, Diane; Dotson, Ebbin

2015-01-01

The infrastructure, financial, and human resource histories of health and education are offered as key components of future strategic planning initiatives in learning cities, and 10 key components of strategic planning initiatives designed to enhance the health and wealth of citizens of learning cities are discussed.

Epigenetic Events in Liver Cancer Resulting From Alcoholic Liver Disease

PubMed Central

French, Samuel W.

2013-01-01

Epigenetic mechanisms play an extensive role in the development of liver cancer (i.e., hepatocellular carcinoma [HCC]) associated with alcoholic liver disease (ALD) as well as in liver disease associated with other conditions. For example, epigenetic mechanisms, such as changes in the methylation and/or acetylation pattern of certain DNA regions or of the histone proteins around which the DNA is wrapped, contribute to the reversion of normal liver cells into progenitor and stem cells that can develop into HCC. Chronic exposure to beverage alcohol (i.e., ethanol) can induce all of these epigenetic changes. Thus, ethanol metabolism results in the formation of compounds that can cause changes in DNA methylation and interfere with other components of the normal processes regulating DNA methylation. Alcohol exposure also can alter histone acetylation/deacetylation and methylation patterns through a variety of mechanisms and signaling pathways. Alcohol also acts indirectly on another molecule called toll-like receptor 4 (TLR4) that is a key component in a crucial regulatory pathway in the cells and whose dysregulation is involved in the development of HCC. Finally, alcohol use regulates an epigenetic mechanism involving small molecules called miRNAs that control transcriptional events and the expression of genes important to ALD. PMID:24313165

Profiling of proteins secreted in the bovine oviduct reveals diverse functions of this luminal microenvironment.

PubMed

Pillai, Viju Vijayan; Weber, Darren M; Phinney, Brett S; Selvaraj, Vimal

2017-01-01

The oviductal microenvironment is a site for key events that involve gamete maturation, fertilization and early embryo development. Secretions into the oviductal lumen by either the lining epithelium or by transudation of plasma constituents are known to contain elements conducive for reproductive success. Although previous studies have identified some of these factors involved in reproduction, knowledge of secreted proteins in the oviductal fluid remains rudimentary with limited definition of function even in extensively studied species like cattle. In this study, we used a shotgun proteomics approach followed by bioinformatics sequence prediction to identify secreted proteins present in the bovine oviductal fluid (ex vivo) and secretions from the bovine oviductal epithelial cells (in vitro). From a total of 2087 proteins identified, 266 proteins could be classified as secreted, 109 (41%) of which were common for both in vivo and in vitro conditions. Pathway analysis indicated different classes of proteins that included growth factors, metabolic regulators, immune modulators, enzymes, and extracellular matrix components. Functional analysis revealed mechanisms in the oviductal lumen linked to immune homeostasis, gamete maturation, fertilization and early embryo development. These results point to several novel components that work together with known elements mediating functional homeostasis, and highlight the diversity of machinery associated with oviductal physiology and early events in cattle fertility.

NAD(P)H quinone oxidoreductase 1 inhibits the proteasomal degradation of homocysteine-induced endoplasmic reticulum protein

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

Maeda, Tomoji, E-mail: t-maeda@nichiyaku.ac.jp; Tanabe-Fujimura, Chiaki; Fujita, Yu

2016-05-13

Homocysteine-induced endoplasmic reticulum (ER) protein (Herp) is an ER stress-inducible key regulatory component of ER-associated degradation (ERAD) that has been implicated in insulin hypersecretion in diabetic mouse models. Herp expression is tightly regulated. Additionally, Herp is a highly labile protein and interacts with various proteins, which are characteristic features of ubiquitinated protein. Previously, we reported that ubiquitination is not required for Herp degradation. In addition, we found that the lysine residues of Herp (which are ubiquitinated by E3 ubiquitin ligase) are not sufficient for regulation of Herp degradation. In this study, we found that NAD(P)H quinone oxidoreductase 1 (NQO1)-mediated targetingmore » of Herp to the proteasome was involved in Herp degradation. In addition, we found that Herp protein levels were markedly elevated in synoviolin-null cells. The E3 ubiquitin ligase synoviolin is a central component of ERAD and is involved in the degradation of nuclear factor E2-related factor-2 (Nrf2), which regulates cellular reactive oxygen species. Additionally, NQO1 is a target of Nrf2. Thus, our findings indicated that NQO1 could stabilize Herp protein expression via indirect regulation of synoviolin. -- Highlights: •Herp interacts with NQO1. •NQO1 regulates Herp degradation.« less

Role of Silicon on Plant–Pathogen Interactions

PubMed Central

Wang, Min; Gao, Limin; Dong, Suyue; Sun, Yuming; Shen, Qirong; Guo, Shiwei

2017-01-01

Although silicon (Si) is not recognized as an essential element for general higher plants, it has beneficial effects on the growth and production of a wide range of plant species. Si is known to effectively mitigate various environmental stresses and enhance plant resistance against both fungal and bacterial pathogens. In this review, the effects of Si on plant–pathogen interactions are analyzed, mainly on physical, biochemical, and molecular aspects. In most cases, the Si-induced biochemical/molecular resistance during plant–pathogen interactions were dominated as joint resistance, involving activating defense-related enzymes activates, stimulating antimicrobial compound production, regulating the complex network of signal pathways, and activating of the expression of defense-related genes. The most previous studies described an independent process, however, the whole plant resistances were rarely considered, especially the interaction of different process in higher plants. Si can act as a modulator influencing plant defense responses and interacting with key components of plant stress signaling systems leading to induced resistance. Priming of plant defense responses, alterations in phytohormone homeostasis, and networking by defense signaling components are all potential mechanisms involved in Si-triggered resistance responses. This review summarizes the roles of Si in plant–microbe interactions, evaluates the potential for improving plant resistance by modifying Si fertilizer inputs, and highlights future research concerning the role of Si in agriculture. PMID:28529517

Patients' perception of their involvement in shared treatment decision making: Key factors in the treatment of inflammatory bowel disease.

PubMed

Veilleux, Sophie; Noiseux, Isabelle; Lachapelle, Nathalie; Kohen, Rita; Vachon, Luc; Guay, Brian White; Bitton, Alain; Rioux, John D

2018-02-01

This study aims to characterize the relationships between the quality of the information given by the physician, the involvement of the patient in shared decision making (SDM), and outcomes in terms of satisfaction and anxiety pertaining to the treatment of inflammatory bowel disease (IBD). A Web survey was conducted among 200 Canadian patients affected with IBD. The theoretical model of SDM was adjusted using path analysis. SAS software was used for all statistical analyses. The quality of the knowledge transfer between the physician and the patient is significantly associated with the components of SDM: information comprehension, patient involvement and decision certainty about the chosen treatment. In return, patient involvement in SDM is significantly associated with higher satisfaction and, as a result, lower anxiety as regards treatment selection. This study demonstrates the importance of involving patients in shared treatment decision making in the context of IBD. Understanding shared decision making may motivate patients to be more active in understanding the relevant information for treatment selection, as it is related to their level of satisfaction, anxiety and adherence to treatment. This relationship should encourage physicians to promote shared decision making. Copyright © 2017 Elsevier B.V. All rights reserved.

Multicomponent reactions provide key molecules for secret communication.

PubMed

Boukis, Andreas C; Reiter, Kevin; Frölich, Maximiliane; Hofheinz, Dennis; Meier, Michael A R

2018-04-12

A convenient and inherently more secure communication channel for encoding messages via specifically designed molecular keys is introduced by combining advanced encryption standard cryptography with molecular steganography. The necessary molecular keys require large structural diversity, thus suggesting the application of multicomponent reactions. Herein, the Ugi four-component reaction of perfluorinated acids is utilized to establish an exemplary database consisting of 130 commercially available components. Considering all permutations, this combinatorial approach can unambiguously provide 500,000 molecular keys in only one synthetic procedure per key. The molecular keys are transferred nondigitally and concealed by either adsorption onto paper, coffee, tea or sugar as well as by dissolution in a perfume or in blood. Re-isolation and purification from these disguises is simplified by the perfluorinated sidechains of the molecular keys. High resolution tandem mass spectrometry can unequivocally determine the molecular structure and thus the identity of the key for a subsequent decryption of an encoded message.

Doppler Lidar System Design via Interdisciplinary Design Concept at NASA Langley Research Center - Part I

NASA Technical Reports Server (NTRS)

Boyer, Charles M.; Jackson, Trevor P.; Beyon, Jeffrey Y.; Petway, Larry B.

2013-01-01

Optimized designs of the Navigation Doppler Lidar (NDL) instrument for Autonomous Landing Hazard Avoidance Technology (ALHAT) were accomplished via Interdisciplinary Design Concept (IDEC) at NASA Langley Research Center during the summer of 2013. Three branches in the Engineering Directorate and three students were involved in this joint task through the NASA Langley Aerospace Research Summer Scholars (LARSS) Program. The Laser Remote Sensing Branch (LRSB), Mechanical Systems Branch (MSB), and Structural and Thermal Systems Branch (STSB) were engaged to achieve optimal designs through iterative and interactive collaborative design processes. A preliminary design iteration was able to reduce the power consumption, mass, and footprint by removing redundant components and replacing inefficient components with more efficient ones. A second design iteration reduced volume and mass by replacing bulky components with excessive performance with smaller components custom-designed for the power system. Mechanical placement collaboration reduced potential electromagnetic interference (EMI). Through application of newly selected electrical components and thermal analysis data, a total electronic chassis redesign was accomplished. Use of an innovative forced convection tunnel heat sink was employed to meet and exceed project requirements for cooling, mass reduction, and volume reduction. Functionality was a key concern to make efficient use of airflow, and accessibility was also imperative to allow for servicing of chassis internals. The collaborative process provided for accelerated design maturation with substantiated function.

A Multi-Dimensional Functional Principal Components Analysis of EEG Data

PubMed Central

Hasenstab, Kyle; Scheffler, Aaron; Telesca, Donatello; Sugar, Catherine A.; Jeste, Shafali; DiStefano, Charlotte; Şentürk, Damla

2017-01-01

Summary The electroencephalography (EEG) data created in event-related potential (ERP) experiments have a complex high-dimensional structure. Each stimulus presentation, or trial, generates an ERP waveform which is an instance of functional data. The experiments are made up of sequences of multiple trials, resulting in longitudinal functional data and moreover, responses are recorded at multiple electrodes on the scalp, adding an electrode dimension. Traditional EEG analyses involve multiple simplifications of this structure to increase the signal-to-noise ratio, effectively collapsing the functional and longitudinal components by identifying key features of the ERPs and averaging them across trials. Motivated by an implicit learning paradigm used in autism research in which the functional, longitudinal and electrode components all have critical interpretations, we propose a multidimensional functional principal components analysis (MD-FPCA) technique which does not collapse any of the dimensions of the ERP data. The proposed decomposition is based on separation of the total variation into subject and subunit level variation which are further decomposed in a two-stage functional principal components analysis. The proposed methodology is shown to be useful for modeling longitudinal trends in the ERP functions, leading to novel insights into the learning patterns of children with Autism Spectrum Disorder (ASD) and their typically developing peers as well as comparisons between the two groups. Finite sample properties of MD-FPCA are further studied via extensive simulations. PMID:28072468

A multi-dimensional functional principal components analysis of EEG data.

PubMed

Hasenstab, Kyle; Scheffler, Aaron; Telesca, Donatello; Sugar, Catherine A; Jeste, Shafali; DiStefano, Charlotte; Şentürk, Damla

2017-09-01

The electroencephalography (EEG) data created in event-related potential (ERP) experiments have a complex high-dimensional structure. Each stimulus presentation, or trial, generates an ERP waveform which is an instance of functional data. The experiments are made up of sequences of multiple trials, resulting in longitudinal functional data and moreover, responses are recorded at multiple electrodes on the scalp, adding an electrode dimension. Traditional EEG analyses involve multiple simplifications of this structure to increase the signal-to-noise ratio, effectively collapsing the functional and longitudinal components by identifying key features of the ERPs and averaging them across trials. Motivated by an implicit learning paradigm used in autism research in which the functional, longitudinal, and electrode components all have critical interpretations, we propose a multidimensional functional principal components analysis (MD-FPCA) technique which does not collapse any of the dimensions of the ERP data. The proposed decomposition is based on separation of the total variation into subject and subunit level variation which are further decomposed in a two-stage functional principal components analysis. The proposed methodology is shown to be useful for modeling longitudinal trends in the ERP functions, leading to novel insights into the learning patterns of children with Autism Spectrum Disorder (ASD) and their typically developing peers as well as comparisons between the two groups. Finite sample properties of MD-FPCA are further studied via extensive simulations. © 2017, The International Biometric Society.

2006 Precision Strike Technology Symposium

DTIC Science & Technology

2006-10-19

s Navy Unique Joint system 14 A/C Unique Components Framework JMPS Common Components Crypto Key GCCS-M Interface Carrier Intel Feed Carrier...210 GPS Prediction CUPC GPS Crypto Key TAMMAC SLAM-ER GPS Almanac ETIRMS PMA-281 NGMS PMA-209 Boeing PMA-201 Raytheon ESC (USAF) Hill AFB PMA-234 PMA...242 F/A-18 UPC GPS Prediction CUPC GPS Crypto Key TAMMAC SLAM-ER GPS Almanac HARM WASP Framework ARC-210 ETIRMS PMA-281 Integration/Test/ Support TLAM

RegA Plays a Key Role in Oxygen-Dependent Establishment of Persistence and in Isocitrate Lyase Activity, a Critical Determinant of In vivo Brucella suis Pathogenicity

PubMed Central

Abdou, Elias; Jiménez de Bagüés, María P.; Martínez-Abadía, Ignacio; Ouahrani-Bettache, Safia; Pantesco, Véronique; Occhialini, Alessandra; Al Dahouk, Sascha; Köhler, Stephan; Jubier-Maurin, Véronique

2017-01-01

For aerobic human pathogens, adaptation to hypoxia is a critical factor for the establishment of persistent infections, as oxygen availability is low inside the host. The two-component system RegB/A of Brucella suis plays a central role in the control of respiratory systems adapted to oxygen deficiency, and in persistence in vivo. Using an original “in vitro model of persistence” consisting in gradual oxygen depletion, we compared transcriptomes and proteomes of wild-type and ΔregA strains to identify the RegA-regulon potentially involved in the set-up of persistence. Consecutive to oxygen consumption resulting in growth arrest, 12% of the genes in B. suis were potentially controlled directly or indirectly by RegA, among which numerous transcriptional regulators were up-regulated. In contrast, genes or proteins involved in envelope biogenesis and in cellular division were repressed, suggesting a possible role for RegA in the set-up of a non-proliferative persistence state. Importantly, the greatest number of the RegA-repressed genes and proteins, including aceA encoding the functional IsoCitrate Lyase (ICL), were involved in energy production. A potential consequence of this RegA impact may be the slowing-down of the central metabolism as B. suis progressively enters into persistence. Moreover, ICL is an essential determinant of pathogenesis and long-term interactions with the host, as demonstrated by the strict dependence of B. suis on ICL activity for multiplication and persistence during in vivo infection. RegA regulates gene or protein expression of all functional groups, which is why RegA is a key regulator of B. suis in adaptation to oxygen depletion. This function may contribute to the constraint of bacterial growth, typical of chronic infection. Oxygen-dependent activation of two-component systems that control persistence regulons, shared by several aerobic human pathogens, has not been studied in Brucella sp. before. This work therefore contributes significantly to the unraveling of persistence mechanisms in this important zoonotic pathogen. PMID:28573107

Secure content objects

DOEpatents

Evans, William D [Cupertino, CA

2009-02-24

A secure content object protects electronic documents from unauthorized use. The secure content object includes an encrypted electronic document, a multi-key encryption table having at least one multi-key component, an encrypted header and a user interface device. The encrypted document is encrypted using a document encryption key associated with a multi-key encryption method. The encrypted header includes an encryption marker formed by a random number followed by a derivable variation of the same random number. The user interface device enables a user to input a user authorization. The user authorization is combined with each of the multi-key components in the multi-key encryption key table and used to try to decrypt the encrypted header. If the encryption marker is successfully decrypted, the electronic document may be decrypted. Multiple electronic documents or a document and annotations may be protected by the secure content object.

Stable isotope probing to study functional components of complex microbial ecosystems.

PubMed

Mazard, Sophie; Schäfer, Hendrik

2014-01-01

This protocol presents a method of dissecting the DNA or RNA of key organisms involved in a specific biochemical process within a complex ecosystem. Stable isotope probing (SIP) allows the labelling and separation of nucleic acids from community members that are involved in important biochemical transformations, yet are often not the most numerically abundant members of a community. This pure culture-independent technique circumvents limitations of traditional microbial isolation techniques or data mining from large-scale whole-community metagenomic studies to tease out the identities and genomic repertoires of microorganisms participating in biological nutrient cycles. SIP experiments can be applied to virtually any ecosystem and biochemical pathway under investigation provided a suitable stable isotope substrate is available. This versatile methodology allows a wide range of analyses to be performed, from fatty-acid analyses, community structure and ecology studies, and targeted metagenomics involving nucleic acid sequencing. SIP experiments provide an effective alternative to large-scale whole-community metagenomic studies by specifically targeting the organisms or biochemical transformations of interest, thereby reducing the sequencing effort and time-consuming bioinformatics analyses of large datasets.

Responding to the mental health and substance abuse needs of youth in the juvenile justice system: Ohio's Behavioral Health/Juvenile Justice Initiative.

PubMed

Kretschmar, Jeff M; Butcher, Fredrick; Kanary, Patrick J; Devens, Rebecca

2015-11-01

Nearly half a million inmates with mental health issues are housed in our country’s jails and prisons. The majority of juvenile justice-involved (JJI) youth have a history of behavioral health (mental health or substance use) problems. Multiple studies estimate that between 65% to 75% of juvenile justice-involved youth have at least one behavioral health disorder, and 20% to 30% report suffering from a serious behavioral disorder. With so many juveniles with behavioral health issues entering a system that was not designed to provide comprehensive treatment, communities are reevaluating their approach to juvenile justice. This article describes the origins and the results of Ohio’s Behavioral Health Juvenile Justice Initiative (BHJJ), a diversion program for juvenile justice-involved youth with behavioral health issues. The authors also discuss the key components of program success, offer advice to other jurisdictions considering implementing similar programming, and identify ways to take diversion programs to scale. (PsycINFO Database Record (c) 2016 APA, all rights reserved) (c) 2015 APA, all rights reserved).

4-alkyl-L-(Dehydro)proline biosynthesis in actinobacteria involves N-terminal nucleophile-hydrolase activity of γ-glutamyltranspeptidase homolog for C-C bond cleavage

NASA Astrophysics Data System (ADS)

Zhong, Guannan; Zhao, Qunfei; Zhang, Qinglin; Liu, Wen

2017-07-01

γ-Glutamyltranspeptidases (γ-GTs), ubiquitous in glutathione metabolism for γ-glutamyl transfer/hydrolysis, are N-terminal nucleophile (Ntn)-hydrolase fold proteins that share an autoproteolytic process for self-activation. γ-GT homologues are widely present in Gram-positive actinobacteria where their Ntn-hydrolase activities, however, are not involved in glutathione metabolism. Herein, we demonstrate that the formation of 4-Alkyl-L-(dehydro)proline (ALDP) residues, the non-proteinogenic α-amino acids that serve as vital components of many bioactive metabolites found in actinobacteria, involves unprecedented Ntn-hydrolase activity of γ-GT homologue for C-C bond cleavage. The related enzymes share a key Thr residue, which acts as an internal nucleophile for protein hydrolysis and then as a newly released N-terminal nucleophile for carboxylate side-chain processing likely through the generation of an oxalyl-Thr enzyme intermediate. These findings provide mechanistic insights into the biosynthesis of various ALDP residues/associated natural products, highlight the versatile functions of Ntn-hydrolase fold proteins, and particularly generate interest in thus far less-appreciated γ-GT homologues in actinobacteria.

Aging and Intermittent Fasting Impact on Transcriptional Regulation and Physiological Responses of Adult Drosophila Neuronal and Muscle Tissues

PubMed Central

Zhang, Sharon; Ratliff, Eric P.; Molina, Brandon; El-Mecharrafie, Nadja; Mastroianni, Jessica; Kotzebue, Roxanne W.; Achal, Madhulika; Mauntz, Ruth E.; Gonzalez, Arysa; Barekat, Ayeh; Bray, William A.; Macias, Andrew M.; Daugherty, Daniel; Harris, Greg L.; Edwards, Robert A.; Finley, Kim D.

2018-01-01

The progressive decline of the nervous system, including protein aggregate formation, reflects the subtle dysregulation of multiple functional pathways. Our previous work has shown intermittent fasting (IF) enhances longevity, maintains adult behaviors and reduces aggregates, in part, by promoting autophagic function in the aging Drosophila brain. To clarify the impact that IF-treatment has upon aging, we used high throughput RNA-sequencing technology to examine the changing transcriptome in adult Drosophila tissues. Principle component analysis (PCA) and other analyses showed ~1200 age-related transcriptional differences in head and muscle tissues, with few genes having matching expression patterns. Pathway components showing age-dependent expression differences were involved with stress response, metabolic, neural and chromatin remodeling functions. Middle-aged tissues also showed a significant increase in transcriptional drift-variance (TD), which in the CNS included multiple proteolytic pathway components. Overall, IF-treatment had a demonstrably positive impact on aged transcriptomes, partly ameliorating both fold and variance changes. Consistent with these findings, aged IF-treated flies displayed more youthful metabolic, behavioral and basal proteolytic profiles that closely correlated with transcriptional alterations to key components. These results indicate that even modest dietary changes can have therapeutic consequences, slowing the progressive decline of multiple cellular systems, including proteostasis in the aging nervous system. PMID:29642630

Aging and Intermittent Fasting Impact on Transcriptional Regulation and Physiological Responses of Adult Drosophila Neuronal and Muscle Tissues.

PubMed

Zhang, Sharon; Ratliff, Eric P; Molina, Brandon; El-Mecharrafie, Nadja; Mastroianni, Jessica; Kotzebue, Roxanne W; Achal, Madhulika; Mauntz, Ruth E; Gonzalez, Arysa; Barekat, Ayeh; Bray, William A; Macias, Andrew M; Daugherty, Daniel; Harris, Greg L; Edwards, Robert A; Finley, Kim D

2018-04-10

The progressive decline of the nervous system, including protein aggregate formation, reflects the subtle dysregulation of multiple functional pathways. Our previous work has shown intermittent fasting (IF) enhances longevity, maintains adult behaviors and reduces aggregates, in part, by promoting autophagic function in the aging Drosophila brain. To clarify the impact that IF-treatment has upon aging, we used high throughput RNA-sequencing technology to examine the changing transcriptome in adult Drosophila tissues. Principle component analysis (PCA) and other analyses showed ~1200 age-related transcriptional differences in head and muscle tissues, with few genes having matching expression patterns. Pathway components showing age-dependent expression differences were involved with stress response, metabolic, neural and chromatin remodeling functions. Middle-aged tissues also showed a significant increase in transcriptional drift-variance (TD), which in the CNS included multiple proteolytic pathway components. Overall, IF-treatment had a demonstrably positive impact on aged transcriptomes, partly ameliorating both fold and variance changes. Consistent with these findings, aged IF-treated flies displayed more youthful metabolic, behavioral and basal proteolytic profiles that closely correlated with transcriptional alterations to key components. These results indicate that even modest dietary changes can have therapeutic consequences, slowing the progressive decline of multiple cellular systems, including proteostasis in the aging nervous system.

Chemical interaction: enhancement and inhibition of clastogenicity.

PubMed Central

Anwar, W A

1993-01-01

Most environmental exposures involve concurrent or sequential exposure to multiple chemicals in air, water, and food. Interactive effects in carcinogenesis have been described for certain combinations of agents. They are described in terms of enhancement or inhibition of carcinogenesis. Enhancement effects have been documented for cigarette smoking in combination with exposure to asbestos, radon, alcohol, or other exposures. A variety of inhibitors of carcinogenesis have also been described. They are classified into agents preventing formation of carcinogens; blocking agents; and suppressing agents. Assessment of risk from exposure to multiple agents can be derived either from epidemiological studies in relation to actual exposure or from laboratory studies after controlled exposure to different agents. Prediction of how toxic components of mixtures will interact should be based on an understanding of the mechanisms of such interactions. Compounds may interact chemically, yielding new toxic components or causing a change in the biological availability of the existing components or metabolites. In humans, great individual variability in response is to be expected because of genetic heterogeneity or acquired host susceptibility factors. Interaction is thus a key component in the risk assessment process. In this paper, the definition of interaction and the theoretical basis for different types of interaction in cancer causation are reviewed. Epidemiological and experimental studies showing interactive effects of two chemical carcinogens are also presented. PMID:8143617

Probing Complex Free-Radical Reaction Pathways of Fuel Model Compounds

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

Buchanan III, A C; Kidder, Michelle; Beste, Ariana

2012-01-01

Fossil (e.g. coal) and renewable (e.g. woody biomass) organic energy resources have received considerable attention as possible sources of liquid transportation fuels and commodity chemicals. Knowledge of the reactivity of these complex materials has been advanced through fundamental studies of organic compounds that model constituent substructures. In particular, an improved understanding of thermochemical reaction pathways involving free-radical intermediates has arisen from detailed experimental kinetic studies and, more recently, advanced computational investigations. In this presentation, we will discuss our recent investigations of the fundamental pyrolysis pathways of model compounds that represent key substructures in the lignin component of woody biomass withmore » a focus on molecules representative of the dominant beta-O-4 aryl ether linkages. Additional mechanistic insights gleaned from DFT calculations on the kinetics of key elementary reaction steps will also be presented, as well as a few thoughts on the significant contributions of Jim Franz to this area of free radical chemistry.« less

The personal health record: consumers banking on their health.

PubMed

Ball, Marion J; Costin, Melinda Y; Lehmann, Christoph

2008-01-01

With personal health records (PHRs) acting much like ATM cards, increasingly wired consumers can "bank on health", accessing their own personal health information and a wide array of services. Consumer-owned, the PHR is dependent upon the existence of the legal electronic medical record (EMR) and interoperability. Working PHRs are in place in Veterans Health Administration, private health care institutions, and in the commercial sector. By allowing consumers to become involved in their own care, the PHR creates new roles and relationships. New tools change the clinician's workflow and thought flow, and pose new challenges for consumers. Key components of the PHR include the EMR and regional health information organizations (RHIOs); key strategies focus on human factors in successful project management. Online resources provided by the National Library of Medicine and Health On the Net help address consumer needs for information that is reliable and understandable. The growth of self-management tools adds to the challenge and the promise of PHRs for clinicians and consumers alike.

Around and beyond 53BP1 Nuclear Bodies

PubMed Central

Fernandez-Vidal, Anne; Vignard, Julien

2017-01-01

Within the nucleus, sub-nuclear domains define territories where specific functions occur. Nuclear bodies (NBs) are dynamic structures that concentrate nuclear factors and that can be observed microscopically. Recently, NBs containing the p53 binding protein 1 (53BP1), a key component of the DNA damage response, were defined. Interestingly, 53BP1 NBs are visualized during G1 phase, in daughter cells, while DNA damage was generated in mother cells and not properly processed. Unlike most NBs involved in transcriptional processes, replication has proven to be key for 53BP1 NBs, with replication stress leading to the formation of these large chromatin domains in daughter cells. In this review, we expose the composition and organization of 53BP1 NBs and focus on recent findings regarding their regulation and dynamics. We then concentrate on the importance of the replication stress, examine the relation of 53BP1 NBs with DNA damage and discuss their dysfunction. PMID:29206178

A FYVE zinc finger domain protein specifically links mRNA transport to endosome trafficking.

PubMed

Pohlmann, Thomas; Baumann, Sebastian; Haag, Carl; Albrecht, Mario; Feldbrügge, Michael

2015-05-18

An emerging theme in cellular logistics is the close connection between mRNA and membrane trafficking. A prominent example is the microtubule-dependent transport of mRNAs and associated ribosomes on endosomes. This coordinated process is crucial for correct septin filamentation and efficient growth of polarised cells, such as fungal hyphae. Despite detailed knowledge on the key RNA-binding protein and the molecular motors involved, it is unclear how mRNAs are connected to membranes during transport. Here, we identify a novel factor containing a FYVE zinc finger domain for interaction with endosomal lipids and a new PAM2-like domain required for interaction with the MLLE domain of the key RNA-binding protein. Consistently, loss of this FYVE domain protein leads to specific defects in mRNA, ribosome, and septin transport without affecting general functions of endosomes or their movement. Hence, this is the first endosomal component specific for mRNP trafficking uncovering a new mechanism to couple mRNPs to endosomes.

The facial nerve: anatomy and associated disorders for oral health professionals.

PubMed

Takezawa, Kojiro; Townsend, Grant; Ghabriel, Mounir

2018-04-01

The facial nerve, the seventh cranial nerve, is of great clinical significance to oral health professionals. Most published literature either addresses the central connections of the nerve or its peripheral distribution but few integrate both of these components and also highlight the main disorders affecting the nerve that have clinical implications in dentistry. The aim of the current study is to provide a comprehensive description of the facial nerve. Multiple aspects of the facial nerve are discussed and integrated, including its neuroanatomy, functional anatomy, gross anatomy, clinical problems that may involve the nerve, and the use of detailed anatomical knowledge in the diagnosis of the site of facial nerve lesion in clinical neurology. Examples are provided of disorders that can affect the facial nerve during its intra-cranial, intra-temporal and extra-cranial pathways, and key aspects of clinical management are discussed. The current study is complemented by original detailed dissections and sketches that highlight key anatomical features and emphasise the extent and nature of anatomical variations displayed by the facial nerve.

Genetics and Molecular Pathogenesis of Gastric Adenocarcinoma.

PubMed

Tan, Patrick; Yeoh, Khay-Guan

2015-10-01

Gastric cancer (GC) is globally the fifth most common cancer and third leading cause of cancer death. A complex disease arising from the interaction of environmental and host-associated factors, key contributors to GC's high mortality include its silent nature, late clinical presentation, and underlying biological and genetic heterogeneity. Achieving a detailed molecular understanding of the various genomic aberrations associated with GC will be critical to improving patient outcomes. The recent years has seen considerable progress in deciphering the genomic landscape of GC, identifying new molecular components such as ARID1A and RHOA, cellular pathways, and tissue populations associated with gastric malignancy and progression. The Cancer Genome Atlas (TCGA) project is a landmark in the molecular characterization of GC. Key challenges for the future will involve the translation of these molecular findings to clinical utility, by enabling novel strategies for early GC detection, and precision therapies for individual GC patients. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Skeletal muscle plasticity induced by seasonal acclimatization in carp involves differential expression of rRNA and molecules that epigenetically regulate its synthesis.

PubMed

Fuentes, Eduardo N; Zuloaga, Rodrigo; Nardocci, Gino; Fernandez de la Reguera, Catalina; Simonet, Nicolas; Fumeron, Robinson; Valdes, Juan Antonio; Molina, Alfredo; Alvarez, Marco

2014-01-01

Ribosomal biogenesis controls cellular growth in living organisms, with the rate-limiting step of this process being the transcription of ribosomal DNA (rDNA). Considering that epigenetic mechanisms allow an organism to respond to environmental changes, the expression in muscle of several molecules that regulate epigenetic rRNA synthesis, as well as rDNA transcription, were evaluated during the seasonal acclimatization of the carp. First, the nucleotide sequences encoding the components forming the NoRC (ttf-I, tip5) and eNoSC (sirt1, nml, suv39h1), two chromatin remodeling complexes that silence rRNA synthesis, as well as the sequence of ubf1, a key regulator of rDNA transcription, were obtained. Subsequently the transcriptional regulation of the aforementioned molecules, and other key molecules involved in rRNA synthesis (mh2a1, mh2a2, h2a.z, h2a.z.7, nuc, p80), was assessed. The carp sequences for TTF-I, TIP5, SIRT1, NML, SUV39H1, and UBF1 showed a high conservation of domains and key amino acids in comparison with other fish and higher vertebrates. The mRNA contents in muscle for ttf-I, tip5, sirt1, nml, suv39h1, mh2a1, mh2a.z, and nuc were up-regulated during winter in comparison with summer, whereas the mRNA levels of mh2a2, ubf1, and p80 were down-regulated. Also, the contents of molecules involved in processing the rRNA (snoRNAs) and pRNA, a stabilizer of NoRC complex, were analyzed, finding that these non-coding RNAs were not affected by seasonal acclimatization. These results suggest that variations in the expression of rRNA and the molecules that epigenetically regulate its synthesis are contributing to the muscle plasticity induced by seasonal acclimatization in carp. Copyright © 2014 Elsevier Inc. All rights reserved.

Stannous Fluoride Effects on Gene Expression of Streptococcus mutans and Actinomyces viscosus.

PubMed

Shi, Y; Li, R; White, D J; Biesbrock, A R

2018-02-01

A genome-wide transcriptional analysis was performed to elucidate the bacterial cellular response of Streptococcus mutans and Actinomyces viscosus to NaF and SnF 2 . The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of SnF 2 were predetermined before microarray study. Gene expression profiling microarray experiments were carried out in the absence (control) and presence (experimental) of 10 ppm and 100 ppm Sn 2+ (in the form of SnF 2 ) and fluoride controls for 10-min exposures (4 biological replicates/treatment). These Sn 2+ levels and treatment time were chosen because they have been shown to slow bacterial growth of S. mutans (10 ppm) and A. viscosus (100 ppm) without affecting cell viability. All data generated by microarray experiments were analyzed with bioinformatics tools by applying the following criteria: 1) a q value should be ≤0.05, and 2) an absolute fold change in transcript level should be ≥1.5. Microarray results showed SnF 2 significantly inhibited several genes encoding enzymes of the galactose pathway upon a 10-min exposure versus a negative control: lacA and lacB (A and B subunits of the galactose-6-P isomerase), lacC (tagatose-6-P kinase), lacD (tagatose-1,6-bP adolase), galK (galactokinase), galT (galactose-1-phosphate uridylyltransferase), and galE (UDP-glucose 4-epimerase). A gene fruK encoding fructose-1-phosphate kinase in the fructose pathway was also significantly inhibited. Several genes encoding fructose/mannose-specific enzyme IIABC components in the phosphotransferase system (PTS) were also downregulated, as was ldh encoding lactate dehydrogenase, a key enzyme involved in lactic acid synthesis. SnF 2 downregulated the transcription of most key enzyme genes involved in the galactose pathway and also suppressed several key genes involved in the PTS, which transports sugars into the cell in the first step of glycolysis.

An Exploratory Qualitative Inquiry of Key Indicators on IT Disaster Recovery Planning

ERIC Educational Resources Information Center

Gardner, Brian

2016-01-01

Disaster recovery planning is a crucial component to maintaining a business's economic stability. However, it is unclear how key performance indicators (KPIs) are perceived in the emergency medical service (EMS) industry during the disaster recover planning process. The problem addressed in this study was to understand KPIs and their components.…

Assuring Quality in Online Course Delivery

ERIC Educational Resources Information Center

Matuga, Julia M.; Wooldridge, Deborah G.; Poirier, Sandra

2011-01-01

This paper examines the critical issue of assuring quality online course delivery by examining four key components of online teaching and learning. The topic of course delivery is viewed as a cultural issue that permeates processes from the design of an online course to its evaluation. First, the authors examine and review key components of and…

Identification of TOEFAZ1-interacting proteins reveals key regulators of Trypanosoma brucei cytokinesis.

PubMed

Hilton, Nicholas A; Sladewski, Thomas E; Perry, Jenna A; Pataki, Zemplen; Sinclair-Davis, Amy N; Muniz, Richard S; Tran, Holly L; Wurster, Jenna I; Seo, Jiwon; de Graffenried, Christopher L

2018-05-21

The protist parasite Trypanosoma brucei is an obligate extracellular pathogen that retains its highly-polarized morphology during cell division and has evolved a novel cytokinetic process independent of non-muscle myosin II. The polo-like kinase homolog TbPLK is essential for transmission of cell polarity during division and for cytokinesis. We previously identified a putative TbPLK substrate named Tip of the Extending FAZ 1 (TOEFAZ1) as an essential kinetoplastid-specific component of the T. brucei cytokinetic machinery. We performed a proximity-dependent biotinylation (BioID) screen using TOEFAZ1 as a means to identify additional proteins that are involved in cytokinesis. Using quantitative proteomic methods, we identified nearly 500 TOEFAZ1-proximal proteins and characterized 59 in further detail. Among the candidates, we identified an essential putative phosphatase that regulates the expression level and localization of both TOEFAZ1 and TbPLK, a previously uncharacterized protein that is necessary for the assembly of a new cell posterior, and a microtubule plus-end directed orphan kinesin that is required for completing cleavage furrow ingression. The identification of these proteins provides new insight into T. brucei cytokinesis and establishes TOEFAZ1 as a key component of this essential and uniquely-configured process in kinetoplastids. This article is protected by copyright. All rights reserved. © 2018 John Wiley & Sons Ltd.

Designing an oral health module for the Bachelor of Midwifery program at an Australian University.

PubMed

Duff, Margaret; Dahlen, Hannah G; Burns, Elaine; Priddis, Holly; Schmied, Virginia; George, Ajesh

2017-03-01

Maternal oral health is important yet many pregnant women are unaware of its significance. Midwives are advised to promote oral health during pregnancy and are supported to do this in Australia through the Midwifery Initiated Oral Health training program. However, limited undergraduate education is being provided to midwifery students in this area. The objective of this paper is to describe how an innovative oral health education module for an undergraduate midwifery course in Australia was designed using a multidisciplinary approach. Midwives experienced in curriculum development and key investigators from the Midwifery Initiated Oral Health program designed the module using existing literature. Constructive alignment, blended learning and scaffolding were used in the design process. The draft module was then reviewed by midwifery academics and their feedback incorporated. The final module involves 4 h of teaching and learning and contains three components incorporated into first year course units. Each component is aligned with existing learning outcomes and incorporates blended learning approaches and tutorials/class activities as well as online quizzes and personal reflection. The module details key information (current evidence; basic anatomy/physiology; common oral conditions; and guidelines during pregnancy) that could better prepare students to promote oral health in clinical practice. This is the first time such an innovative, multidisciplinary approach has been undertaken embedding oral health in an undergraduate midwifery program in Australia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Drug discrimination under two concurrent fixed-interval fixed-interval schedules.

PubMed

McMillan, D E; Li, M

2000-07-01

Pigeons were trained to discriminate 5.0 mg/kg pentobarbital from saline under a two-key concurrent fixed-interval (FI) 100-s FI 200-s schedule of food presentation, and later tinder a concurrent FI 40-s FI 80-s schedule, in which the FI component with the shorter time requirement reinforced responding on one key after drug administration (pentobarbital-biased key) and on the other key after saline administration (saline-biased key). After responding stabilized under the concurrent FI 100-s FI 200-s schedule, pigeons earned an average of 66% (after pentobarbital) to 68% (after saline) of their reinforcers for responding under the FI 100-s component of the concurrent schedule. These birds made an average of 70% of their responses on both the pentobarbital-biased key after the training dose of pentobarbital and the saline-biased key after saline. After responding stabilized under the concurrent FI 40-s FI 80-s schedule, pigeons earned an average of 67% of their reinforcers for responding under the FI 40 component after both saline and the training dose of pentobarbital. These birds made an average of 75% of their responses on the pentobarbital-biased key after the training dose of pentobarbital, but only 55% of their responses on the saline-biased key after saline. In test sessions preceded by doses of pentobarbital, chlordiazepoxide, ethanol, phencyclidine, or methamphetamine, the dose-response curves were similar under these two concurrent schedules. Pentobarbital, chlordiazepoxide, and ethanol produced dose-dependent increases in responding on the pentobarbital-biased key as the doses increased. For some birds, at the highest doses of these drugs, the dose-response curve turned over. Increasing doses of phencyclidine produced increased responding on the pentobarbital-biased key in some, but not all, birds. After methamphetamine, responding was largely confined to the saline-biased key. These data show that pigeons can perform drug discriminations under concurrent schedules in which the reinforcement frequency under the schedule components differs only by a factor of two, and that when other drugs are substituted for the training drugs they produce dose-response curves similar to the curves produced by these drugs under other concurrent interval schedules.

PAMPs, PRRs, effectors and R-genes associated with citrus–pathogen interactions

PubMed Central

Dalio, Ronaldo J. D.; Magalhães, Diogo M.; Rodrigues, Carolina M.; Arena, Gabriella D.; Oliveira, Tiago S.; Souza-Neto, Reinaldo R.; Picchi, Simone C.; Martins, Paula M. M.; Santos, Paulo J. C.; Maximo, Heros J.; Pacheco, Inaiara S.; De Souza, Alessandra A.

2017-01-01

Abstract Background Recent application of molecular-based technologies has considerably advanced our understanding of complex processes in plant–pathogen interactions and their key components such as PAMPs, PRRs, effectors and R-genes. To develop novel control strategies for disease prevention in citrus, it is essential to expand and consolidate our knowledge of the molecular interaction of citrus plants with their pathogens. Scope This review provides an overview of our understanding of citrus plant immunity, focusing on the molecular mechanisms involved in the interactions with viruses, bacteria, fungi, oomycetes and vectors related to the following diseases: tristeza, psorosis, citrus variegated chlorosis, citrus canker, huanglongbing, brown spot, post-bloom, anthracnose, gummosis and citrus root rot. PMID:28065920

An overview on forensic analysis devoted to analytical chemists.

PubMed

Castillo-Peinado, L S; Luque de Castro, M D

2017-05-15

The present article has as main aim to show analytical chemists interested in forensic analysis the world they will face if decision in favor of being a forensic analytical chemist is adopted. With this purpose, the most outstanding aspects of forensic analysis in dealing with sampling (involving both bodily and no bodily samples), sample preparation, and analytical equipment used in detection, identification and quantitation of key sample components are critically discussed. The role of the great omics in forensic analysis, and the growing role of the youngest of the great omics -metabolomics- are also discussed. The foreseeable role of integrative omics is also outlined. Copyright © 2017 Elsevier B.V. All rights reserved.

The role of colonic metabolism in lactose intolerance.

PubMed

He, T; Venema, K; Priebe, M G; Welling, G W; Brummer, R-J M; Vonk, R J

2008-08-01

Lactose maldigestion and intolerance affect a large part of the world population. The underlying factors of lactose intolerance are not fully understood. In this review, the role of colonic metabolism is discussed, i.e. fermentation of lactose by the colonic microbiota, colonic processing of the fermentation metabolites and how these processes would play a role in the pathophysiology of lactose intolerance. We suggest that the balance between the removal and production rate of osmotic-active components (lactose, and intermediate metabolites, e.g. lactate, succinate, etc.) in the colon is a key factor in the development of symptoms. The involvement of the colon may provide the basis for designing new targeted strategies for dietary and clinical management of lactose intolerance.

Metal Transport across Biomembranes: Emerging Models for a Distinct Chemistry*

PubMed Central

Argüello, José M.; Raimunda, Daniel; González-Guerrero, Manuel

2012-01-01

Transition metals are essential components of important biomolecules, and their homeostasis is central to many life processes. Transmembrane transporters are key elements controlling the distribution of metals in various compartments. However, due to their chemical properties, transition elements require transporters with different structural-functional characteristics from those of alkali and alkali earth ions. Emerging structural information and functional studies have revealed distinctive features of metal transport. Among these are the relevance of multifaceted events involving metal transfer among participating proteins, the importance of coordination geometry at transmembrane transport sites, and the presence of the largely irreversible steps associated with vectorial transport. Here, we discuss how these characteristics shape novel transition metal ion transport models. PMID:22389499

Living the Golden Rule: Reciprocal Exchanges Among African Americans With Cancer

PubMed Central

Hamilton, Jill B.; Sandelowski, Margarete

2010-01-01

Giving is receiving, and receiving is giving. This is the key finding from interviews conducted with 28 African American women and men with cancer who were active participants in dynamic relationships characterized by both giving and receiving. These participants engaged in reciprocal relationships varying in the number of persons involved, types of resources exchanged, and timing of exchange. Findings suggest the need to reconceptualize social support as caregiving and caregiving as social support. This study also points to the need to redesign intervention studies to be more inclusive of components that allow the elderly in illness-related situations to maintain their status as givers in their social networks. PMID:12756686

Metal transport across biomembranes: emerging models for a distinct chemistry.

PubMed

Argüello, José M; Raimunda, Daniel; González-Guerrero, Manuel

2012-04-20

Transition metals are essential components of important biomolecules, and their homeostasis is central to many life processes. Transmembrane transporters are key elements controlling the distribution of metals in various compartments. However, due to their chemical properties, transition elements require transporters with different structural-functional characteristics from those of alkali and alkali earth ions. Emerging structural information and functional studies have revealed distinctive features of metal transport. Among these are the relevance of multifaceted events involving metal transfer among participating proteins, the importance of coordination geometry at transmembrane transport sites, and the presence of the largely irreversible steps associated with vectorial transport. Here, we discuss how these characteristics shape novel transition metal ion transport models.

Role of plant hormones in plant defence responses.

PubMed

Bari, Rajendra; Jones, Jonathan D G

2009-03-01

Plant hormones play important roles in regulating developmental processes and signaling networks involved in plant responses to a wide range of biotic and abiotic stresses. Significant progress has been made in identifying the key components and understanding the role of salicylic acid (SA), jasmonates (JA) and ethylene (ET) in plant responses to biotic stresses. Recent studies indicate that other hormones such as abscisic acid (ABA), auxin, gibberellic acid (GA), cytokinin (CK), brassinosteroids (BR) and peptide hormones are also implicated in plant defence signaling pathways but their role in plant defence is less well studied. Here, we review recent advances made in understanding the role of these hormones in modulating plant defence responses against various diseases and pests.

Gene doping.

PubMed

Harridge, Stephen D R; Velloso, Cristiana P

2008-01-01

Gene doping is the misuse of gene therapy to enhance athletic performance. It has recently been recognised as a potential threat and subsequently been prohibited by the World Anti-Doping Agency. Despite concerns with safety and efficacy of gene therapy, the technology is progressing steadily. Many of the genes/proteins which are involved in determining key components of athletic performance have been identified. Naturally occurring mutations in humans as well as gene-transfer experiments in adult animals have shown that altered expression of these genes does indeed affect physical performance. For athletes, however, the gains in performance must be weighed against the health risks associated with the gene-transfer process, whereas the detection of such practices will provide new challenges for the anti-doping authorities.

Flavones: From Biosynthesis to Health Benefits

PubMed Central

Jiang, Nan; Doseff, Andrea I.; Grotewold, Erich

2016-01-01

Flavones correspond to a flavonoid subgroup that is widely distributed in the plants, and which can be synthesized by different pathways, depending on whether they contain C- or O-glycosylation and hydroxylated B-ring. Flavones are emerging as very important specialized metabolites involved in plant signaling and defense, as well as key ingredients of the human diet, with significant health benefits. Here, we appraise flavone formation in plants, emphasizing the emerging theme that biosynthesis pathway determines flavone chemistry. Additionally, we briefly review the biological activities of flavones, both from the perspective of the functions that they play in biotic and abiotic plant interactions, as well as their roles as nutraceutical components of the human and animal diet. PMID:27338492

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

Carmack, William Jonathan; Braase, Lori Ann

Fuel recovery from severe accidents requires careful planning and execution. The Idaho National Laboratory played a key role in the Three Mile Island (TMI) fuel and core recovery. This involved technology development to locate and handle the damaged fuel; characterization of fuel and debris; analysis of fuel interaction with structural components and materials; development of fuel drying technology for long-term storage. However, one of the critical activities from the TMI project was the extensive effort document all the activities and archive the reports and photos. A historical review of the TMI project at the INL leads to the identification ofmore » current applications and considerations for facility designs, fuel handling, robotic applications, material characterization, etc.« less

Biologically Inspired Model for Visual Cognition Achieving Unsupervised Episodic and Semantic Feature Learning.

PubMed

Qiao, Hong; Li, Yinlin; Li, Fengfu; Xi, Xuanyang; Wu, Wei

2016-10-01

Recently, many biologically inspired visual computational models have been proposed. The design of these models follows the related biological mechanisms and structures, and these models provide new solutions for visual recognition tasks. In this paper, based on the recent biological evidence, we propose a framework to mimic the active and dynamic learning and recognition process of the primate visual cortex. From principle point of view, the main contributions are that the framework can achieve unsupervised learning of episodic features (including key components and their spatial relations) and semantic features (semantic descriptions of the key components), which support higher level cognition of an object. From performance point of view, the advantages of the framework are as follows: 1) learning episodic features without supervision-for a class of objects without a prior knowledge, the key components, their spatial relations and cover regions can be learned automatically through a deep neural network (DNN); 2) learning semantic features based on episodic features-within the cover regions of the key components, the semantic geometrical values of these components can be computed based on contour detection; 3) forming the general knowledge of a class of objects-the general knowledge of a class of objects can be formed, mainly including the key components, their spatial relations and average semantic values, which is a concise description of the class; and 4) achieving higher level cognition and dynamic updating-for a test image, the model can achieve classification and subclass semantic descriptions. And the test samples with high confidence are selected to dynamically update the whole model. Experiments are conducted on face images, and a good performance is achieved in each layer of the DNN and the semantic description learning process. Furthermore, the model can be generalized to recognition tasks of other objects with learning ability.

Decreased levels of PSD95 and two associated proteins and increased levels of BCl2 and caspase 3 in hippocampus from subjects with amnestic mild cognitive impairment: Insights into their potential roles for loss of synapses and memory, accumulation of Abeta, and neurodegeneration in a prodromal stage of Alzheimer's disease.

PubMed

Sultana, Rukhsana; Banks, William A; Butterfield, D Allan

2010-02-15

Alzheimer's disease (AD) is the most common form of dementia and is pathologically characterized by senile plaques, neurofibrillary tangles, synaptic disruption and loss, and progressive neuronal deficits. The exact mechanism(s) of AD pathogenesis largely remain unknown. With advances in technology diagnosis of a pre-AD stage referred to as amnestic mild cognitive impairment (MCI) has become possible. Amnestic MCI is characterized clinically by memory deficit, but normal activities of daily living and no dementia. In the present study, compared to controls, we observed in hippocampus from subjects with MCI a significantly decreased level of PSD95, a key synaptic protein, and also decreased levels of two proteins associated with PSD95, the N-methyl-D-aspartate receptor, subunit 2A (NR2A) and the low-density lipoprotein receptor-1 (LRP1). PSD95 and NR2A are involved in long-term potentiation, a key component of memory formation, and LRP1 is involved in efflux of amyloid beta-peptide (1-42). Abeta (1-42) conceivably is critical to the pathogenesis of MCI and AD, including the oxidative stress under which brain in both conditions exist. The data obtained from the current study suggest a possible involvement of these proteins in synaptic alterations, apoptosis and consequent decrements in learning and memory associated with the progression of MCI to AD. Copyright 2009 Wiley-Liss, Inc.

78 FR 3081 - Petition for Exemption From the Federal Motor Vehicle Motor Theft Prevention Standard; Toyota

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-15

... receiver, electrical key and an electronic control module (ECM). The conventional key components consist of a transponder key ECU assembly, transponder key coil, security indicator, ignition key and an ECM... certification ECU and steering lock ECU receive confirmation of the valid key, allowing the ECM to start the...

Blood and bombs: the demand and use of blood following the London Bombings of 7 July 2005--a retrospective review.

PubMed

Glasgow, S M; Allard, S; Doughty, H; Spreadborough, P; Watkins, E

2012-08-01

Mass casualty events (MCE) present health systems with a sudden demand on key services. The overall objective of this study was to describe the experience of the National Blood Service (NBS) following the largest UK MCE in recent times. Data was collated from the NBS database and directly from the hospitals involved. All data was collected immediately following the event and included: all blood components requested, issued and transfused in relation to the bombings, blood stock levels at the time and the injury profiles of the casualties transfused. The total NBS order from hospitals for the event was 1455 units of blood components. All requests were fulfilled, this included: 978 units of red cells (RC), 36 doses of platelets, 141 units of fresh frozen plasma (FFP) and 300 doses of cryoprecipitate. The amount of blood ordered was three times that initially used and the total number of RC transfused in treating all victims from admission to discharge was approximately 440 units. The greatest use of blood components was for those casualties who had sustained traumatic amputations amongst their injury profile. Published data with which to compare these results is lacking, although the RC use was similar to the initial mean individual usage described in previous military and civilian bombings. The overall implication for any blood service remains, there is now likely to be a far greater demand for plasma, platelets and cryoprecipitate in any future incidents involving victims suffering major haemorrhage. © 2012 The Authors. Transfusion Medicine © 2012 British Blood Transfusion Society.

A Stakeholder-Based System Dynamics Model of Return-to-Work: A Research Protocol.

PubMed

Jetha, Arif; Pransky, Glenn; Fish, Jon; Jeffries, Susan; Hettinger, Lawrence J

2015-07-16

Returning to work following a job-related injury or illness can be a complex process, influenced by a range of interrelated personal, psychosocial, and organizational components. System dynamics modelling (SDM) takes a sociotechnical systems perspective to view return-to-work (RTW) as a system made up of multiple feedback relationships between influential components. To build the RTW SDM, a mixed-method approach will be used. The first stage, that has already been completed, involved creating a baseline model using key informant interviews. Second, in two manufacturing companies, stakeholder-based models will be developed through interviews and focus groups with senior management, frontline workers, and frontline supervisors. Participants will be asked about the RTW process in general and more targeted questions regarding influential components. Participants will also be led through a reference mode exercise where they will be asked to estimate the direction, shape and magnitude of relationships between influential components. Data will be entered into the software program Vensim that provides a platform for visualizing system-structure and simulating the effects of adapting components. Finally, preliminary model validity testing will be conducted to provide insights on model generalizability and sensitivity. The proposed methodology will create a SDM of the RTW process using feedback relationships of influential components. It will also provide an important simulation tool to understand system behaviour that underlies complex RTW cases, and examine anticipated and unanticipated consequences of disability management policies. Significance for public healthWhile the incidence of occupational injuries and illnesses has declined over the past two decades, the proportion resulting in sickness absence has actually increased. Implementing strategies to address sickness absences and promote return-to-work (RTW) can significantly benefit physical and mental health, and work outcomes like worker engagement, job satisfaction and job strain. As a key social determinant of health, participation in paid work can also ensure that work-disabled individuals generate income necessary for access to housing, education, food, and social services that also benefit health. Improving RTW outcomes can also have significant societal benefits such as a reduction in workers compensation costs, increased economic activity and less burden on social assistance programs. Despite its benefits, returning to work after injury or illness is not a straightforward process and can be complicated by the individual, psychosocial, organizational and regulatory components that influence a disabled person's ability to resume work activities.

Exploring the Conserved Role of MANF in the Unfolded Protein Response in Drosophila melanogaster

PubMed Central

Lindström, Riitta; Lindholm, Päivi; Kallijärvi, Jukka; Palgi, Mari; Saarma, Mart; Heino, Tapio I.

2016-01-01

Disturbances in the homeostasis of endoplasmic reticulum (ER) referred to as ER stress is involved in a variety of human diseases. ER stress activates unfolded protein response (UPR), a cellular mechanism the purpose of which is to restore ER homeostasis. Previous studies show that Mesencephalic Astrocyte-derived Neurotrophic Factor (MANF) is an important novel component in the regulation of UPR. In vertebrates, MANF is upregulated by ER stress and protects cells against ER stress-induced cell death. Biochemical studies have revealed an interaction between mammalian MANF and GRP78, the major ER chaperone promoting protein folding. In this study we discovered that the upregulation of MANF expression in response to drug-induced ER stress is conserved between Drosophila and mammals. Additionally, by using a genetic in vivo approach we found genetic interactions between Drosophila Manf and genes encoding for Drosophila homologues of GRP78, PERK and XBP1, the key components of UPR. Our data suggest a role for Manf in the regulation of Drosophila UPR. PMID:26975047

Protein and DNA Modifications: Evolutionary Imprints of Bacterial Biochemical Diversification and Geochemistry on the Provenance of Eukaryotic Epigenetics

PubMed Central

Aravind, L.; Burroughs, A. Maxwell; Zhang, Dapeng; Iyer, Lakshminarayan M.

2014-01-01

Epigenetic information, which plays a major role in eukaryotic biology, is transmitted by covalent modifications of nuclear proteins (e.g., histones) and DNA, along with poorly understood processes involving cytoplasmic/secreted proteins and RNAs. The origin of eukaryotes was accompanied by emergence of a highly developed biochemical apparatus for encoding, resetting, and reading covalent epigenetic marks in proteins such as histones and tubulins. The provenance of this apparatus remained unclear until recently. Developments in comparative genomics show that key components of eukaryotic epigenetics emerged as part of the extensive biochemical innovation of secondary metabolism and intergenomic/interorganismal conflict systems in prokaryotes, particularly bacteria. These supplied not only enzymatic components for encoding and removing epigenetic modifications, but also readers of some of these marks. Diversification of these prokaryotic systems and subsequently eukaryotic epigenetics appear to have been considerably influenced by the great oxygenation event in the Earth’s history. PMID:24984775

Protein and DNA modifications: evolutionary imprints of bacterial biochemical diversification and geochemistry on the provenance of eukaryotic epigenetics.

PubMed

Aravind, L; Burroughs, A Maxwell; Zhang, Dapeng; Iyer, Lakshminarayan M

2014-07-01

Epigenetic information, which plays a major role in eukaryotic biology, is transmitted by covalent modifications of nuclear proteins (e.g., histones) and DNA, along with poorly understood processes involving cytoplasmic/secreted proteins and RNAs. The origin of eukaryotes was accompanied by emergence of a highly developed biochemical apparatus for encoding, resetting, and reading covalent epigenetic marks in proteins such as histones and tubulins. The provenance of this apparatus remained unclear until recently. Developments in comparative genomics show that key components of eukaryotic epigenetics emerged as part of the extensive biochemical innovation of secondary metabolism and intergenomic/interorganismal conflict systems in prokaryotes, particularly bacteria. These supplied not only enzymatic components for encoding and removing epigenetic modifications, but also readers of some of these marks. Diversification of these prokaryotic systems and subsequently eukaryotic epigenetics appear to have been considerably influenced by the great oxygenation event in the Earth's history. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

Multivariate Associations of Fluid Intelligence and NAA.

PubMed

Nikolaidis, Aki; Baniqued, Pauline L; Kranz, Michael B; Scavuzzo, Claire J; Barbey, Aron K; Kramer, Arthur F; Larsen, Ryan J

2017-04-01

Understanding the neural and metabolic correlates of fluid intelligence not only aids scientists in characterizing cognitive processes involved in intelligence, but it also offers insight into intervention methods to improve fluid intelligence. Here we use magnetic resonance spectroscopic imaging (MRSI) to measure N-acetyl aspartate (NAA), a biochemical marker of neural energy production and efficiency. We use principal components analysis (PCA) to examine how the distribution of NAA in the frontal and parietal lobes relates to fluid intelligence. We find that a left lateralized frontal-parietal component predicts fluid intelligence, and it does so independently of brain size, another significant predictor of fluid intelligence. These results suggest that the left motor regions play a key role in the visualization and planning necessary for spatial cognition and reasoning, and we discuss these findings in the context of the Parieto-Frontal Integration Theory of intelligence. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Shoulder dystocia documentation: an evaluation of a documentation training intervention.

PubMed

LeRiche, Tammy; Oppenheimer, Lawrence; Caughey, Sharon; Fell, Deshayne; Walker, Mark

2015-03-01

To evaluate the quality and content of nurse and physician shoulder dystocia delivery documentation before and after MORE training in shoulder dystocia management skills and documentation. Approximately 384 charts at the Ottawa Hospital General Campus involving a diagnosis of shoulder dystocia between the years of 2000 and 2006 excluding the training year of 2003 were identified. The charts were evaluated for 14 key components derived from a validated instrument. The delivery notes were then scored based on these components by 2 separate investigators who were blinded to delivery note author, date, and patient identification to further quantify delivery record quality. Approximately 346 charts were reviewed for physician and nurse delivery documentation. The average score for physician notes was 6 (maximum possible score of 14) both before and after the training intervention. The nurses' average score was 5 before and after the training intervention. Negligible improvement was observed in the content and quality of shoulder dystocia documentation before and after nurse and physician training.

A comprehensive model of ion diffusion and charge exchange in the cold Io torus

NASA Technical Reports Server (NTRS)

Barbosa, D. D.; Moreno, M. A.

1988-01-01

A comprehensive analytic model of radial diffusion in the cold Io torus is developed. The model involves a generalized molecular cloud theory of SO2 and its dissociation fragments SO, O2, S, and O, which are formed at a relatively large rate by solar UV photodissociation of SO2. The key component of the new theory is SO, which can react with S(+) through a near-resonant charge exchange process that is exothermic. This provides a mechanism for the rapid depletion of singly ionized sulfur in the cold torus and can account for the large decrease in the total flux tube content inward of Io's orbit. The model is used to demonstrate quantitatively the effects of radial diffusion in a charge exchange environment that acts as a combined source and sink for ions in various charge states. A detailed quantitative explanation for the O(2+) component of the cold torus is given, and insight is derived into the workings of the so-called plasma 'ribbon'.

Exploiting the Gastric Epithelial Barrier: Helicobacter pylori's Attack on Tight and Adherens Junctions.

PubMed

Backert, Steffen; Schmidt, Thomas P; Harrer, Aileen; Wessler, Silja

2017-01-01

Highly organized intercellular tight and adherens junctions are crucial structural components for establishing and maintenance of epithelial barrier functions, which control the microbiota and protect against intruding pathogens in humans. Alterations in these complexes represent key events in the development and progression of multiple infectious diseases as well as various cancers. The gastric pathogen Helicobacter pylori exerts an amazing set of strategies to manipulate these epithelial cell-to-cell junctions, which are implicated in changing cell polarity, migration and invasive growth as well as pro-inflammatory and proliferative responses. This chapter focuses on the H. pylori pathogenicity factors VacA, CagA, HtrA and urease, and how they can induce host cell signaling involved in altering cell-to-cell permeability. We propose a stepwise model for how H. pylori targets components of tight and adherens junctions in order to disrupt the gastric epithelial cell layer, giving fresh insights into the pathogenesis of this important bacterium.

Laser-assisted manufacturing of super-insulation materials

NASA Astrophysics Data System (ADS)

Wang, Zhen; Zhang, Tao; Park, Byung Kyu; Lee, Woo Il; Hwang, David

2017-02-01

Being lightweight materials with good mechanical and thermal properties, hollow glass micro-particles (HGMPs) have been widely studied for multiple applications. In this study, it is shown that by using reduced binder fraction diluted in solvent, enables minimal contacts among the HGMPs assisted by a natural capillary trend, as confirmed by optical and electron microscope imaging. Such material architecture fabricated in a composite level proves to have enhanced thermal insulation performance through quantitative thermal conductivity measurement. Mechanical strength has also been evaluated in terms of particle-binder bonding by tensile test via in-situ microscope inspection. Effect of laser treatment was examined for further improvement of thermal and mechanical properties by selective binder removal and efficient redistribution of remaining binder components. The fabricated composite materials have potential applications to building insulation materials for their scalable manufacturing nature, improved thermal insulation performance and reasonable mechanical strength. Further studies are needed to understand mechanical and thermal properties of the resulting composites, and key fabrication mechanisms involved with laser treatment of complex multi-component and multi-phase systems.

Control of developmentally primed erythroid genes by combinatorial co-repressor actions

PubMed Central

Stadhouders, Ralph; Cico, Alba; Stephen, Tharshana; Thongjuea, Supat; Kolovos, Petros; Baymaz, H. Irem; Yu, Xiao; Demmers, Jeroen; Bezstarosti, Karel; Maas, Alex; Barroca, Vilma; Kockx, Christel; Ozgur, Zeliha; van Ijcken, Wilfred; Arcangeli, Marie-Laure; Andrieu-Soler, Charlotte; Lenhard, Boris; Grosveld, Frank; Soler, Eric

2015-01-01

How transcription factors (TFs) cooperate within large protein complexes to allow rapid modulation of gene expression during development is still largely unknown. Here we show that the key haematopoietic LIM-domain-binding protein-1 (LDB1) TF complex contains several activator and repressor components that together maintain an erythroid-specific gene expression programme primed for rapid activation until differentiation is induced. A combination of proteomics, functional genomics and in vivo studies presented here identifies known and novel co-repressors, most notably the ETO2 and IRF2BP2 proteins, involved in maintaining this primed state. The ETO2–IRF2BP2 axis, interacting with the NCOR1/SMRT co-repressor complex, suppresses the expression of the vast majority of archetypical erythroid genes and pathways until its decommissioning at the onset of terminal erythroid differentiation. Our experiments demonstrate that multimeric regulatory complexes feature a dynamic interplay between activating and repressing components that determines lineage-specific gene expression and cellular differentiation. PMID:26593974

A novel Hsp70 inhibitor prevents cell intoxication with the actin ADP-ribosylating Clostridium perfringens iota toxin

PubMed Central

Ernst, Katharina; Liebscher, Markus; Mathea, Sebastian; Granzhan, Anton; Schmid, Johannes; Popoff, Michel R.; Ihmels, Heiko; Barth, Holger; Schiene-Fischer, Cordelia

2016-01-01

Hsp70 family proteins are folding helper proteins involved in a wide variety of cellular pathways. Members of this family interact with key factors in signal transduction, transcription, cell-cycle control, and stress response. Here, we developed the first Hsp70 low molecular weight inhibitor specifically targeting the peptide binding site of human Hsp70. After demonstrating that the inhibitor modulates the Hsp70 function in the cell, we used the inhibitor to show for the first time that the stress-inducible chaperone Hsp70 functions as molecular component for entry of a bacterial protein toxin into mammalian cells. Pharmacological inhibition of Hsp70 protected cells from intoxication with the binary actin ADP-ribosylating iota toxin from Clostridium perfringens, the prototype of a family of enterotoxins from pathogenic Clostridia and inhibited translocation of its enzyme component across cell membranes into the cytosol. This finding offers a starting point for novel therapeutic strategies against certain bacterial toxins. PMID:26839186

Ranking of critical species to preserve the functionality of mutualistic networks using the k-core decomposition

PubMed Central

García-Algarra, Javier; Pastor, Juan Manuel; Iriondo, José María

2017-01-01

Background Network analysis has become a relevant approach to analyze cascading species extinctions resulting from perturbations on mutualistic interactions as a result of environmental change. In this context, it is essential to be able to point out key species, whose stability would prevent cascading extinctions, and the consequent loss of ecosystem function. In this study, we aim to explain how the k-core decomposition sheds light on the understanding the robustness of bipartite mutualistic networks. Methods We defined three k-magnitudes based on the k-core decomposition: k-radius, k-degree, and k-risk. The first one, k-radius, quantifies the distance from a node to the innermost shell of the partner guild, while k-degree provides a measure of centrality in the k-shell based decomposition. k-risk is a way to measure the vulnerability of a network to the loss of a particular species. Using these magnitudes we analyzed 89 mutualistic networks involving plant pollinators or seed dispersers. Two static extinction procedures were implemented in which k-degree and k-risk were compared against other commonly used ranking indexes, as for example MusRank, explained in detail in Material and Methods. Results When extinctions take place in both guilds, k-risk is the best ranking index if the goal is to identify the key species to preserve the giant component. When species are removed only in the primary class and cascading extinctions are measured in the secondary class, the most effective ranking index to identify the key species to preserve the giant component is k-degree. However, MusRank index was more effective when the goal is to identify the key species to preserve the greatest species richness in the second class. Discussion The k-core decomposition offers a new topological view of the structure of mutualistic networks. The new k-radius, k-degree and k-risk magnitudes take advantage of its properties and provide new insight into the structure of mutualistic networks. The k-risk and k-degree ranking indexes are especially effective approaches to identify key species to preserve when conservation practitioners focus on the preservation of ecosystem functionality over species richness. PMID:28533969

Ranking of critical species to preserve the functionality of mutualistic networks using the k-core decomposition.

PubMed

García-Algarra, Javier; Pastor, Juan Manuel; Iriondo, José María; Galeano, Javier

2017-01-01

Network analysis has become a relevant approach to analyze cascading species extinctions resulting from perturbations on mutualistic interactions as a result of environmental change. In this context, it is essential to be able to point out key species, whose stability would prevent cascading extinctions, and the consequent loss of ecosystem function. In this study, we aim to explain how the k -core decomposition sheds light on the understanding the robustness of bipartite mutualistic networks. We defined three k -magnitudes based on the k -core decomposition: k -radius, k -degree, and k -risk. The first one, k -radius, quantifies the distance from a node to the innermost shell of the partner guild, while k -degree provides a measure of centrality in the k -shell based decomposition. k -risk is a way to measure the vulnerability of a network to the loss of a particular species. Using these magnitudes we analyzed 89 mutualistic networks involving plant pollinators or seed dispersers. Two static extinction procedures were implemented in which k -degree and k -risk were compared against other commonly used ranking indexes, as for example MusRank, explained in detail in Material and Methods. When extinctions take place in both guilds, k -risk is the best ranking index if the goal is to identify the key species to preserve the giant component. When species are removed only in the primary class and cascading extinctions are measured in the secondary class, the most effective ranking index to identify the key species to preserve the giant component is k -degree. However, MusRank index was more effective when the goal is to identify the key species to preserve the greatest species richness in the second class. The k -core decomposition offers a new topological view of the structure of mutualistic networks. The new k -radius, k -degree and k -risk magnitudes take advantage of its properties and provide new insight into the structure of mutualistic networks. The k -risk and k -degree ranking indexes are especially effective approaches to identify key species to preserve when conservation practitioners focus on the preservation of ecosystem functionality over species richness.

Combinations of Response-Dependent and Response-Independent Schedule-Correlated Stimulus Presentation in an Observing Procedure

ERIC Educational Resources Information Center

DeFulio, Anthony; Hackenberg, Timothy D.

2008-01-01

Pigeons pecked a response key on a variable-interval (VI) schedule, in which responses produced food every 40 s, on average. These VI periods, or components, alternated in irregular fashion with extinction components in which food was unavailable. Pecks on a second (observing) key briefly produced exteroceptive stimuli (houselight flashes)…

Bacterial decolorization of textile dyes is an extracellular process requiring a multicomponent electron transfer pathway

PubMed Central

Brigé, Ann; Motte, Bart; Borloo, Jimmy; Buysschaert, Géraldine; Devreese, Bart; Van Beeumen, Jozef J.

2008-01-01

Summary Many studies have reported microorganisms as efficient biocatalysts for colour removal of dye‐containing industrial wastewaters. We present the first comprehensive study to identify all molecular components involved in decolorization by bacterial cells. Mutants from the model organism Shewanella oneidensis MR‐1, generated by random transposon and targeted insertional mutagenesis, were screened for defects in decolorization of an oxazine and diazo dye. We demonstrate that decolorization is an extracellular reduction process requiring a multicomponent electron transfer pathway that consists of cytoplasmic membrane, periplasmic and outer membrane components. The presence of melanin, a redox‐active molecule excreted by S. oneidensis, was shown to enhance the dye reduction rates. Menaquinones and the cytochrome CymA are the crucial cytoplasmic membrane components of the pathway, which then branches off via a network of periplasmic cytochromes to three outer membrane cytochromes. The key proteins of this network are MtrA and OmcB in the periplasm and outer membrane respectively. A model of the complete dye reduction pathway is proposed in which the dye molecules are reduced by the outer membrane cytochromes either directly or indirectly via melanin. PMID:21261820

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

Ramuhalli, Pradeep; Hirt, Evelyn H.; Coles, Garill A.

Advanced small modular reactors (AdvSMRs) can contribute to safe, sustainable, and carbon-neutral energy production. The economics of small reactors (including AdvSMRs) will be impacted by the reduced economy-of-scale savings when compared to traditional light water reactors. The most significant controllable element of the day-to-day costs involves operations and maintenance (O&M). Enhancing affordability of AdvSMRs through technologies that help control O&M costs will be critical to ensuring their practicality for wider deployment.A significant component of O&M costs is the management and mitigation of degradation of components due to their impact on planning maintenance activities and staffing levels. Technologies that help characterizemore » real-time risk of failure of key components are important in this context. Given the possibility of frequently changing AdvSMR plant configurations, approaches are needed to integrate three elements – advanced plant configuration information, equipment condition information, and risk monitors – to provide a measure of risk that is customized for each AdvSMR unit and support real-time decisions on O&M. This article describes an overview of ongoing research into diagnostics/prognostics and enhanced predictive risk monitors (ERM) for this purpose.« less

Emerging themes in heterotrimeric G-protein signaling in plants.

PubMed

Pandey, Sona; Vijayakumar, Anitha

2018-05-01

Heterotrimeric G-proteins are key signaling components involved during the regulation of a multitude of growth and developmental pathways in all eukaryotes. Although the core proteins (Gα, Gβ, Gγ subunits) and their basic biochemistries are conserved between plants and non-plant systems, seemingly different inherent properties of specific components, altered wirings of G-protein network architectures, and the presence of novel receptors and effector proteins make plant G-protein signaling mechanisms somewhat distinct from the well-established animal paradigm. G-protein research in plants is getting a lot of attention recently due to the emerging roles of these proteins in controlling many agronomically important traits. New findings on both canonical and novel G-protein components and their conserved and unique signaling mechanisms are expected to improve our understanding of this important module in affecting critical plant growth and development pathways and eventually their utilization to produce plants for the future needs. In this review, we briefly summarize what is currently known in plant G-protein research, describe new findings and how they are changing our perceptions of the field, and discuss important issues that still need to be addressed. Copyright © 2018 Elsevier B.V. All rights reserved.

Understanding Female Receiver Psychology in Reproductive Contexts.

PubMed

Lynch, Kathleen S

2017-10-01

Mate choice decision-making requires four components: sensory, cognitive, motivation, and salience. During the breeding season, the neural mechanisms underlying these components act in concert to radically transform the way a female perceives the social cues around her as well as the way in which cognitive and motivational processes influence her decision to respond to courting males. The role of each of these four components in mate choice responses will be discussed here as well as the brain regions involved in regulating each component. These components are not independent, modular systems. Instead, they are dependent on one another. This review will discuss the many ways in which these components interact and affect one another. The interaction of these components, however, ultimately leads back to a few key neuromodulators that thread motivation, sensory, salience, and cognitive components into a set of inter-dependent processes. These neuromodulators are estrogens and catecholamines. This review will highlight the need to understand estrogens in reproductive contexts not just as simply a 'sexual motivation modulator' or catecholamines as 'cognitive regulators' but as neuromodulators that work together to fully transform a non-breeding female into a completely reproductive female displaying: heightened sexual interest in courting males, greater arousal and selective attention toward courtship signals, improved signal detection and discrimination abilities, enhanced contextual signal memory, and increased motivation to respond to signals assigned incentive salience. The aim of this review is to build a foundation in which to understand the brain regions associated with cognitive, sensory, motivational, and signal salience not as independently acting systems but as a set of interacting processes that function together in a context-appropriate manner. © The Author 2017. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Photoperiod- and temperature-mediated control of phenology in trees - a molecular perspective.

PubMed

Singh, Rajesh Kumar; Svystun, Tetiana; AlDahmash, Badr; Jönsson, Anna Maria; Bhalerao, Rishikesh P

2017-01-01

Contents 511 I. 511 II. 512 III. 513 IV. 513 V. 517 VI. 517 VII. 521 VIII. 521 Acknowledgements 521 References 521 SUMMARY: Trees growing in boreal and temperate regions synchronize their growth with seasonal climatic changes in adaptive responses that are essential for their survival. These trees cease growth before the winter and establish a dormant state during which growth cessation is maintained by repression of responses to growth-promotive signals. Reactivation of growth in the spring follows the release from dormancy promoted by prolonged exposure to low temperature during the winter. The timing of the key events and regulation of the molecular programs associated with the key stages of the annual growth cycle are controlled by two main environmental cues: photoperiod and temperature. Recently, key components mediating photoperiodic control of growth cessation and bud set have been identified, and striking similarities have been observed in signaling pathways controlling growth cessation in trees and floral transition in Arabidopsis. Although less well understood, the regulation of bud dormancy and bud burst may involve cell-cell communication and chromatin remodeling. Here, we discuss current knowledge of the molecular-level regulation of the annual growth cycle of woody trees in temperate and boreal regions, and identify key questions that need to be addressed in the future. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Exploring how ward staff engage with the implementation of a patient safety intervention: a UK-based qualitative process evaluation

PubMed Central

Sheard, Laura; Marsh, Claire; O’Hara, Jane; Armitage, Gerry; Wright, John; Lawton, Rebecca

2017-01-01

Objectives A patient safety intervention was tested in a 33-ward randomised controlled trial. No statistically significant difference between intervention and control wards was found. We conducted a process evaluation of the trial and our aim in this paper is to understand staff engagement across the 17 intervention wards. Design Large qualitative process evaluation of the implementation of a patient safety intervention. Setting and participants National Health Service staff based on 17 acute hospital wards located at five hospital sites in the North of England. Data We concentrate on three sources here: (1) analysis of taped discussion between ward staff during action planning meetings; (2) facilitators’ field notes and (3) follow-up telephone interviews with staff focusing on whether action plans had been achieved. The analysis involved the use of pen portraits and adaptive theory. Findings First, there were palpable differences in the ways that the 17 ward teams engaged with the key components of the intervention. Five main engagement typologies were evident across the life course of the study: consistent, partial, increasing, decreasing and disengaged. Second, the intensity of support for the intervention at the level of the organisation does not predict the strength of engagement at the level of the individual ward team. Third, the standardisation of facilitative processes provided by the research team does not ensure that implementation standardisation of the intervention occurs by ward staff. Conclusions A dilution of the intervention occurred during the trial because wards engaged with Patient Reporting and Action for a Safe Environment (PRASE) in divergent ways, despite the standardisation of key components. Facilitative processes were not sufficiently adequate to enable intervention wards to successfully engage with PRASE components. PMID:28710206

Effects of prescribed fire in the coastal prairies of Texas

USGS Publications Warehouse

Grace, James B.; Allain, Larry K.; Baldwin, Heather Q.; Billock, Arlene G.; Eddleman, William R.; Given, Aaron M.; Jeske, Clint W.; Moss, Rebecca

2005-01-01

Prescribed fire is widely applied for habitat management in coastal ecosystems. Fire management plans typically list a variety of objectives for prescribed burning, including succession management, promotion of native flora and fauna, providing habitat for species of importance, wildfire risk reduction (fuels management), as well as reduction and/or prevention of invasive species. In most cases, the information needed to determine the degree to which management objectives are met is not available. This study sought to provide an assessment of key objectives of fire management at the U.S. Fish and Wildlife Service (USFWS) Texas Mid-coast National Wildlife Refuge Complex. The main purpose of this work was to provide information and recommendations that will support Region 2 of the USFWS in the conduct of their fire and habitat management activities in the Western Gulf coast region. There were four main components of this project: (1) a historical analysis of the role of fire in this ecosystem, (2) the development of standard methodology for assessing and monitoring fire effects in this system, (3) an evaluation of the effects of prescribed burning on the habitat being managed, and (4) an evaluation of the effects of burning on select fauna of special concern. A team of researchers, including some from the U.S. Geological Survey (USGS), Southeast Missouri State University, and Louisiana State University were involved in the various components of this project. Extensive support by USFWS personnel, both at the Texas Mid-coast National Wildlife Refuge Complex and in the Regional Office (Region 2, USFWS), was a key component in this work. Data from the three years of this study were combined with the results of previous USGS studies performed at the site to strengthen our conclusions.

Membrane lipid alterations in the metabolic syndrome and the role of dietary oils.

PubMed

Perona, Javier S

2017-09-01

The metabolic syndrome is a cluster of pathological conditions, including hypertension, hyperglycemia, hypertriglyceridemia, obesity and low HDL levels that is of great concern worldwide, as individuals with metabolic syndrome have an increased risk of type-2 diabetes and cardiovascular disease. Insulin resistance, the key feature of the metabolic syndrome, might be at the same time cause and consequence of impaired lipid composition in plasma membranes of insulin-sensitive tissues like liver, muscle and adipose tissue. Diet intervention has been proposed as a powerful tool to prevent the development of the metabolic syndrome, since healthy diets have been shown to have a protective role against the components of the metabolic syndrome. Particularly, dietary fatty acids are capable of modulating the deleterious effects of these conditions, among other mechanisms, by modifications of the lipid composition of the membranes in insulin-sensitive tissues. However, there is still scarce data based of high-level evidence on the effects of dietary oils on the effects of the metabolic syndrome and its components. This review summarizes the current knowledge on the effects of dietary oils on improving alterations of the components of the metabolic syndrome. It also examines their influence in the modulation of plasma membrane lipid composition and in the functionality of membrane proteins involved in insulin activity, like the insulin receptor, GLUT-4, CD36/FAT and ABCA-1, and their effect in the metabolism of glucose, fatty acids and cholesterol, and, in turn, the key features of the metabolic syndrome. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá. Copyright © 2017 Elsevier B.V. All rights reserved.

An Integrative Perspective on Interpersonal Coordination in Interactive Team Sports

PubMed Central

Steiner, Silvan; Macquet, Anne-Claire; Seiler, Roland

2017-01-01

Interpersonal coordination is a key factor in team performance. In interactive team sports, the limited predictability of a constantly changing context makes coordination challenging. Approaches that highlight the support provided by environmental information and theories of shared mental models provide potential explanations of how interpersonal coordination can nonetheless be established. In this article, we first outline the main assumptions of these approaches and consider criticisms that have been raised with regard to each. The aim of this article is to define a theoretical perspective that integrates the coordination mechanisms of the two approaches. In doing so, we borrow from a theoretical outline of group action. According to this outline, group action based on a priori shared mental models is an example of how interpersonal coordination is established from the top down. Interpersonal coordination in reaction to the perception of affordances represents the bottom-up component of group action. Both components are inextricably involved in the coordination of interactive sports teams. We further elaborate on the theoretical outline to integrate a third, constructivist approach. Integrating this third approach helps to explain interpersonal coordination in game situations for which no shared mental models are established and game situations that remain ambiguous in terms of perceived affordances. The article describes how hierarchical, sequential, and complex dimensions of action organization are important aspects of this constructivist perspective and how mental models may be involved. A basketball example is used to illustrate how top-down, bottom-up and constructivist processes may be simultaneously involved in enabling interpersonal coordination. Finally, we present the implications for research and practice. PMID:28894428

Trimethylamine and Trimethylamine N-Oxide, a Flavin-Containing Monooxygenase 3 (FMO3)-Mediated Host-Microbiome Metabolic Axis Implicated in Health and Disease

PubMed Central

Fennema, Diede; Phillips, Ian R.

2016-01-01

Flavin-containing monooxygenase 3 (FMO3) is known primarily as an enzyme involved in the metabolism of therapeutic drugs. On a daily basis, however, we are exposed to one of the most abundant substrates of the enzyme trimethylamine (TMA), which is released from various dietary components by the action of gut bacteria. FMO3 converts the odorous TMA to nonodorous TMA N-oxide (TMAO), which is excreted in urine. Impaired FMO3 activity gives rise to the inherited disorder primary trimethylaminuria (TMAU). Affected individuals cannot produce TMAO and, consequently, excrete large amounts of TMA. A dysbiosis in gut bacteria can give rise to secondary TMAU. Recently, there has been much interest in FMO3 and its catalytic product, TMAO, because TMAO has been implicated in various conditions affecting health, including cardiovascular disease, reverse cholesterol transport, and glucose and lipid homeostasis. In this review, we consider the dietary components that can give rise to TMA, the gut bacteria involved in the production of TMA from dietary precursors, the metabolic reactions by which bacteria produce and use TMA, and the enzymes that catalyze the reactions. Also included is information on bacteria that produce TMA in the oral cavity and vagina, two key microbiome niches that can influence health. Finally, we discuss the importance of the TMA/TMAO microbiome-host axis in health and disease, considering factors that affect bacterial production and host metabolism of TMA, the involvement of TMAO and FMO3 in disease, and the implications of the host-microbiome axis for management of TMAU. PMID:27190056

Research on criticality analysis method of CNC machine tools components under fault rate correlation

NASA Astrophysics Data System (ADS)

Gui-xiang, Shen; Xian-zhuo, Zhao; Zhang, Ying-zhi; Chen-yu, Han

2018-02-01

In order to determine the key components of CNC machine tools under fault rate correlation, a system component criticality analysis method is proposed. Based on the fault mechanism analysis, the component fault relation is determined, and the adjacency matrix is introduced to describe it. Then, the fault structure relation is hierarchical by using the interpretive structure model (ISM). Assuming that the impact of the fault obeys the Markov process, the fault association matrix is described and transformed, and the Pagerank algorithm is used to determine the relative influence values, combined component fault rate under time correlation can obtain comprehensive fault rate. Based on the fault mode frequency and fault influence, the criticality of the components under the fault rate correlation is determined, and the key components are determined to provide the correct basis for equationting the reliability assurance measures. Finally, taking machining centers as an example, the effectiveness of the method is verified.

Review of concrete biodeterioration in relation to nuclear waste.

PubMed

Turick, Charles E; Berry, Christopher J

2016-01-01

Storage of radioactive waste in concrete structures is a means of containing wastes and related radionuclides generated from nuclear operations in many countries. Previous efforts related to microbial impacts on concrete structures that are used to contain radioactive waste showed that microbial activity can play a significant role in the process of concrete degradation and ultimately structural deterioration. This literature review examines the research in this field and is focused on specific parameters that are applicable to modeling and prediction of the fate of concrete structures used to store or dispose of radioactive waste. Rates of concrete biodegradation vary with the environmental conditions, illustrating a need to understand the bioavailability of key compounds involved in microbial activity. Specific parameters require pH and osmotic pressure to be within a certain range to allow for microbial growth as well as the availability and abundance of energy sources such as components involved in sulfur, iron and nitrogen oxidation. Carbon flow and availability are also factors to consider in predicting concrete biodegradation. The microbial contribution to degradation of the concrete structures containing radioactive waste is a constant possibility. The rate and degree of concrete biodegradation is dependent on numerous physical, chemical and biological parameters. Parameters to focus on for modeling activities and possible options for mitigation that would minimize concrete biodegradation are discussed and include key conditions that drive microbial activity on concrete surfaces. Copyright © 2015. Published by Elsevier Ltd.

An accurate empirical method to predict the adsorption strength for π-orbital contained molecules on two dimensional materials.

PubMed

Li, Hongping; Wang, Changwei; Xun, Suhang; He, Jing; Jiang, Wei; Zhang, Ming; Zhu, Wenshuai; Li, Huaming

2018-06-01

To obtain the adsorption strength is the key point for materials design and parameters optimization in chemical engineering. Here we report a simple but accuracy method to estimate the adsorptive energies by counting the number of π-orbital involved atoms based on theoretical computations for hexagonal boron nitride (h-BN) and graphene. Computational results by density function theory (DFT) as well as spin-component scaled second-order Møller-Plesset perturbation theory (SCS-MP2) both confirm that the adsorptive energies correlate well with the number of π-orbital involved atoms for π-orbital contained molecules. The selected molecules (adsorbates) are commonly used in chemical industry, which contains C, N, S, O atoms. The predicted results for the proposed formulas agree well with the current and previous DFT calculated values both on h-BN and graphene surfaces. Further, it can be also used to predict the adsorptive energies for small π-orbital contained molecules on BN and carbon nanotubes. The interaction type for these adsorptions is typical π-π interaction. Further investigations show that the physical origin of these interactions source from the polar interactions between the adsorbents and adsorbates. Hence, for separation or removal of aromatic molecules, how to modify the aromaticity and polarity of both adsorbents and adsorbates will be the key points for experiments. Copyright © 2018 Elsevier Inc. All rights reserved.

Programmed Cell Death During Caenorhabditis elegans Development

PubMed Central

Conradt, Barbara; Wu, Yi-Chun; Xue, Ding

2016-01-01

Programmed cell death is an integral component of Caenorhabditis elegans development. Genetic and reverse genetic studies in C. elegans have led to the identification of many genes and conserved cell death pathways that are important for the specification of which cells should live or die, the activation of the suicide program, and the dismantling and removal of dying cells. Molecular, cell biological, and biochemical studies have revealed the underlying mechanisms that control these three phases of programmed cell death. In particular, the interplay of transcriptional regulatory cascades and networks involving multiple transcriptional regulators is crucial in activating the expression of the key death-inducing gene egl-1 and, in some cases, the ced-3 gene in cells destined to die. A protein interaction cascade involving EGL-1, CED-9, CED-4, and CED-3 results in the activation of the key cell death protease CED-3, which is tightly controlled by multiple positive and negative regulators. The activation of the CED-3 caspase then initiates the cell disassembly process by cleaving and activating or inactivating crucial CED-3 substrates; leading to activation of multiple cell death execution events, including nuclear DNA fragmentation, mitochondrial elimination, phosphatidylserine externalization, inactivation of survival signals, and clearance of apoptotic cells. Further studies of programmed cell death in C. elegans will continue to advance our understanding of how programmed cell death is regulated, activated, and executed in general. PMID:27516615

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

Hamann, Thomas

Dye-sensitized solar cells (DSSCs) have attracted a lot of interest as they proffer the possibility of extremely inexpensive and efficient solar energy conversion. The excellent performance of the most efficient DSSCs relies on two main features: 1) a high surface area nanoparticle semiconductor photoanode to allow for excellent light absorption with moderate extinction molecular dyes and 2) slow recombination rates from the photoanode to I 3 - allowing good charge collection. The I 3 -/I - couple, however, has some disadvantages, notably the redox potential limits the maximum open-circuit voltage, and the dye regeneration requires a large driving force whichmore » constrains the light harvesting ability. Thus, the design features that allow DSSCs to perform as well as they do also prevent further significant improvements in performance. As a consequence, the most efficient device configuration, and the maximum efficiency, has remained essentially unchanged over the last 16 years. Significant gains in performance are possible; however it will likely require a substantial paradigm shift. The general goal of this project is to understand the fundamental role of dye-sensitized solar cell, DSSC, components (sensitizer, redox shuttle, and photoanode) involved in key processes in order to overcome the kinetic and energetic constraints of current generation DSSCs. For example, the key to achieving high energy conversion efficiency DSSCs is the realization of a redox shuttle which fulfills the dual requirements of 1) efficient dye regeneration with a minimal driving force and 2) efficient charge collection. In current generation DSSCs, however, only one or the other of these requirements is met. We are currently primarily interested in understanding the physical underpinnings of the regeneration and recombination reactions. Our approach is to systematically vary the components involved in reactions and interrogate them with a series of photoelectrochemical (PEC) measurements. The lessons learned will ultimately be used to develop design rules for next generation DSSCs.« less

Review of Concrete Biodeterioration in Relation to Buried Nuclear Waste

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

Turick, C; Berry, C.

Long-term storage of low level radioactive material in below ground concrete disposal units (DUs) (Saltstone Disposal Facility) is a means of depositing wastes generated from nuclear operations of the U.S. Department of Energy. Based on the currently modeled degradation mechanisms, possible microbial induced effects on the structural integrity of buried low level wastes must be addressed. Previous international efforts related to microbial impacts on concrete structures that house low level radioactive waste showed that microbial activity can play a significant role in the process of concrete degradation and ultimately structural deterioration. This literature review examines the recent research in thismore » field and is focused on specific parameters that are applicable to modeling and prediction of the fate of concrete vaults housing stored wastes and the wastes themselves. Rates of concrete biodegradation vary with the environmental conditions, illustrating a need to understand the bioavailability of key compounds involved in microbial activity. Specific parameters require pH and osmotic pressure to be within a certain range to allow for microbial growth as well as the availability and abundance of energy sources like components involved in sulfur, iron and nitrogen oxidation. Carbon flow and availability are also factors to consider in predicting concrete biodegradation. The results of this review suggest that microbial activity in Saltstone, (grouted low level radioactive waste) is unlikely due to very high pH and osmotic pressure. Biodegradation of the concrete vaults housing the radioactive waste however, is a possibility. The rate and degree of concrete biodegradation is dependent on numerous physical, chemical and biological parameters. Results from this review point to parameters to focus on for modeling activities and also, possible options for mitigation that would minimize concrete biodegradation. In addition, key chemical components that drive microbial activity on concrete surfaces are discussed.« less

Proteomic identification of OsCYP2, a rice cyclophilin that confers salt tolerance in rice (Oryza sativa L.) seedlings when overexpressed

PubMed Central

2011-01-01

Background High Salinity is a major environmental stress influencing growth and development of rice. Comparative proteomic analysis of hybrid rice shoot proteins from Shanyou 10 seedlings, a salt-tolerant hybrid variety, and Liangyoupeijiu seedlings, a salt-sensitive hybrid variety, was performed to identify new components involved in salt-stress signaling. Results Phenotypic analysis of one protein that was upregulated during salt-induced stress, cyclophilin 2 (OsCYP2), indicated that OsCYP2 transgenic rice seedlings had better tolerance to salt stress than did wild-type seedlings. Interestingly, wild-type seedlings exhibited a marked reduction in maximal photochemical efficiency under salt stress, whereas no such change was observed for OsCYP2-transgenic seedlings. OsCYP2-transgenic seedlings had lower levels of lipid peroxidation products and higher activities of antioxidant enzymes than wild-type seedlings. Spatiotemporal expression analysis of OsCYP2 showed that it could be induced by salt stress in both Shanyou 10 and Liangyoupeijiu seedlings, but Shanyou 10 seedlings showed higher OsCYP2 expression levels. Moreover, circadian rhythm expression of OsCYP2 in Shanyou 10 seedlings occurred earlier than in Liangyoupeijiu seedlings. Treatment with PEG, heat, or ABA induced OsCYP2 expression in Shanyou 10 seedlings but inhibited its expression in Liangyoupeijiu seedlings. Cold stress inhibited OsCYP2 expression in Shanyou 10 and Liangyoupeijiu seedlings. In addition, OsCYP2 was strongly expressed in shoots but rarely in roots in two rice hybrid varieties. Conclusions Together, these data suggest that OsCYP2 may act as a key regulator that controls ROS level by modulating activities of antioxidant enzymes at translation level. OsCYP2 expression is not only induced by salt stress, but also regulated by circadian rhythm. Moreover, OsCYP2 is also likely to act as a key component that is involved in signal pathways of other types of stresses-PEG, heat, cold, or ABA. PMID:21324151

Spatial and temporal regulation of the metabolism of reactive oxygen and nitrogen species during the early development of pepper (Capsicum annuum) seedlings

PubMed Central

Airaki, Morad; Leterrier, Marina; Valderrama, Raquel; Chaki, Mounira; Begara-Morales, Juan C.; Barroso, Juan B.; del Río, Luis A.; Palma, José M.; Corpas, Francisco J.

2015-01-01

Background and Aims The development of seedlings involves many morphological, physiological and biochemical processes, which are controlled by many factors. Some reactive oxygen and nitrogen species (ROS and RNS, respectively) are implicated as signal molecules in physiological and phytopathological processes. Pepper (Capsicum annuum) is a very important crop and the goal of this work was to provide a framework of the behaviour of the key elements in the metabolism of ROS and RNS in the main organs of pepper during its development. Methods The main seedling organs (roots, hypocotyls and green cotyledons) of pepper seedlings were analysed 7, 10 and 14 d after germination. Activity and gene expression of the main enzymatic antioxidants (catalase, ascorbate–glutathione cycle enzymes), NADP-generating dehydrogenases and S-nitrosoglutathione reductase were determined. Cellular distribution of nitric oxide (·NO), superoxide radical (O2·–) and peroxynitrite (ONOO–) was investigated using confocal laser scanning microscopy. Key Results The metabolism of ROS and RNS during pepper seedling development was highly regulated and showed significant plasticity, which was co-ordinated among the main seedling organs, resulting in correct development. Catalase showed higher activity in the aerial parts of the seedling (hypocotyls and green cotyledons) whereas roots of 7-d-old seedlings contained higher activity of the enzymatic components of the ascorbate glutathione cycle, NADP-isocitrate dehydrogenase and NADP-malic enzyme. Conclusions There is differential regulation of the metabolism of ROS, nitric oxide and NADP dehydrogenases in the different plant organs during seedling development in pepper in the absence of stress. The metabolism of ROS and RNS seems to contribute significantly to plant development since their components are involved directly or indirectly in many metabolic pathways. Thus, specific molecules such as H2O2 and NO have implications for signalling, and their temporal and spatial regulation contributes to the success of seedling establishment. PMID:25808658

Electronic Voting Protocol Using Identity-Based Cryptography.

PubMed

Gallegos-Garcia, Gina; Tapia-Recillas, Horacio

2015-01-01

Electronic voting protocols proposed to date meet their properties based on Public Key Cryptography (PKC), which offers high flexibility through key agreement protocols and authentication mechanisms. However, when PKC is used, it is necessary to implement Certification Authority (CA) to provide certificates which bind public keys to entities and enable verification of such public key bindings. Consequently, the components of the protocol increase notably. An alternative is to use Identity-Based Encryption (IBE). With this kind of cryptography, it is possible to have all the benefits offered by PKC, without neither the need of certificates nor all the core components of a Public Key Infrastructure (PKI). Considering the aforementioned, in this paper we propose an electronic voting protocol, which meets the privacy and robustness properties by using bilinear maps.

Electronic Voting Protocol Using Identity-Based Cryptography

PubMed Central

Gallegos-Garcia, Gina; Tapia-Recillas, Horacio

2015-01-01

Electronic voting protocols proposed to date meet their properties based on Public Key Cryptography (PKC), which offers high flexibility through key agreement protocols and authentication mechanisms. However, when PKC is used, it is necessary to implement Certification Authority (CA) to provide certificates which bind public keys to entities and enable verification of such public key bindings. Consequently, the components of the protocol increase notably. An alternative is to use Identity-Based Encryption (IBE). With this kind of cryptography, it is possible to have all the benefits offered by PKC, without neither the need of certificates nor all the core components of a Public Key Infrastructure (PKI). Considering the aforementioned, in this paper we propose an electronic voting protocol, which meets the privacy and robustness properties by using bilinear maps. PMID:26090515

Innovative Educational Restructuring for America 2000: Time To Bury Political Bureaucracies and Begin Systematic Assessment, Profiling & Technological Improvement of School Organizations.

ERIC Educational Resources Information Center

Packard, Richard D.; Dereshiwsky, Mary I.

Despite current interest with the concept of the "New American School" model discussed in "America 2000," school systems continue to approach educational reform and restructuring by tinkering with key organizational components in isolation. The total school organization requires assessment and profiling to determine which key components are drags…

[Testing method research for key performance indicator of imaging acousto-optic tunable filter (AOTF)].

PubMed

Hu, Shan-Zhou; Chen, Fen-Fei; Zeng, Li-Bo; Wu, Qiong-Shui

2013-01-01

Imaging AOTF is an important optical filter component for new spectral imaging instruments developed in recent years. The principle of imaging AOTF component was demonstrated, and a set of testing methods for some key performances were studied, such as diffraction efficiency, wavelength shift with temperature, homogeneity in space for diffraction efficiency, imaging shift, etc.

Does grazing of cover crops impact biologically active soil C and N fractions under inversion and no tillage management

USDA-ARS?s Scientific Manuscript database

Cover crops are a key component of conservation cropping systems. They can also be a key component of integrated crop-livestock systems by offering high-quality forage during short periods between cash crops. The impact of cattle grazing on biologically active soil C and N fractions has not receiv...

Gender-Mainstreaming in Technical and Vocational Education and Training

NASA Astrophysics Data System (ADS)

Nurhaeni, I. D. A.; Kurniawan, Y.

2018-02-01

Gender differences should be considered in vocational high schools so women and men can develop their potentials without being inhibited by gender bias. Gender mainstreaming in vocational high schools is a strategy to integrate gender differences at all stages in teaching-learning process for achieving gender equality and equity. This research evaluates the implementation of gender mainstreaming in vocational high schools consisting of seven key components of gender mainstreaming. Four vocational high schools in Sragen Regency Indonesia have been purposively selected. The data were obtained through in-depth interviews and documentation studies. The data were analyzed using Kabeer’s model of gender analysis. The findings show that not all key components of gender mainstreaming have been implemented in vocational high schools. Most vocational high schools have implemented three of seven key components of gender mainstreaming, namely political will and leadership, policy framework and gender statistics. Meanwhile four of seven key components of gender mainstreaming, namely structure and mechanism, resources, infra structures and civil society have not been well-implemented. In conclusion gender mainstreaming has not been implemented effectively in vocational high schools. Accordingly, the government’s education office should continue to encourage and publish guidelines on the implementation of gender-mainstreaming in vocational high schools.

Fire ant venom alkaloids act as key attractants for the parasitic phorid fly, Pseudacteon tricuspis (Diptera: Phoridae).

PubMed

Chen, Li; Sharma, Kavita R; Fadamiro, Henry Y

2009-12-01

The phorid fly, Pseudacteon tricuspis Borgmeier, is an introduced parasitoid of imported fire ants, Solenopsis spp., in the USA. Although the assumption that phorid flies use fire ant alarm pheromones for host location is probably true, we demonstrated in a previous study the possible involvement of other ant semiochemicals in the response of P. tricuspis to fire ants. This study was conducted to determine the glandular sources and identity of the semiochemicals mediating this interaction. First, we tested the electroantennogram response of P. tricuspis to extracts of key body parts and glands of workers of the red imported fire ant, S. invicta Buren. The results confirm that the poison (venom) gland/sac is the key source of compounds which elicited strong antennal activity in P. tricuspis. Follow-up studies were conducted by using a combination of bioassay-guided fractionation and behavioral bioassays to test the hypothesis that attraction of this parasitoid to fire ants is mediated by venom alkaloids. The results confirm the response of P. tricuspis to physiologically relevant amounts of the two venom alkaloid fractions (cis and trans alkaloid fractions) of S. invicta. Further analysis by coupled gas chromatography-electroantennogram detection revealed nine venom alkaloid components including two novel 2,6-dialkylpiperideines that elicited significant antennal activity in P. tricuspis. This is the first demonstration of the role of venom alkaloids of ants as attractants for their natural enemies. We propose a semiochemical-mediated host location mechanism for P. tricuspis involving both alarm pheromones and venom alkaloids. The ecological significance of these findings, including the attraction of male P. tricuspis to fire ant venom alkaloids, possibly for mate location, is discussed.

WRKY transcription factors: key components in abscisic acid signalling.

PubMed

Rushton, Deena L; Tripathi, Prateek; Rabara, Roel C; Lin, Jun; Ringler, Patricia; Boken, Ashley K; Langum, Tanner J; Smidt, Lucas; Boomsma, Darius D; Emme, Nicholas J; Chen, Xianfeng; Finer, John J; Shen, Qingxi J; Rushton, Paul J

2012-01-01

WRKY transcription factors (TFs) are key regulators of many plant processes, including the responses to biotic and abiotic stresses, senescence, seed dormancy and seed germination. For over 15 years, limited evidence has been available suggesting that WRKY TFs may play roles in regulating plant responses to the phytohormone abscisic acid (ABA), notably some WRKY TFs are ABA-inducible repressors of seed germination. However, the roles of WRKY TFs in other aspects of ABA signalling, and the mechanisms involved, have remained unclear. Recent significant progress in ABA research has now placed specific WRKY TFs firmly in ABA-responsive signalling pathways, where they act at multiple levels. In Arabidopsis, WRKY TFs appear to act downstream of at least two ABA receptors: the cytoplasmic PYR/PYL/RCAR-protein phosphatase 2C-ABA complex and the chloroplast envelope-located ABAR-ABA complex. In vivo and in vitro promoter-binding studies show that the target genes for WRKY TFs that are involved in ABA signalling include well-known ABA-responsive genes such as ABF2, ABF4, ABI4, ABI5, MYB2, DREB1a, DREB2a and RAB18. Additional well-characterized stress-inducible genes such as RD29A and COR47 are also found in signalling pathways downstream of WRKY TFs. These new insights also reveal that some WRKY TFs are positive regulators of ABA-mediated stomatal closure and hence drought responses. Conversely, many WRKY TFs are negative regulators of seed germination, and controlling seed germination appears a common function of a subset of WRKY TFs in flowering plants. Taken together, these new data demonstrate that WRKY TFs are key nodes in ABA-responsive signalling networks. © 2011 The Authors. Plant Biotechnology Journal © 2011 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

Oligomeric status of the dihydropyridine receptor in aged skeletal muscle.

PubMed

Ryan, M; Carlson, B M; Ohlendieck, K

2000-10-01

A prominent feature of aging is represented by a decrease in muscle mass and strength. Abnormalities in Ca2+ -regulatory membrane complexes are involved in many muscular disorders. In analogy, we determined potential age-related changes in a key component of excitation-contraction coupling, the dihydropyridine receptor. Immunoblotting of the microsomal fraction from aged rabbit muscle revealed a drastic decline in the voltage-sensing alpha1-subunit of this transverse-tubular receptor, but only marginally altered expression of its auxiliary alpha(2)-subunit and the Na+/K+ -ATPase. A shift to slower fibre type characteristics was indicated by an age-related increase in the slow calsequestrin isoform. Chemical crosslinking analysis showed that the triad receptor complex has a comparable tendency of protein-protein interactions in young and aged muscles. Hence, a reduced expression and not modified oligomerization of the principal dihydropyridine receptor subunit might be involved in triggering impaired triadic signal transduction and abnormal Ca2+ -homeostasis resulting in a progressive functional decline of skeletal muscles. Copyright 2001 Academic Press.

The cyanobacterial bicarbonate transporter BicA: its physiological role and the implications of structural similarities with human SLC26 transporters.

PubMed

Price, G Dean; Howitt, Susan M

2011-04-01

The cyanobacterial Na+-dependent HCO3- transporter BicA is a member of the ubiquitous and important SulP/SLC26 family of anion transporters found in eukaryotes and prokaryotes. BicA is an important component of the cyanobacterial CO2 concentrating mechanism, an adaptation that contributes to cyanobacteria being able to achieve an estimated 25% of global primary productivity, largely in the oceans. The human SLC26 members are involved in a range of key cellular functions involving a diverse range of anion transport activities including Cl-/HCO3-, I-/HCO3-, and SO42-/HCO3- exchange; mutations in SLC26 members are known to be associated with debilitating diseases such as Pendred syndrome, chondrodysplasias, and congenital chloride diarrhoea. We have recently experimentally determined the membrane topology of BicA using the phoA-lacZ reporter system and here consider some of the extrapolated implications for topology of the human SLC26 family and the Sultr plant sulphate transporters.

NADPH-generating systems in bacteria and archaea

PubMed Central

Spaans, Sebastiaan K.; Weusthuis, Ruud A.; van der Oost, John; Kengen, Servé W. M.

2015-01-01

Reduced nicotinamide adenine dinucleotide phosphate (NADPH) is an essential electron donor in all organisms. It provides the reducing power that drives numerous anabolic reactions, including those responsible for the biosynthesis of all major cell components and many products in biotechnology. The efficient synthesis of many of these products, however, is limited by the rate of NADPH regeneration. Hence, a thorough understanding of the reactions involved in the generation of NADPH is required to increase its turnover through rational strain improvement. Traditionally, the main engineering targets for increasing NADPH availability have included the dehydrogenase reactions of the oxidative pentose phosphate pathway and the isocitrate dehydrogenase step of the tricarboxylic acid (TCA) cycle. However, the importance of alternative NADPH-generating reactions has recently become evident. In the current review, the major canonical and non-canonical reactions involved in the production and regeneration of NADPH in prokaryotes are described, and their key enzymes are discussed. In addition, an overview of how different enzymes have been applied to increase NADPH availability and thereby enhance productivity is provided. PMID:26284036

SNAP-25 requirement for dendritic growth of hippocampal neurons.

PubMed

Grosse, G; Grosse, J; Tapp, R; Kuchinke, J; Gorsleben, M; Fetter, I; Höhne-Zell, B; Gratzl, M; Bergmann, M

1999-06-01

Structure and dimension of the dendritic arbor are important determinants of information processing by the nerve cell, but mechanisms and molecules involved in dendritic growth are essentially unknown. We investigated early mechanisms of dendritic growth using mouse fetal hippocampal neurons in primary culture, which form processes during the first week in vitro. We detected a key component of regulated exocytosis, SNAP-25 (synaptosomal associated protein of 25 kDa), in axons and axonal terminals as well as in dendrites identified by the occurrence of the dendritic markers transferrin receptor and MAP2. Selective inactivation of SNAP-25 by botulinum neurotoxin A (BoNTA) resulted in inhibition of axonal growth and of vesicle recycling in axonal terminals. In addition, dendritic growth of hippocampal pyramidal and granule neurons was significantly inhibited by BoNTA. In contrast, cleavage of synaptobrevin by tetanus toxin had an effect on neither axonal nor dendritic growth. Our observations indicate that SNAP-25, but not synaptobrevin, is involved in constitutive axonal growth and dendrite formation by hippocampal neurons.

The mirror neuron system and the strange case of Broca's area.

PubMed

Cerri, Gabriella; Cabinio, Monia; Blasi, Valeria; Borroni, Paola; Iadanza, Antonella; Fava, Enrica; Fornia, Luca; Ferpozzi, Valentina; Riva, Marco; Casarotti, Alessandra; Martinelli Boneschi, Filippo; Falini, Andrea; Bello, Lorenzo

2015-03-01

Mirror neurons, originally described in the monkey premotor area F5, are embedded in a frontoparietal network for action execution and observation. A similar Mirror Neuron System (MNS) exists in humans, including precentral gyrus, inferior parietal lobule, and superior temporal sulcus. Controversial is the inclusion of Broca's area, as homologous to F5, a relevant issue in light of the mirror hypothesis of language evolution, which postulates a key role of Broca's area in action/speech perception/production. We assess "mirror" properties of this area by combining neuroimaging and intraoperative neurophysiological techniques. Our results show that Broca's area is minimally involved in action observation and has no motor output on hand or phonoarticulatory muscles, challenging its inclusion in the MNS. The presence of these functions in premotor BA6 makes this area the likely homologue of F5 suggesting that the MNS may be involved in the representation of articulatory rather than semantic components of speech. © 2014 Wiley Periodicals, Inc.

Molecular Pathways: Hippo Signaling, a Critical Tumor Suppressor.

PubMed

Sebio, Ana; Lenz, Heinz-Josef

2015-11-15

The Salvador-Warts-Hippo pathway controls cell fate and tissue growth. The main function of the Hippo pathway is to prevent YAP and TAZ translocation to the nucleus where they induce the transcription of genes involved in cell proliferation, survival, and stem cell maintenance. Hippo signaling is, thus, a complex tumor suppressor, and its deregulation is a key feature in many cancers. Recent mounting evidence suggests that the overexpression of Hippo components can be useful prognostic biomarkers. Moreover, Hippo signaling appears to be intimately linked to some of the most important signaling pathways involved in cancer development and progression. A better understanding of the Hippo pathway is thus essential to untangle tumor biology and to develop novel anticancer therapies. Here, we comment on the progress made in understanding Hippo signaling and its connections, and also on how new drugs modulating this pathway, such as Verteporfin and C19, are highly promising cancer therapeutics. ©2015 American Association for Cancer Research.

Regulation of body growth by microRNAs.

PubMed

Lui, Julian C

2017-11-15

Regulation of body growth remains a fascinating and unresolved biological mystery. One key component of body growth is skeletal and longitudinal bone growth. Children grow taller because their bones grew longer, and the predominant driver of longitudinal bone growth is a cartilaginous structure found near the ends of long bone named the growth plate. Numerous recent studies have started to unveil the importance of microRNAs in regulation of growth plate functions, therefore contributing to regulation of linear growth. In addition to longitudinal growth, other organs in our body need to increase in size and cell number as we grow, and the regulation of organ growth involves both systemic factors like hormones; and other intrinsic mechanisms, which we are just beginning to understand. This review aims to summarize some recent important findings on how microRNAs are involved in both of these processes: the regulation of longitudinal bone growth, and the regulation of organs and overall body growth. Published by Elsevier B.V.

Mechanisms for eco-immunity in a changing enviroment: how does the coral innate immune system contend with climate change?

NASA Astrophysics Data System (ADS)

Traylor-Knowles, N. G.

2016-02-01

Innate immunity plays a central role in maintaining homeostasis, and within the context of impending climate change scenarios, understanding how this system works is critical. However, the actual mechanisms involved in the evolution of the innate immune system are largely unknown. Cnidaria (including corals, sea anemones and jellyfish) are well suited for studying the fundamental functions of innate immunity because they share a common ancestor with bilaterians. This study will highlight the transcriptomic changes during a heat shock in the coral Acropora hyacinthus of American Samoa, examining the temporal changes, every half an hour for 5 hours. We hypothesize that genes involved in innate immunity, and extracellular matrix maintenance will be key components to the heat stress response. This presentation will highlight the novel role of the tumor necrosis factor receptor gene family as a responder to heat stress and present future directions for this developing field in coral reef research.

[Micro and Macro Social Work Practice in the Context of Tuberculosis].

PubMed

Moya, Eva M; Chavez-Baray, Silvia M; Martínez, Omar

2017-07-01

The study of tuberculosis (TB) in the U.S.-Mexico border involves the consideration of three key components, which are complex and interrelated: the difficulty tracking and providing appropriate TB care due to the epidemiological and pathological characteristics of TB; the border itself is a geographical and epidemiological area that interweaves two nations, two cultures, two health systems and different laws; and the need for prevention and treatment approaches to TB that involve comprehensive clinical care and prevention while also taking into consideration stigma, social context and knowledge. This manuscript describes the work of ten studies conducted in Mexico and in the U.S.-Mexico border region from 2006 to 2013. It also provides an understanding of the social and public health implications of TB, the environment and communities, as well as the identification and application of advocacy and social mobilization practices. The work presented provides an understanding of different interventions related to adherence, stigma reduction, person-centered approaches, and effective micro and macro practices in social work.

Myelin basic protein stimulates plasminogen activation via tissue plasminogen activator following binding to independent l-lysine-containing domains.

PubMed

Gonzalez-Gronow, Mario; Fiedler, Jenny L; Farias Gomez, Cristian; Wang, Fang; Ray, Rupa; Ferrell, Paul D; Pizzo, Salvatore V

2017-08-26

Myelin basic protein (MBP) is a key component of myelin, the specialized lipid membrane that encases the axons of all neurons. Both plasminogen (Pg) and tissue-type plasminogen activator (t-PA) bind to MBP with high affinity. We investigated the kinetics and mechanisms involved in this process using immobilized MBP and found that Pg activation by t-PA is significantly stimulated by MBP. This mechanism involves the binding of t-PA via a lysine-dependent mechanism to the Lys 91 residue of the MBP NH 2 -terminal region Asp 82 -Pro 99 , and the binding of Pg via a lysine-dependent mechanism to the Lys 122 residue of the MBP COOH-terminal region Leu 109 -Gly 126 . In this context, MBP mimics fibrin and because MBP is a plasmin substrate, our results suggest direct participation of the Pg activation system on MBP physiology. Copyright © 2017 Elsevier Inc. All rights reserved.

User involvement: children's participation in a parent-baby group.

PubMed

Maconochie, Heloise; McNeill, Fiona

2010-08-01

According to the National Service Framework, children have a right to participate in the development of healthcare services and yet research suggests that young children are at risk of exclusion from user involvement initiatives. This paper outlines the findings of a participatory action research project conducted with families attending a health visitors' parent-baby group. A combination of participatory research methods were used to ascertain the infants' perspectives of the service and this led to a number of changes in terms of professional attitudes, service provision and working practices. Changes in professional attitudes included acknowledging the importance of social interaction to the children, recognising young children's views as embodied and produced within social interactions, and respecting children as active contributors and not simply as passive recipients of healthcare services. Changes in service provision resulted in redistributing resources, structures and spaces to take account of children's perspectives. Finally, reciprocity and responsiveness were seen as key components in enhancing young children's participation.

Development of an integrated control and measurement system

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

Manges, W.W.

1984-03-01

This thesis presents a tutorial on the issues involved in the development of a minicomputer-based, distributed intelligence data acquisition and process control system to support complex experimental facilities. The particular system discussed in this thesis is under development for the Atomic Vapor Laser Isotope Separation (AVLIS) Program at the Oak Ridge Gaseous Diffusion Plant (ORGDP). In the AVLIS program, we were careful to integrate the computer sections of the implementation into the instrumentation system rather than adding them as an appendage. We then addressed the reliability and availability of the system as a separate concern. Thus, our concept of anmore » integrated control and measurement (ICAM) system forms the basis for this thesis. This thesis details the logic and philosophy that went into the development of this system and explains why the commercially available turn-key systems generally are not suitable. Also, the issues involved in the specification of the components for such an integrated system are emphasized.« less

The Transmembrane Region of Guard Cell SLAC1 Channels Perceives CO2 Signals via an ABA-Independent Pathway in Arabidopsis.

PubMed

Yamamoto, Yoshiko; Negi, Juntaro; Wang, Cun; Isogai, Yasuhiro; Schroeder, Julian I; Iba, Koh

2016-02-01

The guard cell S-type anion channel, SLOW ANION CHANNEL1 (SLAC1), a key component in the control of stomatal movements, is activated in response to CO2 and abscisic acid (ABA). Several amino acids existing in the N-terminal region of SLAC1 are involved in regulating its activity via phosphorylation in the ABA response. However, little is known about sites involved in CO2 signal perception. To dissect sites that are necessary for the stomatal CO2 response, we performed slac1 complementation experiments using transgenic plants expressing truncated SLAC1 proteins. Measurements of gas exchange and stomatal apertures in the truncated transgenic lines in response to CO2 and ABA revealed that sites involved in the stomatal CO2 response exist in the transmembrane region and do not require the SLAC1 N and C termini. CO2 and ABA regulation of S-type anion channel activity in guard cells of the transgenic lines confirmed these results. In vivo site-directed mutagenesis experiments targeted to amino acids within the transmembrane region of SLAC1 raise the possibility that two tyrosine residues exposed on the membrane are involved in the stomatal CO2 response. © 2016 American Society of Plant Biologists. All rights reserved.

The Immune Response and the Pathogenesis of Idiopathic Inflammatory Myositis: a Critical Review.

PubMed

Ceribelli, Angela; De Santis, Maria; Isailovic, Natasa; Gershwin, M Eric; Selmi, Carlo

2017-02-01

The pathogenesis of idiopathic inflammatory myositis (IIMs, including polymyositis and dermatomyositis) remains largely enigmatic, despite advances in the study of the role played by innate immunity, adaptive immunity, genetic predisposition, and environmental factors in an orchestrated response. Several factors are involved in the inflammatory state that characterizes the different forms of IIMs which share features and mechanisms but are clearly different with respect to the involved sites and characteristics of the inflammation. Cellular and non-cellular mechanisms of both the immune and non-immune systems have been identified as key regulators of inflammation in polymyositis/dermatomyositis, particularly at different stages of disease, leading to the fibrotic state that characterizes the end stage. Among these, a special role is played by an interferon signature and complement cascade with different mechanisms in polymyositis and dermatomyositis; these differences can be identified also histologically in muscle biopsies. Numerous cellular components of the adaptive and innate immune response are present in the site of tissue inflammation, and the complexity of idiopathic inflammatory myositis is further supported by the involvement of non-immune mechanisms such as hypoxia and autophagy. The aim of this comprehensive review is to describe the major pathogenic mechanisms involved in the onset of idiopathic inflammatory myositis and to report on the major working hypothesis with therapeutic implications.

The Transmembrane Region of Guard Cell SLAC1 Channels Perceives CO2 Signals via an ABA-Independent Pathway in Arabidopsis

PubMed Central

Yamamoto, Yoshiko; Negi, Juntaro; Isogai, Yasuhiro; Schroeder, Julian I.; Iba, Koh

2016-01-01

The guard cell S-type anion channel, SLOW ANION CHANNEL1 (SLAC1), a key component in the control of stomatal movements, is activated in response to CO2 and abscisic acid (ABA). Several amino acids existing in the N-terminal region of SLAC1 are involved in regulating its activity via phosphorylation in the ABA response. However, little is known about sites involved in CO2 signal perception. To dissect sites that are necessary for the stomatal CO2 response, we performed slac1 complementation experiments using transgenic plants expressing truncated SLAC1 proteins. Measurements of gas exchange and stomatal apertures in the truncated transgenic lines in response to CO2 and ABA revealed that sites involved in the stomatal CO2 response exist in the transmembrane region and do not require the SLAC1 N and C termini. CO2 and ABA regulation of S-type anion channel activity in guard cells of the transgenic lines confirmed these results. In vivo site-directed mutagenesis experiments targeted to amino acids within the transmembrane region of SLAC1 raise the possibility that two tyrosine residues exposed on the membrane are involved in the stomatal CO2 response. PMID:26764376

Identifying Patterns in Implementation of Hospital Pressure Ulcer Prevention Programs: A Multisite Qualitative Study.

PubMed

Soban, Lynn M; Finley, Erin P; Miltner, Rebecca S

2016-01-01

To describe the presence or absence of key components of hospital pressure ulcer (PU) prevention programs in 6 acute care hospitals. Multisite comparative case study. Using purposeful selection based on PU rates (high vs low) and hospital size, 6 hospitals within the Veterans Health Administration health care system were invited to participate. Key informant interviews (n = 48) were conducted in each of the 6 participating hospitals among individuals playing key roles in PU prevention: senior nursing leadership (n = 9), nurse manager (n = 7), wound care specialist (n = 6), frontline RNs (n = 26). Qualitative data were collected during face-to-face, semistructured interviews. Interview protocols were tailored to each interviewee's role with a core set of common questions covering 3 major content areas: (1) practice environment (eg, policies and wound care specialists), (2) current prevention practices (eg, conduct of PU risk assessment and skin inspection), and (3) barriers to PU prevention. We conducted structured coding of 5 key components of PU prevention programs and cross-case analysis to identify patterns in operationalization and implementation of program components across hospitals based on facility size and PU rates (low vs high). All hospitals had implemented all PU prevention program components. Component operationalization varied considerably across hospitals. Wound care specialists were integral to the operationalization of the 4 other program components examined; however, staffing levels and work assignments of wound care specialists varied widely. Patterns emerged among hospitals with low and high PU rates with respect to wound care specialist staffing, data monitoring, and staff education. We found hospital-level variations in PU prevention programs. Wound care specialist staffing may represent a potential point of leverage in achieving other PU program components, particularly performance monitoring and staff education.

Enhancing Parent Involvement in NC-CCSS for K-2 Mathematics

NASA Astrophysics Data System (ADS)

Johnson, D.

2014-12-01

Key Terms:Parent Involvement, Common Core State Standards, Homework, K - 2 Mathematics In this study, the 2014 REU math team developed and provided a workshop that assisted parents in understanding the North Carolina Common Core State Standards for K-2 Mathematics to assist with student homework assignments. Parent involvement is defined as parent participating in the educational processes and experiences of their children. A chi-square analysis was used to analyze data collected from the pre survey and the post survey administered to participants in the workshop. The study revealed all of the individual components of parent involvement were positively and significantly related to educational goals. The study identified various aspects of parent involvement that yielded statistically significant results in affirming that parent involvement attributed to urban student achievement. These findings were particularly helpful for indicating which kinds of parent involvement influenced academic success. Most notably, parent expectations and styles demonstrated a strong relationship with scholastic outcomes. Parent expectations and styles created an educationally oriented ambience that established an understanding of the certain level of support the child needed to succeed academically. The REU mathematics team focused on three essential questions in this study: (1) What practices will increase parent awareness of K-2 NC-CCSS for mathematics at P. W. Moore Elementary School? (2) What methods can be used to strengthen parent skills in assisting with mathematics homework assignments at P. W. Moore Elementary School? (3) What actions can be taken to motivate parent involvement in the school improvement process focusing on mathematics at P. W. Moore Elementary School?

Preparation and evaporation of Hanford Waste treatment plant direct feed low activity waste effluent management facility simulant

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

Adamson, D.; Nash, C.; Howe, A.

The Hanford Waste Treatment and Immobilization Plant (WTP) Low Activity Waste (LAW) vitrification facility will generate an aqueous condensate recycle stream (LAW Melter Off-Gas Condensate, LMOGC) from the off-gas system. The baseline plan for disposition of this stream during full WTP operations is to send it to the WTP Pretreatment Facility, where it will be blended with LAW, concentrated by evaporation, and recycled to the LAW vitrification facility. However, during the Direct Feed LAW (DFLAW) scenario, planned disposition of this stream involves concentrating the condensate in a new evaporator at the Effluent Management Facility (EMF) and returning it to themore » LAW melter. The LMOGC stream will contain components, e.g. halides and sulfates, that are volatile at melter temperatures, have limited solubility in glass waste forms, and present a material corrosion concern. Because this stream will recycle within WTP, these components are expected to accumulate in the LMOGC stream, exacerbating their impact on the number of LAW glass containers that must be produced. Diverting the stream reduces the halides and sulfates in the glass and is a key objective of this program. In order to determine the disposition path, it is key to experimentally determine the fate of contaminants. To do this, testing is needed to account for the buffering chemistry of the components, determine the achievable evaporation end point, identify insoluble solids that form, determine the formation and distribution of key regulatoryimpacting constituents, and generate an aqueous stream that can be used in testing of the subsequent immobilization step. This overall program examines the potential treatment and immobilization of the LMOGC stream to enable alternative disposal. The objective of this task was to (1) prepare a simulant of the LAW Melter Off-gas Condensate expected during DFLAW operations, (2) demonstrate evaporation in order to predict the final composition of the effluents from the EMF evaporator to aid in planning for their disposition, and (3) generate concentrated evaporator bottoms for use in immobilization testing.« less

Procurement engineering - the productivity factor

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

Bargerstock, S.B.

1993-01-01

The industry is several years on the road to implementation of the Nuclear Management and Resources Council (NUMARC) initiatives on commercial-grade item dedication and procurement. Utilities have taken several approaches to involve engineering in the procurement process. A common result for the approaches is the additional operations and maintenance (O M) cost imposed by the added resource requirements. Procurement engineering productivity is a key element in controlling this business area. Experience shows that 400 to 500% improvements in productivity are possible with a 2-yr period. Improving the productivity of the procurement engineering function is important in today's competitive utility environment.more » Procurement engineering typically involves four distinct technical evaluation responsibilities along with several administrative areas. Technical evaluations include the functionally based safety classification of replacement components and parts (lacking a master parts list), the determination of dedication requirements for safety-related commercial-grade items, the preparation of a procurement specification to maintain the licensed design bases, and the equivalency evaluation of alternate items not requiring the design-change process. Administrative duties include obtaining technical review of vendor-supplied documentation, identifying obsolete parts and components, resolving material nonconformances, initiating the design-change process for replacement items (as needed), and providing technical support to O M. Although most utilities may not perform or require all the noted activities, a large percentage will apply to each utility station.« less

Interactions between lipids and proteins are critical for organization of plasma membrane-ordered domains in tobacco BY-2 cells.

PubMed

Grosjean, Kevin; Der, Christophe; Robert, Franck; Thomas, Dominique; Mongrand, Sébastien; Simon-Plas, Françoise; Gerbeau-Pissot, Patricia

2018-06-27

The laterally heterogeneous plant plasma membrane (PM) is organized into finely controlled specialized areas that include membrane-ordered domains. Recently, the spatial distribution of such domains within the PM has been identified as playing a key role in cell responses to environmental challenges. To examine membrane order at a local level, BY-2 tobacco suspension cell PMs were labelled with an environment-sensitive probe (di-4-ANEPPDHQ). Four experimental models were compared to identify mechanisms and cell components involved in short-term (1 h) maintenance of the ordered domain organization in steady-state cell PMs: modulation of the cytoskeleton or the cell wall integrity of tobacco BY-2 cells; and formation of giant vesicles using either a lipid mixture of tobacco BY-2 cell PMs or the original lipid and protein combinations of the tobacco BY-2 cell PM. Whilst inhibiting phosphorylation or disrupting either the cytoskeleton or the cell wall had no observable effects, we found that lipids and proteins significantly modified both the abundance and spatial distribution of ordered domains. This indicates the involvement of intrinsic membrane components in the local physical state of the plant PM. Our findings support a major role for the 'lipid raft' model, defined as the sterol-dependent ordered assemblies of specific lipids and proteins in plant PM organization.

Lean Six Sigma implementation and organizational culture.

PubMed

Knapp, Susan

2015-01-01

The purpose of this paper is to examine the relationship between four organizational cultural types defined by the Competing Values Framework and three Lean Six Sigma implementation components - management involvement, use of Lean Six Sigma methods and Lean Six Sigma infrastructure. The study involved surveying 446 human resource and quality managers from 223 hospitals located in Maine, New Hampshire, Vermont, Massachusetts and Rhode Island using the Organizational Culture Assessment Instrument. Findings - In total, 104 completed responses were received and analyzed using multivariate analysis of variance. Follow-up analysis of variances showed management support was significant, F(3, 100)=4.89, p < 0.01, η2=1.28; infrastructure was not significant, F(3, 100)=1.55, p=0.21, η2=0.05; and using Lean Six Sigma methods was also not significant, F(3, 100)=1.34, p=0.26, η2=0.04. Post hoc analysis identified group and development cultures having significant interactions with management support. The relationship between organizational culture and Lean Six Sigma in hospitals provides information on how specific cultural characteristics impact the Lean Six Sigma initiative key components. This information assists hospital staff who are considering implementing quality initiatives by providing an understanding of what cultural values correspond to effective Lean Six Sigma implementation. Managers understanding the quality initiative cultural underpinnings, are attentive to the culture-shared values and norm's influence can utilize strategies to better implement Lean Six Sigma.

Cbp80 is needed for the expression of piRNA components and piRNAs

PubMed Central

Colombo, Martino; Hernandez, Greco; Beuchle, Dirk; Berger, Fabienne; Peischl, Stephan; Bruggmann, Rémy

2017-01-01

Cap binding protein 80 (Cbp80) is the larger subunit of the nuclear cap-binding complex (nCBC), which is known to play important roles in nuclear mRNA processing, export, stability and quality control events. Reducing Cbp80 mRNA levels in the female germline revealed that Cbp80 is also involved in defending the germline against transposable elements. Combining such knockdown experiments with large scale sequencing of small RNAs further showed that Cbp80 is involved in the initial biogenesis of piRNAs as well as in the secondary biogenesis pathway, the ping-pong amplification cycle. We further found that Cbp80 knockdown not only led to the upregulation of transposons, but also to delocalization of Piwi, Aub and Ago3, key factors in the piRNA biosynthesis pathway. Furthermore, compared to controls, levels of Piwi and Aub were also reduced upon knock down of Cbp80. On the other hand, with the same treatment we could not detect significant changes in levels or subcellular distribution (nuage localization) of piRNA precursor transcripts. This shows that Cbp80 plays an important role in the production and localization of the protein components of the piRNA pathway and it seems to be less important for the production and export of the piRNA precursor transcripts. PMID:28746365

How to Involve Concessionaires & Vendors in Your Recycling Program

EPA Pesticide Factsheets

This fact sheet is written for operations managers, recycling and event coordinators, and other key decisionmakers involved in planning and managing public venues and events. It explains the key role in recycling played by concessionaires.

Alternative Respiratory Pathway Component Genes (AOX and ND) in Rice and Barley and Their Response to Stress

PubMed Central

Dametto, Lettee; Shavrukov, Yuri; Jenkins, Colin L. D.

2018-01-01

Plants have a non-energy conserving bypass of the classical mitochondrial cytochrome c pathway, known as the alternative respiratory pathway (AP). This involves type II NAD(P)H dehydrogenases (NDs) on both sides of the mitochondrial inner membrane, ubiquinone, and the alternative oxidase (AOX). The AP components have been widely characterised from Arabidopsis, but little is known for monocot species. We have identified all the genes encoding components of the AP in rice and barley and found the key genes which respond to oxidative stress conditions. In both species, AOX is encoded by four genes; in rice OsAOX1a, 1c, 1d and 1e representing four clades, and in barley, HvAOX1a, 1c, 1d1 and 1d2, but no 1e. All three subfamilies of plant ND genes, NDA, NDB and NDC are present in both rice and barley, but there are fewer NDB genes compared to Arabidopsis. Cyanide treatment of both species, along with salt treatment of rice and drought treatment of barley led to enhanced expression of various AP components; there was a high level of co-expression of AOX1a and AOX1d, along with NDB3 during the stress treatments, reminiscent of the co-expression that has been well characterised in Arabidopsis for AtAOX1a and AtNDB2. PMID:29558397

Key biosynthetic gene subfamily recruited for pheromone production prior to the extensive radiation of Lepidoptera

PubMed Central

2008-01-01

Background Moths have evolved highly successful mating systems, relying on species-specific mixtures of sex pheromone components for long-distance mate communication. Acyl-CoA desaturases are key enzymes in the biosynthesis of these compounds and to a large extent they account for the great diversity of pheromone structures in Lepidoptera. A novel desaturase gene subfamily that displays Δ11 catalytic activities has been highlighted to account for most of the unique pheromone signatures of the taxonomically advanced ditrysian species. To assess the mechanisms driving pheromone evolution, information is needed about the signalling machinery of primitive moths. The currant shoot borer, Lampronia capitella, is the sole reported primitive non-ditrysian moth known to use unsaturated fatty-acid derivatives as sex-pheromone. By combining biochemical and molecular approaches we elucidated the biosynthesis paths of its main pheromone component, the (Z,Z)-9,11-tetradecadien-1-ol and bring new insights into the time point of the recruitment of the key Δ11-desaturase gene subfamily in moth pheromone biosynthesis. Results The reconstructed evolutionary tree of desaturases evidenced two ditrysian-specific lineages (the Δ11 and Δ9 (18C>16C)) to have orthologs in the primitive moth L. capitella despite being absent in Diptera and other insect genomes. Four acyl-CoA desaturase cDNAs were isolated from the pheromone gland, three of which are related to Δ9-desaturases whereas the fourth cDNA clusters with Δ11-desaturases. We demonstrated that this transcript (Lca-KPVQ) exclusively accounts for both steps of desaturation involved in pheromone biosynthesis. This enzyme possesses a Z11-desaturase activity that allows transforming the palmitate precursor (C16:0) into (Z)-11-hexadecenoic acid and the (Z)-9-tetradecenoic acid into the conjugated intermediate (Z,Z)-9,11-tetradecadienoic acid. Conclusion The involvement of a single Z11-desaturase in pheromone biosynthesis of a non-ditrysian moth species, supports that the duplication event leading to the origin of the Lepidoptera-specific Δ11-desaturase gene subfamily took place before radiation of ditrysian moths and their divergence from other heteroneuran lineages. Our findings uncover that this novel class of enzymes affords complex combinations of unique unsaturated fatty acyl-moieties of variable chain-lengths, regio- and stereo-specificities since early in moth history and contributes a notable innovation in the early evolution of moth-pheromones. PMID:18831750

Small Group Discussion as a Key Component in Online Assessment Training for Enhanced Student Learning in Web-Based Peer Assessment

ERIC Educational Resources Information Center

Liu, Xiongyi; Li, Lan; Zhang, Zhihong

2018-01-01

The purpose of this study is to examine the effect of online assessment training, with synchronous group discussion as a key component, on subsequent web-based peer assessment results. Participants included 81 college students, mostly women, taking a business writing class. After initial submission of a draft counter-offer letter, they completed…

Successful Stepwise Development of Patient Research Partnership: 14 Years' Experience of Actions and Consequences in Outcome Measures in Rheumatology (OMERACT).

PubMed

de Wit, Maarten; Kirwan, John R; Tugwell, Peter; Beaton, Dorcas; Boers, Maarten; Brooks, Peter; Collins, Sarah; Conaghan, Philip G; D'Agostino, Maria-Antonietta; Hofstetter, Cathie; Hughes, Rod; Leong, Amye; Lyddiatt, Ann; March, Lyn; May, James; Montie, Pamela; Richards, Pamela; Simon, Lee S; Singh, Jasvinder A; Strand, Vibeke; Voshaar, Marieke; Bingham, Clifton O; Gossec, Laure

2017-04-01

There is increasing interest in making patient participation an integral component of medical research. However, practical guidance on optimizing this engagement in healthcare is scarce. Since 2002, patient involvement has been one of the key features of the Outcome Measures in Rheumatology (OMERACT) international consensus effort. Based on a review of cumulative data from qualitative studies and internal surveys among OMERACT participants, we explored the potential benefits and challenges of involving patient research partners in conferences and working group activities. We supplemented our review with personal experiences and reflections regarding patient participation in the OMERACT process. We found that between 2002 and 2016, 67 patients have attended OMERACT conferences, of whom 28 had sustained involvement; many other patients contributed to OMERACT working groups. Their participation provided face validity to the OMERACT process and expanded the research agenda. Essential facilitators have been the financial commitment to guarantee sustainable involvement of patients at these conferences, procedures for recruitment, selection and support, and dedicated time allocated in the program for patient issues. Current challenges include the representativeness of the patient panel, risk of pseudo-professionalization, and disparity in patients' and researchers' perception of involvement. In conclusion, OMERACT has embedded long-term patient involvement in the consensus-building process on the measurement of core health outcomes. This integrative process continues to evolve iteratively. We believe that the practical points raised here can improve participatory research implementation.

Advances in mechanisms of systemic lupus erythematosus.

PubMed

Dema, Barbara; Charles, Nicolas

2014-05-01

Systemic lupus erythematosus (SLE) is a complex autoimmune disease associated with hormonal, environmental, and genetic factors and linked to the tolerance breakdown of B and T cells to self-antigens. SLE is characterized by the presence in patient serum of autoantibodies raised against nuclear components. Association of these antibodies to self-antigens, complement factors, DNA, and particular proteins will form circulating immune complexes (CIC) which can deposit in several organs, causing tissue damage and clinical manifestations. Historically, SLE is considered as an adaptive immune system disorder. Over the past decade, advances in the understanding of SLE pathogenesis placed the innate immune system as a key player in perpetuating and amplifying this systemic disease. In this review, we summarize some recent key advances in understanding the SLE immune-pathogenesis with a particular focus on newly discovered key factors from the innate immune system and how they influence the pathogenic adaptive immune system: neutrophils and neutrophil extracellular traps (NETs), plasmacytoid dendritic cells (pDCs) and type I interferons, basophils and autoreactive IgE, monocytes/macrophages and the inflammasome. Recent advances on B and T cell involvement in the SLE pathogenesis mechanisms are also discussed. Although the disease is clinically, genetically, and immunologically heterogeneous between affected individuals, the latest discoveries are offering new promising therapeutic strategies.

Tumor-host signaling interaction reveals a systemic, age-dependent splenic immune influence on tumor development

PubMed Central

Beheshti, Afshin; Wage, Justin; McDonald, J. Tyson; Lamont, Clare; Peluso, Michael; Hahnfeldt, Philip; Hlatky, Lynn

2015-01-01

The concept of age-dependent host control of cancer development raises the natural question of how these effects manifest across the host tissue/organ types with which a tumor interacts, one important component of which is the aging immune system. To investigate this, changes in the spleen, an immune nexus in the mouse, was examined for its age-dependent interactive influence on the carcinogenesis process. The model is the C57BL/6 male mice (adolescent, young adult, middle-aged, and old or 68, 143, 551 and 736 days old respectively) with and without a syngeneic murine tumor implant. Through global transcriptome analysis, immune-related functions were found to be key regulators in the spleen associated with tumor progression as a function of age with CD2, CD3ε, CCL19, and CCL5 being the key molecules involved. Surprisingly, other than CCL5, all key factors and immune-related functions were not active in spleens from non-tumor bearing old mice. Our findings of age-dependent tumor-spleen signaling interaction suggest the existence of a global role of the aging host in carcinogenesis. Suggested is a new avenue for therapeutic improvement that capitalizes on the pervasive role of host aging in dictating the course of this disease. PMID:26497558

The Genetic Drift Inventory: A Tool for Measuring What Advanced Undergraduates Have Mastered about Genetic Drift

PubMed Central

Price, Rebecca M.; Andrews, Tessa C.; McElhinny, Teresa L.; Mead, Louise S.; Abraham, Joel K.; Thanukos, Anna; Perez, Kathryn E.

2014-01-01

Understanding genetic drift is crucial for a comprehensive understanding of biology, yet it is difficult to learn because it combines the conceptual challenges of both evolution and randomness. To help assess strategies for teaching genetic drift, we have developed and evaluated the Genetic Drift Inventory (GeDI), a concept inventory that measures upper-division students’ understanding of this concept. We used an iterative approach that included extensive interviews and field tests involving 1723 students across five different undergraduate campuses. The GeDI consists of 22 agree–disagree statements that assess four key concepts and six misconceptions. Student scores ranged from 4/22 to 22/22. Statements ranged in mean difficulty from 0.29 to 0.80 and in discrimination from 0.09 to 0.46. The internal consistency, as measured with Cronbach's alpha, ranged from 0.58 to 0.88 across five iterations. Test–retest analysis resulted in a coefficient of stability of 0.82. The true–false format means that the GeDI can test how well students grasp key concepts central to understanding genetic drift, while simultaneously testing for the presence of misconceptions that indicate an incomplete understanding of genetic drift. The insights gained from this testing will, over time, allow us to improve instruction about this key component of evolution. PMID:24591505

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

Railo, Antti; Nagy, Irina I.; Kilpelaeinen, Pekka

The Wnt family of glycoprotein growth factors controls a number of central cellular processes such as proliferation, differentiation and ageing. All the Wnt proteins analyzed so far either activate or inhibit the canonical {beta}-catenin signaling pathway that regulates transcription of the target genes. In addition, some of them activate noncanonical signaling pathways that involve components such as the JNK, heterotrimeric G proteins, protein kinase C, and calmodulin-dependent protein kinase II, although the precise signaling mechanisms are only just beginning to be revealed. We demonstrate here that Wnt-11 signaling is sufficient to inhibit not only the canonical {beta}-catenin mediated Wnt signalingmore » but also JNK/AP-1 and NF-{kappa}B signaling in the CHO cells, thus serving as a noncanonical Wnt ligand in this system. Inhibition of the JNK/AP-1 pathway is mediated in part by the MAPK kinase MKK4 and Akt. Moreover, protein kinase C is involved in the regulation of JNK/AP-1 by Wnt-11, but not of the NF-{kappa}B pathway. Consistent with the central role of Akt, JNK and NF-{kappa}B in cell survival and stress responses, Wnt-11 signaling promotes cell viability. Hence Wnt-11 is involved in coordination of key signaling pathways.« less

Strengthening Community Involvement in Grant Review: Insights from the Community–University Research Partnership (CURES) Pilot Review Process

PubMed Central

Piechowski, Patricia; Warrick, Debra; Grawi, Carolyn; Choate, Celeste; Sneed, Glenda; Carr, Diane; Lota, Kanchan; Key, Kent; Alexander, Valerie; Ghosh, Pratik; Sampselle, Carolyn

2014-01-01

Abstract In 2007, the Michigan Institute for Clinical and Health Research (MICHR) at the University of Michigan received a Clinical and Translational Science Award (CTSA). Within MICHR, the Community Engagement (CE) program supports partnership efforts between researchers, practitioners, and community‐based organizations in specific focal communities throughout Michigan. A key component of the CE program is the Community Engagement Coordinating Council, a group that provides input and guidance on program priorities, strategic planning, and reviews pilot funding proposals for community–academic partnerships. This paper will describe a unique MICHR pilot funding mechanism for Community–University Research Partnerships (CURES) with an emphasis on the ways that community partners are involved in the review process, as well as the benefits, challenges, and insights gained over 5 years of pilot review. There is a growing need for community involvement and expertise in review of funding proposals for community‐engaged research at both institutional and federal levels. The CURES pilot review process is one example of an institutional effort to engage community partners in university funding decisions and has demonstrated clear benefit toward accomplishing the aims of the CTSA. PMID:24456508

Trpac1, a pH response transcription regulator, is involved in cellulase gene expression in Trichoderma reesei.

PubMed

He, Ronglin; Ma, Lijuan; Li, Chen; Jia, Wendi; Li, Demao; Zhang, Dongyuan; Chen, Shulin

2014-12-01

Fungi grow over a relatively wide pH range and adapt to extracellular pH through a genetic regulatory system mediated by a key component PacC, which is a pH transcription regulator. The cellulase production of the filamentous fungi Trichoderma reesei is sensitive to ambient pH. To investigate the connection between cellulase expression regulation and ambient pH, an ortholog of Aspergillus nidulans pacC, Trpac1, was identified and functionally characterized using a target gene deletion strategy. Deleting Trpac1 dramatically increased the cellulase production and the transcription levels of the major cellulase genes at neutral pH, which suggested Trpac1 is involved in the regulation of cellulase production. It was further observed that the expression levels of transcription factors xyr1 and ace2 also increased in the ΔTrpac1 mutant at neutral pH. In addition, the ΔTrpac1 mutant exhibited conidiation defects under neutral and alkaline pH. These results implied that Trpac1 in involved in growth and development process and cellulase gene expression in T. reesei. Copyright © 2014 Elsevier Inc. All rights reserved.

NASA Intelligent Systems Project: Results, Accomplishments and Impact on Science Missions.

NASA Astrophysics Data System (ADS)

Coughlan, J. C.

2005-12-01

The Intelligent Systems Project was responsible for much of NASA's programmatic investment in artificial intelligence and advanced information technologies. IS has completed three major project milestones which demonstrated increased capabilities in autonomy, human centered computing, and intelligent data understanding. Autonomy involves the ability of a robot to place an instrument on a remote surface with a single command cycle, human centered computing supported a collaborative, mission centric data and planning system for the Mars Exploration Rovers and data understanding has produced key components of a terrestrial satellite observation system with automated modeling and data analysis capabilities. This paper summarizes the technology demonstrations and metrics which quantify and summarize these new technologies which are now available for future NASA missions.

Automatic streak endpoint localization from the cornerness metric

NASA Astrophysics Data System (ADS)

Sease, Brad; Flewelling, Brien; Black, Jonathan

2017-05-01

Streaked point sources are a common occurrence when imaging unresolved space objects from both ground- and space-based platforms. Effective localization of streak endpoints is a key component of traditional techniques in space situational awareness related to orbit estimation and attitude determination. To further that goal, this paper derives a general detection and localization method for streak endpoints based on the cornerness metric. Corners detection involves searching an image for strong bi-directional gradients. These locations typically correspond to robust structural features in an image. In the case of unresolved imagery, regions with a high cornerness score correspond directly to the endpoints of streaks. This paper explores three approaches for global extraction of streak endpoints and applies them to an attitude and rate estimation routine.

NASA Intelligent Systems Project: Results, Accomplishments and Impact on Science Missions

NASA Technical Reports Server (NTRS)

Coughlan, Joseph C.

2005-01-01

The Intelligent Systems Project was responsible for much of NASA's programmatic investment in artificial intelligence and advanced information technologies. IS has completed three major project milestones which demonstrated increased capabilities in autonomy, human centered computing, and intelligent data understanding. Autonomy involves the ability of a robot to place an instrument on a remote surface with a single command cycle. Human centered computing supported a collaborative, mission centric data and planning system for the Mars Exploration Rovers and data understanding has produced key components of a terrestrial satellite observation system with automated modeling and data analysis capabilities. This paper summarizes the technology demonstrations and metrics which quantify and summarize these new technologies which are now available for future Nasa missions.

"Maintaining connections but wanting more": the continuity of familial relationships among assisted-living residents.

PubMed

Tompkins, Catherine J; Ihara, Emily S; Cusick, Alison; Park, Nan Sook

2012-01-01

Social support is a key component of well-being for older adults, particularly for those who have moved from independent living to assisted living involving a transformation of roles, relationships, and responsibilities. Twenty-nine assisted-living facility residents were interviewed to understand the perceived continuity of relationships with family and friends. An inductive approach to thematic analysis revealed 1 main theme and 3 subthemes. The main theme that emerged was: maintaining connections but wanting more. Residents appreciated maintaining connections with family and friends, but often expressed feelings of discontentment with the continuity of former relationships. The subthemes included: appreciating family and friends, waiting for more, and losing control. Implications for research and practice are discussed.

Cannabinoids and cancer: pros and cons of an antitumour strategy

PubMed Central

Bifulco, Maurizio; Laezza, Chiara; Pisanti, Simona; Gazzerro, Patrizia

2006-01-01

In the last two decades, research has dramatically increased the knowledge of cannabinoids biology and pharmacology. In mammals, compounds with properties similar to active components of Cannabis sativa, the so called ‘endocannabinoids', have been shown to modulate key cell-signalling pathways involved in cancer cell growth, invasion and metastasis. To date, cannabinoids have been licensed for clinical use as palliative treatment of chemotherapy, but increased evidences showed direct antiproliferative actions of cannabinoid agonists on several tumour cells in vitro and in animal models. In this article, we will review the principal molecular pathways modulated by cannabinoids on cancer and summarize pros and cons evidence on the possible future use of endocannabinoid-based drugs in cancer therapy. PMID:16501583

Silicon-on-insulator multimode-interference waveguide-based arrayed optical tweezers (SMART) for two-dimensional microparticle trapping and manipulation.

PubMed

Lei, Ting; Poon, Andrew W

2013-01-28

We demonstrate two-dimensional optical trapping and manipulation of 1 μm and 2.2 μm polystyrene particles in an 18 μm-thick fluidic cell at a wavelength of 1565 nm using the recently proposed Silicon-on-insulator Multimode-interference (MMI) waveguide-based ARrayed optical Tweezers (SMART) technique. The key component is a 100 μm square-core silicon waveguide with mm length. By tuning the fiber-coupling position at the MMI waveguide input facet, we demonstrate various patterns of arrayed optical tweezers that enable optical trapping and manipulation of particles. We numerically simulate the physical mechanisms involved in the arrayed trap, including the optical force, the heat transfer and the thermal-induced microfluidic flow.

Catalytic bismetallative multicomponent coupling reactions: scope, applications, and mechanisms

PubMed Central

Cho, Hee Yeon

2014-01-01

Catalytic reactions have played an indispensable role in organic chemistry for the last several decades. In particular, catalytic multicomponent reactions have attracted a lot of attention due to their efficiency and expediency towards complex molecule synthesis. The presence of bismetallic reagents (e.g. B–B, Si–Si, B–Si, Si–Sn, etc.) in this process renders the products enriched with various functional groups and multiple stereocenters. For this reason, catalytic bismetallative coupling is considered an effective method to generate the functional and stereochemical complexity of simple hydrocarbon substrates. This review highlights key developments of transition-metal catalyzed bismetallative reactions involving multiple π components. Specifically, it will highlight the scope, synthetic applications, and proposed mechanistic pathways of this process. PMID:24736839

Hilbert transform evaluation for electron-phonon self-energies

NASA Astrophysics Data System (ADS)

Bevilacqua, Giuseppe; Menichetti, Guido; Pastori Parravicini, Giuseppe

2016-01-01

The electron tunneling current through nanostructures is considered in the presence of the electron-phonon interactions. In the Keldysh nonequilibrium formalism, the lesser, greater, advanced and retarded self-energies components are expressed by means of appropriate Langreth rules. We discuss the key role played by the entailed Hilbert transforms, and provide an analytic way for their evaluation. Particular attention is given to the current-conserving lowest-order-expansion for the treament of the electron-phonon interaction; by means of an appropriate elaboration of the analytic properties and pole structure of the Green's functions and of the Fermi functions, we arrive at a surprising simple, elegant, fully analytic and easy-to-use expression of the Hilbert transforms and involved integrals in the energy domain.

CRISPR-Cas adaptation: insights into the mechanism of action.

PubMed

Amitai, Gil; Sorek, Rotem

2016-02-01

Since the first demonstration that CRISPR-Cas systems provide bacteria and archaea with adaptive immunity against phages and plasmids, numerous studies have yielded key insights into the molecular mechanisms governing how these systems attack and degrade foreign DNA. However, the molecular mechanisms underlying the adaptation stage, in which new immunological memory is formed, have until recently represented a major unresolved question. In this Progress article, we discuss recent discoveries that have shown both how foreign DNA is identified by the CRISPR-Cas adaptation machinery and the molecular basis for its integration into the chromosome to form an immunological memory. Furthermore, we describe the roles of each of the specific CRISPR-Cas components that are involved in memory formation, and consider current models for their evolutionary origin.

Systems Analysis Approach for the NASA Environmentally Responsible Aviation Project

NASA Technical Reports Server (NTRS)

Kimmel, William M.

2011-01-01

This conference paper describes the current systems analysis approach being implemented for the Environmentally Responsible Aviation Project within the Integrated Systems Research Program under the NASA Aeronautics Research Mission Directorate. The scope and purpose of these systems studies are introduced followed by a methodology overview. The approach involves both top-down and bottoms-up components to provide NASA s stakeholders with a rationale for the prioritization and tracking of a portfolio of technologies which enable the future fleet of aircraft to operate with a simultaneous reduction of aviation noise, emissions and fuel-burn impacts to our environment. Examples of key current results and relevant decision support conclusions are presented along with a forecast of the planned analyses to follow.

Redox mediators in visible light photocatalysis: photocatalytic radical thiol-ene additions.

PubMed

Tyson, Elizabeth L; Niemeyer, Zachary L; Yoon, Tehshik P

2014-02-07

Synthetically useful radical thiol-ene reactions can be initiated by visible light irradiation in the presence of transition metal polypyridyl photocatalysts. The success of this method relies upon the use of p-toluidine as an essential additive. Using these conditions, high-yielding thiol-ene reactions of cysteine-containing biomolecules can be accomplished using biocompatibile wavelengths of visible light, under aqueous conditions, and with the thiol component as the limiting reagent. We present evidence that p-toluidine serves as a redox mediator that is capable of catalyzing the otherwise inefficient photooxidation of thiols to the key thiyl radical intermediate. Thus, we show that co-catalytic oxidants can be important in the design of synthetic reactions involving visible light photoredox catalysis.

Aeropropulsion 1987. Session 6: High-Speed Propulsion Technology

NASA Technical Reports Server (NTRS)

1987-01-01

NASA is conducting aeronautical research over a broad range of Mach numbers. In addition to the advanced CTOL propulsion research described in a separate session, the Lewis Research Center has intensified its efforts towards propulsion technology for selected high-speed flight applications. In a companion program, the Langley Research Center has also accomplished excellent research in Supersonic Combustion Ramjet (SCRAM) propulsion. What is presented in this session is an unclassified review of some of the propulsion research results that are applicable for supersonic to hypersonic vehicles. Not only is a review provided for several key work areas, it also presents a viewpoint on future research directions by calling attention to cycles, components, and facilities involved in this rapidly expanding field of work.

High-Throughput Method of Whole-Brain Sectioning, Using the Tape-Transfer Technique.

PubMed

Pinskiy, Vadim; Jones, Jamie; Tolpygo, Alexander S; Franciotti, Neil; Weber, Kevin; Mitra, Partha P

2015-01-01

Cryostat sectioning is a popular but labor-intensive method for preparing histological brain sections. We have developed a modification of the commercially available CryoJane tape collection method that significantly improves the ease of collection and the final quality of the tissue sections. The key modification involves an array of UVLEDs to achieve uniform polymerization of the glass slide and robust adhesion between the section and slide. This report presents system components and detailed procedural steps, and provides examples of end results; that is, 20 μm mouse brain sections that have been successfully processed for routine Nissl, myelin staining, DAB histochemistry, and fluorescence. The method is also suitable for larger brains, such as rat and monkey.

High-Throughput Method of Whole-Brain Sectioning, Using the Tape-Transfer Technique

PubMed Central

Pinskiy, Vadim; Jones, Jamie; Tolpygo, Alexander S.; Franciotti, Neil; Weber, Kevin; Mitra, Partha P.

2015-01-01

Cryostat sectioning is a popular but labor-intensive method for preparing histological brain sections. We have developed a modification of the commercially available CryoJane tape collection method that significantly improves the ease of collection and the final quality of the tissue sections. The key modification involves an array of UVLEDs to achieve uniform polymerization of the glass slide and robust adhesion between the section and slide. This report presents system components and detailed procedural steps, and provides examples of end results; that is, 20μm mouse brain sections that have been successfully processed for routine Nissl, myelin staining, DAB histochemistry, and fluorescence. The method is also suitable for larger brains, such as rat and monkey. PMID:26181725

Improved ALE mesh velocities for complex flows

DOE PAGES

Bakosi, Jozsef; Waltz, Jacob I.; Morgan, Nathaniel Ray

2017-05-31

A key choice in the development of arbitrary Lagrangian-Eulerian solution algorithms is how to move the computational mesh. The most common approaches are smoothing and relaxation techniques, or to compute a mesh velocity field that produces smooth mesh displacements. We present a method in which the mesh velocity is specified by the irrotational component of the fluid velocity as computed from a Helmholtz decomposition, and excess compression of mesh cells is treated through a noniterative, local spring-force model. This approach allows distinct and separate control over rotational and translational modes. In conclusion, the utility of the new mesh motion algorithmmore » is demonstrated on a number of 3D test problems, including problems that involve both shocks and significant amounts of vorticity.« less

Understanding and responding when things go wrong: key principles for primary care educators.

PubMed

McNab, Duncan; Bowie, Paul; Ross, Alastair; Morrison, Jill

2016-07-01

Learning from events with unwanted outcomes is an important part of workplace based education and providing evidence for medical appraisal and revalidation. It has been suggested that adopting a 'systems approach' could enhance learning and effective change. We believe the following key principles should be understood by all healthcare staff, especially those with a role in developing and delivering educational content for safety and improvement in primary care. When things go wrong, professional accountability involves accepting there has been a problem, apologising if necessary and committing to learn and change. This is easier in a 'Just Culture' where wilful disregard of safe practice is not tolerated but where decisions commensurate with training and experience do not result in blame and punishment. People usually attempt to achieve successful outcomes, but when things go wrong the contribution of hindsight and attribution bias as well as a lack of understanding of conditions and available information (local rationality) can lead to inappropriately blame 'human error'. System complexity makes reduction into component parts difficult; thus attempting to 'find-and-fix' malfunctioning components may not always be a valid approach. Finally, performance variability by staff is often needed to meet demands or cope with resource constraints. We believe understanding these core principles is a necessary precursor to adopting a 'systems approach' that can increase learning and reduce the damaging effects on morale when 'human error' is blamed. This may result in 'human error' becoming the starting point of an investigation and not the endpoint.

Iron-sulfur cluster biogenesis in mammalian cells: new insights into the molecular mechanisms of cluster delivery

PubMed Central

Maio, Nunziata; Rouault, Tracey. A.

2014-01-01

Iron-sulfur (Fe-S) clusters are ancient, ubiquitous cofactors composed of iron and inorganic sulfur. The combination of the chemical reactivity of iron and sulfur, together with many variations of cluster composition, oxidation states and protein environments, enables Fe-S clusters to participate in numerous biological processes. Fe-S clusters are essential to redox catalysis in nitrogen fixation, mitochondrial respiration and photosynthesis, to regulatory sensing in key metabolic pathways (i. e. cellular iron homeostasis and oxidative stress response), and to the replication and maintenance of the nuclear genome. Fe-S cluster biogenesis is a multistep process that involves a complex sequence of catalyzed protein- protein interactions and coupled conformational changes between the components of several dedicated multimeric complexes. Intensive studies of the assembly process have clarified key points in the biogenesis of Fe-S proteins. However several critical questions still remain, such as: what is the role of frataxin? Why do some defects of Fe-S cluster biogenesis cause mitochondrial iron overload? How are specific Fe-S recipient proteins recognized in the process of Fe-S transfer? This review focuses on the basic steps of Fe-S cluster biogenesis, drawing attention to recent advances achieved on the identification of molecular features that guide selection of specific subsets of nascent Fe-S recipients by the cochaperone HSC20. Additionally, it outlines the distinctive phenotypes of human diseases due to mutations in the components of the basic pathway. PMID:25245479

Recent advances quantifying the large wood dynamics in river basins: New methods and remaining challenges

NASA Astrophysics Data System (ADS)

Ruiz-Villanueva, Virginia; Piégay, Hervé; Gurnell, Angela A.; Marston, Richard A.; Stoffel, Markus

2016-09-01

Large wood is an important physical component of woodland rivers and significantly influences river morphology. It is also a key component of stream ecosystems. However, large wood is also a source of risk for human activities as it may damage infrastructure, block river channels, and induce flooding. Therefore, the analysis and quantification of large wood and its mobility are crucial for understanding and managing wood in rivers. As the amount of large-wood-related studies by researchers, river managers, and stakeholders increases, documentation of commonly used and newly available techniques and their effectiveness has also become increasingly relevant as well. Important data and knowledge have been obtained from the application of very different approaches and have generated a significant body of valuable information representative of different environments. This review brings a comprehensive qualitative and quantitative summary of recent advances regarding the different processes involved in large wood dynamics in fluvial systems including wood budgeting and wood mechanics. First, some key definitions and concepts are introduced. Second, advances in quantifying large wood dynamics are reviewed; in particular, how measurements and modeling can be combined to integrate our understanding of how large wood moves through and is retained within river systems. Throughout, we present a quantitative and integrated meta-analysis compiled from different studies and geographical regions. Finally, we conclude by highlighting areas of particular research importance and their likely future trajectories, and we consider a particularly underresearched area so as to stress the future challenges for large wood research.

The iron-sulfur cluster assembly network component NARFL is a key element in the cellular defense against oxidative stress.

PubMed

Corbin, Monique V; Rockx, Davy A P; Oostra, Anneke B; Joenje, Hans; Dorsman, Josephine C

2015-12-01

Aim of this study was to explore cellular changes associated with increased resistance to atmospheric oxygen using high-resolution DNA and RNA profiling combined with functional studies. Two independently selected oxygen-resistant substrains of HeLa cells (capable of proliferating at >80% O2, i.e. hyperoxia) were compared with their parental cells (adapted to growth at 20% O2, but unable to grow at >80% O2). A striking consistent alteration found to be associated with the oxygen-resistant state appeared to be an amplified and overexpressed region on chromosome 16p13.3 harboring 21 genes. The driver gene of this amplification was identified by functional studies as NARFL, which encodes a component of the cytosolic iron-sulfur cluster assembly system. In line with this result we found the cytosolic c-aconitase activity as well as the nuclear protein RTEL1, both Fe-S dependent proteins, to be protected by NARFL overexpression under hyperoxia. In addition, we observed a protective effect of NARFL against hyperoxia-induced loss of sister-chromatid cohesion. NARFL thus appeared to be a key factor in the cellular defense against hyperoxia-induced oxidative stress in human cells. Our findings suggest that new insight into age-related degenerative processes may come from studies that specifically address the involvement of iron-sulfur proteins. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Doctors on the move: a European case study on the key characteristics of national recertification systems

PubMed Central

Govaerts, Marjan J; Mitchell, Sharon; Rohde, Gernot G U; Smeenk, Frank W J M; Driessen, Erik W

2018-01-01

Objectives With increased cross-border movement, ensuring safe and high-quality healthcare has gained primacy. The purpose of recertification is to ensure quality of care through periodically attesting doctors’ professional proficiency in their field. Professional migration and facilitated cross-border recognition of qualifications, however, make us question the fitness of national policies for safeguarding patient care and the international accountability of doctors. Design and setting We performed document analyses and conducted 19 semistructured interviews to identify and describe key characteristics and effective components of 10 different European recertification systems, each representing one case (collective case study). We subsequently compared these systems to explore similarities and differences in terms of assessment criteria used to determine process quality. Results Great variety existed between countries in terms and assessment formats used, targeting cognition, competence and performance (Miller’s assessment pyramid). Recertification procedures and requirements also varied significantly, ranging from voluntary participation in professional development modules to the mandatory collection of multiple performance data in a competency-based portfolio. Knowledge assessment was fundamental to recertification in most countries. Another difference concerned the stakeholders involved in the recertification process: while some systems exclusively relied on doctors’ self-assessment, others involved multiple stakeholders but rarely included patients in assessment of doctors’ professional competence. Differences between systems partly reflected different goals and primary purposes of recertification. Conclusion Recertification systems differ substantially internationally with regard to the criteria they apply to assess doctors’ competence, their aims, requirements, assessment formats and patient involvement. In the light of professional mobility and associated demands for accountability, we recommend that competence assessment includes patients’ perspectives, and recertification practices be shared internationally to enhance transparency. This can help facilitate cross-border movement, while guaranteeing high-quality patient care. PMID:29666131

Transactivation mediated by B-Myb is dependent on TAF(II)250.

PubMed

Bartusel, Thorsten; Klempnauer, Karl-Heinz

2003-05-15

B-Myb is a highly conserved member of the Myb family of transcription factors, which has been implicated in cell cycle regulation. B-Myb is expressed in most proliferating cells and its activity is highly regulated around the G1/S-phase border of the cell cycle. It is generally assumed that B-Myb regulates the expression of genes that are crucial for cell proliferation; however, the identity of these genes, the molecular mechanisms by which B-Myb stimulates their expression and the involvement of other proteins have not been sufficiently clarified. We have employed the hamster cell line ts13 as a tool to demonstrate a functional link between B-Myb and the coactivator TAF(II)250, a key component of the transcriptional machinery which itself is essential for cell proliferation. ts13 cells express a point-mutated version of TAF(II)250 whose intrinsic histone acetyl transferase activity is temperature sensitive. Transactivation of Myb-responsive reporter genes by B-Myb is temperature-dependent in ts13 cells but not in ts13 cells, which have been rescued by transfection with an expression vector for wild-type TAF(II)250. Furthermore, B-Myb and TAF(II)250 can be coprecipitated, suggesting that both proteins are present in a complex. The formation of this complex is dependent on the DNA-binding domain of B-Myb and not on its transactivation domain. Taken together, these observations provide the first evidence that the coactivator TAF(II)250 is involved in the activation of Myb responsive promoters by B-Myb. The finding that B-Myb transactivation is dependent on a key coactivator involved in cell cycle control is consistent with and strengthens the idea that B-Myb plays a crucial role as a transcription factor in proliferating cells.

The CreB deubiquitinating enzyme does not directly target the CreA repressor protein in Aspergillus nidulans.

PubMed

Alam, Md Ashiqul; Kamlangdee, Niyom; Kelly, Joan M

2017-08-01

Ubiquitination/deubiquitination pathways are now recognized as key components of gene regulatory mechanisms in eukaryotes. The major transcriptional repressor for carbon catabolite repression in Aspergillus nidulans is CreA, and mutational analysis led to the suggestion that a regulatory ubiquitination/deubiquitination pathway is involved. A key unanswered question is if and how this pathway, comprising CreB (deubiquitinating enzyme) and HulA (ubiquitin ligase) and other proteins, is involved in the regulatory mechanism. Previously, missense alleles of creA and creB were analysed for genetic interactions, and here we extended this to complete loss-of-function alleles of creA and creB, and compared morphological and biochemical phenotypes, which confirmed genetic interaction between the genes. We investigated whether CreA, or a protein in a complex with it, is a direct target of the CreB deubiquitination enzyme, using co-purifications of CreA and CreB, first using strains that overexpress the proteins and then using strains that express the proteins from their native promoters. The Phos-tag system was used to show that CreA is a phosphorylated protein, but no ubiquitination was detected using anti-ubiquitin antibodies and Western analysis. These findings were confirmed using mass spectrometry, which confirmed that CreA was differentially phosphorylated but not ubiquitinated. Thus, CreA is not a direct target of CreB, and nor are proteins that form part of a stable complex with CreA a target of CreB. These results open up new questions regarding the molecular mechanism of CreA repressing activity, and how the ubiquitination pathway involving CreB interacts with this regulatory network.

The roles of SSU processome components and surveillance factors in the initial processing of human ribosomal RNA

PubMed Central

Sloan, Katherine E.; Bohnsack, Markus T.; Schneider, Claudia; Watkins, Nicholas J.

2014-01-01

During eukaryotic ribosome biogenesis, three of the mature ribosomal (r)RNAs are released from a single precursor transcript (pre-rRNA) by an ordered series of endonucleolytic cleavages and exonucleolytic processing steps. Production of the 18S rRNA requires the removal of the 5′ external transcribed spacer (5′ETS) by endonucleolytic cleavages at sites A0 and A1/site 1. In metazoans, an additional cleavage in the 5′ETS, at site A′, upstream of A0, has also been reported. Here, we have investigated how A′ processing is coordinated with assembly of the early preribosomal complex. We find that only the tUTP (UTP-A) complex is critical for A′ cleavage, while components of the bUTP (UTP-B) and U3 snoRNP are important, but not essential, for efficient processing at this site. All other factors involved in the early stages of 18S rRNA processing that were tested here function downstream from this processing step. Interestingly, we show that the RNA surveillance factors XRN2 and MTR4 are also involved in A′ cleavage in humans. A′ cleavage is largely bypassed when XRN2 is depleted, and we also discover that A′ cleavage is not always the initial processing event in all cell types. Together, our data suggest that A′ cleavage is not a prerequisite for downstream pre-rRNA processing steps and may, in fact, represent a quality control step for initial pre-rRNA transcripts. Furthermore, we show that components of the RNA surveillance machinery, including the exosome and TRAMP complexes, also play key roles in the recycling of excised spacer fragments and degradation of aberrant pre-rRNAs in human cells. PMID:24550520

Optoelectronics in TESLA, LHC, and pi-of-the-sky experiments

NASA Astrophysics Data System (ADS)

Romaniuk, Ryszard S.; Pozniak, Krzysztof T.; Wrochna, Grzegorz; Simrock, Stefan

2004-09-01

Optical and optoelectronics technologies are more and more widely used in the biggest world experiments of high energy and nuclear physics, as well as in the astronomy. The paper is a kind of a broad digest describing the usage of optoelectronics is such experiments and information about some of the involved teams. The described experiments include: TESLA linear accelerator and FEL, Compact Muon Solenoid at LHC and recently started π-of-the-sky global gamma ray bursts (with asociated optical flashes) observation experiment. Optoelectornics and photonics offer several key features which are either extending the technical parameters of existing solutions or adding quite new practical application possibilities. Some of these favorable features of photonic systems are: high selectivity of optical sensors, immunity to some kinds of noise processes, extremely broad bandwidth exchangeable for either terabit rate transmission or ultrashort pulse generation, parallel image processing capability, etc. The following groups of photonic components and systems were described: (1) discrete components applications like: LED, PD, LD, CCD and CMOS cameras, active optical crystals and optical fibers in radiation dosimetry, astronomical image processing and for building of more complex photonic systems; (2) optical fiber networks serving as very stable phase distribution, clock signal distribution, distributed dosimeters, distributed gigabit transmission for control, diagnostics and data acquisition/processing; (3) fast and stable coherent femtosecond laser systems with active optical components for electro-optical sampling and photocathode excitation in the RF electron gun for linac; The parameters of some of these systems were quoted and discussed. A number of the debated solutions seems to be competitive against the classical ones. Several future fields seem to emerge involving direct coupling between the ultrafast photonic and the VLSI FPGA based technologies.

Drosophila SMN complex proteins Gemin2, Gemin3, and Gemin5 are components of U bodies

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

Cauchi, Ruben J.; Sanchez-Pulido, Luis; Liu, Ji-Long, E-mail: jilong.liu@dpag.ox.ac.uk

2010-08-15

Uridine-rich small nuclear ribonucleoproteins (U snRNPs) play key roles in pre-mRNA processing in the nucleus. The assembly of most U snRNPs takes place in the cytoplasm and is facilitated by the survival motor neuron (SMN) complex. Discrete cytoplasmic RNA granules called U bodies have been proposed to be specific sites for snRNP assembly because they contain U snRNPs and SMN. U bodies invariably associate with P bodies, which are involved in mRNA decay and translational control. However, it remains unknown whether other SMN complex proteins also localise to U bodies. In Drosophila there are four SMN complex proteins, namely SMN,more » Gemin2/CG10419, Gemin3 and Gemin5/Rigor mortis. Drosophila Gemin3 was originally identified as the Drosophila orthologue of human and yeast Dhh1, a component of P bodies. Through an in silico analysis of the DEAD-box RNA helicases we confirmed that Gemin3 is the bona fide Drosophila orthologue of vertebrate Gemin3 whereas the Drosophila orthologue of Dhh1 is Me31B. We then made use of the Drosophila egg chamber as a model system to study the subcellular distribution of the Gemin proteins as well as Me31B. Our cytological investigations show that Gemin2, Gemin3 and Gemin5 colocalise with SMN in U bodies. Although they are excluded from P bodies, as components of U bodies, Gemin2, Gemin3 and Gemin5 are consistently found associated with P bodies, wherein Me31B resides. In addition to a role in snRNP biogenesis, SMN complexes residing in U bodies may also be involved in mRNP assembly and/or transport.« less

Sizing Power Components of an Electrically Driven Tail Cone Thruster and a Range Extender

NASA Technical Reports Server (NTRS)

Jansen, Ralph H.; Bowman, Cheryl; Jankovsky, Amy

2016-01-01

The aeronautics industry has been challenged on many fronts to increase efficiency, reduce emissions, and decrease dependency on carbon-based fuels. This paper provides an overview of the turboelectric and hybrid electric technologies being developed under NASA's Advanced Air Transportation Technology (AATT) Project and discusses how these technologies can impact vehicle design. The discussion includes an overview of key hybrid electric studies and technology investments, the approach to making informed investment decisions based on key performance parameters and mission studies, and the power system architectures for two candidate aircraft. Finally, the power components for a single-aisle turboelectric aircraft with an electrically driven tail cone thruster and for a hybrid-electric nine-passenger aircraft with a range extender are parametrically sized, and the sensitivity of these components to key parameters is presented.

Alternative Designs for Evaluating Workplace Literacy Programs. Conference Proceedings and Commissioned Papers at the "Design Guidance for Evaluating Workplace Literacy Programs" Work Group Conference (Washington, D.C. April 13, 1993).

ERIC Educational Resources Information Center

Research Triangle Inst., Research Triangle Park, NC.

This document contains the five papers presented at a meeting at which key issues in evaluating workplace literacy programs were discussed. In "Key Components of Workplace Liteacy Projects and Definitions of Project 'Modules,'" Judith A. Alamprese describes the context for evaluating the National Extension Program, components of workplace literacy…

Air Reserve Component: Key to the Air Force’s Future

DTIC Science & Technology

2013-03-01

REPORT TYPE STRATEGY RESEARCH PROJECT .33 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE Air Reserve Component: Key to the Air Force’s...b. ABSTRACT UU c. THIS PAGE UU 19b. TELEPHONE NUMBER (Include area code) USAWC STRATEGY RESEARCH PROJECT...RAND Corporation, Prepared for the Office of Secretary of Defense, 2008), XV. 64 T.X. Hammes, "Offshore Control: A Proposed Strategy ," Infinity

Refining the aggregate exposure pathway.

PubMed

Tan, Yu-Mei; Leonard, Jeremy A; Edwards, Stephen; Teeguarden, Justin; Egeghy, Peter

2018-03-01

Advancements in measurement technologies and modeling capabilities continue to result in an abundance of exposure information, adding to that currently in existence. However, fragmentation within the exposure science community acts as an obstacle for realizing the vision set forth in the National Research Council's report on Exposure Science in the 21 st century to consider exposures from source to dose, on multiple levels of integration, and to multiple stressors. The concept of an Aggregate Exposure Pathway (AEP) was proposed as a framework for organizing and integrating diverse exposure information that exists across numerous repositories and among multiple scientific fields. A workshop held in May 2016 followed introduction of the AEP concept, allowing members of the exposure science community to provide extensive evaluation and feedback regarding the framework's structure, key components, and applications. The current work briefly introduces topics discussed at the workshop and attempts to address key challenges involved in refining this framework. The resulting evolution in the AEP framework's features allows for facilitating acquisition, integration, organization, and transparent application and communication of exposure knowledge in a manner that is independent of its ultimate use, thereby enabling reuse of such information in many applications.

A FYVE zinc finger domain protein specifically links mRNA transport to endosome trafficking

PubMed Central

Pohlmann, Thomas; Baumann, Sebastian; Haag, Carl; Albrecht, Mario; Feldbrügge, Michael

2015-01-01

An emerging theme in cellular logistics is the close connection between mRNA and membrane trafficking. A prominent example is the microtubule-dependent transport of mRNAs and associated ribosomes on endosomes. This coordinated process is crucial for correct septin filamentation and efficient growth of polarised cells, such as fungal hyphae. Despite detailed knowledge on the key RNA-binding protein and the molecular motors involved, it is unclear how mRNAs are connected to membranes during transport. Here, we identify a novel factor containing a FYVE zinc finger domain for interaction with endosomal lipids and a new PAM2-like domain required for interaction with the MLLE domain of the key RNA-binding protein. Consistently, loss of this FYVE domain protein leads to specific defects in mRNA, ribosome, and septin transport without affecting general functions of endosomes or their movement. Hence, this is the first endosomal component specific for mRNP trafficking uncovering a new mechanism to couple mRNPs to endosomes. DOI: http://dx.doi.org/10.7554/eLife.06041.001 PMID:25985087

The orphan nuclear receptor Tlx regulates Pax2 and is essential for vision.

PubMed

Yu, R T; Chiang, M Y; Tanabe, T; Kobayashi, M; Yasuda, K; Evans, R M; Umesono, K

2000-03-14

Although the development of the vertebrate eye is well described, the number of transcription factors known to be key to this process is still limited. The localized expression of the orphan nuclear receptor Tlx in the optic cup and discrete parts of the central nervous system suggested the possible role of Tlx in the formation or function of these structures. Analyses of Tlx targeted mice revealed that, in addition to the central nervous system cortical defects, lack of Tlx function results in progressive retinal and optic nerve degeneration with associated blindness. An extensive screen of Tlx-positive and Tlx-negative P19 neural precursors identified Pax2 as a candidate target gene. This identification is significant, because Pax2 is known to be involved in retinal development in both the human and the mouse eye. We find that Pax2 is a direct target and that the Tlx binding site in its promoter is conserved between mouse and human. These studies show that Tlx is a key component of retinal development and vision and an upstream regulator of the Pax2 signaling cascade.

The orphan nuclear receptor Tlx regulates Pax2 and is essential for vision

PubMed Central

Yu, Ruth T.; Chiang, Ming-Yi; Tanabe, Teruyo; Kobayashi, Mime; Yasuda, Kunio; Evans, Ronald M.; Umesono, Kazuhiko

2000-01-01

Although the development of the vertebrate eye is well described, the number of transcription factors known to be key to this process is still limited. The localized expression of the orphan nuclear receptor Tlx in the optic cup and discrete parts of the central nervous system suggested the possible role of Tlx in the formation or function of these structures. Analyses of Tlx targeted mice revealed that, in addition to the central nervous system cortical defects, lack of Tlx function results in progressive retinal and optic nerve degeneration with associated blindness. An extensive screen of Tlx-positive and Tlx-negative P19 neural precursors identified Pax2 as a candidate target gene. This identification is significant, because Pax2 is known to be involved in retinal development in both the human and the mouse eye. We find that Pax2 is a direct target and that the Tlx binding site in its promoter is conserved between mouse and human. These studies show that Tlx is a key component of retinal development and vision and an upstream regulator of the Pax2 signaling cascade. PMID:10706625

Morphology, Kinematics, and Dynamics: The Mechanics of Suction Feeding in Fishes.

PubMed

Day, Steven W; Higham, Timothy E; Holzman, Roi; Van Wassenbergh, Sam

2015-07-01

Suction feeding is pervasive among aquatic vertebrates, and our understanding of the functional morphology and biomechanics of suction feeding has recently been advanced by combining experimental and modeling approaches. Key advances include the visualization of the patterns of flow in front of the mouth of a feeding fish, the measurement of pressure inside their mouth cavity, and the employment of analytical and computational models. Here, we review the key components of the morphology and kinematics of the suction-feeding system of anatomically generalized, adult ray-finned fishes, followed by an overview of the hydrodynamics involved. In the suction-feeding apparatus, a strong mechanistic link among morphology, kinematics, and the capture of prey is manifested through the hydrodynamic interactions between the suction flows and solid surfaces (the mouth cavity and the prey). It is therefore a powerful experimental system in which the ecology and evolution of the capture of prey can be studied based on first principals. © The Author 2015. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Biocuration at the Saccharomyces genome database.

PubMed

Skrzypek, Marek S; Nash, Robert S

2015-08-01

Saccharomyces Genome Database is an online resource dedicated to managing information about the biology and genetics of the model organism, yeast (Saccharomyces cerevisiae). This information is derived primarily from scientific publications through a process of human curation that involves manual extraction of data and their organization into a comprehensive system of knowledge. This system provides a foundation for further analysis of experimental data coming from research on yeast as well as other organisms. In this review we will demonstrate how biocuration and biocurators add a key component, the biological context, to our understanding of how genes, proteins, genomes and cells function and interact. We will explain the role biocurators play in sifting through the wealth of biological data to incorporate and connect key information. We will also discuss the many ways we assist researchers with their various research needs. We hope to convince the reader that manual curation is vital in converting the flood of data into organized and interconnected knowledge, and that biocurators play an essential role in the integration of scientific information into a coherent model of the cell. © 2015 Wiley Periodicals, Inc.

Biocuration at the Saccharomyces Genome Database

PubMed Central

Skrzypek, Marek S.; Nash, Robert S.

2015-01-01

Saccharomyces Genome Database is an online resource dedicated to managing information about the biology and genetics of the model organism, yeast (Saccharomyces cerevisiae). This information is derived primarily from scientific publications through a process of human curation that involves manual extraction of data and their organization into a comprehensive system of knowledge. This system provides a foundation for further analysis of experimental data coming from research on yeast as well as other organisms. In this review we will demonstrate how biocuration and biocurators add a key component, the biological context, to our understanding of how genes, proteins, genomes and cells function and interact. We will explain the role biocurators play in sifting through the wealth of biological data to incorporate and connect key information. We will also discuss the many ways we assist researchers with their various research needs. We hope to convince the reader that manual curation is vital in converting the flood of data into organized and interconnected knowledge, and that biocurators play an essential role in the integration of scientific information into a coherent model of the cell. PMID:25997651

Dynamic autophosphorylation of mps1 kinase is required for faithful mitotic progression.

PubMed

Wang, Xinghui; Yu, Huijuan; Xu, Leilei; Zhu, Tongge; Zheng, Fan; Fu, Chuanhai; Wang, Zhiyong; Dou, Zhen

2014-01-01

The spindle assembly checkpoint (SAC) is a surveillance mechanism monitoring cell cycle progression, thus ensuring accurate chromosome segregation. The conserved mitotic kinase Mps1 is a key component of the SAC. The human Mps1 exhibits comprehensive phosphorylation during mitosis. However, the related biological relevance is largely unknown. Here, we demonstrate that 8 autophosphorylation sites within the N-terminus of Mps1, outside of the catalytic domain, are involved in regulating Mps1 kinetochore localization. The phospho-mimicking mutant of the 8 autophosphorylation sites impairs Mps1 localization to kinetochore and also affects the kinetochore recruitment of BubR1 and Mad2, two key SAC effectors, subsequently leading to chromosome segregation errors. Interestingly, the non-phosphorylatable mutant of the 8 autophosphorylation sites enhances Mps1 kinetochore localization and delays anaphase onset. We further show that the Mps1 phospho-mimicking and non-phosphorylatable mutants do not affect metaphase chromosome congression. Thus, our results highlight the importance of dynamic autophosphorylation of Mps1 in regulating accurate chromosome segregation and ensuring proper mitotic progression.

Dynamic Autophosphorylation of Mps1 Kinase Is Required for Faithful Mitotic Progression

PubMed Central

Wang, Xinghui; Yu, Huijuan; Xu, Leilei; Zhu, Tongge; Zheng, Fan; Fu, Chuanhai; Wang, Zhiyong; Dou, Zhen

2014-01-01

The spindle assembly checkpoint (SAC) is a surveillance mechanism monitoring cell cycle progression, thus ensuring accurate chromosome segregation. The conserved mitotic kinase Mps1 is a key component of the SAC. The human Mps1 exhibits comprehensive phosphorylation during mitosis. However, the related biological relevance is largely unknown. Here, we demonstrate that 8 autophosphorylation sites within the N-terminus of Mps1, outside of the catalytic domain, are involved in regulating Mps1 kinetochore localization. The phospho-mimicking mutant of the 8 autophosphorylation sites impairs Mps1 localization to kinetochore and also affects the kinetochore recruitment of BubR1 and Mad2, two key SAC effectors, subsequently leading to chromosome segregation errors. Interestingly, the non-phosphorylatable mutant of the 8 autophosphorylation sites enhances Mps1 kinetochore localization and delays anaphase onset. We further show that the Mps1 phospho-mimicking and non-phosphorylatable mutants do not affect metaphase chromosome congression. Thus, our results highlight the importance of dynamic autophosphorylation of Mps1 in regulating accurate chromosome segregation and ensuring proper mitotic progression. PMID:25265012

Bond Graph Modeling of Chemiosmotic Biomolecular Energy Transduction.

PubMed

Gawthrop, Peter J

2017-04-01

Engineering systems modeling and analysis based on the bond graph approach has been applied to biomolecular systems. In this context, the notion of a Faraday-equivalent chemical potential is introduced which allows chemical potential to be expressed in an analogous manner to electrical volts thus allowing engineering intuition to be applied to biomolecular systems. Redox reactions, and their representation by half-reactions, are key components of biological systems which involve both electrical and chemical domains. A bond graph interpretation of redox reactions is given which combines bond graphs with the Faraday-equivalent chemical potential. This approach is particularly relevant when the biomolecular system implements chemoelectrical transduction - for example chemiosmosis within the key metabolic pathway of mitochondria: oxidative phosphorylation. An alternative way of implementing computational modularity using bond graphs is introduced and used to give a physically based model of the mitochondrial electron transport chain To illustrate the overall approach, this model is analyzed using the Faraday-equivalent chemical potential approach and engineering intuition is used to guide affinity equalisation: a energy based analysis of the mitochondrial electron transport chain.

Role of Complement on Broken Surfaces After Trauma.

PubMed

Huber-Lang, Markus; Ignatius, Anita; Brenner, Rolf E

2015-01-01

Activation of both the complement and coagulation cascade after trauma and subsequent local and systemic inflammatory response represent a major scientific and clinical problem. After severe tissue injury and bone fracture, exposure of innate immunity to damaged cells and molecular debris is considered a main trigger of the posttraumatic danger response. However, the effects of cellular fragments (e.g., histones) on complement activation remain enigmatic. Furthermore, direct effects of "broken" bone and cartilage surfaces on the fluid phase response of complement and its interaction with key cells of connective tissues are still unknown. Here, we summarize data suggesting direct and indirect complement activation by extracellular and cellular danger associated molecular patterns. In addition, key complement components and the corresponding receptors (such as C3aR, C5aR) have been detected on "exposed surfaces" of the damaged regions. On a cellular level, multiple effects of complement activation products on osteoblasts, osteoclasts, chondrocytes and mesenchymal stem cells have been found.In conclusion, the complement system may be activated by trauma-altered surfaces and is crucially involved in connective tissue healing and posttraumatic systemic inflammatory response.

Preventing alcohol misuse in young people aged 9-11 years through promoting family communication: an exploratory evaluation of the Kids, Adults Together (KAT) Programme

PubMed Central

2011-01-01

Background Alcohol misuse by young people is an important public health issue, and has led to the development of a range of prevention interventions. Evidence concerning the most effective approaches to intervention design and implementation is limited. Parental involvement in school-based interventions is important, but many programmes fail to recruit large numbers of parents. This paper reports findings from an exploratory evaluation of a new alcohol misuse prevention programme - Kids, Adults Together (KAT), which comprised a classroom component, engagement with parents through a fun evening for families with children aged 9-11 years, and a DVD. The evaluation aimed to establish the programme's theoretical basis, explore implementation processes and acceptability, and identify plausible precursors of the intended long-term outcomes. Methods Documentary analysis and interviews with key personnel examined the programme's development. Classroom preparation and KAT family events in two schools were observed. Focus groups with children, and interviews with parents who attended KAT family events were held immediately after programme delivery, and again after three months. Interviews with head teachers and with teachers who delivered the classroom preparation were conducted. Follow-up interviews with programme personnel were undertaken. Questionnaires were sent to parents of all children involved in classroom preparation. Results KAT achieved high levels of acceptability and involvement among both children and parents. Main perceived impacts of the programme were increased pro-social communication within families (including discussions about harmful parental alcohol consumption), heightened knowledge and awareness of the effects of alcohol consumption and key legal and health issues, and changes in parental drinking behaviours. Conclusions KAT demonstrated promise as a prevention intervention, primarily through its impact on knowledge and communication processes within families, and its ability to engage with large numbers of parents. A key programme mechanism was the classroom preparation's facilitation of parental involvement in the family fun evening. The programme also incorporated features identified in the literature as likely to increase effectiveness, including a focus on harm reduction, interactive delivery, and targeting primary-school-age children. Further research is needed to test and develop programme theory through implementation in different school contexts, and to examine potential longer-term impacts, and the feasibility of large scale delivery. PMID:22004185

One Step Quantum Key Distribution Based on EPR Entanglement.

PubMed

Li, Jian; Li, Na; Li, Lei-Lei; Wang, Tao

2016-06-30

A novel quantum key distribution protocol is presented, based on entanglement and dense coding and allowing asymptotically secure key distribution. Considering the storage time limit of quantum bits, a grouping quantum key distribution protocol is proposed, which overcomes the vulnerability of first protocol and improves the maneuverability. Moreover, a security analysis is given and a simple type of eavesdropper's attack would introduce at least an error rate of 46.875%. Compared with the "Ping-pong" protocol involving two steps, the proposed protocol does not need to store the qubit and only involves one step.

Nurse practitioner integration: Qualitative experiences of the change management process.

PubMed

Lowe, Grainne; Plummer, Virginia; Boyd, Leanne

2018-04-30

The aim of this qualitative research was to explore perceptions of organisational change related to the integration of nurse practitioners from key nursing stakeholders. The ongoing delivery of effective and efficient patient services is reliant upon the development and sustainability of nurse practitioner roles. Examination of the factors contributing to the underutilization of nurse practitioner roles is crucial to inform future management policies. A change management theory is used to reveal the complexity involved. Qualitative interviews were undertaken using a purposive sampling strategy of key stakeholders. Thematic analysis was undertaken and key themes were correlated to the theoretical framework. The results confirm the benefits of nurse practitioner roles, but suggest organisational structures and embedded professional cultures present barriers to full role optimization. Complicated policy processes are creating barriers to the integration of nurse practitioner roles. The findings increase understanding of the links between strategic planning, human resource management, professional and organisational cultures, governance and politics in change management. Effective leadership drives the change process through the ability to align key components necessary for success. Sustainability of nurse practitioners relies on recognition of their full potential in the health care team. The results of this study highlight the importance of management and leadership in the promotion of advanced nursing skills and experience to better meet patient outcomes. The findings reinforce the potential of nurse practitioners to deliver patient centred, timely and efficient health care. © 2018 John Wiley & Sons Ltd.

Empirical Analysis of Optical Attenuator Performance in Quantum Key Distribution Systems Using a Particle Model

DTIC Science & Technology

2012-03-01

EMPIRICAL ANALYSIS OF OPTICAL ATTENUATOR PERFORMANCE IN QUANTUM KEY DISTRIBUTION SYSTEMS USING A...DISTRIBUTION IS UNLIMITED AFIT/GCS/ENG/12-01 EMPIRICAL ANALYSIS OF OPTICAL ATTENUATOR PERFORMANCE IN QUANTUM KEY DISTRIBUTION SYSTEMS USING ...challenging as the complexity of actual implementation specifics are considered. Two components common to most quantum key distribution

Zinc transporters YbtX and ZnuABC are required for the virulence of Yersinia pestis in bubonic and pneumonic plague in mice.

PubMed

Bobrov, Alexander G; Kirillina, Olga; Fosso, Marina Y; Fetherston, Jacqueline D; Miller, M Clarke; VanCleave, Tiva T; Burlison, Joseph A; Arnold, William K; Lawrenz, Matthew B; Garneau-Tsodikova, Sylvie; Perry, Robert D

2017-06-21

A number of bacterial pathogens require the ZnuABC Zinc (Zn 2+ ) transporter and/or a second Zn 2+ transport system to overcome Zn 2+ sequestration by mammalian hosts. Previously we have shown that in addition to ZnuABC, Yersinia pestis possesses a second Zn 2+ transporter that involves components of the yersiniabactin (Ybt), siderophore-dependent iron transport system. Synthesis of the Ybt siderophore and YbtX, a member of the major facilitator superfamily, are both critical components of the second Zn 2+ transport system. Here we demonstrate that a ybtX znu double mutant is essentially avirulent in mouse models of bubonic and pneumonic plague while a ybtX mutant retains high virulence in both plague models. While sequestration of host Zn is a key nutritional immunity factor, excess Zn appears to have a significant antimicrobial role in controlling intracellular bacterial survival. Here, we demonstrate that ZntA, a Zn 2+ exporter, plays a role in resistance to Zn toxicity in vitro, but that a zntA zur double mutant retains high virulence in both pneumonic and bubonic plague models and survival in macrophages. We also confirm that Ybt does not directly bind Zn 2+ in vitro under the conditions tested. However, we detect a significant increase in Zn 2+ -binding ability of filtered supernatants from a Ybt + strain compared to those from a strain unable to produce the siderophore, supporting our previously published data that Ybt biosynthetic genes are involved in the production of a secreted Zn-binding molecule (zincophore). Our data suggest that Ybt or a modified Ybt participate in or promote Zn-binding activity in culture supernatants and is involved in Zn acquisition in Y. pestis.

Control of Diapause in Calanid Copepods: Identification of Regulatory Pathways using In Silico Data Mining

NASA Astrophysics Data System (ADS)

Lenz, P. H.; Roncalli, V.; Hopcroft, R. R.; Christie, A. E.

2016-02-01

As water temperatures and seasonal cycles change with global warming, questions are being raised on how these factors might affect the life cycles of copepods in the family Calanidae. These species depend on the completion of a seasonal diapause for the annual recruitment of the spring population. Diapause is a developmental program that includes induction, preparation, initiation, maintenance and termination. A lipid hypothesis has been proposed to explain the regulation of diapause in Calanus finmarchicus. While lipids may be critical for the diapause program, lipid metabolism is typically under neuroendocrine control. In insects, there is an extensive literature showing that juvenile hormone, ecdysteroids, and many neuropeptides are involved in the regulation of diapause. In particular, insulin signaling has been proposed as a key component in the diapause phenotype in a wide variety of insects, and through the actions of the transcription factor FOXO, many features of diapause can be linked to the insulin pathway, e.g., fat accumulation and enhancement of stress tolerance. Using the insects as models, we identified transcripts and predicted the protein components of the insulin/FOXO pathway (e.g., insulin-like peptide precursors, insulin receptors, juvenile hormone acid O-methyltransferase and FOXO), as well as a wide variety of neuropeptides (e.g., members of the diapause hormone family) and other proteins (e.g., those putatively involved in biological timing such as circadian and seasonal rhythmicity) that might be involved in the regulation of lipid metabolism and diapause in the calanid copepods C. finmarchicus and Neocalanus flemingeri. Our goal is to use the identified transcripts to start to understand the physiological processes underlying diapause in these calanids.

Involvement of the CasK/R two-component system in optimal unsaturation of the Bacillus cereus fatty acids during low-temperature growth.

PubMed

Diomandé, Sara Esther; Nguyen-the, Christophe; Abee, Tjakko; Tempelaars, Marcel H; Broussolle, Véronique; Brillard, Julien

2015-11-20

Bacillus cereus sensu lato is composed of a set of ubiquitous strains including human pathogens that can survive a range of food processing conditions, grow in refrigerated food, and sometimes cause food poisoning. We previously identified the two-component system CasK/R that plays a key role in cold adaptation. To better understand the CasK/R-controlled mechanisms that support low-temperature adaptation, we performed a transcriptomic analysis on the ATCC 14579 strain and its isogenic ∆casK/R mutant grown at 12°C. Several genes involved in fatty acid (FA) metabolism were downregulated in the mutant, including desA and desB encoding FA acyl-lipid desaturases that catalyze the formation of a double-bond on the FA chain in positions ∆5 and ∆10, respectively. A lower proportion of FAs presumably unsaturated by DesA was observed in the ΔcasK/R strain compared to the parental strain while no difference was found for FAs presumably unsaturated by DesB. Addition of phospholipids from egg yolk lecithin rich in unsaturated FAs, to growth medium, abolished the cold-growth impairment of ΔcasK/R suggesting that exogenous unsaturated FAs can support membrane-level modifications and thus compensate for the decreased production of these FAs in the B. cereus ∆casK/R mutant during growth at low temperature. Our findings indicate that CasK/R is involved in the regulation of FA metabolism, and is necessary for cold adaptation of B. cereus unless an exogenous source of unsaturated FAs is available. Copyright © 2015 Elsevier B.V. All rights reserved.

Parental involvement and association with adolescents' fruit and vegetable intake at follow-up: Process evaluation results from the multi-component school-based Boost intervention.

PubMed

Jørgensen, Sanne Ellegård; Jørgensen, Thea Suldrup; Aarestrup, Anne Kristine; Due, Pernille; Krølner, Rikke

2016-10-26

Based on the assumption of parental influence on adolescent behavior, multicomponent school-based dietary interventions often include a parental component. The effect of this intervention component is seldom reported and the evidence is inconsistent. We conducted a systematic process evaluation of the parental component and examined whether the leveal of parental involvement in a large multi-component intervention: the Boost study was associated with adolescents' fruit and vegetable (FV) intake at follow-up. The Boost study was targeting FV intake among 1,175 Danish 7 th graders (≈13- year-olds) in the school year 2010/11. The study included a school component: free FV in class and curricular activities; a local community component: fact sheets for sports- and youth clubs; and a parental component: presentation of Boost at a parent-school meeting, 6 newsletters to parents, 3 guided student-parent curricular activities, and a student-parent Boost event. Students whose parent replied to the follow-up survey (n = 347). Questionnaire data from students, parents and teachers at 20 intervention schools. Process evaluation measures: dose delivered, dose received, appreciation and level of parental involvement. Parental involvement was trichotomized into: low/no (0-2 points), medium (3 points) and high (4-6 points). The association between level of parental involvement and self-reported FV intake (24-h recall), was analyzed using multilevel regression analyses. The Boost study was presented at a parent-school meeting at all intervention schools. The dose delivered was low to moderate for the three other parental elements. Most parents appreciated the intervention and talked with their child about Boost (83.5 %). High, medium and low parental involvement was found among 30.5 %, 29.6 % and 39.4 % of the students respectively. Parental involvement was highest among women. More men agreed that the parental newsletters provided new information. Students with a medium and high level of parental involvement ate 47.5 and 95.2 g more FV per day compared to students with low level/no parental involvement (p = 0.02). Students with a high level of parental involvement ate significantly more FV at follow-up compared to students with a low level/no parental involvement. Parental involvement in interventions may improve adolescents' FV intake if challenges of implementation can be overcome. ISRCTN11666034 . Registered 06/01/2012. Retrospectively registered.

Known plaintext attack on double random phase encoding using fingerprint as key and a method for avoiding the attack.

PubMed

Tashima, Hideaki; Takeda, Masafumi; Suzuki, Hiroyuki; Obi, Takashi; Yamaguchi, Masahiro; Ohyama, Nagaaki

2010-06-21

We have shown that the application of double random phase encoding (DRPE) to biometrics enables the use of biometrics as cipher keys for binary data encryption. However, DRPE is reported to be vulnerable to known-plaintext attacks (KPAs) using a phase recovery algorithm. In this study, we investigated the vulnerability of DRPE using fingerprints as cipher keys to the KPAs. By means of computational experiments, we estimated the encryption key and restored the fingerprint image using the estimated key. Further, we propose a method for avoiding the KPA on the DRPE that employs the phase retrieval algorithm. The proposed method makes the amplitude component of the encrypted image constant in order to prevent the amplitude component of the encrypted image from being used as a clue for phase retrieval. Computational experiments showed that the proposed method not only avoids revealing the cipher key and the fingerprint but also serves as a sufficiently accurate verification system.

Autoshaping the pigeon's gape response: acquisition and topography as a function of reinforcer type and magnitude.

PubMed Central

Allan, R W; Zeigler, H P

1994-01-01

The pigeon's key-pecking response is experimentally dissociable into transport (head movement) and gape (jaw movement) components. During conditioning of the key-pecking response, both components come under the control of the conditioned stimulus. To study the acquisition of gape conditioned responses and to clarify the contribution of unconditioned stimulus (reinforcer) variables to the form of the response, gape and key-contact responses were recorded during an autoshaping procedure and reinforcer properties were systematically varied. One group of 8 pigeons was food deprived and subgroups of 2 birds each were exposed to four different pellet sizes as reinforcers, each reinforcer signaled by a keylight conditioned stimulus. A second group was water deprived and received water reinforcers paired with the conditioned stimulus. Water- or food-deprived control groups received appropriate water or food reinforcers that were randomly delivered with respect to the keylight stimulus. Acquisition of the conditioned gape response frequently preceded key-contact responses, and gape conditioned responses were generally elicited at higher rates than were key contacts. The form of the conditioned gape was similar to, but not identical with, the form of the unconditioned gape. The gape component is a critical topographical feature of the conditioned key peck, a sensitive measure of conditioning during autoshaping, and an important source of the observed similarities in the form of conditioned and consummatory responses. PMID:7964365

Autoshaping the pigeon's gape response: acquisition and topography as a function of reinforcer type and magnitude.

PubMed

Allan, R W; Zeigler, H P

1994-09-01

The pigeon's key-pecking response is experimentally dissociable into transport (head movement) and gape (jaw movement) components. During conditioning of the key-pecking response, both components come under the control of the conditioned stimulus. To study the acquisition of gape conditioned responses and to clarify the contribution of unconditioned stimulus (reinforcer) variables to the form of the response, gape and key-contact responses were recorded during an autoshaping procedure and reinforcer properties were systematically varied. One group of 8 pigeons was food deprived and subgroups of 2 birds each were exposed to four different pellet sizes as reinforcers, each reinforcer signaled by a keylight conditioned stimulus. A second group was water deprived and received water reinforcers paired with the conditioned stimulus. Water- or food-deprived control groups received appropriate water or food reinforcers that were randomly delivered with respect to the keylight stimulus. Acquisition of the conditioned gape response frequently preceded key-contact responses, and gape conditioned responses were generally elicited at higher rates than were key contacts. The form of the conditioned gape was similar to, but not identical with, the form of the unconditioned gape. The gape component is a critical topographical feature of the conditioned key peck, a sensitive measure of conditioning during autoshaping, and an important source of the observed similarities in the form of conditioned and consummatory responses.

The Emerging Role of Insulin and Insulin-Like Growth Factor Signaling in Cancer Stem Cells

PubMed Central

Malaguarnera, Roberta; Belfiore, Antonino

2014-01-01

Cancer cells frequently exploit the IGF signaling, a fundamental pathway mediating development, cell growth, and survival. As a consequence, several components of the IGF signaling are deregulated in cancer and sustain cancer progression. However, specific targeting of IGF-IR in humans has resulted efficacious only in small subsets of cancers, making researches wondering whether IGF system targeting is still worth pursuing in the clinical setting. Although no definite answer is yet available, it has become increasingly clear that other components of the IGF signaling pathway, such as IR-A, may substitute for the lack of IGF-IR, and induce cancer resistance and/or clonal selection. Moreover, accumulating evidence now indicates that IGF signaling is a central player in the induction/maintenance of epithelial mesenchymal transition (EMT) and cell stemness, two strictly related programs, which play a key role in metastatic spread and resistance to cancer treatments. Here we review the evidences indicating that IGF signaling enhances the expression of transcription factors implicated in the EMT program and has extensive cross-talk with specific pathways involved in cell pluripotency and stemness maintenance. In turn, EMT and cell stemness activate positive feed-back mechanisms causing up-regulation of various IGF signaling components. These findings may have novel translational implications. PMID:24550888

TBK1-targeted suppression of TRIF-dependent signaling pathway of Toll-like receptors by 6-shogaol, an active component of ginger.

PubMed

Park, Se-Jeong; Lee, Mi-Young; Son, Bu-Soon; Youn, Hyung-Sun

2009-07-01

Toll-like receptors (TLRs) are primary sensors that detect a wide variety of microbial components involving induction of innate immune responses. After recognition of microbial components, TLRs trigger the activation of myeloid differential factor 88 (MyD88) and Toll-interleukin-1 (IL-1) receptor domain-containing adapter inducing interferon-beta (TRIF)-dependent downstream signaling pathways. 6-Shoagol, an active ingredient of ginger, inhibits the MyD88-dependent signaling pathway by inhibiting inhibitor-kappaB kinase activity. Inhibitor-kappaB kinase is a key kinase in nuclear factor kappaB (NF-kappaB) activation. However, it is not known whether 6-shogaol inhibits the TRIF-dependent signaling pathway. Our goal was to identify the molecular target of 6-shogaol in the TRIF-dependent pathway of TLRs. 6-Shogaol inhibited the activation of interferon-regulatory factor 3 (IRF3) induced by lipopolysaccharide (LPS) and by polyriboinosinic polyribocytidylic acid (poly[I:C]), overexpression of TRIF, TANK-binding kinase1 (TBK1), and IRF3. Furthermore, 6-shogaol inhibited TBK1 activity in vitro. Together, these results suggest that 6-shogaol inhibits the TRIF-dependent signaling pathway of TLRs by targeting TBK1, and, they imply that 6-shogaol can modulate TLR-derived immune/inflammatory target gene expression induced by microbial infection.

Conceptual design and analysis of a dynamic scale model of the Space Station Freedom

NASA Technical Reports Server (NTRS)

Davis, D. A.; Gronet, M. J.; Tan, M. K.; Thorne, J.

1994-01-01

This report documents the conceptual design study performed to evaluate design options for a subscale dynamic test model which could be used to investigate the expected on-orbit structural dynamic characteristics of the Space Station Freedom early build configurations. The baseline option was a 'near-replica' model of the SSF SC-7 pre-integrated truss configuration. The approach used to develop conceptual design options involved three sets of studies: evaluation of the full-scale design and analysis databases, conducting scale factor trade studies, and performing design sensitivity studies. The scale factor trade study was conducted to develop a fundamental understanding of the key scaling parameters that drive design, performance and cost of a SSF dynamic scale model. Four scale model options were estimated: 1/4, 1/5, 1/7, and 1/10 scale. Prototype hardware was fabricated to assess producibility issues. Based on the results of the study, a 1/4-scale size is recommended based on the increased model fidelity associated with a larger scale factor. A design sensitivity study was performed to identify critical hardware component properties that drive dynamic performance. A total of 118 component properties were identified which require high-fidelity replication. Lower fidelity dynamic similarity scaling can be used for non-critical components.

Traversing the Links between Heavy Metal Stress and Plant Signaling

PubMed Central

Jalmi, Siddhi K.; Bhagat, Prakash K.; Verma, Deepanjali; Noryang, Stanzin; Tayyeba, Sumaira; Singh, Kirti; Sharma, Deepika; Sinha, Alok K.

2018-01-01

Plants confront multifarious environmental stresses widely divided into abiotic and biotic stresses, of which heavy metal stress represents one of the most damaging abiotic stresses. Heavy metals cause toxicity by targeting crucial molecules and vital processes in the plant cell. One of the approaches by which heavy metals act in plants is by over production of reactive oxygen species (ROS) either directly or indirectly. Plants act against such overdose of metal in the environment by boosting the defense responses like metal chelation, sequestration into vacuole, regulation of metal intake by transporters, and intensification of antioxidative mechanisms. This response shown by plants is the result of intricate signaling networks functioning in the cell in order to transmit the extracellular stimuli into an intracellular response. The crucial signaling components involved are calcium signaling, hormone signaling, and mitogen activated protein kinase (MAPK) signaling that are discussed in this review. Apart from signaling components other regulators like microRNAs and transcription factors also have a major contribution in regulating heavy metal stress. This review demonstrates the key role of MAPKs in synchronously controlling the other signaling components and regulators in metal stress. Further, attempts have been made to focus on metal transporters and chelators that are regulated by MAPK signaling. PMID:29459874

TPV Power Source Using Infrared-Sensitive Cells with Commercially Available Radiant Tube Burner

NASA Astrophysics Data System (ADS)

Fraas, Lewis; Minkin, Leonid; Hui, She; Avery, James; Howells, Christopher

2004-11-01

Over the last several years, JX Crystals has invented and systematically developed the key components for thermophotovoltaic systems. These key components include GaSb infrared sensitive cells, high power density shingle circuits, dielectric filters, and hydrocarbon-fueled radiant tube burners. Most recently, we invented and demonstrated an antireflection (AR)-coated tungsten IR emitter which when integrated with the other key components should make TPV systems with efficiencies over 10% practical. However, the use of the AR tungsten emitter requires an oxygen-free hermetic seal enclosure. During a 2003 Small Business Innovative Research (SBIR) Phase I contract, we integrated a tungsten emitter foil and a commercial SiC radiant tube burner within an emitter thermos and successfully demonstrated its operation at high temperature. We also designed a complete stand alone 500 W TPV generator. During the upcoming SBIR Phase II, we plan to implement this design in hardware.

Zero-Power Radio Device.

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

Brocato, Robert W.

This report describes an unpowered radio receiver capable of detecting and responding to weak signals transmit ted from comparatively long distances . This radio receiver offers key advantages over a short range zero - power radio receiver previously described in SAND2004 - 4610, A Zero - Power Radio Receiver . The device described here can be fabricated as an integrated circuit for use in portable wireless devices, as a wake - up circuit, or a s a stand - alone receiver operating in conjunction with identification decoders or other electroni cs. It builds on key sub - components developed atmore » Sandia National Laboratories over many years. It uses surface acoustic wave (SAW) filter technology. It uses custom component design to enable the efficient use of small aperture antennas. This device uses a key component, the pyroelectric demodulator , covered by Sandia owned U.S. Patent 7397301, Pyroelectric Demodulating Detector [1] . This device is also described in Sandia owned U.S. Patent 97266446, Zero Power Receiver [2].« less

Analysis of proteome dynamics inside the silk gland lumen of Bombyx mori.

PubMed

Dong, Zhaoming; Zhao, Ping; Zhang, Yan; Song, Qianru; Zhang, Xiaolu; Guo, Pengchao; Wang, Dandan; Xia, Qingyou

2016-04-22

The silk gland is the only organ where silk proteins are synthesized and secreted in the silkworm, Bombyx mori. Silk proteins are stored in the lumen of the silk gland for around eight days during the fifth instar. Determining their dynamic changes is helpful for clarifying the secretion mechanism of silk proteins. Here, we identified the proteome in the silk gland lumen using liquid chromatography-tandem mass spectrometry, and demonstrated its changes during two key stages. From day 5 of the fifth instar to day 1 of wandering, the abundances of fibroins, sericins, seroins, and proteins of unknown functions increased significantly in different compartments of the silk gland lumen. As a result, these accumulated proteins constituted the major cocoon components. In contrast, the abundances of enzymes and extracellular matrix proteins decreased in the silk gland lumen, suggesting that they were not the structural constituents of silk. Twenty-five enzymes may be involved in the regulation of hormone metabolism for proper silk gland function. In addition, the metabolism of other non-proteinous components such as chitin and pigment were also discussed in this study.

Analysis of proteome dynamics inside the silk gland lumen of Bombyx mori

PubMed Central

Dong, Zhaoming; Zhao, Ping; Zhang, Yan; Song, Qianru; Zhang, Xiaolu; Guo, Pengchao; Wang, Dandan; Xia, Qingyou

2016-01-01

The silk gland is the only organ where silk proteins are synthesized and secreted in the silkworm, Bombyx mori. Silk proteins are stored in the lumen of the silk gland for around eight days during the fifth instar. Determining their dynamic changes is helpful for clarifying the secretion mechanism of silk proteins. Here, we identified the proteome in the silk gland lumen using liquid chromatography–tandem mass spectrometry, and demonstrated its changes during two key stages. From day 5 of the fifth instar to day 1 of wandering, the abundances of fibroins, sericins, seroins, and proteins of unknown functions increased significantly in different compartments of the silk gland lumen. As a result, these accumulated proteins constituted the major cocoon components. In contrast, the abundances of enzymes and extracellular matrix proteins decreased in the silk gland lumen, suggesting that they were not the structural constituents of silk. Twenty-five enzymes may be involved in the regulation of hormone metabolism for proper silk gland function. In addition, the metabolism of other non-proteinous components such as chitin and pigment were also discussed in this study. PMID:27102218

Steam generator design for solar towers using solar salt as heat transfer fluid

NASA Astrophysics Data System (ADS)

González-Gómez, Pedro Ángel; Petrakopoulou, Fontina; Briongos, Javier Villa; Santana, Domingo

2017-06-01

Since the operation of a concentrating solar power plant depends on the intermittent character of solar energy, the steam generator is subject to daily start-ups, stops and load variations. Faster start-up and load changes increase the plant flexibility and the daily energy production. However, it involves high thermal stresses on thick-walled components. Continuous operational conditions may eventually lead to a material failure. For these reasons, it is important to evaluate the transient behavior of the proposed designs in order to assure the reliability. The aim of this work is to analyze different steam generator designs for solar power tower plants using molten salt as heat transfer fluid. A conceptual steam generator design is proposed and associated heat transfer areas and steam drum size are calculated. Then, dynamic models for the main parts of the steam generator are developed to represent its transient performance. A temperature change rate that ensures safe hot start-up conditions is studied for the molten salt. The thermal stress evolution on the steam drum is calculated as key component of the steam generator.

A review of fracture mechanics life technology

NASA Technical Reports Server (NTRS)

Besuner, P. M.; Harris, D. O.; Thomas, J. M.

1986-01-01

Lifetime prediction technology for structural components subjected to cyclic loads is examined. The central objectives of the project are: (1) to report the current state of the art, and (2) recommend future development of fracture mechanics-based analytical tools for modeling subcritical fatigue crack growth in structures. Of special interest is the ability to apply these tools to practical engineering problems and the developmental steps necessary to bring vital technologies to this stage. The authors conducted a survey of published literature and numerous discussions with experts in the field of fracture mechanics life technology. One of the key points made is that fracture mechanics analyses of crack growth often involve consideration of fatigue and fracture under extreme conditions. Therefore, inaccuracies in predicting component lifetime will be dominated by inaccuracies in environment and fatigue crack growth relations, stress intensity factor solutions, and methods used to model given loads and stresses. Suggestions made for reducing these inaccuracies include development of improved models of subcritical crack growth, research efforts aimed at better characterizing residual and assembly stresses that can be introduced during fabrication, and more widespread and uniform use of the best existing methods.

Cost-Benefit of Improving the Efficiency of Room Air Conditioners (Inverter and Fixed Speed) in India

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

Phadke, Amol; Shah, Nihar; Abhyankar, Nikit

Improving efficiency of air conditioners (ACs) typically involves improving the efficiency of various components such as compressors, heat exchangers, expansion valves, refrigerant,and fans. We estimate the incremental cost of improving the efficiency of room ACs based on the cost of improving the efficiency of its key components. Further, we estimate the retail price increase required to cover the cost of efficiency improvement, compare it with electricity bill savings, and calculate the payback period for consumers to recover the additional price of a more efficient AC. The finding that significant efficiency improvement is cost effective from a consumer perspective is robustmore » over a wide range of assumptions. If we assume a 50% higher incremental price compared to our baseline estimate, the payback period for the efficiency level of 3.5 ISEER is 1.1 years. Given the findings of this study, establishing more stringent minimum efficiency performance criteria (one-star level) should be evaluated rigorously considering significant benefits to consumers, energy security, and environment« less

Structure and mechanism of the essential two-component signal-transduction system WalKR in Staphylococcus aureus

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

Ji, Quanjiang; Chen, Peter J.; Qin, Guangrong

Most low GC Gram-positive bacteria possess an essential walKR two-component system (TCS) for signal transduction involved in regulating cell wall homoeostasis. Despite the well-established intracellular regulatory mechanism, the role of this TCS in extracellular signal recognition and factors that modulate the activity of this TCS remain largely unknown. Here we identify the extracellular receptor of the kinase ‘WalK’ (erWalK) as a key hub for bridging extracellular signal input and intracellular kinase activity modulation in Staphylococcus aureus. Characterization of the crystal structure of erWalK revealed a canonical Per-Arnt-Sim (PAS) domain for signal sensing. Single amino-acid mutation of potential signal-transduction residues resultedmore » in severely impaired function of WalKR. A small molecule derived from structure-based virtual screening against erWalK is capable of selectively activating the walKR TCS. Lastly, the molecular level characterization of erWalK will not only facilitate exploration of natural signal(s) but also provide a template for rational design of erWalK inhibitors.« less

Effects of plume afterburning on infrared spectroscopy

NASA Astrophysics Data System (ADS)

Zhu, Xijuan; Xu, Ying; Ma, Jing; Duan, Ran; Wu, Jie

2017-10-01

Contains H2, CO and unburned components of high-temperature plume of rocket engine, then injected into the atmosphere, continue to carry out the oxidation reaction in the plume near field region with the volume in the plume of oxygen in the air, two times burning. The afterburning is an important cause of infrared radiation intensification of propellant plume, which increases the temperature of the flame and changes the components of the gas, thus enhancing the infrared radiation intensity of the flame. [1]. Two the combustion numerical using chemical reaction mechanism involving HO2 intermediate reaction, the study confirmed that HO2 is a key intermediate, plays a decisive role to trigger early response, on afterburning temperature and flow concentration distribution effect. A finite rate chemical reaction model is used to describe the two burning phenomenon in high temperature plume[2]. In this paper, a numerical simulation of the flame flow field and radiative transfer is carried out for the afterburning phenomenon. The effects of afterburning on the composition, temperature and infrared radiation of the plume are obtained by comparison.

Gut microbiota functions: metabolism of nutrients and other food components.

PubMed

Rowland, Ian; Gibson, Glenn; Heinken, Almut; Scott, Karen; Swann, Jonathan; Thiele, Ines; Tuohy, Kieran

2018-02-01

The diverse microbial community that inhabits the human gut has an extensive metabolic repertoire that is distinct from, but complements the activity of mammalian enzymes in the liver and gut mucosa and includes functions essential for host digestion. As such, the gut microbiota is a key factor in shaping the biochemical profile of the diet and, therefore, its impact on host health and disease. The important role that the gut microbiota appears to play in human metabolism and health has stimulated research into the identification of specific microorganisms involved in different processes, and the elucidation of metabolic pathways, particularly those associated with metabolism of dietary components and some host-generated substances. In the first part of the review, we discuss the main gut microorganisms, particularly bacteria, and microbial pathways associated with the metabolism of dietary carbohydrates (to short chain fatty acids and gases), proteins, plant polyphenols, bile acids, and vitamins. The second part of the review focuses on the methodologies, existing and novel, that can be employed to explore gut microbial pathways of metabolism. These include mathematical models, omics techniques, isolated microbes, and enzyme assays.

A systems level analysis of the mirror neuron hypothesis and imitation impairments in autism spectrum disorders.

PubMed

Kana, Rajesh K; Wadsworth, Heather M; Travers, Brittany G

2011-01-01

Although several studies suggest an imitation deficit as a key feature of autism, questions have been raised about the consistency of this finding and about the component skills involved in imitation. The primary aim of this review is to examine the uneven profile of imitation deficits found in autism in the context of the mirror neuron system (MNS) dysfunction hypothesis. We use the cortical underconnectivity framework (Just et al., 2004) to examine the coordination of brain areas that orchestrate the communication between the component skills underlying imitation. A comprehensive account of imitation deficit in autism should take into account the regions that are at the core of the MNS (e.g., IFG and IPL) and related regions that feed into the MNS (e.g., STS, Cerebellum) in their functioning and in their coordination. Our findings suggest that the MNS may be associated with mediating familiarity, attention, self-other matching, and social relevance, which may be vital in characterizing the imitation deficits in autism. Such an analysis may have greater clinical and therapeutic value. Published by Elsevier Ltd.

S phase activation of the histone H2B promoter by OCA-S, a coactivator complex that contains GAPDH as a key component.

PubMed

Zheng, Lei; Roeder, Robert G; Luo, Yan

2003-07-25

We have isolated and functionally characterized a multicomponent Oct-1 coactivator, OCA-S which is essential for S phase-dependent histone H2B transcription. The p38 component of OCA-S binds directly to Oct-1, exhibits potent transactivation potential, is selectively recruited to the H2B promoter in S phase, and is essential for S phase-specific H2B transcription in vivo and in vitro. Surprisingly, p38 represents a nuclear form of glyceraldehyde-3-phosphate dehydrogenase, and binding to Oct-1, as well as OCA-S function, is stimulated by NAD(+) but inhibited by NADH. OCA-S also interacts with NPAT, a cyclin E/cdk2 substrate that is broadly involved in histone gene transcription. These studies thus link the H2B transcriptional machinery to cell cycle regulators, and possibly to cellular metabolic state (redox status), and set the stage for studies of the underlying mechanisms and the basis for coordinated histone gene expression and coupling to DNA replication.

NF-κB and the link between inflammation and cancer.

PubMed

DiDonato, Joseph A; Mercurio, Frank; Karin, Michael

2012-03-01

The nuclear factor-κB (NF-κB) transcription factor family has been considered the central mediator of the inflammatory process and a key participant in innate and adaptive immune responses. Coincident with the molecular cloning of NF-κB/RelA and identification of its kinship to the v-Rel oncogene, it was anticipated that NF-κB itself would be involved in cancer development. Oncogenic activating mutations in NF-κB genes are rare and have been identified only in some lymphoid malignancies, while most NF-κB activating mutations in lymphoid malignancies occur in upstream signaling components that feed into NF-κB. NF-κB activation is also prevalent in carcinomas, in which NF-κB activation is mainly driven by inflammatory cytokines within the tumor microenvironment. Importantly, however, in all malignancies, NF-κB acts in a cell type-specific manner: activating survival genes within cancer cells and inflammation-promoting genes in components of the tumor microenvironment. Yet, the complex biological functions of NF-κB have made its therapeutic targeting a challenge. © 2012 John Wiley & Sons A/S.

Structure and mechanism of the essential two-component signal-transduction system WalKR in Staphylococcus aureus

DOE PAGES

Ji, Quanjiang; Chen, Peter J.; Qin, Guangrong; ...

2016-03-18

Most low GC Gram-positive bacteria possess an essential walKR two-component system (TCS) for signal transduction involved in regulating cell wall homoeostasis. Despite the well-established intracellular regulatory mechanism, the role of this TCS in extracellular signal recognition and factors that modulate the activity of this TCS remain largely unknown. Here we identify the extracellular receptor of the kinase ‘WalK’ (erWalK) as a key hub for bridging extracellular signal input and intracellular kinase activity modulation in Staphylococcus aureus. Characterization of the crystal structure of erWalK revealed a canonical Per-Arnt-Sim (PAS) domain for signal sensing. Single amino-acid mutation of potential signal-transduction residues resultedmore » in severely impaired function of WalKR. A small molecule derived from structure-based virtual screening against erWalK is capable of selectively activating the walKR TCS. Lastly, the molecular level characterization of erWalK will not only facilitate exploration of natural signal(s) but also provide a template for rational design of erWalK inhibitors.« less

Brain-heart coupling at the P300 latency is linked to anterior cingulate cortex and insula--a cardio-electroencephalographic covariance tracing study.

PubMed

Panitz, Christian; Wacker, Jan; Stemmler, Gerhard; Mueller, Erik M

2013-09-01

Prior work on the coupling of cortical and cardiac responses to feedback demonstrated that feedback-evoked single-trial EEG magnitudes 300 ms post-stimulus predict the degree of subsequent cardiac acceleration. The main goal of the current study was to explore the neural sources of this phenomenon using (a) independent component analysis in conjunction with dipole fitting and (b) low resolution electromagnetic tomography (LORETA) in N=14 participants who performed a gambling task with feedback presented after each trial. It was shown that independent components localized near anterior cingulate cortex produced robust within-subjects correlations with feedback-evoked heart-period, suggesting that anterior cingulate cortex activity 300ms after feedback presentation predicts the strength of subsequent cardiac acceleration. Moreover, interindividual differences in evoked left insular cortex LORETA-estimated activity at around 300ms moderated within-subjects EEG-heart period correlations. These results suggest that key regions of central autonomic control are involved in cortico-cardiac coupling evoked by feedback stimuli. Copyright © 2013 Elsevier B.V. All rights reserved.

A review of fracture mechanics life technology

NASA Technical Reports Server (NTRS)

Thomas, J. M.; Besuner, P. M.; Harris, D. O.

1985-01-01

Current lifetime prediction technology for structural components subjected to cyclic loads was reviewed. The central objectives of the project were to report the current state of and recommend future development of fracture mechanics-based analytical tools for modeling and forecasting subcritical fatigue crack growth in structures. Of special interest to NASA was the ability to apply these tools to practical engineering problems and the developmental steps necessary to bring vital technologies to this stage. A survey of published literature and numerous discussions with experts in the field of fracture mechanics life technology were conducted. One of the key points made is that fracture mechanics analyses of crack growth often involve consideration of fatigue and fracture under extreme conditions. Therefore, inaccuracies in predicting component lifetime will be dominated by inaccuracies in environment and fatigue crack growth relations, stress intensity factor solutions, and methods used to model given loads and stresses. Suggestions made for reducing these inaccuracies include: development of improved models of subcritical crack growth, research efforts aimed at better characterizing residual and assembly stresses that can be introduced during fabrication, and more widespread and uniform use of the best existing methods.

Computational model of precision grip in Parkinson's disease: a utility based approach

PubMed Central

Gupta, Ankur; Balasubramani, Pragathi P.; Chakravarthy, V. Srinivasa

2013-01-01

We propose a computational model of Precision Grip (PG) performance in normal subjects and Parkinson's Disease (PD) patients. Prior studies on grip force generation in PD patients show an increase in grip force during ON medication and an increase in the variability of the grip force during OFF medication (Ingvarsson et al., 1997; Fellows et al., 1998). Changes in grip force generation in dopamine-deficient PD conditions strongly suggest contribution of the Basal Ganglia, a deep brain system having a crucial role in translating dopamine signals to decision making. The present approach is to treat the problem of modeling grip force generation as a problem of action selection, which is one of the key functions of the Basal Ganglia. The model consists of two components: (1) the sensory-motor loop component, and (2) the Basal Ganglia component. The sensory-motor loop component converts a reference position and a reference grip force, into lift force and grip force profiles, respectively. These two forces cooperate in grip-lifting a load. The sensory-motor loop component also includes a plant model that represents the interaction between two fingers involved in PG, and the object to be lifted. The Basal Ganglia component is modeled using Reinforcement Learning with the significant difference that the action selection is performed using utility distribution instead of using purely Value-based distribution, thereby incorporating risk-based decision making. The proposed model is able to account for the PG results from normal and PD patients accurately (Ingvarsson et al., 1997; Fellows et al., 1998). To our knowledge the model is the first model of PG in PD conditions. PMID:24348373

Conducting indirect-treatment-comparison and network-meta-analysis studies: report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: part 2.

PubMed

Hoaglin, David C; Hawkins, Neil; Jansen, Jeroen P; Scott, David A; Itzler, Robbin; Cappelleri, Joseph C; Boersma, Cornelis; Thompson, David; Larholt, Kay M; Diaz, Mireya; Barrett, Annabel

2011-06-01

Evidence-based health care decision making requires comparison of all relevant competing interventions. In the absence of randomized controlled trials involving a direct comparison of all treatments of interest, indirect treatment comparisons and network meta-analysis provide useful evidence for judiciously selecting the best treatment(s). Mixed treatment comparisons, a special case of network meta-analysis, combine direct evidence and indirect evidence for particular pairwise comparisons, thereby synthesizing a greater share of the available evidence than traditional meta-analysis. This report from the International Society for Pharmacoeconomics and Outcomes Research Indirect Treatment Comparisons Good Research Practices Task Force provides guidance on technical aspects of conducting network meta-analyses (our use of this term includes most methods that involve meta-analysis in the context of a network of evidence). We start with a discussion of strategies for developing networks of evidence. Next we briefly review assumptions of network meta-analysis. Then we focus on the statistical analysis of the data: objectives, models (fixed-effects and random-effects), frequentist versus Bayesian approaches, and model validation. A checklist highlights key components of network meta-analysis, and substantial examples illustrate indirect treatment comparisons (both frequentist and Bayesian approaches) and network meta-analysis. A further section discusses eight key areas for future research. Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Chronic unpredictable stress regulates visceral adipocyte‐mediated glucose metabolism and inflammatory circuits in male rats

PubMed Central

Karagiannides, Iordanes; Golovatscka, Viktoriya; Bakirtzi, Kyriaki; Sideri, Aristea; Salas, Martha; Stavrakis, Dimitris; Polytarchou, Christos; Iliopoulos, Dimitrios; Pothoulakis, Charalabos; Bradesi, Sylvie

2014-01-01

Abstract Chronic psychological stress is a prominent risk factor involved in the pathogenesis of many complex diseases, including major depression, obesity, and type II diabetes. Visceral adipose tissue is a key endocrine organ involved in the regulation of insulin action and an important component in the development of insulin resistance. Here, we examined for the first time the changes on visceral adipose tissue physiology and on adipocyte‐associated insulin sensitivity and function after chronic unpredictable stress in rats. Male rats were subjected to chronic unpredictable stress for 35 days. Total body and visceral fat was measured. Cytokines and activated intracellular kinase levels were determined using high‐throughput multiplex assays. Adipocyte function was assessed via tritiated glucose uptake assay. Stressed rats showed no weight gain, and their fat/lean mass ratio increased dramatically compared to control animals. Stressed rats had significantly higher mesenteric fat content and epididymal fat pad weight and demonstrated reduced serum glucose clearing capacity following glucose challenge. Alterations in fat depot size were mainly due to changes in adipocyte numbers and not size. High‐throughput molecular screening in adipocytes isolated from stressed rats revealed activation of intracellular inflammatory, glucose metabolism, and MAPK networks compared to controls, as well as significantly reduced glucose uptake capacity in response to insulin stimulation. Our study identifies the adipocyte as a key regulator of the effects of chronic stress on insulin resistance, and glucose metabolism, with important ramifications in the pathophysiology of several stress‐related disease states. PMID:24819750

A qualitative study of GPs' attitudes to self-management of chronic disease

PubMed Central

Blakeman, Tom; Macdonald, Wendy; Bower, Peter; Gately, Claire; Chew-Graham, Carolyn

2006-01-01

Background Improving the quality of care for patients living with a chronic illness is a key policy goal. Alongside systems to ensure care is delivered according to evidence-based guidelines, an essential component of these new models of care is the facilitation of self-management. However, changes to the way professionals deliver care is complex, and it is important to understand the key drivers and barriers that may operate in the primary care setting. Aim To explore GPs' perspectives on their involvement in the facilitation of chronic disease self-management. Design of study Qualitative study. Setting General practices located in two primary care trusts in northern England. Method Data were collected through in-depth, semi-structured interviews with a purposive sample of GPs. During analysis, categories of response were organised into themes that relate to Howie's theoretical model for understanding general practice consultations: content, values, context. Results The GPs' responses highlighted tensions and trade-offs regarding their role in facilitating self-management. Although GPs valued increased patient involvement in their health care, this was in conflict with other values concerning professional responsibility. Furthermore, contextual factors also limited the degree to which they could assist in encouraging self-management. Conclusions Providing GPs with training in consultation skills is required in order to encourage the delivery of effective self-management. In addition, the context in which GPs work also needs to be modified for this to be achieved. PMID:16762121

Chromophoric and fluorescent dissolved organic matter in and above the oxygen minimum zone off Peru

NASA Astrophysics Data System (ADS)

Loginova, A. N.; Thomsen, S.; Engel, A.

2016-11-01

As a result of nutrient upwelling, the Peruvian coastal system is one of the most productive regions in the ocean. Sluggish ventilation of intermediate waters, characteristic for the Eastern Tropical South Pacific (ETSP) and microbial degradation of a high organic matter load promotes deoxygenation at depth. Dissolved organic matter (DOM) plays a key role in microbial respiration and carbon cycling, but little is known on DOM distribution and cycling in the ETSP. DOM optical properties give important insights on DOM sources, structure and biogeochemical reactivity. Here, we present data and a conceptual view on distribution and cycling of chromophoric (CDOM) and fluorescent (FDOM) DOM in and above the oxygen minimum zone (OMZ) off Peru. Five fluorescent components were identified during PARAFAC analysis. Highest intensities of CDOM and of the amino acid-like fluorescent component (C3) occurred above the OMZ and coincided with maximum chl a concentrations, suggesting phytoplankton productivity as major source. High intensities of a marine humic-like fluorescent component (C1), observed in subsurface waters, indicated in situ microbial reworking of DOM. FDOM release from inner shelf sediment was determined by seawater analysis and continuous glider sensor measurement and included a humic-like component (C2) with a signature typical for terrestrially derived humic acids. Upwelling supplied humic-like substances to the euphotic zone. Photo-reactions were likely involved in the production of a humic-like fluorescent component (C5). Our data show that variable biological and physical processes need to be considered for understanding DOM cycling in a highly dynamic coastal upwelling system like the ETSP off Peru.

A multi-level qualitative analysis of Telehomecare in Ontario: challenges and opportunities.

PubMed

Hunting, Gemma; Shahid, Nida; Sahakyan, Yeva; Fan, Iris; Moneypenny, Crystal R; Stanimirovic, Aleksandra; North, Taylor; Petrosyan, Yelena; Krahn, Murray D; Rac, Valeria E

2015-12-09

Despite research demonstrating the potential effectiveness of Telehomecare for people with Chronic Obstructive Pulmonary Disease and Heart Failure, broad-scale comprehensive evaluations are lacking. This article discusses the qualitative component of a mixed-method program evaluation of Telehomecare in Ontario, Canada. The objective of the qualitative component was to explore the multi-level factors and processes which facilitate or impede the implementation and adoption of the program across three regions where it was first implemented. The study employs a multi-level framework as a conceptual guide to explore the facilitators and barriers to Telehomecare implementation and adoption across five levels: technology, patients, providers, organizations, and structures. In-depth semi-structured interviews and ethnographic observations with program stakeholders, as well as a Telehomecare document review were used to elicit key themes. Study participants (n = 89) included patients and/or informal caregivers (n = 39), health care providers (n = 23), technicians (n = 2), administrators (n = 12), and decision makers (n = 13) across three different Local Health Integration Networks in Ontario. Key facilitators to Telehomecare implementation and adoption at each level of the multi-level framework included: user-friendliness of Telehomecare technology, patient motivation to participate in the program, support for Telehomecare providers, the integration of Telehomecare into broader health service provision, and comprehensive program evaluation. Key barriers included: access-related issues to using the technology, patient language (if not English or French), Telehomecare provider time limitations, gaps in health care provision for patients, and structural barriers to patient participation related to geography and social location. Though Telehomecare has the potential to positively impact patient lives and strengthen models of health care provision, a number of key challenges remain. As such, further implementation and expansion of Telehomecare must involve continuous assessments of what is working and not working with all stakeholders. Increased dialogue, evaluation, and knowledge translation within and across regions to understand the contextual factors influencing Telehomecare implementation and adoption is required. This can inform decision-making that better reflects and addresses the needs of all program stakeholders.

23 CFR 450.210 - Interested parties, public involvement, and consultation.

Code of Federal Regulations, 2012 CFR

2012-04-01

... opportunities for public review and comment at key decision points. (1) The State's public involvement process... agencies, representatives of public transportation employees, freight shippers, private providers of... comment at key decision points, including but not limited to a reasonable opportunity to comment on the...

23 CFR 450.210 - Interested parties, public involvement, and consultation.

Code of Federal Regulations, 2013 CFR

2013-04-01

... opportunities for public review and comment at key decision points. (1) The State's public involvement process... agencies, representatives of public transportation employees, freight shippers, private providers of... comment at key decision points, including but not limited to a reasonable opportunity to comment on the...

23 CFR 450.210 - Interested parties, public involvement, and consultation.

Code of Federal Regulations, 2014 CFR

2014-04-01

... opportunities for public review and comment at key decision points. (1) The State's public involvement process... agencies, representatives of public transportation employees, freight shippers, private providers of... comment at key decision points, including but not limited to a reasonable opportunity to comment on the...

Birth preparedness and complication readiness among the women beneficiaries of selected rural primary health centers of Dakshina Kannada district, Karnataka, India.

PubMed

Akshaya, Kibballi Madhukeshwar; Shivalli, Siddharudha

2017-01-01

Birth preparedness and complication readiness (BPCR) is a strategy to promote timely use of skilled maternal and neonatal care during childbirth. According to World Health Organization, BPCR should be a key component of focused antenatal care. Dakshina Kannada, a coastal district of Karnataka state, is categorized as a high-performing district (institutional delivery rate >25%) under the National Rural Health Mission. However, a substantial proportion of women in the district experience complications during pregnancy (58.3%), childbirth (45.7%), and postnatal (17.4%) period. There is a paucity of data on BPCR practice and the factors associated with it in the district. Exploring this would be of great use in the evidence-based fine-tuning of ongoing maternal and child health interventions. To assess BPCR practice and the factors associated with it among the beneficiaries of two rural Primary Health Centers (PHCs) of Dakshina Kannada district, Karnataka, India. A facility-based cross-sectional study was conducted among 217 pregnant (>28 weeks of gestation) and recently delivered (in the last 6 months) women in two randomly selected PHCs from June -September 2013. Exit interviews were conducted using a pre-designed semi-structured interview schedule. Information regarding socio-demographic profile, obstetric variables, and knowledge of key danger signs was collected. BPCR included information on five key components: identified the place of delivery, saved money to pay for expenses, mode of transport identified, identified a birth companion, and arranged a blood donor if the need arises. In this study, a woman who recalled at least two key danger signs in each of the three phases, i.e., pregnancy, childbirth, and postpartum (total six) was considered as knowledgeable on key danger signs. Optimal BPCR practice was defined as following at least three out of five key components of BPCR. Proportion, Odds ratio, and adjusted Odds ratio (adj OR) for optimal BPCR practice. A total of 184 women completed the exit interview (mean age: 26.9±3.9 years). Optimal BPCR practice was observed in 79.3% (95% CI: 73.5-85.2%) of the women. Multivariate logistic regression revealed that age >26 years (adj OR = 2.97; 95%CI: 1.15-7.7), economic status of above poverty line (adj OR = 4.3; 95%CI: 1.12-16.5), awareness of minimum two key danger signs in each of the three phases, i.e., pregnancy, childbirth, and postpartum (adj OR = 3.98; 95%CI: 1.4-11.1), preference to private health sector for antenatal care/delivery (adj OR = 2.9; 95%CI: 1.1-8.01), and woman's discussion about the BPCR with her family members (adj OR = 3.4; 95%CI: 1.1-10.4) as the significant factors associated with optimal BPCR practice. In this study population, BPCR practice was better than other studies reported from India. Healthcare workers at the grassroots should be encouraged to involve women's family members while explaining BPCR and key danger signs with a special emphasis on young (<26 years) and economically poor women. Ensuring a reinforcing discussion between woman and her family members may further enhance the BPCR practice.

Birth preparedness and complication readiness among the women beneficiaries of selected rural primary health centers of Dakshina Kannada district, Karnataka, India

PubMed Central

Akshaya, Kibballi Madhukeshwar

2017-01-01

Introduction Birth preparedness and complication readiness (BPCR) is a strategy to promote timely use of skilled maternal and neonatal care during childbirth. According to World Health Organization, BPCR should be a key component of focused antenatal care. Dakshina Kannada, a coastal district of Karnataka state, is categorized as a high-performing district (institutional delivery rate >25%) under the National Rural Health Mission. However, a substantial proportion of women in the district experience complications during pregnancy (58.3%), childbirth (45.7%), and postnatal (17.4%) period. There is a paucity of data on BPCR practice and the factors associated with it in the district. Exploring this would be of great use in the evidence-based fine-tuning of ongoing maternal and child health interventions. Objective To assess BPCR practice and the factors associated with it among the beneficiaries of two rural Primary Health Centers (PHCs) of Dakshina Kannada district, Karnataka, India. Methods A facility-based cross-sectional study was conducted among 217 pregnant (>28 weeks of gestation) and recently delivered (in the last 6 months) women in two randomly selected PHCs from June -September 2013. Exit interviews were conducted using a pre-designed semi-structured interview schedule. Information regarding socio-demographic profile, obstetric variables, and knowledge of key danger signs was collected. BPCR included information on five key components: identified the place of delivery, saved money to pay for expenses, mode of transport identified, identified a birth companion, and arranged a blood donor if the need arises. In this study, a woman who recalled at least two key danger signs in each of the three phases, i.e., pregnancy, childbirth, and postpartum (total six) was considered as knowledgeable on key danger signs. Optimal BPCR practice was defined as following at least three out of five key components of BPCR. Outcome measures Proportion, Odds ratio, and adjusted Odds ratio (adj OR) for optimal BPCR practice. Results A total of 184 women completed the exit interview (mean age: 26.9±3.9 years). Optimal BPCR practice was observed in 79.3% (95% CI: 73.5–85.2%) of the women. Multivariate logistic regression revealed that age >26 years (adj OR = 2.97; 95%CI: 1.15–7.7), economic status of above poverty line (adj OR = 4.3; 95%CI: 1.12–16.5), awareness of minimum two key danger signs in each of the three phases, i.e., pregnancy, childbirth, and postpartum (adj OR = 3.98; 95%CI: 1.4–11.1), preference to private health sector for antenatal care/delivery (adj OR = 2.9; 95%CI: 1.1–8.01), and woman’s discussion about the BPCR with her family members (adj OR = 3.4; 95%CI: 1.1–10.4) as the significant factors associated with optimal BPCR practice. Conclusion In this study population, BPCR practice was better than other studies reported from India. Healthcare workers at the grassroots should be encouraged to involve women’s family members while explaining BPCR and key danger signs with a special emphasis on young (<26 years) and economically poor women. Ensuring a reinforcing discussion between woman and her family members may further enhance the BPCR practice. PMID:28837683

Perception of touch quality in piano tones.

PubMed

Goebl, Werner; Bresin, Roberto; Fujinaga, Ichiro

2014-11-01

Both timbre and dynamics of isolated piano tones are determined exclusively by the speed with which the hammer hits the strings. This physical view has been challenged by pianists who emphasize the importance of the way the keyboard is touched. This article presents empirical evidence from two perception experiments showing that touch-dependent sound components make sounds with identical hammer velocities but produced with different touch forms clearly distinguishable. The first experiment focused on finger-key sounds: musicians could identify pressed and struck touches. When the finger-key sounds were removed from the sounds, the effect vanished, suggesting that these sounds were the primary identification cue. The second experiment looked at key-keyframe sounds that occur when the key reaches key-bottom. Key-bottom impact was identified from key motion measured by a computer-controlled piano. Musicians were able to discriminate between piano tones that contain a key-bottom sound from those that do not. However, this effect might be attributable to sounds associated with the mechanical components of the piano action. In addition to the demonstrated acoustical effects of different touch forms, visual and tactile modalities may play important roles during piano performance that influence the production and perception of musical expression on the piano.

The Impact of Armor on the Design, Utilization and Survivability of Ground Vehicles: The History of Armor Development and Use

DTIC Science & Technology

2012-09-01

control functions. Components that are included in this category include the steering column / linkages as well as brakes . D. FIREPOWER COMPONENTS...COMPONENTS: STEERING AND BRAKES ......................48 D. FIREPOWER COMPONENTS: TURRET AND ARMAMENT .............49 E. PROTECTION COMPONENTS: HULL AND...Key Functional Area Propulsion Powertrain (Engine / Transmission) Tracks / Wheels Control Steering Brakes / Suspension Firepower Turret Armament

ROLE OF DOM PHOTOREACTIONS IN CONTROLLING UV EXPOSURE OF CORAL ASSEMBLAGES IN THE FLORIDA KEYS

EPA Science Inventory

Recent studies have indicated that solar LTV radiation is a significant stressor of coral assemblages in tropical and subtropical marine environments. Here evidence is presented that UV exposure of coral reefs in the Florida Keys near Key West is controlled by the colored compone...

One Step Quantum Key Distribution Based on EPR Entanglement

PubMed Central

Li, Jian; Li, Na; Li, Lei-Lei; Wang, Tao

2016-01-01

A novel quantum key distribution protocol is presented, based on entanglement and dense coding and allowing asymptotically secure key distribution. Considering the storage time limit of quantum bits, a grouping quantum key distribution protocol is proposed, which overcomes the vulnerability of first protocol and improves the maneuverability. Moreover, a security analysis is given and a simple type of eavesdropper’s attack would introduce at least an error rate of 46.875%. Compared with the “Ping-pong” protocol involving two steps, the proposed protocol does not need to store the qubit and only involves one step. PMID:27357865

Service user involvement in mental health care: an evolutionary concept analysis.

PubMed

Millar, Samantha L; Chambers, Mary; Giles, Melanie

2016-04-01

The concept of service user involvement is an evolving concept in the mental health-care literature. This study sought to explore and analyse the concept of service user involvement as used in within the field of mental health care. An evolutionary concept analysis was conducted using a literature-based sample extracted from an electronic database search. One hundred and thirty-four papers met the inclusion criteria and were analysed to discover key attributes, antecedents and consequences of service user involvement and to produce a definition of the concept. Five key attributes of service user involvement within the context of mental health care were identified: a person-centred approach, informed decision making, advocacy, obtaining service user views and feedback and working in partnership. Clarity of the attributes and definition of the concept of service user involvement aims to promote understanding of the concept among key stakeholders including mental health professionals, service users and community and voluntary organizations. The findings of the research have utility in the areas of theory and policy development, research on service user involvement in mental health care and service user involvement in mental health practice. Directions for further research regarding the concept are identified. © 2015 John Wiley & Sons Ltd.

Discrete Event Simulation Modeling and Analysis of Key Leader Engagements

DTIC Science & Technology

2012-06-01

to offer. GreenPlayer agents require four parameters, pC, pKLK, pTK, and pRK , which give probabilities for being corrupt, having key leader...HandleMessageRequest component. The same parameter constraints apply to these four parameters. The parameter pRK is the same parameter from the CreatePlayers component...whether the local Green player has resource critical knowledge by using the parameter pRK . It schedules an EndResourceKnowledgeRequest event, passing

Reliability Assessment Approach for Stirling Convertors and Generators

NASA Technical Reports Server (NTRS)

Shah, Ashwin R.; Schreiber, Jeffrey G.; Zampino, Edward; Best, Timothy

2004-01-01

Stirling power conversion is being considered for use in a Radioisotope Power System for deep-space science missions because it offers a multifold increase in the conversion efficiency of heat to electric power. Quantifying the reliability of a Radioisotope Power System that utilizes Stirling power conversion technology is important in developing and demonstrating the capability for long-term success. A description of the Stirling power convertor is provided, along with a discussion about some of the key components. Ongoing efforts to understand component life, design variables at the component and system levels, related sources, and the nature of uncertainties is discussed. The requirement for reliability also is discussed, and some of the critical areas of concern are identified. A section on the objectives of the performance model development and a computation of reliability is included to highlight the goals of this effort. Also, a viable physics-based reliability plan to model the design-level variable uncertainties at the component and system levels is outlined, and potential benefits are elucidated. The plan involves the interaction of different disciplines, maintaining the physical and probabilistic correlations at all the levels, and a verification process based on rational short-term tests. In addition, both top-down and bottom-up coherency were maintained to follow the physics-based design process and mission requirements. The outlined reliability assessment approach provides guidelines to improve the design and identifies governing variables to achieve high reliability in the Stirling Radioisotope Generator design.

Constructivism in Practice: an Exploratory Study of Teaching Patterns and Student Motivation in Physics Classrooms in Finland, Germany and Switzerland

NASA Astrophysics Data System (ADS)

Beerenwinkel, Anne; von Arx, Matthias

2017-04-01

For the last three decades, moderate constructivism has become an increasingly prominent perspective in science education. Researchers have defined characteristics of constructivist-oriented science classrooms, but the implementation of such science teaching in daily classroom practice seems difficult. Against this background, we conducted a sub-study within the tri-national research project Quality of Instruction in Physics (QuIP) analysing 60 videotaped physics classes involving a large sample of students ( N = 1192) from Finland, Germany and Switzerland in order to investigate the kinds of constructivist components and teaching patterns that can be found in regular classrooms without any intervention. We applied a newly developed coding scheme to capture constructivist facets of science teaching and conducted principal component and cluster analyses to explore which components and patterns were most prominent in the classes observed. Two underlying components were found, resulting in two scales—Structured Knowledge Acquisition and Fostering Autonomy—which describe key aspects of constructivist teaching. Only the first scale was rather well established in the lessons investigated. Classes were clustered based on these scales. The analysis of the different clusters suggested that teaching physics in a structured way combined with fostering students' autonomy contributes to students' motivation. However, our regression models indicated that content knowledge is a more important predictor for students' motivation, and there was no homogeneous pattern for all gender- and country-specific subgroups investigated. The results are discussed in light of recent discussions on the feasibility of constructivism in practice.

A literature review of learning collaboratives in mental health care: used but untested.

PubMed

Nadeem, Erum; Olin, S Serene; Hill, Laura Campbell; Hoagwood, Kimberly Eaton; Horwitz, Sarah McCue

2014-09-01

Policy makers have increasingly turned to learning collaboratives (LCs) as a strategy for improving usual care through the dissemination of evidence-based practices. The purpose of this review was to characterize the state of the evidence for use of LCs in mental health care. A systematic search of major academic databases for peer-reviewed articles on LCs in mental health care generated 421 unique articles across a range of disciplines; 28 mental health articles were selected for full-text review, and 20 articles representing 16 distinct studies met criteria for final inclusion. Articles were coded to identify the LC components reported, the focus of the research, and key findings. Most of the articles included assessments of provider- or patient-level variables at baseline and post-LC. Only one study included a comparison condition. LC targets ranged widely, from use of a depression screening tool to implementation of evidence-based treatments. Fourteen crosscutting LC components (for example, in-person learning sessions, phone meetings, data reporting, leadership involvement, and training in quality improvement methods) were identified. The LCs reviewed reported including, on average, seven components, most commonly in-person learning sessions, plan-do-study-act cycles, multidisciplinary quality improvement teams, and data collection for quality improvement. LCs are being used widely in mental health care, although there is minimal evidence of their effectiveness and unclear reporting in regard to specific components. Rigorous observational and controlled research studies on the impact of LCs on targeted provider- and patient-level outcomes are greatly needed.

A UV-B-specific signaling component orchestrates plant UV protection

PubMed Central

Brown, Bobby A.; Cloix, Catherine; Jiang, Guang Huai; Kaiserli, Eirini; Herzyk, Pawel; Kliebenstein, Daniel J.; Jenkins, Gareth I.

2005-01-01

UV-B radiation in sunlight has diverse effects on humans, animals, plants, and microorganisms. UV-B can cause damage to molecules and cells, and consequently organisms need to protect against and repair UV damage to survive in sunlight. In plants, low nondamaging levels of UV-B stimulate transcription of genes involved in UV-protective responses. However, remarkably little is known about the underlying mechanisms of UV-B perception and signal transduction. Here we report that Arabidopsis UV RESISTANCE LOCUS 8 (UVR8) is a UV-B-specific signaling component that orchestrates expression of a range of genes with vital UV-protective functions. Moreover, we show that UVR8 regulates expression of the transcription factor HY5 specifically when the plant is exposed to UV-B. We demonstrate that HY5 is a key effector of the UVR8 pathway, and that it is required for survival under UV-B radiation. UVR8 has sequence similarity to the eukaryotic guanine nucleotide exchange factor RCC1, but we found that it has little exchange activity. However, UVR8, like RCC1, is located principally in the nucleus and associates with chromatin via histones. Chromatin immunoprecipitation showed that UVR8 associates with chromatin in the HY5 promoter region, providing a mechanistic basis for its involvement in regulating transcription. We conclude that UVR8 defines a UV-B-specific signaling pathway in plants that orchestrates the protective gene expression responses to UV-B required for plant survival in sunlight. PMID:16330762

The Development Of Drosophila Melanogaster under Different Duration Space Flight and Subsequent Adaptation to Earth Gravity.

PubMed

Ogneva, Irina V; Belyakin, Stepan N; Sarantseva, Svetlana V

2016-01-01

In prospective human exploration of outer space, the need to preserve a species over several generations under changed gravity conditions may arise. This paper demonstrates our results in the creation of the third generation of fruit fly Drosophila melanogaster (third-stage larvae) during the 44.5-day space flight (Foton-M4 satellite (2014, Russia)), then the fourth generation on Earth and the fifth generation again in conditions of the 12-day space flight (2014, in the Russian Segment of the ISS). The species preserves fertility despite a number of changes in the level of expression and content of cytoskeletal proteins, which are the key components of the cleavage spindle and the contractile ring of cells. The results of transcriptome screening and space analysis of cytoskeletal proteins show that the exposure to weightless conditions leads to the increased transcription of metabolic genes, cuticle components and the decreased transcription of genes involved in morphogenesis, cell differentiation, cytoskeletal organization and genes associated with the plasma membrane. "Subsequent" exposure to the microgravity for 12 days resulted in an even more significant increase/decrease in the transcription of the same genes. On the contrary, the transition from the microgravity conditions to the gravity of Earth leads to the increased transcription of genes whose products are involved in the morphogenesis, cytoskeletal organization, motility of cells and transcription regulation, and to the decreased transcription of cuticle genes and proteolytic processes.

Library Screen Identifies Enterococcus faecalis CcpA, the Catabolite Control Protein A, as an Effector of Ace, a Collagen Adhesion Protein Linked to Virulence

PubMed Central

Gao, Peng; Pinkston, Kenneth L.; Bourgogne, Agathe; Cruz, Melissa R.; Garsin, Danielle A.; Murray, Barbara E.

2013-01-01

The Enterococcus faecalis cell wall-anchored protein Ace is an important virulence factor involved in cell adhesion and infection. Expression of Ace on the cell surface is affected by many factors, including stage of growth, culture temperature, and environmental components, such as serum, urine, and collagen. However, the mechanisms that regulate or modulate Ace display are not well understood. With interest in identifying genes associated with Ace expression, we utilized a whole-cell enzyme-linked immunosorbent assay (ELISA)-based screening method to identify mutants from a transposon insertion mutant library which exhibited distinct Ace surface expression profiles. We identified a ccpA insertion mutant which showed significantly decreased levels of Ace surface expression at early growth phase versus those of wild-type OG1RF. Confirmation of the observation was achieved through flow cytometry and complementation analysis. Compared to the wild type, the E. faecalis ccpA mutant had an impaired ability to adhere to collagen when grown to early exponential phase, consistent with the lack of Ace expression in the early growth phase. As a key component of carbon catabolite regulation, CcpA has been previously reported to play a critical role in regulating expression of proteins involved in E. faecalis carbohydrate uptake and utilization. Our discovery is the first to associate CcpA with the production of a major E. faecalis virulence factor, providing new insights into the regulation of E. faecalis pathogenesis. PMID:23974022

The Development Of Drosophila Melanogaster under Different Duration Space Flight and Subsequent Adaptation to Earth Gravity

PubMed Central

Belyakin, Stepan N.; Sarantseva, Svetlana V.

2016-01-01

In prospective human exploration of outer space, the need to preserve a species over several generations under changed gravity conditions may arise. This paper demonstrates our results in the creation of the third generation of fruit fly Drosophila melanogaster (third-stage larvae) during the 44.5-day space flight (Foton-M4 satellite (2014, Russia)), then the fourth generation on Earth and the fifth generation again in conditions of the 12-day space flight (2014, in the Russian Segment of the ISS). The species preserves fertility despite a number of changes in the level of expression and content of cytoskeletal proteins, which are the key components of the cleavage spindle and the contractile ring of cells. The results of transcriptome screening and space analysis of cytoskeletal proteins show that the exposure to weightless conditions leads to the increased transcription of metabolic genes, cuticle components and the decreased transcription of genes involved in morphogenesis, cell differentiation, cytoskeletal organization and genes associated with the plasma membrane. “Subsequent” exposure to the microgravity for 12 days resulted in an even more significant increase/decrease in the transcription of the same genes. On the contrary, the transition from the microgravity conditions to the gravity of Earth leads to the increased transcription of genes whose products are involved in the morphogenesis, cytoskeletal organization, motility of cells and transcription regulation, and to the decreased transcription of cuticle genes and proteolytic processes. PMID:27861601

Pathogenesis and therapeutic approaches for improved topical treatment in localized scleroderma and systemic sclerosis.

PubMed

Badea, I; Taylor, M; Rosenberg, A; Foldvari, M

2009-03-01

SSc is a chronic progressive disorder of unknown aetiology characterized by excess synthesis and deposition of collagen and other extracellular matrix components in a variety of tissues and organs. Localized scleroderma (LS) differs from SSc in that with LS only skin and occasionally subcutaneous tissues are involved. Although rarely life threatening, LS can be disfiguring and disabling and, consequently, can adversely affect quality of life. There is no known effective treatment for LS, and various options, including, as examples, corticosteroids and other immunomodulatory agents, ultraviolet radiation and vitamin D analogues, are of unproven efficacy. Clinical trials evaluating combination therapy such as corticosteroids with MTX or UVA1 exposure with psoralens have not been established as consistently effective. New immunomodulators such as tacrolimus and thalidomide are also being evaluated. A better understanding of the molecular and cellular mechanisms of LS has led to evaluation of new treatments that modulate profibrotic cytokines such as TGF-beta and IL-4, regulate assembly and deposition of extracellular matrix components, and restore Th1/Th2 immune balance by administering IL-12 or IFN-gamma. IFN-gamma acts by directly inhibiting collagen synthesis and by restoring immune balance. In this review, we evaluate current and future treatment options for LS and cutaneous involvement in SSc. Recent advances in therapy focus mainly on anti-fibrotic agents. Delivery of these drugs into the skin as the target tissue might be a key factor in developing more effective and safer therapy.

The structure of the cysteine protease and lectin-like domains of Cwp84, a surface layer-associated protein from Clostridium difficile

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

Bradshaw, William J.; Public Health England, Porton Down, Salisbury SP4 0JG; Kirby, Jonathan M.

2014-07-01

The crystal structure of Cwp84, an S-layer protein from Clostridium difficile is presented for the first time. The cathepsin L-like fold of cysteine protease domain, a newly observed ‘lectin-like’ domain and several other features are described. Clostridium difficile is a major problem as an aetiological agent for antibiotic-associated diarrhoea. The mechanism by which the bacterium colonizes the gut during infection is poorly understood, but undoubtedly involves a myriad of components present on the bacterial surface. The mechanism of C. difficile surface-layer (S-layer) biogenesis is also largely unknown but involves the post-translational cleavage of a single polypeptide (surface-layer protein A; SlpA)more » into low- and high-molecular-weight subunits by Cwp84, a surface-located cysteine protease. Here, the first crystal structure of the surface protein Cwp84 is described at 1.4 Å resolution and the key structural components are identified. The truncated Cwp84 active-site mutant (amino-acid residues 33–497; C116A) exhibits three regions: a cleavable propeptide and a cysteine protease domain which exhibits a cathepsin L-like fold followed by a newly identified putative carbohydrate-binding domain with a bound calcium ion, which is referred to here as a lectin-like domain. This study thus provides the first structural insights into Cwp84 and a strong base to elucidate its role in the C. difficile S-layer maturation mechanism.« less

Daily Eating Patterns and Their Impact on Health and Disease.

PubMed

Zarrinpar, Amir; Chaix, Amandine; Panda, Satchidananda

2016-02-01

Cyclical expression of cell-autonomous circadian clock components and key metabolic regulators coordinate often discordant and distant cellular processes for efficient metabolism. Perturbation of these cycles, either by genetic manipulation, disruption of light/dark cycles, or, most relevant to the human population, via eating patterns, contributes to obesity and dysmetabolism. Time-restricted feeding (TRF), during which time of access to food is restricted to a few hours, without caloric restriction, supports robust metabolic cycles and protects against nutritional challenges that predispose to obesity and dysmetabolism. The mechanism by which TRF imparts its benefits is not fully understood but likely involves entrainment of metabolically active organs through gut signaling. Understanding the relationship of feeding pattern and metabolism could yield novel therapies for the obesity pandemic. Copyright © 2015. Published by Elsevier Ltd.

TECHNICAL APPROACHES TO CHARACTERIZING AND ...

EPA Pesticide Factsheets

The document provides brownfields planners with an overview of the technical methods that can be used to achieve successful site assessment and cleanup which are two key components of the brownfields redevelopment process. No two brownfields sites are identical and planners will need to base assessment and cleanup activities on the conditions of the particular sites with which they are dealing. A site assessment strategy should address: the type and extent of contamination, if any, that is present, the types of data needed to adequately assess the site; appropriate sampling and analytical methods to characterize the contamination; acceptable level of uncertainty and cleanup technologies that contain or treat the types of wastes present.This document includes references to state agency roles including the Voluntary Cleanup Program, public involvement and other guidances that may be used. Information

Can Drosophila melanogaster represent a model system for the detection of reproductive adverse drug reactions?

PubMed

Avanesian, Agnesa; Semnani, Sahar; Jafari, Mahtab

2009-08-01

Once a molecule is identified as a potential drug, the detection of adverse drug reactions is one of the key components of its development and the FDA approval process. We propose using Drosophila melanogaster to screen for reproductive adverse drug reactions in the early stages of drug development. Compared with other non-mammalian models, D. melanogaster has many similarities to the mammalian reproductive system, including putative sex hormones and conserved proteins involved in genitourinary development. Furthermore, the D. melanogaster model would present significant advantages in time efficiency and cost-effectiveness compared with mammalian models. We present data on methotrexate (MTX) reproductive adverse events in multiple animal models, including fruit flies, as proof-of-concept for the use of the D. melanogaster model.

Daily Eating Patterns and Their Impact on Health and Disease

PubMed Central

Zarrinpar, Amir; Chaix, Amandine; Panda, Satchidananda

2016-01-01

Cyclical expression of cell-autonomous circadian clock components and key metabolic regulators coordinate often discordant and distant cellular processes for efficient metabolism. Perturbation of these cycles, either by genetic manipulation, disruption of light/dark cycles, or, most relevant to the human population, via eating patterns, contributes to obesity and dysmetabolism. Time-restricted feeding (TRF), during which time of access to food is restricted to a few hours, without caloric restriction, supports robust metabolic cycles and protects against nutritional challenges that predispose to obesity and dysmetabolism. The mechanism by which TRF imparts its benefits is not fully understood but likely involves entrainment of metabolically active organs through gut signaling. Understanding the relationship of feeding pattern and metabolism could yield novel therapies for the obesity pandemic. PMID:26706567

Solar Wind Strahl Broadening by Self-Generated Plasma Waves

NASA Technical Reports Server (NTRS)

Pavan, J.; Vinas, A. F.; Yoon, P. H.; Ziebell, L. F.; Gaelzer, R.

2013-01-01

This Letter reports on the results of numerical simulations which may provide a possible explanation for the strahl broadening during quiet solar conditions. The relevant processes involved in the broadening are due to kinetic quasi-linear wave-particle interaction. Making use of static analytical electron distribution in an inhomogeneous field, it is found that self-generated electrostatic waves at the plasma frequency, i.e., Langmuir waves, are capable of scattering the strahl component, resulting in energy and pitch-angle diffusion that broadens its velocity distribution significantly. The present theoretical results provide an alternative or complementary explanation to the usual whistler diffusion scenario, suggesting that self-induced electrostatic waves at the plasma frequency might play a key role in broadening the solar wind strahl during quiet solar conditions.

Advancement of the Artificial Pancreas through the Development of Interoperability Standards

PubMed Central

Picton, Peter E.; Yeung, Melanie; Hamming, Nathaniel; Desborough, Lane; Dassau, Eyal; Cafazzo, Joseph A.

2013-01-01

Despite advancements in the development of the artificial pancreas, barriers in the form of proprietary data and communication protocols of diabetes devices have made the integration of these components challenging. The Artificial Pancreas Standards and Technical Platform Project is an initiative funded by the JDRF Canadian Clinical Trial Network with the goal of developing device communication standards for the interoperability of diabetes devices. Stakeholders from academia, industry, regulatory agencies, and medical and patient communities have been engaged in advancing this effort. In this article, we describe this initiative along with the process involved in working with the standards organizations and stakeholders that are key to ensuring effective standards are developed and adopted. Discussion from a special session of the 12th Annual Diabetes Technology Meeting is also provided. PMID:23911190

FILTSoft: A computational tool for microstrip planar filter design

NASA Astrophysics Data System (ADS)

Elsayed, M. H.; Abidin, Z. Z.; Dahlan, S. H.; Cholan N., A.; Ngu, Xavier T. I.; Majid, H. A.

2017-09-01

Filters are key component of any communication system to control spectrum and suppress interferences. Designing a filter involves long process as well as good understanding of the basic hardware technology. Hence this paper introduces an automated design tool based on Matlab-GUI, called the FILTSoft (acronym for Filter Design Software) to ease the process. FILTSoft is a user friendly filter design tool to aid, guide and expedite calculations from lumped elements level to microstrip structure. Users just have to provide the required filter specifications as well as the material description. FILTSoft will calculate and display the lumped element details, the planar filter structure, and the expected filter's response. An example of a lowpass filter design was calculated using FILTSoft and the results were validated through prototype measurement for comparison purposes.

HSP70 and heat shock factor 1 cooperate to repress Ras-induced transcriptional activation of the c-fos gene.

PubMed

He, H; Chen, C; Xie, Y; Asea, A; Calderwood, S K

2000-11-01

Heat shock protein 70 (HSP70) is a molecular chaperone involved in protein folding and resistance to the deleterious effects of stress. Here we show that HSP70 suppresses transcription of c-fos, an early response gene that is a key component of the ubiquitous AP-1 transcription factor complex. HSP70 repressed Ras-induced c-fos transcription only in the presence of functional heat shock factor1 (HSF1). This suggests that HSP70 functions as a corepressor with HSF1 to inhibit c-fos gene transcription. Therefore, besides its known function in the stress response, HSP70 also has the property of a corepressor and combines with HSF1 to antagonize Fos expression and may thus impact multiple aspects of cell regulation.

Pseudomonas aeruginosa uses a cyclic-di-GMP-regulated adhesin to reinforce the biofilm extracellular matrix

PubMed Central

Borlee, Bradley R; Goldman, Aaron D; Murakami, Keiji; Samudrala, Ram; Wozniak, Daniel J; Parsek, Matthew R

2010-01-01

Pseudomonas aeruginosa, the principal pathogen of cystic fibrosis patients, forms antibiotic-resistant biofilms promoting chronic colonization of the airways. The extracellular (EPS) matrix is a crucial component of biofilms that provides the community multiple benefits. Recent work suggests that the secondary messenger, cyclic-di-GMP, promotes biofilm formation. An analysis of factors specifically expressed in P. aeruginosa under conditions of elevated c-di-GMP, revealed functions involved in the production and maintenance of the biofilm extracellular matrix. We have characterized one of these components, encoded by the PA4625 gene, as a putative adhesin and designated it cdrA. CdrA shares structural similarities to extracellular adhesins that belong to two-partner secretion systems. The cdrA gene is in a two gene operon that also encodes a putative outer membrane transporter, CdrB. The cdrA gene encodes a 220 KDa protein that is predicted to be rod-shaped protein harbouring a β-helix structural motif. Western analysis indicates that the CdrA is produced as a 220 kDa proprotein and processed to 150 kDa before secretion into the extracellular medium. We demonstrated that cdrAB expression is minimal in liquid culture, but is elevated in biofilm cultures. CdrAB expression was found to promote biofilm formation and auto-aggregation in liquid culture. Aggregation mediated by CdrA is dependent on the Psl polysaccharide and can be disrupted by adding mannose, a key structural component of Psl. Immunoprecipitation of Psl present in culture supernatants resulted in co-immunoprecipitation of CdrA, providing additional evidence that CdrA directly binds to Psl. A mutation in cdrA caused a decrease in biofilm biomass and resulted in the formation of biofilms exhibiting decreased structural integrity. Psl-specific lectin staining suggests that CdrA either cross-links Psl polysaccharide polymers and/or tethers Psl to the cells, resulting in increased biofilm structural stability. Thus, this study identifies a key protein structural component of the P. aeruginosa EPS matrix. PMID:20088866

Enery Efficient Press and Sinter of Titanium Powder for Low-Cost Components in Vehicle Applications

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

Thomas Zwitter; Phillip Nash; Xiaoyan Xu

2011-03-31

This is the final technical report for the Department of Energy NETL project NT01931 Energy Efficient Press and Sinter of Titanium Powder for Low-Cost Components in Vehicle Applications. Titanium has been identified as one of the key materials with the required strength that can reduce the weight of automotive components and thereby reduce fuel consumption. Working with newly developed sources of titanium powder, Webster-Hoff will develop the processing technology to manufacture low cost vehicle components using the single press/single sinter techniques developed for iron based powder metallurgy today. Working with an automotive or truck manufacturer, Webster-Hoff will demonstrate the feasibilitymore » of manufacturing a press and sinter titanium component for a vehicle application. The project objective is two-fold, to develop the technology for manufacturing press and sinter titanium components, and to demonstrate the feasibility of producing a titanium component for a vehicle application. The lowest cost method for converting metal powder into a net shape part is the Powder Metallurgy Press and Sinter Process. The method involves compaction of the metal powder in a tool (usually a die and punches, upper and lower) at a high pressure (up to 60 TSI or 827 MPa) to form a green compact with the net shape of the final component. The powder in the green compact is held together by the compression bonds between the powder particles. The sinter process then converts the green compact to a metallurgically bonded net shape part through the process of solid state diffusion. The goal of this project is to expand the understanding and application of press and sinter technology to Titanium Powder applications, developing techniques to manufacture net shape Titanium components via the press and sinter process. In addition, working with a vehicle manufacturer, demonstrate the feasibility of producing a titanium component for a vehicle. This is not a research program, but rather a project to develop a process for press and sinter of net shape Titanium components. All of these project objectives have been successfully completed.« less

Keeping It All Going-Complement Meets Metabolism.

PubMed

Kolev, Martin; Kemper, Claudia

2017-01-01

The complement system is an evolutionary old and crucial component of innate immunity, which is key to the detection and removal of invading pathogens. It was initially discovered as a liver-derived sentinel system circulating in serum, the lymph, and interstitial fluids that mediate the opsonization and lytic killing of bacteria, fungi, and viruses and the initiation of the general inflammatory responses. Although work performed specifically in the last five decades identified complement also as a critical instructor of adaptive immunity-indicating that complement's function is likely broader than initially anticipated-the dominant opinion among researchers and clinicians was that the key complement functions were in principle defined. However, there is now a growing realization that complement activity goes well beyond "classic" immune functions and that this system is also required for normal (neuronal) development and activity and general cell and tissue integrity and homeostasis. Furthermore, the recent discovery that complement activation is not confined to the extracellular space but occurs within cells led to the surprising understanding that complement is involved in the regulation of basic processes of the cell, particularly those of metabolic nature-mostly via novel crosstalks between complement and intracellular sensor, and effector, pathways that had been overlooked because of their spatial separation. These paradigm shifts in the field led to a renaissance in complement research and provide new platforms to now better understand the molecular pathways underlying the wide-reaching effects of complement functions in immunity and beyond. In this review, we will cover the current knowledge about complement's emerging relationship with the cellular metabolism machinery with a focus on the functional differences between serum-circulating versus intracellularly active complement during normal cell survival and induction of effector functions. We will also discuss how taking a closer look into the evolution of key complement components not only made the functional connection between complement and metabolism rather "predictable" but how it may also give clues for the discovery of additional roles for complement in basic cellular processes.

Improving the management and referral of patients with transient ischaemic attacks: a change strategy for a health community

PubMed Central

Wright, J; Harrison, S; McGeorge, M; Patterson, C; Russell, I; Russell, D; Small, N; Taylor, M; Walsh, M; Warren, E; Young, J

2006-01-01

Problem Rapid referral and management of patients with transient ischaemic attacks is a key component in the national strategy for stroke prevention. However, patients with transient ischaemic attacks are poorly identified and undertreated. Design and setting Before and after evaluation of quality improvement programme with controlled comparison in three primary care trusts reflecting diverse populations and organisational structures in an urban district in the North of England. Key measures for improvement The proportion of patients receiving antiplatelet drugs and safe driving advice on referral to a speciality clinic, and the numbers of referrals, adjusted for age, to the specialist clinic before and after the improvement programme. Strategies for change Interviews with patient and professionals to identify gaps and barriers to good practice; development of evidence based guidelines for the management of patients with transient ischaemic attacks; interactive multidisciplinary workshops for each primary care trust with feedback of individual audit results of referral practice; outreach visits to teams who were unable to attend the workshops; referral templates and desktop summaries to provide reminders of the guidelines to clinicians; incorporation of standards into professional contracts. Effects of change A significant improvement occurred in identification and referral of patients with transient ischaemic attacks to specialist clinics, with a 41% increase in referrals from trained practices compared with control practices. There were also significant improvements in the early treatment and safety advice provided to patients before referral. Lessons learnt A strategic approach to effective quality improvement across a diverse health community is feasible and achievable. Careful planning with patient and professional involvement to develop a tailored and multifaceted quality improvement programme to implement evidence based practice can work in very different primary care settings. Key components of the effectiveness of the model include contextual analysis, strong professional support, clear recommendations based on robust evidence, simplicity of adoption, good communication, and use of established networks and opinion leaders. PMID:16456203

Transcriptional and physiological analyses of Fe deficiency response in maize reveal the presence of Strategy I components and Fe/P interactions.

PubMed

Zanin, Laura; Venuti, Silvia; Zamboni, Anita; Varanini, Zeno; Tomasi, Nicola; Pinton, Roberto

2017-02-13

Under limited iron (Fe) availability maize, a Strategy II plant, improves Fe acquisition through the release of phytosiderophores (PS) into the rhizosphere and the subsequent uptake of Fe-PS complexes into root cells. Occurrence of Strategy-I-like components and interactions with phosphorous (P) nutrition has been hypothesized based on molecular and physiological studies in grasses. In this report transcriptomic analysis (NimbleGen microarray) of Fe deficiency response revealed that maize roots modulated the expression levels of 724 genes (508 up- and 216 down-regulated, respectively). As expected, roots of Fe-deficient maize plants overexpressed genes involved in the synthesis and release of 2'-deoxymugineic acid (the main PS released by maize roots). A strong modulation of genes involved in regulatory aspects, Fe translocation, root morphological modification, primary metabolic pathways and hormonal metabolism was induced by the nutritional stress. Genes encoding transporters for Fe 2+ (ZmNRAMP1) and P (ZmPHT1;7 and ZmPHO1) were also up-regulated under Fe deficiency. Fe-deficient maize plants accumulated higher amounts of P than the Fe-sufficient ones, both in roots and shoots. The supply of 1 μM 59 Fe, as soluble (Fe-Citrate and Fe-PS) or sparingly soluble (Ferrihydrite) sources to deficient plants, caused a rapid down-regulation of genes coding for PS and Fe(III)-PS transport, as well as of ZmNRAMP1 and ZmPHT1;7. Levels of 32 P absorption essentially followed the rates of 59 Fe uptake in Fe-deficient plants during Fe resupply, suggesting that P accumulation might be regulated by Fe uptake in maize plants. The transcriptional response to Fe-deficiency in maize roots confirmed the modulation of known genes involved in the Strategy II and revealed the presence of Strategy I components usually described in dicots. Moreover, data here presented provide evidence of a close relationship between two essential nutrients for plants, Fe and P, and highlight a key role played by Fe and P transporters to preserve the homeostasis of these two nutrients in maize plants.

Framework for a U.S. Geological Survey Hydrologic Climate-Response Program in Maine

USGS Publications Warehouse

Hodgkins, Glenn A.; Lent, Robert M.; Dudley, Robert W.; Schalk, Charles W.

2009-01-01

This report presents a framework for a U.S. Geological Survey (USGS) hydrologic climate-response program designed to provide early warning of changes in the seasonal water cycle of Maine. Climate-related hydrologic changes on Maine's rivers and lakes in the winter and spring during the last century are well documented, and several river and lake variables have been shown to be sensitive to air-temperature changes. Monitoring of relevant hydrologic data would provide important baseline information against which future climate change can be measured. The framework of the hydrologic climate-response program presented here consists of four major parts: (1) identifying homogeneous climate-response regions; (2) identifying hydrologic components and key variables of those components that would be included in a hydrologic climate-response data network - as an example, streamflow has been identified as a primary component, with a key variable of streamflow being winter-spring streamflow timing; the data network would be created by maintaining existing USGS data-collection stations and establishing new ones to fill data gaps; (3) regularly updating historical trends of hydrologic data network variables; and (4) establishing basins for process-based studies. Components proposed for inclusion in the hydrologic climate-response data network have at least one key variable for which substantial historical data are available. The proposed components are streamflow, lake ice, river ice, snowpack, and groundwater. The proposed key variables of each component have extensive historical data at multiple sites and are expected to be responsive to climate change in the next few decades. These variables are also important for human water use and (or) ecosystem function. Maine would be divided into seven climate-response regions that follow major river-basin boundaries (basins subdivided to hydrologic units with 8-digit codes or larger) and have relatively homogeneous climates. Key hydrologic variables within each climate-response region would be analyzed regularly to maintain up-to-date analyses of year-to-year variability, decadal variability, and longer term trends. Finally, one basin in each climate-response region would be identified for process-based hydrologic and ecological studies.

Public perceptions of key performance indicators of healthcare in Alberta, Canada.

PubMed

Northcott, Herbert C; Harvey, Michael D

2012-06-01

To examine the relationship between public perceptions of key performance indicators assessing various aspects of the health-care system. Cross-sequential survey research. Annual telephone surveys of random samples of adult Albertans selected by random digit dialing and stratified according to age, sex and region (n = 4000 for each survey year). The survey questionnaires included single-item measures of key performance indicators to assess public perceptions of availability, accessibility, quality, outcome and satisfaction with healthcare. Cronbach's α and factor analysis were used to assess the relationship between key performance indicators focusing on the health-care system overall and on a recent interaction with the health-care system. The province of Alberta, Canada during the years 1996-2004. Four thousand adults randomly selected each survey year. Survey questions measuring public perceptions of healthcare availability, accessibility, quality, outcome and satisfaction with healthcare. Factor analysis identified two principal components with key performance indicators focusing on the health system overall loading most strongly on the first component and key performance indicators focusing on the most recent health-care encounter loading most strongly on the second component. Assessments of the quality of care most recently received, accessibility of that care and perceived outcome of care tended to be higher than the more general assessments of overall health system quality and accessibility. Assessments of specific health-care encounters and more general assessments of the overall health-care system, while related, nevertheless comprise separate dimensions for health-care evaluation.

Community Involvement Components in Culturally-Oriented Teacher Preparation.

ERIC Educational Resources Information Center

Mahan, James M.

1982-01-01

Describes community involvement components in culturally oriented teacher education program, i.e., preservice and inservice community agency assignments, oncampus cultural preparation. Reveals that cultural immersion student teacher programs are attractive and professionally advantageous. (AH)

Light Stable Isotopic Compositions of Enriched Mantle Sources: Resolving the Dehydration Paradox

NASA Astrophysics Data System (ADS)

Dixon, J. E.; Bindeman, I. N.; Kingsley, R. H.

2017-12-01

An outstanding puzzle in mantle geochemistry has been the origin and evolution of Earth's volatile components. The "dehydration paradox" refers to the following conundrum. Mantle compositions for some enriched mid-ocean ridge (MORB) and ocean island (OIB) basalts basalts require involvement of a mostly dehydrated slab component to explain the trace element ratios and radiogenic isotopic compositions, but a fully hydrated slab component to explain the stable isotopic compositions. Volatile and stable isotopic data on enriched MORB show a diversity of enriched components. Pacific PREMA-type basalts (H2O/Ce = 215 ± 30, δDSMOW = -45 ± 5 ‰) are similar to those in the north Atlantic (H2O/Ce = 220 ± 30; δDSMOW = -30 to -40 ‰). Basalts with EM-type signatures have regionally variable volatile compositions. North Atlantic EM-type basalts are wetter (H2O/Ce = 330 ± 30) and have isotopically heavier hydrogen (δDSMOW = -57 ± 5 ‰) than north Atlantic MORB. South Atlantic EM-type basalts are damp (H2O/Ce = 120 ± 10) with intermediate δDSMOW (-68 ± 2 ‰), similar to dDSMOW for Pacific MORB. North EPR EM-type basalts are dry (H2O/Ce = 110 ± 20) and isotopically light (δDSMOW = -94 ± 3 ‰). Boron and lithium isotopic ratios parallel the trends observed for dDSMOW. A multi-stage metasomatic and melting model accounts for the origin of the enriched components by extending the subduction factory concept down through the mantle transition zone, with slab temperature a key variable. The dehydration paradox is resolved by decoupling of volatiles from lithophile elements, reflecting primary dehydration of the slab followed by secondary rehydration and re-equilibration by fluids derived from subcrustal hydrous phases (e.g., antigorite) in cooler, deeper parts of the slab. The "expanded subduction factory" model includes melting at several key depths, including 1) 180 to 280 km, where EM-type mantle compositions are generated above slabs with average to hot thermal profiles by addition of <1% carbonated sediment-derived supercritical fluids/melts to depleted asthenospheric or subcontinental lithospheric mantle, and 2) 410 to 660 km, where PREMA-type mantle sources are generated, above slabs with average to cool thermal profiles, by addition of <1% carbonated eclogite ± sediment-derived supercritical fluids to depleted mantle.

Connexins, pannexins and their channels in fibroproliferative diseases

PubMed Central

Willebrords, Joost; Da Silva, Tereza Cristina; Maes, Michaël; Pereira, Isabel Veloso Alves; Crespo-Yanguas, Sara; Hernandez-Blazquez, Francisco Javier; Dagli, Maria Lúcia Zaidan; Vinken, Mathieu

2017-01-01

Cellular and molecular mechanisms of wound healing, tissue repair and fibrogenesis are established in different organs and are essential for the maintenance of function and tissue integrity after cell injury. These mechanisms are also involved in a plethora of fibroproliferative diseases or organ-specific fibrotic disorders, all of which are associated with the excessive deposition of extracellular matrix components. Fibroblasts, which are key cells in tissue repair and fibrogenesis, rely on communicative cellular networks to ensure efficient control of these processes and to prevent abnormal accumulation of extracellular matrix into the tissue. Despite the significant impact on human health, and thus the epidemiologic relevance, there is still no effective treatment for most fibrosis-related diseases. This paper provides an overview of current concepts and mechanisms involved in the participation of cellular communication via connexin-based pores as well as pannexin-based channels in the processes of tissue repair and fibrogenesis in chronic diseases. Understanding these mechanisms may contribute to the development of new therapeutic strategies to clinically manage fibroproliferative diseases and organ-specific fibrotic disorders. PMID:26914707

The Consequences of Surface Confinement on Free Radical Chemistry

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

Birtt, P.F.; Buchanan, A.C., III

1999-08-22

Mass transport limitations impact the thermochemical processing of fossil and renewable energy resources, which involves the breakdown of cross-linked, macromolecular networks. To Investigate the molecular level details of the consequences of molecular confinement on high temperature (275-500°C) free-radical reaction pathways, we have been examining the pyrolysis of model compounds attached to the surface of non-porous silica nanoparticles through a thermally robust Si-O-C aryl, tetha. Pyrolysis of silica-immobilized diphenylalkanes and related ethers have been studied in detail and compared with the corresponding behavior in fluid phases. The diffusional constraints can lead to reduced rates of radical termination on the surface, andmore » enhancement of neophyl-like rearrangements, cyclization-dehydrogenation pathways, and ipso- aromatic substitutions. Furthermore, studies of two-component surfaces have revealed the importance of a radical relay mechanism involving rapid serial hydrogen transfer steps resulting from the molecular pre-organization on the low fractal dimension silica surface. Key findings are reviewed in this paper, and the implications of these results for fuel processing are described.« less

The role of materials in global competitiveness

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

NONE

A symposium on global competitiveness was sponsored by ASM`s Advisory Technical Awareness Council during Materials Week in Cleveland last October. Carpenter Technology`s approach to internationalization and diversification involves three steps: internationalization of core businesses, diversification into engineered products, and focused research and development. Aluminum`s potential was the basis of the Audi-Alcoa relationship, and the result was a true breakthrough: a spaceframe structure designed to integrate every component surface as a structural entity, featuring straight and curved extruded sections joined by complex diecast nodes at key intersections and connection points. Through the support of research and development, many federal departments andmore » agencies have long been involved directly or indirectly in the support of civilian as well as defense industries. New copper alloys and fabrication techniques are enhancing global competitiveness, based largely on copper`s natural advantages of conductivity and corrosion resistance. The heavy equipment industry is a major transformer and user of steel, rubber, aluminum, welding consumables and equipment; glass, plastics, microprocessors and electronics; machine tools, and energy. It comprises the construction, farming, mining, and powertrain equipment manufacturers.« less

Fish pigmentation and the melanocortin system.

PubMed

Cal, Laura; Suarez-Bregua, Paula; Cerdá-Reverter, José Miguel; Braasch, Ingo; Rotllant, Josep

2017-09-01

The melanocortin system is a complex neuroendocrine signaling mechanism involved in numerous physiological processes in vertebrates, including pigmentation, steroidogenesis and metabolic control. This review focuses at one of its most fascinating function in fish, its regulatory role in the control of pigmentation, in which the melanocortin 1 receptor (Mc1r), its agonist α-melanocyte stimulating hormone (α-Msh), and the endogenous antagonist agouti signaling protein (Asip1) are the main players. Functional control of Mc1r, which is highly expressed in fish skin and whose activation stimulates melanin production and melanosome dispersion in fish melanophores, is considered a key mechanism for vertebrate pigment phenotypes. The α-Msh peptide, the most documented Mc1r agonist involved in pigmentation, is produced in the pituitary gland, activating melanin synthesis by binding to Mc1r in fish melanophores. Finally, Asip1 is the putative factor for establishing the evolutionarily conserved dorso-ventral pigment pattern found across vertebrates. However, we are just starting to understand how other melanocortin system components are acting in this complex regulatory network. Copyright © 2017 Elsevier Inc. All rights reserved.

Pearls and pitfalls in genetic studies of migraine.

PubMed

Eising, Else; de Vries, Boukje; Ferrari, Michel D; Terwindt, Gisela M; van den Maagdenberg, Arn M J M

2013-06-01

Migraine is a prevalent neurovascular brain disorder with a strong genetic component, and different methodological approaches have been implemented to identify the genes involved. This review focuses on pearls and pitfalls of these approaches and genetic findings in migraine. Common forms of migraine (i.e. migraine with and without aura) are thought to have a polygenic make-up, whereas rare familial hemiplegic migraine (FHM) presents with a monogenic pattern of inheritance. Until a few years ago only studies in FHM yielded causal genes, which were identified by a classical linkage analysis approach. Functional analyses of FHM gene mutations in cellular and transgenic animal models suggest abnormal glutamatergic neurotransmission as a possible key disease mechanism. Recently, a number of genes were discovered for the common forms of migraine using a genome-wide association (GWA) approach, which sheds first light on the pathophysiological mechanisms involved. Novel technological strategies such as next-generation sequencing, which can be implemented in future genetic migraine research, may aid the identification of novel FHM genes and promote the search for the missing heritability of common migraine.

Biosimulation of Inflammation and Healing in Surgically Injured Vocal Folds

PubMed Central

Li, Nicole Y. K.; Vodovotz, Yoram; Hebda, Patricia A.; Abbott, Katherine Verdolini

2010-01-01

Objectives The pathogenesis of vocal fold scarring is complex and remains to be deciphered. The current study is part of research endeavors aimed at applying systems biology approaches to address the complex biological processes involved in the pathogenesis of vocal fold scarring and other lesions affecting the larynx. Methods We developed a computational agent-based model (ABM) to quantitatively characterize multiple cellular and molecular interactions involved in inflammation and healing in vocal fold mucosa after surgical trauma. The ABM was calibrated with empirical data on inflammatory mediators (eg, tumor necrosis factor) and extracellular matrix components (eg, hyaluronan) from published studies on surgical vocal fold injury in the rat population. Results The simulation results reproduced and predicted trajectories seen in the empirical data from the animals. Moreover, the ABM studies suggested that hyaluronan fragments might be the clinical surrogate of tissue damage, a key variable that in these simulations both is enhanced by and further induces inflammation. Conclusions A relatively simple ABM such as the one reported in this study can provide new understanding of laryngeal wound healing and generate working hypotheses for further wet-lab studies. PMID:20583741

The CD63-Syntenin-1 Complex Controls Post-Endocytic Trafficking of Oncogenic Human Papillomaviruses.

PubMed

Gräßel, Linda; Fast, Laura Aline; Scheffer, Konstanze D; Boukhallouk, Fatima; Spoden, Gilles A; Tenzer, Stefan; Boller, Klaus; Bago, Ruzica; Rajesh, Sundaresan; Overduin, Michael; Berditchevski, Fedor; Florin, Luise

2016-08-31

Human papillomaviruses enter host cells via a clathrin-independent endocytic pathway involving tetraspanin proteins. However, post-endocytic trafficking required for virus capsid disassembly remains unclear. Here we demonstrate that the early trafficking pathway of internalised HPV particles involves tetraspanin CD63, syntenin-1 and ESCRT-associated adaptor protein ALIX. Following internalisation, viral particles are found in CD63-positive endosomes recruiting syntenin-1, a CD63-interacting adaptor protein. Electron microscopy and immunofluorescence experiments indicate that the CD63-syntenin-1 complex controls delivery of internalised viral particles to multivesicular endosomes. Accordingly, infectivity of high-risk HPV types 16, 18 and 31 as well as disassembly and post-uncoating processing of viral particles was markedly suppressed in CD63 or syntenin-1 depleted cells. Our analyses also present the syntenin-1 interacting protein ALIX as critical for HPV infection and CD63-syntenin-1-ALIX complex formation as a prerequisite for intracellular transport enabling viral capsid disassembly. Thus, our results identify the CD63-syntenin-1-ALIX complex as a key regulatory component in post-endocytic HPV trafficking.

Biosimulation of inflammation and healing in surgically injured vocal folds.

PubMed

Li, Nicole Y K; Vodovotz, Yoram; Hebda, Patricia A; Abbott, Katherine Verdolini

2010-06-01

The pathogenesis of vocal fold scarring is complex and remains to be deciphered. The current study is part of research endeavors aimed at applying systems biology approaches to address the complex biological processes involved in the pathogenesis of vocal fold scarring and other lesions affecting the larynx. We developed a computational agent-based model (ABM) to quantitatively characterize multiple cellular and molecular interactions involved in inflammation and healing in vocal fold mucosa after surgical trauma. The ABM was calibrated with empirical data on inflammatory mediators (eg, tumor necrosis factor) and extracellular matrix components (eg, hyaluronan) from published studies on surgical vocal fold injury in the rat population. The simulation results reproduced and predicted trajectories seen in the empirical data from the animals. Moreover, the ABM studies suggested that hyaluronan fragments might be the clinical surrogate of tissue damage, a key variable that in these simulations both is enhanced by and further induces inflammation. A relatively simple ABM such as the one reported in this study can provide new understanding of laryngeal wound healing and generate working hypotheses for further wet-lab studies.