Academic Motivation, Self-Concept, Engagement, and Performance in High School: Key Processes from a Longitudinal Perspective

ERIC Educational Resources Information Center

Green, Jasmine; Liem, Gregory Arief D.; Martin, Andrew J.; Colmar, Susan; Marsh, Herbert W.; McInerney, Dennis

2012-01-01

The study tested three theoretically/conceptually hypothesized longitudinal models of academic processes leading to academic performance. Based on a longitudinal sample of 1866 high-school students across two consecutive years of high school (Time 1 and Time 2), the model with the most superior heuristic value demonstrated: (a) academic motivation…

Paths of Adoption: Routes to Continuous Process Improvement

DTIC Science & Technology

2014-07-01

To obtain a process the team will use: The Team Lead has worked on teams with good processes and wants their new team to start out on the right foot ...eventually going to have to eat the entire process-improvement elephant . So, how do you get the “Never- Adopters” to undertake the effort? The key is to...Air Warfare Center Abstract. This paper covers the different types of teams the authors have en- countered as NAVAIR Internal Process Coaches and how

Nano-catalysts: Key to the Greener Pathways Leading to Sustainability

EPA Science Inventory

Synthetic processes using alternative energy input in combination with nano-catalysts shorten the reaction time that eliminate or minimize side product formation. This concept is already finding acceptance in the syntheses of pharmaceuticals, fine chemicals, and polymers and may ...

Optical hiding with visual cryptography

NASA Astrophysics Data System (ADS)

Shi, Yishi; Yang, Xiubo

2017-11-01

We propose an optical hiding method based on visual cryptography. In the hiding process, we convert the secret information into a set of fabricated phase-keys, which are completely independent of each other, intensity-detected-proof and image-covered, leading to the high security. During the extraction process, the covered phase-keys are illuminated with laser beams and then incoherently superimposed to extract the hidden information directly by human vision, without complicated optical implementations and any additional computation, resulting in the convenience of extraction. Also, the phase-keys are manufactured as the diffractive optical elements that are robust to the attacks, such as the blocking and the phase-noise. Optical experiments verify that the high security, the easy extraction and the strong robustness are all obtainable in the visual-cryptography-based optical hiding.

The evolution of concepts for soil erosion modelling

NASA Astrophysics Data System (ADS)

Kirkby, Mike

2013-04-01

From the earliest models for soil erosion, based on power laws relating sediment discharge or yield to slope length and gradient, the development of the Universal Soil Loss Equation was a natural step, although one that has long continued to hinder the development of better perceptual models for erosion processes. Key stumbling blocks have been: 1. The failure to go through runoff generation as a key intermediary 2. The failure to separate hydrological and strength parameters of the soil 3. The failure to treat sediment transport along a slope as a routing problem 4. The failure to analyse the nature of the dependence on vegetation Key advances have been in these directions (among others) 1. Improved understanding of the hydrological processes (e.g. infiltration and runoff, sediment entrainment) leading to KINEROS, LISEM,WEPP, PESERA 2. Recognition of selective sediment transport (e.g. transport- or supply-limited removal, grain travel distances) leading e.g. to MAHLERAN 3. Development of models adapted to particular time/space scales Some major remaining problems 1. Failure to integrate geomorphological and agronomic approaches 2. Tillage erosion - Is erosion loss of sediment or lowering of centre of mass? 3. Dynamic change during an event, as rills etc form.

Multi-Omics Reveals that Lead Exposure Disturbs Gut Microbiome Development, Key Metabolites, and Metabolic Pathways.

PubMed

Gao, Bei; Chi, Liang; Mahbub, Ridwan; Bian, Xiaoming; Tu, Pengcheng; Ru, Hongyu; Lu, Kun

2017-04-17

Lead exposure remains a global public health issue, and the recent Flint water crisis has renewed public concern about lead toxicity. The toxicity of lead has been well established in a variety of systems and organs. The gut microbiome has been shown to be highly involved in many critical physiological processes, including food digestion, immune system development, and metabolic homeostasis. However, despite the key role of the gut microbiome in human health, the functional impact of lead exposure on the gut microbiome has not been studied. The aim of this study is to define gut microbiome toxicity induced by lead exposure in C57BL/6 mice using multiomics approaches, including 16S rRNA sequencing, whole genome metagenomics sequencing, and gas chromatography-mass spectrometry (GC-MS) metabolomics. 16S rRNA sequencing revealed that lead exposure altered the gut microbiome trajectory and phylogenetic diversity. Metagenomics sequencing and metabolomics profiling showed that numerous metabolic pathways, including vitamin E, bile acids, nitrogen metabolism, energy metabolism, oxidative stress, and the defense/detoxification mechanism, were significantly disturbed by lead exposure. These perturbed molecules and pathways may have important implications for lead toxicity in the host. Taken together, these results demonstrated that lead exposure not only altered the gut microbiome community structures/diversity but also greatly affected metabolic functions, leading to gut microbiome toxicity.

Human Subject Research Protocol: Computer-Aided Human Centric Cyber Situation Awareness: Understanding Cognitive Processes of Cyber Analysts

DTIC Science & Technology

2013-11-01

by existing cyber-attack detection tools far exceeds the analysts’ cognitive capabilities. Grounded in perceptual and cognitive theory , many visual...Processes Inspired by the sense-making theory discussed earlier, we model the analytical reasoning process of cyber analysts using three key...analyst are called “working hypotheses”); each hypothesis could trigger further actions to confirm or disconfirm it. New actions will lead to new

Entropy driven key-lock assembly.

PubMed

Odriozola, G; Jiménez-Angeles, F; Lozada-Cassou, M

2008-09-21

The effective interaction between a sphere with an open cavity (lock) and a spherical macroparticle (key), both immersed in a hard sphere fluid, is studied by means of Monte Carlo simulations. As a result, a two-dimensional map of the key-lock effective interaction potential is constructed, which leads to the proposal of a self-assembling mechanism: There exists trajectories through which the key-lock pair could assemble avoiding trespassing potential barriers. Hence, solely the entropic contribution can induce their self-assembling even in the absence of attractive forces. This study points out the solvent contribution within the underlying mechanisms of substrate-protein assemblydisassembly processes, which are important steps of the enzyme catalysis and protein mediated transport.

Entropy driven key-lock assembly

NASA Astrophysics Data System (ADS)

Odriozola, G.; Jiménez-Ángeles, F.; Lozada-Cassou, M.

2008-09-01

The effective interaction between a sphere with an open cavity (lock) and a spherical macroparticle (key), both immersed in a hard sphere fluid, is studied by means of Monte Carlo simulations. As a result, a two-dimensional map of the key-lock effective interaction potential is constructed, which leads to the proposal of a self-assembling mechanism: There exists trajectories through which the key-lock pair could assemble avoiding trespassing potential barriers. Hence, solely the entropic contribution can induce their self-assembling even in the absence of attractive forces. This study points out the solvent contribution within the underlying mechanisms of substrate-protein assembly/disassembly processes, which are important steps of the enzyme catalysis and protein mediated transport.

Body of Knowledge (BOK) for Leadless Quad Flat No-Lead/bottom Termination Components (QFN/BTC) Package Trends and Reliability

NASA Technical Reports Server (NTRS)

Ghaffarian, Reza

2014-01-01

Bottom terminated components and quad flat no-lead (BTC/QFN) packages have been extensively used by commercial industry for more than a decade. Cost and performance advantages and the closeness of the packages to the boards make them especially unique for radio frequency (RF) applications. A number of high-reliability parts are now available in this style of package configuration. This report presents a summary of literature surveyed and provides a body of knowledge (BOK) gathered on the status of BTC/QFN and their advanced versions of multi-row QFN (MRQFN) packaging technologies. The report provides a comprehensive review of packaging trends and specifications on design, assembly, and reliability. Emphasis is placed on assembly reliability and associated key design and process parameters because they show lower life than standard leaded package assembly under thermal cycling exposures. Inspection of hidden solder joints for assuring quality is challenging and is similar to ball grid arrays (BGAs). Understanding the key BTC/QFN technology trends, applications, processing parameters, workmanship defects, and reliability behavior is important when judicially selecting and narrowing the follow-on packages for evaluation and testing, as well as for the low risk insertion in high-reliability applications.

Body of Knowledge (BOK) for Leadless Quad Flat No-Lead/Bottom Termination Components (QFN/BTC) Package Trends and Reliability

NASA Technical Reports Server (NTRS)

Ghaffarian, Reza

2014-01-01

Bottom terminated components and quad flat no-lead (BTC/QFN) packages have been extensively used by commercial industry for more than a decade. Cost and performance advantages and the closeness of the packages to the boards make them especially unique for radio frequency (RF) applications. A number of high-reliability parts are now available in this style of package configuration. This report presents a summary of literature surveyed and provides a body of knowledge (BOK) gathered on the status of BTC/QFN and their advanced versions of multi-row QFN (MRQFN) packaging technologies. The report provides a comprehensive review of packaging trends and specifications on design, assembly, and reliability. Emphasis is placed on assembly reliability and associated key design and process parameters because they show lower life than standard leaded package assembly under thermal cycling exposures. Inspection of hidden solder joints for assuring quality is challenging and is similar to ball grid arrays (BGAs). Understanding the key BTC/QFN technology trends, applications, processing parameters, workmanship defects, and reliability behavior is important when judicially selecting and narrowing the follow-on packages for evaluation and testing, as well as for the low risk insertion in high-reliability applications.

Executive Development: Key Factors for Success.

ERIC Educational Resources Information Center

Fenwick-Magrath, Julie A.

1988-01-01

Reports results from a survey of 12 leading corporations concerning their management of the executive development process. Indicates that involvement of the chief executive officer, a clear policy, a relationship between executive development and business strategies and objectives, annual succession planning, and management responsibility are key…

Lean-driven improvements slash wait times, drive up patient satisfaction scores.

PubMed

2012-07-01

Administrators at LifePoint Hospitals, based in Brentwood, TN, used lean manufacturing techniques to slash wait times by as much as 30 minutes and achieve double-digit increases in patient satisfaction scores in the EDs at three hospitals. In each case, front-line workers took the lead on identifying opportunities for improvement and redesigning the patient-flow process. As a result of the new efficiencies, patient volume is up by about 25% at all three hospitals. At each hospital, the improvement process began with Kaizen, a lean process that involves bringing personnel together to flow-chart the current system, identify problem areas, and redesign the process. Improvement teams found big opportunities for improvement at the front end of the flow process. Key to the approach was having a plan up front to deal with non-compliance. To sustain improvements, administrators gather and disseminate key metrics on a daily basis.

Safety, risk and mental health: decision-making processes prescribed by Australian mental health legislation.

PubMed

Smith-Merry, Jennifer; Caple, Andrew

2014-03-01

Adverse events in mental health care occur frequently and cause significant distress for those who experience them, derailing treatment and sometimes leading to death. These events are clustered around particular aspects of care and treatment and are therefore avoidable if practices in these areas are strengthened. The research reported in this article takes as its starting point coronial recommendations made in relation to mental health. We report on those points and processes in treatment and discharge where coronial recommendations are most frequently made. We then examine the legislative requirements around these points and processes in three Australian States. We find that the key areas that need to be strengthened to avoid adverse events are assessment processes, communication and information transfer, documentation, planning and training. We make recommendations for improvements in these key areas.

Role of inflammation in cardiopulmonary health effects of PM

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

Donaldson, Ken; Mills, Nicholas; MacNee, William

2005-09-01

The relationship between increased exposure to PM and adverse cardiovascular effects is well documented in epidemiological studies. Inflammation in the lungs, caused by deposited particles, can be seen as a key process that could mediate adverse effects on the cardiovascular system. There are at least three potential pathways that could lead from pulmonary inflammation to adverse cardiovascular effects. Firstly, inflammation in the lung could lead to systemic inflammation, which is well known to be linked to sudden death from cardiovascular causes. Systemic inflammation can lead to destabilization by activation of inflammatory processes in atheromatous plaques. Secondly, inflammation can cause anmore » imbalance in coagulation factors that favor propagation of thrombi if thrombosis is initiated. Thirdly, inflammation could affect the autonomic nervous system activity in ways that could lead to alterations in the control of heart rhythm which could culminate in fatal dysrhythmia.« less

Testing a key assumption in animal communication: between-individual variation in female visual systems alters perception of male signals

PubMed Central

Ensminger, Amanda L.; Shawkey, Matthew D.; Lucas, Jeffrey R.; Fernández-Juricic, Esteban

2017-01-01

ABSTRACT Variation in male signal production has been extensively studied because of its relevance to animal communication and sexual selection. Although we now know much about the mechanisms that can lead to variation between males in the properties of their signals, there is still a general assumption that there is little variation in terms of how females process these male signals. Variation between females in signal processing may lead to variation between females in how they rank individual males, meaning that one single signal may not be universally attractive to all females. We tested this assumption in a group of female wild-caught brown-headed cowbirds (Molothrus ater), a species that uses a male visual signal (e.g. a wingspread display) to make its mate-choice decisions. We found that females varied in two key parameters of their visual sensory systems related to chromatic and achromatic vision: cone densities (both total and proportions) and cone oil droplet absorbance. Using visual chromatic and achromatic contrast modeling, we then found that this between-individual variation in visual physiology leads to significant between-individual differences in how females perceive chromatic and achromatic male signals. These differences may lead to variation in female preferences for male visual signals, which would provide a potential mechanism for explaining individual differences in mate-choice behavior. PMID:29247048

Testing a key assumption in animal communication: between-individual variation in female visual systems alters perception of male signals.

PubMed

Ronald, Kelly L; Ensminger, Amanda L; Shawkey, Matthew D; Lucas, Jeffrey R; Fernández-Juricic, Esteban

2017-12-15

Variation in male signal production has been extensively studied because of its relevance to animal communication and sexual selection. Although we now know much about the mechanisms that can lead to variation between males in the properties of their signals, there is still a general assumption that there is little variation in terms of how females process these male signals. Variation between females in signal processing may lead to variation between females in how they rank individual males, meaning that one single signal may not be universally attractive to all females. We tested this assumption in a group of female wild-caught brown-headed cowbirds ( Molothrus ater ), a species that uses a male visual signal (e.g. a wingspread display) to make its mate-choice decisions. We found that females varied in two key parameters of their visual sensory systems related to chromatic and achromatic vision: cone densities (both total and proportions) and cone oil droplet absorbance. Using visual chromatic and achromatic contrast modeling, we then found that this between-individual variation in visual physiology leads to significant between-individual differences in how females perceive chromatic and achromatic male signals. These differences may lead to variation in female preferences for male visual signals, which would provide a potential mechanism for explaining individual differences in mate-choice behavior. © 2017. Published by The Company of Biologists Ltd.

Warmer temperatures reduce net carbon uptake, but not water use, in a mature southern Appalachian forest

EPA Science Inventory

Increasing air temperature is expected to extend growing season length in temperate, broadleaf forests, leading to potential increases in evapotranspiration and net carbon uptake. However, other key processes affecting water and carbon cycles are also highly temperature-dependent...

Ecdysone receptor agonism leading to lethal molting disruption in arthropods: Review and adverse outcome pathway development

EPA Science Inventory

Molting is a key biological process in growth, development, reproduction and survival in arthropods. Complex neuroendocrine pathways are involved in the regulation of molting and may potentially become targets of environmental endocrine disrupting compounds (EDCs). For example, s...

Un-Believing the Matrix: Queering Consensual Heteronormativity

ERIC Educational Resources Information Center

Atkinson, Elizabeth; DePalma, Renee

2009-01-01

Two key concepts arising from Butler's work are the heterosexual matrix--the conflation of sex-gender-sexuality which leads to the normalisation of heterosexuality--and performative reinscription--the discursive process by which the marginalised Other brings new meanings to normative identity constructions. While we have found both concepts…

Transcriptional and physiological responses of nitrifying bacteria to heavy metal inhibition

EPA Science Inventory

Heavy metals have been shown to inhibit nitrification, a key process in the removal of nitrogen in wastewater treatment plants. In the present study, the effects of nickel, zinc, lead and cadmium on nitrifying enrichment cultures were studied in batch reactors. The transcriptiona...

Chromatographic analysis of age-related changes in mucosal serotonin transmission in the murine distal ileum

PubMed Central

2012-01-01

Background In the upper bowel, alterations in motility and absorption of key nutrients have been observed as part of the normal ageing process. Serotonin (5-HT) is a key signalling molecule in the gastrointestinal tract and is known to influence motility, however little is known of how the ageing process alters 5-HT signalling processes in the bowel. Results An isocratic chromatographic method was able to detect all 5-HT precursors and metabolites. Using extracellular and intracellular sampling approaches, we were able to monitor all key parameters associated with the transmission process. There was no alteration in the levels of tryptophan and 5-HTP between 3 and 18 month old animals. There was a significant increase in the ratio of 5-HT:5-HTP and an increase in intracellular 5-HT between 3 and 18 month old animals suggesting an increase in 5-HT synthesis. There was also a significant increase in extracellular 5-HT with age, suggesting increased 5-HT release. There was an age-related decrease in the ratio of intracellular 5-HIAA:extracellular 5-HT, whilst the amount of 5-HIAA did not change with age. In the presence of an increase in extracellular 5-HT, the lack of an age-related change in 5-HIAA is suggestive of a decrease in re-uptake via the serotonin transporter (SERT). Conclusions We have used intracellular and extracellular sampling to provide more insight into alterations in the neurotransmission process of 5-HT during normal ageing. We observed elevated 5-HT synthesis and release and a possible decrease in the activity of SERT. Taken together these changes lead to increased 5-HT availability and may alter motility function and could lead to the changes in adsorption observed in the elderly. PMID:22494644

Health system decentralisation in Nepal: identifying the issues.

PubMed

Collins, Charles; Omar, Mayeh; Adhikari, Damodar; Dhakal, Ramji; Emmel, Nick; Dhakal, Megha Raj; Chand, Padam; Thapa, Druba; Singh, Arjun B

2007-01-01

The purpose of this paper is to describe and discuss policy analysis in Nepal and review the wide range of choices feasible in decentralisation decision making. In this paper an iterative qualitative method was developed and used in the research, which consisted of focus group interviews, key informant interviews, document analysis, including descriptive statistics, and analysis of the policy context. Participants in the research reflected the urban/rural mix of districts and the geography of Nepal. Analysis combined transcribed interviews with findings from document searches and analysis of the policy context. Coding was pre-determined during the training workshop and further codes were generated during and after the fieldwork. The paper finds that Nepal is in the process of decentralising public services from the central level to the local level, particularly to local bodies: District Development Committees (DDCs), Village Development Committees (VDCs) and Municipalities. Key contextual factors referred to are the overall structure of decentralisation, the social context of poverty and the political instability leading to a fluid political situation characterised by political tension, armed conflict, controversies and agreements while carrying out the research. The key issues identified and discussed in the paper are the policy process leading to decentralisation, the organisational structure and tension in the proposed system, the systems of resource generation, allocation, planning and management and lastly the forms of accountability, participation, public-private relations and collaborative strategies. The paper discusses the challenges faced in conducting such a policy analysis, the broad ranging and unremitting nature of the decentralisation process, and the contextual setting of the process of change.

Electron Transport Modeling of Molecular Nanoscale Bridges Used in Energy Conversion Schemes

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

Dunietz, Barry D

2016-08-09

The goal of the research program is to reliably describe electron transport and transfer processes at the molecular level. Such insight is essential for improving molecular applications of solar and thermal energy conversion. We develop electronic structure models to study (1) photoinduced electron transfer and transport processes in organic semiconducting materials, and (2) charge and heat transport through molecular bridges. We seek fundamental understanding of key processes, which lead to design new experiments and ultimately to achieve systems with improved properties.

The Routledge International Handbook of the Sociology of Education

ERIC Educational Resources Information Center

Apple, Michael W., Ed.; Ball, Stephen J., Ed.; Gandin, Luis Armando, Ed.

2009-01-01

This collection brings together many of the world's leading sociologists of education to explore and address key issues and concerns within the discipline. The thirty-seven newly commissioned chapters draw upon theory and research to provide new accounts of contemporary educational processes, global trends, and changing and enduring forms of…

Innovative Work in School Development: Exploring Leadership Enactment

ERIC Educational Resources Information Center

Vennebo, Kirsten Foshaug

2017-01-01

Leadership is recognised in both policy and research as a key enabler of innovation in schools. Numerous researchers have focused on how school leaders formally narrate their experiences of leading innovations including their observations of effect; however, modest attention has been paid to the processes through which leaders engage in innovative…

Choice-Making in Vocational Activities Planning: Recommendations from Job Coaches

ERIC Educational Resources Information Center

Cobigo, Virginie; Lachapelle, Yves; Morin, Diane

2010-01-01

Choice in the job seeking process may lead to increased satisfaction with the chosen job, and improve attention, performance, and motivation. Consequently, providing opportunities to express choices and interests while planning vocational activities is a key factor in achieving employment outcomes. Despite their commitment to promoting…

ICT and Marketing Challenges in Latin American Libraries.

ERIC Educational Resources Information Center

Feria, Lourdes

Latin American libraries have experienced an important development in the last two decades. Telecommunications and Information Technologies (ITC) have been key elements in this process. There are leading institutions with remarkable programs; nevertheless it is necessary to design marketing strategies to improve their benefits. A case study based…

Enhancing the use of research in health-promoting, anti-racism policy.

PubMed

Ferdinand, Angeline S; Paradies, Yin; Kelaher, Margaret

2017-07-11

The Localities Embracing and Accepting Diversity (LEAD) programme was established to improve the health of ethnic minority communities through the reduction of racial discrimination. Local governments in the state of Victoria, Australia, were at the forefront of LEAD implementation in collaboration with leading state and national organisations. Key aims included expanding the available evidence regarding effective anti-racism interventions and facilitating the uptake of this evidence in organisational policies and practices. One rural and one metropolitan local government areas were selected to participate in LEAD. Key informant interviews and discussions were conducted with individuals who had participated in LEAD implementation and members of LEAD governance structures. Data were also collected on programme processes and implementation, partnership formation and organisational assessments. The LEAD model demonstrated both strengths and weaknesses in terms of facilitating the use of evidence in a complex, community-based health promotion initiative. Representation of implementing, funding and advisory bodies at different levels of governance enabled the input of technical advice and guidance alongside design and implementation. The representation structure assisted in ensuring the development of a programme that was acceptable to all partners and informed by the best available evidence. Simultaneous evaluation also enhanced perceived validity of the intervention, allowed for strategy correction when necessary and supported the process of double-loop organisational learning. However, due to the model's demand for simultaneous and intensive effort by various organisations, when particular elements of the intervention were not functional, there was a considerable loss of time and resources across the partner organisations. The complexity of the model also presented a challenge in ensuring clarity regarding roles, functions and the direction of the programme. The example of LEAD provides guidance on mechanisms to strengthen the entry of evidence into complex community-based health promotion programmes. The paper highlights some of the strengths and weaknesses of the LEAD model and implications for practical collaboration between policymakers, implementers and researchers.

Pseudomaster equation for the no-count process in a continuous photodetection

NASA Technical Reports Server (NTRS)

Lee, Ching-Tsung

1994-01-01

The detection of cavity radiation with the detector placed outside the cavity is studied. Each leaked photon has a certain probability of propagating away without being detected. It is viewed as a continuous quantum measurement in which the density matrix is continuously revised according to the readout of the detector. The concept of pseudomaster equation for the no-count process is introduced; its solution leads to the discovery of the superoperator for the same process. It has the potential to become the key equation for continuous measurement process.

High speed and adaptable error correction for megabit/s rate quantum key distribution.

PubMed

Dixon, A R; Sato, H

2014-12-02

Quantum Key Distribution is moving from its theoretical foundation of unconditional security to rapidly approaching real world installations. A significant part of this move is the orders of magnitude increases in the rate at which secure key bits are distributed. However, these advances have mostly been confined to the physical hardware stage of QKD, with software post-processing often being unable to support the high raw bit rates. In a complete implementation this leads to a bottleneck limiting the final secure key rate of the system unnecessarily. Here we report details of equally high rate error correction which is further adaptable to maximise the secure key rate under a range of different operating conditions. The error correction is implemented both in CPU and GPU using a bi-directional LDPC approach and can provide 90-94% of the ideal secure key rate over all fibre distances from 0-80 km.

High speed and adaptable error correction for megabit/s rate quantum key distribution

PubMed Central

Dixon, A. R.; Sato, H.

2014-01-01

Quantum Key Distribution is moving from its theoretical foundation of unconditional security to rapidly approaching real world installations. A significant part of this move is the orders of magnitude increases in the rate at which secure key bits are distributed. However, these advances have mostly been confined to the physical hardware stage of QKD, with software post-processing often being unable to support the high raw bit rates. In a complete implementation this leads to a bottleneck limiting the final secure key rate of the system unnecessarily. Here we report details of equally high rate error correction which is further adaptable to maximise the secure key rate under a range of different operating conditions. The error correction is implemented both in CPU and GPU using a bi-directional LDPC approach and can provide 90–94% of the ideal secure key rate over all fibre distances from 0–80 km. PMID:25450416

Lead recovery and glass microspheres synthesis from waste CRT funnel glasses through carbon thermal reduction enhanced acid leaching process.

PubMed

Mingfei, Xing; Yaping, Wang; Jun, Li; Hua, Xu

2016-03-15

In this study, a novel process for detoxification and reutilization of waste cathode ray tube (CRT) funnel glass was developed by carbon thermal reduction enhanced acid leaching process. The key to this process is removal of lead from the CRT funnel glass and synchronous preparation of glass microspheres. Carbon powder was used as an isolation agent and a reducing agent. Under the isolation of the carbon powder, the funnel glass powder was sintered into glass microspheres. In thermal reduction, PbO in the funnel glass was first reduced to elemental Pb by carbon monoxide and then located on the surface of glass microspheres which can be removed easily by acid leaching. Experimental results showed that temperature, carbon adding amount and holding time were the major parameters that controlled lead removal rate. The maximum lead removal rate was 94.80% and glass microspheres that measured 0.73-14.74μm were obtained successfully by setting the temperature, carbon adding amount and holding time at 1200°C, 10% and 30min, respectively. The prepared glass microspheres may be used as fillers in polymer materials and abrasive materials, among others. Accordingly, this study proposed a practical and economical process for detoxification and recycling of waste lead-containing glass. Copyright © 2015 Elsevier B.V. All rights reserved.

Aqueous organic chemistry in the atmosphere: sources and chemical processing of organic aerosols.

PubMed

McNeill, V Faye

2015-02-03

Over the past decade, it has become clear that aqueous chemical processes occurring in cloud droplets and wet atmospheric particles are an important source of organic atmospheric particulate matter. Reactions of water-soluble volatile (or semivolatile) organic gases (VOCs or SVOCs) in these aqueous media lead to the formation of highly oxidized organic particulate matter (secondary organic aerosol; SOA) and key tracer species, such as organosulfates. These processes are often driven by a combination of anthropogenic and biogenic emissions, and therefore their accurate representation in models is important for effective air quality management. Despite considerable progress, mechanistic understanding of some key aqueous processes is still lacking, and these pathways are incompletely represented in 3D atmospheric chemistry and air quality models. In this article, the concepts, historical context, and current state of the science of aqueous pathways of SOA formation are discussed.

What makes us think? A three-stage dual-process model of analytic engagement.

PubMed

Pennycook, Gordon; Fugelsang, Jonathan A; Koehler, Derek J

2015-08-01

The distinction between intuitive and analytic thinking is common in psychology. However, while often being quite clear on the characteristics of the two processes ('Type 1' processes are fast, autonomous, intuitive, etc. and 'Type 2' processes are slow, deliberative, analytic, etc.), dual-process theorists have been heavily criticized for being unclear on the factors that determine when an individual will think analytically or rely on their intuition. We address this issue by introducing a three-stage model that elucidates the bottom-up factors that cause individuals to engage Type 2 processing. According to the model, multiple Type 1 processes may be cued by a stimulus (Stage 1), leading to the potential for conflict detection (Stage 2). If successful, conflict detection leads to Type 2 processing (Stage 3), which may take the form of rationalization (i.e., the Type 1 output is verified post hoc) or decoupling (i.e., the Type 1 output is falsified). We tested key aspects of the model using a novel base-rate task where stereotypes and base-rate probabilities cued the same (non-conflict problems) or different (conflict problems) responses about group membership. Our results support two key predictions derived from the model: (1) conflict detection and decoupling are dissociable sources of Type 2 processing and (2) conflict detection sometimes fails. We argue that considering the potential stages of reasoning allows us to distinguish early (conflict detection) and late (decoupling) sources of analytic thought. Errors may occur at both stages and, as a consequence, bias arises from both conflict monitoring and decoupling failures. Copyright © 2015 Elsevier Inc. All rights reserved.

Brain metabolic stress and neuroinflammation at the basis of cognitive impairment in Alzheimer’s disease

PubMed Central

De Felice, Fernanda G.; Lourenco, Mychael V.

2015-01-01

Brain metabolic dysfunction is known to influence brain activity in several neurological disorders, including Alzheimer’s disease (AD). In fact, deregulation of neuronal metabolism has been postulated to play a key role leading to the clinical outcomes observed in AD. Besides deficits in glucose utilization in AD patients, recent evidence has implicated neuroinflammation and endoplasmic reticulum (ER) stress as components of a novel form of brain metabolic stress that develop in AD and other neurological disorders. Here we review findings supporting this novel paradigm and further discuss how these mechanisms seem to participate in synapse and cognitive impairments that are germane to AD. These deleterious processes resemble pathways that act in peripheral tissues leading to insulin resistance and glucose intolerance, in an intriguing molecular connection linking AD to diabetes. The discovery of detailed mechanisms leading to neuronal metabolic stress may be a key step that will allow the understanding how cognitive impairment develops in AD, thereby offering new avenues for effective disease prevention and therapeutic targeting. PMID:26042036

Components of a comprehensive capital equipment planning program.

PubMed

Gresch, Alan

2010-01-01

As you may have already figured out, there is crossover and gaps between all of these capital equipment components. CE often will, and proactively should, make recommendations based on the CE, clinical, and financial components but rarely has direct knowledge of the strategic element. The clinical, finance, and administrative folks likely have visibility to most of these, but may lack full awareness of at least one component. The key is to engage key stakeholders from all these critical areas and develop a process to pull all this information together in one nice, neat package. Defining the person or persons responsible for taking the lead on this in your organization will depend greatly on the organization's type and size. For a single, standalone community hospital, it will likely be the facility administrator. For an integrated delivery network (IDN), a corporate entity, led by supply chain, finance, or both, may take the lead. Your organization may also employ consultative services or software to help facilitate this function. Regardless of who takes the lead, a weighting or scoring system that assigns certain values in all the outlined component categories, is clearly defined, and is easy to understand for all the contributors will need to be developed. If you are unaware or unclear of what the process is, find out and figure out how you can be a vital contributor to the process. This is one more way you can demonstrate the value you and your department bring to your organization.

Innovative techniques for the production of energetic radicals for lunar materials processing including photogeneration via concentrated solar energy

NASA Technical Reports Server (NTRS)

Osborn, D. E.; Lynch, D. C.; Fazzolari, R.

1990-01-01

The Department of Materials Science and Engineering (MSE) is investigating the use of monatomic chlorine produced in a cold plasma to recover oxygen and metallurgically significant metals from lunar materials. Development of techniques for the production of the chlorine radical (and other energetic radicals for these processes) using local planetary resources is a key step for a successful approach. It was demonstrated terrestrially that the use of UV light to energize the photogeneration of OH radicals from ozone or hydrogen peroxide in aqueous solutions can lead to rapid reaction rates for the breakdown of toxic organic compounds in water. A key question is how to use the expanded solar resource at the lunar surface to generate process-useful radicals. This project is aimed at investigating that question.

Studying neuroanatomy using MRI.

PubMed

Lerch, Jason P; van der Kouwe, André J W; Raznahan, Armin; Paus, Tomáš; Johansen-Berg, Heidi; Miller, Karla L; Smith, Stephen M; Fischl, Bruce; Sotiropoulos, Stamatios N

2017-02-23

The study of neuroanatomy using imaging enables key insights into how our brains function, are shaped by genes and environment, and change with development, aging and disease. Developments in MRI acquisition, image processing and data modeling have been key to these advances. However, MRI provides an indirect measurement of the biological signals we aim to investigate. Thus, artifacts and key questions of correct interpretation can confound the readouts provided by anatomical MRI. In this review we provide an overview of the methods for measuring macro- and mesoscopic structure and for inferring microstructural properties; we also describe key artifacts and confounds that can lead to incorrect conclusions. Ultimately, we believe that, although methods need to improve and caution is required in interpretation, structural MRI continues to have great promise in furthering our understanding of how the brain works.

The Key Factors of an Active Learning Method in a Microprocessors Course

ERIC Educational Resources Information Center

Carpeno, A.; Arriaga, J.; Corredor, J.; Hernandez, J.

2011-01-01

The creation of the European Higher Education Area (EHEA) is promoting a change toward a new model of education focused on the student. It is impelling methodological innovation processes in many European universities, leading more teachers to apply methods based on active and cooperative learning in their classrooms. However, the successful…

Performance of a Zerovalent Iron Reactive Barrier for the Treatment of Arsenic in Groundwater: Part 2. Geochemical Modeling and Solid Phase Studies

EPA Science Inventory

Arsenic uptake processes were evaluated in a zerovalent iron reactive barrier installed at a lead smelting facility using geochemical modeling, solid-phase analysis, and X-ray absorption spectroscopy techniques. Aqueous speciation of arsenic plays a key role in directing arsenic...

Microwave processing of cement and concrete materials – towards an industrial reality?

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

Buttress, Adam, E-mail: adam.buttress@nottingham.ac.uk; Jones, Aled; Kingman, Sam

2015-02-15

Each year a substantial body of literature is published on the use of microwave to process cement and concrete materials. Yet to date, very few if any have lead the realisation of a commercial scale industrial system and is the context under which this review has been undertaken. The state-of the–art is evaluated for opportunities, and the key barriers to the development of new microwave-based processing techniques to enhance production, processing and recycling of cement and concrete materials. Applications reviewed include pyro-processing of cement clinker; accelerated curing, non-destructive testing and evaluation (NDT&E), and end-of-life processing including radionuclide decontamination.

Chemistry challenges in lead optimization: silicon isosteres in drug discovery.

PubMed

Showell, Graham A; Mills, John S

2003-06-15

During the lead optimization phase of drug discovery projects, the factors contributing to subsequent failure might include poor portfolio decision-making and a sub-optimal intellectual property (IP) position. The pharmaceutical industry has an ongoing need for new, safe medicines with a genuine biomedical benefit, a clean IP position and commercial viability. Inherent drug-like properties and chemical tractability are also essential for the smooth development of such agents. The introduction of bioisosteres, to improve the properties of a molecule and obtain new classes of compounds without prior art in the patent literature, is a key strategy used by medicinal chemists during the lead optimization process. Sila-substitution (C/Si exchange) of existing drugs is an approach to search for new drug-like candidates that have beneficial biological properties and a clear IP position. Some of the fundamental differences between carbon and silicon can lead to marked alterations in the physicochemical and biological properties of the silicon-containing analogues and the resulting benefits can be exploited in the drug design process.

A case study detailing key considerations for implementing a telehealth approach to office ergonomics.

PubMed

Ritchie, Catherine L W; Miller, Linda L; Antle, David M

2017-01-01

Telehealth approaches to delivering ergonomics assessment hold great potential to improve service delivery in rural and remote settings. This case study describes a telehealth-based ergonomics service delivery process, and compares in-person and telehealth-based ergonomics approaches at an Alberta-based non-profit advocacy group. This project demonstrates that telehealth approaches to ergonomics do not lead to significantly different scoring outcomes for assessment of ergonomics issues, when compared to in-person assessments. This project also outlines the importance of live real-time video conferencing to improving communication, attaining key assessment information, and demonstrating ergonomic adjustments. However, some key considerations of bandwidth and hardware capabilities need to be taken into account. Key communication strategies are outlined to improve rapport, maintain employee confidentiality, and reduce client anxiety around telehealth ergonomics assessments. This project provides further support for telehealth approaches to office ergonomics, and outlines some key implementation strategies and barriers that should be considered.

Research on autonomous identification of airport targets based on Gabor filtering and Radon transform

NASA Astrophysics Data System (ADS)

Yi, Juan; Du, Qingyu; Zhang, Hong jiang; Zhang, Yao lei

2017-11-01

Target recognition is a leading key technology in intelligent image processing and application development at present, with the enhancement of computer processing ability, autonomous target recognition algorithm, gradually improve intelligence, and showed good adaptability. Taking the airport target as the research object, analysis the airport layout characteristics, construction of knowledge model, Gabor filter and Radon transform based on the target recognition algorithm of independent design, image processing and feature extraction of the airport, the algorithm was verified, and achieved better recognition results.

Improvement of Selected Logistics Processes Using Quality Engineering Tools

NASA Astrophysics Data System (ADS)

Zasadzień, Michał; Žarnovský, Jozef

2018-03-01

Increase in the number of orders, the increasing quality requirements and the speed of order preparation require implementation of new solutions and improvement of logistics processes. Any disruption that occurs during execution of an order often leads to customer dissatisfaction, as well as loss of his/her confidence. The article presents a case study of the use of quality engineering methods and tools to improve the e-commerce logistic process. This made it possible to identify and prioritize key issues, identify their causes, and formulate improvement and prevention measures.

A data mining paradigm for identifying key factors in biological processes using gene expression data.

PubMed

Li, Jin; Zheng, Le; Uchiyama, Akihiko; Bin, Lianghua; Mauro, Theodora M; Elias, Peter M; Pawelczyk, Tadeusz; Sakowicz-Burkiewicz, Monika; Trzeciak, Magdalena; Leung, Donald Y M; Morasso, Maria I; Yu, Peng

2018-06-13

A large volume of biological data is being generated for studying mechanisms of various biological processes. These precious data enable large-scale computational analyses to gain biological insights. However, it remains a challenge to mine the data efficiently for knowledge discovery. The heterogeneity of these data makes it difficult to consistently integrate them, slowing down the process of biological discovery. We introduce a data processing paradigm to identify key factors in biological processes via systematic collection of gene expression datasets, primary analysis of data, and evaluation of consistent signals. To demonstrate its effectiveness, our paradigm was applied to epidermal development and identified many genes that play a potential role in this process. Besides the known epidermal development genes, a substantial proportion of the identified genes are still not supported by gain- or loss-of-function studies, yielding many novel genes for future studies. Among them, we selected a top gene for loss-of-function experimental validation and confirmed its function in epidermal differentiation, proving the ability of this paradigm to identify new factors in biological processes. In addition, this paradigm revealed many key genes in cold-induced thermogenesis using data from cold-challenged tissues, demonstrating its generalizability. This paradigm can lead to fruitful results for studying molecular mechanisms in an era of explosive accumulation of publicly available biological data.

Insertion of Isocyanides into N-Si Bonds: Multicomponent Reactions with Azines Leading to Potent Antiparasitic Compounds.

PubMed

Kishore, Kranti G; Ghashghaei, Ouldouz; Estarellas, Carolina; Mestre, M Mar; Monturiol, Cristina; Kielland, Nicola; Kelly, John M; Francisco, Amanda Fortes; Jayawardhana, Shiromani; Muñoz-Torrero, Diego; Pérez, Belén; Luque, F Javier; Gámez-Montaño, Rocío; Lavilla, Rodolfo

2016-07-25

Trimethylsilyl chloride is an efficient activating agent for azines in isocyanide-based reactions, which then proceed through a key insertion of the isocyanide into a N-Si bond. The reaction is initiated by N activation of the azine, followed by nucleophilic attack of an isocyanide in a Reissert-type process. Finally, a second equivalent of the same or a different isocyanide inserts into the N-Si bond leading to the final adduct. The use of distinct nucleophiles leads to a variety of α-substituted dihydroazines after a selective cascade process. Based on computational studies, a mechanistic hypothesis for the course of these reactions was proposed. The resulting products exhibit significant activity against Trypanosoma brucei and T. cruzi, featuring favorable drug-like properties and safety profiles. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Vortex line topology during vortex tube reconnection

NASA Astrophysics Data System (ADS)

McGavin, P.; Pontin, D. I.

2018-05-01

This paper addresses reconnection of vortex tubes, with particular focus on the topology of the vortex lines (field lines of the vorticity). This analysis of vortex line topology reveals key features of the reconnection process, such as the generation of many small flux rings, formed when reconnection occurs in multiple locations in the vortex sheet between the tubes. Consideration of three-dimensional reconnection principles leads to a robust measurement of the reconnection rate, even once instabilities break the symmetry. It also allows us to identify internal reconnection of vortex lines within the individual vortex tubes. Finally, the introduction of a third vortex tube is shown to render the vortex reconnection process fully three-dimensional, leading to a fundamental change in the topological structure of the process. An additional interesting feature is the generation of vorticity null points.

Ecdysone receptor agonism leading to lethal molting ...

EPA Pesticide Factsheets

Molting is a key biological process in growth, development, reproduction and survival in arthropods. Complex neuroendocrine pathways are involved in the regulation of molting and may potentially become targets of environmental endocrine disrupting compounds (EDCs). For example, several classes of pesticides used in agriculture and aquaculture specifically target key endocrine regulators of the molting process. These chemicals may also pose hazards to non-target species by causing molting defects, thus affecting the health of the ecosystems. The present review summarized the available knowledge on molting-related endocrine regulation and disruption in arthropods (with special focus on insects and crustaceans), in order to identify research gaps and develop a toxicity mechanism-based model for environmental hazard and risk assessment. Based on the review, multiple targets in the molting processes that EDCs can interact with were characterized to inform future studies. An adverse outcome pathway (AOP) describing ecdysone receptor agonism leading to incomplete ecdysis associated mortality was developed according to the OECD guideline and evaluated for weight of evidence using the Evolved Bradford Hill Criteria. This review proposed the first invertebrate endocrine disruption AOP and may serve as a knowledge foundation for future environmental studies and AOP development. Development of high throughput toxicology (HTT) programs (e.g., ToxCast, Tox21) and potential a

Six Sigma in healthcare delivery.

PubMed

Liberatore, Matthew J

2013-01-01

The purpose of this paper is to conduct a comprehensive review and assessment of the extant Six Sigma healthcare literature, focusing on: application, process changes initiated and outcomes, including improvements in process metrics, cost and revenue. Data were obtained from an extensive literature search. Healthcare Six Sigma applications were categorized by functional area and department, key process metric, cost savings and revenue generation (if any) and other key implementation characteristics. Several inpatient care areas have seen most applications, including admission, discharge, medication administration, operating room (OR), cardiac and intensive care. About 42.1 percent of the applications have error rate as their driving metric, with the remainder focusing on process time (38 percent) and productivity (18.9 percent). While 67 percent had initial improvement in the key process metric, only 10 percent reported sustained improvement. Only 28 percent reported cost savings and 8 percent offered revenue enhancement. These results do not favorably assess Six Sigma's overall effectiveness and the value it offers healthcare. Results are based on reported applications. Future research can include directly surveying healthcare organizations to provide additional data for assessment. Future application should emphasize obtaining improvements that lead to significant and sustainable value. Healthcare staff can use the results to target promising areas. This article comprehensively assesses Six Sigma healthcare applications and impact.

Using a theory driven approach to develop and evaluate a complex mental health intervention: the friendship bench project in Zimbabwe.

PubMed

Chibanda, Dixon; Verhey, Ruth; Munetsi, Epiphany; Cowan, Frances M; Lund, Crick

2016-01-01

There is a paucity of data on how to deliver complex interventions that seek to reduce the treatment gap for mental disorders, particularly in sub-Saharan Africa. The need for well-documented protocols which clearly describe the development and the scale-up of programs and interventions is necessary if such interventions are to be replicated elsewhere. This article describes the use of a theory of change (ToC) model to develop a brief psychological intervention for common mental disorders and its' evaluation through a cluster randomized controlled trial in Zimbabwe. A total of eight ToC workshops were held with a range of stakeholders over a 6-month period with a focus on four key components of the program: formative work, piloting, evaluation and scale-up. A ToC map was developed as part of the process with defined causal pathways leading to the desired impact. Interventions, indicators, assumptions and rationale for each point along the causal pathway were considered. Political buy-in from stakeholders together with key resources, which included human, facility/infrastructure, communication and supervision were identified as critical needs using the ToC approach. Ten (10) key interventions with specific indicators, assumptions and rationale formed part of the final ToC map, which graphically illustrated the causal pathway leading to the development of a psychological intervention and the successful implementation of a cluster randomized controlled trial. ToC workshops can enhance stakeholder engagement through an iterative process leading to a shared vision that can improve outcomes of complex mental health interventions particularly where scaling up of the intervention is desired.

Scientifically-Based Reading Research: A Primer for Adult and Family Literacy Educators. Research to Practice.

ERIC Educational Resources Information Center

Padak, Nancy; Rasinski, Tim; Mraz, Maryann

The National Reading Panel (NRP) reviewed quantitative reading research focusing on grades K-3 to identify methods leading to reading success. The following areas were identified as key areas in the process of beginning to read: (1) phonemic awareness; (2) phonics; (3) fluency; (4) vocabulary; and (5) comprehension. The research findings were…

Warmer temperatures reduce net carbon uptake, but do not affect water use, in a mature southern Appalachian forest

Treesearch

A. Christopher Oishi; Chelcy F. Miniat; Kimberly A. Novick; Steven T. Brantley; James M. Vose; John T. Walker

2018-01-01

Increasing air temperature is expected to extend growing season length in temperate, broadleaf forests, leading to potential increases in evapotranspiration and net carbon uptake. However, other key processes affecting water and carbon cycles are also highly temperature-dependent. Warmer temperatures may result in higher ecosystem carbon loss through...

No Recovery of Memory When Cognitive Load Is Decreased

ERIC Educational Resources Information Center

Ricker, Timothy J.; Vergauwe, Evie; Hinrichs, Garrett A.; Blume, Christopher L.; Cowan, Nelson

2015-01-01

There is substantial debate in the field of short-term memory (STM) as to whether the process of active maintenance occurs through memory-trace reactivation or repair. A key difference between these 2 potential mechanisms is that a repair mechanism should lead to recovery of forgotten information. The ability to recover forgotten memories would be…

The Added Value of Conducting Learning Design Meeting to the Online Course Development Process

ERIC Educational Resources Information Center

Shaver, Denise

2017-01-01

Do you find it challenging to have discussions with instructors about designing online courses and best practices in teaching? This article will highlight key components to conducting effective Learning Design meetings. It outlines techniques used by this institution that inspires faculty to design coherent courses that lead to meaningful learning…

Supercritical processing as a route to high internal surface areas and permanent microporosity in metal-organic framework materials.

PubMed

Nelson, Andrew P; Farha, Omar K; Mulfort, Karen L; Hupp, Joseph T

2009-01-21

Careful processing of four representative metal-organic framework (MOF) materials with liquid and supercritical carbon dioxide (ScD) leads to substantial, or in some cases spectacular (up to 1200%), increases in gas-accessible surface area. Maximization of surface area is key to the optimization of MOFs for many potential applications. Preliminary evidence points to inhibition of mesopore collapse, and therefore micropore accessibility, as the basis for the extraordinarily efficacious outcome of ScD-based activation.

NASA's Solar Dynamics Observatory (SDO): A Systems Approach to a Complex Mission

NASA Technical Reports Server (NTRS)

Ruffa, John A.; Ward, David K.; Bartusek, LIsa M.; Bay, Michael; Gonzales, Peter J.; Pesnell, William D.

2012-01-01

The Solar Dynamics Observatory (SDO) includes three advanced instruments, massive science data volume, stringent science data completeness requirements, and a custom ground station to meet mission demands. The strict instrument science requirements imposed a number of challenging drivers on the overall mission system design, leading the SDO team to adopt an integrated systems engineering presence across all aspects of the mission to ensure that mission science requirements would be met. Key strategies were devised to address these system level drivers and mitigate identified threats to mission success. The global systems engineering team approach ensured that key drivers and risk areas were rigorously addressed through all phases of the mission, leading to the successful SDO launch and on-orbit operation. Since launch, SDO's on-orbit performance has met all mission science requirements and enabled groundbreaking science observations, expanding our understanding of the Sun and its dynamic processes.

NASA's Solar Dynamics Observatory (SDO): A Systems Approach to a Complex Mission

NASA Technical Reports Server (NTRS)

Ruffa, John A.; Ward, David K.; Bartusek, Lisa M.; Bay, Michael; Gonzales, Peter J.; Pesnell, William D.

2012-01-01

The Solar Dynamics Observatory (SDO) includes three advanced instruments, massive science data volume, stringent science data completeness requirements, and a custom ground station to meet mission demands. The strict instrument science requirements imposed a number of challenging drivers on the overall mission system design, leading the SDO team to adopt an integrated systems engineering presence across all aspects of the mission to ensure that mission science requirements would be met. Key strategies were devised to address these system level drivers and mitigate identified threats to mission success. The global systems engineering team approach ensured that key drivers and risk areas were rigorously addressed through all phases of the mission, leading to the successful SDO launch and on-orbit operation. Since launch, SDO s on-orbit performance has met all mission science requirements and enabled groundbreaking science observations, expanding our understanding of the Sun and its dynamic processes.

Traumatic Brain Injury as a Risk Factor for Alzheimer's Disease: Is Inflammatory Signaling a Key Player?

PubMed

Djordjevic, Jelena; Sabbir, Mohammad Golam; Albensi, Benedict C

2016-01-01

Traumatic brain injury (TBI) has become a significant medical and social concern within the last 30 years. TBI has acute devastating effects, and in many cases, seems to initiate long-term neurodegeneration. With advances in medical technology, many people are now surviving severe brain injuries and their long term consequences. Post trauma effects include communication problems, sensory deficits, emotional and behavioral problems, physical complications and pain, increased suicide risk, dementia, and an increased risk for chronic CNS diseases, such as Alzheimer's disease (AD). In this review, we provide an introduction to TBI and hypothesize how it may lead to neurodegenerative disease in general and AD in particular. In addition, we discuss the evidence that supports the hypothesis that TBI may lead to AD. In particular, we focus on inflammatory responses as key processes in TBI-induced secondary injury, with emphasis on nuclear factor kappa B (NF-κB) signaling.

Isostrychnine synthesis mediated by hypervalent iodine reagent.

PubMed

Jacquemot, Guillaume; Maertens, Gaëtan; Canesi, Sylvain

2015-05-18

Althought there are several reported synthetic routes to strychnine, one of the most widely recognized alkaloids, we report an unexplored route with an oxidative dearomatizing process mediated by hypervalent iodine as the key step. The new syntheses of isostrychnine and strychnine have been achieved from an readily available phenol in nine and ten steps. In addition to the key step, these syntheses involve an aza Michael-ether-enol tandem transformation, two heck type cyclizations, a reductive isomerization, and a double reductive amination in cascade leading to the alkaloid main core. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Degradation of lead-zirconate-titanate ceramics under different dc loads

NASA Astrophysics Data System (ADS)

Balke, Nina; Granzow, Torsten; Rödel, Jürgen

2009-05-01

During poling and application in actuators, piezoelectric ceramics like lead-zirconate-titanate are exposed to static or cyclically varying electric fields, often leading to pronounced changes in the electromechanical properties. These fatigue phenomena depend on time, peak electric load, and temperature. Although this process impacts the performance of many actuator materials, its physical understanding remains elusive. This paper proposes a set of key experiments to systematically investigate the changes in the ferroelectric hysteresis, field-dependent relative permittivity, and piezoelectric coefficient after submitting the material to dc loads of varying amplitude and duration. The observed effects are explained based on a model of domain stabilization due to charge accumulation at domain boundaries.

Design and implementation of an automated compound management system in support of lead optimization.

PubMed

Quintero, Catherine; Kariv, Ilona

2009-06-01

To meet the needs of the increasingly rapid and parallelized lead optimization process, a fully integrated local compound storage and liquid handling system was designed and implemented to automate the generation of assay-ready plates directly from newly submitted and cherry-picked compounds. A key feature of the system is the ability to create project- or assay-specific compound-handling methods, which provide flexibility for any combination of plate types, layouts, and plate bar-codes. Project-specific workflows can be created by linking methods for processing new and cherry-picked compounds and control additions to produce a complete compound set for both biological testing and local storage in one uninterrupted workflow. A flexible cherry-pick approach allows for multiple, user-defined strategies to select the most appropriate replicate of a compound for retesting. Examples of custom selection parameters include available volume, compound batch, and number of freeze/thaw cycles. This adaptable and integrated combination of software and hardware provides a basis for reducing cycle time, fully automating compound processing, and ultimately increasing the rate at which accurate, biologically relevant results can be produced for compounds of interest in the lead optimization process.

Developing Research Paper Writing Programs for EFL/ESL Undergraduate Students Using Process Genre Approach

ERIC Educational Resources Information Center

Tuyen, Kim Thanh; Bin Osman, Shuki; Dan, Thai Cong; Ahmad, Nor Shafrin Binti

2016-01-01

Research Paper Writing (RPW) plays a key role in completing all research work. Poor writing could lead to the postponement of publications. Therefore, it is necessary to develop a program of (RPW) to improve RPW ability for EFL/ESL writers, especially for undergraduate students in Higher Education (HE) institutions, which has caught less attention…

The Effect of Peer and Teacher Feedback on Changes in EFL Students' Writing Self-Efficacy

ERIC Educational Resources Information Center

Ruegg, Rachael

2018-01-01

Literature from education, educational psychology and second language acquisition has consistently found that self-efficacy is a key factor leading to increased language learning success. Students with more self-efficacy are claimed to have higher motivation and to expend more effort in the learning process. On the other hand, those with less…

High-severity fire: Evaluating its key drivers and mapping its probability across western US forests

Treesearch

Sean A. Parks; Lisa M. Holsinger; Matthew H. Panunto; W. Matt Jolly; Solomon Z. Dobrowski; Gregory K. Dillon

2018-01-01

Wildland fire is a critical process in forests of the western United States (US). Variation in fire behavior, which is heavily influenced by fuel loading, terrain, weather, and vegetation type, leads to heterogeneity in fire severity across landscapes. The relative influence of these factors in driving fire severity, however, is poorly understood. Here, we explore the...

Developmental programming: the concept, large animal models, and the key role of uteroplacental vascular development.

PubMed

Reynolds, L P; Borowicz, P P; Caton, J S; Vonnahme, K A; Luther, J S; Hammer, C J; Maddock Carlin, K R; Grazul-Bilska, A T; Redmer, D A

2010-04-01

Developmental programming refers to the programming of various bodily systems and processes by a stressor of the maternal system during pregnancy or during the neonatal period. Such stressors include nutritional stress, multiple pregnancy (i.e., increased numbers of fetuses in the gravid uterus), environmental stress (e.g., high environmental temperature, high altitude, prenatal steroid exposure), gynecological immaturity, and maternal or fetal genotype. Programming refers to impaired function of numerous bodily systems or processes, leading to poor growth, altered body composition, metabolic dysfunction, and poor productivity (e.g., poor growth, reproductive dysfunction) of the offspring throughout their lifespan and even across generations. A key component of developmental programming seems to be placental dysfunction, leading to altered fetal growth and development. We discuss various large animal models of developmental programming and how they have and will continue to contribute to our understanding of the mechanisms underlying altered placental function and developmental programming, and, further, how large animal models also will be critical to the identification and application of therapeutic strategies that will alleviate the negative consequences of developmental programming to improve offspring performance in livestock production and human medicine.

Hunting, Sale, and Consumption of Bushmeat Killed by Lead-Based Ammunition in Benin.

PubMed

Ahmadi, Shukrullah; Maman, Suzanne; Zoumenou, Roméo; Massougbodji, Achille; Cot, Michel; Glorennec, Philippe; Bodeau-Livinec, Florence

2018-06-01

Human consumption of animal meat killed by lead ammunition has been reported as a risk factor for elevated blood lead levels. However, little is known about how meat killed by lead ammunition is hunted, prepared, sold, and consumed. We explored the process from hunting to consumption within communities in Benin from the perspective of preventive measures. We conducted 38 semi-structured interviews with hunters ( n = 9) and sellers ( n = 8) of bushmeat and families ( n = 21) as consumers of bushmeat killed by lead ammunition. Data were transcribed, translated, and coded for analysis. We conducted content analysis to identify and describe key themes and processes from hunting to consumption. Many hunters ( n = 7/9) used lead-based ammunition. After the meat is hunted, market sellers often buy it directly from the hunters. Amongst the hunters and sellers, few ( n = 4/17) acknowledged removing the meat impacted by lead shot prior to sale. Many families ( n = 15/21) mentioned consumption of the hunted bushmeat. The meat is cooked before sharing with children. Many families ( n = 19/21) mentioned they look for the remains of the lead shot or remove the meat impacted by the shot. The finding suggests that hunting, sale, and consumption of bushmeat killed by lead ammunition are well-known practices in Allada, Benin. The bushmeat often hunted illegally with lead shot is sold in the markets and eventually consumed by families who attempt to clean the meat impacted by the lead shot before cooking it.

Developing a 360-degree, value-based performance review model.

PubMed

Allen, M L

1997-01-01

In healthcare, competency assessment continues to be a concern. Even the JCAHO stresses its importance, along with ongoing education for employees. Many healthcare facilities have developed specific technical-competency requirements to ensure quality of service. The leadership at the University of Kansas Hospital (UKMC) wanted to develop a value-driven performance review process that focused on values and interpersonal skills for its employees. The current set of values lacked focus on key quality, behavior and service values, and it was felt employees had not committed to these values. A task force, made up of representatives from key hospital groups, was formed to create a process that would emphasize and assess key leadership skills and values. This team discussed various review mechanisms, including Micheli's 360-degree review process, which uses various sources (supervisors, colleagues and peers, for example) to give input that will be broader and more comprehensive of employee performance. The team incorporated such key leadership expectations as visioning, empowering, modeling, communication, stewardship and self-development into the tool. Called Leadership Enhancement And Development (LEAD), the tool could be completed by a peer, supervisor, direct report or even used for self-review. Results were kept confidential through the use of numbers and letters yet could be incorporated into a spreadsheet for analysis. Starting with managers and supervisors, the process has been piloted in a few larger departments at UKMC where it has been well received. Over time, the process will be used for all employees where it will continue to stress the importance of hospital values and commitment to patients and other employees.

Community-based research in action: tales from the Ktunaxa community learning centres project.

PubMed

Stacy, Elizabeth; Wisener, Katherine; Liman, Yolanda; Beznosova, Olga; Lauscher, Helen Novak; Ho, Kendall; Jarvis-Selinger, Sandra

2014-01-01

Rural communities, particularly Aboriginal communities, often have limited access to health information, a situation that can have significant negative consequences. To address the lack of culturally and geographically relevant health information, a community-university partnership was formed to develop, implement, and evaluate Aboriginal Community Learning Centres (CLCs). The objective of this paper is to evaluate the community-based research process used in the development of the CLCs. It focuses on the process of building relationships among partners and the CLC's value and sustainability. Semistructured interviews were conducted with key stakeholders, including principal investigators, community research leads, and supervisors. The interview transcripts were analyzed using an open-coding process to identify themes. Key challenges included enacting shared project governance, negotiating different working styles, and hiring practices based on commitment to project objectives rather than skill set. Technological access provided by the CLCs increased capacity for learning and collective community initiatives, as well as building community leads' skills, knowledge, and self-efficacy. An important lesson was to meet all partners "where they are" in building trusting relationships and adapting research methods to fit the project's context and strengths. Successful results were dependent upon persistence and patience in working through differences, and breaking the project into achievable goals, which collectively contributed to trust and capacity building. The process of building these partnerships resulted in increased capacity of communities to facilitate learning and change initiatives, and the capacity of the university to engage in successful research partnerships with Aboriginal communities in the future.

Secret information reconciliation based on punctured low-density parity-check codes for continuous-variable quantum key distribution

NASA Astrophysics Data System (ADS)

Jiang, Xue-Qin; Huang, Peng; Huang, Duan; Lin, Dakai; Zeng, Guihua

2017-02-01

Achieving information theoretic security with practical complexity is of great interest to continuous-variable quantum key distribution in the postprocessing procedure. In this paper, we propose a reconciliation scheme based on the punctured low-density parity-check (LDPC) codes. Compared to the well-known multidimensional reconciliation scheme, the present scheme has lower time complexity. Especially when the chosen punctured LDPC code achieves the Shannon capacity, the proposed reconciliation scheme can remove the information that has been leaked to an eavesdropper in the quantum transmission phase. Therefore, there is no information leaked to the eavesdropper after the reconciliation stage. This indicates that the privacy amplification algorithm of the postprocessing procedure is no more needed after the reconciliation process. These features lead to a higher secret key rate, optimal performance, and availability for the involved quantum key distribution scheme.

Dying scenarios improve recall as much as survival scenarios.

PubMed

Burns, Daniel J; Hart, Joshua; Kramer, Melanie E

2014-01-01

Merely contemplating one's death improves retention for entirely unrelated material learned subsequently. This "dying to remember" effect seems conceptually related to the survival processing effect, whereby processing items for their relevance to being stranded in the grasslands leads to recall superior to that of other deep processing control conditions. The present experiments directly compared survival processing scenarios with "death processing" scenarios. Results showed that when the survival and dying scenarios are closely matched on key dimensions, and possible congruency effects are controlled, the dying and survival scenarios produced equivalently high recall levels. We conclude that the available evidence (cf. Bell, Roer, & Buchner, 2013; Klein, 2012), while not definitive, is consistent with the possibility of overlapping mechanisms.

Historical perspective on lead biokinetic models.

PubMed Central

Rabinowitz, M

1998-01-01

A historical review of the development of biokinetic model of lead is presented. Biokinetics is interpreted narrowly to mean only physiologic processes happening within the body. Proceeding chronologically, for each epoch, the measurements of lead in the body are presented along with mathematical models in an attempt to trace the convergence of observations from two disparate fields--occupational medicine and radiologic health--into some unified models. Kehoe's early balance studies and the use of radioactive lead tracers are presented. The 1960s saw the joint application of radioactive lead techniques and simple compartmental kinetic models used to establish the exchange rates and residence times of lead in body pools. The applications of stable isotopes to questions of the magnitudes of respired and ingested inputs required the development of a simple three-pool model. During the 1980s more elaborate models were developed. One of their key goals was the establishment of the dose-response relationship between exposure to lead and biologic precursors of adverse health effects. PMID:9860905

[Molecular mechanisms in sex determination: from gene regulation to pathology].

PubMed

Ravel, C; Chantot-Bastaraud, S; Siffroi, J-P

2004-01-01

Testis determination is the complex process by which the bipotential gonad becomes a normal testis during embryo development. As a consequence, this process leads to sexual differentiation corresponding to the masculinization of both genital track and external genitalia. The whole phenomenon is under genetic control and is particularly driven by the presence of the Y chromosome and by the SRY gene, which acts as the key initiator of the early steps of testis determination. However, many other autosomal genes, present in both males and females, are expressed during testis formation in a gene activation pathway, which is far to be totally elucidated. All these genes act in a dosage-sensitive manner by which quantitative gene abnormalities, due to chromosomal deletions, duplications or mosaicism, may lead to testis determination failure and sex reversal.

Preferential flow from pore to landscape scales

NASA Astrophysics Data System (ADS)

Koestel, J. K.; Jarvis, N.; Larsbo, M.

2017-12-01

In this presentation, we give a brief personal overview of some recent progress in quantifying preferential flow in the vadose zone, based on our own work and those of other researchers. One key challenge is to bridge the gap between the scales at which preferential flow occurs (i.e. pore to Darcy scales) and the scales of interest for management (i.e. fields, catchments, regions). We present results of recent studies that exemplify the potential of 3-D non-invasive imaging techniques to visualize and quantify flow processes at the pore scale. These studies should lead to a better understanding of how the topology of macropore networks control key state variables like matric potential and thus the strength of preferential flow under variable initial and boundary conditions. Extrapolation of this process knowledge to larger scales will remain difficult, since measurement technologies to quantify macropore networks at these larger scales are lacking. Recent work suggests that the application of key concepts from percolation theory could be useful in this context. Investigation of the larger Darcy-scale heterogeneities that generate preferential flow patterns at the soil profile, hillslope and field scales has been facilitated by hydro-geophysical measurement techniques that produce highly spatially and temporally resolved data. At larger regional and global scales, improved methods of data-mining and analyses of large datasets (machine learning) may help to parameterize models as well as lead to new insights into the relationships between soil susceptibility to preferential flow and site attributes (climate, land uses, soil types).

Childhood lead poisoning in a Somali refugee resettlement community in New Hampshire.

PubMed

Caron, Rosemary M; Tshabangu-Soko, Thandi; Finefrock, Krysten

2013-08-01

Despite the gradual decrease in childhood lead poisoning in the United States, the risk for lead poisoning among African refugee children who resettle in the United States remains elevated. Communication methods implemented by resettlement agencies in the public health system for preventing childhood lead poisoning in this at-risk population warrant further investigation. We utilized structured interviews with key stakeholders (resettlement agencies, social service agencies developed by African refugees and resettled Somali refugees) involved in the refugee resettlement process to (1) describe the agency's role in the refugee resettlement process; (2) examine communication methods utilized and barriers experienced by the public health system in reference to childhood lead poisoning; (3) describe the refugee population's perception of childhood lead poisoning; (4) examine general challenges experienced by the public health system and the refugee population during the resettlement process; and (5) describe stakeholders' recommendations to improve health communication efforts. Based on our findings, we propose that communities are important determinants in health-related problems for refugee populations. Each community has its own environment and public health system that interacts with each other to influence health risks and risk perceptions of its populations. We advocate that understanding a community's ecology and implementing a culture-centered approach is essential for the public health system to help educate and prevent communication inequalities and health disparities among an at-risk African refugee population. This action can reduce a population's resistance to communication and help build a community's capacity to address a persistent public health problem, such as childhood lead poisoning.

Oncogenomic disruptions in arsenic-induced carcinogenesis

PubMed Central

Ng, Kevin W.; Stewart, Greg L.; Dummer, Trevor J.B.; Lam, Wan L.; Martinez, Victor D

2017-01-01

Chronic exposure to arsenic affects more than 200 million people worldwide, and has been associated with many adverse health effects, including cancer in several organs. There is accumulating evidence that arsenic biotransformation, a step in the elimination of arsenic from the human body, can induce changes at a genetic and epigenetic level, leading to carcinogenesis. At the genetic level, arsenic interferes with key cellular processes such as DNA damage-repair and chromosomal structure, leading to genomic instability. At the epigenetic level, arsenic places a high demand on the cellular methyl pool, leading to global hypomethylation and hypermethylation of specific gene promoters. These arsenic-associated DNA alterations result in the deregulation of both oncogenic and tumour-suppressive genes. Furthermore, recent reports have implicated aberrant expression of non-coding RNAs and the consequential disruption of signaling pathways in the context of arsenic-induced carcinogenesis. This article provides an overview of the oncogenomic anomalies associated with arsenic exposure and conveys the importance of non-coding RNAs in the arsenic-induced carcinogenic process. PMID:28179585

Alternative splicing regulation in tumor necrosis factor-mediated inflammation.

PubMed

López-Urrutia, Eduardo; Campos-Parra, Alma; Herrera, Luis Alonso; Pérez-Plasencia, Carlos

2017-11-01

It is generally accepted that alternative splicing has an effect on disease when it leads to conspicuous changes in relevant proteins, but that the combinatorial effect of several small modifications can have marked outcomes as well. Inflammation is a complex process involving numerous signaling pathways, among which the tumor necrosis factor (TNF) pathway is one of the most studied. Signaling pathways are commonly represented as intricate cascades of molecular interactions that eventually lead to the activation of one or several genes. Alternative splicing is a common means of controlling protein expression in time and space; therefore, it can modulate the outcome of signaling pathways through small changes in their elements. Notably, the overall process is tightly regulated, which is easily overlooked when analyzing the pathway as a whole. The present review summarizes recent studies of the alternative splicing of key players of the TNF pathway leading to inflammation, and hypothesizes on the cumulative results of those modifications and the impact on cancer development.

Alternative splicing regulation in tumor necrosis factor-mediated inflammation

PubMed Central

López-Urrutia, Eduardo; Campos-Parra, Alma; Herrera, Luis Alonso; Pérez-Plasencia, Carlos

2017-01-01

It is generally accepted that alternative splicing has an effect on disease when it leads to conspicuous changes in relevant proteins, but that the combinatorial effect of several small modifications can have marked outcomes as well. Inflammation is a complex process involving numerous signaling pathways, among which the tumor necrosis factor (TNF) pathway is one of the most studied. Signaling pathways are commonly represented as intricate cascades of molecular interactions that eventually lead to the activation of one or several genes. Alternative splicing is a common means of controlling protein expression in time and space; therefore, it can modulate the outcome of signaling pathways through small changes in their elements. Notably, the overall process is tightly regulated, which is easily overlooked when analyzing the pathway as a whole. The present review summarizes recent studies of the alternative splicing of key players of the TNF pathway leading to inflammation, and hypothesizes on the cumulative results of those modifications and the impact on cancer development. PMID:29113151

Signature and Mechanism of the Epithelial-to-Mesenchymal Transition

DTIC Science & Technology

2010-05-01

breast cancer . This study seeks to identify genes commonly regulated in the EMT, and identify key regulators of the process. The transcription factor...8 Introduction Breast cancer is one of the leading causes of death in women of the developed world. Mortality...results not from the primary tumor, but from complications arising from metastases that have spread to vital organs. The study of breast cancer

The Science of Climate Change

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

Makundi, Willy R.

2002-09-20

What constitutes 'dangerous anthropogenic interference' is a value judgment arrived at through a socio-political process, taking issues like equity and sustainability into account. Science provides key information needed to arrive at an informed judgment. However, that judgment is primarily a political one, and not a purely scientific decision. Such judgments are based on risk assessment, and lead to risk management choices by decision makers, about actions and policies.

Uncovering Common Sleep Disorders and Their Impacts on Occupational Performance.

PubMed

Judd, Sylvia R

2017-05-01

Sleep is an active process; the body undergoes restoration and regeneration. Adequate sleep is essential to health and cognitive function. Sleep is critical for cell repair, a healthy immune system, and hormonal regulation, and aids in the process of learning, memory, and emotion. Inadequate sleep can lead to multiple chronic health and mental conditions over time. The occupational health nurse can be instrumental in screening for two of the most common sleep disorders, insomnia and obstructive sleep apnea, by asking workers key questions and using simple screening tools.

Optimization of hybrid laser arc welding of 42CrMo steel to suppress pore formation

NASA Astrophysics Data System (ADS)

Zhang, Yan; Chen, Genyu; Mao, Shuai; Zhou, Cong; Chen, Fei

2017-06-01

The hybrid laser arc welding (HLAW) of 42CrMo quenched and tempered steel was conducted. The effect of the processing parameters, such as the relative positions of the laser and the arc, the shielding gas flow rate, the defocusing distance, the laser power, the wire feed rate and the welding speed, on the pore formation was analyzed, the morphological characteristics of the pores were analyzed using scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). The results showed that the majority of the pores were invasive. The pores formed at the leading a laser (LA) welding process were fewer than those at the leading a arc (AL) welding process. Increasing the shielding gas flow rate could also facilitate the reduction of pores. The laser power and the welding speed were two key process parameters to reduce the pores. The flow of the molten pool, the weld cooling rate and the pore escaping rate as a result of different parameters could all affect pore formation. An ideal pore-free weld was obtained for the optimal welding process parameters.

Why Do Anxious Children Become Depressed Teenagers?: The Role of Social Evaluative Threat and Reward Processing

PubMed Central

Silk, Jennifer S.; Davis, Stephanie; McMakin, Dana L.; Dahl, Ronald E.; Forbes, Erika E.

2012-01-01

Background Depression is a leading cause of worldwide disability. Adolescence represents a key developmental window in which rates of this disorder increase markedly. Children with an anxiety disorder show a particular risk of developing depression during adolescence. Method We present and review evidence for a developmental model that considers the intersection of two vulnerabilities relevant to the trajectory from anxiety to depression: difficulties in response to potential social evaluation and changes in reward processing at puberty. Results Evidence suggests that these vulnerabilities (a) have been associated with depression, (b) are likely to be problematic in many but not all anxious youth, and (c) may be exacerbated by maturational processes that occur around pubertal development in ways that can create a negative spiral into a depressive disorder. Conclusions We discuss the possibility that early intervention strategies targeting key aspects of these vulnerabilities could alter the trajectory away from depression for many anxious youth. PMID:22340187

A comparison of the effect of lead nitrate on rat liver chromatin, DNA and histone proteins in solution.

PubMed

Rabbani-Chadegani, Azra; Abdosamadi, Sayeh; Fani, Nesa; Mohammadian, Shayesteh

2009-06-01

Although lead is widely recognized as a toxic substance in the environment and directly damage DNA, no studies are available on lead interaction with chromatin and histone proteins. In this work, we have examined the effect of lead nitrate on EDTA-soluble chromatin (SE chromatin), DNA and histones in solution using absorption and fluorescence spectroscopy, thermal denaturation and gel electrophoresis techniques. The results demonstrate that lead nitrate binds with higher affinity to chromatin than to DNA and produces an insoluble complex as monitored at 400 nm. Binding of lead to DNA decreases its Tm, increases its fluorescence intensity and exhibits hypochromicity at 210 nm which reveal that both DNA bases and the backbone participate in the lead-DNA interaction. Lead also binds strongly to histone proteins in the absence of DNA. The results suggest that although lead destabilizes DNA structure, in the chromatin, the binding of lead introduces some sort of compaction and aggregation, and the histone proteins play a key role in this aspect. This chromatin condensation, upon lead exposure, in turn may decrease fidelity of DNA, and inhibits DNA and RNA synthesis, the process that introduces lead toxicity at the chromatin level.

A role for clock genes in sleep homeostasis.

PubMed

Franken, Paul

2013-10-01

The timing and quality of both sleep and wakefulness are thought to be regulated by the interaction of two processes. One of these two processes keeps track of the prior sleep-wake history and controls the homeostatic need for sleep while the other sets the time-of-day that sleep preferably occurs. The molecular pathways underlying the latter, circadian process have been studied in detail and their key role in physiological time-keeping has been well established. Analyses of sleep in mice and flies lacking core circadian clock gene proteins have demonstrated, however, that besides disrupting circadian rhythms, also sleep homeostatic processes were affected. Subsequent studies revealed that sleep loss alters both the mRNA levels and the specific DNA-binding of the key circadian transcriptional regulators to their target sequences in the mouse brain. The fact that sleep loss impinges on the very core of the molecular circadian circuitry might explain why both inadequate sleep and disrupted circadian rhythms can similarly lead to metabolic pathology. The evidence for a role for clock genes in sleep homeostasis will be reviewed here. Copyright © 2013 Elsevier Ltd. All rights reserved.

Investigating on the fermentation behavior of six lactic acid bacteria strains in barley malt wort reveals limitation in key amino acids and buffer capacity.

PubMed

Nsogning, Sorelle Dongmo; Fischer, Susann; Becker, Thomas

2018-08-01

Understanding lactic acid bacteria (LAB) fermentation behavior in malt wort is a milestone towards flavor improvement of lactic acid fermented malt beverages. Therefore, this study aims to outline deficiencies that may exist in malt wort fermentation. First, based on six LAB strains, cell viability and vitality were evaluated. Second, sugars, organic acids, amino acids, pH value and buffering capacity (BC) were monitored. Finally, the implication of key amino acids, fructose and wort BC on LAB growth was determined. Short growth phase coupled with prompt cell death and a decrease in metabolic activity was observed. Low wort BC caused rapid pH drop with lactic acid accumulation, which conversely increased the BC leading to less pH change at late-stage fermentation. Lactic acid content (≤3.9 g/L) was higher than the reported inhibitory concentration (1.8 g/L). Furthermore, sugars were still available but fructose and key amino acids lysine, arginine and glutamic acid were considerably exhausted (≤98%). Wort supplementations improved cell growth and viability leading to conclude that key amino acid depletion coupled with low BC limits LAB growth in malt wort. Then, a further increase in organic acid reduces LAB viability. This knowledge opens doors for LAB fermentation process optimization in malt wort. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Role of Nrf2-Mediated Pathway in Cardiac Remodeling and Heart Failure

PubMed Central

Sun, Wanqing; Zhang, Zhiguo; Zheng, Yang

2014-01-01

Heart failure (HF) is frequently the consequence of sustained, abnormal neurohormonal, and mechanical stress and remains a leading cause of death worldwide. The key pathophysiological process leading to HF is cardiac remodeling, a term referring to maladaptation to cardiac stress at the molecular, cellular, tissue, and organ levels. HF and many of the conditions that predispose one to HF are associated with oxidative stress. Increased generation of reactive oxygen species (ROS) in the heart can directly lead to increased necrosis and apoptosis of cardiomyocytes which subsequently induce cardiac remodeling and dysfunction. Nuclear factor-erythroid-2- (NF-E2-) related factor 2 (Nrf2) is a transcription factor that controls the basal and inducible expression of a battery of antioxidant genes and other cytoprotective phase II detoxifying enzymes that are ubiquitously expressed in the cardiovascular system. Emerging evidence has revealed that Nrf2 and its target genes are critical regulators of cardiovascular homeostasis via the suppression of oxidative stress, which is the key player in the development and progression of HF. The purpose of this review is to summarize evidence that activation of Nrf2 enhances endogenous antioxidant defenses and counteracts oxidative stress-associated cardiac remodeling and HF. PMID:25101151

Two symmetry-breaking mechanisms for the development of orientation selectivity in a neural system

NASA Astrophysics Data System (ADS)

Cho, Myoung Won; Chun, Min Young

2015-11-01

Orientation selectivity is a remarkable feature of the neurons located in the primary visual cortex. Provided that the visual neurons acquire orientation selectivity through activity-dependent Hebbian learning, the development process could be understood as a kind of symmetry-breaking phenomenon in the view of physics. This paper examines the key mechanisms of the orientation selectivity development process. Be found that at least two different mechanisms, which lead to the development of orientation selectivity by breaking the radial symmetry in receptive fields. The first is a simultaneous symmetry-breaking mechanism occurring based on the competition between neighboring neurons, and the second is a spontaneous one occurring based on the nonlinearity in interactions. Only the second mechanism leads to the formation of a columnar pattern whose characteristics is in accord with those observed in an animal experiment.

Analytical treatment of particle motion in circularly polarized slab-mode wave fields

NASA Astrophysics Data System (ADS)

Schreiner, Cedric; Vainio, Rami; Spanier, Felix

2018-02-01

Wave-particle interaction is a key process in particle diffusion in collisionless plasmas. We look into the interaction of single plasma waves with individual particles and discuss under which circumstances this is a chaotic process, leading to diffusion. We derive the equations of motion for a particle in the fields of a magnetostatic, circularly polarized, monochromatic wave and show that no chaotic particle motion can arise under such circumstances. A novel and exact analytic solution for the equations is presented. Additional plasma waves lead to a breakdown of the analytic solution and chaotic particle trajectories become possible. We demonstrate this effect by considering a linearly polarized, monochromatic wave, which can be seen as the superposition of two circularly polarized waves. Test particle simulations are provided to illustrate and expand our analytical considerations.

Key Trends in Institutional Changes Under Sustainable Development

NASA Astrophysics Data System (ADS)

Karpova, Olga; Pevneva, Inna; Dymova, Irina; Kostina, Tatiana; Li, Sergey

2017-11-01

The article is devoted to the consideration of the essential problems of accounting institution formation under the sustainable development of the country and the region. The research is based on the key research the field of the intuition economics and considers the trends of institutional changes including incremental, evolutionary and revolutionary. Approaches to the analysis of institutions are presented as well. The first approach states that economic efficiency is guaranteed by newly emerging institutions. The second approach involves certain internal and external incentives for changing institutions. Whereas the third approach insists on considering institutional changes to be the relation of individual economic entities to institutional innovations in terms of the net benefit from their implementation. The conclusion draws the leading role of the state in the process of the emergence and further development of newly created institutions focusing on the fact that not every change leads to greater efficiency. Thus it is crucial to consider the previous background of institutions development at implementing changes in accounting and control.

Understanding blue-light photoreceptors

NASA Astrophysics Data System (ADS)

Crane, Brian

Blue-light sensing proteins coordinate many biological processes that include phototropism, photomorphism, stress responses, virulence and the entrainment of circadian clocks. Three major types of blue-light sensors all bind flavin nucleotides as chromophores, but the photochemistry employed and conformational responses invoked differ considerably among the classes. Nevertheless, photoinduced electron transfer reactions play a key role in many mechanisms. How such reactivity leads to conformational signaling will be discussed for both cryptochromes (CRYs) and light- oxygen- voltage (LOV) domains. In CRYs, blue-light mediated flavin reduction promotes proton transfer within the active center that then leads to displacement of a key signaling element. For LOV proteins, blue light causes formation of a covalent cysteinyl-flavin adduct, which rearranges hydrogen bonding and restructures the N-terminal region of the protein. Interestingly, a new class of LOV-like sensor does not undergo adduct formation and instead can operate by flavin photoreduction, like CRY. Conserved aspects of reactivity in these proteins provide lessons for the design of new photosensors, which may find use as tools in optogenetics Supported by NIH GM079679.

Biomarkers and patient selection for PI3K/Akt/mTOR targeted therapies: current status and future directions.

PubMed

Bartlett, John M S

2010-11-01

The phosphatidylinositol 3-kinase (PI3K)/Akt/ mammalian target of rapamycin (mTOR) pathway regulates a broad spectrum of physiologic and pathologic processes. In breast cancer mutation, amplification, deletion, methylation, and posttranslational modifications lead to significant dysregulation of this pathway leading to more aggressive and potentially drug-resistant disease. Multiple novel agents, targeting different nodes within the pathway are currently under development by both commercial and academic partners. The key to the successful validation of these markers is selection of the appropriate patient groups using biomarkers. This article reviews current progress in this area, highlighting the key molecular alterations described in genes within the PI3K/Akt/mTOR pathway that may have an effect on response to current and future therapeutic interventions. Herein, gaps in current knowledge are highlighted and suggestions for future research directions given that may facilitate biomarker development in partnership with current drug development.

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.

Neutrality and Robustness in Evo-Devo: Emergence of Lateral Inhibition

PubMed Central

Munteanu, Andreea; Solé, Ricard V.

2008-01-01

Embryonic development is defined by the hierarchical dynamical process that translates genetic information (genotype) into a spatial gene expression pattern (phenotype) providing the positional information for the correct unfolding of the organism. The nature and evolutionary implications of genotype–phenotype mapping still remain key topics in evolutionary developmental biology (evo-devo). We have explored here issues of neutrality, robustness, and diversity in evo-devo by means of a simple model of gene regulatory networks. The small size of the system allowed an exhaustive analysis of the entire fitness landscape and the extent of its neutrality. This analysis shows that evolution leads to a class of robust genetic networks with an expression pattern characteristic of lateral inhibition. This class is a repertoire of distinct implementations of this key developmental process, the diversity of which provides valuable clues about its underlying causal principles. PMID:19023404

Scientific governance and the process for exposure scenario development in REACH.

PubMed

Money, Chris D; Van Hemmen, Joop J; Vermeire, Theo G

2007-12-01

The primary process established by the European Commission to address the science needed to define key REACH concepts and to help rationally implement REACH's ambitions is enshrined in a series of activities known as the REACH Implementation Projects (RIPs). These are projects that aim to define the methodology that could be used, and present the basis for guidance on the actual principles and procedures that may be (are proposed to be) followed in the development of the required documentation that ensures the safe use of chemicals. In order to develop soundly based and equitable regulation, it is necessary that science governance using established and accepted scientific principles must take a leading role. The extent to which such governance is embraced will be determined by many factors, but notably the process adopted to enable scientific discussion to take place. This article addresses the issues of science as they have impacted on the exemplification of the Exposure Scenario concept under REACH. The current RIP activities have created a non-adversarial process in which the key stakeholders are able to discuss the key REACH challenges. But the RIP activities will be finalised before REACH comes into force. A suitable mechanism should perhaps now be identified to ensure that this positive spirit of scientific discussion and collaboration can continue to benefit REACH and those that it serves well into the future.

Vaccination policies and programs: the federal government's role in making the system work.

PubMed

Schwartz, B; Orenstein, W A

2001-12-01

Government agencies play a key role, from preclinical development to postlicensure monitoring, in making vaccinations one of the leading public health interventions. Important steps in this process include development and testing of vaccine antigens, evaluation of clinical and manufacturing data leading to licensure, formulation of recommendations, vaccine purchase, defining strategies to improve coverage, compensation of those injured by vaccine adverse reactions, and monitoring vaccine impact and safety. Using examples of newly recommended vaccines, this article describes the infrastructure that underlies a safe and effective program and highlights some of the opportunities and threats likely to impact the system in coming years.

Nrf2-p62 autophagy pathway and its response to oxidative stress in hepatocellular carcinoma.

PubMed

Bartolini, Desirée; Dallaglio, Katiuscia; Torquato, Pierangelo; Piroddi, Marta; Galli, Francesco

2018-03-01

Deregulation of autophagy is proposed to play a key pathogenic role in hepatocellular carcinoma (HCC), the most common primary malignancy of the liver and the third leading cause of cancer death. Autophagy is an evolutionarily conserved catabolic process activated to degrade and recycle cell's components. Under stress conditions, such as oxidative stress and nutrient deprivation, autophagy is an essential survival pathway that operates in harmony with other stress response pathways. These include the redox-sensitive transcription complex Nrf2-Keap1 that controls groups of genes with roles in detoxification and antioxidant processes, intermediary metabolism, and cell cycle regulation. Recently, a functional association between a dysfunctional autophagy and Nrf2 pathway activation has been identified in HCC. This appears to occur through the physical interaction of the autophagy adaptor p62 with the Nrf2 inhibitor Keap1, thus leading to increased stabilization and transcriptional activity of Nrf2, a key event in reprogramming metabolic and stress response pathways of proliferating hepatocarcinoma cells. These emerging molecular mechanisms and the therapeutic perspective of targeting Nrf2-p62 interaction in HCC are discussed in this paper along with the prognostic value of autophagy in this type of cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

Use of dietary phytochemicals to target inflammation, fibrosis, proliferation, and angiogenesis in uterine tissues: Promising options for prevention and treatment of uterine fibroids?

PubMed Central

Islam, Md Soriful; Akhtar, Most Mauluda; Ciavattini, Andrea; Giannubilo, Stefano Raffaele; Protic, Olga; Janjusevic, Milijana; Procopio, Antonio Domenico; Segars, James H.; Castellucci, Mario; Ciarmela, Pasquapina

2014-01-01

Uterine leiomyomas (fibroids, myomas) are the most common benign tumors of female reproductive tract. They are highly prevalent, with 70–80% of women burdened by the end of their reproductive years. Fibroids are a leading cause of pelvic pain, abnormal vaginal bleeding, pressure on the bladder, miscarriage, and infertility. They are the leading indication for hysterectomy, and costs exceed 6 billion dollars annually in the United States. Unfortunately, no long-term medical treatments are available. Dysregulation of inflammatory processes are thought to be involved in the initiation of leiomyoma and extracellular matrix deposition, cell proliferation, and angiogenesis are the key cellular events implicated in leiomyoma growth. In modern pharmaceutical industries, dietary phytochemicals are used as source of new potential drugs for many kinds of tumors. Dietary phytochemicals may exert therapeutic effects by interfering with key cellular events of the tumorigenesis process. At present, a negligible number of phytochemicals have been tested as therapeutic agents against fibroids. In this context, our aim was to introduce some of the potential dietary phytochemicals that have shown anti-inflammatory, antiproliferative, antifibrotic, and antiangiogenic activities in different biological systems. This review could be useful to stimulate the evaluation of these phytochemicals as possible therapies for uterine fibroids. PMID:24976593

DNA reactivity as a mode of action and its relevance to cancer risk assessment.

PubMed

Preston, R Julian

2013-02-01

The ability of a chemical to induce mutations has long been a driver in the cancer risk assessment process. The default strategy has been that mutagenic chemicals demonstrate linear cancer dose responses, especially at low exposure levels. In the absence of additional confounding information, this is a reasonable approach, because risk assessment is appropriately considered as being protective of human health. The concept of mode of action has allowed for an opportunity to move off this default position; mutagenicity is now not considered as the driver but rather the mode of action is. In a more precise way, it is the set of key events that define a mode of action that is fundamental in defining the shape of a cancer dose response. A key event is an informative bioindicator of the cancer response and as such should be predictive of the tumor response, at least in a qualitative way. A clear example of the use of key events in cancer risk assessment is for DNA reactive chemicals. A series of such key events is initiated by the production of DNA damage in target cells from direct interaction of the chemical with DNA leading to the production of mutations by misreplication that results in enhanced cell replication. This enhanced cell replication eventually leads to the development of preneoplastic cells and ultimately overt neoplasms. The response of each of these key events to dose of the chemical can inform the cancer dose-response curve shape. Thus, the dose-response curve for any DNA-reactive chemical can be predicted from knowledge of its mode of action and the behavior of the induced key events.

Roles, processes, and outcomes of interprofessional shared decision-making in a neonatal intensive care unit: A qualitative study.

PubMed

Dunn, Sandra I; Cragg, Betty; Graham, Ian D; Medves, Jennifer; Gaboury, Isabelle

2018-05-01

Shared decision-making provides an opportunity for the knowledge and skills of care providers to synergistically influence patient care. Little is known about interprofessional shared decision-making processes in critical care settings. The aim of this study was to explore interprofessional team members' perspectives about the nature of interprofessional shared decision-making in a neonatal intensive care unit (NICU) and to determine if there are any differences in perspectives across professional groups. An exploratory qualitative approach was used consisting of semi-structured interviews with 22 members of an interprofessional team working in a tertiary care NICU in Canada. Participants identified four key roles involved in interprofessional shared decision-making: leader, clinical experts, parents, and synthesizer. Participants perceived that interprofessional shared decision-making happens through collaboration, sharing, and weighing the options, the evidence and the credibility of opinions put forward. The process of interprofessional shared decision-making leads to a well-informed decision and participants feeling valued. Findings from this study identified key concepts of interprofessional shared decision-making, increased awareness of differing professional perspectives about this process of shared decision-making, and clarified understanding of the different roles involved in the decision-making process in an NICU.

Managing distributed software development in the Virtual Astronomical Observatory

NASA Astrophysics Data System (ADS)

Evans, Janet D.; Plante, Raymond L.; Boneventura, Nina; Busko, Ivo; Cresitello-Dittmar, Mark; D'Abrusco, Raffaele; Doe, Stephen; Ebert, Rick; Laurino, Omar; Pevunova, Olga; Refsdal, Brian; Thomas, Brian

2012-09-01

The U.S. Virtual Astronomical Observatory (VAO) is a product-driven organization that provides new scientific research capabilities to the astronomical community. Software development for the VAO follows a lightweight framework that guides development of science applications and infrastructure. Challenges to be overcome include distributed development teams, part-time efforts, and highly constrained schedules. We describe the process we followed to conquer these challenges while developing Iris, the VAO application for analysis of 1-D astronomical spectral energy distributions (SEDs). Iris was successfully built and released in less than a year with a team distributed across four institutions. The project followed existing International Virtual Observatory Alliance inter-operability standards for spectral data and contributed a SED library as a by-product of the project. We emphasize lessons learned that will be folded into future development efforts. In our experience, a well-defined process that provides guidelines to ensure the project is cohesive and stays on track is key to success. Internal product deliveries with a planned test and feedback loop are critical. Release candidates are measured against use cases established early in the process, and provide the opportunity to assess priorities and make course corrections during development. Also key is the participation of a stakeholder such as a lead scientist who manages the technical questions, advises on priorities, and is actively involved as a lead tester. Finally, frequent scheduled communications (for example a bi-weekly tele-conference) assure issues are resolved quickly and the team is working toward a common vision.

The UK Earth System Model project

NASA Astrophysics Data System (ADS)

Tang, Yongming

2016-04-01

In this talk we will describe the development and current status of the UK Earth System Model (UKESM). This project is a NERC/Met Office collaboration and has two objectives; to develop and apply a world-leading Earth System Model, and to grow a community of UK Earth System Model scientists. We are building numerical models that include all the key components of the global climate system, and contain the important process interactions between global biogeochemistry, atmospheric chemistry and the physical climate system. UKESM will be used to make key CMIP6 simulations as well as long-time (e.g. millennium) simulations, large ensemble experiments and investigating a range of future carbon emission scenarios.

The Role of Oxidative Stress in Parkinson’s Disease

PubMed Central

Dias, Vera; Junn, Eunsung; Mouradian, M. Maral

2014-01-01

Oxidative stress plays an important role in the degeneration of dopaminergic neurons in Parkinson’s disease (PD). Disruptions in the physiologic maintenance of the redox potential in neurons interfere with several biological processes, ultimately leading to cell death. Evidence has been developed for oxidative and nitrative damage to key cellular components in the PD substantia nigra. A number of sources and mechanisms for the generation of reactive oxygen species (ROS) are recognized including the metabolism of dopamine itself, mitochondrial dysfunction, iron, neuroinflammatory cells, calcium, and aging. PD causing gene products including DJ-1, PINK1, parkin, alpha-synuclein and LRRK2 also impact in complex ways mitochondrial function leading to exacerbation of ROS generation and susceptibility to oxidative stress. Additionally, cellular homeostatic processes including the ubiquitin-proteasome system and mitophagy are impacted by oxidative stress. It is apparent that the interplay between these various mechanisms contributes to neurodegeneration in PD as a feed forward scenario where primary insults lead to oxidative stress, which damages key cellular pathogenetic proteins that in turn cause more ROS production. Animal models of PD have yielded some insights into the molecular pathways of neuronal degeneration and highlighted previously unknown mechanisms by which oxidative stress contributes to PD. However, therapeutic attempts to target the general state of oxidative stress in clinical trials have failed to demonstrate an impact on disease progression. Recent knowledge gained about the specific mechanisms related to PD gene products that modulate ROS production and the response of neurons to stress may provide targeted new approaches towards neuroprotection. PMID:24252804

Antisense targeting of 3' end elements involved in DUX4 mRNA processing is an efficient therapeutic strategy for facioscapulohumeral dystrophy: a new gene-silencing approach.

PubMed

Marsollier, Anne-Charlotte; Ciszewski, Lukasz; Mariot, Virginie; Popplewell, Linda; Voit, Thomas; Dickson, George; Dumonceaux, Julie

2016-04-15

Defects in mRNA 3'end formation have been described to alter transcription termination, transport of the mRNA from the nucleus to the cytoplasm, stability of the mRNA and translation efficiency. Therefore, inhibition of polyadenylation may lead to gene silencing. Here, we choose facioscapulohumeral dystrophy (FSHD) as a model to determine whether or not targeting key 3' end elements involved in mRNA processing using antisense oligonucleotide drugs can be used as a strategy for gene silencing within a potentially therapeutic context. FSHD is a gain-of-function disease characterized by the aberrant expression of the Double homeobox 4 (DUX4) transcription factor leading to altered pathogenic deregulation of multiple genes in muscles. Here, we demonstrate that targeting either the mRNA polyadenylation signal and/or cleavage site is an efficient strategy to down-regulate DUX4 expression and to decrease the abnormally high-pathological expression of genes downstream of DUX4. We conclude that targeting key functional 3' end elements involved in pre-mRNA to mRNA maturation with antisense drugs can lead to efficient gene silencing and is thus a potentially effective therapeutic strategy for at least FSHD. Moreover, polyadenylation is a crucial step in the maturation of almost all eukaryotic mRNAs, and thus all mRNAs are virtually eligible for this antisense-mediated knockdown strategy. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The Role of HCG in Implantation: A Mini-Review of Molecular and Clinical Evidence

PubMed Central

Makrigiannakis, Antonis; Vrekoussis, Thomas; Zoumakis, Emmanouel; Kalantaridou, Sophia N.; Jeschke, Udo

2017-01-01

Embryo implantation is a complex process involving continuous molecular cross-talk between the embryo and the decidua. One of the key molecules during this process is human chorionic gonadotropin (HCG). HCG effectively modulates several metabolic pathways within the decidua contributing to endometrial receptivity. Herein, a brief overview of the molecular mechanisms regulated by HCG is presented. Furthermore, we summarize the existing evidence regarding the clinical impact on reproductive outcomes after endometrial priming with HCG prior to embryo transfer. Although promising, further evidence is needed to clarify the protocol that would lead to beneficial outcomes. PMID:28629172

The Key Points of Maintenance Therapy for Dental Implants: A Literature Review.

PubMed

Pirc, Miha; Dragan, Irina F

2017-04-01

Dental implants require lifelong maintenance and care. Success is defined by biologic factors (presence of inflamed soft tissues surrounding dental implants and radiographic changes in the crestal bone levels) and mechanical factors (stability of the implant fixture and implant supported restoration, etc). Most implant failures are initiated by incipient stages of inflammatory processes, which lead to peri-mucositis and peri-implantitis. The evidence regarding the value of maintenance protocol regarding implants is sparse compared with the one for teeth. This article addresses the existing literature on processes for oral hygiene for implant care.

Disruption of the Gut Ecosystem by Antibiotics

PubMed Central

2018-01-01

The intestinal microbiota is a complex ecosystem consisting of various microorganisms that expands human genetic repertoire and therefore affects human health and disease. The metabolic processes and signal transduction pathways of the host and intestinal microorganisms are intimately linked, and abnormal progression of each process leads to changes in the intestinal environment. Alterations in microbial communities lead to changes in functional structures based on the metabolites produced in the gut, and these environmental changes result in various bacterial infections and chronic enteric inflammatory diseases. Here, we illustrate how antibiotics are associated with an increased risk of antibiotic-associated diseases by driving intestinal environment changes that favor the proliferation and virulence of pathogens. Understanding the pathogenesis caused by antibiotics would be a crucial key to the treatment of antibiotic-associated diseases by mitigating changes in the intestinal environment and restoring it to its original state. PMID:29214770

Pretreatment methods for bioethanol production.

PubMed

Xu, Zhaoyang; Huang, Fang

2014-09-01

Lignocellulosic biomass, such as wood, grass, agricultural, and forest residues, are potential resources for the production of bioethanol. The current biochemical process of converting biomass to bioethanol typically consists of three main steps: pretreatment, enzymatic hydrolysis, and fermentation. For this process, pretreatment is probably the most crucial step since it has a large impact on the efficiency of the overall bioconversion. The aim of pretreatment is to disrupt recalcitrant structures of cellulosic biomass to make cellulose more accessible to the enzymes that convert carbohydrate polymers into fermentable sugars. This paper reviews several leading acidic, neutral, and alkaline pretreatments technologies. Different pretreatment methods, including dilute acid pretreatment (DAP), steam explosion pretreatment (SEP), organosolv, liquid hot water (LHW), ammonia fiber expansion (AFEX), soaking in aqueous ammonia (SAA), sodium hydroxide/lime pretreatments, and ozonolysis are intensively introduced and discussed. In this minireview, the key points are focused on the structural changes primarily in cellulose, hemicellulose, and lignin during the above leading pretreatment technologies.

Laser-based surface preparation of composite laminates leads to improved electrodes for electrical measurements

NASA Astrophysics Data System (ADS)

Almuhammadi, Khaled; Selvakumaran, Lakshmi; Alfano, Marco; Yang, Yang; Bera, Tushar Kanti; Lubineau, Gilles

2015-12-01

Electrical impedance tomography (EIT) is a low-cost, fast and effective structural health monitoring technique that can be used on carbon fiber reinforced polymers (CFRP). Electrodes are a key component of any EIT system and as such they should feature low resistivity as well as high robustness and reproducibility. Surface preparation is required prior to bonding of electrodes. Currently this task is mostly carried out by traditional sanding. However this is a time consuming procedure which can also induce damage to surface fibers and lead to spurious electrode properties. Here we propose an alternative processing technique based on the use of pulsed laser irradiation. The processing parameters that result in selective removal of the electrically insulating resin with minimum surface fiber damage are identified. A quantitative analysis of the electrical contact resistance is presented and the results are compared with those obtained using sanding.

Closing the Gap: Supporting Patients’ Transition to Self-Management after Hospitalization

PubMed Central

Pollack, Ari H; Backonja, Uba; Miller, Andrew D.; Mishra, Sonali R.; Khelifi, Maher; Kendall, Logan; Pratt, Wanda

2016-01-01

Patients going home after a hospitalization face many challenges. This transition period exposes patients to unnecessary risks related to inadequate preparation prior to leaving the hospital, potentially leading to errors and patient harm. Although patients engaging in self-management have better health outcomes and increased self-efficacy, little is known about the processes in place to support and develop these skills for patients leaving the hospital. Through qualitative interviews and observations of 28 patients during and after their hospitalizations, we explore the challenges they face transitioning from hospital care to self-management. We identify three key elements in this process: knowledge, resources, and self-efficacy. We describe how both system and individual factors contribute to breakdowns leading to ineffective patient management. This work expands our understanding of the unique challenges faced by patients during this difficult transition and uncovers important design opportunities for supporting crucial yet unmet patient needs. PMID:27500285

Metabolic Dysregulation in Amyotrophic Lateral Sclerosis: Challenges and Opportunities

PubMed Central

Joardar, Archi; Manzo, Ernesto

2017-01-01

Purpose of Review Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease for which there is no cure and treatments are at best palliative. Several genes have been linked to ALS, which highlight defects in multiple cellular processes including RNA processing, proteostasis and metabolism. Clinical observations have identified glucose intolerance and dyslipidemia as key features of ALS however the causes of these metabolic alterations remain elusive. Recent Findings Recent studies reveal that motor neurons and muscle cells may undergo cell type specific metabolic changes that lead to utilization of alternate fuels. For example, ALS patients’ muscles exhibit reduced glycolysis and increased reliance on fatty acids. In contrast, ALS motor neurons contain damaged mitochondria and exhibit impaired lipid beta oxidation, potentially leading to increased glycolysis as a compensatory mechanism. Summary These findings highlight the complexities of metabolic alterations in ALS and provide new opportunities for designing therapeutic strategies based on restoring cellular energetics. PMID:29057168

Metabolic Dysregulation in Amyotrophic Lateral Sclerosis: Challenges and Opportunities.

PubMed

Joardar, Archi; Manzo, Ernesto; Zarnescu, Daniela C

2017-06-01

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease for which there is no cure and treatments are at best palliative. Several genes have been linked to ALS, which highlight defects in multiple cellular processes including RNA processing, proteostasis and metabolism. Clinical observations have identified glucose intolerance and dyslipidemia as key features of ALS however the causes of these metabolic alterations remain elusive. Recent studies reveal that motor neurons and muscle cells may undergo cell type specific metabolic changes that lead to utilization of alternate fuels. For example, ALS patients' muscles exhibit reduced glycolysis and increased reliance on fatty acids. In contrast, ALS motor neurons contain damaged mitochondria and exhibit impaired lipid beta oxidation, potentially leading to increased glycolysis as a compensatory mechanism. These findings highlight the complexities of metabolic alterations in ALS and provide new opportunities for designing therapeutic strategies based on restoring cellular energetics.

Nitrogen stress response and stringent response are coupled in Escherichia coli

PubMed Central

Brown, Daniel R.; Barton, Geraint; Pan, Zhensheng; Buck, Martin; Wigneshweraraj, Sivaramesh

2014-01-01

Assimilation of nitrogen is an essential process in bacteria. The nitrogen regulation stress response is an adaptive mechanism used by nitrogen-starved Escherichia coli to scavenge for alternative nitrogen sources and requires the global transcriptional regulator NtrC. In addition, nitrogen-starved E. coli cells synthesize a signal molecule, guanosine tetraphosphate (ppGpp), which serves as an effector molecule of many processes including transcription to initiate global physiological changes, collectively termed the stringent response. The regulatory mechanisms leading to elevated ppGpp levels during nutritional stresses remain elusive. Here, we show that transcription of relA, a key gene responsible for the synthesis of ppGpp, is activated by NtrC during nitrogen starvation. The results reveal that NtrC couples these two major bacterial stress responses to manage conditions of nitrogen limitation, and provide novel mechanistic insights into how a specific nutritional stress leads to elevating ppGpp levels in bacteria. PMID:24947454

Wavefront attributes in anisotropic media

NASA Astrophysics Data System (ADS)

Vanelle, C.; Abakumov, I.; Gajewski, D.

2018-07-01

Surface-measured wavefront attributes are the key ingredient to multiparameter methods, which are nowadays standard tools in seismic data processing. However, most operators are restricted to application to isotropic media. Whereas application of an isotropic operator will still lead to satisfactory stack results, further processing steps that interpret isotropic stacking parameters in terms of wavefront attributes will lead to erroneous results if anisotropy is present but not accounted for. In this paper, we derive relationships between the stacking parameters and anisotropic wavefront attributes that allow us to apply the common reflection surface type operator to 3-D media with arbitrary anisotropy for the zero-offset and finite-offset configurations including converted waves. The operator itself is expressed in terms of wavefront attributes that are measured in the acquisition surface, that is, no model assumptions are made. Numerical results confirm that the accuracy of the new anisotropic operator is of the same magnitude as that of its isotropic counterpart.

Research on a Defects Detection Method in the Ferrite Phase Shifter Cementing Process Based on a Multi-Sensor Prognostic and Health Management (PHM) System.

PubMed

Wan, Bo; Fu, Guicui; Li, Yanruoyue; Zhao, Youhu

2016-08-10

The cementing manufacturing process of ferrite phase shifters has the defect that cementing strength is insufficient and fractures always appear. A detection method of these defects was studied utilizing the multi-sensors Prognostic and Health Management (PHM) theory. Aiming at these process defects, the reasons that lead to defects are analyzed in this paper. In the meanwhile, the key process parameters were determined and Differential Scanning Calorimetry (DSC) tests during the cure process of resin cementing were carried out. At the same time, in order to get data on changing cementing strength, multiple-group cementing process tests of different key process parameters were designed and conducted. A relational model of cementing strength and cure temperature, time and pressure was established, by combining data of DSC and process tests as well as based on the Avrami formula. Through sensitivity analysis for three process parameters, the on-line detection decision criterion and the process parameters which have obvious impact on cementing strength were determined. A PHM system with multiple temperature and pressure sensors was established on this basis, and then, on-line detection, diagnosis and control for ferrite phase shifter cementing process defects were realized. It was verified by subsequent process that the on-line detection system improved the reliability of the ferrite phase shifter cementing process and reduced the incidence of insufficient cementing strength defects.

Behavioral and language variants of frontotemporal dementia: a review of key symptoms.

PubMed

Laforce, Robert

2013-12-01

While recent advances in the development of neuroimaging and molecular biomarkers for studying neurodegenerative conditions have revolutionized the field, dementia remains a clinical diagnosis. No component of the diagnostic process is more crucial than obtaining a good history. Getting to know the first manifestations of the disease, tracking their evolution and functional impact, combined with a targeted neurological examination, further guides differential diagnosis. This paper summarizes the key symptoms of the behavioral and language variants of frontotemporal dementia. The behavioral variant of frontotemporal dementia (bvFTD) is characterized by severe changes in behavior and personality such as disinhibition, apathy, loss of empathy, or stereotypic behavior, leading to a loss of social competence. Executive functions are impaired, while memory and visuospatial skills are relatively better preserved. By contrast, the language variants or primary progressive aphasias (PPAs) are marked by prominent language disturbances that can be subclassified into a non-fluent/agrammatic variant (naPPA), a semantic variant (svPPA), and a logopenic variant (lvPPA). Although combined characterization of clinical, imaging, biological and genetic biomarkers is essential to establish a detailed diagnosis of such heterogeneous conditions, the author emphasizes the importance of accurate recognition of key symptoms that can lead to better identification of underlying neuropathology and appropriate treatment approaches.

Chemical thermodynamic data. 1. The concept of links to the chemical elements and the historical development of key thermodynamic data

NASA Astrophysics Data System (ADS)

Wolery, Thomas J.; Jové Colón, Carlos F.

2017-09-01

Chemical thermodynamic data remain a keystone for geochemical modeling and reactive transport simulation as applied to an increasing number of applications in the earth sciences, as well as applications in other areas including metallurgy, material science, and industrial process design. The last century has seen the development of a large body of thermodynamic data and a number of major compilations. The past several decades have seen the development of thermodynamic databases in digital form designed to support computer calculations. However, problems with thermodynamic data appear to be persistent. One problem pertains to the use of inconsistent primary key reference data. Such data pertain to elemental reference forms and key, stoichiometrically simple chemical species including metal oxides, CO2, water, and aqueous species such as Na+ and Cl-. A consistent set of primary key data (standard Gibbs energies, standard enthalpies, and standard entropies for key chemical species) for 298.15 K and 1 bar pressure is essential. Thermochemical convention is to define the standard Gibbs energy and the standard enthalpy of an individual chemical species in terms of formation from reference forms of the constituent chemical elements. We propose a formal concept of "links" to the elemental reference forms. This concept involves a documented understanding of all reactions and calculations leading to values for a formation property (standard Gibbs energy or enthalpy). A valid link consists of two parts: (a) the path of reactions and corrections and (b) the associated data, which are key data. Such a link differs from a bare "key" or "reference" datum in that it requires additional information. Some or all of its associated data may also be key data. In evaluating a reported thermodynamic datum, one should identify the links to the chemical elements, a process which can be time-consuming and which may lead to a dead end (an incomplete link). The use of two or more inconsistent links to the same elemental reference form in a thermodynamic database will result in an inconsistency in the database. Thus, in constructing a database, it is important to establish a set of reliable links (generally resulting in a set of primary reference data) and then correct all data adopted subsequently for consistency with that set. Recommended values of key data have not been constant through history. We review some of this history through the lens of major compilations and other influential reports, and note a number of problem areas. Finally, we illustrate the concepts developed in this paper by applying them to some key species of geochemical interest, including liquid water; quartz and aqueous silica; and gibbsite, corundum, and the aqueous aluminum ion.

The Impact of Special Education Litigation upon the Key Factors of Job Satisfaction, Level of Stress, and Self-Esteem That Lead to Teacher Attrition and Retention

ERIC Educational Resources Information Center

DeSio, Mary Jo Ann

2011-01-01

This research study reveals the stories of 19 special educators who participated in, or were summoned to testify, in one of the forms of special education litigation in the state of California. For most participants, their involvement was in a due process hearing conducted by the Office of Administrative Hearings under contract with the California…

From patterns to emerging processes in mechanistic urban ecology.

PubMed

Shochat, Eyal; Warren, Paige S; Faeth, Stanley H; McIntyre, Nancy E; Hope, Diane

2006-04-01

Rapid urbanization has become an area of crucial concern in conservation owing to the radical changes in habitat structure and loss of species engendered by urban and suburban development. Here, we draw on recent mechanistic ecological studies to argue that, in addition to altered habitat structure, three major processes contribute to the patterns of reduced species diversity and elevated abundance of many species in urban environments. These activities, in turn, lead to changes in animal behavior, morphology and genetics, as well as in selection pressures on animals and plants. Thus, the key to understanding urban patterns is to balance studying processes at the individual level with an integrated examination of environmental forces at the ecosystem scale.

Uncovering a Predictive Molecular Signature for the Onset of NASH-Related Fibrosis in a Translational NASH Mouse Model.

PubMed

van Koppen, Arianne; Verschuren, Lars; van den Hoek, Anita M; Verheij, Joanne; Morrison, Martine C; Li, Kelvin; Nagabukuro, Hiroshi; Costessi, Adalberto; Caspers, Martien P M; van den Broek, Tim J; Sagartz, John; Kluft, Cornelis; Beysen, Carine; Emson, Claire; van Gool, Alain J; Goldschmeding, Roel; Stoop, Reinout; Bobeldijk-Pastorova, Ivana; Turner, Scott M; Hanauer, Guido; Hanemaaijer, Roeland

2018-01-01

The incidence of nonalcoholic steatohepatitis (NASH) is increasing. The pathophysiological mechanisms of NASH and the sequence of events leading to hepatic fibrosis are incompletely understood. The aim of this study was to gain insight into the dynamics of key molecular processes involved in NASH and to rank early markers for hepatic fibrosis. A time-course study in low-density lipoprotein-receptor knockout. Leiden mice on a high-fat diet was performed to identify the temporal dynamics of key processes contributing to NASH and fibrosis. An integrative systems biology approach was used to elucidate candidate markers linked to the active fibrosis process by combining transcriptomics, dynamic proteomics, and histopathology. The translational value of these findings were confirmed using human NASH data sets. High-fat-diet feeding resulted in obesity, hyperlipidemia, insulin resistance, and NASH with fibrosis in a time-dependent manner. Temporal dynamics of key molecular processes involved in the development of NASH were identified, including lipid metabolism, inflammation, oxidative stress, and fibrosis. A data-integrative approach enabled identification of the active fibrotic process preceding histopathologic detection using a novel molecular fibrosis signature. Human studies were used to identify overlap of genes and processes and to perform a network biology-based prioritization to rank top candidate markers representing the early manifestation of fibrosis. An early predictive molecular signature was identified that marked the active profibrotic process before histopathologic fibrosis becomes manifest. Early detection of the onset of NASH and fibrosis enables identification of novel blood-based biomarkers to stratify patients at risk, development of new therapeutics, and help shorten (pre)clinical experimental time frames.

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.

Pathophysiology of chronic subdural haematoma: inflammation, angiogenesis and implications for pharmacotherapy.

PubMed

Edlmann, Ellie; Giorgi-Coll, Susan; Whitfield, Peter C; Carpenter, Keri L H; Hutchinson, Peter J

2017-05-30

Chronic subdural haematoma (CSDH) is an encapsulated collection of blood and fluid on the surface of the brain. Historically considered a result of head trauma, recent evidence suggests there are more complex processes involved. Trauma may be absent or very minor and does not explain the progressive, chronic course of the condition. This review focuses on several key processes involved in CSDH development: angiogenesis, fibrinolysis and inflammation. The characteristic membrane surrounding the CSDH has been identified as a source of fluid exudation and haemorrhage. Angiogenic stimuli lead to the creation of fragile blood vessels within membrane walls, whilst fibrinolytic processes prevent clot formation resulting in continued haemorrhage. An abundance of inflammatory cells and markers have been identified within the membranes and subdural fluid and are likely to contribute to propagating an inflammatory response which stimulates ongoing membrane growth and fluid accumulation. Currently, the mainstay of treatment for CSDH is surgical drainage, which has associated risks of recurrence requiring repeat surgery. Understanding of the underlying pathophysiological processes has been applied to developing potential drug treatments. Ongoing research is needed to identify if these therapies are successful in controlling the inflammatory and angiogenic disease processes leading to control and resolution of CSDH.

Added value of involving patients in the first step of multidisciplinary guideline development: a qualitative interview study among infertile patients.

PubMed

den Breejen, Elvira M E; Hermens, Rosella P M G; Galama, Wienke H; Willemsen, Wim N P; Kremer, Jan A M; Nelen, Willianne L D M

2016-06-01

Patient involvement in scoping the guideline is emphasized, but published initiatives actively involving patients are generally limited to the writing and reviewing phase. To assess patients' added value to the scoping phase of a multidisciplinary guideline on infertility. Qualitative interview study. We conducted interviews among 12 infertile couples and 17 professionals. We listed and compared the couples' and professionals' key clinical issues (=care aspects that need improvement) to be addressed in the guideline according to four domains: current guidelines, professionals, patients and organization of care. Main key clinical issues suggested by more than three quarters of the infertile couples and/or at least two professionals were identified and compared. Overall, we identified 32 key clinical issues among infertile couples and 23 among professionals. Of the defined main key clinical issues, infertile couples mentioned eight issues that were not mentioned by the professionals. These main key clinical issues mainly concerned patient-centred (e.g. poor information provision and poor alignment of care) aspects of care on the professional and organizational domain. Both groups mentioned two main key clinical issues collectively that were interpreted differently: the lack of emotional support and respect for patients' values. Including patients from the first phase of the guideline development process leads to valuable additional main key clinical issues for the next step of a multidisciplinary guideline development process and broadens the scope of the guideline, particularly regarding patient-centredness and organizational issues from a patients' perspective. © The Author 2016. Published by Oxford University Press in association with the International Society for Quality in Health Care; all rights reserved.

Investigating the Metastability of Clathrate Hydrates for Energy Storage

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

Koh, Carolyn Ann

2014-11-18

Important breakthrough discoveries have been achieved from the DOE award on the key processes controlling the synthesis and structure-property relations of clathrate hydrates, which are critical to the development of clathrate hydrates as energy storage materials. Key achievements include: (i) the discovery of key clathrate hydrate building blocks (stable and metastable) leading to clathrate hydrate nucleation and growth; (ii) development of a rapid clathrate hydrate synthesis route via a seeding mechanism; (iii) synthesis-structure relations of H2 + CH4/CO2 binary hydrates to control thermodynamic requirements for energy storage and sequestration applications; (iv) discovery of a new metastable phase present during clathratemore » hydrate structural transitions. The success of our research to-date is demonstrated by the significant papers we have published in high impact journals, including Science, Angewandte Chemie, J. Am. Chem. Soc. Intellectual Merits of Project Accomplishments: The intellectual merits of the project accomplishments are significant and transformative, in which the fundamental coupled computational and experimental program has provided new and critical understanding on the key processes controlling the nucleation, growth, and thermodynamics of clathrate hydrates containing hydrogen, methane, carbon dioxide, and other guest molecules for energy storage. Key examples of the intellectual merits of the accomplishments include: the first discovery of the nucleation pathways and dominant stable and metastable structures leading to clathrate hydrate formation; the discovery and experimental confirmation of new metastable clathrate hydrate structures; the development of new synthesis methods for controlling clathrate hydrate formation and enclathration of molecular hydrogen. Broader Impacts of Project Accomplishments: The molecular investigations performed in this project on the synthesis (nucleation & growth)-structure-stability relations of clathrate hydrate systems are pivotal in the fundamental understanding of crystalline clathrate hydrates and the discovery of new clathrate hydrate properties and novel materials for a broad spectrum of energy applications, including: energy storage (hydrogen, natural gas); carbon dioxide sequestration; controlling hydrate formation in oil/gas transportation in subsea pipelines. The Project has also enabled the training of undergraduate, graduate and postdoctoral students in computational methods, molecular spectroscopy and diffraction, and measurement methods at extreme conditions of high pressure and low temperature.« less

Optimizing Requirements Decisions with KEYS

NASA Technical Reports Server (NTRS)

Jalali, Omid; Menzies, Tim; Feather, Martin

2008-01-01

Recent work with NASA's Jet Propulsion Laboratory has allowed for external access to five of JPL's real-world requirements models, anonymized to conceal proprietary information, but retaining their computational nature. Experimentation with these models, reported herein, demonstrates a dramatic speedup in the computations performed on them. These models have a well defined goal: select mitigations that retire risks which, in turn, increases the number of attainable requirements. Such a non-linear optimization is a well-studied problem. However identification of not only (a) the optimal solution(s) but also (b) the key factors leading to them is less well studied. Our technique, called KEYS, shows a rapid way of simultaneously identifying the solutions and their key factors. KEYS improves on prior work by several orders of magnitude. Prior experiments with simulated annealing or treatment learning took tens of minutes to hours to terminate. KEYS runs much faster than that; e.g for one model, KEYS ran 13,000 times faster than treatment learning (40 minutes versus 0.18 seconds). Processing these JPL models is a non-linear optimization problem: the fewest mitigations must be selected while achieving the most requirements. Non-linear optimization is a well studied problem. With this paper, we challenge other members of the PROMISE community to improve on our results with other techniques.

Community Advisory Boards Guiding Engaged Research Efforts within a Clinical Translational Sciences Award: Key Contextual Factors Explored.

PubMed

Halladay, Jacqueline R; Donahue, Katrina E; Sleath, Betsy; Reuland, Dan; Black, Adina; Mitchell, C Madeline; Breland, Carol E; Coyne-Beasley, Tamera; Mottus, Kathleen; Watson, Sable Noelle; Lewis, Virginia; Wynn, Mysha; Corbie-Smith, Giselle

2017-01-01

Engaging stakeholders in research carries the promise of enhancing the research relevance, transparency, and speed of getting findings into practice. By describing the context and functional aspects of stakeholder groups, like those working as community advisory boards (CABs), others can learn from these experiences and operationalize their own CABs. Our objective is to describe our experiences with diverse CABs affiliated with our community engagement group within our institution's Clinical Translational Sciences Award (CTSA). We identify key contextual elements that are important to administering CABs. A group of investigators, staff, and community members engaged in a 6-month collaboration to describe their experiences of working with six research CABs. We identified the key contextual domains that illustrate how CABS are developed and sustained. Two lead authors, with experience with CABs and identifying contextual domains in other work, led a team of 13 through the process. Additionally, we devised a list of key tips to consider when devising CABs. The final domains include (1) aligned missions among stakeholders (2) resources/support, (3) defined operational processes/shared power, (4) well-described member roles, and (5) understanding and mitigating challenges. The tips are a set of actions that support the domains. Identifying key contextual domains was relatively easy, despite differences in the respective CAB's condition of focus, overall mission, or patient demographics represented. By contextualizing these five domains, other research and community partners can take an informed approach to move forward with CAB planning and engaged research.

'Governance of' and 'Governance by': implementing a clinical governance framework in an area mental health service.

PubMed

O'Connor, Nick; Paton, Michael

2008-04-01

A framework developed to promote the understanding and application of clinical governance principles in an area mental health service is described. The framework is operationalized through systems, processes, roles and responsibilities. The development of an explicit and operationalizable framework for clinical governance arose from the authors' experiences in leading and managing mental health services. There is a particular emphasis on improvement of quality of care and patient safety. The framework is informed by recent developments in thinking about clinical governance, including key documents from Australia and the United Kingdom. The operational nature of the framework allows for key components of clinical governance to be described explicitly, communicated effectively, and continually tested and improved. Further consideration and assessment of the value of differing approaches to this task are required. For example, a general, illustrative approach to raise clinician awareness can be contrasted with prescriptive and specified approaches which progressively encompass the many functions and processes of a mental health service. Mental health clinicians and managers can be guided by a framework that will ensure safe, high quality and continually improving processes of care.

Intestinal Microbiota and Its Relationship with Necrotizing Enterocolitis

PubMed Central

Patel, Ravi Mangal; Denning, Patricia W.

2015-01-01

Necrotizing enterocolitis is a leading cause of morbidity and mortality in infants born prematurely. After birth, the neonatal gut must acquire a healthy complement of commensal bacteria. Disruption or delay of this critical process, leading to deficient or abnormal microbial colonization of the gut, has been implicated as key risk factor in the pathogenesis of NEC. Conversely, a beneficial complement of commensal intestinal microbiota may protect the immature gut from inflammation and injury. Interventions aimed at providing or restoring a healthy complement of commensal bacteria, such as probiotic therapy, are currently the most promising treatment to prevent NEC. Shifting the balance of intestinal microbiota from a pathogenic to protective complement of bacteria can protect the gut from inflammation and subsequent injury that leads to NEC. Herein, we review the relationship of intestinal microbiota and NEC in preterm infants. PMID:25992911

Transmission fidelity is the key to the build-up of cumulative culture

PubMed Central

Lewis, Hannah M.; Laland, Kevin N.

2012-01-01

Many animals have socially transmitted behavioural traditions, but human culture appears unique in that it is cumulative, i.e. human cultural traits increase in diversity and complexity over time. It is often suggested that high-fidelity cultural transmission is necessary for cumulative culture to occur through refinement, a process known as ‘ratcheting’, but this hypothesis has never been formally evaluated. We discuss processes of information transmission and loss of traits from a cognitive viewpoint alongside other cultural processes of novel invention (generation of entirely new traits), modification (refinement of existing traits) and combination (bringing together two established traits to generate a new trait). We develop a simple cultural transmission model that does not assume major evolutionary changes (e.g. in brain architecture) and show that small changes in the fidelity with which information is passed between individuals can lead to cumulative culture. In comparison, modification and combination have a lesser influence on, and novel invention appears unimportant to, the ratcheting process. Our findings support the idea that high-fidelity transmission is the key driver of human cumulative culture, and that progress in cumulative culture depends more on trait combination than novel invention or trait modification. PMID:22734060

Transmission fidelity is the key to the build-up of cumulative culture.

PubMed

Lewis, Hannah M; Laland, Kevin N

2012-08-05

Many animals have socially transmitted behavioural traditions, but human culture appears unique in that it is cumulative, i.e. human cultural traits increase in diversity and complexity over time. It is often suggested that high-fidelity cultural transmission is necessary for cumulative culture to occur through refinement, a process known as 'ratcheting', but this hypothesis has never been formally evaluated. We discuss processes of information transmission and loss of traits from a cognitive viewpoint alongside other cultural processes of novel invention (generation of entirely new traits), modification (refinement of existing traits) and combination (bringing together two established traits to generate a new trait). We develop a simple cultural transmission model that does not assume major evolutionary changes (e.g. in brain architecture) and show that small changes in the fidelity with which information is passed between individuals can lead to cumulative culture. In comparison, modification and combination have a lesser influence on, and novel invention appears unimportant to, the ratcheting process. Our findings support the idea that high-fidelity transmission is the key driver of human cumulative culture, and that progress in cumulative culture depends more on trait combination than novel invention or trait modification.

Who runs public health? A mixed-methods study combining qualitative and network analyses.

PubMed

Oliver, Kathryn; de Vocht, Frank; Money, Annemarie; Everett, Martin

2013-09-01

Persistent health inequalities encourage researchers to identify new ways of understanding the policy process. Informal relationships are implicated in finding evidence and making decisions for public health policy (PHP), but few studies use specialized methods to identify key actors in the policy process. We combined network and qualitative data to identify the most influential individuals in PHP in a UK conurbation and describe their strategies to influence policy. Network data were collected by asking for nominations of powerful and influential people in PHP (n = 152, response rate 80%), and 23 semi-structured interviews were analysed using a framework approach. The most influential PHP makers in this conurbation were mid-level managers in the National Health Service and local government, characterized by managerial skills: controlling policy processes through gate keeping key organizations, providing policy content and managing selected experts and executives to lead on policies. Public health professionals and academics are indirectly connected to policy via managers. The most powerful individuals in public health are managers, not usually considered targets for research. As we show, they are highly influential through all stages of the policy process. This study shows the importance of understanding the daily activities of influential policy individuals.

Health-care process improvement decisions: a systems perspective.

PubMed

Walley, Paul; Silvester, Kate; Mountford, Shaun

2006-01-01

The paper seeks to investigate decision-making processes within hospital improvement activity, to understand how performance measurement systems influence decisions and potentially lead to unsuccessful or unsustainable process changes. A longitudinal study over a 33-month period investigates key events, decisions and outcomes at one medium-sized hospital in the UK. Process improvement events are monitored using process control methods and by direct observation. The authors took a systems perspective of the health-care processes, ensuring that the impacts of decisions across the health-care supply chain were appropriately interpreted. The research uncovers the ways in which measurement systems disguise failed decisions and encourage managers to take a low-risk approach of "symptomatic relief" when trying to improve performance metrics. This prevents many managers from trying higher risk, sustainable process improvement changes. The behaviour of the health-care system is not understood by many managers and this leads to poor analysis of problem situations. Measurement using time-series methodologies, such as statistical process control are vital for a better understanding of the systems impact of changes. Senior managers must also be aware of the behavioural influence of similar performance measurement systems that discourage sustainable improvement. There is a risk that such experiences will tarnish the reputation of performance management as a discipline. Recommends process control measures as a way of creating an organization memory of how decisions affect performance--something that is currently lacking.

Microfluidic Device for Studying Tumor Cell Extravasation in Cancer Metastasis

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

Lin, Henry K; Thundat, Thomas George; Evans III, Boyd Mccutchen

Metastasis is the process by which cancer spreads to form secondary tumors at downstream locations throughout the body. This uncontrolled spreading is the leading cause of death in patients with epithelial cancers and is the main reason that suppressing and targeting cancer has proven to be so challenging. Tumor cell extravasation is one of the key steps in cancer s progression towards a metastatic state. This occurs when circulating tumor cells found within the blood stream are able to transmigrate through the endothelium lining and basement membrane of the vasculature to form metastatic tumors at secondary sites within the body.more » Predicting the likelihood of this occurrence in patients, or being able to determine specific markers involved in this process could lead to preventative measures targeting these types of cancer; moreover, this may lead to the discovery of novel anti-metastatic drugs. We have developed a microfluidic device that has shown the extravasation of fluorescently labeled tumor cells across an endothelial cell lined membrane coated with matrigel followed by the formation of colonies. This device provides the advantages of combining a controlled environment, mimicking that found within the body, with real-time monitoring capabilities allowing for the study of these biomarkers and cellular interactions along with other potential mechanisms involved in the process of extravasation.« less

Activation of the hypoxia-inducible factor 1α promotes myogenesis through the noncanonical Wnt pathway, leading to hypertrophic myotubes.

PubMed

Cirillo, Federica; Resmini, Giulia; Ghiroldi, Andrea; Piccoli, Marco; Bergante, Sonia; Tettamanti, Guido; Anastasia, Luigi

2017-05-01

Regeneration of skeletal muscle is a complex process that requires the activation of quiescent adult stem cells, called satellite cells, which are resident in hypoxic niches in the tissue. Hypoxia has been recognized as a key factor to maintain stem cells in an undifferentiated state. Herein we report that hypoxia plays a fundamental role also in activating myogenesis. In particular, we found that the activation of the hypoxia-inducible factor (HIF)-1α under hypoxia, in murine skeletal myoblasts, leads to activation of MyoD through the noncanonical Wnt/β-catenin pathway. Moreover, chemical inhibition of HIF-1α activity significantly reduces differentiation, thus confirming its crucial role in the process. Furthermore, hypoxia-preconditioned myoblasts, once induced to differentiate under normoxic conditions, tend to form hypertrophic myotubes. These results support the notion that hypoxia plays a pivotal role in activating the regeneration process by directly inducing myogenesis through HIF-1α. Although preliminary, these findings may suggest new perspective for novel therapeutic targets in the treatment of several muscle diseases.-Cirillo, F., Resmini, G., Ghiroldi, A., Piccoli, M., Bergante, S., Tettamanti, G., Anastasia, L. Activation of the hypoxia-inducible factor 1α promotes myogenesis through the noncanonical Wnt pathway, leading to hypertrophic myotubes. © FASEB.

Quantum cryptography with finite resources: unconditional security bound for discrete-variable protocols with one-way postprocessing.

PubMed

Scarani, Valerio; Renner, Renato

2008-05-23

We derive a bound for the security of quantum key distribution with finite resources under one-way postprocessing, based on a definition of security that is composable and has an operational meaning. While our proof relies on the assumption of collective attacks, unconditional security follows immediately for standard protocols such as Bennett-Brassard 1984 and six-states protocol. For single-qubit implementations of such protocols, we find that the secret key rate becomes positive when at least N approximately 10(5) signals are exchanged and processed. For any other discrete-variable protocol, unconditional security can be obtained using the exponential de Finetti theorem, but the additional overhead leads to very pessimistic estimates.

The molecular bases of the suicidal brain

PubMed Central

Turecki, Gustavo

2017-01-01

Suicide ranks among the leading causes of death around the world, and takes a heavy emotional and public health toll on most societies. Both distal and proximal factors contribute to suicidal behaviour. Distal factors — such as familial and genetic predisposition, as well as early-life adversity — increase the lifetime risk of suicide. They alter responses to stress and other processes through epigenetic modification of genes and associated changes in gene expression, and through the regulation of emotional and behavioural traits. Proximal factors associate with the precipitation of a suicidal event and include alterations in key neurotransmitter systems, inflammatory changes and glial dysfunction in the brain. This Review explores the key molecular changes associated with suicidality, and presents some promising avenues for future research. PMID:25354482

Plant Hormones: Key Players in Gut Microbiota and Human Diseases?

PubMed

Chanclud, Emilie; Lacombe, Benoît

2017-09-01

It is well established that plant hormones such as auxins, cytokinins (CKs), and abscisic acid (ABA) not only govern important plant physiological traits but are key players in plant-microbe interactions. A poorly appreciated fact, however, is that both microbes and animals produce and perceive plant hormones and their mimics. Moreover, dietary plant hormones impact on human physiological process such as glucose assimilation, inflammation, and cell division. This leads us to wonder whether plant hormones could ensure functions in microbes per se as well as in animal-microbe interactions. We propose here and explore the hypothesis that plant hormones play roles in animal-microbiota relationships, with consequences for human health. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mechanisms of fibrosis: therapeutic translation for fibrotic disease

PubMed Central

Wynn, Thomas A; Ramalingam, Thirumalai R

2012-01-01

Fibrosis is a pathological feature of most chronic inflammatory diseases. Fibrosis, or scarring, is defined by the accumulation of excess extracellular matrix components. If highly progressive, the fibrotic process eventually leads to organ malfunction and death. Fibrosis affects nearly every tissue in the body. Here we discuss how key components of the innate and adaptive immune response contribute to the pathogenesis of fibrosis. We also describe how cell-intrinsic changes in important structural cells can perpetuate the fibrotic response by regulating the differentiation, recruitment, proliferation and activation of extracellular matrix–producing myofibroblasts. Finally, we highlight some of the key mechanisms and pathways of fibrosis that are being targeted as potential therapies for a variety of important human diseases. PMID:22772564

Chemical thermodynamic data. 1. The concept of links to the chemical elements and the historical development of key thermodynamic data [plus Supplementary Electronic Annex 2

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

Wolery, Thomas J.; Jove Colon, Carlos F.

Chemical thermodynamic data remain a keystone for geochemical modeling and reactive transport simulation as applied to an increasing number of applications in the earth sciences, as well as applications in other areas including metallurgy, material science, and industrial process design. The last century has seen the development of a large body of thermodynamic data and a number of major compilations. The past several decades have seen the development of thermodynamic databases in digital form designed to support computer calculations. However, problems with thermodynamic data appear to be persistent. One problem pertains to the use of inconsistent primary key reference data.more » Such data pertain to elemental reference forms and key, stoichiometrically simple chemical species including metal oxides, CO 2, water, and aqueous species such as Na + and Cl -. A consistent set of primary key data (standard Gibbs energies, standard enthalpies, and standard entropies for key chemical species) for 298.15K and 1 bar pressure is essential. Thermochemical convention is to define the standard Gibbs energy and the standard enthalpy of an individual chemical species in terms of formation from reference forms of the constituent chemical elements. We propose a formal concept of “links” to the elemental reference forms. This concept involves a documented understanding of all reactions and calculations leading to values for a formation property (standard Gibbs energy or enthalpy). A valid link consists of two parts: (a) the path of reactions and corrections and (b) the associated data, which are key data. Such a link differs from a bare “key” or “reference” datum in that it requires additional information. Some or all of its associated data may also be key data. In evaluating a reported thermodynamic datum, one should identify the links to the chemical elements, a process which can be time-consuming and which may lead to a dead end (an incomplete link). The use of two or more inconsistent links to the same elemental reference form in a thermodynamic database will result in an inconsistency in the database. Thus, in constructing a database, it is important to establish a set of reliable links (generally resulting in a set of primary reference data) and then correct all data adopted subsequently for consistency with that set. Recommended values of key data have not been constant through history. We review some of this history through the lens of major compilations and other influential reports, and note a number of problem areas. Finally, we illustrate the concepts developed in this paper by applying them to some key species of geochemical interest, including liquid water; quartz and aqueous silica; and gibbsite, corundum, and the aqueous aluminum ion.« less

Chemical thermodynamic data. 1. The concept of links to the chemical elements and the historical development of key thermodynamic data [plus Supplementary Electronic Annex 2

DOE PAGES

Wolery, Thomas J.; Jove Colon, Carlos F.

2016-09-26

Chemical thermodynamic data remain a keystone for geochemical modeling and reactive transport simulation as applied to an increasing number of applications in the earth sciences, as well as applications in other areas including metallurgy, material science, and industrial process design. The last century has seen the development of a large body of thermodynamic data and a number of major compilations. The past several decades have seen the development of thermodynamic databases in digital form designed to support computer calculations. However, problems with thermodynamic data appear to be persistent. One problem pertains to the use of inconsistent primary key reference data.more » Such data pertain to elemental reference forms and key, stoichiometrically simple chemical species including metal oxides, CO 2, water, and aqueous species such as Na + and Cl -. A consistent set of primary key data (standard Gibbs energies, standard enthalpies, and standard entropies for key chemical species) for 298.15K and 1 bar pressure is essential. Thermochemical convention is to define the standard Gibbs energy and the standard enthalpy of an individual chemical species in terms of formation from reference forms of the constituent chemical elements. We propose a formal concept of “links” to the elemental reference forms. This concept involves a documented understanding of all reactions and calculations leading to values for a formation property (standard Gibbs energy or enthalpy). A valid link consists of two parts: (a) the path of reactions and corrections and (b) the associated data, which are key data. Such a link differs from a bare “key” or “reference” datum in that it requires additional information. Some or all of its associated data may also be key data. In evaluating a reported thermodynamic datum, one should identify the links to the chemical elements, a process which can be time-consuming and which may lead to a dead end (an incomplete link). The use of two or more inconsistent links to the same elemental reference form in a thermodynamic database will result in an inconsistency in the database. Thus, in constructing a database, it is important to establish a set of reliable links (generally resulting in a set of primary reference data) and then correct all data adopted subsequently for consistency with that set. Recommended values of key data have not been constant through history. We review some of this history through the lens of major compilations and other influential reports, and note a number of problem areas. Finally, we illustrate the concepts developed in this paper by applying them to some key species of geochemical interest, including liquid water; quartz and aqueous silica; and gibbsite, corundum, and the aqueous aluminum ion.« less

The Manufacture of W-UO2 Fuel Elements for NTP Using the Hot Isostatic Pressing Consolidation Process

NASA Technical Reports Server (NTRS)

Broadway, Jeramie; Hickman, Robert; Mireles, Omar

2012-01-01

NTP is attractive for space exploration because: (1) Higher Isp than traditional chemical rockets (2)Shorter trip times (3) Reduced propellant mass (4) Increased payload. Lack of qualified fuel material is a key risk (cost, schedule, and performance). Development of stable fuel form is a critical path, long lead activity. Goals of this project are: Mature CERMET and Graphite based fuel materials and Develop and demonstrate critical technologies and capabilities.

Description of Mixed-Phase Clouds in Weather Forecast and Climate Models

DTIC Science & Technology

2014-09-30

deficits, leading to freeze-up of both sea ice and the ocean surface. The surface albedo and processes impacting the energy content of the upper ocean...appear key to producing a temporal difference be- tween the freeze-up of the sea - ice surface and adjacent open water. While synoptic conditions, atmos...Leck, 2013: Cloud and boundary layer interactions over the Arctic sea - ice in late summer, Atmos. Chem. Phys. Discuss., 13, 13191-13244, doi

Electronic Data Interchange in Defense Transportation

DTIC Science & Technology

1987-10-01

entry into a nearly paperless transportation environment. • Prescribe DoD’s use of the EDI standards developed by the transportation industry and lead...information into a format for internal use so that it can be processed. * Key Entry Costs. Data will no longer need to be entered manually into a terminal or...that commercial standards cannot meet, DoD must create standards. A vehicle for creating those DoD-unique standards now exists. That vehicle , the

Materials Analysis: A Key to Unlocking the Mystery of the Columbia Tragedy

NASA Technical Reports Server (NTRS)

Mayeaux, Brian M.; Collins, Thomas E.; Piascik, Robert S.; Russel, Richard W.; Jerman, Gregory A.; Shah, Sandeep R.; McDanels, Steven J.

2004-01-01

Materials analyses of key forensic evidence helped unlock the mystery of the loss of space shuttle Columbia that disintegrated February 1, 2003 while returning from a 16-day research mission. Following an intensive four-month recovery effort by federal, state, and local emergency management and law officials, Columbia debris was collected, catalogued, and reassembled at the Kennedy Space Center. Engineers and scientists from the Materials and Processes (M&P) team formed by NASA supported Columbia reconstruction efforts, provided factual data through analysis, and conducted experiments to validate the root cause of the accident. Fracture surfaces and thermal effects of selected airframe debris were assessed, and process flows for both nondestructive and destructive sampling and evaluation of debris were developed. The team also assessed left hand (LH) airframe components that were believed to be associated with a structural breach of Columbia. Analytical data collected by the M&P team showed that a significant thermal event occurred at the left wing leading edge in the proximity of LH reinforced carbon carbon (RCC) panels 8 and 9. The analysis also showed exposure to temperatures in excess of 1,649 C, which would severely degrade the support structure, tiles, and RCC panel materials. The integrated failure analysis of wing leading edge debris and deposits strongly supported the hypothesis that a breach occurred at LH RCC panel 8.

Prefrontal Cortex and Social Cognition in Mouse and Man

PubMed Central

Bicks, Lucy K.; Koike, Hiroyuki; Akbarian, Schahram; Morishita, Hirofumi

2015-01-01

Social cognition is a complex process that requires the integration of a wide variety of behaviors, including salience, reward-seeking, motivation, knowledge of self and others, and flexibly adjusting behavior in social groups. Not surprisingly, social cognition represents a sensitive domain commonly disrupted in the pathology of a variety of psychiatric disorders including Autism Spectrum Disorder (ASD) and Schizophrenia (SCZ). Here, we discuss convergent research from animal models to human disease that implicates the prefrontal cortex (PFC) as a key regulator in social cognition, suggesting that disruptions in prefrontal microcircuitry play an essential role in the pathophysiology of psychiatric disorders with shared social deficits. We take a translational perspective of social cognition, and review three key behaviors that are essential to normal social processing in rodents and humans, including social motivation, social recognition, and dominance hierarchy. A shared prefrontal circuitry may underlie these behaviors. Social cognition deficits in animal models of neurodevelopmental disorders like ASD and SCZ have been linked to an altered balance of excitation and inhibition (E/I ratio) within the cortex generally, and PFC specifically. A clear picture of the mechanisms by which altered E/I ratio in the PFC might lead to disruptions of social cognition across a variety of behaviors is not well understood. Future studies should explore how disrupted developmental trajectory of prefrontal microcircuitry could lead to altered E/I balance and subsequent deficits in the social domain. PMID:26635701

Ribosome Synthesis and MAPK Activity Modulate Ionizing Radiation-Induced Germ Cell Apoptosis in Caenorhabditis elegans

PubMed Central

Eberhard, Ralf; Stergiou, Lilli; Hofmann, E. Randal; Hofmann, Jen; Haenni, Simon; Teo, Youjin; Furger, André; Hengartner, Michael O.

2013-01-01

Synthesis of ribosomal RNA by RNA polymerase I (RNA pol I) is an elemental biological process and is key for cellular homeostasis. In a forward genetic screen in C. elegans designed to identify DNA damage-response factors, we isolated a point mutation of RNA pol I, rpoa-2(op259), that leads to altered rRNA synthesis and a concomitant resistance to ionizing radiation (IR)-induced germ cell apoptosis. This weak apoptotic IR response could be phenocopied when interfering with other factors of ribosome synthesis. Surprisingly, despite their resistance to DNA damage, rpoa-2(op259) mutants present a normal CEP-1/p53 response to IR and increased basal CEP-1 activity under normal growth conditions. In parallel, rpoa-2(op259) leads to reduced Ras/MAPK pathway activity, which is required for germ cell progression and physiological germ cell death. Ras/MAPK gain-of-function conditions could rescue the IR response defect in rpoa-2(op259), pointing to a function for Ras/MAPK in modulating DNA damage-induced apoptosis downstream of CEP-1. Our data demonstrate that a single point mutation in an RNA pol I subunit can interfere with multiple key signalling pathways. Ribosome synthesis and growth-factor signalling are perturbed in many cancer cells; such an interplay between basic cellular processes and signalling might be critical for how tumours evolve or respond to treatment. PMID:24278030

Use of dietary phytochemicals to target inflammation, fibrosis, proliferation, and angiogenesis in uterine tissues: promising options for prevention and treatment of uterine fibroids?

PubMed

Islam, Md Soriful; Akhtar, Most Mauluda; Ciavattini, Andrea; Giannubilo, Stefano Raffaele; Protic, Olga; Janjusevic, Milijana; Procopio, Antonio Domenico; Segars, James H; Castellucci, Mario; Ciarmela, Pasquapina

2014-08-01

Uterine leiomyomas (fibroids, myomas) are the most common benign tumors of female reproductive tract. They are highly prevalent, with 70-80% of women burdened by the end of their reproductive years. Fibroids are a leading cause of pelvic pain, abnormal vaginal bleeding, pressure on the bladder, miscarriage, and infertility. They are the leading indication for hysterectomy, and costs exceed 6 billion dollars annually in the United States. Unfortunately, no long-term medical treatments are available. Dysregulation of inflammatory processes are thought to be involved in the initiation of leiomyoma and extracellular matrix deposition, cell proliferation, and angiogenesis are the key cellular events implicated in leiomyoma growth. In modern pharmaceutical industries, dietary phytochemicals are used as source of new potential drugs for many kinds of tumors. Dietary phytochemicals may exert therapeutic effects by interfering with key cellular events of the tumorigenesis process. At present, a negligible number of phytochemicals have been tested as therapeutic agents against fibroids. In this context, our aim was to introduce some of the potential dietary phytochemicals that have shown anti-inflammatory, antiproliferative, antifibrotic, and antiangiogenic activities in different biological systems. This review could be useful to stimulate the evaluation of these phytochemicals as possible therapies for uterine fibroids. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Implementation and benefits of advanced process control for lithography CD and overlay

NASA Astrophysics Data System (ADS)

Zavyalova, Lena; Fu, Chong-Cheng; Seligman, Gary S.; Tapp, Perry A.; Pol, Victor

2003-05-01

Due to the rapidly reduced imaging process windows and increasingly stingent device overlay requirements, sub-130 nm lithography processes are more severely impacted than ever by systamic fault. Limits on critical dimensions (CD) and overlay capability further challenge the operational effectiveness of a mix-and-match environment using multiple lithography tools, as such mode additionally consumes the available error budgets. Therefore, a focus on advanced process control (APC) methodologies is key to gaining control in the lithographic modules for critical device levels, which in turn translates to accelerated yield learning, achieving time-to-market lead, and ultimately a higher return on investment. This paper describes the implementation and unique challenges of a closed-loop CD and overlay control solution in high voume manufacturing of leading edge devices. A particular emphasis has been placed on developing a flexible APC application capable of managing a wide range of control aspects such as process and tool drifts, single and multiple lot excursions, referential overlay control, 'special lot' handling, advanced model hierarchy, and automatic model seeding. Specific integration cases, including the multiple-reticle complementary phase shift lithography process, are discussed. A continuous improvement in the overlay and CD Cpk performance as well as the rework rate has been observed through the implementation of this system, and the results are studied.

Key Recommendations from the MedtecHTA Project.

PubMed

Tarricone, Rosanna; Torbica, Aleksandra; Drummond, Michael

2017-02-01

There are particular characteristics of Medical Devices, such as the device-user interaction, the incremental nature of innovation and the broader organizational impact that lead to additional challenges for health technology assessment (HTA). The project explored key aspects of the conduct and methods of HTA for MDs. Systematic reviews and original research studies were conducted to determine improvements in processes and methods that could enhance the potential for HTA and optimize the diffusion of MDs. Regulatory processes for MDs should be more closely aligned, the HTA evaluative framework should be harmonized and processes for conditional coverage and evidence development should be used. The methods for HTA should consider MDs as complex interventions, require the establishment of high quality registries, consider an iterative approach to the evaluation over time, recognize and allow for the particular characteristics of devices and use appropriate approaches for confounder adjustment in comparative effectiveness studies. To optimize the diffusion, a common classification should be developed across countries in order to facilitate international comparisons, factors driving diffusion should be explored in HTA reports and physicians' personal goals and motivation should be better understood. The key recommendations of the MedtecHTA project should improve the conduct and use of HTA for MDs. © 2017 The Authors. Health Economics published by John Wiley & Sons, Ltd. © 2017 The Authors. Health Economics published by John Wiley & Sons, Ltd.

Succesful Lean Manufacturing Implementation: Internal Key Influencing Factors

NASA Astrophysics Data System (ADS)

Virginia, Iuga; Claudiu, Kifor

2015-09-01

Manufacturing sectors and companies all over the world are successfully implementing lean principles within their processes. Nowadays, lean has become an indispensable part of global players. Companies worldwide need to be aware of multiple factors which weigh heavily on the success or failure of lean implementation. This paper focuses on giving a brief and structured overview over the fundamental organizational factors which play a substantial role for the lean manufacturing (LM) implementation process. The study below focuses on internal factors which are indispensable for a successful LM implementation within organizations. It is imperative that these internal factors are known, recognized and taken into consideration during the whole LM implementation process. Ignoring their influence on the process's implementation may lead to endangering the expected results or to making the process more difficult which could result in much higher human resource consumption.

Health hazards of China's lead-acid battery industry: a review of its market drivers, production processes, and health impacts.

PubMed

van der Kuijp, Tsering Jan; Huang, Lei; Cherry, Christopher R

2013-08-03

Despite China's leaded gasoline phase out in 2000, the continued high rates of lead poisoning found in children's blood lead levels reflect the need for identifying and controlling other sources of lead pollution. From 2001 to 2007, 24% of children in China studied (N = 94,778) were lead poisoned with levels exceeding 100 μg/L. These levels stand well above the global average of 16%. These trends reveal that China still faces significant public health challenges, with millions of children currently at risk of lead poisoning. The unprecedented growth of China's lead-acid battery industry from the electric bike, automotive, and photovoltaic industries may explain these persistently high levels, as China remains the world's leading producer, refiner, and consumer of both lead and lead-acid batteries.This review assesses the role of China's rising lead-acid battery industry on lead pollution and exposure. It starts with a synthesis of biological mechanisms of lead exposure followed by an analysis of the key technologies driving the rapid growth of this industry. It then details the four main stages of lead battery production, explaining how each stage results in significant lead loss and pollution. A province-level accounting of each of these industrial operations is also included. Next, reviews of the literature describe how this industry may have contributed to mass lead poisonings throughout China. Finally, the paper closes with a discussion of new policies that address the lead-acid battery industry and identifies policy frameworks to mitigate exposure.This paper is the first to integrate the market factors, production processes, and health impacts of China's growing lead-acid battery industry to illustrate its vast public health consequences. The implications of this review are two-fold: it validates calls for a nationwide assessment of lead exposure pathways and levels in China as well as for a more comprehensive investigation into the health impacts of the lead-acid battery industry. The continuous growth of this industry signals the urgent need for effective regulatory action to protect the health and lives of China's future generations.

Health hazards of China’s lead-acid battery industry: a review of its market drivers, production processes, and health impacts

PubMed Central

2013-01-01

Despite China’s leaded gasoline phase out in 2000, the continued high rates of lead poisoning found in children’s blood lead levels reflect the need for identifying and controlling other sources of lead pollution. From 2001 to 2007, 24% of children in China studied (N = 94,778) were lead poisoned with levels exceeding 100 μg/L. These levels stand well above the global average of 16%. These trends reveal that China still faces significant public health challenges, with millions of children currently at risk of lead poisoning. The unprecedented growth of China’s lead-acid battery industry from the electric bike, automotive, and photovoltaic industries may explain these persistently high levels, as China remains the world’s leading producer, refiner, and consumer of both lead and lead-acid batteries. This review assesses the role of China’s rising lead-acid battery industry on lead pollution and exposure. It starts with a synthesis of biological mechanisms of lead exposure followed by an analysis of the key technologies driving the rapid growth of this industry. It then details the four main stages of lead battery production, explaining how each stage results in significant lead loss and pollution. A province-level accounting of each of these industrial operations is also included. Next, reviews of the literature describe how this industry may have contributed to mass lead poisonings throughout China. Finally, the paper closes with a discussion of new policies that address the lead-acid battery industry and identifies policy frameworks to mitigate exposure. This paper is the first to integrate the market factors, production processes, and health impacts of China’s growing lead-acid battery industry to illustrate its vast public health consequences. The implications of this review are two-fold: it validates calls for a nationwide assessment of lead exposure pathways and levels in China as well as for a more comprehensive investigation into the health impacts of the lead-acid battery industry. The continuous growth of this industry signals the urgent need for effective regulatory action to protect the health and lives of China’s future generations. PMID:23915167

MicroRNAs in the pathobiology of atherosclerosis

PubMed Central

Laffont, Benoit; Rayner, Katey J

2017-01-01

MicroRNAs are short non-coding RNAs, expressed in humans and involved in sequence-specific post-transcriptional regulation of gene expression. They have emerged as key players in a wide array of biological processes, and changes in their expression and/or function have been associated with plethora of human diseases. Atherosclerosis and its related clinical complications, such as myocardial infarction or stroke, represent the leading cause of death in the western world. Accumulating experimental evidence has revealed a key role for microRNAs in regulating cellular and molecular processes related to atherosclerosis development, ranging from risk factors, to plaque initiation and progression, up to atherosclerotic plaque rupture. In this review, we will focus on how microRNAs can influence atherosclerosis biology, as well as the potential clinical applications of microRNAs which are being developed as both targets and therapeutics for a growing industry hoping to harness the power of RNA-guided gene regulation to fight disease and infection. PMID:28232017

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

The uncertainty of crop yield projections is reduced by improved temperature response functions.

PubMed

Wang, Enli; Martre, Pierre; Zhao, Zhigan; Ewert, Frank; Maiorano, Andrea; Rötter, Reimund P; Kimball, Bruce A; Ottman, Michael J; Wall, Gerard W; White, Jeffrey W; Reynolds, Matthew P; Alderman, Phillip D; Aggarwal, Pramod K; Anothai, Jakarat; Basso, Bruno; Biernath, Christian; Cammarano, Davide; Challinor, Andrew J; De Sanctis, Giacomo; Doltra, Jordi; Fereres, Elias; Garcia-Vila, Margarita; Gayler, Sebastian; Hoogenboom, Gerrit; Hunt, Leslie A; Izaurralde, Roberto C; Jabloun, Mohamed; Jones, Curtis D; Kersebaum, Kurt C; Koehler, Ann-Kristin; Liu, Leilei; Müller, Christoph; Naresh Kumar, Soora; Nendel, Claas; O'Leary, Garry; Olesen, Jørgen E; Palosuo, Taru; Priesack, Eckart; Eyshi Rezaei, Ehsan; Ripoche, Dominique; Ruane, Alex C; Semenov, Mikhail A; Shcherbak, Iurii; Stöckle, Claudio; Stratonovitch, Pierre; Streck, Thilo; Supit, Iwan; Tao, Fulu; Thorburn, Peter; Waha, Katharina; Wallach, Daniel; Wang, Zhimin; Wolf, Joost; Zhu, Yan; Asseng, Senthold

2017-07-17

Increasing the accuracy of crop productivity estimates is a key element in planning adaptation strategies to ensure global food security under climate change. Process-based crop models are effective means to project climate impact on crop yield, but have large uncertainty in yield simulations. Here, we show that variations in the mathematical functions currently used to simulate temperature responses of physiological processes in 29 wheat models account for >50% of uncertainty in simulated grain yields for mean growing season temperatures from 14 °C to 33 °C. We derived a set of new temperature response functions that when substituted in four wheat models reduced the error in grain yield simulations across seven global sites with different temperature regimes by 19% to 50% (42% average). We anticipate the improved temperature responses to be a key step to improve modelling of crops under rising temperature and climate change, leading to higher skill of crop yield projections.

The Uncertainty of Crop Yield Projections Is Reduced by Improved Temperature Response Functions

NASA Technical Reports Server (NTRS)

Wang, Enli; Martre, Pierre; Zhao, Zhigan; Ewert, Frank; Maiorano, Andrea; Rotter, Reimund P.; Kimball, Bruce A.; Ottman, Michael J.; White, Jeffrey W.; Reynolds, Matthew P.;

Development of World Health Organization (WHO) recommendations for appropriate clinical trial endpoints for next-generation Human Papillomavirus (HPV) vaccines.

PubMed

Prabhu, Malavika; Eckert, Linda O

2016-12-01

The World Health Organization (WHO) serves as a key organization to bring together experts along the continuum of vaccine development and regulatory approval, among its other functions. Using the revision of WHO's guidelines on prophylactic human papillomavirus (HPV) vaccine as an example, we describe the process by which (1) a need to revise the guidelines was identified; (2) a group of stakeholders with complementary expertise and key questions were identified; (3) a scientific review was conducted; (4) consensus on revisions was achieved; (5) guidelines were updated, reviewed widely, and approved. This multi-year process resulted in the consensus that regulatory agencies could consider additional endpoints, such as persistent HPV infection or immune equivalence, depending on the design of the HPV vaccine trials. Updating the guidelines will now accelerate vaccine development, reduce costs of clinical trials, and lead to faster regulatory approval. Copyright © 2016. Published by Elsevier B.V.

SMN control of RNP assembly: from post-transcriptional gene regulation to motor neuron disease

PubMed Central

Li, Darrick K.; Tisdale, Sarah; Lotti, Francesco; Pellizzoni, Livio

2014-01-01

At the post-transcriptional level, expression of protein-coding genes is controlled by a series of RNA regulatory events including nuclear processing of primary transcripts, transport of mature mRNAs to specific cellular compartments, translation and ultimately, turnover. These processes are orchestrated through the dynamic association of mRNAs with RNA binding proteins and ribonucleoprotein (RNP) complexes. Accurate formation of RNPs in vivo is fundamentally important to cellular development and function, and its impairment often leads to human disease. The survival motor neuron (SMN) protein is key to this biological paradigm: SMN is essential for the biogenesis of various RNPs that function in mRNA processing, and genetic mutations leading to SMN deficiency cause the neurodegenerative disease spinal muscular atrophy. Here we review the expanding role of SMN in the regulation of gene expression through its multiple functions in RNP assembly. We discuss advances in our understanding of SMN activity as a chaperone of RNPs and how disruption of SMN-dependent RNA pathways can cause motor neuron disease. PMID:24769255

Formation of aqueous-phase sulfate during the haze period in China: Kinetics and atmospheric implications

NASA Astrophysics Data System (ADS)

Zhang, Haijie; Chen, Shilu; Zhong, Jie; Zhang, Shaowen; Zhang, Yunhong; Zhang, Xiuhui; Li, Zesheng; Zeng, Xiao Cheng

2018-03-01

Sulfate is one of the most important components in the aerosol due to its key role in air pollution and global climate change. Recent work has suggested that reactive nitrogen chemistry in aqueous water can explain the missing source of sulfate in the aqueous water. Herein, we have mapped out the energy profile of the oxidization process of SO2 leading from NO2 and two feasible three-step mechanisms have been proposed. For the oxidation of HOSO2- and HSO3- by the dissolved NO2 in weakly acidic and neutral aerosol (pH ≤ 7), the main contribution to the missing sulfate production comes from the oxidation of HOSO2-. The whole process is a self-sustaining process. For the oxidation of SO32- in alkaline aerosol (pH > 7), the third step - decomposition step of H2O or hydrolysis of SO3 step which are two parallel processes are the rate-limiting steps. The present results are of avail to better understand the missing source of sulfate in the aerosol and hence may lead to better science-based solutions for resolving the severe haze problems in China.

Human Mars EDL Pathfinder Study: Assessment of Technology Development Gaps and Mitigations

NASA Technical Reports Server (NTRS)

Lillard, Randolph; Olejniczak, Joe; Polsgrove, Tara; Cianciolo, Alice Dwyer; Munk, Michelle; Whetsel, Charles; Drake, Bret

2017-01-01

This paper presents the results of a NASA initiated Agency-wide assessment to better characterize the risks and potential mitigation approaches associated with landing human class Entry, Descent, and Landing (EDL) systems on Mars. Due to the criticality and long-lead nature of advancing EDL techniques, it is necessary to determine an appropriate strategy to improve the capability to land large payloads. A key focus of this study was to understand the key EDL risks and with a focus on determining what "must" be tested at Mars. This process identified the various risks and potential risk mitigation strategies along with the key near term technology development efforts required and in what environment those technology demonstrations were best suited. The study identified key risks along with advantages to each entry technology. In addition, it was identified that provided the EDL concept of operations (con ops) minimized large scale transition events, there was no technology requirement for a Mars pre-cursor demonstration. Instead, NASA should take a direct path to a human-scale lander.

Giant photostriction in organic–inorganic lead halide perovskites

PubMed Central

Zhou, Yang; You, Lu; Wang, Shiwei; Ku, Zhiliang; Fan, Hongjin; Schmidt, Daniel; Rusydi, Andrivo; Chang, Lei; Wang, Le; Ren, Peng; Chen, Liufang; Yuan, Guoliang; Chen, Lang; Wang, Junling

2016-01-01

Among the many materials investigated for next-generation photovoltaic cells, organic–inorganic lead halide perovskites have demonstrated great potential thanks to their high power conversion efficiency and solution processability. Within a short period of about 5 years, the efficiency of solar cells based on these materials has increased dramatically from 3.8 to over 20%. Despite the tremendous progress in device performance, much less is known about the underlying photophysics involving charge–orbital–lattice interactions and the role of the organic molecules in this hybrid material remains poorly understood. Here, we report a giant photostrictive response, that is, light-induced lattice change, of >1,200 p.p.m. in methylammonium lead iodide, which could be the key to understand its superior optical properties. The strong photon-lattice coupling also opens up the possibility of employing these materials in wireless opto-mechanical devices. PMID:27044485

Scratching the surface: the processing of pain from deep tissues.

PubMed

Sikandar, Shafaq; Aasvang, Eske Kvanner; Dickenson, Anthony H

2016-04-01

Although most pain research focuses on skin, muscles, joints and viscerae are major sources of pain. We discuss the mechanisms of deep pains arising from somatic and visceral structures and how this can lead to widespread manifestations and chronification. We include how both altered peripheral and central sensory neurotransmission lead to deep pain states and comment on key areas such as top-down modulation where little is known. It is vital that the clinical characterization of deep pain in patients is improved to allow for back translation to preclinical models so that the missing links can be ascertained. The contribution of deeper somatic and visceral tissues to various chronic pain syndromes is common but there is much we need to know.

Topological nature of the inertiality of a nonequilibrium system far from equilibrium

NASA Astrophysics Data System (ADS)

Saikhanov, M. B.

2017-04-01

We consider inertial and topological properties of a nonequilibrium system far from the equilibrium. We show that from the topological standpoint, the layered structure of the energy levels of a nonequilibrium system leads to the concept of connectivity. We state an assumption on the key role of the dimension of the hypersurface of the full entropy production in the study of the inertiality of an irreversible process in a nonequilibrium system including in the region of unstable states.

Human Planetary Landing System (HPLS) Capability Roadmap NRC Progress Review

NASA Technical Reports Server (NTRS)

Manning, Rob; Schmitt, Harrison H.; Graves, Claude

2005-01-01

Capability Roadmap Team. Capability Description, Scope and Capability Breakdown Structure. Benefits of the HPLS. Roadmap Process and Approach. Current State-of-the-Art, Assumptions and Key Requirements. Top Level HPLS Roadmap. Capability Presentations by Leads. Mission Drivers Requirements. "AEDL" System Engineering. Communication & Navigation Systems. Hypersonic Systems. Super to Subsonic Decelerator Systems. Terminal Descent and Landing Systems. A Priori In-Situ Mars Observations. AEDL Analysis, Test and Validation Infrastructure. Capability Technical Challenges. Capability Connection Points to other Roadmaps/Crosswalks. Summary of Top Level Capability. Forward Work.

Single service point: it's all in the design.

PubMed

Bradigan, Pamela S; Rodman, Ruey L

2008-01-01

"Design thinking" principles from a leading design firm, IDEO, were key elements in the planning process for a one-desk service model, the ASK Desk, at the John A. Prior Health Sciences Library. The library administration and staff employed the methodology to enhance customer experiences, meet technology challenges, and compete in a changing education environment. The most recent renovations demonstrate how the principles were applied. The concept of "continuous design thinking" is important in the library's daily operations to serve customers most effectively.

Enantioselective Syntheses of (−)-Alloyohimbane and (−)-Yohimbane by an Efficient Enzymatic Desymmetrization Process

PubMed Central

Ghosh, Arun K.; Sarkar, Anindya

2016-01-01

Enantioselective syntheses of (−)-alloyohimbane and (−)-yohimbane was accomplished in a convergent manner. The key step involved a modified mild protocol for the enantioselective enzymatic desymmetrization of meso-diacetate. The protocol provided convenient access to an optically active monoacetate in multi-gram scale in high enantiomeric purity. This monoacetate was converted to (−)-alloyohimbane. Reductive amination of the derived aldehyde causes the isomerization leading to the trans-product and allows the synthesis of (−)-yohimbane. PMID:28757804

Structural, Thermodynamic, and Functional Mechanisms of Adaptations WrbA and AdoMetDC Proteins in Extremophilic Organisms

DTIC Science & Technology

2007-08-15

thermophilic ) and low (psychrophilic). A model protein used in this study, S- adenosyl-methionine decarboxylase (AdoMetDC), is a key enzyme in the polyamine...experimental characterization of the thermophilic AdoMtDC from Termatoga maritima. The processing of TmAdoMetDC that leads to catalytically active enzyme is... thermophilic organisms. One of the open questions of structural biology is the understanding of the mechanisms by which enzymes adapt to extreme temperatures

The art of delegation.

PubMed

Linney, B J

1998-01-01

Effective delegation is a large of a manager's position. Physician executives are expected to be skilled delegators and able to lead team efforts to meet larger organizational goals. Delegation should be a five-step process: (1) Describe the results you want; (2) Listen for suggestions about how the task should be done; (3) Give autonomy and freedom to accomplish the task; (4) Follow up; and (5) Give feedback and credit. This column explores the art of delegating and how to assess your skills in this key management area.

Extrasolar planets: constraints for planet formation models.

PubMed

Santos, Nuno C; Benz, Willy; Mayor, Michel

2005-10-14

Since 1995, more than 150 extrasolar planets have been discovered, most of them in orbits quite different from those of the giant planets in our own solar system. The number of discovered extrasolar planets demonstrates that planetary systems are common but also that they may possess a large variety of properties. As the number of detections grows, statistical studies of the properties of exoplanets and their host stars can be conducted to unravel some of the key physical and chemical processes leading to the formation of planetary systems.

An Insoluble Titanium-Lead Anode for Sulfate Electrolytes

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

Ferdman, Alla

2005-05-11

The project is devoted to the development of novel insoluble anodes for copper electrowinning and electrolytic manganese dioxide (EMD) production. The anodes are made of titanium-lead composite material produced by techniques of powder metallurgy, compaction of titanium powder, sintering and subsequent lead infiltration. The titanium-lead anode combines beneficial electrochemical behavior of a lead anode with high mechanical properties and corrosion resistance of a titanium anode. In the titanium-lead anode, the titanium stabilizes the lead, preventing it from spalling, and the lead sheathes the titanium, protecting it from passivation. Interconnections between manufacturing process, structure, composition and properties of the titanium-lead compositemore » material were investigated. The material containing 20-30 vol.% of lead had optimal combination of mechanical and electrochemical properties. Optimal process parameters to manufacture the anodes were identified. Prototypes having optimized composition and structure were produced for testing in operating conditions of copper electrowinning and EMD production. Bench-scale, mini-pilot scale and pilot scale tests were performed. The test anodes were of both a plate design and a flow-through cylindrical design. The cylindrical anodes were composed of cylinders containing titanium inner rods and fitting over titanium-lead bushings. The cylindrical design allows the electrolyte to flow through the anode, which enhances diffusion of the electrolyte reactants. The cylindrical anodes demonstrate higher mass transport capabilities and increased electrical efficiency compared to the plate anodes. Copper electrowinning represents the primary target market for the titanium-lead anode. A full-size cylindrical anode performance in copper electrowinning conditions was monitored over a year. The test anode to cathode voltage was stable in the 1.8 to 2.0 volt range. Copper cathode morphology was very smooth and uniform. There was no measurable anode weight loss during this time period. Quantitative chemical analysis of the anode surface showed that the lead content after testing remained at its initial level. No lead dissolution or transfer from the anode to the product occurred.A key benefit of the titanium-lead anode design is that cobalt additions to copper electrolyte should be eliminated. Cobalt is added to the electrolyte to help stabilize the lead oxide surface of conventional lead anodes. The presence of the titanium intimately mixed with the lead should eliminate the need for cobalt stabilization of the lead surface. The anode should last twice as long as the conventional lead anode. Energy savings should be achieved due to minimizing and stabilizing the anode-cathode distance in the electrowinning cells. The anode is easily substitutable into existing tankhouses without a rectifier change.The copper electrowinning test data indicate that the titanium-lead anode is a good candidate for further testing as a possible replacement for a conventional lead anode. A key consideration is the cost. Titanium costs have increased. One of the ways to get the anode cost down is manufacturing the anodes with fewer cylinders. Additional prototypes having different number of cylinders were constructed for a long-term commercial testing in a circuit without cobalt. The objective of the testing is to evaluate the need for cobalt, investigate the effect of decreasing the number of cylinders on the anode performance, and to optimize further the anode design in order to meet the operating requirements, minimize the voltage, maximize the life of the anode, and to balance this against a reasonable cost for the anode. It is anticipated that after testing of the additional prototypes, a whole cell commercial test will be conducted to complete evaluation of the titanium-lead anode costs/benefits.« less

Biogas Production: Microbiology and Technology.

PubMed

Schnürer, Anna

Biogas, containing energy-rich methane, is produced by microbial decomposition of organic material under anaerobic conditions. Under controlled conditions, this process can be used for the production of energy and a nutrient-rich residue suitable for use as a fertilising agent. The biogas can be used for production of heat, electricity or vehicle fuel. Different substrates can be used in the process and, depending on substrate character, various reactor technologies are available. The microbiological process leading to methane production is complex and involves many different types of microorganisms, often operating in close relationships because of the limited amount of energy available for growth. The microbial community structure is shaped by the incoming material, but also by operating parameters such as process temperature. Factors leading to an imbalance in the microbial community can result in process instability or even complete process failure. To ensure stable operation, different key parameters, such as levels of degradation intermediates and gas quality, are often monitored. Despite the fact that the anaerobic digestion process has long been used for industrial production of biogas, many questions need still to be resolved to achieve optimal management and gas yields and to exploit the great energy and nutrient potential available in waste material. This chapter discusses the different aspects that need to be taken into consideration to achieve optimal degradation and gas production, with particular focus on operation management and microbiology.

AgMIP: Next Generation Models and Assessments

NASA Astrophysics Data System (ADS)

Rosenzweig, C.

2014-12-01

Next steps in developing next-generation crop models fall into several categories: significant improvements in simulation of important crop processes and responses to stress; extension from simplified crop models to complex cropping systems models; and scaling up from site-based models to landscape, national, continental, and global scales. Crop processes that require major leaps in understanding and simulation in order to narrow uncertainties around how crops will respond to changing atmospheric conditions include genetics; carbon, temperature, water, and nitrogen; ozone; and nutrition. The field of crop modeling has been built on a single crop-by-crop approach. It is now time to create a new paradigm, moving from 'crop' to 'cropping system.' A first step is to set up the simulation technology so that modelers can rapidly incorporate multiple crops within fields, and multiple crops over time. Then the response of these more complex cropping systems can be tested under different sustainable intensification management strategies utilizing the updated simulation environments. Model improvements for diseases, pests, and weeds include developing process-based models for important diseases, frameworks for coupling air-borne diseases to crop models, gathering significantly more data on crop impacts, and enabling the evaluation of pest management strategies. Most smallholder farming in the world involves integrated crop-livestock systems that cannot be represented by crop modeling alone. Thus, next-generation cropping system models need to include key linkages to livestock. Livestock linkages to be incorporated include growth and productivity models for grasslands and rangelands as well as the usual annual crops. There are several approaches for scaling up, including use of gridded models and development of simpler quasi-empirical models for landscape-scale analysis. On the assessment side, AgMIP is leading a community process for coordinated contributions to IPCC AR6 that involves the key modeling groups from around the world including North America, Europe, South America, Sub-Saharan Africa, South Asia, East Asia, and Australia and Oceania. This community process will lead to mutually agreed protocols for coordinated global and regional assessments.

DNA-PKcs deficiency leads to persistence of oxidatively-induced clustered DNA lesions in human tumor cells

PubMed Central

Peddi, Prakash; Loftin, Charles W.; Dickey, Jennifer S.; Hair, Jessica M.; Burns, Kara J.; Aziz, Khaled; Francisco, Dave C.; Panayiotidis, Mihalis I.; Sedelnikova, Olga A.; Bonner, William M.; Winters, Thomas A.; Georgakilas, Alexandros G.

2010-01-01

DNA-dependent protein kinase (DNA-PK) is a key non-homologous end joining (NHEJ) nuclear serine/threonine protein kinase involved in various DNA metabolic and damage signaling pathways contributing to the maintenance of genomic stability and prevention of cancer. In order to examine the role of DNA-PK in processing of non-DSB clustered DNA damage, we have used three different models of DNA-PK deficiency i.e. chemical inactivation of its kinase activity by novel inhibitors IC86621 and NU7026, knock-down and complete absence of the protein in human breast cancer (MCF-7) and glioblastoma cell lines (MO59-J/K). Compromised DNA-PK repair pathway has lead to accumulation of clustered DNA lesions induced by γ-rays. Tumor cells lacking protein expression or with inhibited kinase activity showed a marked decrease in their ability to process oxidatively-induced non-DSB clustered DNA lesions measured using a modified version of pulsed field gel electrophoresis or single cell gel electrophoresis (Comet assay). In all cases, DNA-PK inactivation lead to a higher level of lesion persistence even after 24–72 hrs of repair. We suggest a model in which DNA-PK deficiency affects the processing of these clusters by first compromising base excision repair and second by the presence of catalytically inactive DNA-PK inhibiting the efficient processing of these lesions due to the failure of DNA-PK to disassociate from the DNA ends. The information rendered will be important not only for understating cancer etiology in the presence of a NHEJ deficiency but also lead to a better understanding of cancer treatments based on the induction of oxidative stress and inhibition of cluster repair. PMID:20193758

At the interface of antioxidant signalling and cellular function: Key polyphenol effects

PubMed Central

Kerimi, Asimina

2016-01-01

The hypothesis that dietary (poly)phenols promote well‐being by improving chronic disease‐risk biomarkers, such as endothelial dysfunction, chronic inflammation and plasma uric acid, is the subject of intense current research, involving human interventions studies, animal models and in vitro mechanistic work. The original claim that benefits were due to the direct antioxidant properties of (poly)phenols has been mostly superseded by detailed mechanistic studies on specific molecular targets. Nevertheless, many proposed mechanisms in vivo and in vitro are due to modulation of oxidative processes, often involving binding to specific proteins and effects on cell signalling. We review the molecular mechanisms for 3 actions of (poly)phenols on oxidative processes where there is evidence in vivo from human intervention or animal studies. (1) Effects of (poly) phenols on pathways of chronic inflammation leading to prevention of some of the damaging effects associated with the metabolic syndrome. (2) Interaction of (poly)phenols with endothelial cells and smooth muscle cells, leading to effects on blood pressure and endothelial dysfunction, and consequent reduction in cardiovascular disease risk. (3) The inhibition of xanthine oxidoreductase leading to modulation of intracellular superoxide and plasma uric acid, a risk factor for developing type 2 diabetes. PMID:26887821

Mixed-Initiative Constraint-Based Activity Planning for Mars Exploration Rovers

NASA Technical Reports Server (NTRS)

Bresina, John; Jonsson, Ari K.; Morris, Paul H.; Rajan, Kanna

2004-01-01

In January, 2004, two NASA rovers, named Spirit and Opportunity, successfully landed on Mars, starting an unprecedented exploration of the Martian surface. Power and thermal concerns constrained the duration of this mission, leading to an aggressive plan for commanding both rovers every day. As part of the process for generating these command loads, the MAPGEN tool provides engineers and scientists an intelligent activity planning tool that allows them to more effectively generate complex plans that maximize the science return each day. The key to'the effectiveness of the MAPGEN tool is an underlying artificial intelligence plan and constraint reasoning engine. In this paper we outline the design and functionality of the MAEPGEN tool and focus on some of the key capabilities it offers to the MER mission engineers.

The challenge of causal inference in gene-environment interaction research: leveraging research designs from the social sciences.

PubMed

Fletcher, Jason M; Conley, Dalton

2013-10-01

The integration of genetics and the social sciences will lead to a more complex understanding of the articulation between social and biological processes, although the empirical difficulties inherent in this integration are large. One key challenge is the implications of moving "outside the lab" and away from the experimental tools available for research with model organisms. Social science research methods used to examine human behavior in nonexperimental, real-world settings to date have not been fully taken advantage of during this disciplinary integration, especially in the form of gene-environment interaction research. This article outlines and provides examples of several prominent research designs that should be used in gene-environment research and highlights a key benefit to geneticists of working with social scientists.

Mathematical models of the AIDS epidemic: An historical perspective

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

Stanley, E.A.

1988-01-01

Researchers developing mathematical models of the spreading of HIV, the Human Immunodeficiency Virus that causes AIDS, hope to achieve a number of goals. These goals may be classified rather broadly into three categories: understanding, prediction, and control. Understanding which are the key biological and sociological processes spreading this epidemic and leading to the deaths of those infected will allow AIDS researchers to collect better data and to identify ways of slowing the epidemic. Predicting the groups at risk and future numbers of ill people will allow an appropriate allocation of health-care resources. Analysis and comparison of proposed control methods willmore » point out unexpected consequences and allow a better design of these programs. The processes which lead to the spread of HIV are biologically and sociologically complex. Mathematical models allow us to organize our knowledge into a coherent picture and examine the logical consequences, therefore they have the potential to be extremely useful in the search to control this disease. 24 refs., 3 figs.« less

One-pot aldol condensation and hydrodeoxygenation of biomass-derived carbonyl compounds for biodiesel synthesis.

PubMed

Faba, Laura; Díaz, Eva; Ordóñez, Salvador

2014-10-01

Integrating reaction steps is of key interest in the development of processes for transforming lignocellulosic materials into drop-in fuels. We propose a procedure for performing the aldol condensation (reaction between furfural and acetone is taken as model reaction) and the total hydrodeoxygenation of the resulting condensation adducts in one step, yielding n-alkanes. Different combinations of catalysts (bifunctional catalysts or mechanical mixtures), reaction conditions, and solvents (aqueous and organic) have been tested for performing these reactions in an isothermal batch reactor. The results suggest that the use of bifunctional catalysts and aqueous phase lead to an effective integration of both reactions. Therefore, selectivities to n-alkanes higher than 50% were obtained using this catalyst at typical hydrogenation conditions (T=493 K, P=4.5 MPa, 24 h reaction time). The use of organic solvent, carbonaceous supports, or mechanical mixtures of monofunctional catalysts leads to poorer results owing to side effects; mainly, hydrogenation of reactants and adsorption processes. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dissecting genomic imprinting and genetic conflict from a game theory prospective. Comment on: ;Epigenetic game theory: How to compute the epigenetic control of maternal-to-zygotic transition; by Qian Wang et al.

NASA Astrophysics Data System (ADS)

Cui, Yuehua; Yang, Haitao

2017-03-01

Epigenetics typically refers to changes in the structure of a chromosome that affect gene activity and expression. Genomic imprinting is a special type of epigenetic phenomenon in which the expression of an allele depends on its parental origin. When an allele inherited from the mother (or father) is imprinted (i.e., silent), it is termed as maternal (or paternal) imprinting. Imprinting is often resulted from DNA methylation and tends to cluster together in the genome [1]. It has been shown to play a key role in many genetic disorders in humans [2]. Imprinting is heritable and undergoes a reprogramming process in gametes before and after fertilization [1]. Sometimes the reprogramming process is not reversible, leading to the loss of imprinting [3]. Although efforts have been made to experimentally or computationally infer imprinting genes, the underlying molecular mechanism that leads to unbalanced allelic expression is still largely unknown.

The graphene oxide membrane immersing in the aqueous solution studied by electrochemical impedance spectroscopy

NASA Astrophysics Data System (ADS)

Zhang, Yongjing; Chen, Zhe; Yao, Lei; Wang, Xiao; Fu, Ping; Lin, Zhidong

2018-04-01

The interlayer spacing of graphene oxide (GO) is a key property for GO membrane. To probe the variation of interlayer spacing of the GO membrane immersing in KCl aqueous solution, electrochemical impedance spectroscopy (EIS), x-ray diffraction (XRD) and computational calculation was utilized in this study. The XRD patterns show that soaking in KCl aqueous solution leads to an increase of interlayer spacing of GO membrane. And the EIS results indicate that during the immersing process, the charge transfer resistance of GO membrane decreases first and then increases. Computational calculation confirms that intercalated water molecules can result in an increase of interlayer spacing of GO membrane, while the permeation of K+ ions would lead to a decrease of interlayer spacing. All the results are in agreement with each other. It suggests that during the immersing process, the interlayer spacing of GO enlarges first and then decreases. EIS can be a promisingly online method for examining the interlayer spacing of GO in the aqueous solution.

Ethylene Control of Fruit Ripening: Revisiting the Complex Network of Transcriptional Regulation1

PubMed Central

Chervin, Christian; Bouzayen, Mondher

2015-01-01

The plant hormone ethylene plays a key role in climacteric fruit ripening. Studies on components of ethylene signaling have revealed a linear transduction pathway leading to the activation of ethylene response factors. However, the means by which ethylene selects the ripening-related genes and interacts with other signaling pathways to regulate the ripening process are still to be elucidated. Using tomato (Solanum lycopersicum) as a reference species, the present review aims to revisit the mechanisms by which ethylene regulates fruit ripening by taking advantage of new tools available to perform in silico studies at the genome-wide scale, leading to a global view on the expression pattern of ethylene biosynthesis and response genes throughout ripening. Overall, it provides new insights on the transcriptional network by which this hormone coordinates the ripening process and emphasizes the interplay between ethylene and ripening-associated developmental factors and the link between epigenetic regulation and ethylene during fruit ripening. PMID:26511917

Development of a Hybrid Deep Drawing Process to Reduce Springback of AHSS

NASA Astrophysics Data System (ADS)

Boskovic, Vladimir; Sommitsch, Christoph; Kicin, Mustafa

2017-09-01

In future, the steel manufacturers will strive for the implementation of Advanced High Strength Steels (AHSS) in the automotive industry to reduce mass and improve structural performance. A key challenge is the definition of optimal and cost effective processes as well as solutions to introduce complex steel products in cold forming. However, the application of these AHSS often leads to formability problems such as springback. One promising approach in order to minimize springback is the relaxation of stress through the targeted heating of materials in the radius area after the deep drawing process. In this study, experiments are conducted on a Dual Phase (DP) and TWining Induced Plasticity (TWIP) steel for the process feasibility study. This work analyses the influence of various heat treatment temperatures on the springback reduction of deep drawn AHSS.

Small Molecule Modulators of Pre-mRNA Splicing in Cancer Therapy.

PubMed

Salton, Maayan; Misteli, Tom

2016-01-01

Pre-mRNA splicing is a fundamental process in mammalian gene expression and alternative RNA splicing plays a considerable role in generating protein diversity. RNA splicing events are also key to the pathology of numerous diseases, particularly cancers. Some tumors are molecularly addicted to specific RNA splicing isoforms making interference with pre-mRNA processing a viable therapeutic strategy. Several RNA splicing modulators have recently been characterized, some showing promise in preclinical studies. While the targets of most splicing modulators are constitutive RNA processing components, possibly leading to undesirable side effects, selectivity for individual splicing events has been observed. Given the high prevalence of splicing defects in cancer, small molecule modulators of RNA processing represent a potentially promising novel therapeutic strategy in cancer treatment. Here, we review their reported effects, mechanisms, and limitations. Published by Elsevier Ltd.

Evolving trends in mAb production processes

PubMed Central

Wolfe, Leslie S.; Mostafa, Sigma S.; Norman, Carnley

2017-01-01

Abstract Monoclonal antibodies (mAbs) have established themselves as the leading biopharmaceutical therapeutic modality. The establishment of robust manufacturing platforms are key for antibody drug discovery efforts to seamlessly translate into clinical and commercial successes. Several drivers are influencing the design of mAb manufacturing processes. The advent of biosimilars is driving a desire to achieve lower cost of goods and globalize biologics manufacturing. High titers are now routinely achieved for mAbs in mammalian cell culture. These drivers have resulted in significant evolution in process platform approaches. Additionally, several new trends in bioprocessing have arisen in keeping with these needs. These include the consideration of alternative expression systems, continuous biomanufacturing and non‐chromatographic separation formats. This paper discusses these drivers in the context of the kinds of changes they are driving in mAb production processes. PMID:29313024

Lattice Boltzmann simulations of immiscible displacement process with large viscosity ratios

NASA Astrophysics Data System (ADS)

Rao, Parthib; Schaefer, Laura

2017-11-01

Immiscible displacement is a key physical mechanism involved in enhanced oil recovery and carbon sequestration processes. This multiphase flow phenomenon involves a complex interplay of viscous, capillary, inertial and wettability effects. The lattice Boltzmann (LB) method is an accurate and efficient technique for modeling and simulating multiphase/multicomponent flows especially in complex flow configurations and media. In this presentation we present numerical simulation results of displacement process in thin long channels. The results are based on a new psuedo-potential multicomponent LB model with multiple relaxation time collision (MRT) model and explicit forcing scheme. We demonstrate that the proposed model is capable of accurately simulating the displacement process involving fluids with a wider range of viscosity ratios (>100) and which also leads to viscosity-independent interfacial tension and reduction of some important numerical artifacts.

ER Stress-Mediated Signaling: Action Potential and Ca(2+) as Key Players.

PubMed

Bahar, Entaz; Kim, Hyongsuk; Yoon, Hyonok

2016-09-15

The proper functioning of the endoplasmic reticulum (ER) is crucial for multiple cellular activities and survival. Disturbances in the normal ER functions lead to the accumulation and aggregation of unfolded proteins, which initiates an adaptive response, the unfolded protein response (UPR), in order to regain normal ER functions. Failure to activate the adaptive response initiates the process of programmed cell death or apoptosis. Apoptosis plays an important role in cell elimination, which is essential for embryogenesis, development, and tissue homeostasis. Impaired apoptosis can lead to the development of various pathological conditions, such as neurodegenerative and autoimmune diseases, cancer, or acquired immune deficiency syndrome (AIDS). Calcium (Ca(2+)) is one of the key regulators of cell survival and it can induce ER stress-mediated apoptosis in response to various conditions. Ca(2+) regulates cell death both at the early and late stages of apoptosis. Severe Ca(2+) dysregulation can promote cell death through apoptosis. Action potential, an electrical signal transmitted along the neurons and muscle fibers, is important for conveying information to, from, and within the brain. Upon the initiation of the action potential, increased levels of cytosolic Ca(2+) (depolarization) lead to the activation of the ER stress response involved in the initiation of apoptosis. In this review, we discuss the involvement of Ca(2+) and action potential in ER stress-mediated apoptosis.

Simulating Complex, Cold-region Process Interactions Using a Multi-scale, Variable-complexity Hydrological Model

NASA Astrophysics Data System (ADS)

Marsh, C.; Pomeroy, J. W.; Wheater, H. S.

2017-12-01

Accurate management of water resources is necessary for social, economic, and environmental sustainability worldwide. In locations with seasonal snowcovers, the accurate prediction of these water resources is further complicated due to frozen soils, solid-phase precipitation, blowing snow transport, and snowcover-vegetation-atmosphere interactions. Complex process interactions and feedbacks are a key feature of hydrological systems and may result in emergent phenomena, i.e., the arising of novel and unexpected properties within a complex system. One example is the feedback associated with blowing snow redistribution, which can lead to drifts that cause locally-increased soil moisture, thus increasing plant growth that in turn subsequently impacts snow redistribution, creating larger drifts. Attempting to simulate these emergent behaviours is a significant challenge, however, and there is concern that process conceptualizations within current models are too incomplete to represent the needed interactions. An improved understanding of the role of emergence in hydrological systems often requires high resolution distributed numerical hydrological models that incorporate the relevant process dynamics. The Canadian Hydrological Model (CHM) provides a novel tool for examining cold region hydrological systems. Key features include efficient terrain representation, allowing simulations at various spatial scales, reduced computational overhead, and a modular process representation allowing for an alternative-hypothesis framework. Using both physics-based and conceptual process representations sourced from long term process studies and the current cold regions literature allows for comparison of process representations and importantly, their ability to produce emergent behaviours. Examining the system in a holistic, process-based manner can hopefully derive important insights and aid in development of improved process representations.

Role of Australian primary healthcare organisations (PHCOs) in primary healthcare (PHC) workforce planning: lessons from abroad.

PubMed

Naccarella, Lucio; Buchan, James; Newton, Bill; Brooks, Peter

2011-08-01

To review international experience in order to inform Australian PHC workforce policy on the role of primary healthcare organisations (PHCOs/Medicare Locals) in PHC workforce planning. A NZ and UK study tour was conducted by the lead author, involving 29 key informant interviews with regard to PHCOs roles and the effect on PHC workforce planning. Interviews were audio-taped with consent, transcribed and analysed thematically. Emerging themes included: workforce planning is a complex, dynamic, iterative process and key criteria exist for doing workforce planning well; PHCOs lacked a PHC workforce policy framework to do workforce planning; PHCOs lacked authority, power and appropriate funding to do workforce planning; there is a need to align workforce planning with service planning; and a PHC Workforce Planning and Development Benchmarking Database is essential for local planning and evaluating workforce reforms. With the Australian government promoting the role of PHCOs in health system reform, reflections from abroad highlight the key action within PHC and PHCOs required to optimise PHC workforce planning.

Country watch: Zimbabwe.

PubMed

Laver, S

1999-01-01

Tsungirirai is a counseling and information service developed during 1994 in response to the growing problem of HIV/AIDS in the small town of Norton, southwest of Harare, Zimbabwe. The objectives of the project include identification of key leaders in the area, determination of the setting in which HIV was spreading, and community consultation in program design and implementation. Tsungirirai's initial activities included a series of workshops on participatory techniques particularly the LADA (Listening-Appraisal-Dialogue-Action) method for key leaders, community men, women, and adolescents. Workshop participants demonstrated different views concerning HIV/AIDS problems. Key leaders viewed the HIV/AIDS problem within the context of existing laws that contradict traditional mores, while the youth linked the problem of HIV to the issue of unemployment and lack of recreation. Lessons learned include the following: 1) stop talking and listen; 2) start where people are at instead of telling them what they already know; 3) let the people decide; 4) turn a dream into reality; and 5) facilitate awareness process instead of leading it.

Strengthening ecological mindfulness through hybrid learning in vital coalitions

NASA Astrophysics Data System (ADS)

Sol, Jifke; Wals, Arjen E. J.

2015-03-01

In this contribution a key policy `tool' used in the Dutch Environmental Education and Learning for Sustainability Policy framework is introduced as a means to develop a sense of place and associated ecological mindfulness. The key elements of this tool, called the vital coalition, are described while an example of its use in practice, is analysed using a form of reflexive monitoring and evaluation. The example focuses on a multi-stakeholder learning process around the transformation of a somewhat sterile pre-school playground into an intergenerational green place suitable for play, discovery and engagement. Our analysis of the policy-framework and the case leads us to pointing out the importance of critical interventions at so-called tipping points within the transformation process and a discussion of the potential of hybrid learning in vital coalitions in strengthening ecological mindfulness. This paper does not focus on establishing an evidence base for the causality between this type of learning and a change in behavior or mindfulness among participants as a result contributing to a vital coalition but rather focusses on the conditions, processes and interventions that allow for such learning to take place in the first place.

Perturbations to trophic interactions and the stability of complex food webs

PubMed Central

O'Gorman, Eoin J.; Emmerson, Mark C.

2009-01-01

The pattern of predator–prey interactions is thought to be a key determinant of ecosystem processes and stability. Complex ecological networks are characterized by distributions of interaction strengths that are highly skewed, with many weak and few strong interactors present. Theory suggests that this pattern promotes stability as weak interactors dampen the destabilizing potential of strong interactors. Here, we present an experimental test of this hypothesis and provide empirical evidence that the loss of weak interactors can destabilize communities in nature. We ranked 10 marine consumer species by the strength of their trophic interactions. We removed the strongest and weakest of these interactors from experimental food webs containing >100 species. Extinction of strong interactors produced a dramatic trophic cascade and reduced the temporal stability of key ecosystem process rates, community diversity and resistance to changes in community composition. Loss of weak interactors also proved damaging for our experimental ecosystems, leading to reductions in the temporal and spatial stability of ecosystem process rates, community diversity, and resistance. These results highlight the importance of conserving species to maintain the stabilizing pattern of trophic interactions in nature, even if they are perceived to have weak effects in the system. PMID:19666606

Application of System Operational Effectiveness Methodology to Space Launch Vehicle Development and Operations

NASA Technical Reports Server (NTRS)

Watson, Michael D.; Kelley, Gary W.

2012-01-01

The Department of Defense (DoD) defined System Operational Effectiveness (SOE) model provides an exceptional framework for an affordable approach to the development and operation of space launch vehicles and their supporting infrastructure. The SOE model provides a focal point from which to direct and measure technical effectiveness and process efficiencies of space launch vehicles. The application of the SOE model to a space launch vehicle's development and operation effort leads to very specific approaches and measures that require consideration during the design phase. This paper provides a mapping of the SOE model to the development of space launch vehicles for human exploration by addressing the SOE model key points of measurement including System Performance, System Availability, Technical Effectiveness, Process Efficiency, System Effectiveness, Life Cycle Cost, and Affordable Operational Effectiveness. In addition, the application of the SOE model to the launch vehicle development process is defined providing the unique aspects of space launch vehicle production and operations in lieu of the traditional broader SOE context that examines large quantities of fielded systems. The tailoring and application of the SOE model to space launch vehicles provides some key insights into the operational design drivers, capability phasing, and operational support systems.

The first thousand days - intestinal microbiology of early life: establishing a symbiosis.

PubMed

Wopereis, Harm; Oozeer, Raish; Knipping, Karen; Belzer, Clara; Knol, Jan

2014-08-01

The development of the intestinal microbiota in the first years of life is a dynamic process significantly influenced by early-life nutrition. Pioneer bacteria colonizing the infant intestinal tract and the gradual diversification to a stable climax ecosystem plays a crucial role in establishing host-microbe interactions essential for optimal symbiosis. This colonization process and establishment of symbiosis may profoundly influence health throughout life. Recent developments in microbiologic cultivation-independent methods allow a detailed view of the key players and factors involved in this process and may further elucidate their roles in a healthy gut and immune maturation. Aberrant patterns may lead to identifying key microbial signatures involved in developing immunologic diseases into adulthood, such as asthma and atopic diseases. The central role of early-life nutrition in the developmental human microbiota, immunity, and metabolism offers promising strategies for prevention and treatment of such diseases. This review provides an overview of the development of the intestinal microbiota, its bidirectional relationship with the immune system, and its role in impacting health and disease, with emphasis on allergy, in early life. © 2014 Danone Nutricia Research. Pediatric Allergy and Immunology published by John Wiley & Sons Ltd.

Influences of thermal environment on fish growth.

PubMed

Boltaña, Sebastián; Sanhueza, Nataly; Aguilar, Andrea; Gallardo-Escarate, Cristian; Arriagada, Gabriel; Valdes, Juan Antonio; Soto, Doris; Quiñones, Renato A

2017-09-01

Thermoregulation in ectothermic animals is influenced by the ability to effectively respond to thermal variations. While it is known that ectotherms are affected by thermal changes, it remains unknown whether physiological and/or metabolic traits are impacted by modifications to the thermal environment. Our research provides key evidence that fish ectotherms are highly influenced by thermal variability during development, which leads to important modifications at several metabolic levels (e.g., growth trajectories, microstructural alterations, muscle injuries, and molecular mechanisms). In Atlantic salmon ( Salmo salar ), a wide thermal range (Δ T 6.4°C) during development (posthatch larvae to juveniles) was associated with increases in key thermal performance measures for survival and growth trajectory. Other metabolic traits were also significantly influenced, such as size, muscle cellularity, and molecular growth regulators possibly affected by adaptive processes. In contrast, a restricted thermal range (Δ T 1.4°C) was detrimental to growth, survival, and cellular microstructure as muscle growth could not keep pace with increased metabolic demands. These findings provide a possible basic explanation for the effects of thermal environment during growth. In conclusion, our results highlight the key role of thermal range amplitude on survival and on interactions with major metabolism-regulating processes that have positive adaptive effects for organisms.

Curated Collections for Educators: Five Key Papers about Residents as Teachers Curriculum Development.

PubMed

Krzyzaniak, Sara M; Cherney, Alan; Messman, Anne; Natesan, Sreeja; Overbeck, Michael; Schnapp, Benjamin; Boysen-Osborn, Megan

2018-02-04

The Accreditation Council for Graduate Medical Education (ACGME) requires residency programs to prepare residents to teach and assess medical students and other learners. In order to achieve this, many programs develop formal residents as teachers (RAT) curricula. Medical educators may seek the guidance of previously published literature during the development of RAT programs at their institutions. The authors sought to identify key articles published on the subject of RAT programs over the last 10 years. The authors utilized a formal literature search with the help of a medical librarian and identified additional articles from virtual discussions among the author group and an open call for articles on Twitter using the hashtag #MedEd. Virtual discussions occurred within an online community of practice, the Academic Life in Emergency Medicine (ALiEM) Faculty Incubator. The lead author conducted a four-round modified Delphi process among the author group in order to narrow the broad article list to five key articles on RAT programs. The authors summarize each article and provide considerations for junior faculty as well as faculty developers. Curriculum development and program evaluation should utilize established frameworks and evidence-based approaches. The papers identified by this Delphi process will help faculty use best practices when creating or revising new RAT curriculum. In addition, faculty tasked with guiding junior faculty in this process or creating faculty development programs around curriculum development will find these articles to be a great resource for building content.

Alignment and political will: upscaling an Australian respectful relationships program.

PubMed

Joyce, Andrew; Green, Celia; Kearney, Sarah; Leung, Loksee; Ollis, Debbie

2018-05-29

Many small scale efficacious programs and interventions need to be 'scaled-up' in order to reach a larger population. Although it has been argued that interventions deemed suitable for upscaling need to have demonstrated effectiveness, be able to be implemented cost-effectively and be accepted by intended recipients, these factors alone are insufficient in explaining which programs are adopted more broadly. Upscaling research often identifies political will as a key factor in explaining whether programs are supported and up-scaled, but this research lacks any depth into how political will is formed and has not applied policy theories to understanding the upscaling process. This article uses a political science lens to examine the key factors in the upscaling process of a Respectful Relationships in Schools Program. Focus groups and interviews were conducted with project staff, managers and community organizations involved in the program. The results reveal how a key focusing event related to a highly profiled personal tragedy propelled family violence into the national spotlight. At the same time, the organization leading the respectful relationships program leveraged their networks to position the program within the education department which enabled the government to quickly respond to the issue. The study highlights that political will is not a stand-alone factor as depicted by up-scaling models, but rather is the end point of a complex process that involves many elements including the establishment of networks and aligned programs that can capitalize when opportunities arise.

Curated Collections for Educators: Five Key Papers about Residents as Teachers Curriculum Development

PubMed Central

Cherney, Alan; Messman, Anne; Natesan, Sreeja; Overbeck, Michael; Schnapp, Benjamin; Boysen-Osborn, Megan

2018-01-01

The Accreditation Council for Graduate Medical Education (ACGME) requires residency programs to prepare residents to teach and assess medical students and other learners. In order to achieve this, many programs develop formal residents as teachers (RAT) curricula. Medical educators may seek the guidance of previously published literature during the development of RAT programs at their institutions. The authors sought to identify key articles published on the subject of RAT programs over the last 10 years. The authors utilized a formal literature search with the help of a medical librarian and identified additional articles from virtual discussions among the author group and an open call for articles on Twitter using the hashtag #MedEd. Virtual discussions occurred within an online community of practice, the Academic Life in Emergency Medicine (ALiEM) Faculty Incubator. The lead author conducted a four-round modified Delphi process among the author group in order to narrow the broad article list to five key articles on RAT programs. The authors summarize each article and provide considerations for junior faculty as well as faculty developers. Curriculum development and program evaluation should utilize established frameworks and evidence-based approaches. The papers identified by this Delphi process will help faculty use best practices when creating or revising new RAT curriculum. In addition, faculty tasked with guiding junior faculty in this process or creating faculty development programs around curriculum development will find these articles to be a great resource for building content. PMID:29637035

Forward Genetics Defines Xylt1 as a Key, Conserved Regulator of Early Chondrocyte Maturation and Skeletal Length

PubMed Central

Mis, Emily K.; Liem, Karel F.; Kong, Yong; Schwartz, Nancy B.; Domowicz, Miriam; Weatherbee, Scott D.

2014-01-01

The long bones of the vertebrate body are built by the initial formation of a cartilage template that is later replaced by mineralized bone. The proliferation and maturation of the skeletal precursor cells (chondrocytes) within the cartilage template and their replacement by bone is a highly coordinated process which, if misregulated, can lead to a number of defects including dwarfism and other skeletal deformities. This is exemplified by the fact that abnormal bone development is one of the most common types of human birth defects. Yet, many of the factors that initiate and regulate chondrocyte maturation are not known. We identified a recessive dwarf mouse mutant (pug) from an N-ethyl-N-nitrosourea (ENU) mutagenesis screen. pug mutant skeletal elements are patterned normally during development, but display a ~20% length reduction compared to wild-type embryos. We show that the pug mutation does not lead to changes in chondrocyte proliferation but instead promotes premature maturation and early ossification, which ultimately leads to disproportionate dwarfism. Using sequence capture and high-throughput sequencing, we identified a missense mutation in the Xylosyltransferase 1 (Xylt1) gene in pug mutants. Xylosyltransferases catalyze the initial step in glycosaminoglycan (GAG) chain addition to proteoglycan core proteins, and these modifications are essential for normal proteoglycan function. We show that the pug mutation disrupts Xylt1 activity and subcellular localization, leading to a reduction in GAG chains in pug mutants. The pug mutant serves as a novel model for mammalian dwarfism and identifies a key role for proteoglycan modification in the initiation of chondrocyte maturation. PMID:24161523

Effective treatment of olive mill effluents from two-phase and three-phase extraction processes by batch membranes in series operation upon threshold conditions.

PubMed

Ochando-Pulido, J M; Hodaifa, G; Victor-Ortega, M D; Rodriguez-Vives, S; Martinez-Ferez, A

2013-12-15

Production of olive oil results in the generation of high amounts of heavy polluted effluents characterized by extremely variable contaminants degree, leading to sensible complexity in treatment. In this work, batch membrane processes in series comprising ultrafiltration (UF), nanofiltration (NF) and reverse osmosis (RO) are used to purify the effluents exiting both the two-phase and tree-phase extraction processes to a grade compatible to the discharge in municipal sewer systems in Spain and Italy. However, one main problem in applying this technology to wastewater management issues is given by membrane fouling. In the last years, the threshold flux theory was introduced as a key tool to understand fouling problems, and threshold flux measurement can give valuable information regarding optimal membrane process design and operation. In the present manuscript, mathematical approach of threshold flux conditions for membranes operation is addressed, also implementing proper pretreatment processes such as pH-T flocculation and UV/TiO2 photocatalysis with ferromagnetic-core nanoparticles in order to reduce membranes fouling. Both influence the organic matter content as well as the particle size distribution of the solutes surviving in the wastewater stream, leading, when properly applied, to reduced fouling, higher rejection and recovery values, thus enhancing the economic feasibility of the process. Copyright © 2013 Elsevier B.V. All rights reserved.

A process model of technology innovation in governmental agencies: Insights from NASA’s science directorate

NASA Astrophysics Data System (ADS)

Szajnfarber, Zoe; Weigel, Annalisa L.

2013-03-01

This paper investigates the process through which new technical concepts are matured in the NASA innovation ecosystem. We propose an "epoch-shock" conceptualization as an alternative mental model to the traditional stage-gate view. The epoch-shock model is developed inductively, based on detailed empirical observations of the process, and validated, to the extent possible, through expert review. The paper concludes by illustrating how the new epoch-shock conceptualization could provide a useful basis for rethinking feasible interventions to improve innovation management in the space agency context. Where the more traditional stage-gate model leads to an emphasis on centralized flow control, the epoch-shock model acknowledges the decentralized, probabilistic nature of key interactions and highlights which aspects may be influenced.

Improving the relevance and efficiency of human exposure assessments within the process of regulatory risk assessment.

PubMed

Money, Chris

2018-01-24

The process for undertaking exposure assessments varies dependent on its purpose. But for exposure assessments to be relevant and accurate, they are reliant on access to reliable information on key exposure determinants. Acquiring such information is seldom straightforward and can take significant time and resources. This articles examines how the application of tiered and targeted approaches to information acquisition, within the context of European human health risk assessments, can not only lead to improvements in the efficiency and effectiveness of the process but also in the confidence of stakeholders in its outputs. The article explores how the benefits might be further improved through the coordination of such activities, as well as those areas that represent barriers to wider international harmonisation.

Foundational Report Series: Advanced Distribution Management Systems for Grid Modernization, High-Level Use Cases for DMS

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

Wang, Jianhui; Lu, Xiaonan; Martino, Sal

Many distribution management systems (DMS) projects have achieved limited success because the electric utility did not sufficiently plan for actual use of the DMS functions in the control room environment. As a result, end users were not clear on how to use the new application software in actual production environments with existing, well-established business processes. An important first step in the DMS implementation process is development and refinement of the “to be” business processes. Development of use cases for the required DMS application functions is a key activity that leads to the formulation of the “to be” requirements. It ismore » also an important activity that is needed to develop specifications that are used to procure a new DMS.« less

Double Beta Decay

NASA Astrophysics Data System (ADS)

Shirai, Junpei

Double beta decay is a key process to reveal a fundamental property of neutrinos. If neutrinos are Majorana particles, that is they are equivalent to their antiparticles, neutrinoless double beta (0νββ) decay, (A,Z) → (A,Z + 2) + 2e‑, would occur. The process is beyond the standard model and would lead to a scenario which can explain the extremely small masses of neutrinos and provide a solution to the current matter dominance of the world. In this talk experimental efforts searching for 0νββ decays are presented. Then, major 0νββ experiments together with searches using 136Xe nuclei are described, followed by the current status of the KamLAND-Zen experiment.

Public Health Systems Research: Setting a National Agenda

PubMed Central

Lenaway, Dennis; Halverson, Paul; Sotnikov, Sergey; Tilson, Hugh; Corso, Liza; Millington, Wayne

2006-01-01

The Institute of Medicine has recommended that policy decisions about improvement of national public health systems be guided by sound scientific evidence. However, to date there is no national research agenda to help guide public health systems. The Centers for Disease Control and Prevention was called upon to lead a collaborative consensus-based process to define key research questions and establish a framework to create opportunities to better coordinate, leverage, and identify public health resources, which are increasingly scarce. The public health systems research agenda that emerged from this process has 14 overarching priority research themes. This national agenda should stimulate and guide research to meet the urgent need to improve the nation’s public health systems. PMID:16449601

Adaptive harvest management of North American waterfowl populations: a brief history and future prospects

USGS Publications Warehouse

Nichols, J.D.; Runge, M.C.; Johnson, F.A.; Williams, B.K.

2007-01-01

Since 1995, the US Fish and Wildlife Service has used an adaptive approach to the management of sport harvest of mid-continent Mallard ducks (Anas platyrhynchos) in North America. This approach differs from many current approaches to conservation and management in requiring close collaboration between managers and scientists. Key elements of this process are objectives, alternative management actions, models permitting prediction of system responses, and a monitoring program. The iterative process produces optimal management decisions and leads to reduction in uncertainty about response of populations to management. This general approach to management has a number of desirable features and is recommended for use in many other programs of management and conservation.

Engineering evidence for carbon monoxide toxicity cases.

PubMed

Galatsis, Kosmas

2016-07-01

Unintentional carbon monoxide poisonings and fatalities lead to many toxicity cases. Given the unusual physical properties of carbon monoxide-in that the gas is odorless and invisible-unorganized and erroneous methods in obtaining engineering evidence as required during the discovery process often occurs. Such evidence gathering spans domains that include building construction, appliance installation, industrial hygiene, mechanical engineering, combustion and physics. In this paper, we attempt to place a systematic framework that is relevant to key aspects in engineering evidence gathering for unintentional carbon monoxide poisoning cases. Such a framework aims to increase awareness of this process and relevant issues to help guide legal counsel and expert witnesses. © The Author(s) 2015.

Selective mutism: a consensus based care pathway of good practice.

PubMed

Keen, D V; Fonseca, S; Wintgens, A

2008-10-01

Selective mutism (SM) now acknowledged as an anxiety condition, tends to be a poorly understood, highly complex and vastly under-recognised clinical entity. Children with SM are a vulnerable group as the condition is not the remit of any one professional group. This inevitably leads to delay in formal diagnosis and management. There is a lack of systematic research on which to base guidelines for management. To develop, agree and validate key principles underlying the management of SM through a consensus process involving international experts, in order to create a local care pathway. A local multi-agency consultation process developed 11 statements, which were felt to be the key principles underpinning a potential care pathway for managing SM. Thirteen recognised experts from North America, Europe and Australia participated in a modified Delphi process involving two rounds using a Likert-scale and free commentary. Both quantitative and qualitative analyses were used in the validation or revision of the statements at each stage. Response rates were 100% for Round 1 and 84.6% for Round 2. Despite the differing professional backgrounds and service contexts, by successive revision and/or revalidation of statements, it was possible to arrive at a consensus about key principles relating to early recognition, assessment and intervention. The agreed key principles are presented together with the resulting local care pathway. Through a Delphi process, agreement was reached by a multidisciplinary group of professionals, on key principles that underpin the timely identification, assessment and management of children with SM. These include the potential for staff in school/preschool settings to identify SM and that intervention programmes should generally be based in these settings. Children with SM should receive assessment for possible coexisting disorders, whether developmental, emotional or behavioural and additional specific intervention given for these. Agreement was reached as to what constitutes clinical progress, intervals for monitoring progress, criteria for referral onwards for multidisciplinary specialist assessment and the role of selective serotonin reuptake inhibitor (SSRI) medication. A consensus methodology has been successfully used to compensate for the lack of evidence base and harness the expertise of a relatively small number of experienced professionals in order to provide a basis for the future development of services.

A QUICK KEY TO THE SUBFAMILIES AND GENERA OF ANTS OF THE SAVANNAH RIVER SITE

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

Martin, D

2007-09-04

This taxonomic key was devised to support development of a Rapid Bioassessment Protocol using ants at the Savannah River Site. The emphasis is on 'rapid' and, because the available keys contained a very large number of genera not known to occur at the Savannah River Site, we found that the available keys were unwieldy. Because these keys contained many more genera than we would ever encounter and because this larger number of genera required more couplets in the key and often required examination of characters that are difficult to assess without higher magnifications (60X or higher), more time was requiredmore » to process samples. In developing this set of keys I emphasized character states that are easier for nonspecialists to recognize. I recognize that the character sets used may lead to some errors but I believe that the error rate will be small and, for the purpose of rapid bioassessment, this error rate will be acceptable provided that overall sample sizes are adequate. Oliver and Beattie (1996a, 1996b) found that for rapid assessment of biodiversity the same results were found when identifications were done to morphospecies by people with minimal expertise as when the same data sets were identified by subject matter experts. Basset et al. (2004) concluded that it was not as important to correctly identify all species as it was to be sure that the study included as many functional groups as possible. If your study requires high levels of accuracy, it is highly recommended that, when you key out a specimen and have any doubts concerning the identification, you should refer to keys in Bolton (1994) or to the other keys used to develop this area specific taxonomic key.« less

A QUICK KEY TO THE SUBFAMILIES AND GENERA OF ANTS OF THE SAVANNAH RIVER SITE, AIKEN, SC

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

Martin, D

2006-10-04

This taxonomic key was devised to support development of a Rapid Bioassessment Protocol using ants at the Savannah River Site. The emphasis is on ''rapid'' and, because the available keys contained a large number of genera not known to occur at the Savannah River Site, we found that the available keys were unwieldy. Because these keys contained more genera than we would likely encounter and because this larger number of genera required both more couplets in the key and often required examination of characters that are difficult to assess without higher magnifications (60X or higher) more time was required tomore » process samples. In developing this set of keys I recognize that the character sets used may lead to some errors but I believe that the error rate will be small and, for the purpose of rapid bioassessment, this error rate will be acceptable provided that overall sample sizes are adequate. Oliver and Beattie (1996a, 1996b) found that for rapid assessment of biodiversity the same results were found when identifications were done to morphospecies by people with minimal expertise as when the same data sets were identified by subject matter experts. Basset et al. (2004) concluded that it was not as important to correctly identify all species as it was to be sure that the study included as many functional groups as possible. If your study requires high levels of accuracy, it is highly recommended that when you key out a specimen and have any doubts concerning the identification, you should refer to keys in Bolton (1994) or to the other keys used to develop this area specific taxonomic key.« less

The recognition heuristic: a review of theory and tests.

PubMed

Pachur, Thorsten; Todd, Peter M; Gigerenzer, Gerd; Schooler, Lael J; Goldstein, Daniel G

2011-01-01

The recognition heuristic is a prime example of how, by exploiting a match between mind and environment, a simple mental strategy can lead to efficient decision making. The proposal of the heuristic initiated a debate about the processes underlying the use of recognition in decision making. We review research addressing four key aspects of the recognition heuristic: (a) that recognition is often an ecologically valid cue; (b) that people often follow recognition when making inferences; (c) that recognition supersedes further cue knowledge; (d) that its use can produce the less-is-more effect - the phenomenon that lesser states of recognition knowledge can lead to more accurate inferences than more complete states. After we contrast the recognition heuristic to other related concepts, including availability and fluency, we carve out, from the existing findings, some boundary conditions of the use of the recognition heuristic as well as key questions for future research. Moreover, we summarize developments concerning the connection of the recognition heuristic with memory models. We suggest that the recognition heuristic is used adaptively and that, compared to other cues, recognition seems to have a special status in decision making. Finally, we discuss how systematic ignorance is exploited in other cognitive mechanisms (e.g., estimation and preference).

Reliable Multihop Broadcast Protocol with a Low-Overhead Link Quality Assessment for ITS Based on VANETs in Highway Scenarios

PubMed Central

Galaviz-Mosqueda, Alejandro; Villarreal-Reyes, Salvador; Galeana-Zapién, Hiram; Rubio-Loyola, Javier; Covarrubias-Rosales, David H.

2014-01-01

Vehicular ad hoc networks (VANETs) have been identified as a key technology to enable intelligent transport systems (ITS), which are aimed to radically improve the safety, comfort, and greenness of the vehicles in the road. However, in order to fully exploit VANETs potential, several issues must be addressed. Because of the high dynamic of VANETs and the impairments in the wireless channel, one key issue arising when working with VANETs is the multihop dissemination of broadcast packets for safety and infotainment applications. In this paper a reliable low-overhead multihop broadcast (RLMB) protocol is proposed to address the well-known broadcast storm problem. The proposed RLMB takes advantage of the hello messages exchanged between the vehicles and it processes such information to intelligently select a relay set and reduce the redundant broadcast. Additionally, to reduce the hello messages rate dependency, RLMB uses a point-to-zone link evaluation approach. RLMB performance is compared with one of the leading multihop broadcast protocols existing to date. Performance metrics show that our RLMB solution outperforms the leading protocol in terms of important metrics such as packet dissemination ratio, overhead, and delay. PMID:25133224

Temperature-driven decoupling of key phases of organic matter degradation in marine sediments.

PubMed

Weston, Nathaniel B; Joye, Samantha B

2005-11-22

The long-term burial of organic carbon in sediments results in the net accumulation of oxygen in the atmosphere, thereby mediating the redox state of the Earth's biosphere and atmosphere. Sediment microbial activity plays a major role in determining whether particulate organic carbon is recycled or buried. A diverse consortium of microorganisms that hydrolyze, ferment, and terminally oxidize organic compounds mediates anaerobic organic matter mineralization in anoxic sediments. Variable temperature regulation of the sequential processes, leading from the breakdown of complex particulate organic carbon to the production and subsequent consumption of labile, low-molecular weight, dissolved intermediates, could play a key role in controlling rates of overall organic carbon mineralization. We examined sediment organic carbon cycling in a sediment slurry and in flow through bioreactor experiments. The data show a variable temperature response of the microbial functional groups mediating organic matter mineralization in anoxic marine sediments, resulting in the temperature-driven decoupling of the production and consumption of organic intermediates. This temperature-driven decoupling leads to the accumulation of labile, low-molecular weight, dissolved organic carbon at low temperatures and low-molecular weight dissolved organic carbon limitation of terminal metabolism at higher temperatures.

New Frontiers AO: Advanced Materials Bi-propellant Rocket (AMBR) Engine Information Summary

NASA Technical Reports Server (NTRS)

Liou, Larry C.

2008-01-01

The Advanced Material Bi-propellant Rocket (AMBR) engine is a high performance (I(sub sp)), higher thrust, radiation cooled, storable bi-propellant space engine of the same physical envelope as the High Performance Apogee Thruster (HiPAT(TradeMark)). To provide further information about the AMBR engine, this document provides details on performance, development, mission implementation, key spacecraft integration considerations, project participants and approach, contact information, system specifications, and a list of references. The In-Space Propulsion Technology (ISPT) project team at NASA Glenn Research Center (GRC) leads the technology development of the AMBR engine. Their NASA partners were Marshall Space Flight Center (MSFC) and Jet Propulsion Laboratory (JPL). Aerojet leads the industrial partners selected competitively for the technology development via the NASA Research Announcement (NRA) process.

Understanding ultrafine nanodiamond formation using nanostructured explosives

PubMed Central

Pichot, Vincent; Risse, Benedikt; Schnell, Fabien; Mory, Julien; Spitzer, Denis

2013-01-01

The detonation process is able to build new materials with a bottom-up approach. Diamond, the hardest material on earth, can be synthesized in this way. This unconventional synthesis route is possible due to the presence of carbon inside the high-explosive molecules: firing high-explosive mixtures with a negative oxygen balance in a non-oxidative environment leads to the formation of nanodiamond particles. Trinitrotoluene (TNT) and hexogen (RDX) are the explosives primarily used to synthesize nanodiamonds. Here we show that the use of nanostructured explosive charges leads to the formation of smaller detonation nanodiamonds, and it also provides new understanding of nanodiamond formation-mechanisms. The discontinuity of the explosive at the nanoscale level plays the key role in modifying the diamond particle size, and therefore varying the size with microstructured charges is impossible. PMID:23831716

Proposed Mode of Action for Acrolein Respiratory Toxicity Associated with Inhaled Tobacco Smoke.

PubMed

Yeager, R Philip; Kushman, Mary; Chemerynski, Susan; Weil, Roxana; Fu, Xin; White, Marcella; Callahan-Lyon, Priscilla; Rosenfeldt, Hans

2016-06-01

This article presents a mode of action (MOA) analysis that identifies key mechanisms in the respiratory toxicity of inhaled acrolein and proposes key acrolein-related toxic events resulting from the inhalation of tobacco smoke. Smoking causes chronic obstructive pulmonary disorder (COPD) and acrolein has been previously linked to the majority of smoking-induced noncancer respiratory toxicity. In contrast to previous MOA analyses for acrolein, this MOA focuses on the toxicity of acrolein in the lower respiratory system, reflecting the exposure that smokers experience upon tobacco smoke inhalation. The key mechanisms of acrolein toxicity identified in this proposed MOA include (1) acrolein chemical reactivity with proteins and other macromolecules of cells lining the respiratory tract, (2) cellular oxidative stress, including compromise of the important anti-oxidant glutathione, (3) chronic inflammation, (4) necrotic cell death leading to a feedback loop where necrosis-induced inflammation leads to more necrosis and oxidative damage and vice versa, (5) tissue remodeling and destruction, and (6) loss of lung elasticity and enlarged lung airspaces. From these mechanisms, the proposed MOA analysis identifies the key cellular processes in acrolein respiratory toxicity that consistently occur with the development of COPD: inflammation and necrosis in the middle and lower regions of the respiratory tract. Moreover, the acrolein exposures that occur as a result of smoking are well above exposures that induce both inflammation and necrosis in laboratory animals, highlighting the importance of the role of acrolein in smoking-related respiratory disease. Published by Oxford University Press on behalf of the Society of Toxicology 2016. This work is written by US Government employees and is in the public domain in the US.

Nitrogen reactive ion etch processes for the selective removal of poly-(4-vinylpyridine) in block copolymer films.

PubMed

Flynn, Shauna P; Bogan, Justin; Lundy, Ross; Khalafalla, Khalafalla E; Shaw, Matthew; Rodriguez, Brian J; Swift, Paul; Daniels, Stephen; O'Connor, Robert; Hughes, Greg; Kelleher, Susan M

2018-08-31

Self-assembling block copolymer (BCP) patterns are one of the main contenders for the fabrication of nanopattern templates in next generation lithography technology. Transforming these templates to hard mark materials is key for pattern transfer and in some cases, involves selectively removing one block from the nanopattern. For poly(styrene)-block-poly(4-vinylpyridine) (PS-b-P4VP), a high χ BCP system which could be potentially incorporated into semiconductor nanofabrication, this selective removal is predominantly done by a wet etch/activation process. Conversely, this process has numerous disadvantages including lack of control and high generation of waste leading to high cost. For these reasons, our motivation was to move away from the wet etch process and optimise a dry etch which would overcome the limitations associated with the activation process. The work presented herein shows the development of a selective plasma etch process for the removal of P4VP cores from PS-b-P4VP nanopatterned film. Results have shown that a nitrogen reactive ion etch plasma has a selectivity for P4VP of 2.2:1 and suggest that the position of the nitrogen in the aromatic ring of P4VP plays a key role in this selectivity. In situ plasma etching and x-ray photoelectron spectrometry measurements were made without breaking vacuum, confirming that the nitrogen plasma has selectivity for removal of P4VP over PS.

Ionizing radiation processing and its potential in advancing biorefining and nanocellulose composite materials manufacturing

NASA Astrophysics Data System (ADS)

Postek, Michael T.; Poster, Dianne L.; Vládar, András E.; Driscoll, Mark S.; LaVerne, Jay A.; Tsinas, Zois; Al-Sheikhly, Mohamad I.

2018-02-01

Nanocellulose is a high value material that has gained increasing attention because of its high strength, stiffness, unique photonic and piezoelectric properties, high stability and uniform structure. Through utilization of a biorefinery concept, nanocellulose can be produced in large volumes from wood at relatively low cost via ionizing radiation processing. Ionizing radiation causes significant break down of the polysaccharide and leads to the production of potentially useful gaseous products such as H2 and CO. The application of radiation processing to the production of nanocellulose from woody and non-wood sources, such as field grasses, bio-refining by-products, industrial pulp waste, and agricultural surplus materials remains an open field, ripe for innovation and application. Elucidating the mechanisms of the radiolytic decomposition of cellulose and the mass generation of nanocellulose by radiation processing is key to tapping into this source of nanocelluose for the growth of nanocellulostic-product development. More importantly, understanding the structural break-up of the cell walls as a function of radiation exposure is a key goal and only through careful, detailed characterization and dimensional metrology can this be achieved at the level of detail that is needed to further the growth of large scale radiation processing of plant materials. This work is resulting from strong collaborations between NIST and its academic partners who are pursuing the unique demonstration of applied ionizing radiation processing to plant materials as well as the development of manufacturing metrology for novel nanomaterials.

The design briefing process matters: a case study on telehealthcare device providers in the UK.

PubMed

Yang, Fan; Renda, Gianni

2018-01-23

The telehealthcare sector has been expanding steadily in the UK. However, confusing, complex and unwieldy designs of telehealthcare devices are at best, less effective than they could be, at worst, they are potentially dangerous to the users. This study investigated the factors within the new product development process that hindered satisfactory product design outcomes, through working collaboratively with a leading provider based in the UK. This study identified that there are too many costly late-stage design changes; a critical and persistent problem area ripe for improvement. The findings from analyzing 30 recent devices, interviewing key stakeholders and observing on-going projects further revealed that one major cause of the issue was poor practice in defining and communicating the product design criteria and requirements. Addressing the characteristics of the telehealthcare industry, such as multiple design commissioners and frequent deployment of design subcontracts, this paper argues that undertaking a robust process of creating the product design brief is the key to improving the outcomes of telehealthcare device design, particularly for the small and medium-sized enterprises dominating the sector. Implications for rehabilitation Product design criteria and requirements are frequently ill-defined and ineffectively communicated to the designers within the processes of developing new telehealthcare devices. The absence of a (robust) process of creating the design brief is the root cause of the identified issues in defining and communicating the design task. Deploying a formal process of creating the product design brief is particularly important for the telehealthcare sector.

Ionizing radiation processing and its potential in advancing biorefining and nanocellulose composite materials manufacturing.

PubMed

Postek, Michael T; Poster, Dianne L; Vládar, András E; Driscoll, Mark S; LaVerne, Jay A; Tsinas, Zois; Al-Sheikhly, Mohamad I

2018-02-01

Nanocellulose is a high value material that has gained increasing attention because of its high strength, stiffness, unique photonic and piezoelectric properties, high stability and uniform structure. Through utilization of a biorefinery concept, nanocellulose can be produced in large volumes from wood at relatively low cost via ionizing radiation processing. Ionizing radiation causes significant break down of the polysaccharide and leads to the production of potentially useful gaseous products such as H 2 and CO. The application of radiation processing to the production of nanocellulose from woody and non-wood sources, such as field grasses, bio-refining byproducts, industrial pulp waste, and agricultural surplus materials remains an open field, ripe for innovation and application. Elucidating the mechanisms of the radiolytic decomposition of cellulose and the mass generation of nanocellulose by radiation processing is key to tapping into this source of nanocelluose for the growth of nanocellulostic-product development. More importantly, understanding the structural break-up of the cell walls as a function of radiation exposure is a key goal and only through careful, detailed characterization and dimensional metrology can this be achieved at the level of detail that is needed to further the growth of large scale radiation processing of plant materials. This work is resulting from strong collaborations between NIST and its academic partners who are pursuing the unique demonstration of applied ionizing radiation processing to plant materials as well as the development of manufacturing metrology for novel nanomaterials.

A Framework for Developing the Structure of Public Health Economic Models.

PubMed

Squires, Hazel; Chilcott, James; Akehurst, Ronald; Burr, Jennifer; Kelly, Michael P

2016-01-01

A conceptual modeling framework is a methodology that assists modelers through the process of developing a model structure. Public health interventions tend to operate in dynamically complex systems. Modeling public health interventions requires broader considerations than clinical ones. Inappropriately simple models may lead to poor validity and credibility, resulting in suboptimal allocation of resources. This article presents the first conceptual modeling framework for public health economic evaluation. The framework presented here was informed by literature reviews of the key challenges in public health economic modeling and existing conceptual modeling frameworks; qualitative research to understand the experiences of modelers when developing public health economic models; and piloting a draft version of the framework. The conceptual modeling framework comprises four key principles of good practice and a proposed methodology. The key principles are that 1) a systems approach to modeling should be taken; 2) a documented understanding of the problem is imperative before and alongside developing and justifying the model structure; 3) strong communication with stakeholders and members of the team throughout model development is essential; and 4) a systematic consideration of the determinants of health is central to identifying the key impacts of public health interventions. The methodology consists of four phases: phase A, aligning the framework with the decision-making process; phase B, identifying relevant stakeholders; phase C, understanding the problem; and phase D, developing and justifying the model structure. Key areas for further research involve evaluation of the framework in diverse case studies and the development of methods for modeling individual and social behavior. This approach could improve the quality of Public Health economic models, supporting efficient allocation of scarce resources. Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Linking micro- and macro-evolution at the cell type level: a view from the lophotrochozoan Platynereis dumerilii.

PubMed

Simakov, Oleg; Larsson, Tomas A; Arendt, Detlev

2013-09-01

Ever since the origin of the first metazoans over 600 million years ago, cell type diversification has been driven by micro-evolutionary processes at population level, leading to macro-evolution changes above species level. In this review, we introduce the marine annelid Platynereis dumerilii, a member of the lophotrochozoan clade (a key yet most understudied superphylum of bilaterians), as a suitable model system for the simultaneous study, at cellular resolution, of macro-evolutionary processes across phyla and of micro-evolutionary processes across highly polymorphic populations collected worldwide. Recent advances in molecular and experimental techniques, easy maintenance and breeding, and the fast, synchronous and stereotypical development have facilitated the establishment of Platynereis as one of the leading model species in the eco-evo-devo field. Most importantly, Platynereis allows the combination of expression profiling, morphological and physiological characterization at the single cell level. Here, we discuss recent advances in the collection of -omics data for the lab strain and for natural populations collected world-wide that can be integrated with population-specific cellular analyses to result in a cellular atlas integrating genetic, phenotypic and ecological variation. This makes Platynereis a tractable system to begin understanding the interplay between macro- and micro-evolutionary processes and cell type diversity.

Numerical simulations of an advection fog event over Shanghai Pudong International Airport with the WRF model

NASA Astrophysics Data System (ADS)

Lin, Caiyan; Zhang, Zhongfeng; Pu, Zhaoxia; Wang, Fengyun

2017-10-01

A series of numerical simulations is conducted to understand the formation, evolution, and dissipation of an advection fog event over Shanghai Pudong International Airport (ZSPD) with the Weather Research and Forecasting (WRF) model. Using the current operational settings at the Meteorological Center of East China Air Traffic Management Bureau, the WRF model successfully predicts the fog event at ZSPD. Additional numerical experiments are performed to examine the physical processes associated with the fog event. The results indicate that prediction of this particular fog event is sensitive to microphysical schemes for the time of fog dissipation but not for the time of fog onset. The simulated timing of the arrival and dissipation of the fog, as well as the cloud distribution, is substantially sensitive to the planetary boundary layer and radiation (both longwave and shortwave) processes. Moreover, varying forecast lead times also produces different simulation results for the fog event regarding its onset and duration, suggesting a trade-off between more accurate initial conditions and a proper forecast lead time that allows model physical processes to spin up adequately during the fog simulation. The overall outcomes from this study imply that the complexity of physical processes and their interactions within the WRF model during fog evolution and dissipation is a key area of future research.

Spatiotemporal imaging of cortical activation during verb generation and picture naming.

PubMed

Edwards, Erik; Nagarajan, Srikantan S; Dalal, Sarang S; Canolty, Ryan T; Kirsch, Heidi E; Barbaro, Nicholas M; Knight, Robert T

2010-03-01

One hundred and fifty years of neurolinguistic research has identified the key structures in the human brain that support language. However, neither the classic neuropsychological approaches introduced by Broca (1861) and Wernicke (1874), nor modern neuroimaging employing PET and fMRI has been able to delineate the temporal flow of language processing in the human brain. We recorded the electrocorticogram (ECoG) from indwelling electrodes over left hemisphere language cortices during two common language tasks, verb generation and picture naming. We observed that the very high frequencies of the ECoG (high-gamma, 70-160 Hz) track language processing with spatial and temporal precision. Serial progression of activations is seen at a larger timescale, showing distinct stages of perception, semantic association/selection, and speech production. Within the areas supporting each of these larger processing stages, parallel (or "incremental") processing is observed. In addition to the traditional posterior vs. anterior localization for speech perception vs. production, we provide novel evidence for the role of premotor cortex in speech perception and of Wernicke's and surrounding cortex in speech production. The data are discussed with regards to current leading models of speech perception and production, and a "dual ventral stream" hybrid of leading speech perception models is given. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Multiscale Processes in Magnetic Reconnection

NASA Astrophysics Data System (ADS)

Surjalal Sharma, A.; Jain, Neeraj

The characteristic scales of the plasma processes in magnetic reconnection range from the elec-tron skin-depth to the magnetohydrodynamic (MHD) scale, and cross-scale coupling among them play a key role. Modeling these processes requires different physical models, viz. kinetic, electron-magnetohydrodynamics (EMHD), Hall-MHD, and MHD. The shortest scale processes are at the electron scale and these are modeled using an EMHD code, which provides many features of the multiscale behavior. In simulations using initial conditions consisting of pertur-bations with many scale sizes the reconnection takes place at many sites and the plasma flows from these interact with each other. This leads to thin current sheets with length less than 10 electron skin depths. The plasma flows also generate current sheets with multiple peaks, as observed by Cluster. The quadrupole structure of the magnetic field during reconnection starts on the electron scale and the interaction of inflow to the secondary sites and outflow from the dominant site generates a nested structure. In the outflow regions, the interaction of the electron outflows generated at the neighboring sites lead to the development of electron vortices. A signature of the nested structure of the Hall field is seen in Cluster observations, and more details of these features are expected from MMS.

New HSP27 inhibitors efficiently suppress drug resistance development in cancer cells.

PubMed

Heinrich, Jörg C; Donakonda, Sainitin; Haupt, V Joachim; Lennig, Petra; Zhang, Yixin; Schroeder, Michael

2016-10-18

Drug resistance is an important open problem in cancer treatment. In recent years, the heat shock protein HSP27 (HSPB1) was identified as a key player driving resistance development. HSP27 is overexpressed in many cancer types and influences cellular processes such as apoptosis, DNA repair, recombination, and formation of metastases. As a result cancer cells are able to suppress apoptosis and develop resistance to cytostatic drugs. To identify HSP27 inhibitors we follow a novel computational drug repositioning approach. We exploit a similarity between a predicted HSP27 binding site to a viral thymidine kinase to generate lead inhibitors for HSP27. Six of these leads were verified experimentally. They bind HSP27 and down-regulate its chaperone activity. Most importantly, all six compounds inhibit development of drug resistance in cellular assays. One of the leads - chlorpromazine - is an antipsychotic, which has a positive effect on survival time in human breast cancer. In summary, we make two important contributions: First, we put forward six novel leads, which inhibit HSP27 and tackle drug resistance. Second, we demonstrate the power of computational drug repositioning.

The Role of Oxidative Stress in Cerebral Aneurysm Formation and Rupture

PubMed Central

Starke, Robert M.; Chalouhi, Nohra; Ali, Muhammad S.; Jabbour, Pascal M.; Tjoumakaris, Stavropoula I.; Gonzalez, L. Fernando; Rosenwasser, Robert H.; Koch, Walter J.; Dumont, Aaron S.

2013-01-01

Oxidative stress is known to contribute to the progression of cerebrovascular disease. Additionally, oxidative stress may be increased by, but also augment inflammation, a key contributor to cerebral aneurysm development and rupture. Oxidative stress can induce important processes leading to cerebral aneurysm formation including direct endothelial injury as well as smooth muscle cell phenotypic switching to an inflammatory phenotype and ultimately apoptosis. Oxidative stress leads to recruitment and invasion of inflammatory cells through upregulation of chemotactic cytokines and adhesion molecules. Matrix metalloproteinases can be activated by free radicals leading to vessel wall remodeling and breakdown. Free radicals mediate lipid peroxidation leading to atherosclerosis and contribute to hemodynamic stress and hypertensive pathology, all integral elements of cerebral aneurysm development. Preliminary studies suggest that therapies targeted at oxidative stress may provide a future beneficial treatment for cerebral aneurysms, but further studies are indicated to define the role of free radicals in cerebral aneurysm formation and rupture. The goal of this review is to assess the role of oxidative stress in cerebral aneurysm pathogenesis. PMID:23713738

Leading change: a challenge for leaders in Nordic health care.

PubMed

Fagerström, Lisbeth; Salmela, Susanne

2010-07-01

The aim of the present study was to describe personnel's attitudes to change processes between a regional hospital and the primary health care centre as well as investigate these results with regards to theories pertaining to change and leading change. Leadership has three crucial dimensions: focusing on personnel, results/key processes and the ethical base of activities. A survey was conducted in 2003 using a comprehensive questionnaire. The total sample consisted of the personnel (n = 899) at the two organizations (answering rate was 68.8%). The data were analysed descriptively. Approximately two-thirds of the respondents understood why the merger was occurring. Only one-third expressed that they had received sufficient information regarding the merger. In total 67% felt that the merger would create conflict while approximately one-fourth expressed uncertainty. Despite such negative responses, approximately two-thirds felt there were advantages to the merger. Significant differences were seen between the groups. In times of change personnel expect leaders to focus on dialogue with their personnel and to anchor the vision of the change process amongst the personnel. By identifying the 'prison of thought' and creating an atmosphere where reflection and discussion are valued the nurse leader can help prevent resistance to change.

Advances in surfaces and osseointegration in implantology. Biomimetic surfaces

PubMed Central

Albertini, Matteo; Fernandez-Yague, Marc; Lázaro, Pedro; Herrero-Climent, Mariano; Bullon, Pedro; Gil, Francisco-Javier

2015-01-01

The present work is a revision of the processes occurring in osseointegration of titanium dental implants according to different types of surfaces -namely, polished surfaces, rough surfaces obtained from subtraction methods, as well as the new hydroxyapatite biomimetic surfaces obtained from thermochemical processes. Hydroxyapatite’s high plasma-projection temperatures have proven to prevent the formation of crystalline apatite on the titanium dental implant, but lead to the formation of amorphous calcium phosphate (i.e., with no crystal structure) instead. This layer produce some osseointegration yet the calcium phosphate layer will eventually dissolve and leave a gap between the bone and the dental implant, thus leading to osseointegration failure due to bacterial colonization. A new surface -recently obtained by thermochemical processes- produces, by crystallization, a layer of apatite with the same mineral content as human bone that is chemically bonded to the titanium surface. Osseointegration speed was tested by means of minipigs, showing bone formation after 3 to 4 weeks, with the security that a dental implant can be loaded. This surface can be an excellent candidate for immediate or early loading procedures. Key words:Dental implants, implants surfaces, osseointegration, biomimetics surfaces. PMID:25662555

Experimental and simulation of split semi-torus key in PVC foam core to improve the debonding resistance of composite sandwich panel

NASA Astrophysics Data System (ADS)

Juliyana, M.; Santhana Krishnan, R.

2018-02-01

The sandwich composite panels consisting of facesheet and core material are used as a primary structural member for aerospace, civil and marine areas due to its high stiffness to weight ratio. But the debonding nature of facesheet from the foam core under shear loading conditions leads to failure of the composite structure. To inhibit the debonding, an innovative methodology of introducing semi-torus key is used in the present study. The polyvinyl chloride foam core(PVC) is grooved and filled with semi-torus shaped chopped strand prepregs which are sandwiched between alternate layers of woven roven(WR) and chopped strand mat(CSM) skins by vacuum infusion process. The sandwich panel manufactured with semi-torus keys is evaluated regarding experimental and numerical simulations under shear loading conditions. The present innovative concept delays the debonding between face-sheet and foam core with enhancement the shear load carrying capability as the initial stiffness is higher than the conventional model. Also, the shear behaviour of the proposed concept is in good agreement with experimental results. The split semi-torus keys sustain the shear failure resulting in resistance to debonding capability.

A Summary of Some Discrete-Event System Control Problems

NASA Astrophysics Data System (ADS)

Rudie, Karen

A summary of the area of control of discrete-event systems is given. In this research area, automata and formal language theory is used as a tool to model physical problems that arise in technological and industrial systems. The key ingredients to discrete-event control problems are a process that can be modeled by an automaton, events in that process that cannot be disabled or prevented from occurring, and a controlling agent that manipulates the events that can be disabled to guarantee that the process under control either generates all the strings in some prescribed language or as many strings as possible in some prescribed language. When multiple controlling agents act on a process, decentralized control problems arise. In decentralized discrete-event systems, it is presumed that the agents effecting control cannot each see all event occurrences. Partial observation leads to some problems that cannot be solved in polynomial time and some others that are not even decidable.

Devil is in the details: Using logic models to investigate program process.

PubMed

Peyton, David J; Scicchitano, Michael

2017-12-01

Theory-based logic models are commonly developed as part of requirements for grant funding. As a tool to communicate complex social programs, theory based logic models are an effective visual communication. However, after initial development, theory based logic models are often abandoned and remain in their initial form despite changes in the program process. This paper examines the potential benefits of committing time and resources to revising the initial theory driven logic model and developing detailed logic models that describe key activities to accurately reflect the program and assist in effective program management. The authors use a funded special education teacher preparation program to exemplify the utility of drill down logic models. The paper concludes with lessons learned from the iterative revision process and suggests how the process can lead to more flexible and calibrated program management. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fault-tolerant Control of a Cyber-physical System

NASA Astrophysics Data System (ADS)

Roxana, Rusu-Both; Eva-Henrietta, Dulf

2017-10-01

Cyber-physical systems represent a new emerging field in automatic control. The fault system is a key component, because modern, large scale processes must meet high standards of performance, reliability and safety. Fault propagation in large scale chemical processes can lead to loss of production, energy, raw materials and even environmental hazard. The present paper develops a multi-agent fault-tolerant control architecture using robust fractional order controllers for a (13C) cryogenic separation column cascade. The JADE (Java Agent DEvelopment Framework) platform was used to implement the multi-agent fault tolerant control system while the operational model of the process was implemented in Matlab/SIMULINK environment. MACSimJX (Multiagent Control Using Simulink with Jade Extension) toolbox was used to link the control system and the process model. In order to verify the performance and to prove the feasibility of the proposed control architecture several fault simulation scenarios were performed.

Navigating the Institutional Review Board (IRB) Process for Pharmacy-Related Research

PubMed Central

Abdelghany, Osama; Johnston, Susan; Rarus, Rachel; Austin-Szwak, Jennifer; Kirkwood, Craig

2017-01-01

Pharmacists' specialized training and knowledge qualify them to lead and engage in research pertaining to optimal medication use. Performing research promotes pharmacy professionalism and fosters interdisciplinary collaboration. To conduct research appropriately, one must have thorough knowledge of when institutional review board (IRB) approval is required and how to successfully navigate IRB processes. The overarching mission of the IRB overseeing research at an organization per federal guidelines is to protect the rights and welfare of human subjects participating in research. This article discusses the following general pharmacy practice–based considerations relating to IRB processes: strategies for developing research projects, key distinctions between quality improvement and research, practical considerations for submitting IRB applications and documentation, different categories of IRB submission, informed consent and conditions for waivers or alterations of consent, and principal investigator obligations for approved research. Pharmacists should also account for organization-specific IRB processes when designing, submitting, and implementing research projects. PMID:28321137

Speciation through the lens of biomechanics: locomotion, prey capture and reproductive isolation.

PubMed

Higham, Timothy E; Rogers, Sean M; Langerhans, R Brian; Jamniczky, Heather A; Lauder, George V; Stewart, William J; Martin, Christopher H; Reznick, David N

2016-09-14

Speciation is a multifaceted process that involves numerous aspects of the biological sciences and occurs for multiple reasons. Ecology plays a major role, including both abiotic and biotic factors. Whether populations experience similar or divergent ecological environments, they often adapt to local conditions through divergence in biomechanical traits. We investigate the role of biomechanics in speciation using fish predator-prey interactions, a primary driver of fitness for both predators and prey. We highlight specific groups of fishes, or specific species, that have been particularly valuable for understanding these dynamic interactions and offer the best opportunities for future studies that link genetic architecture to biomechanics and reproductive isolation (RI). In addition to emphasizing the key biomechanical techniques that will be instrumental, we also propose that the movement towards linking biomechanics and speciation will include (i) establishing the genetic basis of biomechanical traits, (ii) testing whether similar and divergent selection lead to biomechanical divergence, and (iii) testing whether/how biomechanical traits affect RI. Future investigations that examine speciation through the lens of biomechanics will propel our understanding of this key process. © 2016 The Author(s).

A case study of exploiting enterprise resource planning requirements

NASA Astrophysics Data System (ADS)

Niu, Nan; Jin, Mingzhou; Cheng, Jing-Ru C.

2011-05-01

The requirements engineering (RE) processes have become a key to conceptualising corporate-wide integrated solutions based on packaged enterprise resource planning (ERP) software. The RE literature has mainly focused on procuring the most suitable ERP package. Little is known about how an organisation exploits the chosen ERP RE model to frame the business application development. This article reports an exploratory case study of a key tenet of ERP RE adoption, namely that aligning business applications to the packaged RE model leads to integral practices and economic development. The case study analysed a series interrelated pilot projects developed for a business division of a large IT manufacturing and service company, using Oracle's appl1ication implementation method (AIM). The study indicated that AIM RE improved team collaboration and project management experience, but needed to make hidden assumptions explicit to support data visibility and integrity. Our study can direct researchers towards rigorous empirical evaluations of ERP RE adoption, collect experiences and lessons learned for practitioners, and help generate more effective and mature processes when exploiting ERP RE methods.

Speciation through the lens of biomechanics: locomotion, prey capture and reproductive isolation

PubMed Central

Rogers, Sean M.; Langerhans, R. Brian; Jamniczky, Heather A.; Lauder, George V.; Stewart, William J.; Martin, Christopher H.; Reznick, David N.

2016-01-01

Speciation is a multifaceted process that involves numerous aspects of the biological sciences and occurs for multiple reasons. Ecology plays a major role, including both abiotic and biotic factors. Whether populations experience similar or divergent ecological environments, they often adapt to local conditions through divergence in biomechanical traits. We investigate the role of biomechanics in speciation using fish predator–prey interactions, a primary driver of fitness for both predators and prey. We highlight specific groups of fishes, or specific species, that have been particularly valuable for understanding these dynamic interactions and offer the best opportunities for future studies that link genetic architecture to biomechanics and reproductive isolation (RI). In addition to emphasizing the key biomechanical techniques that will be instrumental, we also propose that the movement towards linking biomechanics and speciation will include (i) establishing the genetic basis of biomechanical traits, (ii) testing whether similar and divergent selection lead to biomechanical divergence, and (iii) testing whether/how biomechanical traits affect RI. Future investigations that examine speciation through the lens of biomechanics will propel our understanding of this key process. PMID:27629033

GLIS1-3 transcription factors: critical roles in the regulation of multiple physiological processes and diseases.

PubMed

Jetten, Anton M

2018-05-19

Krüppel-like zinc finger proteins form one of the largest families of transcription factors. They function as key regulators of embryonic development and a wide range of other physiological processes, and are implicated in a variety of pathologies. GLI-similar 1-3 (GLIS1-3) constitute a subfamily of Krüppel-like zinc finger proteins that act either as activators or repressors of gene transcription. GLIS3 plays a critical role in the regulation of multiple biological processes and is a key regulator of pancreatic β cell generation and maturation, insulin gene expression, thyroid hormone biosynthesis, spermatogenesis, and the maintenance of normal kidney functions. Loss of GLIS3 function in humans and mice leads to the development of several pathologies, including neonatal diabetes and congenital hypothyroidism, polycystic kidney disease, and infertility. Single nucleotide polymorphisms in GLIS3 genes have been associated with increased risk of several diseases, including type 1 and type 2 diabetes, glaucoma, and neurological disorders. GLIS2 plays a critical role in the kidney and GLIS2 dysfunction leads to nephronophthisis, an end-stage, cystic renal disease. In addition, GLIS1-3 have regulatory functions in several stem/progenitor cell populations. GLIS1 and GLIS3 greatly enhance reprogramming efficiency of somatic cells into induced embryonic stem cells, while GLIS2 inhibits reprogramming. Recent studies have obtained substantial mechanistic insights into several physiological processes regulated by GLIS2 and GLIS3, while a little is still known about the physiological functions of GLIS1. The localization of some GLIS proteins to the primary cilium suggests that their activity may be regulated by a downstream primary cilium-associated signaling pathway. Insights into the upstream GLIS signaling pathway may provide opportunities for the development of new therapeutic strategies for diabetes, hypothyroidism, and other diseases.

Ontario's emergency department process improvement program: the experience of implementation.

PubMed

Rotteau, Leahora; Webster, Fiona; Salkeld, Erin; Hellings, Chelsea; Guttmann, Astrid; Vermeulen, Marian J; Bell, Robert S; Zwarenstein, Merrick; Rowe, Brian H; Nigam, Amit; Schull, Michael J

2015-06-01

In recent years, Lean manufacturing principles have been applied to health care quality improvement efforts to improve wait times. In Ontario, an emergency department (ED) process improvement program based on Lean principles was introduced by the Ministry of Health and Long-Term Care as part of a strategy to reduce ED length of stay (LOS) and to improve patient flow. This article aims to describe the hospital-based teams' experiences during the ED process improvement program implementation and the teams' perceptions of the key factors that influenced the program's success or failure. A qualitative evaluation was conducted based on semistructured interviews with hospital implementation team members, such as team leads, medical leads, and executive sponsors, at 10 purposively selected hospitals in Ontario, Canada. Sites were selected based, in part, on their changes in median ED LOS following the implementation period. A thematic framework approach as used for interviews, and a standard thematic coding framework was developed. Twenty-four interviews were coded and analyzed. The results are organized according to participants' experience and are grouped into four themes that were identified as significantly affecting the implementation experience: local contextual factors, relationship between improvement team and support players, staff engagement, and success and sustainability. The results demonstrate the importance of the context of implementation, establishing strong relationships and communication strategies, and preparing for implementation and sustainability prior to the start of the project. Several key factors were identified as important to the success of the program, such as preparing for implementation, ensuring strong executive support, creation of implementation teams based on the tasks and outcomes of the initiative, and using multiple communication strategies throughout the implementation process. Explicit incorporation of these factors into the development and implementation of future similar interventions in health care settings could be useful. © 2015 by the Society for Academic Emergency Medicine.

Space physiology IV: mathematical modeling of the cardiovascular system in space exploration.

PubMed

Keith Sharp, M; Batzel, Jerry Joseph; Montani, Jean-Pierre

2013-08-01

Mathematical modeling represents an important tool for analyzing cardiovascular function during spaceflight. This review describes how modeling of the cardiovascular system can contribute to space life science research and illustrates this process via modeling efforts to study postflight orthostatic intolerance (POI), a key issue for spaceflight. Examining this application also provides a context for considering broader applications of modeling techniques to the challenges of bioastronautics. POI, which affects a large fraction of astronauts in stand tests upon return to Earth, presents as dizziness, fainting and other symptoms, which can diminish crew performance and cause safety hazards. POI on the Moon or Mars could be more critical. In the field of bioastronautics, POI has been the dominant application of cardiovascular modeling for more than a decade, and a number of mechanisms for POI have been investigated. Modeling approaches include computational models with a range of incorporated factors and hemodynamic sophistication, and also physical models tested in parabolic and orbital flight. Mathematical methods such as parameter sensitivity analysis can help identify key system mechanisms. In the case of POI, this could lead to more effective countermeasures. Validation is a persistent issue in modeling efforts, and key considerations and needs for experimental data to synergistically improve understanding of cardiovascular responses are outlined. Future directions in cardiovascular modeling include subject-specific assessment of system status, as well as research on integrated physiological responses, leading, for instance, to assessment of subject-specific susceptibility to POI or effects of cardiovascular alterations on muscular, vision and cognitive function.

Elevated blood lead levels among adults in Massachusetts, 1991-1995.

PubMed

Tumpowsky, C M; Davis, L K; Rabin, R

2000-01-01

Lead poisoning, the oldest recognized occupational disease, remains a danger for children and adults. Data collected for 664 cases reported to the Massachusetts Occupational Lead Registry in 1991-1995 were summarized in a 1998 state report. Here, the authors present some of the key findings from that report for a wider audience. The authors summarize key findings of the 1998 state report. Construction workers, in particular licensed deleaders and house painters, accounted for almost 70% of occupational cases involving blood lead levels > or = 40 micrograms of lead per deciliter (mcg/dl) of blood. Among 100 workers with the highest blood lead levels (> or = 60 mcg/dl), 29% were house painters. Hispanic workers were over-represented in the Registry. A small proportion of cases were non-occupational, typically associated with recreational use of firing ranges or do-it-yourself home renovations. Lead poisoning is a preventable disease, yet these data indicate that additional prevention efforts are warranted.

Vaccination and healthy aging.

PubMed

Maggi, Stefania

2010-03-01

The aging process in humans is associated with a decrease in immune function (immunosenescence) and an increase in comorbid disorders. When combined with environmental factors this can lead to an increased risk and severity of infectious diseases. Diseases in older adults (>/=70 years) tend to be more severe and have a greater impact on health outcomes such as morbidity, disability, quality of life and mortality. However, some of the more common infections such as influenza and pneumococcal infection are vaccine preventable, but the uptake of such preventive strategies in adults has been poor. In this review some of the key clinical findings supporting the benefits of adult immunization are highlighted. Vaccination of the adult population needs to be a key component of a healthy aging strategy, since there is already convincing evidence that this approach can have an important impact on morbidity, mortality and quality of life.

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

Entropy/information flux in Hawking radiation

NASA Astrophysics Data System (ADS)

Alonso-Serrano, Ana; Visser, Matt

2018-01-01

Blackbody radiation contains (on average) an entropy of 3.9 ± 2.5 bits per photon. If the emission process is unitary, then this entropy is exactly compensated by "hidden information" in the correlations. We extend this argument to the Hawking radiation from GR black holes, demonstrating that the assumption of unitarity leads to a perfectly reasonable entropy/information budget. The key technical aspect of our calculation is a variant of the "average subsystem" approach developed by Page, which we extend beyond bipartite pure systems, to a tripartite pure system that considers the influence of the environment.

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

Avakian, Harut

Studies of the 3D structure of the nucleon encoded in Transverse Momentum Dependent distribution and fragmentation functions of partons and Generalized Parton Distributions are among the key objectives of the JLab 12 GeV upgrade and the Electron Ion Collider. Main challenges in extracting 3D partonic distributions from precision measurements of hard scattering processes include clear understanding of leading twist QCD fundamentals, higher twist effects, and also correlations of hadron production in target and current fragmentation regions. In this contribution we discuss some ongoing studies and future measurements of spin-orbit correlations at Jefferson Lab.

Einstein's creative thinking and the general theory of relativity: a documented report.

PubMed

Rothenberg, A

1979-01-01

A document written by Albert Einstein has recently come to light in which the eminent scientist described the actual sequence of his thoughts leading to the development of the general theory of relativity. The key creative thought was an instance of a type of creative cognition the author has previously designated "Janusian thinking," Janusian thinking consists of actively conceiving two or more opposite or antithetical concepts, ideas, or images simultaneously. This form of high-level secondary process cognition has been found to operate widely in art, science, and other fields.

Selenocysteine incorporation: A trump card in the game of mRNA decay

PubMed Central

Shetty, Sumangala P.; Copeland, Paul R.

2015-01-01

The incorporation of the 21st amino acid, selenocysteine (Sec), occurs on mRNAs that harbor in-frame stop codons because the Sec-tRNASec recognizes a UGA codon. This sets up an intriguing interplay between translation elongation, translation termination and the complex machinery that marks mRNAs that contain premature termination codons for degradation, leading to nonsense mediated mRNA decay (NMD). In this review we discuss the intricate and complex relationship between this key quality control mechanism and the process of Sec incorporation in mammals. PMID:25622574

Chemokines in tumor progression and metastasis

PubMed Central

Sarvaiya, Purvaba J.; Guo, Donna; Ulasov, Ilya; Gabikian, Patrik; Lesniak, Maciej S.

2013-01-01

Chemokines play a vital role in tumor progression and metastasis. Chemokines are involved in the growth of many cancers including breast cancer, ovarian cancer, pancreatic cancer, melanoma, lung cancer, gastric cancer, acute lymphoblastic leukemia, colon cancer, non-small lung cancer and non-hodgkin's lymphoma among many others. The expression of chemokines and their receptors is altered in many malignancies and leads to aberrant chemokine receptor signaling. This review focuses on the role of chemokines in key processes that facilitate tumor progression including proliferation, senescence, angiogenesis, epithelial mesenchymal transition, immune evasion and metastasis. PMID:24259307

A very simple, re-executable neuroimaging publication

PubMed Central

Ghosh, Satrajit S.; Poline, Jean-Baptiste; Keator, David B.; Halchenko, Yaroslav O.; Thomas, Adam G.; Kessler, Daniel A.; Kennedy, David N.

2017-01-01

Reproducible research is a key element of the scientific process. Re-executability of neuroimaging workflows that lead to the conclusions arrived at in the literature has not yet been sufficiently addressed and adopted by the neuroimaging community. In this paper, we document a set of procedures, which include supplemental additions to a manuscript, that unambiguously define the data, workflow, execution environment and results of a neuroimaging analysis, in order to generate a verifiable re-executable publication. Re-executability provides a starting point for examination of the generalizability and reproducibility of a given finding. PMID:28781753

Changes in the Adult Vertebrate Auditory Sensory Epithelium After Trauma

PubMed Central

Oesterle, Elizabeth C.

2012-01-01

Auditory hair cells transduce sound vibrations into membrane potential changes, ultimately leading to changes in neuronal firing and sound perception. This review provides an overview of the characteristics and repair capabilities of traumatized auditory sensory epithelium in the adult vertebrate ear. Injured mammalian auditory epithelium repairs itself by forming permanent scars but is unable to regenerate replacement hair cells. In contrast, injured non-mammalian vertebrate ear generates replacement hair cells to restore hearing functions. Non-sensory support cells within the auditory epithelium play key roles in the repair processes. PMID:23178236

Role of asymmetric cell division in lifespan control in Saccharomyces cerevisiae

PubMed Central

Higuchi-Sanabria, Ryo; Pernice, Wolfgang M A; Vevea, Jason D; Alessi Wolken, Dana M; Boldogh, Istvan R; Pon, Liza A

2014-01-01

Aging determinants are asymmetrically distributed during cell division in S. cerevisiae, which leads to production of an immaculate, age-free daughter cell. During this process, damaged components are sequestered and retained in the mother cell, and higher functioning organelles and rejuvenating factors are transported to and/or enriched in the bud. Here, we will describe the key quality control mechanisms in budding yeast that contribute to asymmetric cell division of aging determinants including mitochondria, endoplasmic reticulum (ER), vacuoles, extrachromosomal rDNA circles (ERCs), and protein aggregates. PMID:25263578

Code orange: Towards transformational leadership of emergency management systems.

PubMed

Caro, Denis H J

2015-09-01

The 21(st) century calls upon health leaders to recognize and respond to emerging threats and systemic emergency management challenges through transformative processes inherent in the LEADS in a caring environment framework. Using a grounded theory approach, this qualitative study explores key informant perspectives of leaders in emergency management across Canada on pressing needs for relevant systemic transformation. The emerging model points to eight specific attributes of transformational leadership central to emergency management and suggests that contextualization of health leadership is of particular import. © 2015 The Canadian College of Health Leaders.

Assessing esophageal dysphagia.

PubMed

Kruger, Danielle

2014-05-01

Dysphagia, or difficulty swallowing, is a common problem. Although most cases are attributable to benign disease processes, dysphagia is also a key symptom in several malignancies, making it an important symptom to evaluate. The differential diagnosis of dysphagia requires an understanding of deglutition, in particular the oropharyngeal versus esophageal stages. Stroke is the leading cause of oropharyngeal dysphagia, which is common in older adults and frequently presents as part of a broader complex of clinical manifestations. In esophageal dysphagia, difficulty swallowing is often the main complaint and is caused by localized neuromuscular disorders or obstructive lesions.

Biosocial factors influencing women to become prostitutes in India.

PubMed

Chattopadhyay, M; Bandyopadhyay, S; Duttagupta, C

1994-01-01

Based on materials collected during a study of risk factors associated with cervix cancer among prostitutes in Domjur, Howrah, West Bengal, this report explores various biosocial factors which may lead women to prostitution. When family and marital ties fail or disintegrate for various reasons, the life situations which a woman encounters may themselves generate a "process" of anchorlessness. The failure of family support along with the lack of ability to provide for themselves due to poverty and illiteracy were key factors why the women in this study had adopted prostitution.

Defining and Modeling Known Adverse Outcome Pathways: Domoic Acid and Neuronal Signaling as a Case Study

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

Watanabe, Karen H.; Andersen, Melvin E.; Basu, Nil

2011-01-01

An adverse outcome pathway (AOP) is a sequence of key events from a molecular-level initiating event and an ensuing cascade of steps to an adverse outcome with population level significance. To implement a predictive strategy for ecotoxicology, the multiscale nature of an AOP requires computational models to link salient processes (e.g., in chemical uptake, toxicokinetics, toxicodynamics, and population dynamics). A case study with domoic acid was used to demonstrate strategies and enable generic recommendations for developing computational models in an effort to move toward a toxicity testing paradigm focused on toxicity pathway perturbations applicable to ecological risk assessment. Domoic acid,more » an algal toxin with adverse effects on both wildlife and humans, is a potent agonist for kainate receptors (ionotropic glutamate receptors whose activation leads to the influx of Na+ and Ca2+). Increased Ca2+ concentrations result in neuronal excitotoxicity and cell death primarily in the hippocampus, which produces seizures, impairs learning and memory, and alters behavior in some species. Altered neuronal Ca2+ is a key process in domoic acid toxicity which can be evaluated in vitro. Further, results of these assays would be amenable to mechanistic modeling for identifying domoic acid concentrations and Ca2+ perturbations that are normal, adaptive, or clearly toxic. In vitro assays with outputs amenable to measurement in exposed populations can link in vitro to in vivo conditions, and toxicokinetic information will aid in linking in vitro results to the individual organism. Development of an AOP required an iterative process with three important outcomes: (1) a critically reviewed, stressor-specific AOP; (2) identification of key processes suitable for evaluation with in vitro assays; and (3) strategies for model development.« less

A transcribed ultraconserved noncoding RNA, Uc.173, is a key molecule for the inhibition of lead-induced neuronal apoptosis

PubMed Central

Chen, Lijian; Liu, Meiling; Zhang, Nan; Zhang, Li; Luo, Yuanwei; Liu, Zhenzhong; Dai, Lijun; Jiang, Yiguo

2016-01-01

As a common toxic metal, lead has significant neurotoxicity to brain development. Long non-coding RNAs (lncRNAs) function in multiple biological processes. However, whether lncRNAs are involved in lead-induced neurotoxicity remains unclear. Uc.173 is a lncRNA from a transcribed ultra-conservative region (T-UCR) of human, mouse and rat genomes. We established a lead-induced nerve injury mouse model. It showed the levels of Uc.173 decreased significantly in hippocampus tissue and serum of the model. We further tested the expression of Uc.173 in serum of lead-exposed children, which also showed a tendency to decrease. To explore the effects of Uc.173 on lead-induced nerve injury, we overexpressed Uc.173 in an N2a mouse nerve cell line and found Uc.173 had an inhibitory effect on lead-induced apoptosis of N2a. To investigate the molecular mechanisms of Uc.173 in apoptosis associated with lead-induced nerve injury, we predicted the target microRNAs of Uc.173 by using miRanda, TargetScan and RegRNA. After performing quantitative real-time PCR and bioinformatics analysis, we showed Uc.173 might inter-regulate with miR-291a-3p in lead-induced apoptosis and regulate apoptosis-associated genes. Our study suggests Uc.173 significantly inhibits the apoptosis of nerve cells, which may be mediated by inter-regulation with miRNAs in lead-induced nerve injury. PMID:26683706

Impact of different post-harvest processing methods on the chemical compositions of peony root.

PubMed

Zhu, Shu; Shirakawa, Aimi; Shi, Yanhong; Yu, Xiaoli; Tamura, Takayuki; Shibahara, Naotoshi; Yoshimatsu, Kayo; Komatsu, Katsuko

2018-06-01

The impact of key processing steps such as boiling, peeling, drying and storing on chemical compositions and morphologic features of the produced peony root was investigated in detail by applying 15 processing methods to fresh roots of Paeonia lactiflora and then monitoring contents of eight main components, as well as internal root color. The results showed that low temperature (4 °C) storage of fresh roots for approximately 1 month after harvest resulted in slightly increased and stable content of paeoniflorin, which might be due to suppression of enzymatic degradation. This storage also prevented roots from discoloring, facilitating production of favorable bright color roots. Boiling process triggered decomposition of polygalloylglucoses, thereby leading to a significant increase in contents of pentagalloylglucose and gallic acid. Peeling process resulted in a decrease of albiflorin and catechin contents. As a result, an optimized and practicable processing method ensuring high contents of the main active components in the produced root was developed.

Evaluation of a 'virtual' approach to commissioning health research.

PubMed

McCourt, Christine A; Morgan, Philip A; Youll, Penny

2006-10-18

The objective of this study was to evaluate the implementation of a 'virtual' (computer-mediated) approach to health research commissioning. This had been introduced experimentally in a DOH programme--the 'Health of Londoners Programme'--in order to assess whether is could enhance the accessibility, transparency and effectiveness of commissioning health research. The study described here was commissioned to evaluate this novel approach, addressing these key questions. A naturalistic-experimental approach was combined with principles of action research. The different commissioning groups within the programme were randomly allocated to either the traditional face-to-face mode or the novel 'virtual' mode. Mainly qualitative data were gathered including observation of all (virtual and face-to-face) commissioning meetings; semi-structured interviews with a purposive sample of participants (n = 32/66); structured questionnaires and interviews with lead researchers of early commissioned projects. All members of the commissioning groups were invited to participate in collaborative enquiry groups which participated actively in the analysis process. The virtual process functioned as intended, reaching timely and relatively transparent decisions that participants had confidence in. Despite the potential for greater access using a virtual approach, few differences were found in practice. Key advantages included physical access, a more flexible and extended time period for discussion, reflection and information gathering and a more transparent decision-making process. Key challenges were the reduction of social cues available in a computer-mediated medium that require novel ways of ensuring appropriate dialogue, feedback and interaction. However, in both modes, the process was influenced by a range of factors and was not technology driven. There is potential for using computer-mediated communication within the research commissioning process. This may enhance access, effectiveness and transparency of decision-making but further development is needed for this to be fully realised, including attention to process as well as the computer-mediated medium.

Evaluation of a 'virtual' approach to commissioning health research

PubMed Central

McCourt, Christine A; Morgan, Philip A; Youll, Penny

2006-01-01

Background The objective of this study was to evaluate the implementation of a 'virtual' (computer-mediated) approach to health research commissioning. This had been introduced experimentally in a DOH programme – the 'Health of Londoners Programme' – in order to assess whether is could enhance the accessibility, transparency and effectiveness of commissioning health research. The study described here was commissioned to evaluate this novel approach, addressing these key questions. Methods A naturalistic-experimental approach was combined with principles of action research. The different commissioning groups within the programme were randomly allocated to either the traditional face-to-face mode or the novel 'virtual' mode. Mainly qualitative data were gathered including observation of all (virtual and face-to-face) commissioning meetings; semi-structured interviews with a purposive sample of participants (n = 32/66); structured questionnaires and interviews with lead researchers of early commissioned projects. All members of the commissioning groups were invited to participate in collaborative enquiry groups which participated actively in the analysis process. Results The virtual process functioned as intended, reaching timely and relatively transparent decisions that participants had confidence in. Despite the potential for greater access using a virtual approach, few differences were found in practice. Key advantages included physical access, a more flexible and extended time period for discussion, reflection and information gathering and a more transparent decision-making process. Key challenges were the reduction of social cues available in a computer-mediated medium that require novel ways of ensuring appropriate dialogue, feedback and interaction. However, in both modes, the process was influenced by a range of factors and was not technology driven. Conclusion There is potential for using computer-mediated communication within the research commissioning process. This may enhance access, effectiveness and transparency of decision-making but further development is needed for this to be fully realised, including attention to process as well as the computer-mediated medium. PMID:17049079

Automated secured cost effective key refreshing technique to enhance WiMAX privacy key management

NASA Astrophysics Data System (ADS)

Sridevi, B.; Sivaranjani, S.; Rajaram, S.

2013-01-01

In all walks of life the way of communication is transformed by the rapid growth of wireless communication and its pervasive use. A wireless network which is fixed and richer in bandwidth is specified as IEEE 802.16, promoted and launched by an industrial forum is termed as Worldwide Interoperability for Microwave Access (WiMAX). This technology enables seamless delivery of wireless broadband service for fixed and/or mobile users. The obscurity is the long delay which occurs during the handoff management in every network. Mobile WiMAX employs an authenticated key management protocol as a part of handoff management in which the Base Station (BS) controls the distribution of keying material to the Mobile Station (MS). The protocol employed is Privacy Key Management Version 2- Extensible Authentication Protocol (PKMV2-EAP) which is responsible for the normal and periodical authorization of MSs, reauthorization as well as key refreshing. Authorization key (AK) and Traffic Encryption key (TEK) plays a vital role in key exchange. When the lifetime of key expires, MS has to request for a new key to BS which in turn leads to repetition of authorization, authentication as well as key exchange. To avoid service interruption during reauthorization , two active keys are transmitted at the same time by BS to MS. The consequences of existing work are hefty amount of bandwidth utilization, time consumption and large storage. It is also endured by Man in the Middle attack and Impersonation due to lack of security in key exchange. This paper designs an automatic mutual refreshing of keys to minimize bandwidth utilization, key storage and time consumption by proposing Previous key and Iteration based Key Refreshing Function (PKIBKRF). By integrating PKIBKRF in key generation, the simulation results indicate that 21.8% of the bandwidth and storage of keys are reduced and PKMV2 mutual authentication time is reduced by 66.67%. The proposed work is simulated with Qualnet model and backed by MATLAB for processing and MYSQL for storing keys.

ATX-LPA1 axis contributes to proliferation of chondrocytes by regulating fibronectin assembly leading to proper cartilage formation

PubMed Central

Nishioka, Tatsuji; Arima, Naoaki; Kano, Kuniyuki; Hama, Kotaro; Itai, Eriko; Yukiura, Hiroshi; Kise, Ryoji; Inoue, Asuka; Kim, Seok-Hyung; Solnica-Krezel, Lilianna; Moolenaar, Wouter H.; Chun, Jerold; Aoki, Junken

2016-01-01

The lipid mediator lysophosphatidic acid (LPA) signals via six distinct G protein-coupled receptors to mediate both unique and overlapping biological effects, including cell migration, proliferation and survival. LPA is produced extracellularly by autotaxin (ATX), a secreted lysophospholipase D, from lysophosphatidylcholine. ATX-LPA receptor signaling is essential for normal development and implicated in various (patho)physiological processes, but underlying mechanisms remain incompletely understood. Through gene targeting approaches in zebrafish and mice, we show here that loss of ATX-LPA1 signaling leads to disorganization of chondrocytes, causing severe defects in cartilage formation. Mechanistically, ATX-LPA1 signaling acts by promoting S-phase entry and cell proliferation of chondrocytes both in vitro and in vivo, at least in part through β1-integrin translocation leading to fibronectin assembly and further extracellular matrix deposition; this in turn promotes chondrocyte-matrix adhesion and cell proliferation. Thus, the ATX-LPA1 axis is a key regulator of cartilage formation. PMID:27005960

ATX-LPA1 axis contributes to proliferation of chondrocytes by regulating fibronectin assembly leading to proper cartilage formation.

PubMed

Nishioka, Tatsuji; Arima, Naoaki; Kano, Kuniyuki; Hama, Kotaro; Itai, Eriko; Yukiura, Hiroshi; Kise, Ryoji; Inoue, Asuka; Kim, Seok-Hyung; Solnica-Krezel, Lilianna; Moolenaar, Wouter H; Chun, Jerold; Aoki, Junken

2016-03-23

The lipid mediator lysophosphatidic acid (LPA) signals via six distinct G protein-coupled receptors to mediate both unique and overlapping biological effects, including cell migration, proliferation and survival. LPA is produced extracellularly by autotaxin (ATX), a secreted lysophospholipase D, from lysophosphatidylcholine. ATX-LPA receptor signaling is essential for normal development and implicated in various (patho)physiological processes, but underlying mechanisms remain incompletely understood. Through gene targeting approaches in zebrafish and mice, we show here that loss of ATX-LPA1 signaling leads to disorganization of chondrocytes, causing severe defects in cartilage formation. Mechanistically, ATX-LPA1 signaling acts by promoting S-phase entry and cell proliferation of chondrocytes both in vitro and in vivo, at least in part through β1-integrin translocation leading to fibronectin assembly and further extracellular matrix deposition; this in turn promotes chondrocyte-matrix adhesion and cell proliferation. Thus, the ATX-LPA1 axis is a key regulator of cartilage formation.

Perspectives of US Direct Care Workers on the Grief Process of Persons with Intellectual and Developmental Disabilities: Implications for Practice.

PubMed

Gray, Jennifer A; Abendroth, Maryann

2016-09-01

The study explored the grief process of persons with intellectual and developmental disabilities (PWIDDs) as perceived by direct care workers (DCWs) and how such workers can guide and support PWIDDs experiencing grief. A thematic analysis approach was used to examine data from nine focus groups with 60 DCWs from five community-based organizations. Findings were supported in the context of seminal grief and bereavement theories. Three themes (i.e. reactions to loss, processing the loss and incorporating the loss) and related subthemes emerged from the data. PWIDDs are susceptible to traumatic grief, and DCWs are often key witnesses to such experiences. DCWs' perspectives can guide the development of grief and bereavement training which can lead to more tailored support systems. © 2015 John Wiley & Sons Ltd.

A Chemical Model of the Coma of Comet C/2009 P1 (Garradd)

NASA Astrophysics Data System (ADS)

Boice, Daniel C.; Kawakita, H.; Kobayashi, H.; Naka, C.; Phelps, L.

2012-10-01

Modeling is essential to understand the important physical and chemical processes that occur in cometary comae. Photochemistry is a major source of ions and electrons that further initiate key gas-phase reactions, leading to the plethora of molecules and atoms observed in comets. The effects of photoelectrons that react via impacts are important to the overall ionization. We identify the relevant processes within a global modeling framework to understand simultaneous observations in the visible and near-IR of Comet C/2009 (Garradd) and to provide valuable insights into the intrinsic properties of its nucleus. Details of these processes are presented in the collision-dominated, inner coma of the comet to evaluate the relative chemical pathways and the relationship between parent and sibling molecules. Acknowledgements: We appreciate support from the NSF Planetary Astronomy Program.

Systems metabolic engineering in an industrial setting.

PubMed

Sagt, Cees M J

2013-03-01

Systems metabolic engineering is based on systems biology, synthetic biology, and evolutionary engineering and is now also applied in industry. Industrial use of systems metabolic engineering focuses on strain and process optimization. Since ambitious yields, titers, productivities, and low costs are key in an industrial setting, the use of effective and robust methods in systems metabolic engineering is becoming very important. Major improvements in the field of proteomics and metabolomics have been crucial in the development of genome-wide approaches in strain and process development. This is accompanied by a rapid increase in DNA sequencing and synthesis capacity. These developments enable the use of systems metabolic engineering in an industrial setting. Industrial systems metabolic engineering can be defined as the combined use of genome-wide genomics, transcriptomics, proteomics, and metabolomics to modify strains or processes. This approach has become very common since the technology for generating large data sets of all levels of the cellular processes has developed quite fast into robust, reliable, and affordable methods. The main challenge and scope of this mini review is how to translate these large data sets in relevant biological leads which can be tested for strain or process improvements. Experimental setup, heterogeneity of the culture, and sample pretreatment are important issues which are easily underrated. In addition, the process of structuring, filtering, and visualization of data is important, but also, the availability of a genetic toolbox and equipment for medium/high-throughput fermentation is a key success factor. For an efficient bioprocess, all the different components in this process have to work together. Therefore, mutual tuning of these components is an important strategy.

First-principles modeling of laser-matter interaction and plasma dynamics in nanosecond pulsed laser shock processing

NASA Astrophysics Data System (ADS)

Zhang, Zhongyang; Nian, Qiong; Doumanidis, Charalabos C.; Liao, Yiliang

2018-02-01

Nanosecond pulsed laser shock processing (LSP) techniques, including laser shock peening, laser peen forming, and laser shock imprinting, have been employed for widespread industrial applications. In these processes, the main beneficial characteristic is the laser-induced shockwave with a high pressure (in the order of GPa), which leads to the plastic deformation with an ultrahigh strain rate (105-106/s) on the surface of target materials. Although LSP processes have been extensively studied by experiments, few efforts have been put on elucidating underlying process mechanisms through developing a physics-based process model. In particular, development of a first-principles model is critical for process optimization and novel process design. This work aims at introducing such a theoretical model for a fundamental understanding of process mechanisms in LSP. Emphasis is placed on the laser-matter interaction and plasma dynamics. This model is found to offer capabilities in predicting key parameters including electron and ion temperatures, plasma state variables (temperature, density, and pressure), and the propagation of the laser shockwave. The modeling results were validated by experimental data.

3Ts for Reducing Lead in Drinking Water: Telling

EPA Pesticide Factsheets

Lead in drinking water in schools or childcare facilities programs should include communicating with parents, teachers, and the public. Transparency and a communication strategy are a key piece to developing a lead testing program.

Quantifying Cell Fate Decisions for Differentiation and Reprogramming of a Human Stem Cell Network: Landscape and Biological Paths

PubMed Central

Li, Chunhe; Wang, Jin

2013-01-01

Cellular reprogramming has been recently intensively studied experimentally. We developed a global potential landscape and kinetic path framework to explore a human stem cell developmental network composed of 52 genes. We uncovered the underlying landscape for the stem cell network with two basins of attractions representing stem and differentiated cell states, quantified and exhibited the high dimensional biological paths for the differentiation and reprogramming process, connecting the stem cell state and differentiated cell state. Both the landscape and non-equilibrium curl flux determine the dynamics of cell differentiation jointly. Flux leads the kinetic paths to be deviated from the steepest descent gradient path, and the corresponding differentiation and reprogramming paths are irreversible. Quantification of paths allows us to find out how the differentiation and reprogramming occur and which important states they go through. We show the developmental process proceeds as moving from the stem cell basin of attraction to the differentiation basin of attraction. The landscape topography characterized by the barrier heights and transition rates quantitatively determine the global stability and kinetic speed of cell fate decision process for development. Through the global sensitivity analysis, we provided some specific predictions for the effects of key genes and regulation connections on the cellular differentiation or reprogramming process. Key links from sensitivity analysis and biological paths can be used to guide the differentiation designs or reprogramming tactics. PMID:23935477

Architectures Toward Reusable Science Data Systems

NASA Astrophysics Data System (ADS)

Moses, J. F.

2014-12-01

Science Data Systems (SDS) comprise an important class of data processing systems that support product generation from remote sensors and in-situ observations. These systems enable research into new science data products, replication of experiments and verification of results. NASA has been building ground systems for satellite data processing since the first Earth observing satellites launched and is continuing development of systems to support NASA science research, NOAA's weather satellites and USGS's Earth observing satellite operations. The basic data processing workflows and scenarios continue to be valid for remote sensor observations research as well as for the complex multi-instrument operational satellite data systems being built today. System functions such as ingest, product generation and distribution need to be configured and performed in a consistent and repeatable way with an emphasis on scalability. This paper will examine the key architectural elements of several NASA satellite data processing systems currently in operation and under development that make them suitable for scaling and reuse. Examples of architectural elements that have become attractive include virtual machine environments, standard data product formats, metadata content and file naming, workflow and job management frameworks, data acquisition, search, and distribution protocols. By highlighting key elements and implementation experience the goal is to recognize architectures that will outlast their original application and be readily adaptable for new applications. Concepts and principles are explored that lead to sound guidance for SDS developers and strategists.

Architectures Toward Reusable Science Data Systems

NASA Technical Reports Server (NTRS)

Moses, John

2015-01-01

Science Data Systems (SDS) comprise an important class of data processing systems that support product generation from remote sensors and in-situ observations. These systems enable research into new science data products, replication of experiments and verification of results. NASA has been building systems for satellite data processing since the first Earth observing satellites launched and is continuing development of systems to support NASA science research and NOAAs Earth observing satellite operations. The basic data processing workflows and scenarios continue to be valid for remote sensor observations research as well as for the complex multi-instrument operational satellite data systems being built today. System functions such as ingest, product generation and distribution need to be configured and performed in a consistent and repeatable way with an emphasis on scalability. This paper will examine the key architectural elements of several NASA satellite data processing systems currently in operation and under development that make them suitable for scaling and reuse. Examples of architectural elements that have become attractive include virtual machine environments, standard data product formats, metadata content and file naming, workflow and job management frameworks, data acquisition, search, and distribution protocols. By highlighting key elements and implementation experience we expect to find architectures that will outlast their original application and be readily adaptable for new applications. Concepts and principles are explored that lead to sound guidance for SDS developers and strategists.

Hospital decentralisation in Romania: stakeholders' perspectives in the newsprint media.

PubMed

Popa, Adela Elena

2014-01-01

In the summer of 2010, Romania undertook a process of hospital decentralisation as part of the reform in the healthcare sector. The national newsprint media covered the process thoroughly. This paper is a study of how key stakeholders' views, attitudes, beliefs and attitudes towards decentralisation are represented in print media. 106 articles, published between June and September 2010, retrieved from the online databases of six leading national dailies were analysed. A mixed methodology was used in the data analysis stage. The qualitative data exploration identified five voices belonging to stakeholders involved directly or indirectly in the process: the representatives of central government, the local authorities (district and local councils, municipal mayors), health professionals (managers and physicians in hospitals), the media (journalists, analysts) and finally voices from civil society, professional associations and advocacy groups. These were the main actors negotiating the subjective meanings of the decentralisation process. An imbalance between these key actors were observed in the frequency, content and tone of the messages delivered in media during the four months. Central government and the local authorities were the most active voices, but the respective discourses differed significantly. An analysis of the accounts identified three main themes: the financial problem (hospitals liabilities and future spending), human resource in hospitals (the impact of decentralisation upon it) and the political character of the decentralisation. Copyright © 2013 John Wiley & Sons, Ltd.

Forward genetics defines Xylt1 as a key, conserved regulator of early chondrocyte maturation and skeletal length.

PubMed

Mis, Emily K; Liem, Karel F; Kong, Yong; Schwartz, Nancy B; Domowicz, Miriam; Weatherbee, Scott D

2014-01-01

The long bones of the vertebrate body are built by the initial formation of a cartilage template that is later replaced by mineralized bone. The proliferation and maturation of the skeletal precursor cells (chondrocytes) within the cartilage template and their replacement by bone is a highly coordinated process which, if misregulated, can lead to a number of defects including dwarfism and other skeletal deformities. This is exemplified by the fact that abnormal bone development is one of the most common types of human birth defects. Yet, many of the factors that initiate and regulate chondrocyte maturation are not known. We identified a recessive dwarf mouse mutant (pug) from an N-ethyl-N-nitrosourea (ENU) mutagenesis screen. pug mutant skeletal elements are patterned normally during development, but display a ~20% length reduction compared to wild-type embryos. We show that the pug mutation does not lead to changes in chondrocyte proliferation but instead promotes premature maturation and early ossification, which ultimately leads to disproportionate dwarfism. Using sequence capture and high-throughput sequencing, we identified a missense mutation in the Xylosyltransferase 1 (Xylt1) gene in pug mutants. Xylosyltransferases catalyze the initial step in glycosaminoglycan (GAG) chain addition to proteoglycan core proteins, and these modifications are essential for normal proteoglycan function. We show that the pug mutation disrupts Xylt1 activity and subcellular localization, leading to a reduction in GAG chains in pug mutants. The pug mutant serves as a novel model for mammalian dwarfism and identifies a key role for proteoglycan modification in the initiation of chondrocyte maturation. © 2013 Published by Elsevier Inc.

NO buffering and conditional NO release in stress response.

PubMed

Begara-Morales, Juan C; Chaki, Mounira; Valderrama, Raquel; Sánchez-Calvo, Beatriz; Mata-Pérez, Capilla; Padilla, María N; Corpas, Francisco J; Barroso, Juan B

2018-03-01

Nitric oxide (NO) has emerged as an essential biological messenger in plant biology that usually transmits its bioactivity by post-translational modifications such as S-nitrosylation, the reversible addition of a NO group to a protein cysteine residue leading to S-nitrosothiols (SNOs). In last year's, SNOs have emerged as key signalling molecules mainly involved in plant response to stress. Chief among SNOs is S-nitrosoglutathione (GSNO), generated by S-nitrosylation of the key antioxidant glutathione (GSH). GSNO is considered the major NO reservoir and a phloem mobile signal that confers to NO the capacity of a long-distance signalling molecule. GSNO is able to regulate protein function and gene expression resulting in a key role of GSNO in fundamental processes in plant such as development and response to a wide range of environmental stresses. In addition, GSNO is also able to regulate total SNO pool and consequently, it could be considered the storage of NO in cells that may control NO signalling under basal and stress-related responses. Thus, GSNO function could be crucial during plant response to environmental stresses. Besides this importance of GSNO in plant biology, its mode of action has not been widely discussed in the literature. In this review, we will firstly discuss the GSNO turnover in cells and secondly the role of GSNO as mediator of physiological and stress-related processes in plants, highlighting aspects in which there is still some controversy.

Reconstructing past ecological networks: the reconfiguration of seed-dispersal interactions after megafaunal extinction.

PubMed

Pires, Mathias M; Galetti, Mauro; Donatti, Camila I; Pizo, Marco A; Dirzo, Rodolfo; Guimarães, Paulo R

2014-08-01

The late Quaternary megafaunal extinction impacted ecological communities worldwide, and affected key ecological processes such as seed dispersal. The traits of several species of large-seeded plants are thought to have evolved in response to interactions with extinct megafauna, but how these extinctions affected the organization of interactions in seed-dispersal systems is poorly understood. Here, we combined ecological and paleontological data and network analyses to investigate how the structure of a species-rich seed-dispersal network could have changed from the Pleistocene to the present and examine the possible consequences of such changes. Our results indicate that the seed-dispersal network was organized into modules across the different time periods but has been reconfigured in different ways over time. The episode of megafaunal extinction and the arrival of humans changed how seed dispersers were distributed among network modules. However, the recent introduction of livestock into the seed-dispersal system partially restored the original network organization by strengthening the modular configuration. Moreover, after megafaunal extinctions, introduced species and some smaller native mammals became key components for the structure of the seed-dispersal network. We hypothesize that such changes in network structure affected both animal and plant assemblages, potentially contributing to the shaping of modern ecological communities. The ongoing extinction of key large vertebrates will lead to a variety of context-dependent rearranged ecological networks, most certainly affecting ecological and evolutionary processes.

What works in implementation of integrated care programs for older adults with complex needs? A realist review

PubMed Central

Kirst, Maritt; Im, Jennifer; Burns, Tim; Baker, G. Ross; Goldhar, Jodeme; O'Campo, Patricia; Wojtak, Anne; Wodchis, Walter P

2017-01-01

Abstract Purpose A realist review of the evaluative evidence was conducted on integrated care (IC) programs for older adults to identify key processes that lead to the success or failure of these programs in achieving outcomes such as reduced healthcare utilization, improved patient health, and improved patient and caregiver experience. Data sources International academic literature was searched in 12 indexed, electronic databases and gray literature through internet searches, to identify evaluative studies. Study selection Inclusion criteria included evaluative literature on integrated, long-stay health and social care programs, published between January 1980 and July 2015, in English. Data extraction Data were extracted on the study purpose, period, setting, design, population, sample size, outcomes, and study results, as well as explanations of mechanisms and contextual factors influencing outcomes. Results of data synthesis A total of 65 articles, representing 28 IC programs, were included in the review. Two context-mechanism-outcome configurations (CMOcs) were identified: (i) trusting multidisciplinary team relationships and (ii) provider commitment to and understanding of the model. Contextual factors such as strong leadership that sets clear goals and establishes an organizational culture in support of the program, along with joint governance structures, supported team collaboration and subsequent successful implementation. Furthermore, time to build an infrastructure to implement and flexibility in implementation, emerged as key processes instrumental to success of these programs. Conclusions This review included a wide range of international evidence, and identified key processes for successful implementation of IC programs that should be considered by program planners, leaders and evaluators. PMID:28992156

Complexity Level Analysis Revisited: What Can 30 Years of Hindsight Tell Us about How the Brain Might Represent Visual Information?

PubMed Central

Tsotsos, John K.

2017-01-01

Much has been written about how the biological brain might represent and process visual information, and how this might inspire and inform machine vision systems. Indeed, tremendous progress has been made, and especially during the last decade in the latter area. However, a key question seems too often, if not mostly, be ignored. This question is simply: do proposed solutions scale with the reality of the brain's resources? This scaling question applies equally to brain and to machine solutions. A number of papers have examined the inherent computational difficulty of visual information processing using theoretical and empirical methods. The main goal of this activity had three components: to understand the deep nature of the computational problem of visual information processing; to discover how well the computational difficulty of vision matches to the fixed resources of biological seeing systems; and, to abstract from the matching exercise the key principles that lead to the observed characteristics of biological visual performance. This set of components was termed complexity level analysis in Tsotsos (1987) and was proposed as an important complement to Marr's three levels of analysis. This paper revisits that work with the advantage that decades of hindsight can provide. PMID:28848458

Pan-Antarctic analysis aggregating spatial estimates of Adélie penguin abundance reveals robust dynamics despite stochastic noise.

PubMed

Che-Castaldo, Christian; Jenouvrier, Stephanie; Youngflesh, Casey; Shoemaker, Kevin T; Humphries, Grant; McDowall, Philip; Landrum, Laura; Holland, Marika M; Li, Yun; Ji, Rubao; Lynch, Heather J

2017-10-10

Colonially-breeding seabirds have long served as indicator species for the health of the oceans on which they depend. Abundance and breeding data are repeatedly collected at fixed study sites in the hopes that changes in abundance and productivity may be useful for adaptive management of marine resources, but their suitability for this purpose is often unknown. To address this, we fit a Bayesian population dynamics model that includes process and observation error to all known Adélie penguin abundance data (1982-2015) in the Antarctic, covering >95% of their population globally. We find that process error exceeds observation error in this system, and that continent-wide "year effects" strongly influence population growth rates. Our findings have important implications for the use of Adélie penguins in Southern Ocean feedback management, and suggest that aggregating abundance across space provides the fastest reliable signal of true population change for species whose dynamics are driven by stochastic processes.Adélie penguins are a key Antarctic indicator species, but data patchiness has challenged efforts to link population dynamics to key drivers. Che-Castaldo et al. resolve this issue using a pan-Antarctic Bayesian model to infer missing data, and show that spatial aggregation leads to more robust inference regarding dynamics.

Requirements Flowdown for Prognostics and Health Management

NASA Technical Reports Server (NTRS)

Goebel, Kai; Saxena, Abhinav; Roychoudhury, Indranil; Celaya, Jose R.; Saha, Bhaskar; Saha, Sankalita

2012-01-01

Prognostics and Health Management (PHM) principles have considerable promise to change the game of lifecycle cost of engineering systems at high safety levels by providing a reliable estimate of future system states. This estimate is a key for planning and decision making in an operational setting. While technology solutions have made considerable advances, the tie-in into the systems engineering process is lagging behind, which delays fielding of PHM-enabled systems. The derivation of specifications from high level requirements for algorithm performance to ensure quality predictions is not well developed. From an engineering perspective some key parameters driving the requirements for prognostics performance include: (1) maximum allowable Probability of Failure (PoF) of the prognostic system to bound the risk of losing an asset, (2) tolerable limits on proactive maintenance to minimize missed opportunity of asset usage, (3) lead time to specify the amount of advanced warning needed for actionable decisions, and (4) required confidence to specify when prognosis is sufficiently good to be used. This paper takes a systems engineering view towards the requirements specification process and presents a method for the flowdown process. A case study based on an electric Unmanned Aerial Vehicle (e-UAV) scenario demonstrates how top level requirements for performance, cost, and safety flow down to the health management level and specify quantitative requirements for prognostic algorithm performance.

Leading change: curriculum reform in graduate education in the biomedical sciences.

PubMed

Dasgupta, Shoumita; Symes, Karen; Hyman, Linda

2015-01-01

The Division of Graduate Medical Sciences at the Boston University School of Medicine houses numerous dynamic graduate programs. Doctoral students began their studies with laboratory rotations and classroom training in a variety of fundamental disciplines. Importantly, with 15 unique pathways of admission to these doctoral programs, there were also 15 unique curricula. Departments and programs offered courses independently, and students participated in curricula that were overlapping combinations of these courses. This system created curricula that were not coordinated and that had redundant course content as well as content gaps. A partnership of key stakeholders began a curriculum reform process to completely restructure doctoral education at the Boston University School of Medicine. The key pedagogical goals, objectives, and elements designed into the new curriculum through this reform process created a curriculum designed to foster the interdisciplinary thinking that students are ultimately asked to utilize in their research endeavors. We implemented comprehensive student and peer evaluation of the new Foundations in Biomedical Sciences integrated curriculum to assess the new curriculum. Furthermore, we detail how this process served as a gateway toward creating a more fully integrated graduate experience, under the umbrella of the Program in Biomedical Sciences. © 2015 The International Union of Biochemistry and Molecular Biology.

Complexity Level Analysis Revisited: What Can 30 Years of Hindsight Tell Us about How the Brain Might Represent Visual Information?

PubMed

Tsotsos, John K

2017-01-01

Much has been written about how the biological brain might represent and process visual information, and how this might inspire and inform machine vision systems. Indeed, tremendous progress has been made, and especially during the last decade in the latter area. However, a key question seems too often, if not mostly, be ignored. This question is simply: do proposed solutions scale with the reality of the brain's resources? This scaling question applies equally to brain and to machine solutions. A number of papers have examined the inherent computational difficulty of visual information processing using theoretical and empirical methods. The main goal of this activity had three components: to understand the deep nature of the computational problem of visual information processing; to discover how well the computational difficulty of vision matches to the fixed resources of biological seeing systems; and, to abstract from the matching exercise the key principles that lead to the observed characteristics of biological visual performance. This set of components was termed complexity level analysis in Tsotsos (1987) and was proposed as an important complement to Marr's three levels of analysis. This paper revisits that work with the advantage that decades of hindsight can provide.

Key role of organic carbon in the sunlight-enhanced atmospheric aging of soot by O2

PubMed Central

Han, Chong; Liu, Yongchun; Ma, Jinzhu; He, Hong

2012-01-01

Soot particles are ubiquitous in the atmosphere and have important climatic and health effects. The aging processes of soot during long-range transport result in variability in its morphology, microstructure, and hygroscopic and optical properties, subsequently leading to the modification of soot’s climatic and health effects. In the present study the aging process of soot by molecular O2 under simulated sunlight irradiation is investigated. Organic carbon components on the surface of soot are found to play a key role in soot aging and are transformed into oxygen-containing organic species including quinones, ketones, aldehydes, lactones, and anhydrides. These oxygen-containing species may become adsorption centers of water and thus enhance the cloud condensation nuclei and ice nuclei activities of soot. Under irradiation of 25 mW·cm−2, the apparent rate constants (k1,obs) for loss or formation of species on soot aged by 20% O2 were larger by factors of 1.5–3.5 than those on soot aged by 100 ppb O3. Considering the abundance of O2 in the troposphere and its higher photoreactivity rate, the photochemical oxidation by O2 under sunlight irradiation should be a very important aging process for soot. PMID:23236134

Computational Methods Used in Hit-to-Lead and Lead Optimization Stages of Structure-Based Drug Discovery.

PubMed

Heifetz, Alexander; Southey, Michelle; Morao, Inaki; Townsend-Nicholson, Andrea; Bodkin, Mike J

2018-01-01

GPCR modeling approaches are widely used in the hit-to-lead (H2L) and lead optimization (LO) stages of drug discovery. The aims of these modeling approaches are to predict the 3D structures of the receptor-ligand complexes, to explore the key interactions between the receptor and the ligand and to utilize these insights in the design of new molecules with improved binding, selectivity or other pharmacological properties. In this book chapter, we present a brief survey of key computational approaches integrated with hierarchical GPCR modeling protocol (HGMP) used in hit-to-lead (H2L) and in lead optimization (LO) stages of structure-based drug discovery (SBDD). We outline the differences in modeling strategies used in H2L and LO of SBDD and illustrate how these tools have been applied in three drug discovery projects.

Supraglacial channel inception: Modeling and processes

NASA Astrophysics Data System (ADS)

Mantelli, E.; Camporeale, C.; Ridolfi, L.

2015-09-01

Supraglacial drainage systems play a key role in glacial hydrology. Nevertheless, physical processes leading to spatial organization in supraglacial networks are still an open issue. In the present work we thus address from a quantitative point of view the question of what is the physics leading to widely observed patterns made up of evenly spaced channels. To this aim, we set up a novel mathematical model describing a condition antecedent channel formation, i.e., the down-glacier flow of a distributed meltwater film. We then perform a linear stability analysis to assess whether the ice-water interface undergoes a morphological instability compatible with observed patterns. The instability is detected, its features depending on glacier surface slope, ice friction factor, and water as well as ice thermal conditions. By contrast, in our model channel spacing is solely hydrodynamically driven and relies on the interplay between pressure perturbations, flow depth response, and Reynolds stresses. Geometrical features of the predicted pattern are quantitatively consistent with available field data. The hydrodynamic origin of supraglacial channel morphogenesis suggests that alluvial patterns might share the same physical controls.

MicroRNAs in right ventricular remodelling.

PubMed

Batkai, Sandor; Bär, Christian; Thum, Thomas

2017-10-01

Right ventricular (RV) remodelling is a lesser understood process of the chronic, progressive transformation of the RV structure leading to reduced functional capacity and subsequent failure. Besides conditions concerning whole hearts, some pathology selectively affects the RV, leading to a distinct RV-specific clinical phenotype. MicroRNAs have been identified as key regulators of biological processes that drive the progression of chronic diseases. The role of microRNAs in diseases affecting the left ventricle has been studied for many years, however there is still limited information on microRNAs specific to diseases in the right ventricle. Here, we review recently described details on the expression, regulation, and function of microRNAs in the pathological remodelling of the right heart. Recently identified strategies using microRNAs as pharmacological targets or biomarkers will be highlighted. Increasing knowledge of pathogenic microRNAs will finally help improve our understanding of underlying distinct mechanisms and help utilize novel targets or biomarkers to develop treatments for patients suffering from right heart diseases. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Structure Basis for Directional R-loop Formation and Substrate Handover Mechanisms in Type I CRISPR-Cas System.

PubMed

Xiao, Yibei; Luo, Min; Hayes, Robert P; Kim, Jonathan; Ng, Sherwin; Ding, Fang; Liao, Maofu; Ke, Ailong

2017-06-29

Type I CRISPR systems feature a sequential dsDNA target searching and degradation process, by crRNA-displaying Cascade and nuclease-helicase fusion enzyme Cas3, respectively. Here we present two cryo-EM snapshots of the Thermobifida fusca type I-E Cascade: (1) unwinding 11 bp of dsDNA at the seed-sequence region to scout for sequence complementarity, and (2) further unwinding of the entire protospacer to form a full R-loop. These structures provide the much-needed temporal and spatial resolution to resolve key mechanistic steps leading to Cas3 recruitment. In the early steps, PAM recognition causes severe DNA bending, leading to spontaneous DNA unwinding to form a seed-bubble. The full R-loop formation triggers conformational changes in Cascade, licensing Cas3 to bind. The same process also generates a bulge in the non-target DNA strand, enabling its handover to Cas3 for cleavage. The combination of both negative and positive checkpoints ensures stringent yet efficient target degradation in type I CRISPR-Cas systems. Copyright © 2017 Elsevier Inc. All rights reserved.

Designing Process Improvement of Finished Good On Time Release and Performance Indicator Tool in Milk Industry Using Business Process Reengineering Method

NASA Astrophysics Data System (ADS)

Dachyar, M.; Christy, E.

2014-04-01

To maintain position as a major milk producer, the Indonesian milk industry should do some business development with the purpose of increasing customer service level. One strategy is to create on time release conditions for finished goods which will be distributed to customers and distributors. To achieve this condition, management information systems of finished goods on time release needs to be improved. The focus of this research is to conduct business process improvement using Business Process Reengineering (BPR). The deliverable key of this study is a comprehensive business strategy which is the solution of the root problems. To achieve the goal, evaluation, reengineering, and improvement of the ERP system are conducted. To visualize the predicted implementation, a simulation model is built by Oracle BPM. The output of this simulation showed that the proposed solution could effectively reduce the process lead time and increase the number of quality releases.

A two-in-one process for reliable graphene transistors processed with photo-lithography

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

Ahlberg, P.; Hinnemo, M.; Song, M.

2015-11-16

Research on graphene field-effect transistors (GFETs) has mainly relied on devices fabricated using electron-beam lithography for pattern generation, a method that has known problems with polymer contaminants. GFETs fabricated via photo-lithography suffer even worse from other chemical contaminations, which may lead to strong unintentional doping of the graphene. In this letter, we report on a scalable fabrication process for reliable GFETs based on ordinary photo-lithography by eliminating the aforementioned issues. The key to making this GFET processing compatible with silicon technology lies in a two-in-one process where a gate dielectric is deposited by means of atomic layer deposition. During thismore » deposition step, contaminants, likely unintentionally introduced during the graphene transfer and patterning, are effectively removed. The resulting GFETs exhibit current-voltage characteristics representative to that of intrinsic non-doped graphene. Fundamental aspects pertaining to the surface engineering employed in this work are investigated in the light of chemical analysis in combination with electrical characterization.« less

Thermooptics of magnetoactive media: Faraday isolators for high average power lasers

NASA Astrophysics Data System (ADS)

Khazanov, E. A.

2016-09-01

The Faraday isolator, one of the key high-power laser elements, provides optical isolation between a master oscillator and a power amplifier or between a laser and its target, for example, a gravitational wave detector interferometer. However, the absorbed radiation inevitably heats the magnetoactive medium and leads to thermally induced polarization and phase distortions in the laser beam. This self-action process limits the use of Faraday isolators in high average power lasers. A unique property of magnetoactive medium thermooptics is that parasitic thermal effects arise on the background of circular birefringence rather than in an isotropic medium. Also, even insignificant polarization distortions of the radiation result in a worse isolation ratio, which is the key characteristic of the Faraday isolator. All possible laser beam distortions are analyzed for their deteriorating effect on the Faraday isolator parameters. The mechanisms responsible for and key physical parameters associated with different kinds of distortions are identified and discussed. Methods for compensating and suppressing parasitic thermal effects are described in detail, the published experimental data are systematized, and avenues for further research are discussed based on the results achieved.

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.

Human body motion capture from multi-image video sequences

NASA Astrophysics Data System (ADS)

D'Apuzzo, Nicola

2003-01-01

In this paper is presented a method to capture the motion of the human body from multi image video sequences without using markers. The process is composed of five steps: acquisition of video sequences, calibration of the system, surface measurement of the human body for each frame, 3-D surface tracking and tracking of key points. The image acquisition system is currently composed of three synchronized progressive scan CCD cameras and a frame grabber which acquires a sequence of triplet images. Self calibration methods are applied to gain exterior orientation of the cameras, the parameters of internal orientation and the parameters modeling the lens distortion. From the video sequences, two kinds of 3-D information are extracted: a three-dimensional surface measurement of the visible parts of the body for each triplet and 3-D trajectories of points on the body. The approach for surface measurement is based on multi-image matching, using the adaptive least squares method. A full automatic matching process determines a dense set of corresponding points in the triplets. The 3-D coordinates of the matched points are then computed by forward ray intersection using the orientation and calibration data of the cameras. The tracking process is also based on least squares matching techniques. Its basic idea is to track triplets of corresponding points in the three images through the sequence and compute their 3-D trajectories. The spatial correspondences between the three images at the same time and the temporal correspondences between subsequent frames are determined with a least squares matching algorithm. The results of the tracking process are the coordinates of a point in the three images through the sequence, thus the 3-D trajectory is determined by computing the 3-D coordinates of the point at each time step by forward ray intersection. Velocities and accelerations are also computed. The advantage of this tracking process is twofold: it can track natural points, without using markers; and it can track local surfaces on the human body. In the last case, the tracking process is applied to all the points matched in the region of interest. The result can be seen as a vector field of trajectories (position, velocity and acceleration). The last step of the process is the definition of selected key points of the human body. A key point is a 3-D region defined in the vector field of trajectories, whose size can vary and whose position is defined by its center of gravity. The key points are tracked in a simple way: the position at the next time step is established by the mean value of the displacement of all the trajectories inside its region. The tracked key points lead to a final result comparable to the conventional motion capture systems: 3-D trajectories of key points which can be afterwards analyzed and used for animation or medical purposes.

Facilitating factors and barriers to malaria research utilization for policy development in Malawi.

PubMed

Mwendera, Chikondi A; de Jager, Christiaan; Longwe, Herbert; Phiri, Kamija; Hongoro, Charles; Mutero, Clifford M

2016-10-19

Research on various determinants of health is key in providing evidence for policy development, thereby leading to successful interventions. Utilization of research is an intricate process requiring an understanding of contextual factors. The study was conducted to assess enhancing factors and barriers of research utilization for malaria policy development in Malawi. Qualitative research approach was used through in-depth interviews with 39 key informants that included malaria researchers, policy makers, programme managers, and key stakeholders. Purposive sampling and snowballing techniques were used in identifying key informants. Interview transcripts were entered in QSR Nvivo 11 software for coding and analysis. Respondents identified global efforts as key in advancing knowledge translation, while local political will has been conducive for research utilization. Other factors were availability of research, availability of diverse local researchers and stakeholders supporting knowledge translation. While barriers included: lack of platforms for researcher-public engagement, politics, researchers' lack of communication skills, lack of research collaborations, funder driven research, unknown World Health Organization policy position, and the lack of a malaria research repository. Overall, the study identified facilitating factors to malaria research utilization for policy development in Malawi. These factors need to be systematically coordinated to address the identified barriers and improve on malaria research utilization in policy development. Malaria research can be key in the implementation of evidence-based interventions to reduce the malaria burden and assist in the paradigm shift from malaria control to elimination in Malawi.

Concept Design of Cryogenic Propellant Storage and Transfer for Space Exploration

NASA Technical Reports Server (NTRS)

Free, James M.; Motil, Susan M.; Kortes, Trudy F.; Meyer, Michael L.; taylor, William J.

2012-01-01

NASA is in the planning and investigation process of developing innovative paths for human space exploration that strengthen the capability to extend human and robotic presence beyond low Earth orbit and throughout the solar system. NASA is establishing the foundations to enable humans to safely reach multiple potential destinations, including the Moon, asteroids, Lagrange points, and Mars and its environs through technology and capability development. To achieve access to these destinations within a reasonable flight time will require the use of high performance cryogenic propulsion systems. Therefore NASA is examining mission concepts for a Cryogenic Propellant Storage and Transfer (CPST) Flight Demonstration which will test and validate key capabilities and technologies required for future exploration elements such as large cryogenic propulsion stages and propellant depots. The CPST project will perform key ground testing in fiscal year 2012 and execute project formulation and implementation leading to a flight demonstration in 2017.

5'-Monophosphate-activated protein kinase (AMPK) improves autophagic activity in diabetes and diabetic complications

PubMed Central

Yao, Fan; Zhang, Ming; Chen, Li

2015-01-01

Diabetes mellitus (DM), an endocrine disorder, will be one of the leading causes of death world-wide in about two decades. Cellular injuries and disorders of energy metabolism are two key factors in the pathogenesis of diabetes, which also become the important causes for the process of diabetic complications. AMPK is a key enzyme in maintaining metabolic homeostasis and has been implicated in the activation of autophagy in distinct tissues. An increasing number of researchers have confirmed that autophagy is a potential factor to affect or induce diabetes and its complications nowadays, which could remove cytotoxic proteins and dysfunctional organelles. This review will summarize the regulation of autophagy and AMPK in diabetes and its complications, and explore how AMPK stimulates autophagy in different diabetic syndromes. A deeper understanding of the regulation and activity of AMPK in autophagy would enhance its development as a promising therapeutic target for diabetes treatment. PMID:26904395

5'-Monophosphate-activated protein kinase (AMPK) improves autophagic activity in diabetes and diabetic complications.

PubMed

Yao, Fan; Zhang, Ming; Chen, Li

2016-01-01

Diabetes mellitus (DM), an endocrine disorder, will be one of the leading causes of death world-wide in about two decades. Cellular injuries and disorders of energy metabolism are two key factors in the pathogenesis of diabetes, which also become the important causes for the process of diabetic complications. AMPK is a key enzyme in maintaining metabolic homeostasis and has been implicated in the activation of autophagy in distinct tissues. An increasing number of researchers have confirmed that autophagy is a potential factor to affect or induce diabetes and its complications nowadays, which could remove cytotoxic proteins and dysfunctional organelles. This review will summarize the regulation of autophagy and AMPK in diabetes and its complications, and explore how AMPK stimulates autophagy in different diabetic syndromes. A deeper understanding of the regulation and activity of AMPK in autophagy would enhance its development as a promising therapeutic target for diabetes treatment.

Relevance of Viroporin Ion Channel Activity on Viral Replication and Pathogenesis

PubMed Central

Nieto-Torres, Jose L.; Verdiá-Báguena, Carmina; Castaño-Rodriguez, Carlos; Aguilella, Vicente M.; Enjuanes, Luis

2015-01-01

Modification of host-cell ionic content is a significant issue for viruses, as several viral proteins displaying ion channel activity, named viroporins, have been identified. Viroporins interact with different cellular membranes and self-assemble forming ion conductive pores. In general, these channels display mild ion selectivity, and, eventually, membrane lipids play key structural and functional roles in the pore. Viroporins stimulate virus production through different mechanisms, and ion channel conductivity has been proved particularly relevant in several cases. Key stages of the viral cycle such as virus uncoating, transport and maturation are ion-influenced processes in many viral species. Besides boosting virus propagation, viroporins have also been associated with pathogenesis. Linking pathogenesis either to the ion conductivity or to other functions of viroporins has been elusive for a long time. This article summarizes novel pathways leading to disease stimulated by viroporin ion conduction, such as inflammasome driven immunopathology. PMID:26151305

Heme oxygenase: the key to renal function regulation

PubMed Central

Cao, Jian; Sacerdoti, David; Li, Xiaoying; Drummond, George

2009-01-01

Heme oxygenase (HO) plays a critical role in attenuating the production of reactive oxygen species through its ability to degrade heme in an enzymatic process that leads to the production of equimolar amounts of carbon monoxide and biliverdin/bilirubin and the release of free iron. The present review examines the beneficial role of HO-1 (inducible form of HO) that is achieved by increased expression of this enzyme in renal tissue. The influence of the HO system on renal physiology, obesity, vascular dysfunction, and blood pressure regulation is reviewed, and the clinical potential of increased levels of HO-1 protein, HO activity, and HO-derived end products of heme degradation is discussed relative to renal disease. The use of pharmacological and genetic approaches to investigate the role of the HO system in the kidney is key to the development of therapeutic approaches to prevent the adverse effects that accrue due to an impairment in renal function. PMID:19570878

Fibroblast growth factors: key players in regeneration and tissue repair.

PubMed

Maddaluno, Luigi; Urwyler, Corinne; Werner, Sabine

2017-11-15

Tissue injury initiates a complex repair process, which in some organisms can lead to the complete regeneration of a tissue. In mammals, however, the repair of most organs is imperfect and results in scar formation. Both regeneration and repair are orchestrated by a highly coordinated interplay of different growth factors and cytokines. Among the key players are the fibroblast growth factors (FGFs), which control the migration, proliferation, differentiation and survival of different cell types. In addition, FGFs influence the expression of other factors involved in the regenerative response. Here, we summarize current knowledge on the roles of endogenous FGFs in regeneration and repair in different organisms and in different tissues and organs. Gaining a better understanding of these FGF activities is important for appropriate modulation of FGF signaling after injury to prevent impaired healing and to promote organ regeneration in humans. © 2017. Published by The Company of Biologists Ltd.

Natural solution to antibiotic resistance: bacteriophages 'The Living Drugs'.

PubMed

Jassim, Sabah A A; Limoges, Richard G

2014-08-01

Antibiotics have been a panacea in animal husbandry as well as in human therapy for decades. The huge amount of antibiotics used to induce the growth and protect the health of farm animals has lead to the evolution of bacteria that are resistant to the drug's effects. Today, many researchers are working with bacteriophages (phages) as an alternative to antibiotics in the control of pathogens for human therapy as well as prevention, biocontrol, and therapy in animal agriculture. Phage therapy and biocontrol have yet to fulfill their promise or potential, largely due to several key obstacles to their performance. Several suggestions are shared in order to point a direction for overcoming common obstacles in applied phage technology. The key to successful use of phages in modern scientific, farm, food processing and clinical applications is to understand the common obstacles as well as best practices and to develop answers that work in harmony with nature.

Unsolved mysteries: How does lipid peroxidation cause ferroptosis?

PubMed Central

Feng, Huizhong

2018-01-01

Ferroptosis is a cell death process driven by damage to cell membranes and linked to numerous human diseases. Ferroptosis is caused by loss of activity of the key enzyme that is tasked with repairing oxidative damage to cell membranes—glutathione peroxidase 4 (GPX4). GPX4 normally removes the dangerous products of iron-dependent lipid peroxidation, protecting cell membranes from this type of damage; when GPX4 fails, ferroptosis ensues. Ferroptosis is distinct from apoptosis, necroptosis, necrosis, and other modes of cell death. Several key mysteries regarding how cells die during ferroptosis remain unsolved. First, the drivers of lipid peroxidation are not yet clear. Second, the subcellular location of lethal lipid peroxides remains an outstanding question. Finally, how exactly lipid peroxidation leads to cell death is an unsolved mystery. Answers to these questions will provide insights into the mechanisms of ferroptotic cell death and associated human diseases, as well as new therapeutic strategies for such diseases. PMID:29795546

Laser dimpling process parameters selection and optimization using surrogate-driven process capability space

NASA Astrophysics Data System (ADS)

Ozkat, Erkan Caner; Franciosa, Pasquale; Ceglarek, Dariusz

2017-08-01

Remote laser welding technology offers opportunities for high production throughput at a competitive cost. However, the remote laser welding process of zinc-coated sheet metal parts in lap joint configuration poses a challenge due to the difference between the melting temperature of the steel (∼1500 °C) and the vapourizing temperature of the zinc (∼907 °C). In fact, the zinc layer at the faying surface is vapourized and the vapour might be trapped within the melting pool leading to weld defects. Various solutions have been proposed to overcome this problem over the years. Among them, laser dimpling has been adopted by manufacturers because of its flexibility and effectiveness along with its cost advantages. In essence, the dimple works as a spacer between the two sheets in lap joint and allows the zinc vapour escape during welding process, thereby preventing weld defects. However, there is a lack of comprehensive characterization of dimpling process for effective implementation in real manufacturing system taking into consideration inherent changes in variability of process parameters. This paper introduces a methodology to develop (i) surrogate model for dimpling process characterization considering multiple-inputs (i.e. key control characteristics) and multiple-outputs (i.e. key performance indicators) system by conducting physical experimentation and using multivariate adaptive regression splines; (ii) process capability space (Cp-Space) based on the developed surrogate model that allows the estimation of a desired process fallout rate in the case of violation of process requirements in the presence of stochastic variation; and, (iii) selection and optimization of the process parameters based on the process capability space. The proposed methodology provides a unique capability to: (i) simulate the effect of process variation as generated by manufacturing process; (ii) model quality requirements with multiple and coupled quality requirements; and (iii) optimize process parameters under competing quality requirements such as maximizing the dimple height while minimizing the dimple lower surface area.

Characterization of Moist Processes Associated With Changes in the Propagation of the MJO With Increasing CO2

PubMed Central

Kim, Daehyun; Sobel, Adam H.; Del Genio, Anthony; Wu, Jingbo

2017-01-01

Abstract The processes that lead to changes in the propagation and maintenance of the Madden‐Julian Oscillation (MJO) as a response to increasing CO2 are examined by analyzing moist static energy budget of the MJO in a series of NASA GISS model simulations. It is found changes in MJO propagation is dominated by several key processes. Horizontal moisture advection, a key process for MJO propagation, is found to enhance predominantly due to an increase in the mean horizontal moisture gradients. The terms that determine the strength of the advecting wind anomalies, the MJO horizontal scale and the dry static stability, are found to exhibit opposing trends that largely cancel out. Furthermore, reduced sensitivity of precipitation to changes in column moisture, i.e., a lengthening in the convective moisture adjustment time scale, also opposes enhanced propagation. The dispersion relationship of Adames and Kim, which accounts for all these processes, predicts an acceleration of the MJO at a rate of ∼3.5% K−1, which is consistent with the actual phase speed changes in the simulation. For the processes that contribute to MJO maintenance, it is found that damping by vertical MSE advection is reduced due to the increasing vertical moisture gradient. This weaker damping is nearly canceled by weaker maintenance by cloud‐radiative feedbacks, yielding the growth rate from the linear moisture mode theory nearly unchanged with the warming. Furthermore, the estimated growth rates are found to be a small, negative values, suggesting that the MJO in the simulation is a weakly damped mode. PMID:29497477

Auditory-musical processing in autism spectrum disorders: a review of behavioral and brain imaging studies.

PubMed

Ouimet, Tia; Foster, Nicholas E V; Tryfon, Ana; Hyde, Krista L

2012-04-01

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by atypical social and communication skills, repetitive behaviors, and atypical visual and auditory perception. Studies in vision have reported enhanced detailed ("local") processing but diminished holistic ("global") processing of visual features in ASD. Individuals with ASD also show enhanced processing of simple visual stimuli but diminished processing of complex visual stimuli. Relative to the visual domain, auditory global-local distinctions, and the effects of stimulus complexity on auditory processing in ASD, are less clear. However, one remarkable finding is that many individuals with ASD have enhanced musical abilities, such as superior pitch processing. This review provides a critical evaluation of behavioral and brain imaging studies of auditory processing with respect to current theories in ASD. We have focused on auditory-musical processing in terms of global versus local processing and simple versus complex sound processing. This review contributes to a better understanding of auditory processing differences in ASD. A deeper comprehension of sensory perception in ASD is key to better defining ASD phenotypes and, in turn, may lead to better interventions. © 2012 New York Academy of Sciences.

Health Care Merged With Senior Housing: Description and Evaluation of a Successful Program.

PubMed

Barry, Theresa Teta

2017-01-01

Objective: This article describes and evaluates a successful partnership between a large health care organization and housing for seniors. The program provides on-site, primary care visits by a physician and a nurse in addition to intensive social services to residents in an affordable senior housing apartment building located in Pennsylvania. Per Donabedian's "Structure-Process-Outcome" model, the program demonstrated positive health care outcomes for its participants via a prescribed structure. To provide guidance for replication in similar settings, we qualitatively evaluated the processes by which successful outcomes were obtained. Methods: With program structures in place and outcomes measured, this case study collected and analyzed qualitative information taken from key informant interviews on care processes involved in the program. Themes were extracted from semistructured interviews and used to describe the processes that helped and hindered the program. Results and Discussion: Common processes were identified across respondents; however, the nuanced processes that lead to successful outcomes suggest that defined structures and processes may not be sufficient to produce similar outcomes in other settings. Further research is needed to determine the program's replicability and policy implications.

The relationship between occupational exposure to lead and manifestation of cardiovascular complications in persons with arterial hypertension

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

Poreba, Rafal, E-mail: sogood@poczta.onet.p; Gac, Pawel; Poreba, Malgorzata

The chronic exposure to lead represents a risk factor of arterial hypertension development. Ambulatory blood pressure monitoring is the most prognostically reliable method of measuring of arterial blood pressure. The study is aimed at evaluating the relationship between occupational exposure to lead and manifestation of cardiovascular complications in patients with arterial hypertension. The studies included 73 men (mean age, 54.26 {+-} 8.17 years) with arterial hypertension, treated with hypotensive drugs: group I-persons occupationally exposed to lead (n = 35) and group II-individuals not exposed to lead (n = 38). An analysis of results obtained during ambulatory blood pressure monitoring disclosedmore » significantly higher values of mean systolic blood pressure, mean blood pressure, pulse pressure, and variability of systolic blood pressure in the group of hypertensive patients occupationally exposed to lead as compared to patients with arterial hypertension but not exposed to lead. The logistic regression showed that a more advanced age, higher concentration of blood zinc protoporphyrin, and a higher mean value of pulse pressure represented independent risk factors of left ventricular hypertrophy in the group of persons with arterial hypertension and chronically exposed to lead (OR{sub age} = 1.11; OR{sub ZnPP} = 1.32; OR{sub PP} = 1,43; p < 0.05). In view of the above data demonstration that occupational exposure to lead represents an independent risk factor of increased pulse pressure may be of key importance in the process of shaping general social awareness as to harmful effects of lead compounds on human health.« less

Participation process and outcome interactions: Exploring participation in water resource management

NASA Astrophysics Data System (ADS)

Carr, G.; Loucks, D. P.; Blöschl, G.

2012-04-01

Evaluating participation programmes, projects and activities aids understanding of effective mechanisms and enables the identification of improvements to current strategies. Characteristics of participation processes, such whether the process is cost effective, adequately facilitated, accessible, includes a representative section of society or interest groups and allocates power equivalently between participants, are commonly described and evaluated in the literature. A key question concerns whether effective processes lead to desirable outcomes. Two types of outcomes can be identified from participation programmes - tangible and non-tangible. Tangible outcomes include resource management changes or resource quality changes. Non tangible outcomes include developing and strengthening communication and action networks, building trust between individuals and/or organisations, developing innovative solutions, or developing shared knowledge and understandings of issues. To better understand how participation impacts upon resource management it is necessary to identify i) how non-tangible outcomes lead to resource management outcomes and ii) which characteristics of the participation process are connected to achieving non-tangible outcomes. This has been attempted with a literature based meta-analysis. Literature has been analysed to identify outcomes from participations programmes, and the process characteristics present that are associated with promoting or inhibiting their achievement. Preliminary analysis shows that process characteristics such as representation, facilitation and accessibility are important for achieving non-tangible outcomes. The relationship between non-tangible outcomes and resource management outcomes is less clear in the literature. This may be due to the different timescales over which the different types of outcomes emerge (resource management outcomes emerge over longer time periods) and the different contexts or settings in which participation takes place.

Genome resequencing in Populus: Revealing large-scale genome variation and implications on specialized-trait genomics

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

Muchero, Wellington; Labbe, Jessy L; Priya, Ranjan

2014-01-01

To date, Populus ranks among a few plant species with a complete genome sequence and other highly developed genomic resources. With the first genome sequence among all tree species, Populus has been adopted as a suitable model organism for genomic studies in trees. However, far from being just a model species, Populus is a key renewable economic resource that plays a significant role in providing raw materials for the biofuel and pulp and paper industries. Therefore, aside from leading frontiers of basic tree molecular biology and ecological research, Populus leads frontiers in addressing global economic challenges related to fuel andmore » fiber production. The latter fact suggests that research aimed at improving quality and quantity of Populus as a raw material will likely drive the pursuit of more targeted and deeper research in order to unlock the economic potential tied in molecular biology processes that drive this tree species. Advances in genome sequence-driven technologies, such as resequencing individual genotypes, which in turn facilitates large scale SNP discovery and identification of large scale polymorphisms are key determinants of future success in these initiatives. In this treatise we discuss implications of genome sequence-enable technologies on Populus genomic and genetic studies of complex and specialized-traits.« less

The Recognition Heuristic: A Review of Theory and Tests

PubMed Central

Pachur, Thorsten; Todd, Peter M.; Gigerenzer, Gerd; Schooler, Lael J.; Goldstein, Daniel G.

2011-01-01

The recognition heuristic is a prime example of how, by exploiting a match between mind and environment, a simple mental strategy can lead to efficient decision making. The proposal of the heuristic initiated a debate about the processes underlying the use of recognition in decision making. We review research addressing four key aspects of the recognition heuristic: (a) that recognition is often an ecologically valid cue; (b) that people often follow recognition when making inferences; (c) that recognition supersedes further cue knowledge; (d) that its use can produce the less-is-more effect – the phenomenon that lesser states of recognition knowledge can lead to more accurate inferences than more complete states. After we contrast the recognition heuristic to other related concepts, including availability and fluency, we carve out, from the existing findings, some boundary conditions of the use of the recognition heuristic as well as key questions for future research. Moreover, we summarize developments concerning the connection of the recognition heuristic with memory models. We suggest that the recognition heuristic is used adaptively and that, compared to other cues, recognition seems to have a special status in decision making. Finally, we discuss how systematic ignorance is exploited in other cognitive mechanisms (e.g., estimation and preference). PMID:21779266

Defining a Computational Framework for the Assessment of ...

EPA Pesticide Factsheets

The Adverse Outcome Pathway (AOP) framework describes the effects of environmental stressors across multiple scales of biological organization and function. This includes an evaluation of the potential for each key event to occur across a broad range of species in order to determine the taxonomic applicability of each AOP. Computational tools are needed to facilitate this process. Recently, we developed a tool that uses sequence homology to evaluate the applicability of molecular initiating events across species (Lalone et al., Toxicol. Sci., 2016). To extend our ability to make computational predictions at higher levels of biological organization, we have created the AOPdb. This database links molecular targets identified associated with key events in the AOPwiki to publically available data (e.g. gene-protein, pathway, species orthology, ontology, chemical, disease) including ToxCast assay information. The AOPdb combines different data types in order to characterize the impacts of chemicals to human health and the environment and serves as a decision support tool for case study development in the area of taxonomic applicability. As a proof of concept, the AOPdb allows identification of relevant molecular targets, biological pathways, and chemical and disease associations across species for four AOPs from the AOP-Wiki (https://aopwiki.org): Estrogen receptor antagonism leading to reproductive dysfunction (Aop:30); Aromatase inhibition leading to reproductive d

Community engagement as conflict prevention: Understanding the social license to operate

NASA Astrophysics Data System (ADS)

Knih, Dejana

This thesis examines community engagement as a form of conflict prevention in order to obtain the social license to operate (SLO) in Alberta's oil and gas industry. It does this by answering the question: what are the key elements of the Social License to Operate and how can these elements be applied to community engagement/consultation in a way that prevents conflicts in Alberta's oil and gas industry? The underlying assumption of this thesis is that building good relationships and working collaboratively functions as a form of conflict prevention and that this in turn leads to the SLO. This thesis outlines the key features of both successful community engagement and of the SLO, to provide a guideline for what is needed to obtain the SLO. Data was collected from semi-structured interviews and through a literature review. The data analysis concluded that there are direct parallels between the key elements of effective community engagement and the key elements of the SLO as identified in the interviews. These parallels are: knowing the community, addressing community needs, corporate social responsibility, relationship building, follow through and evidence for what has been done, executive buy-in, excellent communication, and open dialogue, all within a process which is principled (there is trust, understanding, transparency and respect), inclusive, dynamic, flexible, ongoing, and long-term. Moreover, the key elements of effective community engagement and of the SLO identified in the interviews also overlapped with those found in the literature review, with only one exception. The literature review explicitly named early involvement as a key element of both effective community engagement and the SLO, whereas the interview participants only explicitly indicated it as a key factor of community engagement and implied it to be a key element of the SLO.

Challenges of nickel silicidation in CMOS technologies

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

Breil, Nicolas; Lavoie, Christian; Ozcan, Ahmet

2015-04-01

In our paper, we review some of the key challenges associated with the Ni silicidation process in the most recent CMOS technologies. The introduction of new materials (e.g.SiGe), and of non-planar architectures bring some important changes that require fundamental investigation from a material engineering perspective. Following a discussion of the device architecture and silicide evolution through the last CMOS generations, we focus our study on a very peculiar defect, termed NiSi-Fangs. We describe a mechanism for the defect formation, and present a detailed material analysis that supports this mechanism. We highlight some of the possible metal enrichment processes of themore » nickel monosilicide such as oxidation or various RIE (Reactive Ion Etching) plasma process, leading to a metal source available for defect formation. Furthermore, we investigate the NiSi formation and re-formation silicidation differences between Si and SiGe materials, and between (1 0 0) and (1 1 1) orientations. Finally, we show that the thermal budgets post silicidation can lead to the formation of NiSi-Fangs if the structure and the processes are not optimized. Beyond the understanding of the defect and the discussion on the engineering solutions used to prevent its formation, the interest of this investigation also lies in the fundamental learning within the Ni–Pt–Si–Ge system and some additional perspective on Ni-based contacts to advanced microelectronic devices.« less

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

Kosicek, Marko, E-mail: marko.kosicek@irb.hr; Malnar, Martina, E-mail: martina.malnar@irb.hr; Goate, Alison, E-mail: goate@icarus.wustl.edu

It has been suggested that cholesterol may modulate amyloid-{beta} (A{beta}) formation, a causative factor of Alzheimer's disease (AD), by regulating distribution of the three key proteins in the pathogenesis of AD ({beta}-amyloid precursor protein (APP), {beta}-secretase (BACE1) and/or presenilin 1 (PS1)) within lipid rafts. In this work we tested whether cholesterol accumulation upon NPC1 dysfunction, which causes Niemann Pick type C disease (NPC), causes increased partitioning of APP into lipid rafts leading to increased CTF/A{beta} formation in these cholesterol-rich membrane microdomains. To test this we used CHO NPC1{sup -/-} cells (NPC cells) and parental CHOwt cells. By sucrose density gradientmore » centrifugation we observed a shift in fl-APP/CTF compartmentalization into lipid raft fractions upon cholesterol accumulation in NPC vs. wt cells. Furthermore, {gamma}-secretase inhibitor treatment significantly increased fl-APP/CTF distribution in raft fractions in NPC vs. wt cells, suggesting that upon cholesterol accumulation in NPC1-null cells increased formation of APP-CTF and its increased processing towards A{beta} occurs in lipid rafts. Our results support that cholesterol overload, such as in NPC disease, leads to increased partitioning of APP/CTF into lipid rafts resulting in increased amyloidogenic processing of APP in these cholesterol-rich membranes. This work adds to the mechanism of the cholesterol-effect on APP processing and the pathogenesis of Alzheimer's disease and supports the role of lipid rafts in these processes.« less

Platelets in thrombosis and hemostasis: old topic with new mechanisms.

PubMed

Wang, Yiming; Andrews, Marc; Yang, Yan; Lang, Sean; Jin, Joseph W; Cameron-Vendrig, Alison; Zhu, Guangheng; Reheman, Adili; Ni, Heyu

2012-12-01

Platelets are small anucleate cells generated from megakaryocytes in the bone marrow. After being released into the circulation, platelets play key roles in the surveillance of vascular injury, and can quickly adhere and aggregate at the site of injury, which are critical events for vascular repair and hemostasis. However, the same biological processes of platelet adhesion and aggregation may also cause thrombotic disorders. The formation of a platelet plug at sites of atherosclerotic lesion rupture is the most common mechanism leading to myocardial or cerebral infarction. Platelet-related deep vein thrombosis is also one of the leading causes of mortality worldwide. The contribution of several platelet receptors and their ligands has been highlighted in these processes. In platelet adhesion, particularly at high shear stress, GPIbα-von Willebrand factor (VWF) interaction may initiate this event, which is followed by GPVI signalling and firm platelet adhesion mediated by members of the integrin family, such as β3 (αIIbβ3) and β1 (α2β1, α5β1) integrins. In platelet aggregation, although GPIbα-VWF, P selectin-sulfatides, and other molecules, may be involved, the process is mainly mediated by β3 (αIIbβ3) integrin and its ligands, such as fibrinogen and VWF. It is intriguing that platelet adhesion and aggregation still occur in mice lacking both fibrinogen and VWF, suggesting that other unforeseen molecule(s) may also be important in these processes. Identification and characterization of these molecules will enrich our knowledge in the basic science of hemostasis and thrombosis, and may lead to the development of new therapies against bleeding disorders and thrombotic diseases.

Amyloid Precursor Protein Processing and Alzheimer’s Disease

PubMed Central

O’Brien, Richard J.; Wong, Philip C.

2011-01-01

Alzheimer’s disease (AD), the leading cause of dementia worldwide, is characterized by the accumulation of the β-amyloid peptide (Aβ) within the brain along with hyperphosphorylated and cleaved forms of the microtubule-associated protein tau. Genetic, biochemical, and behavioral research suggest that physiologic generation of the neurotoxic Aβ peptide from sequential amyloid precursor protein (APP) proteolysis is the crucial step in the development of AD. APP is a single-pass transmembrane protein expressed at high levels in the brain and metabolized in a rapid and highly complex fashion by a series of sequential proteases, including the intramembranous γ-secretase complex, which also process other key regulatory molecules. Why Aβ accumulates in the brains of elderly individuals is unclear but could relate to changes in APP metabolism or Aβ elimination. Lessons learned from biochemical and genetic studies of APP processing will be crucial to the development of therapeutic targets to treat AD. PMID:21456963

The Standard Autonomous File Server, A Customized, Off-the-Shelf Success Story

NASA Technical Reports Server (NTRS)

Semancik, Susan K.; Conger, Annette M.; Obenschain, Arthur F. (Technical Monitor)

2001-01-01

The Standard Autonomous File Server (SAFS), which includes both off-the-shelf hardware and software, uses an improved automated file transfer process to provide a quicker, more reliable, prioritized file distribution for customers of near real-time data without interfering with the assets involved in the acquisition and processing of the data. It operates as a stand-alone solution, monitoring itself, and providing an automated fail-over process to enhance reliability. This paper describes the unique problems and lessons learned both during the COTS selection and integration into SAFS, and the system's first year of operation in support of NASA's satellite ground network. COTS was the key factor in allowing the two-person development team to deploy systems in less than a year, meeting the required launch schedule. The SAFS system has been so successful; it is becoming a NASA standard resource, leading to its nomination for NASA's Software of the Year Award in 1999.

Advanced control of dissolved oxygen concentration in fed batch cultures during recombinant protein production.

PubMed

Kuprijanov, A; Gnoth, S; Simutis, R; Lübbert, A

2009-02-01

Design and experimental validation of advanced pO(2) controllers for fermentation processes operated in the fed-batch mode are described. In most situations, the presented controllers are able to keep the pO(2) in fermentations for recombinant protein productions exactly on the desired value. The controllers are based on the gain-scheduling approach to parameter-adaptive proportional-integral controllers. In order to cope with the most often appearing distortions, the basic gain-scheduling feedback controller was complemented with a feedforward control component. This feedforward/feedback controller significantly improved pO(2) control. By means of numerical simulations, the controller behavior was tested and its parameters were determined. Validation runs were performed with three Escherichia coli strains producing different recombinant proteins. It is finally shown that the new controller leads to significant improvements in the signal-to-noise ratio of other key process variables and, thus, to a higher process quality.

Key roles of Arf small G proteins and biosynthetic trafficking for animal development.

PubMed

Rodrigues, Francisco F; Harris, Tony J C

2017-04-14

Although biosynthetic trafficking can function constitutively, it also functions specifically for certain developmental processes. These processes require either a large increase to biosynthesis or the biosynthesis and targeted trafficking of specific players. We review the conserved molecular mechanisms that direct biosynthetic trafficking, and discuss how their genetic disruption affects animal development. Specifically, we consider Arf small G proteins, such as Arf1 and Sar1, and their coat effectors, COPI and COPII, and how these proteins promote biosynthetic trafficking for cleavage of the Drosophila embryo, the growth of neuronal dendrites and synapses, extracellular matrix secretion for bone development, lumen development in epithelial tubes, notochord and neural tube development, and ciliogenesis. Specific need for the biosynthetic trafficking system is also evident from conserved CrebA/Creb3-like transcription factors increasing the expression of secretory machinery during several of these developmental processes. Moreover, dysfunctional trafficking leads to a range of developmental syndromes.

Diversity and specificity: auxin perception and signaling through the TIR1/AFB pathway

DOE PAGES

Wang, Renhou; Estelle, Mark

2014-07-15

Auxin is a versatile plant hormone that plays an essential role in most aspects of plant growth and development. Auxin regulates various growth processes by modulating gene transcription through a SCF TIR1/AFB-Aux/IAA-ARF nuclear signaling module. Recent work has generated clues as to how multiple layers of regulation of the auxin signaling components may result in diverse and specific response outputs. Finally, in particular, interaction and structural studies of key auxin signaling proteins have produced novel insights into the molecular basis of auxin-regulated transcription and may lead to a refined auxin signaling model.

Applying NISHIJIN historical textile technique for e-Textile.

PubMed

Kuroda, Tomohiro; Hirano, Kikuo; Sugimura, Kazushige; Adachi, Satoshi; Igarashi, Hidetsugu; Ueshima, Kazuo; Nakamura, Hideo; Nambu, Masayuki; Doi, Takahiro

2013-01-01

The e-Textile is the key technology for continuous ambient health monitoring to increase quality of life of patients with chronic diseases. The authors introduce techniques of Japanese historical textile, NISHIJIN, which illustrate almost any pattern from one continuous yarn within the machine weaving process, which is suitable for mixed flow production. Thus, NISHIJIN is suitable for e-Textile production, which requires rapid prototyping and mass production of very complicated patterns. The authors prototyped and evaluated a few vests to take twelve-lead electrocardiogram. The result tells that the prototypes obtains electrocardiogram, which is good enough for diagnosis.

Peptidylarginine Deiminases as Drug Targets in Neonatal Hypoxic–Ischemic Encephalopathy

PubMed Central

Lange, Sigrun

2016-01-01

Oxygen deprivation and infection are major causes of perinatal brain injury leading to cerebral palsy and other neurological disabilities. The identification of novel key factors mediating white and gray matter damage are crucial to allow better understanding of the specific contribution of different cell types to the injury processes and pathways for clinical intervention. Recent studies in the Rice–Vannucci mouse model of neonatal hypoxic ischemia (HI) have highlighted novel roles for calcium-regulated peptidylarginine deiminases (PADs) and demonstrated neuroprotective effects of pharmacological PAD inhibition following HI and synergistic infection mimicked by lipopolysaccharide stimulation. PMID:26941709

Understanding Cooperative Chirality at the Nanoscale

NASA Astrophysics Data System (ADS)

Yu, Shangjie; Wang, Pengpeng; Govorov, Alexander; Ouyang, Min

Controlling chirality of organic and inorganic structures plays a key role in many physical, chemical and biochemical processes, and may offer new opportunity to create technology applications based on chiroptical effect. In this talk, we will present a theoretical model and simulation to demonstrate how to engineer nanoscale chirality in inorganic nanostructures via synergistic control of electromagnetic response of both lattice and geometry, leading to rich tunability of chirality at the nanoscale. Our model has also been applied to understand recent materials advancement of related control with excellent agreement, and can elucidate physical origins of circular dichroism features in the experiment.

Pegasus XL CYGNSS Second Launch Attempt

NASA Image and Video Library

2016-12-15

In the Mission Director's Center at Cape Canaveral Air Force Station, Andy Bundy, Avionics lead, left, and Pat Simpkins, director of Kennedy Space Center Engineering, monitor the progress of preparations to launch eight Cyclone Global Navigation Satellite System, or CYGNSS, spacecraft. The CYGNSS satellites will make frequent and accurate measurements of ocean surface winds throughout the life cycle of tropical storms and hurricanes. The data that CYGNSS provides will enable scientists to probe key air-sea interaction processes that take place near the core of storms, which are rapidly changing and play a crucial role in the beginning and intensification of hurricanes.

Functional Interface Considerations within an Exploration Life Support System Architecture

NASA Technical Reports Server (NTRS)

Perry, Jay L.; Sargusingh, Miriam J.; Toomarian, Nikzad

2016-01-01

As notional life support system (LSS) architectures are developed and evaluated, myriad options must be considered pertaining to process technologies, components, and equipment assemblies. Each option must be evaluated relative to its impact on key functional interfaces within the LSS architecture. A leading notional architecture has been developed to guide the path toward realizing future crewed space exploration goals. This architecture includes atmosphere revitalization, water recovery and management, and environmental monitoring subsystems. Guiding requirements for developing this architecture are summarized and important interfaces within the architecture are discussed. The role of environmental monitoring within the architecture is described.

Ideational conflict: the key to promoting creative activity in the workplace.

PubMed

Dagostino, Lorraine

1999-01-01

This article defines the concept of ideational conflict as it applies to the process of identifying a problem and developing a plan of action for resolving the problem. Then the article examines and illustrates how the ideational conflict that is generated by brainstorming can lead to creative thinking that resolves disparate points of view. The illustration extends the generally accepted view of brainstorming and applies it to identifying a problem related to the university/college work environment. The problem situation is that of the loss of high ability faculty and sutdents to other institutions.

Developing and applying the adverse outcome pathway ...

EPA Pesticide Factsheets

To support a paradigm shift in regulatory toxicology testing and risk assessment, the Adverse Outcome Pathway (AOP) concept has recently been proposed. This concept is similar to that for Mode of Action (MOA), describing a sequence of measurable key events triggered by a molecular initiating event in which a stressor interacts with a biological target. The resulting cascade of key events includes molecular, cellular, structural and functional changes in biological systems, resulting in a measurable adverse outcome. Thereby, an AOP ideally provides information relevant to chemical structure-activity relationships as a basis to predict effects for structurally similar compounds. AOPs could potentially also form the basis for qualitative and quantitative predictive modeling of the human adverse outcome resulting from molecular initiating or other key events for which higher-throughput testing methods are available or can be developed.A variety of cellular and molecular processes are known to be critical to normal function of the central (CNS) and peripheral nervous systems (PNS). Because of the biological and functional complexity of the CNS and PNS, it has been challenging to establish causative links and quantitative relationships between key events that comprise the pathways leading from chemical exposure to an adverse outcome in the nervous system. Following introduction of principles of the description and assessment of MOA and AOPs, examples of adverse out

Modern drug discovery technologies: opportunities and challenges in lead discovery.

PubMed

Guido, Rafael V C; Oliva, Glaucius; Andricopulo, Adriano D

2011-12-01

The identification of promising hits and the generation of high quality leads are crucial steps in the early stages of drug discovery projects. The definition and assessment of both chemical and biological space have revitalized the screening process model and emphasized the importance of exploring the intrinsic complementary nature of classical and modern methods in drug research. In this context, the widespread use of combinatorial chemistry and sophisticated screening methods for the discovery of lead compounds has created a large demand for small organic molecules that act on specific drug targets. Modern drug discovery involves the employment of a wide variety of technologies and expertise in multidisciplinary research teams. The synergistic effects between experimental and computational approaches on the selection and optimization of bioactive compounds emphasize the importance of the integration of advanced technologies in drug discovery programs. These technologies (VS, HTS, SBDD, LBDD, QSAR, and so on) are complementary in the sense that they have mutual goals, thereby the combination of both empirical and in silico efforts is feasible at many different levels of lead optimization and new chemical entity (NCE) discovery. This paper provides a brief perspective on the evolution and use of key drug design technologies, highlighting opportunities and challenges.

New HSP27 inhibitors efficiently suppress drug resistance development in cancer cells

PubMed Central

Lennig, Petra; Zhang, Yixin; Schroeder, Michael

2016-01-01

Drug resistance is an important open problem in cancer treatment. In recent years, the heat shock protein HSP27 (HSPB1) was identified as a key player driving resistance development. HSP27 is overexpressed in many cancer types and influences cellular processes such as apoptosis, DNA repair, recombination, and formation of metastases. As a result cancer cells are able to suppress apoptosis and develop resistance to cytostatic drugs. To identify HSP27 inhibitors we follow a novel computational drug repositioning approach. We exploit a similarity between a predicted HSP27 binding site to a viral thymidine kinase to generate lead inhibitors for HSP27. Six of these leads were verified experimentally. They bind HSP27 and down-regulate its chaperone activity. Most importantly, all six compounds inhibit development of drug resistance in cellular assays. One of the leads – chlorpromazine – is an antipsychotic, which has a positive effect on survival time in human breast cancer. In summary, we make two important contributions: First, we put forward six novel leads, which inhibit HSP27 and tackle drug resistance. Second, we demonstrate the power of computational drug repositioning. PMID:27626687

Fragment Screening of Soluble Epoxide Hydrolase for Lead Generation-Structure-Based Hit Evaluation and Chemistry Exploration.

PubMed

Xue, Yafeng; Olsson, Thomas; Johansson, Carina A; Öster, Linda; Beisel, Hans-Georg; Rohman, Mattias; Karis, David; Bäckström, Stefan

2016-03-04

Soluble epoxide hydrolase (sEH) is involved in the regulation of many biological processes by metabolizing the key bioactive lipid mediator, epoxyeicosatrienoic acids. For the development of sEH inhibitors with improved physicochemical properties, we performed both a fragment screening and a high-throughput screening aiming at an integrated hit evaluation and lead generation. Followed by a joint dose-response analysis to confirm the hits, the identified actives were then effectively triaged by a structure-based hit-classification approach to three prioritized series. Two distinct scaffolds were identified as tractable starting points for potential lead chemistry work. The oxoindoline series bind at the right-hand side of the active-site pocket with hydrogen bonds to the protein. The 2-phenylbenzimidazole-4-sulfonamide series bind at the central channel with significant induced fit, which has not been previously reported. On the basis of the encouraging initial results, we envision that a new lead series with improved properties could be generated if a vector is found that could merge the cyclohexyl functionality of the oxoindoline series with the trifluoromethyl moiety of the 2-phenylbenzimidazole-4-sulfonamide series. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Adaptive Swarm Balancing Algorithms for rare-event prediction in imbalanced healthcare data

PubMed Central

Wong, Raymond K.; Mohammed, Sabah; Fiaidhi, Jinan; Sung, Yunsick

2017-01-01

Clinical data analysis and forecasting have made substantial contributions to disease control, prevention and detection. However, such data usually suffer from highly imbalanced samples in class distributions. In this paper, we aim to formulate effective methods to rebalance binary imbalanced dataset, where the positive samples take up only the minority. We investigate two different meta-heuristic algorithms, particle swarm optimization and bat algorithm, and apply them to empower the effects of synthetic minority over-sampling technique (SMOTE) for pre-processing the datasets. One approach is to process the full dataset as a whole. The other is to split up the dataset and adaptively process it one segment at a time. The experimental results reported in this paper reveal that the performance improvements obtained by the former methods are not scalable to larger data scales. The latter methods, which we call Adaptive Swarm Balancing Algorithms, lead to significant efficiency and effectiveness improvements on large datasets while the first method is invalid. We also find it more consistent with the practice of the typical large imbalanced medical datasets. We further use the meta-heuristic algorithms to optimize two key parameters of SMOTE. The proposed methods lead to more credible performances of the classifier, and shortening the run time compared to brute-force method. PMID:28753613

Placebo Response is Driven by UCS Revaluation: Evidence, Neurophysiological Consequences and a Quantitative Model

PubMed Central

Puviani, Luca; Rama, Sidita

2016-01-01

Despite growing scientific interest in the placebo effect and increasing understanding of neurobiological mechanisms, theoretical modeling of the placebo response remains poorly developed. The most extensively accepted theories are expectation and conditioning, involving both conscious and unconscious information processing. However, it is not completely understood how these mechanisms can shape the placebo response. We focus here on neural processes which can account for key properties of the response to substance intake. It is shown that placebo response can be conceptualized as a reaction of a distributed neural system within the central nervous system. Such a reaction represents an integrated component of the response to open substance administration (or to substance intake) and is updated through “unconditioned stimulus (UCS) revaluation learning”. The analysis leads to a theorem, which proves the existence of two distinct quantities coded within the brain, these are the expected or prediction outcome and the reactive response. We show that the reactive response is updated automatically by implicit revaluation learning, while the expected outcome can also be modulated through conscious information processing. Conceptualizing the response to substance intake in terms of UCS revaluation learning leads to the theoretical formulation of a potential neuropharmacological treatment for increasing unlimitedly the effectiveness of a given drug. PMID:27436417

Placebo Response is Driven by UCS Revaluation: Evidence, Neurophysiological Consequences and a Quantitative Model.

PubMed

Puviani, Luca; Rama, Sidita

2016-07-20

Despite growing scientific interest in the placebo effect and increasing understanding of neurobiological mechanisms, theoretical modeling of the placebo response remains poorly developed. The most extensively accepted theories are expectation and conditioning, involving both conscious and unconscious information processing. However, it is not completely understood how these mechanisms can shape the placebo response. We focus here on neural processes which can account for key properties of the response to substance intake. It is shown that placebo response can be conceptualized as a reaction of a distributed neural system within the central nervous system. Such a reaction represents an integrated component of the response to open substance administration (or to substance intake) and is updated through "unconditioned stimulus (UCS) revaluation learning". The analysis leads to a theorem, which proves the existence of two distinct quantities coded within the brain, these are the expected or prediction outcome and the reactive response. We show that the reactive response is updated automatically by implicit revaluation learning, while the expected outcome can also be modulated through conscious information processing. Conceptualizing the response to substance intake in terms of UCS revaluation learning leads to the theoretical formulation of a potential neuropharmacological treatment for increasing unlimitedly the effectiveness of a given drug.

[Technical background of data collection for parametric observation of total mesorectal excision (TME) in rectal cancer].

PubMed

Bláha, M; Hoch, J; Ferko, A; Ryška, A; Hovorková, E

Improvement in any human activity is preconditioned by inspection of results and providing feedback used for modification of the processes applied. Comparison of experts experience in the given field is another indispensable part leading to optimisation and improvement of processes, and optimally to implementation of standards. For the purpose of objective comparison and assessment of the processes, it is always necessary to describe the processes in a parametric way, to obtain representative data, to assess the achieved results, and to provide unquestionable and data-driven feedback based on such analysis. This may lead to a consensus on the definition of standards in the given area of health care. Total mesorectal excision (TME) is a standard procedure of rectal cancer (C20) surgical treatment. However, the quality of performed procedures varies in different health care facilities, which is given, among others, by internal processes and surgeons experience. Assessment of surgical treatment results is therefore of key importance. A pathologist who assesses the resected tissue can provide valuable feedback in this respect. An information system for the parametric assessment of TME performance is described in our article, including technical background in the form of a multicentre clinical registry and the structure of observed parameters. We consider the proposed system of TME parametric assessment as significant for improvement of TME performance, aimed at reducing local recurrences and at improving the overall prognosis of patients. rectal cancer total mesorectal excision parametric data clinical registries TME registry.

A robust seeding technique for the growth of single grain (RE)BCO and (RE)BCO-Ag bulk superconductors

NASA Astrophysics Data System (ADS)

Namburi, Devendra K.; Shi, Yunhua; Dennis, Anthony R.; Durrell, John H.; Cardwell, David A.

2018-04-01

Bulk, single grains of RE-Ba-Cu-O [(RE)BCO] high temperature superconductors have significant potential for a wide range of applications, including trapped field magnets, energy storage flywheels, superconducting mixers and magnetic separators. One of the main challenges in the production of these materials by the so-called top seeded melt growth technique is the reliable seeding of large, single grains, which are required for high field applications. A chemically aggressive liquid phase comprising of BaCuO2 and CuO is generated during the single grain growth process, which comes into direct contact with the seed crystal either instantaneously or via infiltration through a buffer pellet, if employed in the process. This can cause either partial or complete melting of the seed, leading subsequently to growth failure. Here, the underlying mechanisms of seed crystal melting and the role of seed porosity in the single grain growth process are investigated. We identify seed porosity as a key limitation in the reliable and successful fabrication of large grain (RE)BCO bulk superconductors for the first time, and propose the use of Mg-doped NdBCO generic seeds fabricated via the infiltration growth technique to reduce the effects of seed porosity on the melt growth process. Finally, we demonstrate that the use of such seeds leads to better resistance to melting during the single grain growth process, and therefore to a more reliable fabrication technique.

Assessment of Lead Exposure Risk in Locksmiths

PubMed Central

Kondrashov, Vladislav; McQuirter, Joseph L.; Miller, Melba; Rothenberg, Stephen J.

2005-01-01

Exposure to lead has been well recognized in a number of work environments, but little is known about lead exposure associated with machining brass keys containing lead. The brass that is widely used for key manufacturing usually contains 1.5% – 2.5 % of lead. Six (6) licensed locksmiths and 6 case-matched controls successfully completed the pilot study to assess the prevalence of increased body lead burden of professional locksmiths. We measured both Blood Lead (atomic absorption spectrometry), bone-lead (KXRF) and had each subject complete a health and lead exposure risk questionnaire. One locksmith had not cut keys during the past two years, therefore this subject and case-matched control was excluded from the blood lead analysis only. The average blood-lead concentration (±SEM) for the 5 paired subjects was 3.1 (± 0.4) μg/dL and 2.2 (± 0.3) μg /dL for controls. Bone measurements, including all 6 paired subjects, showed tibia lead concentration (±SEM) for locksmiths and controls was 27.8 (± 2.3) μg /g and 13.7 (± 3.3) μg /g, respectively; average calcaneus lead concentration for locksmiths and controls was 31.9 (± 3.7) μg /g and 22.6 (± 4.1) μg /g, respectively: The t-test shows a significantly higher tibia lead (p<0.05) and blood lead (p<0.05) for locksmiths than for their matched controls, but no significant difference for calcaneus lead (p>0.10). Given that the mean tibia bone lead concentration was 13.1μg/g higher in locksmiths than in their matched controls, this average difference in the two groups would translate to an OR of increased hypertension in locksmiths of between 1.1 and 2.3, based on the published literature. Even with the very small number of subjects participating in this pilot study, we were able to demonstrate that locksmiths had significantly higher current exposure to lead (blood lead concentration) and significantly higher past exposure to lead (tibia lead concentration) than their age, sex and ethnically matched controls. Additional research is needed to fully identify the prevalence and associated risk factors for occupational exposure of lead in this previously understudied profession. PMID:16705814

Friction Sensitivity of Primary Explosives

DTIC Science & Technology

1982-09-01

diffeomI from. Report) ISI. SUPPLEMENTARY NOTES It. KEY WORDS (Contflnuo on rvotr.. oldo. it nec~oaoty and Identify by block ri,uobr) Friction...friction senisitivity. Primary explosives RD 1333 lead azide, dextrinated lead azide, polyvinyl-alcohol (PVA)-lead a~.ide, colloidal lead azide, nocrnal lead...results for dextrinated lead azide duPont 52-127 13 4 A comparison of friction data at 10% probability of initiation 14 FIGURES 1 Working surfaces of BAM

A holistic framework for design of cost-effective minimum water utilization network.

PubMed

Wan Alwi, S R; Manan, Z A; Samingin, M H; Misran, N

2008-07-01

Water pinch analysis (WPA) is a well-established tool for the design of a maximum water recovery (MWR) network. MWR, which is primarily concerned with water recovery and regeneration, only partly addresses water minimization problem. Strictly speaking, WPA can only lead to maximum water recovery targets as opposed to the minimum water targets as widely claimed by researchers over the years. The minimum water targets can be achieved when all water minimization options including elimination, reduction, reuse/recycling, outsourcing and regeneration have been holistically applied. Even though WPA has been well established for synthesis of MWR network, research towards holistic water minimization has lagged behind. This paper describes a new holistic framework for designing a cost-effective minimum water network (CEMWN) for industry and urban systems. The framework consists of five key steps, i.e. (1) Specify the limiting water data, (2) Determine MWR targets, (3) Screen process changes using water management hierarchy (WMH), (4) Apply Systematic Hierarchical Approach for Resilient Process Screening (SHARPS) strategy, and (5) Design water network. Three key contributions have emerged from this work. First is a hierarchical approach for systematic screening of process changes guided by the WMH. Second is a set of four new heuristics for implementing process changes that considers the interactions among process changes options as well as among equipment and the implications of applying each process change on utility targets. Third is the SHARPS cost-screening technique to customize process changes and ultimately generate a minimum water utilization network that is cost-effective and affordable. The CEMWN holistic framework has been successfully implemented on semiconductor and mosque case studies and yielded results within the designer payback period criterion.

Development of welding technologies for the manufacturing of European Tritium Breeder blanket modules

NASA Astrophysics Data System (ADS)

Poitevin, Y.; Aubert, Ph.; Diegele, E.; de Dinechin, G.; Rey, J.; Rieth, M.; Rigal, E.; von der Weth, A.; Boutard, J.-L.; Tavassoli, F.

2011-10-01

Europe has developed two reference Tritium Breeder Blankets concepts for a DEMO fusion reactor: the Helium-Cooled Lithium-Lead and the Helium-Cooled Pebble-Bed. Both are using the reduced-activation ferritic-martensitic EUROFER-97 steel as structural material and will be tested in ITER under the form of test blanket modules. The fabrication of their EUROFER structures requires developing welding processes like laser, TIG, EB and diffusion welding often beyond the state-of-the-art. The status of European achievements in this area is reviewed, illustrating the variety of processes and key issues behind retained options, in particular with respect to metallurgical aspects and mechanical properties. Fabrication of mock-ups is highlighted and their characterization and performances with respect to design requirements are reviewed.

Highly accurate and fast optical penetration-based silkworm gender separation system

NASA Astrophysics Data System (ADS)

Kamtongdee, Chakkrit; Sumriddetchkajorn, Sarun; Chanhorm, Sataporn

2015-07-01

Based on our research work in the last five years, this paper highlights our innovative optical sensing system that can identify and separate silkworm gender highly suitable for sericulture industry. The key idea relies on our proposed optical penetration concepts and once combined with simple image processing operations leads to high accuracy in identifying of silkworm gender. Inside the system, there are electronic and mechanical parts that assist in controlling the overall system operation, processing the optical signal, and separating the female from male silkworm pupae. With current system performance, we achieve a very highly accurate more than 95% in identifying gender of silkworm pupae with an average system operational speed of 30 silkworm pupae/minute. Three of our systems are already in operation at Thailand's Queen Sirikit Sericulture Centers.

Gut Microbiota Diversity and Human Diseases: Should We Reintroduce Key Predators in Our Ecosystem?

PubMed Central

Mosca, Alexis; Leclerc, Marion; Hugot, Jean P.

2016-01-01

Most of the Human diseases affecting westernized countries are associated with dysbiosis and loss of microbial diversity in the gut microbiota. The Western way of life, with a wide use of antibiotics and other environmental triggers, may reduce the number of bacterial predators leading to a decrease in microbial diversity of the Human gut. We argue that this phenomenon is similar to the process of ecosystem impoverishment in macro ecology where human activity decreases ecological niches, the size of predator populations, and finally the biodiversity. Such pauperization is fundamental since it reverses the evolution processes, drives life backward into diminished complexity, stability, and adaptability. A simple therapeutic approach could thus be to reintroduce bacterial predators and restore a bacterial diversity of the host microbiota. PMID:27065999

Enhancing the role of science in the decision-making of the European Union.

PubMed

Allio, Lorenzo; Ballantine, Bruce; Meads, Richard

2006-02-01

Used well, science provides effective ways of identifying potential risks, protecting citizens, and using resources wisely. It enables government decisions to be based on evidence and provides a foundation for a rule-based framework that supports global trade. To ensure that the best available science becomes a key input in the decisions made by EU institutions, this abridged version of a working paper produced for the European Policy Centre, a leading, independent think tank, considers how science is currently used in the policy and decision-making processes of the EU, what the limitations of scientific evidence are, and how a risk assessment process based on scientific 'good practices' can be advantageous. Finally, the paper makes recommendations on how to improve the use of science by EU institutions.

Multi-exciton emission from solitary dopant states of carbon nanotubes.

PubMed

Ma, Xuedan; Hartmann, Nicolai F; Velizhanin, Kirill A; Baldwin, Jon K S; Adamska, Lyudmyla; Tretiak, Sergei; Doorn, Stephen K; Htoon, Han

2017-11-02

By separating the photons from slow and fast decays of single and multi-exciton states in a time gated 2 nd order photon correlation experiment, we show that solitary oxygen dopant states of single-walled carbon nanotubes (SWCNTs) allow emission of photon pairs with efficiencies as high as 44% of single exciton emission. Our pump dependent time resolved photoluminescence (PL) studies further reveal diffusion-limited exciton-exciton annihilation as the key process that limits the emission of multi-excitons at high pump fluences. We further postulate that creation of additional permanent exciton quenching sites occurring under intense laser irradiation leads to permanent PL quenching. With this work, we bring out multi-excitonic processes of solitary dopant states as a new area to be explored for potential applications in lasing and entangled photon generation.

Implementation of MCA Method for Identification of Factors for Conceptual Cost Estimation of Residential Buildings

NASA Astrophysics Data System (ADS)

Juszczyk, Michał; Leśniak, Agnieszka; Zima, Krzysztof

2013-06-01

Conceptual cost estimation is important for construction projects. Either underestimation or overestimation of building raising cost may lead to failure of a project. In the paper authors present application of a multicriteria comparative analysis (MCA) in order to select factors influencing residential building raising cost. The aim of the analysis is to indicate key factors useful in conceptual cost estimation in the early design stage. Key factors are being investigated on basis of the elementary information about the function, form and structure of the building, and primary assumptions of technological and organizational solutions applied in construction process. The mentioned factors are considered as variables of the model which aim is to make possible conceptual cost estimation fast and with satisfying accuracy. The whole analysis included three steps: preliminary research, choice of a set of potential variables and reduction of this set to select the final set of variables. Multicriteria comparative analysis is applied in problem solution. Performed analysis allowed to select group of factors, defined well enough at the conceptual stage of the design process, to be used as a describing variables of the model.

Development of a simulation environment to support intercalibration studies over the Algodones Dunes system

NASA Astrophysics Data System (ADS)

Eon, Rehman S.; Gerace, Aaron D.; Montanaro, Matthew; Ambeau, Brittany L.; McCorkel, Joel T.

2018-01-01

The ability of sensors to detect changes in the Earth's environment is dependent on retrieving radiometrically consistent and calibrated measurements from its surface. Intercalibration provides consistency among satellite instruments and ensures fidelity of scientific information. Intercalibration is especially important for spaceborne satellites without any on-board calibration, as accuracy of instruments is significantly affected by changes that occur postlaunch. To better understand the key parameters that impact the intercalibration process, this paper describes a simulation environment that was developed to support the primary mission of the Algodones Dunes campaign. Specifically, measurements obtained from the campaign were utilized to create a synthetic landscape to assess the feasibility of using the Algodones Dunes system as an intercalibration site for spaceborne instruments. The impact of two key parameters (differing view-angles and temporal offsets between instruments) on the intercalibration process was assessed. Results of these studies indicate that although the accuracy of intercalibration is sensitive to these parameters, proper knowledge of their impact leads to situations that minimize their effect. This paper concludes with a case study that addresses the feasibility of performing intercalibration on the International Space Station's platform to support NASA's CLARREO, the climate absolute radiance and refractivity observatory, mission.

Integrated management of depression: improving system quality and creating effective interfaces.

PubMed

Myette, Thomas L

2008-04-01

Depression is a chronic recurrent condition and is a leading cause of work disability. Improving occupational outcomes for depression will require an integrated approach that incorporates best practices from the clinical, community, and workplace systems. This article briefly reviews recent quality improvement initiatives and promising practices in each system and then shifts to the importance of systems integration. An integrated chronic care model uses a sophisticated case management process to support essential relationships, facilitate key plans, and efficiently link the three systems to optimize clinical, economic, and occupational outcomes. An expanded role for employers and their agents in the management of depression and other chronic diseases is seen as fundamental to maintaining a healthy and productive workforce. To improve occupational outcomes for depression by integrating best practices from the clinical, community, and workplace systems. After a brief review of quality improvement initiatives and promising practices in each system, an integrated chronic care model is introduced. A case management process that links critical systems, supports essential relationships, and facilitates key plans is expected to result in improvements in clinical, economic, and occupational outcomes. Employers should be more engaged with clinical and community partners in the prevention and control of depression in affected employees.

No recovery of memory when cognitive load is decreased.

PubMed

Ricker, Timothy J; Vergauwe, Evie; Hinrichs, Garrett A; Blume, Christopher L; Cowan, Nelson

2015-05-01

There is substantial debate in the field of short-term memory (STM) as to whether the process of active maintenance occurs through memory-trace reactivation or repair. A key difference between these 2 potential mechanisms is that a repair mechanism should lead to recovery of forgotten information. The ability to recover forgotten memories would be a panacea for STM and if possible, would warrant much future research. We examine the topic of STM recovery by varying the cognitive load of a secondary task and duration of retention of word pairs. In our key manipulation, we lighten the cognitive load partway through the retention interval, resulting in an easier task during the later portion of retention and more time for active maintenance processes to take place. Although the natural prediction arising from a repair mechanism is that memory accuracy should increase after transitioning to an easier load, we find that accuracy decreases or levels off at this point. We see this pattern across 3 experiments and can only conclude that the panacea of STM recovery does not exist. Implications for the debate over memory maintenance mechanisms are discussed. (c) 2015 APA, all rights reserved).

Microstructure and electroluminescent performance of chemical vapor deposited zinc sulfide doped with manganese films for integration in thin film electroluminescent devices

NASA Astrophysics Data System (ADS)

Topol, Anna Wanda

Zinc sulfide (ZnS) doped with manganese (Mn), ZnS:Mn, is widely recognized as the brightest and most effective electroluminescent (EL) phosphor used in current thin film electroluminescent (TFEL) devices. ZnS acts as a host lattice for the luminescent activator, Mn, leading to a highly efficient yellow-orange EL emission, and resulting in a wide array of applications in monochrome, multi-color and full color displays. Although this wide band dap (3.7 eV) material can be prepared by several deposition techniques, the chemical vapor deposition (CVD) is the most promising for TFEL applications in terms of viable deposition rates, high thickness and composition uniformity, and excellent yield over large area panels. This study describes the development and optimization of a CVD ZnS:Mn process using diethylzinc [(C2H5)2Zn, DEZ], di-pi-cyclopentadienylmanganese [(C5H5)2Mn, CPMn], and hydrogen sulfide [H2S] as the chemical sources for, respectively, Zn, Mn, and S. The effects of key deposition parameters on resulting Film microstructure and performance are discussed, primarily in the context of identifying an optimized process window for best electroluminescence behavior. In particular, substrate temperature was observed to play a key role in the formation of high quality crystalline ZnS:Mn films leading to improved brightness and EL efficiency. Further investigations of the influence of temperature treatment on the structural characteristics and EL performance of the CVD ZnS:Mn film were carried out. In this study, the influence of post-deposition annealing both in-situ and ex-situ annealing processes, on chemical, structural, and electroluminescent characteristics of the phosphor layer are described. The material properties of the employed dielectric are among the key factors determining the performance, stability and reliability of the TFEL display and therefore, the choice of dielectric material for use in ACTFEL displays is crucial. In addition, the luminous efficiency depends on the density of the interface states and their depth at the insulator-phosphor interfaces. Hence, critical integration issues are discussed in terms of the incorporation of ZnS:Mn films in dielectricsemiconductor-dielectric (DSD) structures with silicon nitride (SiNx) and aluminum titanium oxide (ATO) as top and bottom insulators.

Simulating carbon capture by enhanced weathering with croplands: an overview of key processes highlighting areas of future model development

PubMed Central

Quegan, Shaun; Banwart, Steven A.

2017-01-01

Enhanced weathering (EW) aims to amplify a natural sink for CO2 by incorporating powdered silicate rock with high reactive surface area into agricultural soils. The goal is to achieve rapid dissolution of minerals and release of alkalinity with accompanying dissolution of CO2 into soils and drainage waters. EW could counteract phosphorus limitation and greenhouse gas (GHG) emissions in tropical soils, and soil acidification, a common agricultural problem studied with numerical process models over several decades. Here, we review the processes leading to soil acidification in croplands and how the soil weathering CO2 sink is represented in models. Mathematical models capturing the dominant processes and human interventions governing cropland soil chemistry and GHG emissions neglect weathering, while most weathering models neglect agricultural processes. We discuss current approaches to modelling EW and highlight several classes of model having the potential to simulate EW in croplands. Finally, we argue for further integration of process knowledge in mathematical models to capture feedbacks affecting both longer-term CO2 consumption and crop growth and yields. PMID:28381633

Exploring Mission Concepts with the JPL Innovation Foundry A-Team

NASA Technical Reports Server (NTRS)

Ziemer, John K.; Ervin, Joan; Lang, Jared

2013-01-01

The JPL Innovation Foundry has established a new approach for exploring, developing, and evaluating early concepts called the A-Team. The A-Team combines innovative collaborative methods with subject matter expertise and analysis tools to help mature mission concepts. Science, implementation, and programmatic elements are all considered during an A-Team study. Methods are grouped by Concept Maturity Level (CML), from 1 through 3, including idea generation and capture (CML 1), initial feasibility assessment (CML 2), and trade space exploration (CML 3). Methods used for each CML are presented, and the key team roles are described from two points of view: innovative methods and technical expertise. A-Team roles for providing innovative methods include the facilitator, study lead, and assistant study lead. A-Team roles for providing technical expertise include the architect, lead systems engineer, and integration engineer. In addition to these key roles, each A-Team study is uniquely staffed to match the study topic and scope including subject matter experts, scientists, technologists, flight and instrument systems engineers, and program managers as needed. Advanced analysis and collaborative engineering tools (e.g. cost, science traceability, mission design, knowledge capture, study and analysis support infrastructure) are also under development for use in A-Team studies and will be discussed briefly. The A-Team facilities provide a constructive environment for innovative ideas from all aspects of mission formulation to eliminate isolated studies and come together early in the development cycle when they can provide the biggest impact. This paper provides an overview of the A-Team, its study processes, roles, methods, tools and facilities.

Numerical Modeling of Anaerobic Microzones Development in Bulk Oxic Porous Media: An Assessment of Different Microzone Formation Processes

NASA Astrophysics Data System (ADS)

Roy Chowdhury, S.; Zarnetske, J. P.; Briggs, M. A.; Day-Lewis, F. D.; Singha, K.

2017-12-01

Soil and groundwater research indicates that unique biogeochemical "microzones" commonly form within bulk soil masses. The formation of these microzones at the pore-scale has been attributed to a number of causes, including variability of in situ carbon or nutrient sources, intrinsic physical conditions that lead to dual-porosity and mass transfer conditions, or microbial bioclogging of the porous media. Each of these causes, while documented in different porous media systems, potentially can lead to the presence of anaerobic pores residing in a bulk oxic domain. The relative role of these causes operating independently or in conjunction with each other to form microzones is not known. Here, we use a single numerical modeling framework to assess the relative roles of each process in creating anaerobic microzones. Using a two-dimensional pore-network model, coupled with a microbial growth model based on Monod kinetics, simulations were performed to explore the development of these anoxic microzones and their fate under a range of hydrologic, nutrient, and microbial conditions. Initial results parameterized for a stream-groundwater exchange environment (i.e., a hyporheic zone) indicate that external forcing of fluid flux in the domain is a key soil characteristic to anaerobic microzone development as fluid flux governs the nutrient flux. The initial amount of biomass present in the system also plays a major role in the development of the microzones. In terms of dominant in situ causes, the intrinsic physical structure of the local pore space is found to play the key role in development of anaerobic sites by regulating fluxes to reaction sites. Acknowledging and understanding the drivers of these microzones will improve the ability of multiple disciplines to measure and model reactive mass transport in soils and assess if they play a significant role for particular biogeochemical processes and ecosystem functions, such as denitrification and greenhouse gas production.

Denosumab for the management of bone disease in patients with solid tumors.

PubMed

Body, Jean-Jacques

2012-03-01

Many patients with advanced cancer develop bone metastases, which reduces their quality of life. Bone metastases are associated with an increased risk of skeletal-related events, which can lead to increased morbidity and mortality. In patients with bone metastases, tumor cells disrupt the normal process of bone remodeling, leading to increased bone destruction. Denosumab is a fully human monoclonal antibody against receptor activator of NF-κB ligand (RANKL), a key regulatory factor in bone remodeling. By binding to RANKL, denosumab disrupts the cycle of bone destruction. In clinical studies in patients with prostate or breast cancer and bone metastases, denosumab was superior to the current standard of care, zoledronic acid, for delaying skeletal-related events, while in patients with other solid tumors or multiple myeloma, denosumab was noninferior to zoledronic acid. This article examines the pharmacokinetics, efficacy, and safety and tolerability of denosumab for the management of bone events in patients with cancer.

Adolescent Alcohol Exposure: Burden of Epigenetic Reprogramming, Synaptic Remodeling, and Adult Psychopathology

PubMed Central

Kyzar, Evan J.; Floreani, Christina; Teppen, Tara L.; Pandey, Subhash C.

2016-01-01

Adolescence represents a crucial phase of synaptic maturation characterized by molecular changes in the developing brain that shape normal behavioral patterns. Epigenetic mechanisms play an important role in these neuromaturation processes. Perturbations of normal epigenetic programming during adolescence by ethanol can disrupt these molecular events, leading to synaptic remodeling and abnormal adult behaviors. Repeated exposure to binge levels of alcohol increases the risk for alcohol use disorder (AUD) and comorbid psychopathology including anxiety in adulthood. Recent studies in the field clearly suggest that adolescent alcohol exposure causes widespread and persistent changes in epigenetic, neurotrophic, and neuroimmune pathways in the brain. These changes are manifested by altered synaptic remodeling and neurogenesis in key brain regions leading to adult psychopathology such as anxiety and alcoholism. This review details the molecular mechanisms underlying adolescent alcohol exposure-induced changes in synaptic plasticity and the development of alcohol addiction-related phenotypes in adulthood. PMID:27303256

Single Top Production at Next-to-Leading Order in the Standard Model Effective Field Theory.

PubMed

Zhang, Cen

2016-04-22

Single top production processes at hadron colliders provide information on the relation between the top quark and the electroweak sector of the standard model. We compute the next-to-leading order QCD corrections to the three main production channels: t-channel, s-channel, and tW associated production, in the standard model including operators up to dimension six. The calculation can be matched to parton shower programs and can therefore be directly used in experimental analyses. The QCD corrections are found to significantly impact the extraction of the current limits on the operators, because both of an improved accuracy and a better precision of the theoretical predictions. In addition, the distributions of some of the key discriminating observables are modified in a nontrivial way, which could change the interpretation of measurements in terms of UV complete models.

Pathways leading to an immunological disease: systemic lupus erythematosus

PubMed Central

Zharkova, Olga; Celhar, Teja; Cravens, Petra D.; Satterthwaite, Anne B.; Fairhurst, Anna-Marie

2017-01-01

Abstract SLE is a chronic autoimmune disease caused by perturbations of the immune system. The clinical presentation is heterogeneous, largely because of the multiple genetic and environmental factors that contribute to disease initiation and progression. Over the last 60 years, there have been a number of significant leaps in our understanding of the immunological mechanisms driving disease processes. We now know that multiple leucocyte subsets, together with inflammatory cytokines, chemokines and regulatory mediators that are normally involved in host protection from invading pathogens, contribute to the inflammatory events leading to tissue destruction and organ failure. In this broad overview, we discuss the main pathways involved in SLE and highlight new findings. We describe the immunological changes that characterize this form of autoimmunity. The major leucocytes that are essential for disease progression are discussed, together with key mediators that propagate the immune response and drive the inflammatory response in SLE. PMID:28375453

Interaction of tetraethoxysilane with OH-terminated SiO2 (0 0 1) surface: A first principles study

NASA Astrophysics Data System (ADS)

Deng, Xiaodi; Song, Yixu; Li, Jinchun; Pu, Yikang

2014-06-01

First principles calculates have been performed to investigate the surface reaction mechanism of tetraethoxysilane (TEOS) with fully hydroxylated SiO2(0 0 1) substrate. In semiconductor industry, this is the key step to understand and control the SiO2 film growth in chemical vapor deposition (CVD) and atomic layer deposition (ALD) processes. During the calculation, we proposed a model which breaks the surface dissociative chemisorption into two steps and we calculated the activation barriers and thermochemical energies for each step. Our calculation result for step one shows that the first half reaction is thermodynamically favorable. For the second half reaction, we systematically studied the two potential reaction pathways. The comparing result indicates that the pathway which is more energetically favorable will lead to formation of crystalline SiO2 films while the other will lead to formation of disordered SiO2 films.

The Role and Mechanism of Epithelial-to-Mesenchymal Transition in Prostate Cancer Progression

PubMed Central

Lo, U-Ging; Lee, Cheng-Fan; Lee, Ming-Shyue; Hsieh, Jer-Tsong

2017-01-01

In prostate cancer (PCa), similar to many other cancers, distant organ metastasis symbolizes the beginning of the end disease, which eventually leads to cancer death. Many mechanisms have been identified in this process that can be rationalized into targeted therapy. Among them, epithelial-to-mesenchymal transition (EMT) is originally characterized as a critical step for cell trans-differentiation during embryo development and now recognized in promoting cancer cells invasiveness because of high mobility and migratory abilities of mesenchymal cells once converted from carcinoma cells. Nevertheless, the underlying pathways leading to EMT appear to be very diverse in different cancer types, which certainly represent a challenge for developing effective intervention. In this article, we have carefully reviewed the key factors involved in EMT of PCa with clinical correlation in hope to facilitate the development of new therapeutic strategy that is expected to reduce the disease mortality. PMID:28973968

Theoretical study of the initial non-radiative 1 Bu → 2 Ag transition in the fluorescence quenching of s-trans-butadiene: Electronic structure methods and quantum dynamics

NASA Astrophysics Data System (ADS)

Komainda, A.; Lefrancois, D.; Dreuw, A.; Köppel, H.

2017-01-01

The photodynamics of s-trans-butadiene in the 6 eV excitation energy range is investigated by ab initio quantum dynamical methods, paying particular attention to the nonadiabatic coupling between the 1Bu and 2Ag singlet excited states. The existence of a conical intersection between their potential energy surfaces is confirmed. Key parameters of the system, like the energy gap between the interacting states and their coupling strength, are critically assessed. Up to eight nuclear degrees of freedom are considered in the dynamical treatment and are shown to lead to a more realistic description of the interactions. The gas phase (jet) UV absorption spectrum is well reproduced. The related ultrafast nonradiative population transfer from 1Bu to 2Ag is the initial processes leading to fluorescence quenching of trans-butadiene.

Pheochromocytoma: The First Metabolic Endocrine Cancer

PubMed Central

Jochmanova, Ivana; Pacak, Karel

2016-01-01

Dysregulated metabolism is one of the key characteristics of cancer cells. The most prominent alterations are present during regulation of cell respiration, which leads to a switch from oxidative phosphorylation to aerobic glycolysis. This metabolic shift results in activation of numerous signaling and metabolic pathways supporting cell proliferation and survival. Recent progress in genetics and metabolomics allowed us to take a closer look at the metabolic changes present in pheochromocytomas and paragangliomas (PHEOs/PGLs). These neuroendocrine tumors often exhibit dysregulation of mitochondrial metabolism, which is driven by mutations in genes encoding Krebs cycle enzymes or by activation of hypoxia signaling. Present metabolic changes are involved in processes associated with tumorigenesis, invasiveness, metastasis, and resistance to various cancer therapies. In this review, we discuss the metabolic nature of PHEOs/PGLs and how unveiling the metabolic disturbances present in tumors could lead to identification of new biomarkers and personalized cancer therapies. PMID:27742786

Epigenomics and breast cancer

PubMed Central

Lo, Pang-Kuo

2009-01-01

Breast carcinogenesis involves genetic and epigenetic alterations that cause aberrant gene function. Recent progress in the knowledge of epigenomics has had a profound impact on the understanding of mechanisms leading to breast cancer, and consequently the development of new strategies for diagnosis and treatment of breast cancer. Epigenetic regulation has been known to involve three mutually interacting events – DNA methylation, histone modifications and nucleosomal remodeling. These processes modulate chromatin structure to form euchromatin or heterochromatin, and in turn activate or silence gene expression. Alteration in expression of key genes through aberrant epigenetic regulation in breast cells can lead to initiation, promotion and maintenance of carcinogenesis, and is even implicated in the generation of drug resistance. We currently review known roles of the epigenetic machinery in the development and recurrence of breast cancer. Furthermore, we highlight the significance of epigenetic alterations as predictive biomarkers and as new targets of anticancer therapy. PMID:19072646

MOR23 promotes muscle regeneration and regulates cell adhesion and migration

PubMed Central

Griffin, Christine A.; Kafadar, Kimberly A.; Pavlath, Grace K.

2009-01-01

Summary Odorant receptors (ORs) in the olfactory epithelium bind to volatile small molecules leading to the perception of smell. ORs are expressed in many tissues but their functions are largely unknown. We show multiple ORs display distinct mRNA expression patterns during myogenesis in vitro and muscle regeneration in vivo. Mouse OR23 (MOR23) expression is induced during muscle regeneration when muscle cells are extensively fusing and plays a key role in regulating migration and adhesion of muscle cells in vitro, two processes common during tissue repair. A soluble ligand for MOR23 is secreted by muscle cells in vitro and muscle tissue in vivo. MOR23 is necessary for proper skeletal muscle regeneration as loss of MOR23 leads to increased myofiber branching, commonly associated with muscular dystrophy. Together these data identify a functional role for an OR outside of the nose and suggest a larger role for ORs during tissue repair. PMID:19922870

A tunable azine covalent organic framework platform for visible light-induced hydrogen generation

PubMed Central

Vyas, Vijay S.; Haase, Frederik; Stegbauer, Linus; Savasci, Gökcen; Podjaski, Filip; Ochsenfeld, Christian; Lotsch, Bettina V.

2015-01-01

Hydrogen evolution from photocatalytic reduction of water holds promise as a sustainable source of carbon-free energy. Covalent organic frameworks (COFs) present an interesting new class of photoactive materials, which combine three key features relevant to the photocatalytic process, namely crystallinity, porosity and tunability. Here we synthesize a series of water- and photostable 2D azine-linked COFs from hydrazine and triphenylarene aldehydes with varying number of nitrogen atoms. The electronic and steric variations in the precursors are transferred to the resulting frameworks, thus leading to a progressively enhanced light-induced hydrogen evolution with increasing nitrogen content in the frameworks. Our results demonstrate that by the rational design of COFs on a molecular level, it is possible to precisely adjust their structural and optoelectronic properties, thus resulting in enhanced photocatalytic activities. This is expected to spur further interest in these photofunctional frameworks where rational supramolecular engineering may lead to new material applications. PMID:26419805

Atmospheric rivers and past hydrometeorological extremes: Challenges and opportunities

NASA Astrophysics Data System (ADS)

Sodemann, Harald

2017-04-01

Atmospheric rivers are a key term for describing water vapour transport in extratropical regions. The concept has become particularly valuable for linking meteorological process understanding with research focused on the impacts of heavy precipitation. Atmospheric rivers are narrow, elongated features of high integrated water vapour and water vapour flux can lead to severe precipitation and flooding if moisture is extracted efficiently. The orographic rises at the West Coast of the United States and Western Norway are regions where Atmospheric Rivers are one of the prime mechanisms for moisture delivery and precipitation extremes in the present climate. Due to the small horizontal scales of some of the processes climate models are challenged to represent this important transport process between mid-latitudes and the subtropics faithfully. Recent aircraft data and regional tracer model studies provide new insight into the formation and moisture transport mechanisms. In this study I review the concept and pertinent processes of Atmospheric Rivers, thereby focusing on caveats, challenges and opportunities for understanding past hydrometeorological extremes.

Strategic planning: the first step in the planning process.

PubMed

Gelinas, Marc A

2003-01-01

Strategic planning is a systematic process through which an organization builds commitment among key stakeholders to goals and priorities which are essential to its mission and vision, and responsive to the operating environment. Strategic planning is the first step in a comprehensive planning process that also includes business planning and implementation planning. If all three steps are carried out in sequence, strategic planning can be a very effective means of educating the stakeholders about where the cancer program is and where it is going, gaining support and commitment for the direction that the cancer program will take, and assuring that everyone's expectations can be managed effectively. Unfortunately, some organizations and cancer program leaders misunderstand the process. Too often, strategic planning is used as a stand-alone activity. This article will describe what strategic planning is, how it should smoothly lead into business planning and implementation planning, and how to avoid the pitfalls that sometimes arise during the strategic planning effort.

Key processes for the eastward propagation of the Madden-Julian Oscillation based on multimodel simulations

NASA Astrophysics Data System (ADS)

Jiang, Xianan

2017-01-01

As a prominent climate variability mode with widespread influences on global weather extremes, the Madden-Julian Oscillation (MJO) remains poorly represented in the latest generation of general circulation models (GCMs), with a particular challenge in simulating its eastward propagating convective signals. In this study, by analyzing multimodel simulations from a recent global MJO model evaluation project, an effort is made to identify key processes for the eastward propagation of the MJO through analyses of moisture entropy (ME) processes under a "moisture mode" framework for the MJO. The column-integrated horizontal ME advection is found to play a critical role for the eastward propagation of the MJO in both observations and good MJO models, with a primary contribution through advection of the lower tropospheric seasonal mean ME by the MJO anomalous circulations. By contrast, the horizontal ME advection effect for the eastward propagation is greatly underestimated in poor MJO GCMs, due to model deficiencies in simulating both the seasonal mean ME pattern and MJO circulations, leading to a largely stationary MJO mode in these GCMs. These results thus pinpoint an important guidance toward improved representation of the MJO in climate and weather forecast models. While this study mainly focuses on fundamental physics for the MJO propagation over the Indian Ocean, complex influences by the Maritime Continent on the MJO and also ME processes associated with the MJO over the western Pacific warrant further investigations.

Fourier-transform i.r. gas chromatography—mass spectrometry study of varying light olefin reactivity on dealuminated ZSM-5

NASA Astrophysics Data System (ADS)

Sayed, Moein B.

Olefin oligomerization and alkylation (by methanol) of ethene, propene, and isobutene on HZSM-5 have been studied in typical conditions of the catalytic Mobil methanol to gasoline (MTG) process. This has been to identify the most likely light olefin involved as a key intermediate and the most likely mechanism by which such a light olefin propagates to gasoline in the MTG process. Reactions involving bulky intermediates are restricted within the narrow channels of ZSM-5. The oligomerization of ethene and isobutene appears to be an example of such restricted reactions. Zeolite dealumination seems to assist in overcoming the steric barrier by increasing both the zeolite pore volume and the population of the site (silanol) hosting the adsorbate. Spectral i.r. evidence reveals a role of zeolite Lewis acidity as a precursor in initiating olefin protonation by the zeolite Brønsted acidity. Both i.r. and GC—MS data consistently reveal a product distribution similar to that obtained in the MTG process, which suggests a dominant oligomerization and/or alkylation to be the mechanism leading to gasoline in the MTG process. However, the higher reactivity detected for olefin alkylation indicates alkylation to be the favoured mechanism. Propene is more likely to be a key intermediate, whereas isobutene contributes with a role being increasingly dominant over the more dealuminated ZSM-5 surfaces. Ethene, in contrast, shows poor reactivity, which can be enhanced by the zeolite dealumination.

Setting up an ethics of ecosystem research structure based on the precautionary principle.

PubMed

Farmer, Michael C

2013-01-01

Ethical practices in ecological field research differ from those in laboratory research in more than the technical setting and the important distinction between population-level and individual-based concerns. The number of stakeholders affected by the conduct of field research is far larger; private landholders, public water utilities, public land managers, local industries, and communities large and small are only some of those who may be impacted. As research review boards move to establish specific ethical practices for field biologists, the process of identifying appropriate standards will affect the degree to which research will ultimately be disrupted. Standards that lead to research protocols that alienate key interests are not likely to be sustainable. Already, standards that have conflicted with the primary values of a key interest have resulted in disruptions to research and scientific progress. One way to manage this problem of deeply competing interests is to avoid the deepest offenses to any relevant interest group in the design of a proposed study. This is an application of the precautionary principle and is likely to generate a more sustainable balance among competing interests. Unfortunately, this process is also likely to be a never-ending, consensus-seeking process. Fortunately, scientists can have enormous influence on the process if they choose to engage in it early. If scientists use their expertise to function as honest brokers among affected interests, their own interest in scientific research progress is likely to be better met.

Reverse osmosis desalination: water sources, technology, and today's challenges.

PubMed

Greenlee, Lauren F; Lawler, Desmond F; Freeman, Benny D; Marrot, Benoit; Moulin, Philippe

2009-05-01

Reverse osmosis membrane technology has developed over the past 40 years to a 44% share in world desalting production capacity, and an 80% share in the total number of desalination plants installed worldwide. The use of membrane desalination has increased as materials have improved and costs have decreased. Today, reverse osmosis membranes are the leading technology for new desalination installations, and they are applied to a variety of salt water resources using tailored pretreatment and membrane system design. Two distinct branches of reverse osmosis desalination have emerged: seawater reverse osmosis and brackish water reverse osmosis. Differences between the two water sources, including foulants, salinity, waste brine (concentrate) disposal options, and plant location, have created significant differences in process development, implementation, and key technical problems. Pretreatment options are similar for both types of reverse osmosis and depend on the specific components of the water source. Both brackish water and seawater reverse osmosis (RO) will continue to be used worldwide; new technology in energy recovery and renewable energy, as well as innovative plant design, will allow greater use of desalination for inland and rural communities, while providing more affordable water for large coastal cities. A wide variety of research and general information on RO desalination is available; however, a direct comparison of seawater and brackish water RO systems is necessary to highlight similarities and differences in process development. This article brings to light key parameters of an RO process and process modifications due to feed water characteristics.

Nutritional programming of disease: unravelling the mechanism

PubMed Central

Langley-Evans, Simon C

2009-01-01

Nutritional programming is the process through which variation in the quality or quantity of nutrients consumed during pregnancy exerts permanent effects upon the developing fetus. Programming of fetal development is considered to be an important risk factor for non-communicable diseases of adulthood, including coronary heart disease and other disorders related to insulin resistance. The study of programming in relation to disease processes has been advanced by development of animal models, which have utilized restriction or over-feeding of specific nutrients in either rodents or sheep. These consistently demonstrate the biological plausibility of the nutritional programming hypothesis and, importantly, provide tools with which to examine the mechanisms through which programming may occur. Studies of animals subject to undernutrition in utero generally exhibit changes in the structure of key organs such as the kidney, heart and brain. These appear consistent with remodelling of development, associated with disruption of cellular proliferation and differentiation. Whilst the causal pathways which extend from this tissue remodelling to disease can be easily understood, the processes which lead to this disordered organ development are poorly defined. Even minor variation in maternal nutritional status is capable of producing important shifts in the fetal environment. It is suggested that these environmental changes are associated with altered expression of key genes, which are responsible for driving the tissue remodelling response and future disease risk. Nutrition-related factors may drive these processes by disturbing placental function, including control of materno-fetal endocrine exchanges, or the epigenetic regulation of gene expression. PMID:19175805

A key for the Forest Service hardwood tree grades

Treesearch

Gary W. Miller; Leland F. Hanks; Harry V., Jr. Wiant

1986-01-01

A dichotomous key organizes the USDA Forest Service hardwood tree grade specifications into a stepwise procedure for those learning to grade hardwood sawtimber. The key addresses the major grade factors, tree size, surface characteristics, and allowable cull deductions in a series of paried choices that lead the user to a decision regarding tree grade.

Tumor Necrosis Factor-α Sensitizes Breast Cancer Cells to Natural Products with Proteasome-Inhibitory Activity Leading to Apoptosis

PubMed Central

Lu, Li; Shi, Wenli; Deshmukh, Rahul R.; Long, Jie; Cheng, Xiaoli; Ji, Weidong; Zeng, Guohua; Chen, Xianliang; Zhang, Yajie; Dou, Q. Ping

2014-01-01

The inflammatory microenvironment plays an important role in the process of tumor development. Tumor necrosis factor-α (TNF-α), a key pro-inflammatory cytokine, has a significant role in this process. Natural medicinal products such as Withaferin A (WA) and Celastrol (Cel) have shown anti-cancer and anti-inflammatory properties that can be attributed to multiple mechanisms including, but not limited to, apoptosis induction due to the inhibition of proteasomal activities. This study aimed to investigate the effects of TNF-α in combination with WA or Cel in vitro in MDA-MB-231 breast cancer cells. TNF-α, when combined with WA or Cel, activated caspase-3 and -9 and downregulated XIAP in a dose-dependent manner, leading to induction of apoptosis in MDA-MB-231 breast cancer cells. The combination also caused accumulation of the proteasomal target protein IκBα, resulting in inhibition of the nuclear translocation of nuclear factor-κB (NF-κB). Taken together, these results suggest that TNF-α could sensitize breast cancer cells MDA-MB-231 to WA and Cel, at least in part, through inhibiting the activation of NF-κB signaling, leading to XIAP inhibition with subsequent upregulation of caspase-3 and -9 activities. Thus, the anti-cancer activities of TNF-α are enhanced when combined with the natural proteasome inhibitors, WA or Cel. PMID:25419573

Aqueous route to facile, efficient and functional silica coating of metal nanoparticles at room temperature

NASA Astrophysics Data System (ADS)

Shah, Kwok Wei; Sreethawong, Thammanoon; Liu, Shu-Hua; Zhang, Shuang-Yuan; Tan, Li Sirh; Han, Ming-Yong

2014-09-01

Various metal (Ag, Au, and Pt)@thiol-functionalized silica (SiO2-SH) nanoparticles (NPs) are successfully prepared at room temperature by a facile, efficient, functional, universal and scalable coating process in alcohol-free aqueous solution using pre-hydrolyzed 3-(mercaptopropyl)trimethoxysilane (MPTMS). The controlled pre-hydrolysis of the silane precursor in water and the consecutive condensation processes are the key to achieve the effective and uniform silica coating on metal NPs in aqueous solution. The thickness of the silica shell is tuned by simply varying the coating time. The silica shell can act as an effective protecting layer for Ag NPs in Ag@SiO2-SH NPs under conditions for silica coating in aqueous solution; however, it leads to a directional dissolution of Ag NPs in a more strongly basic ammonia solution. The environmentally friendly silica coating process in water is also applied to prepare highly surface-enhanced Raman scattering (SERS)-active Ag@SiO2-SH NPs with different types of Raman molecules for highly sensitive SERS-based applications in various fields.Various metal (Ag, Au, and Pt)@thiol-functionalized silica (SiO2-SH) nanoparticles (NPs) are successfully prepared at room temperature by a facile, efficient, functional, universal and scalable coating process in alcohol-free aqueous solution using pre-hydrolyzed 3-(mercaptopropyl)trimethoxysilane (MPTMS). The controlled pre-hydrolysis of the silane precursor in water and the consecutive condensation processes are the key to achieve the effective and uniform silica coating on metal NPs in aqueous solution. The thickness of the silica shell is tuned by simply varying the coating time. The silica shell can act as an effective protecting layer for Ag NPs in Ag@SiO2-SH NPs under conditions for silica coating in aqueous solution; however, it leads to a directional dissolution of Ag NPs in a more strongly basic ammonia solution. The environmentally friendly silica coating process in water is also applied to prepare highly surface-enhanced Raman scattering (SERS)-active Ag@SiO2-SH NPs with different types of Raman molecules for highly sensitive SERS-based applications in various fields. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr03306j

The microbiome as engineering tool: Manufacturing and trading between microorganisms.

PubMed

De Vrieze, Jo; Christiaens, Marlies E R; Verstraete, Willy

2017-10-25

The integration of microbial technologies within the framework of the water-energy nexus has been taking place for over a century, but these mixed microbial communities are considered hard to deal with 'black boxes'. Process steering is mainly based on avoiding process failure by monitoring conventional parameters, e.g., pH and temperature, which often leads to operation far below the intrinsic potential. Mixed microbial communities do not reflect a randomised individual mix, but an interacting microbiological entity. Advance monitoring to obtain effective engineering of the microbiome is achievable, and even crucial to obtain the desired performance and products. This can be achieved via a top-down or bottom-up approach. The top-down strategy is reflected in the microbial resource management concept that considers the microbial community as a well-structured network. This network can be monitored by means of molecular techniques that will allow the development of accurate and quick decision tools. In contrast, the bottom-up approach makes use of synthetic cultures that can be composed starting from defined axenic cultures, based on the requirements of the process under consideration. The success of both approaches depends on real-time monitoring and control. Of particular importance is the necessity to identify and characterise the key players in the process. These key players not only relate with the establishment of functional conversions, but also with the interaction between partner bacteria. This emphasises the importance of molecular (screening) techniques to obtain structural and functional insights, minimise energy input, and maximise product output by means of integrated microbiome processes. Copyright © 2017 Elsevier B.V. All rights reserved.

Vertical structure and physical processes of the Madden-Julian oscillation: Exploring key model physics in climate simulations

DOE PAGES

Jiang, Xianan; Waliser, Duane E.; Xavier, Prince K.; ...

2015-05-27

Aimed at reducing deficiencies in representing the Madden-Julian oscillation (MJO) in general circulation models (GCMs), a global model evaluation project on vertical structure and physical processes of the MJO was coordinated. In this paper, results from the climate simulation component of this project are reported. Here, it is shown that the MJO remains a great challenge in these latest generation GCMs. The systematic eastward propagation of the MJO is only well simulated in about one fourth of the total participating models. The observed vertical westward tilt with altitude of the MJO is well simulated in good MJO models but notmore » in the poor ones. Damped Kelvin wave responses to the east of convection in the lower troposphere could be responsible for the missing MJO preconditioning process in these poor MJO models. Several process-oriented diagnostics were conducted to discriminate key processes for realistic MJO simulations. While large-scale rainfall partition and low-level mean zonal winds over the Indo-Pacific in a model are not found to be closely associated with its MJO skill, two metrics, including the low-level relative humidity difference between high- and low-rain events and seasonal mean gross moist stability, exhibit statistically significant correlations with the MJO performance. It is further indicated that increased cloud-radiative feedback tends to be associated with reduced amplitude of intraseasonal variability, which is incompatible with the radiative instability theory previously proposed for the MJO. Finally, results in this study confirm that inclusion of air-sea interaction can lead to significant improvement in simulating the MJO.« less

Reliable Characterization for Pyrolysis Bio-Oils Leads to Enhanced

Science.gov Websites

Upgrading Methods | NREL Reliable Characterization for Pyrolysis Bio-Oils Leads to Enhanced Upgrading Methods Science and Technology Highlights Highlights in Research & Development Reliable Characterization for Pyrolysis Bio-Oils Leads to Enhanced Upgrading Methods Key Research Results Achievement As co

A novel network analysis approach reveals DNA damage, oxidative stress and calcium/cAMP homeostasis-associated biomarkers in frontotemporal dementia

PubMed Central

Ferrari, Raffaele; Graziano, Francesca; Novelli, Valeria; Rossi, Giacomina; Galimberti, Daniela; Rainero, Innocenzo; Benussi, Luisa; Nacmias, Benedetta; Bruni, Amalia C.; Cusi, Daniele; Salvi, Erika; Borroni, Barbara; Grassi, Mario

2017-01-01

Frontotemporal Dementia (FTD) is the form of neurodegenerative dementia with the highest prevalence after Alzheimer’s disease, equally distributed in men and women. It includes several variants, generally characterized by behavioural instability and language impairments. Although few mendelian genes (MAPT, GRN, and C9orf72) have been associated to the FTD phenotype, in most cases there is only evidence of multiple risk loci with relatively small effect size. To date, there are no comprehensive studies describing FTD at molecular level, highlighting possible genetic interactions and signalling pathways at the origin FTD-associated neurodegeneration. In this study, we designed a broad FTD genetic interaction map of the Italian population, through a novel network-based approach modelled on the concepts of disease-relevance and interaction perturbation, combining Steiner tree search and Structural Equation Model (SEM) analysis. Our results show a strong connection between Calcium/cAMP metabolism, oxidative stress-induced Serine/Threonine kinases activation, and postsynaptic membrane potentiation, suggesting a possible combination of neuronal damage and loss of neuroprotection, leading to cell death. In our model, Calcium/cAMP homeostasis and energetic metabolism impairments are primary causes of loss of neuroprotection and neural cell damage, respectively. Secondly, the altered postsynaptic membrane potentiation, due to the activation of stress-induced Serine/Threonine kinases, leads to neurodegeneration. Our study investigates the molecular underpinnings of these processes, evidencing key genes and gene interactions that may account for a significant fraction of unexplained FTD aetiology. We emphasized the key molecular actors in these processes, proposing them as novel FTD biomarkers that could be crucial for further epidemiological and molecular studies. PMID:29020091

A Circadian Clock in Antarctic Krill: An Endogenous Timing System Governs Metabolic Output Rhythms in the Euphausid Species Euphausia superba

PubMed Central

Teschke, Mathias; Wendt, Sabrina; Kawaguchi, So; Kramer, Achim; Meyer, Bettina

2011-01-01

Antarctic krill, Euphausia superba, shapes the structure of the Southern Ocean ecosystem. Its central position in the food web, the ongoing environmental changes due to climatic warming, and increasing commercial interest on this species emphasize the urgency of understanding the adaptability of krill to its environment. Krill has evolved rhythmic physiological and behavioral functions which are synchronized with the daily and seasonal cycles of the complex Southern Ocean ecosystem. The mechanisms, however, leading to these rhythms are essentially unknown. Here, we show that krill possesses an endogenous circadian clock that governs metabolic and physiological output rhythms. We found that expression of the canonical clock gene cry2 was highly rhythmic both in a light-dark cycle and in constant darkness. We detected a remarkable short circadian period, which we interpret as a special feature of the krill's circadian clock that helps to entrain the circadian system to the extreme range of photoperiods krill is exposed to throughout the year. Furthermore, we found that important key metabolic enzymes of krill showed bimodal circadian oscillations (∼9–12 h period) in transcript abundance and enzymatic activity. Oxygen consumption of krill showed ∼9–12 h oscillations that correlated with the temporal activity profile of key enzymes of aerobic energy metabolism. Our results demonstrate the first report of an endogenous circadian timing system in Antarctic krill and its likely link to metabolic key processes. Krill's circadian clock may not only be critical for synchronization to the solar day but also for the control of seasonal events. This study provides a powerful basis for the investigation into the mechanisms of temporal synchronization in this marine key species and will also lead to the first comprehensive analyses of the circadian clock of a polar marine organism through the entire photoperiodic cycle. PMID:22022521

A circadian clock in Antarctic krill: an endogenous timing system governs metabolic output rhythms in the euphausid species Euphausia superba.

PubMed

Teschke, Mathias; Wendt, Sabrina; Kawaguchi, So; Kramer, Achim; Meyer, Bettina

2011-01-01

Antarctic krill, Euphausia superba, shapes the structure of the Southern Ocean ecosystem. Its central position in the food web, the ongoing environmental changes due to climatic warming, and increasing commercial interest on this species emphasize the urgency of understanding the adaptability of krill to its environment. Krill has evolved rhythmic physiological and behavioral functions which are synchronized with the daily and seasonal cycles of the complex Southern Ocean ecosystem. The mechanisms, however, leading to these rhythms are essentially unknown. Here, we show that krill possesses an endogenous circadian clock that governs metabolic and physiological output rhythms. We found that expression of the canonical clock gene cry2 was highly rhythmic both in a light-dark cycle and in constant darkness. We detected a remarkable short circadian period, which we interpret as a special feature of the krill's circadian clock that helps to entrain the circadian system to the extreme range of photoperiods krill is exposed to throughout the year. Furthermore, we found that important key metabolic enzymes of krill showed bimodal circadian oscillations (∼9-12 h period) in transcript abundance and enzymatic activity. Oxygen consumption of krill showed ∼9-12 h oscillations that correlated with the temporal activity profile of key enzymes of aerobic energy metabolism. Our results demonstrate the first report of an endogenous circadian timing system in Antarctic krill and its likely link to metabolic key processes. Krill's circadian clock may not only be critical for synchronization to the solar day but also for the control of seasonal events. This study provides a powerful basis for the investigation into the mechanisms of temporal synchronization in this marine key species and will also lead to the first comprehensive analyses of the circadian clock of a polar marine organism through the entire photoperiodic cycle.

Quantum key distribution with finite resources: Secret key rates via Renyi entropies

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

Abruzzo, Silvestre; Kampermann, Hermann; Mertz, Markus

A realistic quantum key distribution (QKD) protocol necessarily deals with finite resources, such as the number of signals exchanged by the two parties. We derive a bound on the secret key rate which is expressed as an optimization problem over Renyi entropies. Under the assumption of collective attacks by an eavesdropper, a computable estimate of our bound for the six-state protocol is provided. This bound leads to improved key rates in comparison to previous results.

Indicators and measurement tools for health system integration: a knowledge synthesis protocol.

PubMed

Oelke, Nelly D; Suter, Esther; da Silva Lima, Maria Alice Dias; Van Vliet-Brown, Cheryl

2015-07-29

Health system integration is a key component of health system reform with the goal of improving outcomes for patients, providers, and the health system. Although health systems continue to strive for better integration, current delivery of health services continues to be fragmented. A key gap in the literature is the lack of information on what successful integration looks like and how to measure achievement towards an integrated system. This multi-site study protocol builds on a prior knowledge synthesis completed by two of the primary investigators which identified 10 key principles that collectively support health system integration. The aim is to answer two research questions: What are appropriate indicators for each of the 10 key integration principles developed in our previous knowledge synthesis and what measurement tools are used to measure these indicators? To enhance generalizability of the findings, a partnership between Canada and Brazil was created as health system integration is a priority in both countries and they share similar contexts. This knowledge synthesis will follow an iterative scoping review process with emerging information from knowledge-user engagement leading to the refinement of research questions and study selection. This paper describes the methods for each phase of the study. Research questions were developed with stakeholder input. Indicator identification and prioritization will utilize a modified Delphi method and patient/user focus groups. Based on priority indicators, a search of the literature will be completed and studies screened for inclusion. Quality appraisal of relevant studies will be completed prior to data extraction. Results will be used to develop recommendations and key messages to be presented through integrated and end-of-grant knowledge translation strategies with researchers and knowledge-users from the three jurisdictions. This project will directly benefit policy and decision-makers by providing an easy accessible set of indicators and tools to measure health system integration across different contexts and cultures. Being able to evaluate the success of integration strategies and initiatives will lead to better health system design and improved health outcomes for patients.

Interorganizational relationships within state tobacco control networks: a social network analysis.

PubMed

Krauss, Melissa; Mueller, Nancy; Luke, Douglas

2004-10-01

State tobacco control programs are implemented by networks of public and private agencies with a common goal to reduce tobacco use. The degree of a program's comprehensiveness depends on the scope of its activities and the variety of agencies involved in the network. Structural aspects of these networks could help describe the process of implementing a state's tobacco control program, but have not yet been examined. Social network analysis was used to examine the structure of five state tobacco control networks. Semi-structured interviews with key agencies collected quantitative and qualitative data on frequency of contact among network partners, money flow, relationship productivity, level of network effectiveness, and methods for improvement. Most states had hierarchical communication structures in which partner agencies had frequent contact with one or two central agencies. Lead agencies had the highest control over network communication. Networks with denser communication structures had denser productivity structures. Lead agencies had the highest financial influence within the networks, while statewide coalitions were financially influenced by others. Lead agencies had highly productive relationships with others, while agencies with narrow roles had fewer productive relationships. Statewide coalitions that received Robert Wood Johnson Foundation funding had more highly productive relationships than coalitions that did not receive the funding. Results suggest that frequent communication among network partners is related to more highly productive relationships. Results also highlight the importance of lead agencies and statewide coalitions in implementing a comprehensive state tobacco control program. Network analysis could be useful in developing process indicators for state tobacco control programs.

Key management of the double random-phase-encoding method using public-key encryption

NASA Astrophysics Data System (ADS)

Saini, Nirmala; Sinha, Aloka

2010-03-01

Public-key encryption has been used to encode the key of the encryption process. In the proposed technique, an input image has been encrypted by using the double random-phase-encoding method using extended fractional Fourier transform. The key of the encryption process have been encoded by using the Rivest-Shamir-Adelman (RSA) public-key encryption algorithm. The encoded key has then been transmitted to the receiver side along with the encrypted image. In the decryption process, first the encoded key has been decrypted using the secret key and then the encrypted image has been decrypted by using the retrieved key parameters. The proposed technique has advantage over double random-phase-encoding method because the problem associated with the transmission of the key has been eliminated by using public-key encryption. Computer simulation has been carried out to validate the proposed technique.

Lead and Copper Rule Revisions White Paper

EPA Pesticide Factsheets

The Lead and Copper Rule (LCR) Revisions White Paper provides examples of regulatory options to improve the existing rule. The paper highlights key challenges, opportunities, and analytical issues presented by these options.

Advanced High-Level Waste Glass Research and Development Plan

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

Peeler, David K.; Vienna, John D.; Schweiger, Michael J.

2015-07-01

The U.S. Department of Energy Office of River Protection (ORP) has implemented an integrated program to increase the loading of Hanford tank wastes in glass while meeting melter lifetime expectancies and process, regulatory, and product quality requirements. The integrated ORP program is focused on providing a technical, science-based foundation from which key decisions can be made regarding the successful operation of the Hanford Tank Waste Treatment and Immobilization Plant (WTP) facilities. The fundamental data stemming from this program will support development of advanced glass formulations, key process control models, and tactical processing strategies to ensure safe and successful operations formore » both the low-activity waste (LAW) and high-level waste (HLW) vitrification facilities with an appreciation toward reducing overall mission life. The purpose of this advanced HLW glass research and development plan is to identify the near-, mid-, and longer-term research and development activities required to develop and validate advanced HLW glasses and their associated models to support facility operations at WTP, including both direct feed and full pretreatment flowsheets. This plan also integrates technical support of facility operations and waste qualification activities to show the interdependence of these activities with the advanced waste glass (AWG) program to support the full WTP mission. Figure ES-1 shows these key ORP programmatic activities and their interfaces with both WTP facility operations and qualification needs. The plan is a living document that will be updated to reflect key advancements and mission strategy changes. The research outlined here is motivated by the potential for substantial economic benefits (e.g., significant increases in waste throughput and reductions in glass volumes) that will be realized when advancements in glass formulation continue and models supporting facility operations are implemented. Developing and applying advanced glass formulations will reduce the cost of Hanford tank waste management by reducing the schedule for tank waste treatment and reducing the amount of HLW glass for storage, transportation, and disposal. Additional benefits will be realized if advanced glasses are developed that demonstrate more tolerance for key components in the waste (such as Al 2O 3, Cr 2O 3, SO 3 and Na 2O) above the currently defined WTP constraints. Tolerating these higher concentrations of key waste loading limiters may reduce the burden on (or even eliminate the need for) leaching to remove Cr and Al and washing to remove excess S and Na from the HLW fraction. Advanced glass formulations may also make direct vitrification of the HLW fraction without significant pretreatment more cost effective. Finally, the advanced glass formulation efforts seek not only to increase waste loading in glass, but also to increase glass production rate. When coupled with higher waste loading, ensuring that all of the advanced glass formulations are processable at or above the current contract processing rate leads to significant improvements in waste throughput (the amount of waste being processed per unit time),which could significantly reduce the overall WTP mission life. The integration of increased waste loading, reduced leaching/washing requirements, and improved melting rates provides a system-wide approach to improve the effectiveness of the WTP process.« less

Quantum key distribution in a multi-user network at gigahertz clock rates

NASA Astrophysics Data System (ADS)

Fernandez, Veronica; Gordon, Karen J.; Collins, Robert J.; Townsend, Paul D.; Cova, Sergio D.; Rech, Ivan; Buller, Gerald S.

2005-07-01

In recent years quantum information research has lead to the discovery of a number of remarkable new paradigms for information processing and communication. These developments include quantum cryptography schemes that offer unconditionally secure information transport guaranteed by quantum-mechanical laws. Such potentially disruptive security technologies could be of high strategic and economic value in the future. Two major issues confronting researchers in this field are the transmission range (typically <100km) and the key exchange rate, which can be as low as a few bits per second at long optical fiber distances. This paper describes further research of an approach to significantly enhance the key exchange rate in an optical fiber system at distances in the range of 1-20km. We will present results on a number of application scenarios, including point-to-point links and multi-user networks. Quantum key distribution systems have been developed, which use standard telecommunications optical fiber, and which are capable of operating at clock rates of up to 2GHz. They implement a polarization-encoded version of the B92 protocol and employ vertical-cavity surface-emitting lasers with emission wavelengths of 850 nm as weak coherent light sources, as well as silicon single-photon avalanche diodes as the single photon detectors. The point-to-point quantum key distribution system exhibited a quantum bit error rate of 1.4%, and an estimated net bit rate greater than 100,000 bits-1 for a 4.2 km transmission range.

Security of quantum key distribution with iterative sifting

NASA Astrophysics Data System (ADS)

Tamaki, Kiyoshi; Lo, Hoi-Kwong; Mizutani, Akihiro; Kato, Go; Lim, Charles Ci Wen; Azuma, Koji; Curty, Marcos

2018-01-01

Several quantum key distribution (QKD) protocols employ iterative sifting. After each quantum transmission round, Alice and Bob disclose part of their setting information (including their basis choices) for the detected signals. This quantum phase then ends when the basis dependent termination conditions are met, i.e., the numbers of detected signals per basis exceed certain pre-agreed threshold values. Recently, however, Pfister et al (2016 New J. Phys. 18 053001) showed that the basis dependent termination condition makes QKD insecure, especially in the finite key regime, and they suggested to disclose all the setting information after finishing the quantum phase. However, this protocol has two main drawbacks: it requires that Alice possesses a large memory, and she also needs to have some a priori knowledge about the transmission rate of the quantum channel. Here we solve these two problems by introducing a basis-independent termination condition to the iterative sifting in the finite key regime. The use of this condition, in combination with Azuma’s inequality, provides a precise estimation on the amount of privacy amplification that needs to be applied, thus leading to the security of QKD protocols, including the loss-tolerant protocol (Tamaki et al 2014 Phys. Rev. A 90 052314), with iterative sifting. Our analysis indicates that to announce the basis information after each quantum transmission round does not compromise the key generation rate of the loss-tolerant protocol. Our result allows the implementation of wider classes of classical post-processing techniques in QKD with quantified security.

Competing Uses of Underground Systems Related to Energy Supply: Applying Single- and Multiphase Simulations for Site Characterization and Risk-Analysis

NASA Astrophysics Data System (ADS)

Kissinger, A.; Walter, L.; Darcis, M.; Flemisch, B.; Class, H.

2012-04-01

Global climate change, shortage of resources and the resulting turn towards renewable sources of energy lead to a growing demand for the utilization of subsurface systems. Among these competing uses are Carbon Capture and Storage (CCS), geothermal energy, nuclear waste disposal, "renewable" methane or hydrogen storage as well as the ongoing production of fossil resources like oil, gas, and coal. Besides competing among themselves, these technologies may also create conflicts with essential public interests like water supply. For example, the injection of CO2 into the underground causes an increase in pressure reaching far beyond the actual radius of influence of the CO2 plume, potentially leading to large amounts of displaced salt water. Finding suitable sites is a demanding task for several reasons. Natural systems as opposed to technical systems are always characterized by heterogeneity. Therefore, parameter uncertainty impedes reliable predictions towards capacity and safety of a site. State of the art numerical simulations combined with stochastic approaches need to be used to obtain a more reliable assessment of the involved risks and the radii of influence of the different processes. These simulations may include the modeling of single- and multiphase non-isothermal flow, geo-chemical and geo-mechanical processes in order to describe all relevant physical processes adequately. Stochastic approaches have the aim to estimate a bandwidth of the key output parameters based on uncertain input parameters. Risks for these different underground uses can then be made comparable with each other. Along with the importance and the urgency of the competing processes this may lead to a more profound basis for a decision. Communicating risks to stake holders and a concerned public is crucial for the success of finding a suitable site for CCS (or other subsurface utilization). We present and discuss first steps towards an approach for addressing the issue of competitive utilization of the subsurface and the required process of communication between scientists, engineers, policy makers, and societies.

Evaluating the Quality of Patient Decision-Making Regarding Post-Acute Care.

PubMed

Burke, Robert E; Jones, Jacqueline; Lawrence, Emily; Ladebue, Amy; Ayele, Roman; Leonard, Chelsea; Lippmann, Brandi; Matlock, Daniel D; Allyn, Rebecca; Cumbler, Ethan

2018-05-01

Despite a national focus on post-acute care brought about by recent payment reforms, relatively little is known about how hospitalized older adults and their caregivers decide whether to go to a skilled nursing facility (SNF) after hospitalization. We sought to understand to what extent hospitalized older adults and their caregivers are empowered to make a high-quality decision about utilizing an SNF for post-acute care and what contextual or process elements led to satisfaction with the outcome of their decision once in SNF. Qualitative inquiry using the Ottawa Decision Support Framework (ODSF), a conceptual framework that describes key components of high-quality decision-making. Thirty-two previously community-dwelling older adults (≥ 65 years old) and 22 caregivers interviewed at three different hospitals and three skilled nursing facilities. We used key components of the ODSF to identify elements of context and process that affected decision-making and to what extent the outcome was characteristic of a high-quality decision: informed, values based, and not associated with regret or blame. The most important contextual themes were the presence of active medical conditions in the hospital that made decision-making difficult, prior experiences with hospital readmission or SNF, relative level of caregiver support, and pressure to make a decision quickly for which participants felt unprepared. Patients described playing a passive role in the decision-making process and largely relying on recommendations from the medical team. Patients commonly expressed resignation and a perceived lack of choice or autonomy, leading to dissatisfaction with the outcome. Understanding and intervening to improve the quality of decision-making regarding post-acute care supports is essential for improving outcomes of hospitalized older adults. Our results suggest that simply providing information is not sufficient; rather, incorporating key contextual factors and improving the decision-making process for both patients and clinicians are also essential.

An Improved EKG-Based Key Agreement Scheme for Body Area Networks

NASA Astrophysics Data System (ADS)

Ali, Aftab; Khan, Farrukh Aslam

Body area networks (BANs) play an important role in mobile health monitoring such as, monitoring the health of patients in a hospital or physical status of soldiers in a battlefield. By securing the BAN, we actually secure the lives of soldiers or patients. This work presents an electrocardiogram (EKG) based key agreement scheme using discrete wavelet transform (DWT) for the sake of generating a common key in a body area network. The use of EKG brings plug-and-play capability in BANs; i.e., the sensors are just placed on the human body and a secure communication is started among these sensors. The process is made secure by using the iris or fingerprints to lock and then unlock the blocks during exchange between the communicating sensors. The locking and unlocking is done through watermarking. When a watermark is added at the sender side, the block is locked and when it is removed at the receiver side, the block is unlocked. By using iris or fingerprints, the security of the technique improves and its plug-and-play capability is not affected. The analysis is done by using real 2-lead EKG data sampled at a rate of 125 Hz taken from MIT PhysioBank database.

Overcoming Short-Circuit in Lead-Free CH3NH3SnI3 Perovskite Solar Cells via Kinetically Controlled Gas-Solid Reaction Film Fabrication Process.

PubMed

Yokoyama, Takamichi; Cao, Duyen H; Stoumpos, Constantinos C; Song, Tze-Bin; Sato, Yoshiharu; Aramaki, Shinji; Kanatzidis, Mercouri G

2016-03-03

The development of Sn-based perovskite solar cells has been challenging because devices often show short-circuit behavior due to poor morphologies and undesired electrical properties of the thin films. A low-temperature vapor-assisted solution process (LT-VASP) has been employed as a novel kinetically controlled gas-solid reaction film fabrication method to prepare lead-free CH3NH3SnI3 thin films. We show that the solid SnI2 substrate temperature is the key parameter in achieving perovskite films with high surface coverage and excellent uniformity. The resulting high-quality CH3NH3SnI3 films allow the successful fabrication of solar cells with drastically improved reproducibility, reaching an efficiency of 1.86%. Furthermore, our Kelvin probe studies show the VASP films have a doping level lower than that of films prepared from the conventional one-step method, effectively lowering the film conductivity. Above all, with (LT)-VASP, the short-circuit behavior often obtained from the conventional one-step-fabricated Sn-based perovskite devices has been overcome. This study facilitates the path to more successful Sn-perovskite photovoltaic research.

Molecular mechanisms of aging and immune system regulation in Drosophila.

PubMed

Eleftherianos, Ioannis; Castillo, Julio Cesar

2012-01-01

Aging is a complex process that involves the accumulation of deleterious changes resulting in overall decline in several vital functions, leading to the progressive deterioration in physiological condition of the organism and eventually causing disease and death. The immune system is the most important host-defense mechanism in humans and is also highly conserved in insects. Extensive research in vertebrates has concluded that aging of the immune function results in increased susceptibility to infectious disease and chronic inflammation. Over the years, interest has grown in studying the molecular interaction between aging and the immune response to pathogenic infections. The fruit fly Drosophila melanogaster is an excellent model system for dissecting the genetic and genomic basis of important biological processes, such as aging and the innate immune system, and deciphering parallel mechanisms in vertebrate animals. Here, we review the recent advances in the identification of key players modulating the relationship between molecular aging networks and immune signal transduction pathways in the fly. Understanding the details of the molecular events involved in aging and immune system regulation will potentially lead to the development of strategies for decreasing the impact of age-related diseases, thus improving human health and life span.

Sex allocation promotes the stable co-occurrence of competitive species

NASA Astrophysics Data System (ADS)

Kobayashi, Kazuya

2017-03-01

Biodiversity has long been a source of wonder and scientific curiosity. Theoretically, the co-occurrence of competitive species requires niche differentiation, and such differences are well known; however, the neutral theory, which assumes the equivalence of all individuals regardless of the species in a biological community, has successfully recreated observed patterns of biodiversity. In this research, the evolution of sex allocation is demonstrated to be the key to resolving why the neutral theory works well, despite the observed species differences. The sex allocation theory predicts that female-biased allocation evolves in species in declining density and that this allocation improves population growth, which should lead to an increase in density. In contrast, when the density increases, a less biased allocation evolves, which reduces the population growth rate and leads to decreased density. Thus, sex allocation provides a buffer against species differences in population growth. A model incorporating this mechanism demonstrates that hundreds of species can co-occur over 10,000 generations, even in homogeneous environments, and reproduces the observed patterns of biodiversity. This study reveals the importance of evolutionary processes within species for the sustainability of biodiversity. Integrating the entire biological process, from genes to community, will open a new era of ecology.

Wild Roman chamomile extracts and phenolic compounds: enzymatic assays and molecular modelling studies with VEGFR-2 tyrosine kinase.

PubMed

Guimarães, Rafaela; Calhelha, Ricardo C; Froufe, Hugo J C; Abreu, Rui M V; Carvalho, Ana Maria; Queiroz, Maria João R P; Ferreira, Isabel C F R

2016-01-01

Angiogenesis is a process by which new blood vessels are formed from the pre-existing vasculature, and it is a key process that leads to tumour development. Some studies have recognized phenolic compounds as chemopreventive agents; flavonoids, in particular, seem to suppress the growth of tumor cells modifying the cell cycle. Herein, the antiangiogenic activity of Roman chamomile (Chamaemelum nobile L.) extracts (methanolic extract and infusion) and the main phenolic compounds present (apigenin, apigenin-7-O-glucoside, caffeic acid, chlorogenic acid, luteolin, and luteolin-7-O-glucoside) was evaluated through enzymatic assays using the tyrosine kinase intracellular domain of the Vascular Endothelium Growth Factor Receptor-2 (VEGFR-2), which is a transmembrane receptor expressed fundamentally in endothelial cells involved in angiogenesis, and molecular modelling studies. The methanolic extract showed a lower IC50 value (concentration that provided 50% of VEGFR-2 inhibition) than the infusion, 269 and 301 μg mL(-1), respectively. Regarding phenolic compounds, luteolin and apigenin showed the highest capacity to inhibit the phosphorylation of VEGFR-2, leading us to believe that these compounds are involved in the activity revealed by the methanolic extract.

Molecular Mechanisms of Aging and Immune System Regulation in Drosophila

PubMed Central

Eleftherianos, Ioannis; Castillo, Julio Cesar

2012-01-01

Aging is a complex process that involves the accumulation of deleterious changes resulting in overall decline in several vital functions, leading to the progressive deterioration in physiological condition of the organism and eventually causing disease and death. The immune system is the most important host-defense mechanism in humans and is also highly conserved in insects. Extensive research in vertebrates has concluded that aging of the immune function results in increased susceptibility to infectious disease and chronic inflammation. Over the years, interest has grown in studying the molecular interaction between aging and the immune response to pathogenic infections. The fruit fly Drosophila melanogaster is an excellent model system for dissecting the genetic and genomic basis of important biological processes, such as aging and the innate immune system, and deciphering parallel mechanisms in vertebrate animals. Here, we review the recent advances in the identification of key players modulating the relationship between molecular aging networks and immune signal transduction pathways in the fly. Understanding the details of the molecular events involved in aging and immune system regulation will potentially lead to the development of strategies for decreasing the impact of age-related diseases, thus improving human health and life span. PMID:22949833

Cancer risk elicitation and communication: lessons from the psychology of risk perception.

PubMed

Klein, William M P; Stefanek, Michael E

2007-01-01

Cancer risk perceptions are a key predictor of risk-reduction practices, health behaviors, and processing of cancer information. Nevertheless, patients and the general public (as well as health care providers) exhibit a number of errors and biases in the way they think about risk, such that their risk perceptions and decisions deviate greatly from those prescribed by normative decision models and by experts in risk assessment. For example, people are more likely to engage in screening behaviors such as mammography when faced with loss-based messages than gain-framed messages, and they often ignore the base rate of a given disease when assessing their own risk of obtaining this disease. In this article, we review many of the psychological processes that underlie risk perception and discuss how these processes lead to such deviations. Among these processes are difficulties with use of numerical information (innumeracy), cognitive processes (eg, use of time-saving heuristics), motivational factors (eg, loss and regret aversion), and emotion. We conclude with suggestions for future research in the area, as well as implications for improving the elicitation and communication of personal cancer risk.

Faster, Less Expensive Dies Using RSP Tooling

NASA Astrophysics Data System (ADS)

Knirsch, James R.

2007-08-01

RSP Tooling is an indirect spray form additive process that can produce production tooling for virtually any forming process and from virtually any metal. In the past 24 months a significant amount of research and development has been performed. This resulted in an increase in the basic metallurgical understanding of what transpires during the rapid solidification of the metal, significant improvements in the production machine up time, ceramic developments that have improved finish, process changes that have resulted in a shorter lead time for tool delivery, and the testing of many new alloys. RSP stands for Rapid Solidification Process and is the key to the superior metallurgical properties that result from the technology. Most metals that are sprayed in the process leave the machine with the same physical properties as the same metal normally achieves through heat treatment and in some cases the properties are superior. Many new applications are being pursued including INVAR tools for aerospace composite materials, and bimetallic tools made from tool steel and beryllium copper for die casting and plastic injection molding. Recent feasibility studies have been performed with tremendous success.

New hydrate formation methods in a liquid-gas medium

NASA Astrophysics Data System (ADS)

Chernov, A. A.; Pil'Nik, A. A.; Elistratov, D. S.; Mezentsev, I. V.; Meleshkin, A. V.; Bartashevich, M. V.; Vlasenko, M. G.

2017-01-01

Conceptually new methods of hydrate formation are proposed. The first one is based on the shock wave impact on a water-bubble medium. It is shown that the hydrate formation rate in this process is typically very high. A gas hydrate of carbon dioxide was produced. The process was experimentally studied using various initial conditions, as well as different external action magnitudes. The obtained experimental data are in good agreement with the proposed model. Other methods are based on the process of boiling liquefied gas in an enclosed volume of water (explosive boiling of a hydrating agent and the organization of cyclic boiling-condensation process). The key features of the methods are the high hydrate formation rate combined with a comparatively low power consumption leading to a great expected efficiency of the technologies based on them. The set of experiments was carried out. Gas hydrates of refrigerant R134a, carbon dioxide and propane were produced. The investigation of decomposition of a generated gas hydrate sample was made. The criteria of intensification of the hydrate formation process are formulated.

New hydrate formation methods in a liquid-gas medium.

PubMed

Chernov, A A; Pil'nik, A A; Elistratov, D S; Mezentsev, I V; Meleshkin, A V; Bartashevich, M V; Vlasenko, M G

2017-01-18

Conceptually new methods of hydrate formation are proposed. The first one is based on the shock wave impact on a water-bubble medium. It is shown that the hydrate formation rate in this process is typically very high. A gas hydrate of carbon dioxide was produced. The process was experimentally studied using various initial conditions, as well as different external action magnitudes. The obtained experimental data are in good agreement with the proposed model. Other methods are based on the process of boiling liquefied gas in an enclosed volume of water (explosive boiling of a hydrating agent and the organization of cyclic boiling-condensation process). The key features of the methods are the high hydrate formation rate combined with a comparatively low power consumption leading to a great expected efficiency of the technologies based on them. The set of experiments was carried out. Gas hydrates of refrigerant R134a, carbon dioxide and propane were produced. The investigation of decomposition of a generated gas hydrate sample was made. The criteria of intensification of the hydrate formation process are formulated.

New hydrate formation methods in a liquid-gas medium

PubMed Central

Chernov, A. A.; Pil’nik, A. A.; Elistratov, D. S.; Mezentsev, I. V.; Meleshkin, A. V.; Bartashevich, M. V.; Vlasenko, M. G.

2017-01-01

Conceptually new methods of hydrate formation are proposed. The first one is based on the shock wave impact on a water-bubble medium. It is shown that the hydrate formation rate in this process is typically very high. A gas hydrate of carbon dioxide was produced. The process was experimentally studied using various initial conditions, as well as different external action magnitudes. The obtained experimental data are in good agreement with the proposed model. Other methods are based on the process of boiling liquefied gas in an enclosed volume of water (explosive boiling of a hydrating agent and the organization of cyclic boiling-condensation process). The key features of the methods are the high hydrate formation rate combined with a comparatively low power consumption leading to a great expected efficiency of the technologies based on them. The set of experiments was carried out. Gas hydrates of refrigerant R134a, carbon dioxide and propane were produced. The investigation of decomposition of a generated gas hydrate sample was made. The criteria of intensification of the hydrate formation process are formulated. PMID:28098194

Securing non-volatile memory regions

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

Faraboschi, Paolo; Ranganathan, Parthasarathy; Muralimanohar, Naveen

Methods, apparatus and articles of manufacture to secure non-volatile memory regions are disclosed. An example method disclosed herein comprises associating a first key pair and a second key pair different than the first key pair with a process, using the first key pair to secure a first region of a non-volatile memory for the process, and using the second key pair to secure a second region of the non-volatile memory for the same process, the second region being different than the first region.

Data Streams: An Overview and Scientific Applications

NASA Astrophysics Data System (ADS)

Aggarwal, Charu C.

In recent years, advances in hardware technology have facilitated the ability to collect data continuously. Simple transactions of everyday life such as using a credit card, a phone, or browsing the web lead to automated data storage. Similarly, advances in information technology have lead to large flows of data across IP networks. In many cases, these large volumes of data can be mined for interesting and relevant information in a wide variety of applications. When the volume of the underlying data is very large, it leads to a number of computational and mining challenges: With increasing volume of the data, it is no longer possible to process the data efficiently by using multiple passes. Rather, one can process a data item at most once. This leads to constraints on the implementation of the underlying algorithms. Therefore, stream mining algorithms typically need to be designed so that the algorithms work with one pass of the data. In most cases, there is an inherent temporal component to the stream mining process. This is because the data may evolve over time. This behavior of data streams is referred to as temporal locality. Therefore, a straightforward adaptation of one-pass mining algorithms may not be an effective solution to the task. Stream mining algorithms need to be carefully designed with a clear focus on the evolution of the underlying data. Another important characteristic of data streams is that they are often mined in a distributed fashion. Furthermore, the individual processors may have limited processing and memory. Examples of such cases include sensor networks, in which it may be desirable to perform in-network processing of data stream with limited processing and memory [1, 2]. This chapter will provide an overview of the key challenges in stream mining algorithms which arise from the unique setup in which these problems are encountered. This chapter is organized as follows. In the next section, we will discuss the generic challenges that stream mining poses to a variety of data management and data mining problems. The next section also deals with several issues which arise in the context of data stream management. In Sect. 3, we discuss several mining algorithms on the data stream model. Section 4 discusses various scientific applications of data streams. Section 5 discusses the research directions and conclusions.

Minireview: roles of the forkhead transcription factor FOXL2 in granulosa cell biology and pathology.

PubMed

Pisarska, Margareta D; Barlow, Gillian; Kuo, Fang-Ting

2011-04-01

The forkhead transcription factor (FOXL2) is an essential transcription factor in the ovary. It is important in ovarian development and a key factor in female sex determination. In addition, FOXL2 plays a significant role in the postnatal ovary and follicle maintenance. The diverse transcriptional activities of FOXL2 are likely attributable to posttranslational modifications and binding to other key proteins involved in granulosa cell function. Mutations of FOXL2 lead to disorders of ovarian function ranging from premature follicle depletion and ovarian failure to unregulated granulosa cell proliferation leading to tumor formation. Thus, FOXL2 is a key regulator of granulosa cell function and a master transcription factor in these cells.

Minireview: Roles of the Forkhead Transcription Factor FOXL2 in Granulosa Cell Biology and Pathology

PubMed Central

Barlow, Gillian; Kuo, Fang-Ting

2011-01-01

The forkhead transcription factor (FOXL2) is an essential transcription factor in the ovary. It is important in ovarian development and a key factor in female sex determination. In addition, FOXL2 plays a significant role in the postnatal ovary and follicle maintenance. The diverse transcriptional activities of FOXL2 are likely attributable to posttranslational modifications and binding to other key proteins involved in granulosa cell function. Mutations of FOXL2 lead to disorders of ovarian function ranging from premature follicle depletion and ovarian failure to unregulated granulosa cell proliferation leading to tumor formation. Thus, FOXL2 is a key regulator of granulosa cell function and a master transcription factor in these cells. PMID:21248146

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

Thompson, B.G.J.; Grindrod, P.

Her Majesty`s Inspectorate of Polution (HMIP) of the United Kingdom has developed a procedure for the post closure assessment of the underground disposal of radioactive waste. In this paper the method of using theory and ideas from the mathematical sciences for assessment is described. The system simulation methodology seeks to discover key combinations of processes or effects which may yield behaviour of interest by sampling across functional and parametric uncertainties, and treating the systems within a probabilistic framework. This paper also discusses how HMIP assessment methodology has been presented, independent of any current application, for review by leading scientists whomore » are independent of the performance assessment field.« less

Medication adherence monitoring: implications for patients and providers.

PubMed

Gheorghiu, Bobby; Nayani, Seema

2018-05-01

Non-adherence to medication is a key worldwide issue and can lead to adverse patient outcomes and increased health system costs. Would a process facilitating notification of non-adherence infringe upon the autonomy of individuals or breach expectations of privacy? In contrast, patients who are not taking their medication could unknowingly be putting themselves at risk and all the while prescribers are unaware and without the opportunity to intervene. With the advent of electronic methods of medication adherence monitoring, this ethical dilemma now involves a new layer of complexity. We present two scenarios encountered in clinical practice that reflect issues occurring regularly in the Canadian healthcare system.

Chemical event chain model of coupled genetic oscillators.

PubMed

Jörg, David J; Morelli, Luis G; Jülicher, Frank

2018-03-01

We introduce a stochastic model of coupled genetic oscillators in which chains of chemical events involved in gene regulation and expression are represented as sequences of Poisson processes. We characterize steady states by their frequency, their quality factor, and their synchrony by the oscillator cross correlation. The steady state is determined by coupling and exhibits stochastic transitions between different modes. The interplay of stochasticity and nonlinearity leads to isolated regions in parameter space in which the coupled system works best as a biological pacemaker. Key features of the stochastic oscillations can be captured by an effective model for phase oscillators that are coupled by signals with distributed delays.

Bacterial copper storage proteins.

PubMed

Dennison, Christopher; David, Sholto; Lee, Jaeick

2018-03-30

Copper is essential for most organisms as a cofactor for key enzymes involved in fundamental processes such as respiration and photosynthesis. However, copper also has toxic effects in cells, which is why eukaryotes and prokaryotes have evolved mechanisms for safe copper handling. A new family of bacterial proteins uses a Cys-rich four-helix bundle to safely store large quantities of Cu(I). The work leading to the discovery of these proteins, their properties and physiological functions, and how their presence potentially impacts the current views of bacterial copper handling and use are discussed in this review. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Role of RANKL in bone diseases.

PubMed

Anandarajah, Allen P

2009-03-01

Bone remodeling is a tightly regulated process of osteoclast-mediated bone resorption, balanced by osteoblast-mediated bone formation. Disruption of this balance can lead to increased bone turnover, resulting in excessive bone loss or extra bone formation and consequent skeletal disease. The receptor activator of nuclear factor kappaB ligand (RANKL) (along with its receptor), the receptor activator of nuclear factor kappaB and its natural decoy receptor, osteoprotegerin, are the final effector proteins of osteoclastic bone resorption. Here, I provide an overview of recent studies that highlight the key role of RANKL in the pathophysiology of several bone diseases and discuss the novel therapeutic approaches afforded by the modulation of RANKL.

Chemical event chain model of coupled genetic oscillators

NASA Astrophysics Data System (ADS)

Jörg, David J.; Morelli, Luis G.; Jülicher, Frank

2018-03-01

We introduce a stochastic model of coupled genetic oscillators in which chains of chemical events involved in gene regulation and expression are represented as sequences of Poisson processes. We characterize steady states by their frequency, their quality factor, and their synchrony by the oscillator cross correlation. The steady state is determined by coupling and exhibits stochastic transitions between different modes. The interplay of stochasticity and nonlinearity leads to isolated regions in parameter space in which the coupled system works best as a biological pacemaker. Key features of the stochastic oscillations can be captured by an effective model for phase oscillators that are coupled by signals with distributed delays.

Objective comparison of particle tracking methods.

PubMed

Chenouard, Nicolas; Smal, Ihor; de Chaumont, Fabrice; Maška, Martin; Sbalzarini, Ivo F; Gong, Yuanhao; Cardinale, Janick; Carthel, Craig; Coraluppi, Stefano; Winter, Mark; Cohen, Andrew R; Godinez, William J; Rohr, Karl; Kalaidzidis, Yannis; Liang, Liang; Duncan, James; Shen, Hongying; Xu, Yingke; Magnusson, Klas E G; Jaldén, Joakim; Blau, Helen M; Paul-Gilloteaux, Perrine; Roudot, Philippe; Kervrann, Charles; Waharte, François; Tinevez, Jean-Yves; Shorte, Spencer L; Willemse, Joost; Celler, Katherine; van Wezel, Gilles P; Dan, Han-Wei; Tsai, Yuh-Show; Ortiz de Solórzano, Carlos; Olivo-Marin, Jean-Christophe; Meijering, Erik

2014-03-01

Particle tracking is of key importance for quantitative analysis of intracellular dynamic processes from time-lapse microscopy image data. Because manually detecting and following large numbers of individual particles is not feasible, automated computational methods have been developed for these tasks by many groups. Aiming to perform an objective comparison of methods, we gathered the community and organized an open competition in which participating teams applied their own methods independently to a commonly defined data set including diverse scenarios. Performance was assessed using commonly defined measures. Although no single method performed best across all scenarios, the results revealed clear differences between the various approaches, leading to notable practical conclusions for users and developers.

The Sherlock Holmes method in clinical practice.

PubMed

Sopeña, B

2014-04-01

This article lists the integral elements of the Sherlock Holmes method, which is based on the intelligent collection of information through detailed observation, careful listening and thorough examination. The information thus obtained is analyzed to develop the main and alternative hypotheses, which are shaped during the deductive process until the key leading to the solution is revealed. The Holmes investigative method applied to clinical practice highlights the advisability of having physicians reason through and seek out the causes of the disease with the data obtained from acute observation, a detailed review of the medical history and careful physical examination. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Spatiotemporal Regulation of the Anaphase-Promoting Complex in Mitosis

PubMed Central

Sivakumar, Sushama; Gorbsky, Gary J

2015-01-01

The appropriate timing of events that lead to chromosome segregation during mitosis and cytokinesis is essential to prevent aneuploidy, and defects in these processes can contribute to tumorigenesis. Key mitotic regulators are controlled through ubiquitylation and proteasome-mediated degradation. The Anaphase-Promoting Complex or Cyclosome (APC/C) is an E3 ubiquitin ligase that has a crucial function in the regulation of the mitotic cell cycle, particularly at the onset of anaphase and during mitotic exit. Co-activator proteins, inhibitor proteins, protein kinases and phosphatases interact with the APC/C to temporally and spatially control its activity and thus ensure accurate timing of mitotic events. PMID:25604195

Washington State reorganization: more of the story.

PubMed

Gebbie, K M

1997-01-01

The creation of a new Department of Health in Washington State in 1989 provided an opportunity for analysis of the many forces beyond the pressure of interest groups leading to such a change. Interviews with key actors from executive and legislative branches of state government, local government, and interested health organizations were conducted to uncover the full scope considered for the new department, and the interactions that led to the final, narrower entity. A process model based on these findings is presented as a useful tool for those seeking to improve public health at the state level through changes in the organizational units responsible for health activities.

[Technological process of cell disruption for extracting astaxanthin from Phaffia rhodozyma by acid method under autoclave conditions].

PubMed

Lu, Baoju; Xiao, Anfeng; Lil, Lijun; Ni, Hui; Cai, Huinong; Su, Wenjin

2008-07-01

Phaffia rhodozyma is one of the organisms for production of astaxanthin, and the key process for extracting intracellular astaxanthin is cell disruption. In this work, cell disruption for extracting astaxanthin from Phaffia rhodozyma was studied with autoclave method at low acid concentration. The optimum disrupting conditions were: autoclave pressure 0.1 MPa, 121 degrees C; hydrochloric acid concentration 0.5 mol/L; liquid to material ratio (V/W) 30 mL/g dry cell weight and disruption time 2 min. Under the optimum conditions, medium scale experiment showed that astaxanthin and total carotenoids recovery from Phaffia rhodozyma were (84.8 +/- 3.2)% and (93.3 +/- 2)%, respectively. This new method can lead to no poisonous residues and get high extraction yield, which have good prospects to be put into industrial production.

Sociopathic behavior and dementia.

PubMed

Cipriani, Gabriele; Borin, Gemma; Vedovello, Marcella; Di Fiorino, Andrea; Nuti, Angelo

2013-06-01

The maintenance of appropriate social behavior is a very complex process with many contributing factors. Social and moral judgments rely on the proper functioning of neural circuits concerned with complex cognitive and emotional processes. Damage to these systems may lead to distinct social behavior abnormalities. When patients present with dysmoral behavior for the first time, as a change from a prior pervasive pattern of behavior, clinicians need to consider a possible, causative brain disorder. The aim is to explore sociopathy as a manifestation of dementia. We searched electronic databases and key journals for original research and review articles on sociopathy in demented patients using the search terms "sociopathy, acquired sociopathy, sociopathic behavior, dementia, and personality". In conclusion, dementia onset may be heralded by changes in personality including alteration in social interpersonal behavior, personal regulation, and empathy. The sociopathy of dementia differs from antisocial/psychopathic personality disorders.

Analysis of DNA interactions using single-molecule force spectroscopy.

PubMed

Ritzefeld, Markus; Walhorn, Volker; Anselmetti, Dario; Sewald, Norbert

2013-06-01

Protein-DNA interactions are involved in many biochemical pathways and determine the fate of the corresponding cell. Qualitative and quantitative investigations on these recognition and binding processes are of key importance for an improved understanding of biochemical processes and also for systems biology. This review article focusses on atomic force microscopy (AFM)-based single-molecule force spectroscopy and its application to the quantification of forces and binding mechanisms that lead to the formation of protein-DNA complexes. AFM and dynamic force spectroscopy are exciting tools that allow for quantitative analysis of biomolecular interactions. Besides an overview on the method and the most important immobilization approaches, the physical basics of the data evaluation is described. Recent applications of AFM-based force spectroscopy to investigate DNA intercalation, complexes involving DNA aptamers and peptide- and protein-DNA interactions are given.

Born to run: creating the muscle fiber.

PubMed

Schejter, Eyal D; Baylies, Mary K

2010-10-01

From the muscles that control the blink of your eye to those that allow you to walk, the basic architecture of muscle is the same: muscles consist of bundles of the unit muscle cell, the muscle fiber. The unique morphology of the individual muscle fiber is dictated by the functional demands necessary to generate and withstand the forces of contraction, which in turn leads to movement. Contractile muscle fibers are elongated, syncytial cells, which interact with both the nervous and skeletal systems to govern body motion. In this review, we focus on three key cell-cell and cell-matrix contact processes, that are necessary to create this exquisitely specialized cell: cell fusion, cell elongation, and establishment of a myotendinous junction. We address these processes by highlighting recent findings from the Drosophila model system. Copyright © 2010 Elsevier Ltd. All rights reserved.

Development of an ultrasonic weld inspection system based on image processing and neural networks

NASA Astrophysics Data System (ADS)

Roca Barceló, Fernando; Jaén del Hierro, Pedro; Ribes Llario, Fran; Real Herráiz, Julia

2018-04-01

Several types of discontinuities and defects may be present on a weld, thus leading to a considerable reduction of its resistance. Therefore, ensuring a high welding quality and reliability has become a matter of key importance for many construction and industrial activities. Among the non-destructive weld testing and inspection techniques, the time-of-flight diffraction (TOFD) arises as a very safe (no ionising radiation), precise, reliable and versatile practice. However, this technique presents a relevant drawback, associated to the appearance of speckle noise that should be addressed. In this regard, this paper presents a new, intelligent and automatic method for weld inspection and analysis, based on TOFD, image processing and neural networks. The developed system is capable of detecting weld defects and imperfections with accuracy, and classify them into different categories.

Health policy in a new key: setting democratic priorities.

PubMed

Jennings, B

1993-01-01

Health policy in the United States is entering an era in which explicitly value-based allocation decisions require direct attention. Policies concerning access to care, financing, and utilization management will necessarily have redistributive effects. For these policies to command social legitimacy and political support, some consensus will have to emerge around the values and ideals justifying these policies. This article addresses the problems of conceptual clarification and democratic process raised by the prospect of an explicitly value-based allocation policy. It offers a conceptual matrix distinguishing the scope of the issue of allocation in health care. Drawing on the activities of community health decisions projects in several states, it also offers suggestions about building a participatory and educational process at the grassroots level that might lead to a democratic consensus suitable for guiding policy choice.

Information spread of emergency events: path searching on social networks.

PubMed

Dai, Weihui; Hu, Hongzhi; Wu, Tunan; Dai, Yonghui

2014-01-01

Emergency has attracted global attentions of government and the public, and it will easily trigger a series of serious social problems if it is not supervised effectively in the dissemination process. In the Internet world, people communicate with each other and form various virtual communities based on social networks, which lead to a complex and fast information spread pattern of emergency events. This paper collects Internet data based on data acquisition and topic detection technology, analyzes the process of information spread on social networks, describes the diffusions and impacts of that information from the perspective of random graph, and finally seeks the key paths through an improved IBF algorithm. Application cases have shown that this algorithm can search the shortest spread paths efficiently, which may help us to guide and control the information dissemination of emergency events on early warning.

Off-shell production of top-antitop pairs in the lepton+jets channel at NLO QCD

NASA Astrophysics Data System (ADS)

Denner, Ansgar; Pellen, Mathieu

2018-02-01

The production of top-quark pairs that subsequently decay hadronically and leptonically (lepton+jets channel) is one of the key processes for the study of top-quark properties at the LHC. In this article, NLO QCD corrections of order O({α}s^3{α}^4) to the hadronic process pp\\to {μ}-{\\overline{ν}}_{μ}b\\overline{b}jj are presented. The computation includes off-shell as well as non-resonant contributions, and experimental event selections are used in order to provide realistic predictions. The results are provided in the form of cross sections and differential distributions. The QCD corrections are sizeable and different from the ones of the fully leptonic channel. This is due to the different final state where here four jets are present at leading order.

Dilemmas and challenges for the shelter sector: lessons learned from the Sphere revision process.

PubMed

Saunders, Graham

2004-06-01

Key dilemmas and challenges for those involved in the shelter sector are described, based on issues that emerged from the extensive global consultative process undertaken to inform the revision of the Sphere handbook. The range of perspectives on the major themes is presented, with suggestions as to how these issues could be progressed. Themes include the poor definition of the sector and the lack of a consistent approach among the leading shelter actors; the absence of a common terminology; the conflict between "temporary" versus "durable" solutions; the disconnect between technical advisers and the field; the need for greater recognition of local coping strategies and the local context; the involvement of recipients and host governments in policy development; the need for better "how-to" guidance; and the limited incorporation of the emerging themes of livelihoods etc. to date.

The Evaluation Method of the Lightning Strike on Transmission Lines Aiming at Power Grid Reliability

NASA Astrophysics Data System (ADS)

Wen, Jianfeng; Wu, Jianwei; Huang, Liandong; Geng, Yinan; Yu, zhanqing

2018-01-01

Lightning protection of power system focuses on reducing the flashover rate, only distinguishing by the voltage level, without considering the functional differences between the transmission lines, and being lack of analysis the effect on the reliability of power grid. This will lead lightning protection design of general transmission lines is surplus but insufficient for key lines. In order to solve this problem, the analysis method of lightning striking on transmission lines for power grid reliability is given. Full wave process theory is used to analyze the lightning back striking; the leader propagation model is used to describe the process of shielding failure of transmission lines. The index of power grid reliability is introduced and the effect of transmission line fault on the reliability of power system is discussed in detail.

The development of daily monitoring tool in a service part manufacturing company

NASA Astrophysics Data System (ADS)

Marpaung, Seamus Tadeo; Rosyidi, Cucuk Nur

2018-02-01

Production lead time is one of the key measures to assess whether a production system is running well or not. A short lead time will lead to higher customer satisfaction and will be a solid proof that a system is well-organized. To shorten the production lead time, a good production planning and control are required. There are many obstacles which can occur at any time, for instance shortage of material and worker, or poor production scheduling. Service Parts Planning Department works with many parties from the beginning of service parts production until it is delivered to the customer. This research was conducted to find an appropriate production monitoring tool for Service Parts Planning Department, which is a control method that make problems appears to the surface and can be overcome quickly so that the production process can run normally. The tool development started with a field study to find out the production flow from start to finish, a literature review and a interview with some employees who will later use the production control tool, and the creation of a daily control that went through several modifications until finally meet the needs of the department. In this research, a production monitoring tool which is developed can be used to monitor the entire order status, the production lead time, and also serves as the records and reports for presentation.

Getting Inside the Expert's Head: An Analysis of Physician Cognitive Processes During Trauma Resuscitations.

PubMed

White, Matthew R; Braund, Heather; Howes, Daniel; Egan, Rylan; Gegenfurtner, Andreas; van Merrienboer, Jeroen J G; Szulewski, Adam

2018-04-23

Crisis resource management skills are integral to leading the resuscitation of a critically ill patient. Despite their importance, crisis resource management skills (and their associated cognitive processes) have traditionally been difficult to study in the real world. The objective of this study was to derive key cognitive processes underpinning expert performance in resuscitation medicine, using a new eye-tracking-based video capture method during clinical cases. During an 18-month period, a sample of 10 trauma resuscitations led by 4 expert trauma team leaders was analyzed. The physician team leaders were outfitted with mobile eye-tracking glasses for each case. After each resuscitation, participants were debriefed with a modified cognitive task analysis, based on a cued-recall protocol, augmented by viewing their own first-person perspective eye-tracking video from the clinical encounter. Eye-tracking technology was successfully applied as a tool to aid in the qualitative analysis of expert performance in a clinical setting. All participants stated that using these methods helped uncover previously unconscious aspects of their cognition. Overall, 5 major themes were derived from the interviews: logistic awareness, managing uncertainty, visual fixation behaviors, selective attendance to information, and anticipatory behaviors. The novel approach of cognitive task analysis augmented by eye tracking allowed the derivation of 5 unique cognitive processes underpinning expert performance in leading a resuscitation. An understanding of these cognitive processes has the potential to enhance educational methods and to create new assessment modalities of these previously tacit aspects of expertise in this field. Copyright © 2018 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

A vascular biology network model focused on inflammatory processes to investigate atherogenesis and plaque instability

PubMed Central

2014-01-01

Background Numerous inflammation-related pathways have been shown to play important roles in atherogenesis. Rapid and efficient assessment of the relative influence of each of those pathways is a challenge in the era of “omics” data generation. The aim of the present work was to develop a network model of inflammation-related molecular pathways underlying vascular disease to assess the degree of translatability of preclinical molecular data to the human clinical setting. Methods We constructed and evaluated the Vascular Inflammatory Processes Network (V-IPN), a model representing a collection of vascular processes modulated by inflammatory stimuli that lead to the development of atherosclerosis. Results Utilizing the V-IPN as a platform for biological discovery, we have identified key vascular processes and mechanisms captured by gene expression profiling data from four independent datasets from human endothelial cells (ECs) and human and murine intact vessels. Primary ECs in culture from multiple donors revealed a richer mapping of mechanisms identified by the V-IPN compared to an immortalized EC line. Furthermore, an evaluation of gene expression datasets from aortas of old ApoE-/- mice (78 weeks) and human coronary arteries with advanced atherosclerotic lesions identified significant commonalities in the two species, as well as several mechanisms specific to human arteries that are consistent with the development of unstable atherosclerotic plaques. Conclusions We have generated a new biological network model of atherogenic processes that demonstrates the power of network analysis to advance integrative, systems biology-based knowledge of cross-species translatability, plaque development and potential mechanisms leading to plaque instability. PMID:24965703

An Overexpressed Q Allele Leads to Increased Spike Density and Improved Processing Quality in Common Wheat (Triticum aestivum).

PubMed

Xu, Bin-Jie; Chen, Qing; Zheng, Ting; Jiang, Yun-Feng; Qiao, Yuan-Yuan; Guo, Zhen-Ru; Cao, Yong-Li; Wang, Yan; Zhang, Ya-Zhou; Zong, Lu-Juan; Zhu, Jing; Liu, Cai-Hong; Jiang, Qian-Tao; Lan, Xiu-Jin; Ma, Jian; Wang, Ji-Rui; Zheng, You-Liang; Wei, Yu-Ming; Qi, Peng-Fei

2018-03-02

Spike density and processing quality are important traits in modern wheat production and are controlled by multiple gene loci. The associated genes have been intensively studied and new discoveries have been constantly reported during the past few decades. However, no gene playing a significant role in the development of these two traits has been identified. In the current study, a common wheat mutant with extremely compact spikes and good processing quality was isolated and characterized. A new allele ( Q c1 ) of the Q gene (an important domestication gene) responsible for the mutant phenotype was cloned, and the molecular mechanism for the mutant phenotype was studied. Results revealed that Q c1 originated from a point mutation that interferes with the miRNA172-directed cleavage of Q transcripts, leading to its overexpression. It also reduces the longitudinal cell size of rachises, resulting in an increased spike density. Furthermore, Q c1 increases the number of vascular bundles, which suggests a higher efficiency in the transportation of assimilates in the spikes of the mutant than that of wild type. This accounts for the improved processing quality. The effects of Q c1 on spike density and wheat processing quality were confirmed by analyzing nine common wheat mutants possessing four different Q c alleles. These results deepen our understanding of the key roles of Q gene, and provide new insights for the potential application of Q c alleles in wheat quality breeding. Copyright © 2018 Xu et al.

Etiopathology of chronic tubular, glomerular and renovascular nephropathies: Clinical implications

PubMed Central

2011-01-01

Chronic kidney disease (CKD) comprises a group of pathologies in which the renal excretory function is chronically compromised. Most, but not all, forms of CKD are progressive and irreversible, pathological syndromes that start silently (i.e. no functional alterations are evident), continue through renal dysfunction and ends up in renal failure. At this point, kidney transplant or dialysis (renal replacement therapy, RRT) becomes necessary to prevent death derived from the inability of the kidneys to cleanse the blood and achieve hydroelectrolytic balance. Worldwide, nearly 1.5 million people need RRT, and the incidence of CKD has increased significantly over the last decades. Diabetes and hypertension are among the leading causes of end stage renal disease, although autoimmunity, renal atherosclerosis, certain infections, drugs and toxins, obstruction of the urinary tract, genetic alterations, and other insults may initiate the disease by damaging the glomerular, tubular, vascular or interstitial compartments of the kidneys. In all cases, CKD eventually compromises all these structures and gives rise to a similar phenotype regardless of etiology. This review describes with an integrative approach the pathophysiological process of tubulointerstitial, glomerular and renovascular diseases, and makes emphasis on the key cellular and molecular events involved. It further analyses the key mechanisms leading to a merging phenotype and pathophysiological scenario as etiologically distinct diseases progress. Finally clinical implications and future experimental and therapeutic perspectives are discussed. PMID:21251296

Addressing metacognitive capacity for self reflection in the psychotherapy for schizophrenia: a conceptual model of the key tasks and processes.

PubMed

Lysaker, Paul H; Buck, Kelly D; Carcione, Antonino; Procacci, Michelle; Salvatore, Giampaolo; Nicolò, Guiseppe; Dimaggio, Giancarlo

2011-03-01

Recognition that recovery from schizophrenia may involve a deepening of the experience of being in the world has led to the possibility that psychotherapy may play a key role in treatment by enhancing metacognition, or the capacity to think about thinking. While the potential of psychotherapy to enhance metacognition in non-psychotic disorders has been discussed in depth, little has been written about how psychotherapy may systematically address metacognition in schizophrenia. Accordingly, the current paper formulates a model of how psychotherapy might address one specific element of metacognition, namely self-reflectivity. Procedures are outlined for assessing clients' capacity for self-reflectivity within narrative contexts during psychotherapy. Targeted interventions are identified which are tailored to clients' capacities in the moment and which assist clients to think about their own thinking at the level of which they are capable. This may lead clients over time to develop a greater ability to engage in acts of increasingly complex self-reflectivity. Individual psychotherapy can be modified and utilized to assist persons with schizophrenia to move towards recovery by assisting them to develop the capacity for self-reflectivity. This may lead to clients having a fuller experience of themselves as a being in the world with a richer and more coherent personal narrative. © 2010 The British Psychological Society.

Rational approach to identify newer caspase-1 inhibitors using pharmacophore based virtual screening, docking and molecular dynamic simulation studies.

PubMed

Patel, Shivani; Modi, Palmi; Chhabria, Mahesh

2018-05-01

Caspase-1 is a key endoprotease responsible for the post-translational processing of pro-inflammatory cytokines IL-1β, 18 & 33. Excessive secretion of IL-1β leads to numerous inflammatory and autoimmune diseases. Thus caspase-1 inhibition would be considered as an important therapeutic strategy for development of newer anti-inflammatory agents. Here we have employed an integrated virtual screening by combining pharmacophore mapping and docking to identify small molecules as caspase-1 inhibitors. The ligand based 3D pharmacophore model was generated having the essential structural features of (HBA, HY & RA) using a data set of 27 compounds. A validated pharmacophore hypothesis (Hypo 1) was used to screen ZINC and Minimaybridge chemical databases. The retrieved virtual hits were filtered by ADMET properties and molecular docking analysis. Subsequently, the cross-docking study was also carried out using crystal structure of caspase-1, 3, 7 and 8 to identify the key residual interaction for specific caspase-1 inhibition. Finally, the best mapped and top scored (ZINC00885612, ZINC72003647, BTB04175 and BTB04410) molecules were subjected to molecular dynamics simulation for accessing the dynamic structure of protein after ligand binding. This study identifies the most promising hits, which can be leads for the development of novel caspase-1 inhibitors as anti-inflammatory agents. Copyright © 2018 Elsevier Inc. All rights reserved.

Lead with Passion: Effective Leadership Characteristics as Perceived by School Administrators and Teachers

ERIC Educational Resources Information Center

Manuel, La Tanya Antoinette

2017-01-01

The purpose of this mixed methods research study was to examine how educators lead with passion. The study identified key characteristics in school administrators and teachers who lead effective schools. This research study analyzed whether there were any significant differences in the leadership styles of administrators and teachers. Five…

Leading Work with Young People

ERIC Educational Resources Information Center

Harrison, Roger, Ed.; Benjamin, Cathy, Ed.; Curran, Sheila, Ed.; Hunter, Rob, Ed.

2007-01-01

"Leading Work with Young People" provides a selection of writing from a complex and dynamic field of work. The editors bring together key readings and newly commissioned material to present a variety of theoretical and practical perspectives on leading and managing work with young people. The book will equip students with the knowledge, skills,…

The APETALA-2-like transcription factor OsAP2-39 controls key interactions between abscisic acid and gibberellin in rice.

PubMed

Yaish, Mahmoud W; El-Kereamy, Ashraf; Zhu, Tong; Beatty, Perrin H; Good, Allen G; Bi, Yong-Mei; Rothstein, Steven J

2010-09-09

The interaction between phytohormones is an important mechanism which controls growth and developmental processes in plants. Deciphering these interactions is a crucial step in helping to develop crops with enhanced yield and resistance to environmental stresses. Controlling the expression level of OsAP2-39 which includes an APETALA 2 (AP2) domain leads to phenotypic changes in rice. Overexpression of OsAP2-39 leads to a reduction in yield by decreasing the biomass and the number of seeds in the transgenic rice lines. Global transcriptome analysis of the OsAP2-39 overexpression transgenic rice revealed the upregulation of a key abscisic acid (ABA) biosynthetic gene OsNCED-I which codes for 9-cis-epoxycarotenoid dioxygenase and leads to an increase in the endogenous ABA level. In addition to OsNCED-1, the gene expression analysis revealed the upregulation of a gene that codes for the Elongation of Upper most Internode (EUI) protein, an enzyme that catalyzes 16α, 17-epoxidation of non-13-hydroxylated GAs, which has been shown to deactivate gibberellins (GAs) in rice. The exogenous application of GA restores the wild-type phenotype in the transgenic line and ABA application induces the expression of EUI and suppresses the expression of OsAP2-39 in the wild-type line. These observations clarify the antagonistic relationship between ABA and GA and illustrate a mechanism that leads to homeostasis of these hormones. In vivo and in vitro analysis showed that the expression of both OsNCED-1 and EUI are directly controlled by OsAP2-39. Together, these results reveal a novel mechanism for the control of the ABA/GA balance in rice which is regulated by OsAP2-39 that in turn regulates plant growth and seed production.

The APETALA-2-Like Transcription Factor OsAP2-39 Controls Key Interactions between Abscisic Acid and Gibberellin in Rice

PubMed Central

Yaish, Mahmoud W.; El-kereamy, Ashraf; Zhu, Tong; Beatty, Perrin H.; Good, Allen G.; Bi, Yong-Mei; Rothstein, Steven J.

2010-01-01

The interaction between phytohormones is an important mechanism which controls growth and developmental processes in plants. Deciphering these interactions is a crucial step in helping to develop crops with enhanced yield and resistance to environmental stresses. Controlling the expression level of OsAP2-39 which includes an APETALA 2 (AP2) domain leads to phenotypic changes in rice. Overexpression of OsAP2-39 leads to a reduction in yield by decreasing the biomass and the number of seeds in the transgenic rice lines. Global transcriptome analysis of the OsAP2-39 overexpression transgenic rice revealed the upregulation of a key Abscisic Acid (ABA) biosynthetic gene OsNCED-I which codes for 9-cis-epoxycarotenoid dioxygenase and leads to an increase in the endogenous ABA level. In addition to OsNCED-1, the gene expression analysis revealed the upregulation of a gene that codes for the Elongation of Upper most Internode (EUI) protein, an enzyme that catalyzes 16α, 17-epoxidation of non-13-hydroxylated GAs, which has been shown to deactivate gibberellins (GAs) in rice. The exogenous application of GA restores the wild-type phenotype in the transgenic line and ABA application induces the expression of EUI and suppresses the expression of OsAP2-39 in the wild-type line. These observations clarify the antagonistic relationship between ABA and GA and illustrate a mechanism that leads to homeostasis of these hormones. In vivo and in vitro analysis showed that the expression of both OsNCED-1 and EUI are directly controlled by OsAP2-39. Together, these results reveal a novel mechanism for the control of the ABA/GA balance in rice which is regulated by OsAP2-39 that in turn regulates plant growth and seed production. PMID:20838584

Critical transport issues for improving the performance of aqueous redox flow batteries

NASA Astrophysics Data System (ADS)

Zhou, X. L.; Zhao, T. S.; An, L.; Zeng, Y. K.; Wei, L.

2017-01-01

As the fraction of electricity generated from intermittent renewable sources (such as solar and wind) grows, developing reliable energy storage technologies to store electrical energy in large scale is of increasing importance. Redox flow batteries are now enjoying a renaissance and regarded as a leading technology in providing a well-balanced solution for current daunting challenges. In this article, state-of-the-art studies of the complex multicomponent transport phenomena in aqueous redox flow batteries, with a special emphasis on all-vanadium redox flow batteries, are reviewed and summarized. Rather than elaborating on the details of previous experimental and numerical investigations, this article highlights: i) the key transport issues in each battery's component that need to be tackled so that the rate capability and cycling stability of flow batteries can be significantly improved, ii) the basic mechanisms that control the active species/ion/electron transport behaviors in each battery's component, and iii) the key experimental and numerical findings regarding the correlations between the multicomponent transport processes and battery performance.

Overcoming substrate limitations for improved production of ethylene in E. coli

DOE PAGES

Lynch, Sean; Eckert, Carrie; Yu, Jianping; ...

2016-01-04

Ethylene is an important industrial compound for the production of a wide variety of plastics and chemicals. At present, ethylene production involves steam cracking of a fossil-based feedstock, representing the highest CO 2-emitting process in the chemical industry. Biological ethylene production can be achieved via expression of a single protein, the ethylene-forming enzyme (EFE), found in some bacteria and fungi; it has the potential to provide a sustainable alternative to steam cracking, provided that significant increases in productivity can be achieved. A key barrier is determining factors that influence the availability of substrates for the EFE reaction in potential microbialmore » hosts. In the presence of O 2, EFE catalyzes ethylene formation from the substrates α-ketoglutarate (AKG) and arginine. The concentrations of AKG, a key TCA cycle intermediate, and arginine are tightly controlled by an intricate regulatory system that coordinates carbon and nitrogen metabolism. Thus, reliably predicting which genetic changes will ultimately lead to increased AKG and arginine availability is challenging.« less

[Formulation of technical specification for national survey of Chinese materia medica resources].

PubMed

Guo, Lan-Ping; Lu, Jian-Wei; Zhang, Xiao-Bo; Zhao, Run-Huai; Zhang, Ben-Gang; Sun, Li-Ying; Huang, Lu-Qi

2013-04-01

According to the process of the technical specification (TS) design for the fourth national survey of the Chinese materia medica resources (CMMR), we analyzed the assignment and objectives of the national survey and pointed out that the differences about CMMR management around China, the distribution of CMMR and their habitat, the economic and technological level, and even enthusiasm and initiative of the staff, etc. are the most difficult points for TS design. And we adopt the principle of combination of the mandatory and flexibility in TS design. We fixed the key points which would affect the quality of national survey first, then proposed the framework of TS which including 3 parts of organization and 11 parts of technique itself. The framework will serve and lead the TS preparation, which will not only provide an action standard to the national survey but will also have a profound influence to the popularization and application of the survey technology of CMMR. [Key words

Embryonic Cerebrospinal Fluid Increases Neurogenic Activity in the Brain Ventricular-Subventricular Zone of Adult Mice.

PubMed

Alonso, Maria I; Lamus, Francisco; Carnicero, Estela; Moro, Jose A; de la Mano, Anibal; Fernández, Jose M F; Desmond, Mary E; Gato, Angel

2017-01-01

Neurogenesis is a very intensive process during early embryonic brain development, becoming dramatically restricted in the adult brain in terms of extension and intensity. We have previously demonstrated the key role of embryonic cerebrospinal fluid (CSF) in developing brain neurogenic activity. We also showed that cultured adult brain neural stem cells (NSCs) remain competent when responding to the neurogenic influence of embryonic CSF. However, adult CSF loses its neurogenic inductive properties. Here, by means of an organotypic culture of adult mouse brain sections, we show that local administration of embryonic CSF in the subventricular zone (SVZ) niche is able to trigger a neurogenic program in NSCs. This leads to a significant increase in the number of non-differentiated NSCs, and also in the number of new neurons which show normal migration, differentiation and maturation. These new data reveal that embryonic CSF activates adult brain NSCs, supporting the previous idea that it contains key instructive components which could be useful in adult brain neuroregenerative strategies.

Elucidating the Pathogenesis of Pre-eclampsia Using In Vitro Models of Spiral Uterine Artery Remodelling.

PubMed

McNally, Ross; Alqudah, Abdelrahim; Obradovic, Danilo; McClements, Lana

2017-10-23

The aim of the study is to perform a critical assessment of in vitro models of pre-eclampsia using complementary human and cell line-based studies. Molecular mechanisms involved in spiral uterine artery (SUA) remodelling and trophoblast functionality will also be discussed. A number of proteins and microRNAs have been implicated as key in SUA remodelling, which could be explored as early biomarkers or therapeutic targets for prevention of pre-eclampsia. Various 2D and 3D in vitro models involving trophoblast cells, endothelial cells, immune cells and placental tissue were discussed to elucidate the pathogenesis of pre-eclampsia. Nevertheless, pre-eclampsia is a multifactorial disease, and the mechanisms involved in its pathogenesis are complex and still largely unknown. Further studies are required to provide better understanding of the key processes leading to inappropriate placental development which is the root cause of pre-eclampsia. This new knowledge could identify novel biomarkers and treatment strategies.

Key issues in life cycle assessment of ethanol production from lignocellulosic biomass: Challenges and perspectives.

PubMed

Singh, Anoop; Pant, Deepak; Korres, Nicholas E; Nizami, Abdul-Sattar; Prasad, Shiv; Murphy, Jerry D

2010-07-01

Progressive depletion of conventional fossil fuels with increasing energy consumption and greenhouse gas (GHG) emissions have led to a move towards renewable and sustainable energy sources. Lignocellulosic biomass is available in massive quantities and provides enormous potential for bioethanol production. However, to ascertain optimal biofuel strategies, it is necessary to take into account environmental impacts from cradle to grave. Life cycle assessment (LCA) techniques allow detailed analysis of material and energy fluxes on regional and global scales. This includes indirect inputs to the production process and associated wastes and emissions, and the downstream fate of products in the future. At the same time if not used properly, LCA can lead to incorrect and inappropriate actions on the part of industry and/or policy makers. This paper aims to list key issues for quantifying the use of resources and releases to the environment associated with the entire life cycle of lignocellulosic bioethanol production. Copyright 2009 Elsevier Ltd. All rights reserved.

Embryonic Cerebrospinal Fluid Increases Neurogenic Activity in the Brain Ventricular-Subventricular Zone of Adult Mice

PubMed Central

Alonso, Maria I.; Lamus, Francisco; Carnicero, Estela; Moro, Jose A.; de la Mano, Anibal; Fernández, Jose M. F.; Desmond, Mary E.; Gato, Angel

2017-01-01

Neurogenesis is a very intensive process during early embryonic brain development, becoming dramatically restricted in the adult brain in terms of extension and intensity. We have previously demonstrated the key role of embryonic cerebrospinal fluid (CSF) in developing brain neurogenic activity. We also showed that cultured adult brain neural stem cells (NSCs) remain competent when responding to the neurogenic influence of embryonic CSF. However, adult CSF loses its neurogenic inductive properties. Here, by means of an organotypic culture of adult mouse brain sections, we show that local administration of embryonic CSF in the subventricular zone (SVZ) niche is able to trigger a neurogenic program in NSCs. This leads to a significant increase in the number of non-differentiated NSCs, and also in the number of new neurons which show normal migration, differentiation and maturation. These new data reveal that embryonic CSF activates adult brain NSCs, supporting the previous idea that it contains key instructive components which could be useful in adult brain neuroregenerative strategies. PMID:29311854

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.

Analyzing the generality of conflict adaptation effects.

PubMed

Funes, Maria Jesús; Lupiáñez, Juan; Humphreys, Glyn

2010-02-01

Conflict adaptation effects refer to the reduction of interference when the incongruent stimulus occurs immediately after an incongruent trial, compared with when it occurs after a congruent trial. The present study analyzes the key conditions that lead to adaptation effects that are specific to the type of conflict involved versus those that are conflict general. In the first 2 experiments, we combined 2 types of conflict for which compatibility arises from clearly different sources in terms of dimensional overlap while keeping the task context constant across conflict types. We found a clear pattern of specificity on conflict adaptation across conflict types. In subsequent experiments, we tested whether this pattern could be accounted in terms of feature integration processes contributing differently to repetition versus alternation of conflict types. The results clearly indicated that feature integration was not key to generating conflict type specificity on conflict adaptation. The data are consistent with there being separate modes of control for different types of cognitive conflict.

Moving towards Universal Health Coverage through the Development of Integrated Service Delivery Packages for Primary Health Care in the Solomon Islands

PubMed Central

Whiting, Stephen; Postma, Sjoerd; Jamshaid de Lorenzo, Ayesha; Aumua, Audrey

2016-01-01

The Solomon Islands Government is pursuing integrated care with the goal of improving the quality of health service delivery to rural populations. Under the auspices of Universal Health Coverage, integrated service delivery packages were developed which defined the clinical and public health services that should be provided at different levels of the health system. The process of developing integrated service delivery packages helped to identify key policy decisions the government needed to make in order to improve service quality and efficiency. The integrated service delivery packages have instigated the revision of job descriptions and are feeding into the development of a human resource plan for health. They are also being used to guide infrastructure development and health system planning and should lead to better management of resources. The integrated service delivery packages have become a key tool to operationalise the government’s policy to move towards a more efficient, equitable, quality and sustainable health system. PMID:28321177

Spinal cord regeneration: lessons for mammals from non-mammalian vertebrates.

PubMed

Lee-Liu, Dasfne; Edwards-Faret, Gabriela; Tapia, Víctor S; Larraín, Juan

2013-08-01

Unlike mammals, regenerative model organisms such as amphibians and fish are capable of spinal cord regeneration after injury. Certain key differences between regenerative and nonregenerative organisms have been suggested as involved in promoting this process, such as the capacity for neurogenesis and axonal regeneration, which appear to be facilitated by favorable astroglial, inflammatory and immune responses. These traits provide a regenerative-permissive environment that the mammalian spinal cord appears to be lacking. Evidence for the regenerative nonpermissive environment in mammals is given by the fact that they possess neural stem/progenitor cells, which transplanted into permissive environments are able to give rise to new neurons, whereas in the nonpermissive spinal cord they are unable to do so. We discuss the traits that are favorable for regeneration, comparing what happens in mammals with each regenerative organism, aiming to describe and identify the key differences that allow regeneration. This comparison should lead us toward finding how to promote regeneration in organisms that are unable to do so. Copyright © 2013 Wiley Periodicals, Inc.

Thermal runaway of metal nano-tips during intense electron emission

NASA Astrophysics Data System (ADS)

Kyritsakis, A.; Veske, M.; Eimre, K.; Zadin, V.; Djurabekova, F.

2018-06-01

When an electron emitting tip is subjected to very high electric fields, plasma forms even under ultra high vacuum conditions. This phenomenon, known as vacuum arc, causes catastrophic surface modifications and constitutes a major limiting factor not only for modern electron sources, but also for many large-scale applications such as particle accelerators, fusion reactors etc. Although vacuum arcs have been studied thoroughly, the physical mechanisms that lead from intense electron emission to plasma ignition are still unclear. In this article, we give insights to the atomic scale processes taking place in metal nanotips under intense field emission conditions. We use multi-scale atomistic simulations that concurrently include field-induced forces, electron emission with finite-size and space-charge effects, Nottingham and Joule heating. We find that when a sufficiently high electric field is applied to the tip, the emission-generated heat partially melts it and the field-induced force elongates and sharpens it. This initiates a positive feedback thermal runaway process, which eventually causes evaporation of large fractions of the tip. The reported mechanism can explain the origin of neutral atoms necessary to initiate plasma, a missing key process required to explain the ignition of a vacuum arc. Our simulations provide a quantitative description of in the conditions leading to runaway, which shall be valuable for both field emission applications and vacuum arc studies.

Assessment of the GECKO-A modeling tool using chamber observations for C12 alkanes

NASA Astrophysics Data System (ADS)

Aumont, B.; La, S.; Ouzebidour, F.; Valorso, R.; Mouchel-Vallon, C.; Camredon, M.; Lee-Taylor, J. M.; Hodzic, A.; Madronich, S.; Yee, L. D.; Loza, C. L.; Craven, J. S.; Zhang, X.; Seinfeld, J.

2013-12-01

Secondary Organic Aerosol (SOA) production and ageing is the result of atmospheric oxidation processes leading to the progressive formation of organic species with higher oxidation state and lower volatility. Explicit chemical mechanisms reflect our understanding of these multigenerational oxidation steps. Major uncertainties remain concerning the processes leading to SOA formation and the development, assessment and improvement of such explicit schemes is therefore a key issue. The development of explicit mechanism to describe the oxidation of long chain hydrocarbons is however a challenge. Indeed, explicit oxidation schemes involve a large number of reactions and secondary organic species, far exceeding the size of chemical schemes that can be written manually. The chemical mechanism generator GECKO-A (Generator for Explicit Chemistry and Kinetics of Organics in the Atmosphere) is a computer program designed to overcome this difficulty. GECKO-A generates gas phase oxidation schemes according to a prescribed protocol assigning reaction pathways and kinetics data on the basis of experimental data and structure-activity relationships. In this study, we examine the ability of the generated schemes to explain SOA formation observed in the Caltech Environmental Chambers from various C12 alkane isomers and under high NOx and low NOx conditions. First results show that the model overestimates both the SOA yields and the O/C ratios. Various sensitivity tests are performed to explore processes that might be responsible for these disagreements.

Obstructive Sleep Apnea is Linked to Depression and Cognitive Impairment: Evidence and Potential Mechanisms

PubMed Central

Kerner, Nancy A.; Roose, Steven P.

2017-01-01

Obstructive sleep apnea (OSA) is highly prevalent but very frequently undiagnosed. OSA is an independent risk factor for depression and cognitive impairment/dementia. Herein the authors review studies in the literature pertinent to the effects of OSA on the cerebral microvascular and neurovascular systems and present a model to describe the key pathophysiologic mechanisms that may underlie the associations, including hypoperfusion, endothelial dysfunction, and neuroinflammation. Intermittent hypoxia plays a critical role in initiating and amplifying these pathologic processes. Hypoperfusion and impaired cerebral vasomotor reactivity lead to the development or progression of cerebral small vessel disease (C-SVD). Hypoxemia exacerbates these processes, resulting in white matter lesions, white matter integrity abnormalities, and gray matter loss. Blood–brain barrier (BBB) hyperpermeability and neuroinflammation lead to altered synaptic plasticity, neuronal damage, and worsening C-SVD. Thus, OSA may initiate or amplify the pathologic processes of C-SVD and BBB dysfunction, resulting in the development or exacerbation of depressive symptoms and cognitive deficits. Given the evidence that adequate treatment of OSA with continuous positive airway pressure improves depression and neurocognitive functions, it is important to identify OSA when assessing patients with depression or cognitive impairment. Whether treatment of OSA changes the deteriorating trajectory of elderly patients with already-diagnosed vascular depression and cognitive impairment/dementia remains to be determined in randomized controlled trials. PMID:27139243

A novel multimodal chromatography based single step purification process for efficient manufacturing of an E. coli based biotherapeutic protein product.

PubMed

Bhambure, Rahul; Gupta, Darpan; Rathore, Anurag S

2013-11-01

Methionine oxidized, reduced and fMet forms of a native recombinant protein product are often the critical product variants which are associated with proteins expressed as bacterial inclusion bodies in E. coli. Such product variants differ from native protein in their structural and functional aspects, and may lead to loss of biological activity and immunogenic response in patients. This investigation focuses on evaluation of multimodal chromatography for selective removal of these product variants using recombinant human granulocyte colony stimulating factor (GCSF) as the model protein. Unique selectivity in separation of closely related product variants was obtained using combined pH and salt based elution gradients in hydrophobic charge induction chromatography. Simultaneous removal of process related impurities was also achieved in flow-through leading to single step purification process for the GCSF. Results indicate that the product recovery of up to 90.0% can be obtained with purity levels of greater than 99.0%. Binding the target protein at pH

Abelson Interactor 1 (Abi1) and Its Interaction with Wiskott-Aldrich Syndrome Protein (Wasp) Are Critical for Proper Eye Formation in Xenopus Embryos*

PubMed Central

Singh, Arvinder; Winterbottom, Emily F.; Ji, Yon Ju; Hwang, Yoo-Seok; Daar, Ira O.

2013-01-01

Abl interactor 1 (Abi1) is a scaffold protein that plays a central role in the regulation of actin cytoskeleton dynamics as a constituent of several key protein complexes, and homozygous loss of this protein leads to embryonic lethality in mice. Because this scaffold protein has been shown in cultured cells to be a critical component of pathways controlling cell migration and actin regulation at cell-cell contacts, we were interested to investigate the in vivo role of Abi1 in morphogenesis during the development of Xenopus embryos. Using morpholino-mediated translation inhibition, we demonstrate that knockdown of Abi1 in the whole embryo, or specifically in eye field progenitor cells, leads to disruption of eye morphogenesis. Moreover, signaling through the Src homology 3 domain of Abi1 is critical for proper movement of retinal progenitor cells into the eye field and their appropriate differentiation, and this process is dependent upon an interaction with the nucleation-promoting factor Wasp (Wiskott-Aldrich syndrome protein). Collectively, our data demonstrate that the Abi1 scaffold protein is an essential regulator of cell movement processes required for normal eye development in Xenopus embryos and specifically requires an Src homology 3 domain-dependent interaction with Wasp to regulate this complex morphogenetic process. PMID:23558677

A Key Telegram and a Key Press Release on the Recognition of the State of Israel

ERIC Educational Resources Information Center

Byers, CeCe; Alexander, Mary

1978-01-01

Reviews the course of events leading to the founding of Israel in 1947. Presents primary source materials, activities, and discussion questions to help students analyze reasons for the Arab-Israeli conflict. (Author/DB)

The key to success: Gelled-electrolyte and optimized separators for stationary lead-acid batteries

NASA Astrophysics Data System (ADS)

Toniazzo, Valérie

The lead acid technology is nowadays considered one of the best suited for stationary applications. Both gel and AGM batteries are complementary technologies and can provide reliability and efficiency due to the constant optimization of the battery design and components. However, gelled-electrolyte batteries remain the preferred technology due to a better manufacturing background and show better performance mainly at low and moderate discharge rates. Especially, using the gel technology allows to get rid of the numerous problems encountered in most AGM batteries: drainage, stratification, short circuits due to dendrites, and mostly premature capacity loss due to the release of internal cell compression. These limitations are the result of the evident lack of an optimal separation system. In gel batteries, on the contrary, highly efficient polymeric separators are nowadays available. Especially, microporous separators based on PVC and silica have shown the best efficiency for nearly 30 years all over the world, and especially in Europe, where the gel technology was born. The improved performance of these separators is explained by the unique extrusion process, which leads to excellent wettability, and optimized physical properties. Because they are the key for the battery success, continuous research and development on separators have led to improved properties, which render the separator even better adapted to the more recent gel technology: the pore size distribution has been optimized to allow good oxygen transfer while avoiding dendrite growth, the pore volume has been increased, the electrical resistance and acid displacement reduced to such an extent that the electrical output of batteries has been raised both in terms of higher capacity and longer cycle life.

Overactive Epidermal Growth Factor Receptor Signaling Leads to Increased Fibrosis after Severe Acute Respiratory Syndrome Coronavirus Infection

PubMed Central

Venkataraman, Thiagarajan; Coleman, Christopher M.

2017-01-01

ABSTRACT Severe acute respiratory syndrome coronavirus (SARS-CoV) is a highly pathogenic respiratory virus that causes morbidity and mortality in humans. After infection with SARS-CoV, the acute lung injury caused by the virus must be repaired to regain lung function. A dysregulation in this wound healing process leads to fibrosis. Many survivors of SARS-CoV infection develop pulmonary fibrosis (PF), with higher prevalence in older patients. Using mouse models of SARS-CoV pathogenesis, we have identified that the wound repair pathway, controlled by the epidermal growth factor receptor (EGFR), is critical to recovery from SARS-CoV-induced tissue damage. In mice with constitutively active EGFR [EGFR(DSK5) mice], we find that SARS-CoV infection causes enhanced lung disease. Importantly, we show that during infection, the EGFR ligands amphiregulin and heparin-binding EGF-like growth factor (HB-EGF) are upregulated, and exogenous addition of these ligands during infection leads to enhanced lung disease and altered wound healing dynamics. Our data demonstrate a key role of EGFR in the host response to SARS-CoV and how it may be implicated in lung disease induced by other highly pathogenic respiratory viruses. IMPORTANCE PF has many causative triggers, including severe respiratory viruses such as SARS-CoV. Currently there are no treatments to prevent the onset or limit the progression of PF, and the molecular pathways underlying the development of PF are not well understood. In this study, we identified a role for the balanced control of EGFR signaling as a key factor in progression to PF. These data demonstrate that therapeutic treatment modulating EGFR activation could protect against PF development caused by severe respiratory virus infection. PMID:28404843

Overactive Epidermal Growth Factor Receptor Signaling Leads to Increased Fibrosis after Severe Acute Respiratory Syndrome Coronavirus Infection.

PubMed

Venkataraman, Thiagarajan; Coleman, Christopher M; Frieman, Matthew B

2017-06-15

Severe acute respiratory syndrome coronavirus (SARS-CoV) is a highly pathogenic respiratory virus that causes morbidity and mortality in humans. After infection with SARS-CoV, the acute lung injury caused by the virus must be repaired to regain lung function. A dysregulation in this wound healing process leads to fibrosis. Many survivors of SARS-CoV infection develop pulmonary fibrosis (PF), with higher prevalence in older patients. Using mouse models of SARS-CoV pathogenesis, we have identified that the wound repair pathway, controlled by the epidermal growth factor receptor (EGFR), is critical to recovery from SARS-CoV-induced tissue damage. In mice with constitutively active EGFR [EGFR(DSK5) mice], we find that SARS-CoV infection causes enhanced lung disease. Importantly, we show that during infection, the EGFR ligands amphiregulin and heparin-binding EGF-like growth factor (HB-EGF) are upregulated, and exogenous addition of these ligands during infection leads to enhanced lung disease and altered wound healing dynamics. Our data demonstrate a key role of EGFR in the host response to SARS-CoV and how it may be implicated in lung disease induced by other highly pathogenic respiratory viruses. IMPORTANCE PF has many causative triggers, including severe respiratory viruses such as SARS-CoV. Currently there are no treatments to prevent the onset or limit the progression of PF, and the molecular pathways underlying the development of PF are not well understood. In this study, we identified a role for the balanced control of EGFR signaling as a key factor in progression to PF. These data demonstrate that therapeutic treatment modulating EGFR activation could protect against PF development caused by severe respiratory virus infection. Copyright © 2017 American Society for Microbiology.

N-terminal fragment of cardiac myosin binding protein-C triggers pro-inflammatory responses in vitro

PubMed Central

Lipps, Christoph; Nguyen, Jenine H.; Pyttel, Lukas; Lynch, Thomas L.; Liebetrau, Christoph; Aleshcheva, Ganna; Voss, Sandra; Dörr, Oliver; Nef, Holger M.; Möllmann, Helge; Hamm, Christian W.; Sadayappan, Sakthivel; Troidl, Christian

2016-01-01

Myocardial infarction (MI) leads to loss and degradation of contractile cardiac tissue followed by sterile inflammation of the myocardium through activation and recruitment of innate and adaptive cells of the immune system. Recently, it was shown that cardiac myosin binding protein-C (cMyBP-C), a protein of the cardiac sarcomere, is degraded following MI, releasing a predominant N-terminal 40-kDa fragment (C0C1f) into myocardial tissue and the systemic circulation. We hypothesized that early release of C0C1f contributes to the initiation of inflammation and plays a key role in recruitment and activation of immune cells. Therefore, we investigated the role of C0C1f on macrophage / monocyte activation using both mouse bone marrow-derived macrophages and human monocytes. Here we demonstrate that C0C1f leads to macrophage / monocyte activation in vitro. Furthermore, C0C1f induces strong upregulation of pro-inflammatory cytokines (interleukin-6 (IL-6), tumor necrosis factor α (TNFα), and interleukin-1β (IL-1β)) in cultured murine macrophages and human monocytes, resulting in a pro-inflammatory phenotype. We identified the toll-like receptor 4 (TLR4), toll-like receptor 2 (TLR2), and Advanced Glycosylation End Product-Specific Receptor (RAGE) as potential receptors for C0C1f whose activation leads to mobilization of the NFκB signaling pathway, a central mediator of the pro-inflammatory signaling cascade. Thus, C0C1f appears to be a key player in the initiation of inflammatory processes and might also play an important role upon MI. PMID:27616755

Spectral Features and Charge Dynamics of Lead Halide Perovskites: Origins and Interpretations.

PubMed

Sum, Tze Chien; Mathews, Nripan; Xing, Guichuan; Lim, Swee Sien; Chong, Wee Kiang; Giovanni, David; Dewi, Herlina Arianita

2016-02-16

Lead halide perovskite solar cells are presently the forerunner among the third generation solution-processed photovoltaic technologies. With efficiencies exceeding 20% and low production costs, they are prime candidates for commercialization. Critical insights into their light harvesting, charge transport, and loss mechanisms have been gained through time-resolved optical probes such as femtosecond transient absorption spectroscopy (fs-TAS), transient photoluminescence spectroscopy, and time-resolved terahertz spectroscopy. Specifically, the discoveries of long balanced electron-hole diffusion lengths and gain properties in halide perovskites underpin their significant roles in uncovering structure-function relations and providing essential feedback for materials development and device optimization. In particular, fs-TAS is becoming increasingly popular in perovskite characterization studies, with commercial one-box pump-probe systems readily available as part of a researcher's toolkit. Although TAS is a powerful probe in the study of charge dynamics and recombination mechanisms, its instrumentation and data interpretation can be daunting even for experienced researchers. This issue is exacerbated by the sensitive nature of halide perovskites where the kinetics are especially susceptible to pump fluence, sample preparation and handling and even degradation effects that could lead to disparate conclusions. Nonetheless, with end-users having a clear understanding of TAS's capabilities, subtleties, and limitations, cutting-edge work with deep insights can still be performed using commercial setups as has been the trend for ubiquitous spectroscopy instruments like absorption, fluorescence, and transient photoluminescence spectrometers. Herein, we will first briefly examine the photophysical processes in lead halide perovskites, highlighting their novel properties. Next, we proceed to give a succinct overview of the fundamentals of pump-probe spectroscopy in relation to the spectral features of halide perovskites and their origins. In the process, we emphasize some key findings of seminal photophysical studies and draw attention to the interpretations that remain divergent and the open questions. This is followed by a general description into how we prepare and conduct the TAS characterization of CH3NH3PbI3 thin films in our laboratory with specific discussions into the potential pitfalls and the influence of thin film processing on the kinetics. Lastly, we conclude with our views on the challenges and opportunities from the photophysical perspective for the field and our expectations for systems beyond lead halide perovskites.

Manufacturing issues which affect coating erosion performance in wind turbine blades

NASA Astrophysics Data System (ADS)

Cortés, E.; Sánchez, F.; Domenech, L.; Olivares, A.; Young, T. M.; O'Carroll, A.; Chinesta, F.

2017-10-01

Erosion damage, caused by repeated rain droplet impact on the leading edges of wind turbine blades, is a major cause for cost concern. Resin Infusion (RI) is used in wind energy blades where low weight and high mechanical performance materials are demanded. The surface coating plays a crucial role in the manufacturing and performance response. The Leading Edge coating is usually moulded, painted or sprayed onto the blade surface so adequate adhesion in the layers' characterization through the thickness is required for mechanical performance and durability reasons. In the current work, an investigation has been directed into the resulting rain erosion durability of the coating was undertaken through a combination of mass loss testing measurements with manufacturing processing parameter variations. The adhesion and erosion is affected by the shock wave caused by the collapsing water droplet on impact. The stress waves are transmitted to the substrate, so microestructural discontinuities in coating layers and interfaces play a key role on its degradation. Standard industrial systems are based on a multilayer system, with a high number of interfaces that tend to accelerate erosion by delamination. Analytical and numerical models are commonly used to relate lifetime prediction and to identify suitable coating and composite substrate combinations and their potential stress reduction on the interface. In this research, the input parameters for the appropriate definition of the Cohesive Zone Modelling (CZM) of the coating-substrate interface are outlined by means of Pull off testing and Peeling testing results. It allowed one to optimize manufacturing and coating process for blades into a knowledge-based guidance for leading edge coating material development. It was achieved by investigating the erosion degradation process using both numerical and laboratory techniques (Pull off, Peeling and Rain Erosion Testing in a whirling arm rain erosion test facility).

Meeting the Challenge of Practice Quality Improvement: A Study of Seven Family Medicine Residency Training Practices

PubMed Central

Chase, Sabrina M.; Miller, William L.; Shaw, Eric; Looney, Anna; Crabtree, Benjamin F.

2011-01-01

Purpose Incorporating quality improvement (QI) into resident education and clinical care is challenging. This report explores key characteristics shaping the relative success or failure of QI efforts in seven primary care practices serving as family medicine residency training sites. Method The authors used data from the 2002–2008 Using Learning Teams for Reflective Adaptation (ULTRA) study to conduct a comparative case analysis. This secondary data analysis focused on seven residency training practices' experiences with RAP (reflective adaptive process), a 12-week intensive QI process. Field notes, meeting notes, and audiotapes of RAP meetings were used to construct case summaries. A matrix comparing key themes across practices was used to rate practices' QI progress during RAP on a scale of 0 to 3. Results Three practices emerged as unsuccessful (scores of 0–1) and four as successful (scores of 2–3). Larger practices with previous QI experience, faculty with extensive exposure to QI literature, and an office manager, residency director, or medical director who advocated for the process made substantial progress during RAP, succeeding at QI. Smaller practices without these characteristics were unable to do so. Successful practices also engaged residents in the QI process and identified serious problems as potential crises; unsuccessful practices did not. Conclusions Larger residency training practices are more likely to have the resources and characteristics that permit them to create a QI-supportive culture leading to QI success. The authors suggest, however, that smaller practices may increase their chances of success by adopting a developmental approach to QI. PMID:22030767

Process-to-Panel Modeling and Multiprobe Characterization of Silicon Heterojunction Solar Cell Technology

NASA Astrophysics Data System (ADS)

Chavali, Raghu Vamsi Krishna

The large-scale deployment of PV technology is very sensitive to the material and process costs. There are several potential candidates among p-n heterojunction (HJ) solar cells competing for higher efficiencies at lower material and process costs. These systems are, however, generally complex, involve diverse materials, and are not well understood. The direct translation of classical p-n homojunction theory to p-n HJ cells may not always be self-consistent and can lead, therefore, to misinterpretation of experimental results. Ultimately, this translation may not be useful for modeling and characterization of these solar cells. Hence, there is a strong need to redefine/reinterpret the modeling/characterization methodologies for HJ solar cells to produce a self-consistent framework for optimizing HJ solar cell designs. Towards this goal, we explore the physics and interpret characterization experiments of p-n HJs using Silicon HJ (HIT) solar cells. We will: (1) identify the key HJ properties that affect the cell efficiency; (2) analyze the dependence of key HJ properties on the carrier transport under light and dark conditions; (3) provide a selfconsistent multi-probe approach to extract the HJ parameters using several characterization techniques including dark I-V, light I-V, C-V, impedance spectroscopy, and Suns-Voc; (4) propose design guidelines to address the HJ bottlenecks of HIT cells; and (5) develop a process-to-module modeling framework to establish the module performance limits. The guidelines resulting from this multi-scale and self-consistent framework can be used to improve performance of HIT cells as well as other HJ based solar cells.

Nutrients in estuaries--an overview and the potential impacts of climate change.

PubMed

Statham, Peter J

2012-09-15

The fate and cycling of macronutrients introduced into estuaries depend upon a range of interlinked processes. Hydrodynamics and morphology in combination with freshwater inflow control the freshwater flushing time, and the timescale for biogeochemical processes to operate that include microbial activity, particle-dissolved phase interactions, and benthic exchanges. In some systems atmospheric inputs and exchanges with coastal waters can also be important. Climate change will affect nutrient inputs and behaviour through modifications to temperature, wind patterns, the hydrological cycle, and sea level rise. Resulting impacts include: 1) inundation of freshwater systems 2) changes in stratification, flushing times and phytoplankton productivity 3) increased coastal storm activity 4) changes in species and ecosystem function. A combination of continuing high inputs of nutrients through human activity and climate change is anticipated to lead to enhanced eutrophication in the future. The most obvious impacts of increasing global temperature will be in sub-arctic systems where permafrost zones will be reduced in combination with enhanced inputs from glacial systems. Improved process understanding in several key areas including cycling of organic N and P, benthic exchanges, resuspension, impact of bio-irrigation, particle interactions, submarine groundwater discharges, and rates and magnitude of bacterially-driven recycling processes, is needed. Development of high frequency in situ nutrient analysis systems will provide data to improve predictive models that need to incorporate a wider variety of key factors, although the complexity of estuarine systems makes such modelling a challenge. However, overall a more holistic approach is needed to effectively understand, predict and manage the impact of macronutrients on estuaries. Copyright © 2011 Elsevier B.V. All rights reserved.

Computational Cosmology

NASA Astrophysics Data System (ADS)

Abel, Tom

2013-01-01

Gravitational instability of small density fluctuations, possibly created during an early inflationary period, is the key process leading to the formation of all structure in the Universe. New numerical algorithms have recently enabled much progress in understanding the relevant physical processes dominating the first billion years of structure formation. Computational cosmologists are attempting to simulate on their supercomputers how galaxies come about. In recent years first attempts trying to follow the formation and eventual death of every single star in these model galaxies has become to be within reach. The models now include gravity for both dark matter and baryonic matter, hydrodynamics, follow the radiation from massive stars and its impact in shaping the surrounding material, gas chemistry and all the key radiative atomic and molecular physics determining the thermal state of the model gas. In a small number of cases even the rold of magnetic fields on galactic scales is being studied. At the same time we are learning more about the limitations of certain numerical techniques and developing new schemes to more accurately follow the interplay of these many different physical processes. This talk is in two parts. First we consider a birds eye view of the relevant physical processes relevant for structure formation and potential approaches in solving the relevant equations efficiently and accurately on modern supercomputers. Secondly, we focus in on one of those processes. Namely the intricate and fascinating dynamics of the likely collsionless fluid dynamics of dark matter. A novel way of following the intricate evolution of such collisionless fluids in phase space is allowing us to construct new numerical methods to help understand the nature of dark matter halos as well as problems in astrophysical and terrestial plasmas.

A Novel Re-keying Function Protocol (NRFP) For Wireless Sensor Network Security

PubMed Central

Abdullah, Maan Younis; Hua, Gui Wei; Alsharabi, Naif

2008-01-01

This paper describes a novel re-keying function protocol (NRFP) for wireless sensor network security. A re-keying process management system for sensor networks is designed to support in-network processing. The design of the protocol is motivated by decentralization key management for wireless sensor networks (WSNs), covering key deployment, key refreshment, and key establishment. NRFP supports the establishment of novel administrative functions for sensor nodes that derive/re-derive a session key for each communication session. The protocol proposes direct connection, in-direct connection and hybrid connection. NRFP also includes an efficient protocol for local broadcast authentication based on the use of one-way key chains. A salient feature of the authentication protocol is that it supports source authentication without precluding innetwork processing. Security and performance analysis shows that it is very efficient in computation, communication and storage and, that NRFP is also effective in defending against many sophisticated attacks. PMID:27873963

A Novel Re-keying Function Protocol (NRFP) For Wireless Sensor Network Security.

PubMed

Abdullah, Maan Younis; Hua, Gui Wei; Alsharabi, Naif

2008-12-04

This paper describes a novel re-keying function protocol (NRFP) for wireless sensor network security. A re-keying process management system for sensor networks is designed to support in-network processing. The design of the protocol is motivated by decentralization key management for wireless sensor networks (WSNs), covering key deployment, key refreshment, and key establishment. NRFP supports the establishment of novel administrative functions for sensor nodes that derive/re-derive a session key for each communication session. The protocol proposes direct connection, in-direct connection and hybrid connection. NRFP also includes an efficient protocol for local broadcast authentication based on the use of one-way key chains. A salient feature of the authentication protocol is that it supports source authentication without precluding in-network processing. Security and performance analysis shows that it is very efficient in computation, communication and storage and, that NRFP is also effective in defending against many sophisticated attacks.

Electronic manufacturing and packaging in Japan

NASA Technical Reports Server (NTRS)

Kelly, Michael J.; Boulton, William R. (Editor); Kukowski, John A.; Meieran, Eugene S.; Pecht, Michael; Peeples, John W.; Tummala, Rao R.

1995-01-01

This report summarizes the status of electronic manufacturing and packaging technology in Japan in comparison to that in the United States, and its impact on competition in electronic manufacturing in general. In addition to electronic manufacturing technologies, the report covers technology and manufacturing infrastructure, electronics manufacturing and assembly, quality assurance and reliability in the Japanese electronics industry, and successful product realization strategies. The panel found that Japan leads the United States in almost every electronics packaging technology. Japan clearly has achieved a strategic advantage in electronics production and process technologies. Panel members believe that Japanese competitors could be leading U.S. firms by as much as a decade in some electronics process technologies. Japan has established this marked competitive advantage in electronics as a consequence of developing low-cost, high-volume consumer products. Japan's infrastructure, and the remarkable cohesiveness of vision and purpose in government and industry, are key factors in the success of Japan's electronics industry. Although Japan will continue to dominate consumer electronics in the foreseeable future, opportunities exist for the United States and other industrial countries to capture an increasingly large part of the market. The JTEC panel has identified no insurmountable barriers that would prevent the United States from regaining a significant share of the consumer electronics market; in fact, there is ample evidence that the United States needs to aggressively pursue high-volume, low-cost electronic assembly, because it is a critical path leading to high-performance electronic systems.

Advanced Exploration Systems Atmosphere Resource Recovery and Environmental Monitoring

NASA Technical Reports Server (NTRS)

Perry, J.; Abney, M.; Conrad, R.; Garber, A.; Howard, D.; Kayatin, M.; Knox, J.; Newton, R.; Parrish, K.; Roman, M.;

Terroir is a key driver of seed-associated microbial assemblages.

PubMed

Klaedtke, Stephanie; Jacques, Marie-Agnès; Raggi, Lorenzo; Préveaux, Anne; Bonneau, Sophie; Negri, Valeria; Chable, Véronique; Barret, Matthieu

2016-06-01

Seeds have evolved in association with diverse microbial assemblages that may influence plant growth and health. However, little is known about the composition of seed-associated microbial assemblages and the ecological processes shaping their structures. In this work, we monitored the relative influence of the host genotypes and terroir on the structure of the seed microbiota through metabarcoding analysis of different microbial assemblages associated to five different bean cultivars harvested in two distinct farms. Overall, few bacterial and fungal operational taxonomic units (OTUs) were conserved across all seed samples. The lack of shared OTUs between samples is explained by a significant effect of the farm site on the structure of microbial assemblage, which explained 12.2% and 39.7% of variance in bacterial and fungal diversity across samples. This site-specific effect is reflected by the significant enrichment of 70 OTUs in Brittany and 88 OTUs in Luxembourg that lead to differences in co-occurrence patterns. In contrast, variance in microbial assemblage structure was not explained by host genotype. Altogether, these results suggest that seed-associated microbial assemblage is determined by niche-based processes and that the terroir is a key driver of these selective forces. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

Roles of microRNA on cancer cell metabolism

PubMed Central

2012-01-01

Advanced studies of microRNAs (miRNAs) have revealed their manifold biological functions, including control of cell proliferation, cell cycle and cell death. However, it seems that their roles as key regulators of metabolism have drawn more and more attention in the recent years. Cancer cells display increased metabolic autonomy in comparison to non-transformed cells, taking up nutrients and metabolizing them in pathways that support growth and proliferation. MiRNAs regulate cell metabolic processes through complicated mechanisms, including directly targeting key enzymes or transporters of metabolic processes and regulating transcription factors, oncogenes / tumor suppressors as well as multiple oncogenic signaling pathways. MiRNAs like miR-375, miR-143, miR-14 and miR-29b participate in controlling cancer cell metabolism by regulating the expression of genes whose protein products either directly regulate metabolic machinery or indirectly modulate the expression of metabolic enzymes, serving as master regulators, which will hopefully lead to a new therapeutic strategy for malignant cancer. This review focuses on miRNA regulations of cancer cell metabolism,including glucose uptake, glycolysis, tricarboxylic acid cycle and insulin production, lipid metabolism and amino acid biogenesis, as well as several oncogenic signaling pathways. Furthermore, the challenges of miRNA-based strategies for cancer diagnosis, prognosis and therapeutics have been discussed. PMID:23164426

Key enzymes of the retinoid (visual) cycle in vertebrate retina

PubMed Central

Kiser, Philip D.; Golczak, Marcin; Maeda, Akiko; Palczewski, Krzysztof

2011-01-01

A major goal in vision research over the past few decades has been to understand the molecular details of retinoid processing within the retinoid (visual) cycle. This includes the consequences of side reactions that result from delayed all-trans-retinal clearance and condensation with phospholipids that characterize a variety of serious retinal diseases. Knowledge of the basic retinoid biochemistry involved in these diseases is essential for development of effective therapeutics. Photoisomerization of the 11-cis-retinal chromophore of rhodopsin triggers a complex set of metabolic transformations collectively termed phototransduction that ultimately lead to light perception. Continuity of vision depends on continuous conversion of all-trans-retinal back to the 11-cis-retinal isomer. This process takes place in a series of reactions known as the retinoid cycle, which occur in photoreceptor and RPE cells. All-trans-retinal, the initial substrate of this cycle, is a chemically reactive aldehyde that can form toxic conjugates with proteins and lipids. Therefore, much experimental effort has been devoted to elucidate molecular mechanisms of the retinoid cycle and all-trans-retinal-mediated retinal degeneration, resulting in delineation of many key steps involved in regenerating 11-cis-retinal. Three particularly important reactions are catalyzed by enzymes broadly classified as acyltransferases, short-chain dehydrogenases/reductases and carotenoid/retinoid isomerases/oxygenases. PMID:21447403

MicroRNAs modulating angiogenesis: miR-129-1 and miR-133 act as angio-miR in HUVECs.

PubMed

Soufi-Zomorrod, Mina; Hajifathali, Abbas; Kouhkan, Fatemeh; Mehdizadeh, Mahshid; Rad, Seyed Mohammad Ali Hosseini; Soleimani, Masoud

2016-07-01

The sprouting of new blood vessels by angiogenesis is critical in vascular development and homeostasis. Aberrant angiogenesis leads to enormous pathological conditions such as ischemia and cancer. MicroRNAs (also known as miRNAs or miRs) play key roles in regulation of a range of cellular processes by posttranscriptional suppression of their target genes. Recently, new studies have indicated that miRNAs are involved in certain angiogenic settings and signaling pathways use these non-coding RNAs to promote or suppress angiogenic processes. Herein, VEGFR2 and FGFR1 were identified as miR-129-1 and miR-133 targets using bioinformatic algorithms, respectively. Afterwards, using luciferase reporter assay and gene expression analysis at both mRNA and protein levels, VEGFR2 and FGFR1 were validated as miR-129-1 and miR-133 targets. In addition, we showed that miR-129-1 and miR-133 suppress angiogenesis properties such as proliferation rate, cell viability, and migration activity of human umbilical vein endothelial cells (HUVEC) in vitro. We conclude that these miRNAs can suppress key factors of angiogenesis by directly targeting them. These results have important therapeutic implications for a variety of diseases involving deregulation of angiogenesis, including cancer.

Evolution of the Plant Reproduction Master Regulators LFY and the MADS Transcription Factors: The Role of Protein Structure in the Evolutionary Development of the Flower.

PubMed

Silva, Catarina S; Puranik, Sriharsha; Round, Adam; Brennich, Martha; Jourdain, Agnès; Parcy, François; Hugouvieux, Veronique; Zubieta, Chloe

2015-01-01

Understanding the evolutionary leap from non-flowering (gymnosperms) to flowering (angiosperms) plants and the origin and vast diversification of the floral form has been one of the focuses of plant evolutionary developmental biology. The evolving diversity and increasing complexity of organisms is often due to relatively small changes in genes that direct development. These "developmental control genes" and the transcription factors (TFs) they encode, are at the origin of most morphological changes. TFs such as LEAFY (LFY) and the MADS-domain TFs act as central regulators in key developmental processes of plant reproduction including the floral transition in angiosperms and the specification of the male and female organs in both gymnosperms and angiosperms. In addition to advances in genome wide profiling and forward and reverse genetic screening, structural techniques are becoming important tools in unraveling TF function by providing atomic and molecular level information that was lacking in purely genetic approaches. Here, we summarize previous structural work and present additional biophysical and biochemical studies of the key master regulators of plant reproduction - LEAFY and the MADS-domain TFs SEPALLATA3 and AGAMOUS. We discuss the impact of structural biology on our understanding of the complex evolutionary process leading to the development of the bisexual flower.

Cell Fusion Reprogramming Leads to a Specific Hepatic Expression Pattern during Mouse Bone Marrow Derived Hepatocyte Formation In Vivo

PubMed Central

Arza, Elvira; Alvarez-Barrientos, Alberto; Fabregat, Isabel; Garcia-Bravo, Maria; Meza, Nestor W.; Segovia, Jose C.

2012-01-01

The fusion of bone marrow (BM) hematopoietic cells with hepatocytes to generate BM derived hepatocytes (BMDH) is a natural process, which is enhanced in damaged tissues. However, the reprogramming needed to generate BMDH and the identity of the resultant cells is essentially unknown. In a mouse model of chronic liver damage, here we identify a modification in the chromatin structure of the hematopoietic nucleus during BMDH formation, accompanied by the loss of the key hematopoietic transcription factor PU.1/Sfpi1 (SFFV proviral integration 1) and gain of the key hepatic transcriptional regulator HNF-1A homeobox A (HNF-1A/Hnf1a). Through genome-wide expression analysis of laser captured BMDH, a differential gene expression pattern was detected and the chromatin changes observed were confirmed at the level of chromatin regulator genes. Similarly, Tranforming Growth Factor-β1 (TGF-β1) and neurotransmitter (e.g. Prostaglandin E Receptor 4 [Ptger4]) pathway genes were over-expressed. In summary, in vivo BMDH generation is a process in which the hematopoietic cell nucleus changes its identity and acquires hepatic features. These BMDHs have their own cell identity characterized by an expression pattern different from hematopoietic cells or hepatocytes. The role of these BMDHs in the liver requires further investigation. PMID:22457803

Neglected tropical diseases: exploring long term practical approaches to achieve sustainable disease elimination and beyond.

PubMed

Ortu, Giuseppina; Williams, Oliver

2017-09-27

Remarkable progress has been made in the fight against neglected tropical diseases, but new challenges have emerged. Innovative diagnostics, better drugs and new insecticides are often identified as the priority; however, access to these new tools may not be sufficient to achieve and sustain disease elimination, if certain challenges and priorities are not considered. The authors summarise key operational challenges, and based on these, identify two major priorities: strengthening the capacity of the primary health care health system in correctly diagnosing and managing neglected tropical diseases; and establishing an effective disease surveillance process. Five steps are proposed as concrete actions to build an effective primary health care service for neglected tropical diseases, and a health management information system capable of accurately reporting these diseases. Community engagement and formalization of community health workers role are proposed as essential components of these steps. Shift of financial support from disease oriented programmes to disease integrated interventions, improved access to international guidelines for primary health care staff, and availability of donated drugs in health care structures are also suggested as key elements of the proposed process. The authors conclude that failure to address these priorities now may lead to further challenges on the long path towards neglected tropical disease elimination and beyond.

Process control of laser conduction welding by thermal imaging measurement with a color camera.

PubMed

Bardin, Fabrice; Morgan, Stephen; Williams, Stewart; McBride, Roy; Moore, Andrew J; Jones, Julian D C; Hand, Duncan P

2005-11-10

Conduction welding offers an alternative to keyhole welding. Compared with keyhole welding, it is an intrinsically stable process because vaporization phenomena are minimal. However, as with keyhole welding, an on-line process-monitoring system is advantageous for quality assurance to maintain the required penetration depth, which in conduction welding is more sensitive to changes in heat sinking. The maximum penetration is obtained when the surface temperature is just below the boiling point, and so we normally wish to maintain the temperature at this level. We describe a two-color optical system that we have developed for real-time temperature profile measurement of the conduction weld pool. The key feature of the system is the use of a complementary metal-oxide semiconductor standard color camera leading to a simplified low-cost optical setup. We present and discuss the real-time temperature measurement and control performance of the system when a defocused beam from a high power Nd:YAG laser is used on 5 mm thick stainless steel workpieces.

Sparse signal representation and its applications in ultrasonic NDE.

PubMed

Zhang, Guang-Ming; Zhang, Cheng-Zhong; Harvey, David M

2012-03-01

Many sparse signal representation (SSR) algorithms have been developed in the past decade. The advantages of SSR such as compact representations and super resolution lead to the state of the art performance of SSR for processing ultrasonic non-destructive evaluation (NDE) signals. Choosing a suitable SSR algorithm and designing an appropriate overcomplete dictionary is a key for success. After a brief review of sparse signal representation methods and the design of overcomplete dictionaries, this paper addresses the recent accomplishments of SSR for processing ultrasonic NDE signals. The advantages and limitations of SSR algorithms and various overcomplete dictionaries widely-used in ultrasonic NDE applications are explored in depth. Their performance improvement compared to conventional signal processing methods in many applications such as ultrasonic flaw detection and noise suppression, echo separation and echo estimation, and ultrasonic imaging is investigated. The challenging issues met in practical ultrasonic NDE applications for example the design of a good dictionary are discussed. Representative experimental results are presented for demonstration. Copyright © 2011 Elsevier B.V. All rights reserved.

The Standard Autonomous File Server, a Customized, Off-the-Shelf Success Story

NASA Technical Reports Server (NTRS)

Semancik, Susan K.; Conger, Annette M.; Obenschain, Arthur F. (Technical Monitor)

2001-01-01

The Standard Autonomous File Server (SAFS), which includes both off-the-shelf hardware and software, uses an improved automated file transfer process to provide a quicker, more reliable, prioritized file distribution for customers of near real-time data without interfering with the assets involved in the acquisition and processing of the data. It operates as a stand-alone solution, monitoring itself, and providing an automated fail-over process to enhance reliability. This paper will describe the unique problems and lessons learned both during the COTS selection and integration into SAFS, and the system's first year of operation in support of NASA's satellite ground network. COTS was the key factor in allowing the two-person development team to deploy systems in less than a year, meeting the required launch schedule. The SAFS system his been so successful, it is becoming a NASA standard resource, leading to its nomination for NASA's Software or the Year Award in 1999.

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

Corvellec, Herve, E-mail: herve.corvellec@ism.lu.se; Bramryd, Torleif

Highlights: Black-Right-Pointing-Pointer Swedish municipally owned waste management companies are active on political, material, technical, and commercial markets. Black-Right-Pointing-Pointer These markets differ in kind and their demands follow different logics. Black-Right-Pointing-Pointer These markets affect the public service, processing, and marketing of Swedish waste management. Black-Right-Pointing-Pointer Articulating these markets is a strategic challenge for Swedish municipally owned waste management. - Abstract: This paper describes how the business model of two leading Swedish municipally owned solid waste management companies exposes them to four different but related markets: a political market in which their legitimacy as an organization is determined; a waste-as-material market thatmore » determines their access to waste as a process input; a technical market in which these companies choose what waste processing technique to use; and a commercial market in which they market their products. Each of these markets has a logic of its own. Managing these logics and articulating the interrelationships between these markets is a key strategic challenge for these companies.« less

Physico-chemical foundations underpinning microarray and next-generation sequencing experiments

PubMed Central

Harrison, Andrew; Binder, Hans; Buhot, Arnaud; Burden, Conrad J.; Carlon, Enrico; Gibas, Cynthia; Gamble, Lara J.; Halperin, Avraham; Hooyberghs, Jef; Kreil, David P.; Levicky, Rastislav; Noble, Peter A.; Ott, Albrecht; Pettitt, B. Montgomery; Tautz, Diethard; Pozhitkov, Alexander E.

2013-01-01

Hybridization of nucleic acids on solid surfaces is a key process involved in high-throughput technologies such as microarrays and, in some cases, next-generation sequencing (NGS). A physical understanding of the hybridization process helps to determine the accuracy of these technologies. The goal of a widespread research program is to develop reliable transformations between the raw signals reported by the technologies and individual molecular concentrations from an ensemble of nucleic acids. This research has inputs from many areas, from bioinformatics and biostatistics, to theoretical and experimental biochemistry and biophysics, to computer simulations. A group of leading researchers met in Ploen Germany in 2011 to discuss present knowledge and limitations of our physico-chemical understanding of high-throughput nucleic acid technologies. This meeting inspired us to write this summary, which provides an overview of the state-of-the-art approaches based on physico-chemical foundation to modeling of the nucleic acids hybridization process on solid surfaces. In addition, practical application of current knowledge is emphasized. PMID:23307556

ATG16L1: A multifunctional susceptibility factor in Crohn disease

PubMed Central

Salem, Mohammad; Ammitzboell, Mette; Nys, Kris; Seidelin, Jakob Benedict; Nielsen, Ole Haagen

2015-01-01

Genetic variations in the autophagic pathway influence genetic predispositions to Crohn disease. Autophagy, the major lysosomal pathway for degrading and recycling cytoplasmic material, constitutes an important homeostatic cellular process. Of interest, single-nucleotide polymorphisms in ATG16L1 (autophagy-related 16-like 1 [S. cerevisiae]), a key component in the autophagic response to invading pathogens, have been associated with an increased risk of developing Crohn disease. The most common and well-studied genetic variant of ATG16L1 (rs2241880; leading to a T300A conversion) exhibits a strong association with risk for developing Crohn disease. The rs2241880 variant plays a crucial role in pathogen clearance, resulting in imbalanced cytokine production, and is linked to other biological processes, such as the endoplasmic reticulum stress/unfolded protein response. In this review, we focus on the importance of ATG16L1 and its genetic variant (T300A) within the elementary biological processes linked to Crohn disease. PMID:25906181

ATG16L1: A multifunctional susceptibility factor in Crohn disease.

PubMed

Salem, Mohammad; Ammitzboell, Mette; Nys, Kris; Seidelin, Jakob Benedict; Nielsen, Ole Haagen

2015-04-03

Genetic variations in the autophagic pathway influence genetic predispositions to Crohn disease. Autophagy, the major lysosomal pathway for degrading and recycling cytoplasmic material, constitutes an important homeostatic cellular process. Of interest, single-nucleotide polymorphisms in ATG16L1 (autophagy-related 16-like 1 [S. cerevisiae]), a key component in the autophagic response to invading pathogens, have been associated with an increased risk of developing Crohn disease. The most common and well-studied genetic variant of ATG16L1 (rs2241880; leading to a T300A conversion) exhibits a strong association with risk for developing Crohn disease. The rs2241880 variant plays a crucial role in pathogen clearance, resulting in imbalanced cytokine production, and is linked to other biological processes, such as the endoplasmic reticulum stress/unfolded protein response. In this review, we focus on the importance of ATG16L1 and its genetic variant (T300A) within the elementary biological processes linked to Crohn disease.

Labview Based ECG Patient Monitoring System for Cardiovascular Patient Using SMTP Technology.

PubMed

Singh, Om Prakash; Mekonnen, Dawit; Malarvili, M B

2015-01-01

This paper leads to developing a Labview based ECG patient monitoring system for cardiovascular patient using Simple Mail Transfer Protocol technology. The designed device has been divided into three parts. First part is ECG amplifier circuit, built using instrumentation amplifier (AD620) followed by signal conditioning circuit with the operation amplifier (lm741). Secondly, the DAQ card is used to convert the analog signal into digital form for the further process. Furthermore, the data has been processed in Labview where the digital filter techniques have been implemented to remove the noise from the acquired signal. After processing, the algorithm was developed to calculate the heart rate and to analyze the arrhythmia condition. Finally, SMTP technology has been added in our work to make device more communicative and much more cost-effective solution in telemedicine technology which has been key-problem to realize the telediagnosis and monitoring of ECG signals. The technology also can be easily implemented over already existing Internet.

Labview Based ECG Patient Monitoring System for Cardiovascular Patient Using SMTP Technology

PubMed Central

Singh, Om Prakash; Mekonnen, Dawit; Malarvili, M. B.

2015-01-01

This paper leads to developing a Labview based ECG patient monitoring system for cardiovascular patient using Simple Mail Transfer Protocol technology. The designed device has been divided into three parts. First part is ECG amplifier circuit, built using instrumentation amplifier (AD620) followed by signal conditioning circuit with the operation amplifier (lm741). Secondly, the DAQ card is used to convert the analog signal into digital form for the further process. Furthermore, the data has been processed in Labview where the digital filter techniques have been implemented to remove the noise from the acquired signal. After processing, the algorithm was developed to calculate the heart rate and to analyze the arrhythmia condition. Finally, SMTP technology has been added in our work to make device more communicative and much more cost-effective solution in telemedicine technology which has been key-problem to realize the telediagnosis and monitoring of ECG signals. The technology also can be easily implemented over already existing Internet. PMID:27006940

Endogenous antigen processing drives the primary CD4+ T cell response to influenza

PubMed Central

Miller, Michael A.; Ganesan, Asha Purnima V.; Luckashenak, Nancy; Mendonca, Mark; Eisenlohr, Laurence C.

2015-01-01

By convention, CD4+ T lymphocytes recognize foreign and self peptides derived from internalized antigens in combination with MHC class II molecules. Alternative pathways of epitope production have been identified but their contributions to host defense have not been established. We show here in a mouse infection model that the CD4+ T cell response to influenza, critical for durable protection from the virus, is driven principally by unconventional processing of antigen synthesized within the infected antigen-presenting cell, not by classical processing of endocytosed virions or material from infected cells. Investigation of the cellular components involved, including the H2-M molecular chaperone, the proteasome, and gamma-interferon inducible lysosomal thiol reductase revealed considerable heterogeneity in the generation of individual epitopes, an arrangement that ensures peptide diversity and broad CD4+ T cell engagement. These results could fundamentally revise strategies for rational vaccine design and may lead to key insights into the induction of autoimmune and anti-tumor responses. PMID:26413780

Development of the platelet micro-orifice injector. [for liquid propellant rocket engines

NASA Technical Reports Server (NTRS)

La Botz, R. J.

1984-01-01

For some time to come, liquid rocket engines will continue to provide the primary means of propulsion for space transportation. The injector represents a key to the optimization of engine and system performance. The present investigation is concerned with a unique injector design and fabrication process which has demonstrated performance capabilities beyond that achieved with more conventional approaches. This process, which is called the 'platelet process', makes it feasible to fabricate injectors with a pattern an order of magnitude finer than that obtainable by drilling. The fine pattern leads to an achievement of high combustion efficiencies. Platelet injectors have been identified as one of the significant technology advances contributing to the feasibility of advanced dual-fuel booster engines. Platelet injectors are employed in the Space Shuttle Orbit Maneuvering System (OMS) engines. Attention is given to injector design theory as it relates to pattern fineness, a description of platelet injectors, and test data obtained with three different platelet injectors.