Feasibility of developing LSI microcircuit reliability prediction models

NASA Technical Reports Server (NTRS)

Ryerson, C. M.

1972-01-01

In the proposed modeling approach, when any of the essential key factors are not known initially, they can be approximated in various ways with a known impact on the accuracy of the final predictions. For example, on any program where reliability predictions are started at interim states of project completion, a-priori approximate estimates of the key factors are established for making preliminary predictions. Later these are refined for greater accuracy as subsequent program information of a more definitive nature becomes available. Specific steps to develop, validate and verify these new models are described.

A novel glucuronosyltransferase has an unprecedented ability to catalyse continuous two-step glucuronosylation of glycyrrhetinic acid to yield glycyrrhizin.

PubMed

Xu, Guojie; Cai, Wei; Gao, Wei; Liu, Chunsheng

2016-10-01

Glycyrrhizin is an important bioactive compound that is used clinically to treat chronic hepatitis and is also used as a sweetener world-wide. However, the key UDP-dependent glucuronosyltransferases (UGATs) involved in the biosynthesis of glycyrrhizin remain unknown. To discover unknown UGATs, we fully annotated potential UGATs from Glycyrrhiza uralensis using deep transcriptome sequencing. The catalytic functions of candidate UGATs were determined by an in vitro enzyme assay. Systematically screening 434 potential UGATs, we unexpectedly found one unique GuUGAT that was able to catalyse the glucuronosylation of glycyrrhetinic acid to directly yield glycyrrhizin via continuous two-step glucuronosylation. Expression analysis further confirmed the key role of GuUGAT in the biosynthesis of glycyrrhizin. Site-directed mutagenesis revealed that Gln-352 may be important for the initial step of glucuronosylation, and His-22, Trp-370, Glu-375 and Gln-392 may be important residues for the second step of glucuronosylation. Notably, the ability of GuUGAT to catalyse a continuous two-step glucuronosylation reaction was determined to be unprecedented among known glycosyltransferases of bioactive plant natural products. Our findings increase the understanding of traditional glycosyltransferases and pave the way for the complete biosynthesis of glycyrrhizin. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Renewing Liquid Fueled Molten Salt Reactor Research and Development

NASA Astrophysics Data System (ADS)

Towell, Rusty; NEXT Lab Team

2016-09-01

Globally there is a desperate need for affordable, safe, and clean energy on demand. More than anything else, this would raise the living conditions of those in poverty around the world. An advanced reactor that utilizes liquid fuel and molten salts is capable of meeting these needs. Although, this technology was demonstrated in the Molten Salt Reactor Experiment (MSRE) at ORNL in the 60's, little progress has been made since the program was cancelled over 40 years ago. A new research effort has been initiated to advance the technical readiness level of key reactor components. This presentation will explain the motivation and initial steps for this new research initiative.

Asymmetric Total Synthesis of (-)-(3 R)-Inthomycin C.

PubMed

Balcells, Sandra; Haughey, Maxwell B; Walker, Johannes C L; Josa-Culleré, Laia; Towers, Christopher; Donohoe, Timothy J

2018-06-04

A short (10 step) and efficient (15% overall yield) synthesis of the natural product (-)-(3 R)-inthomycin C is reported. The key steps comprise three C-C bond-forming reactions: (i) a vinylogous Mukaiyama aldol, (ii) an olefin cross-metathesis reaction, and (iii) an asymmetric Mukaiyama-Kiyooka aldol. This route is notable for its brevity and has the advantage of lacking stoichiometric tin-promoted cross-coupling reactions present in previous approaches. Initial investigations on the biological activity of (-)-(3 R)-inthomycin C and structural analogues on human cancer cell lines are also described for the first time.

Measuring Stability and Security in Iraq: Report to Congress in Accordance with the Department of Defense Appropriations Act 2007 (Section 9010, Public Law 109-289)

DTIC Science & Technology

2006-11-01

initiatives. Political Stability Iraq’s Council of Representatives has passed key legislation to initiate the constitutional review process, to...facilitate foreign invest- ment, and to outline a process for region formation. Most important for long-term political stability is the success of...November 30, 2006 5 1. Stability and Security in Iraq 1.1 Political Stability 1.1.1 Steps to a Free and Self-Governing Iraq As detailed in the August

Preschool Children's Interpretation of Object-Initial Sentences: Neural Correlates of Their Behavioral Performance

ERIC Educational Resources Information Center

Schipke, Christine S.; Knoll, Lisa J.; Friederici, Angela D.; Oberecker, Regine

2012-01-01

The acquisition of the function of case-marking is a key step in the development of sentence processing for German-speaking children since case-marking reveals the relations between sentential arguments. In this study, we investigated the development of the processing of case-marking and argument structures in children at 3, 4;6 and 6 years of…

Vibrational spectroscopy reveals the initial steps of biological hydrogen evolution.

PubMed

Katz, S; Noth, J; Horch, M; Shafaat, H S; Happe, T; Hildebrandt, P; Zebger, I

2016-11-01

[FeFe] hydrogenases are biocatalytic model systems for the exploitation and investigation of catalytic hydrogen evolution. Here, we used vibrational spectroscopic techniques to characterize, in detail, redox transformations of the [FeFe] and [4Fe4S] sub-sites of the catalytic centre (H-cluster) in a monomeric [FeFe] hydrogenase. Through the application of low-temperature resonance Raman spectroscopy, we discovered a novel metastable intermediate that is characterized by an oxidized [Fe I Fe II ] centre and a reduced [4Fe4S] 1+ cluster. Based on this unusual configuration, this species is assigned to the first, deprotonated H-cluster intermediate of the [FeFe] hydrogenase catalytic cycle. Providing insights into the sequence of initial reaction steps, the identification of this species represents a key finding towards the mechanistic understanding of biological hydrogen evolution.

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

Fan, Yue; Iwashita, Takuya; Egami, Takeshi

Complex states in glasses can be neatly expressed by the potential energy landscape (PEL). But, because PEL is highly multi-dimensional it is difficult to describe how the system moves around in PEL. We demonstrate that it is possible to predict the evolution of macroscopic state in a metallic glass, such as ageing and rejuvenation, through a set of simple equations describing excitations in the PEL. The key to this simplification is the realization that the step of activation from the initial state to the saddle point in PEL and the following step of relaxation to the final state are essentiallymore » decoupled. Furthermore, the model shows that the interplay between activation and relaxation in PEL is the key driving force that simultaneously explains both the equilibrium of supercooled liquid and the thermal hysteresis observed in experiments. It further predicts anomalous peaks in truncated thermal scanning, validated by independent molecular dynamics simulation.« less

Neuroprotective Role of a Brain-Enriched Tyrosine Phosphatase, STEP, in Focal Cerebral Ischemia

PubMed Central

Deb, Ishani; Manhas, Namratta; Poddar, Ranjana; Rajagopal, Sathyanarayanan; Allan, Andrea M.; Lombroso, Paul J.; Rosenberg, Gary A.; Candelario-Jalil, Eduardo

2013-01-01

The striatal-enriched phosphatase (STEP) is a component of the NMDA-receptor-mediated excitotoxic signaling pathway, which plays a key role in ischemic brain injury. Using neuronal cultures and a rat model of ischemic stroke, we show that STEP plays an initial role in neuroprotection, during the insult, by disrupting the p38 MAPK pathway. Degradation of active STEP during reperfusion precedes ischemic brain damage and is associated with secondary activation of p38 MAPK. Application of a cell-permeable STEP-derived peptide that is resistant to degradation and binds to p38 MAPK protects cultured neurons from hypoxia-reoxygenation injury and reduces ischemic brain damage when injected up to 6 h after the insult. Conversely, genetic deletion of STEP in mice leads to sustained p38 MAPK activation and exacerbates brain injury and neurological deficits after ischemia. Administration of the STEP-derived peptide at the onset of reperfusion not only prevents the sustained p38 MAPK activation but also reduces ischemic brain damage in STEP KO mice. The findings indicate a neuroprotective role of STEP and suggest a potential role of the STEP-derived peptide in stroke therapy. PMID:24198371

Development of a Mass Casualty Triage Performance Assessment Tool

DTIC Science & Technology

2015-02-01

mass casualty triage and interviews with members of the unit, the triage assessment development involved three steps: (1) identification of key...Unlimited c. THIS PAGE Unlimited Unlimited Unclassified 35 19b. TELEPHONE NUMBER (include area code ) i Technical...in this report was initiated by ARI-FHRU to develop a prototype measure of performance for one of the three collective tasks identified in the

p15Ink4b is Key in Dendritic Cell Development | Center for Cancer Research

Cancer.gov

An important step in the initiation of leukemia is the ability of pre-leukemic and leukemic cells to evade the immune system. Dendritic cells are instrumental in maintaining the body’s immunity, and CCR scientists have shown for the first time that the tumor suppressor protein p15Ink4b regulates the differentiation and maturation of conventional dendritic cells.

Achievable steps toward building a National Health Information infrastructure in the United States.

PubMed

Stead, William W; Kelly, Brian J; Kolodner, Robert M

2005-01-01

Consensus is growing that a health care information and communication infrastructure is one key to fixing the crisis in the United States in health care quality, cost, and access. The National Health Information Infrastructure (NHII) is an initiative of the Department of Health and Human Services receiving bipartisan support. There are many possible courses toward its objective. Decision makers need to reflect carefully on which approaches are likely to work on a large enough scale to have the intended beneficial national impacts and which are better left to smaller projects within the boundaries of health care organizations. This report provides a primer for use by informatics professionals as they explain aspects of that dividing line to policy makers and to health care leaders and front-line providers. It then identifies short-term, intermediate, and long-term steps that might be taken by the NHII initiative.

Achievable Steps Toward Building a National Health Information Infrastructure in the United States

PubMed Central

Stead, William W.; Kelly, Brian J.; Kolodner, Robert M.

2005-01-01

Consensus is growing that a health care information and communication infrastructure is one key to fixing the crisis in the United States in health care quality, cost, and access. The National Health Information Infrastructure (NHII) is an initiative of the Department of Health and Human Services receiving bipartisan support. There are many possible courses toward its objective. Decision makers need to reflect carefully on which approaches are likely to work on a large enough scale to have the intended beneficial national impacts and which are better left to smaller projects within the boundaries of health care organizations. This report provides a primer for use by informatics professionals as they explain aspects of that dividing line to policy makers and to health care leaders and front-line providers. It then identifies short-term, intermediate, and long-term steps that might be taken by the NHII initiative. PMID:15561783

Mechanisms for regulating step length while running towards and over an obstacle.

PubMed

Larsen, Roxanne J; Jackson, William H; Schmitt, Daniel

2016-10-01

The ability to run across uneven terrain with continuous stable movement is critical to the safety and efficiency of a runner. Successful step-to-step stabilization while running may be mediated by minor adjustments to a few key parameters (e.g., leg stiffness, step length, foot strike pattern). However, it is not known to what degree runners in relatively natural settings (e.g., trails, paved road, curbs) use the same strategies across multiple steps. This study investigates how three readily measurable running parameters - step length, foot placement, and foot strike pattern - are adjusted in response to encountering a typical urban obstacle - a sidewalk curb. Thirteen subjects were video-recorded as they ran at self-selected slow and fast paces. Runners targeted a specific distance before the curb for foot placement, and lengthened their step over the curb (p<0.0001) regardless of where the step over the curb was initiated. These strategies of adaptive locomotion disrupt step cycles temporarily, and may increase locomotor cost and muscle loading, but in the end assure dynamic stability and minimize the risk of injury over the duration of a run. Copyright © 2016 Elsevier B.V. All rights reserved.

Antimalarial peroxide dyads from natural artemisinin and hydroxyalkylated 1,2,4-trioxanes.

PubMed

Griesbeck, Axel G; Neudörfl, Jörg; Hörauf, Achim; Specht, Sabine; Raabe, Angela

2009-05-28

Three synthetic approaches to highly antimalarial peroxide dyads that are composed of the natural artemisinin part (either as dihydroartemisinin or artesunic acid components) and synthetic 1,2,4-trioxanes linked by ether or ester bridges are described. Photooxygenation is the key step to introduce the trioxane group initially or at the end of the reaction sequence, respectively. Dihydroartemisinin or artesunate coupling to hydroxyethyltrioxanes are the two processes that use intact peroxide units from the beginning, whereas the dihydroartemisinin-coupling to an allylic alcohol is a postphotooxygenation route, where the second trioxane ring is installed in the last step of the procedure.

Bringing Value-Based Perspectives to Care: Including Patient and Family Members in Decision-Making Processes

PubMed Central

Kohler, Graeme; Sampalli, Tara; Ryer, Ashley; Porter, Judy; Wood, Les; Bedford, Lisa; Higgins-Bowser, Irene; Edwards, Lynn; Christian, Erin; Dunn, Susan; Gibson, Rick; Ryan Carson, Shannon; Vallis, Michael; Zed, Joanna; Tugwell, Barna; Van Zoost, Colin; Canfield, Carolyn; Rivoire, Eleanor

2017-01-01

Background: Recent evidence shows that patient engagement is an important strategy in achieving a high performing healthcare system. While there is considerable evidence of implementation initiatives in direct care context, there is limited investigation of implementation initiatives in decision-making context as it relates to program planning, service delivery and developing policies. Research has also shown a gap in consistent application of system-level strategies that can effectively translate organizational policies around patient and family engagement into practice. Methods: The broad objective of this initiative was to develop a system-level implementation strategy to include patient and family advisors (PFAs) at decision-making points in primary healthcare (PHC) based on wellestablished evidence and literature. In this opportunity sponsored by the Canadian Foundation for Healthcare Improvement (CFHI) a co-design methodology, also well-established was applied in identifying and developing a suitable implementation strategy to engage PFAs as members of quality teams in PHC. Diabetes management centres (DMCs) was selected as the pilot site to develop the strategy. Key steps in the process included review of evidence, review of the current state in PHC through engagement of key stakeholders and a co-design approach. Results: The project team included a diverse representation of members from the PHC system including patient advisors, DMC team members, system leads, providers, Public Engagement team members and CFHI improvement coaches. Key outcomes of this 18-month long initiative included development of a working definition of patient and family engagement, development of a Patient and Family Engagement Resource Guide and evaluation of the resource guide. Conclusion: This novel initiative provided us an opportunity to develop a supportive system-wide implementation plan and a strategy to include PFAs in decision-making processes in PHC. The well-established co-design methodology further allowed us to include value-based (customer driven quality and experience of care) perspectives of several important stakeholders including patient advisors. The next step will be to implement the strategy within DMCs, spread the strategy PHC, both locally and provincially with a focus on sustainability. PMID:29179292

Optimizing health information technology's role in enabling comparative effectiveness research.

PubMed

Navathe, Amol S; Conway, Patrick H

2010-12-01

Health information technology (IT) is a key enabler of comparative effectiveness research (CER). Health IT standards for data sharing are essential to advancing the research data infrastructure, and health IT is critical to the next step of incorporating clinical data into data sources. Four key principles for advancement of CER are (1) utilization of data as a strategic asset, (2) leveraging public-private partnerships, (3) building robust, scalable technology platforms, and (4) coordination of activities across government agencies. To maximize the value of the resources, payers and providers must contribute data to initiatives, engage with government agencies on lessons learned, continue to develop new technologies that address key challenges, and utilize the data to improve patient outcomes and conduct research.

Generating social impact scenarios: A key step in making technology assessment studies

NASA Technical Reports Server (NTRS)

Jones, M. V.

1975-01-01

The MITRE methodological studies were conducted to define relevant questions in relation to the concept of total impact analysis and to provide a procedure for integrating diverse checklists of questions which trace the initial and secondary impacts of any major technological application or of society's attempts to respond to or redirect that application. Some of the results of that study are presented in tabular form.

Polyfibroblast: A Self-Healing and Galvanic Protection Additive

DTIC Science & Technology

2013-07-25

OBIECTIVES 1 KEY ACCOMPLISHMENTS 3.1 ON SITE INSPECTION OF COATING HEALTH 2 3.2 MICROCAPSULE SHEAR STRENGTH 4 3.3 NEXT STEPS 5 1 Summary Initial...experiments with the handheld fluorescence microscope were successful in imaging Nile Red-loaded microcapsules within the self-healing paint. However...the microcapsule shells were brighter than the entrained fluid, making it difficult to assess the health of the coating. Shear strength

Computer-Mediated Group Processes in Distributed Command and Control Systems

DTIC Science & Technology

1988-06-01

Linville, "Michael J. Liebhaber, and Richard W. Obermayer Vreuls Corporation Jon J. Fallesen Army Research Institute DTIC SELECTEr • AUG I 1. 1988 ARI...control staffs who will operate in a computer- mediated environment. The Army Research Institute has initiated research to examine selected issues...computar-mediated group processes is needed. Procedure: The identification and selection of key research issues followed a three- step procedure. Previous

Synthesis of (1R,2S)-1-amino-2-vinylcyclopropanecarboxylic acid vinyl-ACCA) derivatives: key intermediates for the preparation of inhibitors of the hepatitis C virus NS3 protease.

PubMed

Beaulieu, Pierre L; Gillard, James; Bailey, Murray D; Boucher, Colette; Duceppe, Jean-Simon; Simoneau, Bruno; Wang, Xiao-Jun; Zhang, Li; Grozinger, Karl; Houpis, Ioannis; Farina, Vittorio; Heimroth, Heidi; Krueger, Thomas; Schnaubelt, Jürgen

2005-07-22

(1R,2S)-1-Amino-2-vinylcyclopropanecarboxylic acid (vinyl-ACCA) is a key building block in the synthesis of potent inhibitors of the hepatitis C virus NS3 protease such as BILN 2061, which was recently shown to dramatically reduce viral load after administration to patients infected with HCV genotype 1. We have developed a scalable process that delivers derivatives of this unusual amino acid in >99% ee. The strategy was based on the dialkylation of a glycine Schiff base using trans-1,4-dibromo-2-butene as an electrophile to produce racemic vinyl-ACCA, which was subsequently resolved using a readily available, inexpensive esterase enzyme (Alcalase 2.4L). Factors that affect diastereoselection in the initial dialkylation steps were examined and the conditions optimized to deliver the desired diastereomer selectively. Product inhibition, which was encountered during the enzymatic resolution step, initially resulted in prolonged cycle times. Enrichment of racemic vinyl-ACCA through a chemical resolution via diastereomeric salt formation or the use of forcing conditions in the enzymatic reaction both led to improvements in throughput and the development of a viable process. The chemistry described herein was scaled up to produce multikilogram quantities of this building block.

A Coordinated Initialization Process for the Distributed Space Exploration Simulation

NASA Technical Reports Server (NTRS)

Crues, Edwin Z.; Phillips, Robert G.; Dexter, Dan; Hasan, David

2007-01-01

A viewgraph presentation on the federate initialization process for the Distributed Space Exploration Simulation (DSES) is described. The topics include: 1) Background: DSES; 2) Simulation requirements; 3) Nine Step Initialization; 4) Step 1: Create the Federation; 5) Step 2: Publish and Subscribe; 6) Step 3: Create Object Instances; 7) Step 4: Confirm All Federates Have Joined; 8) Step 5: Achieve initialize Synchronization Point; 9) Step 6: Update Object Instances With Initial Data; 10) Step 7: Wait for Object Reflections; 11) Step 8: Set Up Time Management; 12) Step 9: Achieve startup Synchronization Point; and 13) Conclusions

Development of a standardized training course for laparoscopic procedures using Delphi methodology.

PubMed

Bethlehem, Martijn S; Kramp, Kelvin H; van Det, Marc J; ten Cate Hoedemaker, Henk O; Veeger, Nicolaas J G M; Pierie, Jean Pierre E N

2014-01-01

Content, evaluation, and certification of laparoscopic skills and procedure training lack uniformity among different hospitals in The Netherlands. Within the process of developing a new regional laparoscopic training curriculum, a uniform and transferrable curriculum was constructed for a series of laparoscopic procedures. The aim of this study was to determine regional expert consensus regarding the key steps for laparoscopic appendectomy and cholecystectomy using Delphi methodology. Lists of suggested key steps for laparoscopic appendectomy and cholecystectomy were created using surgical textbooks, available guidelines, and local practice. A total of 22 experts, working for teaching hospitals throughout the region, were asked to rate the suggested key steps for both procedures on a Likert scale from 1-5. Consensus was reached with Crohnbach's α ≥ 0.90. Of the 22 experts, 21 completed and returned the survey (95%). Data analysis already showed consensus after the first round of Delphi on the key steps for laparoscopic appendectomy (Crohnbach's α = 0.92) and laparoscopic cholecystectomy (Crohnbach's α = 0.90). After the second round, 15 proposed key steps for laparoscopic appendectomy and 30 proposed key steps for laparoscopic cholecystectomy were rated as important (≥4 by at least 80% of the expert panel). These key steps were used for the further development of the training curriculum. By using the Delphi methodology, regional consensus was reached on the key steps for laparoscopic appendectomy and cholecystectomy. These key steps are going to be used for standardized training and evaluation purposes in a new regional laparoscopic curriculum. Copyright © 2014 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Guiding gate-etch process development using 3D surface reaction modeling for 7nm and beyond

NASA Astrophysics Data System (ADS)

Dunn, Derren; Sporre, John R.; Deshpande, Vaibhav; Oulmane, Mohamed; Gull, Ronald; Ventzek, Peter; Ranjan, Alok

2017-03-01

Increasingly, advanced process nodes such as 7nm (N7) are fundamentally 3D and require stringent control of critical dimensions over high aspect ratio features. Process integration in these nodes requires a deep understanding of complex physical mechanisms to control critical dimensions from lithography through final etch. Polysilicon gate etch processes are critical steps in several device architectures for advanced nodes that rely on self-aligned patterning approaches to gate definition. These processes are required to meet several key metrics: (a) vertical etch profiles over high aspect ratios; (b) clean gate sidewalls free of etch process residue; (c) minimal erosion of liner oxide films protecting key architectural elements such as fins; and (e) residue free corners at gate interfaces with critical device elements. In this study, we explore how hybrid modeling approaches can be used to model a multi-step finFET polysilicon gate etch process. Initial parts of the patterning process through hardmask assembly are modeled using process emulation. Important aspects of gate definition are then modeled using a particle Monte Carlo (PMC) feature scale model that incorporates surface chemical reactions.1 When necessary, species and energy flux inputs to the PMC model are derived from simulations of the etch chamber. The modeled polysilicon gate etch process consists of several steps including a hard mask breakthrough step (BT), main feature etch steps (ME), and over-etch steps (OE) that control gate profiles at the gate fin interface. An additional constraint on this etch flow is that fin spacer oxides are left intact after final profile tuning steps. A natural optimization required from these processes is to maximize vertical gate profiles while minimizing erosion of fin spacer films.2

Branching Search

NASA Astrophysics Data System (ADS)

Eliazar, Iddo

2017-12-01

Search processes play key roles in various scientific fields. A widespread and effective search-process scheme, which we term Restart Search, is based on the following restart algorithm: i) set a timer and initiate a search task; ii) if the task was completed before the timer expired, then stop; iii) if the timer expired before the task was completed, then go back to the first step and restart the search process anew. In this paper a branching feature is added to the restart algorithm: at every transition from the algorithm's third step to its first step branching takes place, thus multiplying the search effort. This branching feature yields a search-process scheme which we term Branching Search. The running time of Branching Search is analyzed, closed-form results are established, and these results are compared to the coresponding running-time results of Restart Search.

Energy landscape-driven non-equilibrium evolution of inherent structure in disordered material

DOE PAGES

Fan, Yue; Iwashita, Takuya; Egami, Takeshi

2017-05-19

Complex states in glasses can be neatly expressed by the potential energy landscape (PEL). But, because PEL is highly multi-dimensional it is difficult to describe how the system moves around in PEL. We demonstrate that it is possible to predict the evolution of macroscopic state in a metallic glass, such as ageing and rejuvenation, through a set of simple equations describing excitations in the PEL. The key to this simplification is the realization that the step of activation from the initial state to the saddle point in PEL and the following step of relaxation to the final state are essentiallymore » decoupled. Furthermore, the model shows that the interplay between activation and relaxation in PEL is the key driving force that simultaneously explains both the equilibrium of supercooled liquid and the thermal hysteresis observed in experiments. It further predicts anomalous peaks in truncated thermal scanning, validated by independent molecular dynamics simulation.« less

Go ahead, grow a head! A planarian's guide to anterior regeneration

PubMed Central

2016-01-01

Abstract The unique ability of some planarian species to regenerate a head de novo, including a functional brain, provides an experimentally accessible system in which to study the mechanisms underlying regeneration. Here, we summarize the current knowledge on the key steps of planarian head regeneration (head‐versus‐tail decision, anterior pole formation and head patterning) and their molecular and cellular basis. Moreover, instructive properties of the anterior pole as a putative organizer and in coordinating anterior midline formation are discussed. Finally, we highlight that regeneration initiation occurs in a two‐step manner and hypothesize that wound‐induced and existing positional cues interact to detect tissue loss and together determine the appropriate regenerative outcomes. PMID:27606065

Human Cytomegalovirus Strategies to Maintain and Promote mRNA Translation

PubMed Central

Vincent, Heather A.; Ziehr, Benjamin; Moorman, Nathaniel J.

2016-01-01

mRNA translation requires the ordered assembly of translation initiation factors and ribosomal subunits on a transcript. Host signaling pathways regulate each step in this process to match levels of protein synthesis to environmental cues. In response to infection, cells activate multiple defenses that limit viral protein synthesis, which viruses must counteract to successfully replicate. Human cytomegalovirus (HCMV) inhibits host defenses that limit viral protein expression and manipulates host signaling pathways to promote the expression of both host and viral proteins necessary for virus replication. Here we review key regulatory steps in mRNA translation, and the strategies used by HCMV to maintain protein synthesis in infected cells. PMID:27089357

Targeting the eIF4F translation initiation complex: a critical nexus for cancer development.

PubMed

Pelletier, Jerry; Graff, Jeremy; Ruggero, Davide; Sonenberg, Nahum

2015-01-15

Elevated protein synthesis is an important feature of many cancer cells and often arises as a consequence of increased signaling flux channeled to eukaryotic initiation factor 4F (eIF4F), the key regulator of the mRNA-ribosome recruitment phase of translation initiation. In many cellular and preclinical models of cancer, eIF4F deregulation results in changes in translational efficiency of specific mRNA classes. Importantly, many of these mRNAs code for proteins that potently regulate critical cellular processes, such as cell growth and proliferation, enhanced cell survival and cell migration that ultimately impinge on several hallmarks of cancer, including increased angiogenesis, deregulated growth control, enhanced cellular survival, epithelial-to-mesenchymal transition, invasion, and metastasis. By being positioned as the molecular nexus downstream of key oncogenic signaling pathways (e.g., Ras, PI3K/AKT/TOR, and MYC), eIF4F serves as a direct link between important steps in cancer development and translation initiation. Identification of mRNAs particularly responsive to elevated eIF4F activity that typifies tumorigenesis underscores the critical role of eIF4F in cancer and raises the exciting possibility of developing new-in-class small molecules targeting translation initiation as antineoplastic agents. ©2014 American Association for Cancer Research.

Interfacial adhesion improvement in carbon fiber/carbon nanotube reinforced hybrid composites by the application of a reactive hybrid resin initiated by gamma irradiation

NASA Astrophysics Data System (ADS)

Szebényi, G.; Faragó, D.; Lámfalusi, Cs.; Göbl, R.

2018-04-01

Interfacial adhesion is a key factor in composite materials. The effective co-working of the reinforcing materials and matrix is essential for the proper load transfer between them, and to achieve the desired reinforcing effect. In case of nanocomposites, especially carbon nanotube (CNT) reinforced nanocomposites the adhesion between the CNTs and the polymer matrix is poor. To improve the interfacial adhesion and exploit the reinforcing effect of these nanoparticles a two step curable epoxy (EP)/vinylester (VE) hybrid resin system was developed where the EP is cured using hardener in the first step, during the composite production, and in the second step the curing of the VE is initiated by gamma irradiation, which also activates the reinforcing materials and the cured matrix component. A total of six carbon fiber reinforced composite systems were compared with neat epoxy and EP/VE hybrid matrices with and without chemical initiator and MWCNT nano-reinforcement. The effect of gamma irradiation was investigated at four absorbed dose levels. According to our three point bending and interlaminar shear test results the adhesion has improved between all constituents of the composite system. It was demonstrated that gamma irradiation has beneficial effect on the static mechanical, especially interlaminar properties of both micro- and nanocomposites in terms of modulus, strength and interlaminar shear strength.

Search for supporting methodologies - Or how to support SEI for 35 years

NASA Technical Reports Server (NTRS)

Handley, Thomas H., Jr.; Masline, Richard C.

1991-01-01

Concepts relevant to the development of an evolvable information management system are examined in terms of support for the Space Exploration Initiative. The issues of interoperability within NASA and industry initiatives are studied including the Open Systems Interconnection standard and the operating system of the Open Software Foundation. The requirements of partitioning functionality into separate areas are determined with attention given to the infrastructure required to ensure system-wide compliance. The need for a decision-making context is a key to the distributed implementation of the program, and this environment is concluded to be next step in developing an evolvable, interoperable, and securable support network.

Vibrational spectroscopy reveals the initial steps of biological hydrogen evolution† †Electronic supplementary information (ESI) available: Complementary resonance Raman and infrared spectroscopic data. See DOI: 10.1039/c6sc01098a Click here for additional data file.

PubMed Central

Katz, S.; Noth, J.; Shafaat, H. S.; Happe, T.; Hildebrandt, P.

2016-01-01

[FeFe] hydrogenases are biocatalytic model systems for the exploitation and investigation of catalytic hydrogen evolution. Here, we used vibrational spectroscopic techniques to characterize, in detail, redox transformations of the [FeFe] and [4Fe4S] sub-sites of the catalytic centre (H-cluster) in a monomeric [FeFe] hydrogenase. Through the application of low-temperature resonance Raman spectroscopy, we discovered a novel metastable intermediate that is characterized by an oxidized [FeIFeII] centre and a reduced [4Fe4S]1+ cluster. Based on this unusual configuration, this species is assigned to the first, deprotonated H-cluster intermediate of the [FeFe] hydrogenase catalytic cycle. Providing insights into the sequence of initial reaction steps, the identification of this species represents a key finding towards the mechanistic understanding of biological hydrogen evolution. PMID:28451119

Mapping Coaches' Views of Participation in CrossFit to the Integrated Theory of Health Behavior Change and Sense of Community.

PubMed

Heinrich, Katie M; Carlisle, Taran; Kehler, Ainslie; Cosgrove, Sarah J

Group-based training through CrossFit has recently exploded in popularity. Anecdotally, participants often make lifestyle changes and experience improved fitness. Participation factors were mapped to the Integrated Theory of Health Behavior Change and "sense of community" constructs. Key informant interviews were conducted with 6 CrossFit gym owners/coaches. Data were thematically coded with NVivo 10. Results revealed key factors that both facilitated and restricted participation in CrossFit. Findings provide implications for future theory application and highlight how to improve initiation and adherence by capitalizing on community building and taking steps to reduce intimidation and cost, facilitate realistic goals, and ensure social support.

Study the effect of striping in two-step anodizing process on pore arrangement of nano-porous alumina

NASA Astrophysics Data System (ADS)

Rahimi, M. H.; Saramad, S.; Tabaian, S. H.; Marashi, S. P.; Zolfaghari, A.; Mohammadalinezhad, M.

2009-10-01

Two-step anodic oxidation of aluminum is generally employed to produce the ordered porous anodized alumina (PAA). Dissolving away (striping) the oxide film after the first anodizing step plays a key role in the final arrangement of nano-pores. In this work, different striping durations between 1 and 6 h were applied to the sample that was initially anodized at a constant voltage of 40 V at 17 °C for 15 h. The striping duration of 3 h was realized as the optimum time for achieving the best ordering degree for the pores. Scanning electron microscopy (SEM) was used during and at the end of the process to examine the cross section and finishing surface of the specimens. Linear-angular fast Fourier transform (LA-FFT), an in-house technique based on MATLAB software, was employed to assess the ordering degree of the anodized samples.

Bringing Value-Based Perspectives to Care: Including Patient and Family Members in Decision-Making Processes.

PubMed

Kohler, Graeme; Sampalli, Tara; Ryer, Ashley; Porter, Judy; Wood, Les; Bedford, Lisa; Higgins-Bowser, Irene; Edwards, Lynn; Christian, Erin; Dunn, Susan; Gibson, Rick; Ryan Carson, Shannon; Vallis, Michael; Zed, Joanna; Tugwell, Barna; Van Zoost, Colin; Canfield, Carolyn; Rivoire, Eleanor

2017-03-06

Recent evidence shows that patient engagement is an important strategy in achieving a high performing healthcare system. While there is considerable evidence of implementation initiatives in direct care context, there is limited investigation of implementation initiatives in decision-making context as it relates to program planning, service delivery and developing policies. Research has also shown a gap in consistent application of system-level strategies that can effectively translate organizational policies around patient and family engagement into practice. The broad objective of this initiative was to develop a system-level implementation strategy to include patient and family advisors (PFAs) at decision-making points in primary healthcare (PHC) based on wellestablished evidence and literature. In this opportunity sponsored by the Canadian Foundation for Healthcare Improvement (CFHI) a co-design methodology, also well-established was applied in identifying and developing a suitable implementation strategy to engage PFAs as members of quality teams in PHC. Diabetes management centres (DMCs) was selected as the pilot site to develop the strategy. Key steps in the process included review of evidence, review of the current state in PHC through engagement of key stakeholders and a co-design approach. The project team included a diverse representation of members from the PHC system including patient advisors, DMC team members, system leads, providers, Public Engagement team members and CFHI improvement coaches. Key outcomes of this 18-month long initiative included development of a working definition of patient and family engagement, development of a Patient and Family Engagement Resource Guide and evaluation of the resource guide. This novel initiative provided us an opportunity to develop a supportive system-wide implementation plan and a strategy to include PFAs in decision-making processes in PHC. The well-established co-design methodology further allowed us to include value-based (customer driven quality and experience of care) perspectives of several important stakeholders including patient advisors. The next step will be to implement the strategy within DMCs, spread the strategy PHC, both locally and provincially with a focus on sustainability. © 2017 The Author(s); Published by Kerman University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Affordable Exploration of Mars: Recommendations from a Community Workshop on Sustainable Initial Human Missions

NASA Technical Reports Server (NTRS)

Thronson, Harley; Carberry, Chris; Cassady, R. J.; Cooke, Doug; Hopkins, Joshua; Perino, Maria A.; Kirkpatrick, Jim; Raftery, Michael; Westenberg, Artemis; Zucker, Richard

2013-01-01

There is a growing consensus that within two decades initial human missions to Mars are affordable under plausible budget assumptions and with sustained international participation. In response to this idea, a distinguished group of experts from the Mars exploration stakeholder communities attended the "Affording Mars" workshop at George Washington University in December, 2013. Participants reviewed and discussed scenarios for affordable and sustainable human and robotic exploration of Mars, the role of the International Space Station over the coming decade as the essential early step toward humans to Mars, possible "bridge" missions in the 2020s, key capabilities required for affordable initial missions, international partnerships, and a usable definition of affordability and sustainability. We report here the findings, observations, and recommendations that were agreed to at that workshop.

Procedural key steps in laparoscopic colorectal surgery, consensus through Delphi methodology.

PubMed

Dijkstra, Frederieke A; Bosker, Robbert J I; Veeger, Nicolaas J G M; van Det, Marc J; Pierie, Jean Pierre E N

2015-09-01

While several procedural training curricula in laparoscopic colorectal surgery have been validated and published, none have focused on dividing surgical procedures into well-identified segments, which can be trained and assessed separately. This enables the surgeon and resident to focus on a specific segment, or combination of segments, of a procedure. Furthermore, it will provide a consistent and uniform method of training for residents rotating through different teaching hospitals. The goal of this study was to determine consensus on the key steps of laparoscopic right hemicolectomy and laparoscopic sigmoid colectomy among experts in our University Medical Center and affiliated hospitals. This will form the basis for the INVEST video-assisted side-by-side training curriculum. The Delphi method was used for determining consensus on key steps of both procedures. A list of 31 steps for laparoscopic right hemicolectomy and 37 steps for laparoscopic sigmoid colectomy was compiled from textbooks and national and international guidelines. In an online questionnaire, 22 experts in 12 hospitals within our teaching region were invited to rate all steps on a Likert scale on importance for the procedure. Consensus was reached in two rounds. Sixteen experts agreed to participate. Of these 16 experts, 14 (88%) completed the questionnaire for both procedures. Of the 14 who completed the first round, 13 (93%) completed the second round. Cronbach's alpha was 0.79 for the right hemicolectomy and 0.91 for the sigmoid colectomy, showing high internal consistency between the experts. For the right hemicolectomy, 25 key steps were established; for the sigmoid colectomy, 24 key steps were established. Expert consensus on the key steps for laparoscopic right hemicolectomy and laparoscopic sigmoid colectomy was reached. These key steps will form the basis for a video-assisted teaching curriculum.

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.

Initial condition of stochastic self-assembly

NASA Astrophysics Data System (ADS)

Davis, Jason K.; Sindi, Suzanne S.

2016-02-01

The formation of a stable protein aggregate is regarded as the rate limiting step in the establishment of prion diseases. In these systems, once aggregates reach a critical size the growth process accelerates and thus the waiting time until the appearance of the first critically sized aggregate is a key determinant of disease onset. In addition to prion diseases, aggregation and nucleation is a central step of many physical, chemical, and biological process. Previous studies have examined the first-arrival time at a critical nucleus size during homogeneous self-assembly under the assumption that at time t =0 the system was in the all-monomer state. However, in order to compare to in vivo biological experiments where protein constituents inherited by a newly born cell likely contain intermediate aggregates, other possibilities must be considered. We consider one such possibility by conditioning the unique ergodic size distribution on subcritical aggregate sizes; this least-informed distribution is then used as an initial condition. We make the claim that this initial condition carries fewer assumptions than an all-monomer one and verify that it can yield significantly different averaged waiting times relative to the all-monomer condition under various models of assembly.

Pneumolysin plays a key role at the initial step of establishing pneumococcal nasal colonization.

PubMed

Hotomi, Muneki; Yuasa, Jun; Briles, David E; Yamanaka, Noboru

2016-09-01

Nasopharyngeal colonization by Streptococcus pneumoniae is an important initial step for the subsequent development of pneumococcal infections. Pneumococci have many virulence factors that play a role in colonization. Pneumolysin (PLY), a pivotal pneumococcal virulence factor for invasive disease, causes severe tissue damage and inflammation with disruption of epithelial tight junctions. In this study, we evaluated the role of PLY in nasal colonization of S. pneumoniae using a mouse colonization model. A reduction of numbers of PLY-deficient pneumococci recovered from nasal tissue, as well as nasal wash, was observed at days 1 and 2 post-intranasal challenges, but not later. The findings strongly support an important role for PLY in the initial establishment nasal colonization. PLY-dependent invasion of local nasal mucosa may be required to establish nasal colonization with S. pneumoniae. The data help provide a rationale to explain why an organism that exists as an asymptomatic colonizer has evolved virulence factors that enable it to occasionally invade and kill its hosts. Thus, the same pneumococcal virulence factor, PLY that can contribute to killing the host, may also play a role early in the establishment of nasopharynx carriage.

A policy framework for accelerating adoption of new vaccines

PubMed Central

Hajjeh, Rana; Wecker, John; Cherian, Thomas; O'Brien, Katherine L; Knoll, Maria Deloria; Privor-Dumm, Lois; Kvist, Hans; Nanni, Angeline; Bear, Allyson P; Santosham, Mathuram

2010-01-01

Rapid uptake of new vaccines can improve health and wealth and contribute to meeting Millennium Development Goals. In the past, however, the introduction and use of new vaccines has been characterized by delayed uptake in the countries where the need is greatest. Based on experience with accelerating the adoption of Hib, pneumococcal and rotavirus vaccines, we propose here a framework for new vaccine adoption that may be useful for future efforts. The framework organizes the major steps in the process into a continuum from evidence to policy, implementation and finally access. It highlights the important roles of different actors at various times in the process and may allow new vaccine initiatives to save time and improve their efficiency by anticipating key steps and actions. PMID:21150269

A policy framework for accelerating adoption of new vaccines.

PubMed

Levine, Orin S; Hajjeh, Rana; Wecker, John; Cherian, Thomas; O'Brien, Katherine L; Knoll, Maria Deloria; Privor-Dumm, Lois; Kvist, Hans; Nanni, Angeline; Bear, Allyson P; Santosham, Mathuram

2010-12-01

Rapid uptake of new vaccines can improve health and wealth and contribute to meeting Millennium Development Goals. In the past, however, the introduction and use of new vaccines has been characterized by delayed uptake in the countries where the need is greatest. Based on experience with accelerating the adoption of Hib, pneumococcal and rotavirus vaccines, we propose here a framework for new vaccine adoption that may be useful for future efforts. The framework organizes the major steps in the process into a continuum from evidence to policy, implementation and finally access. It highlights the important roles of different actors at various times in the process and may allow new vaccine initiatives to save time and improve their efficiency by anticipating key steps and actions.

Direct visualization reveals kinetics of meiotic chromosome synapsis

DOE PAGES

Rog, Ofer; Dernburg, Abby  F.

2015-03-17

The synaptonemal complex (SC) is a conserved protein complex that stabilizes interactions along homologous chromosomes (homologs) during meiosis. The SC regulates genetic exchanges between homologs, thereby enabling reductional division and the production of haploid gametes. Here, we directly observe SC assembly (synapsis) by optimizing methods for long-term fluorescence recording in C. elegans. We report that synapsis initiates independently on each chromosome pair at or near pairing centers—specialized regions required for homolog associations. Once initiated, the SC extends rapidly and mostly irreversibly to chromosome ends. Quantitation of SC initiation frequencies and extension rates reveals that initiation is a rate-limiting step inmore » homolog interactions. Eliminating the dynein-driven chromosome movements that accompany synapsis severely retards SC extension, revealing a new role for these conserved motions. This work provides the first opportunity to directly observe and quantify key aspects of meiotic chromosome interactions and will enable future in vivo analysis of germline processes.« less

Genes related to antioxidant metabolism are involved in Methylobacterium mesophilicum-soybean interaction.

PubMed

Araújo, Welington Luiz; Santos, Daiene Souza; Dini-Andreote, Francisco; Salgueiro-Londoño, Jennifer Katherine; Camargo-Neves, Aline Aparecida; Andreote, Fernando Dini; Dourado, Manuella Nóbrega

2015-10-01

The genus Methylobacterium is composed of pink-pigmented methylotrophic bacterial species that are widespread in natural environments, such as soils, stream water and plants. When in association with plants, this genus colonizes the host plant epiphytically and/or endophytically. This association is known to promote plant growth, induce plant systemic resistance and inhibit plant infection by phytopathogens. In the present study, we focused on evaluating the colonization of soybean seedling-roots by Methylobacterium mesophilicum strain SR1.6/6. We focused on the identification of the key genes involved in the initial step of soybean colonization by methylotrophic bacteria, which includes the plant exudate recognition and adaptation by planktonic bacteria. Visualization by scanning electron microscopy revealed that M. mesophilicum SR1.6/6 colonizes soybean roots surface effectively at 48 h after inoculation, suggesting a mechanism for root recognition and adaptation before this period. The colonization proceeds by the development of a mature biofilm on roots at 96 h after inoculation. Transcriptomic analysis of the planktonic bacteria (with plant) revealed the expression of several genes involved in membrane transport, thus confirming an initial metabolic activation of bacterial responses when in the presence of plant root exudates. Moreover, antioxidant genes were mostly expressed during the interaction with the plant exudates. Further evaluation of stress- and methylotrophic-related genes expression by qPCR showed that glutathione peroxidase and glutathione synthetase genes were up-regulated during the Methylobacterium-soybean interaction. These findings support that glutathione (GSH) is potentially a key molecule involved in cellular detoxification during plant root colonization. In addition to methylotrophic metabolism, antioxidant genes, mainly glutathione-related genes, play a key role during soybean exudate recognition and adaptation, the first step in bacterial colonization.

The roles of SSU processome components and surveillance factors in the initial processing of human ribosomal RNA

PubMed Central

Sloan, Katherine E.; Bohnsack, Markus T.; Schneider, Claudia; Watkins, Nicholas J.

2014-01-01

During eukaryotic ribosome biogenesis, three of the mature ribosomal (r)RNAs are released from a single precursor transcript (pre-rRNA) by an ordered series of endonucleolytic cleavages and exonucleolytic processing steps. Production of the 18S rRNA requires the removal of the 5′ external transcribed spacer (5′ETS) by endonucleolytic cleavages at sites A0 and A1/site 1. In metazoans, an additional cleavage in the 5′ETS, at site A′, upstream of A0, has also been reported. Here, we have investigated how A′ processing is coordinated with assembly of the early preribosomal complex. We find that only the tUTP (UTP-A) complex is critical for A′ cleavage, while components of the bUTP (UTP-B) and U3 snoRNP are important, but not essential, for efficient processing at this site. All other factors involved in the early stages of 18S rRNA processing that were tested here function downstream from this processing step. Interestingly, we show that the RNA surveillance factors XRN2 and MTR4 are also involved in A′ cleavage in humans. A′ cleavage is largely bypassed when XRN2 is depleted, and we also discover that A′ cleavage is not always the initial processing event in all cell types. Together, our data suggest that A′ cleavage is not a prerequisite for downstream pre-rRNA processing steps and may, in fact, represent a quality control step for initial pre-rRNA transcripts. Furthermore, we show that components of the RNA surveillance machinery, including the exosome and TRAMP complexes, also play key roles in the recycling of excised spacer fragments and degradation of aberrant pre-rRNAs in human cells. PMID:24550520

One-Pot Synthesis of Fused Pyrroles via a Key Gold Catalysis-Triggered Cascade

PubMed Central

Zheng, Zhitong; Tu, Huangfei

2014-01-01

A two-step, one-pot synthesis of fused pyrroles is realized by firstly condensing N-alkynylhydroxammonium salt with readily enolizable ketone under mild basic condition and then subjecting the reaction mixture to a gold catalyst, which triggers a cascade reaction featured by a facile initial 3.3-sigmatropic rearrangement of the gold catalysis product, i.e., an N,O-dialkenylhydroxamine. The reaction provides a facile access to polycyclic pyrroles in moderate to good yields. PMID:24482098

Key Implementation Insights from the Collaborating Districts Initiative: A Multiyear Effort to Help School Districts Integrate Social and Emotional Learning across All Aspects of Their Work: What Have We Learned? What Impact Have We Seen? What's Next?

ERIC Educational Resources Information Center

Collaborative for Academic, Social, and Emotional Learning, 2017

2017-01-01

Six years ago the Collaborative for Academic, Social, and Emotional Learning (CASEL) took the unprecedented step of launching an effort to study and scale high-quality, evidence-based academic, social, and emotional learning in eight of the largest and most complex school systems in the country: Anchorage, Austin, Chicago, Cleveland, Nashville,…

Joint Force Quarterly. Issue 75, 4th Quarter, October 2014

DTIC Science & Technology

2014-10-01

deployment and retrograde as Operation Enduring Freedom winds down. Manning has varied in step with movement tempo, from the initial cadre of 42 to a high...Additionally, T.X. Hammes of the National Defense University pro- motes a distant blockade of China that “establishes a set of concentric rings that denies...Development (USAID) for construction of the Ring Road because it was deemed a “vital economic trade link” and a “key component to stability and

Consequence-driven cyber-informed engineering (CCE)

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

Freeman, Sarah G.; St Michel, Curtis; Smith, Robert

The Idaho National Lab (INL) is leading a high-impact, national security-level initiative to reprioritize the way the nation looks at high-consequence risk within the industrial control systems (ICS) environment of the country’s most critical infrastructure and other national assets. The Consequence-driven Cyber-informed Engineering (CCE) effort provides both private and public organizations with the steps required to examine their own environments for high-impact events/risks; identify implementation of key devices and components that facilitate that risk; illuminate specific, plausible cyber attack paths to manipulate these devices; and develop concrete mitigations, protections, and tripwires to address the high-consequence risk. The ultimate goal ofmore » the CCE effort is to help organizations take the steps necessary to thwart cyber attacks from even top-tier, highly resourced adversaries that would result in a catastrophic physical effect. CCE participants are encouraged to work collaboratively with each other and with key U.S. Government (USG) contributors to establish a coalition, maximizing the positive effect of lessons-learned and further contributing to the protection of critical infrastructure and other national assets.« less

Phosphorylation of a Tyrosine Residue on Zap70 by Lck and Its Subsequent Binding via an SH2 Domain May Be a Key Gatekeeper of T Cell Receptor Signaling In Vivo.

PubMed

Thill, Peter A; Weiss, Arthur; Chakraborty, Arup K

2016-09-15

The initiation of signaling in T lymphocytes in response to the binding of the T cell receptor (TCR) to cognate ligands is a key step in the emergence of adaptive immune responses. Conventional models posit that TCR signaling is initiated by the phosphorylation of receptor-associated immune receptor activation motifs (ITAMs). The cytoplasmic tyrosine kinase Zap70 binds to phosphorylated ITAMs, is subsequently activated, and then propagates downstream signaling. While evidence for such models is provided by experiments with cell lines, in vivo, Zap70 is bound to phosphorylated ITAMs in resting T cells. However, Zap70 is activated only upon TCR binding to cognate ligand. We report the results of computational studies of a new model for the initiation of TCR signaling that incorporates these in vivo observations. Importantly, the new model is shown to allow better and faster TCR discrimination between self-ligands and foreign ligands. The new model is consistent with many past experimental observations, and experiments that could further test the model are proposed. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Mapping Coaches’ Views of Participation in CrossFit to the Integrated Theory of Health Behavior Change and Sense of Community

PubMed Central

Heinrich, Katie M.; Carlisle, Taran; Kehler, Ainslie; Cosgrove, Sarah J.

2017-01-01

Group-based training through CrossFit has recently exploded in popularity. Anecdotally, participants often make lifestyle changes and experience improved fitness. Participation factors were mapped to the Integrated Theory of Health Behavior Change and “sense of community” constructs. Key informant interviews were conducted with 6 CrossFit gym owners/coaches. Data were thematically coded with NVivo 10. Results revealed key factors that both facilitated and restricted participation in CrossFit. Findings provide implications for future theory application and highlight how to improve initiation and adherence by capitalizing on community building and taking steps to reduce intimidation and cost, facilitate realistic goals, and ensure social support. PMID:27870750

The Impact of a Community-Based Chronic Disease Prevention Initiative: Evaluation Findings from "Steps to Health King County"

ERIC Educational Resources Information Center

Cheadle, Allen; Bourcier, Emily; Krieger, James; Beery, William; Smyser, Michael; Vinh, Diana V.; Lessler, Dan; Alfonsi, Lorrie

2011-01-01

"Steps to Health King County" ("Steps KC"; Seattle, Washington) was one of 40 community-level initiatives funded in 2003 as part of the "Steps to a HealthierUS" initiative. "Steps KC" goals included reducing the impact of chronic diseases through a comprehensive, coordinated approach and reducing health…

STEP-TRAMM - A modeling interface for simulating localized rainfall induced shallow landslides and debris flow runout pathways

NASA Astrophysics Data System (ADS)

von Ruette, Jonas; Lehmann, Peter; Fan, Linfeng; Bickel, Samuel; Or, Dani

2017-04-01

Landslides and subsequent debris-flows initiated by rainfall represent a ubiquitous natural hazard in steep mountainous regions. We integrated a landslide hydro-mechanical triggering model and associated debris flow runout pathways with a graphical user interface (GUI) to represent these natural hazards in a wide range of catchments over the globe. The STEP-TRAMM GUI provides process-based locations and sizes of landslides patterns using digital elevation models (DEM) from SRTM database (30 m resolution) linked with soil maps from global database SoilGrids (250 m resolution) and satellite based information on rainfall statistics for the selected region. In a preprocessing step STEP-TRAMM models soil depth distribution and complements soil information that jointly capture key hydrological and mechanical properties relevant to local soil failure representation. In the presentation we will discuss feature of this publicly available platform and compare landslide and debris flow patterns for different regions considering representative intense rainfall events. Model outcomes will be compared for different spatial and temporal resolutions to test applicability of web-based information on elevation and rainfall for hazard assessment.

One Step Quantum Key Distribution Based on EPR Entanglement.

PubMed

Li, Jian; Li, Na; Li, Lei-Lei; Wang, Tao

2016-06-30

A novel quantum key distribution protocol is presented, based on entanglement and dense coding and allowing asymptotically secure key distribution. Considering the storage time limit of quantum bits, a grouping quantum key distribution protocol is proposed, which overcomes the vulnerability of first protocol and improves the maneuverability. Moreover, a security analysis is given and a simple type of eavesdropper's attack would introduce at least an error rate of 46.875%. Compared with the "Ping-pong" protocol involving two steps, the proposed protocol does not need to store the qubit and only involves one step.

Evaluation of operating conditions for sustainable harvesting of microalgal biomass applying electrochemical method using non sacrificial electrodes.

PubMed

Misra, Rohit; Guldhe, Abhishek; Singh, Poonam; Rawat, Ismail; Stenström, Thor Axel; Bux, Faizal

2015-01-01

The efficient harvesting of microalgae is considered to be one of the challenging steps of algal biofuel production and a key factor limiting the commercial use of microalgae. To overcome the limitation of metallic electrodes depletion, the application of non-sacrificial electrode was investigated for the electrochemical harvesting (ECH) of microalgae. The effect of applied current, addition of electrolyte and initial pH were parameters investigated. The highest recovery efficiency of 83% was obtained for Scenedesmus obliquus at 1.5A, initial pH 9 and 6gL(-)(1) NaCl with power consumption of 3.84kWhkg(-)(1). Recovery efficiency of ECH process was comparable to literature reported centrifugation, filtration and chemical flocculation techniques but with a much lower power consumption. The ECH process with addition of electrolyte enhanced the lipid extraction by 22% without any adverse effects. The ECH process with non sacrificial carbon electrodes could be a possible harvesting step at commercial scale microalgal biomass production. Copyright © 2014 Elsevier Ltd. All rights reserved.

A National Cohort Study of U.S. Medical School Students Who Initially Failed Step 1 of the United States Medical Licensing Examination

PubMed Central

Andriole, Dorothy A.; Jeffe, Donna B.

2012-01-01

Purpose To describe educational outcomes for a national cohort of U.S. medical students who initially failed Step 1 of the United States Medical Licensing Examination Method The authors analyzed de-identified, individualized records for the 1993–2000 cohort of U.S. medical school matriculants who both initially failed Step l and were no longer in medical school as of March 2, 2009, using multivariable logistic regression to identify factors associated with attempting, and initially passing, Step 2 Clinical Knowledge (CK). Results Of 6,594 students who failed Step l, 5,985 (90.8%) took Step 2CK. Women and Asian/Pacific Islander students were more likely to attempt Step 2CK; more recent matriculants and students with lower failing Step 1 scores were less likely. Of the 5,985 students who attempted Step 2CK, 4,168 (69.6%) initially passed. Women, students with higher Medical College Admission Test scores, and more recent matriculants were more likely to pass Step 2CK; Asian/Pacific Islander students, underrepresented minority students, older students, and students with lower failing Step 1 scores were less likely. Ninety percent of students in the study sample (5,952/6,594) ultimately graduated from medical school, including 99.5% (4,148/4,168) of those who initially passed, 96.7% (1,757/1,817) of those who initially failed, and 7.7% (47/609) of those who never attempted Step 2CK. Conclusions The authors identified variables associated with educational outcomes among students who failed Step l. These findings can inform medical schools’ efforts to develop tailored interventions to maximize the likelihood that students will take Step 2CK and pass it on the first attempt. PMID:22361789

Oxidation of F-actin controls the terminal steps of cytokinesis

PubMed Central

Frémont, Stéphane; Hammich, Hussein; Bai, Jian; Wioland, Hugo; Klinkert, Kerstin; Rocancourt, Murielle; Kikuti, Carlos; Stroebel, David; Romet-Lemonne, Guillaume; Pylypenko, Olena; Houdusse, Anne; Echard, Arnaud

2017-01-01

Cytokinetic abscission, the terminal step of cell division, crucially depends on the local constriction of ESCRT-III helices after cytoskeleton disassembly. While the microtubules of the intercellular bridge are cut by the ESCRT-associated enzyme Spastin, the mechanism that clears F-actin at the abscission site is unknown. Here we show that oxidation-mediated depolymerization of actin by the redox enzyme MICAL1 is key for ESCRT-III recruitment and successful abscission. MICAL1 is recruited to the abscission site by the Rab35 GTPase through a direct interaction with a flat three-helix domain found in MICAL1 C terminus. Mechanistically, in vitro assays on single actin filaments demonstrate that MICAL1 is activated by Rab35. Moreover, in our experimental conditions, MICAL1 does not act as a severing enzyme, as initially thought, but instead induces F-actin depolymerization from both ends. Our work reveals an unexpected role for oxidoreduction in triggering local actin depolymerization to control a fundamental step of cell division. PMID:28230050

Characterization of Developer Application Methods Used in Fluorescent Penetrant Inspection

NASA Astrophysics Data System (ADS)

Brasche, L. J. H.; Lopez, R.; Eisenmann, D.

2006-03-01

Fluorescent penetrant inspection (FPI) is the most widely used inspection method for aviation components seeing use for production as well as an inservice inspection applications. FPI is a multiple step process requiring attention to the process parameters for each step in order to enable a successful inspection. A multiyear program is underway to evaluate the most important factors affecting the performance of FPI, to determine whether existing industry specifications adequately address control of the process parameters, and to provide the needed engineering data to the public domain. The final step prior to the inspection is the application of developer with typical aviation inspections involving the use of dry powder (form d) usually applied using either a pressure wand or dust storm chamber. Results from several typical dust storm chambers and wand applications have shown less than optimal performance. Measurements of indication brightness and recording of the UVA image, and in some cases, formal probability of detection (POD) studies were used to assess the developer application methods. Key conclusions and initial recommendations are provided.

Secretory immunoglobulin purification from whey by chromatographic techniques.

PubMed

Matlschweiger, Alexander; Engelmaier, Hannah; Himmler, Gottfried; Hahn, Rainer

2017-08-15

Secretory immunoglobulins (SIg) are a major fraction of the mucosal immune system and represent potential drug candidates. So far, platform technologies for their purification do not exist. SIg from animal whey was used as a model to develop a simple, efficient and potentially generic chromatographic purification process. Several chromatographic stationary phases were tested. A combination of two anion-exchange steps resulted in the highest purity. The key step was the use of a small-porous anion exchanger operated in flow-through mode. Diffusion of SIg into the resin particles was significantly hindered, while the main impurities, IgG and serum albumin, were bound. In this step, initial purity was increased from 66% to 89% with a step yield of 88%. In a second anion-exchange step using giga-porous material, SIg was captured and purified by step or linear gradient elution to obtain fractions with purities >95%. For the step gradient elution step yield of highly pure SIg was 54%. Elution of SIgA and SIgM with a linear gradient resulted in a step yield of 56% and 35%, respectively. Overall yields for both anion exchange steps were 43% for the combination of flow-through and step elution mode. Combination of flow-through and linear gradient elution mode resulted in a yield of 44% for SIgA and 39% for SIgM. The proposed process allows the purification of biologically active SIg from animal whey in preparative scale. For future applications, the process can easily be adopted for purification of recombinant secretory immunoglobulin species. Copyright © 2017 Elsevier B.V. All rights reserved.

A morphing-based scheme for large deformation analysis with stereo-DIC

NASA Astrophysics Data System (ADS)

Genovese, Katia; Sorgente, Donato

2018-05-01

A key step in the DIC-based image registration process is the definition of the initial guess for the non-linear optimization routine aimed at finding the parameters describing the pixel subset transformation. This initialization may result very challenging and possibly fail when dealing with pairs of largely deformed images such those obtained from two angled-views of not-flat objects or from the temporal undersampling of rapidly evolving phenomena. To address this problem, we developed a procedure that generates a sequence of intermediate synthetic images for gradually tracking the pixel subset transformation between the two extreme configurations. To this scope, a proper image warping function is defined over the entire image domain through the adoption of a robust feature-based algorithm followed by a NURBS-based interpolation scheme. This allows a fast and reliable estimation of the initial guess of the deformation parameters for the subsequent refinement stage of the DIC analysis. The proposed method is described step-by-step by illustrating the measurement of the large and heterogeneous deformation of a circular silicone membrane undergoing axisymmetric indentation. A comparative analysis of the results is carried out by taking as a benchmark a standard reference-updating approach. Finally, the morphing scheme is extended to the most general case of the correspondence search between two largely deformed textured 3D geometries. The feasibility of this latter approach is demonstrated on a very challenging case: the full-surface measurement of the severe deformation (> 150% strain) suffered by an aluminum sheet blank subjected to a pneumatic bulge test.

Infrared traffic image enhancement algorithm based on dark channel prior and gamma correction

NASA Astrophysics Data System (ADS)

Zheng, Lintao; Shi, Hengliang; Gu, Ming

2017-07-01

The infrared traffic image acquired by the intelligent traffic surveillance equipment has low contrast, little hierarchical differences in perceptions of image and the blurred vision effect. Therefore, infrared traffic image enhancement, being an indispensable key step, is applied to nearly all infrared imaging based traffic engineering applications. In this paper, we propose an infrared traffic image enhancement algorithm that is based on dark channel prior and gamma correction. In existing research dark channel prior, known as a famous image dehazing method, here is used to do infrared image enhancement for the first time. Initially, in the proposed algorithm, the original degraded infrared traffic image is transformed with dark channel prior as the initial enhanced result. A further adjustment based on the gamma curve is needed because initial enhanced result has lower brightness. Comprehensive validation experiments reveal that the proposed algorithm outperforms the current state-of-the-art algorithms.

Errors in Postural Preparation Lead to Increased Choice Reaction Times for Step Initiation in Older Adults

PubMed Central

Nutt, John G.; Horak, Fay B.

2011-01-01

Background. This study asked whether older adults were more likely than younger adults to err in the initial direction of their anticipatory postural adjustment (APA) prior to a step (indicating a motor program error), whether initial motor program errors accounted for reaction time differences for step initiation, and whether initial motor program errors were linked to inhibitory failure. Methods. In a stepping task with choice reaction time and simple reaction time conditions, we measured forces under the feet to quantify APA onset and step latency and we used body kinematics to quantify forward movement of center of mass and length of first step. Results. Trials with APA errors were almost three times as common for older adults as for younger adults, and they were nine times more likely in choice reaction time trials than in simple reaction time trials. In trials with APA errors, step latency was delayed, correlation between APA onset and step latency was diminished, and forward motion of the center of mass prior to the step was increased. Participants with more APA errors tended to have worse Stroop interference scores, regardless of age. Conclusions. The results support the hypothesis that findings of slow choice reaction time step initiation in older adults are attributable to inclusion of trials with incorrect initial motor preparation and that these errors are caused by deficits in response inhibition. By extension, the results also suggest that mixing of trials with correct and incorrect initial motor preparation might explain apparent choice reaction time slowing with age in upper limb tasks. PMID:21498431

One Step Quantum Key Distribution Based on EPR Entanglement

PubMed Central

Li, Jian; Li, Na; Li, Lei-Lei; Wang, Tao

2016-01-01

A novel quantum key distribution protocol is presented, based on entanglement and dense coding and allowing asymptotically secure key distribution. Considering the storage time limit of quantum bits, a grouping quantum key distribution protocol is proposed, which overcomes the vulnerability of first protocol and improves the maneuverability. Moreover, a security analysis is given and a simple type of eavesdropper’s attack would introduce at least an error rate of 46.875%. Compared with the “Ping-pong” protocol involving two steps, the proposed protocol does not need to store the qubit and only involves one step. PMID:27357865

Investigation of infrared radiation in rubidium vapor upon two-photon and step-by-step excitations of the initial level

NASA Astrophysics Data System (ADS)

Bimagambetov, T. S.

2011-12-01

Stimulated infrared (IR) 5.231-μm line radiation is obtained upon two-photon and step-by-step excitations of the initial level. Dependences of the line power on the concentration of atoms and laser frequency are investigated. The mechanism of initial level occupation is explained.

Investigation Of In-Line Monitoring Options At H Canyon/HB Line For Plutonium Oxide Production

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

Sexton, L.

2015-10-14

H Canyon and HB Line have a production goal of 1 MT per year of plutonium oxide feedstock for the MOX facility by FY17 (AFS-2 mission). In order to meet this goal, steps will need to be taken to improve processing efficiency. One concept for achieving this goal is to implement in-line process monitoring at key measurement points within the facilities. In-line monitoring during operations has the potential to increase throughput and efficiency while reducing costs associated with laboratory sample analysis. In the work reported here, we mapped the plutonium oxide process, identified key measurement points, investigated alternate technologies thatmore » could be used for in-line analysis, and initiated a throughput benefit analysis.« less

A framework for engaging stakeholders on the management of alien species.

PubMed

Novoa, Ana; Shackleton, Ross; Canavan, Susan; Cybèle, Cathleen; Davies, Sarah J; Dehnen-Schmutz, Katharina; Fried, Jana; Gaertner, Mirijam; Geerts, Sjirk; Griffiths, Charles L; Kaplan, Haylee; Kumschick, Sabrina; Le Maitre, David C; Measey, G John; Nunes, Ana L; Richardson, David M; Robinson, Tamara B; Touza, Julia; Wilson, John R U

2018-01-01

Alien species can have major ecological and socioeconomic impacts in their novel ranges and so effective management actions are needed. However, management can be contentious and create conflicts, especially when stakeholders who benefit from alien species are different from those who incur costs. Such conflicts of interests mean that management strategies can often not be implemented. There is, therefore, increasing interest in engaging stakeholders affected by alien species or by their management. Through a facilitated workshop and consultation process including academics and managers working on a variety of organisms and in different areas (urban and rural) and ecosystems (terrestrial and aquatic), we developed a framework for engaging stakeholders in the management of alien species. The proposed framework for stakeholder engagement consists of 12 steps: (1) identify stakeholders; (2) select key stakeholders for engagement; (3) explore key stakeholders' perceptions and develop initial aims for management; (4) engage key stakeholders in the development of a draft management strategy; (5) re-explore key stakeholders' perceptions and revise the aims of the strategy; (6) co-design general aims, management objectives and time frames with key stakeholders; (7) co-design a management strategy; (8) facilitate stakeholders' ownership of the strategy and adapt as required; and (9) implement the strategy and monitor management actions to evaluate the need for additional or future actions. In case additional management is needed after these actions take place, some extra steps should be taken: (10) identify any new stakeholders, benefits, and costs; (11) monitor engagement; and (12) revise management strategy. Overall, we believe that our framework provides an effective approach to minimize the impact of conflicts created by alien species management. Copyright © 2017 Elsevier Ltd. All rights reserved.

Postural adjustment errors during lateral step initiation in older and younger adults

PubMed Central

Sparto, Patrick J.; Fuhrman, Susan I.; Redfern, Mark S.; Perera, Subashan; Jennings, J. Richard; Furman, Joseph M.

2016-01-01

The purpose was to examine age differences and varying levels of step response inhibition on the performance of a voluntary lateral step initiation task. Seventy older adults (70 – 94 y) and twenty younger adults (21 – 58 y) performed visually-cued step initiation conditions based on direction and spatial location of arrows, ranging from a simple choice reaction time task to a perceptual inhibition task that included incongruous cues about which direction to step (e.g. a left pointing arrow appearing on the right side of a monitor). Evidence of postural adjustment errors and step latencies were recorded from vertical ground reaction forces exerted by the stepping leg. Compared with younger adults, older adults demonstrated greater variability in step behavior, generated more postural adjustment errors during conditions requiring inhibition, and had greater step initiation latencies that increased more than younger adults as the inhibition requirements of the condition became greater. Step task performance was related to clinical balance test performance more than executive function task performance. PMID:25595953

Postural adjustment errors during lateral step initiation in older and younger adults

PubMed Central

Sparto, Patrick J.; Fuhrman, Susan I.; Redfern, Mark S.; Perera, Subashan; Jennings, J. Richard; Furman, Joseph M.

2014-01-01

The purpose was to examine age differences and varying levels of step response inhibition on the performance of a voluntary lateral step initiation task. Seventy older adults (70 – 94 y) and twenty younger adults (21 – 58 y) performed visually-cued step initiation conditions based on direction and spatial location of arrows, ranging from a simple choice reaction time task to a perceptual inhibition task that included incongruous cues about which direction to step (e.g. a left pointing arrow appearing on the right side of a monitor). Evidence of postural adjustment errors and step latencies were recorded from vertical ground reaction forces exerted by the stepping leg. Compared with younger adults, older adults demonstrated greater variability in step behavior, generated more postural adjustment errors during conditions requiring inhibition, and had greater step initiation latencies that increased more than younger adults as the inhibition requirements of the condition became greater. Step task performance was related to clinical balance test performance more than executive function task performance. PMID:25183162

48 CFR 3036.104-90 - Authority for one-step turn-key design-build contracting for the United States Coast Guard (USCG).

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Authority for one-step... General 3036.104-90 Authority for one-step turn-key design-build contracting for the United States Coast Guard (USCG). The Head of the Contracting Activity (HCA) of the U.S. Coast Guard may use one-step turn...

Step-to-step spatiotemporal variables and ground reaction forces of intra-individual fastest sprinting in a single session.

PubMed

Nagahara, Ryu; Mizutani, Mirai; Matsuo, Akifumi; Kanehisa, Hiroaki; Fukunaga, Tetsuo

2018-06-01

We aimed to investigate the step-to-step spatiotemporal variables and ground reaction forces during the acceleration phase for characterising intra-individual fastest sprinting within a single session. Step-to-step spatiotemporal variables and ground reaction forces produced by 15 male athletes were measured over a 50-m distance during repeated (three to five) 60-m sprints using a long force platform system. Differences in measured variables between the fastest and slowest trials were examined at each step until the 22nd step using a magnitude-based inferences approach. There were possibly-most likely higher running speed and step frequency (2nd to 22nd steps) and shorter support time (all steps) in the fastest trial than in the slowest trial. Moreover, for the fastest trial there were likely-very likely greater mean propulsive force during the initial four steps and possibly-very likely larger mean net anterior-posterior force until the 17th step. The current results demonstrate that better sprinting performance within a single session is probably achieved by 1) a high step frequency (except the initial step) with short support time at all steps, 2) exerting a greater mean propulsive force during initial acceleration, and 3) producing a greater mean net anterior-posterior force during initial and middle acceleration.

Anticipatory Postural Adjustment During Self-Initiated, Cued, and Compensatory Stepping in Healthy Older Adults and Patients With Parkinson Disease.

PubMed

Schlenstedt, Christian; Mancini, Martina; Horak, Fay; Peterson, Daniel

2017-07-01

To characterize anticipatory postural adjustments (APAs) across a variety of step initiation tasks in people with Parkinson disease (PD) and healthy subjects. Cross-sectional study. Step initiation was analyzed during self-initiated gait, perceptual cued gait, and compensatory forward stepping after platform perturbation. People with PD were assessed on and off levodopa. University research laboratory. People (N=31) with PD (n=19) and healthy aged-matched subjects (n=12). Not applicable. Mediolateral (ML) size of APAs (calculated from center of pressure recordings), step kinematics, and body alignment. With respect to self-initiated gait, the ML size of APAs was significantly larger during the cued condition and significantly smaller during the compensatory condition (P<.001). Healthy subjects and patients with PD did not differ in body alignment during the stance phase prior to stepping. No significant group effect was found for ML size of APAs between healthy subjects and patients with PD. However, the reduction in APA size from cued to compensatory stepping was significantly less pronounced in PD off medication compared with healthy subjects, as indicated by a significant group by condition interaction effect (P<.01). No significant differences were found comparing patients with PD on and off medications. Specific stepping conditions had a significant effect on the preparation and execution of step initiation. Therefore, APA size should be interpreted with respect to the specific stepping condition. Across-task changes in people with PD were less pronounced compared with healthy subjects. Antiparkinsonian medication did not significantly improve step initiation in this mildly affected PD cohort. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

A practical guide to assessing clinical decision-making skills using the key features approach.

PubMed

Farmer, Elizabeth A; Page, Gordon

2005-12-01

This paper in the series on professional assessment provides a practical guide to writing key features problems (KFPs). Key features problems test clinical decision-making skills in written or computer-based formats. They are based on the concept of critical steps or 'key features' in decision making and represent an advance on the older, less reliable patient management problem (PMP) formats. The practical steps in writing these problems are discussed and illustrated by examples. Steps include assembling problem-writing groups, selecting a suitable clinical scenario or problem and defining its key features, writing the questions, selecting question response formats, preparing scoring keys, reviewing item quality and item banking. The KFP format provides educators with a flexible approach to testing clinical decision-making skills with demonstrated validity and reliability when constructed according to the guidelines provided.

Endothelial cell-initiated extravasation of cancer cells visualized in zebrafish

PubMed Central

Kanada, Masamitsu; Zhang, Jinyan; Yan, Libo; Sakurai, Takashi

2014-01-01

The extravasation of cancer cells, a key step for distant metastasis, is thought to be initiated by disruption of the endothelial barrier by malignant cancer cells. An endothelial covering-type extravasation of cancer cells in addition to conventional cancer cell invasion-type extravasation was dynamically visualized in a zebrafish hematogenous metastasis model. The inhibition of VEGF-signaling impaired the invasion-type extravasation via inhibition of cancer cell polarization and motility. Paradoxically, the anti-angiogenic treatment showed the promotion, rather than the inhibition, of the endothelial covering-type extravasation of cancer cells, with structural changes in the endothelial walls. These findings may be a set of clues to the full understanding of the metastatic process as well as the metastatic acceleration by anti-angiogenic reagents observed in preclinical studies. PMID:25551022

Endothelial cell-initiated extravasation of cancer cells visualized in zebrafish.

PubMed

Kanada, Masamitsu; Zhang, Jinyan; Yan, Libo; Sakurai, Takashi; Terakawa, Susumu

2014-01-01

The extravasation of cancer cells, a key step for distant metastasis, is thought to be initiated by disruption of the endothelial barrier by malignant cancer cells. An endothelial covering-type extravasation of cancer cells in addition to conventional cancer cell invasion-type extravasation was dynamically visualized in a zebrafish hematogenous metastasis model. The inhibition of VEGF-signaling impaired the invasion-type extravasation via inhibition of cancer cell polarization and motility. Paradoxically, the anti-angiogenic treatment showed the promotion, rather than the inhibition, of the endothelial covering-type extravasation of cancer cells, with structural changes in the endothelial walls. These findings may be a set of clues to the full understanding of the metastatic process as well as the metastatic acceleration by anti-angiogenic reagents observed in preclinical studies.

Culturally Adapting an Evidence-Based Parenting Intervention for Latino Immigrants: The Need to Integrate Fidelity and Cultural Relevance1

PubMed Central

Cardona, Jose Ruben Parra; Domenech-Rodriguez, Melanie; Forgatch, Marion; Sullivan, Cris; Bybee, Deborah; Holtrop, Kendal; Escobar-Chew, Ana Rocio; Tams, Lisa; Dates, Brian; Bernal, Guillermo

2011-01-01

Latinos constitute the largest ethnic minority group in the US. However, the cultural adaptation and dissemination of evidence-based parenting interventions among Latino populations continues to be scarce in spite of extensive research that demonstrates the long-term positive effects of these interventions. The purpose of this article is threefold: (a) justify the importance of cultural adaptation research as a key strategy to disseminate efficacious interventions among Latinos, (b) describe the initial steps of a program of prevention research with Latino immigrants aimed at culturally adapting an evidence-based intervention informed by parent management training (PMT) principles, and (c) discuss implications for advancing cultural adaptation prevention practice and research, based on the initial feasibility and cultural acceptability findings of the current investigation. PMID:22428711

Assessing the role of mini-applications in predicting key performance characteristics of scientific and engineering applications

DOE PAGES

Barrett, R. F.; Crozier, P. S.; Doerfler, D. W.; ...

2014-09-28

Computational science and engineering application programs are typically large, complex, and dynamic, and are often constrained by distribution limitations. As a means of making tractable rapid explorations of scientific and engineering application programs in the context of new, emerging, and future computing architectures, a suite of miniapps has been created to serve as proxies for full scale applications. Each miniapp is designed to represent a key performance characteristic that does or is expected to significantly impact the runtime performance of an application program. In this paper we introduce a methodology for assessing the ability of these miniapps to effectively representmore » these performance issues. We applied this methodology to four miniapps, examining the linkage between them and an application they are intended to represent. Herein we evaluate the fidelity of that linkage. This work represents the initial steps required to begin to answer the question, ''Under what conditions does a miniapp represent a key performance characteristic in a full app?''« less

[Comparison between one-step and two-step space closing methods of sliding mechanics using three-dimensional finite element].

PubMed

Han, Yaohui; Mou, Lan; Xu, Gengchi; Yang, Yiqiang; Ge, Zhenlin

2015-03-01

To construct a three-dimensional finite element model comparing between one-step and two-step methods in torque control of anterior teeth during space closure. Dicom image data including maxilla and upper teeth were obtained though cone-beam CT. A three-dimensional model was set up and the maxilla, upper teeth and periodontium were separated using Mimics software. The models were instantiated using Pro/Engineer software, and Abaqus finite element analysis software was used to simulate the sliding mechanics by loading 1.47 Nforce on traction hooks with different heights (2, 4, 6, 8, 10, 12 and 14 mm, respectively) in order to compare the initial displacement between six maxillary anterior teeth (one-step method) and four maxillary anterior teeth (two-step method). When moving anterior teeth bodily, initial displacements of central incisors in two-step method and in one-step method were 29.26 × 10⁻⁶ mm and 15.75 × 10⁻⁶ mm, respectively. The initial displacements of lateral incisors in two-step method and in one-step method were 46.76 × 10(-6) mm and 23.18 × 10(-6) mm, respectively. Under the same amount of light force, the initial displacement of anterior teeth in two-step method was doubled compared with that in one-step method. The root and crown of the canine couldn't obtain the same amount of displacement in one-step method. Two-step method could produce more initial displacement than one-step method. Therefore, two-step method was easier to achieve torque control of the anterior teeth during space closure.

Training Rapid Stepping Responses in an Individual With Stroke

PubMed Central

Inness, Elizabeth L.; Komar, Janice; Biasin, Louis; Brunton, Karen; Lakhani, Bimal; McIlroy, William E.

2011-01-01

Background and Purpose Compensatory stepping reactions are important responses to prevent a fall following a postural perturbation. People with hemiparesis following a stroke show delayed initiation and execution of stepping reactions and often are found to be unable to initiate these steps with the more-affected limb. This case report describes a targeted training program involving repeated postural perturbations to improve control of compensatory stepping in an individual with stroke. Case Description Compensatory stepping reactions of a 68-year-old man were examined 52 days after left hemorrhagic stroke. He required assistance to prevent a fall in all trials administered during his initial examination because he showed weight-bearing asymmetry (with more weight borne on the more-affected right side), was unable to initiate stepping with the right leg (despite blocking of the left leg in some trials), and demonstrated delayed response times. The patient completed 6 perturbation training sessions (30–60 minutes per session) that aimed to improve preperturbation weight-bearing symmetry, to encourage stepping with the right limb, and to reduce step initiation and completion times. Outcomes Improved efficacy of compensatory stepping reactions with training and reduced reliance on assistance to prevent falling were observed. Improvements were noted in preperturbation asymmetry and step timing. Blocking the left foot was effective in encouraging stepping with the more-affected right foot. Discussion This case report demonstrates potential short-term adaptations in compensatory stepping reactions following perturbation training in an individual with stroke. Future work should investigate the links between improved compensatory step characteristics and fall risk in this vulnerable population. PMID:21511992

Subjective parameters markedly limit the referral of transplantation candidates to liver transplant centres.

PubMed

Vidal-Trécan, Gwenaëlle; Kone, Victoria; Pilette, Christophe; Nousbaum, Jean-Baptiste; Doll, Jacques; Buffet, Catherine; Eugene, Claude; Podevin, Philippe; Boutet, Olivier; Puyeo, Jacques; Conti, Filomena; Calmus, Yvon

2016-04-01

Equality of access to organ transplantation is a mandatory public health requirement. Referral from a local to a university hospital and then registration on the national waiting list are the two key steps enabling access to liver transplantation (LT). Although the latter procedure is well defined using the Model for End-stage Liver Disease score that improves equality of access, the former is mostly reliant on the practices of referring physicians. The aim of this study was to clarify the factors determining this initial step. This observational study included consecutive inpatients with cirrhosis of whatever origin in a cohort constituted between 2003 and 2008, using medical records and structured questionnaires concerning patient characteristics and the opinions of hospital clinicians. Candidates for LT were defined in line with these opinions. Four hundred and thirty-three patients, mostly affected by alcoholic cirrhosis, were included, 21.0% of whom were considered to be candidates for LT. Factors independently associated with their candidature were: physician empathy [odds ratio (OR) = 10.8; 95% CI: 4.0-29.5], adherence to treatment (OR = 16.6; 95% CI: 3.7-75.2), geographical area (OR = 6.8; 95% CI: 2.2-21.3) and the patient's physiological age (OR = 2.3; 95% CI: 1.1-4.7). Several subjective markers restrict the referral of patients from local hospitals to liver transplant centres. Their advancement to this second step is thus markedly weakened by initial subjectivity. The development of objective guidelines for local hospital physicians to assist them with their initial decision-making on LT is now necessary. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A 3D particle Monte Carlo approach to studying nucleation

NASA Astrophysics Data System (ADS)

Köhn, Christoph; Enghoff, Martin Bødker; Svensmark, Henrik

2018-06-01

The nucleation of sulphuric acid molecules plays a key role in the formation of aerosols. We here present a three dimensional particle Monte Carlo model to study the growth of sulphuric acid clusters as well as its dependence on the ambient temperature and the initial particle density. We initiate a swarm of sulphuric acid-water clusters with a size of 0.329 nm with densities between 107 and 108 cm-3 at temperatures between 200 and 300 K and a relative humidity of 50%. After every time step, we update the position of particles as a function of size-dependent diffusion coefficients. If two particles encounter, we merge them and add their volumes and masses. Inversely, we check after every time step whether a polymer evaporates liberating a molecule. We present the spatial distribution as well as the size distribution calculated from individual clusters. We also calculate the nucleation rate of clusters with a radius of 0.85 nm as a function of time, initial particle density and temperature. The nucleation rates obtained from the presented model agree well with experimentally obtained values and those of a numerical model which serves as a benchmark of our code. In contrast to previous nucleation models, we here present for the first time a code capable of tracing individual particles and thus of capturing the physics related to the discrete nature of particles.

"Extracting" the key fragment in ETS-10 crystallization and its application in AM-6 assembly.

PubMed

Guo, Meiling; Feng, Zhaochi; Li, Guanna; Hofmann, Jan P; Pidko, Evgeny A; Magusin, Pieter C M M; Guo, Qiang; Weckhuysen, Bert M; Hensen, Emiel J M; Fan, Fengtao; Li, Can

2012-09-17

The mechanism of crystallization of microporous titanosilicate ETS-10 was investigated by Raman spectroscopy combined with (29)Si magic-angle spinning (MAS) NMR spectroscopy, DFT calculations, and SEM imaging. The formation of three-membered ring species is shown to be the key step in the hydrothermal synthesis of ETS-10. They are formed by means of a complex process that involves the interaction of silicate species in the reaction mixture, which promotes the dissolution of TiO(2) particles. These insights into the mechanism of ETS-10 growth led to the successful development of a new synthesis route to the vanadosilicate AM-6 that involves the use of intermediates that contain three-membered ring species as an initiator. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Research activities to improve the utilization of antibiotics in Africa.

PubMed

Massele, Amos; Tiroyakgosi, Celda; Matome, Matshediso; Desta, Abayneh; Muller, Arno; Paramadhas, Bene D Anand; Malone, Brighid; Kurusa, Gobuiwang; Didimalang, Thatayaone; Moyo, Mosana; Godman, Brian

2017-02-01

There is a need to improve the rational use of antibiotics across continents including Africa. This has resulted in initiatives in Botswana including treatment guidelines and the instigation of Antibiotic Stewardship Programs (ASPs). The next steps involve a greater understanding of current antibiotic utilization and resistance patterns (AMR). This resulted in a 2-day meeting involving key stakeholders principally from Botswana to discuss key issues including AMR rates as well as ASPs in both the public and private sectors. Following this, the findings will be used to plan future studies across Africa including point prevalence studies. The findings will be presented in July 2016 at the next Medicines Utilization Research in Africa meeting will ideally serve as a basis for planning future pertinent interventional studies to enhance the rational use of antibiotics in Botswana and wider.

The European Society of Gastrointestinal Endoscopy Quality Improvement Initiative: developing performance measures.

PubMed

Rutter, Matthew D; Senore, Carlo; Bisschops, Raf; Domagk, Dirk; Valori, Roland; Kaminski, Michal F; Spada, Cristiano; Bretthauer, Michael; Bennett, Cathy; Bellisario, Cristina; Minozzi, Silvia; Hassan, Cesare; Rees, Colin; Dinis-Ribeiro, Mário; Hucl, Tomas; Ponchon, Thierry; Aabakken, Lars; Fockens, Paul

2016-02-01

The European Society of Gastrointestinal Endoscopy (ESGE) and United European Gastroenterology (UEG) have a vision to create a thriving community of endoscopy services across Europe, collaborating with each other to provide high quality, safe, accurate, patient-centered and accessible endoscopic care. Whilst the boundaries of what can be achieved by advanced endoscopy are continually expanding, we believe that one of the most fundamental steps to achieving our goal is to raise the quality of everyday endoscopy. The development of robust, consensus- and evidence-based key performance measures is the first step in this vision. ESGE and UEG have identified quality of endoscopy as a major priority. This paper explains the rationale behind the ESGE Quality Improvement Initiative and describes the processes that were followed. We recommend that all units develop mechanisms for audit and feedback of endoscopist and service performance using the ESGE performance measures that will be published in future issues of this journal over the next year. We urge all endoscopists and endoscopy services to prioritize quality and to ensure that these performance measures are implemented and monitored at a local level, so that we can provide the highest possible care for our patients.

NET-VISA, a Bayesian method next-generation automatic association software. Latest developments and operational assessment.

NASA Astrophysics Data System (ADS)

Le Bras, Ronan; Kushida, Noriyuki; Mialle, Pierrick; Tomuta, Elena; Arora, Nimar

2017-04-01

The Preparatory Commission for the Comprehensive Nuclear-Test-Ban Treaty Organization (CTBTO) has been developing a Bayesian method and software to perform the key step of automatic association of seismological, hydroacoustic, and infrasound (SHI) parametric data. In our preliminary testing in the CTBTO, NET_VISA shows much better performance than its currently operating automatic association module, with a rate for automatic events matching the analyst-reviewed events increased by 10%, signifying that the percentage of missed events is lowered by 40%. Initial tests involving analysts also showed that the new software will complete the automatic bulletins of the CTBTO by adding previously missed events. Because products by the CTBTO are also widely distributed to its member States as well as throughout the seismological community, the introduction of a new technology must be carried out carefully, and the first step of operational integration is to first use NET-VISA results within the interactive analysts' software so that the analysts can check the robustness of the Bayesian approach. We report on the latest results both on the progress for automatic processing and for the initial introduction of NET-VISA results in the analyst review process

Mechanistic insights into the dehalogenation reaction of fluoroacetate/fluoroacetic acid

NASA Astrophysics Data System (ADS)

Miranda-Rojas, Sebastián; Toro-Labbé, Alejandro

2015-05-01

Fluoroacetate is a toxic compound whose environmental accumulation may represent an important contamination problem, its elimination is therefore a challenging issue. Fluoroacetate dehalogenase catalyzes its degradation through a two step process initiated by an SN2 reaction in which the aspartate residue performs a nucleophilic attack on the carbon bonded to the fluorine; the second step is hydrolysis that releases the product as glycolate. In this paper, we present a study based on density functional theory calculations of the SN2 initiation reaction modeled through the interaction between the substrate and the propionate anion as the nucleophile. Results are analyzed within the framework of the reaction force and using the reaction electronic flux to identify and characterize the electronic activity that drives the reaction. Our results reveal that the selective protonation of the substrate catalyzes the reaction by decreasing the resistance of the structural and electronic reorganization needed to reach the transition state. Finally, the reaction energy is modulated by the degree of stabilization of the fluoride anion formed after the SN2 reaction. In this way, a site-induced partial protonation acts as a chemical switch in a key process that determines the output of the reaction.

[Molecular mechanisms of protein biosynthesis initiation--biochemical and biomedical implications of a new model of translation enhanced by the RNA hypoxia response element (rHRE)].

PubMed

Master, Adam; Nauman, Alicja

2014-01-01

Translation initiation is a key rate-limiting step in cellular protein synthesis. A cap-dependent initiation is the most effective mechanism of the translation. However, some physiological (mitosis) and pathological (oxidative stress) processes may switch the classic mechanism to an alternative one that is regulated by an mRNA element such as IRES, uORF, IRE, CPE, DICE, AURE or CITE. A recently discovered mechanism of RNA hypoxia response element (rHRE)-dependent translation initiation, may change the view of oxygen-regulated translation and give a new insight into unexplained biochemical processes. Hypoxia is one of the better-known factors that may trigger an alternative mechanism of the translation initiation. Temporal events of oxygen deficiency within tissues and organs may activate processes such as angiogenesis, myogenesis, regeneration, wound healing, and may promote an adaptive response in cardiovascular and neurodegenerative diseases. On the other hand, growth of solid tumors may be accompanied by cyclic hypoxia, allowing for synthesis of proteins required for further progression of cancer cells. This paper provides a review of current knowledge on translational control in the context of alternative models of translation initiation.

The role and mechanics of dendritic cells in tumor antigen acquisition and presentation following laser immunotherapy

NASA Astrophysics Data System (ADS)

Laverty, Sean M.; Dawkins, Bryan A.; Chen, Wei R.

2018-02-01

We extend our model of the antitumor immune response initiated by laser-immunotherapy treatment to more closely examine key steps in the immune response 1) tumor antigen acquisition by antigen-presenting dendritic cells (DCs) and 2) cytotoxic T cell (CTL) priming by lymphatic DCs. Specifically we explore the formation of DC-CTL complexes that lead to CTL priming. We find that the bias in the dissociation rate of the complex influences the outcome of treatment. In particular, a bias towards priming favors a rapid activated CTL response and the clearance of tumors.

Well-Defined Models for the Elusive Dinuclear Intermediates of the Pauson-Khand Reaction.

PubMed

Hartline, Douglas R; Zeller, Matthias; Uyeda, Christopher

2016-05-10

The mechanism of the Pauson-Khand reaction has attracted significant interest due to the unusual dinuclear nature of the Co2 (CO)x active site. Experimental and computational data have indicated that the intermediates following the initial Co2 (CO)6 (alkyne) complex are thermodynamically unstable and do not build up in appreciable concentrations during the course of the reaction. As a consequence, the key steps that control the scope of viable substrates and various aspects of selectivity have remained largely uncharacterized. Herein, a direct experimental investigation of the dinuclear metallacycle-forming step of the Pauson-Khand reaction is reported. These studies capitalize on well-defined d(9) -d(9) dinickel complexes supported by a naphthyridine-diimine (NDI) pincer ligand as functional surrogates of Co2 (CO)8 . © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Excursion set approach: Stratonovich approximation and Cholesky decomposition

NASA Astrophysics Data System (ADS)

Nikakhtar, Farnik; Ayromlou, Mohammadreza; Baghram, Shant; Rahvar, Sohrab; Tabar, M. Reza Rahimi; Sheth, Ravi K.

2018-05-01

The excursion set approach is a framework for estimating how the number density of nonlinear structures in the cosmic web depends on the expansion history of the universe and the nature of gravity. A key part of the approach is the estimation of the first crossing distribution of a suitably chosen barrier by random walks having correlated steps: The shape of the barrier is determined by the physics of nonlinear collapse, and the correlations between steps by the nature of the initial density fluctuation field. We describe analytic and numerical methods for calculating such first up-crossing distributions. While the exact solution can be written formally as an infinite series, we show how to approximate it efficiently using the Stratonovich approximation. We demonstrate its accuracy using Monte-Carlo realizations of the walks, which we generate using a novel Cholesky-decomposition based algorithm, which is significantly faster than the algorithm that is currently in the literature.

Report of the In Situ Resources Utilization Workshop

NASA Technical Reports Server (NTRS)

Fairchild, Kyle (Editor); Mendell, Wendell W. (Editor)

1988-01-01

The results of a workshop of 50 representatives from the public and private sector which investigated the potential joint development of the key technologies and mechanisms that will enable the permanent habitation of space are presented. The workshop is an initial step to develop a joint public/private assessment of new technology requirements of future space options, to share knowledge on required technologies that may exist in the private sector, and to investigate potential joint technology development opportunities. The majority of the material was produced in 5 working groups: (1) Construction, Assembly, Automation and Robotics; (2) Prospecting, Mining, and Surface Transportation; (3) Biosystems and Life Support; (4) Materials Processing; and (5) Innovative Ventures. In addition to the results of the working groups, preliminary technology development recommendations to assist in near-term development priority decisions are presented. Finally, steps are outlined for potential new future activities and relationships among the public, private, and academic sectors.

Human Mission to Europa and Titan - Why Not? Executive Summary

NASA Technical Reports Server (NTRS)

Finarelli, Margaret G.

2005-01-01

Outline a step-by-step Development Plan of the key barriers and their solutions to enable human exploration of the outer solar system. Secondary: Perform a case study which supports and emphasizes the key elements of the Development Plan.

Initiation of movement from quiet stance: comparison of gait and stepping in elderly subjects of different levels of functional ability.

PubMed

Brunt, Denis; Santos, Valeria; Kim, Hyeong Dong; Light, Kathye; Levy, Charles

2005-04-01

This study describes how elderly subjects initiate gait, and step from a position of quiet stance. Based on scores from selected standardized tests subjects were placed in either a high (HFL) or low functional level (LFL) group and were asked to initiate gait, step onto a 10 cm high, 1.22 m wide curb and step over a 10 cm high, 9 cm wide obstacle at a self paced speed. Stepping conditions affected the velocity of movement. It was clear that all subjects decreased initiation velocity for both curb and obstacle compared to gait initiation. Swing and stance limb acceleration ground reaction forces and EMG amplitude were modulated according to initiation velocity. Toe clearance was greater for obstacle than curb and gait initiation. Swing toe-off was significantly earlier and there was a trend for obstacle clearance to be greater for the HFL group. Those in the LFL group appear to be at a greater risk for falling due to the possible effect of slower rate of toe-off that could influence toe clearance over the obstacle.

Oxidative Degradation of 4-chlorophenol in Aqueous Induced by Plasma with Submersed Glow Discharge Electrolysis

NASA Astrophysics Data System (ADS)

Pu, Lumei; Gao, Jinzhang; Yang, Wu; Li, Yan; Yu, Jie; Huang, Dongling

2005-10-01

The oxidative degradation of 4-chlorophenol (4-CP) in aqueous solution induced by plasma with submersed glow discharge has been investigated. The concentration of 4-CP and the reaction intermediates were determined by high performance liquid chromatography (HPLC). Various influencing factors such as the initial pH, the concentration of 4-CP and the catalytic action of Fe2+ were examined. The results indicate that 4-CP is eventually degraded into inorganic ion, dioxide carbon and water. The attack of hydroxyl radicals on the benzene rings of 4-CP in the initial stage of oxidative reactions is presumed to be a key step. They also suggest that the reaction is of a pseudo-first order kinetic reaction and the proposed method is an efficient way for the 4-CP degradation.

Transcription closed and open complex dynamics studies reveal balance between genetic determinants and co-factors

NASA Astrophysics Data System (ADS)

Sala, Adrien; Shoaib, Muhammad; Anufrieva, Olga; Mutharasu, Gnanavel; Jahan Hoque, Rawnak; Yli-Harja, Olli; Kandhavelu, Meenakshisundaram

2015-05-01

In E. coli, promoter closed and open complexes are key steps in transcription initiation, where magnesium-dependent RNA polymerase catalyzes RNA synthesis. However, the exact mechanism of initiation remains to be fully elucidated. Here, using single mRNA detection and dual reporter studies, we show that increased intracellular magnesium concentration affects Plac initiation complex formation resulting in a highly dynamic process over the cell growth phases. Mg2+ regulates transcription transition, which modulates bimodality of mRNA distribution in the exponential phase. We reveal that Mg2+ regulates the size and frequency of the mRNA burst by changing the open complex duration. Moreover, increasing magnesium concentration leads to higher intrinsic and extrinsic noise in the exponential phase. RNAP-Mg2+ interaction simulation reveals critical movements creating a shorter contact distance between aspartic acid residues and Nucleotide Triphosphate residues and increasing electrostatic charges in the active site. Our findings provide unique biophysical insights into the balanced mechanism of genetic determinants and magnesium ion in transcription initiation regulation during cell growth.

Policymakers and mHealth: roles and expectations, with observations from Ethiopia, Ghana and Sweden

PubMed Central

Barkman, Catharina; Weinehall, Lars

2017-01-01

ABSTRACT The rapid increase in mobile phone use and other telecommunication technologies in health care during the past decade has paved the way for optimism. mHealth (mobile health) initiatives need to be integrated into national health systems and priorities and fit into the system that the country has already invested in. Partnership between government, regional governments, health care systems, Community Health Workers, the private sector and universities is considered as a precondition for success. In turn, this requires strategic and integrative policy decisions on the national/regional level to be defined in the action plans as concrete steps. Decision makers are calling for scale-up plans to be in place even in the pilot phases. Hope is expressed that the initial joy and curiosity that new technology generates in the implementation phase will be transferred to routine work. Standards and a common technical architecture that enables interoperability and upscaling are key issues. Based on publications on policy and national strategies, this paper highlights some key areas for decision makers’ role and expectations with regard to mHealth. The paper will also report some mHealth experiences from Ethiopia, Ghana and Sweden. PMID:28838303

Addressing female genital mutilation in Europe: a scoping review of approaches to participation, prevention, protection, and provision of services.

PubMed

Baillot, Helen; Murray, Nina; Connelly, Elaine; Howard, Natasha

2018-02-08

Public and policy attention to female genital mutilation (FGM) in diaspora communities has increased in Europe, but research remains limited and misinformation abounds. As a first step to addressing these issues, this study explored FGM prevention and response interventions in Europe, using a scoping literature review and key informant interviews. A scoping study design was selected, using Arksey and O'Malley's six-stage scoping framework to review identified sources. Key informant interviews were used to inform and add depth to literature findings. Findings were summarised thematically, guided by the Scottish Government's '4Ps' framework for tackling violence against women (i.e. participation, prevention, protection, providing services). Seventy literature sources, of 1095 screened, plus 16 individual and 3 group interview sources were included. Several countries have developed promising interventions supporting FGM resistance and recovery. However, gaps remain including community participation, professional knowledge and linkages, and evaluation of approaches. This scoping review is an initial attempt to describe available primary evidence on European initiatives responding to FGM. Further research is required to determine whether interventions are effective, while policy and practice development must be shaped and driven by the experiences, needs, and views of affected communities.

Consumption of a Mango Fruit Powder Protects Mice from High-Fat Induced Insulin Resistance and Hepatic Fat Accumulation.

PubMed

Sabater, Agustín G; Ribot, Joan; Priego, Teresa; Vazquez, Itxaso; Frank, Sonja; Palou, Andreu; Buchwald-Werner, Sybille

2017-01-01

The aim of this study was to gain more insight into the beneficial effects of mango fruit powder on the early metabolic adverse effects of a high-fat diet. The progressive dose-response effects of mango fruit powder on body composition, circulating parameters, and the expression of genes related to fatty acid oxidation and insulin sensitivity in key tissues were studied in mice fed a moderate (45%) high-fat diet. Findings suggest that mango fruit powder exerts physiological protective effects in the initial steps of insulin resistance and hepatic lipid accumulation induced by a high-fat diet in mice. Moreover, AMPK and SIRT1 appear as key regulators of the observed improvement in fatty acid oxidation capacity, as well as of the improved insulin sensitivity and the increased glucose uptake and metabolism through the glycolytic pathway capacity in liver and skeletal muscle. In summary, this study provides evidence that the functional food ingredient (CarelessTM) from mango fruit prevents early metabolic alterations caused by a high-fat diet in the initial stages of the metabolic syndrome. © 2017 The Author(s). Published by S. Karger AG, Basel.

Le management des projets scientifiques

NASA Astrophysics Data System (ADS)

Perrier, Françoise

2000-12-01

We describe in this paper a new approach for the management of scientific projects. This approach is the result of a long reflexion carried out within the MQDP (Methodology and Quality in the Project Development) group of INSU-CNRS, and continued with Guy Serra. Our reflexion was initiated with the study of the so-called `North-American Paradigm' which was, initially considered as the only relevant management model. Through our active participation in several astrophysical projects we realized that this model could not be applied to our laboratories without major modifications. Therefore, step-by-step, we have constructed our own methodology, using to the fullest human potential resources existing in our research field, their habits and skills. We have also participated in various working groups in industrial and scientific organisms for the benefits of CNRS. The management model presented here is based on a systemic and complex approach. This approach lets us describe the multiple aspects of a scientific project specially taking into account the human dimension. The project system model includes three major interconnected systems, immersed within an influencing and influenced environment: the `System to be Realized' which defines scientific and technical tasks leading to the scientific goals, the `Realizing System' which describes procedures, processes and organization, and the `Actors' System' which implements and boosts all the processes. Each one exists only through a series of successive models, elaborated at predefined dates of the project called `key-points'. These systems evolve with time and under often-unpredictable circumstances and the models have to take it into account. At these key-points, each model is compared to reality and the difference between the predicted and realized tasks is evaluated in order to define the data for the next model. This model can be applied to any kind of projects.

Evaluating investment in quality improvement capacity building: a systematic review

PubMed Central

Mery, Gustavo; Dobrow, Mark J; Baker, G Ross; Im, Jennifer; Brown, Adalsteinn

2017-01-01

Purpose Leading health systems have invested in substantial quality improvement (QI) capacity building, but little is known about the aggregate effect of these investments at the health system level. We conducted a systematic review to identify key steps and elements that should be considered for system-level evaluations of investment in QI capacity building. Methods We searched for evaluations of QI capacity building and evaluations of QI training programmes. We included the most relevant indexed databases in the field and a strategic search of the grey literature. The latter included direct electronic scanning of 85 relevant government and institutional websites internationally. Data were extracted regarding evaluation design and common assessment themes and components. Results 48 articles met the inclusion criteria. 46 articles described initiative-level non-economic evaluations of QI capacity building/training, while 2 studies included economic evaluations of QI capacity building/training, also at the initiative level. No system-level QI capacity building/training evaluations were found. We identified 17 evaluation components that fit within 5 overarching dimensions (characteristics of QI training; characteristics of QI activity; individual capacity; organisational capacity and impact) that should be considered in evaluations of QI capacity building. 8 key steps in return-on-investment (ROI) assessments in QI capacity building were identified: (1) planning—stakeholder perspective; (2) planning—temporal perspective; (3) identifying costs; (4) identifying benefits; (5) identifying intangible benefits that will not be included in the ROI estimation; (6) discerning attribution; (7) ROI calculations; (8) sensitivity analysis. Conclusions The literature on QI capacity building evaluation is limited in the number and scope of studies. Our findings, summarised in a Framework to Guide Evaluations of QI Capacity Building, can be used to start closing this knowledge gap. PMID:28219957

E-referral Solutions: Successful Experiences, Key Features and Challenges- a Systematic Review.

PubMed

Naseriasl, Mansour; Adham, Davoud; Janati, Ali

2015-06-01

around the world health systems constantly face increasing pressures which arise from many factors, such as an ageing population, patients and providers demands for equipment's and services. In order to respond these challenges and reduction of health system's transactional costs, referral solutions are considered as a key factor. This study was carried out to identify referral solutions that have had successes. relevant studies identified using keywords of referrals, consultation, referral system, referral model, referral project, electronic referral, electronic booking, health system, healthcare, health service and medical care. These searches were conducted using PubMed, ProQuest, Google Scholar, Scopus, Emerald, Web of Knowledge, Springer, Science direct, Mosby's index, SID, Medlib and Iran Doc data bases. 4306 initial articles were obtained and refined step by step. Finally, 27 articles met the inclusion criteria. we identified seventeen e-referral systems developed in UK, Norway, Finland, Netherlands, Denmark, Scotland, New Zealand, Canada, Australia, and U.S. Implemented solutions had variant degrees of successes such as improved access to specialist care, reduced wait times, timeliness and quality of referral communication, accurate health information transfer and integration of health centers and services. each one of referral solutions has both positive and changeable aspects that should be addressed according to sociotechnical conditions. These solutions are mainly formed in a small and localized manner.

SU-E-T-502: Initial Results of a Comparison of Treatment Plans Produced From Automated Prioritized Planning Method and a Commercial Treatment Planning System

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

Tiwari, P; Chen, Y; Hong, L

2015-06-15

Purpose We developed an automated treatment planning system based on a hierarchical goal programming approach. To demonstrate the feasibility of our method, we report the comparison of prostate treatment plans produced from the automated treatment planning system with those produced by a commercial treatment planning system. Methods In our approach, we prioritized the goals of the optimization, and solved one goal at a time. The purpose of prioritization is to ensure that higher priority dose-volume planning goals are not sacrificed to improve lower priority goals. The algorithm has four steps. The first step optimizes dose to the target structures, whilemore » sparing key sensitive organs from radiation. In the second step, the algorithm finds the best beamlet weight to reduce toxicity risks to normal tissue while holding the objective function achieved in the first step as a constraint, with a small amount of allowed slip. Likewise, the third and fourth steps introduce lower priority normal tissue goals and beam smoothing. We compared with prostate treatment plans from Memorial Sloan Kettering Cancer Center developed using Eclipse, with a prescription dose of 72 Gy. A combination of liear, quadratic, and gEUD objective functions were used with a modified open source solver code (IPOPT). Results Initial plan results on 3 different cases show that the automated planning system is capable of competing or improving on expert-driven eclipse plans. Compared to the Eclipse planning system, the automated system produced up to 26% less mean dose to rectum and 24% less mean dose to bladder while having the same D95 (after matching) to the target. Conclusion We have demonstrated that Pareto optimal treatment plans can be generated automatically without a trial-and-error process. The solver finds an optimal plan for the given patient, as opposed to database-driven approaches that set parameters based on geometry and population modeling.« less

Management Strategies to Facilitate Optimal Outcomes for Patients Treated with Delayed-release Dimethyl Fumarate.

PubMed

Mayer, Lori; Fink, Mary Kay; Sammarco, Carrie; Laing, Lisa

2018-04-01

Delayed-release dimethyl fumarate is an oral disease-modifying therapy that has demonstrated significant efficacy in adults with relapsing-remitting multiple sclerosis. Incidences of flushing and gastrointestinal adverse events are common in the first month after delayed-release dimethyl fumarate initiation. Our objective was to propose mitigation strategies for adverse events related to initiation of delayed-release dimethyl fumarate in the treatment of patients with multiple sclerosis. Studies of individually developed mitigation strategies and chart reviews were evaluated. Those results, as well as mitigation protocols developed at multiple sclerosis care centers, are summarized. Key steps to optimize the effectiveness of delayed-release dimethyl fumarate treatment include education prior to and at the time of delayed-release dimethyl fumarate initiation, initiation dose protocol gradually increasing to maintenance dose, dietary suggestions for co-administration with food, gastrointestinal symptom management with over-the-counter medications, flushing symptom management with aspirin, and temporary dose reduction. Using the available evidence from clinical trials and evaluations of post-marketing studies, these strategies to manage gastrointestinal and flushing symptoms can be effective and helpful to the patient when initiating delayed-release dimethyl fumarate.

Application of linker technique to trap transiently interacting protein complexes for structural studies

PubMed Central

Reddy Chichili, Vishnu Priyanka; Kumar, Veerendra; Sivaraman, J.

2016-01-01

Protein-protein interactions are key events controlling several biological processes. We have developed and employed a method to trap transiently interacting protein complexes for structural studies using glycine-rich linkers to fuse interacting partners, one of which is unstructured. Initial steps involve isothermal titration calorimetry to identify the minimum binding region of the unstructured protein in its interaction with its stable binding partner. This is followed by computational analysis to identify the approximate site of the interaction and to design an appropriate linker length. Subsequently, fused constructs are generated and characterized using size exclusion chromatography and dynamic light scattering experiments. The structure of the chimeric protein is then solved by crystallization, and validated both in vitro and in vivo by substituting key interacting residues of the full length, unlinked proteins with alanine. This protocol offers the opportunity to study crucial and currently unattainable transient protein interactions involved in various biological processes. PMID:26985443

EDEM2 initiates mammalian glycoprotein ERAD by catalyzing the first mannose trimming step

PubMed Central

Ninagawa, Satoshi; Okada, Tetsuya; Sumitomo, Yoshiki; Kamiya, Yukiko; Kato, Koichi; Horimoto, Satoshi; Ishikawa, Tokiro; Takeda, Shunichi; Sakuma, Tetsushi; Yamamoto, Takashi

2014-01-01

Glycoproteins misfolded in the endoplasmic reticulum (ER) are subjected to ER-associated glycoprotein degradation (gpERAD) in which Htm1-mediated mannose trimming from the oligosaccharide Man8GlcNAc2 to Man7GlcNAc2 is the rate-limiting step in yeast. In contrast, the roles of the three Htm1 homologues (EDEM1/2/3) in mammalian gpERAD have remained elusive, with a key controversy being whether EDEMs function as mannosidases or as lectins. We therefore conducted transcription activator-like effector nuclease–mediated gene knockout analysis in human cell line and found that all endogenous EDEMs possess mannosidase activity. Mannose trimming from Man8GlcNAc2 to Man7GlcNAc2 is performed mainly by EDEM3 and to a lesser extent by EDEM1. Most surprisingly, the upstream mannose trimming from Man9GlcNAc2 to Man8GlcNAc2 is conducted mainly by EDEM2, which was previously considered to lack enzymatic activity. Based on the presence of two rate-limiting steps in mammalian gpERAD, we propose that mammalian cells double check gpERAD substrates before destruction by evolving EDEM2, a novel-type Htm1 homologue that catalyzes the first mannose trimming step from Man9GlcNAc2. PMID:25092655

Step Up-Not On-The Step 2 Clinical Skills Exam: Directors of Clinical Skills Courses (DOCS) Oppose Ending Step 2 CS.

PubMed

Ecker, David J; Milan, Felise B; Cassese, Todd; Farnan, Jeanne M; Madigosky, Wendy S; Massie, F Stanford; Mendez, Paul; Obadia, Sharon; Ovitsh, Robin K; Silvestri, Ronald; Uchida, Toshiko; Daniel, Michelle

2018-05-01

Recently, a student-initiated movement to end the United States Medical Licensing Examination Step 2 Clinical Skills and the Comprehensive Osteopathic Medical Licensing Examination Level 2-Performance Evaluation has gained momentum. These are the only national licensing examinations designed to assess clinical skills competence in the stepwise process through which physicians gain licensure and certification. Therefore, the movement to end these examinations and the ensuing debate merit careful consideration. The authors, elected representatives of the Directors of Clinical Skills Courses, an organization comprising clinical skills educators in the United States and beyond, believe abolishing the national clinical skills examinations would have a major negative impact on the clinical skills training of medical students, and that forfeiting a national clinical skills competency standard has the potential to diminish the quality of care provided to patients. In this Perspective, the authors offer important additional background information, outline key concerns regarding the consequences of ending these national clinical skills examinations, and provide recommendations for moving forward: reducing the costs for students, exploring alternatives, increasing the value and transparency of the current examinations, recognizing and enhancing the strengths of the current examinations, and engaging in a national dialogue about the issue.

Post-processing techniques to enhance reliability of assignment algorithm based performance measures : [technical summary].

DOT National Transportation Integrated Search

2011-01-01

Travel demand modeling plays a key role in the transportation system planning and evaluation process. The four-step sequential travel demand model is the most widely used technique in practice. Traffic assignment is the key step in the conventional f...

Your company's secret change agents.

PubMed

Pascale, Richard Tanner; Sternin, Jerry

2005-05-01

Organizational change has traditionally come about through top-down initiatives such as hiring experts or importing best-of-breed practices. Such methods usually result in companywide rollouts of templates mandated from on high. These do little to get people excited. But within every organization, there are a few individuals who find unique ways to look at problems that seem impossible to solve. Although these change agents start out with the same tools and access to resources as their peers, they are able to see solutions where others do not. They find a way to bridge the divide between what is happening and what is possible. These positive deviants are the key, the authors believe, to a better way of creating organizational change. Your company can make the most of their methods by following six steps. In Step 1, Make the group the guru, the members of the community are engaged in the process of their own evolution. Step 2, Reframe through facts, entails restating the problem in a way that opens minds to new possibilities. Step 3, Make it safe to learn, involves creating an environment that supports innovative ideas. In Step 4, Make the problem concrete, the community combats abstraction by stating uncomfortable truths. In Step 5, Leverage social proof, the community looks to the larger society for examples of solutions that have worked in parallel situations. In Step 6, Confound the immune defense response, solutions are introduced organically from within the group in a way that promotes acceptance. Throughout the steps, the leader must suspend his or her traditional role in favor of more facilitatory practices. The positive-deviance approach has unearthed solutions to such complicated and diverse problems as malnutrition in Mali and human trafficking in East Java. This methodology can help solve even the most extreme dilemmas.

A kinematic analysis of the rapid step test in balance-impaired and unimpaired older women.

PubMed

Schulz, Brian W; Ashton-Miller, James A; Alexander, Neil B

2007-04-01

Little is known about the kinematic and kinetic determinants that might explain age and balance-impairment alterations in the results of volitional stepping performance tests. Maximal unipedal stance time (UST) was used to distinguish "balance-impaired" old (BI, UST<10s, N=15, mean age=76 years) from unimpaired old (O, UST>30s, N=12, mean age=71 years) before they and healthy young females (Y, UST>30s, N=13, mean age=23 years) performed the rapid step test (RST). The RST evaluates the time required to take volitional front, side, and back steps of at least 80% maximum step length in response to verbal commands. Kinematic and kinetic data were recorded during the RST. The results indicate that the initiation phase of the step was the major source of age- and balance impairment-related delays. The delays in BI were primarily caused by increased postural adjustments prior to step initiation, as measured by center-of-pressure (COP) path length (p<0.003). The Step landing phase showed similar, but non-significant, temporal trends. Step length and peak center-of-mass (COM) deceleration during the Step-Out landing decreased in O by 18% (p=0.0002) and 24% (p=0.001), respectively, and a further 12% (p=0.04) and 18% (p=0.08) in BI. We conclude that the delay in BI step initiation was due to the increase in their postural adjustments prior to step initiation.

Standard operating procedures for priapism.

PubMed

Burnett, Arthur L; Sharlip, Ira D

2013-01-01

To provide standard operating procedures for the diagnosis and management of priapism. Review of the literature. Reduction of priapism and preservation of erectile function. Priapism is a persistent penile erection that continues hours beyond, or is unrelated to, sexual stimulation. Priapism requires prompt evaluation and usually requires emergency management. There are two types of priapism: (i) ischemic (veno-occlusive or low flow), which is found in 95% of cases, and (ii) nonischemic (arterial or high flow). Stuttering (intermittent) priapism is a recurrent form of ischemic priapism. To initiate appropriate management, the physician must determine whether the priapism is ischemic or nonischemic. Necessary diagnostic steps are an accurate history, physical examination, and cavernous blood gas analysis and/or color duplex ultrasonography of the corpora cavernosa. Management of ischemic priapism should achieve resolution as promptly as possible. Initial treatment is therapeutic aspiration with or without irrigation of the corpora. If this fails, intracavernous injection of sympathomimetic drugs is the next step. Surgical shunts should be performed if nonsurgical treatment has failed. The initial management of nonischemic priapism should be observation. Selective arterial embolization is recommended for the management of nonischemic priapism in patients who request treatment. The goal of management for a patient with recurrent (stuttering) priapism is prevention of future episodes. Management of priapism has become increasingly successful as scientific understanding of the pathophysiology and molecular biology of priapism improves. The key to further success in the treatment of priapism is basic research of this uncommon but potentially devastating condition. © 2012 International Society for Sexual Medicine.

Variability of Anticipatory Postural Adjustments During Gait Initiation in Individuals With Parkinson Disease.

PubMed

Lin, Cheng-Chieh; Creath, Robert A; Rogers, Mark W

2016-01-01

In people with Parkinson disease (PD), difficulties with initiating stepping may be related to impairments of anticipatory postural adjustments (APAs). Increased variability in step length and step time has been observed in gait initiation in individuals with PD. In this study, we investigated whether the ability to generate consistent APAs during gait initiation is compromised in these individuals. Fifteen subjects with PD and 8 healthy control subjects were instructed to take rapid forward steps after a verbal cue. The changes in vertical force and ankle marker position were recorded via force platforms and a 3-dimensional motion capture system, respectively. Means, standard deviations, and coefficients of variation of both timing and magnitude of vertical force, as well as stepping variables, were calculated. During the postural phase of gait initiation the interval was longer and the force modulation was smaller in subjects with PD. Both the variability of timing and force modulation were larger in subjects with PD. Individuals with PD also had a longer time to complete the first step, but no significant differences were found for the variability of step time, length, and speed between groups. The increased variability of APAs during gait initiation in subjects with PD could affect posture-locomotion coupling, and lead to start hesitation, and even falls. Future studies are needed to investigate the effect of rehabilitation interventions on the variability of APAs during gait initiation in individuals with PD.Video abstract available for more insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A119).

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

The effect of anatase TiO2 surface structure on the behavior of ethanol adsorption and its initial dissociation step: A DFT study

NASA Astrophysics Data System (ADS)

Zhang, Riguang; Liu, Zhixue; Ling, Lixia; Wang, Baojun

2015-10-01

The perfect and defective surfaces of anatase TiO2 including (1 0 1) and (0 0 1) surfaces have been chosen to probe into the effect of anatase TiO2 surface structure on the behavior of ethanol adsorption and initial dissociation step. Here, the results are obtained by density functional theory (DFT) calculation together with the periodic slab model. Our results show that the surface structure of anatase TiO2 can obviously affect the behavior of ethanol adsorption and the catalytic activity of its initial dissociation step; firstly, on the perfect and defective surfaces of anatase (1 0 1), ethanol dominantly exists in the form of molecule adsorption; however, ethanol is the dissociative adsorption on the hydroxylated anatase (0 0 1), and the coexistences of molecular and dissociation adsorption modes on the perfect anatase (0 0 1). On the other hand, the initial dissociation step of ethanol with molecule adsorption prefers to begin with its O-H bond cleavage leading to CH3CH2O and H species rather than the cleavage of its α-C-H, β-C-H, C-C and C-O bonds, namely, the preferable O-H bond cleavage for the initial dissociation step of ethanol is independent of the surface structure of anatase TiO2; however, the corresponding catalytic activity of ethanol initial dissociation step with the O-H bond cleavage on different anatase TiO2 surfaces is in the following order: hydroxylated (0 0 1) > perfect (0 0 1) > defective (1 0 1) > perfect (1 0 1), suggesting that the catalytic activity for the initial dissociation step of ethanol is sensitive to the surface structure of anatase TiO2, and the hydroxylated (0 0 1) is the most favorable surface. Among these surfaces, the most favorable product for the initial dissociation step of ethanol is CH3CH2O species.

Epithelial-mesenchymal Transition---A Hallmark of Breast Cancer Metastasis.

PubMed

Wang, Yifan; Zhou, Binhua P

2013-03-01

Epithelial-mesenchymal transition (EMT) is a highly conserved cellular program that converts polarized, immotile epithelial cells to migratory mesenchymal cells. In addition, EMT was initially recognized as a key step for morphogenesis during embryonic development. Emerging evidences indicate that this important developmental program promotes metastasis, drug resistance, and tumor recurrence, features that are associated with a poor clinical outcome for patients with breast cancer. Therefore, better understanding of regulation and signaling pathways in EMT is essential to develop novel targeted therapeutics. In this review, we present updated developments underlying EMT in tumor progression and metastasis, and discuss the challenges remaining in breast cancer research.

Improvements on the minimax algorithm for the Laplace transformation of orbital energy denominators

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

Helmich-Paris, Benjamin, E-mail: b.helmichparis@vu.nl; Visscher, Lucas, E-mail: l.visscher@vu.nl

2016-09-15

We present a robust and non-heuristic algorithm that finds all extremum points of the error distribution function of numerically Laplace-transformed orbital energy denominators. The extremum point search is one of the two key steps for finding the minimax approximation. If pre-tabulation of initial guesses is supposed to be avoided, strategies for a sufficiently robust algorithm have not been discussed so far. We compare our non-heuristic approach with a bracketing and bisection algorithm and demonstrate that 3 times less function evaluations are required altogether when applying it to typical non-relativistic and relativistic quantum chemical systems.

Flexible displays as key for high-value and unique automotive design

NASA Astrophysics Data System (ADS)

Isele, Robert

2011-03-01

Within the last few years' car industry changed very fast. Information and Communication became more important and displays are now standard in nearly every car. But this is not the only trend which could be recognized in this industry. CO2 emission, fuel price as well as the increasing traffic inside the Mega Cities initialized a big change in the behavior of the customers. The big battle for the car industry will enter the interior extremely fast, and the premium cars need ore innovative design icons. Flexible Displays are one big step that enables totally different designs and a new value of the driver experience.

The European Society of Gastrointestinal Endoscopy Quality Improvement Initiative: developing performance measures.

PubMed

Rutter, Matthew D; Senore, Carlo; Bisschops, Raf; Domagk, Dirk; Valori, Roland; Kaminski, Michal F; Spada, Cristiano; Bretthauer, Michael; Bennett, Cathy; Bellisario, Cristina; Minozzi, Silvia; Hassan, Cesare; Rees, Colin; Dinis-Ribeiro, Mário; Hucl, Tomas; Ponchon, Thierry; Aabakken, Lars; Fockens, Paul

2016-01-01

The European Society of Gastrointestinal Endoscopy (ESGE) and United European Gastroenterology (UEG) have a vision to create a thriving community of endoscopy services across Europe, collaborating with each other to provide high quality, safe, accurate, patient-centered and accessible endoscopic care. Whilst the boundaries of what can be achieved by advanced endoscopy are continually expanding, we believe that one of the most fundamental steps to achieving our goal is to raise the quality of everyday endoscopy. The development of robust, consensus- and evidence-based key performance measures is the first step in this vision.ESGE and UEG have identified quality of endoscopy as a major priority. This paper explains the rationale behind the ESGE Quality Improvement Initiative and describes the processes that were followed. We recommend that all units develop mechanisms for audit and feedback of endoscopist and service performance using the ESGE performance measures that will be published in future issues of this journal over the next year. We urge all endoscopists and endoscopy services to prioritize quality and to ensure that these performance measures are implemented and monitored at a local level, so that we can provide the highest possible care for our patients. © Georg Thieme Verlag KG Stuttgart · New York.

Long range Trp-Trp interaction initiates the folding pathway of a pro-angiogenic β-hairpin peptide

NASA Astrophysics Data System (ADS)

Diana, Donatella; De Rosa, Lucia; Palmieri, Maddalena; Russomanno, Anna; Russo, Luigi; La Rosa, Carmelo; Milardi, Danilo; Colombo, Giorgio; D'Andrea, Luca D.; Fattorusso, Roberto

2015-11-01

HPLW, a designed VEGF (Vascular Endothelium Growth Factor) receptor-binding peptide, assumes a well folded β-hairpin conformation in water and is able to induce angiogenesis in vivo. In this study, we investigated at atomic resolution the thermal folding/unfolding pathway of HPLW by means of an original multi-technique approach combining DSC, NMR, MD and mutagenesis analyses. In particular, careful NMR investigation of the single proton melting temperatures together with DSC analysis accurately delineate the peptide folding mechanism, which is corroborated by computational folding/unfolding simulations. The HPLW folding process consists of two main events, which are successive but do not superimpose. The first folding step initiates at 320 K upon the hydrophobic collapse of the Trp5 and Trp13 side-chains which stabilizes the concurrent β-turn formation, whose COi-HNi + 3 hydrogen bond (Asp10 → Arg7) appears particularly stable. At 316 K, once the β-turn is completely formed, the two β-strands pair, very likely starting by Trp5 and Trp13, which thus play a key role also in the final step of the β-hairpin folding. Overall, here we describe a multi-state hierarchical folding pathway of a highly structured β-hairpin, which can be classified as a broken-zipper mechanism.

Two-Step Mechanism of Membrane Disruption by Aβ through Membrane Fragmentation and Pore Formation

PubMed Central

Sciacca, Michele F.M.; Kotler, Samuel A.; Brender, Jeffrey R.; Chen, Jennifer; Lee, Dong-kuk; Ramamoorthy, Ayyalusamy

2012-01-01

Disruption of cell membranes by Aβ is believed to be one of the key components of Aβ toxicity. However, the mechanism by which this occurs is not fully understood. Here, we demonstrate that membrane disruption by Aβ occurs by a two-step process, with the initial formation of ion-selective pores followed by nonspecific fragmentation of the lipid membrane during amyloid fiber formation. Immediately after the addition of freshly dissolved Aβ1–40, defects form on the membrane that share many of the properties of Aβ channels originally reported from single-channel electrical recording, such as cation selectivity and the ability to be blockaded by zinc. By contrast, subsequent amyloid fiber formation on the surface of the membrane fragments the membrane in a way that is not cation selective and cannot be stopped by zinc ions. Moreover, we observed that the presence of ganglioside enhances both the initial pore formation and the fiber-dependent membrane fragmentation process. Whereas pore formation by freshly dissolved Aβ1–40 is weakly observed in the absence of gangliosides, fiber-dependent membrane fragmentation can only be observed in their presence. These results provide insights into the toxicity of Aβ and may aid in the design of specific compounds to alleviate the neurodegeneration of Alzheimer’s disease. PMID:22947931

Enhancing the far-UV sensitivity of silicon CMOS imaging arrays

NASA Astrophysics Data System (ADS)

Retherford, K. D.; Bai, Yibin; Ryu, Kevin K.; Gregory, J. A.; Welander, Paul B.; Davis, Michael W.; Greathouse, Thomas K.; Winter, Gregory S.; Suntharalingam, Vyshnavi; Beletic, James W.

2014-07-01

We report our progress toward optimizing backside-illuminated silicon PIN CMOS devices developed by Teledyne Imaging Sensors (TIS) for far-UV planetary science applications. This project was motivated by initial measurements at Southwest Research Institute (SwRI) of the far-UV responsivity of backside-illuminated silicon PIN photodiode test structures described in Bai et al., SPIE, 2008, which revealed a promising QE in the 100-200 nm range as reported in Davis et al., SPIE, 2012. Our effort to advance the capabilities of thinned silicon wafers capitalizes on recent innovations in molecular beam epitaxy (MBE) doping processes. Key achievements to date include: 1) Representative silicon test wafers were fabricated by TIS, and set up for MBE processing at MIT Lincoln Laboratory (LL); 2) Preliminary far-UV detector QE simulation runs were completed to aid MBE layer design; 3) Detector fabrication was completed through the pre-MBE step; and 4) Initial testing of the MBE doping process was performed on monitoring wafers, with detailed quality assessments. Early results suggest that potential challenges in optimizing the UV-sensitivity of silicon PIN type CMOS devices, compared with similar UV enhancement methods established for CCDs, have been mitigated through our newly developed methods. We will discuss the potential advantages of our approach and briefly describe future development steps.

DOE Big Idea Summit III: Solving the Information Technology Challenge Beyond Moore's Law: A New Path to Scaling.

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

McCormick, Frederick B.; Shalf, John; Mitchell, Alan

This report captures the initial conclusions of the DOE seven National Lab team collaborating on the “Solving the Information Technology Energy Challenge Beyond Moore’s Law” initiative from the DOE Big Idea Summit III held in April of 2016. The seven Labs held a workshop in Albuquerque, NM in late July 2016 and gathered 40 researchers into 5 working groups: 4 groups spanning the levels of the co-design framework shown below, and a 5th working group focused on extending and advancing manufacturing approaches and coupling their constraints to all of the framework levels. These working groups have identified unique capabilities withinmore » the Labs to support the key challenges of this Beyond Moore’s Law Computing (BMC) vision, as well as example first steps and potential roadmaps for technology development.« less

Neutrophils suppress intraluminal NK-mediated tumor cell clearance and enhance extravasation of disseminated carcinoma cells

PubMed Central

Spiegel, Asaf; Brooks, Mary W.; Houshyar, Samin; Reinhardt, Ferenc; Ardolino, Michele; Fessler, Evelyn; Chen, Michelle B.; Krall, Jordan A.; DeCock, Jasmine; Zervantonakis, Ioannis K.; Iannello, Alexandre; Iwamoto, Yoshiko; Cortez-Retamozo, Virna; Kamm, Roger D.; Pittet, Mikael J.; Raulet, David H.; Weinberg, Robert A.

2016-01-01

Immune cells promote the initial metastatic dissemination of carcinoma cells from primary tumors. In contrast to their well-studied functions in the initial stages of metastasis, the specific roles of immunocytes in facilitating progression through the critical later steps of the invasion-metastasis cascade remain poorly understood. Here we define novel functions of neutrophils in promoting intraluminal survival and extravasation at sites of metastatic dissemination. We show that CD11b+/Ly6G+ neutrophils enhance metastasis formation via two distinct mechanisms. First, neutrophils inhibit natural killer cell function, which leads to a significant increase in the intraluminal survival time of tumor cells. Thereafter, neutrophils operate to facilitate extravasation of tumor cells through the secretion of IL-1β and matrix metalloproteinases. These results identify neutrophils as key regulators of intraluminal survival and extravasation through their crosstalk with host cells and disseminating carcinoma cells. PMID:27072748

School Climate Improvement Action Guide for District Leaders. School Climate Improvement Resource Package

ERIC Educational Resources Information Center

National Center on Safe Supportive Learning Environments, 2017

2017-01-01

Improving school climate takes time and commitment from a variety of people in a variety of roles. This document outlines key action steps that district leaders--including superintendents, assistant superintendents, directors of student support services, or others--can take to support school climate improvements. Key action steps are provided for…

Maelstrom Research guidelines for rigorous retrospective data harmonization

PubMed Central

Fortier, Isabel; Raina, Parminder; Van den Heuvel, Edwin R; Griffith, Lauren E; Craig, Camille; Saliba, Matilda; Doiron, Dany; Stolk, Ronald P; Knoppers, Bartha M; Ferretti, Vincent; Granda, Peter; Burton, Paul

2017-01-01

Abstract Background: It is widely accepted and acknowledged that data harmonization is crucial: in its absence, the co-analysis of major tranches of high quality extant data is liable to inefficiency or error. However, despite its widespread practice, no formalized/systematic guidelines exist to ensure high quality retrospective data harmonization. Methods: To better understand real-world harmonization practices and facilitate development of formal guidelines, three interrelated initiatives were undertaken between 2006 and 2015. They included a phone survey with 34 major international research initiatives, a series of workshops with experts, and case studies applying the proposed guidelines. Results: A wide range of projects use retrospective harmonization to support their research activities but even when appropriate approaches are used, the terminologies, procedures, technologies and methods adopted vary markedly. The generic guidelines outlined in this article delineate the essentials required and describe an interdependent step-by-step approach to harmonization: 0) define the research question, objectives and protocol; 1) assemble pre-existing knowledge and select studies; 2) define targeted variables and evaluate harmonization potential; 3) process data; 4) estimate quality of the harmonized dataset(s) generated; and 5) disseminate and preserve final harmonization products. Conclusions: This manuscript provides guidelines aiming to encourage rigorous and effective approaches to harmonization which are comprehensively and transparently documented and straightforward to interpret and implement. This can be seen as a key step towards implementing guiding principles analogous to those that are well recognised as being essential in securing the foundational underpinning of systematic reviews and the meta-analysis of clinical trials. PMID:27272186

Developmentally programmed DNA deletion in Tetrahymena thermophila by a transposition-like reaction pathway.

PubMed Central

Saveliev, S V; Cox, M M

1996-01-01

We provide a molecular description of key intermediates in the deletion of two internal eliminated sequences (IES elements), the M and R regions, during macronuclear development in Tetrahymena thermophila. Using a variety of PCR-based methods in vivo, double-strand breaks are detected that are generated by hydrolytic cleavage and correspond closely to the observed chromosomal junctions left behind in the macronuclei. The breaks exhibit a temporal and structural relationship to the deletion reaction that provides strong evidence that they are intermediates in the deletion pathway. Breaks in the individual strands are staggered by 4 bp, producing a four nucleotide 5' extension. Evidence is presented that breaks do not occur simultaneously at both ends. The results are most consistent with a deletion mechanism featuring initiation by double-strand cleavage at one end of the deleted element, followed by transesterification to generate the macronuclear junction on one DNA strand. An adenosine residue is found at all the nucleophilic 3' ends used in the postulated transesterification step. Evidence for the transesterification step is provided by detection of a 3' hydroxyl that would be liberated by such a step at a deletion boundary where no other DNA strand ends are detected. Images PMID:8654384

Kinematic Adaptations of Forward And Backward Walking on Land and in Water

PubMed Central

Cadenas-Sanchez, Cristina; Arellano, Raúl; Vanrenterghem, Jos; López-Contreras, Gracia

2015-01-01

The aim of this study was to compare sagittal plane lower limb kinematics during walking on land and submerged to the hip in water. Eight healthy adults (age 22.1 ± 1.1 years, body height 174.8 ± 7.1 cm, body mass 63.4 ± 6.2 kg) were asked to cover a distance of 10 m at comfortable speed with controlled step frequency, walking forward or backward. Sagittal plane lower limb kinematics were obtained from three dimensional video analysis to compare spatiotemporal gait parameters and joint angles at selected events using two-way repeated measures ANOVA. Key findings were a reduced walking speed, stride length, step length and a support phase in water, and step length asymmetry was higher compared to the land condition (p<0.05). At initial contact, knees and hips were more flexed during walking forward in water, whilst, ankles were more dorsiflexed during walking backward in water. At final stance, knees and ankles were more flexed during forward walking, whilst the hip was more flexed during backward walking. These results show how walking in water differs from walking on land, and provide valuable insights into the development and prescription of rehabilitation and training programs. PMID:26839602

Control of mediolateral stability during rapid step initiation with preferred and non-preferred leg: is it symmetrical?

PubMed

Yiou, E; Do, M C

2010-05-01

During voluntary stepping initiation, postural stability along the mediolateral direction is controlled via "anticipatory postural adjustment" (APA). This study tested the hypothesis that, in young healthy subjects, the biomechanical features of mediolateral APA depend on the leg that initiates stepping. Subjects (N=10) initiated a rapid single step with the preferred (P condition) and the non-preferred leg (NP condition) on a force-plate. Results showed that mediolateral APA duration (P=0.020) and amplitude were higher (as attested by the increase in maximal center-of-gravity velocity (P=0.003) and displacement (P<0.001) during APA), and that mediolateral stability was better (as attested by the attenuation in center-of-gravity velocity at time of swing-foot contact (P=0.007)) in P than in NP. These results support the view that stepping initiation in healthy subjects involves postural asymmetry. This statement may have relevant implications in clinical evaluation where postural asymmetry is generally considered as reflecting postural impairment. Copyright 2010 Elsevier B.V. All rights reserved.

Measurement of low-frequency magnetic pulses from negative stepped leaders in rocket-triggered lightning flashes

NASA Astrophysics Data System (ADS)

Lu, Gaopeng

2017-04-01

Measurement of low-frequency magnetic pulses from negative stepped leaders in rocket-triggered lightning flashes Gaopeng Lu,1,2 Yanfeng Fan,1,3 Hongbo Zhang,1,3 Rubin Jiang,1,2 Mingyuan Liu,1,2 and Xiushu Qie,1,2 1. Key Laboratory of Middle Atmosphere and Global Environment Observation, Institute of Atmospheric Physics, Chinese Academy of Sciences, Beijing, 100029, China 2. Collaborative Innovation Center on Forecast and Evaluation of Meteorological Disasters, Nanjing University of Information Science and Technology, Nanjing, Jiangsu 210044, China 3. University of Chinese Academy of Sciences, Beijing 100049, China We report the measurement of magnetic pulses from the negative stepped leaders in positive rocket-triggered lightning flashes with the low-frequency (4 kHz to 420 kHz) magnetic sensor at two different distances (78 m and 970 m, respectively) during the SHantong Artificial Triggered Lightning Experiments (SHATLE) during summer of 2015. Different from the magnetic radiation from positive leaders as observed in the considerably more frequent cases, the impulsive signals from the negative leader sustain for a much longer time interval, while the attenuation of current pulse launched by the stepping of leader is also observed. The general pattern of magnetic pulses observed for the negative stepped leader is different from the positive counterpart. Also, the initial negative leader appears to be brighter than the positive ones, as shown by both high-speed video observation and the magnetic measurement.

In Vitro Modeling of Mechanics in Cancer Metastasis

PubMed Central

2017-01-01

In addition to a multitude of genetic and biochemical alterations, abnormal morphological, structural, and mechanical changes in cells and their extracellular environment are key features of tumor invasion and metastasis. Furthermore, it is now evident that mechanical cues alongside biochemical signals contribute to critical steps of cancer initiation, progression, and spread. Despite its importance, it is very challenging to study mechanics of different steps of metastasis in the clinic or even in animal models. While considerable progress has been made in developing advanced in vitro models for studying genetic and biological aspects of cancer, less attention has been paid to models that can capture both biological and mechanical factors realistically. This is mainly due to lack of appropriate models and measurement tools. After introducing the central role of mechanics in cancer metastasis, we provide an outlook on the emergence of novel in vitro assays and their combination with advanced measurement technologies to probe and recapitulate mechanics in conditions more relevant to the metastatic disease. PMID:29457129

Dynamic cholesteric liquid crystal superstructures photoaligned by one-step polarization holography

NASA Astrophysics Data System (ADS)

Li, Sen-Sen; Shen, Yuan; Chang, Zhen-Ni; Li, Wen-Song; Xu, Yan-Chao; Fan, Xing-Yu; Chen, Lu-Jian

2017-12-01

A convenient approach to modulate the fingerprint textures of methyl red (MR) doped cholesteric liquid crystals by asymmetric photoalignment in the green-light waveband is presented, resulting in the generation of voltage-controllable helical superstructures. The interaction between the MR molecules and the incident light polarization determines the initial twisted planar geometry, providing a multivariant control over the stripe directions of fingerprint textures by applying a proper electric field. The key factors for precise manipulation of fingerprint stripes in a predictable and rewritable manner are analyzed theoretically and investigated experimentally, which involves the alignment asymmetry, the ratio of cell gap to natural pitch length, and the chirality of chiral dopant. Dynamic periodic fingerprint textures in shapes of dashed curve and dashed line are further demonstrated by utilizing a facile one-step polarization holography process using two beams with orthogonal circular and orthogonal linear polarizations, respectively. It is believed that the practical approach described in this study would enrich the research contents of self-assembled hierarchical superstructures using soft liquid crystal building blocks.

An automatic and effective parameter optimization method for model tuning

NASA Astrophysics Data System (ADS)

Zhang, T.; Li, L.; Lin, Y.; Xue, W.; Xie, F.; Xu, H.; Huang, X.

2015-05-01

Physical parameterizations in General Circulation Models (GCMs), having various uncertain parameters, greatly impact model performance and model climate sensitivity. Traditional manual and empirical tuning of these parameters is time consuming and ineffective. In this study, a "three-step" methodology is proposed to automatically and effectively obtain the optimum combination of some key parameters in cloud and convective parameterizations according to a comprehensive objective evaluation metrics. Different from the traditional optimization methods, two extra steps, one determines parameter sensitivity and the other chooses the optimum initial value of sensitive parameters, are introduced before the downhill simplex method to reduce the computational cost and improve the tuning performance. Atmospheric GCM simulation results show that the optimum combination of these parameters determined using this method is able to improve the model's overall performance by 9%. The proposed methodology and software framework can be easily applied to other GCMs to speed up the model development process, especially regarding unavoidable comprehensive parameters tuning during the model development stage.

Dispersive shock waves in systems with nonlocal dispersion of Benjamin-Ono type

NASA Astrophysics Data System (ADS)

El, G. A.; Nguyen, L. T. K.; Smyth, N. F.

2018-04-01

We develop a general approach to the description of dispersive shock waves (DSWs) for a class of nonlinear wave equations with a nonlocal Benjamin-Ono type dispersion term involving the Hilbert transform. Integrability of the governing equation is not a pre-requisite for the application of this method which represents a modification of the DSW fitting method previously developed for dispersive-hydrodynamic systems of Korteweg-de Vries (KdV) type (i.e. reducible to the KdV equation in the weakly nonlinear, long wave, unidirectional approximation). The developed method is applied to the Calogero-Sutherland dispersive hydrodynamics for which the classification of all solution types arising from the Riemann step problem is constructed and the key physical parameters (DSW edge speeds, lead soliton amplitude, intermediate shelf level) of all but one solution type are obtained in terms of the initial step data. The analytical results are shown to be in excellent agreement with results of direct numerical simulations.

Triggers of key calcium signals during erythrocyte invasion by Plasmodium falciparum

PubMed Central

Gao, Xiaohong; Gunalan, Karthigayan; Yap, Sally Shu Lin; Preiser, Peter R.

2013-01-01

Invasion of erythrocytes by Plasmodium falciparum merozoites is a complex multi-step process mediated by specific interactions between host receptors and parasite ligands. Reticulocyte-binding protein homologues (RHs) and erythrocyte-binding-like (EBL) proteins are discharged from specialized organelles and used in early steps of invasion. Here we show that monoclonal antibodies against PfRH1 (an RH) block merozoite invasion by specifically inhibiting calcium signalling in the parasite, whereas invasion-inhibiting monoclonal antibodies targeting EBA175 (an EBL protein) have no effect on signalling. We further show that inhibition of this calcium signalling prevents EBA175 discharge and thereby formation of the junction between parasite and host cell. Our results indicate that PfRH1 has an initial sensing as well as signal transduction role that leads to the subsequent release of EBA175. They also provide new insights on how RH–host cell interactions lead to essential downstream signalling events in the parasite, suggesting new targets for malaria intervention. PMID:24280897

2'-O-methylation in mRNA disrupts tRNA decoding during translation elongation.

PubMed

Choi, Junhong; Indrisiunaite, Gabriele; DeMirci, Hasan; Ieong, Ka-Weng; Wang, Jinfan; Petrov, Alexey; Prabhakar, Arjun; Rechavi, Gideon; Dominissini, Dan; He, Chuan; Ehrenberg, Måns; Puglisi, Joseph D

2018-03-01

Chemical modifications of mRNA may regulate many aspects of mRNA processing and protein synthesis. Recently, 2'-O-methylation of nucleotides was identified as a frequent modification in translated regions of human mRNA, showing enrichment in codons for certain amino acids. Here, using single-molecule, bulk kinetics and structural methods, we show that 2'-O-methylation within coding regions of mRNA disrupts key steps in codon reading during cognate tRNA selection. Our results suggest that 2'-O-methylation sterically perturbs interactions of ribosomal-monitoring bases (G530, A1492 and A1493) with cognate codon-anticodon helices, thereby inhibiting downstream GTP hydrolysis by elongation factor Tu (EF-Tu) and A-site tRNA accommodation, leading to excessive rejection of cognate aminoacylated tRNAs in initial selection and proofreading. Our current and prior findings highlight how chemical modifications of mRNA tune the dynamics of protein synthesis at different steps of translation elongation.

[Discussion on exploitation of foreign traditional chinese medicine resources based on "the Belt and Road"].

PubMed

Zhang, Xiao-Bo; Lyu, Dong-Mei; Huang, Lu-Qi; Li, Meng; Guo, Lan-Ping; Peng, Hua-Sheng

2018-04-01

At the beginning of the ancient "Silk Road", traditional Chinese medicine resources (TCM resources) have long been integrated into it, and it was once the "important part" of the ancient "Silk Road" in Chinese history, benefited from this, the political connections was strengthened, the economic and trade was developed, and Chinese medicine culture was spread. Before Qing Dynasty, people took out the "silk" and brought back "herbs" on the "Silk Road", which enriched China's medicinal resources. While in the later Qing Dynasty and the period of the Republic of China, more scientific and technological methods were brought back from abroad, and this in turn enriched the medical research methods. With more than 2 000 years' development, China's boundaries have changed countless times, therefore the word "Foreign" has different meanings in different historical periods. The import, development and utilization of foreign TCM resources is different in different historical periods, at present, with the continuous enhancement of China's comprehensiv national strength，especially the "Belt And Road" strategy, the communication and import of TCM resources with countries that participating in the "Belt and Road" initiativ became much easier. In order to actively respond to the "Belt and Road" initiative promote the development and utilization of foreign medicinal resources; serve people from the countries participating in the "Belt and Road" initiative we sorted out the foreign TCM resources from different periods in ancient and modern China, and based on this, we proposed the strategy of import of foreign TCM resources under the new situation, those are: "three levels, four steps, one support and one key". And "three levels" refers to intelligence collection level, field investigation level, scientific research level, "Four steps" refers to the original identification research, safety evaluation research, functional positioning research and medicinal properties research; "One support" refers to relying on overseas Chinese or Chinese enterprises with working foundation and network resources, "One key" refers to the protection of the intellectual property rights of foreign TCM resources at the policy level and to mobilize the initiative of all parties. Copyright© by the Chinese Pharmaceutical Association.

School Climate Improvement Action Guide for Instructional Staff. School Climate Improvement Resource Package

ERIC Educational Resources Information Center

National Center on Safe Supportive Learning Environments, 2017

2017-01-01

Improving school climate takes time and commitment from a variety of people in a variety of roles. This document outlines key action steps that instructional staff--including teachers, paraprofessionals, and others in the classroom who provide instruction or assistance--can take to support school climate improvements. Key action steps are provided…

School Climate Improvement Action Guide for School Leaders. School Climate Improvement Resource Package

ERIC Educational Resources Information Center

National Center on Safe Supportive Learning Environments, 2017

2017-01-01

Improving school climate takes time and commitment from a variety of people in a variety of roles. This document outlines key action steps that school leaders--including principals, assistant/vice principals, and building leaders--can take to support school climate improvements. Key action steps are provided for the following strategies: (1)…

School Climate Improvement Action Guide for Working with Students. School Climate Improvement Resource Package

ERIC Educational Resources Information Center

National Center on Safe Supportive Learning Environments, 2017

2017-01-01

Improving school climate takes time and commitment from a variety of people in a variety of roles. This document outlines key action steps to engage students in the school climate improvement process. Key action steps are provided for the following strategies: (1) Participate in planning for school climate improvements; (2) Engage stakeholders in…

Taking Leadership in Initiating a Comprehensive US International Education Policy

ERIC Educational Resources Information Center

Lad, Kaetlyn

2008-01-01

A first step to ensuring that emerging school leaders possess the dispositions and skills necessary to be successful in a global community is for educational leaders to take initiative in moving toward a comprehensive Us International Education Policy. This article introduces possible steps to initiate such a policy.

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

Gehin, Jess C; Godfrey, Andrew T; Evans, Thomas M

The Consortium for Advanced Simulation of Light Water Reactors (CASL) is developing a collection of methods and software products known as VERA, the Virtual Environment for Reactor Applications, including a core simulation capability called VERA-CS. A key milestone for this endeavor is to validate VERA against measurements from operating nuclear power reactors. The first step in validation against plant data is to determine the ability of VERA to accurately simulate the initial startup physics tests for Watts Bar Nuclear Power Station, Unit 1 (WBN1) cycle 1. VERA-CS calculations were performed with the Insilico code developed at ORNL using cross sectionmore » processing from the SCALE system and the transport capabilities within the Denovo transport code using the SPN method. The calculations were performed with ENDF/B-VII.0 cross sections in 252 groups (collapsed to 23 groups for the 3D transport solution). The key results of the comparison of calculations with measurements include initial criticality, control rod worth critical configurations, control rod worth, differential boron worth, and isothermal temperature reactivity coefficient (ITC). The VERA results for these parameters show good agreement with measurements, with the exception of the ITC, which requires additional investigation. Results are also compared to those obtained with Monte Carlo methods and a current industry core simulator.« less

Origin of symbol-using systems: speech, but not sign, without the semantic urge

PubMed Central

Sereno, Martin I.

2014-01-01

Natural language—spoken and signed—is a multichannel phenomenon, involving facial and body expression, and voice and visual intonation that is often used in the service of a social urge to communicate meaning. Given that iconicity seems easier and less abstract than making arbitrary connections between sound and meaning, iconicity and gesture have often been invoked in the origin of language alongside the urge to convey meaning. To get a fresh perspective, we critically distinguish the origin of a system capable of evolution from the subsequent evolution that system becomes capable of. Human language arose on a substrate of a system already capable of Darwinian evolution; the genetically supported uniquely human ability to learn a language reflects a key contact point between Darwinian evolution and language. Though implemented in brains generated by DNA symbols coding for protein meaning, the second higher-level symbol-using system of language now operates in a world mostly decoupled from Darwinian evolutionary constraints. Examination of Darwinian evolution of vocal learning in other animals suggests that the initial fixation of a key prerequisite to language into the human genome may actually have required initially side-stepping not only iconicity, but the urge to mean itself. If sign languages came later, they would not have faced this constraint. PMID:25092671

IL27 controls skin tumorigenesis via accumulation of ETAR-positive CD11b cells in the pre-malignant skin

PubMed Central

Dibra, Denada; Mitra, Abhisek; Newman, Melissa; Xia, Xueqing; Keenan, Camille; Cutrera, Jeffry J.; Mathis, J. Michael; Wang, Xiao-Jing; Myers, Jeffrey; Li, Shulin

2016-01-01

Establishment of a permissive pre-malignant niche in concert with mutant stem are key triggers to initiate skin carcinogenesis. An understudied area of research is finding upstream regulators of both these triggers. IL27, a pleiotropic cytokine with both pro- and anti-inflammatory properties, was found to be a key regulator of both. Two step skin carcinogenesis model and K15-KRASG12D mouse model were used to understand the role of IL27 in skin tumors. CD11b−/− mice and small-molecule of ETAR signaling (ZD4054) inhibitor were used in vivo to understand mechanistically how IL27 promotes skin carcinogenesis. Interestingly, using in vivo studies, IL27 promoted papilloma incidence primarily through IL27 signaling in bone-marrow derived cells. Mechanistically, IL27 initiated the establishment of the pre-malignant niche and expansion of mutated stem cells in K15-KRASG12D mouse model by driving the accumulation of Endothelin A receptor (ETAR)-positive CD11b cells in the skin—a novel category of pro-tumor inflammatory identified in this study. These findings are clinically relevant, as the number of IL27RA-positive cells in the stroma is highly related to tumor de-differentiation in patients with squamous cell carcinomas. PMID:27738312

Sensitivity of Austempering Heat Treatment of Ductile Irons to Changes in Process Parameters

NASA Astrophysics Data System (ADS)

Boccardo, A. D.; Dardati, P. M.; Godoy, L. A.; Celentano, D. J.

2018-06-01

Austempered ductile iron (ADI) is frequently obtained by means of a three-step austempering heat treatment. The parameters of this process play a crucial role on the microstructure of the final product. This paper considers the influence of some process parameters ( i.e., the initial microstructure of ductile iron and the thermal cycle) on key features of the heat treatment (such as minimum required time for austenitization and austempering and microstructure of the final product). A computational simulation of the austempering heat treatment is reported in this work, which accounts for a coupled thermo-metallurgical behavior in terms of the evolution of temperature at the scale of the part being investigated (the macroscale) and the evolution of phases at the scale of microconstituents (the microscale). The paper focuses on the sensitivity of the process by looking at a sensitivity index and scatter plots. The sensitivity indices are determined by using a technique based on the variance of the output. The results of this study indicate that both the initial microstructure and the thermal cycle parameters play a key role in the production of ADI. This work also provides a guideline to help selecting values of the appropriate process parameters to obtain parts with a required microstructural characteristic.

Canadian Adjuvant Initiative Workshop, March 26–27, 2013—Ottawa, Canada

PubMed Central

Krishnan, Lakshmi; Twine, Susan; Gerdts, Volker; Barreto, Luis; Richards, James C

2014-01-01

Novel adjuvants hold the promise for developing effective modern subunit vaccines capable of appropriately modulating the immune response against challenging diseases such as those caused by chronic and/or intracellular pathogens and cancer. Over the past decade there has been intensive research into discovering new adjuvants, however, their translation into routine clinical use is lagging. To stimulate discussion and identify opportunities for networking and collaboration among various stakeholders, a Canadian Adjuvant Initiative Workshop was held in Ottawa. Sponsored by the National Research Council Canada, Canadian Institutes of Health Research and the Vaccine Industry Committee, a two day workshop was held that brought together key Canadian and international stakeholders in adjuvant research from industry, academia and government. To discover innovation gaps and unmet needs, the presentations covered a board range of topics in adjuvant development; criteria for selection of lead adjuvant candidates from an industry perspective, discovery research across Canada, bioprocessing needs and challenges, veterinary vaccines, Canadian vaccine trial capabilities, the Canadian regulatory framework and WHO formulation laboratory experience. The workshop concluded with a discussion on the opportunity to create a Canadian Adjuvant Development Network. This report details the key discussion points and steps forward identified for facilitating adjuvant development research in Canada. PMID:24192752

Continuous track paths reveal additive evidence integration in multistep decision making.

PubMed

Buc Calderon, Cristian; Dewulf, Myrtille; Gevers, Wim; Verguts, Tom

2017-10-03

Multistep decision making pervades daily life, but its underlying mechanisms remain obscure. We distinguish four prominent models of multistep decision making, namely serial stage, hierarchical evidence integration, hierarchical leaky competing accumulation (HLCA), and probabilistic evidence integration (PEI). To empirically disentangle these models, we design a two-step reward-based decision paradigm and implement it in a reaching task experiment. In a first step, participants choose between two potential upcoming choices, each associated with two rewards. In a second step, participants choose between the two rewards selected in the first step. Strikingly, as predicted by the HLCA and PEI models, the first-step decision dynamics were initially biased toward the choice representing the highest sum/mean before being redirected toward the choice representing the maximal reward (i.e., initial dip). Only HLCA and PEI predicted this initial dip, suggesting that first-step decision dynamics depend on additive integration of competing second-step choices. Our data suggest that potential future outcomes are progressively unraveled during multistep decision making.

31P and 13C NMR analyses of the energy metabolism of the thermophilic anaerobe Clostridium thermocellum.

PubMed

Tolman, C J; Kanodia, S; Roberts, M F

1987-08-15

The energy metabolism of an anaerobic obligate thermophile, Clostridium thermocellum, has been examined as a function of incubation temperature using 31P NMR spectroscopy. Specifically investigated were the generation and availability of ATP as a function of temperature, activation energies for key processes in energy metabolism including formation of a pH gradient across the cell membrane, transport of key nutrients, and initial steps in glycolysis, and the existence of a membrane phase transition in the intact organism. Cells generate ATP via glycolysis at all temperatures examined; hence, limitation of the energy supply is not directly responsible for the lack of growth of this organism at low temperatures. Estimations of activation energies show a distinct hierarchy in the ATP-utilizing reactions examined. Conservation of ATP hydrolysis energy as delta pH has the lowest activation energy (less than or equal to 4 kcal/mol), two transport processes exhibit 10 kcal/mol activation energies, and early phosphorylation steps in glycolysis have significantly higher activation energies (approximately 25 kcal/mol). Neither the membrane-bound ATPase responsible for formation of the pH gradient nor the permease involved in phosphate transport shows evidence of a change in behavior around the phase transition temperature determined for extracted lipids of C. thermocellum. Line widths of inorganic phosphate do show a break in behavior around 35-40 degrees C. Possible explanations for this behavior are discussed.

Initial Integration of Noise Prediction Tools for Acoustic Scattering Effects

NASA Technical Reports Server (NTRS)

Nark, Douglas M.; Burley, Casey L.; Tinetti, Ana; Rawls, John W.

2008-01-01

This effort provides an initial glimpse at NASA capabilities available in predicting the scattering of fan noise from a non-conventional aircraft configuration. The Aircraft NOise Prediction Program, Fast Scattering Code, and the Rotorcraft Noise Model were coupled to provide increased fidelity models of scattering effects on engine fan noise sources. The integration of these codes led to the identification of several keys issues entailed in applying such multi-fidelity approaches. In particular, for prediction at noise certification points, the inclusion of distributed sources leads to complications with the source semi-sphere approach. Computational resource requirements limit the use of the higher fidelity scattering code to predict radiated sound pressure levels for full scale configurations at relevant frequencies. And, the ability to more accurately represent complex shielding surfaces in current lower fidelity models is necessary for general application to scattering predictions. This initial step in determining the potential benefits/costs of these new methods over the existing capabilities illustrates a number of the issues that must be addressed in the development of next generation aircraft system noise prediction tools.

Tandem reactions initiated by copper-catalyzed cross-coupling: a new strategy towards heterocycle synthesis.

PubMed

Liu, Yunyun; Wan, Jie-Ping

2011-10-21

Copper-catalyzed cross-coupling reactions which lead to the formation of C-N, C-O, C-S and C-C bonds have been recognized as one of the most useful strategies in synthetic organic chemistry. During past decades, important breakthroughs in the study of Cu-catalyzed coupling processes demonstrated that Cu-catalyzed reactions are broadly applicable to a variety of research fields related to organic synthesis. Representatively, employing these coupling transformations as key steps, a large number of tandem reactions have been developed for the construction of various heterocyclic compounds. These tactics share the advantages of high atom economics of tandem reactions as well as the broad tolerance of Cu-catalyst systems. Therefore, Cu-catalyzed C-X (X = N, O, S, C) coupling transformation-initiated tandem reactions were quickly recognized as a strategy with great potential for synthesizing heterocyclic compounds and gained worldwide attention. In this review, recent research progress in heterocycle syntheses using tandem reactions initiated by copper-catalyzed coupling transformations, including C-N, C-O, C-S as well as C-C coupling processes are summarized.

MESOSCALE MODELING OF DEFLAGRATION-INDUCED DECONSOLIDATION IN POLYMER-BONDED EXPLOSIVES

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

Springer, H K; Glascoe, E A; Reaugh, J E

Initially undamaged polymer-bonded explosives can transition from conductive burning to more violent convective burning via rapid deconsolidation at higher pressures. The pressure-dependent infiltration of cracks and pores, i.e., damage, by product gases at the burn-front is a key step in the transition to convective burning. However, the relative influence of pre-existing damage and the evolution of deflagration-induced damage during the transition to convective burning is not well understood. The objective of this study is to investigate the role of microstructure and initial pressurization on deconsolidation. We performed simulations using the multi-physics hydrocode, ALE3D. HMX-Viton A served as our model explosive.more » A Prout-Tompkins chemical kinetic model, Vielle's Law pressure-dependent burning, Gruneisen equation-of-state, and simplified strength model were used for the HMX. The propensity for deconsolidation increased with increasing defect size and decreasing initial pressurization, as measured by the increase in burning surface area. These studies are important because they enable the development of continuum-scale damage models and the design of inherently safer explosives.« less

Six-sigma application in tire-manufacturing company: a case study

NASA Astrophysics Data System (ADS)

Gupta, Vikash; Jain, Rahul; Meena, M. L.; Dangayach, G. S.

2017-09-01

Globalization, advancement of technologies, and increment in the demand of the customer change the way of doing business in the companies. To overcome these barriers, the six-sigma define-measure-analyze-improve-control (DMAIC) method is most popular and useful. This method helps to trim down the wastes and generating the potential ways of improvement in the process as well as service industries. In the current research, the DMAIC method was used for decreasing the process variations of bead splice causing wastage of material. This six-sigma DMAIC research was initiated by problem identification through voice of customer in the define step. The subsequent step constitutes of gathering the specification data of existing tire bead. This step was followed by the analysis and improvement steps, where the six-sigma quality tools such as cause-effect diagram, statistical process control, and substantial analysis of existing system were implemented for root cause identification and reduction in process variation. The process control charts were used for systematic observation and control the process. Utilizing DMAIC methodology, the standard deviation was decreased from 2.17 to 1.69. The process capability index (C p) value was enhanced from 1.65 to 2.95 and the process performance capability index (C pk) value was enhanced from 0.94 to 2.66. A DMAIC methodology was established that can play a key role for reducing defects in the tire-manufacturing process in India.

Covalent attachment of polymeric monolith to polyether ether ketone (PEEK) tubing.

PubMed

Lv, Chunguang; Heiter, Jaana; Haljasorg, Tõiv; Leito, Ivo

2016-08-17

A new method of reproducible preparation of vinylic polymeric monolithic columns with a key step of covalently anchoring the monolith to PEEK surface is described. In order to chemically attach the polymer monolith to the tube wall, methacrylate functional groups were introduced onto PEEK surface by a three-step procedure, including surface etching, surface reduction and surface methacryloylation. The chemical state of the modified tubing surface was characterized by attenuated total reflectance infrared (ATR-IR) spectroscopy. It was found that the etching step is the key to successfully modifying the PEEK tubing surface. Poly(styrene-co-divinylbenzene) monoliths were in situ synthesized by thermally initiated free radical copolymerization within the confines of surface-vinylized PEEK tubings of dimensions close to ones conventionally used in HPLC and UHPLC (1.6 mm internal diameter, 10.0-12.5 cm length). Adhesion test was done by measuring the operating pressure drop, which the prepared stationary phases can withstand. Good pressure resistance, up to 140 bar/10 cm (flow rate 0.5 mL min(-1), acetonitrile as a mobile phase), indicates strong bonding of monolith to the tubing wall. The monolithic material was proven to have a permeability of 1.7 × 10 (-14) m(2), applying acetonitrile-water 70:30 (v/v) as a mobile phase. The column performance was reproducible from column to column and was evaluated via the isocratic separation of a series of alkylbenzenes in the reversed-phase mode (acetonitrile-water 70:30, v/v). The numbers of plates per meter at optimal flow rate were found to be between 26 000 and 32 000 for the different analytes. Copyright © 2016 Elsevier B.V. All rights reserved.

[Differences in anticipatory postural adjustments between self-generated and triggered gait initiation in 20 healthy subjects].

PubMed

Delval, A; Krystkowiak, P; Blatt, J-L; Labyt, E; Destée, A; Derambure, P; Defebvre, L

2005-01-01

Preparation of upper-limb movements differs between self-paced and triggered conditions. This study analyzed the anticipatory postural adjustments (APAs) of gait initiation in normal subjects in 2 conditions: self-generated and triggered by a "beep" sound. We recorded kinematic, spatiotemporal parameters of the first two steps by means of video motion analysis (6 infrared cameras), and kinetic parameters (using a force platform and the optoelectronic system) in 20 normal subjects. Two conditions: 1) self-generated initiation; and 2) initiation triggered by a "beep" sound were studied to evaluate the APA phase, by recording kinetic data (duration of the APAs, trajectory of the center of pressure, speed and trajectory of the center of mass). Kinematic data (first and second step speed, length and duration) were also recorded. First step speed and length were increased in self-paced gait initiation compared to triggered gait initiation in controls. We found no difference between the 2 conditions in terms of second step kinematic data. It was caused by a significant difference between the 2 conditions for the temporal characteristics of anticipatory postural adjustments (APAs) in the initiation of the first step, which was longer when normal subjects performed self-generated gait initiation. The trajectory of center of pressure and center of mass remained the same in the 2 conditions. APAs of gait initiation process are delayed under self-paced condition, although they do not differ qualitatively between reaction time and self-paced condition. Neuphysiological support of self-generated movement could explain these differences.

Phosphate Tether-Mediated Approach to the Formal Total Synthesis of (-)-Salicylihalamides A and B

PubMed Central

Chegondi, Rambabu; Tan, Mary M. L.; Hanson, Paul R.

2011-01-01

A concise formal synthesis of the cytotoxic macrolides (-)-salicylihalamides A and B is reported. Key features of the synthetic strategy include a chemoselective hydroboration, highly regio- and diastereoselective methyl cuprate addition, Pd-catalyzed formate reduction, and an E-selective ring-closing metathesis to construct the 12-membered macrocycle subunit. Overall, two routes have been developed from a readily prepared bicyclic phosphate (4-steps), a 13-step route and a more efficient 9-step sequence relying on regioselective esterification of a key diol. PMID:21504150

Improving access to important recovery information for heart patients with low health literacy: reflections on practice-based initiatives.

PubMed

Naccarella, Lucio; Biuso, Catuscia; Jennings, Amanda; Patsamanis, Harry

2018-05-29

Evidence exists for the association between health literacy and heart health outcomes. Cardiac rehabilitation is critical for recovery from heart attack and reducing hospital readmissions. Despite this, <30% of people participate in a program. Significant patient, hospital and health system challenges exist to improve recovery through increased heart health literacy. This brief case study reflects and documents practice-based initiatives by Heart Foundation Victoria to improve access to recovery information for patients with low literacy levels. Three key initiatives, namely the Six Steps To Cardiac Recovery resource, the Love Your Heart book and the nurse ambassador program, were implemented informed by mixed methods that assessed need and capacity at the individual, organisational and systems levels. Key outcomes included increased access to recovery information for patients with low health literacy, nurse knowledge and confidence to engage with patients on recovery information, improved education of patients and improved availability and accessibility of information for patients in diverse formats. Given the challenges involved in addressing heart health literacy, multifaceted practice-based approaches are essential to improve access to recovery information for patients with low literacy levels. What is known about the topic? Significant challenges exist for patients with lower health literacy receiving recovery information after a heart attack in hospitals. What does this paper add? This case study provides insights into a practice-based initiative by Heart Foundation Victoria to improve access to recovery information for patients with low literacy levels. What are the implications for practitioners? Strategies to improve recovery through increased heart health literacy must address the needs of patients, nursing staff and the health system within hospitals. Such strategies need to be multifaceted and designed to build the capacity of nurses, heart patients and their carers, as well as support from hospital management.

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.

The role of disease management in the treatment and prevention of obesity with associated comorbidities.

PubMed

May, Jeanette; Buckman, Ellen

2007-06-01

Nearly two thirds of the US population is overweight or obese and those numbers are climbing. Many organizations are beginning to recognize overweight and obesity as severe health threats and to acknowledge that treatment can serve as an important first step in addressing this epidemic. Through its Obesity with Co-morbidities Initiative, the Disease Management Association of America (DMAA) seeks to raise awareness and improve understanding of the role disease management (DM) can play in the treatment and management of obesity with comorbidities. Among the objectives of the Obesity with Co-morbidities Initiative was to develop standard definitions of obesity and obesity with comorbidities and to conduct qualitative research among key DM stakeholders. The first project undertaken and completed by the Obesity with Associated Co-morbidities Steering Committee and work group was to define the term "obesity" for consistent usage within the DM community for the purposes of population-based interventions. As part of this initiative, DMAA partnered with Synovate, a global market research firm, to conduct focus groups and in-depth interviews in order to collect qualitative data on attitudes and practices related to obesity treatment and coverage among key industry stakeholders, including health plans, disease management organizations, employers, and the business community. The findings indicated that obesity was widely recognized as a serious issue, but there remained varying opinions regarding responsibility, health and productivity costs, coverage, and best treatment methods among the participants. DMAA will continue this initiative through 2007 and will continue to develop a knowledge base of obesity guidelines and management practices, create valuable tools and resources including an online resource center, and facilitate partnerships with other organizations involved in the management and prevention of obesity.

Back off! The effect of emotion on backward step initiation.

PubMed

Bouman, Daniëlle; Stins, John F

2018-02-01

The distance regulation (DR) hypothesis states that actors are inclined to increase their distance from an unpleasant stimulus. The current study investigated the relation between emotion and its effect on the control of backward step initiation, which constitutes an avoidance-like behavior. Participants stepped backward on a force plate in response to neutral, high-arousing pleasant and high-arousing unpleasant visual emotional stimuli. Gait initiation parameters and the results of an exploratory analysis of postural sway were compared across the emotion categories using significance testing and Bayesian statistics. Evidence was found that gait initiation parameters were largely unaffected by emotional conditions. In contrast, the exploratory analysis of postural immobility showed a significant effect: highly arousing stimuli (pleasant and unpleasant) resulted in more postural sway immediately preceding gait initiation compared to neutral stimuli. This suggests that arousal, rather than valence, affects pre-step sway. These results contradict the DR hypothesis, since avoidance gait-initiation in response to unpleasant stimuli was no different compared to pleasant stimuli. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Multiple R&D projects scheduling optimization with improved particle swarm algorithm.

PubMed

Liu, Mengqi; Shan, Miyuan; Wu, Juan

2014-01-01

For most enterprises, in order to win the initiative in the fierce competition of market, a key step is to improve their R&D ability to meet the various demands of customers more timely and less costly. This paper discusses the features of multiple R&D environments in large make-to-order enterprises under constrained human resource and budget, and puts forward a multi-project scheduling model during a certain period. Furthermore, we make some improvements to existed particle swarm algorithm and apply the one developed here to the resource-constrained multi-project scheduling model for a simulation experiment. Simultaneously, the feasibility of model and the validity of algorithm are proved in the experiment.

Information adaptive system of NEEDS. [of NASA End to End Data System

NASA Technical Reports Server (NTRS)

Howle, W. M., Jr.; Kelly, W. L.

1979-01-01

The NASA End-to-End Data System (NEEDS) program was initiated by NASA to improve significantly the state of the art in acquisition, processing, and distribution of space-acquired data for the mid-1980s and beyond. The information adaptive system (IAS) is a program element under NEEDS Phase II which addresses sensor specific processing on board the spacecraft. The IAS program is a logical first step toward smart sensors, and IAS developments - particularly the system components and key technology improvements - are applicable to future smart efforts. The paper describes the design goals and functional elements of the IAS. In addition, the schedule for IAS development and demonstration is discussed.

Glyceraldehyde and glycolaldehyde in interstellar ice analogues and the role of aldehydes in cosmochemical evolution

NASA Astrophysics Data System (ADS)

Meierhenrich, U.; de Marcellus, P.; Meinert, C.; Myrgorodska, I.; Nahon, L.; Buhse, T.; d'Hendecourt, L.

2015-10-01

Our understanding of the molecular origin of life is based on amino acids, ribose, and nucleobases that - after their selection by prebiotic processes - initiated the evolutionary assembly of catalytic and informational polymers, being proteins and ribonucleic acids. Following previous amino acid identifications in the room-temperature residues of simulated circumstellar/interstellar ices [1,2] we have searched for a different family of molecules of potential prebiotic interest. Using multidimensional gas chromatography coupled to time-of-flight mass spectrometry, we have detected ten aldehydes, including the sugar-related glycolaldehyde and glyceraldehyde - two species considered as key prebiotic intermediates in the first steps toward the synthesis of ribonucleotides in a planetary environment.

DUV light source sustainability achievements and next steps

NASA Astrophysics Data System (ADS)

Roman, Yzzer; Cacouris, Ted; Raju, Kumar Raja Guvindan; Kanawade, Dinesh; Gillespie, Walt; Luo, Siqi; Mason, Eric; Manley, David; Das, Saptaparna

2018-03-01

Key sustainability opportunities have been executed in support of corporate initiatives to reduce the environmental footprint and decrease the running cost of DUV light sources. Previously, substantial neon savings were demonstrated over several years through optimized gas management technologies. Beyond this work, Cymer is developing the XLGR 100, a self-contained neon recycling system, to enable minimal gas consumption. The high efficiency results of the XLGR 100 in a production factory are validated in this paper. Cymer has also developed new light source modules with 33% longer life in an effort to reduce raw and associated resource consumption. In addition, a progress report is included regarding the improvements developed to reduce light source energy consumption.

Strengthening Biosecurity in Iraq: Development of a National Biorisk Management System

PubMed Central

Al Jewari, Mahdi F. H.; Koblentz, Gregory D.

2016-01-01

Since 2004, the Republic of Iraq has undertaken a concerted effort to comply with all of its international obligations to prevent the proliferation and the use of chemical, biological, radiological, and nuclear (CBRN) weapons. A centerpiece of this effort is Iraq’s development of a National Biorisk Management System. The Iraqi National Monitoring Authority (INMA), which is responsible for CBRN security and non-proliferation in Iraq, has played a key role in establishing this system. This article provides an overview of Iraq’s international non-proliferation commitments, describes the legal and organizational steps it has taken to implement these commitments, and examines current initiatives to strengthen Iraq’s biosecurity. PMID:26952002

A Survey of Usability Practices in Free/Libre/Open Source Software

NASA Astrophysics Data System (ADS)

Paul, Celeste Lyn

A review of case studies about usability in eight Free/Libre/Open Source Software (FLOSS) projects showed that an important issue regarding a usability initiative in the project was the lack of user research. User research is a key component in the user-centered design (UCD) process and a necessary step for creating usable products. Reasons why FLOSS projects suffered from a lack of user research included poor or unclear project leadership, cultural differences between developer and designers, and a lack of usability engineers. By identifying these critical issues, the FLOSS usability community can begin addressing problems in the efficacy of usability activities and work towards creating more usable FLOSS products.

Mechanisms of excitatory synapse maturation by trans-synaptic organizing complexes

PubMed Central

McMahon, Samuel A.; Díaz, Elva

2011-01-01

Synapses are specialized cell-cell adhesion contacts that mediate communication within neural networks. During development, excitatory synapses are generated by step-wise recruitment of pre- and postsynaptic proteins to sites of contact. Several classes of synaptic organizing complexes have been identified that function during the initial stages of synapse formation. However, mechanisms underlying the later stages of synapse development are less well understood. In recent years, molecules have been discovered that appear to play a role in synapse maturation. In this review, we highlight recent findings that have provided key insights for understanding postsynaptic maturation of developing excitatory synapses with a focus on recruitment of AMPA receptors to developing synapses. PMID:21242087

Modelling interactions between mitigation, adaptation and sustainable development

NASA Astrophysics Data System (ADS)

Reusser, D. E.; Siabatto, F. A. P.; Garcia Cantu Ros, A.; Pape, C.; Lissner, T.; Kropp, J. P.

2012-04-01

Managing the interdependence of climate mitigation, adaptation and sustainable development requires a good understanding of the dominant socioecological processes that have determined the pathways in the past. Key variables include water and food availability which depend on climate and overall ecosystem services, as well as energy supply and social, political and economic conditions. We present our initial steps to build a system dynamic model of nations that represents a minimal set of relevant variables of the socio- ecological development. The ultimate goal of the modelling exercise is to derive possible future scenarios and test those for their compatibility with sustainability boundaries. Where dynamics go beyond sustainability boundaries intervention points in the dynamics can be searched.

Aging effect on step adjustments and stability control in visually perturbed gait initiation.

PubMed

Sun, Ruopeng; Cui, Chuyi; Shea, John B

2017-10-01

Gait adaptability is essential for fall avoidance during locomotion. It requires the ability to rapidly inhibit original motor planning, select and execute alternative motor commands, while also maintaining the stability of locomotion. This study investigated the aging effect on gait adaptability and dynamic stability control during a visually perturbed gait initiation task. A novel approach was used such that the anticipatory postural adjustment (APA) during gait initiation were used to trigger the unpredictable relocation of a foot-size stepping target. Participants (10 young adults and 10 older adults) completed visually perturbed gait initiation in three adjustment timing conditions (early, intermediate, late; all extracted from the stereotypical APA pattern) and two adjustment direction conditions (medial, lateral). Stepping accuracy, foot rotation at landing, and Margin of Dynamic Stability (MDS) were analyzed and compared across test conditions and groups using a linear mixed model. Stepping accuracy decreased as a function of adjustment timing as well as stepping direction, with older subjects exhibited a significantly greater undershoot in foot placement to late lateral stepping. Late adjustment also elicited a reaching-like movement (i.e. foot rotation prior to landing in order to step on the target), regardless of stepping direction. MDS measures in the medial-lateral and anterior-posterior direction revealed both young and older adults exhibited reduced stability in the adjustment step and subsequent steps. However, young adults returned to stable gait faster than older adults. These findings could be useful for future study of screening deficits in gait adaptability and preventing falls. Copyright © 2017 Elsevier B.V. All rights reserved.

A mixed-methods research approach to the review of competency standards for orthotist/prosthetists in Australia.

PubMed

Ash, Susan; O'Connor, Jackie; Anderson, Sarah; Ridgewell, Emily; Clarke, Leigh

2015-06-01

The requirement for an allied health workforce is expanding as the global burden of disease increases internationally. To safely meet the demand for an expanded workforce of orthotist/prosthetists in Australia, competency based standards, which are up-to-date and evidence-based, are required. The aims of this study were to determine the minimum level for entry into the orthotic/prosthetic profession; to develop entry level competency standards for the profession; and to validate the developed entry-level competency standards within the profession nationally, using an evidence-based approach. A mixed-methods research design was applied, using a three-step sequential exploratory design, where step 1 involved collecting and analyzing qualitative data from two focus groups; step 2 involved exploratory instrument development and testing, developing the draft competency standards; and step 3 involved quantitative data collection and analysis - a Delphi survey. In stage 1 (steps 1 and 2), the two focus groups - an expert and a recent graduate group of Australian orthotist/prosthetists - were led by an experienced facilitator, to identify gaps in the current competency standards and then to outline a key purpose, and work roles and tasks for the profession. The resulting domains and activities of the first draft of the competency standards were synthesized using thematic analysis. In stage 2 (step 3), the draft-competency standards were circulated to a purposive sample of the membership of the Australian Orthotic Prosthetic Association, using three rounds of Delphi survey. A project reference group of orthotist/prosthetists reviewed the results of both stages. In stage 1, the expert (n = 10) and the new graduate (n = 8) groups separately identified work roles and tasks, which formed the initial draft of the competency standards. Further drafts were refined and performance criteria added by the project reference group, resulting in the final draft-competency standards. In stage 2, the final draft-competency standards were circulated to 56 members (n = 44 final round) of the Association, who agreed on the key purpose, 6 domains, 18 activities, and 68 performance criteria of the final competency standards. This study outlines a rigorous and evidence-based mixed-methods approach for developing and endorsing professional competency standards, which is representative of the views of the profession of orthotist/prosthetists.

On the complexity of search for keys in quantum cryptography

NASA Astrophysics Data System (ADS)

Molotkov, S. N.

2016-03-01

The trace distance is used as a security criterion in proofs of security of keys in quantum cryptography. Some authors doubted that this criterion can be reduced to criteria used in classical cryptography. The following question has been answered in this work. Let a quantum cryptography system provide an ɛ-secure key such that ½‖ρ XE - ρ U ⊗ ρ E ‖1 < ɛ, which will be repeatedly used in classical encryption algorithms. To what extent does the ɛ-secure key reduce the number of search steps (guesswork) as compared to the use of ideal keys? A direct relation has been demonstrated between the complexity of the complete consideration of keys, which is one of the main security criteria in classical systems, and the trace distance used in quantum cryptography. Bounds for the minimum and maximum numbers of search steps for the determination of the actual key have been presented.

Army Independent Risk Assessment Guidebook

DTIC Science & Technology

2014-04-01

17 5.4.2 Step 2: Gather relevant technology and alternative information............... 17 5.4.3 Step 3: Secure SME support for readiness...level assessment. ................... 17 5.4.4 Step 4: SMEs assess TRL, IRL, and MRL for each technology. .............. 17 5.4.5 Step 5: Identify...technical risks, risk ratings, and mitigations. .................. 20 5.4.6 Step 6: SMEs identify key technologies

Implementing a Healthy Food Distribution Program: A Supply Chain Strategy to Increase Fruit and Vegetable Access in Underserved Areas.

PubMed

DeFosset, Amelia R; Kwan, Allison; Rizik-Baer, Daniel; Gutierrez, Luis; Gase, Lauren N; Kuo, Tony

2018-05-24

Increasing access to fresh produce in small retail venues could improve the diet of people in underserved communities. However, small retailers face barriers to stocking fresh produce. In 2014, an innovative distribution program, Community Markets Purchasing Real and Affordable Foods (COMPRA), was launched in Los Angeles with the aim of making it more convenient and profitable for small retailers to stock fresh produce. Our case study describes the key processes and lessons learned in the first 2 years of implementing COMPRA. Considerable investments in staff capacity and infrastructure were needed to launch COMPRA. Early successes included significant week-to-week increases in the volume of produce distributed. Leveraging partnerships, maintaining a flexible operational and funding structure, and broadly addressing store owners' needs contributed to initial gains. We describe key challenges and next steps to scaling the program. Lessons learned from implementing COMPRA could inform other jurisdictions considering supply-side approaches to increase access to healthy food.

AMTD: update of engineering specifications derived from science requirements for future UVOIR space telescopes

NASA Astrophysics Data System (ADS)

Stahl, H. Philip; Postman, Marc; Mosier, Gary; Smith, W. Scott; Blaurock, Carl; Ha, Kong; Stark, Christopher C.

2014-08-01

The Advance Mirror Technology Development (AMTD) project is in Phase 2 of a multiyear effort, initiated in FY12, to mature by at least a half TRL step six critical technologies required to enable 4 meter or larger UVOIR space telescope primary mirror assemblies for both general astrophysics and ultra-high contrast observations of exoplanets. AMTD uses a science-driven systems engineering approach. We mature technologies required to enable the highest priority science AND provide a high-performance low-cost low-risk system. To give the science community options, we are pursuing multiple technology paths. A key task is deriving engineering specifications for advanced normal-incidence monolithic and segmented mirror systems needed to enable both general astrophysics and ultra-high contrast observations of exoplanets missions as a function of potential launch vehicles and their mass and volume constraints. A key finding of this effort is that the science requires an 8 meter or larger aperture telescope.

Phosphoproteomics in bacteria: towards a systemic understanding of bacterial phosphorylation networks.

PubMed

Jers, Carsten; Soufi, Boumediene; Grangeasse, Christophe; Deutscher, Josef; Mijakovic, Ivan

2008-08-01

Bacteria use protein phosphorylation to regulate all kinds of physiological processes. Protein phosphorylation plays a role in several key steps of the infection process of bacterial pathogens, such as adhesion to the host, triggering and regulation of pathogenic functions as well as biochemical warfare; scrambling the host signaling cascades and impairing its defense mechanisms. Recent phosphoproteomic studies indicate that the bacterial protein phosphorylation networks could be more complex than initially expected, comprising promiscuous kinases that regulate several distinct cellular functions by phosphorylating different protein substrates. Recent advances in protein labeling with stable isotopes in the field of quantitative mass spectrometry phosphoproteomics will enable us to chart the global phosphorylation networks and to understand the implication of protein phosphorylation in cellular regulation on the systems scale. For the study of bacterial pathogens, in particular, this research avenue will enable us to dissect phosphorylation-related events during different stages of infection and stimulate our efforts to find inhibitors for key kinases and phosphatases implicated therein.

Identification of Cost Indicators with Significant Economic Impact on the Total Treatment Costs of Chronic Heart Failure Patients - A Meta-Analysis.

PubMed

Hameed, Ahmed S; Modre-Osprian, Robert; Schreier, Günter

2017-01-01

Increasing treatment costs of HF patients affect the initiation of appropriate treatment method. Divergent approaches to measure the costs of treatment and the lack of common cost indicators impede the comparison of therapy settings. In the context of the present meta-analysis, key cost indicators from the perspective of healthcare providers are to be identified, described, analyzed and quantified. This review helps narrowing down the cost indicators, which have the most significant economic impact on the total treatment costs of HF patients. Telemedical services are to be compared to standard therapy methods. The identification process was based on several steps. For the quantitative synthesis, we used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. An additional set of criteria was defined for the following qualitative analysis. 5 key cost indicators were identified with significant economic impact on the treatment costs of HF patients. 95% of the reported treatment costs could be captured based on the identified cost indicators.

The adverse outcome pathway concept: a pragmatic tool in toxicology.

PubMed

Vinken, Mathieu

2013-10-04

Adverse outcome pathways (AOPs) are novel tools in toxicology and human risk assessment with broad potential. AOPs are designed to provide a clear-cut mechanistic representation of critical toxicological effects that span over different layers of biological organization. AOPs share a common structure consisting of a molecular initiating event, a series of intermediate steps and key events, and an adverse outcome. Development of AOPs ideally complies with OECD guidelines. This also holds true for AOP evaluation, which includes consideration of the Bradford Hill criteria for weight-of-evidence assessment and meeting a set of key questions defined by the OECD. Elaborate AOP frameworks have yet been proposed for chemical-induced skin sensitization, cholestasis, liver fibrosis and liver steatosis. These newly postulated AOPs can serve a number of ubiquitous purposes, including the establishment of (quantitative) structure-activity relationships, the development of novel in vitro toxicity screening tests and the elaboration of prioritization strategies. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

AMTD: Update of Engineering Specifications Derived from Science Requirements for Future UVOIR Space Telescopes

NASA Technical Reports Server (NTRS)

Stahl, H. Philip; Postman, Marc; Mosier, Gary; Smith, W. Scott; Blaurock, Carl; Ha, Kong; Stark, Christopher C.

2014-01-01

The Advance Mirror Technology Development (AMTD) project is in Phase 2 of a multiyear effort, initiated in FY12, to mature by at least a half TRL step six critical technologies required to enable 4 meter or larger UVOIR space telescope primary mirror assemblies for both general astrophysics and ultra-high contrast observations of exoplanets. AMTD uses a science-driven systems engineering approach. We mature technologies required to enable the highest priority science AND provide a high-performance low-cost low-risk system. To give the science community options, we are pursuing multiple technology paths. A key task is deriving engineering specifications for advanced normal-incidence monolithic and segmented mirror systems needed to enable both general astrophysics and ultra-high contrast observations of exoplanets missions as a function of potential launch vehicles and their mass and volume constraints. A key finding of this effort is that the science requires an 8 meter or larger aperture telescope

Considerations for sustainable influenza vaccine production in developing countries.

PubMed

Nannei, Claudia; Chadwick, Christopher; Fatima, Hiba; Goldin, Shoshanna; Grubo, Myriam; Ganim, Alexandra

2016-10-26

Through its Global Action Plan for Influenza Vaccines (GAP), the World Health Organization (WHO) in collaboration with the United States Department of Health and Human Services has produced a checklist to support policy-makers and influenza vaccine manufacturers in identifying key technological, political, financial, and logistical issues affecting the sustainability of influenza vaccine production. This checklist highlights actions in five key areas that are beneficial for establishing successful local vaccine manufacturing. These five areas comprise: (1) the policy environment and health-care systems; (2) surveillance systems and influenza evidence; (3) product development and manufacturing; (4) product approval and regulation; and (5) communication to support influenza vaccination. Incorporating the checklist into national vaccine production programmes has identified the policy gaps and next steps for countries involved in GAP's Technology Transfer Initiative. Lessons learnt from country experiences provide context and insight that complement the checklist's goal of simplifying the complexities of influenza prevention, preparedness, and vaccine manufacturing. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Archaeal translation initiation revisited: the initiation factor 2 and eukaryotic initiation factor 2B alpha-beta-delta subunit families

NASA Technical Reports Server (NTRS)

Kyrpides, N. C.; Woese, C. R.

1998-01-01

As the amount of available sequence data increases, it becomes apparent that our understanding of translation initiation is far from comprehensive and that prior conclusions concerning the origin of the process are wrong. Contrary to earlier conclusions, key elements of translation initiation originated at the Universal Ancestor stage, for homologous counterparts exist in all three primary taxa. Herein, we explore the evolutionary relationships among the components of bacterial initiation factor 2 (IF-2) and eukaryotic IF-2 (eIF-2)/eIF-2B, i.e., the initiation factors involved in introducing the initiator tRNA into the translation mechanism and performing the first step in the peptide chain elongation cycle. All Archaea appear to posses a fully functional eIF-2 molecule, but they lack the associated GTP recycling function, eIF-2B (a five-subunit molecule). Yet, the Archaea do posses members of the gene family defined by the (related) eIF-2B subunits alpha, beta, and delta, although these are not specifically related to any of the three eukaryotic subunits. Additional members of this family also occur in some (but by no means all) Bacteria and even in some eukaryotes. The functional significance of the other members of this family is unclear and requires experimental resolution. Similarly, the occurrence of bacterial IF-2-like molecules in all Archaea and in some eukaryotes further complicates the picture of translation initiation. Overall, these data lend further support to the suggestion that the rudiments of translation initiation were present at the Universal Ancestor stage.

ANTICIPATORY POSTURAL ADJUSTMENTS PRIOR TO STEP INITIATION ARE HYPOMETRIC IN UNTREATED PARKINSON'S DISEASE: AN ACCELEROMETER-BASED APPROACH

PubMed Central

Mancini, Martina; Zampieri, Cris; Carlson-Kuhta, Patricia; Chiari, Lorenzo; Horak, Fay B.

2010-01-01

Background and purpose Anticipatory postural adjustments (APAs), prior to step initiation, are bradykinetic in advanced Parkinson's disease (PD) and may be one of the factors associated with ‘start hesitation’. However, little is known about APAs in the early stage of PD. In this study, we determined whether body-worn accelerometers could be used to characterize step initiation deficits in subjects with early-to-moderate, untreated PD. Methods Eleven PD and 12 healthy control subjects were asked to take two steps. Postural adjustments were compared from center of pressure (COP) and from acceleration of the trunk at the center of mass level (L5). Results Our findings show that APAs measured from the peak COP displacement towards the swing leg and the peak trunk acceleration towards the stance leg were smaller in untreated PD compared to control subjects. The magnitude of APAs measured from peak COP displacements and accelerations were correlated. Conclusion These results suggest that quantitative analysis of step initiation from one accelerometer on the trunk could provide useful information for the characterization of patients in early stages of PD, when clinical evidence of start hesitation may not be detectable. Ambulatory monitoring of step initiation is also promising for monitoring patient progression in the home environment, and eventually providing feedback for preventing freezing of gait episodes. PMID:19473350

Proton pump inhibitor step-down therapy for GERD: A multi-center study in Japan

PubMed Central

Tsuzuki, Takao; Okada, Hiroyuki; Kawahara, Yoshiro; Takenaka, Ryuta; Nasu, Junichiro; Ishioka, Hidehiko; Fujiwara, Akiko; Yoshinaga, Fumiya; Yamamoto, Kazuhide

2011-01-01

AIM: To investigate the predictors of success in step-down of proton pump inhibitor and to assess the quality of life (QOL). METHODS: Patients who had heartburn twice a week or more were treated with 20 mg omeprazole (OPZ) once daily for 8 wk as an initial therapy (study 1). Patients whose heartburn decreased to once a week or less at the end of the initial therapy were enrolled in study 2 and treated with 10 mg OPZ as maintenance therapy for an additional 6 mo (study 2). QOL was investigated using the gastrointestinal symptom rating scale (GSRS) before initial therapy, after both 4 and 8 wk of initial therapy, and at 1, 2, 3, and 6 mo after starting maintenance therapy. RESULTS: In study 1, 108 patients were analyzed. Their characteristics were as follows; median age: 63 (range: 20-88) years, sex: 46 women and 62 men. The success rate of the initial therapy was 76%. In the patients with successful initial therapy, abdominal pain, indigestion and reflux GSRS scores were improved. In study 2, 83 patients were analyzed. Seventy of 83 patients completed the study 2 protocol. In the per-protocol analysis, 80% of 70 patients were successful for step-down. On multivariate analysis of baseline demographic data and clinical information, no previous treatment for gastroesophageal reflux disease (GERD) [odds ratio (OR) 0.255, 95% CI: 0.06-0.98] and a lower indigestion score in GSRS at the beginning of step-down therapy (OR 0.214, 95% CI: 0.06-0.73) were found to be the predictors of successful step-down therapy. The improved GSRS scores by initial therapy were maintained through the step-down therapy. CONCLUSION: OPZ was effective for most GERD patients. However, those who have had previous treatment for GERD and experience dyspepsia before step-down require particular monitoring for relapse. PMID:21472108

Does a microprocessor-controlled prosthetic knee affect stair ascent strategies in persons with transfemoral amputation?

PubMed

Aldridge Whitehead, Jennifer M; Wolf, Erik J; Scoville, Charles R; Wilken, Jason M

2014-10-01

Stair ascent can be difficult for individuals with transfemoral amputation because of the loss of knee function. Most individuals with transfemoral amputation use either a step-to-step (nonreciprocal, advancing one stair at a time) or skip-step strategy (nonreciprocal, advancing two stairs at a time), rather than a step-over-step (reciprocal) strategy, because step-to-step and skip-step allow the leading intact limb to do the majority of work. A new microprocessor-controlled knee (Ottobock X2(®)) uses flexion/extension resistance to allow step-over-step stair ascent. We compared self-selected stair ascent strategies between conventional and X2(®) prosthetic knees, examined between-limb differences, and differentiated stair ascent mechanics between X2(®) users and individuals without amputation. We also determined which factors are associated with differences in knee position during initial contact and swing within X2(®) users. Fourteen individuals with transfemoral amputation participated in stair ascent sessions while using conventional and X2(®) knees. Ten individuals without amputation also completed a stair ascent session. Lower-extremity stair ascent joint angles, moment, and powers and ground reaction forces were calculated using inverse dynamics during self-selected strategy and cadence and controlled cadence using a step-over-step strategy. One individual with amputation self-selected a step-over-step strategy while using a conventional knee, while 10 individuals self-selected a step-over-step strategy while using X2(®) knees. Individuals with amputation used greater prosthetic knee flexion during initial contact (32.5°, p = 0.003) and swing (68.2°, p = 0.001) with higher intersubject variability while using X2(®) knees compared to conventional knees (initial contact: 1.6°, swing: 6.2°). The increased prosthetic knee flexion while using X2(®) knees normalized knee kinematics to individuals without amputation during swing (88.4°, p = 0.179) but not during initial contact (65.7°, p = 0.002). Prosthetic knee flexion during initial contact and swing were positively correlated with prosthetic limb hip power during pull-up (r = 0.641, p = 0.046) and push-up/early swing (r = 0.993, p < 0.001), respectively. Participants with transfemoral amputation were more likely to self-select a step-over-step strategy similar to individuals without amputation while using X2(®) knees than conventional prostheses. Additionally, the increased prosthetic knee flexion used with X2(®) knees placed large power demands on the hip during pull-up and push-up/early swing. A modified strategy that uses less knee flexion can be used to allow step-over-step ascent in individuals with less hip strength.

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

Chen, Daohong; Chen, Xi; Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003

Highlights: ► CCCP-induced LC3 lipidation can be independent of initiation/nucleation molecules. ► Atg9-mediated trafficking is critically required for CCCP-induced LC3 lipidation. ► CCCP-induced mitophagy may thus be more dependent on Atg9-positive vesicles. -- Abstract: Treatment of cells with carbonyl cyanide m-chlorophenylhydrazone (CCCP), a mitochondrial proton gradient uncoupler, can result in mitochondrial damage and autophagy activation, which in turn eliminates the injured mitochondria in a Parkin-dependent way. How CCCP mobilizes the autophagy machinery is not fully understood. By analyzing a key autophagy step, LC3 lipidation, we examined the roles of two kinase complexes typically involved in the initiation and nucleation phasesmore » of autophagy, namely the ULK kinase complex (UKC) and the Beclin 1/Atg14 complex. We found that CCCP-induced LC3 lipidation could be independent of Beclin 1 and Atg14. In addition, deletion or knockdown of the UKC component FIP200 or Atg13 only led to a partial reduction in LC3 lipidation, indicating that UKC could be also dispensable for this step during CCCP treatment. In contrast, Atg9, which is important for transporting vesicles to early autophagosomal structure, was required for CCCP-induced LC3 lipidation. Taken together, these data suggest that CCCP-induced autophagy and mitophagy depends more critically on Atg9 vesicles than on UKC and Beclin 1/Atg14 complex.« less

Oxidative and Nitrosative Stress in the Metastatic Microenvironment

PubMed Central

Ortega, Ángel L.; Mena, Salvador; Estrela, José M.

2010-01-01

Metastases that are resistant to conventional therapies are the main cause of most cancer-related deaths in humans. Tumor cell heterogeneity, which associates with genomic and phenotypic instability, represents a major problem for cancer therapy. Additional factors, such as the attack of immune cells or organ-specific microenvironments, also influence metastatic cell behavior and the response to therapy. Interaction of cancer and endothelial cells in capillary beds, involving mechanical contact and transient adhesion, is a critical step in the initiation of metastasis. This interaction initiates a cascade of activation pathways that involves cytokines, growth factors, bioactive lipids and reactive oxygen and nitrogen species (ROS and RNS) produced by either the cancer cell or the endothelium. Vascular endothelium-derived NO and H2O2 are cytotoxic for the cancer cells, but also help to identify some critical molecular targets that appear essential for survival of invasive metastatic cell subsets. Surviving cancer cells that extravasate and start colonization of an organ or tissue can still be attacked by macrophages and be influenced by specific intraorgan microenvironment conditions. At all steps; from the primary tumor until colonization of a distant organ; metastatic cells undergo a dynamic process of constant adaptations that may lead to the survival of highly resistant malignant cell subsets. In this sequence of molecular events both ROS and RNS play key roles. PMID:24281071

Planning, expectation, and image evaluation for PACS at the University of Iowa Hospitals and Clinics

NASA Astrophysics Data System (ADS)

Franken, E. A., Jr.; Smith, Wilbur L.; Berbaum, Kevin S.; Owen, David A.; Hilsenrath, Peter

1990-08-01

Our strategy in studying PACS is to evaluate its clinical implementation working with equipment supplied by an established manufacturer. Fiscal and personnel resources required to design and integrate the hardware components and operational software to develop a functional PACS precluded a bottom up development approach at our institution. Imaging equipment vendors possess more abundant design development resources for this task and therefore can support a more rapid development of the initial components of PACS. For this reason we have chosen to serve as a beta test site to study the viability of the basic PACS components in a clinical setting. Our efforts primarily focus on: (1) image quality; (2) cost effectiveness; (3) PACS/HIS/RIS integration; (4) equipment and software reliability; and (5) overall system performance. The results of our studies are shared with the vendor for future PACS development and refi nement. To attain our investigational goals we have formed an interdisciplinary team of Radiologists, Perceptual Psychologist, Economist, Electrical and Industrial Engineers, Hospital Information System personnel and key departmental administrative staff. For several reasons Pediatric Radiology was targeted as the initial area for our PACS study: a small area representative of the overall operation,tight operational controls and willingness of physicians. We used a step-wise approach, the first step being the installation of PACS exclusively within the physical confines of Pediatric Radiology.

A Pilot Study on Developing a Standardized and Sensitive School Violence Risk Assessment with Manual Annotation.

PubMed

Barzman, Drew H; Ni, Yizhao; Griffey, Marcus; Patel, Bianca; Warren, Ashaki; Latessa, Edward; Sorter, Michael

2017-09-01

School violence has increased over the past decade and innovative, sensitive, and standardized approaches to assess school violence risk are needed. In our current feasibility study, we initialized a standardized, sensitive, and rapid school violence risk approach with manual annotation. Manual annotation is the process of analyzing a student's transcribed interview to extract relevant information (e.g., key words) to school violence risk levels that are associated with students' behaviors, attitudes, feelings, use of technology (social media and video games), and other activities. In this feasibility study, we first implemented school violence risk assessments to evaluate risk levels by interviewing the student and parent separately at the school or the hospital to complete our novel school safety scales. We completed 25 risk assessments, resulting in 25 transcribed interviews of 12-18 year olds from 15 schools in Ohio and Kentucky. We then analyzed structured professional judgments, language, and patterns associated with school violence risk levels by using manual annotation and statistical methodology. To analyze the student interviews, we initiated the development of an annotation guideline to extract key information that is associated with students' behaviors, attitudes, feelings, use of technology and other activities. Statistical analysis was applied to associate the significant categories with students' risk levels to identify key factors which will help with developing action steps to reduce risk. In a future study, we plan to recruit more subjects in order to fully develop the manual annotation which will result in a more standardized and sensitive approach to school violence assessments.

Akt2/ZEB2 may be a biomarker for exfoliant cells in ascitic fluid in advanced grades of serous ovarian carcinoma.

PubMed

Liu, Changmei; Yang, Fangmei

2015-09-01

Ovarian cancers present a mild clinical course when diagnosed early but an aggressive pathway when diagnosed in the peri- and postmenopausal periods. However, the predictability of tumor progression is stochastic and is difficult to predict. In the present study, we hypothesized to examine the key pathways that are dysregulated to promote epithelial-mesenchymal transition in serous ovarian carcinoma. Examination of these steps would help to identify ascitic fluid with cells poised for metastasis or otherwise. We focused on examining the Akt2 expression, mainly because of its report as being overamplified in the aggressive variants of ovarian cancer, as well as TGFbeta-sensitivity of Akt2 that forms the key basis for metastasis initiation of most kinds of carcinoma. We obtained primary ovarian carcinoma samples as well as ascitic fluid and distantly metastatic ovarian carcinoma to examine the expression of Akt2. The results of the study demonstrated that in malignant exfoliated ovarian cancer cells, Smad4 expression was tremendously increased in the nuclei, suggesting nuclear translocation of Smad, which thereafter may have activated ZEB2, and thereafter genomically affected the expression of E-cadherin, myosin II, and vimentin, key components for initiating and sustaining metastasis. All of these may have been stimulated by increased cellular expression of Akt2 in metastatic variants of the serous ovarian carcinoma. The reliance on Akt2 and TGF beta signaling may also potentiate the case for Akt inhibitors or small molecule inhibitors of TGFbeta signaling like doxycycline as adjunct chemotherapy in serous ovarian carcinoma, especially the metastatic variants.

A Spatially Constrained Multi-autoencoder Approach for Multivariate Geochemical Anomaly Recognition

NASA Astrophysics Data System (ADS)

Lirong, C.; Qingfeng, G.; Renguang, Z.; Yihui, X.

2017-12-01

Separating and recognizing geochemical anomalies from the geochemical background is one of the key tasks in geochemical exploration. Many methods have been developed, such as calculating the mean ±2 standard deviation, and fractal/multifractal models. In recent years, deep autoencoder, a deep learning approach, have been used for multivariate geochemical anomaly recognition. While being able to deal with the non-normal distributions of geochemical concentrations and the non-linear relationships among them, this self-supervised learning method does not take into account the spatial heterogeneity of geochemical background and the uncertainty induced by the randomly initialized weights of neurons, leading to ineffective recognition of weak anomalies. In this paper, we introduce a spatially constrained multi-autoencoder (SCMA) approach for multivariate geochemical anomaly recognition, which includes two steps: spatial partitioning and anomaly score computation. The first step divides the study area into multiple sub-regions to segregate the geochemical background, by grouping the geochemical samples through K-means clustering, spatial filtering, and spatial constraining rules. In the second step, for each sub-region, a group of autoencoder neural networks are constructed with an identical structure but different initial weights on neurons. Each autoencoder is trained using the geochemical samples within the corresponding sub-region to learn the sub-regional geochemical background. The best autoencoder of a group is chosen as the final model for the corresponding sub-region. The anomaly score at each location can then be calculated as the euclidean distance between the observed concentrations and reconstructed concentrations of geochemical elements.The experiments using the geochemical data and Fe deposits in the southwestern Fujian province of China showed that our SCMA approach greatly improved the recognition of weak anomalies, achieving the AUC of 0.89, compared with the AUC of 0.77 using a single deep autoencoder approach.

48 CFR 3036.104-90 - Authority for one-step turn-key design-build contracting for the United States Coast Guard (USCG).

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 7 2014-10-01 2014-10-01 false Authority for one-step turn-key design-build contracting for the United States Coast Guard (USCG). 3036.104-90 Section 3036.104-90 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND SECURITY ACQUISITION REGULATION (HSAR) SPECIAL CATEGORIES OF...

Examining racial and ethnic minority differences among YMSM during recruitment for an online HIV prevention intervention study.

PubMed

Du Bois, Steve N; Johnson, Sarah E; Mustanski, Brian

2012-08-01

HIV disproportionately affects racial and ethnic minority young men who have sex with men (YMSM). HIV prevention research does not include these YMSM commensurate to their HIV burden. We examined racial and ethnic differences during a unique three-step recruitment process for an online, YMSM HIV prevention intervention study (N = 660). Step one was completed in-person; steps two and three online. Fewer Black and Latino YMSM completed step two-initiating online participation-than White YMSM. Internet use frequency accounted for the Latino versus White difference in initiating online participation, but not the Black versus White difference. Future online HIV prevention interventions recruiting diverse YMSM should focus on initiating online engagement among Black participants.

Examining Racial and Ethnic Minority Differences among YMSM during Recruitment for an Online HIV Prevention Intervention Study

PubMed Central

Du Bois, Steve N.; Johnson, Sarah E.; Mustanski, Brian

2011-01-01

HIV disproportionately affects racial and ethnic minority young men who have sex with men (YMSM). HIV prevention research does not include these YMSM commensurate to their HIV burden. We examined racial and ethnic differences during a unique three-step recruitment process for an online, YMSM HIV prevention intervention study (N=660). Step one was completed in-person; steps two and three online. Fewer Black and Latino YMSM completed step two – initiating online participation – than White YMSM. Internet use frequency accounted for the Latino vs. White difference in initiating online participation, but not the Black vs. White difference. Future online HIV prevention interventions recruiting diverse YMSM should focus on initiating online engagement among Black participants. PMID:21986869

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.

Results of a prospective clinical study on the diagnostic performance of standard magnetic resonance imaging in comparison to a combination of 3T MRI and additional CT imaging in Kienböck's disease.

PubMed

Stahl, Stephane; Hentschel, Pascal; Ketelsen, Dominik; Grosse, Ulrich; Held, Manuel; Wahler, Theodora; Syha, Roland; Schaller, Hans-Eberhard; Nikolaou, Konstantin; Grözinger, Gerd

2017-05-01

This prospective clinical study examined standard wrist magnetic resonance imaging (MRI) examinations and the incremental value of computed tomography (CT) in the diagnosis of Kienböck's disease (KD) with regard to reliability and precision in the different diagnostic steps during diagnostic work-up. Sixty-four consecutive patients referred between January 2009 and January 2014 with positive initial suspicion of KD according to external standard wrist MRI were prospectively included (step one). Institutional review board approval was obtained. Clinical examination by two handsurgeons were followed by wrist radiographs (step two), ultrathin-section CT, and 3T contrast-enhanced MRI (step three). Final diagnosis was established in a consensus conference involving all examiners and all examinations results available from step three. In 12/64 patients, initial suspicion was discarded at step two and in 34/64 patients, the initial suspicion of KD was finally discarded at step three. The final external MRI positive predictive value was 47%. The most common differential diagnoses at step three were intraosseous cysts (n=15), lunate pseudarthrosis (n=13), and ulnar impaction syndrome (n=5). A correlation between radiograph-based diagnoses (step two) with final diagnosis (step three) showed that initial suspicion of stage I KD had the lowest sensitivity for correct diagnosis (2/11). Technical factors associated with a false positive external MRI KD diagnosis were not found. Standard wrist MRI should be complemented with thin-section CT, and interdisciplinary interpretation of images and clinical data, to increase diagnostic accuracy in patients with suspected KD. Copyright © 2017. Published by Elsevier B.V.

The autumn effect: timing of physical dormancy break in seeds of two winter annual species of Geraniaceae by a stepwise process

PubMed Central

Gama-Arachchige, N. S.; Baskin, J. M.; Geneve, R. L.; Baskin, C. C.

2012-01-01

Background and Aims The involvement of two steps in the physical dormancy (PY)-breaking process previously has been demonstrated in seeds of Fabaceae and Convolvulaceae. Even though there is a claim for a moisture-controlled stepwise PY-breaking in some species of Geraniaceae, no study has evaluated the role of temperature in the PY-breaking process in this family. The aim of this study was to determine whether a temperature-controlled stepwise PY-breaking process occurs in seeds of the winter annuals Geranium carolinianum and G. dissectum. Methods Seeds of G. carolinianum and G. dissectum were stored under different temperature regimes to test the effect of storage temperature on PY-break. The role of temperature and moisture regimes in regulating PY-break was investigated by treatments simulating natural conditions. Greenhouse (non-heated) experiments on seed germination and burial experiments (outdoors) were carried out to determine the PY-breaking behaviour in the natural habitat. Key Results Irrespective of moisture conditions, sensitivity to the PY-breaking step in seeds of G. carolinianum was induced at temperatures ≥20 °C, and exposure to temperatures ≤20 °C made the sensitive seeds permeable. Sensitivity of seeds increased with time. In G. dissectum, PY-break occurred at temperatures ≥20 °C in a single step under constant wet or dry conditions and in two steps under alternate wet–dry conditions if seeds were initially kept wet. Conclusions Timing of seed germination with the onset of autumn can be explained by PY-breaking processes involving (a) two temperature-dependent steps in G. carolinianum and (b) one or two moisture-dependent step(s) along with the inability to germinate under high temperatures in G. dissectum. Geraniaceae is the third of 18 families with PY in which a two-step PY-breaking process has been demonstrated. PMID:22684684

Step-by-step mechanism of DNA damage recognition by human 8-oxoguanine DNA glycosylase.

PubMed

Kuznetsova, Alexandra A; Kuznetsov, Nikita A; Ishchenko, Alexander A; Saparbaev, Murat K; Fedorova, Olga S

2014-01-01

Extensive structural studies of human DNA glycosylase hOGG1 have revealed essential conformational changes of the enzyme. However, at present there is little information about the time scale of the rearrangements of the protein structure as well as the dynamic behavior of individual amino acids. Using pre-steady-state kinetic analysis with Trp and 2-aminopurine fluorescence detection the conformational dynamics of hOGG1 wild-type (WT) and mutants Y203W, Y203A, H270W, F45W, F319W and K249Q as well as DNA-substrates was examined. The roles of catalytically important amino acids F45, Y203, K249, H270, and F319 in the hOGG1 enzymatic pathway and their involvement in the step-by-step mechanism of oxidative DNA lesion recognition and catalysis were elucidated. The results show that Tyr-203 participates in the initial steps of the lesion site recognition. The interaction of the His-270 residue with the oxoG base plays a key role in the insertion of the damaged base into the active site. Lys-249 participates not only in the catalytic stages but also in the processes of local duplex distortion and flipping out of the oxoG residue. Non-damaged DNA does not form a stable complex with hOGG1, although a complex with a flipped out guanine base can be formed transiently. The kinetic data obtained in this study significantly improves our understanding of the molecular mechanism of lesion recognition by hOGG1. © 2013.

Evaluating investment in quality improvement capacity building: a systematic review.

PubMed

Mery, Gustavo; Dobrow, Mark J; Baker, G Ross; Im, Jennifer; Brown, Adalsteinn

2017-02-20

Leading health systems have invested in substantial quality improvement (QI) capacity building, but little is known about the aggregate effect of these investments at the health system level. We conducted a systematic review to identify key steps and elements that should be considered for system-level evaluations of investment in QI capacity building. We searched for evaluations of QI capacity building and evaluations of QI training programmes. We included the most relevant indexed databases in the field and a strategic search of the grey literature. The latter included direct electronic scanning of 85 relevant government and institutional websites internationally. Data were extracted regarding evaluation design and common assessment themes and components. 48 articles met the inclusion criteria. 46 articles described initiative-level non-economic evaluations of QI capacity building/training, while 2 studies included economic evaluations of QI capacity building/training, also at the initiative level. No system-level QI capacity building/training evaluations were found. We identified 17 evaluation components that fit within 5 overarching dimensions (characteristics of QI training; characteristics of QI activity; individual capacity; organisational capacity and impact) that should be considered in evaluations of QI capacity building. 8 key steps in return-on-investment (ROI) assessments in QI capacity building were identified: (1) planning-stakeholder perspective; (2) planning-temporal perspective; (3) identifying costs; (4) identifying benefits; (5) identifying intangible benefits that will not be included in the ROI estimation; (6) discerning attribution; (7) ROI calculations; (8) sensitivity analysis. The literature on QI capacity building evaluation is limited in the number and scope of studies. Our findings, summarised in a Framework to Guide Evaluations of QI Capacity Building , can be used to start closing this knowledge gap. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Different dynamin blockers interfere with distinct phases of synaptic endocytosis during stimulation in motoneurones

PubMed Central

Linares-Clemente, Pedro; Rozas, José L; Mircheski, Josif; García-Junco-Clemente, Pablo; Martínez-López, José A; Nieto-González, José L; Vázquez, M Eugenio; Pintado, C Oscar; Fernández-Chacón, Rafael

2015-01-01

Key points Neurotransmitter release requires a tight coupling between synaptic vesicle exocytosis and endocytosis with dynamin being a key protein in that process. We used imaging techniques to examine the time course of endocytosis at mouse motor nerve terminals expressing synaptopHluorin, a genetically encoded reporter of the synaptic vesicle cycle. We separated two sequential phases of endocytosis taking place during the stimulation train: early and late endocytosis. Freshly released synaptic vesicle proteins are preferentially retrieved during the early phase, which is very sensitive to dynasore, an inhibitor of dynamin GTPase activity. Synaptic vesicle proteins pre-existing at the plasma membrane before the stimulation are preferentially retrieved during the late phase, which is very sensitive to myristyl trimethyl ammonium bromide (MitMAB), an inhibitor of the dynamin–phospholipid interaction. Abstract Synaptic endocytosis is essential at nerve terminals to maintain neurotransmitter release by exocytosis. Here, at the neuromuscular junction of synaptopHluorin (spH) transgenic mice, we have used imaging to study exo- and endocytosis occurring simultaneously during nerve stimulation. We observed two endocytosis components, which occur sequentially during stimulation. The early component of endocytosis apparently internalizes spH molecules freshly exocytosed. This component was sensitive to dynasore, a blocker of dynamin 1 GTPase activity. In contrast, this early component was resistant to myristyl trimethyl ammonium bromide (MiTMAB), a competitive agent that blocks dynamin binding to phospholipid membranes. The late component of endocytosis is likely to internalize spH molecules that pre-exist at the plasma membrane before stimulation starts. This component was blocked by MiTMAB, perhaps by impairing the binding of dynamin or other key endocytic proteins to phospholipid membranes. Our study suggests the co-existence of two sequential synaptic endocytosis steps taking place during stimulation that are susceptible to pharmacological dissection: an initial step, preferentially sensitive to dynasore, that internalizes vesicular components immediately after they are released, and a MiTMAB-sensitive step that internalizes vesicular components pre-existing at the plasma membrane surface. In addition, we report that post-stimulus endocytosis also has several components with different sensitivities to dynasore and MiTMAB. PMID:25981717

THE COST OF POSITIONAL NEGOTIATIONS VERSUS COLLABORATIVE OR RELATIONAL NEGOTIATIONS FOR NEGOTIATING COMPLIANCE MILESTONES AT HANFORD WA

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

HOPKINS, A.M.

The Hanford site is subject to the Hanford Federal Facility Agreement and Consent Order (HFFACO), an order on consent signed by the DOE, the U. S. Environmental Protection Agency, (EPA) and the Washington Department of Ecology (WDOE). Under the HFFCCO, negotiations for transition milestones begin within six months after the issuance of a shutdown order. In the case of the PFP, the Nuclear Materials disposition and stabilization activities, a DOE responsibility, were necessary as precursor activities to Transition. This situation precipitated a crisis in the negotiations between the agencies, and formal negotiations initiated in 1997 ended in failure. The negotiationsmore » reached impasse on several key regulatory and operational issues. The 1997 negotiation was characterized by a strongly positional style. DOE and the regulatory personnel took hard lines early in the negotiations and were unable to move to resolution of key issues after a year and a half. This resulted in unhappy stakeholders, poor publicity, and work delays as well as wounded relationships between DOE and the regulatory community. The PFP is a former plutonium metal production facility. The operating mission of the PFP ended with a DOE Headquarters shutdown letter in October of 1996. Generally, the receipt of a shutdown letter initiates the start of Transition (as the first step of Decommissioning) of a facility. In the 2000-2001 PFP negotiations, a completely different approach was suggested and eventually initiated: Collaborative or Relational Negotiations. The relational negotiation style resulted in agreement between the agencies on all key issues within 6 months of initiation. All parties were very pleased with the results and all parties were relieved that protracted negotiations sessions were not needed with the new style of working together collaboratively to serve each other's interests without compromising each party's needs. The characteristics of collaborative negotiations included building trust, emphasizing equality of team members, problem solving by the entire team, relying on individual communications, and self-management skills. A specific example of positional negotiations is given with the resultant increase in cost, duration of negotiations, and lingering questions regarding trust among the parties.« less

A quality improvement project to reduce the intraoperative use of single-dose fentanyl vials across multiple patients in a pediatric institution.

PubMed

Buck, David; Subramanyam, Rajeev; Varughese, Anna

2016-01-01

The use of a single-dose vial across multiple patients presents a risk to sterility and is against CDC guidelines. We initiated a quality improvement (QI) project to reduce the intraoperative use of single-dose vials of fentanyl across multiple patients at Cincinnati Children's Hospital Medical Center (CCHMC). The initial step of the improvement project was the development of a Key Driver Diagram. The diagram has the SMART aim of the project, key drivers inherent to the process we are trying to improve, and specific interventions targeting the key drivers. The number of patients each week receiving an IV dose of fentanyl, from a vial previously accessed for another patient was tracked in a high turnover operating room (OR). The improvement model used was based on the concept of building Plan-Do-Study-Act (PDSA) cycles. Tests of change included provider education, provision of an increased number of fentanyl vials, alternate wasting processes, and provision of single-use fentanyl syringes by the pharmacy. Prior to initiation of this project, it was common for a single fentanyl vial to be accessed for multiple patients. Our data showed an average percentage of failures of just over 50%. During the end of the project, after 7 months, the mean percentage failures had dropped to 5%. Preparation of 20 mcg single-use fentanyl syringes by pharmacy, combined with education of providers on appropriate use, was successful in reducing failures to below our goal of 25%. Appropriately sized fentanyl syringes prepared by pharmacy, education on correct use of single-dose vials, and reminders in the OR, reduced the percentage of patients receiving a dose of fentanyl from a vial previously accessed for another patient in a high-volume otolaryngology room. © 2015 John Wiley & Sons Ltd.

Using causal loop diagrams for the initialization of stakeholder engagement in soil salinity management in agricultural watersheds in developing countries: a case study in the Rechna Doab watershed, Pakistan.

PubMed

Inam, Azhar; Adamowski, Jan; Halbe, Johannes; Prasher, Shiv

2015-04-01

Over the course of the last twenty years, participatory modeling has increasingly been advocated as an integral component of integrated, adaptive, and collaborative water resources management. However, issues of high cost, time, and expertise are significant hurdles to the widespread adoption of participatory modeling in many developing countries. In this study, a step-wise method to initialize the involvement of key stakeholders in the development of qualitative system dynamics models (i.e. causal loop diagrams) is presented. The proposed approach is designed to overcome the challenges of low expertise, time and financial resources that have hampered previous participatory modeling efforts in developing countries. The methodological framework was applied in a case study of soil salinity management in the Rechna Doab region of Pakistan, with a focus on the application of qualitative modeling through stakeholder-built causal loop diagrams to address soil salinity problems in the basin. Individual causal loop diagrams were developed by key stakeholder groups, following which an overall group causal loop diagram of the entire system was built based on the individual causal loop diagrams to form a holistic qualitative model of the whole system. The case study demonstrates the usefulness of the proposed approach, based on using causal loop diagrams in initiating stakeholder involvement in the participatory model building process. In addition, the results point to social-economic aspects of soil salinity that have not been considered by other modeling studies to date. Copyright © 2015 Elsevier Ltd. All rights reserved.

The role of template superhelicity in the initiation of bacteriophage lambda DNA replication.

PubMed Central

Alfano, C; McMacken, R

1988-01-01

The prepriming steps in the initiation of bacteriophage lambda DNA replication depend on the action of the lambda O and P proteins and on the DnaB helicase, single-stranded DNA binding protein (SSB), and DnaJ and DnaK heat shock proteins of the E. coli host. The binding of multiple copies of the lambda O protein to the phage replication origin (ori lambda) initiates the ordered assembly of a series of nucleoprotein structures that form at ori lambda prior to DNA unwinding, priming and DNA synthesis steps. Since the initiation of lambda DNA replication is known to occur only on supercoiled templates in vivo and in vitro, we examined how the early steps in lambda DNA replication are influenced by superhelical tension. All initiation complexes formed prior to helicase-mediated DNA-unwinding form with high efficiency on relaxed ori lambda DNA. Nonetheless, the DNA templates in these structures must be negatively supertwisted before they can be replicated. Once DNA helicase unwinding is initiated at ori lambda, however, later steps in lambda DNA replication proceed efficiently in the absence of superhelical tension. We conclude that supercoiling is required during the initiation of lambda DNA replication to facilitate entry of a DNA helicase, presumably the DnaB protein, between the DNA strands. Images PMID:2847118

Two-step rocket engine bipropellant valve concept

NASA Technical Reports Server (NTRS)

Capps, J. E.; Ferguson, R. E.; Pohl, H. O.

1969-01-01

Initiating combustion of altitude control rocket engines in a precombustion chamber of ductile material reduces high pressure surges generated by hypergolic propellants. Two-step bipropellant valve concepts control initial propellant flow into precombustion chamber and subsequent full flow into main chamber.

Divergent regeneration‐competent cells adopt a common mechanism for callus initiation in angiosperms

PubMed Central

Hu, Bo; Zhang, Guifang; Liu, Wu; Shi, Jianmin; Wang, Hua; Qi, Meifang; Li, Jiqin; Qin, Peng; Ruan, Ying; Huang, Hai; Zhang, Yijing

2017-01-01

Abstract In tissue culture, the formation of callus from detached explants is a key step in plant regeneration; however, the regenerative abilities in different species are variable. While nearly all parts of organs of the dicot Arabidopsis thaliana are ready for callus formation, mature regions of organs in monocot rice (Oryza sativa) and other cereals are extremely unresponsive to tissue culture. Whether there is a common molecular mechanism beyond these different regenerative phenomena is unclear. Here we show that the Arabidopsis and rice use different regeneration‐competent cells to initiate callus, whereas the cells all adopt WUSCHEL‐RELATED HOMEOBOX 11 (WOX11) and WOX5 during cell fate transition. Different from Arabidopsis which maintains regeneration‐competent cells in mature organs, rice exhausts those cells during organ maturation, resulting in regenerative inability in mature organs. Our study not only explains this old perplexity in agricultural biotechnology, but also provides common molecular markers for tissue culture of different angiosperm species. PMID:28975033

Divergent regeneration-competent cells adopt a common mechanism for callus initiation in angiosperms.

PubMed

Hu, Bo; Zhang, Guifang; Liu, Wu; Shi, Jianmin; Wang, Hua; Qi, Meifang; Li, Jiqin; Qin, Peng; Ruan, Ying; Huang, Hai; Zhang, Yijing; Xu, Lin

2017-06-01

In tissue culture, the formation of callus from detached explants is a key step in plant regeneration; however, the regenerative abilities in different species are variable. While nearly all parts of organs of the dicot Arabidopsis thaliana are ready for callus formation, mature regions of organs in monocot rice ( Oryza sativa ) and other cereals are extremely unresponsive to tissue culture. Whether there is a common molecular mechanism beyond these different regenerative phenomena is unclear. Here we show that the Arabidopsis and rice use different regeneration-competent cells to initiate callus, whereas the cells all adopt WUSCHEL-RELATED HOMEOBOX 11 ( WOX11 ) and WOX5 during cell fate transition. Different from Arabidopsis which maintains regeneration-competent cells in mature organs, rice exhausts those cells during organ maturation, resulting in regenerative inability in mature organs. Our study not only explains this old perplexity in agricultural biotechnology, but also provides common molecular markers for tissue culture of different angiosperm species.

Crossing the Vascular Wall: Common and Unique Mechanisms Exploited by Different Leukocyte Subsets during Extravasation

PubMed Central

Schnoor, Michael; Alcaide, Pilar; Voisin, Mathieu-Benoit; van Buul, Jaap D.

2015-01-01

Leukocyte extravasation is one of the essential and first steps during the initiation of inflammation. Therefore, a better understanding of the key molecules that regulate this process may help to develop novel therapeutics for treatment of inflammation-based diseases such as atherosclerosis or rheumatoid arthritis. The endothelial adhesion molecules ICAM-1 and VCAM-1 are known as the central mediators of leukocyte adhesion to and transmigration across the endothelium. Engagement of these molecules by their leukocyte integrin receptors initiates the activation of several signaling pathways within both leukocytes and endothelium. Several of such events have been described to occur during transendothelial migration of all leukocyte subsets, whereas other mechanisms are known only for a single leukocyte subset. Here, we summarize current knowledge on regulatory mechanisms of leukocyte extravasation from a leukocyte and endothelial point of view, respectively. Specifically, we will focus on highlighting common and unique mechanisms that specific leukocyte subsets exploit to succeed in crossing endothelial monolayers. PMID:26568666

Corynebacterium glutamicum promoters: a practical approach

PubMed Central

Pátek, Miroslav; Holátko, Jiří; Busche, Tobias; Kalinowski, Jörn; Nešvera, Jan

2013-01-01

Summary Transcription initiation is the key step in gene expression in bacteria, and it is therefore studied for both theoretical and practical reasons. Promoters, the traffic lights of transcription initiation, are used as construction elements in biotechnological efforts to coordinate ‘green waves’ in the metabolic pathways leading to the desired metabolites. Detailed analyses of Corynebacterium glutamicum promoters have already provided large amounts of data on their structures, regulatory mechanisms and practical capabilities in metabolic engineering. In this minireview the main aspects of promoter studies, the methods developed for their analysis and their practical use in C. glutamicum are discussed. These include definitions of the consensus sequences of the distinct promoter classes, promoter localization and characterization, activity measurements, the functions of transcriptional regulators and examples of practical uses of constitutive, inducible and modified promoters in biotechnology. The implications of the introduction of novel techniques, such as in vitro transcription and RNA sequencing, to C. glutamicum promoter studies are outlined. PMID:23305350

Physicochemical structural changes of cellulosic substrates during enzymatic saccharification

DOE PAGES

Meng, Xianzhi; Yoo, Chang Geun; Li, Mi; ...

2016-12-30

Enzymatic hydrolysis represents one of the major steps and barriers in the commercialization process of converting cellulosic substrates into biofuels and other value added products. It is usually achieved by a synergistic action of enzyme mixture typically consisting of multiple enzymes such as glucanase, cellobiohydrolase and β-glucosidase with different mode of actions. Due to the innate biomass recalcitrance, enzymatic hydrolysis normally starts with an initial fast rate of hydrolysis followed by a rapid decrease of rate toward the end of hydrolysis. With majority of literature studies focusing on the effect of key substrate characteristics on the initial rate or finalmore » yield of enzymatic hydrolysis, information about physicochemical structural changes of cellulosic substrates during enzymatic hydrolysis is still quite limited. Consequently, what slows down the reaction rate toward the end of hydrolysis is not well understood. Lastly, this review highlights recent advances in understanding the structural changes of cellulosic substrates during the hydrolysis process, to better understand the fundamental mechanisms of enzymatic hydrolysis.« less

Affordable Exploration of Mars: Recommendations from a Community Workshop

NASA Technical Reports Server (NTRS)

Thronson, Harley A.; Carberry, Chris; Cassady, R. Joseph; Cooke, Doug; Kirkpatrick, Jim; Perino, Maria Antonietta; Raftery, Michael; Westenberg, Artemis; Zucker, Richard

2014-01-01

There is a growing opinion that within two decades initial human missions to Mars are affordable under plausible budget scenarios, with sustained international participation, and --- especially --- without requiring those first missions to achieve a burdensome number of goals. In response to this view, a group of experts from the Mars exploration stakeholder communities attended the "Affording Mars" workshop at George Washington University in December 2013. Participants reviewed scenarios for proposed affordable and sustainable human and robotic exploration of Mars, the role of the International Space Station as the essential early step toward humans to Mars, possible "bridge" or "transition" missions in the 2020s, key capabilities required for affordable initial missions, international partnerships, and usable definitions of affordability and sustainability. We report here the findings, observations, and recommendations that were agreed to at that workshop. In the context of affordable early missions to Mars, we also discuss the recent report of the National Research Council on human space flight and a pair of recent scenarios that appear to promise reduced costs.

Enhancing the far-ultraviolet sensitivity of silicon complementary metal oxide semiconductor imaging arrays

NASA Astrophysics Data System (ADS)

Retherford, Kurt D.; Bai, Yibin; Ryu, Kevin K.; Gregory, James A.; Welander, Paul B.; Davis, Michael W.; Greathouse, Thomas K.; Winters, Gregory S.; Suntharalingam, Vyshnavi; Beletic, James W.

2015-10-01

We report our progress toward optimizing backside-illuminated silicon P-type intrinsic N-type complementary metal oxide semiconductor devices developed by Teledyne Imaging Sensors (TIS) for far-ultraviolet (UV) planetary science applications. This project was motivated by initial measurements at Southwest Research Institute of the far-UV responsivity of backside-illuminated silicon PIN photodiode test structures, which revealed a promising QE in the 100 to 200 nm range. Our effort to advance the capabilities of thinned silicon wafers capitalizes on recent innovations in molecular beam epitaxy (MBE) doping processes. Key achievements to date include the following: (1) representative silicon test wafers were fabricated by TIS, and set up for MBE processing at MIT Lincoln Laboratory; (2) preliminary far-UV detector QE simulation runs were completed to aid MBE layer design; (3) detector fabrication was completed through the pre-MBE step; and (4) initial testing of the MBE doping process was performed on monitoring wafers, with detailed quality assessments.

Physicochemical structural changes of cellulosic substrates during enzymatic saccharification

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

Meng, Xianzhi; Yoo, Chang Geun; Li, Mi

Enzymatic hydrolysis represents one of the major steps and barriers in the commercialization process of converting cellulosic substrates into biofuels and other value added products. It is usually achieved by a synergistic action of enzyme mixture typically consisting of multiple enzymes such as glucanase, cellobiohydrolase and β-glucosidase with different mode of actions. Due to the innate biomass recalcitrance, enzymatic hydrolysis normally starts with an initial fast rate of hydrolysis followed by a rapid decrease of rate toward the end of hydrolysis. With majority of literature studies focusing on the effect of key substrate characteristics on the initial rate or finalmore » yield of enzymatic hydrolysis, information about physicochemical structural changes of cellulosic substrates during enzymatic hydrolysis is still quite limited. Consequently, what slows down the reaction rate toward the end of hydrolysis is not well understood. Lastly, this review highlights recent advances in understanding the structural changes of cellulosic substrates during the hydrolysis process, to better understand the fundamental mechanisms of enzymatic hydrolysis.« less

Use of Hybridization Chain Reaction-Fluorescent In Situ Hybridization To Track Gene Expression by Both Partners during Initiation of Symbiosis.

PubMed

Nikolakakis, K; Lehnert, E; McFall-Ngai, M J; Ruby, E G

2015-07-01

The establishment of a productive symbiosis between Euprymna scolopes, the Hawaiian bobtail squid, and its luminous bacterial symbiont, Vibrio fischeri, is mediated by transcriptional changes in both partners. A key challenge to unraveling the steps required to successfully initiate this and many other symbiotic associations is characterization of the timing and location of these changes. We report on the adaptation of hybridization chain reaction-fluorescent in situ hybridization (HCR-FISH) to simultaneously probe the spatiotemporal regulation of targeted genes in both E. scolopes and V. fischeri. This method revealed localized, transcriptionally coregulated epithelial cells within the light organ that responded directly to the presence of bacterial cells while, at the same time, provided a sensitive means to directly show regulated gene expression within the symbiont population. Thus, HCR-FISH provides a new approach for characterizing habitat transition in bacteria and for discovering host tissue responses to colonization. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Postural adjustment errors reveal deficits in inhibition during lateral step initiation in older adults

PubMed Central

Fuhrman, Susan I.; Redfern, Mark S.; Jennings, J. Richard; Perera, Subashan; Nebes, Robert D.; Furman, Joseph M.

2013-01-01

Postural dual-task studies have demonstrated effects of various executive function components on gait and postural control in older adults. The purpose of the study was to explore the role of inhibition during lateral step initiation. Forty older adults participated (range 70–94 yr). Subjects stepped to the left or right in response to congruous and incongruous visual cues that consisted of left and right arrows appearing on left or right sides of a monitor. The timing of postural adjustments was identified by inflection points in the vertical ground reaction forces (VGRF) measured separately under each foot. Step responses could be classified into preferred and nonpreferred step behavior based on the number of postural adjustments that were made. Delays in onset of the first postural adjustment (PA1) and liftoff (LO) of the step leg during preferred steps progressively increased among the simple, choice, congruous, and incongruous tasks, indicating interference in processing the relevant visuospatial cue. Incongruous cues induced subjects to make more postural adjustments than they typically would (i.e., nonpreferred steps), representing errors in selection of the appropriate motor program. During these nonpreferred steps, the onset of the PA1 was earlier than during the preferred steps, indicating a failure to inhibit an inappropriate initial postural adjustment. The functional consequence of the additional postural adjustments was a delay in the LO compared with steps in which they did not make an error. These results suggest that deficits in inhibitory function may detrimentally affect step decision processing, by delaying voluntary step responses. PMID:23114211

Timing paradox of stepping and falls in ageing: not so quick and quick(er) on the trigger

PubMed Central

Mille, Marie‐Laure

2016-01-01

Abstract Physiological and degenerative changes affecting human standing balance are major contributors to falls with ageing. During imbalance, stepping is a powerful protective action for preserving balance that may be voluntarily initiated in recognition of a balance threat, or be induced by an externally imposed mechanical or sensory perturbation. Paradoxically, with ageing and falls, initiation slowing of voluntary stepping is observed together with perturbation‐induced steps that are triggered as fast as or faster than for younger adults. While age‐associated changes in sensorimotor conduction, central neuronal processing and cognitive functions are linked to delayed voluntary stepping, alterations in the coupling of posture and locomotion may also prolong step triggering. It is less clear, however, how these factors may explain the accelerated triggering of induced stepping. We present a conceptual model that addresses this issue. For voluntary stepping, a disruption in the normal coupling between posture and locomotion may underlie step‐triggering delays through suppression of the locomotion network based on an estimation of the evolving mechanical state conditions for stability. During induced stepping, accelerated step initiation may represent an event‐triggering process whereby stepping is released according to the occurrence of a perturbation rather than to the specific sensorimotor information reflecting the evolving instability. In this case, errors in the parametric control of induced stepping and its effectiveness in stabilizing balance would be likely to occur. We further suggest that there is a residual adaptive capacity with ageing that could be exploited to improve paradoxical triggering and other changes in protective stepping to impact fall risk. PMID:26915664

Sensory gating for the initiation of the swing phase in different directions of human infant stepping.

PubMed

Pang, Marco Y C; Yang, Jaynie F

2002-07-01

Humans can make smooth, continuous transitions in walking direction from forward to backward. Thus, the processing of sensory input must allow a similar continuum of possibilities. Hip extension and reduced load are two important conditions that control the transition from the stance to swing phase during forward stepping in human infants. The purpose of this study was to determine whether the same factors also regulate the initiation of the swing phase in other directions of stepping. Thirty-seven infants between the ages of 5 and 13 months were studied during supported forward and sideways stepping on a treadmill. Disturbances were elicited by placing a piece of cardboard under the foot and pulling the cardboard in different directions. In this way, the leg was displaced in a particular direction and simultaneously unloaded. We observed whether the swing phase was immediately initiated after the application of disturbances in various directions. Electromyography, vertical ground reaction forces, and hip motion in frontal and sagittal planes were recorded. The results showed that the most potent sensory input to initiate the swing phase depends on the direction of stepping. Although low load was always necessary to initiate swing for all directions of walking, the preferred hip position was always one directly opposite the direction of walking. The results indicated the presence of selective gating of sensory input from the legs as a function of the direction of stepping.

A highly sensitive and accurate gene expression analysis by sequencing ("bead-seq") for a single cell.

PubMed

Matsunaga, Hiroko; Goto, Mari; Arikawa, Koji; Shirai, Masataka; Tsunoda, Hiroyuki; Huang, Huan; Kambara, Hideki

2015-02-15

Analyses of gene expressions in single cells are important for understanding detailed biological phenomena. Here, a highly sensitive and accurate method by sequencing (called "bead-seq") to obtain a whole gene expression profile for a single cell is proposed. A key feature of the method is to use a complementary DNA (cDNA) library on magnetic beads, which enables adding washing steps to remove residual reagents in a sample preparation process. By adding the washing steps, the next steps can be carried out under the optimal conditions without losing cDNAs. Error sources were carefully evaluated to conclude that the first several steps were the key steps. It is demonstrated that bead-seq is superior to the conventional methods for single-cell gene expression analyses in terms of reproducibility, quantitative accuracy, and biases caused during sample preparation and sequencing processes. Copyright © 2014 Elsevier Inc. All rights reserved.

48 CFR 52.214-25 - Step Two of Two-Step Sealed Bidding.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Step Two of Two-Step... Clauses 52.214-25 Step Two of Two-Step Sealed Bidding. As prescribed in 14.201-6(t), insert the following provision: Step Two of Two-Step Sealed Bidding (APR 1985) (a) This invitation for bids is issued to initiate...

Readiness of communities to engage with childhood obesity prevention initiatives in disadvantaged areas of Victoria, Australia.

PubMed

Cyril, Sheila; Polonsky, Michael; Green, Julie; Agho, Kingsley; Renzaho, Andre

2017-07-01

Objective Disadvantaged communities bear a disproportionate burden of childhood obesity and show low participation in childhood obesity prevention initiatives. This study aims to examine the level of readiness of disadvantaged communities to engage with childhood obesity prevention initiatives. Methods Using the community readiness model, 95 semi-structured interviews were conducted among communities in four disadvantaged areas of Victoria, Australia. Community readiness analysis and paired t-tests were performed to assess the readiness levels of disadvantaged communities to engage with childhood obesity prevention initiatives. Results The results showed that disadvantaged communities demonstrated low levels of readiness (readiness score=4/9, 44%) to engage with the existing childhood obesity prevention initiatives, lacked knowledge of childhood obesity and its prevention, and reported facing challenges in initiating and sustaining participation in obesity prevention initiatives. Conclusion This study highlights the need to improve community readiness by addressing low obesity-related literacy levels among disadvantaged communities and by facilitating the capacity-building of bicultural workers to deliver obesity prevention messages to these communities. Integrating these needs into existing Australian health policy and practice is of paramount importance for reducing obesity-related disparities currently prevailing in Australia. What is known about the topic? Childhood obesity prevalence is plateauing in developed countries including Australia; however, obesity-related inequalities continue to exist in Australia especially among communities living in disadvantaged areas, which experience poor engagement in childhood obesity prevention initiatives. Studies in the USA have found that assessing disadvantaged communities' readiness to participate in health programs is a critical initial step in reducing the disproportionate obesity burden among these communities. However, no studies in Australia have assessed disadvantaged communities' readiness to engage in obesity prevention initiatives. What does this paper add? This paper addresses the current gap in the knowledge of disadvantaged communities' level of readiness to engage in childhood obesity prevention initiatives in Australia. The study also identified the key factors responsible for low readiness of disadvantaged communities to participate in current childhood obesity prevention services. By using the Community Readiness model this study shows the readiness levels specific to the various dimensions of the model; Understanding dimension-specific readiness allows us to identify strategies that are tailored to each dimension, as guided by the model. What are the implications for practitioners? With the increasing burden of childhood obesity on disadvantaged communities, policymakers and health practitioners are facing a crisis in obesity prevention and management. Almost every year, new interventions are being planned and implemented. However if the target communities are not ready to participate in the available interventions these efforts are futile. This study exposes the key factors responsible for low readiness to participate in current obesity prevention services by disadvantaged communities. Addressing these key factors and improving readiness before designing new interventions will improve the participation of disadvantaged communities in those interventions. The study findings ultimately have the potential of reducing obesity-related disparities in Australia.

Demystifying process mapping: a key step in neurosurgical quality improvement initiatives.

PubMed

McLaughlin, Nancy; Rodstein, Jennifer; Burke, Michael A; Martin, Neil A

2014-08-01

Reliable delivery of optimal care can be challenging for care providers. Health care leaders have integrated various business tools to assist them and their teams in ensuring consistent delivery of safe and top-quality care. The cornerstone to all quality improvement strategies is the detailed understanding of the current state of a process, captured by process mapping. Process mapping empowers caregivers to audit how they are currently delivering care to subsequently strategically plan improvement initiatives. As a community, neurosurgery has clearly shown dedication to enhancing patient safety and delivering quality care. A care redesign strategy named NERVS (Neurosurgery Enhanced Recovery after surgery, Value, and Safety) is currently being developed and piloted within our department. Through this initiative, a multidisciplinary team led by a clinician neurosurgeon has process mapped the way care is currently being delivered throughout the entire episode of care. Neurosurgeons are becoming leaders in quality programs, and their education on the quality improvement strategies and tools is essential. The authors present a comprehensive review of process mapping, demystifying its planning, its building, and its analysis. The particularities of using process maps, initially a business tool, in the health care arena are discussed, and their specific use in an academic neurosurgical department is presented.

Bayesian Analysis of Evolutionary Divergence with Genomic Data under Diverse Demographic Models.

PubMed

Chung, Yujin; Hey, Jody

2017-06-01

We present a new Bayesian method for estimating demographic and phylogenetic history using population genomic data. Several key innovations are introduced that allow the study of diverse models within an Isolation-with-Migration framework. The new method implements a 2-step analysis, with an initial Markov chain Monte Carlo (MCMC) phase that samples simple coalescent trees, followed by the calculation of the joint posterior density for the parameters of a demographic model. In step 1, the MCMC sampling phase, the method uses a reduced state space, consisting of coalescent trees without migration paths, and a simple importance sampling distribution without the demography of interest. Once obtained, a single sample of trees can be used in step 2 to calculate the joint posterior density for model parameters under multiple diverse demographic models, without having to repeat MCMC runs. Because migration paths are not included in the state space of the MCMC phase, but rather are handled by analytic integration in step 2 of the analysis, the method is scalable to a large number of loci with excellent MCMC mixing properties. With an implementation of the new method in the computer program MIST, we demonstrate the method's accuracy, scalability, and other advantages using simulated data and DNA sequences of two common chimpanzee subspecies: Pan troglodytes (P. t.) troglodytes and P. t. verus. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Deubiquitylation of histone H2A activates transcriptional initiation via trans-histone cross-talk with H3K4 di- and trimethylation

PubMed Central

Nakagawa, Takeya; Kajitani, Takuya; Togo, Shinji; Masuko, Norio; Ohdan, Hideki; Hishikawa, Yoshitaka; Koji, Takehiko; Matsuyama, Toshifumi; Ikura, Tsuyoshi; Muramatsu, Masami; Ito, Takashi

2008-01-01

Transcriptional initiation is a key step in the control of mRNA synthesis and is intimately related to chromatin structure and histone modification. Here, we show that the ubiquitylation of H2A (ubH2A) correlates with silent chromatin and regulates transcriptional initiation. The levels of ubH2A vary during hepatocyte regeneration, and based on microarray expression data from regenerating liver, we identified USP21, a ubiquitin-specific protease that catalyzes the hydrolysis of ubH2A. When chromatin is assembled in vitro, ubH2A, but not H2A, specifically represses the di- and trimethylation of H3K4. USP21 relieves this ubH2A-specific repression. In addition, in vitro transcription analysis revealed that ubH2A represses transcriptional initiation, but not transcriptional elongation, by inhibiting H3K4 methylation. Notably, ubH2A-mediated repression was not observed when H3 Lys 4 was changed to arginine. Furthermore, overexpression of USP21 in the liver up-regulates a gene that is normally down-regulated during hepatocyte regeneration. Our studies revealed a novel mode of trans-histone cross-talk, in which H2A ubiquitylation controls the di- and trimethylation of H3K4, resulting in regulation of transcriptional initiation. PMID:18172164

Laboratory information management system for membrane protein structure initiative--from gene to crystal.

PubMed

Troshin, Petr V; Morris, Chris; Prince, Stephen M; Papiz, Miroslav Z

2008-12-01

Membrane Protein Structure Initiative (MPSI) exploits laboratory competencies to work collaboratively and distribute work among the different sites. This is possible as protein structure determination requires a series of steps, starting with target selection, through cloning, expression, purification, crystallization and finally structure determination. Distributed sites create a unique set of challenges for integrating and passing on information on the progress of targets. This role is played by the Protein Information Management System (PIMS), which is a laboratory information management system (LIMS), serving as a hub for MPSI, allowing collaborative structural proteomics to be carried out in a distributed fashion. It holds key information on the progress of cloning, expression, purification and crystallization of proteins. PIMS is employed to track the status of protein targets and to manage constructs, primers, experiments, protocols, sample locations and their detailed histories: thus playing a key role in MPSI data exchange. It also serves as the centre of a federation of interoperable information resources such as local laboratory information systems and international archival resources, like PDB or NCBI. During the challenging task of PIMS integration, within the MPSI, we discovered a number of prerequisites for successful PIMS integration. In this article we share our experiences and provide invaluable insights into the process of LIMS adaptation. This information should be of interest to partners who are thinking about using LIMS as a data centre for their collaborative efforts.

The Urban Exploitation Platform - An instrument for the global provision of indicators related to sustainable cities and communities

NASA Astrophysics Data System (ADS)

Esch, Thomas; Asamer, Hubert; Hirner, Andreas; Marconcini, Mattia; Metz, Annekatrin; Uereyen, Soner; Zeidler, Julian; Boettcher, Martin; Permana, Hans; Boissier, Enguerran; Mathot, Emmanuel; Soukop, Tomas; Balhar, Jakub; Svaton, Vaclav; Kuchar, Stepan

2017-04-01

The Sentinel fleet will provide a so-far unique coverage with Earth Observation (EO) data and therewith new opportunities for the implementation of methodologies to generate innovative geo-information products and services supporting the SDG targets. It is here where the TEP Urban project is supposed to initiate a step change by providing an open and participatory platform that allows any interested user to easily exploit large-volume EO data pools, in particular those of the European Sentinel and the US Landsat missions, and derive thematic geo-information, metrics and indicators related to the status and development of the built environment. Key component of TEP Urban initiative is the implementation of a web-based platform (https://urban-tep.eo.esa.int) employing distributed high-level computing infrastructures and providing key functionalities for i) high-performance access to satellite imagery and other data sources such as statistics or topographic data, ii) state-of-the-art pre-processing, analysis, and visualization techniques, iii) customized development and dissemination of algorithms, products and services, and iv) networking and communication. This contribution introduces the main facts about the TEP Urban platform, including a description of the general objectives, the platform systems design and functionalities, and the available portfolio of products and services that can directly serve the global provision of indicators for SDG targets, in particular related to SDG 11.

Cryptosystem based on two-step phase-shifting interferometry and the RSA public-key encryption algorithm

NASA Astrophysics Data System (ADS)

Meng, X. F.; Peng, X.; Cai, L. Z.; Li, A. M.; Gao, Z.; Wang, Y. R.

2009-08-01

A hybrid cryptosystem is proposed, in which one image is encrypted to two interferograms with the aid of double random-phase encoding (DRPE) and two-step phase-shifting interferometry (2-PSI), then three pairs of public-private keys are utilized to encode and decode the session keys (geometrical parameters, the second random-phase mask) and interferograms. In the stage of decryption, the ciphered image can be decrypted by wavefront reconstruction, inverse Fresnel diffraction, and real amplitude normalization. This approach can successfully solve the problem of key management and dispatch, resulting in increased security strength. The feasibility of the proposed cryptosystem and its robustness against some types of attack are verified and analyzed by computer simulations.

Timing paradox of stepping and falls in ageing: not so quick and quick(er) on the trigger.

PubMed

Rogers, Mark W; Mille, Marie-Laure

2016-08-15

Physiological and degenerative changes affecting human standing balance are major contributors to falls with ageing. During imbalance, stepping is a powerful protective action for preserving balance that may be voluntarily initiated in recognition of a balance threat, or be induced by an externally imposed mechanical or sensory perturbation. Paradoxically, with ageing and falls, initiation slowing of voluntary stepping is observed together with perturbation-induced steps that are triggered as fast as or faster than for younger adults. While age-associated changes in sensorimotor conduction, central neuronal processing and cognitive functions are linked to delayed voluntary stepping, alterations in the coupling of posture and locomotion may also prolong step triggering. It is less clear, however, how these factors may explain the accelerated triggering of induced stepping. We present a conceptual model that addresses this issue. For voluntary stepping, a disruption in the normal coupling between posture and locomotion may underlie step-triggering delays through suppression of the locomotion network based on an estimation of the evolving mechanical state conditions for stability. During induced stepping, accelerated step initiation may represent an event-triggering process whereby stepping is released according to the occurrence of a perturbation rather than to the specific sensorimotor information reflecting the evolving instability. In this case, errors in the parametric control of induced stepping and its effectiveness in stabilizing balance would be likely to occur. We further suggest that there is a residual adaptive capacity with ageing that could be exploited to improve paradoxical triggering and other changes in protective stepping to impact fall risk. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Resuscitator’s perceptions and time for corrective ventilation steps during neonatal resuscitation☆

PubMed Central

Sharma, Vinay; Lakshminrusimha, Satyan; Carrion, Vivien; Mathew, Bobby

2016-01-01

Background The 2010 neonatal resuscitation program (NRP) guidelines incorporate ventilation corrective steps (using the mnemonic – MRSOPA) into the resuscitation algorithm. The perception of neonatal providers, time taken to perform these maneuvers or the effectiveness of these additional steps has not been evaluated. Methods Using two simulated clinical scenarios of varying degrees of cardiovascular compromise –perinatal asphyxia with (i) bradycardia (heart rate – 40 min−1) and (ii) cardiac arrest, 35 NRP certified providers were evaluated for preference to performing these corrective measures, the time taken for performing these steps and time to onset of chest compressions. Results The average time taken to perform ventilation corrective steps (MRSOPA) was 48.9 ± 21.4 s. Providers were less likely to perform corrective steps and proceed directly to endotracheal intubation in the scenario of cardiac arrest as compared to a state of bradycardia. Cardiac compressions were initiated significantly sooner in the scenario of cardiac arrest 89 ± 24 s as compared to severe bradycardia 122 ± 23 s, p < 0.0001. There were no differences in the time taken to initiation of chest compressions between physicians or mid-level care providers or with the level of experience of the provider. Conclusions Effective ventilation of the lungs with corrective steps using a mask is important in most cases of neonatal resuscitation. Neonatal resuscitators prefer early endotracheal intubation and initiation of chest compressions in the presence of asystolic cardiac arrest. Corrective ventilation steps can potentially postpone initiation of chest compressions and may delay return of spontaneous circulation in the presence of severe cardiovascular compromise. PMID:25796996

Imaging nanobubble nucleation and hydrogen spillover during electrocatalytic water splitting.

PubMed

Hao, Rui; Fan, Yunshan; Howard, Marco D; Vaughan, Joshua C; Zhang, Bo

2018-06-05

Nucleation and growth of hydrogen nanobubbles are key initial steps in electrochemical water splitting. These processes remain largely unexplored due to a lack of proper tools to probe the nanobubble's interfacial structure with sufficient spatial and temporal resolution. We report the use of superresolution microscopy to image transient formation and growth of single hydrogen nanobubbles at the electrode/solution interface during electrocatalytic water splitting. We found hydrogen nanobubbles can be generated even at very early stages in water electrolysis, i.e., ∼500 mV before reaching its thermodynamic reduction potential. The ability to image single nanobubbles on an electrode enabled us to observe in real time the process of hydrogen spillover from ultrathin gold nanocatalysts supported on indium-tin oxide.

Femtosecond laser cataract surgery: technology and clinical practice.

PubMed

Roberts, Timothy V; Lawless, Michael; Chan, Colin Ck; Jacobs, Mark; Ng, David; Bali, Shveta J; Hodge, Chris; Sutton, Gerard

2013-03-01

The recent introduction of femtosecond lasers to cataract surgery has generated much interest among ophthalmologists around the world. Laser cataract surgery integrates high-resolution anterior segment imaging systems with a femtosecond laser, allowing key steps of the procedure, including the primary and side-port corneal incisions, the anterior capsulotomy and fragmentation of the lens nucleus, to be performed with computer-guided laser precision. There is emerging evidence of reduced phacoemulsification time, better wound architecture and a more stable refractive result with femtosecond cataract surgery, as well as reports documenting an initial learning curve. This article will review the current state of technology and discuss our clinical experience. © 2012 The Authors. Clinical and Experimental Ophthalmology © 2012 Royal Australian and New Zealand College of Ophthalmologists.

Measurement of Richtmyer–Meshkov mode coupling under steady shock conditions and at high energy density

DOE PAGES

Di Stefano, Carlos A.; Malamud, G.; Kuranz, C. C.; ...

2015-10-19

Here, we present experiments observing Richtmyer–Meshkov mode coupling and bubble competition in a system arising from well-characterized initial conditions and driven by a strong (Mach ~ 8) shock. These measurements and the analysis method developed to interpret them provide an important step toward the possibility of observing self-similarity under such conditions, as well as a general platform for performing and analyzing hydrodynamic instability experiments. A key feature of these experiments is that the shock is sustained sufficiently long that this nonlinear behavior occurs without decay of the shock velocity or other hydrodynamic properties of the system, which facilitates analysis andmore » allows the results to be used in the study of analytic models.« less

Cyclic completion of the anamorphic universe

NASA Astrophysics Data System (ADS)

Ijjas, Anna

2018-04-01

Cyclic models of the universe have the advantage of avoiding initial conditions problems related to postulating any sort of beginning in time. To date, the best known viable examples of cyclic models have been ekpyrotic. In this paper, we show that the recently proposed anamorphic scenario can also be made cyclic. The key to the cyclic completion is a classically stable, non-singular bounce. Remarkably, even though the bounce construction was originally developed to connect a period of contraction with a period of expansion both described by Einstein gravity, we show here that it can naturally be modified to connect an ordinary contracting phase described by Einstein gravity with a phase of anamorphic smoothing. The paper will present the basic principles and steps in constructing cyclic anamorphic models.

Books on Prescription - community-based health initiative to increase access to mental health treatment: an evaluation.

PubMed

Carty, Sophie; Thompson, Louise; Berger, Sarah; Jahnke, Katie; Llewellyn, Rebecca

2016-06-01

To evaluate the implementation of a regional Books on Prescription (BoP) programme. Seven data collection pathways were used to provide indicators of program implementation, utilisation, acceptability and reach. BoP is seen by prescribers, librarians and consumers as a valuable mental health resource. Key areas for improvement were identified: booklist literacy level and breadth of topic area; confidentiality; program promotion; and prescriber/librarian training. Recommendations are made regarding the improvement of programme acceptability, accessibility and assessment. The establishment of a national BoP scheme would facilitate sustainable and consistent methods for BoP promotion and assessment. The authors hope this evaluation is a step towards actualising this goal. © 2015 Public Health Association of Australia.

Plasma Discharge Process in a Pulsed Diaphragm Discharge System

NASA Astrophysics Data System (ADS)

Duan, Jianjin; Hu, Jue; Zhang, Chao; Wen, Yuanbin; Meng, Yuedong; Zhang, Chengxu

2014-12-01

As one of the most important steps in wastewater treatment, limited study on plasma discharge process is a key challenge in the development of plasma applications. In this study, we focus on the plasma discharge process of a pulsed diaphragm discharge system. According to the analysis, the pulsed diaphragm discharge proceeds in seven stages: (1) Joule heating and heat exchange stage; (2) nucleated site formation; (3) plasma generation (initiation of the breakdown stage); (4) avalanche growth and plasma expansion; (5) plasma contraction; (6) termination of the plasma discharge; and (7) heat exchange stage. From this analysis, a critical voltage criterion for breakdown is obtained. We anticipate this finding will provide guidance for a better application of plasma discharges, especially diaphragm plasma discharges.

Developing a spinal cord injury research strategy using a structured process of evidence review and stakeholder dialogue. Part II: Background to a research strategy.

PubMed

Bragge, P; Piccenna, L; Middleton, J; Williams, S; Creasey, G; Dunlop, S; Brown, D; Gruen, R

2015-10-01

Literature review/semi-structured interviews. To develop a spinal cord injury (SCI) research strategy for Australia and New Zealand. Australia. The National Trauma Research Institute Forum approach of structured evidence review and stakeholder consultation was employed. This involved gathering from published literature and stakeholder consultation the information necessary to properly consider the challenge, and synthesising this into a briefing document. A research strategy 'roadmap' was developed to define the major steps and key planning questions to consider; next, evidence from published SCI research strategy initiatives was synthesised with information from four one-on-one semi-structured interviews with key SCI research stakeholders to create a research strategy framework, articulating six key themes and associated activities for consideration. These resources, combined with a review of SCI prioritisation literature, were used to generate a list of draft principles for discussion in a structured stakeholder dialogue meeting. The research strategy roadmap and framework informed discussion at a structured stakeholder dialogue meeting of 23 participants representing key SCI research constituencies, results of which are published in a companion paper. These resources could also be of value in other research strategy or planning exercises. This project was funded by the Victorian Transport Accident Commission and the Australian and New Zealand Spinal Cord Injury Network.

Spring-Loaded Model Revisited: Paramyxovirus Fusion Requires Engagement of a Receptor Binding Protein beyond Initial Triggering of the Fusion Protein▿

PubMed Central

Porotto, Matteo; DeVito, Ilaria; Palmer, Samantha G.; Jurgens, Eric M.; Yee, Jia L.; Yokoyama, Christine C.; Pessi, Antonello; Moscona, Anne

2011-01-01

During paramyxovirus entry into a host cell, receptor engagement by a specialized binding protein triggers conformational changes in the adjacent fusion protein (F), leading to fusion between the viral and cell membranes. According to the existing paradigm of paramyxovirus membrane fusion, the initial activation of F by the receptor binding protein sets off a spring-loaded mechanism whereby the F protein progresses independently through the subsequent steps in the fusion process, ending in membrane merger. For human parainfluenza virus type 3 (HPIV3), the receptor binding protein (hemagglutinin-neuraminidase [HN]) has three functions: receptor binding, receptor cleaving, and activating F. We report that continuous receptor engagement by HN activates F to advance through the series of structural rearrangements required for fusion. In contrast to the prevailing model, the role of HN-receptor engagement in the fusion process is required beyond an initiating step, i.e., it is still required even after the insertion of the fusion peptide into the target cell membrane, enabling F to mediate membrane merger. We also report that for Nipah virus, whose receptor binding protein has no receptor-cleaving activity, the continuous stimulation of the F protein by a receptor-engaged binding protein is key for fusion. We suggest a general model for paramyxovirus fusion activation in which receptor engagement plays an active role in F activation, and the continued engagement of the receptor binding protein is essential to F protein function until the onset of membrane merger. This model has broad implications for the mechanism of paramyxovirus fusion and for strategies to prevent viral entry. PMID:21976650

Spring-loaded model revisited: paramyxovirus fusion requires engagement of a receptor binding protein beyond initial triggering of the fusion protein.

PubMed

Porotto, Matteo; Devito, Ilaria; Palmer, Samantha G; Jurgens, Eric M; Yee, Jia L; Yokoyama, Christine C; Pessi, Antonello; Moscona, Anne

2011-12-01

During paramyxovirus entry into a host cell, receptor engagement by a specialized binding protein triggers conformational changes in the adjacent fusion protein (F), leading to fusion between the viral and cell membranes. According to the existing paradigm of paramyxovirus membrane fusion, the initial activation of F by the receptor binding protein sets off a spring-loaded mechanism whereby the F protein progresses independently through the subsequent steps in the fusion process, ending in membrane merger. For human parainfluenza virus type 3 (HPIV3), the receptor binding protein (hemagglutinin-neuraminidase [HN]) has three functions: receptor binding, receptor cleaving, and activating F. We report that continuous receptor engagement by HN activates F to advance through the series of structural rearrangements required for fusion. In contrast to the prevailing model, the role of HN-receptor engagement in the fusion process is required beyond an initiating step, i.e., it is still required even after the insertion of the fusion peptide into the target cell membrane, enabling F to mediate membrane merger. We also report that for Nipah virus, whose receptor binding protein has no receptor-cleaving activity, the continuous stimulation of the F protein by a receptor-engaged binding protein is key for fusion. We suggest a general model for paramyxovirus fusion activation in which receptor engagement plays an active role in F activation, and the continued engagement of the receptor binding protein is essential to F protein function until the onset of membrane merger. This model has broad implications for the mechanism of paramyxovirus fusion and for strategies to prevent viral entry.

Rendezvous missions to temporarily captured near Earth asteroids

NASA Astrophysics Data System (ADS)

Brelsford, S.; Chyba, M.; Haberkorn, T.; Patterson, G.

2016-04-01

Missions to rendezvous with or capture an asteroid present significant interest both from a geophysical and safety point of view. They are key to the understanding of our solar system and are stepping stones for interplanetary human flight. In this paper, we focus on a rendezvous mission with 2006 RH120, an asteroid classified as a Temporarily Captured Orbiter (TCO). TCOs form a new population of near Earth objects presenting many advantages toward that goal. Prior to the mission, we consider the spacecraft hibernating on a Halo orbit around the Earth-Moon's L2 libration point. The objective is to design a transfer for the spacecraft from the parking orbit to rendezvous with 2006 RH120 while minimizing the fuel consumption. Our transfers use indirect methods, based on the Pontryagin Maximum Principle, combined with continuation techniques and a direct method to address the sensitivity of the initialization. We demonstrate that a rendezvous mission with 2006 RH120 can be accomplished with low delta-v. This exploratory work can be seen as a first step to identify good candidates for a rendezvous on a given TCO trajectory.

Protocols and characterization data for 2D, 3D, and slice-based tumor models from the PREDECT project.

PubMed

de Hoogt, Ronald; Estrada, Marta F; Vidic, Suzana; Davies, Emma J; Osswald, Annika; Barbier, Michael; Santo, Vítor E; Gjerde, Kjersti; van Zoggel, Hanneke J A A; Blom, Sami; Dong, Meng; Närhi, Katja; Boghaert, Erwin; Brito, Catarina; Chong, Yolanda; Sommergruber, Wolfgang; van der Kuip, Heiko; van Weerden, Wytske M; Verschuren, Emmy W; Hickman, John; Graeser, Ralph

2017-11-21

Two-dimensional (2D) culture of cancer cells in vitro does not recapitulate the three-dimensional (3D) architecture, heterogeneity and complexity of human tumors. More representative models are required that better reflect key aspects of tumor biology. These are essential studies of cancer biology and immunology as well as for target validation and drug discovery. The Innovative Medicines Initiative (IMI) consortium PREDECT (www.predect.eu) characterized in vitro models of three solid tumor types with the goal to capture elements of tumor complexity and heterogeneity. 2D culture and 3D mono- and stromal co-cultures of increasing complexity, and precision-cut tumor slice models were established. Robust protocols for the generation of these platforms are described. Tissue microarrays were prepared from all the models, permitting immunohistochemical analysis of individual cells, capturing heterogeneity. 3D cultures were also characterized using image analysis. Detailed step-by-step protocols, exemplary datasets from the 2D, 3D, and slice models, and refined analytical methods were established and are presented.

Protocols and characterization data for 2D, 3D, and slice-based tumor models from the PREDECT project

PubMed Central

de Hoogt, Ronald; Estrada, Marta F.; Vidic, Suzana; Davies, Emma J.; Osswald, Annika; Barbier, Michael; Santo, Vítor E.; Gjerde, Kjersti; van Zoggel, Hanneke J. A. A.; Blom, Sami; Dong, Meng; Närhi, Katja; Boghaert, Erwin; Brito, Catarina; Chong, Yolanda; Sommergruber, Wolfgang; van der Kuip, Heiko; van Weerden, Wytske M.; Verschuren, Emmy W.; Hickman, John; Graeser, Ralph

2017-01-01

Two-dimensional (2D) culture of cancer cells in vitro does not recapitulate the three-dimensional (3D) architecture, heterogeneity and complexity of human tumors. More representative models are required that better reflect key aspects of tumor biology. These are essential studies of cancer biology and immunology as well as for target validation and drug discovery. The Innovative Medicines Initiative (IMI) consortium PREDECT (www.predect.eu) characterized in vitro models of three solid tumor types with the goal to capture elements of tumor complexity and heterogeneity. 2D culture and 3D mono- and stromal co-cultures of increasing complexity, and precision-cut tumor slice models were established. Robust protocols for the generation of these platforms are described. Tissue microarrays were prepared from all the models, permitting immunohistochemical analysis of individual cells, capturing heterogeneity. 3D cultures were also characterized using image analysis. Detailed step-by-step protocols, exemplary datasets from the 2D, 3D, and slice models, and refined analytical methods were established and are presented. PMID:29160867

An automatic and effective parameter optimization method for model tuning

NASA Astrophysics Data System (ADS)

Zhang, T.; Li, L.; Lin, Y.; Xue, W.; Xie, F.; Xu, H.; Huang, X.

2015-11-01

Physical parameterizations in general circulation models (GCMs), having various uncertain parameters, greatly impact model performance and model climate sensitivity. Traditional manual and empirical tuning of these parameters is time-consuming and ineffective. In this study, a "three-step" methodology is proposed to automatically and effectively obtain the optimum combination of some key parameters in cloud and convective parameterizations according to a comprehensive objective evaluation metrics. Different from the traditional optimization methods, two extra steps, one determining the model's sensitivity to the parameters and the other choosing the optimum initial value for those sensitive parameters, are introduced before the downhill simplex method. This new method reduces the number of parameters to be tuned and accelerates the convergence of the downhill simplex method. Atmospheric GCM simulation results show that the optimum combination of these parameters determined using this method is able to improve the model's overall performance by 9 %. The proposed methodology and software framework can be easily applied to other GCMs to speed up the model development process, especially regarding unavoidable comprehensive parameter tuning during the model development stage.

The Numerical Simulation of the Shock Wave of Coal Gas Explosions in Gas Pipe*

NASA Astrophysics Data System (ADS)

Chen, Zhenxing; Hou, Kepeng; Chen, Longwei

2018-03-01

For the problem of large deformation and vortex, the method of Euler and Lagrange has both advantage and disadvantage. In this paper we adopt special fuzzy interface method(volume of fluid). Gas satisfies the conditions of conservation equations of mass, momentum, and energy. Based on explosion and three-dimension fluid dynamics theory, using unsteady, compressible, inviscid hydrodynamic equations and state equations, this paper considers pressure gradient’s effects to velocity, mass and energy in Lagrange steps by the finite difference method. To minimize transport errors of material, energy and volume in Finite Difference mesh, it also considers material transport in Euler steps. Programmed with Fortran PowerStation 4.0 and visualized with the software designed independently, we design the numerical simulation of gas explosion with specific pipeline structure, check the key points of the pressure change in the flow field, reproduce the gas explosion in pipeline of shock wave propagation, from the initial development, flame and accelerate the process of shock wave. This offers beneficial reference and experience to coal gas explosion accidents or safety precautions.

Exploring the Process of Implementing Healthy Workplace Initiatives: Mapping to Kotter's Leading Change Model.

PubMed

Chappell, Stacie; Pescud, Melanie; Waterworth, Pippa; Shilton, Trevor; Roche, Dee; Ledger, Melissa; Slevin, Terry; Rosenberg, Michael

2016-10-01

The aim of this study was to use Kotter's leading change model to explore the implementation of workplace health and wellbeing initiatives. Qualitative interviews were conducted with 31 workplace representatives with a healthy workplace initiative. None of the workplaces used a formal change management model when implementing their healthy workplace initiatives. Not all of the steps in Kotter model were considered necessary and the order of the steps was challenged. For example, interviewees perceived that communicating the vision, developing the vision, and creating a guiding coalition were integral parts of the process, although there was less emphasis on the importance of creating a sense of urgency and consolidating change. Although none of the workplaces reported using a formal organizational change model when implementing their healthy workplace initiatives, there did appear to be perceived merit in using the steps in Kotter's model.

Some Key Factors in Policy Implementation.

ERIC Educational Resources Information Center

Rowen, Henry

Business policy texts identify numerous steps that make up the policy implementation process for private firms. On the surface, these steps also appear applicable to the implementation of public policies. However, the problems of carrying out these implementing steps in the public sector are significantly different than in the private sector due…

Structure of the ribosome post-recycling complex probed by chemical cross-linking and mass spectrometry

PubMed Central

Kiosze-Becker, Kristin; Ori, Alessandro; Gerovac, Milan; Heuer, André; Nürenberg-Goloub, Elina; Rashid, Umar Jan; Becker, Thomas; Beckmann, Roland; Beck, Martin; Tampé, Robert

2016-01-01

Ribosome recycling orchestrated by the ATP binding cassette (ABC) protein ABCE1 can be considered as the final—or the first—step within the cyclic process of protein synthesis, connecting translation termination and mRNA surveillance with re-initiation. An ATP-dependent tweezer-like motion of the nucleotide-binding domains in ABCE1 transfers mechanical energy to the ribosome and tears the ribosome subunits apart. The post-recycling complex (PRC) then re-initiates mRNA translation. Here, we probed the so far unknown architecture of the 1-MDa PRC (40S/30S·ABCE1) by chemical cross-linking and mass spectrometry (XL-MS). Our study reveals ABCE1 bound to the translational factor-binding (GTPase) site with multiple cross-link contacts of the helix–loop–helix motif to the S24e ribosomal protein. Cross-linking of the FeS cluster domain to the ribosomal protein S12 substantiates an extreme lever-arm movement of the FeS cluster domain during ribosome recycling. We were thus able to reconstitute and structurally analyse a key complex in the translational cycle, resembling the link between translation initiation and ribosome recycling. PMID:27824037

A lab-controlled simulation of a letter-speech sound binding deficit in dyslexia.

PubMed

Aravena, Sebastián; Snellings, Patrick; Tijms, Jurgen; van der Molen, Maurits W

2013-08-01

Dyslexic and non-dyslexic readers engaged in a short training aimed at learning eight basic letter-speech sound correspondences within an artificial orthography. We examined whether a letter-speech sound binding deficit is behaviorally detectable within the initial steps of learning a novel script. Both letter knowledge and word reading ability within the artificial script were assessed. An additional goal was to investigate the influence of instructional approach on the initial learning of letter-speech sound correspondences. We assigned children from both groups to one of three different training conditions: (a) explicit instruction, (b) implicit associative learning within a computer game environment, or (c) a combination of (a) and (b) in which explicit instruction is followed by implicit learning. Our results indicated that dyslexics were outperformed by the controls on a time-pressured binding task and a word reading task within the artificial orthography, providing empirical support for the view that a letter-speech sound binding deficit is a key factor in dyslexia. A combination of explicit instruction and implicit techniques proved to be a more powerful tool in the initial teaching of letter-sound correspondences than implicit training alone. Copyright © 2013 Elsevier Inc. All rights reserved.

On initial steps of chemical prebiotic evolution: Triggering autocatalytic reaction of oligomerization

NASA Astrophysics Data System (ADS)

Bartsev, S. I.; Mezhevikin, V. V.

2008-12-01

Searching for extraterrestrial life attracts more and more attention. However this searching hardly can be effective without sufficiently universal concept of life origin, which incidentally tackles a problem of origin of life on the Earth. A concept of initial stages of life origin is stated in the paper. The concept eliminates key difficulties in the problem of life origin, and allows experimental verification of it. According to the concept the predecessor of living beings has to be sufficiently simple to provide non-zero probability of self-assembling during short (in geological or cosmic scale) time. In addition the predecessor has to be capable of autocatalysis, and further complication (evolution). A possible scenario of initial stage of life origin, which can be realized both on other planets, and inside experimental facility is considered. In the scope of the scenario a theoretical model of multivariate oligomeric autocatalyst is presented. Results of computer simulation of two versions of oligomeric autocatalytic reactions are presented. It is shown that the contribution of monomer activation reaction is essential, and in some cases autocatalysis in polymerizing reaction can be achieved without catalyzing proper monomer binding reaction.

Mammalian poly(A)-binding protein is a eukaryotic translation initiation factor, which acts via multiple mechanisms.

PubMed

Kahvejian, Avak; Svitkin, Yuri V; Sukarieh, Rami; M'Boutchou, Marie-Noël; Sonenberg, Nahum

2005-01-01

Translation initiation is a multistep process involving several canonical translation factors, which assemble at the 5'-end of the mRNA to promote the recruitment of the ribosome. Although the 3' poly(A) tail of eukaryotic mRNAs and its major bound protein, the poly(A)-binding protein (PABP), have been studied extensively, their mechanism of action in translation is not well understood and is confounded by differences between in vivo and in vitro systems. Here, we provide direct evidence for the involvement of PABP in key steps of the translation initiation pathway. Using a new technique to deplete PABP from mammalian cell extracts, we show that extracts lacking PABP exhibit dramatically reduced rates of translation, reduced efficiency of 48S and 80S ribosome initiation complex formation, and impaired interaction of eIF4E with the mRNA cap structure. Supplementing PABP-depleted extracts with wild-type PABP completely rectified these deficiencies, whereas a mutant of PABP, M161A, which is incapable of interacting with eIF4G, failed to restore translation. In addition, a stronger inhibition (approximately twofold) of 80S as compared to 48S ribosome complex formation (approximately 65% vs. approximately 35%, respectively) by PABP depletion suggests that PABP plays a direct role in 60S subunit joining. PABP can thus be considered a canonical translation initiation factor, integral to initiation complex formation at the 5'-end of mRNA.

Mammalian poly(A)-binding protein is a eukaryotic translation initiation factor, which acts via multiple mechanisms

PubMed Central

Kahvejian, Avak; Svitkin, Yuri V.; Sukarieh, Rami; M'Boutchou, Marie-Noël; Sonenberg, Nahum

2005-01-01

Translation initiation is a multistep process involving several canonical translation factors, which assemble at the 5′-end of the mRNA to promote the recruitment of the ribosome. Although the 3′ poly(A) tail of eukaryotic mRNAs and its major bound protein, the poly(A)-binding protein (PABP), have been studied extensively, their mechanism of action in translation is not well understood and is confounded by differences between in vivo and in vitro systems. Here, we provide direct evidence for the involvement of PABP in key steps of the translation initiation pathway. Using a new technique to deplete PABP from mammalian cell extracts, we show that extracts lacking PABP exhibit dramatically reduced rates of translation, reduced efficiency of 48S and 80S ribosome initiation complex formation, and impaired interaction of eIF4E with the mRNA cap structure. Supplementing PABP-depleted extracts with wild-type PABP completely rectified these deficiencies, whereas a mutant of PABP, M161A, which is incapable of interacting with eIF4G, failed to restore translation. In addition, a stronger inhibition (approximately twofold) of 80S as compared to 48S ribosome complex formation (∼65% vs. ∼35%, respectively) by PABP depletion suggests that PABP plays a direct role in 60S subunit joining. PABP can thus be considered a canonical translation initiation factor, integral to initiation complex formation at the 5′-end of mRNA. PMID:15630022

Some Effects of Procedural Variations on Choice Responding in Concurrent Chains

ERIC Educational Resources Information Center

Moore, J.

2009-01-01

The present research used pigeons in a three-key operant chamber and varied procedural features pertaining to both initial and terminal links of concurrent chains. The initial links randomly alternated on the side keys during a session, while the terminal links always appeared on the center key. Both equal and unequal initial-link schedules were…

Generation of highly purified neural stem cells from human adipose-derived mesenchymal stem cells by Sox1 activation.

PubMed

Feng, Nianhua; Han, Qin; Li, Jing; Wang, Shihua; Li, Hongling; Yao, Xinglei; Zhao, Robert Chunhua

2014-03-01

Neural stem cells (NSCs) are ideal candidates in stem cell-based therapy for neurodegenerative diseases. However, it is unfeasible to get enough quantity of NSCs for clinical application. Generation of NSCs from human adipose-derived mesenchymal stem cells (hAD-MSCs) will provide a solution to this problem. Currently, the differentiation of hAD-MSCs into highly purified NSCs with biological functions is rarely reported. In our study, we established a three-step NSC-inducing protocol, in which hAD-MSCs were induced to generate NSCs with high purity after sequentially cultured in the pre-inducing medium (Step1), the N2B27 medium (Step2), and the N2B27 medium supplement with basic fibroblast growth factor and epidermal growth factor (Step3). These hAD-MSC-derived NSCs (adNSCs) can form neurospheres and highly express Sox1, Pax6, Nestin, and Vimentin; the proportion was 96.1% ± 1.3%, 96.8% ± 1.7%, 96.2% ± 1.3%, and 97.2% ± 2.5%, respectively, as detected by flow cytometry. These adNSCs can further differentiate into astrocytes, oligodendrocytes, and functional neurons, which were able to generate tetrodotoxin-sensitive sodium current. Additionally, we found that the neural differentiation of hAD-MSCs were significantly suppressed by Sox1 interference, and what's more, Step1 was a key step for the following induction, probably because it was associated with the initiation and nuclear translocation of Sox1, an important transcriptional factor for neural development. Finally, we observed that bone morphogenetic protein signal was inhibited, and Wnt/β-catenin signal was activated during inducing process, and both signals were related with Sox1 expression. In conclusion, we successfully established a three-step inducing protocol to derive NSCs from hAD-MSCs with high purity by Sox1 activation. These findings might enable to acquire enough autologous transplantable NSCs for the therapy of neurodegenerative diseases in clinic.

Short bowel mucosal morphology, proliferation and inflammation at first and repeat STEP procedures.

PubMed

Mutanen, Annika; Barrett, Meredith; Feng, Yongjia; Lohi, Jouko; Rabah, Raja; Teitelbaum, Daniel H; Pakarinen, Mikko P

2018-04-17

Although serial transverse enteroplasty (STEP) improves function of dilated short bowel, a significant proportion of patients require repeat surgery. To address underlying reasons for unsuccessful STEP, we compared small intestinal mucosal characteristics between initial and repeat STEP procedures in children with short bowel syndrome (SBS). Fifteen SBS children, who underwent 13 first and 7 repeat STEP procedures with full thickness small bowel samples at median age 1.5 years (IQR 0.7-3.7) were included. The specimens were analyzed histologically for mucosal morphology, inflammation and muscular thickness. Mucosal proliferation and apoptosis was analyzed with MIB1 and Tunel immunohistochemistry. Median small bowel length increased 42% by initial STEP and 13% by repeat STEP (p=0.05), while enteral caloric intake increased from 6% to 36% (p=0.07) during 14 (12-42) months between the procedures. Abnormal mucosal inflammation was frequently observed both at initial (69%) and additional STEP (86%, p=0.52) surgery. Villus height, crypt depth, enterocyte proliferation and apoptosis as well as muscular thickness were comparable at first and repeat STEP (p>0.05 for all). Patients, who required repeat STEP tended to be younger (p=0.057) with less apoptotic crypt cells (p=0.031) at first STEP. Absence of ileocecal valve associated with increased intraepithelial leukocyte count and reduced crypt cell proliferation index (p<0.05 for both). No adaptive mucosal hyperplasia or muscular alterations occurred between first and repeat STEP. Persistent inflammation and lacking mucosal growth may contribute to continuing bowel dysfunction in SBS children, who require repeat STEP procedure, especially after removal of the ileocecal valve. Level IV, retrospective study. Copyright © 2018 Elsevier Inc. All rights reserved.

On the Transition from Initial Leader to Stepped Leader in Negative Cloud-to-ground Lightning

NASA Astrophysics Data System (ADS)

Stolzenburg, M.; Marshall, T. C.; Karunarathne, S.; Orville, R. E.

2017-12-01

High-speed video and electric field change (E-change) data are used to describe the first 5 ms of a natural negative cloud-to-ground (CG) flash. These observations reveal differences in appearance of both the video luminosity and the E-change pulses before the leader transitions to propagating as a negative stepped leader (SL). During the initial breakdown (IB) stage, the initial leader advances intermittently forward in jumps of 78-175 m, at intervals of 100-280 μs, and in separate bursts that are bright for a few 20-μs video frames. The IB pulses accompanying these luminosity bursts have long duration, large amplitude, and a characteristic bipolar shape in nearby E-change observations. In the time between IB pulses, the initial leader is very dim or not visible during the earliest 1-2 ms of the IB stage. Over the next few milliseconds, the leader propagation transitions to an early SL phase, in which the leader tips advance 20-59 m forward at more regular intervals of 40-80 μs during relatively dim and brief steps. In the E-change data, the accompanying SL pulses have very short duration, small amplitude, and are typically unipolar. These data indicate that when the entire initial leader length behind the lower end begins to remain illuminated between bursts, the propagation mode changes from IB bursts to SL steps, and the IB stage ends. Additional differences in initial leader character are evident during the return stroke, as its luminosity speed decreases sharply upon reaching the topmost initial leader section of the channel, and that section of channel does not saturate the video intensity. Results of these analyses support a prior hypothesis that the early initial leader development occurs in the absence of a continuously hot channel, and consequently, the initial leader propagation is unlike the self-propagating advance of the later stepped leader.

Comparison of enamel bond fatigue durability of universal adhesives and two-step self-etch adhesives in self-etch mode.

PubMed

Tsujimoto, Akimasa; Barkmeier, Wayne W; Hosoya, Yumiko; Nojiri, Kie; Nagura, Yuko; Takamizawa, Toshiki; Latta, Mark A; Miyazaki, Masashi

2017-10-01

To comparatively evaluate universal adhesives and two-step self-etch adhesives for enamel bond fatigue durability in self-etch mode. Three universal adhesives (Clearfil Universal Bond; G-Premio Bond; Scotchbond Universal Adhesive) and three two-step self-etch adhesives (Clearfil SE Bond; Clearfil SE Bond 2; OptiBond XTR) were used. The initial shear bond strength and shear fatigue strength of the adhesive to enamel in self-etch mode were determined. The initial shear bond strengths of the universal adhesives to enamel in self-etch mode was significantly lower than those of two-step self-etch adhesives and initial shear bond strengths were not influenced by type of adhesive in each adhesive category. The shear fatigue strengths of universal adhesives to enamel in self-etch mode were significantly lower than that of Clearfil SE Bond and Clearfil SE Bond 2, but similar to that OptiBond XTR. Unlike two-step self-etch adhesives, the initial shear bond strength and shear fatigue strength of universal adhesives to enamel in self-etch mode was not influenced by the type of adhesive. This laboratory study showed that the enamel bond fatigue durability of universal adhesives was lower than Clearfil SE Bond and Clearfil SE Bond 2, similar to Optibond XTR, and was not influenced by type of adhesive, unlike two-step self-etch adhesives.

Harmonized patient-reported data elements in the electronic health record: supporting meaningful use by primary care action on health behaviors and key psychosocial factors

PubMed Central

Boyle, Maureen; Emmons, Karen M; Glasgow, Russell E; Hesse, Bradford W; Kaplan, Robert M; Krist, Alexander H; Moser, Richard P; Taylor, Martina V

2012-01-01

Background Electronic health records (EHR) have the potential to improve patient care through efficient access to complete patient health information. This potential may not be reached because many of the most important determinants of health outcome are rarely included. Successful health promotion and disease prevention requires patient-reported data reflecting health behaviors and psychosocial issues. Furthermore, there is a need to harmonize this information across different EHR systems. Methods To fill this gap a three-phased process was used to conceptualize, identify and recommend patient-reported data elements on health behaviors and psychosocial factors for the EHR. Expert panels (n=13) identified candidate measures (phase 1) that were reviewed and rated by a wide range of health professionals (n=93) using the grid-enabled measures wiki social media platform (phase 2). Recommendations were finalized through a town hall meeting with key stakeholders including patients, providers, researchers, policy makers, and representatives from healthcare settings (phase 3). Results Nine key elements from three areas emerged as the initial critical patient-reported elements to incorporate systematically into EHR—health behaviors (eg, exercise), psychosocial issues (eg, distress), and patient-centered factors (eg, demographics). Recommendations were also made regarding the frequency of collection ranging from a single assessment (eg, demographic characteristics), to annual assessment (eg, health behaviors), or more frequent (eg, patient goals). Conclusions There was strong stakeholder support for this initiative reflecting the perceived value of incorporating patient-reported elements into EHR. The next steps will include testing the feasibility of incorporating these elements into the EHR across diverse primary care settings. PMID:22511015

Central vein perforation during tunneled dialysis catheter insertion: principles of acute management.

PubMed

Pua, Uei

2014-10-01

Central venous perforation during dialysis catheter insertion is a potentially fatal complication. Prompt recognition and judicious initial steps are important in optimizing the outcome. The purpose of this manuscript is to illustrate the imaging features and steps in initial management. © 2014 International Society for Hemodialysis.

Using Mixed Methods to Assess Initiatives with Broad-Based Goals

ERIC Educational Resources Information Center

Inkelas, Karen Kurotsuchi

2017-01-01

This chapter describes a process for assessing programmatic initiatives with broad-ranging goals with the use of a mixed-methods design. Using an example of a day-long teaching development conference, this chapter provides practitioners step-by-step guidance on how to implement this assessment process.

Automatic initial and final segmentation in cleft palate speech of Mandarin speakers

PubMed Central

Liu, Yin; Yin, Heng; Zhang, Junpeng; Zhang, Jing; Zhang, Jiang

2017-01-01

The speech unit segmentation is an important pre-processing step in the analysis of cleft palate speech. In Mandarin, one syllable is composed of two parts: initial and final. In cleft palate speech, the resonance disorders occur at the finals and the voiced initials, while the articulation disorders occur at the unvoiced initials. Thus, the initials and finals are the minimum speech units, which could reflect the characteristics of cleft palate speech disorders. In this work, an automatic initial/final segmentation method is proposed. It is an important preprocessing step in cleft palate speech signal processing. The tested cleft palate speech utterances are collected from the Cleft Palate Speech Treatment Center in the Hospital of Stomatology, Sichuan University, which has the largest cleft palate patients in China. The cleft palate speech data includes 824 speech segments, and the control samples contain 228 speech segments. The syllables are extracted from the speech utterances firstly. The proposed syllable extraction method avoids the training stage, and achieves a good performance for both voiced and unvoiced speech. Then, the syllables are classified into with “quasi-unvoiced” or with “quasi-voiced” initials. Respective initial/final segmentation methods are proposed to these two types of syllables. Moreover, a two-step segmentation method is proposed. The rough locations of syllable and initial/final boundaries are refined in the second segmentation step, in order to improve the robustness of segmentation accuracy. The experiments show that the initial/final segmentation accuracies for syllables with quasi-unvoiced initials are higher than quasi-voiced initials. For the cleft palate speech, the mean time error is 4.4ms for syllables with quasi-unvoiced initials, and 25.7ms for syllables with quasi-voiced initials, and the correct segmentation accuracy P30 for all the syllables is 91.69%. For the control samples, P30 for all the syllables is 91.24%. PMID:28926572

Automatic initial and final segmentation in cleft palate speech of Mandarin speakers.

PubMed

He, Ling; Liu, Yin; Yin, Heng; Zhang, Junpeng; Zhang, Jing; Zhang, Jiang

2017-01-01

The speech unit segmentation is an important pre-processing step in the analysis of cleft palate speech. In Mandarin, one syllable is composed of two parts: initial and final. In cleft palate speech, the resonance disorders occur at the finals and the voiced initials, while the articulation disorders occur at the unvoiced initials. Thus, the initials and finals are the minimum speech units, which could reflect the characteristics of cleft palate speech disorders. In this work, an automatic initial/final segmentation method is proposed. It is an important preprocessing step in cleft palate speech signal processing. The tested cleft palate speech utterances are collected from the Cleft Palate Speech Treatment Center in the Hospital of Stomatology, Sichuan University, which has the largest cleft palate patients in China. The cleft palate speech data includes 824 speech segments, and the control samples contain 228 speech segments. The syllables are extracted from the speech utterances firstly. The proposed syllable extraction method avoids the training stage, and achieves a good performance for both voiced and unvoiced speech. Then, the syllables are classified into with "quasi-unvoiced" or with "quasi-voiced" initials. Respective initial/final segmentation methods are proposed to these two types of syllables. Moreover, a two-step segmentation method is proposed. The rough locations of syllable and initial/final boundaries are refined in the second segmentation step, in order to improve the robustness of segmentation accuracy. The experiments show that the initial/final segmentation accuracies for syllables with quasi-unvoiced initials are higher than quasi-voiced initials. For the cleft palate speech, the mean time error is 4.4ms for syllables with quasi-unvoiced initials, and 25.7ms for syllables with quasi-voiced initials, and the correct segmentation accuracy P30 for all the syllables is 91.69%. For the control samples, P30 for all the syllables is 91.24%.

Stereoselective Total Synthesis of (±)-5- epi-Cyanthiwigin I via an Intramolecular Pauson-Khand Reaction as the Key Step.

PubMed

Chang, Yuanyuan; Shi, Linlin; Huang, Jun; Shi, Lili; Zhang, Zichun; Hao, Hong-Dong; Gong, Jianxian; Yang, Zhen

2018-05-09

A convenient approach to the construction of the 5-6-7 tricarbocyclic fused core structure of cyanthiwigins via a Co-mediated Pauson-Khand reaction as a key step has been developed. The cyathane core intermediate obtained by this strategy was used in the concise synthesis of (±)-5- epi-cyanthiwigin I. The developed chemistry paves the way for the total synthesis of structurally diverse cyanthiwigins.

Step-Initiation Deficits in Children with Faulty Posture Diagnosed with Neurodevelopmental Disorders during Infancy.

PubMed

Stania, Magdalena; Sarat-Spek, Alina; Blacha, Teresa; Kazek, Beata; Słomka, Kajetan J; Emich-Widera, Ewa; Juras, Grzegorz

2017-01-01

Early detection of movement deficits during step initiation will facilitate the selection of the optimal physiotherapy management strategy. The main aim of the study was to assess potential differences in step initiation between 5- and 6-year-old children with faulty posture who had been diagnosed with neurodevelopmental disorders during infancy and healthy children. The experimental group consisted of 19 children aged 5-6 years with faulty posture, who had been diagnosed with neurodevelopmental disorders during infancy and were given physiotherapy in the first year of their lives. The control group comprised 19 nursery school children aged 5-6 years with no postural defects, no history of postural control or movement deficits, and no physiotherapy interventions in the first year of their lives. Step initiation was performed on force platforms under various conditions, i.e., with and without an obstacle, stepping up onto a platform placed at a higher level, stepping down onto a platform placed on a lower level. The recording of center of foot pressure (COP) displacements was divided into three phases: phase 1 (P1)-quiet standing before step initiation, phase 2 (P2)-transit, phase 3 (P3)-quiet standing until measurement completion. The Tukey post hoc test showed that the means of sway range (raCOP) and mean velocity (vCOP) in sagittal ( AP ) plane for phase 1 and vCOP in frontal ( ML ) plane for phase 3 registered in the step-up trial were significantly higher ( p  < 0.05) in children with faulty posture compared to children with typical development. P1vCOP ML , P3vCOP AP , P3raCOP ML , and P3vCOP ML of the step-down trial were also significantly higher in children with faulty posture ( p  < 0.05). Inclusion of functional movement exercises (stair-walking tasks) in physiotherapy interventions for children with postural defects seems well justified.The trial was registered in the Australian and New Zealand Clinical Trials Registry (no. ACTRN12617001068358).

Factors associated with high levels of physical activity among adults with intellectual disability.

PubMed

Temple, Viviene A

2009-03-01

The aim was to identify factors associated with physical activity participation among active (i.e. more than or equal to 10,000 steps per day) individuals with intellectual disability. Staff at day program and supported employment organizations were asked to identify individuals they believed were physically active. To verify participants were active, 7-day pedometer data were collected. Using these data, 13 participants met the inclusion criterion of 10,000 steps per day from 37 individuals identified by staff. Participants (n=13) ranged in age from 18 to 46 years (mean=34, SD= 8) and seven were male. In-depth semistructured interviews were conducted to explore the environmental and social supports for these high levels of physical activity. Three major themes were identified from content and thematic analyses. Key individuals and organizations were important in fostering initial interests and the development of skills. Coaches, staff and parents were important in 'showing them how.' For example, how to vacuum or stack produce, how to bowl, how to use weight training equipment or helping to plan a safe walking route. Motivation for initial and ongoing participation was associated with friendship and social connection. Practical support was needed for continued participation. In particular, transportation and affordable activities were very important. Fostering practical skills, supporting the social aspects of physical activity and keeping activities low cost are important enabling and reinforcing factors for physical activity among active persons with intellectual disability.

Acute coronary syndromes: is there a place for a real pre-hospital treatment for patients "en route" to the coronary intensive care unit?

PubMed

Assez, Nathalie; Smith, Grégoire; Adriansen, Christophe; Aboukais, Wissam; Wiel, Eric; Goldstein, Patrick

2012-08-01

Acute initial management of patients with acute coronary syndrome (ACS) is based on a precise clinical and electrocardiographic diagnosis. Initial risk stratification in the pre-hospital phase is the key step. The last step, adequate patient routing, is decided based on emergency level and reperfusion strategies, considered right from the pre-hospital phase. The management of a patient with an ACS requires close collaboration between emergency physicians and cardiologists, according to simplified protocols for easier access to catheterisation. The next challenges for the pre-hospital management of ACS are based on: - precise knowledge of new antiplatelet and anticoagulant drugs by the emergency physicians, in order to adjust their prescriptions to the patient profile; - developing co-operation between hospitals, according to regional specificities (geographic considerations and distribution of PCI centres) in order to reduce access time to catheterisation rooms; - organising the healthcare network, where the SAMU has an essential role in coordinating the different medical actors; - regular analysis of the evolution of our professional practices, considering, e.g., the guidelines of the "HAS" (French official healthcare guidelines institute);- integrating pre-hospital medicine in health prevention programmes; - improving our understanding of the population's presentations of coronary artery disease, in order to encourage the patients and their families to call the EMS as soon as possible. The challenge of the emergency physician is to adapt the strategies to the patient's needs.

COLLABORATIVE NEGOTIATIONS A SUCCESSFUL APPROACH FOR NEGOTIATING COMPLIANCE MILESTONES FOR THE TRANSITION OF THE PLUTONIUM FINISHING PLANT (PFP), HANFORD NUCLEAR RESERVATION, AND HANFORD, WASHINGTON

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

Hebdon, J.; Yerxa, J.; Romine, L.

The Hanford Nuclear Reservation is a former U. S. Department of Energy Defense Production Site. The site is currently listed on the National Priorities List of the Comprehensive Environmental Response Compensation and Liability Act of 1980 (CERCLA) and is undergoing cleanup and environmental restoration. The PFP is a former Plutonium metal production facility. The operating mission of the PFP ended with a DOE Headquarters shutdown letter in October of 1996. Generally, the receipt of a shutdown letter initiates the start of Transition (as the first step of Decommissioning) of a facility. The Hanford site is subject to the Hanford Federalmore » Facilities Compliance Act and Consent Order (HFFCCO), an order on consent signed by the DOE, the U. S. Environmental Protection Agency, (EPA) and the Washington Department of Ecology (WDOE). Under the HFFCCO, negotiations for transition milestones begin within six months after the issuance of a shutdown order. In the case of the PFP, the Nuclear Materials disposition and stabilization activities, a DOE responsibility, were necessary as precursor activities to Transition. This situation precipitated a crisis in the negotiations between the agencies, and formal negotiations initiated in 1997 ended in failure. The negotiations reached impasse on several key regulatory and operational issues. The 1997 negotiation was characterized by a strongly positional style. DOE and the regulatory personnel took hard lines early in the negotiations and were unable to move to resolution of key issues after a year and a half. This resulted in unhappy stakeholders, poor publicity and work delays as well as wounded relationships between DOE and the regulatory community. In the 2000-2001 PFP negotiations, a completely different approach was suggested and eventually initiated: Collaborative Negotiations. The collaborative negotiation style resulted in agreement between the agencies on all key issues within 6 months of initiation. All parties were very pleased with the results and all parties were relieved that protracted negotiations sessions were not needed with the new style of working together collaboratively to serve each other's interests. The characteristics of collaborative negotiations included building trust, emphasizing equality of team members, problem solving by the entire team, relying on individual communications and self-management skills. The team found that trust building sessions were key to successfully working through issues. Relationship differences were too often ignored in the past negotiations and were recognized and worked through in the collaborative process.« less

Obesity services planning framework for interprofessional primary care organizations.

PubMed

Brauer, Paula; Royall, Dawna; Dwyer, John; Edwards, A Michelle; Hussey, Tracy; Kates, Nick; Smith, Heidi; Kirkconnell, Ross

2017-03-01

Aim We report on a formative project to develop an organization-level planning framework for obesity prevention and management services. It is common when developing new services to first develop a logic model outlining expected outcomes and key processes. This can be onerous for single primary care organizations, especially for complex conditions like obesity. The initial draft was developed by the research team, based on results from provider and patient focus groups in one large Family Health Team (FHT) in Ontario. This draft was reviewed and activities prioritized by 20 FHTs using a moderated electronic consensus process. A national panel then reviewed the draft. Findings Providers identified five main target groups: pregnancy to 2, 3-12, 13-18, 18+ years at health risk, and 18+ with complex care needs. Desired outcomes were identified and activities were prioritized under categories: raising awareness (eg, providing information and resources on weight-health), identification and initial management (eg, wellness care), follow-up management (eg, group programs), expanded services (eg, availability of team services), and practice initiatives (eg, interprofessional education). Overall, there was strong support for raising awareness by providing information on the weight-health connection and on community services. There was also strong support for growth assessment in pediatric care. In adults, there was strong support for wellness care/health check visits and episodic care to identify people for interventions, for group programs, and for additional provider education. Joint development by different teams proved useful for consensus on outcomes and for ensuring relevancy across practices. While priorities will vary depending on local context, the basic descriptions of care processes were endorsed by reviewers. Key next steps are to trial the use of the framework and for further implementation studies to find optimally effective approaches for obesity prevention and management across the lifespan.

The Baby Friendly Hospital Initiative and the ten steps for successful breastfeeding. a critical review of the literature.

PubMed

Gomez-Pomar, Enrique; Blubaugh, Robert

2018-02-07

There is no doubt regarding the multiple benefits of breastfeeding for infants and society in general. Therefore, the World Health Organization (WHO) in a conjoint effort with United Nations International Children's Emergency Fund (UNICEF) developed the "Ten Steps to Successful Breastfeeding" in 1992, which became the backbone of the Baby Friendly Hospital Initiative (BFHI). Following this development, many hospitals and countries intensified their position towards creating a "breastfeeding oriented" practice. Over the past two decades, the interest increased in the BFHI and the Ten Steps. However, alongside the implementation of the initiative, extensive research continues to evaluate the benefits and dangers of the suggested practices. Hence, it is our intention to make a critical evaluation of the current BFHI and the Ten Steps recommendations in consideration of the importance of providing an evidence-based breastfeeding supported environment for our mothers and infants.

Picosecond laser micro/nano surface texturing of nickel for superhydrophobicity

NASA Astrophysics Data System (ADS)

Wang, X. C.; Wang, B.; Xie, H.; Zheng, H. Y.; Lam, Y. C.

2018-03-01

A single step direct picosecond laser texturing process was demonstrated to be able to obtain a superhydrophobic surface on a nickel substrate, a key material for mold fabrication in the manufacture of various devices, including polymeric microfluidic devices. A two-scale hierarchical surface structure of regular 2D array micro-bumps with nano-ripples was produced on a nickel surface. The laser textured surface initially showed superhydrophilicity with almost complete wetting of the structured surface just after laser treatment, then quickly changed to nearly superhydrophobic with a water contact angle (WCA) of 140° in less than 1 d, and finally became superhydrophobic with a WCA of more than 150° and a contact angle hysteresis (CAH) of less than 5°. The mechanism involved in the process is discussed in terms of surface morphology and surface chemistry. The ultra-fast laser induced NiO catalytic effect was thought to play a key role in modifying the surface chemistry so as to lower the surface energy. The developed process has the potential to improve the performance of nickel mold in the fabrication of microfluidic devices.

Origins of Highly Stable Al-evaporated Solution-processed ZnO Thin Film Transistors: Insights from Low Frequency and Random Telegraph Signal Noise

NASA Astrophysics Data System (ADS)

Kim, Joo Hyung; Kang, Tae Sung; Yang, Jung Yup; Hong, Jin Pyo

2015-11-01

One long-standing goal in the emerging field of flexible and transparent electronic devices is to meet the demand of key markets, such as enhanced output performance for metal oxide semiconductor thin film transistors (TFTs) prepared by a solution process. While solution-based fabrication techniques are cost-effective and ensure large-area coverage at low temperature, their utilization has the disadvantage of introducing large trap states into TFTs. Such states, the formation of which is induced by intrinsic defects initially produced during preparation, have a significant impact on electrical performance. Therefore, the ability to enhance the electrical characteristics of solution-processed TFTs, along with attaining a firm understanding of their physical nature, remains a key step towards extending their use. In this study, measurements of low-frequency noise and random telegraph signal noise are employed as generic alternative tools to examine the origins of enhanced output performance for solution-processed ZnO TFTs through the control of defect sites by Al evaporation.

Secure Communications

NASA Astrophysics Data System (ADS)

Bellac, Michel Le

2014-11-01

The first practical application of quantum physics examined in this book is quantum cryptography. Quantum cryptography is a relatively recent invention (it dates back from the mid 1980s) but I chose it because it allows me to illustrate the fundamental principles with a minimum number of intermediate steps. I shall begin with a short summary of classical cryptography, reviewing briefly the two systems which are currently used today: the secret key system and the public key system. Quantum cryptography is not a new method for dissimulating the meaning of a message, but it allows one to be certain that no spy has accessed it. There exist many quantum cryptography protocols and various experimental devices have been proposed for implementing them. The simplest device is based on polarization, a concept which will be introduced first in the case of of light polarization, and then in that of photon polarization. The use of photon polarization gives the simplest implementation of the protocol proposed in 1984 by Bennett and Brassard, which is known by the acronym formed with their initials, the BB84 protocol.

Lateral step initiation behavior in older adults.

PubMed

Sparto, Patrick J; Jennings, J Richard; Furman, Joseph M; Redfern, Mark S

2014-02-01

Older adults have varied postural responses during induced and voluntary lateral stepping. The purpose of the research was to quantify the occurrence of different stepping strategies during lateral step initiation in older adults and to relate the stepping responses to retrospective history of falls. Seventy community-ambulating older adults (mean age 76 y, range 70-94 y) performed voluntary lateral steps as quickly as possible to the right or left in response to a visual cue, in a blocked design. Vertical ground reaction forces were measured using a forceplate, and the number and latency of postural adjustments were quantified. Subjects were assigned to groups based on their stepping strategy. The frequency of trials with one or two postural adjustments was compared with data from 20 younger adults (mean age 38 y, range 21-58 y). Logistic regression was used to relate presence of a fall in the previous year with the number and latency of postural adjustments. In comparison with younger adults, who almost always demonstrated one postural adjustment when stepping laterally, older adults constituted a continuous distribution in the percentage of step trials made with one postural adjustment (from 0% to 100% of trials). Latencies of the initial postural adjustment and foot liftoff varied depending on the number of postural adjustments made. A history of falls was associated a larger percentage of two postural adjustments, and a longer latency of foot liftoff. In conclusion, the number and latency of postural adjustments made during voluntary lateral stepping provides additional evidence that lateral control of posture may be a critical indicator of aging. Copyright © 2013 Elsevier B.V. All rights reserved.

Lateral step initiation behavior in older adults

PubMed Central

Sparto, Patrick J; Jennings, J Richard; Furman, Joseph M; Redfern, Mark S

2013-01-01

Older adults have varied postural responses during induced and voluntary lateral stepping. The purpose of the research was to quantify the occurrence of different stepping strategies during lateral step initiation in older adults and to relate the stepping responses to retrospective history of falls. Seventy community-ambulating older adults (mean age 76 y, range 70–94 y) performed voluntary lateral steps as quickly as possible to the right or left in response to a visual cue, in a blocked design. Vertical ground reaction forces were measured using a forceplate, and the number and latency of postural adjustments were quantified. Subjects were assigned to groups based on their stepping strategy. The frequency of trials with one or two postural adjustments was compared with data from 20 younger adults (mean age 38 y, range 21–58 y). Logistic regression was used to relate presence of a fall in the previous year with the number and latency of postural adjustments. In comparison with younger adults, who almost always demonstrated one postural adjustment when stepping laterally, older adults constituted a continuous distribution in the percentage of step trials made with one postural adjustment (from 0% to 100% of trials). Latencies of the initial postural adjustment and foot liftoff varied depending on the number of postural adjustments made. A history of falls was associated a larger percentage of two postural adjustments, and a longer latency of foot liftoff. In conclusion, the number and latency of postural adjustments made during voluntary lateral stepping provides additional evidence that lateral control of posture may be a critical indicator of aging. PMID:24295896

Design and Processing of a Novel Chaos-Based Stepped Frequency Synthesized Wideband Radar Signal.

PubMed

Zeng, Tao; Chang, Shaoqiang; Fan, Huayu; Liu, Quanhua

2018-03-26

The linear stepped frequency and linear frequency shift keying (FSK) signal has been widely used in radar systems. However, such linear modulation signals suffer from the range-Doppler coupling that degrades radar multi-target resolution. Moreover, the fixed frequency-hopping or frequency-coded sequence can be easily predicted by the interception receiver in the electronic countermeasures (ECM) environments, which limits radar anti-jamming performance. In addition, the single FSK modulation reduces the radar low probability of intercept (LPI) performance, for it cannot achieve a large time-bandwidth product. To solve such problems, we propose a novel chaos-based stepped frequency (CSF) synthesized wideband signal in this paper. The signal introduces chaotic frequency hopping between the coherent stepped frequency pulses, and adopts a chaotic frequency shift keying (CFSK) and phase shift keying (PSK) composited coded modulation in a subpulse, called CSF-CFSK/PSK. Correspondingly, the processing method for the signal has been proposed. According to our theoretical analyses and the simulations, the proposed signal and processing method achieve better multi-target resolution and LPI performance. Furthermore, flexible modulation is able to increase the robustness against identification of the interception receiver and improve the anti-jamming performance of the radar.

A review for identification of initiating events in event tree development process on nuclear power plants

NASA Astrophysics Data System (ADS)

Riyadi, Eko H.

2014-09-01

Initiating event is defined as any event either internal or external to the nuclear power plants (NPPs) that perturbs the steady state operation of the plant, if operating, thereby initiating an abnormal event such as transient or loss of coolant accident (LOCA) within the NPPs. These initiating events trigger sequences of events that challenge plant control and safety systems whose failure could potentially lead to core damage or large early release. Selection for initiating events consists of two steps i.e. first step, definition of possible events, such as by evaluating a comprehensive engineering, and by constructing a top level logic model. Then the second step, grouping of identified initiating event's by the safety function to be performed or combinations of systems responses. Therefore, the purpose of this paper is to discuss initiating events identification in event tree development process and to reviews other probabilistic safety assessments (PSA). The identification of initiating events also involves the past operating experience, review of other PSA, failure mode and effect analysis (FMEA), feedback from system modeling, and master logic diagram (special type of fault tree). By using the method of study for the condition of the traditional US PSA categorization in detail, could be obtained the important initiating events that are categorized into LOCA, transients and external events.

Managing pregnancy of unknown location based on initial serum progesterone and serial serum hCG levels: development and validation of a two-step triage protocol.

PubMed

Van Calster, B; Bobdiwala, S; Guha, S; Van Hoorde, K; Al-Memar, M; Harvey, R; Farren, J; Kirk, E; Condous, G; Sur, S; Stalder, C; Timmerman, D; Bourne, T

2016-11-01

A uniform rationalized management protocol for pregnancies of unknown location (PUL) is lacking. We developed a two-step triage protocol to select PUL at high risk of ectopic pregnancy (EP), based on serum progesterone level at presentation (step 1) and the serum human chorionic gonadotropin (hCG) ratio, defined as the ratio of hCG at 48 h to hCG at presentation (step 2). This was a cohort study of 2753 PUL (301 EP), involving a secondary analysis of prospectively and consecutively collected PUL data from two London-based university teaching hospitals. Using a chronological split we used 1449 PUL for development and 1304 for validation. We aimed to assign PUL as low risk with high confidence (high negative predictive value (NPV)) while classifying most EP as high risk (high sensitivity). The first triage step assigned PUL as low risk using a threshold of serum progesterone at presentation. The remaining PUL were triaged using a novel logistic regression risk model based on hCG ratio and initial serum progesterone (second step), defining low risk as an estimated EP risk of < 5%. On validation, initial serum progesterone ≤ 2 nmol/L (step 1) classified 16.1% PUL as low risk. Second-step classification with the risk model selected an additional 46.0% of all PUL as low risk. Overall, the two-step protocol classified 62.1% of PUL as low risk, with an NPV of 98.6% and a sensitivity of 92.0%. When the risk model was used in isolation (i.e. without the first step), 60.5% of PUL were classified as low risk with 99.1% NPV and 94.9% sensitivity. PUL can be classified efficiently into being either high or low risk for complications using a two-step protocol involving initial progesterone and hCG levels and the hCG ratio. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Self-triggered assistive stimulus training improves step initiation in persons with Parkinson’s disease

PubMed Central

2013-01-01

Background Prior studies demonstrated that hesitation-prone persons with Parkinson’s disease (PDs) acutely improve step initiation using a novel self-triggered stimulus that enhances lateral weight shift prior to step onset. PDs showed reduced anticipatory postural adjustment (APA) durations, earlier step onsets, and faster 1st step speed immediately following stimulus exposure. Objective This study investigated the effects of long-term stimulus exposure. Methods Two groups of hesitation-prone subjects with Parkinson’s disease (PD) participated in a 6-week step-initiation training program involving one of two stimulus conditions: 1) Drop. The stance-side support surface was lowered quickly (1.5 cm); 2) Vibration. A short vibration (100 ms) was applied beneath the stance-side support surface. Stimuli were self-triggered by a 5% reduction in vertical force under the stance foot during the APA. Testing was at baseline, immediately post-training, and 6 weeks post-training. Measurements included timing and magnitude of ground reaction forces, and step speed and length. Results Both groups improved their APA force modulation after training. Contrary to previous results, neither group showed reduced APA durations or earlier step onset times. The vibration group showed 55% increase in step speed and a 39% increase in step length which were retained 6 weeks post-training. The drop group showed no stepping-performance improvements. Conclusions The acute sensitivity to the quickness-enhancing effects of stimulus exposure demonstrated in previous studies was supplanted by improved force modulation following prolonged stimulus exposure. The results suggest a potential approach to reduce the severity of start hesitation in PDs, but further study is needed to understand the relationship between short- and long-term effects of stimulus exposure. PMID:23363975

Implementing Immediate Postpartum Long-Acting Reversible Contraception Programs.

PubMed

Hofler, Lisa G; Cordes, Sarah; Cwiak, Carrie A; Goedken, Peggy; Jamieson, Denise J; Kottke, Melissa

2017-01-01

To understand the most important steps required to implement immediate postpartum long-acting reversible contraception (LARC) programs in different Georgia hospitals and the barriers to implementing such a program. This was a qualitative study. We interviewed 32 key personnel from 10 Georgia hospitals working to establish immediate postpartum LARC programs. Data were analyzed using directed qualitative content analysis principles. We used the Stages of Implementation to organize participant-identified key steps for immediate postpartum LARC into an implementation guide. We compared this guide to hospitals' implementation experiences. At the completion of the study, LARC was available for immediate postpartum placement at 7 of 10 study hospitals. Participants identified common themes for the implementation experience: team member identification and ongoing communication, payer preparedness challenges, interdependent department-specific tasks, and piloting with continuing improvements. Participants expressed a need for anticipatory guidance throughout the process. Key first steps to immediate postpartum LARC program implementation were identifying project champions, creating an implementation team that included all relevant departments, obtaining financial reassurance, and ensuring hospital administration awareness of the project. Potential barriers included lack of knowledge about immediate postpartum LARC, financial concerns, and competing clinical and administrative priorities. Hospitals that were successful at implementing immediate postpartum LARC programs did so by prioritizing clear communication and multidisciplinary teamwork. Although the implementation guide reflects a comprehensive assessment of the steps to implementing immediate postpartum LARC programs, not all hospitals required every step to succeed. Hospital teams report that implementing immediate postpartum LARC programs involves multiple departments and a number of important steps to consider. A stage-based approach to implementation, and a standardized guide detailing these steps, may provide the necessary structure for the complex process of implementing immediate postpartum LARC programs in the hospital setting.

Characteristics and adaptive strategies linked with falls in stroke survivors from analysis of laboratory-induced falls

PubMed Central

Honeycutt, Claire F.; Nevisipour, Masood; Grabiner, Mark D.

2016-01-01

Falls are the most common and expensive medical complication in stroke survivors. There is remarkably little information about what factors lead to a fall in stroke survivors. With few exceptions, the falls literature in stroke has focused on relating metrics of static balance and impairment to fall outcomes in the acute care setting or in community. While informative, these studies provide little information about what specific impairments in a stroke-survivor’s response to dynamic balance challenges lead to a fall. We identified the key kinematic characteristics of stroke survivors’ stepping responses following a balance disturbance that are associated with a fall following dynamic balance challenges. Stroke survivors were exposed to posteriorly-directed translations of a treadmill belt that elicited a stepping response. Kinematics were compared between successful and failed recovery attempts (i.e. a fall). We found that the ability to arrest and reverse trunk flexion and the ability to perform an appropriate initial compensatory step were the most critical response contributors to a successful recovery. We also identified 2 compensatory strategies utilized by stroke survivors to avoid a fall. Despite significant post-stroke functional impairments, the biomechanical causes of trip-related falls by stroke survivors appear to be similar to those of unimpaired older adults and lower extremity amputees. However, compensatory strategies (pivot, hopping) were observed. PMID:27614614

Biomechanics of Step Initiation After Balance Recovery With Implications for Humanoid Robot Locomotion.

PubMed

Miller Buffinton, Christine; Buffinton, Elise M; Bieryla, Kathleen A; Pratt, Jerry E

2016-03-01

Balance-recovery stepping is often necessary for both a human and humanoid robot to avoid a fall by taking a single step or multiple steps after an external perturbation. The determination of where to step to come to a complete stop has been studied, but little is known about the strategy for initiation of forward motion from the static position following such a step. The goal of this study was to examine the human strategy for stepping by moving the back foot forward from a static, double-support position, comparing parameters from normal step length (SL) to those from increasing SLs to the point of step failure, to provide inspiration for a humanoid control strategy. Healthy young adults instrumented with joint reflective markers executed a prescribed-length step from rest while marker positions and ground reaction forces (GRFs) were measured. The participants were scaled to the Gait2354 model in opensim software to calculate body kinematic and joint kinetic parameters, with further post-processing in matlab. With increasing SL, participants reduced both static and push-off back-foot GRF. Body center of mass (CoM) lowered and moved forward, with additional lowering at the longer steps, and followed a path centered within the initial base of support (BoS). Step execution was successful if participants gained enough forward momentum at toe-off to move the instantaneous capture point (ICP) to within the BoS defined by the final position of both feet on the front force plate. All lower extremity joint torques increased with SL except ankle joint. Front knee work increased dramatically with SL, accompanied by decrease in back-ankle work. As SL increased, the human strategy changed, with participants shifting their CoM forward and downward before toe-off, thus gaining forward momentum, while using less propulsive work from the back ankle and engaging the front knee to straighten the body. The results have significance for human motion, suggesting the upper limit of the SL that can be completed with back-ankle push-off before additional knee flexion and torque is needed. For biped control, the results support stability based on capture-point dynamics and suggest strategy for center-of-mass trajectory and distribution of ground force reactions that can be compared with robot controllers for initiation of gait after recovery steps.

Biocatalytic conversion of methane to methanol as a key step for development of methane-based biorefineries.

PubMed

Hwang, In Yeub; Lee, Seung Hwan; Choi, Yoo Seong; Park, Si Jae; Na, Jeong Geol; Chang, In Seop; Kim, Choongik; Kim, Hyun Cheol; Kim, Yong Hwan; Lee, Jin Won; Lee, Eun Yeol

2014-12-28

Methane is considered as a next-generation carbon feedstock owing to the vast reserves of natural and shale gas. Methane can be converted to methanol by various methods, which in turn can be used as a starting chemical for the production of value-added chemicals using existing chemical conversion processes. Methane monooxygenase is the key enzyme that catalyzes the addition of oxygen to methane. Methanotrophic bacteria can transform methane to methanol by inhibiting methanol dehydrogenase. In this paper, we review the recent progress made on the biocatalytic conversion of methane to methanol as a key step for methane-based refinery systems and discuss future prospects for this technology.

Inverting the planning gradient: adjustment of grasps to late segments of multi-step object manipulations.

PubMed

Mathew, Hanna; Kunde, Wilfried; Herbort, Oliver

2017-05-01

When someone grasps an object, the grasp depends on the intended object manipulation and usually facilitates it. If several object manipulation steps are planned, the first step has been reported to primarily determine the grasp selection. We address whether the grasp can be aligned to the second step, if the second step's requirements exceed those of the first step. Participants grasped and rotated a dial first by a small extent and then by various extents in the opposite direction, without releasing the dial. On average, when the requirements of the first and the second step were similar, participants mostly aligned the grasp to the first step. When the requirements of the second step were considerably higher, participants aligned the grasp to the second step, even though the first step still had a considerable impact. Participants employed two different strategies. One subgroup initially aligned the grasp to the first step and then ceased adjusting the grasp to either step. Another group also initially aligned the grasp to the first step and then switched to aligning it primarily to the second step. The data suggest that participants are more likely to switch to the latter strategy when they experienced more awkward arm postures. In summary, grasp selections for multi-step object manipulations can be aligned to the second object manipulation step, if the requirements of this step clearly exceed those of the first step and if participants have some experience with the task.

Key Elements of Observing Practice: A Data Wise DVD and Facilitator's Guide

ERIC Educational Resources Information Center

Boudett, Kathryn Parker; City, Elizabeth A.; Russell, Marcia K.

2010-01-01

Based on the bestselling book "Data Wise: A Step-by-Step Guide to Using Assessment Results to Improve Teaching and Learning", and its companion volume, "Data Wise in Action", this DVD and Facilitator's Guide offer insight into one of the most challenging steps in capturing data about school performance: observing and analyzing instructional…

Key Steps in the Special Review Process

EPA Pesticide Factsheets

EPA uses this process when it has reason to believe that the use of a pesticide may result in unreasonable adverse effects on people or the environment. Steps include comprehensive risk and benefit analyses and multiple Position Documents.

[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.

Compact cancer biomarkers discovery using a swarm intelligence feature selection algorithm.

PubMed

Martinez, Emmanuel; Alvarez, Mario Moises; Trevino, Victor

2010-08-01

Biomarker discovery is a typical application from functional genomics. Due to the large number of genes studied simultaneously in microarray data, feature selection is a key step. Swarm intelligence has emerged as a solution for the feature selection problem. However, swarm intelligence settings for feature selection fail to select small features subsets. We have proposed a swarm intelligence feature selection algorithm based on the initialization and update of only a subset of particles in the swarm. In this study, we tested our algorithm in 11 microarray datasets for brain, leukemia, lung, prostate, and others. We show that the proposed swarm intelligence algorithm successfully increase the classification accuracy and decrease the number of selected features compared to other swarm intelligence methods. Copyright © 2010 Elsevier Ltd. All rights reserved.

Total synthesis and structural revision of the marine macrolide neopeltolide.

PubMed

Custar, Daniel W; Zabawa, Thomas P; Scheidt, Karl A

2008-01-23

The total synthesis and structural revision of the marine natural product neopeltolide is reported. The key bond-forming step involves a Lewis acid-catalyzed intramolecular cyclization to install the tetrahydropyran ring and the macrocycle simultaneously. This type of cyclization is the first of its kind and assembles the carbon backbone of the natural product efficiently. The synthesis of the reported structure revealed differences in the data between the natural and synthetic material. After significant investigation, the diastereomeric molecule with the C11 and C13 configurations inverted was synthesized using the initial route. This compound matches the data reported for neopeltolide (1H, 13C, HRMS, IR, NOESY, [alpha]), thereby establishing the correct overall structure for this potent macrolide natural product, including the relative and absolute stereochemistry.

Controlled chain polymerisation and chemical soldering for single-molecule electronics.

PubMed

Okawa, Yuji; Akai-Kasaya, Megumi; Kuwahara, Yuji; Mandal, Swapan K; Aono, Masakazu

2012-05-21

Single functional molecules offer great potential for the development of novel nanoelectronic devices with capabilities beyond today's silicon-based devices. To realise single-molecule electronics, the development of a viable method for connecting functional molecules to each other using single conductive polymer chains is required. The method of initiating chain polymerisation using the tip of a scanning tunnelling microscope (STM) is very useful for fabricating single conductive polymer chains at designated positions and thereby wiring single molecules. In this feature article, developments in the controlled chain polymerisation of diacetylene compounds and the properties of polydiacetylene chains are summarised. Recent studies of "chemical soldering", a technique enabling the covalent connection of single polydiacetylene chains to single functional molecules, are also introduced. This represents a key step in advancing the development of single-molecule electronics.

Wave dynamics in an extended macroscopic traffic flow model with periodic boundaries

NASA Astrophysics Data System (ADS)

Wang, Yu-Qing; Chu, Xing-Jian; Zhou, Chao-Fan; Yan, Bo-Wen; Jia, Bin; Fang, Chen-Hao

2018-06-01

Motivated by the previous traffic flow model considering the real-time traffic state, a modified macroscopic traffic flow model is established. The periodic boundary condition is applied to the car-following model. Besides, the traffic state factor R is defined in order to correct the real traffic conditions in a more reasonable way. It is a key step that we introduce the relaxation time as a density-dependent function and provide corresponding evolvement of traffic flow. Three different typical initial densities, namely the high density, the medium one and the low one, are intensively investigated. It can be found that the hysteresis loop exists in the proposed periodic-boundary system. Furthermore, the linear and nonlinear stability analyses are performed in order to test the robustness of the system.

29 CFR 1956.52 - Completed developmental steps and certification.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 9 2010-07-01 2010-07-01 false Completed developmental steps and certification. 1956.52... PLANS New York § 1956.52 Completed developmental steps and certification. (a) In accordance with 29 CFR..., 2006 as having successfully completed all developmental steps specified in the plan as initially...

40 CFR 35.2203 - Step 7 projects.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Step 7 projects. 35.2203 Section 35... STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works § 35.2203 Step 7 projects. (a) Prior to initiating action to acquire real property, a Step 7 grantee shall submit for Regional...

Implementation of the Short-Term Ensemble Prediction System (STEPS) in Belgium and verification of case studies

NASA Astrophysics Data System (ADS)

Foresti, Loris; Reyniers, Maarten; Delobbe, Laurent

2014-05-01

The Short-Term Ensemble Prediction System (STEPS) is a probabilistic precipitation nowcasting scheme developed at the Australian Bureau of Meteorology in collaboration with the UK Met Office. In order to account for the multiscaling nature of rainfall structures, the radar field is decomposed into an 8 levels multiplicative cascade using a Fast Fourier Transform. The cascade is advected using the velocity field estimated with optical flow and evolves stochastically according to a hierarchy of auto-regressive processes. This allows reproducing the empirical observation that the rate of temporal evolution of the small scales is faster than the large scales. The uncertainty in radar rainfall measurement and the unknown future development of the velocity field are also considered by stochastic modelling in order to reflect their typical spatial and temporal variability. Recently, a 4 years national research program has been initiated by the University of Leuven, the Royal Meteorological Institute (RMI) of Belgium and 3 other partners: PLURISK ("forecasting and management of extreme rainfall induced risks in the urban environment"). The project deals with the nowcasting of rainfall and subsequent urban inundations, as well as socio-economic risk quantification, communication, warning and prevention. At the urban scale it is widely recognized that the uncertainty of hydrological and hydraulic models is largely driven by the input rainfall estimation and forecast uncertainty. In support to the PLURISK project the RMI aims at integrating STEPS in the current operational deterministic precipitation nowcasting system INCA-BE (Integrated Nowcasting through Comprehensive Analysis). This contribution will illustrate examples of STEPS ensemble and probabilistic nowcasts for a few selected case studies of stratiform and convective rain in Belgium. The paper focuses on the development of STEPS products for potential hydrological users and a preliminary verification of the nowcasts, especially to analyze the spatial distribution of forecast errors. The analysis of nowcast biases reveals the locations where the convective initiation, rainfall growth and decay processes significantly reduce the forecast accuracy, but also points out the need for improving the radar-based quantitative precipitation estimation product that is used both to generate and verify the nowcasts. The collection of fields of verification statistics is implemented using an online update strategy, which potentially enables the system to learn from forecast errors as the archive of nowcasts grows. The study of the spatial or temporal distribution of nowcast errors is a key step to convey to the users an overall estimation of the nowcast accuracy and to drive future model developments.

Interrelations between translation and general mRNA degradation in yeast

PubMed Central

Huch, Susanne; Nissan, Tracy

2014-01-01

Messenger RNA (mRNA) degradation is an important element of gene expression that can be modulated by alterations in translation, such as reductions in initiation or elongation rates. Reducing translation initiation strongly affects mRNA degradation by driving mRNA toward the assembly of a decapping complex, leading to decapping. While mRNA stability decreases as a consequence of translational inhibition, in apparent contradiction several external stresses both inhibit translation initiation and stabilize mRNA. A key difference in these processes is that stresses induce multiple responses, one of which stabilizes mRNAs at the initial and rate-limiting step of general mRNA decay. Because this increase in mRNA stability is directly induced by stress, it is independent of the translational effects of stress, which provide the cell with an opportunity to assess its response to changing environmental conditions. After assessment, the cell can store mRNAs, reinitiate their translation or, alternatively, embark on a program of enhanced mRNA decay en masse. Finally, recent results suggest that mRNA decay is not limited to non-translating messages and can occur when ribosomes are not initiating but are still elongating on mRNA. This review will discuss the models for the mechanisms of these processes and recent developments in understanding the relationship between translation and general mRNA degradation, with a focus on yeast as a model system. How to cite this article: WIREs RNA 2014, 5:747–763. doi: 10.1002/wrna.1244 PMID:24944158

Interrelations between translation and general mRNA degradation in yeast.

PubMed

Huch, Susanne; Nissan, Tracy

2014-01-01

Messenger RNA (mRNA) degradation is an important element of gene expression that can be modulated by alterations in translation, such as reductions in initiation or elongation rates. Reducing translation initiation strongly affects mRNA degradation by driving mRNA toward the assembly of a decapping complex, leading to decapping. While mRNA stability decreases as a consequence of translational inhibition, in apparent contradiction several external stresses both inhibit translation initiation and stabilize mRNA. A key difference in these processes is that stresses induce multiple responses, one of which stabilizes mRNAs at the initial and rate-limiting step of general mRNA decay. Because this increase in mRNA stability is directly induced by stress, it is independent of the translational effects of stress, which provide the cell with an opportunity to assess its response to changing environmental conditions. After assessment, the cell can store mRNAs, reinitiate their translation or, alternatively, embark on a program of enhanced mRNA decay en masse. Finally, recent results suggest that mRNA decay is not limited to non-translating messages and can occur when ribosomes are not initiating but are still elongating on mRNA. This review will discuss the models for the mechanisms of these processes and recent developments in understanding the relationship between translation and general mRNA degradation, with a focus on yeast as a model system. © 2014 The Authors. WIREs RNA published by John Wiley & Sons, Ltd.

Structural characterization of ribosome recruitment and translocation by type IV IRES.

PubMed

Murray, Jason; Savva, Christos G; Shin, Byung-Sik; Dever, Thomas E; Ramakrishnan, V; Fernández, Israel S

2016-05-09

Viral mRNA sequences with a type IV IRES are able to initiate translation without any host initiation factors. Initial recruitment of the small ribosomal subunit as well as two translocation steps before the first peptidyl transfer are essential for the initiation of translation by these mRNAs. Using electron cryomicroscopy (cryo-EM) we have structurally characterized at high resolution how the Cricket Paralysis Virus Internal Ribosomal Entry Site (CrPV-IRES) binds the small ribosomal subunit (40S) and the translocation intermediate stabilized by elongation factor 2 (eEF2). The CrPV-IRES restricts tvhe otherwise flexible 40S head to a conformation compatible with binding the large ribosomal subunit (60S). Once the 60S is recruited, the binary CrPV-IRES/80S complex oscillates between canonical and rotated states (Fernández et al., 2014; Koh et al., 2014), as seen for pre-translocation complexes with tRNAs. Elongation factor eEF2 with a GTP analog stabilizes the ribosome-IRES complex in a rotated state with an extra ~3 degrees of rotation. Key residues in domain IV of eEF2 interact with pseudoknot I (PKI) of the CrPV-IRES stabilizing it in a conformation reminiscent of a hybrid tRNA state. The structure explains how diphthamide, a eukaryotic and archaeal specific post-translational modification of a histidine residue of eEF2, is involved in translocation.

Bridging basic and clinical science with policy studies: The Partners with Transdisciplinary Tobacco Use Research Centers experience.

PubMed

Kobus, Kimberly; Mermelstein, Robin

2009-05-01

The Partners with Transdisciplinary Tobacco Use Research Centers (TTURCs) initiative was a transdisciplinary team-building program, funded by the Robert Wood Johnson Foundation, to expand the policy research capacity of the TTURCs. EXPANSION INTO POLICY RESEARCh: Policy research activities at the TTURCs fell into four broad domains: (a) health services research, (b) examination of the business case for cessation treatment and funding, (c) collaborative teams with key stakeholders, and (d) direct assessment of smoking-related policies. Examples of each domain are presented. Goals of the initiative included efforts to foster collaborative, transdisciplinary research, to bring new investigators into the field, to develop programs of policy research, to answer next-step translational questions, and to enhance awareness of policy relevance. Success at meeting each of these goals is discussed. We offer recommendations for incorporating programs of policy research into full-spectrum transdisciplinary research initiatives, including the roles of research teams, senior researchers, infrastructure, stakeholders, and communications activities. The TTURC Partners initiative represented a first-generation effort to fill the gap between scientific discovery and research translation through expansion into policy studies. While all aspects of the effort were not equally successful, the effort demonstrated that it is possible to develop successful collaborations that extend more basic and applied research into studies that examine their policy and practice implications.

Simplified Two-Time Step Method for Calculating Combustion and Emission Rates of Jet-A and Methane Fuel With and Without Water Injection

NASA Technical Reports Server (NTRS)

Molnar, Melissa; Marek, C. John

2005-01-01

A simplified kinetic scheme for Jet-A, and methane fuels with water injection was developed to be used in numerical combustion codes, such as the National Combustor Code (NCC) or even simple FORTRAN codes. The two time step method is either an initial time averaged value (step one) or an instantaneous value (step two). The switch is based on the water concentration in moles/cc of 1x10(exp -20). The results presented here results in a correlation that gives the chemical kinetic time as two separate functions. This two time step method is used as opposed to a one step time averaged method previously developed to determine the chemical kinetic time with increased accuracy. The first time averaged step is used at the initial times for smaller water concentrations. This gives the average chemical kinetic time as a function of initial overall fuel air ratio, initial water to fuel mass ratio, temperature, and pressure. The second instantaneous step, to be used with higher water concentrations, gives the chemical kinetic time as a function of instantaneous fuel and water mole concentration, pressure and temperature (T4). The simple correlations would then be compared to the turbulent mixing times to determine the limiting rates of the reaction. The NASA Glenn GLSENS kinetics code calculates the reaction rates and rate constants for each species in a kinetic scheme for finite kinetic rates. These reaction rates are used to calculate the necessary chemical kinetic times. Chemical kinetic time equations for fuel, carbon monoxide and NOx are obtained for Jet-A fuel and methane with and without water injection to water mass loadings of 2/1 water to fuel. A similar correlation was also developed using data from NASA's Chemical Equilibrium Applications (CEA) code to determine the equilibrium concentrations of carbon monoxide and nitrogen oxide as functions of overall equivalence ratio, water to fuel mass ratio, pressure and temperature (T3). The temperature of the gas entering the turbine (T4) was also correlated as a function of the initial combustor temperature (T3), equivalence ratio, water to fuel mass ratio, and pressure.

Optimizing identification and management of COPD patients – reviewing the role of the community pharmacist

PubMed Central

van Boven, Job F. M.; Maguire, Terence; Goyal, Pankaj; Altman, Pablo

2016-01-01

The aim of this paper was to propose key steps for community pharmacist integration into a patient care pathway for chronic obstructive pulmonary disease (COPD) management. A literature search was conducted to identify publications focusing on the role of the community pharmacist in identification and management of COPD. The literature search highlighted evidence supporting an important role for pharmacists at each of the four key steps in the patient care pathway for COPD management. Step 1 (primary prevention): pharmacists are ideally placed to provide information on disease awareness and risk prevention campaigns, and to encourage lifestyle interventions, including smoking cessation. Step 2 (early detection/case finding): pharmacists are often the first point of contact between the patient and the healthcare system and can therefore play an important role in the early identification of patients with COPD. Step 3 (management and ongoing support): pharmacists can assist patients by providing advice and education on dosage, inhaler technique, treatment expectations and the importance of adherence, and by supporting self‐management, including recognition and treatment of COPD exacerbations. Step 4 (review and follow‐up): pharmacists can play an important role in monitoring adherence and ongoing inhaler technique in patients with COPD. In summary, pharmacists are ideally positioned to play a vital role in all key stages of an integrated COPD patient care pathway from early disease detection to the support of management plans, including advice and counselling regarding medications, inhaler technique and treatment adherence. Areas requiring additional consideration include pharmacist training, increasing awareness of the pharmacist role, administration and reimbursement, and increasing physician–pharmacist collaboration. PMID:27510273

Advances in Cryptology - EUROCRYPT’ 97

DTIC Science & Technology

1998-05-03

public keys is about T/102. For example, one can choose T ~ 227.67 and M ~ 2 35.65. To obtain the secret session key from the determined internal state...scenario, where the objective is to reconstruct the secret key controlled LFSR initial states from the known keystream sequence, for a survey see... the secret message keys defining different initial internal states. This may open new possibilities for the secret key recovery cryptanalytic attacks

Photodamage: all signs lead to actinic keratosis and early squamous cell carcinoma.

PubMed

Wei, Jerry; Kok, Lai Fong; Byrne, Scott N; Halliday, Gary M

2015-01-01

Ultraviolet (UV) radiation is likely to drive the initiation and progression of skin cancer from actinic keratosis to squamous cell carcinoma. Signs of photodamage occur at multiple steps. UV radiation damages many cellular constituents, including lipids, proteins and DNA, all of which are likely to contribute to UV-induced skin cancer. Two biological events culminating from photodamage are mutations in the genes critical to the control of cell division, differentiation and invasion and immunosuppression. DNA photodamage, if unrepaired prior to cell division, can result in the incorporation of an incorrect nucleotide into newly synthesised DNA. Mutations in critical genes contribute to carcinogenesis. Photodamage to proteins such as those involved in DNA repair or proteins or lipids involved in cellular signalling can interfere with this repair process and contribute to mutagenesis. Mutations in key genes, including TP53, BRM, PTCH1, and HRAS, contribute to skin carcinogenesis. UV also damages immunity. Photodamage to DNA and signalling lipids as well as other molecular changes are detrimental to the key cells that regulate immunity. Photodamaged dendritic cells and altered responses by mast cells lead to the activation of T and B regulatory cells that suppress immunity to the protein products of UV-mutated genes. This stops the immune response from its protective function of destroying mutated cells, enabling the transformed cells to progress to skin cancer. UV appears to play a pivotal role at each of these steps, and therefore, signs of photodamage point to the development of skin cancer. © 2015 S. Karger AG, Basel.

A three-talk model for shared decision making: multistage consultation process

PubMed Central

Durand, Marie Anne; Song, Julia; Aarts, Johanna; Barr, Paul J; Berger, Zackary; Cochran, Nan; Frosch, Dominick; Galasiński, Dariusz; Gulbrandsen, Pål; Han, Paul K J; Härter, Martin; Kinnersley, Paul; Lloyd, Amy; Mishra, Manish; Perestelo-Perez, Lilisbeth; Scholl, Isabelle; Tomori, Kounosuke; Trevena, Lyndal; Witteman, Holly O; Van der Weijden, Trudy

2017-01-01

Objectives To revise an existing three-talk model for learning how to achieve shared decision making, and to consult with relevant stakeholders to update and obtain wider engagement. Design Multistage consultation process. Setting Key informant group, communities of interest, and survey of clinical specialties. Participants 19 key informants, 153 member responses from multiple communities of interest, and 316 responses to an online survey from medically qualified clinicians from six specialties. Results After extended consultation over three iterations, we revised the three-talk model by making changes to one talk category, adding the need to elicit patient goals, providing a clear set of tasks for each talk category, and adding suggested scripts to illustrate each step. A new three-talk model of shared decision making is proposed, based on “team talk,” “option talk,” and “decision talk,” to depict a process of collaboration and deliberation. Team talk places emphasis on the need to provide support to patients when they are made aware of choices, and to elicit their goals as a means of guiding decision making processes. Option talk refers to the task of comparing alternatives, using risk communication principles. Decision talk refers to the task of arriving at decisions that reflect the informed preferences of patients, guided by the experience and expertise of health professionals. Conclusions The revised three-talk model of shared decision making depicts conversational steps, initiated by providing support when introducing options, followed by strategies to compare and discuss trade-offs, before deliberation based on informed preferences. PMID:29109079

Foot and Ankle Kinematics During Descent From Varying Step Heights.

PubMed

Gerstle, Emily E; O'Connor, Kristian; Keenan, Kevin G; Cobb, Stephen C

2017-12-01

In the general population, one-third of incidences during step negotiation occur during the transition to level walking. Furthermore, falls during curb negotiation are a common cause of injury in older adults. Distal foot kinematics may be an important factor in determining injury risk associated with transition step negotiation. The purpose of this study was to identify foot and ankle kinematics of uninjured individuals during descent from varying step heights. A 7-segment foot model was used to quantify kinematics as participants walked on a level walkway, stepped down a single step (heights: 5 cm, 15 cm, 25 cm), and continued walking. As step height increased, landing strategy transitioned from the rearfoot to the forefoot, and the rearfoot, lateral and medial midfoot, and medial forefoot became more plantar flexed. During weight acceptance, sagittal plane range of motion of the rearfoot, lateral midfoot, and medial and lateral forefoot increased as step height increased. The changes in landing strategy and distal foot function suggest a less stable ankle position at initial contact and increased demand on the distal foot at initial contact and through the weight acceptance phase of transition step negotiation as step height increases.

Data specifications for INSPIRE

NASA Astrophysics Data System (ADS)

Portele, Clemens; Woolf, Andrew; Cox, Simon

2010-05-01

In Europe a major recent development has been the entering in force of the INSPIRE Directive in May 2007, establishing an infrastructure for spatial information in Europe to support Community environmental policies, and policies or activities which may have an impact on the environment. INSPIRE is based on the infrastructures for spatial information established and operated by the 27 Member States of the European Union. The Directive addresses 34 spatial data themes needed for environmental applications, with key components specified through technical implementing rules. This makes INSPIRE a unique example of a legislative "regional" approach. One of the requirements of the INSPIRE Directive is to make existing spatial data sets with relevance for one of the spatial data themes available in an interoperable way, i.e. where the spatial data from different sources in Europe can be combined to a coherent result. Since INSPIRE covers a wide range of spatial data themes, the first step has been the development of a modelling framework that provides a common foundation for all themes. This framework is largely based on the ISO 19100 series of standards. The use of common generic spatial modelling concepts across all themes is an important enabler for interoperability. As a second step, data specifications for the first set of themes has been developed based on the modelling framework. The themes include addresses, transport networks, protected sites, hydrography, administrative areas and others. The data specifications were developed by selected experts nominated by stakeholders from all over Europe. For each theme a working group was established in early 2008 working on their specific theme and collaborating with the other working groups on cross-theme issues. After a public review of the draft specifications starting in December 2008, an open testing process and thorough comment resolution process, the draft technical implementing rules for these themes have been approved by the INSPIRE Committee. After they enter into force they become part of the legal framework and European Member States have to implement these rules. The next step is the development of the remaining 25 spatial data themes, which include many themes of interest for the Earth Sciences including geology, meteorological and oceanographic geographic features, atmospheric conditions, habitats and biotopes, species distribution, environmental monitoring facilities, and land cover to name a few. The process will follow in general the same steps as for the first themes and the working groups are expected to start their work in March/April 2010. The first draft specifications for public comment are expected at the end of 2010 and the work is scheduled to be completed in 2012. At the same time, other initiatives like GMES (Global Monitoring for Environment and Security) and GEOSS (Global Earth Observation System of Systems) are also dealing with spatial data from the themes covered by INSPIRE. With the EU-funded project GIGAS, a support action, a step has been made towards architectural coherence between these initiatives. Recommendations to improve the coherence of the information architectures across the initiatives have been discussed in January 2010 with stakeholders from all initiatives, the standards organisations and EU-funded research projects. Based on the general agreements achieved in these discussions, the next step will be to start working towards the implementation of these recommendations, which are in line with the approach taken by the INSPIRE data specifications.

The BeUpstanding Program™: Scaling up the Stand Up Australia Workplace Intervention for Translation into Practice

PubMed Central

Healy, Genevieve N; Goode, Ana; Schultz, Diane; Lee, Donna; Leahy, Bell; Dunstan, David W; Gilson, Nicholas D; Eakin, Elizabeth G

2016-01-01

Context and purpose Too much sitting is now recognised as a common risk factor for several health outcomes, with the workplace identified as a key setting in which to address prolonged sitting time. The Stand Up Australia intervention was designed to reduce prolonged sitting in the workplace by addressing influences at multiple-levels, including the organisation, the environment, and the individual. Intervention success has been achieved within the context of randomised controlled trials, where research staff deliver several of the key intervention components. This study describes the initial step in the multi-phase process of scaling up the Stand Up Australia intervention for workplace translation. Methods A research-government partnership was critical in funding and informing the prototype for the scaled up BeUpstanding program™. Evidence, protocols and materials from Stand Up Australia were adapted in collaboration with funding partner Workplace Health and Safety Queensland to ensure consistency and compatibility with existing government frameworks and resources. In recognition of the key role of workplace champions in facilitating workplace health promotion programs, the BeUpstanding program™ is designed to be delivered through a stand-alone, free, website-based toolkit using a ‘train the champion’ approach. Key findings and significance The BeUpstanding program™ was influenced by the increasing recognition of prolonged sitting as an emerging health issue as well as industry demand. The research-government partnership was critical in informing and resourcing the development of the scaled-up program. PMID:29546167

Employing Simulation to Evaluate Designs: The APEX Approach

NASA Technical Reports Server (NTRS)

Freed, Michael A.; Shafto, Michael G.; Remington, Roger W.; Null, Cynthia H. (Technical Monitor)

1998-01-01

The key innovations of APEX are its integrated approaches to task analysis, procedure definition, and intelligent, resource-constrained multi-tasking. This paper presents a step-by-step description of how APEX is used, from scenario development through trace analysis.

Health information technology and implementation science: partners in progress in the VHA.

PubMed

Hynes, Denise M; Whittier, Erika R; Owens, Arika

2013-03-01

The Department of Veterans Affairs (VA) Quality Enhancement Research Initiative (QUERI) has demonstrated how implementation science can enhance the quality of health care. During this time an increasing number of implementation research projects have developed or utilized health information technology (HIT) innovations to leverage the VA's electronic health record and information systems. To describe the HIT approaches used and to characterize the facilitators and barriers to progress within implementation research projects in the VA QUERI program. Nine case studies were selected from among 88 projects and represented 8 of 14 HIT categories identified. Each case study included key informants whose roles on the project were principal investigator, implementation science and informatics development. We conducted documentation analysis and semistructured in-person interviews with key informants for each of the 9 case studies. We used qualitative analysis software to identify and thematically code information and interview responses. : Thematic analyses revealed 3 domains or pathways critical to progression through the QUERI steps. These pathways addressed: (1) compliance and collaboration with information technology policies and procedures; (2) operating within organizational policies and building collaborations with end users, clinicians, and administrators; and (3) obtaining and maintaining research resources and approvals. Sustained efforts in HIT innovation and in implementation science in the Veterans Health Administration demonstrates the interdependencies of these initiatives and the critical pathways that can contribute to progress. Other health care quality improvement efforts that rely on HIT can learn from the Veterans Health Administration experience.

Translating Developmental Origins: Improving the Health of Women and Their Children Using a Sustainable Approach to Behaviour Change

PubMed Central

Barker, Mary; Baird, Janis; Tinati, Tannaze; Vogel, Christina; Strömmer, Sofia; Rose, Taylor; Begum, Rufia; Jarman, Megan; Davies, Jenny; Thompson, Sue; Taylor, Liz; Inskip, Hazel; Cooper, Cyrus; Nutbeam, Don; Lawrence, Wendy

2017-01-01

Theories of the developmental origins of health and disease imply that optimising the growth and development of babies is an essential route to improving the health of populations. A key factor in the growth of babies is the nutritional status of their mothers. Since women from more disadvantaged backgrounds have poorer quality diets and the worst pregnancy outcomes, they need to be a particular focus. The behavioural sciences have made a substantial contribution to the development of interventions to support dietary changes in disadvantaged women. Translation of such interventions into routine practice is an ideal that is rarely achieved, however. This paper illustrates how re-orientating health and social care services towards an empowerment approach to behaviour change might underpin a new developmental focus to improving long-term health, using learning from a community-based intervention to improve the diets and lifestyles of disadvantaged women. The Southampton Initiative for Health aimed to improve the diets and lifestyles of women of child-bearing age through training health and social care practitioners in skills to support behaviour change. Analysis illustrates the necessary steps in mounting such an intervention: building trust; matching agendas and changing culture. The Southampton Initiative for Health demonstrates that developing sustainable; workable interventions and effective community partnerships; requires commitment beginning long before intervention delivery but is key to the translation of developmental origins research into improvements in human health. PMID:28335519

Translating Developmental Origins: Improving the Health of Women and Their Children Using a Sustainable Approach to Behaviour Change.

PubMed

Barker, Mary; Baird, Janis; Tinati, Tannaze; Vogel, Christina; Strömmer, Sofia; Rose, Taylor; Begum, Rufia; Jarman, Megan; Davies, Jenny; Thompson, Sue; Taylor, Liz; Inskip, Hazel; Cooper, Cyrus; Nutbeam, Don; Lawrence, Wendy

2017-03-20

Theories of the developmental origins of health and disease imply that optimising the growth and development of babies is an essential route to improving the health of populations. A key factor in the growth of babies is the nutritional status of their mothers. Since women from more disadvantaged backgrounds have poorer quality diets and the worst pregnancy outcomes, they need to be a particular focus. The behavioural sciences have made a substantial contribution to the development of interventions to support dietary changes in disadvantaged women. Translation of such interventions into routine practice is an ideal that is rarely achieved, however. This paper illustrates how re-orientating health and social care services towards an empowerment approach to behaviour change might underpin a new developmental focus to improving long-term health, using learning from a community-based intervention to improve the diets and lifestyles of disadvantaged women. The Southampton Initiative for Health aimed to improve the diets and lifestyles of women of child-bearing age through training health and social care practitioners in skills to support behaviour change. Analysis illustrates the necessary steps in mounting such an intervention: building trust; matching agendas and changing culture. The Southampton Initiative for Health demonstrates that developing sustainable; workable interventions and effective community partnerships; requires commitment beginning long before intervention delivery but is key to the translation of developmental origins research into improvements in human health.

Adaptation of catch-up saccades during the initiation of smooth pursuit eye movements.

PubMed

Schütz, Alexander C; Souto, David

2011-04-01

Reduction of retinal speed and alignment of the line of sight are believed to be the respective primary functions of smooth pursuit and saccadic eye movements. As the eye muscles strength can change in the short-term, continuous adjustments of motor signals are required to achieve constant accuracy. While adaptation of saccade amplitude to systematic position errors has been extensively studied, we know less about the adaptive response to position errors during smooth pursuit initiation, when target motion has to be taken into account to program saccades, and when position errors at the saccade endpoint could also be corrected by increasing pursuit velocity. To study short-term adaptation (250 adaptation trials) of tracking eye movements, we introduced a position error during the first catch-up saccade made during the initiation of smooth pursuit-in a ramp-step-ramp paradigm. The target position was either shifted in the direction of the horizontally moving target (forward step), against it (backward step) or orthogonally to it (vertical step). Results indicate adaptation of catch-up saccade amplitude to back and forward steps. With vertical steps, saccades became oblique, by an inflexion of the early or late saccade trajectory. With a similar time course, post-saccadic pursuit velocity was increased in the step direction, adding further evidence that under some conditions pursuit and saccades can act synergistically to reduce position errors.

Reciprocal Signaling between the Ectoderm and a Mesendodermal Left-Right Organizer Directs Left-Right Determination in the Sea Urchin Embryo

PubMed Central

Bessodes, Nathalie; Haillot, Emmanuel; Duboc, Véronique; Röttinger, Eric; Lahaye, François; Lepage, Thierry

2012-01-01

During echinoderm development, expression of nodal on the right side plays a crucial role in positioning of the rudiment on the left side, but the mechanisms that restrict nodal expression to the right side are not known. Here we show that establishment of left-right asymmetry in the sea urchin embryo relies on reciprocal signaling between the ectoderm and a left-right organizer located in the endomesoderm. FGF/ERK and BMP2/4 signaling are required to initiate nodal expression in this organizer, while Delta/Notch signaling is required to suppress formation of this organizer on the left side of the archenteron. Furthermore, we report that the H+/K+-ATPase is critically required in the Notch signaling pathway upstream of the S3 cleavage of Notch. Our results identify several novel players and key early steps responsible for initiation, restriction, and propagation of left-right asymmetry during embryogenesis of a non-chordate deuterostome and uncover a functional link between the H+/K+-ATPase and the Notch signaling pathway. PMID:23271979

A new face of phenalenyl-based radicals in the transition metal-free C-H arylation of heteroarenes at room temperature: trapping the radical initiator via C-C σ-bond formation.

PubMed

Ahmed, Jasimuddin; P, Sreejyothi; Vijaykumar, Gonela; Jose, Anex; Raj, Manthan; Mandal, Swadhin K

2017-11-01

The radical-mediated transition metal-free approach for the direct C-H bond functionalization of arenes is considered as a cost effective alternative to transition metal-based catalysis. An organic ligand-based radical plays a key role by generating an aryl radical which undergoes a subsequent functionalization process. The design principle of the present study takes advantage of a relatively stable odd alternant hydrocarbon-based phenalenyl (PLY) radical. In this study, the first transition metal-free catalyzed direct C-H arylation of a variety of heteroarenes such as azoles, furan, thiophene and pyridine at room temperature has been reported using a phenalenyl-based radical without employing any photoactivation step. This protocol has been successfully applied to the gram scale synthesis of core moieties of bioactive molecules. The phenalenyl-based radical initiator has been characterized crystallographically by trapping it via the formation of a C-C σ-bond between the phenalenyl radical and solvent-based radical species.

Live Cell Imaging Confocal Microscopy Analysis of HBV Myr-PreS1 Peptide Binding and Uptake in NTCP-GFP Expressing HepG2 Cells.

PubMed

König, Alexander; Glebe, Dieter

2017-01-01

To obtain basic knowledge about specific molecular mechanisms involved in the entry of pathogens into cells is the basis for establishing pharmacologic substances blocking initial viral binding, infection, and subsequent viral spread. Lack of information about key cellular factors involved in the initial steps of HBV infection has hampered the characterization of HBV binding and entry for decades. However, recently, the liver-specific sodium-dependent taurocholate cotransporting polypeptide (NTCP) has been discovered as a functional receptor for HBV and HDV, thus opening the field for new concepts of basic binding and entry of HBV and HDV. Here, we describe practical issues of a basic in vitro assay system to examine kinetics and mechanisms of receptor-dependent HBV binding, uptake, and intracellular trafficking by live-cell imaging confocal microscopy. The assay system is comprised of HepG2 cells expressing a NTCP-GFP fusion-protein and chemically synthesized, fluorophore-labeled part of HBV surface protein, spanning the first N-terminal 48 amino acids of preS1 of the large hepatitis B virus surface protein.

Leveraging lean principles in creating a comprehensive quality program: The UCLA health readmission reduction initiative.

PubMed

Afsar-Manesh, Nasim; Lonowski, Sarah; Namavar, Aram A

2017-12-01

UCLA Health embarked to transform care by integrating lean methodology in a key clinical project, Readmission Reduction Initiative (RRI). The first step focused on assembling a leadership team to articulate system-wide priorities for quality improvement. The lean principle of creating a culture of change and accountability was established by: 1) engaging stakeholders, 2) managing the process with performance accountability, and, 3) delivering patient-centered care. The RRI utilized three major lean principles: 1) A3, 2) root cause analyses, 3) value stream mapping. Baseline readmission rate at UCLA from 9/2010-12/2011 illustrated a mean of 12.1%. After the start of the RRI program, for the period of 1/2012-6/2013, the readmission rate decreased to 11.3% (p<0.05). To impact readmissions, solutions must evolve from smaller service- and location-based interventions into strategies with broader approach. As elucidated, a systematic clinical approach grounded in lean methodologies is a viable solution to this complex problem. Copyright © 2017 Elsevier Inc. All rights reserved.

Intragranular cracking as a critical barrier for high-voltage usage of layer-structured cathode for lithium-ion batteries

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

Yan, Pengfei; Zheng, Jianming; Gu, Meng

LiNi 1/3Mn 1/3Co 1/3O 2 (NMC333) layered cathode is often fabricated as secondary particles of consisting of densely packed primary particles, which offers advantage of high energy density and alleviation of cathode side reactions/corrosions, but introduces other drawbacks, such as intergranular cracking. Here, we report unexpected observations on the nucleation and growth of intragranular cracks in the commercial NMC333 layered cathode by using advanced S/TEM. We found that the formation of the intragranular cracks is directly associated with high voltage cycling, which is an electrochemically driven and diffusion controlled process. The intragranular cracks were noticed to be characteristically initiated frommore » grain interior, a consequence of dislocation based crack incubation mechanism. This observation is in sharp contrast with the general theoretical models, predicting the initiation of intragranular cracks from grain boundaries or particle surface. As a result, our study indicates that maintain a structural stability is the key step toward high voltage operation of layered cathode materials.« less

Intragranular cracking as a critical barrier for high-voltage usage of layer-structured cathode for lithium-ion batteries

DOE PAGES

Yan, Pengfei; Zheng, Jianming; Gu, Meng; ...

2017-01-16

LiNi 1/3Mn 1/3Co 1/3O 2 (NMC333) layered cathode is often fabricated as secondary particles of consisting of densely packed primary particles, which offers advantage of high energy density and alleviation of cathode side reactions/corrosions, but introduces other drawbacks, such as intergranular cracking. Here, we report unexpected observations on the nucleation and growth of intragranular cracks in the commercial NMC333 layered cathode by using advanced S/TEM. We found that the formation of the intragranular cracks is directly associated with high voltage cycling, which is an electrochemically driven and diffusion controlled process. The intragranular cracks were noticed to be characteristically initiated frommore » grain interior, a consequence of dislocation based crack incubation mechanism. This observation is in sharp contrast with the general theoretical models, predicting the initiation of intragranular cracks from grain boundaries or particle surface. As a result, our study indicates that maintain a structural stability is the key step toward high voltage operation of layered cathode materials.« less

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

Wilson, Charles

University Park, Maryland (“UP”) is a small town of 2,540 residents, 919 homes, 2 churches, 1 school, 1 town hall, and 1 breakthrough community energy efficiency initiative: the Small Town Energy Program (“STEP”). STEP was developed with a mission to “create a model community energy transformation program that serves as a roadmap for other small towns across the U.S.” STEP first launched in January 2011 in UP and expanded in July 2012 to the neighboring communities of Hyattsville, Riverdale Park, and College Heights Estates, MD. STEP, which concluded in July 2013, was generously supported by a grant from the U.S.more » Department of Energy (DOE). The STEP model was designed for replication in other resource-constrained small towns similar to University Park - a sector largely neglected to date in federal and state energy efficiency programs. STEP provided a full suite of activities for replication, including: energy audits and retrofits for residential buildings, financial incentives, a community-based social marketing backbone and local community delivery partners. STEP also included the highly innovative use of an “Energy Coach” who worked one-on-one with clients throughout the program. Please see www.smalltownenergy.org for more information. In less than three years, STEP achieved the following results in University Park: • 30% of community households participated voluntarily in STEP; • 25% of homes received a Home Performance with ENERGY STAR assessment; • 16% of households made energy efficiency improvements to their home; • 64% of households proceeded with an upgrade after their assessment; • 9 Full Time Equivalent jobs were created or retained, and 39 contractors worked on STEP over the course of the project. Estimated Energy Savings - Program Totals kWh Electricity 204,407 Therms Natural Gas 24,800 Gallons of Oil 2,581 Total Estimated MMBTU Saved (Source Energy) 5,474 Total Estimated Annual Energy Cost Savings $61,343 STEP clients who had a home energy upgrade invested on average $4,500, resulting in a 13% reduction in annual energy use and utility bill savings of $325. Rebates and incentives covered 40%-50% of retrofit cost, resulting in an average simple payback of about 7 years. STEP has created a handbook in which are assembled all the key elements that went into the design and delivery of STEP. The target audiences for the handbook include interested citizens, elected officials and municipal staff who want to establish and run their own efficiency program within a small community or neighborhood, using elements, materials and lessons from STEP.« less

40 CFR 35.2202 - Step 2+3 projects.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Step 2+3 projects. 35.2202 Section 35... STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works § 35.2202 Step 2+3 projects. (a) Prior to initiating action to acquire eligible real property, a Step 2+3 grantee shall submit for...

Stirling to Flight Initiative

NASA Technical Reports Server (NTRS)

Hibbard, Kenneth E.; Mason, Lee S.; Ndu, Obi; Smith, Clayton; Withrow, James P.

2016-01-01

NASA has a consistent need for radioisotope power systems (RPS) to enable robotic scientific missions for planetary exploration that has been present for over four decades and will continue into the foreseeable future, as documented in the most recent Planetary Science Decadal Study Report. As RPS have evolved throughout the years, there has also grown a desire for more efficient power systems, allowing NASA to serve as good stewards of the limited plutonium-238 (238Pu), while also supporting the ever-present need to minimize mass and potential impacts to the desired science measurements. In fact, the recent Nuclear Power Assessment Study (NPAS) released in April 2015 resulted in several key conclusion regarding RPS, including affirmation that RPS will be necessary well into the 2030s (at least) and that 238Pu is indeed a precious resource requiring efficient utilization and preservation. Stirling Radioisotope Generators (SRGs) combine a Stirling cycle engine powered by a radioisotope heater unit into a single generator system. Stirling engine technology has been under development at NASA Glenn Research Center (GRC) in partnership with the Department of Energy (DOE) since the 1970's. The most recent design, the 238Pu-fueled Advanced Stirling Radioisotope Generator (ASRG), was offered as part of the NASA Discovery 2010 Announcement of Opportunity (AO). The Step-2 selections for this AO included two ASRG-enabled concepts, the Titan Mare Explorer (TiME) and the Comet Hopper (CHopper), although the only non-nuclear concept, InSight, was ultimately chosen. The DOE's ASRG contract was terminated in 2013. Given that SRGs utilize significantly less 238Pu than traditional Radioisotope Thermoelectric Generators (RTGs) - approximately one quarter of the nuclear fuel, to produce similar electrical power output - they provide a technology worthy of consideration for meeting the aforementioned NASA objectives. NASA's RPS Program Office has recently investigated a new Stirling to Flight (S2F) initiative with the objective of developing a 100-500 We Stirling generator system. Additionally, a different approach is being devised for this initiative to avoid pitfalls of the past, and apply lessons learned from the recent ASRG experience. Two key aspects of this initiative are a Stirling System Technology Maturation Effort, and a Surrogate Mission Team (SMT) intended to provide clear mission pull and requirements context. The S2F project seeks to lead directly into a DOE flight system development of a new SRG. This paper will detail the proposed S2F initiative, and provide specifics on the key efforts designed to pave a forward path for bringing Stirling technology to flight.

Marshall Space Flight Center Propulsion Systems Department (PSD) KM Initiative

NASA Technical Reports Server (NTRS)

Caraccioli, Paul; Varnadoe, Tom; McCarter, Mike

2006-01-01

NASA Marshall Space Flight Center s Propulsion Systems Department (PSD) is four months into a fifteen month Knowledge Management (KM) initiative to support enhanced engineering decision making and analyses, faster resolution of anomalies (near-term) and effective, efficient knowledge infused engineering processes, reduced knowledge attrition, and reduced anomaly occurrences (long-term). The near-term objective of this initiative is developing a KM Pilot project, within the context of a 3-5 year KM strategy, to introduce and evaluate the use of KM within PSD. An internal NASA/MSFC PSD KM team was established early in project formulation to maintain a practitioner, user-centric focus throughout the conceptual development, planning and deployment of KM technologies and capabilities with in the PSD. The PSD internal team is supported by the University of Alabama's Aging Infrastructure Systems Center Of Excellence (AISCE), Intergraph Corporation, and The Knowledge Institute. The principle product of the initial four month effort has been strategic planning of PSD KM implementation by first determining the "as is" state of KM capabilities and developing, planning and documenting the roadmap to achieve the desired "to be" state. Activities undertaken to support the planning phase have included data gathering; cultural surveys, group work-sessions, interviews, documentation review, and independent research. Assessments and analyses have been performed including industry benchmarking, related local and Agency initiatives, specific tools and techniques used and strategies for leveraging existing resources, people and technology to achieve common KM goals. Key findings captured in the PSD KM Strategic Plan include the system vision, purpose, stakeholders, prioritized strategic objectives mapped to the top ten practitioner needs and analysis of current resource usage. Opportunities identified from research, analyses, cultural/KM surveys and practitioner interviews include: executive and senior management sponsorship, KM awareness, promotion and training, cultural change management, process improvement, leveraging existing resources and new innovative technologies to align with other NASA KM initiatives (convergence: the big picture). To enable results based incremental implementation and future growth of the KM initiative, key performance measures have been identified including stakeholder value, system utility, learning and growth (knowledge capture, sharing, reduced anomaly recurrence), cultural change, process improvement and return-on-investment. The next steps for the initial implementation spiral (focused on SSME Turbomachinery) have been identified, largely based on the organization and compilation of summary level engineering process models, data capture matrices, functional models and conceptual-level systems architecture. Key elements include detailed KM requirements definition, KM technology architecture assessment, evaluation and selection, deployable KM Pilot design, development, implementation and evaluation, and justifying full implementation (estimated Return-on-Investment). Features identified for the notional system architecture include the knowledge presentation layer (and its components), knowledge network layer (and its components), knowledge storage layer (and its components), User Interface and capabilities. This paper provides a snapshot of the progress to date, the near term planning for deploying the KM pilot project and a forward look at results based growth of KM capabilities with-in the MSFC PSD.

Marshall Space Flight Center Propulsion Systems Department (PSD) Knowledge Management (KM) Initiative

NASA Technical Reports Server (NTRS)

Caraccioli, Paul; Varnedoe, Tom; Smith, Randy; McCarter, Mike; Wilson, Barry; Porter, Richard

2006-01-01

NASA Marshall Space Flight Center's Propulsion Systems Department (PSD) is four months into a fifteen month Knowledge Management (KM) initiative to support enhanced engineering decision making and analyses, faster resolution of anomalies (near-term) and effective, efficient knowledge infused engineering processes, reduced knowledge attrition, and reduced anomaly occurrences (long-term). The near-term objective of this initiative is developing a KM Pilot project, within the context of a 3-5 year KM strategy, to introduce and evaluate the use of KM within PSD. An internal NASA/MSFC PSD KM team was established early in project formulation to maintain a practitioner, user-centric focus throughout the conceptual development, planning and deployment of KM technologies and capabilities within the PSD. The PSD internal team is supported by the University of Alabama's Aging Infrastructure Systems Center of Excellence (AISCE), lntergraph Corporation, and The Knowledge Institute. The principle product of the initial four month effort has been strategic planning of PSD KNI implementation by first determining the "as is" state of KM capabilities and developing, planning and documenting the roadmap to achieve the desired "to be" state. Activities undertaken to suppoth e planning phase have included data gathering; cultural surveys, group work-sessions, interviews, documentation review, and independent research. Assessments and analyses have beon pedormed including industry benchmarking, related local and Agency initiatives, specific tools and techniques used and strategies for leveraging existing resources, people and technology to achieve common KM goals. Key findings captured in the PSD KM Strategic Plan include the system vision, purpose, stakeholders, prioritized strategic objectives mapped to the top ten practitioner needs and analysis of current resource usage. Opportunities identified from research, analyses, cultural1KM surveys and practitioner interviews include: executive and senior management sponsorship, KM awareness, promotion and training, cultural change management, process improvement, leveraging existing resources and new innovative technologies to align with other NASA KM initiatives (convergence: the big picture). To enable results based incremental implementation and future growth of the KM initiative, key performance measures have been identified including stakeholder value, system utility, learning and growth (knowledge capture, sharing, reduced anomaly recurrence), cultural change, process improvement and return-on-investment. The next steps for the initial implementation spiral (focused on SSME Turbomachinery) have been identified, largely based on the organization and compilation of summary level engineering process models, data capture matrices, functional models and conceptual-level svstems architecture. Key elements include detailed KM requirements definition, KM technology architecture assessment, - evaluation and selection, deployable KM Pilot design, development, implementation and evaluation, and justifying full implementation (estimated Return-on-Investment). Features identified for the notional system architecture include the knowledge presentation layer (and its components), knowledge network layer (and its components), knowledge storage layer (and its components), User Interface and capabilities. This paper provides a snapshot of the progress to date, the near term planning for deploying the KM pilot project and a forward look at results based growth of KM capabilities with-in the MSFC PSD.

Efficient Inversion of Mult-frequency and Multi-Source Electromagnetic Data

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

Gary D. Egbert

2007-03-22

The project covered by this report focused on development of efficient but robust non-linear inversion algorithms for electromagnetic induction data, in particular for data collected with multiple receivers, and multiple transmitters, a situation extremely common in eophysical EM subsurface imaging methods. A key observation is that for such multi-transmitter problems each step in commonly used linearized iterative limited memory search schemes such as conjugate gradients (CG) requires solution of forward and adjoint EM problems for each of the N frequencies or sources, essentially generating data sensitivities for an N dimensional data-subspace. These multiple sensitivities allow a good approximation to themore » full Jacobian of the data mapping to be built up in many fewer search steps than would be required by application of textbook optimization methods, which take no account of the multiplicity of forward problems that must be solved for each search step. We have applied this idea to a develop a hybrid inversion scheme that combines features of the iterative limited memory type methods with a Newton-type approach using a partial calculation of the Jacobian. Initial tests on 2D problems show that the new approach produces results essentially identical to a Newton type Occam minimum structure inversion, while running more rapidly than an iterative (fixed regularization parameter) CG style inversion. Memory requirements, while greater than for something like CG, are modest enough that even in 3D the scheme should allow 3D inverse problems to be solved on a common desktop PC, at least for modest (~ 100 sites, 15-20 frequencies) data sets. A secondary focus of the research has been development of a modular system for EM inversion, using an object oriented approach. This system has proven useful for more rapid prototyping of inversion algorithms, in particular allowing initial development and testing to be conducted with two-dimensional example problems, before approaching more computationally cumbersome three-dimensional problems.« less

Posture, head stability, and orientation recovery during vestibular regeneration in pigeons.

PubMed

Dickman, J David; Lim, Insook

2004-09-01

Compensatory behavior such as oculomotor, gaze, and postural responses that occur during movement largely depend upon a functioning vestibular system. In the present study, the initial loss and subsequent recovery of postural and head stability in pigeons undergoing vestibular regeneration were examined. Adult pigeons were trained to manipulate a straight run chamber to peck an illuminated key for fluid reward. Six behavioral measures assessing performance, posture, and head stability were quantified. These included run latency, steps (walking), path negotiation (lane changes), gaze saccades, head bobs, and head shakes. Once normative values were obtained for four birds, complete lesion of all receptor cells and denervation of the epithelia in the vestibular endorgans were produced using a single intralabyrinthine application of streptomycin sulfate. Each bird was then tested at specific times during regeneration and the same behavioral measures examined. At 7 days post-streptomycin treatment (PST), all birds exhibited severe postural and head instability, with tremors, head shakes, staggering, and circling predominating. No normal trial runs, walking, gaze saccades, or head bobs were present. Many of these dysfunctions persisted through 3-4 weeks PST. Gradually, tremor and head shakes diminished and were replaced with an increasing number of normal head bobs during steps and gaze saccades. Beginning at 4 weeks PST, but largely inaccurate, was the observed initiation of directed steps, less staggering, and some successful path negotiation. As regeneration progressed, spatial orientation and navigation ability increased and, by 49 days PST, most trials were successful. By 70 days PST, all birds had recovered to pretreatment levels. Thus, it was observed that ataxia must subside, coincident with normalized head and postural stability prior to the recovery of spatial orientation and path navigation recovery. Parallels in recovery were drawn to hair cell regeneration and afferent responsiveness, as inferred from present results and those in other investigations.

Kinematic and behavioral analyses of protective stepping strategies and risk for falls among community living older adults.

PubMed

Bair, Woei-Nan; Prettyman, Michelle G; Beamer, Brock A; Rogers, Mark W

2016-07-01

Protective stepping evoked by externally applied lateral perturbations reveals balance deficits underlying falls. However, a lack of comprehensive information about the control of different stepping strategies in relation to the magnitude of perturbation limits understanding of balance control in relation to age and fall status. The aim of this study was to investigate different protective stepping strategies and their kinematic and behavioral control characteristics in response to different magnitudes of lateral waist-pulls between older fallers and non-fallers. Fifty-two community-dwelling older adults (16 fallers) reacted naturally to maintain balance in response to five magnitudes of lateral waist-pulls. The balance tolerance limit (BTL, waist-pull magnitude where protective steps transitioned from single to multiple steps), first step control characteristics (stepping frequency and counts, spatial-temporal kinematic, and trunk position at landing) of four naturally selected protective step types were compared between fallers and non-fallers at- and above-BTL. Fallers took medial-steps most frequently while non-fallers most often took crossover-back-steps. Only non-fallers varied their step count and first step control parameters by step type at the instants of step initiation (onset time) and termination (trunk position), while both groups modulated step execution parameters (single stance duration and step length) by step type. Group differences were generally better demonstrated above-BTL. Fallers primarily used a biomechanically less effective medial-stepping strategy that may be partially explained by reduced somato-sensation. Fallers did not modulate their step parameters by step type at first step initiation and termination, instances particularly vulnerable to instability, reflecting their limitations in balance control during protective stepping. Copyright © 2016. Published by Elsevier Ltd.

A review for identification of initiating events in event tree development process on nuclear power plants

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

Riyadi, Eko H., E-mail: e.riyadi@bapeten.go.id

2014-09-30

Initiating event is defined as any event either internal or external to the nuclear power plants (NPPs) that perturbs the steady state operation of the plant, if operating, thereby initiating an abnormal event such as transient or loss of coolant accident (LOCA) within the NPPs. These initiating events trigger sequences of events that challenge plant control and safety systems whose failure could potentially lead to core damage or large early release. Selection for initiating events consists of two steps i.e. first step, definition of possible events, such as by evaluating a comprehensive engineering, and by constructing a top level logicmore » model. Then the second step, grouping of identified initiating event's by the safety function to be performed or combinations of systems responses. Therefore, the purpose of this paper is to discuss initiating events identification in event tree development process and to reviews other probabilistic safety assessments (PSA). The identification of initiating events also involves the past operating experience, review of other PSA, failure mode and effect analysis (FMEA), feedback from system modeling, and master logic diagram (special type of fault tree). By using the method of study for the condition of the traditional US PSA categorization in detail, could be obtained the important initiating events that are categorized into LOCA, transients and external events.« less

The impact of a public health department's expansion from a one-step to a two-step refugee screening process on the detection and initiation of treatment of latent tuberculosis.

PubMed

Einterz, E M; Younge, O; Hadi, C

2018-06-01

To determine, subsequent to the expansion of a county health department's refugee screening process from a one-step to a two-step process, the change in early loss to follow-up and time to initiation of treatment of new refugees with latent tuberculosis infection (LTBI). Quasi-experimental, quantitative. Review of patient medical records. Among 384 refugees who met the case definition of LTBI without prior tuberculosis (TB) classification, the number of cases lost to early follow-up fell from 12.5% to 0% after expansion to a two-step screening process. The average interval between in-country arrival and initiation of LTBI treatment was shortened by 41.4%. The addition of a second step to the refugee screening process was correlated with significant improvements in the county's success in tracking and treating cases of LTBI in refugees. Given the disproportionate importance of foreign-born cases of LTBI to the incidence of TB disease in low-incidence countries, these improvements could have a substantial impact on overall TB control, and the process described could serve as a model for other local health department refugee screening programs. Copyright © 2018 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Initiation of forward gait with lateral occurrence of emotional stimuli: general findings and relevance for pedestrians crossing roads.

PubMed

Caffier, D; Gillet, C; Heurley, L P; Bourrelly, A; Barbier, F; Naveteur, J

2017-03-01

With reference to theoretical models regarding links between emotions and actions, the present study examined whether the lateral occurrence of an emotional stimulus influences spatial and temporal parameters of gait initiation in 18 younger and 18 older healthy adults. In order to simulate road-crossing hazard for pedestrians, slides of approaching cars were used and they were presented in counterbalanced order with threatening slides from the International Affective Picture System (IAPS) and control slides of safe walking areas. Each slide was presented on the left side of the participant once the first step was initiated. The results evidenced medio-lateral shifts to the left for the first step (right foot) and to the right for the second step (left foot). These shifts were both modulated by the slide contents in such a way that the resulting distance between the screen and the foot (right or left) was larger with the IAPS and traffic slides than with the control slides. The slides did not affect the base of support, step length, step velocity and time of double support. Advancing age influenced the subjective impact of the slides and gait characteristics, but did not modulate medio-lateral shifts. The data extend evidence of fast, emotional modulation of stepping, with theoretical and applied consequences.

Hybrid method to estimate two-layered superficial tissue optical properties from simulated data of diffuse reflectance spectroscopy.

PubMed

Hsieh, Hong-Po; Ko, Fan-Hua; Sung, Kung-Bin

2018-04-20

An iterative curve fitting method has been applied in both simulation [J. Biomed. Opt.17, 107003 (2012)JBOPFO1083-366810.1117/1.JBO.17.10.107003] and phantom [J. Biomed. Opt.19, 077002 (2014)JBOPFO1083-366810.1117/1.JBO.19.7.077002] studies to accurately extract optical properties and the top layer thickness of a two-layered superficial tissue model from diffuse reflectance spectroscopy (DRS) data. This paper describes a hybrid two-step parameter estimation procedure to address two main issues of the previous method, including (1) high computational intensity and (2) converging to local minima. The parameter estimation procedure contained a novel initial estimation step to obtain an initial guess, which was used by a subsequent iterative fitting step to optimize the parameter estimation. A lookup table was used in both steps to quickly obtain reflectance spectra and reduce computational intensity. On simulated DRS data, the proposed parameter estimation procedure achieved high estimation accuracy and a 95% reduction of computational time compared to previous studies. Furthermore, the proposed initial estimation step led to better convergence of the following fitting step. Strategies used in the proposed procedure could benefit both the modeling and experimental data processing of not only DRS but also related approaches such as near-infrared spectroscopy.

Six steps to an effective denials management program.

PubMed

Robertson, Brian; Doré, Alexander

2005-09-01

The following six steps can help you manage denials management issues in your organization: Create standard definitions of denial types. Establish a denial hierarchy. Establish a centralized denial database. Develop key performance indicators. Build responsibility matrices. Measure, monitor, and take action.

Implementing an Injury Prevention Briefing to aid delivery of key fire safety messages in UK children's centres: qualitative study nested within a multi-centre randomised controlled trial.

PubMed

Beckett, Kate; Goodenough, Trudy; Deave, Toity; Jaeckle, Sally; McDaid, Lisa; Benford, Penny; Hayes, Mike; Towner, Elizabeth; Kendrick, Denise

2014-12-10

To improve the translation of public health evidence into practice, there is a need to increase practitioner involvement in initiative development, to place greater emphasis on contextual knowledge, and to address intervention processes and outcomes. Evidence that demonstrates the need to reduce childhood fire-related injuries is compelling but its translation into practice is inconsistent and limited. With this knowledge the Keeping Children Safe programme developed an "Injury Prevention Briefing (IPB)" using a 7 step process to combine scientific evidence with practitioner contextual knowledge. The IPB was designed specifically for children's centres (CCs) to support delivery of key fire safety messages to parents. This paper reports the findings of a nested qualitative study within a clustered randomised controlled trial of the IPB, in which staff described their experiences of IPB implementation to aid understanding of why or how the intervention worked. Interviews were conducted with key staff at 24 CCs participating in the two intervention arms: 1) IPB supplemented by initial training and regular facilitation; 2) IPB sent by post with no facilitation. Framework Analysis was applied to these interview data to explore intervention adherence including; exposure or dose; quality of delivery; participant responsiveness; programme differentiation; and staff experience of IPB implementation. This included barriers, facilitators and suggested improvements. 83% of CCs regarded the IPB as a simple, accessible tool which raised awareness, and stimulated discussion and behaviour change. 15 CCs suggested minor modifications to format and content. Four levels of implementation were identified according to content, frequency, duration and coverage. Most CCs (75%) achieved 'extended' or 'essential' IPB implementation. Three universal factors affected all CCs: organisational change and resourcing; working with hard to engage groups; additional demands of participating in a research study. Six specific factors were associated with the implementation level achieved: staff engagement and training; staff continuity; adaptability and flexibility; other agency support; conflicting priorities; facilitation. CCs achieving high implementation levels increased from 58% (no facilitation) to 92% with facilitation. Incorporating service provider perspectives and scientific evidence into health education initiatives enhances potential for successful implementation, particularly when supplemented by ongoing training and facilitation.

Measurement needs guided by synthetic radar scans in high-resolution model output

NASA Astrophysics Data System (ADS)

Varble, A.; Nesbitt, S. W.; Borque, P.

2017-12-01

Microphysical and dynamical process interactions within deep convective clouds are not well understood, partly because measurement strategies often focus on statistics of cloud state rather than cloud processes. While processes cannot be directly measured, they can be inferred with sufficiently frequent and detailed scanning radar measurements focused on the life cycleof individual cloud regions. This is a primary goal of the 2018-19 DOE ARM Cloud, Aerosol, and Complex Terrain Interactions (CACTI) and NSF Remote sensing of Electrification, Lightning, And Mesoscale/microscale Processes with Adaptive Ground Observations (RELAMPAGO) field campaigns in central Argentina, where orographic deep convective initiation is frequent with some high-impact systems growing into the tallest and largest in the world. An array of fixed and mobile scanning multi-wavelength dual-polarization radars will be coupled with surface observations, sounding systems, multi-wavelength vertical profilers, and aircraft in situ measurements to characterize convective cloud life cycles and their relationship with environmental conditions. While detailed cloud processes are an observational target, the radar scan patterns that are most ideal for observing them are unclear. They depend on the locations and scales of key microphysical and dynamical processes operating within the cloud. High-resolution simulations of clouds, while imperfect, can provide information on these locations and scales that guide radar measurement needs. Radar locations are set in the model domain based on planned experiment locations, and simulatedorographic deep convective initiation and upscale growth are sampled using a number of different scans involving RHIs or PPIs with predefined elevation and azimuthal angles that approximately conform with radar range and beam width specifications. Each full scan pattern is applied to output atsingle model time steps with time step intervals that depend on the length of time required to complete each scan in the real world. The ability of different scans to detect key processes within the convective cloud life cycle are examined in connection with previous and subsequent dynamical and microphysical transitions. This work will guide strategic scan patterns that will be used during CACTI and RELAMPAGO.

Lean Information Management: Criteria For Selecting Key Performance Indicators At Shop Floor

NASA Astrophysics Data System (ADS)

Iuga, Maria Virginia; Kifor, Claudiu Vasile; Rosca, Liviu-Ion

2015-07-01

Most successful organizations worldwide use key performance indicators as an important part of their corporate strategy in order to forecast, measure and plan their businesses. Performance metrics vary in their purpose, definition and content. Therefore, the way organizations select what they think are the optimal indicators for their businesses varies from company to company, sometimes even from department to department. This study aims to answer the question of what is the most suitable way to define and select key performance indicators. More than that, it identifies the right criteria to select key performance indicators at shop floor level. This paper contributes to prior research by analysing and comparing previously researched selection criteria and proposes an original six-criteria-model, which caters towards choosing the most adequate KPIs. Furthermore, the authors take the research a step further by further steps to closed research gaps within this field of study.

Progress in workforce development since 2000: advanced training opportunities in public and community psychiatry.

PubMed

Sowers, Wesley; Pollack, David; Everett, Anita; Thompson, Kenneth S; Ranz, Jules; Primm, Annelle

2011-07-01

A crisis in the behavioral health care workforce has drawn considerable attention from consumers, families, advocates, clinical professionals, and system administrators at local, state, and federal levels in the past decade. Its effects have been felt in the recruitment, retention, and performance of psychiatrists in the public sector, where a focus on biological aspects of illness and efforts to cut costs have made it difficult for public psychiatrists to engage meaningfully in leadership, consultation, prevention, and psychosocial interventions. An array of training opportunities has recently been created to meet the needs of community psychiatrists at various stages of their careers, from psychiatrists just beginning their careers to those who have been working as medical directors for several years. This article describes the development of these initiatives and their impact on public psychiatry in four key areas--training of experienced psychiatrists, ensuring retention of psychiatrists in community programs, providing fellowship training, and creating professional identity and pride. Although these programs constitute only initial steps, opportunities for psychiatrists to obtain advanced training in community psychiatry are much greater now than they were ten years ago. These initiatives will enhance the professional identity of community psychiatrists and provide a solid foundation for future development of public service psychiatry in the behavioral health workforce.

Concurrent initialization for Bearing-Only SLAM.

PubMed

Munguía, Rodrigo; Grau, Antoni

2010-01-01

Simultaneous Localization and Mapping (SLAM) is perhaps the most fundamental problem to solve in robotics in order to build truly autonomous mobile robots. The sensors have a large impact on the algorithm used for SLAM. Early SLAM approaches focused on the use of range sensors as sonar rings or lasers. However, cameras have become more and more used, because they yield a lot of information and are well adapted for embedded systems: they are light, cheap and power saving. Unlike range sensors which provide range and angular information, a camera is a projective sensor which measures the bearing of images features. Therefore depth information (range) cannot be obtained in a single step. This fact has propitiated the emergence of a new family of SLAM algorithms: the Bearing-Only SLAM methods, which mainly rely in especial techniques for features system-initialization in order to enable the use of bearing sensors (as cameras) in SLAM systems. In this work a novel and robust method, called Concurrent Initialization, is presented which is inspired by having the complementary advantages of the Undelayed and Delayed methods that represent the most common approaches for addressing the problem. The key is to use concurrently two kinds of feature representations for both undelayed and delayed stages of the estimation. The simulations results show that the proposed method surpasses the performance of previous schemes.

Single-Chain Folding of Synthetic Polymers: A Critical Update.

PubMed

Altintas, Ozcan; Barner-Kowollik, Christopher

2015-11-23

The current contribution serves as a critical update to a previous feature article from us (Macromol. Rapid Commun. 2012, 33, 958-971), and highlights the latest advances in the preparation of single chain polymeric nanoparticles and initial-yet promising-attempts towards mimicking the structure of natural biomacromolecules via single-chain folding of well-defined linear polymers via so-called single chain selective point folding and repeat unit folding. The contribution covers selected examples from the literature published up to ca. September 2015. Our aim is not to provide an exhaustive review but rather highlight a selection of new and exciting examples for single-chain folding based on advanced macromolecular precision chemistry. Initially, the discussion focuses on the synthesis and characterization of single-chain folded structures via selective point folding. The second part of the feature article addresses the folding of well-defined single-chain polymers by means of repeat unit folding. The current state of the art in the field of single-chain folding indicates that repeat unit folding-driven nanoparticle preparation is well-advanced, while initial encouraging steps towards building selective point folding systems have been taken. In addition, a summary of the-in our view-open key questions is provided that may guide future biomimetic design efforts. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Series: Clinical Epidemiology in South Africa. Paper 1: Evidence-based health care and policy in Africa: past, present, and future.

PubMed

Young, Taryn; Garner, Paul; Clarke, Mike; Volmink, Jimmy

2017-03-01

Africa has high disease burden and health system challenges but is making progress in recognizing, accepting, and adopting evidence-based health care (EBHC). In this article, we reflect on the developments of the past 2 decades and consider further steps that will help with the translation of reliable research results into the decision making process. There has been a rapid growth in various initiatives to promote EBHC in the African region. These include the conduct and reporting of primary and secondary research, research capacity development and supportive initiatives, access to information, and work with decision makers in getting research into clinical guidelines and health policies. Much, however, still needs to be done to improve the impact on health in the region. A multipronged approach consisting of regionally relevant well-conducted research addressing priority health problems, increased uptake of research in health care policy and practice, dedicated capacity development initiatives to support the conduct as well as use of research, facilitated by wider collaboration, and equitable partnerships will be important. Working together in mutually supporting partnerships is key to advancing both evidence-informed health care practices and better health. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Dissemination of public health information: key tools utilised by the NECOBELAC network in Europe and Latin America

PubMed Central

De Castro, Paola; Marsili, Daniela; Poltronieri, Elisabetta; Calderón, Carlos Agudelo

2012-01-01

Background Open Access (OA) to scientific information is an important step forward in communication patterns, yet we still need to reinforce OA principles to promote a cultural change of traditional publishing practices. The advantages of free access to scientific information are even more evident in public health where knowledge is directly associated with human wellbeing. Objectives An OA ‘consolidation’ initiative in public health is presented to show how the involvement of people and institutions is fundamental to create awareness on OA and promote a cultural change. This initiative is developed within the project NEtwork of COllaboration Between Europe and Latin American Caribbean countries (NECOBELAC), financed by the European Commission. Methods Three actions are envisaged: Capacity building through a flexible and sustainable training programme on scientific writing and OA publishing; creation of training tools based on semantic web technologies; development of a network of supporting institutions. Results In 2010–2011, 23 training initiatives were performed involving 856 participants from 15 countries; topic maps on scientific publication and OA were produced; 195 institutions are included in the network. Conclusions Cultural change in scientific dissemination practices is a long process requiring a flexible approach and strong commitment by all stakeholders. PMID:22630360

Improving student-perceived benefit of academic advising within education of occupational and physical therapy in the United States: a quality improvement initiative.

PubMed

Barnes, Lisa J; Parish, Robin

2017-01-01

Academic advising is a key role for faculty in the educational process of health professionals; however, the best practice of effective academic advising for occupational and physical therapy students has not been identified in the current literature. The purpose of this quality improvement initiative was to assess and improve the faculty/student advisor/advisee process within occupational and physical therapy programs within a school of allied health professions in the United States in 2015. A quality improvement initiative utilizing quantitative and qualitative information was gathered via survey focused on the assessment and improvement of an advisor/advisee process. The overall initiative utilized an adaptive iterative design incorporating the plan-do-study-act model which included a three-step process over a one year time frame utilizing 2 cohorts, the first with 80 students and the second with 88 students. Baseline data were gathered prior to initiating the new process. A pilot was conducted and assessed during the first semester of the occupational and physical therapy programs. Final information was gathered after one full academic year with final comparisons made to baseline. Defining an effective advisory program with an established framework led to improved awareness and participation by students and faculty. Early initiation of the process combined with increased frequency of interaction led to improved student satisfaction. Based on student perceptions, programmatic policies were initiated to promote advisory meetings early and often to establish a positive relationship. The policies focus on academic advising as one of proactivity in which the advisor serves as a portal which the student may access leading to a more successful academic experience.

Specificity in endoplasmic reticulum-stress signaling in yeast entails a step-wise engagement of HAC1 mRNA to clusters of the stress sensor Ire1.

PubMed

van Anken, Eelco; Pincus, David; Coyle, Scott; Aragón, Tomás; Osman, Christof; Lari, Federica; Gómez Puerta, Silvia; Korennykh, Alexei V; Walter, Peter

2014-12-30

Insufficient protein-folding capacity in the endoplasmic reticulum (ER) induces the unfolded protein response (UPR). In the ER lumen, accumulation of unfolded proteins activates the transmembrane ER-stress sensor Ire1 and drives its oligomerization. In the cytosol, Ire1 recruits HAC1 mRNA, mediating its non-conventional splicing. The spliced mRNA is translated into Hac1, the key transcription activator of UPR target genes that mitigate ER-stress. In this study, we report that oligomeric assembly of the ER-lumenal domain is sufficient to drive Ire1 clustering. Clustering facilitates Ire1's cytosolic oligomeric assembly and HAC1 mRNA docking onto a positively charged motif in Ire1's cytosolic linker domain that tethers the kinase/RNase to the transmembrane domain. By the use of a synthetic bypass, we demonstrate that mRNA docking per se is a pre-requisite for initiating Ire1's RNase activity and, hence, splicing. We posit that such step-wise engagement between Ire1 and its mRNA substrate contributes to selectivity and efficiency in UPR signaling.

Two-Stage Dynamics of In Vivo Bacteriophage Genome Ejection

NASA Astrophysics Data System (ADS)

Chen, Yi-Ju; Wu, David; Gelbart, William; Knobler, Charles M.; Phillips, Rob; Kegel, Willem K.

2018-04-01

Biopolymer translocation is a key step in viral infection processes. The transfer of information-encoding genomes allows viruses to reprogram the cell fate of their hosts. Constituting 96% of all known bacterial viruses [A. Fokine and M. G. Rossmann, Molecular architecture of tailed double-stranded DNA phages, Bacteriophage 4, e28281 (2014)], the tailed bacteriophages deliver their DNA into host cells via an "ejection" process, leaving their protein shells outside of the bacteria; a similar scenario occurs for mammalian viruses like herpes, where the DNA genome is ejected into the nucleus of host cells, while the viral capsid remains bound outside to a nuclear-pore complex. In light of previous experimental measurements of in vivo bacteriophage λ ejection, we analyze here the physical processes that give rise to the observed dynamics. We propose that, after an initial phase driven by self-repulsion of DNA in the capsid, the ejection is driven by anomalous diffusion of phage DNA in the crowded bacterial cytoplasm. We expect that this two-step mechanism is general for phages that operate by pressure-driven ejection, and we discuss predictions of our theory to be tested in future experiments.

Isotopic Exchange in Porous and Dense Magnesium Borohydride.

PubMed

Zavorotynska, Olena; Deledda, Stefano; Li, Guanqiao; Matsuo, Motoaki; Orimo, Shin-ichi; Hauback, Bjørn C

2015-09-01

Magnesium borohydride (Mg(BH4)2) is one of the most promising complex hydrides presently studied for energy-related applications. Many of its properties depend on the stability of the BH4(-) anion. The BH4(-) stability was investigated with respect to H→D exchange. In situ Raman measurements on high-surface-area porous Mg(BH4 )2 in 0.3 MPa D2 have shown that the isotopic exchange at appreciable rates occurs already at 373 K. This is the lowest exchange temperature observed in stable borohydrides. Gas-solid isotopic exchange follows the BH4(-) +D˙ →BH3D(-) +H˙ mechanism at least at the initial reaction steps. Ex situ deuteration of porous Mg(BH4)2 and its dense-phase polymorph indicates that the intrinsic porosity of the hydride is the key behind the high isotopic exchange rates. It implies that the solid-state H(D) diffusion is considerably slower than the gas-solid H→D exchange reaction at the surface and it is a rate-limiting steps for hydrogen desorption and absorption in Mg(BH4)2. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Epidemic outbreaks in growing scale-free networks with local structure

NASA Astrophysics Data System (ADS)

Ni, Shunjiang; Weng, Wenguo; Shen, Shifei; Fan, Weicheng

2008-09-01

The class of generative models has already attracted considerable interest from researchers in recent years and much expanded the original ideas described in BA model. Most of these models assume that only one node per time step joins the network. In this paper, we grow the network by adding n interconnected nodes as a local structure into the network at each time step with each new node emanating m new edges linking the node to the preexisting network by preferential attachment. This successfully generates key features observed in social networks. These include power-law degree distribution pk∼k, where μ=(n-1)/m is a tuning parameter defined as the modularity strength of the network, nontrivial clustering, assortative mixing, and modular structure. Moreover, all these features are dependent in a similar way on the parameter μ. We then study the susceptible-infected epidemics on this network with identical infectivity, and find that the initial epidemic behavior is governed by both of the infection scheme and the network structure, especially the modularity strength. The modularity of the network makes the spreading velocity much lower than that of the BA model. On the other hand, increasing the modularity strength will accelerate the propagation velocity.

Optimal Filter Estimation for Lucas-Kanade Optical Flow

PubMed Central

Sharmin, Nusrat; Brad, Remus

2012-01-01

Optical flow algorithms offer a way to estimate motion from a sequence of images. The computation of optical flow plays a key-role in several computer vision applications, including motion detection and segmentation, frame interpolation, three-dimensional scene reconstruction, robot navigation and video compression. In the case of gradient based optical flow implementation, the pre-filtering step plays a vital role, not only for accurate computation of optical flow, but also for the improvement of performance. Generally, in optical flow computation, filtering is used at the initial level on original input images and afterwards, the images are resized. In this paper, we propose an image filtering approach as a pre-processing step for the Lucas-Kanade pyramidal optical flow algorithm. Based on a study of different types of filtering methods and applied on the Iterative Refined Lucas-Kanade, we have concluded on the best filtering practice. As the Gaussian smoothing filter was selected, an empirical approach for the Gaussian variance estimation was introduced. Tested on the Middlebury image sequences, a correlation between the image intensity value and the standard deviation value of the Gaussian function was established. Finally, we have found that our selection method offers a better performance for the Lucas-Kanade optical flow algorithm.

Coordination of rapid stepping with arm pointing: anticipatory changes and step adaptation.

PubMed

Yiou, Eric; Schneider, Cyril; Roussel, Didier

2007-06-01

The present study explored whether rapid stepping is influenced by the coordination of an arm pointing task. Nine participants were instructed to (a) point the index finger of the dominant arm towards a target from the standing posture, (b) initiate a rapid forward step with the contralateral leg, and (c) synchronize stepping and pointing (combined task). Force plate and ankle muscle electromyography (EMG) recordings were contrasted between (b) and (c). In the combined task, the arm acceleration trace most often peaked around foot-off, coinciding with a 15% increase in the forward acceleration of the center of gravity (CoG). Backward displacement of the center of foot pressure at foot-off, duration of anticipatory postural adjustments (APAs) and ankle muscle EMG activity remained unchanged. In contrast, durations of swing phase and whole step were reduced and step length was smaller in the combined task. A reduction in the swing phase was correlated with an increased CoG forward acceleration at foot-off. Changes in the biomechanics of step initiation during the combined task might be ascribed to the postural dynamics elicited by arm pointing, and not to a modulation of the step APAs programming.

Dual initiation strip charge apparatus and methods for making and implementing the same

DOEpatents

Jakaboski, Juan-Carlos [Albuquerque, NM; Todd,; Steven, N [Rio Rancho, NM; Polisar, Stephen [Albuquerque, NM; Hughs, Chance [Tijeras, NM

2011-03-22

A Dual Initiation Strip Charge (DISC) apparatus is initiated by a single initiation source and detonates a strip of explosive charge at two separate contacts. The reflection of explosively induced stresses meet and create a fracture and breach a target along a generally single fracture contour and produce generally fragment-free scattering and no spallation. Methods for making and implementing a DISC apparatus provide numerous advantages over previous methods of creating explosive charges by utilizing steps for rapid prototyping; by implementing efficient steps and designs for metering consistent, repeatable, and controlled amount of high explosive; and by utilizing readily available materials.

Planning for Growth.

ERIC Educational Resources Information Center

Astle, Judy Hughes

2001-01-01

A summer camp expanded into year-round operation one step at a time. Initial steps included identifying the camp mission, history, and assets. Successive steps became larger and included expanding the program within the mission, increasing marketing efforts, developing natural resources, creating plans for maintenance and improvements, and…

Electrification in winter storms and the analysis of thunderstorm overflight data

NASA Technical Reports Server (NTRS)

Brook, Marx

1993-01-01

We have been focusing our study of electrification in winter storms on the lightning initiation process, making inferences about the magnitude of the electric fields from the initial pulses associated with breakdown, i.e., with the formation of the initial streamers. The essence of the most significant finding is as follows: (1) initial breakdown radiation pulses from stepped leaders prior to the first return stroke are very large, reaching values of 20-30 Volts/meter, comparable to return stroke radiation; and (2) the duration of the stepped leader, from the initial detectable radiation pulse to the return stroke onset, is very-short-ranging from a minimum 1.5 ms to a maximum of 4.5 ms. This past summer (June-August of 1991) we participated in the CAPE program at the Kennedy Space Center in order to acquire data on stepped leaders in summer storms with the same equipment used to get the winter storm data. We discovered that the vigorous leaders seen in winter so frequently were present in summer storms, although not as large in amplitude and certainly not as frequent.

A METHOD FOR DETERMINING THE COMPATIBILITY OF HAZARDOUS WASTES

EPA Science Inventory

This report describes a method for determining the compatibility of the binary combinations of hazardous wastes. The method consists of two main parts, namely: (1) the step-by-step compatibility analysis procedures, and (2) the hazardous wastes compatibility chart. The key elemen...

Keys to a Safe, Secure School.

ERIC Educational Resources Information Center

Kennedy, Mike

2002-01-01

Outlines 10 steps that school administrators can take to make their schools safer and more secure for students and staff. These steps encompass crime prevention through environmental design, crisis planning, entrances, lighting, police presence, prevention programs, rapport with students, smaller schools, technology implementation, and staff…

24 CFR Appendix E to Part 3500 - Arithmetic Steps

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Arithmetic Steps E Appendix E to...—Arithmetic Steps I. Example Illustrating Aggregate Analysis: ASSUMPTIONS: Disbursements: $360 for school... Payment: July 1 Step 1—Initial Trial Balance Aggregate pmt disb bal Jun 0 0 0 Jul 130 500 −370 Aug 130 0...

A Psychometric Approach to Theory-Based Behavior Change Intervention Development: Example From the Colorado Meaning-Activity Project.

PubMed

Masters, Kevin S; Ross, Kaile M; Hooker, Stephanie A; Wooldridge, Jennalee L

2018-05-18

There has been a notable disconnect between theories of behavior change and behavior change interventions. Because few interventions are both explicitly and adequately theory-based, investigators cannot assess the impact of theory on intervention effectiveness. Theory-based interventions, designed to deliberately engage the theory's proposed mechanisms of change, are needed to adequately test theories. Thus, systematic approaches to theory-based intervention development are needed. This article will introduce and discuss the psychometric method of developing theory-based interventions. The psychometric approach to intervention development utilizes basic psychometric principles at each step of the intervention development process in order to build a theoretically driven intervention to, subsequently, be tested in process (mechanism) and outcome studies. Five stages of intervention development are presented as follows: (i) Choice of theory; (ii) Identification and characterization of key concepts and expected relations; (iii) Intervention construction; (iv) Initial testing and revision; and (v) Empirical testing of the intervention. Examples of this approach from the Colorado Meaning-Activity Project (COMAP) are presented. Based on self-determination theory integrated with meaning or purpose, and utilizing a motivational interviewing approach, the COMAP intervention is individually based with an initial interview followed by smart phone-delivered interventions for increasing daily activity. The psychometric approach to intervention development is one method to ensure careful consideration of theory in all steps of intervention development. This structured approach supports developing a research culture that endorses deliberate and systematic operationalization of theory into behavior change intervention from the outset of intervention development.

Evolution and simplified terminology of natural orifice transluminal endoscopic surgery (NOTES), laparoendoscopic single-site surgery (LESS), and mini-laparoscopy (ML).

PubMed

Georgiou, A N; Rassweiler, J; Herrmann, T R; Stolzenburg, J U; Liatsikos, E N; Do, Eta Mu; Kallidonis, P; de la Teille, A; van Velthoven, R; Burchardt, M

2012-10-01

Natural orifice transluminal endoscopic surgery (NOTES) and laparoendoscopic single-site surgery (LESS) are the next steps in the evolution of laparoscopic surgery, promising reduced morbidity and improved cosmetic result. The inconsistent terminology initially used led to confusion. Understanding the technical evolution, the current status and a unified and simplified terminology are key issues for further acceptance of both approaches. To present LESS and NOTES in its historical context and to clarify the associated terminology. Extensive literature search took place using the PubMed. Several hundred publications in general surgery and urology regarding LESS are present including the expert opinion of members the European Society of Uro-technology (ESUT). The increasing interest on NOTES and LESS is reflected by a raising number of publications during the last 4 years. The initial confusion with the terminology of single-incision surgery represented a significant issue for further evolution of the technique. Thus, consortiums of experts searched a universally acceptable name for single-incision surgery. They determined that 'laparoendoscopic single-site surgery' (LESS) was both scientifically accurate and colloquially appropriate, the term being also ratified by the NOTES working group (Endourological Society) and the ESUT. For additional use of instruments, the terms hybrid NOTES and hybrid LESS should be used. Any single use of miniaturized instruments for laparoscopy should be called mini-laparoscopy. The evolution of LESS and most likely NOTES to a new standard of minimally invasive surgery could represent an evolutionary step even greater than the one performed by the establishment of laparoscopy over open surgery.

Highly Luminescent Hybrid SiO2-Coated CdTe Quantum Dots Retained Initial Photoluminescence Efficiency in Sol-Gel SiO2 Film.

PubMed

Sun, Hongsheng; Xing, Yugui; Wu, Qinan; Yang, Ping

2015-02-01

A highly luminescent silica film was fabricated using tetraethyl orthosilicate (TEOS) and 3-aminopropyltrimethoxysilane (APS) through a controlled sol-gel reaction. The pre-hydrolysis of TEOS and APS which resulted in the mixture of TEOS and APS in a molecular level is a key for the formation of homogenous films. The aminopropyl groups in APS play an important role for obtaining homogeneous film with high photoluminescence (PL). Red-emitting hybrid SiO2-coated CdTe nano-crystals (NCs) were fabricated by a two-step synthesis including a thin SiO2 coating via a sol-gel process and a subsequent refluxing using green-emitting CdTe NCs. The hybrid SiO2-coated CdTe NCs were embedded in a functional SiO2 film via a two-step process including adding the NCs in SiO2 sol with a high viscosity and almost without ethanol and a subsequent spinning coating. The hybrid SiO2-coated CdTe NCs retained their initial PL efficiency (54%) in the film. Being encapsulated with the hybrid NCs in the film, no change on the absorption and PL spectra of red-emitting CdTe NCs (632 nm) was observed. This indicates the hybrid NCs is stable enough during preparation. This phenomenon is ascribed to the controlled sol-gel process and a hybrid SiO2 shell on CdTe NCs. Because these films exhibited high PL efficiency and stability, they will be utilizable for potential applications in many fields.

Age-related differences in perceptuomotor procedural learning in children.

PubMed

Lejeune, Caroline; Catale, Corinne; Schmitz, Xavier; Quertemont, Etienne; Meulemans, Thierry

2013-10-01

Procedural learning is generally considered to proceed in a series of phases, with cognitive resources playing an important role during the initial step. From a developmental perspective, little is known about the development of procedural learning or the role played by explicit cognitive processes during learning. The main objectives of this study were (a) to determine whether procedural learning performance improves with age by comparing groups of 7-year-old children, 10-year-old children, and adults and (b) to investigate the role played by executive functions during the acquisition in these three age groups. The 76 participants were assessed on a computerized adaptation of the mirror tracing paradigm. Results revealed that the youngest children had more difficulty in adapting to the task (they were slower and committed more errors at the beginning of the learning process) than 10-year-olds, but despite this age effect observed at the outset, all children improved performance across trials and transferred their skill to a different figure as well as adults. Correlational analyses showed that inhibition abilities play a key role in the performance of 10-year-olds and adults at the beginning of the learning but not in that of 7-year-olds. Overall, our results suggest that the age-related differences observed in our procedural learning task are at least partly due to the differential involvement of inhibition abilities, which may facilitate learning (so long as they are sufficiently developed) during the initial steps of the learning process; however, they would not be a necessary condition for skill learning to occur. Copyright © 2013 Elsevier Inc. All rights reserved.

The Neuro-Mechanical Processes That Underlie Goal-Directed Medio-Lateral APA during Gait Initiation.

PubMed

Honeine, Jean-Louis; Schieppati, Marco; Crisafulli, Oscar; Do, Manh-Cuong

2016-01-01

Gait initiation (GI) involves passing from bipedal to unipedal stance. It requires a rapid movement of the center of foot pressure (CoP) towards the future swing foot and of the center of mass (CoM) in the direction of the stance foot prior to the incoming step. This anticipatory postural adjustment (APA) allows disengaging the swing leg from the ground and establishing favorable conditions for stepping. This study aimed to describe the neuro-mechanical process that underlies the goal-directed medio-lateral (ML) APA. We hypothesized that controlled knee flexion of the stance leg contributes to the initial ML displacement of the CoP and to the calibration of the first step. Fourteen subjects initiated gait starting from three different initial stance widths of 15 cm (Small), 30 cm (Medium), and 45 cm (Large). Optoelectronic, force platform and electromyogram (EMG) measurements were performed. During APA, soleus activity diminished bilaterally, while tibialis anterior (TA) activity increased, more so in the stance leg than in the swing leg, and to a larger extent with increasing initial stance width. Knee flexion of the stance leg was observed during APA and correlated with the ML CoP displacement towards the swing leg. ML CoP and CoM displacements during APA increased with increasing stance width. The activity of stance-leg TA was correlated with the degree of knee flexion. Swing-leg tensor fasciae latae (TFL) was also active during APA. Across subjects, when stance-leg tibialis activity was low, TFL activity was large and vice versa. The modulation of the ML CoP position during APA allowed the gravity-driven torque to place the CoM just lateral to the stance foot during step execution. Accordingly, the gravity-driven torque, the ML CoM velocity during step execution, and the step width at foot contact (FC) were lower in the Small and greater in the Large condition. Consequently, the position of the stepping foot at FC remained close to the sagittal plane in all three conditions. Conclusively, coordinated activation of hip abductors and ankle dorsiflexors during APA displaces the CoP towards the swing leg, and sets the contact position for the swing foot.

The Neuro-Mechanical Processes That Underlie Goal-Directed Medio-Lateral APA during Gait Initiation

PubMed Central

Honeine, Jean-Louis; Schieppati, Marco; Crisafulli, Oscar; Do, Manh-Cuong

2016-01-01

Gait initiation (GI) involves passing from bipedal to unipedal stance. It requires a rapid movement of the center of foot pressure (CoP) towards the future swing foot and of the center of mass (CoM) in the direction of the stance foot prior to the incoming step. This anticipatory postural adjustment (APA) allows disengaging the swing leg from the ground and establishing favorable conditions for stepping. This study aimed to describe the neuro-mechanical process that underlies the goal-directed medio-lateral (ML) APA. We hypothesized that controlled knee flexion of the stance leg contributes to the initial ML displacement of the CoP and to the calibration of the first step. Fourteen subjects initiated gait starting from three different initial stance widths of 15 cm (Small), 30 cm (Medium), and 45 cm (Large). Optoelectronic, force platform and electromyogram (EMG) measurements were performed. During APA, soleus activity diminished bilaterally, while tibialis anterior (TA) activity increased, more so in the stance leg than in the swing leg, and to a larger extent with increasing initial stance width. Knee flexion of the stance leg was observed during APA and correlated with the ML CoP displacement towards the swing leg. ML CoP and CoM displacements during APA increased with increasing stance width. The activity of stance-leg TA was correlated with the degree of knee flexion. Swing-leg tensor fasciae latae (TFL) was also active during APA. Across subjects, when stance-leg tibialis activity was low, TFL activity was large and vice versa. The modulation of the ML CoP position during APA allowed the gravity-driven torque to place the CoM just lateral to the stance foot during step execution. Accordingly, the gravity-driven torque, the ML CoM velocity during step execution, and the step width at foot contact (FC) were lower in the Small and greater in the Large condition. Consequently, the position of the stepping foot at FC remained close to the sagittal plane in all three conditions. Conclusively, coordinated activation of hip abductors and ankle dorsiflexors during APA displaces the CoP towards the swing leg, and sets the contact position for the swing foot. PMID:27642280

Freedom of Information Act Requests: Six Keys to Handling Them

DTIC Science & Technology

2016-01-01

Defense AT&L: January–February 2016 50 Freedom of Information Act Requests Six Keys to Handling Them Michael A. Rodgers Rodgers is a professor of...crucial mission tasks. Understanding and using the six steps and keys provided above will free you from FOIA-induced distractions. The author can be contacted at michael.rodgers@dau.mil.

One-time pad, complexity of verification of keys, and practical security of quantum cryptography

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

Molotkov, S. N., E-mail: sergei.molotkov@gmail.com

2016-11-15

A direct relation between the complexity of the complete verification of keys, which is one of the main criteria of security in classical systems, and a trace distance used in quantum cryptography is demonstrated. Bounds for the minimum and maximum numbers of verification steps required to determine the actual key are obtained.

Soliton radiation beat analysis of optical pulses generated from two continuous-wave lasers

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

Zajnulina, M.; Giannone, D.; Haynes, R.

We propose a fibre-based approach for generation of optical frequency combs (OFCs) with the aim of calibration of astronomical spectrographs in the low and medium-resolution range. This approach includes two steps: in the first step, an appropriate state of optical pulses is generated and subsequently moulded in the second step delivering the desired OFC. More precisely, the first step is realised by injection of two continuous-wave (CW) lasers into a conventional single-mode fibre, whereas the second step generates a broad OFC by using the optical solitons generated in step one as initial condition. We investigate the conversion of a bichromaticmore » input wave produced by two initial CW lasers into a train of optical solitons, which happens in the fibre used as step one. Especially, we are interested in the soliton content of the pulses created in this fibre. For that, we study different initial conditions (a single cosine-hump, an Akhmediev breather, and a deeply modulated bichromatic wave) by means of soliton radiation beat analysis and compare the results to draw conclusion about the soliton content of the state generated in the first step. In case of a deeply modulated bichromatic wave, we observed the formation of a collective soliton crystal for low input powers and the appearance of separated solitons for high input powers. An intermediate state showing the features of both, the soliton crystal and the separated solitons, turned out to be most suitable for the generation of OFC for the purpose of calibration of astronomical spectrographs.« less

Soliton radiation beat analysis of optical pulses generated from two continuous-wave lasers.

PubMed

Zajnulina, M; Böhm, M; Blow, K; Rieznik, A A; Giannone, D; Haynes, R; Roth, M M

2015-10-01

We propose a fibre-based approach for generation of optical frequency combs (OFCs) with the aim of calibration of astronomical spectrographs in the low and medium-resolution range. This approach includes two steps: in the first step, an appropriate state of optical pulses is generated and subsequently moulded in the second step delivering the desired OFC. More precisely, the first step is realised by injection of two continuous-wave (CW) lasers into a conventional single-mode fibre, whereas the second step generates a broad OFC by using the optical solitons generated in step one as initial condition. We investigate the conversion of a bichromatic input wave produced by two initial CW lasers into a train of optical solitons, which happens in the fibre used as step one. Especially, we are interested in the soliton content of the pulses created in this fibre. For that, we study different initial conditions (a single cosine-hump, an Akhmediev breather, and a deeply modulated bichromatic wave) by means of soliton radiation beat analysis and compare the results to draw conclusion about the soliton content of the state generated in the first step. In case of a deeply modulated bichromatic wave, we observed the formation of a collective soliton crystal for low input powers and the appearance of separated solitons for high input powers. An intermediate state showing the features of both, the soliton crystal and the separated solitons, turned out to be most suitable for the generation of OFC for the purpose of calibration of astronomical spectrographs.

Soliton radiation beat analysis of optical pulses generated from two continuous-wave lasers

NASA Astrophysics Data System (ADS)

Zajnulina, M.; Böhm, M.; Blow, K.; Rieznik, A. A.; Giannone, D.; Haynes, R.; Roth, M. M.

2015-10-01

We propose a fibre-based approach for generation of optical frequency combs (OFCs) with the aim of calibration of astronomical spectrographs in the low and medium-resolution range. This approach includes two steps: in the first step, an appropriate state of optical pulses is generated and subsequently moulded in the second step delivering the desired OFC. More precisely, the first step is realised by injection of two continuous-wave (CW) lasers into a conventional single-mode fibre, whereas the second step generates a broad OFC by using the optical solitons generated in step one as initial condition. We investigate the conversion of a bichromatic input wave produced by two initial CW lasers into a train of optical solitons, which happens in the fibre used as step one. Especially, we are interested in the soliton content of the pulses created in this fibre. For that, we study different initial conditions (a single cosine-hump, an Akhmediev breather, and a deeply modulated bichromatic wave) by means of soliton radiation beat analysis and compare the results to draw conclusion about the soliton content of the state generated in the first step. In case of a deeply modulated bichromatic wave, we observed the formation of a collective soliton crystal for low input powers and the appearance of separated solitons for high input powers. An intermediate state showing the features of both, the soliton crystal and the separated solitons, turned out to be most suitable for the generation of OFC for the purpose of calibration of astronomical spectrographs.

The promotional effects of cesium promoter on higher alcohol synthesis from syngas over cesium-promoted Cu/ZnO/Al2O3 catalysts

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

Sun, Jie; Cai, Qiuxia; Wan, Yan

In this study, the promotional effects of cesium promoter on higher alcohol (C2+OH) synthesis from syngas over Cs-Cu/ZnO/Al2O3 catalysts were investigated using a combined experimental and theoretical density functional theory (DFT) calculation method. In the presence of cesium, the C2+OH productivity increases from 77.1 g•kgcat-1•h-1 to 157.3 g•kgcat-1•h-1 at 583 K due to the enhancement of the initial C–C bond formation. Detailed analysis of chain growth probabilities (CGPs) confirms that initial C–C bond formation is the rate-determining step in the temperature range of 543-583 K. Addition of cesium promoter significantly increases the productivities of 2-methyl-1-propanol, while the CGPs values (C3*more » to 2-methyl-C3*) is almost unaffected. With the assistance of cesium promoter, the CGPs of the initial C–C bond formation step (C1* to C2*) could be increased from 0.13 to 0.25 at 583 K. DFT calculations indicate that the initial C–C bond formation is mainly contributed by the HCO+HCO coupling reaction over the ZnCu(211) model surface. In the presence of the Cs2O, the stabilities of key reaction intermediates such as HCO and H2CO are enhanced which facilitates both HCO+HCO and HCO+H2CO coupling reaction steps with lower activation barriers over the Cs2O-ZnCu(211) surface. The promotional effects of cesium on the C2+OH productivity are also benefited from the competitive CH+HCO coupling reaction over CH hydrogenation that leads to lower alkane formation. In addition, Bader charge analysis suggests that the presence of cesium ions would facilitate the nucleophilic reaction between HCO and H2CO for initial C–C bond formation. This work was supported by the National Natural Science Foundation of China (No. 91545114 and No. 91545203). We appreciate the joint PhD scholarship support from the China Scholarship Council. The authors would also like to thank the support from Collaborative Innovation Center of Chemistry for Energy Materials (2011-iChEM). DM was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences. Computing time was granted by the William R. Wiley Environmental Molecular Sciences Laboratory (EMSL). EMSL is a national scientific user facility located at Pacific Northwest National Laboratory (PNNL) and sponsored by DOE’s Office of Biological and Environmental Research. PNNL is a multiprogram national laboratory operated for DOE by Battelle Memorial Institute. We also appreciate the support from Sinochem Quanzhou Petrochemical Co. Ltd.« less

Optimizing identification and management of COPD patients - reviewing the role of the community pharmacist.

PubMed

van der Molen, Thys; van Boven, Job F M; Maguire, Terence; Goyal, Pankaj; Altman, Pablo

2017-01-01

The aim of this paper was to propose key steps for community pharmacist integration into a patient care pathway for chronic obstructive pulmonary disease (COPD) management. A literature search was conducted to identify publications focusing on the role of the community pharmacist in identification and management of COPD. The literature search highlighted evidence supporting an important role for pharmacists at each of the four key steps in the patient care pathway for COPD management. Step 1 (primary prevention): pharmacists are ideally placed to provide information on disease awareness and risk prevention campaigns, and to encourage lifestyle interventions, including smoking cessation. Step 2 (early detection/case finding): pharmacists are often the first point of contact between the patient and the healthcare system and can therefore play an important role in the early identification of patients with COPD. Step 3 (management and ongoing support): pharmacists can assist patients by providing advice and education on dosage, inhaler technique, treatment expectations and the importance of adherence, and by supporting self-management, including recognition and treatment of COPD exacerbations. Step 4 (review and follow-up): pharmacists can play an important role in monitoring adherence and ongoing inhaler technique in patients with COPD. In summary, pharmacists are ideally positioned to play a vital role in all key stages of an integrated COPD patient care pathway from early disease detection to the support of management plans, including advice and counselling regarding medications, inhaler technique and treatment adherence. Areas requiring additional consideration include pharmacist training, increasing awareness of the pharmacist role, administration and reimbursement, and increasing physician-pharmacist collaboration. © 2016 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

The effect of cane use on the compensatory step following posterior perturbations.

PubMed

Hall, Courtney D; Jensen, Jody L

2004-08-01

The compensatory step is a critical component of the balance response and is impaired in older fallers. The purpose of this research was to examine whether utilization of a cane modified the compensatory step response following external posterior perturbations. Single subject withdrawal design was employed. Single subject statistical analysis--the standard deviation bandwidth-method--supplemented visual analysis of the data. Four older adults (range: 73-83 years) with balance impairment who habitually use a cane completed this study. Subjects received a series of sudden backward pulls that were large enough to elicit compensatory stepping. We examined the following variables both with and without cane use: timing of cane loading relative to step initiation and center of mass acceleration, stability margin, center of mass excursion and velocity, step length and width. No participant loaded the cane prior to initiation of the first compensatory step. There was no effect of cane use on the stability margin, nor was there an effect of cane use on center of mass excursion or velocity, or step length or width. These data suggest that cane use does not necessarily improve balance recovery following an external posterior perturbation when the individual is forced to rely on compensatory stepping. Instead these data suggest that the strongest factor in modifying step characteristics is experience with the perturbation.

THE EFFECT OF STEP RATE MANIPULATION ON FOOT STRIKE PATTERN OF LONG DISTANCE RUNNERS.

PubMed

Allen, Darrell J; Heisler, Hollie; Mooney, Jennifer; Kring, Richard

2016-02-01

Running gait retraining to change foot strike pattern in runners from a heel strike pattern to a non heel- strike pattern has been shown to reduce impact forces and may help to reduce running related injuries. Step rate manipulation above preferred is known to help decrease step length, foot inclination angle, and vertical mass excursion, but has not yet been evaluated as a method to change foot strike pattern. The purpose of this study was to investigate the effect of step rate manipulation on foot strike pattern in shod recreational runners who run with a heel strike pattern. A secondary purpose was to describe the effect of step rate manipulation at specific percentages above preferred on foot inclination angle at initial contact. Forty volunteer runners, who were self-reported heel strikers and had a weekly running mileage of at least 10 miles, were recruited. Runners were confirmed to be heel strikers during the warm up period on the treadmill. The subject's step rate was determined at their preferred running pace. A metronome was used to increase step rate above the preferred step rate by 5%, 10% and 15%. 2D video motion analysis was utilized to determine foot strike pattern and to measure foot inclination angle at initial contact for each step rate condition. There was a statistically significant change in foot strike pattern from a heel strike pattern to a mid-foot or forefoot strike pattern at both 10% and 15% step rates above preferred. Seven of the 40 subjects (17.5%) changed from a heel- strike pattern to a non- heel strike pattern at +10% and 12 of the 40 subjects (30%) changed to a non-heel strike pattern at +15%. Mean foot inclination angle at initial contact showed a statistically significant change (reduction) as step rate increased. Step rate manipulation of 10% or greater may be enough to change foot strike pattern from a heel strike to a mid-foot or forefoot strike pattern in a small percentage of recreational runners who run in traditional running shoes. If changing the foot strike pattern is the main goal, other gait re-training methods may be needed to make a change from a heel strike to a non-heel strike pattern. Step rate manipulation shows a progressive reduction of foot inclination angle at 5%, 10%, and 15% above preferred step rate which reduces the severity of the heel strike at initial contact. Step rate manipulation of at least +10% above preferred may be an effective running gait retraining method for clinicians to decrease the severity of heel strike and possibly assist a runner to change to a non-heel strike pattern. 3.

Optimizing Fungal DNA Extraction Methods from Aerosol Filters

NASA Astrophysics Data System (ADS)

Jimenez, G.; Mescioglu, E.; Paytan, A.

2016-12-01

Fungi and fungal spores can be picked up from terrestrial ecosystems, transported long distances, and deposited into marine ecosystems. It is important to study dust-borne fungal communities, because they can stay viable and effect the ambient microbial populations, which are key players in biogeochemical cycles. One of the challenges of studying dust-borne fungal populations is that aerosol samples contain low biomass, making extracting good quality DNA very difficult. The aim of this project was to increase DNA yield by optimizing DNA extraction methods. We tested aerosol samples collected from Haifa, Israel (polycarbonate filter), Monterey Bay, CA (quartz filter) and Bermuda (quartz filter). Using the Qiagen DNeasy Plant Kit, we tested the effect of altering bead beating times and incubation times, adding three freeze and thaw steps, initially washing the filters with buffers for various lengths of time before using the kit, and adding a step with 30 minutes of sonication in 65C water. Adding three freeze/thaw steps, adding a sonication step, washing with a phosphate buffered saline overnight, and increasing incubation time to two hours, in that order, resulted in the highest increase in DNA for samples from Israel (polycarbonate). DNA yield of samples from Monterey (quart filter) increased about 5 times when washing with buffers overnight (phosphate buffered saline and potassium phophate buffer), adding a sonication step, and adding three freeze and thaw steps. Samples collected in Bermuda (quartz filter) had the highest increase in DNA yield from increasing incubation to 2 hours, increasing bead beating time to 6 minutes, and washing with buffers overnight (phosphate buffered saline and potassium phophate buffer). Our results show that DNA yield can be increased by altering various steps of the Qiagen DNeasy Plant Kit protocol, but different types of filters collected at different sites respond differently to alterations. These results can be used as preliminary results to continue developing fungi DNA extraction methods. Developing these methods will be important as dust storms are predicted to increase due to increased draughts and anthropogenic activity, and the fungal communities of these dust-storms are currently relatively understudied.

Permeability and kinetic coefficients for mesoscale BCF surface step dynamics: Discrete two-dimensional deposition-diffusion equation analysis

DOE PAGES

Zhao, Renjie; Evans, James W.; Oliveira, Tiago J.

2016-04-08

Here, a discrete version of deposition-diffusion equations appropriate for description of step flow on a vicinal surface is analyzed for a two-dimensional grid of adsorption sites representing the stepped surface and explicitly incorporating kinks along the step edges. Model energetics and kinetics appropriately account for binding of adatoms at steps and kinks, distinct terrace and edge diffusion rates, and possible additional barriers for attachment to steps. Analysis of adatom attachment fluxes as well as limiting values of adatom densities at step edges for nonuniform deposition scenarios allows determination of both permeability and kinetic coefficients. Behavior of these quantities is assessedmore » as a function of key system parameters including kink density, step attachment barriers, and the step edge diffusion rate.« less

Permeability and kinetic coefficients for mesoscale BCF surface step dynamics: Discrete two-dimensional deposition-diffusion equation analysis

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

Zhao, Renjie; Evans, James W.; Oliveira, Tiago J.

Here, a discrete version of deposition-diffusion equations appropriate for description of step flow on a vicinal surface is analyzed for a two-dimensional grid of adsorption sites representing the stepped surface and explicitly incorporating kinks along the step edges. Model energetics and kinetics appropriately account for binding of adatoms at steps and kinks, distinct terrace and edge diffusion rates, and possible additional barriers for attachment to steps. Analysis of adatom attachment fluxes as well as limiting values of adatom densities at step edges for nonuniform deposition scenarios allows determination of both permeability and kinetic coefficients. Behavior of these quantities is assessedmore » as a function of key system parameters including kink density, step attachment barriers, and the step edge diffusion rate.« less

Syntheses of strychnine, norfluorocurarine, dehydrodesacetylretuline, and valparicine enabled by intramolecular cycloadditions of Zincke aldehydes.

PubMed

Martin, David B C; Nguyen, Lucas Q; Vanderwal, Christopher D

2012-01-06

A full account of the development of the base-mediated intramolecular Diels-Alder cycloadditions of tryptamine-derived Zincke aldehydes is described. This important complexity-generating transformation provides the tetracyclic core of many indole monoterpene alkaloids in only three steps from commercially available starting materials and played a key role in short syntheses of norfluorocurarine (five steps), dehydrodesacetylretuline (six steps), valparicine (seven steps), and strychnine (six steps). Reasonable mechanistic possibilities for this reaction, a surprisingly facile dimerization of the products, and an unexpected cycloreversion to regenerate Zincke aldehydes under specific conditions are also discussed.

New Reduced Two-Time Step Method for Calculating Combustion and Emission Rates of Jet-A and Methane Fuel With and Without Water Injection

NASA Technical Reports Server (NTRS)

Molnar, Melissa; Marek, C. John

2004-01-01

A simplified kinetic scheme for Jet-A, and methane fuels with water injection was developed to be used in numerical combustion codes, such as the National Combustor Code (NCC) or even simple FORTRAN codes that are being developed at Glenn. The two time step method is either an initial time averaged value (step one) or an instantaneous value (step two). The switch is based on the water concentration in moles/cc of 1x10(exp -20). The results presented here results in a correlation that gives the chemical kinetic time as two separate functions. This two step method is used as opposed to a one step time averaged method previously developed to determine the chemical kinetic time with increased accuracy. The first time averaged step is used at the initial times for smaller water concentrations. This gives the average chemical kinetic time as a function of initial overall fuel air ratio, initial water to fuel mass ratio, temperature, and pressure. The second instantaneous step, to be used with higher water concentrations, gives the chemical kinetic time as a function of instantaneous fuel and water mole concentration, pressure and temperature (T4). The simple correlations would then be compared to the turbulent mixing times to determine the limiting properties of the reaction. The NASA Glenn GLSENS kinetics code calculates the reaction rates and rate constants for each species in a kinetic scheme for finite kinetic rates. These reaction rates were then used to calculate the necessary chemical kinetic times. Chemical kinetic time equations for fuel, carbon monoxide and NOx were obtained for Jet-A fuel and methane with and without water injection to water mass loadings of 2/1 water to fuel. A similar correlation was also developed using data from NASA's Chemical Equilibrium Applications (CEA) code to determine the equilibrium concentrations of carbon monoxide and nitrogen oxide as functions of overall equivalence ratio, water to fuel mass ratio, pressure and temperature (T3). The temperature of the gas entering the turbine (T4) was also correlated as a function of the initial combustor temperature (T3), equivalence ratio, water to fuel mass ratio, and pressure.

Estimating heterotrophic respiration at large scales: challenges, approaches, and next steps

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

Bond-Lamberty, Benjamin; Epron, Daniel; Harden, Jennifer W.

2016-06-27

Heterotrophic respiration (HR), the aerobic and anaerobic processes mineralizing organic matter, is a key carbon flux but one impossible to measure at scales significantly larger than small experimental plots. This impedes our ability to understand carbon and nutrient cycles, benchmark models, or reliably upscale point measurements. Given that a new generation of highly mechanistic, genomic-specific global models is not imminent, we suggest that a useful step to improve this situation would be the development of "Decomposition Functional Types" (DFTs). Analogous to plant functional types (PFTs), DFTs would abstract and capture important differences in HR metabolism and flux dynamics, allowing modelsmore » to efficiently group and vary these characteristics across space and time. We argue that DFTs should be initially informed by top-down expert opinion, but ultimately developed using bottom-up, data-driven analyses, and provide specific examples of potential dependent and independent variables that could be used. We present and discuss an example clustering analysis to show how model-produced annual HR can be broken into distinct groups associated with global variability in biotic and abiotic factors, and demonstrate that these groups are distinct from already-existing PFTs. A similar analysis, incorporating observational data, could form a basis for future DFTs. Finally, we suggest next steps and critical priorities: collection and synthesis of existing data; more in-depth analyses combining open data with high-performance computing; rigorous testing of analytical results; and planning by the global modeling community for decoupling decomposition from fixed site data. These are all critical steps to build a foundation for DFTs in global models, thus providing the ecological and climate change communities with robust, scalable estimates of HR at large scales.« less

Estimating heterotrophic respiration at large scales: Challenges, approaches, and next steps

DOE PAGES

Bond-Lamberty, Ben; Epron, Daniel; Harden, Jennifer; ...

2016-06-27

Heterotrophic respiration (HR), the aerobic and anaerobic processes mineralizing organic matter, is a key carbon flux but one impossible to measure at scales significantly larger than small experimental plots. This impedes our ability to understand carbon and nutrient cycles, benchmark models, or reliably upscale point measurements. Given that a new generation of highly mechanistic, genomic-specific global models is not imminent, we suggest that a useful step to improve this situation would be the development of Decomposition Functional Types (DFTs). Analogous to plant functional types (PFTs), DFTs would abstract and capture important differences in HR metabolism and flux dynamics, allowing modelersmore » and experimentalists to efficiently group and vary these characteristics across space and time. We argue that DFTs should be initially informed by top-down expert opinion, but ultimately developed using bottom-up, data-driven analyses, and provide specific examples of potential dependent and independent variables that could be used. We present an example clustering analysis to show how annual HR can be broken into distinct groups associated with global variability in biotic and abiotic factors, and demonstrate that these groups are distinct from (but complementary to) already-existing PFTs. A similar analysis incorporating observational data could form the basis for future DFTs. Finally, we suggest next steps and critical priorities: collection and synthesis of existing data; more in-depth analyses combining open data with rigorous testing of analytical results; using point measurements and realistic forcing variables to constrain process-based models; and planning by the global modeling community for decoupling decomposition from fixed site data. Lastly, these are all critical steps to build a foundation for DFTs in global models, thus providing the ecological and climate change communities with robust, scalable estimates of HR.« less

Estimating heterotrophic respiration at large scales: Challenges, approaches, and next steps

USGS Publications Warehouse

Bond-Lamberty, Ben; Epron, Daniel; Harden, Jennifer W.; Harmon, Mark E.; Hoffman, Forrest; Kumar, Jitendra; McGuire, Anthony David; Vargas, Rodrigo

2016-01-01

Heterotrophic respiration (HR), the aerobic and anaerobic processes mineralizing organic matter, is a key carbon flux but one impossible to measure at scales significantly larger than small experimental plots. This impedes our ability to understand carbon and nutrient cycles, benchmark models, or reliably upscale point measurements. Given that a new generation of highly mechanistic, genomic-specific global models is not imminent, we suggest that a useful step to improve this situation would be the development of “Decomposition Functional Types” (DFTs). Analogous to plant functional types (PFTs), DFTs would abstract and capture important differences in HR metabolism and flux dynamics, allowing modelers and experimentalists to efficiently group and vary these characteristics across space and time. We argue that DFTs should be initially informed by top-down expert opinion, but ultimately developed using bottom-up, data-driven analyses, and provide specific examples of potential dependent and independent variables that could be used. We present an example clustering analysis to show how annual HR can be broken into distinct groups associated with global variability in biotic and abiotic factors, and demonstrate that these groups are distinct from (but complementary to) already-existing PFTs. A similar analysis incorporating observational data could form the basis for future DFTs. Finally, we suggest next steps and critical priorities: collection and synthesis of existing data; more in-depth analyses combining open data with rigorous testing of analytical results; using point measurements and realistic forcing variables to constrain process-based models; and planning by the global modeling community for decoupling decomposition from fixed site data. These are all critical steps to build a foundation for DFTs in global models, thus providing the ecological and climate change communities with robust, scalable estimates of HR.

Won't stop or can't stop? Food restriction as a habitual behavior among individuals with anorexia nervosa or atypical anorexia nervosa.

PubMed

Coniglio, Kathryn A; Becker, Kendra R; Franko, Debra L; Zayas, Lazaro V; Plessow, Franziska; Eddy, Kamryn T; Thomas, Jennifer J

2017-08-01

Food restriction among individuals with anorexia nervosa (AN) is regarded as a goal-directed behavior. However, Walsh (2013) theorized that, although restriction is initially maintained by operant conditioning (with successful weight loss and external praise as salient rewards), it ultimately becomes a classically conditioned habit, persisting regardless of the presence of these once-salient rewards. Understanding food restriction as a well-ingrained habit may provide insight into treatment resistance. Further, it is not clear whether habitual food restriction is present among individuals with atypical AN (i.e. who engage in food restriction but are not low-weight). This study evaluated whether strength of habit predicted self-reported restriction above and beyond cognitive restraint. Seventy-eight individuals with AN or atypical AN completed the Eating Pathology Symptoms Inventory Restriction (EPSI-R) and Cognitive Restraint (EPSI-CR) subscales and the Self-Report Habit Index (SRHI) adapted for food restriction. We used a hierarchical multiple regression model to test whether habit strength predicted food restriction above and beyond cognitive restraint. After adding illness duration (step 1) and diagnosis (step 2) to the model, cognitive restraint (step 3) was not significant in explaining variation in restriction, whereas adding habit strength to the model (step 4) explained 27.9% of the variance in restriction (p<0.001). This is the first study to test a key component of Walsh's theory. Results provide support for food restriction maintenance through habit, rather than through effortful cognitive restraint. Because current models of AN characterize food restriction as purposeful, further research is needed to better understand habitual restriction in AN. Copyright © 2017 Elsevier Ltd. All rights reserved.

Numerical modelling of edge-driven convection during rift-to-drift transition: application to the Red Sea

NASA Astrophysics Data System (ADS)

Fierro, Elisa; Capitanio, Fabio A.; Schettino, Antonio; Morena Salerno, V.

2017-04-01

We use numerical modeling to investigate the coupling of mantle instabilities and surface tectonics along lithospheric steps developing during rifting. We address whether edge driven convection (EDC) beneath rifted continental margins and shear flow during rift-drift transition can play a role in the observed post-rift compressive tectonic evolution of the divergent continental margins along the Red Sea. We run a series of 2D simulations to examine the relationship between the maximum compression and key geometrical parameters of the step beneath continental margins, such as the step height due to lithosphere thickness variation and the width of the margins, and test the effect of rheology varying temperature- and stress-dependent viscosity in the lithosphere and asthenosphere. The development of instabilities is initially illustrated as a function of these parameters, to show the controls on the lithosphere strain distribution and magnitude. We then address the transient evolution of the instabilities to characterize their duration. In an additional suite of models, we address the development of EDC during plate motions, thus accounting for the mantle shearing due to spreading. Our results show an increase of strain with the step height as well as with the margin width up to 200 km. After this value the influence of ridge margin can be neglected. Strain rates are, then, quantified for a range of laboratory-constrained constitutive laws for mantle and lithosphere forming minerals. These models propose a viable mechanism to explain the post-rift tectonic inversion observed along the Arabian continental margin and the episodic ultra-fast sea floor spreading in the central Red Sea, where the role of EDC has been invoked.

Towards Developing an Initial Programme Theory: Programme Designers and Managers Assumptions on the Antiretroviral Treatment Adherence Club Programme in Primary Health Care Facilities in the Metropolitan Area of Western Cape Province, South Africa.

PubMed

Mukumbang, Ferdinand C; van Belle, Sara; Marchal, Bruno; van Wyk, Brian

2016-01-01

The antiretroviral adherence club intervention was rolled out in primary health care facilities in the Western Cape province of South Africa to relieve clinic congestion, and improve retention in care, and treatment adherence in the face of growing patient loads. We adopted the realist evaluation approach to evaluate what aspects of antiretroviral club intervention works, for what sections of the patient population, and under which community and health systems contexts, to inform guidelines for scaling up of the intervention. In this article, we report on a step towards the development of a programme theory-the assumptions of programme designers and health service managers with regard to how and why the adherence club intervention is expected to achieve its goals and perceptions on how it has done so (or not). We adopted an exploratory qualitative research design. We conducted a document review of 12 documents on the design and implementation of the adherence club intervention, and key informant interviews with 12 purposively selected programme designers and managers. Thematic content analysis was used to identify themes attributed to the programme actors, context, mechanisms, and outcomes. Using the context-mechanism-outcome configurational tool, we provided an explanatory focus of how the adherence club intervention is roll-out and works guided by the realist perspective. We classified the assumptions of the adherence club designers and managers into the rollout, implementation, and utilisation of the adherence club programme, constructed around the providers, management/operational staff, and patients, respectively. Two rival theories were identified at the patient-perspective level. We used these perspectives to develop an initial programme theory of the adherence club intervention, which will be tested in a later phase. The perspectives of the programme designers and managers provided an important step towards developing an initial programme theory, which will guide our realist evaluation of the adherence club programme in South Africa.

Triggered lightning strikes to aircraft and natural intracloud discharges

NASA Technical Reports Server (NTRS)

Mazur, Vladislav

1989-01-01

The physical model of Mazur (1989) for triggering lightning strikes by aircraft was used to interpret the initiation of intracloud flashes observed by the French UHF-VHF interferometric system. It is shown that both the intracloud discharges and airplane-triggered lightning strikes were initiated by simultaneous bidirectional development of the negative stepped leader and the positive leader-continous current process. However, the negative stepped leader phase in triggered flashes is of shorter duration (tens of milliseconds), than that in intracloud flashes (usually hundreds of milliseconds). This is considered to be due to the fact that, on the aircraft there is a single initiation process, versus the numerous initiation processes that occur inside the cloud.

A case study: the initiative to improve RN scheduling at Hamilton Health Sciences.

PubMed

Wallace, Laurel-Anne; Pierson, Sharon

2008-01-01

In 2003, Hamilton Health Sciences embarked on an initiative to improve and standardize nursing schedules and scheduling practices. The scheduling project was one of several initiatives undertaken by a corporate-wide Nursing Resource Group established to enhance the work environment and patient care and to ensure appropriate utilization of nursing resources across the organization's five hospitals. This article focuses on major activities undertaken in the scheduling initiative. The step-by-step approach described, plus examples of the scheduling resources developed and samples of extended-tour schedules, will all provide insight, potential strategies and practical help for nursing administrators, human resources (HR) personnel and others interested in improving nurse scheduling.

From Diapers to Dating. A Parent's Guide to Raising Sexually Healthy Children.

ERIC Educational Resources Information Center

Haffner, Debra W.

This step-by-step program for raising sexually healthy children helps parents provide accurate information and communicate their own values to their children. Chapter 1, "The Basics"; includes "Sexually Healthy Families"; "The Key: Finding Teachable Moments"; and "Guidelines for Communication." Chapter 2,…

Nurse-led clinics: 10 essential steps to setting up a service.

PubMed

Hatchett, Richard

This article outlines 10 key steps for practitioners to consider when setting up and running a nurse-led clinic. It lays emphasis on careful planning, professional development and the need to audit and evaluate the service to ensure the clinic is measurably effective.

Pregnant & Lactating Mothers' Attitudes and Practice of the Ten Steps to Successful Breastfeeding at King Fahd Hospital of University (KFHU)--Khobar, Saudi Arabia: Appraisal of Baby Friendly Hospital Initiatives

ERIC Educational Resources Information Center

Salem, Laila Younis Abu; Al Madani, Maha Mohammed

2015-01-01

Background: World Health organization (WHO) and the United Nations Children's Fund (UNICEF) have been recommended the application of the Ten Steps to Successful Breastfeeding of the Baby-Friendly Hospital Initiative (BFHI) in order to promote & support breastfeeding. The aim of this study was to assess pregnant and lactating mothers' attitudes…

Post-processing procedure for industrial quantum key distribution systems

NASA Astrophysics Data System (ADS)

Kiktenko, Evgeny; Trushechkin, Anton; Kurochkin, Yury; Fedorov, Aleksey

2016-08-01

We present algorithmic solutions aimed on post-processing procedure for industrial quantum key distribution systems with hardware sifting. The main steps of the procedure are error correction, parameter estimation, and privacy amplification. Authentication of classical public communication channel is also considered.

Angle comparison using an autocollimator

NASA Astrophysics Data System (ADS)

Geckeler, Ralf D.; Just, Andreas; Vasilev, Valentin; Prieto, Emilio; Dvorácek, František; Zelenika, Slobodan; Przybylska, Joanna; Duta, Alexandru; Victorov, Ilya; Pisani, Marco; Saraiva, Fernanda; Salgado, Jose-Antonio; Gao, Sitian; Anusorn, Tonmueanwai; Leng Tan, Siew; Cox, Peter; Watanabe, Tsukasa; Lewis, Andrew; Chaudhary, K. P.; Thalmann, Ruedi; Banreti, Edit; Nurul, Alfiyati; Fira, Roman; Yandayan, Tanfer; Chekirda, Konstantin; Bergmans, Rob; Lassila, Antti

2018-01-01

Autocollimators are versatile optical devices for the contactless measurement of the tilt angles of reflecting surfaces. An international key comparison (KC) on autocollimator calibration, EURAMET.L-K3.2009, was initiated by the European Association of National Metrology Institutes (EURAMET) to provide information on the capabilities in this field. The Physikalisch-Technische Bundesanstalt (PTB) acted as the pilot laboratory, with a total of 25 international participants from EURAMET and from the Asia Pacific Metrology Programme (APMP) providing measurements. This KC was the first one to utilise a high-resolution electronic autocollimator as a standard. In contrast to KCs in angle metrology which usually involve the full plane angle, it focused on relatively small angular ranges (+/-10 arcsec and +/-1000 arcsec) and step sizes (10 arcsec and 0.1 arcsec, respectively). This document represents the approved final report on the results of the KC. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCL, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

CALINX (California Information Exchange): a multi-stakeholder statewide initiative to improve healthcare information flows.

PubMed

Hopkins, D S; Oswald, N; McCaffrey, K; Bressler, S; Davidson, N; Vela, L

2000-01-01

Given the diffusion of responsibilities for gathering and reporting healthcare information in a managed care environment, California stakeholders are taking concrete steps to break the deadlock on data and information flows that has characterized the industry for some time. The California Information Exchange (CALINX) was established to facilitate the implementation of the Health Insurance Portability and Accountability Act (HIPAA) standards in California and to create trust for data exchange between trading partners, without which data exchange still will not occur. Strategic directions are set by the chief executives of key associations and organizations representing purchasers, plans, providers, and consumers. Multi-stakeholder workgroups have produced detailed data guidelines for the HIPAA standards along with rules for exchange of key data sets between trading partners. These rules address frequency, timeliness, and accuracy of data submission. Both the data guidelines and the rules have been tested in live demonstration projects, and the results of these projects have been reported to substantiate the business case for implementation. Further incentives are being built into contracts between purchasers and plans, and between plans and providers. CALINX is currently promoting widespread adoption of the data guidelines and rules for exchange with all members of the industry.

Industrial application for global quantum communication

NASA Astrophysics Data System (ADS)

Mirza, A.; Petruccione, F.

2012-09-01

In the last decade the quantum communication community has witnessed great advances in photonic quantum cryptography technology with the research, development and commercialization of automated Quantum Key Distribution (QKD) devices. These first generation devices are however bottlenecked by the achievable spatial coverage. This is due to the intrinsic absorption of the quantum particle into the communication medium. As QKD is of paramount importance in the future ICT landscape, various innovative solutions have been developed and tested to expand the spatial coverage of these networks such as the Quantum City initiative in Durban, South Africa. To expand this further into a global QKD-secured network, recent efforts have focussed on high-altitude free-space techniques through the use of satellites. This couples the QKD-secured Metropolitan Area Networks (MANs) with secured ground-tosatellite links as access points to a global network. Such a solution, however, has critical limitations that reduce its commercial feasibility. As parallel step to the development of satellitebased global QKD networks, we investigate the use of the commercial aircrafts' network as secure transport mechanisms in a global QKD network. This QKD-secured global network will provide a robust infrastructure to create, distribute and manage encryption keys between the MANs of the participating cities.

The Interaction Between IGF-1, Atherosclerosis and Vascular Aging

PubMed Central

Higashi, Yusuke; Quevedo, Henry C.; Tiwari, Summit; Sukhanov, Sergiy; Shai, Shaw-Yung; Anwar, Asif; Delafontaine, Patrice

2014-01-01

The process of vascular aging encompasses alterations in the function of endothelial (EC) and vascular smooth muscle cells (VSMCs) via oxidation, inflammation, cell senescence and epigenetic modifications, increasing the probability of atherosclerosis. Aged vessels exhibit decreased endothelial antithrombogenic properties, increased reactive oxygen species (ROS) generation and inflammatory signaling, increased migration of VSMCs to the subintimal space, impaired angiogenesis and increased elastin degradation. The key initiating step in atherogenesis is subendothelial accumulation of apolipoprotein-B containing low density lipoproteins resulting in activation of endothelial cells and recruitment of monocytes. Activated endothelial cells secrete “chemokines” that interact with cognate chemokine receptors on monocytes and promote directional migration. Recruitment of immune cells establishes a pro-inflammatory status, further causing elevated oxidative stress, which in turn triggers a series of events including apoptotic or necrotic death of vascular and non-vascular cells. Increased oxidative stress is also considered to be a key factor in mechanisms of aging-associated changes in tissue integrity and function. Experimental evidence indicates that insulin-like growth factor-1 (IGF-1) exerts anti-oxidant, anti-inflammatory and pro-survival effects on the vasculature, reducing atherosclerotic plaque burden and promoting features of atherosclerotic plaque stability. PMID:24943302

Autophagy wins the 2016 Nobel Prize in Physiology or Medicine: Breakthroughs in baker's yeast fuel advances in biomedical research

PubMed Central

Levine, Beth; Klionsky, Daniel J.

2017-01-01

Autophagy is an ancient pathway in which parts of eukaryotic cells are self-digested within the lysosome or vacuole. This process has been studied for the past seven decades; however, we are only beginning to gain a molecular understanding of the key steps required for autophagy. Originally characterized as a hormonal and starvation response, we now know that autophagy has a much broader role in biology, including organellar remodeling, protein and organelle quality control, prevention of genotoxic stress, tumor suppression, pathogen elimination, regulation of immunity and inflammation, maternal DNA inheritance, metabolism, and cellular survival. Although autophagy is usually a degradative pathway, it also participates in biosynthetic and secretory processes. Given that autophagy has a fundamental role in many essential cellular functions, it is not surprising that autophagic dysfunction is associated with a wide range of human diseases. Genetic studies in various fungi, particularly Saccharomyces cerevisiae, provided the key initial breakthrough that led to an explosion of research on the basic mechanisms and the physiological connections of autophagy to health and disease. The Nobel Committee has recognized this breakthrough by the awarding of the 2016 Nobel Prize in Physiology or Medicine for research in autophagy. PMID:28039434

Neonatal resuscitation: advances in training and practice

PubMed Central

Sawyer, Taylor; Umoren, Rachel A; Gray, Megan M

2017-01-01

Each year in the US, some four hundred thousand newborns need help breathing when they are born. Due to the frequent need for resuscitation at birth, it is vital to have evidence-based care guidelines and to provide effective neonatal resuscitation training. Every five years, the International Liaison Committee on Resuscitation (ILCOR) reviews the science of neonatal resuscitation. In the US, the American Heart Association (AHA) develops treatment guidelines based on the ILCOR science review, and the Neonatal Resuscitation Program (NRP) translates the AHA guidelines into an educational curriculum. In this report, we review recent advances in neonatal resuscitation training and practice. We begin with a review of the new 7th edition NRP training curriculum. Then, we examine key changes to the 2015 AHA neonatal resuscitation guidelines. The four components of the NRP curriculum reviewed here include eSim®, Performance Skills Stations, Integrated Skills Station, and Simulation and Debriefing. The key changes to the AHA neonatal resuscitation guidelines reviewed include initial steps of newborn care, positive-pressure ventilation, endotracheal intubation and use of laryngeal mask, chest compressions, medications, resuscitation of preterm newborns, and ethics and end-of-life care. We hope this report provides a succinct review of recent advances in neonatal resuscitation. PMID:28096704

Hairpin Folding of HIV gp41 Abrogates Lipid Mixing Function at Physiologic pH and Inhibits Lipid Mixing by Exposed gp41 Constructs†

PubMed Central

Sackett, Kelly; Nethercott, Matthew J.; Shai, Yechiel; Weliky, David P.

2009-01-01

Conformational changes in the HIV gp41 protein are directly correlated with fusion between the HIV and target cell plasma membranes which is the initial step of infection. Key gp41 fusion conformations include an early extended conformation termed pre-hairpin which contains exposed regions and a final low energy conformation termed hairpin which has compact six-helix bundle structure. Current fusion models debate the roles of hairpin and pre-hairpin conformations in the process of membrane merger. In the present work, gp41 constructs have been engineered which correspond to fusion relevant parts of both pre-hairpin and hairpin conformations, and have been analyzed for their ability to induce lipid mixing between membrane vesicles. The data correlate membrane fusion function with the pre-hairpin conformation and suggest that one of the roles of the final hairpin conformation is sequestration of membrane perturbing gp41 regions with consequent loss of the membrane disruption induced earlier by the pre-hairpin structure. To our knowledge, this is the first biophysical study to delineate the membrane fusion potential of gp41 constructs modeling key fusion conformations. PMID:19222185

Role of the σ 54 Activator Interacting Domain in Bacterial Transcription Initiation

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

Siegel, Alexander R.; Wemmer, David E.

Bacterial sigma factors are subunits of RNA polymerase that direct the holoenzyme to specific sets of promoters in the genome and are a central element of regulating transcription. Most polymerase holoenzymes open the promoter and initiate transcription rapidly after binding. However, polymerase containing the members of the σ 54 family must be acted on by a transcriptional activator before DNA opening and initiation occur. A key domain in these transcriptional activators forms a hexameric AAA + ATPase that acts through conformational changes brought on by ATP hydrolysis. Contacts between the transcriptional activator and σ 54 are primarily made through anmore » N-terminal σ 54 activator interacting domain (AID). To better understand this mechanism of bacterial transcription initiation, we characterized the σ 54 AID by NMR spectroscopy and other biophysical methods and show that it is an intrinsically disordered domain in σ 54 alone. In this paper, we identified a minimal construct of the Aquifex aeolicus σ 54 AID that consists of two predicted helices and retains native-like binding affinity for the transcriptional activator NtrC1. Using the NtrC1 ATPase domain, bound with the non-hydrolyzable ATP analog ADP-beryllium fluoride, we studied the NtrC1–σ 54 AID complex using NMR spectroscopy. We show that the σ 54 AID becomes structured after associating with the core loops of the transcriptional activators in their ATP state and that the primary site of the interaction is the first predicted helix. Finally, understanding this complex, formed as the first step toward initiation, will help unravel the mechanism of σ 54 bacterial transcription initiation.« less

A Comparative Proteome Profile of Female Mouse Gonads Suggests a Tight Link between the Electron Transport Chain and Meiosis Initiation.

PubMed

Shen, Cong; Li, Mingrui; Zhang, Pan; Guo, Yueshuai; Zhang, Hao; Zheng, Bo; Teng, Hui; Zhou, Tao; Guo, Xuejiang; Huo, Ran

2018-01-01

Generation of haploid gametes by meiosis is a unique property of germ cells and is critical for sexual reproduction. Leaving mitosis and entering meiosis is a key step in germ cell development. Several inducers or intrinsic genes are known to be important for meiotic initiation, but the regulation of meiotic initiation, especially at the protein level, is still not well understood. We constructed a comparative proteome profile of female mouse fetal gonads at specific time points (11.5, 12.5, and 13.5 days post coitum), spanning a critical window for initiation of meiosis in female germ cells. We identified 3666 proteins, of which 473 were differentially expressed. Further bioinformatics analysis showed that these differentially expressed proteins were enriched in the mitochondria, especially in the electron transport chain and, notably, 9 proteins in electron transport chain Complex I were differentially expressed. We disrupted the mitochondrial electron transport chain function by adding the complex I inhibitor, rotenone to 11.5 days post coitum female gonads cultured in vitro. This treatment resulted in a decreased proportion of meiotic germ cells, as assessed by staining for histone γH2AX. Rotenone treatment also caused decreased ATP levels, increased reactive oxygen species levels and failure of the germ cells to undergo premeiotic DNA replication. These effects were partially rescued by adding Coenzyme Q10. Taken together, our results suggested that a functional electron transport chain is important for meiosis initiation. Our characterization of the quantitative proteome of female gonads provides an inventory of proteins, useful for understanding the mechanisms of meiosis initiation and female fertility. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Structural characterization of ribosome recruitment and translocation by type IV IRES

PubMed Central

Murray, Jason; Savva, Christos G; Shin, Byung-Sik; Dever, Thomas E; Ramakrishnan, V; Fernández, Israel S

2016-01-01

Viral mRNA sequences with a type IV IRES are able to initiate translation without any host initiation factors. Initial recruitment of the small ribosomal subunit as well as two translocation steps before the first peptidyl transfer are essential for the initiation of translation by these mRNAs. Using electron cryomicroscopy (cryo-EM) we have structurally characterized at high resolution how the Cricket Paralysis Virus Internal Ribosomal Entry Site (CrPV-IRES) binds the small ribosomal subunit (40S) and the translocation intermediate stabilized by elongation factor 2 (eEF2). The CrPV-IRES restricts the otherwise flexible 40S head to a conformation compatible with binding the large ribosomal subunit (60S). Once the 60S is recruited, the binary CrPV-IRES/80S complex oscillates between canonical and rotated states (Fernández et al., 2014; Koh et al., 2014), as seen for pre-translocation complexes with tRNAs. Elongation factor eEF2 with a GTP analog stabilizes the ribosome-IRES complex in a rotated state with an extra ~3 degrees of rotation. Key residues in domain IV of eEF2 interact with pseudoknot I (PKI) of the CrPV-IRES stabilizing it in a conformation reminiscent of a hybrid tRNA state. The structure explains how diphthamide, a eukaryotic and archaeal specific post-translational modification of a histidine residue of eEF2, is involved in translocation. DOI: http://dx.doi.org/10.7554/eLife.13567.001 PMID:27159451

Integrating nitric oxide into salicylic acid and jasmonic acid/ ethylene plant defense pathways.

PubMed

Mur, Luis A J; Prats, Elena; Pierre, Sandra; Hall, Michael A; Hebelstrup, Kim H

2013-01-01

Plant defense against pests and pathogens is known to be conferred by either salicylic acid (SA) or jasmonic acid (JA)/ethylene (ET) pathways, depending on infection or herbivore-grazing strategy. It is well attested that SA and JA/ET pathways are mutually antagonistic allowing defense responses to be tailored to particular biotic stresses. Nitric oxide (NO) has emerged as a major signal influencing resistance mediated by both signaling pathways but no attempt has been made to integrate NO into established SA/JA/ET interactions. NO has been shown to act as an inducer or suppressor of signaling along each pathway. NO will initiate SA biosynthesis and nitrosylate key cysteines on TGA-class transcription factors to aid in the initiation of SA-dependent gene expression. Against this, S-nitrosylation of NONEXPRESSOR OF PATHOGENESIS-RELATED PROTEINS1 (NPR1) will promote the NPR1 oligomerization within the cytoplasm to reduce TGA activation. In JA biosynthesis, NO will initiate the expression of JA biosynthetic enzymes, presumably to over-come any antagonistic effects of SA on JA-mediated transcription. NO will also initiate the expression of ET biosynthetic genes but a suppressive role is also observed in the S-nitrosylation and inhibition of S-adenosylmethionine transferases which provides methyl groups for ET production. Based on these data a model for NO action is proposed but we have also highlighted the need to understand when and how inductive and suppressive steps are used.

Integrating nitric oxide into salicylic acid and jasmonic acid/ ethylene plant defense pathways

PubMed Central

Mur, Luis A. J.; Prats, Elena; Pierre, Sandra; Hall, Michael A.; Hebelstrup, Kim H.

2013-01-01

Plant defense against pests and pathogens is known to be conferred by either salicylic acid (SA) or jasmonic acid (JA)/ethylene (ET) pathways, depending on infection or herbivore-grazing strategy. It is well attested that SA and JA/ET pathways are mutually antagonistic allowing defense responses to be tailored to particular biotic stresses. Nitric oxide (NO) has emerged as a major signal influencing resistance mediated by both signaling pathways but no attempt has been made to integrate NO into established SA/JA/ET interactions. NO has been shown to act as an inducer or suppressor of signaling along each pathway. NO will initiate SA biosynthesis and nitrosylate key cysteines on TGA-class transcription factors to aid in the initiation of SA-dependent gene expression. Against this, S-nitrosylation of NONEXPRESSOR OF PATHOGENESIS-RELATED PROTEINS1 (NPR1) will promote the NPR1 oligomerization within the cytoplasm to reduce TGA activation. In JA biosynthesis, NO will initiate the expression of JA biosynthetic enzymes, presumably to over-come any antagonistic effects of SA on JA-mediated transcription. NO will also initiate the expression of ET biosynthetic genes but a suppressive role is also observed in the S-nitrosylation and inhibition of S-adenosylmethionine transferases which provides methyl groups for ET production. Based on these data a model for NO action is proposed but we have also highlighted the need to understand when and how inductive and suppressive steps are used. PMID:23818890

Elucidating Key Motifs Required for Arp2/3-Dependent and Independent Actin Nucleation by Las17/WASP

PubMed Central

Urbanek, Agnieszka N.; Smaczynska-de Rooij, Iwona I.

2016-01-01

Actin nucleation is the key rate limiting step in the process of actin polymerization, and tight regulation of this process is critical to ensure actin filaments form only at specific times and at defined regions of the cell. Arp2/3 is a well-characterised protein complex that can promote nucleation of new filaments, though its activity requires additional nucleation promotion factors (NPFs). The best recognized of these factors are the WASP family of proteins that contain binding motifs for both monomeric actin and for Arp2/3. Previously we demonstrated that the yeast WASP homologue, Las17, in addition to activating Arp2/3 can also nucleate actin filaments de novo, independently of Arp2/3. This activity is dependent on its polyproline rich region. Through biochemical and in vivo analysis we have now identified key motifs within the polyproline region that are required for nucleation and elongation of actin filaments, and have addressed the role of the WH2 domain in the context of actin nucleation without Arp2/3. We have also demonstrated that full length Las17 is able to bind liposomes giving rise to the possibility of direct linkage of nascent actin filaments to specific membrane sites to which Las17 has been recruited. Overall, we propose that Las17 functions as the key initiator of de novo actin filament formation at endocytic sites by nucleating, elongating and tethering nascent filaments which then serve as a platform for Arp2/3 recruitment and function. PMID:27637067

Establishing a pragmatic framework to optimise health outcomes in heart failure and multimorbidity (ARISE-HF): A multidisciplinary position statement.

PubMed

Stewart, Simon; Riegel, Barbara; Boyd, Cynthia; Ahamed, Yasmin; Thompson, David R; Burrell, Louise M; Carrington, Melinda J; Coats, Andrew; Granger, Bradi B; Hides, Julie; Weintraub, William S; Moser, Debra K; Dickson, Victoria Vaughan; McDermott, Cressida J; Keates, Ashley K; Rich, Michael W

2016-06-01

Multimorbidity in heart failure (HF), defined as HF of any aetiology and multiple concurrent conditions that require active management, represents an emerging problem within the ageing HF patient population worldwide. To inform this position paper, we performed: 1) an initial review of the literature identifying the ten most common conditions, other than hypertension and ischaemic heart disease, complicating the management of HF (anaemia, arrhythmias, cognitive dysfunction, depression, diabetes, musculoskeletal disorders, renal dysfunction, respiratory disease, sleep disorders and thyroid disease) and then 2) a review of the published literature describing the association between HF with each of the ten conditions. From these data we describe a clinical framework, comprising five key steps, to potentially improve historically poor health outcomes in this patient population. We identified five key steps (ARISE-HF) that could potentially improve clinical outcomes if applied in a systematic manner: 1) Acknowledge multimorbidity as a clinical syndrome that is associated with poor health outcomes, 2) Routinely profile (using a standardised protocol - adapted to the local health care system) all patients hospitalised with HF to determine the extent of concurrent multimorbidity, 3) Identify individualised priorities and person-centred goals based on the extent and nature of multimorbidity, 4) Support individualised, home-based, multidisciplinary, case management to supplement standard HF management, and 5) Evaluate health outcomes well beyond acute hospitalisation and encompass all-cause events and a person-centred perspective in affected individuals. We propose ARISE-HF as a framework for improving typically poor health outcomes in those affected by multimorbidity in HF. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

A three-talk model for shared decision making: multistage consultation process.

PubMed

Elwyn, Glyn; Durand, Marie Anne; Song, Julia; Aarts, Johanna; Barr, Paul J; Berger, Zackary; Cochran, Nan; Frosch, Dominick; Galasiński, Dariusz; Gulbrandsen, Pål; Han, Paul K J; Härter, Martin; Kinnersley, Paul; Lloyd, Amy; Mishra, Manish; Perestelo-Perez, Lilisbeth; Scholl, Isabelle; Tomori, Kounosuke; Trevena, Lyndal; Witteman, Holly O; Van der Weijden, Trudy

2017-11-06

Objectives  To revise an existing three-talk model for learning how to achieve shared decision making, and to consult with relevant stakeholders to update and obtain wider engagement. Design  Multistage consultation process. Setting  Key informant group, communities of interest, and survey of clinical specialties. Participants  19 key informants, 153 member responses from multiple communities of interest, and 316 responses to an online survey from medically qualified clinicians from six specialties. Results  After extended consultation over three iterations, we revised the three-talk model by making changes to one talk category, adding the need to elicit patient goals, providing a clear set of tasks for each talk category, and adding suggested scripts to illustrate each step. A new three-talk model of shared decision making is proposed, based on "team talk," "option talk," and "decision talk," to depict a process of collaboration and deliberation. Team talk places emphasis on the need to provide support to patients when they are made aware of choices, and to elicit their goals as a means of guiding decision making processes. Option talk refers to the task of comparing alternatives, using risk communication principles. Decision talk refers to the task of arriving at decisions that reflect the informed preferences of patients, guided by the experience and expertise of health professionals. Conclusions  The revised three-talk model of shared decision making depicts conversational steps, initiated by providing support when introducing options, followed by strategies to compare and discuss trade-offs, before deliberation based on informed preferences. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Whole-body Magnetic Resonance Imaging in Inflammatory Arthritis: Systematic Literature Review and First Steps Toward Standardization and an OMERACT Scoring System.

PubMed

Østergaard, Mikkel; Eshed, Iris; Althoff, Christian E; Poggenborg, Rene P; Diekhoff, Torsten; Krabbe, Simon; Weckbach, Sabine; Lambert, Robert G W; Pedersen, Susanne J; Maksymowych, Walter P; Peterfy, Charles G; Freeston, Jane; Bird, Paul; Conaghan, Philip G; Hermann, Kay-Geert A

2017-11-01

Whole-body magnetic resonance imaging (WB-MRI) is a relatively new technique that can enable assessment of the overall inflammatory status of people with arthritis, but standards for image acquisition, definitions of key pathologies, and a quantification system are required. Our aim was to perform a systematic literature review (SLR) and to develop consensus definitions of key pathologies, anatomical locations for assessment, a set of MRI sequences and imaging planes for the different body regions, and a preliminary scoring system for WB-MRI in inflammatory arthritis. An SLR was initially performed, searching for WB-MRI studies in arthritis, osteoarthritis, spondyloarthritis, or enthesitis. These results were presented to a meeting of the MRI in Arthritis Working Group together with an MR image review. Following this, preliminary standards for WB-MRI in inflammatory arthritides were developed with further iteration at the Working Group meetings at the Outcome Measures in Rheumatology (OMERACT) 2016. The SLR identified 10 relevant original articles (7 cross-sectional and 3 longitudinal, mostly focusing on synovitis and/or enthesitis in spondyloarthritis, 4 with reproducibility data). The Working Group decided on inflammation in peripheral joints and entheses as primary focus areas, and then developed consensus MRI definitions for these pathologies, selected anatomical locations for assessment, agreed on a core set of MRI sequences and imaging planes for the different regions, and proposed a preliminary scoring system. It was decided to test and further develop the system by iterative multireader exercises. These first steps in developing an OMERACT WB-MRI scoring system for use in inflammatory arthritides offer a framework for further testing and refinement.

Slow Starter Enzymes: Role of Active Site Architecture in the Catalytic Control in the Biosynthesis of Taxadiene by Taxadiene Synthase.

PubMed

Ansbacher, Tamar; Freud, Yehoshua; Major, Dan Thomas

2018-05-23

Taxadiene synthase (TXS) catalyzes the formation of the natural product Taxa-4(5),11(12)-diene (henceforth Taxadiene). Taxadiene is the precursor in the formation of Taxol, which is an important natural anti-cancer agent. In the current study, we present a detailed mechanistic view of the biosynthesis of Taxadiene by TXS, using a hybrid quantum mechanics-molecular mechanics potential in conjunction with free energy simulation methods. The obtained free energy landscape displays initial endergonic steps followed by a step-wise downhill profile, which is an emerging free energy fingerprint for type I terpene synthases. We identify an active site Trp residue (W753) as a key feature of the TXS active site architecture and propose that this residue stabilized intermediate cations via -cation interactions. To validate our proposed active TXS model, we examine a previously reported W753H mutation, which leads to exclusive formation of the side product, cembrene A. The simulations of the W753H mutant show that in the mutant structure, the His side-chain is in perfect position to deprotonate the cembrenyl cation en route to cembrene formation, and that this abortive deprotonation is an energetically facile process. Based on the current model, we propose that an analogous mutation of Y841 to His could possibly lead to verticillane. The current simulations stress the importance of precise positioning of key active site residues in stabilizing intermediate carbocations. In view of the great pharmaceutical importance of taxadiene, a detailed understanding of the TXS mechanism can provide important clues towards a synthetic strategy for taxol manufacturing.

Compliance With WHO/UNICEF BFHI Standards in Croatia After Implementation of the BFHI.

PubMed

Zakarija-Grković, Irena; Boban, Marija; Janković, Sunčana; Ćuže, Anamarija; Burmaz, Tea

2018-02-01

The primary goal of the Baby-Friendly Hospital Initiative (BFHI) is to create conditions in maternity facilities that enable women to initiate and sustain the practice of breastfeeding exclusively. Research aim: This study aimed to determine hospital practices and breastfeeding rates before and after BFHI implementation and assess compliance with UNICEF/World Health Organization (WHO) standards for seven of the BFHI's Ten Steps to Successful Breastfeeding ( Ten Steps). Mothers of healthy, term infants ( N = 1,115) were recruited from the postnatal ward of the University Hospital of Split, Croatia, between February 2008 and July 2011 and followed for 12 months in a repeated-measures, prospective, longitudinal, three-group, nonequivalent, cohort study. Breastfeeding rates, hospital practices-including seven of the Ten Steps-and maternal sociodemographic data were collected. Parts of all seven Ten Steps that were assessed improved significantly post-BFHI. Step 3 ("antenatal education") showed the least improvement, whereas Step 7 ("rooming-in"; 2.6% pre-BFHI vs. 98.5% post-BFHI) and Step 9 ("no pacifiers/teats"; 21.8% pre-BFHI vs. 99.4% post-BFHI) showed the greatest improvement. Six months after Baby-Friendly designation, only Steps 7 and 9 were in full compliance with UNICEF/WHO standards. In-hospital, exclusive-breastfeeding rates rose markedly ( p < .001), but no change occurred in breastfeeding rates at 3, 6, or 12 months. Full implementation of the BFHI was associated with significant improvement in hospital practices and in-hospital, exclusive-breastfeeding rates, but it did not affect breastfeeding rates postdischarge, emphasizing the vital role of community support. Baby-Friendly Hospital Initiative standards declined rapidly post-hospital designation, indicating the need for regular monitoring and reassessment as well as ongoing, effective training for hospital staff.

Does footwear type impact the number of steps required to reach gait steady state?: an innovative look at the impact of foot orthoses on gait initiation.

PubMed

Najafi, Bijan; Miller, Daniel; Jarrett, Beth D; Wrobel, James S

2010-05-01

Many studies have attempted to better elucidate the effect of foot orthoses on gait dynamics. To our knowledge, most previous studies exclude the first few steps of gait and begin analysis at steady state walking. These unanalyzed steps of gait may contain important information about the dynamic and complex processes required to achieve equilibrium for a given gait velocity. The purpose of this study was to quantify gait initiation and determine how many steps were required to reach steady state walking under three footwear conditions: barefoot, habitual shoes, and habitual shoes with a prefabricated foot orthoses. Fifteen healthy subjects walked 50m at habitual speed in each condition. Wearing habitual shoes with the prefabricated orthoses enabled subjects to reach steady state walking in fewer steps (3.5 steps+/-2.0) compared to the barefoot condition (5.2 steps+/-3.0; p=0.02) as well as compared to the habitual shoes condition (4.7 steps+/-1.6; p=0.05). Interestingly, the subjects' dynamic medial-lateral balance was significantly improved (22%, p<0.05) by using foot orthoses compared to other footwear conditions. These findings suggest that foot orthoses may help individuals reach steady state more quickly and with a better dynamic balance in the medial-lateral direction, independent of foot type. The findings of this pilot study may open new avenues for objectively assessing the impact of prescription footwear on dynamic balance and spatio-temporal parameters of gait. Further work to better assess the impact of foot orthoses on gait initiation in patients suffering from gait and instability pathologies may be warranted. Copyright 2010 Elsevier B.V. All rights reserved.

An optimized fed-batch culture strategy integrated with a one-step fermentation improves L-lactic acid production by Rhizopus oryzae.

PubMed

Fu, Yongqian; Sun, Xiaolong; Zhu, Huayue; Jiang, Ru; Luo, Xi; Yin, Longfei

2018-05-21

In previous work, we proposed a novel modified one-step fermentation fed-batch strategy to efficiently generate L-lactic acid (L-LA) using Rhizopus oryzae. In this study, to further enhance efficiency of L-LA production through one-step fermentation in fed-batch cultures, we systematically investigated the initial peptone- and glucose-feeding approaches, including different initial peptone and glucose concentrations and maintained residual glucose levels. Based on the results of this study, culturing R. oryzae with initial peptone and glucose concentrations of 3.0 and 50.0 g/l, respectively, using a fed-batch strategy is an effective approach of producing L-LA through one-step fermentation. Changing the residual glucose had no obvious effect on the generation of L-LA. We determined the maximum LA production and productivity to be 162 g/l and 6.23 g/(l·h), respectively, during the acid production stage. Compared to our previous work, there was almost no change in L-LA production or yield; however, the productivity of L-LA increased by 14.3%.

Effect of 24-h continuous rotigotine treatment on stationary and non-stationary locomotion in de novo patients with Parkinson disease in an open-label uncontrolled study.

PubMed

Serrao, Mariano; Ranavolo, Alberto; Conte, Carmela; Davassi, Chiara; Mari, Silvia; Fasano, Alfonso; Chini, Giorgia; Coppola, Gianluca; Draicchio, Francesco; Pierelli, Francesco

2015-11-01

The aim of this study was to investigate the effect of a rotigotine transdermal patch on stationary and non-stationary locomotion in de novo Parkinson disease (PD) patients in an open-label uncontrolled study. A 3-D gait analysis system was used to investigate four different locomotor tasks: steady-state linear walking, gait initiation, gait termination and 180°-turning. A series of gait variables were measured for each locomotor task. PD patients who received rotigotine treatment (4-8 mg) displayed: (1) increased step length, gait speed, cadence and arm oscillations, and reduced double support duration and step asymmetry during steady-state linear gait; (2) increased initial step length during gait initiation; (3) increased final step length and gait speed, and decreased stability index during gait termination; (4) decreased duration of turning and head-pelvis delays during 180°-turning. The main finding that emerges from the present study is that the dopamine agonist rotigotine can improve various aspects of gait in de novo PD patients.

Combustion efficiency determined from wall pressure and temperature measurement in a Mach 2 combustor

NASA Technical Reports Server (NTRS)

Segal, Corin; Mcdaniel, James C.; Whitehurst, Robert B.; Krauss, Roland H.

1991-01-01

A study of transverse hydrogen injection behind a rearward facing step in a Mach 2 airflow was conducted to determine the combustion efficiency and the combustor/inlet interactions at the low temperature lean-mixture operational end of a scramjet combustor model. The fuel was injected at sonic conditions into the electrically heated airstream, which was maintained at 850 K or below. The static pressure delivered at the entrance of the combustor ranged between 0.25 to 0.5 atm. Injector configurations included single and staged injectors placed at 3 or 3-and-7 step-heights downstream of the step, respectively, with injector diameters of 1, 1.5, and 2 mm. Ignition was achieved by initially unstarting the test section. The constant area combustor and the low initial temperatures caused thermal choking and upstream interaction to occur at very low equivalence ratios. Typically, most of the fuel was burned in the recirculation region behind the step and around the jets. The effects of initial conditions (temperature and pressure), fuel-to-air dynamic pressure ratio, and boundaries (thermal vs adiabatic) are presented.

Stepping responses to treadmill perturbations vary with severity of motor deficits in human SCI.

PubMed

Chu, Virginia Way Tong; Hornby, T George; Schmit, Brian D

2018-04-18

In this study, we investigated the responses to tread perturbations during human stepping on a treadmill. Our approach was to test the effects of perturbations to a single leg using a split-belt treadmill in healthy participants and in participants with varying severity of spinal cord injury (SCI). We recruited 11 people with incomplete SCI and 5 noninjured participants. As participants walked on an instrumented treadmill, the belt on one side was stopped or accelerated briefly during mid to late stance. A majority of participants initiated an unnecessary swing when the treadmill was stopped in mid stance, although the likelihood of initiating a step was decreased in participants with more severe SCI. Accelerating or decelerating one belt of the treadmill during stance altered the characteristics of swing. We observed delayed swing initiation when the belt was decelerated (i.e. the hip was in a more flexed position at time of swing) and advanced swing initiation with acceleration (i.e. hip extended at swing initiation). Further, the timing and leg posture of heel strike appeared to remain constant, reflected by a sagittal plane hip angle at heel strike that remained the same regardless of the perturbation. In summary, our results supported the current understanding of the role of sensory feedback and central drive in the control of stepping in participants with incomplete SCI and noninjured participants. In particular, the observation of unnecessary swing during a stop perturbation highlights the interdependence of central and sensory drive in walking control.

[Design method of convex master gratings for replicating flat-field concave gratings].

PubMed

Zhou, Qian; Li, Li-Feng

2009-08-01

Flat-field concave diffraction grating is the key device of a portable grating spectrometer with the advantage of integrating dispersion, focusing and flat-field in a single device. It directly determines the quality of a spectrometer. The most important two performances determining the quality of the spectrometer are spectral image quality and diffraction efficiency. The diffraction efficiency of a grating depends mainly on its groove shape. But it has long been a problem to get a uniform predetermined groove shape across the whole concave grating area, because the incident angle of the ion beam is restricted by the curvature of the concave substrate, and this severely limits the diffraction efficiency and restricts the application of concave gratings. The authors present a two-step method for designing convex gratings, which are made holographically with two exposure point sources placed behind a plano-convex transparent glass substrate, to solve this problem. The convex gratings are intended to be used as the master gratings for making aberration-corrected flat-field concave gratings. To achieve high spectral image quality for the replicated concave gratings, the refraction effect at the planar back surface and the extra optical path lengths through the substrate thickness experienced by the two divergent recording beams are considered during optimization. This two-step method combines the optical-path-length function method and the ZEMAX software to complete the optimization with a high success rate and high efficiency. In the first step, the optical-path-length function method is used without considering the refraction effect to get an approximate optimization result. In the second step, the approximate result of the first step is used as the initial value for ZEMAX to complete the optimization including the refraction effect. An example of design problem was considered. The simulation results of ZEMAX proved that the spectral image quality of a replicated concave grating is comparable with that of a directly recorded concave grating.

Nucleation of uniform mono- and bilayer epitaxial graphene on SiC(0001)

NASA Astrophysics Data System (ADS)

Wu, Xiaosong; Zhang, Rui; Dong, Yunliang; Guo, Shuai; Kong, Wenjie; Liao, Zhimin; Yu, Dapeng

2012-02-01

Early stage of epitaxial graphene growth on SiC(0001) has been investigated. Using the confinement controlled sublimation (CCS) method, we has achieved well controlled growth and been able to see the formation of mono- and bilayer graphene islands. The growth features reveal the intriguing growth mechanism. In particular, a new ``stepdown'' growth mode has been identified. Graphene can propagate tens of micrometers across many SiC steps, while, most importantly, step bunching is avoided and the initial regular stepped SiC surface morphology is preserved. The stepdown growth demonstrates a route towards uniform epitaxial graphene in wafer size without sacrificing the initial substrate surface morphology.

The role of public-private partnerships in addressing the biomedical innovation challenge.

PubMed

Said, Maya; Zerhouni, Elias

2014-11-01

Without a step change in the productivity of pharmaceutical research and development, it will be difficult to tackle the public health challenges facing societies worldwide. Public–private partnerships could play a key role in achieving this step change, but they need to be well designed and led.

A facile synthesis of the basic steroidal skeleton using a Pauson-Khand reaction as a key step.

PubMed

Kim, Do Han; Kim, Kwang; Chung, Young Keun

2006-10-13

A high-yield synthesis of steroid-type molecules under mild reaction conditions is achieved in two steps involving nucleophilic addition of alkynyl cerium reagent to an easily enolizable carbonyl compound (beta-tetralone) followed by an intramolecular Pauson-Khand reaction.

Essentials of Millon Inventories Assessment. Essentials of Psychological Assessment Series.

ERIC Educational Resources Information Center

Strack, Stephen

This step-by-step reference guide to the five key Millon personality inventories includes vital information about each of the tests, including information on psychometric characteristics, special populations, assets-limitations, reliability-validity, and interpretation. The tests are: the Millon Clinical Multiaxial Inventory III (MCMI-III); the…

Strategic Marketing: The President's Perspective.

ERIC Educational Resources Information Center

Pappas, Richard J.; Shaink, M. Richard

1994-01-01

Provides a step-by-step guide to developing a college marketing plan. Identifying a target market and determining an appropriate mix of promotional strategies are considered key to the process. Highlights the college president's role in the marketing process, indicating that, although the president is the chief marketer, all employees must be…

Development of a critical appraisal tool to assess the quality of cross-sectional studies (AXIS)

PubMed Central

Downes, Martin J; Brennan, Marnie L; Williams, Hywel C; Dean, Rachel S

2016-01-01

Objectives The aim of this study was to develop a critical appraisal (CA) tool that addressed study design and reporting quality as well as the risk of bias in cross-sectional studies (CSSs). In addition, the aim was to produce a help document to guide the non-expert user through the tool. Design An initial scoping review of the published literature and key epidemiological texts was undertaken prior to the formation of a Delphi panel to establish key components for a CA tool for CSSs. A consensus of 80% was required from the Delphi panel for any component to be included in the final tool. Results An initial list of 39 components was identified through examination of existing resources. An international Delphi panel of 18 medical and veterinary experts was established. After 3 rounds of the Delphi process, the Appraisal tool for Cross-Sectional Studies (AXIS tool) was developed by consensus and consisted of 20 components. A detailed explanatory document was also developed with the tool, giving expanded explanation of each question and providing simple interpretations and examples of the epidemiological concepts being examined in each question to aid non-expert users. Conclusions CA of the literature is a vital step in evidence synthesis and therefore evidence-based decision-making in a number of different disciplines. The AXIS tool is therefore unique and was developed in a way that it can be used across disciplines to aid the inclusion of CSSs in systematic reviews, guidelines and clinical decision-making. PMID:27932337

The French Infectious Diseases Society's readiness and response to epidemic or biological risk-the current situation following the Middle East respiratory syndrome coronavirus and Ebola virus disease alerts.

PubMed

Coignard-Biehler, H; Rapp, C; Chapplain, J M; Hoen, B; Che, D; Berthelot, P; Cazenave-Roblot, F; Rabaud, C; Brouqui, P; Leport, C

2018-03-01

In 2012, the French Infectious Diseases Society (French acronym SPILF) initiated the "Coordination of epidemic and biological risk" (SPILF-COREB - Emergences [SCE]) group to support the readiness and response of healthcare workers (HCWs) to new alerts. To present the SCE group, its functioning, and the main support it provided for frontline HCWs. A multidisciplinary group of heads of infectious disease departments from reference hospitals was created to build a network of clinical expertise for care, training, and research in the field of epidemic and biological risk (EBR). The network developed a set of standardized operational procedures (SOPs) to guide interventions to manage EBR-suspect patients. A working group created the SOP aimed at frontline HCWs taking care of patients. Priority was given to the development of a generic procedure, which was then adapted according to the current alert. Five key steps were identified and hierarchized: detecting, protecting, caring for, alerting, and referring the EBR patient. The interaction between clinicians and those responsible for the protection of the community was crucial. The SOPs validated by the SPILF and its affiliates were disseminated to a wide range of key stakeholders through various media including workshops and the SPILF's website. SPILF can easily adapt and timely mobilize the EBR expertise in case of an alert. The present work suggests that sharing and discussing this experience, initiated at the European level, can generate a new collective expertise and needs to be further developed and strengthened. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Adapting Natural Resource Management to Climate Change: The Blue Mountains and Northern Rockies Adaptation Partnerships

NASA Astrophysics Data System (ADS)

Halofsky, J.; Peterson, D. L.

2014-12-01

Concrete ways to adapt to climate change are needed to help natural resource managers take the first steps to incorporate climate change into management and take advantage of opportunities to balance the negative effects of climate change. We recently initiated two science-management climate change adaptation partnerships, one with three national forests and other key stakeholders in the Blue Mountains region of northeastern Oregon, and the other with 16 national forests, three national parks and other stakeholders in the northern Rockies region. Goals of both partnerships were to: (1) synthesize published information and data to assess the exposure, sensitivity, and adaptive capacity of key resource areas, including water use, infrastructure, fisheries, and vegetation and disturbance; (2) develop science-based adaptation strategies and tactics that will help to mitigate the negative effects of climate change and assist the transition of biological systems and management to a warmer climate; (3) ensure adaptation strategies and tactics are incorporated into relevant planning documents; and (4) foster an enduring partnership to facilitate ongoing dialogue and activities related to climate change in the partnerships regions. After an initial vulnerability assessment by agency and university scientists and local resource specialists, adaptation strategies and tactics were developed in a series of scientist-manager workshops. The final vulnerability assessments and adaptation actions are incorporated in technical reports. The partnerships produced concrete adaptation options for national forest and other natural resource managers and illustrated the utility of place-based vulnerability assessments and scientist-manager workshops in adapting to climate change.

Adverse Outcome Pathways can drive non-animal approaches for safety assessment

PubMed Central

Burden, Natalie; Sewell, Fiona; Andersen, Melvin E; Boobis, Alan; Chipman, J Kevin; Cronin, Mark T D; Hutchinson, Thomas H; Kimber, Ian; Whelan, Maurice

2015-01-01

Adverse Outcome Pathways (AOPs) provide an opportunity to develop new and more accurate safety assessment processes for drugs and other chemicals, and may ultimately play an important role in regulatory decision making. Not only can the development and application of AOPs pave the way for the development of improved evidence-based approaches for hazard and risk assessment, there is also the promise of a significant impact on animal welfare, with a reduced reliance on animal-based methods. The establishment of a useable and coherent knowledge framework under which AOPs will be developed and applied has been a first critical step towards realizing this opportunity. This article explores how the development of AOPs under this framework, and their application in practice, could benefit the science and practice of safety assessment, while in parallel stimulating a move away from traditional methods towards an increased acceptance of non-animal approaches. We discuss here the key areas where current, and future initiatives should be focused to enable the translation of AOPs into routine chemical safety assessment, and lasting 3Rs benefits. © 2015 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd. This article explores how the development and application of Adverse Outcome Pathways (AOPs) could benefit the science and practice of chemical safety assessment, with a particular focus on how their use in practice could reduce reliance on traditional animal toxicity tests. This includes discussion of the key areas where current and future initiatives should be focused to enable the translation of AOPs into routine chemical safety assessment, and lasting 3Rs benefits. PMID:25943792

A Systematic Review of Health System Barriers and Enablers for Antiretroviral Therapy (ART) for HIV-Infected Pregnant and Postpartum Women

PubMed Central

Colvin, Christopher J.; Konopka, Sarah; Chalker, John C.; Jonas, Edna; Albertini, Jennifer; Amzel, Anouk; Fogg, Karen

2014-01-01

Background Despite global progress in the fight to reduce maternal mortality, HIV-related maternal deaths remain persistently high, particularly in much of Africa. Lifelong antiretroviral therapy (ART) appears to be the most effective way to prevent these deaths, but the rates of three key outcomes—ART initiation, retention in care, and long-term ART adherence—remain low. This systematic review synthesized evidence on health systems factors affecting these outcomes in pregnant and postpartum women living with HIV. Methods Searches were conducted for studies addressing the population of interest (HIV-infected pregnant and postpartum women), the intervention of interest (ART), and the outcomes of interest (initiation, adherence, and retention). Quantitative and qualitative studies published in English since January 2008 were included. A four-stage narrative synthesis design was used to analyze findings. Review findings from 42 included studies were categorized according to five themes: 1) models of care, 2) service delivery, 3) resource constraints and governance challenges, 4) patient-health system engagement, and 5) maternal ART interventions. Results Low prioritization of maternal ART and persistent dropout along the maternal ART cascade were key findings. Service delivery barriers included poor communication and coordination among health system actors, poor clinical practices, and gaps in provider training. The few studies that assessed maternal ART interventions demonstrated the importance of multi-pronged, multi-leveled interventions. Conclusions There has been a lack of emphasis on the experiences, needs and vulnerabilities particular to HIV-infected pregnant and postpartum women. Supporting these women to successfully traverse the maternal ART cascade requires carefully designed and targeted interventions throughout the steps. Careful design of integrated service delivery models is of critical importance in this effort. Key knowledge gaps and research priorities were also identified, including definitions and indicators of adherence rates, and the importance of cumulative measures of dropout along the maternal ART cascade. PMID:25303241

Novel synthesis and characterization of a collagen-based biopolymer initiated by hydroxyapatite nanoparticles.

PubMed

Bhuiyan, D; Jablonsky, M J; Kolesov, I; Middleton, J; Wick, T M; Tannenbaum, R

2015-03-01

In this study, we developed a novel synthesis method to create a complex collagen-based biopolymer that promises to possess the necessary material properties for a bone graft substitute. The synthesis was carried out in several steps. In the first step, a ring-opening polymerization reaction initiated by hydroxyapatite nanoparticles was used to polymerize d,l-lactide and glycolide monomers to form poly(lactide-co-glycolide) co-polymer. In the second step, the polymerization product was coupled with succinic anhydride, and subsequently was reacted with N-hydroxysuccinimide in the presence of dicyclohexylcarbodiimide as the cross-linking agent, in order to activate the co-polymer for collagen attachment. In the third and final step, the activated co-polymer was attached to calf skin collagen type I, in hydrochloric acid/phosphate buffer solution and the precipitated co-polymer with attached collagen was isolated. The synthesis was monitored by proton nuclear magnetic resonance, infrared and Raman spectroscopies, and the products after each step were characterized by thermal and mechanical analysis. Calculations of the relative amounts of the various components, coupled with initial dynamic mechanical analysis testing of the resulting biopolymer, afforded a preliminary assessment of the structure of the complex biomaterial formed by this novel polymerization process. Copyright © 2015. Published by Elsevier Ltd.

The Mentor Kit. A Step-by-Step Guide To Creating an Effective Mentor Program in Your School [and] Reproducible Forms To Accompany the Mentor Program in Your School.

ERIC Educational Resources Information Center

Nash, Diane; Treffinger, Don

Mentorships, the art of a creatively productive person teaching, counseling, and inspiring a student with similar interests, can be the result of circumstance or they can be the result of mentorship programs engineered in the academic world. Data collected from over 25 different academic models of mentorship have been distilled into 7 key steps to…

Eight-step method to build the clinical content of an evidence-based care pathway: the case for COPD exacerbation

PubMed Central

2012-01-01

Background Optimization of the clinical care process by integration of evidence-based knowledge is one of the active components in care pathways. When studying the impact of a care pathway by using a cluster-randomized design, standardization of the care pathway intervention is crucial. This methodology paper describes the development of the clinical content of an evidence-based care pathway for in-hospital management of chronic obstructive pulmonary disease (COPD) exacerbation in the context of a cluster-randomized controlled trial (cRCT) on care pathway effectiveness. Methods The clinical content of a care pathway for COPD exacerbation was developed based on recognized process design and guideline development methods. Subsequently, based on the COPD case study, a generalized eight-step method was designed to support the development of the clinical content of an evidence-based care pathway. Results A set of 38 evidence-based key interventions and a set of 24 process and 15 outcome indicators were developed in eight different steps. Nine Belgian multidisciplinary teams piloted both the set of key interventions and indicators. The key intervention set was judged by the teams as being valid and clinically applicable. In addition, the pilot study showed that the indicators were feasible for the involved clinicians and patients. Conclusions The set of 38 key interventions and the set of process and outcome indicators were found to be appropriate for the development and standardization of the clinical content of the COPD care pathway in the context of a cRCT on pathway effectiveness. The developed eight-step method may facilitate multidisciplinary teams caring for other patient populations in designing the clinical content of their future care pathways. PMID:23190552

Three-Dimensional Structure of Boundary Layers in Transition to Turbulence

DTIC Science & Technology

1989-03-01

step-by-step Orr- Sommerfeld solution and integration. What is needed is an initial condition and initial wavenumber. These data can be obtained from a ...general than unsteady boundary-layer equations and Orr- Sommerfeld equation which are special cases. There- fore, the PSE will be a valuable tool for...spectra (discrete, continuous) result in a given problem is discussed in monographs and journal articles. Here, we try to find solutions to the

A management system for accidental water pollution risk in a harbour: The Barcelona case study

NASA Astrophysics Data System (ADS)

Grifoll, Manel; Jordà, Gabriel; Espino, Manuel; Romo, Javier; García-Sotillo, Marcos

2011-10-01

Water quality degradation in harbour domains can have an important negative impact from an economic, touristic and environmental point of view. In that sense, water quality management is becoming a main concern for harbour managers. In this paper, we present the research behind the initiative started in Spanish harbours to control water quality degradation due to accidental pollution. This management system is already operationally running in the Barcelona harbour (NW Mediterranean Sea). The system is based on a recent published risk assessment, which takes into account not only the different activities in the harbour and their inherent risk of accident but also the physical behaviour of harbour waters. In this methodology, a key element is to get hydrodynamic forecasts. Thus, the system is composed of a hierarchy of nested hydrodynamic models covering from the basin scale to the harbour scale and a module that computes the different parameters needed for risk assessment. Special emphasis is made on describing the steps followed for system implementation because such implementation is far from a mere technical problem. The first step is to identify the main forcing factors for the harbour hydrodynamics from both field data and numerical experiments, which has never been done before for the Barcelona harbour. Wind and shelf currents are suggested as the main forcing factors for the harbour circulation. The second step is to identify the requirements that a numerical model must fulfil in order to properly solve the Barcelona harbour's hydrodynamics. A high resolution (< 50 m) three dimensional model able to prognostically calculate temperature and salinity evolution; full air-sea coupling is needed as well. The third step is to investigate the best operational strategy. We have found that small errors in the initial density profiles are acceptable for surface current forecasts but not for deep circulation. A cold start must be avoided and a 72 h spin-up is recommended. The minimum wind forcing resolution has been determined to be 1 h. A scaling factor should be included to account for the energy contribution of the higher frequency processes. Finally, an example of its application to a real case is presented and the comparison to other harbour environmental management systems is discussed.

Multilevel Evaluation Alignment: An Explication of a Four-Step Model

ERIC Educational Resources Information Center

Yang, Huilan; Shen, Jianping; Cao, Honggao; Warfield, Charles

2004-01-01

Using the evaluation work on the W.K. Kellogg Foundation's Unleashing Resources Initiative as an example, in this article we explicate a general four-step model appropriate for multilevel evaluation alignment. We review the relevant literature, argue for the need for evaluation alignment in a multilevel context, explain the four-step model,…

Melatonin: a universal time messenger.

PubMed

Erren, Thomas C; Reiter, Russel J

2015-01-01

Temporal organization plays a key role in humans, and presumably all species on Earth. A core building block of the chronobiological architecture is the master clock, located in the suprachi asmatic nuclei [SCN], which organizes "when" things happen in sub-cellular biochemistry, cells, organs and organisms, including humans. Conceptually, time messenging should follow a 5 step-cascade. While abundant evidence suggests how steps 1 through 4 work, step 5 of "how is central time information transmitted througout the body?" awaits elucidation. Step 1: Light provides information on environmental (external) time; Step 2: Ocular interfaces between light and biological (internal) time are intrinsically photosensitive retinal ganglion cells [ipRGS] and rods and cones; Step 3: Via the retinohypothalamic tract external time information reaches the light-dependent master clock in the brain, viz the SCN; Step 4: The SCN translate environmental time information into biological time and distribute this information to numerous brain structures via a melanopsin-based network. Step 5: Melatonin, we propose, transmits, or is a messenger of, internal time information to all parts of the body to allow temporal organization which is orchestrated by the SCN. Key reasons why we expect melatonin to have such role include: First, melatonin, as the chemical expression of darkness, is centrally involved in time- and timing-related processes such as encoding clock and calendar information in the brain; Second, melatonin travels throughout the body without limits and is thus a ubiquitous molecule. The chemial conservation of melatonin in all tested species could make this molecule a candidate for a universal time messenger, possibly constituting a legacy of an all-embracing evolutionary history.

Differential Effects of Monovalent Cations and Anions on Key Nanoparticle Attributes

EPA Science Inventory

Understanding the key particle attributes such as particle size, size distribution and surface charge of both the nano- and micron-sized particles is the first step in drug formulation as such attributes are known to directly influence several characteristics of drugs including d...

A 24-Week, Randomized, Controlled Study to Evaluate the Tolerability, Safety and Efficacy of 2 Different Titration Schemes of the Rivastigmine Patch in Japanese Patients with Mild to Moderate Alzheimer's Disease.

PubMed

Nakamura, Yu; Strohmaier, Christine; Tamura, Kaoru; Kataoka, Naoko; Nakano, Masayuki; Oda, Shoichiro; Nishimura, Kazuma; Homma, Akira

2015-01-01

To investigate whether 1-step titration of the rivastigmine patch (initiated at 5 cm(2) and titrated to 10 cm(2) after 4 weeks) is well tolerated in Japanese patients with Alzheimer's disease (AD) as compared to 3-step titration (initiated at 2.5 cm(2) and titrated by 2.5 cm(2) every 4 weeks to 10 cm(2)). A 24-week, multicenter, randomized, double-blind study was conducted in Japan between July 2012 and May 2014. Patients with mild to moderate AD aged 50-85 years were randomized 1:1 to 1-step or 3-step titration of the rivastigmine once-daily patch. The primary endpoint was the proportion of patients with adverse events leading to discontinuation. Of 216 patients randomized, 215 (1-step, n = 107; 3-step, n = 108) were included in the safety analysis. The primary endpoint outcome was 15.0% in the 1-step group and 18.5% in the 3-step group. The observed treatment difference was -3.6% (95% confidence interval: -17.0, 9.6), falling within the prespecified acceptance range. The tolerability of two different titration schemes was similar in Japanese patients with AD.

A 24-Week, Randomized, Controlled Study to Evaluate the Tolerability, Safety and Efficacy of 2 Different Titration Schemes of the Rivastigmine Patch in Japanese Patients with Mild to Moderate Alzheimer's Disease

PubMed Central

Nakamura, Yu; Strohmaier, Christine; Tamura, Kaoru; Kataoka, Naoko; Nakano, Masayuki; Oda, Shoichiro; Nishimura, Kazuma; Homma, Akira

2015-01-01

Aim To investigate whether 1-step titration of the rivastigmine patch (initiated at 5 cm2 and titrated to 10 cm2 after 4 weeks) is well tolerated in Japanese patients with Alzheimer's disease (AD) as compared to 3-step titration (initiated at 2.5 cm2 and titrated by 2.5 cm2 every 4 weeks to 10 cm2). Methods A 24-week, multicenter, randomized, double-blind study was conducted in Japan between July 2012 and May 2014. Patients with mild to moderate AD aged 50-85 years were randomized 1:1 to 1-step or 3-step titration of the rivastigmine once-daily patch. The primary endpoint was the proportion of patients with adverse events leading to discontinuation. Results Of 216 patients randomized, 215 (1-step, n = 107; 3-step, n = 108) were included in the safety analysis. The primary endpoint outcome was 15.0% in the 1-step group and 18.5% in the 3-step group. The observed treatment difference was −3.6% (95% confidence interval: −17.0, 9.6), falling within the prespecified acceptance range. Conclusion The tolerability of two different titration schemes was similar in Japanese patients with AD. PMID:26557135

Measured close lightning leader-step electric-field-derivative waveforms.

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

Jordan, Doug M.; Hill, Dustin; Biagi, Christopher J.

2010-12-01

We characterize the measured electric field-derivative (dE/dt) waveforms of lightning stepped-leader steps from three negative lightning flashes at distances of tens to hundreds of meters. Electromagnetic signatures of leader steps at such close distances have rarely been documented in previous literature. Individual leader-step three-dimensional locations are determined by a dE/dt TOA system. The leader-step field derivative is typically a bipolar pulse with a sharp initial half-cycle of the same polarity as that of the return stroke, followed by an opposite polarity overshoot that decays relatively slowly to background level. This overshoot increases in amplitude relative to the initial peak andmore » becomes dominant as range decreases. The initial peak is often preceded by a 'slow front,' similar to the slow front that precedes the fast transition to peak in first return stroke dE/dt and E waveforms. The overall step-field waveform duration is typically less than 1 {micro}s. The mean initial peak of dE/dt, range-normalized to 100 km, is 7.4 V m{sup -1} {micro}s{sup -1} (standard deviation (S.D.), 3.7 V m{sup -1} {micro}s{sup -1}, N = 103), the mean half-peak width is 33.5 ns (S.D., 11.9 ns, N = 69), and the mean 10-to-90% risetime is 43.6 ns (S.D., 24.2 ns, N = 69). From modeling, we determine the properties of the leader step currents which produced two typical measured field derivatives, and we use one of these currents to calculate predicted leader step E and dE/dt as a function of source range and height, the results being in good agreement with our observations. The two modeled current waveforms had maximum rates of current rise-to-peak near 100 kA {micro}s{sup -1}, peak currents in the 5-7 kA range, current half-peak widths of about 300 ns, and charge transfers of {approx}3 mC. As part of the modeling, those currents were propagated upward at 1.5 x 10{sup 8} m s{sup -1}, with their amplitudes decaying exponentially with a decay height constant of 25 m.« less

Master Logic Diagram: An Approach to Identify Initiating Events of HTGRs

NASA Astrophysics Data System (ADS)

Purba, J. H.

2018-02-01

Initiating events of a nuclear power plant being evaluated need to be firstly identified prior to applying probabilistic safety assessment on that plant. Various types of master logic diagrams (MLDs) have been proposedforsearching initiating events of the next generation of nuclear power plants, which have limited data and operating experiences. Those MLDs are different in the number of steps or levels and different in the basis for developing them. This study proposed another type of MLD approach to find high temperature gas cooled reactor (HTGR) initiating events. It consists of five functional steps starting from the top event representing the final objective of the safety functions to the basic event representing the goal of the MLD development, which is an initiating event. The application of the proposed approach to search for two HTGR initiating events, i.e. power turbine generator trip and loss of offsite power, is provided. The results confirmed that the proposed MLD is feasiblefor finding HTGR initiating events.

Different dynamin blockers interfere with distinct phases of synaptic endocytosis during stimulation in motoneurones.

PubMed

Linares-Clemente, Pedro; Rozas, José L; Mircheski, Josif; García-Junco-Clemente, Pablo; Martínez-López, José A; Nieto-González, José L; Vázquez, M Eugenio; Pintado, C Oscar; Fernández-Chacón, Rafael

2015-07-01

Neurotransmitter release requires a tight coupling between synaptic vesicle exocytosis and endocytosis with dynamin being a key protein in that process. We used imaging techniques to examine the time course of endocytosis at mouse motor nerve terminals expressing synaptopHluorin, a genetically encoded reporter of the synaptic vesicle cycle. We separated two sequential phases of endocytosis taking place during the stimulation train: early and late endocytosis. Freshly released synaptic vesicle proteins are preferentially retrieved during the early phase, which is very sensitive to dynasore, an inhibitor of dynamin GTPase activity. Synaptic vesicle proteins pre-existing at the plasma membrane before the stimulation are preferentially retrieved during the late phase, which is very sensitive to myristyl trimethyl ammonium bromide (MitMAB), an inhibitor of the dynamin-phospholipid interaction. Synaptic endocytosis is essential at nerve terminals to maintain neurotransmitter release by exocytosis. Here, at the neuromuscular junction of synaptopHluorin (spH) transgenic mice, we have used imaging to study exo- and endocytosis occurring simultaneously during nerve stimulation. We observed two endocytosis components, which occur sequentially during stimulation. The early component of endocytosis apparently internalizes spH molecules freshly exocytosed. This component was sensitive to dynasore, a blocker of dynamin 1 GTPase activity. In contrast, this early component was resistant to myristyl trimethyl ammonium bromide (MiTMAB), a competitive agent that blocks dynamin binding to phospholipid membranes. The late component of endocytosis is likely to internalize spH molecules that pre-exist at the plasma membrane before stimulation starts. This component was blocked by MiTMAB, perhaps by impairing the binding of dynamin or other key endocytic proteins to phospholipid membranes. Our study suggests the co-existence of two sequential synaptic endocytosis steps taking place during stimulation that are susceptible to pharmacological dissection: an initial step, preferentially sensitive to dynasore, that internalizes vesicular components immediately after they are released, and a MiTMAB-sensitive step that internalizes vesicular components pre-existing at the plasma membrane surface. In addition, we report that post-stimulus endocytosis also has several components with different sensitivities to dynasore and MiTMAB. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

The problem of predicting the size distribution of sediment supplied by hillslopes to rivers

NASA Astrophysics Data System (ADS)

Sklar, Leonard S.; Riebe, Clifford S.; Marshall, Jill A.; Genetti, Jennifer; Leclere, Shirin; Lukens, Claire L.; Merces, Viviane

2017-01-01

Sediments link hillslopes to river channels. The size of sediments entering channels is a key control on river morphodynamics across a range of scales, from channel response to human land use to landscape response to changes in tectonic and climatic forcing. However, very little is known about what controls the size distribution of particles eroded from bedrock on hillslopes, and how particle sizes evolve before sediments are delivered to channels. Here we take the first steps toward building a geomorphic transport law to predict the size distribution of particles produced on hillslopes and supplied to channels. We begin by identifying independent variables that can be used to quantify the influence of five key boundary conditions: lithology, climate, life, erosion rate, and topography, which together determine the suite of geomorphic processes that produce and transport sediments on hillslopes. We then consider the physical and chemical mechanisms that determine the initial size distribution of rock fragments supplied to the hillslope weathering system, and the duration and intensity of weathering experienced by particles on their journey from bedrock to the channel. We propose a simple modeling framework with two components. First, the initial rock fragment sizes are set by the distribution of spacing between fractures in unweathered rock, which is influenced by stresses encountered by rock during exhumation and by rock resistance to fracture propagation. That initial size distribution is then transformed by a weathering function that captures the influence of climate and mineralogy on chemical weathering potential, and the influence of erosion rate and soil depth on residence time and the extent of particle size reduction. Model applications illustrate how spatial variation in weathering regime can lead to bimodal size distributions and downstream fining of channel sediment by down-valley fining of hillslope sediment supply, two examples of hillslope control on river sediment size. Overall, this work highlights the rich opportunities for future research into the controls on the size of sediments produced on hillslopes and delivered to channels.

Net-VISA used as a complement to standard software at the CTBTO: initial operational experience with next-generation software.

NASA Astrophysics Data System (ADS)

Le Bras, R. J.; Arora, N. S.; Kushida, N.; Kebede, F.; Feitio, P.; Tomuta, E.

2017-12-01

The International Monitoring System of the Comprehensive Nuclear-Test-Ban Treaty Organization (CTBTO) has reached out to the broader scientific community through a series of conferences, the later one of which took place in June 2017 in Vienna, Austria. Stemming out of this outreach effort, after the inception of research and development efforts in 2009, the NET-VISA software, following a Bayesian modelling approach, has been elaborated to improve on the key step of automatic association of joint seismic, hydro-acoustic, and infrasound detections. When compared with the current operational system, it has been consistently shown on off-line tests to improve the overlap with the analyst-reviewed Reviewed Event Bulletin (REB) by ten percent for an average of 85% overlap, while the inconsistency rate is essentially the same at about 50%. Testing by analysts in realistic conditions on a few days of data has also demonstrated the software performance in finding additional events which qualify for publication in the REB. Starting in August 2017, the automatic events produced by the software will be reviewed by analysts at the CTBTO, and we report on the initial evaluation of this introduction into operations.

Transcription regulation by the Mediator complex.

PubMed

Soutourina, Julie

2018-04-01

Alterations in the regulation of gene expression are frequently associated with developmental diseases or cancer. Transcription activation is a key phenomenon in the regulation of gene expression. In all eukaryotes, mediator of RNA polymerase II transcription (Mediator), a large complex with modular organization, is generally required for transcription by RNA polymerase II, and it regulates various steps of this process. The main function of Mediator is to transduce signals from the transcription activators bound to enhancer regions to the transcription machinery, which is assembled at promoters as the preinitiation complex (PIC) to control transcription initiation. Recent functional studies of Mediator with the use of structural biology approaches and functional genomics have revealed new insights into Mediator activity and its regulation during transcription initiation, including how Mediator is recruited to transcription regulatory regions and how it interacts and cooperates with PIC components to assist in PIC assembly. Novel roles of Mediator in the control of gene expression have also been revealed by showing its connection to the nuclear pore and linking Mediator to the regulation of gene positioning in the nuclear space. Clear links between Mediator subunits and disease have also encouraged studies to explore targeting of this complex as a potential therapeutic approach in cancer and fungal infections.

Numerical simulation of conservation laws

NASA Technical Reports Server (NTRS)

Chang, Sin-Chung; To, Wai-Ming

1992-01-01

A new numerical framework for solving conservation laws is being developed. This new approach differs substantially from the well established methods, i.e., finite difference, finite volume, finite element and spectral methods, in both concept and methodology. The key features of the current scheme include: (1) direct discretization of the integral forms of conservation laws, (2) treating space and time on the same footing, (3) flux conservation in space and time, and (4) unified treatment of the convection and diffusion fluxes. The model equation considered in the initial study is the standard one dimensional unsteady constant-coefficient convection-diffusion equation. In a stability study, it is shown that the principal and spurious amplification factors of the current scheme, respectively, are structurally similar to those of the leapfrog/DuFort-Frankel scheme. As a result, the current scheme has no numerical diffusion in the special case of pure convection and is unconditionally stable in the special case of pure diffusion. Assuming smooth initial data, it will be shown theoretically and numerically that, by using an easily determined optimal time step, the accuracy of the current scheme may reach a level which is several orders of magnitude higher than that of the MacCormack scheme, with virtually identical operation count.

Computational Identification and Analysis of the Key Biosorbent Characteristics for the Biosorption Process of Reactive Black 5 onto Fungal Biomass

PubMed Central

Yang, Yu-Yi; Li, Ze-Li; Wang, Guan; Zhao, Xiao-Ping; Crowley, David E.; Zhao, Yu-Hua

2012-01-01

The performances of nine biosorbents derived from dead fungal biomass were investigated for their ability to remove Reactive Black 5 from aqueous solution. The biosorption data for removal of Reactive Black 5 were readily modeled using the Langmuir adsorption isotherm. Kinetic analysis based on both pseudo-second-order and Weber-Morris models indicated intraparticle diffusion was the rate limiting step for biosorption of Reactive Black 5 on to the biosorbents. Sorption capacities of the biosorbents were not correlated with the initial biosorption rates. Sensitivity analysis of the factors affecting biosorption examined by an artificial neural network model showed that pH was the most important parameter, explaining 22%, followed by nitrogen content of biosorbents (16%), initial dye concentration (15%) and carbon content of biosorbents (10%). The biosorption capacities were not proportional to surface areas of the sorbents, but were instead influenced by their chemical element composition. The main functional groups contributing to dye sorption were amine, carboxylic, and alcohol moieties. The data further suggest that differences in carbon and nitrogen contents of biosorbents may be used as a selection index for identifying effective biosorbents from dead fungal biomass. PMID:22442697

From good ideas to actions: a model-driven community collaborative to prevent childhood obesity.

PubMed

Huberty, Jennifer L; Balluff, Mary; O'Dell, Molly; Peterson, Kerri

2010-01-01

Activate Omaha Kids, a community collaborative, was designed, implemented, and evaluated with the aim of preventing childhood obesity in the Omaha community. Activate Omaha Kids brought together key stakeholders and community leaders to create a community coalition. The coalition's aim was to oversee a long-term sustainable approach to preventing obesity. Following a planning phase, a business plan was developed that prioritized best practices to be implemented in Omaha. The business plan was developed using the Ecological Model, Health Policy Model, and Robert Wood Johnson Foundation Active Living by Design 5P model. The three models helped the community identify target populations and activities that then created a single model for sustainable change. Twenty-four initiatives were identified, over one million dollars in funding was secured, and evaluation strategies were identified. By using the models from the initial steps through evaluation, a clear facilitation of the process was possible, and the result was a comprehensive, feasible plan. The use of the models to design a strategic plan was pivotal in building a sustainable coalition to achieve measurable improvements in the health of children and prove replicable over time.

Dissemination of public health information: key tools utilised by the NECOBELAC network in Europe and Latin America.

PubMed

De Castro, Paola; Marsili, Daniela; Poltronieri, Elisabetta; Calderón, Carlos Agudelo

2012-06-01

 Open Access (OA) to scientific information is an important step forward in communication patterns, yet we still need to reinforce OA principles to promote a cultural change of traditional publishing practices. The advantages of free access to scientific information are even more evident in public health where knowledge is directly associated with human wellbeing.  An OA 'consolidation' initiative in public health is presented to show how the involvement of people and institutions is fundamental to create awareness on OA and promote a cultural change. This initiative is developed within the project NEtwork of COllaboration Between Europe and Latin American Caribbean countries (NECOBELAC), financed by the European Commission.  Three actions are envisaged: Capacity building through a flexible and sustainable training programme on scientific writing and OA publishing; creation of training tools based on semantic web technologies; development of a network of supporting institutions.  In 2010-2011, 23 training initiatives were performed involving 856 participants from 15 countries; topic maps on scientific publication and OA were produced; 195 institutions are included in the network.  Cultural change in scientific dissemination practices is a long process requiring a flexible approach and strong commitment by all stakeholders. © 2012 The authors. Health Information and Libraries Journal © 2012 Health Libraries Group Health Information and Libraries Journal.

Concurrent Initialization for Bearing-Only SLAM

PubMed Central

Munguía, Rodrigo; Grau, Antoni

2010-01-01

Simultaneous Localization and Mapping (SLAM) is perhaps the most fundamental problem to solve in robotics in order to build truly autonomous mobile robots. The sensors have a large impact on the algorithm used for SLAM. Early SLAM approaches focused on the use of range sensors as sonar rings or lasers. However, cameras have become more and more used, because they yield a lot of information and are well adapted for embedded systems: they are light, cheap and power saving. Unlike range sensors which provide range and angular information, a camera is a projective sensor which measures the bearing of images features. Therefore depth information (range) cannot be obtained in a single step. This fact has propitiated the emergence of a new family of SLAM algorithms: the Bearing-Only SLAM methods, which mainly rely in especial techniques for features system-initialization in order to enable the use of bearing sensors (as cameras) in SLAM systems. In this work a novel and robust method, called Concurrent Initialization, is presented which is inspired by having the complementary advantages of the Undelayed and Delayed methods that represent the most common approaches for addressing the problem. The key is to use concurrently two kinds of feature representations for both undelayed and delayed stages of the estimation. The simulations results show that the proposed method surpasses the performance of previous schemes. PMID:22294884

Nucleosome occupancy as a novel chromatin parameter for replication origin functions

PubMed Central

Rodriguez, Jairo; Lee, Laura; Lynch, Bryony; Tsukiyama, Toshio

2017-01-01

Eukaryotic DNA replication initiates from multiple discrete sites in the genome, termed origins of replication (origins). Prior to S phase, multiple origins are poised to initiate replication by recruitment of the pre-replicative complex (pre-RC). For proper replication to occur, origin activation must be tightly regulated. At the population level, each origin has a distinct firing time and frequency of activation within S phase. Many studies have shown that chromatin can strongly influence initiation of DNA replication. However, the chromatin parameters that affect properties of origins have not been thoroughly established. We found that nucleosome occupancy in G1 varies greatly around origins across the S. cerevisiae genome, and nucleosome occupancy around origins significantly correlates with the activation time and efficiency of origins, as well as pre-RC formation. We further demonstrate that nucleosome occupancy around origins in G1 is established during transition from G2/M to G1 in a pre-RC-dependent manner. Importantly, the diminished cell-cycle changes in nucleosome occupancy around origins in the orc1-161 mutant are associated with an abnormal global origin usage profile, suggesting that proper establishment of nucleosome occupancy around origins is a critical step for regulation of global origin activities. Our work thus establishes nucleosome occupancy as a novel and key chromatin parameter for proper origin regulation. PMID:27895110

Regional survey supports national initiative for 'water-only' schools in New Zealand.

PubMed

Mansoor, Osman David; Ali, Rukhsana; Richards, Ruth

2017-10-01

To support a national initiative to remove sugary drinks from schools and limit drinks to water or unflavoured milk ('water-only'). We emailed all 201 schools with primary school aged children in the Greater Wellington region with a survey on (1) current status of, (2) support needs for, and (3) barriers to or lessons learned from, a 'water-only' school policy. Only 78 (39%) of schools responded. Most supported 'water-only': 22 (28%) had implemented a policy; 10 (13%) in process of doing so; 22 (28%) were considering it; and 12 (15%) were 'water-only', but did not have a policy. Only 12 (15%) were not considering a 'water-only' policy. The main barrier reported was lack of community and/or family support. Many schools did not see any barriers beyond the time needed for consultation. Monitoring and communication were identified as key to success. A quarter of schools requested public health nurse support for a 'water-only' policy. The survey elicited a range of views on 'water-only' policies for schools, but suggests that 'water-only' may be an emerging norm for schools. Implications for public health: Our survey shows how local assessment can support a national initiative by providing a baseline, identifying schools that want support, and sharing lessons. Making schools 'water-only' could be a first step in changing our children's environment to prevent obesity. © 2017 Regional Public Health.

The New Hampshire Ten Steps to Successful Breastfeeding Collaborative: A Statewide QI Initiative.

PubMed

Whalen, Bonny L; Kelly, Joyce; Holmes, Alison Volpe

2015-06-01

Despite national recognition for their breastfeeding-friendly practices, many New Hampshire hospitals are still not achieving the Ten Steps to Successful Breastfeeding. To increase achievement of the Ten Steps in New Hampshire's birthing hospitals, facilitate Baby-Friendly Hospital Initiative (BFHI) designation for interested hospitals, and improve rates of in-hospital any and exclusive breastfeeding. After a 2010 needs assessment, we conducted 2 statewide workshops targeting 6 of the Ten Steps found to be most deficient among New Hampshire birthing hospitals. Eighteen of 20 hospitals attended at least 1 workshop, and 6 participated in an intensive collaborative. In 2013, we analyzed interval Ten Step achievement and in-hospital breastfeeding trends. Staff education showed the greatest improvement, increasing step 2 achievement from 1 to 6 hospitals (P=.05). Although the number of hospitals implementing step 6 (breast milk only) and step 9 (no artificial nipples) increased, differences were not statistically significant. Intensive collaborative hospitals achieved an average of 1.5 new steps, whereas non-Baby Friendly hospitals lost 0.7 steps (P=.05). In-hospital breastfeeding rates increased in intensive collaborative hospitals and were significantly higher than those in non-Baby Friendly hospitals by the end of the study (any breastfeeding, 89% vs 73%, P=.03; exclusive breastfeeding, 84% vs 61%, P<.001). A statewide improvement collaborative facilitated increases in Ten Step achievement and in-hospital breastfeeding for hospitals participating in an intensive collaborative. Active work in Ten Step implementation, including staff education, appears to be more effective in increasing in-hospital breastfeeding than does BFHI designation alone. Copyright © 2015 by the American Academy of Pediatrics.

A short and efficient synthesis of the pharmacological research tool GW501516 for the peroxisome proliferator-activated receptor delta.

PubMed

Wei, Zhi-Liang; Kozikowski, Alan P

2003-11-14

The most potent and selective peroxisome proliferator-activated receptor delta (PPARdelta) agonist GW501516 (1) was synthesized in 4 steps and 78% overall yield starting from o-cresol by using a one-pot regiocontrolled dialkylation of mercaptophenol 5 as the key step.

A Miniature Wastewater Cleaning Plant to Demonstrate Primary Treatment in the Classroom

ERIC Educational Resources Information Center

Ne´el, Bastien; Cardoso, Catia; Perret, Didier; Bakker, Eric

2015-01-01

A small-scale wastewater cleaning plant is described that includes the key physical pretreatment steps followed by the chemical treatment of mud by flocculation. Water, clay particles, and riverside deposits mimicked odorless wastewater. After a demonstration of the optimization step, the flocculation process was carried out with iron(III)…

Strengthening the revenue cycle: a 4-step method for optimizing payment.

PubMed

Clark, Jonathan J

2008-10-01

Four steps for enhancing the revenue cycle to ensure optimal payment are: *Establish key performance indicator dashboards in each department that compare current with targeted performance; *Create proper organizational structures for each department; *Ensure that high-performing leaders are hired in all management and supervisory positions; *Implement efficient processes in underperforming operations.

First Steps to School Readiness: South Carolina's Response to At-Risk Early Childhood Population.

ERIC Educational Resources Information Center

Buford, Rhonda; Stegelin, Dolores A.

2003-01-01

Describes South Carolina's new state early childhood program, First Steps to School Readiness. Includes a profile of the state's at-risk child population, noting poverty and education risk indicators, and describing key program components. The article discusses program oversight, local program partnerships, program funding mechanisms, and local…

Client-centered counseling improves client satisfaction with family planning visits: evidence from Irbid, Jordan

PubMed Central

Kamhawi, Sarah; Underwood, Carol; Murad, Huda; Jabre, Bushra

2013-01-01

ABSTRACT Background: High levels of unmet need for family planning and high contraceptive discontinuation rates persist in Jordan, prompting the Jordan Health Communication Partnership (JHCP) to initiate a client-centered family planning service program called “Consult and Choose” (CC), together with community-based activities to encourage women with unmet need to visit health centers. Methods: We held exit interviews with 461 family planning clients between November–December 2011 to assess, from the clients' perspective, whether trained providers followed the CC protocol and used the CC tools, as well as to measure client satisfaction. We also tracked referral card information from community-based activities to health centers and examined service statistics to explore trends in family planning use. Results: On average, clients reported that providers performed 5.6 of the 7 steps outlined in the CC protocol. Nearly 83% of respondents were very satisfied with their clinic visits. Logistic regression analysis found that the odds of being “very satisfied” increases by 20% with each additional counseling protocol step performed and by 70% with each increase in the number of CC materials used. Between June 2011 and August 2012, 14,490 referral cards from community-based activities were collected in health centers, 59% of which were for family planning services. Service statistic trends indicate an increase in the number of new family planning users and in couple-years of protection after starting the CC program. Conclusions: Implementation of the CC program at health centers nationally, in tandem with community-based interventions, could play a key role in attaining Jordan's goal of reducing its total fertility rate to 2.1 by 2030. Although this initiative would likely be replicated most readily in other middle-income countries, lower-resource countries could also adapt the tested CC approach. PMID:25276531

Intracellular Trafficking and Persistence of Acinetobacter baumannii Requires Transcription Factor EB

PubMed Central

Parra-Millán, Raquel; Guerrero-Gómez, David; Ayerbe-Algaba, Rafael; Pachón-Ibáñez, Maria Eugenia; Miranda-Vizuete, Antonio

2018-01-01

ABSTRACT Acinetobacter baumannii is a significant human pathogen associated with hospital-acquired infections. While adhesion, an initial and important step in A. baumannii infection, is well characterized, the intracellular trafficking of this pathogen inside host cells remains poorly studied. Here, we demonstrate that transcription factor EB (TFEB) is activated after A. baumannii infection of human lung epithelial cells (A549). We also show that TFEB is required for the invasion and persistence inside A549 cells. Consequently, lysosomal biogenesis and autophagy activation were observed after TFEB activation which could increase the death of A549 cells. In addition, using the Caenorhabditis elegans infection model by A. baumannii, the TFEB orthologue HLH-30 was required for survival of the nematode to infection, although nuclear translocation of HLH-30 was not required. These results identify TFEB as a conserved key factor in the pathogenesis of A. baumannii. IMPORTANCE Adhesion is an initial and important step in Acinetobacter baumannii infections. However, the mechanism of entrance and persistence inside host cells is unclear and remains to be understood. In this study, we report that, in addition to its known role in host defense against Gram-positive bacterial infection, TFEB also plays an important role in the intracellular trafficking of A. baumannii in host cells. TFEB was activated shortly after A. baumannii infection and is required for its persistence within host cells. Additionally, using the C. elegans infection model by A. baumannii, the TFEB orthologue HLH-30 was required for survival of the nematode to infection, although nuclear translocation of HLH-30 was not required. PMID:29600279

Neural circuitry coordinating male copulation

PubMed Central

Pavlou, Hania J; Lin, Andrew C; Neville, Megan C; Nojima, Tetsuya; Diao, Fengqiu; Chen, Brian E; White, Benjamin H; Goodwin, Stephen F

2016-01-01

Copulation is the goal of the courtship process, crucial to reproductive success and evolutionary fitness. Identifying the circuitry underlying copulation is a necessary step towards understanding universal principles of circuit operation, and how circuit elements are recruited into the production of ordered action sequences. Here, we identify key sex-specific neurons that mediate copulation in Drosophila, and define a sexually dimorphic motor circuit in the male abdominal ganglion that mediates the action sequence of initiating and terminating copulation. This sexually dimorphic circuit composed of three neuronal classes – motor neurons, interneurons and mechanosensory neurons – controls the mechanics of copulation. By correlating the connectivity, function and activity of these neurons we have determined the logic for how this circuitry is coordinated to generate this male-specific behavior, and sets the stage for a circuit-level dissection of active sensing and modulation of copulatory behavior. DOI: http://dx.doi.org/10.7554/eLife.20713.001 PMID:27855059

Defining the key pharmacophore elements of PF-04620110: discovery of a potent, orally-active, neutral DGAT-1 inhibitor.

PubMed

Dow, Robert L; Andrews, Melissa P; Li, Jian-Cheng; Michael Gibbs, E; Guzman-Perez, Angel; Laperle, Jennifer L; Li, Qifang; Mather, Dawn; Munchhof, Michael J; Niosi, Mark; Patel, Leena; Perreault, Christian; Tapley, Susan; Zavadoski, William J

2013-09-01

DGAT-1 is an enzyme that catalyzes the final step in triglyceride synthesis. mRNA knockout experiments in rodent models suggest that inhibitors of this enzyme could be of value in the treatment of obesity and type II diabetes. The carboxylic acid-based DGAT-1 inhibitor 1 was advanced to clinical trials for the treatment of type 2 diabetes, despite of the low passive permeability of 1. Because of questions relating to the potential attenuation of distribution and efficacy of a poorly permeable agent, efforts were initiated to identify compounds with improved permeability. Replacement of the acid moiety in 1 with an oxadiazole led to the discovery of 52, which possesses substantially improved passive permeability. The resulting pharmacodynamic profile of this neutral DGAT-1 inhibitor was found to be similar to 1 at comparable plasma exposures. Copyright © 2013 Elsevier Ltd. All rights reserved.

A Decentralized Approach to the Formulation of Hypotheses: A Hierarchical Structural Model for a Prion Self-Assembled System

NASA Astrophysics Data System (ADS)

Wang, Mingyang; Zhang, Feifei; Song, Chao; Shi, Pengfei; Zhu, Jin

2016-07-01

Innovation in hypotheses is a key transformative driver for scientific development. The conventional centralized hypothesis formulation approach, where a dominant hypothesis is typically derived from a primary phenomenon, can, inevitably, impose restriction on the range of conceivable experiments and legitimate hypotheses, and ultimately impede understanding of the system of interest. We report herein the proposal of a decentralized approach for the formulation of hypotheses, through initial preconception-free phenomenon accumulation and subsequent reticular logical reasoning processes. The two-step approach can provide an unbiased, panoramic view of the system and as such should enable the generation of a set of more coherent and therefore plausible hypotheses. As a proof-of-concept demonstration of the utility of this open-ended approach, a hierarchical model has been developed for a prion self-assembled system, allowing insight into hitherto elusive static and dynamic features associated with this intriguing structure.

Degradation of paracetamol by Pseudomonas aeruginosa strain HJ1012.

PubMed

Hu, Jun; Zhang, Li L; Chen, Jian M; Liu, Yu

2013-01-01

Pseudomonas aeruginosa strain HJ1012 was isolated on paracetamol as a sole carbon and energy source. This organism could completely degrade paracetamol as high as 2200 mg/L. Following paracetamol consumption, a CO₂ yield rate up to 71.4% proved that the loss of paracetamol was mainly via mineralization. Haldane's equation adequately described the relationship between the specific growth rate and substrate concentration. The maximum specific growth rate and yield coefficient were 0.201 g-Paracetamol/g-VSS·h and 0.101 mg of biomass yield/mg of paracetamol consumed, respectively. A total of 8 metabolic intermediates was identified and classified into aromatic compounds, carboxylic acids, and inorganic species (nitrite and nitrate ions). P-aminophenol and hydroquinone are the two key metabolites of the initial steps in the paracetamol catabolic pathway. Paracetamol is degraded predominantly via p-aminophenol to hydroquinone with subsequent ring fission, suggesting partially new pathways for paracetamol-degrading bacteria.

Raindrops of synaptic noise on dual excitability landscape: an approach to astrocyte network modelling

NASA Astrophysics Data System (ADS)

Verisokin, Andrey Yu.; Postnov, Dmitry E.; Verveyko, Darya V.; Brazhe, Alexey R.

2018-04-01

The most abundant non-neuronal cells in the brain, astrocytes, populate all parts of the central nervous system (CNS). Astrocytic calcium activity ranging from subcellular sparkles to intercellular waves is believed to be the key to a plethora of regulatory pathways in the central nervous system from synaptic plasticity to blood flow regulation. Modeling of the calcium wave initiation and transmission and their spatiotemporal dynamics is therefore an important step stone in understanding the crucial cogs of cognition. Astrocytes are active sensors of ongoing neuronal and synaptic activity, and neurotransmitters diffusing from the synaptic cleft make a strong impact on the astrocytic activity. Here we propose a model describing the patterns of calcium wave formation at a single cell level and discuss the interplay between astrocyte shape the calcium waves dynamics driven by local stochastic surges of glutamate simulating synaptic activity.

Towards a Graphene-Based Low Intensity Photon Counting Photodetector

PubMed Central

Williams, Jamie O. D.; Alexander-Webber, Jack A.; Lapington, Jon S.; Roy, Mervyn; Hutchinson, Ian B.; Sagade, Abhay A.; Martin, Marie-Blandine; Braeuninger-Weimer, Philipp; Cabrero-Vilatela, Andrea; Wang, Ruizhi; De Luca, Andrea; Udrea, Florin; Hofmann, Stephan

2016-01-01

Graphene is a highly promising material in the development of new photodetector technologies, in particular due its tunable optoelectronic properties, high mobilities and fast relaxation times coupled to its atomic thinness and other unique electrical, thermal and mechanical properties. Optoelectronic applications and graphene-based photodetector technology are still in their infancy, but with a range of device integration and manufacturing approaches emerging this field is progressing quickly. In this review we explore the potential of graphene in the context of existing single photon counting technologies by comparing their performance to simulations of graphene-based single photon counting and low photon intensity photodetection technologies operating in the visible, terahertz and X-ray energy regimes. We highlight the theoretical predictions and current graphene manufacturing processes for these detectors. We show initial experimental implementations and discuss the key challenges and next steps in the development of these technologies. PMID:27563903

Development of seals for a geothermal downhole intensifier. Progress report

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

Captain, K.M.; Harvey, A.C.; Caskey, B.C.

1985-08-01

A system using high-velocity fluid jets in conjunction with a rotary diamond bit is currently considered as the best candidate for reducing the cost of drilling geothermal wells. Technical, safety and cost considerations indicate that the required jet supply pressure can best be established by a downhole pressure intensifier. Key intensifier components are the check valve and plunger seals, which must prevent leakage of the high-pressure, high-temperature abrasive fluid (drilling mud). To achieve the required performance, novel ceramic seals are currently being developed. The check valve seal includes a tapered polymeric plug and ceramic stop acting against a ceramic seat.more » The ceramic plunger seal is a variant of the ''stepped-joint'' piston ring and is designed to minimize contact pressure and abrasive wear. Initial testing of these seals in the laboratory shows encouraging results; design refinement and further testing is in progress. 2 refs., 6 figs., 3 tabs.« less

The Biology of Bone Metastasis.

PubMed

Esposito, Mark; Guise, Theresa; Kang, Yibin

2018-06-01

Bone metastasis, or the development of secondary tumors within the bone of cancer patients, is a debilitating and incurable disease. Despite its morbidity, the biology of bone metastasis represents one of the most complex and intriguing of all oncogenic processes. This complexity derives from the intricately organized bone microenvironment in which the various stages of hematopoiesis, osteogenesis, and osteolysis are jointly regulated but spatially restricted. Disseminated tumor cells (DTCs) from various common malignancies such as breast, prostate, lung, and kidney cancers or myeloma are uniquely primed to subvert these endogenous bone stromal elements to grow into pathological osteolytic or osteoblastic lesions. This colonization process can be separated into three key steps: seeding, dormancy, and outgrowth. Targeting the processes of dormancy and initial outgrowth offers the most therapeutic promise. Here, we discuss the concepts of the bone metastasis niche, from controlling tumor-cell survival to growth into clinically detectable disease. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Forces Driving Chaperone Action

PubMed Central

Koldewey, Philipp; Stull, Frederick; Horowitz, Scott; Martin, Raoul; Bardwell, James C. A.

2016-01-01

SUMMARY It is still unclear what molecular forces drive chaperone-mediated protein folding. Here, we obtain a detailed mechanistic understanding of the forces that dictate the four key steps of chaperone-client interaction: initial binding, complex stabilization, folding, and release. Contrary to the common belief that chaperones recognize unfolding intermediates by their hydrophobic nature, we discover that the model chaperone Spy uses long-range electrostatic interactions to rapidly bind to its unfolded client protein Im7. Short-range hydrophobic interactions follow, which serve to stabilize the complex. Hydrophobic collapse of the client protein then drives its folding. By burying hydrophobic residues in its core, the client’s affinity to Spy decreases, which causes client release. By allowing the client to fold itself, Spy circumvents the need for client-specific folding instructions. This mechanism might help explain how chaperones can facilitate the folding of various unrelated proteins. PMID:27293188

NASA Post-Columbia Safety & Mission Assurance, Review and Assessment Initiatives

NASA Astrophysics Data System (ADS)

Newman, J. Steven; Wander, Stephen M.; Vecellio, Don; Miller, Andrew J.

2005-12-01

On February 1, 2003, NASA again experienced a tragic accident as the Space Shuttle Columbia broke apart upon reentry, resulting in the loss of seven astronauts. Several of the findings and observations of the Columbia Accident Investigation Board addressed the need to strengthen the safety and mission assurance function at NASA. This paper highlights key steps undertaken by the NASA Office of Safety and Mission Assurance (OSMA) to establish a stronger and more- robust safety and mission assurance function for NASA programs, projects, facilities and operations. This paper provides an overview of the interlocking OSMA Review and Assessment Division (RAD) institutional and programmatic processes designed to 1) educate, inform, and prepare for audits, 2) verify requirements flow-down, 3) verify process capability, 4) verify compliance with requirements, 5) support risk management decision making, 6) facilitate secure web- based collaboration, and 7) foster continual improvement and the use of lessons learned.

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

Poudel, Saroj; Aryal, Niranjan; Lu, Chaofu

Camelina sativa is an annual oilseed crop that is under intensive development for renewable resources of biofuels and industrial oils. MicroRNAs, or miRNAs, are endogenously encoded small RNAs that play key roles in diverse plant biological processes. Here, we conducted deep sequencing on small RNA libraries prepared from camelina leaves, flower buds and two stages of developing seeds corresponding to initial and peak storage products accumulation. Computational analyses identified 207 known miRNAs belonging to 63 families, as well as 5 novel miRNAs. These miRNAs, especially members of the miRNA families, varied greatly in different tissues and developmental stages. The predictedmore » miRNA target genes are involved in a broad range of physiological functions including lipid metabolism. This report is the first step toward elucidating roles of miRNAs in C. sativa and will provide additional tools to improve this oilseed crop for biofuels and biomaterials.« less

System Identification Applied to Dynamic CFD Simulation and Wind Tunnel Data

NASA Technical Reports Server (NTRS)

Murphy, Patrick C.; Klein, Vladislav; Frink, Neal T.; Vicroy, Dan D.

2011-01-01

Demanding aerodynamic modeling requirements for military and civilian aircraft have provided impetus for researchers to improve computational and experimental techniques. Model validation is a key component for these research endeavors so this study is an initial effort to extend conventional time history comparisons by comparing model parameter estimates and their standard errors using system identification methods. An aerodynamic model of an aircraft performing one-degree-of-freedom roll oscillatory motion about its body axes is developed. The model includes linear aerodynamics and deficiency function parameters characterizing an unsteady effect. For estimation of unknown parameters two techniques, harmonic analysis and two-step linear regression, were applied to roll-oscillatory wind tunnel data and to computational fluid dynamics (CFD) simulated data. The model used for this study is a highly swept wing unmanned aerial combat vehicle. Differences in response prediction, parameters estimates, and standard errors are compared and discussed

[A bomb attack in the Netherlands; how would we provide hospital care?

PubMed

Haverkort, J J M; de Jong, M B; van Spengler, L L; Leenen, L P H

2017-01-01

- There is an ever-present threat of large-scale incidents and disasters, such as terrorism and natural disasters.- Preparation and planning are the key to successful response to major incidents and disasters, which is why education, training sessions and exercises take place in the Netherlands.- Analysis of recent large-scale incidents in Europe and the USA emphasises the importance of adequate distribution of the wounded to centres where the correct care can be provided.- A major step has been taken in the Netherlands to provide for such an eventuality with the introduction of distribution plans for the wounded, and other initiatives such as a regional hospital disaster plan.- If a large-scale incident should take place the Netherlands also has a Major Incident Hospital at its disposal; this is a unique facility that can guarantee availability of 200 spare beds to the Netherlands healthcare system within 30 minutes.

A hybrid-type quantum random number generator

NASA Astrophysics Data System (ADS)

Hai-Qiang, Ma; Wu, Zhu; Ke-Jin, Wei; Rui-Xue, Li; Hong-Wei, Liu

2016-05-01

This paper proposes a well-performing hybrid-type truly quantum random number generator based on the time interval between two independent single-photon detection signals, which is practical and intuitive, and generates the initial random number sources from a combination of multiple existing random number sources. A time-to-amplitude converter and multichannel analyzer are used for qualitative analysis to demonstrate that each and every step is random. Furthermore, a carefully designed data acquisition system is used to obtain a high-quality random sequence. Our scheme is simple and proves that the random number bit rate can be dramatically increased to satisfy practical requirements. Project supported by the National Natural Science Foundation of China (Grant Nos. 61178010 and 11374042), the Fund of State Key Laboratory of Information Photonics and Optical Communications (Beijing University of Posts and Telecommunications), China, and the Fundamental Research Funds for the Central Universities of China (Grant No. bupt2014TS01).

Monte Carlo study of the hetero-polytypical growth of cubic on hexagonal silicon carbide polytypes

NASA Astrophysics Data System (ADS)

Camarda, Massimo

2012-08-01

In this article we use three dimensional kinetic Monte Carlo simulations on super-lattices to study the hetero-polytypical growth of cubic silicon carbide polytype (3C-SiC) on misoriented hexagonal (4H and 6H) substrates. We analyze the quality of the 3C-SiC film varying the polytype, the miscut angle and the initial surface morphology of the substrate. We find that the use of 6H misoriented (4°-10° off) substrates, with step bunched surfaces, can strongly improve the quality of the cubic epitaxial film whereas the 3C/4H growth is affected by the generation of dislocations, due to the incommensurable periodicity of the 3C (3) and the 4H (4) polytypes. For these reasons, a proper pre-growth treatment of 6H misoriented substrates can be the key for the growth of high quality, twin free, 3C-SiC films.

Cu-catalyzed aerobic oxidative cyclizations of 3-N-hydroxyamino-1,2-propadienes with alcohols, thiols, and amines to form α-O-, S-, and N-substituted 4-methylquinoline derivatives.

PubMed

Sharma, Pankaj; Liu, Rai-Shung

2015-03-16

A one-pot, two-step synthesis of α-O-, S-, and N-substituted 4-methylquinoline derivatives through Cu-catalyzed aerobic oxidations of N-hydroxyaminoallenes with alcohols, thiols, and amines is described. This reaction sequence involves an initial oxidation of N-hydroxyaminoallenes with NuH (Nu = OH, OR, NHR, and SR) to form 3-substituted 2-en-1-ones, followed by Brønsted acid catalyzed intramolecular cyclizations of the resulting products. Our mechanistic analysis suggests that the reactions proceed through a radical-type mechanism rather than a typical nitrone-intermediate route. The utility of this new Cu-catalyzed reaction is shown by its applicability to the synthesis of several 2-amino-4-methylquinoline derivatives, which are known to be key precursors to several bioactive molecules. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Decomposition Techniques for Icesat/glas Full-Waveform Data

NASA Astrophysics Data System (ADS)

Liu, Z.; Gao, X.; Li, G.; Chen, J.

2018-04-01

The geoscience laser altimeter system (GLAS) on the board Ice, Cloud, and land Elevation Satellite (ICESat), is the first long-duration space borne full-waveform LiDAR for measuring the topography of the ice shelf and temporal variation, cloud and atmospheric characteristics. In order to extract the characteristic parameters of the waveform, the key step is to process the full waveform data. In this paper, the modified waveform decomposition method is proposed to extract the echo components from full-waveform. First, the initial parameter estimation is implemented through data preprocessing and waveform detection. Next, the waveform fitting is demonstrated using the Levenberg-Marquard (LM) optimization method. The results show that the modified waveform decomposition method can effectively extract the overlapped echo components and missing echo components compared with the results from GLA14 product. The echo components can also be extracted from the complex waveforms.

Clinical research data sharing: what an open science world means for researchers involved in evidence synthesis.

PubMed

Ross, Joseph S

2016-09-20

The International Committee of Medical Journal Editors (ICMJE) recently announced a bold step forward to require data generated by interventional clinical trials that are published in its member journals to be responsibly shared with external investigators. The movement toward a clinical research culture that supports data sharing has important implications for the design, conduct, and reporting of systematic reviews and meta-analyses. While data sharing is likely to enhance the science of evidence synthesis, facilitating the identification and inclusion of all relevant research, it will also pose key challenges, such as requiring broader search strategies and more thorough scrutiny of identified research. Furthermore, the adoption of data sharing initiatives by the clinical research community should challenge the community of researchers involved in evidence synthesis to follow suit, including the widespread adoption of systematic review registration, results reporting, and data sharing, to promote transparency and enhance the integrity of the research process.

Economic Efficiency and Investment Timing for Dual Water Systems

NASA Astrophysics Data System (ADS)

Leconte, Robert; Hughes, Trevor C.; Narayanan, Rangesan

1987-10-01

A general methodology to evaluate the economic feasibility of dual water systems is presented. In a first step, a static analysis (evaluation at a single point in time) is developed. The analysis requires the evaluation of consumers' and producer's surpluses from water use and the capital cost of the dual (outdoor) system. The analysis is then extended to a dynamic approach where the water demand increases with time (as a result of a population increase) and where the dual system is allowed to expand. The model determines whether construction of a dual system represents a net benefit, and if so, what is the best time to initiate the system (corresponding to maximization of social welfare). Conditions under which an analytic solution is possible are discussed and results of an application are summarized (including sensitivity to different parameters). The analysis allows identification of key parameters influencing attractiveness of dual water systems.

Applying Structural Systems Thinking to Frame Perspectives on Social Work Innovation.

PubMed

Stringfellow, Erin J

2017-03-01

Innovation will be key to the success of the Grand Challenges Initiative in social work. A structural systems framework based in system dynamics could be useful for considering how to advance innovation. Diagrams using system dynamics conventions were developed to link common themes across concept papers written by social work faculty members and graduate students ( N = 19). Transdisciplinary teams and ethical partnerships with communities and practitioners will be needed to responsibly develop high-quality innovative solutions. A useful next step would be to clarify to what extent factors that could "make or break" these partnerships arise from within versus outside of the field of social work and how this has changed over time. Advancing innovation in social work will mean making decisions in a complex, ever-changing system. Principles and tools from methods that account for complexity, such as system dynamics, can help improve this decision-making process.

Applying Structural Systems Thinking to Frame Perspectives on Social Work Innovation

PubMed Central

Stringfellow, Erin J.

2017-01-01

Objective Innovation will be key to the success of the Grand Challenges Initiative in social work. A structural systems framework based in system dynamics could be useful for considering how to advance innovation. Method Diagrams using system dynamics conventions were developed to link common themes across concept papers written by social work faculty members and graduate students (N = 19). Results Transdisciplinary teams and ethical partnerships with communities and practitioners will be needed to responsibly develop high-quality innovative solutions. A useful next step would be to clarify to what extent factors that could “make or break” these partnerships arise from within versus outside of the field of social work and how this has changed over time. Conclusions Advancing innovation in social work will mean making decisions in a complex, ever-changing system. Principles and tools from methods that account for complexity, such as system dynamics, can help improve this decision-making process. PMID:28298877

Comparison against 186 canid whole-genome sequences reveals survival strategies of an ancient clonally transmissible canine tumor

PubMed Central

Decker, Brennan; Davis, Brian W.; Rimbault, Maud; Long, Adrienne H.; Karlins, Eric; Jagannathan, Vidhya; Reiman, Rebecca; Parker, Heidi G.; Drögemüller, Cord; Corneveaux, Jason J.; Chapman, Erica S.; Trent, Jeffery M.; Leeb, Tosso; Huentelman, Matthew J.; Wayne, Robert K.; Karyadi, Danielle M.; Ostrander, Elaine A.

2015-01-01

Canine transmissible venereal tumor (CTVT) is a parasitic cancer clone that has propagated for thousands of years via sexual transfer of malignant cells. Little is understood about the mechanisms that converted an ancient tumor into the world's oldest known continuously propagating somatic cell lineage. We created the largest existing catalog of canine genome-wide variation and compared it against two CTVT genome sequences, thereby separating alleles derived from the founder's genome from somatic mutations that must drive clonal transmissibility. We show that CTVT has undergone continuous adaptation to its transmissible allograft niche, with overlapping mutations at every step of immunosurveillance, particularly self-antigen presentation and apoptosis. We also identified chronologically early somatic mutations in oncogenesis- and immune-related genes that may represent key initiators of clonal transmissibility. Thus, we provide the first insights into the specific genomic aberrations that underlie CTVT's dogged perseverance in canids around the world. PMID:26232412

Food Fraud Prevention: Policy, Strategy, and Decision-Making - Implementation Steps for a Government Agency or Industry.

PubMed

Spink, John; Fortin, Neal D; Moyer, Douglas C; Miao, Hong; Wu, Yongning

2016-01-01

This paper addresses the role of governments, industry, academics, and non-governmental organizations in Food Fraud prevention. Before providing strategic concepts for governments and authorities, definitions of Food Fraud are reviewed and discussed. Next there is a review of Food Fraud activities by the Global Food Safety Initiative (GFSI), the Elliott Review in the United Kingdom, the European Commission resolution on Food Fraud, and the US Food Safety Modernization Act including the Preventative Controls Rule. Two key concepts for governments or a company are: (1) formally, and specifically, mention food fraud as a food issue and (2) create an enterprise-wide Food Fraud prevention plan. The research includes a case study of the implementation of the concepts by a state or provincial agency. This analysis provides a foundation to review the role of science and technology in detection, deterrence and then contributing to prevention.

Inflammatory and immunological aspects of dental pulp repair

PubMed Central

Goldberg, Michel; Farges, Jean-Christophe; Lacerda-Pinheiro, Sally; Six, Ngampis; Jegat, Nadège; Decup, Frank; Septier, Dominique; Carrouel, Florence; Durand, Stéphanie; Chaussain-Miller, Catherine; DenBesten, Pamela; Veis, Arthur; Poliard, Anne

2010-01-01

The repair of dental pulp by direct capping with calcium hydroxide or by implantation of bioactive extracellular matrix (ECM) molecules implies a cascade of four steps: a moderate inflammation, the commitment of adult reserve stem cells, their proliferation and terminal differentiation. The link between the initial inflammation and cell commitment is not yet well established but appears as a potential key factor in the reparative process. Either the release of cytokines due to inflammatory events activates resident stem (progenitor) cells, or inflammatory cells or pulp fibroblasts undergo a phenotypic conversion into osteoblast/odontoblast-like progenitors implicated in reparative dentin formation. Activation of antigen-presenting dendritic cells by mild inflammatory processes may also promote osteoblast/odontoblast-like differentiation and expression of ECM molecules implicated in mineralization. Recognition of bacteria by specific odontoblast and fibroblast membrane receptors triggers an inflammatory and immune response within the pulp tissue that would also modulate the repair process. PMID:18602009

In Vivo Delivery of Nanoparticles into Plant Leaves.

PubMed

Wu, Honghong; Santana, Israel; Dansie, Joshua; Giraldo, Juan P

2017-12-14

Plant nanobiotechnology is an interdisciplinary field at the interface of nanotechnology and plant biology that aims to utilize nanomaterials as tools to study, augment or impart novel plant functions. The delivery of nanoparticles to plants in vivo is a key initial step to investigate plant nanoparticle interactions and the impact of nanoparticles on plant function. Quantum dots are smaller than plant cell wall pores, have versatile surface chemistry, bright fluorescence and do not photobleach, making them ideal for the study of nanoparticle uptake, transport, and distribution in plants by widely available confocal microscopy tools. Herein, we describe three different methods for quantum dot delivery into leaves of living plants: leaf lamina infiltration, whole shoot vacuum infiltration, and root to leaf translocation. These methods can be potentially extended to other nanoparticles, including nanosensors and drug delivery nanoparticles. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

High-performance mesoporous LiFePO₄ from Baker's yeast.

PubMed

Zhang, Xudong; Zhang, Xueguang; He, Wen; Sun, Caiyun; Ma, Jingyun; Yuan, Junling; Du, Xiaoyong

2013-03-01

Based on the biomineralization assembly concept, a simple and inexpensive biomimetic sol-gel method is found to synthesize high-performance mesoporous LiFePO(4) (HPM-LFP). The key step of this approach is to apply Baker's yeast cells as both a structural template and a biocarbon source. The formation mechanism of ordered hierarchical mesoporous network structure is revealed by characterizing its morphology and microstructure. The HPM-LFP exhibits outstanding electrochemical performances. The HPM-LFP has a high discharge capacity (about 153 mAh g(-1) at a 0.1 C rate), only 2% capacity loss from the initial value after 100 cycles at a current density of 0.1 C. This simple and potentially universal design strategy is currently being pursued in the synthesis of an ideal cathode-active material for high power applications. Copyright © 2012 Elsevier B.V. All rights reserved.

In Silico Constraint-Based Strain Optimization Methods: the Quest for Optimal Cell Factories

PubMed Central

Maia, Paulo; Rocha, Miguel

2015-01-01

SUMMARY Shifting from chemical to biotechnological processes is one of the cornerstones of 21st century industry. The production of a great range of chemicals via biotechnological means is a key challenge on the way toward a bio-based economy. However, this shift is occurring at a pace slower than initially expected. The development of efficient cell factories that allow for competitive production yields is of paramount importance for this leap to happen. Constraint-based models of metabolism, together with in silico strain design algorithms, promise to reveal insights into the best genetic design strategies, a step further toward achieving that goal. In this work, a thorough analysis of the main in silico constraint-based strain design strategies and algorithms is presented, their application in real-world case studies is analyzed, and a path for the future is discussed. PMID:26609052

Distance underestimation in virtual space is sensitive to gender but not activity-passivity or mode of interaction.

PubMed

Foreman, Nigel; Sandamas, George; Newson, David

2004-08-01

Four groups of undergraduates (half of each gender) experienced a movement along a corridor containing three distinctive objects, in a virtual environment (VE) with wide-screen projection. One group simulated walking along the virtual corridor using a proprietary step-exercise device. A second group moved along the corridor in conventional flying mode, depressing a keyboard key to initiate continuous forward motion. Two further groups observed the walking and flying participants, by viewing their progress on the screen. Participants then had to walk along a real equivalent but empty corridor, and indicate the positions of the three objects. All groups underestimated distances in the real corridor, the greatest underestimates occurring for the middle distance object. Males' underestimations were significantly lower than females' at all distances. However, there was no difference between the active participants and passive observers, nor between walking and flying conditions.

Cooperative working of bacterial chromosome replication proteins generated by a reconstituted protein expression system

PubMed Central

Fujiwara, Kei; Katayama, Tsutomu; Nomura, Shin-ichiro M.

2013-01-01

Replication of all living cells relies on the multirounds flow of the central dogma. Especially, expression of DNA replication proteins is a key step to circulate the processes of the central dogma. Here we achieved the entire sequential transcription–translation–replication process by autonomous expression of chromosomal DNA replication machineries from a reconstituted transcription–translation system (PURE system). We found that low temperature is essential to express a complex protein, DNA polymerase III, in a single tube using the PURE system. Addition of the 13 genes, encoding initiator, DNA helicase, helicase loader, RNA primase and DNA polymerase III to the PURE system gave rise to a DNA replication system by a coupling manner. An artificial genetic circuit demonstrated that the DNA produced as a result of the replication is able to provide genetic information for proteins, indicating the in vitro central dogma can sequentially undergo two rounds. PMID:23737447

Accidental Turbulent Discharge Rate Estimation from Videos

NASA Astrophysics Data System (ADS)

Ibarra, Eric; Shaffer, Franklin; Savaş, Ömer

2015-11-01

A technique to estimate the volumetric discharge rate in accidental oil releases using high speed video streams is described. The essence of the method is similar to PIV processing, however the cross correlation is carried out on the visible features of the efflux, which are usually turbulent, opaque and immiscible. The key step in the process is to perform a pixelwise time filtering on the video stream, in which the parameters are commensurate with the scales of the large eddies. The velocity field extracted from the shell of visible features is then used to construct an approximate velocity profile within the discharge. The technique has been tested on laboratory experiments using both water and oil jets at Re ~105 . The technique is accurate to 20%, which is sufficient for initial responders to deploy adequate resources for containment. The software package requires minimal user input and is intended for deployment on an ROV in the field. Supported by DOI via NETL.

Using Key Performance Indicators to Drive Strategic Decision Making.

ERIC Educational Resources Information Center

Dolence, Michael G.; Norris, Donald M.

1994-01-01

A nine-step method for defining and pursuing key performance indicators (KPIs), derived from a strategic planning process, is outlined, and its applications at the University of Northern Colorado and Illinois Benedictine College are described and tabulated. A chart summarizes current and projected KPIs for Illinois Benedictine College for each…

Twenty-six key research questions in urban stream ecology: an assessment of the state of the science

EPA Science Inventory

Although urban streams have been the focus of much research activity in recent years, there remain many unanswered questions about the mechanisms driving the “urban stream syndrome.” Identification of these key research questions is an important step toward effective, efficient ...

The space program's impact on society

NASA Astrophysics Data System (ADS)

Toffler, Alvin

In terms of human evolution, when viewed from 500 or 1000 years from now, today's primitive, still faltering steps beyond the Earth will be recognized as the most important human project of our era, matched only by what is going on in computers and biology. In this paper the social effects of space activity are addressed at three different levels: key social institutions, key social groups, and key social processes.

Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium

PubMed Central

Pavlov, Tengis S.; Ilatovskaya, Daria V.; Palygin, Oleg; Levchenko, Vladislav; Pochynyuk, Oleh; Staruschenko, Alexander

2015-01-01

Cyst initiation and expansion during polycystic kidney disease is a complex process characterized by abnormalities in tubular cell proliferation, luminal fluid accumulation and extracellular matrix formation. Activity of ion channels and intracellular calcium signaling are key physiologic parameters which determine functions of tubular epithelium. We developed a method suitable for real-time observation of ion channels activity with patch-clamp technique and registration of intracellular Ca2+ level in epithelial monolayers freshly isolated from renal cysts. PCK rats, a genetic model of autosomal recessive polycystic kidney disease (ARPKD), were used here for ex vivo analysis of ion channels and calcium flux. Described here is a detailed step-by-step procedure designed to isolate cystic monolayers and non-dilated tubules from PCK or normal Sprague Dawley (SD) rats, and monitor single channel activity and intracellular Ca2+ dynamics. This method does not require enzymatic processing and allows analysis in a native setting of freshly isolated epithelial monolayer. Moreover, this technique is very sensitive to intracellular calcium changes and generates high resolution images for precise measurements. Finally, isolated cystic epithelium can be further used for staining with antibodies or dyes, preparation of primary cultures and purification for various biochemical assays. PMID:26381526

Dynamics of transcriptomic response to infection by the nematode Heterorhabditis bacteriophora and its bacterial symbiont Photorhabdus temperata in Heliothis virescens larvae.

PubMed

An, R; Suri, K S; Jurat-Fuentes, J L; Grewal, P S

2017-10-01

Entomopathogenic nematodes in the Heterorhabditis genus and their symbiotic Photorhabdus bacteria are important biocontrol agents of insect pests and models for the study of microbe-host interactions. In this work, we used larvae of the tobacco budworm (Heliothis virescens) as a model to study its defensive mechanisms against Heterorhabditis bacteriophora nematodes carrying symbiotic Photorhabdus temperata. We first determined time points of initial nematode entry and release of bacteria into the haemolymph to perform transcriptional analysis of insect gene expression during these steps in the infective process. RNA-Sequencing analyses were then performed to profile differential gene expression in the insect during nematode invasion, bacterial release and final steps of infection, relative to the untreated controls. Our results support the theory that insect immune response genes are induced upon nematode invasion, but the majority of these genes are suppressed upon the release of bacteria by the nematodes into the haemolymph. Overall, these findings provide information on the dynamics of the insect's response to a progressing infection by this entomopathogenic nematode-bacteria complex and facilitate development of Hel. virescens as a pest model for future functional studies of the key insect defence factors. © 2017 The Royal Entomological Society.

Studying Policy Changes in Disaster Management in India: A Tale of Two Cyclones.

PubMed

Jha, Ayan; Basu, Rivu; Basu, Atreyee

2016-02-01

The mainstay of India's disaster management policy until the early 2000s had been relief and rescue operations. The Odisha Super Cyclone (1999) with 10,000 deaths and US $3 billion economic damage provided a rude awakening. Recognizing the importance of preemptive preparedness, the government initiated systematic steps to implement a national framework interlinking economic, environmental, and overall developmental issues for efficient response to and mitigation of disasters. We attempted a critical analysis of this paradigm shift in India's disaster management policy through the prism of 2 cyclones, 14 years apart in time. With improved preparedness and response measures, the death toll in 2013 Cyclone Phailin was 0.5% and the economic loss was about one-third of that during 1999. Concomitant improvements in the technological expertise of the early warning system, an integrated approach at all levels of administration including joint planning with major nongovernmental organizations, and improved community participation were identified as game-changers. An unbelievable 1 million people were evacuated to safety. Our essay aims to highlight key steps in this success and calls for futuristic approaches like insurance programs and gender-sensitive recovery plans. With thorough scrutiny, India's model may well stand to be replicated in resource-restricted settings.

TEMPO-Oxidized Nanofibrillated Cellulose as a High Density Carrier for Bioactive Molecules.

PubMed

Weishaupt, Ramon; Siqueira, Gilberto; Schubert, Mark; Tingaut, Philippe; Maniura-Weber, Katharina; Zimmermann, Tanja; Thöny-Meyer, Linda; Faccio, Greta; Ihssen, Julian

2015-11-09

Controlled and efficient immobilization of specific biomolecules is a key technology to introduce new, favorable functions to materials suitable for biomedical applications. Here, we describe an innovative and efficient, two-step methodology for the stable immobilization of various biomolecules, including small peptides and enzymes onto TEMPO oxidized nanofibrillated cellulose (TO-NFC). The introduction of carboxylate groups to NFC by TEMPO oxidation provided a high surface density of negative charges able to drive the adsorption of biomolecules and take part in covalent cross-linking reactions with 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDAC) and glutaraldehyde (Ga) chemistry. Up to 0.27 μmol of different biomolecules per mg of TO-NFC could be reversibly immobilized by electrostatic interaction. An additional chemical cross-linking step prevented desorption of more than 80% of these molecules. Using the cysteine-protease papain as model, a highly active papain-TO-NFC conjugate was achieved. Once papain was immobilized, 40% of the initial enzymatic activity was retained, with an increase in kcat from 213 to >700 s(-1) for the covalently immobilized enzymes. The methodology presented in this work expands the range of application for TO-NFC in the biomedical field by enabling well-defined hybrid biomaterials with a high density of functionalization.

Solar-mediated thermo-electrochemical oxidation of sodium dodecyl benzene sulfonate by modulating the effective oxidation potential and pathway for green remediation of wastewater.

PubMed

Gu, Di; Gao, Simeng; Jiang, TingTing; Wang, Baohui

2017-03-15

To match the relentless pursuit of three research hot points - efficient solar utilization, green and sustainable remediation of wastewater and advanced oxidation processes, solar-mediated thermo-electrochemical oxidation of surfactant was proposed and developed for green remediation of surfactant wastewater. The solar thermal electrochemical process (STEP), fully driven with solar energy to electric energy and heat and without an input of other energy, sustainably serves as efficient thermo-electrochemical oxidation of surfactant, exemplified by SDBS, in wastewater with the synergistic production of hydrogen. The electrooxidation-resistant surfactant is thermo-electrochemically oxidized to CO 2 while hydrogen gas is generated by lowing effective oxidation potential and suppressing the oxidation activation energy originated from the combination of thermochemical and electrochemical effect. A clear conclusion on the mechanism of SDBS degradation can be proposed and discussed based on the theoretical analysis of electrochemical potential by quantum chemical method and experimental analysis of the CV, TG, GC, FT-IR, UV-vis, Fluorescence spectra and TOC. The degradation data provide a pilot for the treatment of SDBS wastewater that appears to occur via desulfonation followed by aromatic-ring opening. The solar thermal utilization that can initiate the desulfonation and activation of SDBS becomes one key step in the degradation process.

Markov State Models Reveal a Two-Step Mechanism of miRNA Loading into the Human Argonaute Protein: Selective Binding followed by Structural Re-arrangement.

PubMed

Jiang, Hanlun; Sheong, Fu Kit; Zhu, Lizhe; Gao, Xin; Bernauer, Julie; Huang, Xuhui

2015-07-01

Argonaute (Ago) proteins and microRNAs (miRNAs) are central components in RNA interference, which is a key cellular mechanism for sequence-specific gene silencing. Despite intensive studies, molecular mechanisms of how Ago recognizes miRNA remain largely elusive. In this study, we propose a two-step mechanism for this molecular recognition: selective binding followed by structural re-arrangement. Our model is based on the results of a combination of Markov State Models (MSMs), large-scale protein-RNA docking, and molecular dynamics (MD) simulations. Using MSMs, we identify an open state of apo human Ago-2 in fast equilibrium with partially open and closed states. Conformations in this open state are distinguished by their largely exposed binding grooves that can geometrically accommodate miRNA as indicated in our protein-RNA docking studies. miRNA may then selectively bind to these open conformations. Upon the initial binding, the complex may perform further structural re-arrangement as shown in our MD simulations and eventually reach the stable binary complex structure. Our results provide novel insights in Ago-miRNA recognition mechanisms and our methodology holds great potential to be widely applied in the studies of other important molecular recognition systems.

Solar-mediated thermo-electrochemical oxidation of sodium dodecyl benzene sulfonate by modulating the effective oxidation potential and pathway for green remediation of wastewater

PubMed Central

Gu, Di; Gao, Simeng; Jiang, TingTing; Wang, Baohui

2017-01-01

To match the relentless pursuit of three research hot points - efficient solar utilization, green and sustainable remediation of wastewater and advanced oxidation processes, solar-mediated thermo-electrochemical oxidation of surfactant was proposed and developed for green remediation of surfactant wastewater. The solar thermal electrochemical process (STEP), fully driven with solar energy to electric energy and heat and without an input of other energy, sustainably serves as efficient thermo-electrochemical oxidation of surfactant, exemplified by SDBS, in wastewater with the synergistic production of hydrogen. The electrooxidation-resistant surfactant is thermo-electrochemically oxidized to CO2 while hydrogen gas is generated by lowing effective oxidation potential and suppressing the oxidation activation energy originated from the combination of thermochemical and electrochemical effect. A clear conclusion on the mechanism of SDBS degradation can be proposed and discussed based on the theoretical analysis of electrochemical potential by quantum chemical method and experimental analysis of the CV, TG, GC, FT-IR, UV-vis, Fluorescence spectra and TOC. The degradation data provide a pilot for the treatment of SDBS wastewater that appears to occur via desulfonation followed by aromatic-ring opening. The solar thermal utilization that can initiate the desulfonation and activation of SDBS becomes one key step in the degradation process. PMID:28294180

Solar-mediated thermo-electrochemical oxidation of sodium dodecyl benzene sulfonate by modulating the effective oxidation potential and pathway for green remediation of wastewater

NASA Astrophysics Data System (ADS)

Gu, Di; Gao, Simeng; Jiang, Tingting; Wang, Baohui

2017-03-01

To match the relentless pursuit of three research hot points - efficient solar utilization, green and sustainable remediation of wastewater and advanced oxidation processes, solar-mediated thermo-electrochemical oxidation of surfactant was proposed and developed for green remediation of surfactant wastewater. The solar thermal electrochemical process (STEP), fully driven with solar energy to electric energy and heat and without an input of other energy, sustainably serves as efficient thermo-electrochemical oxidation of surfactant, exemplified by SDBS, in wastewater with the synergistic production of hydrogen. The electrooxidation-resistant surfactant is thermo-electrochemically oxidized to CO2 while hydrogen gas is generated by lowing effective oxidation potential and suppressing the oxidation activation energy originated from the combination of thermochemical and electrochemical effect. A clear conclusion on the mechanism of SDBS degradation can be proposed and discussed based on the theoretical analysis of electrochemical potential by quantum chemical method and experimental analysis of the CV, TG, GC, FT-IR, UV-vis, Fluorescence spectra and TOC. The degradation data provide a pilot for the treatment of SDBS wastewater that appears to occur via desulfonation followed by aromatic-ring opening. The solar thermal utilization that can initiate the desulfonation and activation of SDBS becomes one key step in the degradation process.

How to harvest solar energy with the photosynthetic reaction center

NASA Astrophysics Data System (ADS)

Balaeff, Alexander; Reyes, Justin

Photosynthetic reaction center (PRC) is a protein complex that performs a key step in photosynthesis: the electron-hole separation driven by photon absorbtion. The PRC has a great promise for applications in solar energy harvesting and photosensing. Such applications, however, are hampered by the difficulty in extracting the photogenerated electric charge from the PRC. To that end, it was proposed to attach the PRC to a molecular wire through which the charge could be collected. In order to find the attachment point for the wire that would maximize the rate of charge outflow from the PRC, we performed a computational study of the PRC from the R. virdis bacterium. An ensemble of PRC structures generated by a molecular dynamics simulation was used to calculate the rate of charge transport from the site of initial charge separation to several trial sites on the protein surface. The Pathways model was used to calculate the charge transfer rate in each step of the network of heme co-factors through which the charge transport was presumed to proceed. A simple kinetic model was then used to determine the overall rate of the multistep charge transport. The calculations revealed several candidate sites for the molecular wire attachment, recommended for experimental verification.

Baby-Friendly Hospital Initiative: evaluation of the Ten Steps to Successful Breastfeeding

PubMed Central

Lopes, Soraia da Silva; Laignier, Mariana Rabello; Primo, Cândida Caniçali; Leite, Franciéle Marabotti C.

2013-01-01

OBJECTIVE: To asses the performance of the Ten Steps to Successful Breastfeeding in an university hospital. METHODS: Descriptive and quantitative research, in which 103 people were interviewed in the outpatient prenatal clinic, in the maternity-ward and in the Neonatal Intensive Care Unit of a university hospital in Vitória, Southeast Brazil. The "Institutional Self-Evaluation Questionnaire" of the Baby Friendly Hospital Initiative was applied. Using this tool, the outcome was measured by the concordance index (CI) proposed by the World Health Organization and by the United Nations Children's Fund. RESULTS: Although the hospital does not have a policy that addresses promotion, protection and support for breastfeeding, 93.3% of the mothers had contact with their babies immediately after birth (step 4), 83.3% of the professionals guided mothers how to breastfeed (step 5), 86.6% of the neonates did not receive any food or drink other than breast milk (step 6), 100% of babies were housed together with their mothers (step 7), 83.3% of the women were encouraged for breastfeeding on demand (step 8) and 100% of the infants did not use bottles or pacifiers (step 9). CONCLUSIONS: 60% of the steps were completed by the hospital. The greatest difficulty was to inform pregnant women about the importance and the management of breastfeeding (step 3). Therefore, visits to pregnant women are recommended, in order to prepare them for breastfeeding and to explain about the infants' healthy feeding habits. PMID:24473954