Functional Complexity and Web Site Design : Evaluating the Online Presence of UNESCO World Heritage Sites

NARCIS (Netherlands)

De Jong, Menno D.T.; Wu, Yuguang

2018-01-01

Functional complexity is a widespread and underresearched phenomenon in Web sites. This article explores a specific case of functional complexity by analyzing the content of UNESCO World Heritage Web sites, which have to meet demands from both World Heritage and tourism perspectives. Based on a

Primer on the implementation of a pharmacy intranet site to improve department communication.

Science.gov (United States)

Hale, Holly J

2013-07-01

The purpose of the article is to describe the experience of selecting, developing, and implementing a pharmacy department intranet site with commentary regarding application to other institutions. Clinical practitioners and supporting staff need an effective, efficient, organized, and user-friendly communication tool to utilize and relay information required to optimize patient care. To create a functional and user-friendly department intranet site, department leadership and staff should be involved in the process from selection of product through implementation. A product that supports both document storage management and communication delivery and has the capability to be customized to provide varied levels of site access is desirable. The designation of an intranet site owner/developer within the department will facilitate purposeful site design and site maintenance execution. A well-designed and up-to-date site along with formal end-user training are essential for staff adoption and continued utilization. Development of a department intranet site requires a considerable time investment by several members of the department. The implementation of an intranet site can be an important step toward achieving improved communications. Staff utilization of this resource is key to its success.

RISM theory distribution functions for Lennard--Jones interaction site fluids

International Nuclear Information System (INIS)

Johnson, E.; Hazoume, R.P.

1978-01-01

Reference interaction site model (RISM) theory distribution functions for Lennard-Jones interaction site fluids are discussed. The comparison with computer simulation results suggests that these distribution functions are as accurate as RISM distribution functions for fused hard sphere molecular fluids

Improved ethanol electrooxidation performance by shortening Pd–Ni active site distance in Pd–Ni–P nanocatalysts

Science.gov (United States)

Chen, Lin; Lu, Lilin; Zhu, Hengli; Chen, Yueguang; Huang, Yu; Li, Yadong; Wang, Leyu

2017-01-01

Incorporating oxophilic metals into noble metal-based catalysts represents an emerging strategy to improve the catalytic performance of electrocatalysts in fuel cells. However, effects of the distance between the noble metal and oxophilic metal active sites on the catalytic performance have rarely been investigated. Herein, we report on ultrasmall (∼5 nm) Pd–Ni–P ternary nanoparticles for ethanol electrooxidation. The activity is improved up to 4.95 A per mgPd, which is 6.88 times higher than commercial Pd/C (0.72 A per mgPd), by shortening the distance between Pd and Ni active sites, achieved through shape transformation from Pd/Ni–P heterodimers into Pd–Ni–P nanoparticles and tuning the Ni/Pd atomic ratio to 1:1. Density functional theory calculations reveal that the improved activity and stability stems from the promoted production of free OH radicals (on Ni active sites) which facilitate the oxidative removal of carbonaceous poison and combination with CH3CO radicals on adjacent Pd active sites. PMID:28071650

Enzyme functional evolution through improved catalysis of ancestrally nonpreferred substrates

Science.gov (United States)

Huang, Ruiqi; Hippauf, Frank; Rohrbeck, Diana; Haustein, Maria; Wenke, Katrin; Feike, Janie; Sorrelle, Noah; Piechulla, Birgit; Barkman, Todd J.

2012-01-01

In this study, we investigated the role for ancestral functional variation that may be selected upon to generate protein functional shifts using ancestral protein resurrection, statistical tests for positive selection, forward and reverse evolutionary genetics, and enzyme functional assays. Data are presented for three instances of protein functional change in the salicylic acid/benzoic acid/theobromine (SABATH) lineage of plant secondary metabolite-producing enzymes. In each case, we demonstrate that ancestral nonpreferred activities were improved upon in a daughter enzyme after gene duplication, and that these functional shifts were likely coincident with positive selection. Both forward and reverse mutagenesis studies validate the impact of one or a few sites toward increasing activity with ancestrally nonpreferred substrates. In one case, we document the occurrence of an evolutionary reversal of an active site residue that reversed enzyme properties. Furthermore, these studies show that functionally important amino acid replacements result in substrate discrimination as reflected in evolutionary changes in the specificity constant (kcat/KM) for competing substrates, even though adaptive substitutions may affect KM and kcat separately. In total, these results indicate that nonpreferred, or even latent, ancestral protein activities may be coopted at later times to become the primary or preferred protein activities. PMID:22315396

Quantification of amine functional groups and their influence on OM/OC in the IMPROVE network

Science.gov (United States)

Kamruzzaman, Mohammed; Takahama, Satoshi; Dillner, Ann M.

2018-01-01

Recently, we developed a method using FT-IR spectroscopy coupled with partial least squares (PLS) regression to measure the four most abundant organic functional groups, aliphatic C-H, alcohol OH, carboxylic acid OH and carbonyl C=O, in atmospheric particulate matter. These functional groups are summed to estimate organic matter (OM) while the carbon from the functional groups is summed to estimate organic carbon (OC). With this method, OM and OM/OC can be estimated for each sample rather than relying on one assumed value to convert OC measurements to OM. This study continues the development of the FT-IR and PLS method for estimating OM and OM/OC by including the amine functional group. Amines are ubiquitous in the atmosphere and come from motor vehicle exhaust, animal husbandry, biomass burning, and vegetation among other sources. In this study, calibration standards for amines are produced by aerosolizing individual amine compounds and collecting them on PTFE filters using an IMPROVE sampler, thereby mimicking the filter media and collection geometry of ambient standards. The moles of amine functional group on each standard and a narrow range of amine-specific wavenumbers in the FT-IR spectra (wavenumber range 1 550-1 500 cm-1) are used to develop a PLS calibration model. The PLS model is validated using three methods: prediction of a set of laboratory standards not included in the model, a peak height analysis and a PLS model with a broader wavenumber range. The model is then applied to the ambient samples collected throughout 2013 from 16 IMPROVE sites in the USA. Urban sites have higher amine concentrations than most rural sites, but amine functional groups account for a lower fraction of OM at urban sites. Amine concentrations, contributions to OM and seasonality vary by site and sample. Amine has a small impact on the annual average OM/OC for urban sites, but for some rural sites including amine in the OM/OC calculations increased OM/OC by 0.1 or more.

Structure-based Markov random field model for representing evolutionary constraints on functional sites.

Science.gov (United States)

Jeong, Chan-Seok; Kim, Dongsup

2016-02-24

Elucidating the cooperative mechanism of interconnected residues is an important component toward understanding the biological function of a protein. Coevolution analysis has been developed to model the coevolutionary information reflecting structural and functional constraints. Recently, several methods have been developed based on a probabilistic graphical model called the Markov random field (MRF), which have led to significant improvements for coevolution analysis; however, thus far, the performance of these models has mainly been assessed by focusing on the aspect of protein structure. In this study, we built an MRF model whose graphical topology is determined by the residue proximity in the protein structure, and derived a novel positional coevolution estimate utilizing the node weight of the MRF model. This structure-based MRF method was evaluated for three data sets, each of which annotates catalytic site, allosteric site, and comprehensively determined functional site information. We demonstrate that the structure-based MRF architecture can encode the evolutionary information associated with biological function. Furthermore, we show that the node weight can more accurately represent positional coevolution information compared to the edge weight. Lastly, we demonstrate that the structure-based MRF model can be reliably built with only a few aligned sequences in linear time. The results show that adoption of a structure-based architecture could be an acceptable approximation for coevolution modeling with efficient computation complexity.

Benchmarking and Performance Improvement at Rocky Flats Environmental Technology Site

Energy Technology Data Exchange (ETDEWEB)

Elliott, C. [Kaiser-Hill Co., LLC, Golden, CO (United States)], Doyle, D. [USDOE Rocky Flats Office, Golden, CO (United States)], Featherman, W.D. [Project Performance Corp., Sterline, VA (United States)

1997-12-31

The Rocky Flats Environmental Technology Site (RFETS) has initiated a major work process improvement campaign using the tools of formalized benchmarking and streamlining. This paper provides insights into some of the process improvement activities performed at Rocky Flats from November 1995 through December 1996. It reviews the background, motivation, methodology, results, and lessons learned from this ongoing effort. The paper also presents important gains realized through process analysis and improvement including significant cost savings, productivity improvements, and an enhanced understanding of site work processes.

Functional Sites Induce Long-Range Evolutionary Constraints in Enzymes.

Directory of Open Access Journals (Sweden)

Benjamin R Jack

2016-05-01

Full Text Available Functional residues in proteins tend to be highly conserved over evolutionary time. However, to what extent functional sites impose evolutionary constraints on nearby or even more distant residues is not known. Here, we report pervasive conservation gradients toward catalytic residues in a dataset of 524 distinct enzymes: evolutionary conservation decreases approximately linearly with increasing distance to the nearest catalytic residue in the protein structure. This trend encompasses, on average, 80% of the residues in any enzyme, and it is independent of known structural constraints on protein evolution such as residue packing or solvent accessibility. Further, the trend exists in both monomeric and multimeric enzymes and irrespective of enzyme size and/or location of the active site in the enzyme structure. By contrast, sites in protein-protein interfaces, unlike catalytic residues, are only weakly conserved and induce only minor rate gradients. In aggregate, these observations show that functional sites, and in particular catalytic residues, induce long-range evolutionary constraints in enzymes.

DARC 2.0: Improved Docking and Virtual Screening at Protein Interaction Sites.

Directory of Open Access Journals (Sweden)

Ragul Gowthaman

Full Text Available Over the past decade, protein-protein interactions have emerged as attractive but challenging targets for therapeutic intervention using small molecules. Due to the relatively flat surfaces that typify protein interaction sites, modern virtual screening tools developed for optimal performance against "traditional" protein targets perform less well when applied instead at protein interaction sites. Previously, we described a docking method specifically catered to the shallow binding modes characteristic of small-molecule inhibitors of protein interaction sites. This method, called DARC (Docking Approach using Ray Casting, operates by comparing the topography of the protein surface when "viewed" from a vantage point inside the protein against the topography of a bound ligand when "viewed" from the same vantage point. Here, we present five key enhancements to DARC. First, we use multiple vantage points to more accurately determine protein-ligand surface complementarity. Second, we describe a new scheme for rapidly determining optimal weights in the DARC scoring function. Third, we incorporate sampling of ligand conformers "on-the-fly" during docking. Fourth, we move beyond simple shape complementarity and introduce a term in the scoring function to capture electrostatic complementarity. Finally, we adjust the control flow in our GPU implementation of DARC to achieve greater speedup of these calculations. At each step of this study, we evaluate the performance of DARC in a "pose recapitulation" experiment: predicting the binding mode of 25 inhibitors each solved in complex with its distinct target protein (a protein interaction site. Whereas the previous version of DARC docked only one of these inhibitors to within 2 Å RMSD of its position in the crystal structure, the newer version achieves this level of accuracy for 12 of the 25 complexes, corresponding to a statistically significant performance improvement (p < 0.001. Collectively then, we find

Intra-operative multi-site stimulation: Expanding methodology for cortical brain mapping of language functions.

Science.gov (United States)

Gonen, Tal; Gazit, Tomer; Korn, Akiva; Kirschner, Adi; Perry, Daniella; Hendler, Talma; Ram, Zvi

2017-01-01

Direct cortical stimulation (DCS) is considered the gold-standard for functional cortical mapping during awake surgery for brain tumor resection. DCS is performed by stimulating one local cortical area at a time. We present a feasibility study using an intra-operative technique aimed at improving our ability to map brain functions which rely on activity in distributed cortical regions. Following standard DCS, Multi-Site Stimulation (MSS) was performed in 15 patients by applying simultaneous cortical stimulations at multiple locations. Language functioning was chosen as a case-cognitive domain due to its relatively well-known cortical organization. MSS, performed at sites that did not produce disruption when applied in a single stimulation point, revealed additional language dysfunction in 73% of the patients. Functional regions identified by this technique were presumed to be significant to language circuitry and were spared during surgery. No new neurological deficits were observed in any of the patients following surgery. Though the neuro-electrical effects of MSS need further investigation, this feasibility study may provide a first step towards sophistication of intra-operative cortical mapping.

European commission contribution to improving off-site emergency preparedness

International Nuclear Information System (INIS)

Kelly, G.N.

1996-01-01

Increasing attention is being given by the European Commission to off-site emergency preparedness as part of its broader contribution to improving nuclear safety in Eastern Europe. The main initiatives being taken or planned by the Commission in this area are summarized. Particular attention is given to two topics: firstly, the development of the RODOS (Real-time On-line Decision Support) system for supporting off-site emergency management in the event of a nuclear accident; and, secondly, the work of an Inter-Service Group on nuclear Off-Site Emergency Preparedness (OSEP) in Eastern Europe that has recently been established within the Commission. The contribution that each is making to improving emergency preparedness, both in Eastern Europe and in Europe more widely, is described

Improving regulatory effectiveness in Federal/State siting actions. State perspectives on energy facility siting

International Nuclear Information System (INIS)

Stevens, D.W.; Helminski, E.L.

1978-03-01

The National Governors' Association, through its Committee on Natural Resources and Environmental Management, has been concerned with the growing administrative difficulties, both at the federal and state levels, of certifying sites for new major energy facilities. This concern led, early in 1977, to the creation of a Subcommittee on Energy Facility Siting to comprehensively analyze current conditions and determine how basic improvements might be made to the process. The report is meant to further clarify the issues that confront States and the Federal government in the siting of energy facilities

Sacrifical sites, types and function

Directory of Open Access Journals (Sweden)

Örnulv Vorren

1987-01-01

Full Text Available Much has been written and said about Saami mythology and pre-Christian religion. There is, however, considerably less documentation of concrete cultural elements in scholarly descriptions. These investigations are considered important not only because they aim to provide documentation that can be used for studies of Saami mythology and pre-Christian religion. They also provide material that can throw light on the function of the holy places in a social context through analysis of their origin, their connections with certain families and persons, their associations with the siidas, their location within the areas where the Saamis from these siidas gained their livelihood, etc. The materials collected about the sacrificial sites also play an important role in studying the course of events leading up to the differentiation of Saami hunting and gathering culture. A question that has frequently arisen in the course of this work is with what powers or deities the different sacrificial sites were associated. This is naturally connected with their origin and their form. This, in turn, is reflected in the traditions and legends recounted concerning them. It is also reflected in their location in the physical environment and in the kinds of offerings that have been found. In the materials so far collected it is possible to distinguish between about eight different types of sacrificial site and holy mountain or fell according to their form and location: holy fells, rock formations, stone boulders, holes, cracks in fells, springs, lakes, ring-shaped sacrificial sites. Missionaries were urged to destroy the offering sites.

Active chemisorption sites in functionalized ionic liquids for carbon capture.

Science.gov (United States)

Cui, Guokai; Wang, Jianji; Zhang, Suojiang

2016-07-25

Development of novel technologies for the efficient and reversible capture of CO2 is highly desired. In the last decade, CO2 capture using ionic liquids has attracted intensive attention from both academia and industry, and has been recognized as a very promising technology. Recently, a new approach has been developed for highly efficient capture of CO2 by site-containing ionic liquids through chemical interaction. This perspective review focuses on the recent advances in the chemical absorption of CO2 using site-containing ionic liquids, such as amino-based ionic liquids, azolate ionic liquids, phenolate ionic liquids, dual-functionalized ionic liquids, pyridine-containing ionic liquids and so on. Other site-containing liquid absorbents such as amine-based solutions, switchable solvents, and functionalized ionic liquid-amine blends are also investigated. Strategies have been discussed for how to activate the existent reactive sites and develop novel reactive sites by physical and chemical methods to enhance CO2 absorption capacity and reduce absorption enthalpy. The carbon capture mechanisms of these site-containing liquid absorbents are also presented. Particular attention has been paid to the latest progress in CO2 capture in multiple-site interactions by amino-free anion-functionalized ionic liquids. In the last section, future directions and prospects for carbon capture by site-containing ionic liquids are outlined.

Site-Specific Antibody Functionalization Using Tetrazine-Styrene Cycloaddition.

Science.gov (United States)

Umlauf, Benjamin J; Mix, Kalie A; Grosskopf, Vanessa A; Raines, Ronald T; Shusta, Eric V

2018-05-03

Biologics, such as antibody-drug conjugates, are becoming mainstream therapeutics. Consequently, methods to functionalize biologics without disrupting their native properties are essential for identifying, characterizing, and translating candidate biologics from the bench to clinical practice. Here, we present a method for site-specific, carboxy-terminal modification of single-chain antibody fragments (scFvs). ScFvs displayed on the surface of yeast were isolated and functionalized by combining intein-mediated expressed protein ligation (EPL) with inverse electron-demand Diels-Alder (IEDDA) cycloaddition using a styrene-tetrazine pair. The high thiol concentration required to trigger EPL can hinder the subsequent chemoselective ligation reactions; therefore, the EPL reaction was used to append styrene to the scFv, limiting tetrazine exposure to damaging thiols. Subsequently, the styrene-functionalized scFv was reacted with tetrazine-conjugated compounds in an IEDDA cycloaddition to generate functionalized scFvs that retain their native binding activity. Rapid functionalization of yeast surface-derived scFv in a site-directed manner could find utility in many downstream laboratory and preclinical applications.

Quality improvement initiative: Preventative Surgical Site Infection Protocol in Vascular Surgery.

Science.gov (United States)

Parizh, David; Ascher, Enrico; Raza Rizvi, Syed Ali; Hingorani, Anil; Amaturo, Michael; Johnson, Eric

2018-02-01

Objective A quality improvement initiative was employed to decrease single institution surgical site infection rate in open lower extremity revascularization procedures. In an attempt to lower patient morbidity, we developed and implemented the Preventative Surgical Site Infection Protocol in Vascular Surgery. Surgical site infections lead to prolonged hospital stays, adjunctive procedure, and additive costs. We employed targeted interventions to address the common risk factors that predispose patients to post-operative complications. Methods Retrospective review was performed between 2012 and 2016 for all surgical site infections after revascularization procedures of the lower extremity. A quality improvement protocol was initiated in January 2015. Primary outcome was the assessment of surgical site infection rate reduction in the pre-protocol vs. post-protocol era. Secondary outcomes evaluated patient demographics, closure method, perioperative antibiotic coverage, and management outcomes. Results Implementation of the protocol decreased the surgical site infection rate from 6.4% to 1.6% p = 0.0137). Patient demographics and comorbidities were assessed and failed to demonstrate a statistically significant difference among the infection and no-infection groups. Wound closure with monocryl suture vs. staple proved to be associated with decreased surgical site infection rate ( p site infections in the vascular surgery population are effective and necessary. Our data suggest that there may be benefit in the incorporation of MRSA and Gram-negative coverage as part of the Surgical Care Improvement Project perioperative guidelines.

The polyproline site in hinge 2 influences the functional capacity of truncated dystrophins.

Directory of Open Access Journals (Sweden)

Glen B Banks

2010-05-01

Full Text Available Mutations in dystrophin can lead to Duchenne muscular dystrophy or the more mild form of the disease, Becker muscular dystrophy. The hinge 3 region in the rod domain of dystrophin is particularly prone to deletion mutations. In-frame deletions of hinge 3 are predicted to lead to BMD, however the severity of disease can vary considerably. Here we performed extensive structure-function analyses of truncated dystrophins with modified hinges and spectrin-like repeats in mdx mice. We found that the polyproline site in hinge 2 profoundly influences the functional capacity of a microdystrophin(DeltaR4-R23/DeltaCT with a large deletion in the hinge 3 region. Inclusion of polyproline in microdystrophin(DeltaR4-R23/DeltaCT led to small myofibers (12% smaller than wild-type, Achilles myotendinous disruption, ringed fibers, and aberrant neuromuscular junctions in the mdx gastrocnemius muscles. Replacing hinge 2 of microdystrophin(DeltaR4-R23/DeltaCT with hinge 3 significantly improved the functional capacity to prevent muscle degeneration, increase muscle fiber area, and maintain the junctions. We conclude that the rigid alpha-helical structure of the polyproline site significantly impairs the functional capacity of truncated dystrophins to maintain appropriate connections between the cytoskeleton and extracellular matrix.

Improving functional value of meat products.

Science.gov (United States)

Zhang, Wangang; Xiao, Shan; Samaraweera, Himali; Lee, Eun Joo; Ahn, Dong U

2010-09-01

In recent years, much attention has been paid to develop meat and meat products with physiological functions to promote health conditions and prevent the risk of diseases. This review focuses on strategies to improve the functional value of meat and meat products. Value improvement can be realized by adding functional compounds including conjugated linoneleic acid, vitamin E, n3 fatty acids and selenium in animal diets to improve animal production, carcass composition and fresh meat quality. In addition, functional ingredients such as vegetable proteins, dietary fibers, herbs and spices, and lactic acid bacteria can be directly incorporated into meat products during processing to improve their functional value for consumers. Functional compounds, especially peptides, can also be generated from meat and meat products during processing such as fermentation, curing and aging, and enzymatic hydrolysis. This review further discusses the current status, consumer acceptance, and market for functional foods from the global viewpoints. Future prospects for functional meat and meat products are also discussed.

Functionalization of silicon-doped single walled carbon nanotubes at the doping site: An ab initio study

International Nuclear Information System (INIS)

Song Chen; Xia Yueyuan; Zhao Mingwen; Liu Xiangdong; Li Feng; Huang Boda; Zhang Hongyu; Zhang Bingyun

2006-01-01

We performed ab initio calculations on the cytosine-functionalized silicon-doped single walled carbon nanotubes (SWNT). The results show that silicon substitutional doping to SWNT can dramatically change the atomic and electronic structures of the SWNT. And more importantly, it may provide an efficient pathway for further sidewall functionalization to synthesize more complicated SWNT based complex materials, for example, our previously proposed base-functionalized SWNTs, because the doping silicon atom can improve the reaction activity of the tube at the doping site due to its preference to form sp3 hybridization bonding

Improving web site performance using commercially available analytical tools.

Science.gov (United States)

Ogle, James A

2010-10-01

It is easy to accurately measure web site usage and to quantify key parameters such as page views, site visits, and more complex variables using commercially available tools that analyze web site log files and search engine use. This information can be used strategically to guide the design or redesign of a web site (templates, look-and-feel, and navigation infrastructure) to improve overall usability. The data can also be used tactically to assess the popularity and use of new pages and modules that are added and to rectify problems that surface. This paper describes software tools used to: (1) inventory search terms that lead to available content; (2) propose synonyms for commonly used search terms; (3) evaluate the effectiveness of calls to action; (4) conduct path analyses to targeted content. The American Academy of Orthopaedic Surgeons (AAOS) uses SurfRay's Behavior Tracking software (Santa Clara CA, USA, and Copenhagen, Denmark) to capture and archive the search terms that have been entered into the site's Google Mini search engine. The AAOS also uses Unica's NetInsight program to analyze its web site log files. These tools provide the AAOS with information that quantifies how well its web sites are operating and insights for making improvements to them. Although it is easy to quantify many aspects of an association's web presence, it also takes human involvement to analyze the results and then recommend changes. Without a dedicated resource to do this, the work often is accomplished only sporadically and on an ad hoc basis.

Alternative approaches to improve site investigations

International Nuclear Information System (INIS)

Beach, R.B.; Silka, L.R.

1992-01-01

Common complaints about standard investigations at hazardous waste sites include high costs and long time frames. Investigations at military bases as part of the installation restoration program or base closures suffer additionally from nonuniformity of approach and results and redundancy of work effort conducted by multiple environmental contractors. The problems of high costs and long time frames can be minimized by the consistent use of alternative sampling methods (such as soil gas surveys) and the utilization of analytical screening procedures at both on-site and off-site laboratories. Acceptable data quality is maintained by several procedures. Incorporation of quality control measures (10 % frequency), such as matrix spikes and duplicates, into the alternative analytical techniques allows assessment of the data quality relative to predetermined data quality objectives (DQOs). Confirmation of the screening results (10% frequency) using standard US EPA methods, such as the contract laboratory program (CLP) statement of work (SOW), allows an additional evaluation of the data accuracy. Depending on the investigative objectives, knowledge based computer systems (expert systems,) could be used to improve uniformity of site evaluations. Several case histories will be presented demonstrating how soil gas surveys, screening analyses and standard analyses can be utilized to give increased site information in a reduced time frame and at a cost savings of 30 to 40%. One case history illustrates a screening technique developed by the author for polynuclear aromatics (semi-volatile organic compounds) that can be conducted at a cost savings of 90% relative to a standard US EPA method. A comparison of the phased investigative approach to one using an integrated field team is presented for fuel spill or UST areas

Improving Site-Specific Radiological Performance Assessments - 13431

Energy Technology Data Exchange (ETDEWEB)

Tauxe, John; Black, Paul; Catlett, Kate; Lee, Robert; Perona, Ralph; Stockton, Tom; Sully, Mike [Neptune and Company, Inc., Los Alamos, New Mexico 87544 (United States)

2013-07-01

An improved approach is presented for conducting complete and defensible radiological site-specific performance assessments (PAs) to support radioactive waste disposal decisions. The basic tenets of PA were initiated some thirty years ago, focusing on geologic disposals and evaluating compliance with regulations. Some of these regulations were inherently probabilistic (i.e., addressing uncertainty in a quantitative fashion), such as the containment requirements of the U.S. Environmental Protection Agency's (EPA's) 40 CFR 191, Environmental Radiation Protection Standards for Management and Disposal of Spent Nuclear Fuel, High-Level and Transuranic Radioactive Wastes, Chap. 191.13 [1]. Methods of analysis were developed to meet those requirements, but at their core early PAs used 'conservative' parameter values and modeling approaches. This limited the utility of such PAs to compliance evaluation, and did little to inform decisions about optimizing disposal, closure and long-term monitoring and maintenance, or, in general, maintaining doses 'as low as reasonably achievable' (ALARA). This basic approach to PA development in the United States was employed essentially unchanged through the end of the 20. century, principally by the U.S. Department of Energy (DOE). Performance assessments developed in support of private radioactive waste disposal operations, regulated by the U.S. Nuclear Regulatory Commission (NRC) and its agreement states, were typically not as sophisticated. Discussion of new approaches to PA is timely, since at the time of this writing, the DOE is in the midst of revising its Order 435.1, Radioactive Waste Management [2], and the NRC is revising 10 CFR 61, Licensing Requirements for Land Disposal of Radioactive Waste [3]. Over the previous decade, theoretical developments and improved computational technology have provided the foundation for integrating decision analysis (DA) concepts and objective-focused thinking, plus

Improving Site-Specific Radiological Performance Assessments - 13431

International Nuclear Information System (INIS)

Tauxe, John; Black, Paul; Catlett, Kate; Lee, Robert; Perona, Ralph; Stockton, Tom; Sully, Mike

2013-01-01

An improved approach is presented for conducting complete and defensible radiological site-specific performance assessments (PAs) to support radioactive waste disposal decisions. The basic tenets of PA were initiated some thirty years ago, focusing on geologic disposals and evaluating compliance with regulations. Some of these regulations were inherently probabilistic (i.e., addressing uncertainty in a quantitative fashion), such as the containment requirements of the U.S. Environmental Protection Agency's (EPA's) 40 CFR 191, Environmental Radiation Protection Standards for Management and Disposal of Spent Nuclear Fuel, High-Level and Transuranic Radioactive Wastes, Chap. 191.13 [1]. Methods of analysis were developed to meet those requirements, but at their core early PAs used 'conservative' parameter values and modeling approaches. This limited the utility of such PAs to compliance evaluation, and did little to inform decisions about optimizing disposal, closure and long-term monitoring and maintenance, or, in general, maintaining doses 'as low as reasonably achievable' (ALARA). This basic approach to PA development in the United States was employed essentially unchanged through the end of the 20. century, principally by the U.S. Department of Energy (DOE). Performance assessments developed in support of private radioactive waste disposal operations, regulated by the U.S. Nuclear Regulatory Commission (NRC) and its agreement states, were typically not as sophisticated. Discussion of new approaches to PA is timely, since at the time of this writing, the DOE is in the midst of revising its Order 435.1, Radioactive Waste Management [2], and the NRC is revising 10 CFR 61, Licensing Requirements for Land Disposal of Radioactive Waste [3]. Over the previous decade, theoretical developments and improved computational technology have provided the foundation for integrating decision analysis (DA) concepts and objective-focused thinking, plus a Bayesian approach to

Semipalatinsk nuclear test site: History of building and function

International Nuclear Information System (INIS)

Sergazina, G.M.; Balmukhanov, S.B.

1999-01-01

A vast materials on history of Semipalatinsk nuclear test site creation and it building and function are presented. Authors with big reliability report one page of Kazakhstan's history. In steppe on naked place thousands of soldiers and officers, construct and military specialists have built the nuclear site on which during 40 years were conducting nuclear tests . Prolonged chronic radiation on population living near by site results to tragedy which is confessed by General Assembly of United Nations. In the book aspects of test site conversion and rehabilitation of injured population are considered. The book consists of introduction, three chapters and conclusion. The book is intended to wide circle of readers. (author)

Site-specific differences in the association between plantar tactile perception and mobility function in older adults

Directory of Open Access Journals (Sweden)

Yenisel eCruz-Almeida

2014-04-01

Full Text Available Introduction Impaired somatosensation is common in older adults and contributes to age-related loss of mobility function. However, little is known about whether somatosensation at different sites on the plantar surface of the foot are differentially related to mobility function. Such a finding may have important implications for clinical care of older adults and other at-risk populations, such as for optimizing interventions (e.g., footwear for augmenting somatosensory feedback and for improving the efficiency of clinical assessment. Materials and Methods Tactile perception was evaluated with a 10g monofilament at four sites on the plantar surface of each foot: great toe (GT, first metatarsal head (MT1, heel (H and fifth metatarsal head (MT5. Mobility function was assessed with the Berg Balance Scale and walking speed. Results Sixty-one older adults participated. Tactile perception was significantly positively associated with Berg Balance Score (adjusted R2 = 0.30 - 0.75; p = 0.03 - Discussion The present findings indicate that tactile perception at MT1 is more closely linked to mobility function than is tactile perception at GT, MT5 or H. These findings warrant further research to examine whether interventions (e.g., textured insoles and assessments that preferentially or exclusively focus on the site of MT1 may be more effective for optimizing clinical care.

Efficient multi-site two-photon functional imaging of neuronal circuits.

Science.gov (United States)

Castanares, Michael Lawrence; Gautam, Vini; Drury, Jack; Bachor, Hans; Daria, Vincent R

2016-12-01

Two-photon imaging using high-speed multi-channel detectors is a promising approach for optical recording of cellular membrane dynamics at multiple sites. A main bottleneck of this technique is the limited number of photons captured within a short exposure time (~1ms). Here, we implement temporal gating to improve the two-photon fluorescence yield from holographically projected multiple foci whilst maintaining a biologically safe incident average power. We observed up to 6x improvement in the signal-to-noise ratio (SNR) in Fluorescein and cultured hippocampal neurons showing evoked calcium transients. With improved SNR, we could pave the way to achieving multi-site optical recording of fluorogenic probes with response times in the order of ~1ms.

Number of on-site personnel and their functions

International Nuclear Information System (INIS)

Recker, M.

1986-01-01

After the definition of the general tasks, the development of an organization chart for on-site personnel is shown, the number and qualifications are indicated relating to the specific jobs. The functions of the different people are explained in detail. (orig.)

Conserved Functional Motifs and Homology Modeling to Predict Hidden Moonlighting Functional Sites

KAUST Repository

Wong, Aloysius Tze

2015-06-09

Moonlighting functional centers within proteins can provide them with hitherto unrecognized functions. Here, we review how hidden moonlighting functional centers, which we define as binding sites that have catalytic activity or regulate protein function in a novel manner, can be identified using targeted bioinformatic searches. Functional motifs used in such searches include amino acid residues that are conserved across species and many of which have been assigned functional roles based on experimental evidence. Molecules that were identified in this manner seeking cyclic mononucleotide cyclases in plants are used as examples. The strength of this computational approach is enhanced when good homology models can be developed to test the functionality of the predicted centers in silico, which, in turn, increases confidence in the ability of the identified candidates to perform the predicted functions. Computational characterization of moonlighting functional centers is not diagnostic for catalysis but serves as a rapid screening method, and highlights testable targets from a potentially large pool of candidates for subsequent in vitro and in vivo experiments required to confirm the functionality of the predicted moonlighting centers.

Conserved Functional Motifs and Homology Modeling to Predict Hidden Moonlighting Functional Sites

KAUST Repository

Wong, Aloysius Tze; Gehring, Christoph A; Irving, Helen R.

2015-01-01

Moonlighting functional centers within proteins can provide them with hitherto unrecognized functions. Here, we review how hidden moonlighting functional centers, which we define as binding sites that have catalytic activity or regulate protein function in a novel manner, can be identified using targeted bioinformatic searches. Functional motifs used in such searches include amino acid residues that are conserved across species and many of which have been assigned functional roles based on experimental evidence. Molecules that were identified in this manner seeking cyclic mononucleotide cyclases in plants are used as examples. The strength of this computational approach is enhanced when good homology models can be developed to test the functionality of the predicted centers in silico, which, in turn, increases confidence in the ability of the identified candidates to perform the predicted functions. Computational characterization of moonlighting functional centers is not diagnostic for catalysis but serves as a rapid screening method, and highlights testable targets from a potentially large pool of candidates for subsequent in vitro and in vivo experiments required to confirm the functionality of the predicted moonlighting centers.

improving education programme at pmtct sites in liberia

African Journals Online (AJOL)

among the HIV positive mother under 6 months, in order to improve nutritional education program at PMTCT sites level. A total of 90 ... practice among the HIV positive mothers of child under 6 months in terms of nutrition and infant feeding. Keywords: .... the replacement feeding is the sustainability of this. Even though they ...

DbPTM 3.0: an informative resource for investigating substrate site specificity and functional association of protein post-translational modifications.

Science.gov (United States)

Lu, Cheng-Tsung; Huang, Kai-Yao; Su, Min-Gang; Lee, Tzong-Yi; Bretaña, Neil Arvin; Chang, Wen-Chi; Chen, Yi-Ju; Chen, Yu-Ju; Huang, Hsien-Da

2013-01-01

Protein modification is an extremely important post-translational regulation that adjusts the physical and chemical properties, conformation, stability and activity of a protein; thus altering protein function. Due to the high throughput of mass spectrometry (MS)-based methods in identifying site-specific post-translational modifications (PTMs), dbPTM (http://dbPTM.mbc.nctu.edu.tw/) is updated to integrate experimental PTMs obtained from public resources as well as manually curated MS/MS peptides associated with PTMs from research articles. Version 3.0 of dbPTM aims to be an informative resource for investigating the substrate specificity of PTM sites and functional association of PTMs between substrates and their interacting proteins. In order to investigate the substrate specificity for modification sites, a newly developed statistical method has been applied to identify the significant substrate motifs for each type of PTMs containing sufficient experimental data. According to the data statistics in dbPTM, >60% of PTM sites are located in the functional domains of proteins. It is known that most PTMs can create binding sites for specific protein-interaction domains that work together for cellular function. Thus, this update integrates protein-protein interaction and domain-domain interaction to determine the functional association of PTM sites located in protein-interacting domains. Additionally, the information of structural topologies on transmembrane (TM) proteins is integrated in dbPTM in order to delineate the structural correlation between the reported PTM sites and TM topologies. To facilitate the investigation of PTMs on TM proteins, the PTM substrate sites and the structural topology are graphically represented. Also, literature information related to PTMs, orthologous conservations and substrate motifs of PTMs are also provided in the resource. Finally, this version features an improved web interface to facilitate convenient access to the resource.

Detection and characterization of 3D-signature phosphorylation site motifs and their contribution towards improved phosphorylation site prediction in proteins

Directory of Open Access Journals (Sweden)

Selbig Joachim

2009-04-01

Full Text Available Abstract Background Phosphorylation of proteins plays a crucial role in the regulation and activation of metabolic and signaling pathways and constitutes an important target for pharmaceutical intervention. Central to the phosphorylation process is the recognition of specific target sites by protein kinases followed by the covalent attachment of phosphate groups to the amino acids serine, threonine, or tyrosine. The experimental identification as well as computational prediction of phosphorylation sites (P-sites has proved to be a challenging problem. Computational methods have focused primarily on extracting predictive features from the local, one-dimensional sequence information surrounding phosphorylation sites. Results We characterized the spatial context of phosphorylation sites and assessed its usability for improved phosphorylation site predictions. We identified 750 non-redundant, experimentally verified sites with three-dimensional (3D structural information available in the protein data bank (PDB and grouped them according to their respective kinase family. We studied the spatial distribution of amino acids around phosphorserines, phosphothreonines, and phosphotyrosines to extract signature 3D-profiles. Characteristic spatial distributions of amino acid residue types around phosphorylation sites were indeed discernable, especially when kinase-family-specific target sites were analyzed. To test the added value of using spatial information for the computational prediction of phosphorylation sites, Support Vector Machines were applied using both sequence as well as structural information. When compared to sequence-only based prediction methods, a small but consistent performance improvement was obtained when the prediction was informed by 3D-context information. Conclusion While local one-dimensional amino acid sequence information was observed to harbor most of the discriminatory power, spatial context information was identified as

School Improvement Policy--Site-Based Management

Directory of Open Access Journals (Sweden)

C. Kenneth Tanner

1998-03-01

Full Text Available Have administrative functions of principals changed in schools practicing site-based management (SBM with shared governance? To deal with this issue we employed the Delphi technique and a panel of 24 experts from 14 states. The experts, which included educational specialists, researchers, writers, and elementary school principals, agreed that the implementation of SBM dramatically influences the roles of the principal in management/administration and leadership. Data revealed that the elementary principal's leadership role requires specialized skills to support shared governance, making it necessary to form professional development programs that adapt to innovations evolving from the implementation of SBM.

Oil and gas site contamination risks : improved oversight needed

International Nuclear Information System (INIS)

2010-02-01

British Columbia has seen record levels of activities in the oil and gas sector. Upstream petroleum processes include exploration, well completion and production. Site contamination can occur during all of these activities, resulting in potential environmental and human health impacts. Although well operators are responsible by law for site restoration, there is a potential risk that some operators will not fulfill their responsibilities, thereby leaving the province liable for the site restoration costs. In British Columbia, the BC Oil and Gas Commission (OGC) is responsible for managing these risks through oversight activities designed to ensure that industry meets its obligations. The OGC also manages the orphan sites reclamation fund. This report presented an audit of the OGC in order to determine if it is providing adequate oversight of upstream oil and gas site contamination risks. The audit examined whether the agency responsibilities are clear and whether the OGC is fully aware of the environmental and financial risks associated with upstream oil and gas site contamination. The audit also examined if the OGC has established appropriate procedures to oversee the risks and to inform the public of how effectively site contamination risks are being managed. The report presented the audit background, audit expectations, findings, conclusions and recommendations. It was concluded that the OGC's oversight of the environmental and financial risks associated with oil and gas site contamination needs improving. tabs., figs.

Investigation and identification of functional post-translational modification sites associated with drug binding and protein-protein interactions.

Science.gov (United States)

Su, Min-Gang; Weng, Julia Tzu-Ya; Hsu, Justin Bo-Kai; Huang, Kai-Yao; Chi, Yu-Hsiang; Lee, Tzong-Yi

2017-12-21

Protein post-translational modification (PTM) plays an essential role in various cellular processes that modulates the physical and chemical properties, folding, conformation, stability and activity of proteins, thereby modifying the functions of proteins. The improved throughput of mass spectrometry (MS) or MS/MS technology has not only brought about a surge in proteome-scale studies, but also contributed to a fruitful list of identified PTMs. However, with the increase in the number of identified PTMs, perhaps the more crucial question is what kind of biological mechanisms these PTMs are involved in. This is particularly important in light of the fact that most protein-based pharmaceuticals deliver their therapeutic effects through some form of PTM. Yet, our understanding is still limited with respect to the local effects and frequency of PTM sites near pharmaceutical binding sites and the interfaces of protein-protein interaction (PPI). Understanding PTM's function is critical to our ability to manipulate the biological mechanisms of protein. In this study, to understand the regulation of protein functions by PTMs, we mapped 25,835 PTM sites to proteins with available three-dimensional (3D) structural information in the Protein Data Bank (PDB), including 1785 modified PTM sites on the 3D structure. Based on the acquired structural PTM sites, we proposed to use five properties for the structural characterization of PTM substrate sites: the spatial composition of amino acids, residues and side-chain orientations surrounding the PTM substrate sites, as well as the secondary structure, division of acidity and alkaline residues, and solvent-accessible surface area. We further mapped the structural PTM sites to the structures of drug binding and PPI sites, identifying a total of 1917 PTM sites that may affect PPI and 3951 PTM sites associated with drug-target binding. An integrated analytical platform (CruxPTM), with a variety of methods and online molecular docking

The Ironbridge Gorge Heritage Site and its local and regional functions

Directory of Open Access Journals (Sweden)

Cudny Waldemar

2017-06-01

Full Text Available The article is devoted to the issue of heritage and its functions. Based on the existing literature, the author presents the definition of heritage, the classification of heritage resources, and its most important impacts. The aim of the article was to show the functions that may be performed by a heritage site, locally and regionally. The example used by the author is the Ironbridge Gorge Heritage Site in the United Kingdom. Most heritage functions described by other authors are confirmed in this case study. The cultural heritage of the Ironbridge Gorge creates an opportunity to undertake various local and regional activities, having first of all an educational influence on the inhabitants, school youth and tourists. We must not ignore the economicinfluences, such as financing the activity of the Ironbridge Trust (the institution administering the site, generating income for local firms providing service to tourists, or for construction companies. This income helps to preserve and conserve the tangible heritage of the Ironbridge Gorge, as well as to generate jobs in heritage management, conservation and heritage tourism. Other effects of the Ironbridge Gorge Site include a socio-cultural impact or that related to sustainable development.

NREL Studies Wind Farm Aerodynamics to Improve Siting (Fact Sheet)

Energy Technology Data Exchange (ETDEWEB)

2012-04-01

NREL researchers have used high-tech instruments and high-performance computing to understand atmospheric turbulence and turbine wake behavior in order to improve wind turbine design and siting within wind farms.

SITEX 2.0: Projections of protein functional sites on eukaryotic genes. Extension with orthologous genes.

Science.gov (United States)

Medvedeva, Irina V; Demenkov, Pavel S; Ivanisenko, Vladimir A

2017-04-01

Functional sites define the diversity of protein functions and are the central object of research of the structural and functional organization of proteins. The mechanisms underlying protein functional sites emergence and their variability during evolution are distinguished by duplication, shuffling, insertion and deletion of the exons in genes. The study of the correlation between a site structure and exon structure serves as the basis for the in-depth understanding of sites organization. In this regard, the development of programming resources that allow the realization of the mutual projection of exon structure of genes and primary and tertiary structures of encoded proteins is still the actual problem. Previously, we developed the SitEx system that provides information about protein and gene sequences with mapped exon borders and protein functional sites amino acid positions. The database included information on proteins with known 3D structure. However, data with respect to orthologs was not available. Therefore, we added the projection of sites positions to the exon structures of orthologs in SitEx 2.0. We implemented a search through database using site conservation variability and site discontinuity through exon structure. Inclusion of the information on orthologs allowed to expand the possibilities of SitEx usage for solving problems regarding the analysis of the structural and functional organization of proteins. Database URL: http://www-bionet.sscc.ru/sitex/ .

Functional mimicry of a discontinuous antigenic site by a designed synthetic peptide

NARCIS (Netherlands)

Villen, J.; Borras, E.; Schaaper, W.M.M.; Meloen, R.H.; Davila, M.; Domingo, E.; Giralt, E.; Andreu, D.

2002-01-01

Functional reproduction of the discontinuous antigenic site D of foot-and-mouth disease virus (FMDV) has been achieved by means of synthetic peptide constructions that integrate each of the three protein loops that define the antigenic site into a single molecule. The site D mimics were designed on

Improving Surveillance and Prevention of Surgical Site Infection in Pediatric Cardiac Surgery.

Science.gov (United States)

Cannon, Melissa; Hersey, Diane; Harrison, Sheilah; Joy, Brian; Naguib, Aymen; Galantowicz, Mark; Simsic, Janet

2016-03-01

Postoperative cardiovascular surgical site infections are preventable events that may lead to increased morbidity, mortality, and health care costs. To improve surgical wound surveillance and reduce the incidence of surgical site infections. An institutional review of surgical site infections led to implementation of 8 surveillance and process measures: appropriate preparation the night before surgery and the day of surgery, use of appropriate preparation solution in the operating room, appropriate timing of preoperative antibiotic administration, placement of a photograph of the surgical site in the patient's chart at discharge, sending a photograph of the surgical site to the patient's primary care physician, 30-day follow-up of the surgical site by an advanced nurse practitioner, and placing a photograph of the surgical site obtained on postoperative day 30 in the patient's chart. Mean overall compliance with the 8 measures from March 2013 through February 2014 was 88%. Infections occurred in 10 of 417 total operative cases (2%) in 2012, in 8 of 437 total operative cases (2%) in 2013, and in 7 of 452 total operative cases (1.5%) in 2014. Institution of the surveillance process has resulted in improved identification of suspected surgical site infections via direct rather than indirect measures, accurate identification of all surgical site infections based on definitions of the National Healthcare Safety Network, collaboration with all persons involved, and enhanced communication with patients' family members and referring physicians. ©2016 American Association of Critical-Care Nurses.

Panax ginseng Improves Functional Recovery after Contusive Spinal Cord Injury by Regulating the Inflammatory Response in Rats: An In Vivo Study

Directory of Open Access Journals (Sweden)

Young Ock Kim

2015-01-01

Full Text Available Spinal cord injury (SCI results in permanent loss of motor function below the injured site. Neuroinflammatory reaction following SCI can aggravate neural injury and functional impairment. Ginseng is well known to possess anti-inflammatory effects. The present study investigated the neuroprotective effects of Panax ginseng C.A. Mayer (P. ginseng after SCI. A spinal contusion was made at the T11-12 spinal cord in adult male Sprague-Dawley rats (n=47 using the NYU impactor. Motor function was assessed using the Basso-Beattie-Bresnahan (BBB score in P. ginseng (0.1, 0.5, 1, 3, and 5 mg/kg or vehicle (saline treated after SCI. We also assessed the protein expression of cyclooxygenase-2 (COX-2 and inducible nitric oxide synthase (iNOS at the lesion site by western blot and then measured the cavity area using luxol fast blue/cresyl violet staining. P. ginseng treated group in SCI showed a significant improvement in locomotor function after the injury. The protein expression of COX-2 and iNOS at the lesion site and the cavity area were decreased following SCI by P. ginseng treatment. These results suggest that P. ginseng may improve the recovery of motor function after SCI which provides neuroprotection by alleviating posttraumatic inflammatory responses.

Improving 1D Site Specific Velocity Profiles for the Kik-Net Network

Science.gov (United States)

Holt, James; Edwards, Benjamin; Pilz, Marco; Fäh, Donat; Rietbrock, Andreas

2017-04-01

Ground motion predication equations (GMPEs) form the cornerstone of modern seismic hazard assessments. When produced to a high standard they provide reliable estimates of ground motion/spectral acceleration for a given site and earthquake scenario. This information is crucial for engineers to optimise design and for regulators who enforce legal minimum safe design capacities. Classically, GMPEs were built upon the assumption that variability around the median model could be treated as aleatory. As understanding improved, it was noted that the propagation could be segregated into the response of the average path from the source and the response of the site. This is because the heterogeneity of the near-surface lithology is significantly different from that of the bulk path. It was then suggested that the semi-ergodic approach could be taken if the site response could be determined, moving uncertainty away from aleatory to epistemic. The determination of reliable site-specific response models is therefore becoming increasingly critical for ground motion models used in engineering practice. Today it is common practice to include proxies for site response within the scope of a GMPE, such as Vs30 or site classification, in an effort to reduce the overall uncertainty of the predication at a given site. However, these proxies are not always reliable enough to give confident ground motion estimates, due to the complexity of the near-surface. Other approaches of quantifying the response of the site include detailed numerical simulations (1/2/3D - linear, EQL, non-linear etc.). However, in order to be reliable, they require highly detailed and accurate velocity and, for non-linear analyses, material property models. It is possible to obtain this information through invasive methods, but is expensive, and not feasible for most projects. Here we propose an alternative method to derive reliable velocity profiles (and their uncertainty), calibrated using almost 20 years of

Analyzing Web Server Logs to Improve a Site's Usage. The Systems Librarian

Science.gov (United States)

Breeding, Marshall

2005-01-01

This column describes ways to streamline and optimize how a Web site works in order to improve both its usability and its visibility. The author explains how to analyze logs and other system data to measure the effectiveness of the Web site design and search engine.

Hanford Site Welding Program Successfully Providing A Single Site Function For Use By Multiple Contractors

International Nuclear Information System (INIS)

Cannell, G.R.

2009-01-01

The Department of Energy, Richland Operations (DOE-RL) recently restructured its Hanford work scope, awarding two new contracts over the past several months for a total of three contracts to manage the sites cleanup efforts. DOE-RL met with key contractor personnel prior to and during contract transition to ensure site welding activities had appropriate oversight and maintained code compliance. The transition also provided an opportunity to establish a single site-wide function that would provide welding and materials engineering services to the Hanford site contractors: CH2M HILL Plateau Remediation Company (CHPRC); Mission Support Alliance (MSA); Washington River Protection Solutions (WRPS); and Washington Closure Hanford (WCH). Over the years, multiple and separate welding programs (amongst the several contractors) existed at the Hanford site leading to inefficiencies resulting from duplication of administrative efforts, maintenance of welding procedures, welder performance certifications, etc. The new, single program eliminates these inefficiencies. The new program, co-managed by two of the sites' new contractors, the CHPRC ('owner' of the program and responsible for construction welding services) and the MSA (provides maintenance welding services), provides more than just the traditional construction and maintenance welding services. Also provided, are welding engineering, specialty welding development/qualification for the closure of radioactive materials containers and materials evaluation/failure analysis. The following describes the new Hanford site welding program.

Functional molecular markers for crop improvement.

Science.gov (United States)

Kage, Udaykumar; Kumar, Arun; Dhokane, Dhananjay; Karre, Shailesh; Kushalappa, Ajjamada C

2016-10-01

A tremendous decline in cultivable land and resources and a huge increase in food demand calls for immediate attention to crop improvement. Though molecular plant breeding serves as a viable solution and is considered as "foundation for twenty-first century crop improvement", a major stumbling block for crop improvement is the availability of a limited functional gene pool for cereal crops. Advancement in the next generation sequencing (NGS) technologies integrated with tools like metabolomics, proteomics and association mapping studies have facilitated the identification of candidate genes, their allelic variants and opened new avenues to accelerate crop improvement through development and use of functional molecular markers (FMMs). The FMMs are developed from the sequence polymorphisms present within functional gene(s) which are associated with phenotypic trait variations. Since FMMs obviate the problems associated with random DNA markers, these are considered as "the holy grail" of plant breeders who employ targeted marker assisted selections (MAS) for crop improvement. This review article attempts to consider the current resources and novel methods such as metabolomics, proteomics and association studies for the identification of candidate genes and their validation through virus-induced gene silencing (VIGS) for the development of FMMs. A number of examples where the FMMs have been developed and used for the improvement of cereal crops for agronomic, food quality, disease resistance and abiotic stress tolerance traits have been considered.

Multi-Site Diagnostic Classification of Schizophrenia Using Discriminant Deep Learning with Functional Connectivity MRI

Directory of Open Access Journals (Sweden)

Ling-Li Zeng

2018-04-01

Full Text Available Background: A lack of a sufficiently large sample at single sites causes poor generalizability in automatic diagnosis classification of heterogeneous psychiatric disorders such as schizophrenia based on brain imaging scans. Advanced deep learning methods may be capable of learning subtle hidden patterns from high dimensional imaging data, overcome potential site-related variation, and achieve reproducible cross-site classification. However, deep learning-based cross-site transfer classification, despite less imaging site-specificity and more generalizability of diagnostic models, has not been investigated in schizophrenia. Methods: A large multi-site functional MRI sample (n = 734, including 357 schizophrenic patients from seven imaging resources was collected, and a deep discriminant autoencoder network, aimed at learning imaging site-shared functional connectivity features, was developed to discriminate schizophrenic individuals from healthy controls. Findings: Accuracies of approximately 85·0% and 81·0% were obtained in multi-site pooling classification and leave-site-out transfer classification, respectively. The learned functional connectivity features revealed dysregulation of the cortical-striatal-cerebellar circuit in schizophrenia, and the most discriminating functional connections were primarily located within and across the default, salience, and control networks. Interpretation: The findings imply that dysfunctional integration of the cortical-striatal-cerebellar circuit across the default, salience, and control networks may play an important role in the “disconnectivity” model underlying the pathophysiology of schizophrenia. The proposed discriminant deep learning method may be capable of learning reliable connectome patterns and help in understanding the pathophysiology and achieving accurate prediction of schizophrenia across multiple independent imaging sites. Keywords: Schizophrenia, Deep learning, Connectome, f

Multi-Site Diagnostic Classification of Schizophrenia Using Discriminant Deep Learning with Functional Connectivity MRI.

Science.gov (United States)

Zeng, Ling-Li; Wang, Huaning; Hu, Panpan; Yang, Bo; Pu, Weidan; Shen, Hui; Chen, Xingui; Liu, Zhening; Yin, Hong; Tan, Qingrong; Wang, Kai; Hu, Dewen

2018-04-01

A lack of a sufficiently large sample at single sites causes poor generalizability in automatic diagnosis classification of heterogeneous psychiatric disorders such as schizophrenia based on brain imaging scans. Advanced deep learning methods may be capable of learning subtle hidden patterns from high dimensional imaging data, overcome potential site-related variation, and achieve reproducible cross-site classification. However, deep learning-based cross-site transfer classification, despite less imaging site-specificity and more generalizability of diagnostic models, has not been investigated in schizophrenia. A large multi-site functional MRI sample (n = 734, including 357 schizophrenic patients from seven imaging resources) was collected, and a deep discriminant autoencoder network, aimed at learning imaging site-shared functional connectivity features, was developed to discriminate schizophrenic individuals from healthy controls. Accuracies of approximately 85·0% and 81·0% were obtained in multi-site pooling classification and leave-site-out transfer classification, respectively. The learned functional connectivity features revealed dysregulation of the cortical-striatal-cerebellar circuit in schizophrenia, and the most discriminating functional connections were primarily located within and across the default, salience, and control networks. The findings imply that dysfunctional integration of the cortical-striatal-cerebellar circuit across the default, salience, and control networks may play an important role in the "disconnectivity" model underlying the pathophysiology of schizophrenia. The proposed discriminant deep learning method may be capable of learning reliable connectome patterns and help in understanding the pathophysiology and achieving accurate prediction of schizophrenia across multiple independent imaging sites. Copyright © 2018 German Center for Neurodegenerative Diseases (DZNE). Published by Elsevier B.V. All rights reserved.

Orthogonal use of a human tRNA synthetase active site to achieve multi-functionality

Science.gov (United States)

Zhou, Quansheng; Kapoor, Mili; Guo, Min; Belani, Rajesh; Xu, Xiaoling; Kiosses, William B.; Hanan, Melanie; Park, Chulho; Armour, Eva; Do, Minh-Ha; Nangle, Leslie A.; Schimmel, Paul; Yang, Xiang-Lei

2011-01-01

Protein multi-functionality is an emerging explanation for the complexity of higher organisms. In this regard, while aminoacyl tRNA synthetases catalyze amino acid activation for protein synthesis, some also act in pathways for inflammation, angiogenesis, and apoptosis. How multiple functions evolved and their relationship to the active site is not clear. Here structural modeling analysis, mutagenesis, and cell-based functional studies show that the potent angiostatic, natural fragment of human TrpRS associates via Trp side chains that protrude from the cognate cellular receptor VE-cadherin. Modeling indicates that (I prefer the way it was because the conclusion was reached not only by modeling, but more so by experimental studies.)VE-cadherin Trp side chains fit into the Trp-specific active site of the synthetase. Thus, specific side chains of the receptor mimic (?) amino acid substrates and expand the functionality of the active site of the synthetase. We propose that orthogonal use of the same active site may be a general way to develop multi-functionality of human tRNA synthetases and other proteins. PMID:20010843

Fast dynamics perturbation analysis for prediction of protein functional sites

Directory of Open Access Journals (Sweden)

Cohn Judith D

2008-01-01

Full Text Available Abstract Background We present a fast version of the dynamics perturbation analysis (DPA algorithm to predict functional sites in protein structures. The original DPA algorithm finds regions in proteins where interactions cause a large change in the protein conformational distribution, as measured using the relative entropy Dx. Such regions are associated with functional sites. Results The Fast DPA algorithm, which accelerates DPA calculations, is motivated by an empirical observation that Dx in a normal-modes model is highly correlated with an entropic term that only depends on the eigenvalues of the normal modes. The eigenvalues are accurately estimated using first-order perturbation theory, resulting in a N-fold reduction in the overall computational requirements of the algorithm, where N is the number of residues in the protein. The performance of the original and Fast DPA algorithms was compared using protein structures from a standard small-molecule docking test set. For nominal implementations of each algorithm, top-ranked Fast DPA predictions overlapped the true binding site 94% of the time, compared to 87% of the time for original DPA. In addition, per-protein recall statistics (fraction of binding-site residues that are among predicted residues were slightly better for Fast DPA. On the other hand, per-protein precision statistics (fraction of predicted residues that are among binding-site residues were slightly better using original DPA. Overall, the performance of Fast DPA in predicting ligand-binding-site residues was comparable to that of the original DPA algorithm. Conclusion Compared to the original DPA algorithm, the decreased run time with comparable performance makes Fast DPA well-suited for implementation on a web server and for high-throughput analysis.

National Ignition Facility subsystem design requirements NIF site improvements SSDR 1.2.1

International Nuclear Information System (INIS)

Kempel, P.; Hands, J.

1996-01-01

This Subsystem Design Requirements (SSDR) document establishes the performance, design, and verification requirements associated with the NIF Project Site at Lawrence Livermore National Laboratory (LLNL) at Livermore, California. It identifies generic design conditions for all NIF Project facilities, including siting requirements associated with natural phenomena, and contains specific requirements for furnishing site-related infrastructure utilities and services to the NIF Project conventional facilities and experimental hardware systems. Three candidate sites were identified as potential locations for the NIF Project. However, LLNL has been identified by DOE as the preferred site because of closely related laser experimentation underway at LLNL, the ability to use existing interrelated infrastructure, and other reasons. Selection of a site other than LLNL will entail the acquisition of site improvements and infrastructure additional to those described in this document. This SSDR addresses only the improvements associated with the NIF Project site located at LLNL, including new work and relocation or demolition of existing facilities that interfere with the construction of new facilities. If the Record of Decision for the PEIS on Stockpile Stewardship and Management were to select another site, this SSDR would be revised to reflect the characteristics of the selected site. Other facilities and infrastructure needed to support operation of the NIF, such as those listed below, are existing and available at the LLNL site, and are not included in this SSDR. Office Building. Target Receiving and Inspection. General Assembly Building. Electro- Mechanical Shop. Warehousing and General Storage. Shipping and Receiving. General Stores. Medical Facilities. Cafeteria services. Service Station and Garage. Fire Station. Security and Badging Services

Alternative off-site power supply improves nuclear power plant safety

International Nuclear Information System (INIS)

Gjorgiev, Blaže; Volkanovski, Andrija; Kančev, Duško; Čepin, Marko

2014-01-01

Highlights: • Additional power supply for mitigation of the station blackout event in NPP is used. • A hydro power plant is considered as an off-site alternative power supply. • An upgrade of the probabilistic safety assessment from its traditional use is made. • The obtained results show improvement of nuclear power plant safety. - Abstract: A reliable power system is important for safe operation of the nuclear power plants. The station blackout event is of great importance for nuclear power plant safety. This event is caused by the loss of all alternating current power supply to the safety and non-safety buses of the nuclear power plant. In this study an independent electrical connection between a pumped-storage hydro power plant and a nuclear power plant is assumed as a standpoint for safety and reliability analysis. The pumped-storage hydro power plant is considered as an alternative power supply. The connection with conventional accumulation type of hydro power plant is analysed in addition. The objective of this paper is to investigate the improvement of nuclear power plant safety resulting from the consideration of the alternative power supplies. The safety of the nuclear power plant is analysed through the core damage frequency, a risk measure assess by the probabilistic safety assessment. The presented method upgrades the probabilistic safety assessment from its common traditional use in sense that it considers non-plant sited systems. The obtained results show significant decrease of the core damage frequency, indicating improvement of nuclear safety if hydro power plant is introduced as an alternative off-site power source

Improvement of Off-site Dose Assessment Code for Operating Nuclear Power Plant

Energy Technology Data Exchange (ETDEWEB)

Kim, Juyub; Kim, Juyoul; Shin, Kwangyoung [FNC Technology Co. Ltd., Yongin (Korea, Republic of); You, Songjae; Moon, Jongyi [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

2014-05-15

XOQDOQ code which calculates atmospheric Dispersion factor was included into INDAC also. A research on the improvement of off-site dose assessment system for an operating nuclear power plant was performed by KINS in 2011. As a result, following improvements were derived: - Separation of dose assessment for new and existing facilities - Update of food ingestion data - Consideration of multi-unit operation and so on In order to reflect the results, INDAC is under modification. INDAC is an integrated dose assessment code for an operating nuclear power plant and consists of three main modules: XOQDOQ, GASDOS and LIQDOS. The modules are under modification in order to improve the accuracy of assessment and usability. Assessment points for multi-unit release can be calculated through the improved code and the method on dose assessment for multi-unit release has been modified, so that the dose assessment result of multi-unit site becomes more realistic by relieving excessive conservatism. Finally, as the accuracy of calculation modules has been improved, the reliability of dose assessment result has been strengthened.

Composite Structural Motifs of Binding Sites for Delineating Biological Functions of Proteins

Science.gov (United States)

Kinjo, Akira R.; Nakamura, Haruki

2012-01-01

Most biological processes are described as a series of interactions between proteins and other molecules, and interactions are in turn described in terms of atomic structures. To annotate protein functions as sets of interaction states at atomic resolution, and thereby to better understand the relation between protein interactions and biological functions, we conducted exhaustive all-against-all atomic structure comparisons of all known binding sites for ligands including small molecules, proteins and nucleic acids, and identified recurring elementary motifs. By integrating the elementary motifs associated with each subunit, we defined composite motifs that represent context-dependent combinations of elementary motifs. It is demonstrated that function similarity can be better inferred from composite motif similarity compared to the similarity of protein sequences or of individual binding sites. By integrating the composite motifs associated with each protein function, we define meta-composite motifs each of which is regarded as a time-independent diagrammatic representation of a biological process. It is shown that meta-composite motifs provide richer annotations of biological processes than sequence clusters. The present results serve as a basis for bridging atomic structures to higher-order biological phenomena by classification and integration of binding site structures. PMID:22347478

A method for improving global pyranometer measurements by modeling responsivity functions

Energy Technology Data Exchange (ETDEWEB)

Lester, A. [Smith College, Northampton, MA 01063 (United States); Myers, D.R. [National Renewable Energy Laboratory, 1617 Cole Blvd., Golden, CO 80401 (United States)

2006-03-15

Accurate global solar radiation measurements are crucial to climate change research and the development of solar energy technologies. Pyranometers produce an electrical signal proportional to global irradiance. The signal-to-irradiance ratio is the responsivity (RS) of the instrument (RS=signal/irradiance=microvolts/(W/m{sup 2})). Most engineering measurements are made using a constant RS. It is known that RS varies with day of year, zenith angle, and net infrared radiation. This study proposes a method to find an RS function to model a pyranometer's changing RS. Using a reference irradiance calculated from direct and diffuse instruments, we found instantaneous RS for two global pyranometers over 31 sunny days in a two-year period. We performed successive independent regressions of the error between the constant and instantaneous RS with respect to zenith angle, day of year, and net infrared to obtain an RS function. An alternative method replaced the infrared regression with an independently developed technique to account for thermal offset. Results show improved uncertainties with the function method than with the single-calibration value. Lower uncertainties also occur using a black-and-white (8-48), rather than all-black (PSP), shaded pyranometer as the diffuse reference instrument. We conclude that the function method is extremely effective in reducing uncertainty in the irradiance measurements for global PSP pyranometers if they are calibrated at the deployment site. Furthermore, it was found that the function method accounts for the pyranometer's thermal offset, rendering further corrections unnecessary. The improvements in irradiance data achieved in this study will serve to increase the accuracy of solar energy assessments and atmospheric research. (author)

Engraftment Site and Effectiveness of the Pan-Caspase Inhibitor F573 to Improve Engraftment in Mouse and Human Islet Transplantation in Mice.

Science.gov (United States)

Pepper, Andrew R; Bruni, Antonio; Pawlick, Rena; Wink, John; Rafiei, Yasmin; Gala-Lopez, Boris; Bral, Mariusz; Abualhassan, Nasser; Kin, Tatsuya; Shapiro, A M James

2017-10-01

Islet transplantation is an effective therapy in type 1 diabetes and recalcitrant hypoglycemia. However, there is an ongoing need to circumvent islet loss posttransplant. We explore herein the potential of the pan-caspase inhibitor F573 to mitigate early apoptosis-mediated islet death within portal and extrahepatic portal sites in mice. Mouse or human islets were cultured in standard media ±100 μM F573 and subsequently assessed for viability and apoptosis via terminal deoxynucleotidyl transferase dUTP nick end labeling staining and caspase-3 activation. Diabetic mice were transplanted with syngeneic islets placed under the kidney capsule (KC) or into the subcutaneous deviceless (DL) site at a marginal islet dose (150 islets), or into the portal vein (PV) at a full dose (500 islets). Human islets were transplanted under the KC of diabetic immunodeficient mice at a marginal dose (500 islet equivalents). Islets were cultured in the presence of F573, and F573 was administered subcutaneously on days 0 to 5 posttransplant. Control mice were transplanted with nontreated islets and were injected with saline. Graft function was measured by nonfasting blood glucose and glucose tolerance testing. F573 markedly reduced human and mouse islet apoptosis after in vitro culture (P islet function when transplanted under the KC (P islet marginal KC transplants. Conversely, F573 significantly improved mouse islet engraftment in the PV and DL site (P islet apoptosis and improves engraftment most effectively in the portal and DL subcutaneous sites.

A discrimlnant function approach to ecological site classification in northern New England

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James M. Fincher; Marie-Louise Smith

1994-01-01

Describes one approach to ecologically based classification of upland forest community types of the White and Green Mountain physiographic regions. The classification approach is based on an intensive statistical analysis of the relationship between the communities and soil-site factors. Discriminant functions useful in distinguishing between types based on soil-site...

Lessons learned: Needs for improving human health risk assessment at USDOE Sites

International Nuclear Information System (INIS)

Hamilton, L.D.; Holtzman, S.; Meinhold, A.F.; Morris, S.C.; Rowe, M.D.; Daniels, J.I.; Layton, D.W.; Anspaugh, L.R.

1993-09-01

Realistic health risk assessments were performed in a pilot study of three U.S. Department of Energy (USDOE) sites. These assessments, covering a broad spectrum of data and methods, were used to identify needs for improving future health risk assessments at USDOE sites. Topics receiving specific recommendations for additional research include: choice of distributions for Monte Carlo simulation; estimation of risk reduction; analysis of the U.S. Department of Agriculture Database on food and nutrient intakes; investigations on effects of food processing on contaminant levels; background food and environmental concentrations of contaminants; method for handling exposures to groundwater plumes, methods for analyzing less than lifetime exposure to carcinogens; and improvement of bioaccumulation factors

Making perceptual learning practical to improve visual functions.

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Polat, Uri

2009-10-01

Task-specific improvement in performance after training is well established. The finding that learning is stimulus-specific and does not transfer well between different stimuli, between stimulus locations in the visual field, or between the two eyes has been used to support the notion that neurons or assemblies of neurons are modified at the earliest stage of cortical processing. However, a debate regarding the proposed mechanism underlying perceptual learning is an ongoing issue. Nevertheless, generalization of a trained task to other functions is an important key, for both understanding the neural mechanisms and the practical value of the training. This manuscript describes a structured perceptual learning method that previously used (amblyopia, myopia) and a novel technique and results that were applied for presbyopia. In general, subjects were trained for contrast detection of Gabor targets under lateral masking conditions. Training improved contrast sensitivity and diminished the lateral suppression when it existed (amblyopia). The improvement was transferred to unrelated functions such as visual acuity. The new results of presbyopia show substantial improvement of the spatial and temporal contrast sensitivity, leading to improved processing speed of target detection as well as reaction time. Consequently, the subjects, who were able to eliminate the need for reading glasses, benefited. Thus, here we show that the transfer of functions indicates that the specificity of improvement in the trained task can be generalized by repetitive practice of target detection, covering a sufficient range of spatial frequencies and orientations, leading to an improvement in unrelated visual functions. Thus, perceptual learning can be a practical method to improve visual functions in people with impaired or blurred vision.

Functional analysis of a potential regulatory K+-binding site in the Na+, K+-ATPase

DEFF Research Database (Denmark)

Schack, Vivien Rodacker; Vilsen, Bente

The Na+, K+-ATPase functions by actively transporting 3 Na+ ions out of and 2 K+ ions into the cell, thereby creating ion gradients crucial for many physiological processes. Recently, a combined structural and functional study of the closely related Ca2+-ATPase indicated the presence...... of a regulatory K+-binding site in the P-domain of the enzyme, identifying E732 as being of particular importance (Sorensen, Clausen et al. 2004). In addition, P709 is thought to play a significant role in the structural organization of this site. Both E732 and P709 are highly conserved among P-type ATPases (E732...... is present as either glutamic acid or aspartic acid), which supports their importance and additionally raises the question whether this site may play a general role among P-type ATPases. In Na+, K+-ATPase, K+ functions directly as a substrate for membrane binding sites, however, an additional regulatory...

Site-selective three-component reaction for dual-functionalization of peptides

DEFF Research Database (Denmark)

Munch, Henrik Kofoed; Rasmussen, Jakob Ewald; Popa, Gina

2013-01-01

A site-selective dual-functionalization of peptides is presented, involving readily available maleimides as well as N-hydroxylamines. The modification proceeds through a three component 1,3-dipolar cycloaddition, forming a stable product. This was exemplified by the one-pot attachment of two...

msCentipede: Modeling Heterogeneity across Genomic Sites and Replicates Improves Accuracy in the Inference of Transcription Factor Binding.

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Anil Raj

Full Text Available Understanding global gene regulation depends critically on accurate annotation of regulatory elements that are functional in a given cell type. CENTIPEDE, a powerful, probabilistic framework for identifying transcription factor binding sites from tissue-specific DNase I cleavage patterns and genomic sequence content, leverages the hypersensitivity of factor-bound chromatin and the information in the DNase I spatial cleavage profile characteristic of each DNA binding protein to accurately infer functional factor binding sites. However, the model for the spatial profile in this framework fails to account for the substantial variation in the DNase I cleavage profiles across different binding sites. Neither does it account for variation in the profiles at the same binding site across multiple replicate DNase I experiments, which are increasingly available. In this work, we introduce new methods, based on multi-scale models for inhomogeneous Poisson processes, to account for such variation in DNase I cleavage patterns both within and across binding sites. These models account for the spatial structure in the heterogeneity in DNase I cleavage patterns for each factor. Using DNase-seq measurements assayed in a lymphoblastoid cell line, we demonstrate the improved performance of this model for several transcription factors by comparing against the Chip-seq peaks for those factors. Finally, we explore the effects of DNase I sequence bias on inference of factor binding using a simple extension to our framework that allows for a more flexible background model. The proposed model can also be easily applied to paired-end ATAC-seq and DNase-seq data. msCentipede, a Python implementation of our algorithm, is available at http://rajanil.github.io/msCentipede.

msCentipede: Modeling Heterogeneity across Genomic Sites and Replicates Improves Accuracy in the Inference of Transcription Factor Binding.

Science.gov (United States)

Raj, Anil; Shim, Heejung; Gilad, Yoav; Pritchard, Jonathan K; Stephens, Matthew

2015-01-01

Understanding global gene regulation depends critically on accurate annotation of regulatory elements that are functional in a given cell type. CENTIPEDE, a powerful, probabilistic framework for identifying transcription factor binding sites from tissue-specific DNase I cleavage patterns and genomic sequence content, leverages the hypersensitivity of factor-bound chromatin and the information in the DNase I spatial cleavage profile characteristic of each DNA binding protein to accurately infer functional factor binding sites. However, the model for the spatial profile in this framework fails to account for the substantial variation in the DNase I cleavage profiles across different binding sites. Neither does it account for variation in the profiles at the same binding site across multiple replicate DNase I experiments, which are increasingly available. In this work, we introduce new methods, based on multi-scale models for inhomogeneous Poisson processes, to account for such variation in DNase I cleavage patterns both within and across binding sites. These models account for the spatial structure in the heterogeneity in DNase I cleavage patterns for each factor. Using DNase-seq measurements assayed in a lymphoblastoid cell line, we demonstrate the improved performance of this model for several transcription factors by comparing against the Chip-seq peaks for those factors. Finally, we explore the effects of DNase I sequence bias on inference of factor binding using a simple extension to our framework that allows for a more flexible background model. The proposed model can also be easily applied to paired-end ATAC-seq and DNase-seq data. msCentipede, a Python implementation of our algorithm, is available at http://rajanil.github.io/msCentipede.

Analysis of functional importance of binding sites in the Drosophila gap gene network model.

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Kozlov, Konstantin; Gursky, Vitaly V; Kulakovskiy, Ivan V; Dymova, Arina; Samsonova, Maria

2015-01-01

The statistical thermodynamics based approach provides a promising framework for construction of the genotype-phenotype map in many biological systems. Among important aspects of a good model connecting the DNA sequence information with that of a molecular phenotype (gene expression) is the selection of regulatory interactions and relevant transcription factor bindings sites. As the model may predict different levels of the functional importance of specific binding sites in different genomic and regulatory contexts, it is essential to formulate and study such models under different modeling assumptions. We elaborate a two-layer model for the Drosophila gap gene network and include in the model a combined set of transcription factor binding sites and concentration dependent regulatory interaction between gap genes hunchback and Kruppel. We show that the new variants of the model are more consistent in terms of gene expression predictions for various genetic constructs in comparison to previous work. We quantify the functional importance of binding sites by calculating their impact on gene expression in the model and calculate how these impacts correlate across all sites under different modeling assumptions. The assumption about the dual interaction between hb and Kr leads to the most consistent modeling results, but, on the other hand, may obscure existence of indirect interactions between binding sites in regulatory regions of distinct genes. The analysis confirms the previously formulated regulation concept of many weak binding sites working in concert. The model predicts a more or less uniform distribution of functionally important binding sites over the sets of experimentally characterized regulatory modules and other open chromatin domains.

BSSF: a fingerprint based ultrafast binding site similarity search and function analysis server

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Jiang Hualiang

2010-01-01

Full Text Available Abstract Background Genome sequencing and post-genomics projects such as structural genomics are extending the frontier of the study of sequence-structure-function relationship of genes and their products. Although many sequence/structure-based methods have been devised with the aim of deciphering this delicate relationship, there still remain large gaps in this fundamental problem, which continuously drives researchers to develop novel methods to extract relevant information from sequences and structures and to infer the functions of newly identified genes by genomics technology. Results Here we present an ultrafast method, named BSSF(Binding Site Similarity & Function, which enables researchers to conduct similarity searches in a comprehensive three-dimensional binding site database extracted from PDB structures. This method utilizes a fingerprint representation of the binding site and a validated statistical Z-score function scheme to judge the similarity between the query and database items, even if their similarities are only constrained in a sub-pocket. This fingerprint based similarity measurement was also validated on a known binding site dataset by comparing with geometric hashing, which is a standard 3D similarity method. The comparison clearly demonstrated the utility of this ultrafast method. After conducting the database searching, the hit list is further analyzed to provide basic statistical information about the occurrences of Gene Ontology terms and Enzyme Commission numbers, which may benefit researchers by helping them to design further experiments to study the query proteins. Conclusions This ultrafast web-based system will not only help researchers interested in drug design and structural genomics to identify similar binding sites, but also assist them by providing further analysis of hit list from database searching.

Site preference of Mg acceptors and improvement of p-type doping efficiency in nitride alloys.

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Park, Ji-Sang; Chang, K J

2013-06-19

We perform first-principles density functional calculations to investigate the effect of Al and In on the formation energy and acceptor level of Mg in group-III nitride alloys. Our calculations reveal a tendency for the Mg dopants to prefer to occupy the lattice sites surrounded with Al atoms, whereas hole carriers are generated in In- or Ga-rich sites. The separation of the Mg dopants and hole carriers is energetically more favourable than a random distribution of dopants, being attributed to the local bonding effect of weak In and strong Al potentials in alloys. As a consequence, the Mg acceptor level, which represents the activation energy of Mg, tends to decrease with increasing numbers of Al next-nearest neighbours, whereas it increases as the number of In next-nearest neighbours increases. Based on the results, we suggest that the incorporation of higher Al and lower In compositions will improve the p-type doping efficiency in quaternary alloys, in comparison with GaN or AlGaN ternary alloys with similar band gaps.

Does bariatric surgery improve adipose tissue function?

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Frikke-Schmidt, H.; O’Rourke, R. W.; Lumeng, C. N.; Sandoval, D. A.; Seeley, R. J.

2017-01-01

Summary Bariatric surgery is currently the most effective treatment for obesity. Not only do these types of surgeries produce significant weight loss but also they improve insulin sensitivity and whole body metabolic function. The aim of this review is to explore how altered physiology of adipose tissue may contribute to the potent metabolic effects of some of these procedures. This includes specific effects on various fat depots, the function of individual adipocytes and the interaction between adipose tissue and other key metabolic tissues. Besides a dramatic loss of fat mass, bariatric surgery shifts the distribution of fat from visceral to the subcutaneous compartment favoring metabolic improvement. The sensitivity towards lipolysis controlled by insulin and catecholamines is improved, adipokine secretion is altered and local adipose inflammation as well as systemic inflammatory markers decreases. Some of these changes have been shown to be weight loss independent, and novel hypothesis for these effects includes include changes in bile acid metabolism, gut microbiota and central regulation of metabolism. In conclusion bariatric surgery is capable of improving aspects of adipose tissue function and do so in some cases in ways that are not entirely explained by the potent effect of surgery. PMID:27272117

Improving the web site's effectiveness by considering each page's temporal information

NARCIS (Netherlands)

Li, ZG; Sun, MT; Dunham, MH; Xiao, YQ; Dong, G; Tang, C; Wang, W

2003-01-01

Improving the effectiveness of a web site is always one of its owner's top concerns. By focusing on analyzing web users' visiting behavior, web mining researchers have developed a variety of helpful methods, based upon association rules, clustering, prediction and so on. However, we have found

Enhanced Neuroplasticity by the Metabolic Enhancer Piracetam Associated with Improved Mitochondrial Dynamics and Altered Permeability Transition Pore Function.

Science.gov (United States)

Stockburger, Carola; Miano, Davide; Pallas, Thea; Friedland, Kristina; Müller, Walter E

2016-01-01

The mitochondrial cascade hypothesis of dementia assumes mitochondrial dysfunction leading to reduced energy supply, impaired neuroplasticity, and finally cell death as one major pathomechanism underlying the continuum from brain aging over mild cognitive impairment to initial and advanced late onset Alzheimer's disease. Accordingly, improving mitochondrial function has become an important strategy to treat the early stages of this continuum. The metabolic enhancer piracetam has been proposed as possible prototype for those compounds by increasing impaired mitochondrial function and related aspects like mechanisms of neuroplasticity. We here report that piracetam at therapeutically relevant concentrations improves neuritogenesis in the human cell line SH-SY5Y over conditions mirroring the whole spectrum of age-associated cognitive decline. These effects go parallel with improvement of impaired mitochondrial dynamics shifting back fission and fusion balance to the energetically more favorable fusion site. Impaired fission and fusion balance can also be induced by a reduction of the mitochondrial permeability transition pore (mPTP) function as atractyloside which indicates the mPTP has similar effects on mitochondrial dynamics. These changes are also reduced by piracetam. These findings suggest the mPTP as an important target for the beneficial effects of piracetam on mitochondrial function.

Virtual reality training improves balance function.

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Mao, Yurong; Chen, Peiming; Li, Le; Huang, Dongfeng

2014-09-01

Virtual reality is a new technology that simulates a three-dimensional virtual world on a computer and enables the generation of visual, audio, and haptic feedback for the full immersion of users. Users can interact with and observe objects in three-dimensional visual space without limitation. At present, virtual reality training has been widely used in rehabilitation therapy for balance dysfunction. This paper summarizes related articles and other articles suggesting that virtual reality training can improve balance dysfunction in patients after neurological diseases. When patients perform virtual reality training, the prefrontal, parietal cortical areas and other motor cortical networks are activated. These activations may be involved in the reconstruction of neurons in the cerebral cortex. Growing evidence from clinical studies reveals that virtual reality training improves the neurological function of patients with spinal cord injury, cerebral palsy and other neurological impairments. These findings suggest that virtual reality training can activate the cerebral cortex and improve the spatial orientation capacity of patients, thus facilitating the cortex to control balance and increase motion function.

Virtual reality training improves balance function

Science.gov (United States)

Mao, Yurong; Chen, Peiming; Li, Le; Huang, Dongfeng

2014-01-01

Virtual reality is a new technology that simulates a three-dimensional virtual world on a computer and enables the generation of visual, audio, and haptic feedback for the full immersion of users. Users can interact with and observe objects in three-dimensional visual space without limitation. At present, virtual reality training has been widely used in rehabilitation therapy for balance dysfunction. This paper summarizes related articles and other articles suggesting that virtual reality training can improve balance dysfunction in patients after neurological diseases. When patients perform virtual reality training, the prefrontal, parietal cortical areas and other motor cortical networks are activated. These activations may be involved in the reconstruction of neurons in the cerebral cortex. Growing evidence from clinical studies reveals that virtual reality training improves the neurological function of patients with spinal cord injury, cerebral palsy and other neurological impairments. These findings suggest that virtual reality training can activate the cerebral cortex and improve the spatial orientation capacity of patients, thus facilitating the cortex to control balance and increase motion function. PMID:25368651

Improvement of Endovascular Stroke Treatment: A 24-Hour Neuroradiological On-Site Service Is Not Enough

Directory of Open Access Journals (Sweden)

Omid Nikoubashman

2018-01-01

Full Text Available Background and Purpose. With the advent of endovascular stroke treatment (EST with mechanical thrombectomy, stroke treatment has also become more challenging. Purpose of this study was to investigate whether a fulltime neuroradiological on-site service and workflow optimization with a structured documentation of the interdisciplinary stroke workflow resulted in improved procedural times. Material and Methods. Procedural times of 322 consecutive patients, who received EST (1 before (n=96 and (2 after (n=126 establishing a 24-hour neuroradiological on-site service as well as (3 after implementation of a structured interdisciplinary workflow documentation (“Stroke Check” (n=100, were analysed. Results. A fulltime neuroradiological on-site service resulted in a nonsignificant improvement of procedural times during out-of-hours admissions (p≥0.204. Working hours and out-of-hours procedural times improved significantly, if additional workflow optimization was realized (p≤0.026. Conclusions. A 24-hour interventional on-site service is a major prerequisite to adequately provide modern reperfusion therapies in patients with acute ischemic stroke. However, simple measures like standardized and focused documentation that affect the entire interdisciplinary pre- and intrahospital stroke rescue chain seem to be important.

Exploring functionally related enzymes using radially distributed properties of active sites around the reacting points of bound ligands

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Ueno Keisuke

2012-04-01

Full Text Available Abstract Background Structural genomics approaches, particularly those solving the 3D structures of many proteins with unknown functions, have increased the desire for structure-based function predictions. However, prediction of enzyme function is difficult because one member of a superfamily may catalyze a different reaction than other members, whereas members of different superfamilies can catalyze the same reaction. In addition, conformational changes, mutations or the absence of a particular catalytic residue can prevent inference of the mechanism by which catalytic residues stabilize and promote the elementary reaction. A major hurdle for alignment-based methods for prediction of function is the absence (despite its importance of a measure of similarity of the physicochemical properties of catalytic sites. To solve this problem, the physicochemical features radially distributed around catalytic sites should be considered in addition to structural and sequence similarities. Results We showed that radial distribution functions (RDFs, which are associated with the local structural and physicochemical properties of catalytic active sites, are capable of clustering oxidoreductases and transferases by function. The catalytic sites of these enzymes were also characterized using the RDFs. The RDFs provided a measure of the similarity among the catalytic sites, detecting conformational changes caused by mutation of catalytic residues. Furthermore, the RDFs reinforced the classification of enzyme functions based on conventional sequence and structural alignments. Conclusions Our results demonstrate that the application of RDFs provides advantages in the functional classification of enzymes by providing information about catalytic sites.

In silico determination of intracellular glycosylation and phosphorylation sites in human selectins: Implications for biological function

DEFF Research Database (Denmark)

Ahmad, I.; Hoessli, D.C.; Gupta, Ramneek

2007-01-01

Post-translational modifications provide the proteins with the possibility to perform functions in addition to those determined by their primary sequence. However, analysis of multifunctional protein structures in the environment of cells and body fluids is made especially difficult by the presence...... both modifications are likely to occur can also be predicted (YinYang sites), to suggest further functional versatility. Structural modifications of hydroxyl groups of P-, E-, and L-selectins have been predicted and possible functions resulting from such modifications are proposed. Functional changes...... of the three selectins are based on the assumption that transitory and reversible protein modifications by phosphate and O-GlcNAc cause specific conformational changes and generate binding sites for other proteins. The computer-assisted prediction of glycosylation and phosphorylation sites in selectins should...

Diagnosing and improving functioning in interdisciplinary health care teams.

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Blackmore, Gail; Persaud, D David

2012-01-01

Interdisciplinary teams play a key role in the delivery of health care. Team functioning can positively or negatively impact the effective and efficient delivery of health care services as well as the personal well-being of group members. Additionally, teams must be able and willing to work together to achieve team goals within a climate that reflects commitment to team goals, accountability, respect, and trust. Not surprisingly, dysfunctional team functioning can limit the success of interdisciplinary health care teams. The first step in improving dysfunctional team function is to conduct an analysis based on criteria necessary for team success, and this article provides meaningful criteria for doing such an analysis. These are the following: a common team goal, the ability and willingness to work together to achieve team goals, decision making, communication, and team member relationships. High-functioning interdisciplinary teams must exhibit features of good team function in all key domains. If a team functions well in some domains and needs to improve in others, targeted strategies are described that can be used to improve team functioning.

Making Benefit Transfers Work: Deriving and Testing Principles for Value Transfers for Similar and Dissimilar Sites Using a Case Study of the Non-Market Benefits of Water Quality Improvements Across Europe

DEFF Research Database (Denmark)

Bateman, Ian; Brouwer, Roy; Ferreri, Silvia

2011-01-01

We implement a controlled, multi-site experiment to develop and test guidance principles for benefits transfers. These argue that when transferring across relatively similar sites, simple mean value transfers are to be preferred but that when sites are relatively dissimilar then value function...... transfers will yield lower errors. The paper also provides guidance on the appropriate specification of transferable value functions arguing that these should be developed from theoretical rather than ad-hoc statistical approaches. These principles are tested via a common format valuation study of water...... quality improvements across five countries. While this provides an idealised tested, results support the above principles and suggest directions for future transfer studies....

Improving Geoscience Outreach Through Multimedia Enhanced Web Sites - An Example From Connecticut

Science.gov (United States)

Hyatt, J. A.; Coron, C. R.; Schroeder, T. J.; Fleming, T.; Drzewiecki, P. A.

2005-12-01

Although large governmental web sites (e.g. USGS, NASA etc.) are important resources, particularly in relation to phenomena with global to regional significance (e.g. recent Tsunami and Hurricane disasters), smaller academic web portals continue to make substantive contributions to web-based learning in the geosciences. The strength of "home-grown" web sites is that they easily can be tailored to specific classes, they often focus on local geologic content, and they potentially integrate classroom, laboratory, and field-based learning in ways that improve introductory classes. Furthermore, innovative multimedia techniques including virtual reality, image manipulations, and interactive streaming video can improve visualization and be particularly helpful for first-time geology students. This poster reports on one such web site, Learning Tools in Earth Science (LTES, http://www.easternct .edu/personal/faculty/hyattj/LTES-v2/), a site developed by geoscience faculty at two state institutions. In contrast to some large web sites with media development teams, LTES geoscientists, with strong support from media and IT service departments, are responsible for geologic content and verification, media development and editing, and web development and authoring. As such, we have considerable control over both content and design of this site. At present the main content modules for LTES include "mineral" and "virtual field trip" links. The mineral module includes an interactive mineral gallery, and a virtual mineral box of 24 unidentified samples that are identical to those used in some of our classes. Students navigate an intuitive web portal to manipulate images and view streaming video segments that explain and undertake standard mineral identification tests. New elements highlighted in our poster include links to a virtual petrographic microscope, in which users can manipulate images to simulate stage rotation in both plane- and cross-polarized light. Virtual field trips

Siting and sizing of distributed generators based on improved simulated annealing particle swarm optimization.

Science.gov (United States)

Su, Hongsheng

2017-12-18

Distributed power grids generally contain multiple diverse types of distributed generators (DGs). Traditional particle swarm optimization (PSO) and simulated annealing PSO (SA-PSO) algorithms have some deficiencies in site selection and capacity determination of DGs, such as slow convergence speed and easily falling into local trap. In this paper, an improved SA-PSO (ISA-PSO) algorithm is proposed by introducing crossover and mutation operators of genetic algorithm (GA) into SA-PSO, so that the capabilities of the algorithm are well embodied in global searching and local exploration. In addition, diverse types of DGs are made equivalent to four types of nodes in flow calculation by the backward or forward sweep method, and reactive power sharing principles and allocation theory are applied to determine initial reactive power value and execute subsequent correction, thus providing the algorithm a better start to speed up the convergence. Finally, a mathematical model of the minimum economic cost is established for the siting and sizing of DGs under the location and capacity uncertainties of each single DG. Its objective function considers investment and operation cost of DGs, grid loss cost, annual purchase electricity cost, and environmental pollution cost, and the constraints include power flow, bus voltage, conductor current, and DG capacity. Through applications in an IEEE33-node distributed system, it is found that the proposed method can achieve desirable economic efficiency and safer voltage level relative to traditional PSO and SA-PSO algorithms, and is a more effective planning method for the siting and sizing of DGs in distributed power grids.

Parallel sites implicate functional convergence of the hearing gene prestin among echolocating mammals.

Science.gov (United States)

Liu, Zhen; Qi, Fei-Yan; Zhou, Xin; Ren, Hai-Qing; Shi, Peng

2014-09-01

Echolocation is a sensory system whereby certain mammals navigate and forage using sound waves, usually in environments where visibility is limited. Curiously, echolocation has evolved independently in bats and whales, which occupy entirely different environments. Based on this phenotypic convergence, recent studies identified several echolocation-related genes with parallel sites at the protein sequence level among different echolocating mammals, and among these, prestin seems the most promising. Although previous studies analyzed the evolutionary mechanism of prestin, the functional roles of the parallel sites in the evolution of mammalian echolocation are not clear. By functional assays, we show that a key parameter of prestin function, 1/α, is increased in all echolocating mammals and that the N7T parallel substitution accounted for this functional convergence. Moreover, another parameter, V1/2, was shifted toward the depolarization direction in a toothed whale, the bottlenose dolphin (Tursiops truncatus) and a constant-frequency (CF) bat, the Stoliczka's trident bat (Aselliscus stoliczkanus). The parallel site of I384T between toothed whales and CF bats was responsible for this functional convergence. Furthermore, the two parameters (1/α and V1/2) were correlated with mammalian high-frequency hearing, suggesting that the convergent changes of the prestin function in echolocating mammals may play important roles in mammalian echolocation. To our knowledge, these findings present the functional patterns of echolocation-related genes in echolocating mammals for the first time and rigorously demonstrate adaptive parallel evolution at the protein sequence level, paving the way to insights into the molecular mechanism underlying mammalian echolocation. © The Author 2014. 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.

Improvement of the Russian system of medical care at the site of space crew landing

Science.gov (United States)

Rukavishnikov, Ilya; Bogomolov, Valery; Polyakov, Alexey

The crew members are delivered to ISS and return back to the Earth on the space craft "Soyuz TMA" at present time. The technical means providing the safe landing of space crews are reliable enough. In spite of that the complex of negative factors (long lasting alternating and shock overloads, effects of landing apparatus rotation on vestibular system) affects the crew during landing and can reach the extreme values under the certain conditions. According to this fact there is a possibility of appearance of bodily damages of different weight besides the traditional functional disturbances. The group of search and rescue on the landing site includes the medical specialists appropriately equipped to stop the symptoms of medical contingency (strong vestibule-vegetative reactions, traumas of different weight, etc.) Medical evacuation complex which provides the acceptable conditions for the cosmonauts including the conditions for medical care is delivered to the landing site as well. The long term experience of search and rescue assurance at the landing site have shown that the specialists successfully cope with this task. In some cases it was required to give the medical help which allowed to improve the general condition and physical capacity of crewmembers and provide their evacuation to the places of postflight rehabilitation. At the same time the solution of some of the problems from our point of view could increase the efficacy of medical care for the landing crew. The organization of the training on emergency under the field conditions for medical specialists on the regular basis (not less that once a year) is extremely important. The equipment of medical specialists requires the regular improvement and modernization due to the fast changing medical technologies and standards. Wearable medical sets must provide the first aid performing in accordance to the modern medical requirements. It is also necessary to include in the list of equipment the textbook of

IgG-Fc-mediated effector functions: molecular definition of interaction sites for effector ligands and the role of glycosylation.

Science.gov (United States)

Jefferis, R; Lund, J; Pound, J D

1998-06-01

The Fc region of human IgG expresses interaction sites for many effector ligands. In this review the topographical distributions of ten of these sites are discussed in relation to functional requirement. It is apparent that interaction sites localised to the inter-CH2-CH3 domain region of the Fc allow for functional divalency, whereas sites localised to the hinge proximal region of the CH2 domain are functionally monovalent, with expression of the latter sites being particularly dependent on glycosylation. All x-ray crystal structures for Fc and Fc-ligand complexes report that the protein structure of the hinge proximal region of the CH2 domain is "disordered", suggesting "internal mobility". We propose a model in which such "internal mobility" results in the generation of a dynamic equilibrium between multiple conformers, certain of which express interaction sites specific to individual ligands. The emerging understanding of the influence of oligosaccharide/protein interactions on protein conformation and biological function of IgG antibodies suggests a potential to generate novel glycoforms of antibody molecules having unique profiles of effector functions.

Enhanced Neuroplasticity by the Metabolic Enhancer Piracetam Associated with Improved Mitochondrial Dynamics and Altered Permeability Transition Pore Function

Directory of Open Access Journals (Sweden)

Carola Stockburger

2016-01-01

Full Text Available The mitochondrial cascade hypothesis of dementia assumes mitochondrial dysfunction leading to reduced energy supply, impaired neuroplasticity, and finally cell death as one major pathomechanism underlying the continuum from brain aging over mild cognitive impairment to initial and advanced late onset Alzheimer’s disease. Accordingly, improving mitochondrial function has become an important strategy to treat the early stages of this continuum. The metabolic enhancer piracetam has been proposed as possible prototype for those compounds by increasing impaired mitochondrial function and related aspects like mechanisms of neuroplasticity. We here report that piracetam at therapeutically relevant concentrations improves neuritogenesis in the human cell line SH-SY5Y over conditions mirroring the whole spectrum of age-associated cognitive decline. These effects go parallel with improvement of impaired mitochondrial dynamics shifting back fission and fusion balance to the energetically more favorable fusion site. Impaired fission and fusion balance can also be induced by a reduction of the mitochondrial permeability transition pore (mPTP function as atractyloside which indicates the mPTP has similar effects on mitochondrial dynamics. These changes are also reduced by piracetam. These findings suggest the mPTP as an important target for the beneficial effects of piracetam on mitochondrial function.

A new functional site W115 in CdtA is critical for Aggregatibacter actinomycetemcomitans cytolethal distending toxin.

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Lu Li

Full Text Available Aggregatibacter actinomycetemcomitans, a specific pathogen of localized aggressive periodontitis, produces a cytolethal distending toxin (CDT that arrests eukaryotic cells irreversibly in G0/G1 or G2/M phase of the cell cycle. Although structural studies show that the aromatic patch region of CdtA plays an important role in its biological activity, the functional sites of CdtA have not been firmly established. In this study, site-specific mutagenesis strategy was employed for cdtA point mutations construction so as to examine the contributions of individual amino acids to receptor binding and the biological activity of holotoxin. The binding ability was reduced in CdtA(Y181ABC holotoxin and the biological function of CDT was not weaken in CdtA(Y105ABC, CdtA(Y125ABC, CdtA(F109ABC and CdtA(S106NBC holotoxin suggesting that these sites were not critical to CDT. But the binding activity and cell cycle arrest ability of holotoxin complexes were inhibited in CdtA(W115GBC. And this site did not affect the holotoxin assembly by size exclusion chromatography. Therefore, W115 might be a critical site of CdtA binding ability. These findings suggest that the functional sites of CdtA are not only in the aromatic patch region. W115, the new functional site is critical for receptor binding and cell cycle arrest, which provides potential targets for pharmacological disruption of CDT activity.

Improved quasi-static nodal green's function method

International Nuclear Information System (INIS)

Li Junli; Jing Xingqing; Hu Dapu

1997-01-01

Improved Quasi-Static Green's Function Method (IQS/NGFM) is presented, as an new kinetic method. To solve the three-dimensional transient problem, improved Quasi-Static Method is adopted to deal with the temporal problem, which will increase the time step as long as possible so as to decrease the number of times of space calculation. The time step of IQS/NGFM can be increased to 5∼10 times longer than that of Full Implicit Differential Method. In spatial calculation, the NGFM is used to get the distribution of shape function, and it's spatial mesh can be nearly 20 times larger than that of Definite Differential Method. So the IQS/NGFM is considered as an efficient kinetic method

Stone tool function at the paleolithic sites of Starosele and Buran Kaya III, Crimea: behavioral implications.

Science.gov (United States)

Hardy, B L; Kay, M; Marks, A E; Monigal, K

2001-09-11

Stone tools are often the most abundant type of cultural remains at Paleolithic sites, yet their function is often poorly understood. Investigations of stone tool function, including microscopic use-wear and residue analyses, were performed on a sample of artifacts from the Paleolithic sites of Starosele (40,000-80,000 years BP) and Buran Kaya III (32,000-37,000 years BP). The Middle Paleolithic levels at Starosele exhibit a typical variant of the local Micoquian Industry. The artifacts from Buran Kaya III most closely resemble an Early Streletskayan Industry associated with the early Upper Paleolithic. The results of the functional analyses suggest that hominids at both sites were exploiting woody and starchy plant material as well as birds and mammals. Both sites show evidence of hafting of a wide variety of tools and the possible use of projectile or thrusting spears. These analyses were performed by using two different techniques conducted by independent researchers. Combined residue and use-wear analyses suggest that both the Upper Paleolithic and Middle Paleolithic hominids at these sites were broad-based foragers capable of exploiting a wide range of resources.

Improving the safety of remote site emergency airway management.

Science.gov (United States)

Wijesuriya, Julian; Brand, Jonathan

2014-01-01

Airway management, particularly in non-theatre settings, is an area of anaesthesia and critical care associated with significant risk of morbidity & mortality, as highlighted during the 4th National Audit Project of the Royal College of Anaesthetists (NAP4). A survey of junior anaesthetists at our hospital highlighted a lack of confidence and perceived lack of safety in emergency airway management, especially in non-theatre settings. We developed and implemented a multifaceted airway package designed to improve the safety of remote site airway management. A Rapid Sequence Induction (RSI) checklist was developed; this was combined with new advanced airway equipment and drugs bags. Additionally, new carbon dioxide detector filters were procured in order to comply with NAP4 monitoring recommendations. The RSI checklists were placed in key locations throughout the hospital and the drugs and advanced airway equipment bags were centralised in the Intensive Care Unit (ICU). It was agreed with the senior nursing staff that an appropriately trained ICU nurse would attend all emergency situations with new airway resources upon request. Departmental guidelines were updated to include details of the new resources and the on-call anaesthetist's responsibilities regarding checks and maintenance. Following our intervention trainees reported higher confidence levels regarding remote site emergency airway management. Nine trusts within the Northern Region were surveyed and we found large variations in the provision of remote site airway management resources. Complications in remote site airway management due lack of available appropriate drugs, equipment or trained staff are potentially life threatening and completely avoidable. Utilising the intervention package an anaesthetist would be able to safely plan and prepare for airway management in any setting. They would subsequently have the drugs, equipment, and trained assistance required to manage any difficulties or complications

Improvement in cognitive function after surgery for low-grade glioma.

Science.gov (United States)

Barzilai, Ori; Ben Moshe, Shlomit; Sitt, Razi; Sela, Gal; Shofty, Ben; Ram, Zvi

2018-03-23

OBJECTIVE Cognition is a key component in health-related quality of life (HRQoL) and is currently incorporated as a major parameter of outcome assessment in patients treated for brain tumors. The effect of surgery on cognition and HRQoL remains debatable. The authors investigated the impact of resection of low-grade gliomas (LGGs) on cognition and the correlation with various histopathological markers. METHODS A retrospective analysis of patients with LGG who underwent craniotomy for tumor resection at a single institution between 2010 and 2014 was conducted. Of 192 who underwent resective surgery for LGG during this period, 49 had complete pre- and postoperative neurocognitive evaluations and were included in the analysis. These patients completed a full battery of neurocognitive tests (memory, language, attention and working memory, visuomotor organization, and executive functions) pre- and postoperatively. Tumor and surgical characteristics were analyzed, including volumetric measurements and histopathological markers (IDH, p53, GFAP). RESULTS Postoperatively, significant improvement was found in memory and executive functions. A subgroup analysis of patients with dominant-side tumors, most of whom underwent intraoperative awake mapping, revealed significant improvement in the same domains. Patients whose tumors were on the nondominant side displayed significant improvement only in memory functions. Positive staining for p53 testing was associated with improved language function and greater extent of resection in dominant-side tumors. GFAP positivity was associated with improved memory in patients whose tumors were on the nondominant side. No correlation was found between cognitive outcome and preoperative tumor volume, residual volume, extent of resection, or IDH1 status. CONCLUSIONS Resection of LGG significantly improves memory and executive function and thus is likely to improve functional outcome in addition to providing oncological benefit. GFAP and pP53

Improved Density Functional Tight Binding Potentials for Metalloid Aluminum Clusters

Science.gov (United States)

2016-06-01

unlimited IMPROVED DENSITY-FUNCTIONAL TIGHT BINDING POTENTIALS FOR METALLOID ALUMINUM CLUSTERS by Joon H. Kim June 2016 Thesis Advisor...DATES COVERED Master’s thesis 4. TITLE AND SUBTITLE IMPROVED DENSITY-FUNCTIONAL TIGHT BINDING POTENTIALS FOR METALLOID ALUMINUM CLUSTERS 5. FUNDING...repulsive potentials for use in density-functional tight binding (DFTB) simulations of low-valence aluminum metalloid clusters . These systems are under

Predicting Multicomponent Adsorption Isotherms in Open-Metal Site Materials Using Force Field Calculations Based on Energy Decomposed Density Functional Theory.

Science.gov (United States)

Heinen, Jurn; Burtch, Nicholas C; Walton, Krista S; Fonseca Guerra, Célia; Dubbeldam, David

2016-12-12

For the design of adsorptive-separation units, knowledge is required of the multicomponent adsorption behavior. Ideal adsorbed solution theory (IAST) breaks down for olefin adsorption in open-metal site (OMS) materials due to non-ideal donor-acceptor interactions. Using a density-function-theory-based energy decomposition scheme, we develop a physically justifiable classical force field that incorporates the missing orbital interactions using an appropriate functional form. Our first-principles derived force field shows greatly improved quantitative agreement with the inflection points, initial uptake, saturation capacity, and enthalpies of adsorption obtained from our in-house adsorption experiments. While IAST fails to make accurate predictions, our improved force field model is able to correctly predict the multicomponent behavior. Our approach is also transferable to other OMS structures, allowing the accurate study of their separation performances for olefins/paraffins and further mixtures involving complex donor-acceptor interactions. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Using Improved Entropy-Cloud Model to Select High-Speed Railway Express Freight Train Service Sites

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Wencheng Huang

2017-01-01

Full Text Available High-speed railway (HSR express freight train service sites selection is critical to the development of China’s Third Party Logistics market. In this paper, we formulate an improved entropy-cloud model based approach to solve the HSR express sites selection problem for the first time. The basic data of the indicators, for example, existing railway network conditions, traffic environment, express freight market demand, and policy, will be used as the inputs. We apply improved entropy method to obtain each subindicator’s weight. The cloud model will be used to select and classify each station under evaluation.

Executive function needs to be targeted to improve social functioning with Cognitive Remediation Therapy (CRT) in schizophrenia.

Science.gov (United States)

Penadés, Rafael; Catalán, Rosa; Puig, Olga; Masana, Guillem; Pujol, Núria; Navarro, Víctor; Guarch, Joana; Gastó, Cristóbal

2010-05-15

While the role of impaired cognition in accounting for functional outcome in schizophrenia is generally established, the relationship between cognitive and functional change in the context of treatments is far from clear. The current paper tries to identify which cognitive changes lead to improvements in daily functioning among persons with chronic schizophrenia who had current negative symptoms and evidenced neuropsychological impairments. In a previous work, Cognitive Remediation Therapy (CRT) was compared with a control therapy, involving similar length of therapist contact but different targets. At the end of treatment, CRT conferred a benefit to people with schizophrenia in cognition and functioning [Schizophrenia Research, 87 (2006) 323-331]. Subsequently, analyses of covariance (ANCOVA) were conducted with baseline and cognitive change scores as covariates to test whether cognitive change predicted change in functioning. Additionally, statistical tests to establish the mediation path with significant variables were performed. Although verbal memory, but not executive functioning, was associated with functioning at baseline, it was the improvement in executive functioning that predicted improved daily functioning. Verbal memory played a mediator role in the change process. Consequently, in order to improve daily functioning with CRT, executive function still needs to be targeted in despite of multiple cognitive impairments being present. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Improved wave functions for large-N expansions

International Nuclear Information System (INIS)

Imbo, T.; Sukhatme, U.

1985-01-01

Existing large-N expansions of radial wave functions phi/sub n/,l(r) are only accurate near the minimum of the effective potential. Within the framework of the shifted 1/N expansion, we use known analytic results to motivate a simple modification so that the improved wave functions are accurate over a wide range of r and any choice of quantum numbers n and l. It is shown that these wave functions yield simple and accurate analytic expressions for certain quantities of interest in quarkonium physics

An integrated CRISPR Bombyx mori genome editing system with improved efficiency and expanded target sites.

Science.gov (United States)

Ma, Sanyuan; Liu, Yue; Liu, Yuanyuan; Chang, Jiasong; Zhang, Tong; Wang, Xiaogang; Shi, Run; Lu, Wei; Xia, Xiaojuan; Zhao, Ping; Xia, Qingyou

2017-04-01

Genome editing enabled unprecedented new opportunities for targeted genomic engineering of a wide variety of organisms ranging from microbes, plants, animals and even human embryos. The serial establishing and rapid applications of genome editing tools significantly accelerated Bombyx mori (B. mori) research during the past years. However, the only CRISPR system in B. mori was the commonly used SpCas9, which only recognize target sites containing NGG PAM sequence. In the present study, we first improve the efficiency of our previous established SpCas9 system by 3.5 folds. The improved high efficiency was also observed at several loci in both BmNs cells and B. mori embryos. Then to expand the target sites, we showed that two newly discovered CRISPR system, SaCas9 and AsCpf1, could also induce highly efficient site-specific genome editing in BmNs cells, and constructed an integrated CRISPR system. Genome-wide analysis of targetable sites was further conducted and showed that the integrated system cover 69,144,399 sites in B. mori genome, and one site could be found in every 6.5 bp. The efficiency and resolution of this CRISPR platform will probably accelerate both fundamental researches and applicable studies in B. mori, and perhaps other insects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Improved adsorption energetics within density-functional theory using revised Perdew-Burke-Ernzerhof functionals

DEFF Research Database (Denmark)

Hammer, Bjørk; Hansen, Lars Bruno; Nørskov, Jens Kehlet

1999-01-01

A simple formulation of a generalized gradient approximation for the exchange and correlation energy of electrons has been proposed by Perdew, Burke, and Ernzerhof (PBE) [Phys. Rev. Lett. 77, 3865 (1996)]. Subsequently Zhang and Yang [Phys. Rev. Lett. 80, 890 (1998)] have shown that a slight...... revision of the PBE functional systematically improves the atomization energies for a large database of small molecules. In the present work, we show that the Zhang and Yang functional (revPBE) also improves the chemisorption energetics of atoms and molecules on transition-metal surfaces. Our test systems...

Functional improvement of dystrophic muscle by repression of utrophin: let-7c interaction.

Directory of Open Access Journals (Sweden)

Manoj K Mishra

Full Text Available Duchenne muscular dystrophy (DMD is a fatal genetic disease caused by an absence of the 427kD muscle-specific dystrophin isoform. Utrophin is the autosomal homolog of dystrophin and when overexpressed, can compensate for the absence of dystrophin and rescue the dystrophic phenotype of the mdx mouse model of DMD. Utrophin is subject to miRNA mediated repression by several miRNAs including let-7c. Inhibition of utrophin: let-7c interaction is predicted to 'repress the repression' and increase utrophin expression. We developed and tested the ability of an oligonucleotide, composed of 2'-O-methyl modified bases on a phosphorothioate backbone, to anneal to the utrophin 3'UTR and prevent let-7c miRNA binding, thereby upregulating utrophin expression and improving the dystrophic phenotype in vivo. Suppression of utrophin: let-7c interaction using bi-weekly intraperitoneal injections of let7 site blocking oligonucleotides (SBOs for 1 month in the mdx mouse model for DMD, led to increased utrophin expression along with improved muscle histology, decreased fibrosis and increased specific force. The functional improvement of dystrophic muscle achieved using let7-SBOs suggests a novel utrophin upregulation-based therapeutic strategy for DMD.

Probing dopamine transporter structure and function by Zn2+-site engineering

DEFF Research Database (Denmark)

Loland, Claus Juul; Norgaard-Nielsen, Kristine; Gether, Ulrik

2003-01-01

, it will be described how we have used Zn2+-binding sites as a tool to probe the structure and function of Na+/Cl--coupled biogenic amine transporters with specific focus on the human DAT (hDAT). The work has not only led to the definition of the first structural constrains in the tertiary structure of this class...

Investigation of the metal binding site in methionine aminopeptidase by density functional theory

DEFF Research Database (Denmark)

Jørgensen, Anne Techau; Norrby, Per-Ola; Liljefors, Tommy

2002-01-01

All methionine aminopeptidases exhibit the same conserved metal binding site. The structure of this site with either Co2+ ions or Zn2+ ions was investigated using density functional theory. The calculations showed that the structure of the site was not influenced by the identity of the metal ions....... This was the case for both of the systems studied; one based on the X-ray structure of the human methionine aminopeptidase type 2 (hMetAP-2) and the other based on the X-ray structure of the E. coli methionine aminopeptidase type 1 (eMetAP-1). Another important structural issue is the identity of the bridging...

Personalized neuromusculoskeletal modeling to improve treatment of mobility impairments: a perspective from European research sites

Directory of Open Access Journals (Sweden)

Fregly Benjamin J

2012-03-01

Full Text Available Abstract Mobility impairments due to injury or disease have a significant impact on quality of life. Consequently, development of effective treatments to restore or replace lost function is an important societal challenge. In current clinical practice, a treatment plan is often selected from a standard menu of options rather than customized to the unique characteristics of the patient. Furthermore, the treatment selection process is normally based on subjective clinical experience rather than objective prediction of post-treatment function. The net result is treatment methods that are less effective than desired at restoring lost function. This paper discusses the possible use of personalized neuromusculoskeletal computer models to improve customization, objectivity, and ultimately effectiveness of treatments for mobility impairments. The discussion is based on information gathered from academic and industrial research sites throughout Europe, and both clinical and technical aspects of personalized neuromusculoskeletal modeling are explored. On the clinical front, we discuss the purpose and process of personalized neuromusculoskeletal modeling, the application of personalized models to clinical problems, and gaps in clinical application. On the technical front, we discuss current capabilities of personalized neuromusculoskeletal models along with technical gaps that limit future clinical application. We conclude by summarizing recommendations for future research efforts that would allow personalized neuromusculoskeletal models to make the greatest impact possible on treatment design for mobility impairments.

An integrative computational framework based on a two-step random forest algorithm improves prediction of zinc-binding sites in proteins.

Directory of Open Access Journals (Sweden)

Cheng Zheng

Full Text Available Zinc-binding proteins are the most abundant metalloproteins in the Protein Data Bank where the zinc ions usually have catalytic, regulatory or structural roles critical for the function of the protein. Accurate prediction of zinc-binding sites is not only useful for the inference of protein function but also important for the prediction of 3D structure. Here, we present a new integrative framework that combines multiple sequence and structural properties and graph-theoretic network features, followed by an efficient feature selection to improve prediction of zinc-binding sites. We investigate what information can be retrieved from the sequence, structure and network levels that is relevant to zinc-binding site prediction. We perform a two-step feature selection using random forest to remove redundant features and quantify the relative importance of the retrieved features. Benchmarking on a high-quality structural dataset containing 1,103 protein chains and 484 zinc-binding residues, our method achieved >80% recall at a precision of 75% for the zinc-binding residues Cys, His, Glu and Asp on 5-fold cross-validation tests, which is a 10%-28% higher recall at the 75% equal precision compared to SitePredict and zincfinder at residue level using the same dataset. The independent test also indicates that our method has achieved recall of 0.790 and 0.759 at residue and protein levels, respectively, which is a performance better than the other two methods. Moreover, AUC (the Area Under the Curve and AURPC (the Area Under the Recall-Precision Curve by our method are also respectively better than those of the other two methods. Our method can not only be applied to large-scale identification of zinc-binding sites when structural information of the target is available, but also give valuable insights into important features arising from different levels that collectively characterize the zinc-binding sites. The scripts and datasets are available at http://protein.cau.edu.cn/zincidentifier/.

Improving executive function using transcranial infrared laser stimulation.

Science.gov (United States)

Blanco, Nathaniel J; Maddox, W Todd; Gonzalez-Lima, Francisco

2017-03-01

Transcranial infrared laser stimulation is a new non-invasive form of low-level light therapy that may have a wide range of neuropsychological applications. It entails using low-power and high-energy-density infrared light from lasers to increase metabolic energy. Preclinical work showed that this intervention can increase cortical metabolic energy, thereby improving frontal cortex-based memory function in rats. Barrett and Gonzalez-Lima (2013, Neuroscience, 230, 13) discovered that transcranial laser stimulation can enhance sustained attention and short-term memory in humans. We extend this line of work to executive function. Specifically, we ask whether transcranial laser stimulation enhances performance in the Wisconsin Card Sorting Task that is considered the gold standard of executive function and is compromised in normal ageing and a number of neuropsychological disorders. We used a laser of a specific wavelength (1,064 nm) that photostimulates cytochrome oxidase - the enzyme catalysing oxygen consumption for metabolic energy production. Increased cytochrome oxidase activity is considered the primary mechanism of action of this intervention. Participants who received laser treatment made fewer errors and showed improved set-shifting ability relative to placebo controls. These results suggest that transcranial laser stimulation improves executive function and may have exciting potential for treating or preventing deficits resulting from neuropsychological disorders or normal ageing. © 2015 The British Psychological Society.

N-Glycosylation Improves the Pepsin Resistance of Histidine Acid Phosphatase Phytases by Enhancing Their Stability at Acidic pHs and Reducing Pepsin's Accessibility to Its Cleavage Sites

Science.gov (United States)

Niu, Canfang; Luo, Huiying; Shi, Pengjun; Huang, Huoqing; Wang, Yaru; Yang, Peilong

2015-01-01

N-Glycosylation can modulate enzyme structure and function. In this study, we identified two pepsin-resistant histidine acid phosphatase (HAP) phytases from Yersinia kristensenii (YkAPPA) and Yersinia rohdei (YrAPPA), each having an N-glycosylation motif, and one pepsin-sensitive HAP phytase from Yersinia enterocolitica (YeAPPA) that lacked an N-glycosylation site. Site-directed mutagenesis was employed to construct mutants by altering the N-glycosylation status of each enzyme, and the mutant and wild-type enzymes were expressed in Pichia pastoris for biochemical characterization. Compared with those of the N-glycosylation site deletion mutants and N-deglycosylated enzymes, all N-glycosylated counterparts exhibited enhanced pepsin resistance. Introduction of the N-glycosylation site into YeAPPA as YkAPPA and YrAPPA conferred pepsin resistance, shifted the pH optimum (0.5 and 1.5 pH units downward, respectively) and improved stability at acidic pH (83.2 and 98.8% residual activities at pH 2.0 for 1 h). Replacing the pepsin cleavage sites L197 and L396 in the immediate vicinity of the N-glycosylation motifs of YkAPPA and YrAPPA with V promoted their resistance to pepsin digestion when produced in Escherichia coli but had no effect on the pepsin resistance of N-glycosylated enzymes produced in P. pastoris. Thus, N-glycosylation may improve pepsin resistance by enhancing the stability at acidic pH and reducing pepsin's accessibility to peptic cleavage sites. This study provides a strategy, namely, the manipulation of N-glycosylation, for improvement of phytase properties for use in animal feed. PMID:26637601

Improving surgical site infection prevention practices through a multifaceted educational intervention.

LENUS (Irish Health Repository)

Owens, P

2015-03-01

As part of the National Clinical Programme on healthcare-associated infection prevention, a Royal College of Surgeons in Ireland (RCSI) and Royal College of Physicians of Ireland (RCPI) working group developed a quality improvement tool for prevention of surgical site infection (SS). We aimed to validate the effectiveness of an educational campaign, which utilises this quality improvement tool to prevent SSI in a tertiary hospital. Prior to the SSI educational campaign, surgical patients were prospectively audited and details of antibiotic administration recorded. Prophylactic antibiotic administration recommendations were delivered via poster and educational presentations. Post-intervention, the audit was repeated. 50 patients were audited pre-intervention, 45 post-intervention. Post-intervention, prophylaxis within 60 minutes prior to incision increased from 54% to 68% (p = 0.266). Appropriate postoperative prescribing improved from 71% to 92% (p = 0.075). A multifaceted educational program may be effective in changing SSI prevention practices.

78 FR 73144 - Acceleration of Broadband Deployment by Improving Wireless Facilities Siting Policies

Science.gov (United States)

2013-12-05

... license is required, which in turn extends to any apparatus for the transmission of energy, or... No. 11-59; FCC 13-122] Acceleration of Broadband Deployment by Improving Wireless Facilities Siting... of new wireless facilities and on rules to implement statutory provisions governing State and local...

Implementation of surgical quality improvement: auditing tool for surgical site infection prevention practices.

Science.gov (United States)

Hechenbleikner, Elizabeth M; Hobson, Deborah B; Bennett, Jennifer L; Wick, Elizabeth C

2015-01-01

Surgical site infections are a potentially preventable patient harm. Emerging evidence suggests that the implementation of evidence-based process measures for infection reduction is highly variable. The purpose of this work was to develop an auditing tool to assess compliance with infection-related process measures and establish a system for identifying and addressing defects in measure implementation. This was a retrospective cohort study using electronic medical records. We used the auditing tool to assess compliance with 10 process measures in a sample of colorectal surgery patients with and without postoperative infections at an academic medical center (January 2012 to March 2013). We investigated 59 patients with surgical site infections and 49 patients without surgical site infections. First, overall compliance rates for the 10 process measures were compared between patients with infection vs patients without infection to assess if compliance was lower among patients with surgical site infections. Then, because of the burden of data collection, the tool was used exclusively to evaluate quarterly compliance rates among patients with infection. The results were reviewed, and the key factors contributing to noncompliance were identified and addressed. Ninety percent of process measures had lower compliance rates among patients with infection. Detailed review of infection cases identified many defects that improved following the implementation of system-level changes: correct cefotetan redosing (education of anesthesia personnel), temperature at surgical incision >36.0°C (flags used to identify patients for preoperative warming), and the use of preoperative mechanical bowel preparation with oral antibiotics (laxative solutions and antibiotics distributed in clinic before surgery). Quarterly compliance improved for 80% of process measures by the end of the study period. This study was conducted on a small surgical cohort within a select subspecialty. The

Forced, not voluntary, exercise improves motor function in Parkinson's disease patients.

Science.gov (United States)

Ridgel, Angela L; Vitek, Jerrold L; Alberts, Jay L

2009-01-01

Animal studies indicate forced exercise (FE) improves overall motor function in Parkinsonian rodents. Global improvements in motor function following voluntary exercise (VE) are not widely reported in human Parkinson's disease (PD) patients. The aim of this study was to compare the effects of VE and FE on PD symptoms, motor function, and bimanual dexterity. Ten patients with mild to moderate PD were randomly assigned to complete 8 weeks of FE or VE. With the assistance of a trainer, patients in the FE group pedaled at a rate 30% greater than their preferred voluntary rate, whereas patients in the VE group pedaled at their preferred rate. Aerobic intensity for both groups was identical, 60% to 80% of their individualized training heart rate. Aerobic fitness improved for both groups. Following FE, Unified Parkinson's Disease Rating Scale (UPDRS) motor scores improved 35%, whereas patients completing VE did not exhibit any improvement. The control and coordination of grasping forces during the performance of a functional bimanual dexterity task improved significantly for patients in the FE group, whereas no changes in motor performance were observed following VE. Improvements in clinical measures of rigidity and bradykinesia and biomechanical measures of bimanual dexterity were maintained 4 weeks after FE cessation. Aerobic fitness can be improved in PD patients following both VE and FE interventions. However, only FE results in significant improvements in motor function and bimanual dexterity. Biomechanical data indicate that FE leads to a shift in motor control strategy, from feedback to a greater reliance on feedforward processes, which suggests FE may be altering central motor control processes.

The conserved WW-domain binding sites in Dystroglycan C-terminus are essential but partially redundant for Dystroglycan function

Directory of Open Access Journals (Sweden)

Deng W-M

2009-02-01

Full Text Available Abstract Background Dystroglycan (Dg is a transmembrane protein that is a part of the Dystrophin Glycoprotein Complex (DGC which connects the extracellular matrix to the actin cytoskeleton. The C-terminal end of Dg contains a number of putative SH3, SH2 and WW domain binding sites. The most C-terminal PPXY motif has been established as a binding site for Dystrophin (Dys WW-domain. However, our previous studies indicate that both Dystroglycan PPXY motives, WWbsI and WWbsII can bind Dystrophin protein in vitro. Results We now find that both WW binding sites are important for maintaining full Dg function in the establishment of oocyte polarity in Drosophila. If either WW binding site is mutated, the Dg protein can still be active. However, simultaneous mutations in both WW binding sites abolish the Dg activities in both overexpression and loss-of-function oocyte polarity assays in vivo. Additionally, sequence comparisons of WW binding sites in 12 species of Drosophila, as well as in humans, reveal a high level of conservation. This preservation throughout evolution supports the idea that both WW binding sites are functionally required. Conclusion Based on the obtained results we propose that the presence of the two WW binding sites in Dystroglycan secures the essential interaction between Dg and Dys and might further provide additional regulation for the cytoskeletal interactions of this complex.

Efficacy of Interventions to Improve Respiratory Function After Stroke.

Science.gov (United States)

Menezes, Kênia Kp; Nascimento, Lucas R; Avelino, Patrick R; Alvarenga, Maria Tereza Mota; Teixeira-Salmela, Luci F

2018-07-01

The aim of this study was to systematically review all current interventions that have been utilized to improve respiratory function and activity after stroke. Specific searches were conducted. The experimental intervention had to be planned, structured, repetitive, purposive, and delivered with the aim of improving respiratory function. Outcomes included respiratory strength (maximum inspiratory pressure [P Imax ], maximum expiratory pressure [P Emax ]) and endurance, lung function (FVC, FEV 1 , and peak expiratory flow [PEF]), dyspnea, and activity. The quality of the randomized trials was assessed by the PEDro scale using scores from the Physiotherapy Evidence Database (www.pedro.org.au), and risk of bias was assessed in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. The 17 included trials had a mean PEDro score of 5.7 (range 4-8) and involved 616 participants. Meta-analyses showed that respiratory muscle training significantly improved all outcomes of interest: P Imax (weighted mean difference 11 cm H 2 O, 95% CI 7-15, I 2 = 0%), P Emax (8 cm H 2 O, 95% CI 2-15, I 2 = 65%), FVC (0.25 L, 95% CI 0.12-0.37, I 2 = 29%), FEV 1 (0.24 L, 95% CI 0.17-0.30, I 2 = 0%), PEF (0.51 L/s, 95% CI 0.10-0.92, I 2 = 0%), dyspnea (standardized mean difference -1.6 points, 95% CI -2.2 to -0.9; I 2 = 0%), and activity (standardized mean difference 0.78, 95% CI 0.22-1.35, I 2 = 0%). Meta-analyses found no significant results for the effects of breathing exercises on lung function. For the remaining interventions (ie, aerobic and postural exercises) and the addition of electrical stimulation, meta-analyses could not be performed. This systematic review reports 5 possible interventions used to improve respiratory function after stroke. Respiratory muscle training proved to be effective for improving inspiratory and expiratory strength, lung function, and dyspnea, and benefits were carried over to activity. However, there is still no evidence to accept or

A multi-state, multi-site, multi-sector healthcare improvement model: implementing evidence for practice.

Science.gov (United States)

Edward, Karen-Leigh; Walker, Kim; Duff, Jed

2017-10-01

Healthcare is complex and we know that evidence takes nearly 20 years to find its way into clinical practice. The slow process of translating research points to the need for effective translational research models to ensure patient care quality and safety are not compromised by such an epistemic failure. Our model to achieve reasonably rapid and enduring improvements to clinical care draws on that developed and promulgated by the Institute for Healthcare Improvement in the United States of America model as well as that developed by the Johns Hopkins Quality and Safety Group known as the Translating Research into Practice implementation model. The core principle of our hybrid model was to engage those most likely to be affected by the changes being introduced through a series of face-to-face and web-enabled meetings that act both as drivers of information but also as a means of engaging all stakeholders across the healthcare system involved in the change towards their pre-established goals. The model was piloted on the focused topic of the management of inadvertent perioperative hypothermia across nine hospitals within Australia (four sites in Victoria, three sites in New South Wales and two sites in Queensland). Improvement in management of hypothermia in these patients was achieved and sustained over time. Our model aims to engage the hearts and minds of healthcare clinicians, and others in order to empower them to make the necessary improvements to enhance patient care quality and safety. © The Author 2017. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Improving the Quality of Voluntary Medical Male Circumcision through Use of the Continuous Quality Improvement Approach: A Pilot in 30 PEPFAR-Supported Sites in Uganda

Science.gov (United States)

Opio, Alex; Calnan, Jacqueline; Njeuhmeli, Emmanuel

2015-01-01

Background Uganda adopted voluntary medical male circumcision (VMMC) (also called Safe Male Circumcision in Uganda), as part of its HIV prevention strategy in 2010. Since then, the Ministry of Health (MOH) has implemented VMMC mostly with support from the United States President’s Emergency Plan for AIDS Relief (PEPFAR) through its partners. In 2012, two PEPFAR-led external quality assessments evaluated compliance of service delivery sites with minimum quality standards. Quality gaps were identified, including lack of standardized forms or registers, lack of documentation of client consent, poor preparedness for emergencies and use of untrained service providers. In response, PEPFAR, through a USAID-supported technical assistance project, provided support in quality improvement to the MOH and implementing partners to improve quality and safety in VMMC services and build capacity of MOH staff to continuously improve VMMC service quality. Methods and Findings Sites were supported to identify barriers in achieving national standards, identify possible solutions to overcome the barriers and carry out improvement plans to test these changes, while collecting performance data to objectively measure whether they had bridged gaps. A 53-indicator quality assessment tool was used by teams as a management tool to measure progress; teams also measured client-level indicators through self-assessment of client records. At baseline (February-March 2013), less than 20 percent of sites scored in the “good” range (>80%) for supplies and equipment, patient counseling and surgical procedure; by November 2013, the proportion of sites scoring “good” rose to 67 percent, 93 percent and 90 percent, respectively. Significant improvement was noted in post-operative follow-up at 48 hours, sexually transmitted infection assessment, informed consent and use of local anesthesia but not rate of adverse events. Conclusion Public sector providers can be engaged to address the quality of

Improving the Quality of Voluntary Medical Male Circumcision through Use of the Continuous Quality Improvement Approach: A Pilot in 30 PEPFAR-Supported Sites in Uganda.

Science.gov (United States)

Byabagambi, John; Marks, Pamela; Megere, Humphrey; Karamagi, Esther; Byakika, Sarah; Opio, Alex; Calnan, Jacqueline; Njeuhmeli, Emmanuel

2015-01-01

Uganda adopted voluntary medical male circumcision (VMMC) (also called Safe Male Circumcision in Uganda), as part of its HIV prevention strategy in 2010. Since then, the Ministry of Health (MOH) has implemented VMMC mostly with support from the United States President's Emergency Plan for AIDS Relief (PEPFAR) through its partners. In 2012, two PEPFAR-led external quality assessments evaluated compliance of service delivery sites with minimum quality standards. Quality gaps were identified, including lack of standardized forms or registers, lack of documentation of client consent, poor preparedness for emergencies and use of untrained service providers. In response, PEPFAR, through a USAID-supported technical assistance project, provided support in quality improvement to the MOH and implementing partners to improve quality and safety in VMMC services and build capacity of MOH staff to continuously improve VMMC service quality. Sites were supported to identify barriers in achieving national standards, identify possible solutions to overcome the barriers and carry out improvement plans to test these changes, while collecting performance data to objectively measure whether they had bridged gaps. A 53-indicator quality assessment tool was used by teams as a management tool to measure progress; teams also measured client-level indicators through self-assessment of client records. At baseline (February-March 2013), less than 20 percent of sites scored in the "good" range (>80%) for supplies and equipment, patient counseling and surgical procedure; by November 2013, the proportion of sites scoring "good" rose to 67 percent, 93 percent and 90 percent, respectively. Significant improvement was noted in post-operative follow-up at 48 hours, sexually transmitted infection assessment, informed consent and use of local anesthesia but not rate of adverse events. Public sector providers can be engaged to address the quality of VMMC using a continuous quality improvement approach.

Identification of E-cadherin signature motifs functioning as cleavage sites for Helicobacter pylori HtrA

Science.gov (United States)

Schmidt, Thomas P.; Perna, Anna M.; Fugmann, Tim; Böhm, Manja; Jan Hiss; Haller, Sarah; Götz, Camilla; Tegtmeyer, Nicole; Hoy, Benjamin; Rau, Tilman T.; Neri, Dario; Backert, Steffen; Schneider, Gisbert; Wessler, Silja

2016-03-01

The cell adhesion protein and tumour suppressor E-cadherin exhibits important functions in the prevention of gastric cancer. As a class-I carcinogen, Helicobacter pylori (H. pylori) has developed a unique strategy to interfere with E-cadherin functions. In previous studies, we have demonstrated that H. pylori secretes the protease high temperature requirement A (HtrA) which cleaves off the E-cadherin ectodomain (NTF) on epithelial cells. This opens cell-to-cell junctions, allowing bacterial transmigration across the polarised epithelium. Here, we investigated the molecular mechanism of the HtrA-E-cadherin interaction and identified E-cadherin cleavage sites for HtrA. Mass-spectrometry-based proteomics and Edman degradation revealed three signature motifs containing the [VITA]-[VITA]-x-x-D-[DN] sequence pattern, which were preferentially cleaved by HtrA. Based on these sites, we developed a substrate-derived peptide inhibitor that selectively bound and inhibited HtrA, thereby blocking transmigration of H. pylori. The discovery of HtrA-targeted signature sites might further explain why we detected a stable 90 kDa NTF fragment during H. pylori infection, but also additional E-cadherin fragments ranging from 105 kDa to 48 kDa in in vitro cleavage experiments. In conclusion, HtrA targets E-cadherin signature sites that are accessible in in vitro reactions, but might be partially masked on epithelial cells through functional homophilic E-cadherin interactions.

Bariatric surgery is associated with renal function improvement.

Science.gov (United States)

Holcomb, Carla N; Goss, Lauren E; Almehmi, Ammar; Grams, Jayleen M; Corey, Britney L

2018-01-01

Weight loss after bariatric surgery improves both blood pressure and glycemic control following surgery. The effect of bariatric surgery on renal function is not well characterized. In this study, we sought to quantify the change in renal function over time following surgery. We retrospectively reviewed all patients who underwent laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) between 2012 and 2014 at our institution. The glomerular filtration rate (GFR, mL/min) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Body mass index (BMI, kg/m 2 ) and percent weight loss (%WL) were calculated following the surgery. A total of 149 patients who underwent bariatric surgery were included in this study: LRYGB (n = 86 and LSG (n = 63). In LRYGB group, baseline BMI (kg/m 2 , ±SD) and GFR (mL/min, ±SD) were 48.5 ± 6.8 and 94.7 ± 23.8, respectively. In comparison, BMI and GFR were 49.1 ± 11.9 kg/m 2 and 93.1 ± 28.0 mL/min in the LSG group, respectively. Over the follow-up period (19.89 ± 10.93 months), the patients who underwent LRGYB lost a larger percentage of weight as compared to those in the LSG group (29.9 ± 11.7% vs 22.3 ± 10.7%; p = weight loss surgery (n = 62), 42% had improvement of their GFR to > 90 mL/min postoperatively (p weight loss percentage and GFR improvement (p = 0.8703). Bariatric surgery was associated with improvement in postoperative renal function at almost two years following surgery but was not different for LRYGB versus LSG. The gain in GFR was independent of percentage of weight lost suggesting an alternate mechanism in the improvement of renal function other than weight loss alone.

Improving Video Generation for Multi-functional Applications

OpenAIRE

Kratzwald, Bernhard; Huang, Zhiwu; Paudel, Danda Pani; Dinesh, Acharya; Van Gool, Luc

2017-01-01

In this paper, we aim to improve the state-of-the-art video generative adversarial networks (GANs) with a view towards multi-functional applications. Our improved video GAN model does not separate foreground from background nor dynamic from static patterns, but learns to generate the entire video clip conjointly. Our model can thus be trained to generate - and learn from - a broad set of videos with no restriction. This is achieved by designing a robust one-stream video generation architectur...

A data-model integration approach toward improved understanding on wetland functions and hydrological benefits at the catchment scale

Science.gov (United States)

Yeo, I. Y.; Lang, M.; Lee, S.; Huang, C.; Jin, H.; McCarty, G.; Sadeghi, A.

2017-12-01

The wetland ecosystem plays crucial roles in improving hydrological function and ecological integrity for the downstream water and the surrounding landscape. However, changing behaviours and functioning of wetland ecosystems are poorly understood and extremely difficult to characterize. Improved understanding on hydrological behaviours of wetlands, considering their interaction with surrounding landscapes and impacts on downstream waters, is an essential first step toward closing the knowledge gap. We present an integrated wetland-catchment modelling study that capitalizes on recently developed inundation maps and other geospatial data. The aim of the data-model integration is to improve spatial prediction of wetland inundation and evaluate cumulative hydrological benefits at the catchment scale. In this paper, we highlight problems arising from data preparation, parameterization, and process representation in simulating wetlands within a distributed catchment model, and report the recent progress on mapping of wetland dynamics (i.e., inundation) using multiple remotely sensed data. We demonstrate the value of spatially explicit inundation information to develop site-specific wetland parameters and to evaluate model prediction at multi-spatial and temporal scales. This spatial data-model integrated framework is tested using Soil and Water Assessment Tool (SWAT) with improved wetland extension, and applied for an agricultural watershed in the Mid-Atlantic Coastal Plain, USA. This study illustrates necessity of spatially distributed information and a data integrated modelling approach to predict inundation of wetlands and hydrologic function at the local landscape scale, where monitoring and conservation decision making take place.

3D Information System of Historical Site – Proposal and Realisation of a Functional Prototype

Directory of Open Access Journals (Sweden)

J. Hodač

2005-01-01

Full Text Available The development of methods for 3D data acquisition, together with progress in information technologies raises the question of creating and using 3D models and 3D information systems (IS of historical sites and buildings. This paper presents the current state of the “Live Theatre” project. The theme of the project is the proposal and realisation of a 3D IS of the baroque theatre at Eeský Krumlov castle (UNESCO site.The project is divided into three main stages – creation of a 3D model, proposal of a conception for a 3D IS, and realisation of a functional prototype. 3D data was acquired by means of photogrammetric and surveying methods. An accurate 3D model (photo-realistic, textured was built up with MicroStation CAD system. The proposal of a conception of a 3D IS was the main outcome of the author’s dissertation. The essential feature of the proposed conception is the creation of subsystems targeted on three spheres – management, research and presentation of the site. The functionality of each subsystem is connected with its related sphere; however, each subsystem uses the same database. The present stage of the project involves making a functional prototype (with sample data. During this stage we are working on several basic technological topics. At present we are concerned with 3D data, its formats, format conversions (e.g. DGN _ VRML and its connection to other types of data. After that, we will be seeking a convenient technical solution based on network technologies (Internet and an appropriate layout for the data (database. The project is being carried out in close co-operation with the administration of the castle and some other partners. This stage of the project will be completed in December 2005.A functional prototype and the information acquired by testing it will form the basis for the final proposal of a complex IS of a historical site. The final proposal and appropriate technology will be the outcome of the project. The

Effect of self-deflection on a totally asymmetric simple exclusion process with functions of site assignments

Science.gov (United States)

Tsuzuki, Satori; Yanagisawa, Daichi; Nishinari, Katsuhiro

2018-04-01

This study proposes a model of a totally asymmetric simple exclusion process on a single-channel lane with functions of site assignments along the pit lane. The system model attempts to insert a new particle to the leftmost site at a certain probability by randomly selecting one of the empty sites in the pit lane, and reserving it for the particle. Thereafter, the particle is directed to stop at the site only once during its travel. Recently, the system was determined to show a self-deflection effect, in which the site usage distribution biases spontaneously toward the leftmost site, and the throughput becomes maximum when the site usage distribution is slightly biased to the rightmost site. Our exact analysis describes this deflection effect and show a good agreement with simulations.

Density functional study the interaction of oxygen molecule with defect sites of graphene

Energy Technology Data Exchange (ETDEWEB)

Qi Xuejun [State Key Laboratory of Coal Combustion, Wuhan 430074 (China); Guo Xin, E-mail: guoxin@mail.hust.edu.cn [State Key Laboratory of Coal Combustion, Wuhan 430074 (China); Zheng Chuguang [State Key Laboratory of Coal Combustion, Wuhan 430074 (China)

2012-10-15

Highlights: Black-Right-Pointing-Pointer The defect sites existed on the graphite surface create active sites and enhance the reactivity of carbonaceous material. Black-Right-Pointing-Pointer Oxygen molecule more favor chemisorbed on the graphene surface contains defect sites than the perfect surface. Black-Right-Pointing-Pointer The single active oxygen atom adsorbed on the defect surfaces, it completely insert into the surface. - Abstract: The present article reports a theoretical study of oxygen interacted with graphene surface containing defect sites on the atomic level by employing the density functional theory combined with the graphene cluster model. It was founded that oxygen molecule prefers to be chemisorbed on the graphene surface containing defect sites compared to the perfect surface. The adsorption energy of O{sub 2} on the double defect site is about 2.5 times as large as that on the perfect graphene surface. Moreover, the oxygen molecule interacts with S-W defect site gives rise to stable epoxy structure, which pulling the carbon atom outward from the original site in the direction perpendicular to the surface. If the oxygen molecule is adsorbed on the single vacancy site, two C-O bonds are formed on the graphene surface. However, when the oxygen molecule is chemisorbed on the double vacancy site, the oxygen atoms substitute the missing carbon atom's position in the carbon plane and form a hexagonal structure on the graphene network. The results indicate that single active oxygen atom approaches the defect site, it's completely adsorbed in the plane and high energy is released. In all cases, the interaction of an oxygen atom with defect surface involves an exothermic process. The defect site creates active sites on the surface of graphene and produces catalytic effects during the process of oxidation of carbonaceous materials.

Application of Improved Wavelet Thresholding Function in Image Denoising Processing

Directory of Open Access Journals (Sweden)

Hong Qi Zhang

2014-07-01

Full Text Available Wavelet analysis is a time – frequency analysis method, time-frequency localization problems are well solved, this paper analyzes the basic principles of the wavelet transform and the relationship between the signal singularity Lipschitz exponent and the local maxima of the wavelet transform coefficients mold, the principles of wavelet transform in image denoising are analyzed, the disadvantages of traditional wavelet thresholding function are studied, wavelet threshold function, the discontinuity of hard threshold and constant deviation of soft threshold are improved, image is denoised through using the improved threshold function.

Assessing the structural conservation of protein pockets to study functional and allosteric sites: implications for drug discovery

Directory of Open Access Journals (Sweden)

Daura Xavier

2010-03-01

Full Text Available Abstract Background With the classical, active-site oriented drug-development approach reaching its limits, protein ligand-binding sites in general and allosteric sites in particular are increasingly attracting the interest of medicinal chemists in the search for new types of targets and strategies to drug development. Given that allostery represents one of the most common and powerful means to regulate protein function, the traditional drug discovery approach of targeting active sites can be extended by targeting allosteric or regulatory protein pockets that may allow the discovery of not only novel drug-like inhibitors, but activators as well. The wealth of available protein structural data can be exploited to further increase our understanding of allosterism, which in turn may have therapeutic applications. A first step in this direction is to identify and characterize putative effector sites that may be present in already available structural data. Results We performed a large-scale study of protein cavities as potential allosteric and functional sites, by integrating publicly available information on protein sequences, structures and active sites for more than a thousand protein families. By identifying common pockets across different structures of the same protein family we developed a method to measure the pocket's structural conservation. The method was first parameterized using known active sites. We characterized the predicted pockets in terms of sequence and structural conservation, backbone flexibility and electrostatic potential. Although these different measures do not tend to correlate, their combination is useful in selecting functional and regulatory sites, as a detailed analysis of a handful of protein families shows. We finally estimated the numbers of potential allosteric or regulatory pockets that may be present in the data set, finding that pockets with putative functional and effector characteristics are widespread across

Improving Mitochondrial Function Protects Bumblebees from Neonicotinoid Pesticides.

Directory of Open Access Journals (Sweden)

Michael B Powner

Full Text Available Global pollination is threatened by declining insect pollinator populations that may be linked to neonicotinoid pesticide use. Neonicotinoids over stimulate neurons and depolarize their mitochondria, producing immobility and death. However, mitochondrial function can be improved by near infrared light absorbed by cytochrome c oxidase in mitochondrial respiration. In flies, daily exposure to 670nm light throughout life increases average lifespan and aged mobility, and reduces systemic inflammation. Here we treat bumble bees with Imidacloprid a common neonicotinoid. This undermined ATP and rapidly induced immobility and reduced visual function and survival. Bees exposed to insecticide and daily to 670nm light showed corrected ATP levels and significantly improved mobility allowing them to feed. Physiological recordings from eyes revealed that light exposure corrected deficits induced by the pesticide. Overall, death rates in bees exposed to insecticide but also given 670nm light were indistinguishable from controls. When Imidacloprid and light exposure were withdrawn, survival was maintained. Bees and insects generally cannot see deep red light so it does not disturb their behaviour. Hence, we show that deep red light exposure that improves mitochondrial function, reverses the sensory and motor deficits induced by Imidacloprid. These results may have important implications as light delivery is economic and can be placed in hives/colonies.

Improvement of Left Ventricular Function by Permanent Direct His-Bundle Pacing in a Case with Dilated Cardiomyopathy

Directory of Open Access Journals (Sweden)

Yukiko Sashida, MD

2006-01-01

Full Text Available The patient was a 67-year-old female diagnosed with dilated cardiomyopathy. She had chronic atrial fibrillation (AF with bradycardia and low left ventricular function (left ventricular ejection fraction (LVEF 40%. She was admitted for congestive heart failure. She remained New York Heart Association (NYHA functional class III due to AF bradycardia. Pacemaker implantation was necessary for treatment of heart failure and administration of dose intensive β-blockers. As she had normal His-Purkinje activation, we examined the optimal pacing sites. Hemodynamics of His-bundle pacing and biventricular pacing were compared. Pulmonary capillary wedge pressure (PCWP was significantly lower on Hisbundle pacing than right ventricular (RV apical pacing and biventricular pacing (13mmHg, 19mmHg, and 19mmHg, respectively with an almost equal cardiac index. Based on the examination we implanted a permanent pacemaker for Direct His-bundle pacing (DHBP. After the DHBP implantation, the LVEF immediately improved from 40% to 55%, and BNP level decreased from 422 pg/ml to 42 pg/ml. The number of premature ventricular complex (PVC was decreased, and non sustained ventricular tachycardia (NSVT disappeared. Pacing threshold for His-bundle pacing has remained at the same level. His-bundle pacing has been maintained during 27 months and her long-term DHBP can improve cardiac function and the NYHA functional class.

Novel factor VIII variants with a modified furin cleavage site improve the efficacy of gene therapy for hemophilia A.

Science.gov (United States)

Nguyen, G N; George, L A; Siner, J I; Davidson, R J; Zander, C B; Zheng, X L; Arruda, V R; Camire, R M; Sabatino, D E

2017-01-01

Essentials Factor (F) VIII is an inefficiently expressed protein. Furin deletion FVIII variants were purified and characterized using in vitro and in vivo assays. These minimally modified novel FVIII variants have enhanced function. These variants provide a strategy for increasing FVIII expression in hemophilia A gene therapy. Background The major challenge for developing gene-based therapies for hemophilia A is that human factor VIII (hFVIII) has intrinsic properties that result in inefficient biosynthesis. During intracellular processing, hFVIII is predominantly cleaved at a paired basic amino acid cleaving enzyme (PACE) or furin cleavage site to yield a heterodimer that is the major form of secreted protein. Previous studies with B-domain-deleted (BDD) canine FVIII and hFVIII-R1645H, both differing from hFVIII by a single amino acid at this site, suggested that these proteins are secreted mainly in a single polypeptide chain (SC) form and exhibit enhanced function. Objective We hypothesized that deletion(s) of the furin site modulates FVIII biology and may enhance its function. Methods A series of recombinant hFVIII-furin deletion variants were introduced into hFVIII-BDD [Δ1645, 1645-46(Δ2), 1645-47(Δ3), 1645-48(Δ4), or Δ1648] and characterized. Results In vitro, recombinant purified Δ3 and Δ4 were primarily SC and, interestingly, had 2-fold higher procoagulant activity compared with FVIII-BDD. In vivo, the variants also have improved hemostatic function. After adeno-associated viral (AAV) vector delivery, the expression of these variants is 2-4-fold higher than hFVIII-BDD. Protein challenges of each variant in mice tolerant to hFVIII-BDD showed no anti-FVIII immune response. Conclusions These data suggest that the furin deletion hFVIII variants are superior to hFVIII-BDD without increased immunogenicity. In the setting of gene-based therapeutics, these novel variants provide a unique strategy to increase FVIII expression, thus lowering the vector dose, a

Is the relationship between increased knee muscle strength and improved physical function following exercise dependent on baseline physical function status?

Science.gov (United States)

Hall, Michelle; Hinman, Rana S; van der Esch, Martin; van der Leeden, Marike; Kasza, Jessica; Wrigley, Tim V; Metcalf, Ben R; Dobson, Fiona; Bennell, Kim L

2017-12-08

Clinical guidelines recommend knee muscle strengthening exercises to improve physical function. However, the amount of knee muscle strength increase needed for clinically relevant improvements in physical function is unclear. Understanding how much increase in knee muscle strength is associated with improved physical function could assist clinicians in providing appropriate strength gain targets for their patients in order to optimise outcomes from exercise. The aim of this study was to investigate whether an increase in knee muscle strength is associated with improved self-reported physical function following exercise; and whether the relationship differs according to physical function status at baseline. Data from 100 participants with medial knee osteoarthritis enrolled in a 12-week randomised controlled trial comparing neuromuscular exercise to quadriceps strengthening exercise were pooled. Participants were categorised as having mild, moderate or severe physical dysfunction at baseline using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Associations between 12-week changes in physical function (dependent variable) and peak isometric knee extensor and flexor strength (independent variables) were evaluated with and without accounting for baseline physical function status and covariates using linear regression models. In covariate-adjusted models without accounting for baseline physical function, every 1-unit (Nm/kg) increase in knee extensor strength was associated with physical function improvement of 17 WOMAC units (95% confidence interval (CI) -29 to -5). When accounting for baseline severity of physical function, every 1-unit increase in knee extensor strength was associated with physical function improvement of 24 WOMAC units (95% CI -42 to -7) in participants with severe physical dysfunction. There were no associations between change in strength and change in physical function in participants with mild or moderate physical

Improved measurement of aluminum in irradiated fuel reprocessed at the Savannah River Site

International Nuclear Information System (INIS)

Maxwell, S.L. III.

1991-01-01

At the Savannah River Site (SRS), irradiated fuel from research reactor operators or their contract fuel service companies is reprocessed in the H-Canyon Separations Facility. Final processing costs are based on analytical measurements of the amount of total metal dissolved. Shipper estimates for uranium and uranium-235 and measured values at SRS have historically agreed very well. There have occasionally been significant differences between shipper estimates for aluminum and the aluminum content determined at SRS. To minimize analytical error that might contribute to poor shipper-receiver agreement for the reprocessing of off-site fuel, a new analytical method to measure aluminum was developed by SRS Analytical Laboratories at the Central Laboratory Facilities. An EDTA (ethylenediaminetetraacetic acid) titration method, subject to dissolver matrix interferences, was previously used at SRS to measure aluminum in H-Canyon dissolver during the reprocessing of offsite fuel. The new method combines rapid ion exchange technology with direct current argon plasma spectrometry to enhance the reliability of aluminum measurements for off-site fuel. The technique rapidly removes spectral interferences such as uranium and significantly lowers gamma levels due to fission products. Aluminium is separated quantitatively by using an anion exchange technique that employs oxalate complexing, small particle size resin and rapid flow rates. The new method, which has eliminated matrix interference problems with these analyses and improved the quality of aluminum measurements, has improved the overall agreement between shipper-receiver values for offsite fuel processed SRS

Estimation of Community Land Model parameters for an improved assessment of net carbon fluxes at European sites

Science.gov (United States)

Post, Hanna; Vrugt, Jasper A.; Fox, Andrew; Vereecken, Harry; Hendricks Franssen, Harrie-Jan

2017-03-01

The Community Land Model (CLM) contains many parameters whose values are uncertain and thus require careful estimation for model application at individual sites. Here we used Bayesian inference with the DiffeRential Evolution Adaptive Metropolis (DREAM(zs)) algorithm to estimate eight CLM v.4.5 ecosystem parameters using 1 year records of half-hourly net ecosystem CO2 exchange (NEE) observations of four central European sites with different plant functional types (PFTs). The posterior CLM parameter distributions of each site were estimated per individual season and on a yearly basis. These estimates were then evaluated using NEE data from an independent evaluation period and data from "nearby" FLUXNET sites at 600 km distance to the original sites. Latent variables (multipliers) were used to treat explicitly uncertainty in the initial carbon-nitrogen pools. The posterior parameter estimates were superior to their default values in their ability to track and explain the measured NEE data of each site. The seasonal parameter values reduced with more than 50% (averaged over all sites) the bias in the simulated NEE values. The most consistent performance of CLM during the evaluation period was found for the posterior parameter values of the forest PFTs, and contrary to the C3-grass and C3-crop sites, the latent variables of the initial pools further enhanced the quality-of-fit. The carbon sink function of the forest PFTs significantly increased with the posterior parameter estimates. We thus conclude that land surface model predictions of carbon stocks and fluxes require careful consideration of uncertain ecological parameters and initial states.

An integrated approach to site selection for nuclear power plants

International Nuclear Information System (INIS)

Hassan, E.M.A.

1975-01-01

A method of analysing and evaluating the large number of factors influencing site selection is proposed, which can interrelate these factors and associated problems in an integrated way and at the same time establish a technique for site evaluation. The objective is to develop an integrated programme that illustrates the complexity and dynamic interrelationships of the various factors to develop an improved understanding of the functions and objectives of siting nuclear power plants and would aim finally at the development of an effective procedure and technique for site evaluation and/or comparative evaluation for making rational site-selection decisions. (author)

[Effects on salivation, xerostomia and halitosis in elders after oral function improvement exercises].

Science.gov (United States)

Kim, Young Jin; Park, Kyung Min

2012-12-01

The purpose of this study was to investigate effects of Oral Function Improvement Exercises on salivation, xerostomia and halitosis in elderly people. The participants in the study were 48 female community-dwelling elders in D city. The Oral Function Improvement Exercises were given 3 times a week, for a total of 24 times from August to October 2011. Spitting method, Visual Analogue Scale, and halimeter (mBA-21) were used to evaluate the effects of Oral Function Improvement Exercises on salivation, xerostomia, and halitosis. The data were analyzed using χ²-test and t-test with the SPSS program. The experimental group had significantly better salivation, and less xerostomia and halitosis than the control group. The results indicate that Oral Function Improvement Exercises were effective for salivation, xerostomia and halitosis in the elders. Therefore, it was suggested that Oral Function Improvement Exercise are applicable in a community nursing intervention program to improve the quality of life for elders.

Obesity impedes functional improvement in youth with chronic pain: An initial investigation.

Science.gov (United States)

Stoner, A M; Jastrowski Mano, K E; Weisman, S J; Hainsworth, K R

2017-10-01

Youth with chronic pain are at higher risk for obesity than the general population. In youth with chronic pain, obesity exacerbates pain-specific activity limitations, and in adults with chronic pain, obesity perpetuates a cycle of disability. The current study examined whether weight status predicts functional disability outcomes over time in youth with chronic pain. Data were obtained from a retrospective chart review of patients who consented to participate in a longitudinal outcomes study. The Child Activity Limitations Questionnaire was used to assess functional disability at intake, 1-, and 3-month follow-up. Height and weight were measured at intake. A linear mixed model was used to test whether weight status and time predicted functional disability. Trend analysis with polynomial contrasts was used to test whether improvements in functional disability showed a linear trend over time. The linear mixed model analysis showed a main effect of weight, suggesting that youth with higher BMI demonstrated less improvement in functional disability over time. The trend analysis suggested that improvements in functional disability were consistent with a linear trend for both healthy weight and overweight participants, but not for obese participants. These findings demonstrate that obesity impedes improvement in functioning for youth with chronic pain. Despite multidisciplinary pain treatment, youth with comorbid chronic pain and obesity demonstrate greater functional disability at follow-up and little improvement over time. These results support the need for interventions specifically tailored to the unique challenges faced by youth with comorbid chronic pain and obesity. This study shows that obesity impedes improvement in functioning for youth with chronic pain. On the basis of these findings, interventions should be tailored to the unique challenges of this population. © 2017 European Pain Federation - EFIC®.

Function of site. Chapter 2

International Nuclear Information System (INIS)

1999-01-01

In Semipalatinsk test site's history there are two stages for nuclear tests. In first stage (1949-1962) when the nuclear tests have being conducted in atmosphere, and second one (1963-1989) when underground nuclear explosions have being carried out. There were 456 nuclear tests, from which 117 were both the surface and the atmospheric explosions and other underground ones. In the chapter general characteristics of atmospheric nuclear tests, conducted on Semipalatinsk test site in 1949-1962 (chronology of conducting, release energy and kinds of nuclear explosions) are presented in tabular form. Most powerful of explosion was test of hydro- nuclear (hydrogen) bomb - prototype of thermonuclear charge in 1955 with capacity 1.6 Mt. In 1990-1992 the target-oriented radioecological investigation of territory around Semipalatinsk test site was carried out. Specialists dividing all atmospheric explosions by rate local traces, forming out of test site into 4 groups: with very strong contamination, with strong contamination, with weak contamination, and with very weak contamination. To nuclear explosions with very strong contamination were attributed the four explosions carrying out in 29.08.1949, 24.09.1951, 12.08.1953, 24.08.1956. Estimations of radiological situation including external doses of radiation and environment contamination and content of radioactive substances in human body was given by 10 European experts in collaboration with Kazakstan scientists. Results of investigation show that during past period surface contamination, called by nuclear weapons' fissile products was subjected to considerable decay. External doses completely coincidence with natural background. Remains of long living radionuclides are insignificant as well, and in 1995 its approximately were equal to annual exposition doses. One of most damaged settlements is Chagan. On it territory 530 radioactive sources with doses capacity from 100 up to 400 μR/h. Scientists of Semipalatinsk defined

Both ATPase sites of Escherichia coli UvrA have functional roles in nucleotide excision repair

International Nuclear Information System (INIS)

Thiagalingam, S.; Grossman, L.

1991-01-01

The roles of the two tandemly arranged putative ATP binding sites of Escherichia coli UvrA in UvrABC endonuclease-mediated excision repair were analyzed by site-directed mutagenesis and biochemical characterization of the representative mutant proteins. Evidence is presented that UvrA has two functional ATPase sites which coincide with the putative ATP binding motifs predicted from its amino acid sequence. The individual ATPase sites can independently hydrolyze ATP. The C-terminal ATPase site has a higher affinity for ATP than the N-terminal site. The invariable lysine residues at the ends of the glycine-rich loops of the consensus Walker type A motifs are indispensable for ATP hydrolysis. However, the mutations at these lysine residues do not significantly affect ATP binding. UvrA, with bound ATP, forms the most favored conformation for DNA binding. The initial binding of UvrA to DNA is chiefly at the undamaged sites. In contrast to the wild type UvrA, the ATPase site mutants bind equally to damaged and undamaged sites. Dissociation of tightly bound nucleoprotein complexes from the undamaged sites requires hydrolysis of ATP by the C-terminal ATPase site of UvrA. Thus, both ATP binding and hydrolysis are required for the damage recognition step enabling UvrA to discriminate between damaged and undamaged sites on DNA

A short executive function training program improves preschoolers’ working memory

Directory of Open Access Journals (Sweden)

Emma eBlakey

2015-11-01

Full Text Available Cognitive training has been shown to improve executive functions in middle childhood and adulthood. However, fewer studies have targeted the preschool years – a time when executive functions undergo rapid development. The present study tested the effects of a short four session executive function training program in 54 four-year-olds. The training group significantly improved their working memory from pre-training relative to an active control group. Notably, this effect extended to a task sharing few surface features with the trained tasks, and continued to be apparent three months later. In addition, the benefits of training extended to a measure of mathematical reasoning three months later, indicating that training executive functions during the preschool years has the potential to convey benefits that are both long-lasting and wide-ranging.

Surfactant treatment before reperfusion improves the immediate function of lung transplants in rats

NARCIS (Netherlands)

Erasmus, ME; Petersen, AH; Hofstede, G; Haagsman, HP; Oetomo, SB; Prop, J

An impaired function of alveolar surfactant can cause lung transplant dysfunction early after reperfusion. In this study it was investigated whether treatment with surfactant before reperfusion improves the immediate function of lung transplants and whether an improved transplant function was

Selenization of Cu2ZnSnS4 Enhanced the Performance of Dye-Sensitized Solar Cells: Improved Zinc-Site Catalytic Activity for I3.

Science.gov (United States)

Wang, Xiuwen; Xie, Ying; Bateer, Buhe; Pan, Kai; Jiao, Yanqing; Xiong, Ni; Wang, Song; Fu, Honggang

2017-11-01

Cu 2 ZnSnS 4 (CZTS) and Cu 2 ZnSn(S,Se) 4 (CZTSSe) as promising photovoltaic materials have drawn much attention because they are environmentally benign and earth-abundant elements. In this work, the monodispersed, low-cost Cu 2 ZnSnS 4 nanocrystals with small size have been controllably synthesized via a wet chemical routine. And CZTSSe could be easily prepared after selenization of CZTS. When they are employed as counter electrodes (CEs) for dye-sensitized solar cells (DSSCs), the power conversion efficiency (PCE) has been improved from 3.54% to 7.13% as CZTS is converted to CZTSSe, which is also compared to that of Pt (7.62%). The exact reason for the enhanced catalytic activity of I 3 - is discussed with the work function and density functional theory (DFT) when CZTSSe converted from CZTS. The results of a Kelvin probe suggest that the work function of CZTSSe (5.61 eV) is closer to that of Pt (5.65 eV) and higher than that of CZTS, which matched the redox shuttle potential better. According to the theory calculation, all the atomic and bond populations changed significantly when Se replaced partly the S on the CZTS system, especially in the Zn site. During the catalytic process as CEs, the adsorption energy obviously increased compared to those at other sites when I 3 - adsorbed on the Zn site in CZTSSe. So, Zn plays an important role for the reduction of I 3 - after CZTS is converted to CZTSSe. Based on above analysis, the reason for enhanced performance of DSSCs when CZTS converted to CZTSSe is mainly due to the enhancement of Zn-site activity. This work is beneficial for understanding the catalytic reaction mechanism of CZTS(Se) as CEs of DSSCs.

Flavanol-rich cocoa consumption enhances exercise-induced executive function improvements in humans.

Science.gov (United States)

Tsukamoto, Hayato; Suga, Tadashi; Ishibashi, Aya; Takenaka, Saki; Tanaka, Daichi; Hirano, Yoshitaka; Hamaoka, Takafumi; Goto, Kazushige; Ebi, Kumiko; Isaka, Tadao; Hashimoto, Takeshi

2018-02-01

Aerobic exercise is known to acutely improve cognitive functions, such as executive function (EF) and memory function (MF). Additionally, consumption of flavanol-rich cocoa has been reported to acutely improve cognitive function. The aim of this study was to determine whether high cocoa flavanol (CF; HCF) consumption would enhance exercise-induced improvement in cognitive function. To test this hypothesis, we examined the combined effects of HCF consumption and moderate-intensity exercise on EF and MF during postexercise recovery. Ten healthy young men received either an HCF (563 mg of CF) or energy-matched low CF (LCF; 38 mg of CF) beverage 70 min before exercise in a single-blind counterbalanced manner. The men then performed moderate-intensity cycling exercise at 60% of peak oxygen uptake for 30 min. The participants performed a color-word Stroop task and face-name matching task to evaluate EF and MF, respectively, during six time periods throughout the experimental session. EF significantly improved immediately after exercise compared with before exercise in both conditions. However, EF was higher after HCF consumption than after LCF consumption during all time periods because HCF consumption improved EF before exercise. In contrast, HCF consumption and moderate-intensity exercise did not improve MF throughout the experiment. The present findings demonstrated that HCF consumption before moderate-intensity exercise could enhance exercise-induced improvement in EF, but not in MF. Therefore, we suggest that the combination of HCF consumption and aerobic exercise may be beneficial for improving EF. Copyright © 2017 Elsevier Inc. All rights reserved.

Improvement of swallowing function in patients with esophageal cancer treated by radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Sugahara, Shinji; Nakajima, Kotaro; Nozawa, Kumiko [Hitachi Ltd., Ibaraki (Japan). Hitachi General Hospital; Ohara, Kiyoshi; Yoshioka, Hiroshi; Tatsuzaki, Hideo; Tanaka, Naomi; Fukao, Katashi; Itai, Yuji

1996-12-01

This study investigated the impact of radiotherapy on swallowing function in 152 patients with esophageal cancer. Swallowing function was retrospectively assessed in these patients using a swallowing-function scoring system. Total tumor dose ranged from 22.5 Gy in 14 fractions to 104.4 Gy in 50 fractions. Improvement in dysphagia was noted in 62.3% of these patients, with a median time to improvement of 6 weeks. Improvement rate of patients irradiated with 20.0 to 34.9 Gy, 35.0 to 59.9 Gy and 60.0 Gy or more was 23.1%, 58.3% and 71.6%, respectively. Patients with T1-3 showed, a greater improvement rate than patients with T4 cancer (72.2% versus 54.1%). On multivariate analysis, the initial score, total dose and T factor correlated with improvements in swallowing function. Our results suggest that 35.0 Gy or more is necessary to improve swallowing function. The median duration in which patients could swallow soft or solid foods, was 8 months in patients receiving 60.0 Gy or more and 2 months in patients receiving 50.0 to 59.9 Gy, respectively. There was a significant difference between these periods (p<0.01). Regarding duration of palliation, median duration for patients receiving 60.0 Gy or more was 30 weeks, while it was 22 weeks for patients treated with lesser doses (p=0.053). We recommend 60.0 Gy or more as the optimal dosage for improving dysphagia. (author)

Inducible Activation of ERK5 MAP Kinase Enhances Adult Neurogenesis in the Olfactory Bulb and Improves Olfactory Function

Science.gov (United States)

Wang, Wenbin; Lu, Song; Li, Tan; Pan, Yung-Wei; Zou, Junhui; Abel, Glen M.; Xu, Lihong; Storm, Daniel R.

2015-01-01

Recent discoveries have suggested that adult neurogenesis in the subventricular zone (SVZ) and olfactory bulb (OB) may be required for at least some forms of olfactory behavior in mice. However, it is unclear whether conditional and selective enhancement of adult neurogenesis by genetic approaches is sufficient to improve olfactory function under physiological conditions or after injury. Furthermore, specific signaling mechanisms regulating adult neurogenesis in the SVZ/OB are not fully defined. We previously reported that ERK5, a MAP kinase selectively expressed in the neurogenic regions of the adult brain, plays a critical role in adult neurogenesis in the SVZ/OB. Using a site-specific knock-in mouse model, we report here that inducible and targeted activation of the endogenous ERK5 in adult neural stem/progenitor cells enhances adult neurogenesis in the OB by increasing cell survival and neuronal differentiation. This conditional ERK5 activation also improves short-term olfactory memory and odor-cued associative olfactory learning under normal physiological conditions. Furthermore, these mice show enhanced recovery of olfactory function and have more adult-born neurons after a zinc sulfate-induced lesion of the main olfactory epithelium. We conclude that ERK5 MAP kinase is an important endogenous signaling pathway regulating adult neurogenesis in the SVZ/OB, and that conditional activation of endogenous ERK5 is sufficient to enhance adult neurogenesis in the OB thereby improving olfactory function both under normal conditions and after injury. PMID:25995470

Improved Functional Characteristics of Whey Protein Hydrolysates in Food Industry

Science.gov (United States)

Jeewanthi, Renda Kankanamge Chaturika; Lee, Na-Kyoung; Paik, Hyun-Dong

2015-01-01

This review focuses on the enhanced functional characteristics of enzymatic hydrolysates of whey proteins (WPHs) in food applications compared to intact whey proteins (WPs). WPs are applied in foods as whey protein concentrates (WPCs), whey protein isolates (WPIs), and WPHs. WPs are byproducts of cheese production, used in a wide range of food applications due to their nutritional validity, functional activities, and cost effectiveness. Enzymatic hydrolysis yields improved functional and nutritional benefits in contrast to heat denaturation or native applications. WPHs improve solubility over a wide range of pH, create viscosity through water binding, and promote cohesion, adhesion, and elasticity. WPHs form stronger but more flexible edible films than WPC or WPI. WPHs enhance emulsification, bind fat, and facilitate whipping, compared to intact WPs. Extensive hydrolyzed WPHs with proper heat applications are the best emulsifiers and addition of polysaccharides improves the emulsification ability of WPHs. Also, WPHs improve the sensorial properties like color, flavor, and texture but impart a bitter taste in case where extensive hydrolysis (degree of hydrolysis greater than 8%). It is important to consider the type of enzyme, hydrolysis conditions, and WPHs production method based on the nature of food application. PMID:26761849

Functional Improvements in Parkinson’s Disease Following a Randomized Trial of Yoga

Directory of Open Access Journals (Sweden)

Marieke Van Puymbroeck

2018-01-01

Full Text Available Individuals with Parkinson’s Disease (PD experience significant limitations in motor function, functional gait, postural stability, and balance. These limitations often lead to higher incidences of falls, which have significant complications for individuals with PD. Yoga may improve these functional deficits in individuals with PD. The objective of this study was to determine changes in motor function, functional gait, postural stability, and balance control for community dwelling individuals with PD. This randomized, wait-list controlled pilot study examined the influence of an 8-week yoga intervention for people with PD who met the following inclusion criteria: endorsing a fear of falling, being able to speak English, scoring 4/6 on the minimental state exam, and being willing to attend the intervention twice weekly for 8-weeks. Participants in the yoga group (n=15 experienced improvements in motor function, postural stability, functional gait, and freezing gait, as well as reductions in fall risk. Participants in the wait-list control (n=12 also significantly improved in postural stability, although their fall risk was not reduced. Individuals in the yoga group significantly reduced their fall risk. An 8-week yoga intervention may reduce fall risk and improve postural stability, and functional and freezing gait in individuals with PD. This clinical trial is registered as protocol record Pro00041068 in clinicaltrials.gov.

Patterns of functional improvement after revision knee arthroplasty.

Science.gov (United States)

Ghomrawi, Hassan M K; Kane, Robert L; Eberly, Lynn E; Bershadsky, Boris; Saleh, Khaled J

2009-12-01

Despite the increase in the number of total knee arthroplasty revisions, outcomes of such surgery and their correlates are poorly understood. The aim of this study was to characterize patterns of functional improvement after revision total knee arthroplasty over a two-year period and to investigate factors that affect such improvement patterns. Three hundred and eight patients in need of revision surgery were enrolled into the study, conducted at seventeen centers, and 221 (71.8%) were followed for two years. Short Form-36 (SF-36), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Lower-Extremity Activity Scale (LEAS) scores were collected at baseline and every six months for two years postoperatively. A piecewise general linear mixed model, which models correlation between repeated measures and estimates separate slopes for different follow-up time periods, was employed to examine functional improvement patterns. Separate regression slopes were estimated for the zero to twelve-month and the twelve to twenty-four-month periods. The slopes for zero to twelve months showed significant improvement in all measures in the first year. The slopes for twelve to twenty-four months showed deterioration in the scores of the WOMAC pain subscale (slope = 0.67 +/- 0.21, p coefficient = -5.46 +/- 1.91, p coefficient = 5.41 +/- 2.35, p coefficient = 1.42 +/- 0.69, p < 0.05]). Factors related to the surgical technique did not predict outcomes. The onset of worsening pain and knee-specific function in the second year following revision total knee arthroplasty indicates the need to closely monitor patients, irrespective of the mode of failure of the primary procedure or the surgical technique for the revision. This information may be especially important for patients with multiple comorbidities.

Kinesthetic taping improves walking function in patients with stroke

DEFF Research Database (Denmark)

Boeskov, Birgitte; Carver, Line Tornehøj; von Essen-Leise, Anders

2014-01-01

BACKGROUND: Stroke is an important cause of severe disability and impaired motor function. Treatment modalities that improve motor function in patients with stroke are needed. The objective of this study was to investigate the effect of kinesthetic taping of the anterior thigh and knee on maximal...... be a valuable adjunct in physical therapy and rehabilitation of patients with stroke....

Computational identification of developmental enhancers:conservation and function of transcription factor binding-site clustersin drosophila melanogaster and drosophila psedoobscura

Energy Technology Data Exchange (ETDEWEB)

Berman, Benjamin P.; Pfeiffer, Barret D.; Laverty, Todd R.; Salzberg, Steven L.; Rubin, Gerald M.; Eisen, Michael B.; Celniker, SusanE.

2004-08-06

The identification of sequences that control transcription in metazoans is a major goal of genome analysis. In a previous study, we demonstrated that searching for clusters of predicted transcription factor binding sites could discover active regulatory sequences, and identified 37 regions of the Drosophila melanogaster genome with high densities of predicted binding sites for five transcription factors involved in anterior-posterior embryonic patterning. Nine of these clusters overlapped known enhancers. Here, we report the results of in vivo functional analysis of 27 remaining clusters. We generated transgenic flies carrying each cluster attached to a basal promoter and reporter gene, and assayed embryos for reporter gene expression. Six clusters are enhancers of adjacent genes: giant, fushi tarazu, odd-skipped, nubbin, squeeze and pdm2; three drive expression in patterns unrelated to those of neighboring genes; the remaining 18 do not appear to have enhancer activity. We used the Drosophila pseudoobscura genome to compare patterns of evolution in and around the 15 positive and 18 false-positive predictions. Although conservation of primary sequence cannot distinguish true from false positives, conservation of binding-site clustering accurately discriminates functional binding-site clusters from those with no function. We incorporated conservation of binding-site clustering into a new genome-wide enhancer screen, and predict several hundred new regulatory sequences, including 85 adjacent to genes with embryonic patterns. Measuring conservation of sequence features closely linked to function--such as binding-site clustering--makes better use of comparative sequence data than commonly used methods that examine only sequence identity.

INR targets and site-level anticoagulation control: results from the Veterans AffaiRs Study to Improve Anticoagulation (VARIA).

Science.gov (United States)

Rose, A J; Berlowitz, D R; Miller, D R; Hylek, E M; Ozonoff, A; Zhao, S; Reisman, J I; Ash, A S

2012-04-01

Not all clinicians target the same International Normalized Ratio (INR) for patients with a guideline-recommended target range of 2-3. A patient's mean INR value suggests the INR that was actually targeted. We hypothesized that sites would vary by mean INR, and that sites of care with mean values nearest to 2.5 would achieve better anticoagulation control, as measured by per cent time in therapeutic range (TTR). To examine variations among sites in mean INR and the relationship with anticoagulation control in an integrated system of care. We studied 103,897 patients receiving oral anticoagulation with an expected INR target between 2 and 3 at 100 Veterans Health Administration (VA) sites from 1 October 2006 to 30 September 2008. Key site-level variables were: proportion near 2.5 (that is, percentage of patients with mean INR between 2.3 and 2.7) and mean risk-adjusted TTR. Site mean INR ranged from 2.22 to 2.89; proportion near 2.5, from 30 to 64%. Sites' proportions of patients near 2.5, below 2.3 and above 2.7 were consistent from year to year. A 10 percentage point increase in the proportion near 2.5 predicted a 3.8 percentage point increase in risk-adjusted TTR (P < 0.001). Proportion of patients with mean INR near 2.5 is a site-level 'signature' of care and an implicit measure of targeted INR. This proportion varies by site and is strongly associated with site-level TTR. Our study suggests that sites wishing to improve TTR, and thereby improve patient outcomes, should avoid the explicit or implicit pursuit of non-standard INR targets. © 2012 International Society on Thrombosis and Haemostasis.

[An oral function improvement program utilizing health behavior theories ameliorates oral functions and oral hygienic conditions of pre-frail elderly persons].

Science.gov (United States)

Sakaguchi, Hideo

2014-06-01

Oral function improvement programs utilizing health behavior theories are considered to be effective in preventing the need for long-term social care. In the present study, an oral function improvement program based upon health behavior theories was designed, and its utility was assessed in 102 pre-frail elderly persons (33 males, 69 females, mean age: 76.9 +/- 5.7) considered to be in potential need of long-term social care and attending a long-term care prevention class in Sayama City, Saitama Prefecture, Japan. The degree of improvement in oral functions (7 items) and oral hygienic conditions (3 items) was assessed by comparing oral health before and after participation in the program. The results showed statistically significant improvements in the following oral functions: (1) lip functions (oral diadochokinesis, measured by the regularity of the repetition of the syllable "Pa"), (2) tongue functions, (3) tongue root motor skills (oral diadochokinesis, measured by the regularity of the repetition of the syllables "Ta" and "Ka"), (4) tongue extension/retraction, (5) side-to-side tongue movement functions, (6) cheek motor skills, and (7) repetitive saliva swallowing test (RSST). The following measures of oral hygiene also showed a statistically significant improvement: (1) debris on dentures or teeth, (2) coated tongue, and (3) frequency of oral cleaning. These findings demonstrated that an improvement program informed by health behavior theories is useful in improving oral functions and oral hygiene conditions.

Site-Specific Incorporation of Functional Components into RNA by an Unnatural Base Pair Transcription System

Directory of Open Access Journals (Sweden)

Rie Kawai

2012-03-01

Full Text Available Toward the expansion of the genetic alphabet, an unnatural base pair between 7-(2-thienylimidazo[4,5-b]pyridine (Ds and pyrrole-2-carbaldehyde (Pa functions as a third base pair in replication and transcription, and provides a useful tool for the site-specific, enzymatic incorporation of functional components into nucleic acids. We have synthesized several modified-Pa substrates, such as alkylamino-, biotin-, TAMRA-, FAM-, and digoxigenin-linked PaTPs, and examined their transcription by T7 RNA polymerase using Ds-containing DNA templates with various sequences. The Pa substrates modified with relatively small functional groups, such as alkylamino and biotin, were efficiently incorporated into RNA transcripts at the internal positions, except for those less than 10 bases from the 3′-terminus. We found that the efficient incorporation into a position close to the 3′-terminus of a transcript depended on the natural base contexts neighboring the unnatural base, and that pyrimidine-Ds-pyrimidine sequences in templates were generally favorable, relative to purine-Ds-purine sequences. The unnatural base pair transcription system provides a method for the site-specific functionalization of large RNA molecules.

Corticosteroid therapy for duchenne muscular dystrophy: improvement of psychomotor function.

Science.gov (United States)

Sato, Yuko; Yamauchi, Akemi; Urano, Mari; Kondo, Eri; Saito, Kayoko

2014-01-01

Of the numerous clinical trials for Duchenne muscular dystrophy, only the corticosteroid prednisolone has shown potential for temporal improvement in motor ability. In this study, the effects of prednisolone on intellectual ability are examined in 29 cases of Duchenne muscular dystrophy because little information has been reported. And also, motor functions and cardiac functions were evaluated. The treated group was administered prednisolone (0.75 mg/kg) orally on alternate days and the compared with the untreated control group. Gene mutations were investigated. The patients were examined for intelligence quotient adequate for age, brain natriuretic peptide, creatine kinase, and manual muscle testing before treatment and after the period 6 months to 2 years. Intelligence quotient scores of the treated increased to 6.5 ± 11.9 (mean ± standard deviation) were compared with the controls 2.1 ± 4.9 (P = 0.009). Intelligence quotient scores of the patients with nonsense point mutations improved significantly (21.0 ± 7.9) more than those with deletion or duplication (1.9 ± 9.0; P = 0.015). Motor function, such as time to stand up, of those treated improved significantly and brain natriuretic peptide level was reduced to a normal level after treatment in 15 patients (73%). Our results demonstrate the effectiveness of prednisolone in improving intellectual impairment as well as in preserving motor function and brain natriuretic peptide levels. We presume that prednisolone has a read-through effect on the stop codons in the central nervous systems of Duchenne muscular dystrophy because intelligence quotient of point mutation case was improved significantly. Copyright © 2014 Elsevier Inc. All rights reserved.

How Can a Ketogenic Diet Improve Motor Function?

Directory of Open Access Journals (Sweden)

Charlotte Veyrat-Durebex

2018-01-01

Full Text Available A ketogenic diet (KD is a normocaloric diet composed by high fat (80–90%, low carbohydrate, and low protein consumption that induces fasting-like effects. KD increases ketone body (KBs production and its concentration in the blood, providing the brain an alternative energy supply that enhances oxidative mitochondrial metabolism. In addition to its profound impact on neuro-metabolism and bioenergetics, the neuroprotective effect of specific polyunsaturated fatty acids and KBs involves pleiotropic mechanisms, such as the modulation of neuronal membrane excitability, inflammation, or reactive oxygen species production. KD is a therapy that has been used for almost a century to treat medically intractable epilepsy and has been increasingly explored in a number of neurological diseases. Motor function has also been shown to be improved by KD and/or medium-chain triglyceride diets in rodent models of Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and spinal cord injury. These studies have proposed that KD may induce a modification in synaptic morphology and function, involving ionic channels, glutamatergic transmission, or synaptic vesicular cycling machinery. However, little is understood about the molecular mechanisms underlying the impact of KD on motor function and the perspectives of its use to acquire the neuromuscular effects. The aim of this review is to explore the conditions through which KD might improve motor function. First, we will describe the main consequences of KD exposure in tissues involved in motor function. Second, we will report and discuss the relevance of KD in pre-clinical and clinical trials in the major diseases presenting motor dysfunction.

FES-assisted Cycling Improves Aerobic Capacity and Locomotor Function Postcerebrovascular Accident.

Science.gov (United States)

Aaron, Stacey E; Vanderwerker, Catherine J; Embry, Aaron E; Newton, Jennifer H; Lee, Samuel C K; Gregory, Chris M

2018-03-01

After a cerebrovascular accident (CVA) aerobic deconditioning contributes to diminished physical function. Functional electrical stimulation (FES)-assisted cycling is a promising exercise paradigm designed to target both aerobic capacity and locomotor function. This pilot study aimed to evaluate the effects of an FES-assisted cycling intervention on aerobic capacity and locomotor function in individuals post-CVA. Eleven individuals with chronic (>6 months) post-CVA hemiparesis completed an 8-wk (three times per week; 24 sessions) progressive FES-assisted cycling intervention. V˙O2peak, self-selected, and fastest comfortable walking speeds, gait, and pedaling symmetry, 6-min walk test (6MWT), balance, dynamic gait movements, and health status were measured at baseline and posttraining. Functional electrical stimulation-assisted cycling significantly improved V˙O2peak (12%, P = 0.006), self-selected walking speed (SSWS, 0.05 ± 0.1 m·s, P = 0.04), Activities-specific Balance Confidence scale score (12.75 ± 17.4, P = 0.04), Berg Balance Scale score (3.91 ± 4.2, P = 0.016), Dynamic Gait Index score (1.64 ± 1.4, P = 0.016), and Stroke Impact Scale participation/role domain score (12.74 ± 16.7, P = 0.027). Additionally, pedal symmetry, represented by the paretic limb contribution to pedaling (paretic pedaling ratio [PPR]) significantly improved (10.09% ± 9.0%, P = 0.016). Although step length symmetry (paretic step ratio [PSR]) did improve, these changes were not statistically significant (-0.05% ± 0.1%, P = 0.09). Exploratory correlations showed moderate association between change in SSWS and 6-min walk test (r = 0.74), and moderate/strong negative association between change in PPR and PSR. These results support FES-assisted cycling as a means to improve both aerobic capacity and locomotor function. Improvements in SSWS, balance, dynamic walking movements, and participation in familial and societal roles are important targets for rehabilitation of individuals

Sleep extension improves neurocognitive functions in chronically sleep-deprived obese individuals.

Directory of Open Access Journals (Sweden)

Eliane A Lucassen

Full Text Available Sleep deprivation and obesity, are associated with neurocognitive impairments. Effects of sleep deprivation and obesity on cognition are unknown, and the cognitive long-term effects of improvement of sleep have not been prospectively assessed in short sleeping, obese individuals.To characterize neurocognitive functions and assess its reversibility.Prospective cohort study.Tertiary Referral Research Clinical Center.A cohort of 121 short-sleeping (<6.5 h/night obese (BMI 30-55 kg/m(2 men and pre-menopausal women.Sleep extension (468±88 days with life-style modifications.Neurocognitive functions, sleep quality and sleep duration.At baseline, 44% of the individuals had an impaired global deficit score (t-score 0-39. Impaired global deficit score was associated with worse subjective sleep quality (p = 0.02, and lower urinary dopamine levels (p = 0.001. Memory was impaired in 33%; attention in 35%; motor skills in 42%; and executive function in 51% of individuals. At the final evaluation (N = 74, subjective sleep quality improved by 24% (p<0.001, self-reported sleep duration increased by 11% by questionnaires (p<0.001 and by 4% by diaries (p = 0.04, and daytime sleepiness tended to improve (p = 0.10. Global cognitive function and attention improved by 7% and 10%, respectively (both p = 0.001, and memory and executive functions tended to improve (p = 0.07 and p = 0.06. Serum cortisol increased by 17% (p = 0.02. In a multivariate mixed model, subjective sleep quality and sleep efficiency, urinary free cortisol and dopamine and plasma total ghrelin accounted for 1/5 of the variability in global cognitive function.Drop-out rate.Chronically sleep-deprived obese individuals exhibit substantial neurocognitive deficits that are partially reversible upon improvement of sleep in a non-pharmacological way. These findings have clinical implications for large segments of the US population.www.ClinicalTrials.gov NCT00261898

Breaking bad habits by improving executive function in individuals with obesity.

Science.gov (United States)

Allom, Vanessa; Mullan, Barbara; Smith, Evelyn; Hay, Phillipa; Raman, Jayanthi

2018-04-16

Two primary factors that contribute to obesity are unhealthy eating and sedentary behavior. These behaviors are particularly difficult to change in the long-term because they are often enacted habitually. Cognitive Remediation Therapy has been modified and applied to the treatment of obesity (CRT-O) with preliminary results of a randomized controlled trial demonstrating significant weight loss and improvements in executive function. The objective of this study was to conduct a secondary data analysis of the CRT-O trial to evaluate whether CRT-O reduces unhealthy habits that contribute to obesity via improvements in executive function. Eighty participants with obesity were randomized to CRT-O or control. Measures of executive function (Wisconsin Card Sort Task and Trail Making Task) and unhealthy eating and sedentary behavior habits were administered at baseline, post-intervention and at 3 month follow-up. Participants receiving CRT-O demonstrated improvements in both measures of executive function and reductions in both unhealthy habit outcomes compared to control. Mediation analyses revealed that change in one element of executive function performance (Wisconsin Card Sort Task perseverance errors) mediated the effect of CRT-O on changes in both habit outcomes. These results suggest that the effectiveness of CRT-O may result from the disruption of unhealthy habits made possible by improvements in executive function. In particular, it appears that cognitive flexibility, as measured by the Wisconsin Card Sort task, is a key mechanism in this process. Improving cognitive flexibility may enable individuals to capitalise on interruptions in unhealthy habits by adjusting their behavior in line with their weight loss goals rather than persisting with an unhealthy choice. The RCT was registered with the Australian New Zealand Registry of Clinical Trials (trial id: ACTRN12613000537752 ).

Genome-wide screens for in vivo Tinman binding sites identify cardiac enhancers with diverse functional architectures.

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Hong Jin

Full Text Available The NK homeodomain factor Tinman is a crucial regulator of early mesoderm patterning and, together with the GATA factor Pannier and the Dorsocross T-box factors, serves as one of the key cardiogenic factors during specification and differentiation of heart cells. Although the basic framework of regulatory interactions driving heart development has been worked out, only about a dozen genes involved in heart development have been designated as direct Tinman target genes to date, and detailed information about the functional architectures of their cardiac enhancers is lacking. We have used immunoprecipitation of chromatin (ChIP from embryos at two different stages of early cardiogenesis to obtain a global overview of the sequences bound by Tinman in vivo and their linked genes. Our data from the analysis of ~50 sequences with high Tinman occupancy show that the majority of such sequences act as enhancers in various mesodermal tissues in which Tinman is active. All of the dorsal mesodermal and cardiac enhancers, but not some of the others, require tinman function. The cardiac enhancers feature diverse arrangements of binding motifs for Tinman, Pannier, and Dorsocross. By employing these cardiac and non-cardiac enhancers in machine learning approaches, we identify a novel motif, termed CEE, as a classifier for cardiac enhancers. In vivo assays for the requirement of the binding motifs of Tinman, Pannier, and Dorsocross, as well as the CEE motifs in a set of cardiac enhancers, show that the Tinman sites are essential in all but one of the tested enhancers; although on occasion they can be functionally redundant with Dorsocross sites. The enhancers differ widely with respect to their requirement for Pannier, Dorsocross, and CEE sites, which we ascribe to their different position in the regulatory circuitry, their distinct temporal and spatial activities during cardiogenesis, and functional redundancies among different factor binding sites.

SiteBinder: an improved approach for comparing multiple protein structural motifs.

Science.gov (United States)

Sehnal, David; Vařeková, Radka Svobodová; Huber, Heinrich J; Geidl, Stanislav; Ionescu, Crina-Maria; Wimmerová, Michaela; Koča, Jaroslav

2012-02-27

There is a paramount need to develop new techniques and tools that will extract as much information as possible from the ever growing repository of protein 3D structures. We report here on the development of a software tool for the multiple superimposition of large sets of protein structural motifs. Our superimposition methodology performs a systematic search for the atom pairing that provides the best fit. During this search, the RMSD values for all chemically relevant pairings are calculated by quaternion algebra. The number of evaluated pairings is markedly decreased by using PDB annotations for atoms. This approach guarantees that the best fit will be found and can be applied even when sequence similarity is low or does not exist at all. We have implemented this methodology in the Web application SiteBinder, which is able to process up to thousands of protein structural motifs in a very short time, and which provides an intuitive and user-friendly interface. Our benchmarking analysis has shown the robustness, efficiency, and versatility of our methodology and its implementation by the successful superimposition of 1000 experimentally determined structures for each of 32 eukaryotic linear motifs. We also demonstrate the applicability of SiteBinder using three case studies. We first compared the structures of 61 PA-IIL sugar binding sites containing nine different sugars, and we found that the sugar binding sites of PA-IIL and its mutants have a conserved structure despite their binding different sugars. We then superimposed over 300 zinc finger central motifs and revealed that the molecular structure in the vicinity of the Zn atom is highly conserved. Finally, we superimposed 12 BH3 domains from pro-apoptotic proteins. Our findings come to support the hypothesis that there is a structural basis for the functional segregation of BH3-only proteins into activators and enablers.

Constraint-Induced Movement Therapy Combined with Transcranial Direct Current Stimulation over Premotor Cortex Improves Motor Function in Severe Stroke: A Pilot Randomized Controlled Trial

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Suellen M. Andrade

2017-01-01

Full Text Available Objective. We compared the effects of transcranial direct current stimulation at different cortical sites (premotor and motor primary cortex combined with constraint-induced movement therapy for treatment of stroke patients. Design. Sixty patients were randomly distributed into 3 groups: Group A, anodal stimulation on premotor cortex and constraint-induced movement therapy; Group B, anodal stimulation on primary motor cortex and constraint-induced movement therapy; Group C, sham stimulation and constraint-induced movement therapy. Evaluations involved analysis of functional independence, motor recovery, spasticity, gross motor function, and muscle strength. Results. A significant improvement in primary outcome (functional independence after treatment in the premotor group followed by primary motor group and sham group was observed. The same pattern of improvement was highlighted among all secondary outcome measures regarding the superior performance of the premotor group over primary motor and sham groups. Conclusions. Premotor cortex can contribute to motor function in patients with severe functional disabilities in early stages of stroke. This study was registered in ClinicalTrials.gov database (NCT 02628561.

Adaptation and impairment of DNA repair function in pollen of Betula verrucosa and seeds of Oenothera biennis from differently radionuclide-contaminated sites of Chernobyl.

Science.gov (United States)

Boubriak, I I; Grodzinsky, D M; Polischuk, V P; Naumenko, V D; Gushcha, N P; Micheev, A N; McCready, S J; Osborne, D J

2008-01-01

The plants that have remained in the contaminated areas around Chernobyl since 1986 encapsulate the effects of radiation. Such plants are chronically exposed to radionuclides that they have accumulated internally as well as to alpha-, beta- and gamma-emitting radionuclides from external sources and from the soil. This radiation leads to genetic damage that can be countered by DNA repair systems. The objective of this study is to follow DNA repair and adaptation in haploid cells (birch pollen) and diploid cells (seed embryos of the evening primrose) from plants that have been growing in situ in different radionuclide fall-out sites in monitored regions surrounding the Chernobyl explosion of 1986. Radionuclide levels in soil were detected using gamma-spectroscopy and radiochemistry. DNA repair assays included measurement of unscheduled DNA synthesis, electrophoretic determination of single-strand DNA breaks and image analysis of rDNA repeats after repair intervals. Nucleosome levels were established using an ELISA kit. Birch pollen collected in 1987 failed to perform unscheduled DNA synthesis, but pollen at gamma/beta-emitter sites has now recovered this ability. At a site with high levels of combined alpha- and gamma/beta-emitters, pollen still exhibits hidden damage, as shown by reduced unscheduled DNA synthesis and failure to repair lesions in rDNA repeats properly. Evening primrose seed embryos generated on plants at the same gamma/beta-emitter sites now show an improved DNA repair capacity and ability to germinate under abiotic stresses (salinity and accelerated ageing). Again those from combined alpha- and gamma/beta-contaminated site do not show this improvement. Chronic irradiation at gamma/beta-emitter sites has provided opportunities for plant cells (both pollen and embryo cells) to adapt to ionizing irradiation and other environmental stresses. This may be explained by facilitation of DNA repair function.

Improvements MOIRA system for application to nuclear sites Spanish river

International Nuclear Information System (INIS)

Gallego Diaz, E.; Iglesias Ferrer, R.; Dvorzhak, A.; Hofman, D.

2011-01-01

Possible consequences of a nuclear accident must have radioactive contamination in the medium and long-term freshwater aquatic systems. Faced with this problem, it is essential to have a realistic assessment of the radiological impact, ecological, social and economic potential management strategies, to take the best decisions rationally. MOIRA is a system of decision support developed in the course of the European Framework Programmes with participation of the UPM, which has been improved and adapted to Spanish nuclear sites in recent years in the context ISIDRO Project, sponsored by the Council Nuclear, with the participation of CIEMAT and UPM. The paper focuses on these advances, primarily related to complex hydraulic systems such as rivers Tajo, Ebro and Jucar, which are located several Spanish plants.

Using Operational Analysis to Improve Access to Pulmonary Function Testing

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Ada Ip

2016-01-01

Full Text Available Background. Timely pulmonary function testing is crucial to improving diagnosis and treatment of pulmonary diseases. Perceptions of poor access at an academic pulmonary function laboratory prompted analysis of system demand and capacity to identify factors contributing to poor access. Methods. Surveys and interviews identified stakeholder perspectives on operational processes and access challenges. Retrospective data on testing demand and resource capacity was analyzed to understand utilization of testing resources. Results. Qualitative analysis demonstrated that stakeholder groups had discrepant views on access and capacity in the laboratory. Mean daily resource utilization was 0.64 (SD 0.15, with monthly average utilization consistently less than 0.75. Reserved testing slots for subspecialty clinics were poorly utilized, leaving many testing slots unfilled. When subspecialty demand exceeded number of reserved slots, there was sufficient capacity in the pulmonary function schedule to accommodate added demand. Findings were shared with stakeholders and influenced scheduling process improvements. Conclusion. This study highlights the importance of operational data to identify causes of poor access, guide system decision-making, and determine effects of improvement initiatives in a variety of healthcare settings. Importantly, simple operational analysis can help to improve efficiency of health systems with little or no added financial investment.

Prediction of FAD binding sites in electron transport proteins according to efficient radial basis function networks and significant amino acid pairs.

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Le, Nguyen-Quoc-Khanh; Ou, Yu-Yen

2016-07-30

Cellular respiration is a catabolic pathway for producing adenosine triphosphate (ATP) and is the most efficient process through which cells harvest energy from consumed food. When cells undergo cellular respiration, they require a pathway to keep and transfer electrons (i.e., the electron transport chain). Due to oxidation-reduction reactions, the electron transport chain produces a transmembrane proton electrochemical gradient. In case protons flow back through this membrane, this mechanical energy is converted into chemical energy by ATP synthase. The convert process is involved in producing ATP which provides energy in a lot of cellular processes. In the electron transport chain process, flavin adenine dinucleotide (FAD) is one of the most vital molecules for carrying and transferring electrons. Therefore, predicting FAD binding sites in the electron transport chain is vital for helping biologists understand the electron transport chain process and energy production in cells. We used an independent data set to evaluate the performance of the proposed method, which had an accuracy of 69.84 %. We compared the performance of the proposed method in analyzing two newly discovered electron transport protein sequences with that of the general FAD binding predictor presented by Mishra and Raghava and determined that the accuracy of the proposed method improved by 9-45 % and its Matthew's correlation coefficient was 0.14-0.5. Furthermore, the proposed method enabled reducing the number of false positives significantly and can provide useful information for biologists. We developed a method that is based on PSSM profiles and SAAPs for identifying FAD binding sites in newly discovered electron transport protein sequences. This approach achieved a significant improvement after we added SAAPs to PSSM features to analyze FAD binding proteins in the electron transport chain. The proposed method can serve as an effective tool for predicting FAD binding sites in electron

Sleep extension improves neurocognitive functions in chronically sleep-deprived obese individuals.

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Lucassen, Eliane A; Piaggi, Paolo; Dsurney, John; de Jonge, Lilian; Zhao, Xiong-ce; Mattingly, Megan S; Ramer, Angela; Gershengorn, Janet; Csako, Gyorgy; Cizza, Giovanni

2014-01-01

Sleep deprivation and obesity, are associated with neurocognitive impairments. Effects of sleep deprivation and obesity on cognition are unknown, and the cognitive long-term effects of improvement of sleep have not been prospectively assessed in short sleeping, obese individuals. To characterize neurocognitive functions and assess its reversibility. Prospective cohort study. Tertiary Referral Research Clinical Center. A cohort of 121 short-sleeping (Sleep extension (468±88 days) with life-style modifications. Neurocognitive functions, sleep quality and sleep duration. At baseline, 44% of the individuals had an impaired global deficit score (t-score 0-39). Impaired global deficit score was associated with worse subjective sleep quality (p = 0.02), and lower urinary dopamine levels (p = 0.001). Memory was impaired in 33%; attention in 35%; motor skills in 42%; and executive function in 51% of individuals. At the final evaluation (N = 74), subjective sleep quality improved by 24% (psleep duration increased by 11% by questionnaires (pattention improved by 7% and 10%, respectively (both p = 0.001), and memory and executive functions tended to improve (p = 0.07 and p = 0.06). Serum cortisol increased by 17% (p = 0.02). In a multivariate mixed model, subjective sleep quality and sleep efficiency, urinary free cortisol and dopamine and plasma total ghrelin accounted for 1/5 of the variability in global cognitive function. Drop-out rate. Chronically sleep-deprived obese individuals exhibit substantial neurocognitive deficits that are partially reversible upon improvement of sleep in a non-pharmacological way. These findings have clinical implications for large segments of the US population. www.ClinicalTrials.gov NCT00261898. NIDDK protocol 06-DK-0036.

Resveratrol: A Multifunctional Compound Improving Endothelial Function

OpenAIRE

Li, Huige; F?rstermann, Ulrich

2009-01-01

The red wine polyphenol resveratrol boosts endothelium-dependent and -independent vasorelaxations. The improvement of endothelial function by resveratrol is largely attributable to nitric oxide (NO) derived from endothelial NO synthase (eNOS). By stimulating eNOS expression, eNOS phosphorylation and eNOS deacetylation, resveratrol enhances endothelial NO production. By upregulating antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) and suppressing the expression a...

Structural and Functional Consequences of Chaperone Site Deletion in αA-Crystallin

Science.gov (United States)

Santhoshkumar, Puttur; Karmakar, Srabani; Sharma, Krishna K.

2016-01-01

The chaperone-like activity of αA-crystallin has an important role in maintaining lens transparency. Previously we identified residues 70–88 as a chaperone site in αA-crystallin. In this study, we deleted the chaperone site residues to generate αAΔ70–76 and αAΔ70–88 mutants and investigated if there are additional substrate-binding sites in αA-crystallin. Both mutant proteins when expressed in E. coli formed inclusion bodies, and on solubilizing and refolding, they exhibited similar structural properties, with a 2- to 3-fold increase in molar mass compared to the molar mass of wild-type protein. The deletion mutants were less stable than the wild-type αA-crystallin. Functionally αAΔ70–88 was completely inactive as a chaperone, while αAΔ70–76 demonstrated a 40–50% reduction in anti-aggregation activity against alcohol dehydrogenase (ADH). Deletion of residues 70–88 abolished the ADH binding sites in αA-crystallin at physiological temperature. At 45 °C, cryptic ADH binding site(s) became exposed, which contributed subtly to the chaperone-like activity of αAΔ70–88. Both of the deletion mutants were completely inactive in suppressing aggregation of βL-crystallin at 53 °C. The mutants completely lost the anti-apoptotic property that αA-crystallin exhibits while they protected ARPE-19 (a human retinal pigment epithelial cell line) and primary human lens epithelial (HLE) cells from oxidative stress. Our studies demonstrate that residues 70–88 in αA-crystallin act as a primary substrate binding site and account for the bulk of the total chaperone activity. The β3 and β4 strands in αA-crystallin comprising 70–88 residues play an important role in maintenance of the structure and in preventing aggregation of denaturing proteins. PMID:27524665

Resistance training improves muscle strength and functional capacity in multiple sclerosis

DEFF Research Database (Denmark)

Dalgas, U; Stenager, E; Jakobsen, J

2009-01-01

strength and functional capacity in patients with multiple sclerosis, the effects persisting after 12 weeks of self-guided physical activity. Level of evidence: The present study provides level III evidence supporting the hypothesis that lower extremity progressive resistance training can improve muscle......OBJECTIVE: To test the hypothesis that lower extremity progressive resistance training (PRT) can improve muscle strength and functional capacity in patients with multiple sclerosis (MS) and to evaluate whether the improvements are maintained after the trial. METHODS: The present study was a 2-arm...... and was afterward encouraged to continue training. After the trial, the control group completed the PRT intervention. Both groups were tested before and after 12 weeks of the trial and at 24 weeks (follow-up), where isometric muscle strength of the knee extensors (KE MVC) and functional capacity (FS; combined score...

Structural Fingerprints of Transcription Factor Binding Site Regions

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Peter Willett

2009-03-01

Full Text Available Fourier transforms are a powerful tool in the prediction of DNA sequence properties, such as the presence/absence of codons. We have previously compiled a database of the structural properties of all 32,896 unique DNA octamers. In this work we apply Fourier techniques to the analysis of the structural properties of human chromosomes 21 and 22 and also to three sets of transcription factor binding sites within these chromosomes. We find that, for a given structural property, the structural property power spectra of chromosomes 21 and 22 are strikingly similar. We find common peaks in their power spectra for both Sp1 and p53 transcription factor binding sites. We use the power spectra as a structural fingerprint and perform similarity searching in order to find transcription factor binding site regions. This approach provides a new strategy for searching the genome data for information. Although it is difficult to understand the relationship between specific functional properties and the set of structural parameters in our database, our structural fingerprints nevertheless provide a useful tool for searching for function information in sequence data. The power spectrum fingerprints provide a simple, fast method for comparing a set of functional sequences, in this case transcription factor binding site regions, with the sequences of whole chromosomes. On its own, the power spectrum fingerprint does not find all transcription factor binding sites in a chromosome, but the results presented here show that in combination with other approaches, this technique will improve the chances of identifying functional sequences hidden in genomic data.

An improved method for estimating the frequency correlation function

KAUST Repository

Chelli, Ali; Pä tzold, Matthias

2012-01-01

For time-invariant frequency-selective channels, the transfer function is a superposition of waves having different propagation delays and path gains. In order to estimate the frequency correlation function (FCF) of such channels, the frequency averaging technique can be utilized. The obtained FCF can be expressed as a sum of auto-terms (ATs) and cross-terms (CTs). The ATs are caused by the autocorrelation of individual path components. The CTs are due to the cross-correlation of different path components. These CTs have no physical meaning and leads to an estimation error. We propose a new estimation method aiming to improve the estimation accuracy of the FCF of a band-limited transfer function. The basic idea behind the proposed method is to introduce a kernel function aiming to reduce the CT effect, while preserving the ATs. In this way, we can improve the estimation of the FCF. The performance of the proposed method and the frequency averaging technique is analyzed using a synthetically generated transfer function. We show that the proposed method is more accurate than the frequency averaging technique. The accurate estimation of the FCF is crucial for the system design. In fact, we can determine the coherence bandwidth from the FCF. The exact knowledge of the coherence bandwidth is beneficial in both the design as well as optimization of frequency interleaving and pilot arrangement schemes. © 2012 IEEE.

An improved method for estimating the frequency correlation function

KAUST Repository

Chelli, Ali

2012-04-01

For time-invariant frequency-selective channels, the transfer function is a superposition of waves having different propagation delays and path gains. In order to estimate the frequency correlation function (FCF) of such channels, the frequency averaging technique can be utilized. The obtained FCF can be expressed as a sum of auto-terms (ATs) and cross-terms (CTs). The ATs are caused by the autocorrelation of individual path components. The CTs are due to the cross-correlation of different path components. These CTs have no physical meaning and leads to an estimation error. We propose a new estimation method aiming to improve the estimation accuracy of the FCF of a band-limited transfer function. The basic idea behind the proposed method is to introduce a kernel function aiming to reduce the CT effect, while preserving the ATs. In this way, we can improve the estimation of the FCF. The performance of the proposed method and the frequency averaging technique is analyzed using a synthetically generated transfer function. We show that the proposed method is more accurate than the frequency averaging technique. The accurate estimation of the FCF is crucial for the system design. In fact, we can determine the coherence bandwidth from the FCF. The exact knowledge of the coherence bandwidth is beneficial in both the design as well as optimization of frequency interleaving and pilot arrangement schemes. © 2012 IEEE.

Improving the corrosion resistance of proton exchange membrane fuel cell carbon supports by pentafluorophenyl surface functionalization

Science.gov (United States)

Forouzandeh, Farisa; Li, Xiaoan; Banham, Dustin W.; Feng, Fangxia; Joseph Kakanat, Abraham; Ye, Siyu; Birss, Viola

2018-02-01

In this study, the effect of surface functionalization on the electrochemical corrosion resistance of a high surface area, mesoporous colloid imprinted carbon powder (CIC), as well as microporous Vulcan carbon (VC, serving as the benchmark), was demonstrated, primarily for PEM fuel cell applications. CIC-22, which is highly hydrophilic and was synthesized with 22 nm silica colloid templates, and as-received, mildly hydrophobic, VC powders, were functionalized with 2,3,4,5,6-pentafluorophenyl (-PhF5) surface groups using a straightforward diazonium reduction reaction. These carbons were then subjected to corrosion testing, involving a potential cycling-step sequence in room temperature 0.5 M H2SO4. Using cyclic voltammetry and charge/time analysis, the double layer and pseudo-capacitive gravimetric charges of the carbons, prior to and after the application of these potential steps, were tracked in order to obtain information about surface area changes and the extent of carbon oxidation, respectively. It is shown that the corrosion resistance was improved by ca. 50-80% by surface functionalization, likely due to a combination of surface passivation (loss of carbon active sites) and increased surface hydrophobicity.

Inducible activation of ERK5 MAP kinase enhances adult neurogenesis in the olfactory bulb and improves olfactory function.

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Wang, Wenbin; Lu, Song; Li, Tan; Pan, Yung-Wei; Zou, Junhui; Abel, Glen M; Xu, Lihong; Storm, Daniel R; Xia, Zhengui

2015-05-20

Recent discoveries have suggested that adult neurogenesis in the subventricular zone (SVZ) and olfactory bulb (OB) may be required for at least some forms of olfactory behavior in mice. However, it is unclear whether conditional and selective enhancement of adult neurogenesis by genetic approaches is sufficient to improve olfactory function under physiological conditions or after injury. Furthermore, specific signaling mechanisms regulating adult neurogenesis in the SVZ/OB are not fully defined. We previously reported that ERK5, a MAP kinase selectively expressed in the neurogenic regions of the adult brain, plays a critical role in adult neurogenesis in the SVZ/OB. Using a site-specific knock-in mouse model, we report here that inducible and targeted activation of the endogenous ERK5 in adult neural stem/progenitor cells enhances adult neurogenesis in the OB by increasing cell survival and neuronal differentiation. This conditional ERK5 activation also improves short-term olfactory memory and odor-cued associative olfactory learning under normal physiological conditions. Furthermore, these mice show enhanced recovery of olfactory function and have more adult-born neurons after a zinc sulfate-induced lesion of the main olfactory epithelium. We conclude that ERK5 MAP kinase is an important endogenous signaling pathway regulating adult neurogenesis in the SVZ/OB, and that conditional activation of endogenous ERK5 is sufficient to enhance adult neurogenesis in the OB thereby improving olfactory function both under normal conditions and after injury. Copyright © 2015 the authors 0270-6474/15/357833-17$15.00/0.

Granulocyte Colony-Stimulating Factor Combined with Methylprednisolone Improves Functional Outcomes in Rats with Experimental Acute Spinal Cord Injury

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William Gemio Jacobsen Teixeira

2018-02-01

Full Text Available OBJECTIVES: To evaluate the effects of combined treatment with granulocyte colony-stimulating factor (G-CSF and methylprednisolone in rats subjected to experimental spinal cord injury. METHODS: Forty Wistar rats received a moderate spinal cord injury and were divided into four groups: control (no treatment; G-CSF (G-CSF at the time of injury and daily over the next five days; methylprednisolone (methylprednisolone for 24 h; and G-CSF/Methylprednisolone (methylprednisolone for 24 h and G-CSF at the time of injury and daily over the next five days. Functional evaluation was performed using the Basso, Beattie and Bresnahan score on days 2, 7, 14, 21, 28, 35 and 42 following injury. Motor-evoked potentials were evaluated. Histological examination of the spinal cord lesion was performed immediately after euthanasia on day 42. RESULTS: Eight animals were excluded (2 from each group due to infection, a normal Basso, Beattie and Bresnahan score at their first evaluation, or autophagy, and 32 were evaluated. The combination of methylprednisolone and G-CSF promoted greater functional improvement than methylprednisolone or G-CSF alone (p<0.001. This combination also exhibited a synergistic effect, with improvements in hyperemia and cellular infiltration at the injury site (p<0.001. The groups displayed no neurophysiological differences (latency p=0.85; amplitude p=0.75. CONCLUSION: Methylprednisolone plus G-CSF promotes functional and histological improvements superior to those achieved by either of these drugs alone when treating spinal cord contusion injuries in rats. Combining the two drugs did have a synergistic effect.

A three-dimensional model of mammalian tyrosinase active site accounting for loss of function mutations.

Science.gov (United States)

Schweikardt, Thorsten; Olivares, Concepción; Solano, Francisco; Jaenicke, Elmar; García-Borrón, José Carlos; Decker, Heinz

2007-10-01

Tyrosinases are the first and rate-limiting enzymes in the synthesis of melanin pigments responsible for colouring hair, skin and eyes. Mutation of tyrosinases often decreases melanin production resulting in albinism, but the effects are not always understood at the molecular level. Homology modelling of mouse tyrosinase based on recently published crystal structures of non-mammalian tyrosinases provides an active site model accounting for loss-of-function mutations. According to the model, the copper-binding histidines are located in a helix bundle comprising four densely packed helices. A loop containing residues M374, S375 and V377 connects the CuA and CuB centres, with the peptide oxygens of M374 and V377 serving as hydrogen acceptors for the NH-groups of the imidazole rings of the copper-binding His367 and His180. Therefore, this loop is essential for the stability of the active site architecture. A double substitution (374)MS(375) --> (374)GG(375) or a single M374G mutation lead to a local perturbation of the protein matrix at the active site affecting the orientation of the H367 side chain, that may be unable to bind CuB reliably, resulting in loss of activity. The model also accounts for loss of function in two naturally occurring albino mutations, S380P and V393F. The hydroxyl group in S380 contributes to the correct orientation of M374, and the substitution of V393 for a bulkier phenylalanine sterically impedes correct side chain packing at the active site. Therefore, our model explains the mechanistic necessity for conservation of not only active site histidines but also adjacent amino acids in tyrosinase.

The HIVToolbox 2 web system integrates sequence, structure, function and mutation analysis.

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David P Sargeant

Full Text Available There is enormous interest in studying HIV pathogenesis for improving the treatment of patients with HIV infection. HIV infection has become one of the best-studied systems for understanding how a virus can hijack a cell. To help facilitate discovery, we previously built HIVToolbox, a web system for visual data mining. The original HIVToolbox integrated information for HIV protein sequence, structure, functional sites, and sequence conservation. This web system has been used for almost 40,000 searches. We report improvements to HIVToolbox including new functions and workflows, data updates, and updates for ease of use. HIVToolbox2, is an improvement over HIVToolbox with new functions. HIVToolbox2 has new functionalities focused on HIV pathogenesis including drug-binding sites, drug-resistance mutations, and immune epitopes. The integrated, interactive view enables visual mining to generate hypotheses that are not readily revealed by other approaches. Most HIV proteins form multimers, and there are posttranslational modification and protein-protein interaction sites at many of these multimerization interfaces. Analysis of protease drug binding sites reveals an anatomy of drug resistance with different types of drug-resistance mutations regionally localized on the surface of protease. Some of these drug-resistance mutations have a high prevalence in specific HIV-1 M subtypes. Finally, consolidation of Tat functional sites reveals a hotspot region where there appear to be 30 interactions or posttranslational modifications. A cursory analysis with HIVToolbox2 has helped to identify several global patterns for HIV proteins. An initial analysis with this tool identifies homomultimerization of almost all HIV proteins, functional sites that overlap with multimerization sites, a global drug resistance anatomy for HIV protease, and specific distributions of some DRMs in specific HIV M subtypes. HIVToolbox2 is an open-access web application available at

Two site spin correlation function in Bethe-Peierls approximation for Ising model

Energy Technology Data Exchange (ETDEWEB)

Kumar, D [Roorkee Univ. (India). Dept. of Physics

1976-07-01

Two site spin correlation function for an Ising model above Curie temperature has been calculated by generalising Bethe-Peierls approximation. The results derived by a graphical method due to Englert are essentially the same as those obtained earlier by Elliott and Marshall, and Oguchi and Ono. The earlier results were obtained by a direct generalisation of the cluster method of Bethe, while these results are derived by retaining that class of diagrams , which is exact on Bethe lattice.

Improve the functional status of students using the proposed method recovery

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Evtukh M.I.

2012-12-01

Full Text Available Purpose - to improve the organizational and methodological foundations of physical education for the improvement of high school students in training. The study involved 152 students of the second year of the International Economics and Humanities University named after Stepan Demyanchuk. Students were divided into control (n = 76 and primary (n = 76 groups, which were similar in age and physical development. At the end of the study, through the application of the proposed technique improvement in students the core group, was able to restore the function of the respiratory and cardiovascular systems to the possibilities of healthy untrained people. A similar increase in the functionality of the core group of students registered with the definition of the index Skibinski - held a combined evaluation of functions of the respiratory and cardiovascular systems of students and determine its growth with satisfactory to good level.

UET: a database of evolutionarily-predicted functional determinants of protein sequences that cluster as functional sites in protein structures.

Science.gov (United States)

Lua, Rhonald C; Wilson, Stephen J; Konecki, Daniel M; Wilkins, Angela D; Venner, Eric; Morgan, Daniel H; Lichtarge, Olivier

2016-01-04

The structure and function of proteins underlie most aspects of biology and their mutational perturbations often cause disease. To identify the molecular determinants of function as well as targets for drugs, it is central to characterize the important residues and how they cluster to form functional sites. The Evolutionary Trace (ET) achieves this by ranking the functional and structural importance of the protein sequence positions. ET uses evolutionary distances to estimate functional distances and correlates genotype variations with those in the fitness phenotype. Thus, ET ranks are worse for sequence positions that vary among evolutionarily closer homologs but better for positions that vary mostly among distant homologs. This approach identifies functional determinants, predicts function, guides the mutational redesign of functional and allosteric specificity, and interprets the action of coding sequence variations in proteins, people and populations. Now, the UET database offers pre-computed ET analyses for the protein structure databank, and on-the-fly analysis of any protein sequence. A web interface retrieves ET rankings of sequence positions and maps results to a structure to identify functionally important regions. This UET database integrates several ways of viewing the results on the protein sequence or structure and can be found at http://mammoth.bcm.tmc.edu/uet/. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

The Importance of Social Cognition in Improving Functional Outcomes in Schizophrenia

Science.gov (United States)

Javed, Afzal; Charles, Asha

2018-01-01

Social cognition has become recognized as an important driver of functional outcomes and overall recovery in patients with schizophrenia, mediating the relationship between neurocognition and social functioning. Since antipsychotic therapy targeting remission of clinical symptoms has been shown to have a limited impact on social cognition, there has been an increasing drive to develop therapeutic strategies to specifically improve social cognition in schizophrenia. We sought to review current evidence relating to social cognition in schizophrenia and its clinical implications, including interventions designed to target the core domains of social cognition (emotion processing, theory of mind, attributional bias, and social perception) as a means of improving functional outcomes and thereby increasing the likelihood of recovery. Relevant articles were identified by conducting a literature search in PubMed using the search terms “schizophrenia” AND “cognition” AND “social functioning,” limited to Title/Abstract, over a time period of the past 10 years. Current evidence demonstrates that schizophrenia is associated with impairments in all four core domains of social cognition, during the pre-first-episode, first-episode, early, and chronic phases of the disease, and that such impairments are important determinants of functional outcome. Interventions targeting the four core domains of social cognition comprise psychosocial approaches (social cognition training programs) and pharmacological therapies. Social cognition training programs targeting multiple and specific core domains of social cognition have shown promise in improving social cognition skills, which, in some cases, has translated into improvements in functional outcomes. Use of some psychosocial interventions has additionally resulted in improvements in clinical symptoms and/or quality of life. Pharmacological therapies, including oxytocin and certain antipsychotics, have yielded more mixed

The Importance of Social Cognition in Improving Functional Outcomes in Schizophrenia

Directory of Open Access Journals (Sweden)

Afzal Javed

2018-04-01

Full Text Available Social cognition has become recognized as an important driver of functional outcomes and overall recovery in patients with schizophrenia, mediating the relationship between neurocognition and social functioning. Since antipsychotic therapy targeting remission of clinical symptoms has been shown to have a limited impact on social cognition, there has been an increasing drive to develop therapeutic strategies to specifically improve social cognition in schizophrenia. We sought to review current evidence relating to social cognition in schizophrenia and its clinical implications, including interventions designed to target the core domains of social cognition (emotion processing, theory of mind, attributional bias, and social perception as a means of improving functional outcomes and thereby increasing the likelihood of recovery. Relevant articles were identified by conducting a literature search in PubMed using the search terms “schizophrenia” AND “cognition” AND “social functioning,” limited to Title/Abstract, over a time period of the past 10 years. Current evidence demonstrates that schizophrenia is associated with impairments in all four core domains of social cognition, during the pre-first-episode, first-episode, early, and chronic phases of the disease, and that such impairments are important determinants of functional outcome. Interventions targeting the four core domains of social cognition comprise psychosocial approaches (social cognition training programs and pharmacological therapies. Social cognition training programs targeting multiple and specific core domains of social cognition have shown promise in improving social cognition skills, which, in some cases, has translated into improvements in functional outcomes. Use of some psychosocial interventions has additionally resulted in improvements in clinical symptoms and/or quality of life. Pharmacological therapies, including oxytocin and certain antipsychotics, have

A novel subcutaneous site of islet transplantation superior to the liver.

Science.gov (United States)

Yasunami, Yohichi; Nakafusa, Yuki; Nitta, Naoyoshi; Nakamura, Masafumi; Goto, Masafumi; Ono, Junko; Taniguchi, Masaru

2018-03-08

Islet transplantation is an attractive treatment for patients with insulin-dependent diabetes mellitus, and currently the liver is the favored transplantation site. However, an alternative site is desirable because of the low efficiency of hepatic transplantation, requiring 2-3 donors for a single recipient, and because the transplanted islets cannot be accessed or retrieved. We developed a novel procedure of islet transplantation to the inguinal subcutaneous white adipose tissue (ISWAT) of mice and described functional and morphological characteristics of transplanted syngeneic islets. Also, it was determined whether islet allograft rejection in the ISWAT can be prevented by immunosuppressive agents. Furthermore, it was examined whether human islets function when grafted in this particular site of immune-deficient mice. In this site, transplanted islets are engrafted as clusters and function to reverse STZ-induced diabetes in mice. Importantly, transplanted islets can be visualized by CT and are easily retrievable, and allograft rejection is preventable by blockade of co-stimulatory signals. Of much importance, the efficiency of islet transplantation in this site is superior to the liver, in which hyperglycemia of diabetic recipient mice is ameliorated after transplantation of 200 syngeneic islets (the islet number yielded from 1 mouse pancreas) to the ISWAT but not to the liver. Furthermore, human islets transplanted in this particular site function to reverse diabetes in immune-deficient mice. Thus, the ISWAT is superior to the liver as the site of islet transplantation, which may lead to improved outcome of clinical islet transplantation.

Developing models of how cognitive improvements change functioning: Mediation, moderation and moderated mediation

Science.gov (United States)

Wykes, Til; Reeder, Clare; Huddy, Vyv; Taylor, Rumina; Wood, Helen; Ghirasim, Natalia; Kontis, Dimitrios; Landau, Sabine

2012-01-01

Background Cognitive remediation (CRT) affects functioning but the extent and type of cognitive improvements necessary are unknown. Aim To develop and test models of how cognitive improvement transfers to work behaviour using the data from a current service. Method Participants (N49) with a support worker and a paid or voluntary job were offered CRT in a Phase 2 single group design with three assessments: baseline, post therapy and follow-up. Working memory, cognitive flexibility, planning and work outcomes were assessed. Results Three models were tested (mediation — cognitive improvements drive functioning improvement; moderation — post treatment cognitive level affects the impact of CRT on functioning; moderated mediation — cognition drives functioning improvements only after a certain level is achieved). There was evidence of mediation (planning improvement associated with improved work quality). There was no evidence that cognitive flexibility (total Wisconsin Card Sorting Test errors) and working memory (Wechsler Adult Intelligence Scale III digit span) mediated work functioning despite significant effects. There was some evidence of moderated mediation for planning improvement if participants had poorer memory and/or made fewer WCST errors. The total CRT effect on work quality was d = 0.55, but the indirect (planning-mediated CRT effect) was d = 0.082 Conclusion Planning improvements led to better work quality but only accounted for a small proportion of the total effect on work outcome. Other specific and non-specific effects of CRT and the work programme are likely to account for some of the remaining effect. This is the first time complex models have been tested and future Phase 3 studies need to further test mediation and moderated mediation models. PMID:22503640

Mechanism of Cerebralcare Granule® for Improving Cognitive Function in Resting-State Brain Functional Networks of Sub-healthy Subjects

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Jing Li

2017-07-01

Full Text Available Cerebralcare Granule® (CG, a Chinese herbal medicine, has been used to ameliorate cognitive impairment induced by ischemia or mental disorders. The ability of CG to improve health status and cognitive function has drawn researchers' attention, but the relevant brain circuits that underlie the ameliorative effects of CG remain unclear. The present study aimed to explore the underlying neurobiological mechanisms of CG in ameliorating cognitive function in sub-healthy subjects using resting-state functional magnetic resonance imaging (fMRI. Thirty sub-healthy participants were instructed to take one 2.5-g package of CG three times a day for 3 months. Clinical cognitive functions were assessed with the Chinese Revised Wechsler Adult Intelligence Scale (WAIS-RC and Wechsler Memory Scale (WMS, and fMRI scans were performed at baseline and the end of intervention. Functional brain network data were analyzed by conventional network metrics (CNM and frequent subgraph mining (FSM. Then 21 other sub-healthy participants were enrolled as a blank control group of cognitive functional. We found that administrating CG can improve the full scale of intelligence quotient (FIQ and Memory Quotient (MQ scores. At the same time, following CG treatment, in CG group, the topological properties of functional brain networks were altered in various frontal, temporal, occipital cortex regions, and several subcortical brain regions, including essential components of the executive attention network, the salience network, and the sensory-motor network. The nodes involved in the FSM results were largely consistent with the CNM findings, and the changes in nodal metrics correlated with improved cognitive function. These findings indicate that CG can improve sub-healthy subjects' cognitive function through altering brain functional networks. These results provide a foundation for future studies of the potential physiological mechanism of CG.

Controlled, Site-Specific Functionalization of Carbon Nanotubes with Diazonium Salts

Science.gov (United States)

Tour, James M.

2013-01-01

capacities and uses. Site-specific functionalization may enable the use of nanotubes in molecular electronic applications because device functionality is critical at the cross points.

Handling Internet-Based Health Information: Improving Health Information Web Site Literacy Among Undergraduate Nursing Students.

Science.gov (United States)

Wang, Weiwen; Sun, Ran; Mulvehill, Alice M; Gilson, Courtney C; Huang, Linda L

2017-02-01

Patient care problems arise when health care consumers and professionals find health information on the Internet because that information is often inaccurate. To mitigate this problem, nurses can develop Web literacy and share that skill with health care consumers. This study evaluated a Web-literacy intervention for undergraduate nursing students to find reliable Web-based health information. A pre- and postsurvey queried undergraduate nursing students in an informatics course; the intervention comprised lecture, in-class practice, and assignments about health Web site evaluation tools. Data were analyzed using Wilcoxon and ANOVA signed-rank tests. Pre-intervention, 75.9% of participants reported using Web sites to obtain health information. Postintervention, 87.9% displayed confidence in using an evaluation tool. Both the ability to critique health Web sites (p = .005) and confidence in finding reliable Internet-based health information (p = .058) increased. Web-literacy education guides nursing students to find, evaluate, and use reliable Web sites, which improves their ability to deliver safer patient care. [J Nurs Educ. 2017;56(2):110-114.]. Copyright 2017, SLACK Incorporated.

Playing piano can improve upper extremity function after stroke: case studies.

Science.gov (United States)

Villeneuve, Myriam; Lamontagne, Anouk

2013-01-01

Music-supported therapy (MST) is an innovative approach that was shown to improve manual dexterity in acute stroke survivors. The feasibility of such intervention in chronic stroke survivors and its longer-term benefits, however, remain unknown. The objective of this pilot study was to estimate the short- and long-term effects of a 3-week piano training program on upper extremity function in persons with chronic stroke. A multiple pre-post sequential design was used, with measurements taken at baseline (week0, week3), prior to (week6) and after the intervention (week9), and at 3-week follow-up (week12). Three persons with stroke participated in the 3-week piano training program that combined structured piano lessons to home practice program. The songs, played on an electronic keyboard, involved all 5 digits of the affected hand and were displayed using a user-friendly MIDI program. After intervention, all the three participants showed improvements in their fine (nine hole peg test) and gross (box and block test) manual dexterity, as well as in the functional use of the upper extremity (Jebsen hand function test). Improvements were maintained at follow-up. These preliminary results support the feasibility of using an MST approach that combines structured lessons to home practice to improve upper extremity function in chronic stroke.

Playing Piano Can Improve Upper Extremity Function after Stroke: Case Studies

Directory of Open Access Journals (Sweden)

Myriam Villeneuve

2013-01-01

Full Text Available Music-supported therapy (MST is an innovative approach that was shown to improve manual dexterity in acute stroke survivors. The feasibility of such intervention in chronic stroke survivors and its longer-term benefits, however, remain unknown. The objective of this pilot study was to estimate the short- and long-term effects of a 3-week piano training program on upper extremity function in persons with chronic stroke. A multiple pre-post sequential design was used, with measurements taken at baseline (week0, week3, prior to (week6 and after the intervention (week9, and at 3-week follow-up (week12. Three persons with stroke participated in the 3-week piano training program that combined structured piano lessons to home practice program. The songs, played on an electronic keyboard, involved all 5 digits of the affected hand and were displayed using a user-friendly MIDI program. After intervention, all the three participants showed improvements in their fine (nine hole peg test and gross (box and block test manual dexterity, as well as in the functional use of the upper extremity (Jebsen hand function test. Improvements were maintained at follow-up. These preliminary results support the feasibility of using an MST approach that combines structured lessons to home practice to improve upper extremity function in chronic stroke.

Defining a similarity threshold for a functional proteinsequence pattern: The signal peptide cleavage site

DEFF Research Database (Denmark)

Nielsen, Henrik; Engelbrecht, Jacob; von Heijne, Gunnar

1996-01-01

When preparing data sets of amino acid or nucleotide sequences it is necessary to exclude redundant or homologous sequences in order to avoid overestimating the predictive performance of an algorithm. For some time methods for doing this have been available in the area of protein structure...... prediction. We have developed a similar procedure based on pair-wise alignments for sequences with functional sites. We show how a correlation coefficient between sequence similarity and functional homology can be used to compare the efficiency of different similarity measures and choose a nonarbitrary...

Towards improved local hybrid functionals by calibration of exchange-energy densities

International Nuclear Information System (INIS)

Arbuznikov, Alexei V.; Kaupp, Martin

2014-01-01

A new approach for the calibration of (semi-)local and exact exchange-energy densities in the context of local hybrid functionals is reported. The calibration functions are derived from only the electron density and its spatial derivatives, avoiding spatial derivatives of the exact-exchange energy density or other computationally unfavorable contributions. The calibration functions fulfill the seven more important out of nine known exact constraints. It is shown that calibration improves substantially the definition of a non-dynamical correlation energy term for generalized gradient approximation (GGA)-based local hybrids. Moreover, gauge artifacts in the potential-energy curves of noble-gas dimers may be corrected by calibration. The developed calibration functions are then evaluated for a large range of energy-related properties (atomization energies, reaction barriers, ionization potentials, electron affinities, and total atomic energies) of three sets of local hybrids, using a simple one-parameter local-mixing. The functionals are based on (a) local spin-density approximation (LSDA) or (b) Perdew-Burke-Ernzerhof (PBE) exchange and correlation, and on (c) Becke-88 (B88) exchange and Lee-Yang-Parr (LYP) correlation. While the uncalibrated GGA-based functionals usually provide very poor thermochemical data, calibration allows a dramatic improvement, accompanied by only a small deterioration of reaction barriers. In particular, an optimized BLYP-based local-hybrid functional has been found that is a substantial improvement over the underlying global hybrids, as well as over previously reported LSDA-based local hybrids. It is expected that the present calibration approach will pave the way towards new generations of more accurate hyper-GGA functionals based on a local mixing of exchange-energy densities

Transmembrane helix M6 in sarco(endo)plasmic reticulum Ca(2+)-ATPase forms a functional interaction site with phospholamban. Evidence for physical interactions at other sites.

Science.gov (United States)

Asahi, M; Kimura, Y; Kurzydlowski, K; Tada, M; MacLennan, D H

1999-11-12

In an earlier study (Kimura, Y., Kurzydlowski, K., Tada, M., and MacLennan, D. H. (1997) J. Biol. Chem. 272, 15061-15064), mutation of amino acids on one face of the phospholamban (PLN) transmembrane helix led to loss of PLN inhibition of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) molecules. This helical face was proposed to form a site of PLN interaction with a transmembrane helix in SERCA molecules. To determine whether predicted transmembrane helices M4, M5, M6, or M8 in SERCA1a interact with PLN, SERCA1a mutants were co-expressed with wild-type PLN and effects on Ca(2+) dependence of Ca(2+) transport were measured. Wild-type inhibitory interactions shifted apparent Ca(2+) affinity of SERCA1a by an average of -0.34 pCa units, but four of the seven mutations in M4 led to a more inhibitory shift in apparent Ca(2+) affinity, averaging -0.53 pCa units. Seven mutations in M5 led to an average shift of -0.32 pCa units and seven mutations in M8 led to an average shift of -0.30 pCa units. Among 11 mutations in M6, 1, Q791A, increased the inhibitory shift (-0.59 pCa units) and 5, V795A (-0.11), L802A (-0.07), L802V (-0.04), T805A (-0.11), and F809A (-0.12), reduced the inhibitory shift, consistent with the view that Val(795), Leu(802), Thr(805), and Phe(809), located on one face of a predicted M6 helix, form a site in SERCA1a for interaction with PLN. Those mutations in M4, M6, or M8 of SERCA1a that enhanced PLN inhibitory function did not enhance PLN physical association with SERCA1a, but mutants V795A and L802A in M6, which decreased PLN inhibitory function, decreased physical association, as measured by co-immunoprecipitation. In related studies, those PLN mutants that gained inhibitory function also increased levels of co-immunoprecipitation of wild-type SERCA1a and those that lost inhibitory function also reduced association, correlating functional interaction sites with physical interaction sites. Thus, both functional and physical data confirm that PLN

Improving Preservice Teachers' Knowledge and Application of Functional Behavioral Assessments Using Multimedia

Science.gov (United States)

Hirsch, Shanna Eisner; Kennedy, Michael J.; Haines, Shana J.; Thomas, Cathy Newman; Alves, Kat D.

2015-01-01

Functional behavioral assessment (FBA) is an empirically supported intervention associated with decreasing problem behavior and increasing appropriate behavior. To date, few studies have examined multimedia approaches to FBA training. This paper provides the outcomes of a randomized controlled trial across three university sites and evaluates…

TREHALOSE-BASED ADDITIVE IMPROVED INTER-PRIMER BINDING SITE REACTIONS FOR DNA ISOLATED FROM RECALCITRANT PLANTS

Directory of Open Access Journals (Sweden)

Veronika Lancíková

2014-02-01

Full Text Available Trehalose-based (TBT-PAR additive was tested in order to optimize PCR amplification for DNA isolated from recalcitrant plants. Retrotransposon-based inter-primer binding site reactions were significantly improved with TBT-PAR solution using genomic DNA isolated from flax (Linum usitatissimum L., genotypes Kyivskyi, Bethune grown in radio-contaminated and non-radioactive remediated Chernobyl experimental fields. Additionally, similar improvements were observed using 19 recalcitrant genotypes of maize (Zea mays L. and three genotypes of yacon (Smallanthus sonchifolius, Poepp. et Endl., genotypes PER05, ECU45, BOL22 grown in standard field conditions.

Improving older people's life satisfaction via social networking site use: Evidence from China.

Science.gov (United States)

Zhou, Junjie

2018-03-01

This study aimed to examine the pathways by which social networking sites (SNSs) can improve older people's life satisfaction. We conducted an online survey in China that lasted eight weeks. Respondents were required to report their demographic characteristics and feelings regarding SNS use. Data were analysed using SPSS 20 and Amos 21. We collected 596 valid samples. The empirical results show that SNS use improves older people's life satisfaction by reducing their loneliness and improving their self-efficacy. Social support alleviates the negative effect of loneliness and enhances the positive effect of self-efficacy on life satisfaction. Sex differences and education differences were significant. Men and less educated people had higher levels of life satisfaction. Policymakers should offer support to SNSs targeting older people and encourage them to provide more useful services. SNS operators should encourage social support among older users and pay attention to sex differences and education differences. © 2018 AJA Inc.

QUALITY IMPROVEMENT INITIATIVES FOR SUPPORT FUNCTIONS IN AN INDUSTRY: TWO CASES

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Shirshendu Roy

2011-09-01

Full Text Available The concept of quality improvement in industry has originated from the involvement of inspector which has become the most important part of manufacturing process or development activity. Over years, this initiative is migrated to various support functions of the industry. In this paper, emphasis has been given particularly in the areas related to support functions where improvement project s can be effectively done and hence organization wide impact is assessed. Two case studies are presented here in this context. The first study shows how smaller change in content structure and delivery met hod can drastically improve the training feedback and the second one demonstrates minimizing lead time to recruitment with a cost-effective process modification.

Identification and functional analysis of novel phosphorylation sites in the RNA surveillance protein Upf1.

Science.gov (United States)

Lasalde, Clarivel; Rivera, Andrea V; León, Alfredo J; González-Feliciano, José A; Estrella, Luis A; Rodríguez-Cruz, Eva N; Correa, María E; Cajigas, Iván J; Bracho, Dina P; Vega, Irving E; Wilkinson, Miles F; González, Carlos I

2014-02-01

One third of inherited genetic diseases are caused by mRNAs harboring premature termination codons as a result of nonsense mutations. These aberrant mRNAs are degraded by the Nonsense-Mediated mRNA Decay (NMD) pathway. A central component of the NMD pathway is Upf1, an RNA-dependent ATPase and helicase. Upf1 is a known phosphorylated protein, but only portions of this large protein have been examined for phosphorylation sites and the functional relevance of its phosphorylation has not been elucidated in Saccharomyces cerevisiae. Using tandem mass spectrometry analyses, we report the identification of 11 putative phosphorylated sites in S. cerevisiae Upf1. Five of these phosphorylated residues are located within the ATPase and helicase domains and are conserved in higher eukaryotes, suggesting a biological significance for their phosphorylation. Indeed, functional analysis demonstrated that a small carboxy-terminal motif harboring at least three phosphorylated amino acids is important for three Upf1 functions: ATPase activity, NMD activity and the ability to promote translation termination efficiency. We provide evidence that two tyrosines within this phospho-motif (Y-738 and Y-742) act redundantly to promote ATP hydrolysis, NMD efficiency and translation termination fidelity.

Preventing E-cadherin aberrant N-glycosylation at Asn-554 improves its critical function in gastric cancer

Science.gov (United States)

Carvalho, S; Catarino, TA; Dias, AM; Kato, M; Almeida, A; Hessling, B; Figueiredo, J; Gärtner, F; Sanches, JM; Ruppert, T; Miyoshi, E; Pierce, M; Carneiro, F; Kolarich, D; Seruca, R; Yamaguchi, Y; Taniguchi, N; Reis, CA; Pinho, SS

2016-01-01

E-cadherin is a central molecule in the process of gastric carcinogenesis and its posttranslational modifications by N-glycosylation have been described to induce a deleterious effect on cell adhesion associated with tumor cell invasion. However, the role that site-specific glycosylation of E-cadherin has in its defective function in gastric cancer cells needs to be determined. Using transgenic mice models and human clinical samples, we demonstrated that N-acetylglucosaminyltransferase V (GnT-V)-mediated glycosylation causes an abnormal pattern of E-cadherin expression in the gastric mucosa. In vitro models further indicated that, among the four potential N-glycosylation sites of E-cadherin, Asn-554 is the key site that is selectively modified with β1,6 GlcNAc-branched N-glycans catalyzed by GnT-V. This aberrant glycan modification on this specific asparagine site of E-cadherin was demonstrated to affect its critical functions in gastric cancer cells by affecting E-cadherin cellular localization, cis-dimer formation, molecular assembly and stability of the adherens junctions and cell–cell aggregation, which was further observed in human gastric carcinomas. Interestingly, manipulating this site-specific glycosylation, by preventing Asn-554 from receiving the deleterious branched structures, either by a mutation or by silencing GnT-V, resulted in a protective effect on E-cadherin, precluding its functional dysregulation and contributing to tumor suppression. PMID:26189796

Ceruloplasmin revisited: structural and functional roles of various metal cation-binding sites

International Nuclear Information System (INIS)

Bento, Isabel; Peixoto, Cristina; Zaitsev, Vjacheslav N.; Lindley, Peter F.

2007-01-01

The three-dimensional molecular structure of human serum ceruloplasmin has been reinvestigated using X-ray synchrotron data collected at 100 K from a crystal frozen to liquid-nitrogen temperature. The three-dimensional molecular structure of human serum ceruloplasmin has been reinvestigated using X-ray synchrotron data collected at 100 K from a crystal frozen to liquid-nitrogen temperature. The resulting model, with an increase in resolution from 3.1 to 2.8 Å, gives an overall improvement of the molecular structure, in particular the side chains. In addition, it enables the clear definition of previously unidentified Ca 2+ -binding and Na + -binding sites. The Ca 2+ cation is located in domain 1 in a configuration very similar to that found in the activated bovine factor Va. The Na + sites appear to play a structural role in providing rigidity to the three protuberances on the top surface of the molecule. These features probably help to steer substrates towards the mononuclear copper sites prior to their oxidation and to restrict the size of the approaching substrate. The trinuclear copper centre appears to differ from the room-temperature structure in that a dioxygen moiety is bound in a similar way to that found in the endospore coat protein CotA from Bacillus subtilis

Nuclear event time histories and computed site transfer functions for locations in the Los Angeles region

Science.gov (United States)

Rogers, A.M.; Covington, P.A.; Park, R.B.; Borcherdt, R.D.; Perkins, D.M.

1980-01-01

This report presents a collection of Nevada Test Site (NTS) nuclear explosion recordings obtained at sites in the greater Los Angeles, Calif., region. The report includes ground velocity time histories, as well as, derived site transfer functions. These data have been collected as part of a study to evaluate the validity of using low-level ground motions to predict the frequency-dependent response of a site during an earthquake. For this study 19 nuclear events were recorded at 98 separate locations. Some of these sites have recorded more than one of the nuclear explosions, and, consequently, there are a total of 159, three-component station records. The location of all the recording sites are shown in figures 1–5, the station coordinates and abbreviations are given in table 1. The station addresses are listed in table 2, and the nuclear explosions that were recorded are listed in table 3. The recording sites were chosen on the basis of three criteria: (1) that the underlying geological conditions were representative of conditions over significant areas of the region, (2) that the site was the location of a strong-motion recording of the 1971 San Fernando earthquake, or (3) that more complete geographical coverage was required in that location.

Exercise training improves selected aspects of daytime functioning in adults with obstructive sleep apnea.

Science.gov (United States)

Kline, Christopher E; Ewing, Gary B; Burch, James B; Blair, Steven N; Durstine, J Larry; Davis, J Mark; Youngstedt, Shawn D

2012-08-15

To explore the utility of exercise training for improving daytime functioning in adults with obstructive sleep apnea (OSA). Forty-three sedentary and overweight/obese adults aged 18-55 years with at least moderate-severity untreated OSA (apnea-hypopnea index ≥ 15) were randomized to 12 weeks of moderate-intensity aerobic and resistance exercise training (n = 27) or low-intensity stretching control treatment (n = 16). As part of a trial investigating the efficacy of exercise training on OSA severity, daytime functioning was assessed before and following the intervention. Sleepiness, functional impairment due to sleepiness, depressive symptoms, mood, and quality of life (QOL) were evaluated with validated questionnaires, and cognitive function was assessed with a neurobehavioral performance battery. OSA severity was measured with one night of laboratory polysomnography before and following the intervention. Compared with stretching control, exercise training resulted in significant improvements in depressive symptoms, fatigue and vigor, and aspects of QOL (p improved following exercise versus control to a similar degree in terms of effect sizes (d > 0.5), though these changes were not statistically significant. No neurobehavioral performance improvements were found. Reduced fatigue following exercise training was mediated by a reduction in OSA severity, but changes in OSA severity did not significantly mediate improvement in any other measure of daytime functioning. These data provide preliminary evidence that exercise training may be helpful for improving aspects of daytime functioning of adults with OSA. Larger trials are needed to further verify the observed improvements.

Targeting paretic propulsion to improve poststroke walking function: a preliminary study.

Science.gov (United States)

Awad, Louis N; Reisman, Darcy S; Kesar, Trisha M; Binder-Macleod, Stuart A

2014-05-01

To determine the feasibility and safety of implementing a 12-week locomotor intervention targeting paretic propulsion deficits during walking through the joining of 2 independent interventions, walking at maximal speed on a treadmill and functional electrical stimulation of the paretic ankle musculature (FastFES); to determine the effects of FastFES training on individual subjects; and to determine the influence of baseline impairment severity on treatment outcomes. Single group pre-post preliminary study investigating a novel locomotor intervention. Research laboratory. Individuals (N=13) with locomotor deficits after stroke. FastFES training was provided for 12 weeks at a frequency of 3 sessions per week and 30 minutes per session. Measures of gait mechanics, functional balance, short- and long-distance walking function, and self-perceived participation were collected at baseline, posttraining, and 3-month follow-up evaluations. Changes after treatment were assessed using pairwise comparisons and compared with known minimal clinically important differences or minimal detectable changes. Correlation analyses were run to determine the correlation between baseline clinical and biomechanical performance versus improvements in walking speed. Twelve of the 13 subjects that were recruited completed the training. Improvements in paretic propulsion were accompanied by improvements in functional balance, walking function, and self-perceived participation (each Pstudy of this promising locomotor intervention for persons poststroke. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Positive selection neighboring functionally essential sites and disease-implicated regions of mammalian reproductive proteins.

LENUS (Irish Health Repository)

Morgan, Claire C

2010-01-01

ABSTRACT: BACKGROUND: Reproductive proteins are central to the continuation of all mammalian species. The evolution of these proteins has been greatly influenced by environmental pressures induced by pathogens, rival sperm, sexual selection and sexual conflict. Positive selection has been demonstrated in many of these proteins with particular focus on primate lineages. However, the mammalia are a diverse group in terms of mating habits, population sizes and germ line generation times. We have examined the selective pressures at work on a number of novel reproductive proteins across a wide variety of mammalia. RESULTS: We show that selective pressures on reproductive proteins are highly varied. Of the 10 genes analyzed in detail, all contain signatures of positive selection either across specific sites or in specific lineages or a combination of both. Our analysis of SP56 and Col1a1 are entirely novel and the results show positively selected sites present in each gene. Our findings for the Col1a1 gene are suggestive of a link between positive selection and severe disease type. We find evidence in our dataset to suggest that interacting proteins are evolving in symphony: most likely to maintain interacting functionality. CONCLUSION: Our in silico analyses show positively selected sites are occurring near catalytically important regions suggesting selective pressure to maximize efficient fertilization. In those cases where a mechanism of protein function is not fully understood, the sites presented here represent ideal candidates for mutational study. This work has highlighted the widespread rate heterogeneity in mutational rates across the mammalia and specifically has shown that the evolution of reproductive proteins is highly varied depending on the species and interacting partners. We have shown that positive selection and disease are closely linked in the Col1a1 gene.

CPAP therapy improves erectile function in patients with severe obstructive sleep apnea.

Science.gov (United States)

Schulz, Richard; Bischof, Fabian; Galetke, Wolfgang; Gall, Henning; Heitmann, Jörg; Hetzenecker, Andrea; Laudenburg, Markus; Magnus, Till Jonas; Nilius, Georg; Priegnitz, Christina; Randerath, Winfried; Schröder, Maik; Treml, Marcel; Arzt, Michael

2018-04-10

Erectile dysfunction (ED) is highly prevalent in obstructive sleep apnea (OSA), however, the effect of continuous positive airway pressure (CPAP) therapy on erectile function has not yet been thoroughly investigated in these patients. Ninety-four men with severe OSA (ie, with an apnea-hypopnea-index ≥ 30/h of sleep) were prospectively evaluated for the presence and severity of ED before and after 6-12 months of CPAP therapy. The abbreviated version of the International Index of Erectile Function, (the IIEF-5) was used to rate erectile function. Furthermore, all study participants responded to standard questionnaires of daytime sleepiness (Epworth Sleepiness Scale), quality of life (WHO Wellbeing 5 questionnaire) and depression (Major Depression Inventory). ED as defined by an IIEF-5 score of ≤21 was present in 64 patients (68.1%). CPAP treatment significantly improved erectile function in those patients suffering from moderate and severe ED. Additionally, a trend for a correlation between the improvement of erectile function under CPAP and the hours of its use was observed. Finally, this effect was associated with larger improvements of quality of life in affected patients. ED is very frequent in men with severe OSA and can at least partly be reversed by long-term CPAP therapy in most seriously affected patients. The beneficial effect on erectile function may depend on CPAP compliance and is accompanied by improvements of quality of life. Randomized controlled trials are needed to confirm these findings. Copyright © 2018 Elsevier B.V. All rights reserved.

To what extent do site-based training, mentoring, and operational research improve district health system management and leadership in low- and middle-income countries: a systematic review protocol.

Science.gov (United States)

Belrhiti, Zakaria; Booth, Andrew; Marchal, Bruno; Verstraeten, Roosmarijn

2016-04-27

District health managers play a key role in the effectiveness of decentralized health systems in low- and middle-income countries. Inadequate management and leadership skills often hamper their ability to improve quality of care and effectiveness of health service delivery. Nevertheless, significant investments have been made in capacity-building programmes based on site-based training, mentoring, and operational research. This systematic review aims to review the effectiveness of site-based training, mentoring, and operational research (or action research) on the improvement of district health system management and leadership. Our secondary objectives are to assess whether variations in composition or intensity of the intervention influence its effectiveness and to identify enabling and constraining contexts and underlying mechanisms. We will search the following databases: MEDLINE, PsycInfo, Cochrane Library, CRD database (DARE), Cochrane Effective Practice and Organisation of Care (EPOC) group, ISI Web of Science, Health Evidence.org, PDQ-Evidence, ERIC, EMBASE, and TRIP. Complementary search will be performed (hand-searching journals and citation and reference tracking). Studies that meet the following PICO (Population, Intervention, Comparison, Outcome) criteria will be included: P: professionals working at district health management level; I: site-based training with or without mentoring, or operational research; C: normal institutional arrangements; and O: district health management functions. We will include cluster randomized controlled trials, controlled before-and-after studies, interrupted time series analysis, quasi-experimental designs, and cohort and longitudinal studies. Qualitative research will be included to contextualize findings and identify barriers and facilitators. Primary outcomes that will be reported are district health management and leadership functions. We will assess risk of bias with the Cochrane Collaboration's tools for randomized

Will Incremental Hemodialysis Preserve Residual Function and Improve Patient Survival?

Science.gov (United States)

Davenport, Andrew

2015-01-01

The progressive loss of residual renal function in peritoneal dialysis patients is associated with increased mortality. It has been suggested that incremental dialysis may help preserve residual renal function and improve patient survival. Residual renal function depends upon both patient related and dialysis associated factors. Maintaining patients in an over-hydrated state may be associated with better preservation of residual renal function but any benefit comes with a significant risk of cardiovascular consequences. Notably, it is only observational studies that have reported an association between dialysis patient survival and residual renal function; causality has not been established for dialysis patient survival. The tenuous connections between residual renal function and outcomes and between incremental hemodialysis and residual renal function should temper our enthusiasm for interventions in this area. PMID:25385441

Assigning Quantitative Function to Post-Translational Modifications Reveals Multiple Sites of Phosphorylation That Tune Yeast Pheromone Signaling Output

Energy Technology Data Exchange (ETDEWEB)

Pincus, David; Ryan, Christopher J.; Smith, Richard D.; Brent, Roger; Resnekov, Orna; Hakimi, Mohamed Ali

2013-03-12

Cell signaling systems transmit information by post-­translationally modifying signaling proteins, often via phosphorylation. While thousands of sites of phosphorylation have been identified in proteomic studies, the vast majority of sites have no known function. Assigning functional roles to the catalog of uncharacterized phosphorylation sites is a key research challenge. Here we present a general approach to address this challenge and apply it to a prototypical signaling pathway, the pheromone response pathway in Saccharomyces cerevisiae. The pheromone pathway includes a mitogen activated protein kinase (MAPK) cascade activated by a G-­protein coupled receptor (GPCR). We used mass spectrometry-based proteomics to identify sites whose phosphorylation changed when the system was active, and evolutionary conservation to assign priority to a list of candidate MAPK regulatory sites. We made targeted alterations in those sites, and measured the effects of the mutations on pheromone pathway output in single cells. Our work identified six new sites that quantitatively tuned system output. We developed simple computational models to find system architectures that recapitulated the quantitative phenotypes of the mutants. Our results identify a number of regulated phosphorylation events that contribute to adjust the input-­output relationship of this model eukaryotic signaling system. We believe this combined approach constitutes a general means not only to reveal modification sites required to turn a pathway on and off, but also those required for more subtle quantitative effects that tune pathway output. Our results further suggest that relatively small quantitative influences from individual regulatory phosphorylation events endow signaling systems with plasticity that evolution may exploit to quantitatively tailor signaling outcomes.

Improvement of standards on functional reliability of electric power systems

International Nuclear Information System (INIS)

Barinov, V.A.; Volkov, G.A.; Kalita, V.V.; Kogan, F.L.; Makarov, S.F.; Manevich, A.S.; Mogirev, V.V.; Sin'chugov, F.I.; Skopintsev, V.A.; Khvoshchinskaya, Z.G.

1993-01-01

Analysis of the most principal aspects of the existing standards and requirements on assuring safety and stability of electric power systems (EPS) and effective (reliable and economical) power supply of consumers is given. The reliability is determined as ability to accomplish the assigned functions. Basic recommendations on improving the standards regulating the safety and reliability of the NPP functioning are formulated

Independent assessment to continue improvement: Implementing statistical process control at the Hanford Site

International Nuclear Information System (INIS)

Hu, T.A.; Lo, J.C.

1994-11-01

A Quality Assurance independent assessment has brought about continued improvement in the PUREX Plant surveillance program at the Department of Energy's Hanford Site. After the independent assessment, Quality Assurance personnel were closely involved in improving the surveillance program, specifically regarding storage tank monitoring. The independent assessment activities included reviewing procedures, analyzing surveillance data, conducting personnel interviews, and communicating with management. Process improvement efforts included: (1) designing data collection methods; (2) gaining concurrence between engineering and management, (3) revising procedures; and (4) interfacing with shift surveillance crews. Through this process, Statistical Process Control (SPC) was successfully implemented and surveillance management was improved. The independent assessment identified several deficiencies within the surveillance system. These deficiencies can be grouped into two areas: (1) data recording and analysis and (2) handling off-normal conditions. By using several independent assessment techniques, Quality Assurance was able to point out program weakness to senior management and present suggestions for improvements. SPC charting, as implemented by Quality Assurance, is an excellent tool for diagnosing the process, improving communication between the team members, and providing a scientific database for management decisions. In addition, the surveillance procedure was substantially revised. The goals of this revision were to (1) strengthen the role of surveillance management, engineering and operators and (2) emphasize the importance of teamwork for each individual who performs a task. In this instance we believe that the value independent assessment adds to the system is the continuous improvement activities that follow the independent assessment. Excellence in teamwork between the independent assessment organization and the auditee is the key to continuing improvement

New anion-exchange resins for improved separations of nuclear materials

International Nuclear Information System (INIS)

Barr, M.E.; Bartsch, R.A.

1998-01-01

'The overall objective of this research is to develop a predictive capability which allows the facile design and implementation of multi-functionalized anion-exchange materials which selectively sorb metal complexes of interest from targeted process, waste, and environmental streams. The basic scientific issues addressed are actinide complex speciation along with modeling of the metal complex/functional-site interactions in order to determine optimal binding-site characteristics. The new ion-exchange resins interface the rapidly developing field of ion-specific chelating ligands with robust, commercial ion-exchange technology. Various Focus Areas and Crosscutting Programs have described needs that would be favorably impacted by the new materials: Efficient Separations and Processing; Plutonium; Plumes; Mixed Waste; High-Level Tank Waste. Sites within the DOE complex which would benefit from the improved anion-exchange technology include Hanford, INEL, Los Alamos, Oak Ridge, and Savannah River. As of April 1998, this report summarizes work after 1.6 years of a 3-year project. The authors technical approach combines empirical testing with theoretical modeling (applied in an iterative mode) in order to determine optimal binding-site characteristics. They determine actinide-complex speciation in specific media, then develop models for the metal complex/functional-site interactions Synthesis and evaluation of multi-functionalized extractants and ion-exchange materials that implement key features of the optimized binding site provide feedback to the modeling and design activities. Resin materials which actively facilitate the uptake of actinide complexes from solution should display both improved selectivity and kinetic properties. The implementation of the bifunctionality concept involves N-derivatization of pyridinium units from a base poly(4-vinylpyridine) resin with a second cationic site such that the two anion-exchange sites are linked by spacer arms of varying

High-intensity functional training improves functional movement and body composition among cancer survivors: a pilot study.

Science.gov (United States)

Heinrich, K M; Becker, C; Carlisle, T; Gilmore, K; Hauser, J; Frye, J; Harms, C A

2015-11-01

This pilot study investigated feasibility and preliminary efficacy of a high-intensity functional training (HIFT) group-exercise programme among adult cancer survivors within 5 years of last cancer treatment. Eight participants were assigned to a 5-week, 3 days/week HIFT intervention with four testing sessions and 12 workouts along with mobility and stretching exercises. Feasibility was assessed by initiation, adherence, and acceptability. Efficacy was determined by changes from baseline to post-test in health-related quality of life, body composition and functional movement. The recruitment rate was 80% and the adherence rate was 75%. Significant improvements were found for emotional functioning (P = 0.042) and body composition (lean mass +3.8 ± 2.1 kg, P = 0.008; fat mass -3.3 ± 1.0 kg, P = 0.001; body fat percentage -4.7 ± 1.2%, P body strength and power (P = 0.009), aerobic capacity and endurance (P = 0.039), and perceived difficulty for flexibility (P = 0.012). Five weeks of HIFT training was well-received and feasible for most cancer survivors, and effective for improving emotional functioning, body composition and functional movement. © 2015 John Wiley & Sons Ltd.

Improved framework model to allocate optimal rainwater harvesting sites in small watersheds for agro-forestry uses

Science.gov (United States)

Terêncio, D. P. S.; Sanches Fernandes, L. F.; Cortes, R. M. V.; Pacheco, F. A. L.

2017-07-01

This study introduces an improved rainwater harvesting (RWH) suitability model to help the implementation of agro-forestry projects (irrigation, wildfire combat) in catchments. The model combines a planning workflow to define suitability of catchments based on physical, socio-economic and ecologic variables, with an allocation workflow to constrain suitable RWH sites as function of project specific features (e.g., distance from rainfall collection to application area). The planning workflow comprises a Multi Criteria Analysis (MCA) implemented on a Geographic Information System (GIS), whereas the allocation workflow is based on a multiple-parameter ranking analysis. When compared to other similar models, improvement comes with the flexible weights of MCA and the entire allocation workflow. The method is tested in a contaminated watershed (the Ave River basin) located in Portugal. The pilot project encompasses the irrigation of a 400 ha crop land that consumes 2.69 Mm3 of water per year. The application of harvested water in the irrigation replaces the use of stream water with excessive anthropogenic nutrients that may raise nitrosamines in the food and accumulation in the food chain, with severe consequences to human health (cancer). The selected rainfall collection catchment is capable to harvest 12 Mm3·yr-1 (≈ 4.5 × the requirement) and is roughly 3 km far from the application area assuring crop irrigation by gravity flow with modest transport costs. The RWH system is an 8-meter high that can be built in earth with reduced costs.

Improvement of worker safety through the investigation of the site response to rockbursts.

CSIR Research Space (South Africa)

Durrheim, RJ

1997-12-01

Full Text Available Committee DRAFT FINAL REPORT Improvement of worker safety through the investigation of the site response to rockbursts R J Durrheim, A M Milev, S M Spottiswoode, and B Vakalisa Research agency CSIR: Division of Mining Technology Project number GAP2OI... in the application of current technology, such as numerical modelling for mine design, were also identified. It was also found that published guidelines, e.g. for pillar design, have limitations which are not explicitly stated. The performance of new technologies...

Improvement of Myocardial Function Following Catheter-Based Renal Denervation in Heart Failure

Directory of Open Access Journals (Sweden)

Song-Yan Liao, MD

2017-06-01

Full Text Available Summary: Renal denervation (RD is a potential novel nonpharmacological therapy for heart failure (HF. We performed bilateral catheter-based RD in 10 adult pigs and compared them with 10 control subjects after induction of HF to investigate the long-term beneficial effects of RD on left ventricular (LV function and regional norepinephrine gradient after conventional HF pharmacological therapy. Compared with control subjects, animals treated with RD demonstrated an improvement in LV function and reduction of norepinephrine gradients over the myocardium and kidney at 10-week follow-up. Our results demonstrated that effective bilateral RD decrease regional norepinephrine gradients and improve LV contractile function compared with medical therapy alone. Key Words: heart failure, left ventricular function, norepinephrine, renal denervation

Effects of functionalization on the targeting site of carbon nanotubes inside cells

Energy Technology Data Exchange (ETDEWEB)

Porter, A E; Bendall, J S; Welland, M [UK SuperSTEM, Daresbury Laboratory, Daresbury, Cheshire WA4 4AD (United Kingdom); Gass, M [The Nanoscience Centre, University of Cambridge, 11 J. J. Thompson Avenue, Cambridge CB3 OFF (United Kingdom); Muller, K; Skepper, J [Multiimaging Centre, Department of PDN, Physiology, Development and Neuroscience, Anatomy Building, University of Cambridge, Downing Street, Cambridge CB2 3DY (United Kingdom); Midgley, P, E-mail: a.porter@imperial.ac.u [Department of Materials Science and Metallurgy, University of Cambridge, Pembroke Street, Cambridge CB2 3QZ (United Kingdom)

2010-07-01

Functionalized single-walled carbon nanotubes (SWNTs) are currently being investigated for a variety of applications, including contrast agents for medical imaging{sup 1}. However before they can be used commercially it is necessary to assess whether they enter cells, the site they target within the cell and whether they cause any cytotoxicity. Here we characterize uptake of unlabelled, acid-treated, COO{sup -} functionalized SWNTs by human monocyte derived macrophage cells using both low-loss and energy loss spectroscopy and compare our findings to previous work on unpurified SWNTs. The acid-treated SWNTs were less aggregated within cells than unpurified SWNTs. Acid treatment was found to affect the distribution of intracellular SWNTs. Bundles, and also individual acid treated SWNTs, were found frequently inside lysosomes, cytoplasm and also inserting into the plasma membrane whereas unpurified non-functionalised SWNTs entered lysosomes and occasionally the nucleus.

Effects of functionalization on the targeting site of carbon nanotubes inside cells

International Nuclear Information System (INIS)

Porter, A E; Bendall, J S; Welland, M; Gass, M; Muller, K; Skepper, J; Midgley, P

2010-01-01

Functionalized single-walled carbon nanotubes (SWNTs) are currently being investigated for a variety of applications, including contrast agents for medical imaging 1 . However before they can be used commercially it is necessary to assess whether they enter cells, the site they target within the cell and whether they cause any cytotoxicity. Here we characterize uptake of unlabelled, acid-treated, COO - functionalized SWNTs by human monocyte derived macrophage cells using both low-loss and energy loss spectroscopy and compare our findings to previous work on unpurified SWNTs. The acid-treated SWNTs were less aggregated within cells than unpurified SWNTs. Acid treatment was found to affect the distribution of intracellular SWNTs. Bundles, and also individual acid treated SWNTs, were found frequently inside lysosomes, cytoplasm and also inserting into the plasma membrane whereas unpurified non-functionalised SWNTs entered lysosomes and occasionally the nucleus.

Empirical estimation of school siting parameter towards improving children's safety

Science.gov (United States)

Aziz, I. S.; Yusoff, Z. M.; Rasam, A. R. A.; Rahman, A. N. N. A.; Omar, D.

2014-02-01

Distance from school to home is a key determination in ensuring the safety of hildren. School siting parameters are made to make sure that a particular school is located in a safe environment. School siting parameters are made by Department of Town and Country Planning Malaysia (DTCP) and latest review was on June 2012. These school siting parameters are crucially important as they can affect the safety, school reputation, and not to mention the perception of the pupil and parents of the school. There have been many studies to review school siting parameters since these change in conjunction with this ever-changing world. In this study, the focus is the impact of school siting parameter on people with low income that live in the urban area, specifically in Johor Bahru, Malaysia. In achieving that, this study will use two methods which are on site and off site. The on site method is to give questionnaires to people and off site is to use Geographic Information System (GIS) and Statistical Product and Service Solutions (SPSS), to analyse the results obtained from the questionnaire. The output is a maps of suitable safe distance from school to house. The results of this study will be useful to people with low income as their children tend to walk to school rather than use transportation.

Functional high-intensity training improves pancreatic β-cell function in adults with type 2 diabetes.

Science.gov (United States)

Nieuwoudt, Stephan; Fealy, Ciarán E; Foucher, Julie A; Scelsi, Amanda R; Malin, Steven K; Pagadala, Mangesh; Rocco, Michael; Burguera, Bartolome; Kirwan, John P

2017-09-01

Type 2 diabetes (T2D) is characterized by reductions in β-cell function and insulin secretion on the background of elevated insulin resistance. Aerobic exercise has been shown to improve β-cell function, despite a subset of T2D patients displaying "exercise resistance." Further investigations into the effectiveness of alternate forms of exercise on β-cell function in the T2D patient population are needed. We examined the effect of a novel, 6-wk CrossFit functional high-intensity training (F-HIT) intervention on β-cell function in 12 sedentary adults with clinically diagnosed T2D (54 ± 2 yr, 166 ± 16 mg/dl fasting glucose). Supervised training was completed 3 days/wk, comprising functional movements performed at a high intensity in a variety of 10- to 20-min sessions. All subjects completed an oral glucose tolerance test and anthropometric measures at baseline and following the intervention. The mean disposition index, a validated measure of β-cell function, was significantly increased (PRE: 8.4 ± 3.1, POST: 11.5 ± 3.5, P = 0.02) after the intervention. Insulin processing inefficiency in the β-cell, expressed as the fasting proinsulin-to-insulin ratio, was also reduced (PRE: 2.40 ± 0.37, POST: 1.78 ± 0.30, P = 0.04). Increased β-cell function during the early-phase response to glucose correlated significantly with reductions in abdominal body fat ( R 2 = 0.56, P = 0.005) and fasting plasma alkaline phosphatase ( R 2 = 0.55, P = 0.006). Mean total body-fat percentage decreased significantly (Δ: -1.17 0.30%, P = 0.003), whereas lean body mass was preserved (Δ: +0.05 ± 0.68 kg, P = 0.94). We conclude that F-HIT is an effective exercise strategy for improving β-cell function in adults with T2D. Copyright © 2017 the American Physiological Society.

Functional outcomes following surgical-site infections after operative fixation of closed ankle fractures.

Science.gov (United States)

Naumann, Markus G; Sigurdsen, Ulf; Utvåg, Stein Erik; Stavem, Knut

2017-12-01

To compare the functional outcomes between patients with and without postoperative surgical-site infection (SSI) after surgical treatment in closed ankle fractures. Retrospective cohort study with prospective follow-up. Of 1011 treated patients, 959 were eligible for inclusion in a postal survey. Functional outcomes were assessed using three self-reported questionnaires. In total 567 patients responded a median of 4.3 years (range 3.1-6.2 years) after surgery. In total 29/567 had an SSI. The mean Olerud and Molander Ankle Score was 19.8 points lower for patients with a deep SSI (p=0.02), the Lower Extremity Functional Scale score was 10.2 points lower (p<0.01) and the Self-Reported Foot & Ankle Questionnaire score was 5.0 points higher (p=0.10) than for those without an SSI, after adjusting for age, sex, smoking status, diabetes, physical status, fracture classification and duration of surgery. Patients with a deep SSI had worse long-term functional outcomes than those without an SSI. Copyright © 2016 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

FAB (Functionally Alert Behavior Strategies) to Improve Self-Control

Science.gov (United States)

Pagano, John

2015-01-01

This paper describes the FAB (Functionally Alert Behavior) Strategies approach to improve behavior in children and adolescents with complex behavioral challenges. FAB Strategies include evidence-based environmental adaptations, sensory modulation, positive behavioral support, and physical self-regulation strategies. FAB Strategies can be used by…

Cardiac pacing in heart failure patients with left bundle branch block: impact of pacing site for optimizing left ventricular resynchronization.

Science.gov (United States)

Pappone, C; Rosanio, S; Oreto, G; Tocchi, M; Gulletta, S; Salvati, A; Dicandia, C; Santinelli, V; Mazzone, P; Veglia, F; Ding, J; Sallusti, L; Spinelli, J; Vicedomini, G

2000-07-01

Acute left ventricular pacing has been associated with hemodynamic improvement in patients with congestive heart failure and wide QRS complex. We hypothesized that pacing two left ventricular sites simultaneously would produce faster activation and better systolic function than single-site pacing. We selected 14 heart failure patients (NYHA functional class III or IV) in normal sinus rhythm with left bundle branch block and QRS > 150 ms. An 8F dual micromanometer catheter was placed in the aorta for measuring +dP/dt (mmHg/s), aortic pulse pressure (mmHg), and end-diastolic pressure (mmHg). Pacing leads were positioned via coronary veins at the posterior base and lateral wall. Patients were acutely paced VDD at the posterior base, lateral wall, and both sites (dual-site) with 5 atrioventricular delays (from 8 ms to PR -30 ms). Pacing sequences were executed in randomized order using a custom external computer (FlexStim, Guidant CRM). Dual-site pacing increased peak +dP/dt significantly more than posterior base and lateral wall pacing. Dual-site and posterior base pacing raised aortic pulse pressure significantly more than lateral wall pacing. Dual-site pacing shortened QRS duration by 22 %, whereas posterior base and lateral wall pacing increased it by 2 and 12%, respectively (p = 0.006). In heart failure patients with left bundle branch block, dual-site pacing improves systolic function more than single-site stimulation. Improved ventricular activation synchrony, expressed by paced QRS narrowing, may account for the additional benefit of dual- vs single-site pacing in enhancing contractility. This novel approach deserves consideration for future heart failure pacing studies.

Immediate improvement of motor function after epilepsy surgery in congenital hemiparesis.

Science.gov (United States)

Pascoal, Tharick; Paglioli, Eliseu; Palmini, André; Menezes, Rafael; Staudt, Martin

2013-08-01

Hemispherectomy often leads to a loss of contralateral hand function. In some children with congenital hemiparesis, however, paretic hand function remains unchanged. An immediate improvement of hand function has never been reported. A 17-year-old boy with congenital hemiparesis and therapy-refractory seizures due to a large infarction in the territory of the middle cerebral artery underwent epilepsy surgery. Intraoperatively, electrical cortical stimulation of the affected hemisphere demonstrated preserved motor projections from the sensorimotor cortex to the (contralateral) paretic hand. A frontoparietal resection was performed, which included a complete disconnection of all motor projections originating in the sensorimotor cortex of the affected hemisphere. Surprisingly, the paretic hand showed a significant functional improvement immediately after the operation. This observation demonstrates that, in congenital hemiparesis, crossed motor projections from the affected hemisphere are not always beneficial, but can be dysfunctional, interfering with ipsilateral motor control over the paretic hand by the contralesional hemisphere. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

PSA Model Improvement Using Maintenance Rule Function Mapping

Energy Technology Data Exchange (ETDEWEB)

Seo, Mi Ro [KHNP-CRI, Nuclear Safety Laboratory, Daejeon (Korea, Republic of)

2011-10-15

The Maintenance Rule (MR) program, in nature, is a performance-based program. Therefore, the risk information derived from the Probabilistic Safety Assessment model is introduced into the MR program during the Safety Significance determination and Performance Criteria selection processes. However, this process also facilitates the determination of the vulnerabilities in currently utilized PSA models and offers means of improving them. To find vulnerabilities in an existing PSA model, an initial review determines whether the safety-related MR functions are included in the PSA model. Because safety-related MR functions are related to accident prevention and mitigation, it is generally necessary for them to be included in the PSA model. In the process of determining the safety significance of each functions, quantitative risk importance levels are determined through a process known as PSA model basic event mapping to MR functions. During this process, it is common for some inadequate and overlooked models to be uncovered. In this paper, the PSA model and the MR program of Wolsong Unit 1 were used as references

Renal function improves with the treatment of hypothyroidism.

Science.gov (United States)

Bulur, Oktay; Dal, Kursat; Ertugrul, Derun Taner; Eser, Murat; Kaplan Efe, Fatma; Karakaya, Serdar; Şahin, Kubilay; Baser, Salih; Ata, Naim; Aybal Kutlugun, Aysun; Beyan, Esin

2017-08-01

It has been known that thyroid hormones may affect renal function. In this study, we aimed to investigate the effect of levothyroxine replacement on renal function in hypothyroid patients before and after treatment. We retrospectively investigated free T3 (fT3), free T4 (fT4), TSH, creatinine, and eGFR measurements during both hypothyroid and euthyroid states of hypothyroid patients. The eGFR was calculated using the simplified Modification of Diet in Renal Disease formula. fT3, fT4, and eGFR measurements increased, meanwhile creatinine and TSH levels decreased significantly after euthyroidism was achieved with levothyroxine treatment (p treatment (r: 0.288, p treatment (r: -0.272, p hypothyroidism and found out that renal function improved in most patients after euthyroidism was achieved. In some patients, above-normal creatinine levels completely returned to normal once the patients became euthyroid.

Identification of Key Functional Residues in the Active Site of Human β1,4-Galactosyltransferase 7

Science.gov (United States)

Talhaoui, Ibtissam; Bui, Catherine; Oriol, Rafael; Mulliert, Guillermo; Gulberti, Sandrine; Netter, Patrick; Coughtrie, Michael W. H.; Ouzzine, Mohamed; Fournel-Gigleux, Sylvie

2010-01-01

Glycosaminoglycans (GAGs) play a central role in many pathophysiological events, and exogenous xyloside substrates of β1,4-galactosyltransferase 7 (β4GalT7), a major enzyme of GAG biosynthesis, have interesting biomedical applications. To predict functional peptide regions important for substrate binding and activity of human β4GalT7, we conducted a phylogenetic analysis of the β1,4-galactosyltransferase family and generated a molecular model using the x-ray structure of Drosophila β4GalT7-UDP as template. Two evolutionary conserved motifs, 163DVD165 and 221FWGWGREDDE230, are central in the organization of the enzyme active site. This model was challenged by systematic engineering of point mutations, combined with in vitro and ex vivo functional assays. Investigation of the kinetic properties of purified recombinant wild-type β4GalT7 and selected mutants identified Trp224 as a key residue governing both donor and acceptor substrate binding. Our results also suggested the involvement of the canonical carboxylate residue Asp228 acting as general base in the reaction catalyzed by human β4GalT7. Importantly, ex vivo functional tests demonstrated that regulation of GAG synthesis is highly responsive to modification of these key active site amino acids. Interestingly, engineering mutants at position 224 allowed us to modify the affinity and to modulate the specificity of human β4GalT7 toward UDP-sugars and xyloside acceptors. Furthermore, the W224H mutant was able to sustain decorin GAG chain substitution but not GAG synthesis from exogenously added xyloside. Altogether, this study provides novel insight into human β4GalT7 active site functional domains, allowing manipulation of this enzyme critical for the regulation of GAG synthesis. A better understanding of the mechanism underlying GAG assembly paves the way toward GAG-based therapeutics. PMID:20843813

Improvement in cognitive and psychosocial functioning and self image among adolescent inpatient suicide attempters.

Science.gov (United States)

Hintikka, Ulla; Marttunen, Mauri; Pelkonen, Mirjami; Laukkanen, Eila; Viinamäki, Heimo; Lehtonen, Johannes

2006-12-29

Psychiatric treatment of suicidal youths is often difficult and non-compliance in treatment is a significant problem. This prospective study compared characteristics and changes in cognitive functioning, self image and psychosocial functioning among 13 to 18 year-old adolescent psychiatric inpatients with suicide attempts (n = 16) and with no suicidality (n = 39) The two-group pre-post test prospective study design included assessments by a psychiatrist, a psychologist and medical staff members as well as self-rated measures. DSM-III-R diagnoses were assigned using the SCID and thereafter transformed to DSM-IV diagnoses. Staff members assessed psychosocial functioning using the Global Assessment Scale (GAS). Cognitive performance was assessed using the Wechsler Adult Intelligence Scale, while the Offer Self-Image Questionnaire (OSIQ) was used to assess the subjects' self-image. ANCOVA with repeated measures was used to test changes from entry to discharge among the suicide attempters and non suicidal patients. Logistic regression modeling was used to assess variables associated with an improvement of 10 points or more in the GAS score. Among suicide attempter patients, psychosocial functioning, cognitive performance and both the psychological self and body-image improved during treatment and their treatment compliance and outcome were as good as that of the non-suicidal patients. Suicidal ideation and hopelessness declined, and psychosocial functioning improved. Changes in verbal cognitive performance were more pronounced among the suicide attempters. Having an improved body-image associated with a higher probability of improvement in psychosocial functioning while higher GAS score at entry was associated with lower probability of functional improvement in both patient groups. These findings illustrate that a multimodal treatment program seems to improve psychosocial functioning and self-image among severely disordered suicidal adolescent inpatients. There were no

Improvement in cognitive and psychosocial functioning and self image among adolescent inpatient suicide attempters

Directory of Open Access Journals (Sweden)

Laukkanen Eila

2006-12-01

Full Text Available Abstract Background Psychiatric treatment of suicidal youths is often difficult and non-compliance in treatment is a significant problem. This prospective study compared characteristics and changes in cognitive functioning, self image and psychosocial functioning among 13 to 18 year-old adolescent psychiatric inpatients with suicide attempts (n = 16 and with no suicidality (n = 39 Methods The two-group pre-post test prospective study design included assessments by a psychiatrist, a psychologist and medical staff members as well as self-rated measures. DSM-III-R diagnoses were assigned using the SCID and thereafter transformed to DSM-IV diagnoses. Staff members assessed psychosocial functioning using the Global Assessment Scale (GAS. Cognitive performance was assessed using the Wechsler Adult Intelligence Scale, while the Offer Self-Image Questionnaire (OSIQ was used to assess the subjects' self-image. ANCOVA with repeated measures was used to test changes from entry to discharge among the suicide attempters and non suicidal patients. Logistic regression modeling was used to assess variables associated with an improvement of 10 points or more in the GAS score. Results Among suicide attempter patients, psychosocial functioning, cognitive performance and both the psychological self and body-image improved during treatment and their treatment compliance and outcome were as good as that of the non-suicidal patients. Suicidal ideation and hopelessness declined, and psychosocial functioning improved. Changes in verbal cognitive performance were more pronounced among the suicide attempters. Having an improved body-image associated with a higher probability of improvement in psychosocial functioning while higher GAS score at entry was associated with lower probability of functional improvement in both patient groups. Conclusion These findings illustrate that a multimodal treatment program seems to improve psychosocial functioning and self-image among

Microbes from mined sites: Harnessing their potential for reclamation of derelict mine sites

International Nuclear Information System (INIS)

Thavamani, Palanisami; Samkumar, R. Amos; Satheesh, Viswanathan; Subashchandrabose, Suresh R.; Ramadass, Kavitha; Naidu, Ravi; Venkateswarlu, Kadiyala; Megharaj, Mallavarapu

2017-01-01

Derelict mines pose potential risks to environmental health. Several factors such as soil structure, organic matter, and nutrient content are the greatly affected qualities in mined soils. Soil microbial communities are an important element for successful reclamation because of their major role in nutrient cycling, plant establishment, geochemical transformations, and soil formation. Yet, microorganisms generally remain an undervalued asset in mined sites. The microbial diversity in derelict mine sites consists of diverse species belonging to four key phyla: Proteobacteria, Acidobacteria, Firmicutes, and Bacteroidetes. The activity of plant symbiotic microorganisms including root-colonizing rhizobacteria and ectomycorrhizal fungi of existing vegetation in the mined sites is very high since most of these microbes are extremophiles. This review outlines the importance of microorganisms to soil health and the rehabilitation of derelict mines and how microbial activity and diversity can be exploited to better plan the soil rehabilitation. Besides highlighting the major breakthroughs in the application of microorganisms for mined site reclamation, we provide a critical view on plant−microbiome interactions to improve revegetation at the mined sites. Also, the need has been emphasized for deciphering the molecular mechanisms of adaptation and resistance of rhizosphere and non-rhizosphere microbes in abandoned mine sites, understanding their role in remediation, and subsequent harnessing of their potential to pave the way in future rehabilitation strategies for mined sites. - Highlights: • Abandoned mines pose potential risks to human and environmental health. • Re-establishment of a self-sustaining vegetative cover at derelict mines is a major challenge. • Soil microbial communities are very important for successful reclamation of mined sites. • Role of microorganisms in soil function in derelict mines needs to be understood.

Improvement of methodical approaches to higher schools' marketing activity assessment on the basis of Internet technologies application

OpenAIRE

Elizaveta E. Tarasova; Evgeny A. Shein

2014-01-01

The paper substantiates the necessity of higher schools marketing activity developing on the basis of Internet technologies; suggests the technique of comprehensive assessment of functioning and quality of the site as the main tool of marketing activity on the Internet, substantiates the stages of its implementation and provides the approbation results; suggests strategic directions for the improvement of functioning and quality improvement of a higher school site, which makes it possible to ...

Using Low Levels of Stochastic Vestibular Stimulation to Improve Balance Function.

Directory of Open Access Journals (Sweden)

Rahul Goel

Full Text Available Low-level stochastic vestibular stimulation (SVS has been associated with improved postural responses in the medio-lateral (ML direction, but its effect in improving balance function in both the ML and anterior-posterior (AP directions has not been studied. In this series of studies, the efficacy of applying low amplitude SVS in 0-30 Hz range between the mastoids in the ML direction on improving cross-planar balance function was investigated. Forty-five (45 subjects stood on a compliant surface with their eyes closed and were instructed to maintain a stable upright stance. Measures of stability of the head, trunk, and whole body were quantified in ML, AP and combined APML directions. Results show that binaural bipolar SVS given in the ML direction significantly improved balance performance with the peak of optimal stimulus amplitude predominantly in the range of 100-500 μA for all the three directions, exhibiting stochastic resonance (SR phenomenon. Objective perceptual and body motion thresholds as estimates of internal noise while subjects sat on a chair with their eyes closed and were given 1 Hz bipolar binaural sinusoidal electrical stimuli were also measured. In general, there was no significant difference between estimates of perceptual and body motion thresholds. The average optimal SVS amplitude that improved balance performance (peak SVS amplitude normalized to perceptual threshold was estimated to be 46% in ML, 53% in AP, and 50% in APML directions. A miniature patch-type SVS device may be useful to improve balance function in people with disabilities due to aging, Parkinson's disease or in astronauts returning from long-duration space flight.

Geoscientific evaluation factors and criteria for siting and site evaluation. Progress report

International Nuclear Information System (INIS)

Stroem, A.; Ericsson, Lars O.; Svemar, C.; Almen, K.E.; Andersson, Johan

1999-03-01

The purposes of the present report are to: present the work that has been done to identify the parameters that need to be determined in a geoscientific site investigation and that serve as the basis for the work with geoscientific evaluation factors; give a progress report from the project that was initiated in 1997 named Siting Factors and Criteria for Site Evaluation, with an emphasis on definitions, outline and structure for the execution of the work; present geoscientific requirements on function both general and in detail in the form of an example for the discipline rock mechanics; present geoscientific evaluation factors associated with different stages in the siting work in the form of an example for the discipline hydrogeochemical composition; present plans for further work as regards criteria for site evaluation in different siting stages. The project is under way, and this is to be regarded as a progress report since e.g. criteria for site evaluation will be presented at a later date. The long-term performance and safety of the deep repository must always be evaluated by means of an integrated safety assessment. The work with factors and criteria can never take the place of such an assessment, but can provide guidance regarding its outcome. Requirements and preferences regarding the function of the rock in the deep repository have been clarified in this progress report. What is new here is the structuring that has been carried out, with a classification into different geoscientific disciplines, and the formalism that has been given to the terms requirement, preference and function. Based on fundamental safety and construction functions, requirements on function have been specified for the disciplines geology, thermal properties, hydro-geology, rock mechanics, chemistry and transport properties. Furthermore, function analyses have been identified by means of which it is possible to concretize requirements on function and which geoscientific parameters are

Geoscientific evaluation factors and criteria for siting and site evaluation. Progress report

Energy Technology Data Exchange (ETDEWEB)

Stroem, A.; Ericsson, Lars O.; Svemar, C. [Swedish Nuclear Fuel and Waste Management Co., Stockholm (Sweden); Almen, K.E. [KEA GEO-konsult AB (Sweden); Andersson, Johan [Golder Grundteknik KB (Sweden)

1999-03-01

The purposes of the present report are to: present the work that has been done to identify the parameters that need to be determined in a geoscientific site investigation and that serve as the basis for the work with geoscientific evaluation factors; give a progress report from the project that was initiated in 1997 named Siting Factors and Criteria for Site Evaluation, with an emphasis on definitions, outline and structure for the execution of the work; present geoscientific requirements on function both general and in detail in the form of an example for the discipline rock mechanics; present geoscientific evaluation factors associated with different stages in the siting work in the form of an example for the discipline hydrogeochemical composition; present plans for further work as regards criteria for site evaluation in different siting stages. The project is under way, and this is to be regarded as a progress report since e.g. criteria for site evaluation will be presented at a later date. The long-term performance and safety of the deep repository must always be evaluated by means of an integrated safety assessment. The work with factors and criteria can never take the place of such an assessment, but can provide guidance regarding its outcome. Requirements and preferences regarding the function of the rock in the deep repository have been clarified in this progress report. What is new here is the structuring that has been carried out, with a classification into different geoscientific disciplines, and the formalism that has been given to the terms requirement, preference and function. Based on fundamental safety and construction functions, requirements on function have been specified for the disciplines geology, thermal properties, hydro-geology, rock mechanics, chemistry and transport properties. Furthermore, function analyses have been identified by means of which it is possible to concretize requirements on function and which geoscientific parameters are

Structural and functional implications in the eubacterial ribosome as revealed by protein-rRNA and antibiotic contact sites.

Science.gov (United States)

Wittmann-Liebold, B; Uhlein, M; Urlaub, H; Müller, E C; Otto, A; Bischof, O

1995-01-01

Contact sites between protein and rRNA in 30S and 50S ribosomal subunits of Escherichia coli and Bacillus stearothermophilus were investigated at the molecular level using UV and 2-iminothiolane as cross-linkers. Thirteen ribosomal proteins (S3, S4, S7, S14, S17, L2, L4, L6, L14, L27, L28, L29, and L36) from these organisms were cross-linked in direct contact with the RNAs, and the peptide stretches as well as amino acids involved were identified. Further, the binding sites of puromycin and spiramycin were established at the peptide level in several proteins that were found to constitute the antibiotic-binding sites. Peptide stretches of puromycin binding were identified from proteins S7, S14, S18, L18, AND L29; those of spiramycin attachment were derived from proteins S12, S14, L17, L18, L27, and L35. Comparison of the RNA-peptide contact sites with the peptides identified for antibiotic binding and with those altered in antibiotic-resistant mutants clearly showed identical peptide areas to be involved and, hence, demonstrated the functional importance of these peptides. Further evidence for a functional implication of ribosomal proteins in the translational process came from complementation experiments in which protein L2 from Halobacterium marismortui was incorporated into the E. coli ribosomes that were active. The incorporated protein was present in 50S subunits and 70S particles, in disomes, and in higher polysomes. These results clearly demonstrate the functional implication of protein L2 in protein biosynthesis. Incorporation studies with a mutant of HmaL2 with a replacement of histidine-229 by glycine completely abolished the functional activity of the ribosome. Accordingly, protein L2 with histidine-229 is a crucial element of the translational machinery.

Transition and Closeout of the Former DOE Mound Plant Site: Lessons Learned

International Nuclear Information System (INIS)

Carpenter, C. P.; Marks, M. L.; Smiley, S.L.; Gallaher, D. M.

2006-01-01

The U.S. Department of Energy's (DOE's) Office of Environmental Management (EM) manages the Miamisburg Closure Project (MCP) by cleaning up the Mound site, located in Miamisburg, Ohio, to specific environmental standards, conveying all excess land parcels to the Miamisburg Mound Community Improvement Corporation, and transferring all continuing DOE post-closure responsibilities to the Office of Legacy Management (LM). Presently, the EM cleanup contract of the Mound site with CH2M Hill Mound Inc. is scheduled for completion on March 31, 2006. LM manages the Mound transition efforts and also post-closure responsibilities at other DOE sites via a contract with the S.M. Stoller Corporation. The programmatic transfer from EM to LM is scheduled to take place on October 1, 2006. The transition of the Mound site has required substantial integration and coordination between the EM and LM. Several project management principles have been implemented to help facilitate the transfer of programmatic responsibility. As a result, several lessons learned have been identified to help streamline and improve integration and coordination of the transfer process. Lessons learned from the Mound site transition project are considered a work in progress and have been summarized according to a work breakdown structure for specific functional areas in the transition schedule. The functional areas include program management, environmental, records management, information technology, property management, stakeholder and regulatory relations, procurement, worker pension and benefits, and project closeout. Specific improvements or best practices have been recognized and documented by the Mound transition team. The Mound site is one of three major cleanup sites within the EM organization scheduled for completion in 2006. EM, EM cleanup contractor, LM, and LM post-closure contractor have identified lessons learned during the transition and closure of the Mound site. The transition effort from

Identifying functional transcription factor binding sites in yeast by considering their positional preference in the promoters.

Directory of Open Access Journals (Sweden)

Fu-Jou Lai

Full Text Available Transcription factor binding site (TFBS identification plays an important role in deciphering gene regulatory codes. With comprehensive knowledge of TFBSs, one can understand molecular mechanisms of gene regulation. In the recent decades, various computational approaches have been proposed to predict TFBSs in the genome. The TFBS dataset of a TF generated by each algorithm is a ranked list of predicted TFBSs of that TF, where top ranked TFBSs are statistically significant ones. However, whether these statistically significant TFBSs are functional (i.e. biologically relevant is still unknown. Here we develop a post-processor, called the functional propensity calculator (FPC, to assign a functional propensity to each TFBS in the existing computationally predicted TFBS datasets. It is known that functional TFBSs reveal strong positional preference towards the transcriptional start site (TSS. This motivates us to take TFBS position relative to the TSS as the key idea in building our FPC. Based on our calculated functional propensities, the TFBSs of a TF in the original TFBS dataset could be reordered, where top ranked TFBSs are now the ones with high functional propensities. To validate the biological significance of our results, we perform three published statistical tests to assess the enrichment of Gene Ontology (GO terms, the enrichment of physical protein-protein interactions, and the tendency of being co-expressed. The top ranked TFBSs in our reordered TFBS dataset outperform the top ranked TFBSs in the original TFBS dataset, justifying the effectiveness of our post-processor in extracting functional TFBSs from the original TFBS dataset. More importantly, assigning functional propensities to putative TFBSs enables biologists to easily identify which TFBSs in the promoter of interest are likely to be biologically relevant and are good candidates to do further detailed experimental investigation. The FPC is implemented as a web tool at http://santiago.ee.ncku.edu.tw/FPC/.

Assessing Riparian Vegetation Condition and Function in Disturbed Sites of the Arid Northwestern Mexico

Directory of Open Access Journals (Sweden)

Lara Cornejo-Denman

2018-01-01

Full Text Available Transformation or modification of vegetation distribution and structure in arid riparian ecosystems can lead to the loss of ecological function. Mexico has 101,500,000 ha of arid lands, however there is a general lack of information regarding how arid riparian ecosystems are being modified. To assess these modifications, we use eight sites in the San Miguel River (central Sonora to analyze (1 riparian vegetation composition, structure and distribution using field sampling and remote sensing data from Unmanned Aerial Vehicles (UAV; (2 productivity (proxies, using vegetation indices derived from satellite data; and (3 variability posed by riparian vegetation and vegetation adjacent to riparian habitats. The development of a simple yet informative Anthropogenic-disturbance Index (ADI allowed us to classify and describe each study site. We found sharp differences in vegetation composition and structure between sites due to the absence/presence of obligate-riparian species. We also report significant difference between EVI (Enhanced Vegetation Index values for the dry season among vegetation types that develop near the edges of the river but differ in composition, suggesting that land cover changes form obligate-riparian to facultative-riparian species can lead to a loss in potential productivity. Finally, our tests suggest that sites with higher disturbance present lower photosynthetic activity.

CHERISH (collaboration for hospitalised elders reducing the impact of stays in hospital): protocol for a multi-site improvement program to reduce geriatric syndromes in older inpatients.

Science.gov (United States)

Mudge, Alison M; Banks, Merrilyn D; Barnett, Adrian G; Blackberry, Irene; Graves, Nicholas; Green, Theresa; Harvey, Gillian; Hubbard, Ruth E; Inouye, Sharon K; Kurrle, Sue; Lim, Kwang; McRae, Prue; Peel, Nancye M; Suna, Jessica; Young, Adrienne M

2017-01-09

Older inpatients are at risk of hospital-associated geriatric syndromes including delirium, functional decline, incontinence, falls and pressure injuries. These contribute to longer hospital stays, loss of independence, and death. Effective interventions to reduce geriatric syndromes remain poorly implemented due to their complexity, and require an organised approach to change care practices and systems. Eat Walk Engage is a complex multi-component intervention with structured implementation, which has shown reduced geriatric syndromes and length of stay in pilot studies at one hospital. This study will test effectiveness of implementing Eat Walk Engage using a multi-site cluster randomised trial to inform transferability of this intervention. A hybrid study design will evaluate the effectiveness and implementation strategy of Eat Walk Engage in a real-world setting. A multisite cluster randomised study will be conducted in 8 medical and surgical wards in 4 hospitals, with one ward in each site randomised to implement Eat Walk Engage (intervention) and one to continue usual care (control). Intervention wards will be supported to develop and implement locally tailored strategies to enhance early mobility, nutrition, and meaningful activities. Resources will include a trained, mentored facilitator, audit support, a trained healthcare assistant, and support by an expert facilitator team using the i-PARIHS implementation framework. Patient outcomes and process measures before and after intervention will be compared between intervention and control wards. Primary outcomes are any hospital-associated geriatric syndrome (delirium, functional decline, falls, pressure injuries, new incontinence) and length of stay. Secondary outcomes include discharge destination; 30-day mortality, function and quality of life; 6 month readmissions; and cost-effectiveness. Process measures including patient interviews, activity mapping and mealtime audits will inform interventions in each

Using Quality Function Deployment To Improve Academic Advising Processes.

Science.gov (United States)

Barrows, Richard; Murray, Bruce

1997-01-01

Quality Function Deployment, a set of concepts and tools used in manufacturing engineering to link consumer needs with product design, can also improve academic advising systems and processes. The technique promotes structured, logical examination of students' advising needs and their relationship to advising system design, processes, methods,…

Vagal activation by sham feeding improves gastric motility in functional dyspepsia.

Science.gov (United States)

Lunding, J A; Nordström, L M; Haukelid, A-O; Gilja, O H; Berstad, A; Hausken, T

2008-06-01

Antral hypomotility and impaired gastric accommodation in patients with functional dyspepsia have been ascribed to vagal dysfunction. We investigated whether vagal stimulation by sham feeding would improve meal-induced gastric motor function in these patients. Fourteen healthy volunteers and 14 functional dyspepsia patients underwent a drink test twice, once with and once without simultaneous sham feeding. After ingesting 500 mL clear meat soup (20 kcal, 37 degrees C) in 4 min, sham feeding was performed for 10 min by chewing a sugar-containing chewing gum while spitting out saliva. Using two- and three-dimensional ultrasound, antral motility index (contraction amplitude x frequency) and intragastric volumes were estimated. Without sham feeding, functional dyspepsia patients had lower motility index than healthy volunteers (area under curve 8.0 +/- 1.2 vs 4.4 +/- 1.0 min(-1), P = 0.04). In functional dyspepsia patients, but not in healthy volunteers, motility index increased and intragastric volume tended to increase by sham feeding (P = 0.04 and P = 0.06 respectively). The change in motility index was negatively correlated to the change in pain score (r = -0.59, P = 0.007). In functional dyspepsia patients, vagal stimulation by sham feeding improves antral motility in response to a soup meal. The result supports the view that impaired vagal stimulation is implicated in the pathogenesis of gastric motility disturbances in functional dyspepsia.

Physiotherapy improves patient reported shoulder function and health status in patients with subacromial impingement syndrome

DEFF Research Database (Denmark)

Storgaard, Filip Holst; Pedersen, Christina Gravgaard; Jensen, Majbritt Lykke

Physiotherapy improves patient reported shoulder function and health status in patients with subacromial impingement syndrome.......Physiotherapy improves patient reported shoulder function and health status in patients with subacromial impingement syndrome....

Improvement of a Pneumatic Control Valve with Self-Holding Function

Science.gov (United States)

Dohta, Shujiro; Akagi, Tetsuya; Kobayashi, Wataru; Shimooka, So; Masago, Yusuke

2017-10-01

The purpose of this study is to develop a small-sized, lightweight and low-cost control valve with low energy consumption and to apply it to the assistive system. We have developed some control valves; a tiny on/off valve using a vibration motor, and an on/off valve with self-holding function. We have also proposed and tested the digital servo valve with self-holding function using permanent magnets and a small-sized servo motor. In this paper, in order to improve the valve, an analytical model of the digital servo valve is proposed. And the simulated results by using the analytical model and identified parameters were compared with the experimental results. Then, the improved digital servo valve was designed based on the calculated results and tested. As a result, we realized the digital servo valve that can control the flow rate more precisely while maintaining its volume and weight compared with the previous valve. As an application of the improved valve, a position control system of rubber artificial muscle was built and the position control was performed successfully.

Acute limb heating improves macro- and microvascular dilator function in the leg of aged humans.

Science.gov (United States)

Romero, Steven A; Gagnon, Daniel; Adams, Amy N; Cramer, Matthew N; Kouda, Ken; Crandall, Craig G

2017-01-01

Local heating of an extremity increases blood flow and vascular shear stress throughout the arterial tree. Local heating acutely improves macrovascular dilator function in the upper limbs of young healthy adults through a shear stress-dependent mechanism but has no such effect in the lower limbs of this age group. The effect of acute limb heating on dilator function within the atherosclerotic prone vasculature of the lower limbs of aged adults is unknown. Therefore, the purpose of this study was to test the hypothesis that acute lower limb heating improves macro- and microvascular dilator function within the leg vasculature of aged adults. Nine young and nine aged adults immersed their lower limbs at a depth of ~33 cm into a heated (~42°C) circulated water bath for 45 min. Before and 30 min after heating, macro (flow-mediated dilation)- and microvascular (reactive hyperemia) dilator functions were assessed in the lower limb, following 5 min of arterial occlusion, via Doppler ultrasound. Compared with preheat, macrovascular dilator function was unchanged following heating in young adults (P = 0.6) but was improved in aged adults (P = 0.04). Similarly, microvascular dilator function, as assessed by peak reactive hyperemia, was unchanged following heating in young adults (P = 0.1) but was improved in aged adults (P lower limb heating improves both macro- and microvascular dilator function in an age dependent manner. We demonstrate that lower limb heating acutely improves macro- and microvascular dilator function within the atherosclerotic prone vasculature of the leg in aged adults. These findings provide evidence for a potential therapeutic use of chronic lower limb heating to improve vascular health in primary aging and various disease conditions. Copyright © 2017 the American Physiological Society.

Improved dielectric functions in metallic films obtained via template stripping

Science.gov (United States)

Hyuk Park, Jong; Nagpal, Prashant; Oh, Sang-Hyun; Norris, David J.

2012-02-01

We compare the dielectric functions of silver interfaces obtained via thermal evaporation with those obtained with template stripping. Ellipsometry measurements show that the smoother template-stripped surfaces exhibit effective dielectric functions with a more negative real component and a smaller imaginary component, implying higher conductivity and less energy loss, respectively. These results agree with the relation between dielectric function and surface roughness derived from combining the effective-medium model and the Drude-Lorentz model. The improvement in the effective dielectric properties shows that metallic films prepared via template stripping can be favorable for applications in electronics, nanophotonics, and plasmonics.

Prosthetic Smart Socket Technology to Improve Patient Interaction, Usability, Comfort, Fit and Function

Science.gov (United States)

2017-10-01

impact on society beyond science and technology ? Nothing to report at this time. 5. CHANGES/PROBLEMS: Changes in approach and reasons for...AWARD NUMBER: W81XWH-16-1-0785 TITLE: Prosthetic Smart Socket Technology to Improve Patient Interaction, Usability, Comfort, Fit and Function...2016 - 29 Sep 2017 4. TITLE AND SUBTITLE Prosthetic Smart Socket Technology to Improve Patient Interaction, Usability, Comfort, Fit and Function 5a

Quality assurance in functional MRI

DEFF Research Database (Denmark)

Liu, Thomas T; Glover, Gary H; Mueller, Bryon A

2015-01-01

Over the past 20 years, functional magnetic resonance imaging (fMRI) has ben- efited greatly from improvements in MRI hardware and software. At the same time, fMRI researchers have pushed the technical limits of MRI systems and greatly in- fluenced the development of state-of-the-art systems...... consistent data throughout the course of a study, and consistent stability across time and sites is needed to allow data from different time periods or acquisition sites to be optimally integrated....

Methylphenidate improves motor functions in children diagnosed with Hyperkinetic Disorder

Directory of Open Access Journals (Sweden)

Iversen Synnøve

2009-05-01

Full Text Available Abstract Background A previous study showed that a high percentage of children diagnosed with Hyperkinetic Disorder (HKD displayed a consistent pattern of motor function problems. The purpose of this study was to investigate the effect of methylphenidate (MPH on such motor performance in children with HKD Methods 25 drug-naïve boys, aged 8–12 yr with a HKD-F90.0 diagnosis, were randomly assigned into two groups within a double blind cross-over design, and tested with a motor assessment instrument, during MPH and placebo conditions. Results The percentage of MFNU scores in the sample indicating 'severe motor problems' ranged from 44–84%, typically over 60%. Highly significant improvements in motor performance were observed with MPH compared to baseline ratings on all the 17 subtests of the MFNU 1–2 hr after administration of MPH. There were no significant placebo effects. The motor improvement was consistent with improvement of clinical symptoms. Conclusion The study confirmed our prior clinical observations showing that children with ADHD typically demonstrate marked improvements of motor functions after a single dose of 10 mg MPH. The most pronounced positive MPH response was seen in subtests measuring either neuromotor inhibition, or heightened muscular tone in the gross movement muscles involved in maintaining the alignment and balance of the body. Introduction of MPH generally led to improved balance and a generally more coordinated and controlled body movement.

Single-site Green function of the Dirac equation for full-potential electron scattering

Energy Technology Data Exchange (ETDEWEB)

Kordt, Pascal

2012-05-30

I present an elaborated analytical examination of the Green function of an electron scattered at a single-site potential, for both the Schroedinger and the Dirac equation, followed by an efficient numerical solution, in both cases for potentials of arbitrary shape without an atomic sphere approximation. A numerically stable way to calculate the corresponding regular and irregular wave functions and the Green function is via the angular Lippmann-Schwinger integral equations. These are solved based on an expansion in Chebyshev polynomials and their recursion relations, allowing to rewrite the Lippmann-Schwinger equations into a system of algebraic linear equations. Gonzales et al. developed this method for the Schroedinger equation, where it gives a much higher accuracy compared to previous perturbation methods, with only modest increase in computational effort. In order to apply it to the Dirac equation, I developed relativistic Lippmann-Schwinger equations, based on a decomposition of the potential matrix into spin spherical harmonics, exploiting certain properties of this matrix. The resulting method was embedded into a Korringa-Kohn-Rostoker code for density functional calculations. As an example, the method is applied by calculating phase shifts and the Mott scattering of a tungsten impurity. (orig.)

Single-site Green function of the Dirac equation for full-potential electron scattering

International Nuclear Information System (INIS)

Kordt, Pascal

2012-01-01

I present an elaborated analytical examination of the Green function of an electron scattered at a single-site potential, for both the Schroedinger and the Dirac equation, followed by an efficient numerical solution, in both cases for potentials of arbitrary shape without an atomic sphere approximation. A numerically stable way to calculate the corresponding regular and irregular wave functions and the Green function is via the angular Lippmann-Schwinger integral equations. These are solved based on an expansion in Chebyshev polynomials and their recursion relations, allowing to rewrite the Lippmann-Schwinger equations into a system of algebraic linear equations. Gonzales et al. developed this method for the Schroedinger equation, where it gives a much higher accuracy compared to previous perturbation methods, with only modest increase in computational effort. In order to apply it to the Dirac equation, I developed relativistic Lippmann-Schwinger equations, based on a decomposition of the potential matrix into spin spherical harmonics, exploiting certain properties of this matrix. The resulting method was embedded into a Korringa-Kohn-Rostoker code for density functional calculations. As an example, the method is applied by calculating phase shifts and the Mott scattering of a tungsten impurity. (orig.)

Improving the performance of brine wells at Gulf Coast strategic petroleum reserve sites

Energy Technology Data Exchange (ETDEWEB)

Owen, L.B.; Quong, R. (eds.)

1979-11-05

At the request of the Department of Energy, field techniques were developed to evaluate and improve the injection of brine into wells at Strategic Petroleum Reserve (SPR) sites. These wells are necessary for the disposal of saturated brine removed from salt domes where oil is being stored. The wells, which were accepting brine at 50 percent or less of their initial design rates, were impaired by saturated brine containing particulates that deposited on the sand face and in the geologic formation next to the wellbore. Corrosion of the brine-disposal pipelines and injection wells contributed to the impairment by adding significant amounts of particulates in the form of corrosion products. When tests were implemented at the SPR sites, it was found that the poor quality of injected brines was the primary cause of impaired injection; that granular-media filtration, when used with chemical pretreatment, is an effective method for removing particulates from hypersaline brine; that satisfactory injection-well performance can be attained with prefiltered brines; and that corrosion rates can be substantially reduced by oxygen-scavenging.

Functional Improvement in Older Adults after a Falls Prevention Pilot Study

Directory of Open Access Journals (Sweden)

Pei-Fen J. Chang Ph.D., OTR

2013-02-01

Full Text Available Falls are a costly, disabling, and life-threatening risk in the elderly. Improvements in physical function, balance, lower extremity strength, and health-related quality of life are hypothesized to help mitigate fall risk. In this pilot study, six women and men with an average age of 81 years participated in a 6-week exercise andeducation program created to reduce risk of falls. Evaluations were made at baseline and at 6 weeks on four tests: the Functional Status Questionnaire, the Berg Balance Scale (BBS, the Six-minute Walk Test, and the World Health Organization Quality of Life–BREF 26-question test. Scores indicated significant improvement in functional physical status (activities of daily living, balance, distance walked in 6 min, and quality of life in the physical health domain. The size of this study limits the generalizability of its findings, but its evidence warrants undertaking a larger trial.

Physical Activity to Improve Erectile Function

DEFF Research Database (Denmark)

Gerbild, Helle; Larsen, Camilla Marie; Graugaard, Christian

2018-01-01

, and metabolic syndrome. Physical activity (PA) has proved to be a protective factor against erectile problems, and it has been shown to improve erectile function for men affected by vascular ED. This systematic review estimated the levels of PA needed to decrease ED for men with physical inactivity, obesity......, hypertension, metabolic syndrome, and/or manifest cardiovascular diseases. Aim To provide recommendations of levels of PA needed to decrease ED for men with physical inactivity, obesity, hypertension, metabolic syndrome, and/or cardiovascular diseases. Methods In accord with the Preferred Reporting Items...... intensity 4 times per week. Overall, weekly exercise of 160 minutes for 6 months contributes to decreasing erectile problems in men with ED caused by physical inactivity, obesity, hypertension, metabolic syndrome, and/or cardiovascular diseases....

Improving Balance Function Using Low Levels of Electrical Stimulation of the Balance Organs

Science.gov (United States)

Bloomberg, Jacob; Reschke, Millard; Mulavara, Ajitkumar; Wood, Scott; Serrador, Jorge; Fiedler, Matthew; Kofman, Igor; Peters, Brian T.; Cohen, Helen

2012-01-01

Crewmembers returning from long-duration space flight face significant challenges due to the microgravity-induced inappropriate adaptations in balance/ sensorimotor function. The Neuroscience Laboratory at JSC is developing a method based on stochastic resonance to enhance the brain s ability to detect signals from the balance organs of the inner ear and use them for rapid improvement in balance skill, especially when combined with balance training exercises. This method involves a stimulus delivery system that is wearable/portable providing imperceptible electrical stimulation to the balance organs of the human body. Stochastic resonance (SR) is a phenomenon whereby the response of a nonlinear system to a weak periodic input signal is optimized by the presence of a particular non-zero level of noise. This phenomenon of SR is based on the concept of maximizing the flow of information through a system by a non-zero level of noise. Application of imperceptible SR noise coupled with sensory input in humans has been shown to improve motor, cardiovascular, visual, hearing, and balance functions. SR increases contrast sensitivity and luminance detection; lowers the absolute threshold for tone detection in normal hearing individuals; improves homeostatic function in the human blood pressure regulatory system; improves noise-enhanced muscle spindle function; and improves detection of weak tactile stimuli using mechanical or electrical stimulation. SR noise has been shown to improve postural control when applied as mechanical noise to the soles of the feet, or when applied as electrical noise at the knee and to the back muscles.

Site-specific mouth rinsing can improve oral odor by altering bacterial counts. Blind crossover clinical study.

Science.gov (United States)

Alqumber, Mohammed A; Arafa, Khaled A

2014-11-01

To determine whether site-specific mouth rinsing with oral disinfectants can improve oral odor beyond the traditional panoral mouth disinfection with mouth rinses by targeting specifically oral malodor implicated anaerobic bacteria. Twenty healthy fasting subjects volunteered for a blinded prospective, descriptive correlational crossover cross-section clinical trial conducted during the month of Ramadan between July and August 2013 in Albaha province in Saudi Arabia involving the application of Listerine Cool Mint mouth rinse by either the traditional panoral rinsing method, or a site-specific disinfection method targeting the subgingival and supragingival plaque and the posterior third of the tongue dorsum, while avoiding the remaining locations within the oral cavity. The viable anaerobic and aerobic bacterial counts, volatile sulfur compounds (VSCs) levels, organoleptic assessment of oral odor, and the tongue-coating index were compared at baseline, one, 5, and 9 hours after the treatment. The site-specific disinfection method reduced the VSCs and anaerobic bacterial loads while keeping the aerobic bacterial numbers higher than the traditional panoral rinsing method. Site-specific disinfection can more effectively maintain a healthy oral cavity by predominantly disinfecting the niches of anaerobic bacteria within the oral cavity.

Milk protein tailoring to improve functional and biological properties

Directory of Open Access Journals (Sweden)

JEAN-MARC CHOBERT

2012-01-01

Full Text Available Proteins are involved in every aspects of life: structure, motion, catalysis, recognition and regulation. Today's highly sophisticated science of the modifications of proteins has ancient roots. The tailoring of proteins for food and medical uses precedes the beginning of what is called biochemistry. Chemical modification of proteins was pursued early in the twentieth century as an analytical procedure for side-chain amino acids. Later, methods were developed for specific inactivation of biologically active proteins and titration of their essential groups. Enzymatic modifications were mainly developed in the seventies when many more enzymes became economically available. Protein engineering has become a valuable tool for creating or improving proteins for practical use and has provided new insights into protein structure and function. The actual and potential use of milk proteins as food ingredients has been a popular topic for research over the past 40 years. With today's sophisticated analytical, biochemical and biological research tools, the presence of compounds with biological activity has been demonstrated. Improvements in separation techniques and enzyme technology have enabled efficient and economic isolation and modification of milk proteins, which has made possible their use as functional foods, dietary supplements, nutraceuticals and medical foods. In this review, some chemical and enzymatic modifications of milk proteins are described, with particular focus on their functional and biological properties.

Facile Site-Directed Mutagenesis of Large Constructs Using Gibson Isothermal DNA Assembly.

Science.gov (United States)

Yonemoto, Isaac T; Weyman, Philip D

2017-01-01

Site-directed mutagenesis is a commonly used molecular biology technique to manipulate biological sequences, and is especially useful for studying sequence determinants of enzyme function or designing proteins with improved activity. We describe a strategy using Gibson Isothermal DNA Assembly to perform site-directed mutagenesis on large (>~20 kbp) constructs that are outside the effective range of standard techniques such as QuikChange II (Agilent Technologies), but more reliable than traditional cloning using restriction enzymes and ligation.

Development and Application of SITES

International Nuclear Information System (INIS)

Park, Jo Wan; Yoon; Yoon, Jeong Hyoun; Kim, Chank Lak; Cho, Sung IL

2008-01-01

SITES (Site Information and Total Environmental Data Management System) has been developed for the purpose of systematically managing site characteristics and environmental data produced during the pre-operational, operational, and post-closure phases of a radioactive waste disposal facility. SITES is an integration system, which consists of 4 modules, to be available for maintenance of site characteristics data, for safety assessment, and for site/environment monitoring; site environmental data management module (SECURE), integrated safety assessment module (SAINT), site/environment monitoring module (SUDAL) and geological information module for geological data management (SITES-GIS). Each module has its database with the functions of browsing, storing, and reporting data and information. Data from SECURE and SUDAL are interconnected to be utilized as inputs to SAINT. SAINT has the functions that multi-user can access simultaneously via client-server system, and the safety assessment results can be managed with its embedded Quality Assurance feature. Comparison between assessment results and environmental monitoring data can be made and visualized in SUDAL and SITES-GIS. Also, SUDAL is designed that the periodic monitoring data and information could be opened to the public via internet homepage. SITES has applied to the Wolsong low- and intermediate-level radioactive waste disposal center in Korea, and is expected to enhance the function of site/environment monitoring in other nuclear-related facilities and also in industrial facilities handling hazardous materials.

A comprehensive software suite for protein family construction and functional site prediction.

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David Renfrew Haft

Full Text Available In functionally diverse protein families, conservation in short signature regions may outperform full-length sequence comparisons for identifying proteins that belong to a subgroup within which one specific aspect of their function is conserved. The SIMBAL workflow (Sites Inferred by Metabolic Background Assertion Labeling is a data-mining procedure for finding such signature regions. It begins by using clues from genomic context, such as co-occurrence or conserved gene neighborhoods, to build a useful training set from a large number of uncharacterized but mutually homologous proteins. When training set construction is successful, the YES partition is enriched in proteins that share function with the user's query sequence, while the NO partition is depleted. A selected query sequence is then mined for short signature regions whose closest matches overwhelmingly favor proteins from the YES partition. High-scoring signature regions typically contain key residues critical to functional specificity, so proteins with the highest sequence similarity across these regions tend to share the same function. The SIMBAL algorithm was described previously, but significant manual effort, expertise, and a supporting software infrastructure were required to prepare the requisite training sets. Here, we describe a new, distributable software suite that speeds up and simplifies the process for using SIMBAL, most notably by providing tools that automate training set construction. These tools have broad utility for comparative genomics, allowing for flexible collection of proteins or protein domains based on genomic context as well as homology, a capability that can greatly assist in protein family construction. Armed with this new software suite, SIMBAL can serve as a fast and powerful in silico alternative to direct experimentation for characterizing proteins and their functional interactions.

Using Biomass to Improve Site Quality and Carbon Sequestration

Science.gov (United States)

Bryce J. Stokes; Felipe G. Sanchez; Emily A. Carter

1998-01-01

The future demands on forest lands are a concern because of reduced productivity, especially on inherently poor sites, sites with long-depleted soils, or those soils that bear repeated, intensive short rotations. Forests are also an important carbon sink and, when well managed, can make even more significant contributions to sequestration and to reduction of greenhouse...

The Use of Non-Variant Sites to Improve the Clinical Assessment of Whole-Genome Sequence Data.

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Alberto Ferrarini

Full Text Available Genetic testing, which is now a routine part of clinical practice and disease management protocols, is often based on the assessment of small panels of variants or genes. On the other hand, continuous improvements in the speed and per-base costs of sequencing have now made whole exome sequencing (WES and whole genome sequencing (WGS viable strategies for targeted or complete genetic analysis, respectively. Standard WGS/WES data analytical workflows generally rely on calling of sequence variants respect to the reference genome sequence. However, the reference genome sequence contains a large number of sites represented by rare alleles, by known pathogenic alleles and by alleles strongly associated to disease by GWAS. It's thus critical, for clinical applications of WGS and WES, to interpret whether non-variant sites are homozygous for the reference allele or if the corresponding genotype cannot be reliably called. Here we show that an alternative analytical approach based on the analysis of both variant and non-variant sites from WGS data allows to genotype more than 92% of sites corresponding to known SNPs compared to 6% genotyped by standard variant analysis. These include homozygous reference sites of clinical interest, thus leading to a broad and comprehensive characterization of variation necessary to an accurate evaluation of disease risk. Altogether, our findings indicate that characterization of both variant and non-variant clinically informative sites in the genome is necessary to allow an accurate clinical assessment of a personal genome. Finally, we propose a highly efficient extended VCF (eVCF file format which allows to store genotype calls for sites of clinical interest while remaining compatible with current variant interpretation software.

Improving the activity of the subtilisin nattokinase by site-directed mutagenesis and molecular dynamics simulation.

Science.gov (United States)

Weng, Meizhi; Deng, Xiongwei; Bao, Wei; Zhu, Li; Wu, Jieyuan; Cai, Yongjun; Jia, Yan; Zheng, Zhongliang; Zou, Guolin

2015-09-25

Nattokinase (NK), a bacterial serine protease from Bacillus subtilis var. natto, is a potential cardiovascular drug exhibiting strong fibrinolytic activity. To broaden its commercial and medical applications, we constructed a single-mutant (I31L) and two double-mutants (M222A/I31L and T220S/I31L) by site-directed mutagenesis. Active enzymes were expressed in Escherichia coli with periplasmic secretion and were purified to homogeneity. The kinetic parameters of enzymes were examined by spectroscopy assay and isothermal titration calorimetry (ITC), and their fibrinolytic activities were determined by fibrin plate method. The substitution of Leu(31) for Ile(31) resulted in about 2-fold enhancement of catalytic efficiency (Kcat/KM) compared with wild-type NK. The specific activities of both double-mutants (M222A/I31L and T220S/I31L) were significantly increased when compared with the single-mutants (M222A and T220S) and the oxidative stability of M222A/I31L mutant was enhanced with respect to wild-type NK. This study demonstrates the feasibility of improving activity of NK by site-directed mutagenesis and shows successful protein engineering cases to improve the activity of NK as a potent therapeutic agent. Copyright © 2015 Elsevier Inc. All rights reserved.

Modification of a deoxynivalenol-antigen-mimicking nanobody to improve immunoassay sensitivity by site-saturation mutagenesis.

Science.gov (United States)

Qiu, Yu-Lou; He, Qing-Hua; Xu, Yang; Wang, Wei; Liu, Yuan-Yuan

2016-01-01

A nanobody (N-28) which can act as a deoxynivalenol (DON) antigen has been generated, and its residues Thr102-Ser106 were identified to bind with anti-DON monoclonal antibody by alanine-scanning mutagenesis. Site-saturation mutagenesis was used to analyze the plasticity of five residues and to improve the sensitivity of the N-28-based immunoassay. After mutagenesis, three mutants were selected by phage immunoassay and were sequenced. The half-maximal inhibitory concentrations of the immunoassay based on mutants N-28-T102Y, N-28-V103L, and N-28-Y105F were 24.49 ± 1.0, 51.83 ± 2.5, and 35.65 ± 1.6 ng/mL, respectively, showing the assay was, respectively, 3.2, 1.5, and 2.2 times more sensitive than the wild-type-based assay. The best mutant, N-28-T102Y, was used to develop a competitive phage ELISA to detect DON in cereals with high specificity and accuracy. In addition, the structural properties of N-28-T102Y and N-28 were investigated, revealing that the affinity of N-28-T102Y decreased because of increased steric hindrance with the large side chain. The lower-binding-affinity antigen mimetic may contribute to the improvement of the sensitivity of competitive immunoassays. These results demonstrate that nanobodies would be a favorable tool for engineering. Moreover, our results have laid a solid foundation for site-saturation mutagenesis of antigen-mimicking nanobodies to improve immunoassay sensitivity for small molecules.

Social Skills Intervention Participation and Associated Improvements in Executive Function Performance

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Shawn E. Christ

2017-01-01

Full Text Available Autism spectrum disorder (ASD is a neurodevelopmental disorder characterized by impairments in social communication. It has been postulated that such difficulties are related to disruptions in underlying cognitive processes such as executive function. The present study examined potential changes in executive function performance associated with participation in the Social Competence Intervention (SCI program, a short-term intervention designed to improve social competence in adolescents with ASD. Laboratory behavioral performance measures were used to separately evaluate potential intervention-related changes in individual executive function component processes (i.e., working memory, inhibitory control, and cognitive flexibility in a sample of 22 adolescents with ASD both before and after intervention. For comparison purposes, a demographically matched sample of 14 individuals without ASD was assessed at identical time intervals. Intervention-related improvements were observed on the working memory task, with gains evident in spatial working memory and, to a slightly lesser degree, verbal working memory. Significant improvements were also found for a working memory-related aspect of the task switching test (i.e., mixing costs. Taken together, these findings provide preliminary support for the hypothesis that participation in the SCI program is accompanied by changes in underlying neurocognitive processes such as working memory.

A Multimodal, Nonpharmacologic Intervention Improves Mood and Cognitive Function in People with Multiple Sclerosis.

Science.gov (United States)

Lee, Jennifer E; Bisht, Babita; Hall, Michael J; Rubenstein, Linda M; Louison, Rebecca; Klein, Danielle T; Wahls, Terry L

2017-01-01

The objective of this study was to examine whether participation in a 12-month multimodal intervention would improve mood and cognitive function in adults with progressive multiple sclerosis (MS). In this one-arm, open-label feasibility trial, participants were prescribed a home-based multimodal intervention, including (1) a modified Paleolithic diet; (2) an exercise program (stretching and strengthening of the trunk and lower limb muscles); (3) neuromuscular electrical stimulation (EStim) of trunk and lower limb muscles; and (4) stress management (meditation and self-massage). Individuals completed measures of mood (Beck Anxiety and Depression Inventories) and cognitive (Cognitive Stability Index, Cognitive Screening Test, Delis-Kaplan Executive Function System) and executive function (Wechsler Adult Intelligence Scale) at baseline and 3, 6, 9, and 12 months after the start of the intervention. Dosage of the multimodal intervention was assessed at 3, 6, 9, and 12 months. The more individuals participated in the intervention activities, the greater improvements they had from baseline to 12 months on self-report measures of anxiety (Beck Anxiety Inventory [BAI]; ps = 0.001 to 0.02), depression (Beck Depression Inventory [BDI]; ps = Mood and cognitive improvements were more closely related to a higher intake of the modified Paleolithic diet than to exercise and stress management dosage. Anxiety and depression changes were evident after just a few months, whereas changes in cognitive function were generally not observed until later in the intervention period. Mood and cognitive function changes from baseline to 12 months were significantly associated with fatigue improvements (ps = exercise, EStim, and stress management intervention like this one has the potential to improve the mood and cognitive symptoms that can lead to considerable suffering in people with MS, potentially improving quality of life and function for people with progressive MS.

Mesenchymal stromal cells improve human islet function through released products and extracellular matrix.

Science.gov (United States)

Arzouni, Ahmed A; Vargas-Seymour, Andreia; Rackham, Chloe L; Dhadda, Paramjeet; Huang, Guo-Cai; Choudhary, Pratik; Nardi, Nance; King, Aileen J F; Jones, Peter M

2017-12-01

The aims of the present study were (i) to determine whether the reported beneficial effects of mesenchymal stromal cells (MSCs) on mouse islet function extend to clinically relevant human tissues (islets and MSCs), enabling translation into improved protocols for clinical human islet transplantation; and (ii) to identify possible mechanisms through which human MSCs influence human islet function. Human islets were co-cultured with human adipose tissue-derived MSCs (hASCs) or pre-treated with its products - extracellular matrix (ECM) and annexin A1 (ANXA1). Mouse islets were pre-treated with mouse MSC-derived ECM. Islet insulin secretory function was assessed in vitro by radioimmunoassay. Quantitative RT-PCR was used to screen human adipMSCs for potential ligands of human islet G-protein-coupled receptors. We show that co-culture with hASCs improves human islet secretory function in vitro , as measured by glucose-stimulated insulin secretion, confirming previous reports using rodent tissues. Furthermore, we demonstrate that these beneficial effects on islet function can be partly attributed to the MSC-derived products ECM and ANXA1. Our results suggest that hASCs have the potential to improve the quality of human islets isolated for transplantation therapy of Type 1 diabetes. Furthermore, it may be possible to achieve improvements in human islet quality in a cell-free culture system by using the MSC-derived products ANXA1 and ECM. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

EXERCISE IMPROVES SEXUAL FUNCTION IN WOMEN TAKING ANTIDEPRESSANTS: RESULTS FROM A RANDOMIZED CROSSOVER TRIAL

Science.gov (United States)

Lorenz, Tierney Ahrold; Meston, Cindy May

2014-01-01

Background In laboratory studies, exercise immediately before sexual stimuli improved sexual arousal of women taking antidepressants [1]. We evaluated if exercise improves sexual desire, orgasm, and global sexual functioning in women experiencing antidepressant-induced sexual side effects. Methods Fifty-two women who were reporting antidepressant sexual side effects were followed for 3 weeks of sexual activity only. They were randomized to complete either three weeks of exercise immediately before sexual activity (3×/week) or 3 weeks of exercise separate from sexual activity (3×/week). At the end of the first exercise arm, participants crossed to the other. We measured sexual functioning, sexual satisfaction, depression, and physical health. Results Exercise immediately prior to sexual activity significantly improved sexual desire and, for women with sexual dysfunction at baseline, global sexual function. Scheduling regular sexual activity significantly improved orgasm function; exercise did not increase this benefit. Neither regular sexual activity nor exercise significantly changed sexual satisfaction. Conclusions Scheduling regular sexual activity and exercise may be an effective tool for the behavioral management of sexual side effects of antidepressants. PMID:24754044

Modulating Cytotoxic Effector Functions by Fc Engineering to Improve Cancer Therapy.

Science.gov (United States)

Kellner, Christian; Otte, Anna; Cappuzzello, Elisa; Klausz, Katja; Peipp, Matthias

2017-09-01

In the last two decades, monoclonal antibodies have revolutionized the therapy of cancer patients. Although antibody therapy has continuously been improved, still a significant number of patients do not benefit from antibody therapy. Therefore, rational optimization of the antibody molecule by Fc engineering represents a major area of translational research to further improve this potent therapeutic option. Monoclonal antibodies are able to trigger a variety of effector mechanisms. Especially Fc-mediated effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement- dependent cytotoxicity (CDC) are considered important in antibody therapy of cancer. Novel mechanistic insights into the action of monoclonal antibodies allowed the development of various Fc engineering approaches to modulate antibodies' effector functions. Strategies in modifying the Fc glycosylation profile (Fc glyco-engineering) or approaches in engineering the protein backbone (Fc protein engineering) have been intensively evaluated. In the current review, Fc engineering strategies resulting in improved ADCC, ADCP and CDC activity are summarized and discussed.

On Improving Density Estimators which are not Bona Fide Functions

OpenAIRE

Gajek, Leslaw

1986-01-01

In order to improve the rate of decrease of the IMSE for nonparametric kernel density estimators with nonrandom bandwidth beyond $O(n^{-4/5})$ all current methods must relax the constraint that the density estimate be a bona fide function, that is, be nonnegative and integrate to one. In this paper we show how to achieve similar improvement without relaxing any of these constraints. The method can also be applied for orthogonal series, adaptive orthogonal series, spline, jackknife, and other ...

Dejian Mind-Body Intervention Improves the Cognitive Functions of a Child with Autism

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Agnes S. Chan

2011-01-01

Full Text Available There has been increasing empirical evidence for the enhancing effects of Dejian Mind-Body Intervention (DMBI, a traditional Chinese Shaolin healing approach, on human frontal brain activity/functions, including patients with autism who are well documented to have frontal lobe problems. This study aims to compare the effects of DMBI with a conventional behavioural/cognitive intervention (CI on enhancing the executive functions and memory of a nine-year-old boy with low-functioning autism (KY and to explore possible underlying neural mechanism using EEG theta cordance. At post-one-month DMBI, KY's inhibitory control, cognitive flexibility, and memory functioning have significantly improved from “severely-to-moderately impaired” to “within-normal” range. This improvement was not observed from previous 12-month CI. Furthermore, KY showed increased cordance gradually extending from the anterior to the posterior brain region, suggesting possible neural mechanism underlying his cognitive improvement. These findings have implicated potential applicability of DMBI as a rehabilitation program for patients with severe frontal lobe and/or memory disorders.

Site-Specific Modification Using the 2′-Methoxyethyl Group Improves the Specificity and Activity of siRNAs

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Xinyun Song

2017-12-01

Full Text Available Rapid progress has been made toward small interfering RNA (siRNA-based therapy for human disorders, but rationally optimizing siRNAs for high specificity and potent silencing remains a challenge. In this study, we explored the effect of chemical modification at the cleavage site of siRNAs. We found that modifications at positions 9 and 10 markedly reduced the silencing potency of the unmodified strand of siRNAs but were well tolerated by the modified strand. Intriguingly, addition of the 2′-methoxyethyl (MOE group at the cleavage site improved both the specificity and silencing activity of siRNAs by facilitating the oriented RNA-induced silencing complex (RISC loading of the modified strand. Furthermore, we combined MOE modifications at positions 9 and 10 of one strand together with 2′-O-methylation (OMe at position 14 of the other strand and found a synergistic effect that improved the specificity of siRNAs. The surprisingly beneficial effect of the combined modification was validated using siRNA-targeting endogenous gene intercellular adhesion molecule 1 (ICAM1. We found that the combined modifications eliminated its off-target effects. In conclusion, we established effective strategies to optimize siRNAs using site-specific MOE modifications. The findings may allow the creation of superior siRNAs for therapy in terms of activity and specificity.

Physical Activity to Improve Erectile Function

DEFF Research Database (Denmark)

Gerbild, Helle; Larsen, Camilla Marie; Graugaard, Christian

2018-01-01

, and metabolic syndrome. Physical activity (PA) has proved to be a protective factor against erectile problems, and it has been shown to improve erectile function for men affected by vascular ED. This systematic review estimated the levels of PA needed to decrease ED for men with physical inactivity, obesity...... for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review was performed of research articles specifically investigating PA as a possible treatment of ED. The review included research on ED from physical inactivity, obesity, hypertension, metabolic syndrome, and/or cardiovascular diseases......Introduction The leading cause of erectile dysfunction (ED) is arterial dysfunction, with cardiovascular disease as the most common comorbidity. Therefore, ED is typically linked to a web of closely interrelated cardiovascular risk factors such as physical inactivity, obesity, hypertension...

Evolutionarily conserved sites in yeast tropomyosin function in cell polarity, transport and contractile ring formation

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Susanne Cranz-Mileva

2015-08-01

Full Text Available Tropomyosin is a coiled-coil protein that binds and regulates actin filaments. The tropomyosin gene in Schizosaccharomyces pombe, cdc8, is required for formation of actin cables, contractile rings, and polar localization of actin patches. The roles of conserved residues were investigated in gene replacement mutants. The work validates an evolution-based approach to identify tropomyosin functions in living cells and sites of potential interactions with other proteins. A cdc8 mutant with near-normal actin affinity affects patch polarization and vacuole fusion, possibly by affecting Myo52p, a class V myosin, function. The presence of labile residual cell attachments suggests a delay in completion of cell division and redistribution of cell patches following cytokinesis. Another mutant with a mild phenotype is synthetic negative with GFP-fimbrin, inferring involvement of the mutated tropomyosin sites in interaction between the two proteins. Proteins that assemble in the contractile ring region before actin do so in a mutant cdc8 strain that cannot assemble condensed actin rings, yet some cells can divide. Of general significance, LifeAct-GFP negatively affects the actin cytoskeleton, indicating caution in its use as a biomarker for actin filaments.

Improvement of CNT dispersion in HDPE by acid and octadecylamine functionalizations

International Nuclear Information System (INIS)

Menezes, Beatriz Rossi Canuto de; Ferreira, Filipe Vargas; Franceschi, Wesley; Brito, Felipe Sales; Nunes, Evelyn Alves; Rodrigues, Karla Faquine; Cividanes, Luciana de Simone; Thim, Gilmar Patrocínio; Rosa, Cintia

2016-01-01

Full text: Since their discovery in 1991, carbon nanotubes (CNTs) have attracted great attention due to their extraordinary structure and exceptional mechanical properties that make them a suitable candidate for polymer-based nanocomposites reinforcement [1]. However, CNTs full potential can only be achieved with a proper dispersion in the matrix, that depends of Van der Waals interactions among CNTs due to the large surface area and the small size. These interactions decrease the CNT dispersion due to the formation of agglomerates. In order to overcome this limitation, surface functionalization with acid and alkyl groups has been used to increase the CNTs dispersion and compatibility with polymer matrix [2]. Therefore, the focus of the present work is to improve the dispersion of CNTs in high density polyethylene (HDPE) matrix through their functionalization with acid (H 2 SO 4 +HNO 3 ) and octadecylamine (ODA:CH 3 (CH 2 ) 17 NH 2 ). The CNT/HDPE nanocomposites (0.8%wt of CNTs) were prepared by mechanical agitation of the melted mixture of CNTs and HDPE and subsequent compression molding. Three nanocomposites were prepared: (1) HDPE + pristine CNTs, (2) HDPE + acid functionalized CNTs, and (3) HDPE + ODA functionalized CNTs. In order to confirm the surface treatment, CNTs was characterized by FT-IR, XPS, Raman, and TEM. The improvement in CNTs dispersion and compatibility with HDPE was verified by tensile test, microhardness, SEM-FEG. The results showed an improvement in the CNTs dispersion for HDPE with acid and ODA functionalized CNTs. The Young's modulus and Vickers microhardness increased significantly for HDPE with treated CNTs when compared with pristine CNTs. References: [1] S Iijima, Nature 354, 56-58 (1991). [2] R Ansari, S Ajori, S Rouhi, Appl Surf Sci 332, 640-647 (2015). (author)

Improvement of sexual function in men with benign prostatic hyperplasia by pharmacologic therapy

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Stojanović Nebojša

2014-01-01

Full Text Available Introduction. Benign prostatic hyperplasia (BPH causes disorders of voiding and sexual function. Pharmacologic therapy reduces symptoms of voiding thus impacting sexual function. Objective. To determine sex life status in men with BPH before and after pharmacologic treatment adapted to achieve satisfactory sexual function. Methods. We studied 117 sexually active BPH patients, not previously treated for BPH. After clinical examinations, symptoms of voiding, sexual and ejaculatory function were measured using standardized IPSS, IIEF and MSHQ-EjD questionnaires. After obtaining patients’ personal opinion about the importance of their sex life, therapy was chosen and possible side effects explained. Three groups of 39 patients each were formed. The first group was treated with alpha-blocker, tamsulosin, the second with 5-alpha reductase inhibitor, finasteride, while the third group was administered a combination therapy. The complete examination procedure was repeated after 3 and 6 months of therapy. Results. The average age of patients was 61.34±3.04 years. Eighty-seven percent reported that their sex life was important to a certain degree. Satisfaction with their sex life was reported by 47% of patients before treatment and by 67% of respondents 6 months after treatment. Questionnaire scores indicated general improvement of sexual function in all groups, which was statistically significant compared to baseline only in the group on tamsulosin alpha-blocker (2.95±7.81; p=0.028. The overall satisfaction with sex life as a component of sexual function, improved significantly in the group on the combined therapy (0.78±1.81; p=0.012. Conclusion. Before BPH treatment sexual function should be assessed and therapy customized to the patient’s expectations. Side effects of drugs should be presented especially to patients who emphasize the importance of sex life. In the manifested stages of the disease overall satisfaction with sex life may be

Improvement of cardiac function persists long term with medical therapy for left ventricular systolic dysfunction.

Science.gov (United States)

Chen, David; Chang, Richard; Umakanthan, Branavan; Stoletniy, Liset N; Heywood, J Thomas

2007-09-01

In certain patients with left ventricular (LV) systolic dysfunction, improvements in cardiac function are seen after initiation of medical therapy; however, the long-term stability of ventricular function in such patients is not well described. We retrospectively analyzed 171 patients who had a baseline ejection fraction of 45% or less, a follow-up echocardiogram at 2 to 12 months after initiation of medical therapy, and a final echocardiogram. We found that 48.5% of the patients demonstrated initial improvements in LV function after initiation of medical therapy, and the improvements appear to be sustained (88% of patients) at 44 +/- 21 months follow-up. A nonischemic etiology and younger age were the only independent predictors of change of LV ejection fraction of 10 or more at a mean 8.4 +/- 3.4 months after optimal medical therapy. Our study revealed a trend toward improved long-term survival in individuals with an early improvement in LV ejection fraction with medical therapy, especially in those with sustained improvement.

Using a Full Complex Site Transfer Function to Estimate Strong Ground Motion in Port-au-Prince (Haiti).

Science.gov (United States)

ST Fleur, S.; Courboulex, F.; Bertrand, E.; Mercier De Lepinay, B. F.; Hough, S. E.; Boisson, D.; Momplaisir, R.

2017-12-01

To assess the possible impact of a future earthquake in the urban area of Port-au-Prince (Haiti), we have implemented a simulation approach for complex ground motions produced by an earthquake. To this end, we have integrated local site effect in the prediction of strong ground motions in Port-au-Prince using the complex transfer functions method, which takes into account amplitude changes as well as phase changes. This technique is particularly suitable for basins where a conventional 1D digital approach proves inadequate, as is the case in Port-au-Prince. To do this, we use the results of the Standard Spectral Ratio (SSR) approach of St Fleur et al. (2016) to estimate the amplitude of the response of the site to a nearby rock site. Then, we determine the phase difference between sites, interpreted as changes in the phase of the signal related to local site conditions, using the signals of the 2010 earthquake aftershocks records. Finally, the accelerogram of the simulated earthquake is obtain using the technique of the inverse Fourier transform. The results of this study showed that the strongest soil motions are expected in neighborhoods of downtown Port-au-Prince and adjacent hills. In addition, this simulation method by complex transfer functions was validated by comparison with recorded actual data. Our simulated response spectra reproduce very well both the amplitude and the shape of the response spectra of recorded earthquakes. This new approach allowed to reproduce the lengthening of the signal that could be generated by surface waves at certain stations in the city of Port-au-Prince. However, two points of vigilance must be considered: (1) a good signal-to-noise ratio is necessary to obtain a robust estimate of the site-reference phase shift (ratio at least equal to 10); (2) unless the amplitude and phase changes are measured on strong motion records, this technique does not take non-linear effects into account.

Declining ambient air pollution and lung function improvement in Austrian children

Science.gov (United States)

Neuberger, Manfred; Moshammer, Hanns; Kundi, Michael

Three thousand four hundred fifty-one Austrian elementary school children were examined (between 2 and 8 times) by spirometry by standardized methods, over a 5 yr period. The districts where they lived were grouped into those where NO 2 declined during this period (by at least 30 μg/m 3 measured as half year means) and those with less or no decline in ambient NO 2. In both groups of districts, SO 2 and TSP fell by similar amounts over this period. A continuous improvement of MEF25 (maximum exspiratory flow rate at 25% vital capacity) was found in districts with declining ambient NO 2. Populations did not differ in respect of anthropometric factors, passive smoking or socioeconomic status. A birth cohort from this study population which was followed up to age 18 confirmed the improved growth of MEF25 with decline in NO 2, while the improved growth of forced vital capacity was more related to decline in SO 2. This study provides the first evidence that improvements in the outdoor air quality during the 1980s are correlated with health benefits, and suggest that adverse effects on lung function related to ambient air pollution are reversible before adulthood. Improvement of small airway functions appeared to be more dependent on reductions of NO 2 than reduction in SO 2 and TSP.

Levomilnacipran Extended-Release Treatment in Patients With Major Depressive Disorder: Improvements in Functional Impairment Categories

Science.gov (United States)

Gommoll, Carl P.; Chen, Changzheng; Greenberg, William M.; Ruth, Adam

2015-01-01

Objective: In this post hoc analysis, improvement in functional impairment in patients with major depressive disorder (MDD) treated with levomilnacipran extended release (ER) was evaluated by assessing shifts from more severe to less severe functional impairment categories on individual Sheehan Disability Scale (SDS) subscales. Method: SDS data were pooled from 5 phase II/III studies conducted between December 2006 and March 2012 of levomilnacipran ER versus placebo in adult patients with MDD (DSM-IV-TR criteria). Proportions of patients shifting from moderate-extreme baseline impairment (score ≥ 4) to mild-no impairment (score ≤ 3) at end of treatment were assessed for each SDS subscale. Proportions of patients shifting from marked-extreme (score ≥ 7) baseline impairment to moderate-no (score ≤ 6) or mild-no impairment (score ≤ 3) at end of treatment, and shifts in which patients worsened from moderate-no to marked-extreme impairment, were also evaluated. Results: A significantly higher proportion of patients treated with levomilnacipran ER than placebo-treated patients improved from more severe categories of functional impairment at baseline to less severe impairment categories across all SDS subscales: work/school, social life, and family life/home responsibilities (P impairment at baseline improved to mild or no impairment, compared with no more than 40% of placebo patients on any subscale. Almost half (42%–47%) of levomilnacipran ER–treated patients versus only about one-third (29%–34%) of placebo patients improved from marked-extreme to mild or no impairment across functional domains. Conclusions: These results suggest that functional improvement was observed across the SDS functional domains. To our knowledge, this is the first such categorical analysis of functional improvement, as measured by the SDS, for an antidepressant. Trial Registration: ClinicalTrials.gov identifiers: NCT00969709, NCT01377194, NCT00969150, and NCT01034462 and Eudra

Moments of unpolarized nucleon structure functions in chirally improved lattice QCD

Energy Technology Data Exchange (ETDEWEB)

Goeckeler, Meinulf; Maurer, Thilo; Schaefer, Andreas [University of Regensburg (Germany); Lang, Christian B.; Limmer, Markus [University of Graz (Austria)

2008-07-01

We present our results for the lowest moments of unpolarized nucleon structure functions at leading twist. We employ lattice quantum chromodynamics using chirally improved fermions in quenched as well as dynamical simulations.

Targeted reduction of advanced glycation improves renal function in obesity

DEFF Research Database (Denmark)

Harcourt, Brooke E; Sourris, Karly C; Coughlan, Melinda T

2011-01-01

-lowering pharmaceutical, alagebrium, and mice in which the receptor for AGE (RAGE) was deleted. Obesity, resulting from a diet high in both fat and AGE, caused renal impairment; however, treatment of the RAGE knockout mice with alagebrium improved urinary albumin excretion, creatinine clearance, the inflammatory profile...... if treatments that lower tissue AGE burden in patients and mice would improve obesity-related renal dysfunction. Overweight and obese individuals (body mass index (BMI) 26-39¿kg/m(2)) were recruited to a randomized, crossover clinical trial involving 2 weeks each on a low- and a high-AGE-containing diet. Renal......, and renal oxidative stress. Alagebrium treatment, however, resulted in decreased weight gain and improved glycemic control compared with wild-type mice on a high-fat Western diet. Thus, targeted reduction of the advanced glycation pathway improved renal function in obesity....

Accuracy Improvement of Boron Meter Adopting New Fitting Function and Multi-Detector

Directory of Open Access Journals (Sweden)

Chidong Kong

2016-12-01

Full Text Available This paper introduces a boron meter with improved accuracy compared with other commercially available boron meters. Its design includes a new fitting function and a multi-detector. In pressurized water reactors (PWRs in Korea, many boron meters have been used to continuously monitor boron concentration in reactor coolant. However, it is difficult to use the boron meters in practice because the measurement uncertainty is high. For this reason, there has been a strong demand for improvement in their accuracy. In this work, a boron meter evaluation model was developed, and two approaches were considered to improve the boron meter accuracy: the first approach uses a new fitting function and the second approach uses a multi-detector. With the new fitting function, the boron concentration error was decreased from 3.30 ppm to 0.73 ppm. With the multi-detector, the count signals were contaminated with noise such as field measurement data, and analyses were repeated 1,000 times to obtain average and standard deviations of the boron concentration errors. Finally, using the new fitting formulation and multi-detector together, the average error was decreased from 5.95 ppm to 1.83 ppm and its standard deviation was decreased from 0.64 ppm to 0.26 ppm. This result represents a great improvement of the boron meter accuracy.

Accuracy improvement of boron meter adopting new fitting function and multi-detector

Energy Technology Data Exchange (ETDEWEB)

Kong, Chidong; Lee, Hyun Suk; Tak, Tae Woo; Lee, Deok Jung [Ulsan National Institute of Science and Technology, Ulsan (Korea, Republic of); KIm, Si Hwan; Lyou, Seok Jean [Users Incorporated Company, Hansin S-MECA, Daejeon (Korea, Republic of)

2016-12-15

This paper introduces a boron meter with improved accuracy compared with other commercially available boron meters. Its design includes a new fitting function and a multi-detector. In pressurized water reactors (PWRs) in Korea, many boron meters have been used to continuously monitor boron concentration in reactor coolant. However, it is difficult to use the boron meters in practice because the measurement uncertainty is high. For this reason, there has been a strong demand for improvement in their accuracy. In this work, a boron meter evaluation model was developed, and two approaches were considered to improve the boron meter accuracy: the first approach uses a new fitting function and the second approach uses a multi-detector. With the new fitting function, the boron concentration error was decreased from 3.30 ppm to 0.73 ppm. With the multi-detector, the count signals were contaminated with noise such as field measurement data, and analyses were repeated 1,000 times to obtain average and standard deviations of the boron concentration errors. Finally, using the new fitting formulation and multi-detector together, the average error was decreased from 5.95 ppm to 1.83 ppm and its standard deviation was decreased from 0.64 ppm to 0.26 ppm. This result represents a great improvement of the boron meter accuracy.

Distinct phosphorylation sites on the ghrelin receptor, GHSR1a, establish a code that determines the functions of ß-arrestins

Science.gov (United States)

Bouzo-Lorenzo, Monica; Santo-Zas, Icía; Lodeiro, Maria; Nogueiras, Rubén; Casanueva, Felipe F.; Castro, Marian; Pazos, Yolanda; Tobin, Andrew B; Butcher, Adrian J.; Camiña, Jesús P.

2016-01-01

The growth hormone secretagogue receptor, GHSR1a, mediates the biological activities of ghrelin, which includes the secretion of growth hormone, as well as the stimulation of appetite, food intake and maintenance of energy homeostasis. Mapping phosphorylation sites on GHSR1a and knowledge of how these sites control specific functional consequences unlocks new strategies for the development of therapeutic agents targeting individual functions. Herein, we have identified the phosphorylation of different sets of sites within GHSR1a which engender distinct functionality of ß-arrestins. More specifically, the Ser362, Ser363 and Thr366 residues at the carboxyl-terminal tail were primarily responsible for ß-arrestin 1 and 2 binding, internalization and ß-arrestin-mediated proliferation and adipogenesis. The Thr350 and Ser349 are not necessary for ß-arrestin recruitment, but are involved in the stabilization of the GHSR1a-ß-arrestin complex in a manner that determines the ultimate cellular consequences of ß-arrestin signaling. We further demonstrated that the mitogenic and adipogenic effect of ghrelin were mainly dependent on the ß-arrestin bound to the phosphorylated GHSR1a. In contrast, the ghrelin function on GH secretion was entirely mediated by G protein signaling. Our data is consistent with the hypothesis that the phosphorylation pattern on the C terminus of GHSR1a determines the signaling and physiological output. PMID:26935831

Enhancing Cooperativity in Bifunctional Acid–Pd Catalysts with Carboxylic Acid-Functionalized Organic Monolayers

Energy Technology Data Exchange (ETDEWEB)

Coan, Patrick D. [Department of Chemical and Biological Engineering, University of Colorado—Boulder, Boulder, Colorado 80309, United States; Ellis, Lucas D. [Department of Chemical and Biological Engineering, University of Colorado—Boulder, Boulder, Colorado 80309, United States; Griffin, Michael B. [National Bioenergy Center, National Renewable Energy Laboratory, Golden, Colorado 80401, United States; Schwartz, Daniel K. [Department of Chemical and Biological Engineering, University of Colorado—Boulder, Boulder, Colorado 80309, United States; Medlin, J. Will [Department of Chemical and Biological Engineering, University of Colorado—Boulder, Boulder, Colorado 80309, United States

2018-03-01

Cooperative catalysts containing a combination of noble metal hydrogenation sites and Bronsted acid sites are critical for many reactions, including the deoxygenation (DO) of biomass-derived oxygenates in the upgrading of pyrolysis oil. One route toward the design of cooperative catalysts is to tether two different catalytically active functions so that they are in close proximity while avoiding undesirable interactions that can block active sites. Here, we deposited carboxylic acid (CA)-functionalized organophosphonate monolayers onto Al2O3-supported Pd nanoparticle catalysts to prepare bifunctional catalysts containing both Bronsted acid and metal sites. Modification with phosphonic acids (PAs) improved activity and selectivity for gas-phase DO reactions, but the degree of improvement was highly sensitive to both the presence and positioning of the CA group, suggesting a significant contribution from both the PA and CA sites. Short spacer lengths of 1-2 methylene groups between the phosphonate head and CA tail were found to yield the best DO rates and selectivities, whereas longer chains performed similarly to self-assembled monolayers having alkyl tails. Results from a combination of density functional theory and Fourier transform infrared spectroscopy suggested that the enhanced catalyst performance on the optimally positioned CAs was due to the generation of strong acid sites on the Al2O3 support adjacent to the metal. Furthermore, the high activity of these sites was found to result from a hydrogen-bonded cyclic structure involving cooperativity between the phosphonate head group and CA tail function. More broadly, these results indicate that functional groups tethered to supports via organic ligands can influence catalytic chemistry on metal nanoparticles.

Effects of B site doping on electronic structures of InNbO4 based on hybrid density functional calculations

Science.gov (United States)

Lu, M. F.; Zhou, C. P.; Li, Q. Q.; Zhang, C. L.; Shi, H. F.

2018-01-01

In order to improve the photocatalytic activity under visible-light irradiation, we adopted first principle calculations based on density functional theory (DFT) to calculate the electronic structures of B site transition metal element doped InNbO4. The results indicated that the complete hybridization of Nb 4d states and some Ti 3d states contributed to the new conduction band of Ti doped InNbO4, barely changing the position of band edge. For Cr doping, some localized Cr 3d states were introduced into the band gap. Nonetheless, the potential of localized levels was too positive to cause visible-light reaction. When it came to Cu doping, the band gap was almost same with that of InNbO4 as well as some localized Cu 3d states appeared above the top of VB. The introduction of localized energy levels benefited electrons to migrate from valence band (VB) to conduction band (CB) by absorbing lower energy photons, realizing visible-light response.

IMPROVING CORRELATION FUNCTION FITTING WITH RIDGE REGRESSION: APPLICATION TO CROSS-CORRELATION RECONSTRUCTION

International Nuclear Information System (INIS)

Matthews, Daniel J.; Newman, Jeffrey A.

2012-01-01

Cross-correlation techniques provide a promising avenue for calibrating photometric redshifts and determining redshift distributions using spectroscopy which is systematically incomplete (e.g., current deep spectroscopic surveys fail to obtain secure redshifts for 30%-50% or more of the galaxies targeted). In this paper, we improve on the redshift distribution reconstruction methods from our previous work by incorporating full covariance information into our correlation function fits. Correlation function measurements are strongly covariant between angular or spatial bins, and accounting for this in fitting can yield substantial reduction in errors. However, frequently the covariance matrices used in these calculations are determined from a relatively small set (dozens rather than hundreds) of subsamples or mock catalogs, resulting in noisy covariance matrices whose inversion is ill-conditioned and numerically unstable. We present here a method of conditioning the covariance matrix known as ridge regression which results in a more well behaved inversion than other techniques common in large-scale structure studies. We demonstrate that ridge regression significantly improves the determination of correlation function parameters. We then apply these improved techniques to the problem of reconstructing redshift distributions. By incorporating full covariance information, applying ridge regression, and changing the weighting of fields in obtaining average correlation functions, we obtain reductions in the mean redshift distribution reconstruction error of as much as ∼40% compared to previous methods. We provide a description of POWERFIT, an IDL code for performing power-law fits to correlation functions with ridge regression conditioning that we are making publicly available.

Maintained improvement in neurocognitive function in major depressive disorders 6 months after ECT

Directory of Open Access Journals (Sweden)

Christine Mohn

2016-12-01

Full Text Available Both impaired and improved cognitive function after electroconvulsive treatment (ECT in major depressive disorder (MDD patients may occur. We have previously found improved cognitive function 6 weeks after ECT in this group. The aim of this study was to report 6-month follow-up results from the same prospective project monitoring cognitive effects of ECT. Thirty-one patients with major depressive disorder were assessed with the MATRICS Consensus Cognitive Battery (MCCB, the Everyday Memory Questionnaire (EMQ, and the Montgomery-Åsberg Depression Rating Scale (MADRS prior to, 6 weeks, and 6 months after ECT.Compared to baseline, the Speed of Processing, Attention/Vigilance, and Reasoning/Problem Solving test results were significantly improved. The depression score was significantly reduced. There were no changes in subjective memory complaint. There were no significant relationship between the EMQ and the MCCB subtests, but a significant correlation between current depression level and the EMQ.Six months after ECT the cognitive improvement reported at 6 weeks follow-up was maintained and extended. The corresponding decrease in depressive symptoms and stability in subjectively reported memory complaints suggests that the antidepressant effects of ECT do not occur at the expense of cognitive function.

Virtual reality training improves turning capacity and functional reach in stroke patients

International Nuclear Information System (INIS)

Malik, A.N.; Masood, T.

2017-01-01

Objective: To determine the added effects of virtual reality training on turning capacity, gait parameters and functional reach capacity of stroke patients compared to task oriented training alone. Methodology: A randomized control trial was conducted from February 2016 to July 2106 at Physical Rehabilitation Department Pakistan Railway Hospital, Rawalpindi, Pakistan. Twenty stroke patients were selected through purposive sampling. The patients were randomly assigned through sealed envelope method into two groups; Task Oriented Training (TOT) and Virtual Reality Training (VRT) Group. The standardized tools were used for assessment. The TOT was provided for 4 days per week for 6 weeks while VRT group received additional exer-gaming training during sessions. Results: Significant improvement was observed in both groups regarding reaching forward, turning 360, gait pivot turn (p a 0.01) and FRT (p a 0.001). The two groups were statistically different from each other in terms of turning capacity, reaching forward, gait pivot turn and functional reach after 6 weeks of intervention (p a 0.05) Conclusion: Addition of virtual reality training further improves the significant improvement caused by task oriented training on turning capacity, reaching forward, gait pivot turn and functional reach in stroke patients. (author)

Test-retest and between-site reliability in a multicenter fMRI study.

Science.gov (United States)

Friedman, Lee; Stern, Hal; Brown, Gregory G; Mathalon, Daniel H; Turner, Jessica; Glover, Gary H; Gollub, Randy L; Lauriello, John; Lim, Kelvin O; Cannon, Tyrone; Greve, Douglas N; Bockholt, Henry Jeremy; Belger, Aysenil; Mueller, Bryon; Doty, Michael J; He, Jianchun; Wells, William; Smyth, Padhraic; Pieper, Steve; Kim, Seyoung; Kubicki, Marek; Vangel, Mark; Potkin, Steven G

2008-08-01

In the present report, estimates of test-retest and between-site reliability of fMRI assessments were produced in the context of a multicenter fMRI reliability study (FBIRN Phase 1, www.nbirn.net). Five subjects were scanned on 10 MRI scanners on two occasions. The fMRI task was a simple block design sensorimotor task. The impulse response functions to the stimulation block were derived using an FIR-deconvolution analysis with FMRISTAT. Six functionally-derived ROIs covering the visual, auditory and motor cortices, created from a prior analysis, were used. Two dependent variables were compared: percent signal change and contrast-to-noise-ratio. Reliability was assessed with intraclass correlation coefficients derived from a variance components analysis. Test-retest reliability was high, but initially, between-site reliability was low, indicating a strong contribution from site and site-by-subject variance. However, a number of factors that can markedly improve between-site reliability were uncovered, including increasing the size of the ROIs, adjusting for smoothness differences, and inclusion of additional runs. By employing multiple steps, between-site reliability for 3T scanners was increased by 123%. Dropping one site at a time and assessing reliability can be a useful method of assessing the sensitivity of the results to particular sites. These findings should provide guidance toothers on the best practices for future multicenter studies.

Recent trends in robot-assisted therapy environments to improve real-life functional performance after stroke

OpenAIRE

Johnson, Michelle J

2006-01-01

Abstract Upper and lower limb robotic tools for neuro-rehabilitation are effective in reducing motor impairment but they are limited in their ability to improve real world function. There is a need to improve functional outcomes after robot-assisted therapy. Improvements in the effectiveness of these environments may be achieved by incorporating into their design and control strategies important elements key to inducing motor learning and cerebral plasticity such as mass-practice, feedback, t...

Automated container transportation using self-guided vehicles: Fernald site requirements

International Nuclear Information System (INIS)

Hazen, F.B.

1993-09-01

A new opportunity to improve the safety and efficiency of environmental restoration operations, using robotics has emerged from advances in industry, academia, and government labs. Self-Guided Vehicles (SGV's) have recently been developed in industry and early systems have already demonstrated much, though not all, of the functionality necessary to support driverless transportation of waste within and between processing facilities. Improved materials databases are being developed by at least two DOE remediation sites, the Fernald Environmental Management Project (FEME) in the State of Ohio and the Hanford Complex in the State of Washington. SGV's can be developed that take advantage of the information in these databases and yield improved dispatch, waste tracking, report and shipment documentation. In addition, they will reduce the radiation hazard to workers and the risk of damaging containers through accidental collision. In this document, features of remediation sites that dictate the design of both the individual SGV's and the collective system of SGV's are presented, through the example of the site requirements at Fernald. Some concepts borrowed from the world of manufacturing are explained and then used to develop an integrated, holistic view of the remediation site as a pseudo-factory. Transportation methods at Fernald and anticipated growth in transport demand are analyzed. The new site-wide database under development at Fernald is presented so that advantageous and synergistic links between SGV's and information systems can be analyzed. Details of the SGV development proposed are submitted, and some results of a recently completed state of the art survey for SGV use in this application are also presented

Stimuli-Responsive Nanodiamond-Based Biosensor for Enhanced Metastatic Tumor Site Detection.

Science.gov (United States)

Wang, Xin; Gu, Mengjie; Toh, Tan Boon; Abdullah, Nurrul Lissa Binti; Chow, Edward Kai-Hua

2018-02-01

Metastasis is often critical to cancer progression and linked to poor survival and drug resistance. Early detection of metastasis, as well as identification of metastatic tumor sites, can improve cancer patient survival. Thus, developing technology to improve the detection of cancer metastasis biomarkers can improve both diagnosis and treatment. In this study, we investigated the use of nanodiamonds to develop a stimuli-responsive metastasis detection complex that utilizes matrix metalloproteinase 9 (MMP9) as a metastasis biomarker, as MMP9 increased expression has been shown to be indicative of metastasis. The nanodiamond-MMP9 biosensor complex consists of nanodiamonds functionalized with MMP9-specific fluorescent-labeled substrate peptides. Using this design, protease activity of MMP9 can be accurately measured and correlated to MMP9 expression. The nanodiamond-MMP9 biosensor also demonstrated an enhanced ability to protect the base sensor peptide from nonspecific serum protease cleavage. This enhanced peptide stability, combined with a quantitative stimuli-responsive output function, provides strong evidence for the further development of a nanodiamond-MMP9 biosensor for metastasis site detection. More importantly, this work provides the foundation for use of nanodiamonds as a platform for stimuli-responsive biosensors and theranostic complexes that can be implemented across a wide range of biomedical applications.

Principles of brain plasticity in improving sensorimotor function of the knee and leg in healthy subjects

DEFF Research Database (Denmark)

Ageberg, Eva; Bjorkman, Anders; Rosen, Birgitta

2009-01-01

ABSTRACT: BACKGROUND: Principles of brain plasticity are used in the treatment of patients with functional limitations to improve sensorimotor function. Training is included in the treatment of knee injury to improve both patient-reported function and sensorimotor function. However, impairment...... in sensorimotor function often persists despite training. Therefore, it was suggested that training programs need to be more effective to improve sensorimotor function after knee injury. The aim of the current study was to investigate if principles of brain plasticity that have been successfully used on the hand...... age 26 years, range 19-34, 50% women) were randomized to temporary local cutaneous application of anesthetic (EMLA) (n=14) or placebo cream (n=14). Fifty grams of EMLA, or placebo, was applied on the leg 10 cm above and 10 cm below the center of patella, leaving the area around the knee without cream...

Finite element analysis of functionally graded bone plate at femur bone fracture site

Science.gov (United States)

Satapathy, Pravat Kumar; Sahoo, Bamadev; Panda, L. N.; Das, S.

2018-03-01

This paper focuses on the analysis of fractured Femur bone with functionally graded bone plate. The Femur bone is modeled by using the data from the CT (Computerized Tomography) scan and the material properties are assigned using Mimics software. The fracture fixation plate used here is composed of Functionally Graded Material (FGM). The functionally graded bone plate is considered to be composed of different layers of homogeneous materials. Finite element method approach is adopted for analysis. The volume fraction of the material is calculated by considering its variation along the thickness direction (z) according to a power law and the effective properties of the homogeneous layers are estimated. The model developed is validated by comparing numerical results available in the literature. Static analysis has been performed for the bone plate system by considering both axial compressive load and torsional load. The investigation shows that by introducing FG bone plate instead of titanium, the stress at the fracture site increases by 63 percentage and the deformation decreases by 15 percentage, especially when torsional load is taken into consideration. The present model yields better results in comparison with the commercially available bone plates.

Spironolactone in chronic hemodialysis patients improves cardiac function

International Nuclear Information System (INIS)

Taheri, Shahram; Mortazavi, Mojhgan; Shahidi Shahrzad; Seirafian, Shiva; Pourmoghadas, Ali; Garakyaraghi, Mohammad; Eshaghian, Afrooz; Ghassami, Maryam

2009-01-01

We performed this study to assess whether low dose spironolactone could be administered in hemodialysis (HD) patients with moderate to severe heart failure to improve cardiovascular function and reduce hospitalization without inducing hyperkalemia. We enrolled 16 chronic HD patients with moderate to severe heart failure and left ventricle ejection fraction :5 45%. In a double blinded randomized placebo controlled study, one group of 8 patients received 25 mg of spironolactone after each dialysis session within six months, and the rest received a placebo. Echocardiography was performed on all the patients to assess ejection fraction and left ventricular mass during 12 hours after completion of hemodialysis at the beginning and the end of study. Serum potassium was measured predialysis every 4 weeks. The mean ejection fraction increased significantly more in spironolactone group during the study period than in the placebo group (6.2 + - 1.64 vs. 0.83 + - 4.9, P0.046). The mean left ventricular mass decreased in the spironolactone group, but increased significantly in the placebo group during the period (-8.4 + - 4.72 vs. 3 + -7.97. 95%, P= 0.021). The incidence of hyperkalemia was not significantly increased in the study or controlled groups. In conclusion, we found in this study that administration of spironolactone in chronic HD patients with moderate to severe heart failure substantially improved their cardiac function and decreases left ventricular mass without development of significant hyperkalemia. (author)

Functional improvement of antibody fragments using a novel phage coat protein III fusion system

DEFF Research Database (Denmark)

Jensen, Kim Bak; Larsen, Martin; Pedersen, Jesper Søndergaard

2002-01-01

Functional expressions of proteins often depend on the presence of host specific factors. Frequently recombinant expression strategies of proteins in foreign hosts, such as bacteria, have been associated with poor yields or significant loss of functionality. Improvements in the performance of het......(s) of the filamentous phage coat protein III. Furthermore, it will be shown that the observed effect is neither due to improved stability nor increased avidity....

XenoSite: accurately predicting CYP-mediated sites of metabolism with neural networks.

Science.gov (United States)

Zaretzki, Jed; Matlock, Matthew; Swamidass, S Joshua

2013-12-23

Understanding how xenobiotic molecules are metabolized is important because it influences the safety, efficacy, and dose of medicines and how they can be modified to improve these properties. The cytochrome P450s (CYPs) are proteins responsible for metabolizing 90% of drugs on the market, and many computational methods can predict which atomic sites of a molecule--sites of metabolism (SOMs)--are modified during CYP-mediated metabolism. This study improves on prior methods of predicting CYP-mediated SOMs by using new descriptors and machine learning based on neural networks. The new method, XenoSite, is faster to train and more accurate by as much as 4% or 5% for some isozymes. Furthermore, some "incorrect" predictions made by XenoSite were subsequently validated as correct predictions by revaluation of the source literature. Moreover, XenoSite output is interpretable as a probability, which reflects both the confidence of the model that a particular atom is metabolized and the statistical likelihood that its prediction for that atom is correct.

Improved Functional Performance in Geriatric Patients During Hospital Stay

DEFF Research Database (Denmark)

Karlsen, Anders; Loeb, Mads Rohde; Andersen, Kristine Bramsen

2017-01-01

OBJECTIVE: The aim of this work was to evaluate the time course of changes in strength and functional performance in elderly hospitalized medical patients. DESIGN: This was a prospective observational study in elderly medical patients of age 65 years or older at a geriatric department.Measurement......OBJECTIVE: The aim of this work was to evaluate the time course of changes in strength and functional performance in elderly hospitalized medical patients. DESIGN: This was a prospective observational study in elderly medical patients of age 65 years or older at a geriatric department.......Measurements were obtained on days 2 to 4, day 5 to 8, and days 9 to 13. Functional performance was measured with De Morton Mobility Index (DEMMI) test and a 30-second chair stand test (30-s CST). Muscular strength was measured with handgrip strength. Activity level was determined with accelerometry (Activ...... in 30-s CST (P performance of the lower extremities in geriatric patients improves moderately over the time of a hospital stay...

Risk-based technical specifications program: Site interview results

International Nuclear Information System (INIS)

Andre, G.R.; Baker, A.J.; Johnson, R.L.

1991-08-01

The Electric Power Research Institute and Pacific Gas and Electric Company are sponsoring a program directed at improving Technical Specifications using risk-based methods. The major objectives of the program are to develop risk-based approaches to improve Technical Specifications and to develop an Interactive Risk Advisor (IRA) prototype. The IRA is envisioned as an interactive system that is available to plant personnel to assist in controlling plant operation. Use of an IRA is viewed as a method to improve plant availability while maintaining or improving plant safety. In support of the program, interviews were conducted at several PWR and BWR plant sites, to elicit opinions and information concerning risk-based approaches to Technical Specifications and IRA requirements. This report presents the results of these interviews, including the functional requirements of an IRA. 2 refs., 6 figs., 2 tabs

Increasing Muscle Mass Improves Vascular Function in Obese (db/db) Mice

Science.gov (United States)

Qiu, Shuiqing; Mintz, James D.; Salet, Christina D.; Han, Weihong; Giannis, Athanassios; Chen, Feng; Yu, Yanfang; Su, Yunchao; Fulton, David J.; Stepp, David W.

2014-01-01

Background A sedentary lifestyle is an independent risk factor for cardiovascular disease and exercise has been shown to ameliorate this risk. Inactivity is associated with a loss of muscle mass, which is also reversed with isometric exercise training. The relationship between muscle mass and vascular function is poorly defined. The aims of the current study were to determine whether increasing muscle mass by genetic deletion of myostatin, a negative regulator of muscle growth, can influence vascular function in mesenteric arteries from obese db/db mice. Methods and Results Myostatin expression was elevated in skeletal muscle of obese mice and associated with reduced muscle mass (30% to 50%). Myostatin deletion increased muscle mass in lean (40% to 60%) and obese (80% to 115%) mice through increased muscle fiber size (PMyostatin deletion decreased adipose tissue in lean mice, but not obese mice. Markers of insulin resistance and glucose tolerance were improved in obese myostatin knockout mice. Obese mice demonstrated an impaired endothelial vasodilation, compared to lean mice. This impairment was improved by superoxide dismutase mimic Tempol. Deletion of myostatin improved endothelial vasodilation in mesenteric arteries in obese, but not in lean, mice. This improvement was blunted by nitric oxide (NO) synthase inhibitor l‐NG‐nitroarginine methyl ester (l‐NAME). Prostacyclin (PGI2)‐ and endothelium‐derived hyperpolarizing factor (EDHF)‐mediated vasodilation were preserved in obese mice and unaffected by myostatin deletion. Reactive oxygen species) was elevated in the mesenteric endothelium of obese mice and down‐regulated by deletion of myostatin in obese mice. Impaired vasodilation in obese mice was improved by NADPH oxidase inhibitor (GKT136901). Treatment with sepiapterin, which increases levels of tetrahydrobiopterin, improved vasodilation in obese mice, an improvement blocked by l‐NAME. Conclusions Increasing muscle mass by genetic deletion of

Identifying Functional Neighborhoods within the Cell Nucleus: Proximity Analysis of Early S-Phase Replicating Chromatin Domains to Sites of Transcription, RNA Polymerase II, HP1γ, Matrin 3 and SAF-A

Science.gov (United States)

Malyavantham, Kishore S; Bhattacharya, Sambit; Barbeitos, Marcos; Mukherjee, Lopamudra; Xu, Jinhui; Fackelmayer, Frank O; Berezney, Ronald

2009-01-01

Higher order chromatin organization in concert with epigenetic regulation is a key process that determines gene expression at the global level. The organization of dynamic chromatin domains and their associated protein factors is intertwined with nuclear function to create higher levels of functional zones within the cell nucleus. As a step towards elucidating the organization and dynamics of these functional zones, we have investigated the spatial proximities among a constellation of functionally related sites that are found within euchromatic regions of the cell nucleus including: HP1γ, nascent transcript sites (TS), active DNA replicating sites in early S phase (PCNA) and RNA polymerase II sites. We report close associations among these different sites with proximity values specific for each combination. Analysis of matrin 3 and SAF-A sites demonstrates that these nuclear matrix proteins are highly proximal with the functionally related sites as well as to each other and display closely aligned and overlapping regions following application of the minimal spanning tree (MST) algorithm to visualize higher order network-like patterns. Our findings suggest that multiple factors within the nuclear microenvironment collectively form higher order combinatorial arrays of function. We propose a model for the organization of these functional neighborhoods which takes into account the proximity values of the individual sites and their spatial organization within the nuclear architecture. PMID:18618731

Leukocyte and platelet depletion improves blood flow and function in a renal transplant model.

Science.gov (United States)

Yates, Phillip J; Hosgood, Sarah A; Nicholson, Michael L

2012-01-01

Donation after cardiac death (DCD) donors are an important source of organs for transplantation. Due to warm and cold ischemic injury, DCD kidneys undergo a significant reperfusion insult when transplanted. This is manifested clinically as a high incidence of delayed graft function (DGF) and primary non-function (PNF). The importance of leukocytes in the generation of reperfusion injury is pivotal. Using an ex vivo porcine model of kidney transplantation, the effects of reperfusion with leukocyte and platelet depleted blood (LDB) and whole blood (WB) on renal blood flow and function were compared. Hemodynamic measurements were recorded, and biochemical, hematological, and histologic samples taken at set time-points. Reperfusion with LDB improved renal blood flow significantly compared with WB reperfusion. In addition, there was a significant improvement in creatinine clearance and renal oxygen consumption, but not fractional excretion of sodium, acid-base homeostasis, urinary nitric oxide (NO), or 8-isoprostane levels. This study represents a good model for the initial reperfusion period in renal transplantation. Improvement in only some functional markers and neither urinary NO nor 8-isoprostane levels indicates that improved blood flow alone is not sufficient to reverse the severe ischemic insult endured by DCD kidneys. Copyright © 2012 Elsevier Inc. All rights reserved.

New application of Exp-function method for improved Boussinesq equation

Energy Technology Data Exchange (ETDEWEB)

Abdou, M.A. [Theoretical Research Group, Physics Department, Faculty of Science, Mansoura University, 35516 Mansoura (Egypt); Department of Physics, Faculty of Education for Girls, Science Departments, King Khalid University, Bisha (Saudi Arabia)], E-mail: m_abdou_eg@yahoo.com; Soliman, A.A. [Department of Mathematics, Faculty of Education (AL-Arish) Suez Canal University, AL-Arish 45111 (Egypt); Department of Mathematics, Teacher' s College (Bisha), King Khalid University, Bisha, PO Box 551 (Saudi Arabia)], E-mail: asoliman_99@yahoo.com; El-Basyony, S.T. [Theoretical Research Group, Physics Department, Faculty of Science, Mansoura University, 35516 Mansoura (Egypt)

2007-10-01

The Exp-function method is used to obtain generalized solitary solutions and periodic solutions for nonlinear evolution equations arising in mathematical physics with the aid of symbolic computation method, namely, the improved Boussinesq equation. The method is straightforward and concise, and its applications is promising for other nonlinear evolution equations in mathematical physics.

Wii-based movement therapy to promote improved upper extremity function post-stroke: a pilot study.

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Mouawad, Marie R; Doust, Catherine G; Max, Madeleine D; McNulty, Penelope A

2011-05-01

Virtual-reality is increasingly used to improve rehabilitation outcomes. The Nintendo Wii offers an in-expensive alternative to more complex systems. To investigate the efficacy of Wii-based therapy for post-stroke rehabilitation. Seven patients (5 men, 2 women, aged 42-83 years; 1-38 months post-stroke, mean 15.3 months) and 5 healthy controls (3 men, 2 women, aged 41-71 years) undertook 1 h of therapy on 10 consecutive weekdays. Patients progressively increased home practice to 3 h per day. Functional ability improved for every patient. The mean performance time significantly decreased per Wolf Motor Function Test task, from 3.2 to 2.8 s, and Fugl-Meyer Assessment scores increased from 42.3 to 47.3. Upper extremity range-of-motion increased by 20.1º and 14.33º for passive and active movements, respectively. Mean Motor Activity Log (Quality of Movement scale) scores increased from 63.2 to 87.5, reflecting a transfer of functional recovery to everyday activities. Balance and dexterity did not improve significantly. No significant change was seen in any of these measures for healthy controls, despite improved skill levels for Wii games. An intensive 2-week protocol resulted in significant and clinically relevant improvements in functional motor ability post-stroke. These gains translated to improvement in activities of daily living.

Better assessment of physical function: item improvement is neglected but essential.

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Bruce, Bonnie; Fries, James F; Ambrosini, Debbie; Lingala, Bharathi; Gandek, Barbara; Rose, Matthias; Ware, John E

2009-01-01

Physical function is a key component of patient-reported outcome (PRO) assessment in rheumatology. Modern psychometric methods, such as Item Response Theory (IRT) and Computerized Adaptive Testing, can materially improve measurement precision at the item level. We present the qualitative and quantitative item-evaluation process for developing the Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function item bank. The process was stepwise: we searched extensively to identify extant Physical Function items and then classified and selectively reduced the item pool. We evaluated retained items for content, clarity, relevance and comprehension, reading level, and translation ease by experts and patient surveys, focus groups, and cognitive interviews. We then assessed items by using classic test theory and IRT, used confirmatory factor analyses to estimate item parameters, and graded response modeling for parameter estimation. We retained the 20 Legacy (original) Health Assessment Questionnaire Disability Index (HAQ-DI) and the 10 SF-36's PF-10 items for comparison. Subjects were from rheumatoid arthritis, osteoarthritis, and healthy aging cohorts (n = 1,100) and a national Internet sample of 21,133 subjects. We identified 1,860 items. After qualitative and quantitative evaluation, 124 newly developed PROMIS items composed the PROMIS item bank, which included revised Legacy items with good fit that met IRT model assumptions. Results showed that the clearest and best-understood items were simple, in the present tense, and straightforward. Basic tasks (like dressing) were more relevant and important versus complex ones (like dancing). Revised HAQ-DI and PF-10 items with five response options had higher item-information content than did comparable original Legacy items with fewer response options. IRT analyses showed that the Physical Function domain satisfied general criteria for unidimensionality with one-, two-, three-, and four-factor models

Functional analysis, a resilience improvement tool applied to a waste management system - application to the "household waste management chain"

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Beraud, H.; Barroca, B.; Hubert, G.

2012-12-01

A waste management system plays a leading role in the capacity of an area to restart after flooding, as their impact on post-crisis management can be very considerable. Improving resilience, i.e. enabling it to maintain or recover acceptable operating levels after flooding is primordial. To achieve this, we must understand how the system works for bringing any potential dysfunctions to light and taking preventive measures. Functional analysis has been used for understanding the complexity of this type of system. The purpose of this article is to show the interest behind this type of method and the limits in its use for improving resilience of waste management system as well as other urban technical systems1, by means of theoretical modelling and its application on a study site. 1In a systemic vision of the city, urban technical systems combine all the user service systems that are essential for the city to operate (electricity, water supplies, transport, sewerage, etc.). These systems are generally organised in the form of networks (Coutard, 2010; CERTU, 2005).

Virtual Reality Training with Cognitive Load Improves Walking Function in Chronic Stroke Patients.

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Cho, Ki Hun; Kim, Min Kyu; Lee, Hwang-Jae; Lee, Wan Hee

2015-08-01

Virtual reality training is considered as an effective intervention method of stroke patients, and the virtual reality system for therapeutic rehabilitation has emphasized the cognitive factors to improve walking function. The purpose of current study was to investigate the effect of virtual reality training with cognitive load (VRTCL) on walking function of chronic stroke. Chronic stroke patients were randomly assigned to the VRTCL group (11 patients, including 5 men; mean age, 60.0 years; post-stroke duration, 273.9 days) or control group (11 patients, including 2 men; mean age, 58.6 years; post-stroke duration, 263.9 days). All subjects participated in the standard rehabilitation program that consisted of physical and occupational therapies. In addition, VRTCL group participated in the VRTCL for 4 weeks (30 min per day and five times a week), while those in the control group participated in virtual reality treadmill training. Walking function under single (walking alone) and dual task (walking with cognitive tasks) conditions was assessed using an electrical walkway system. After the 4-week intervention, under both single and dual task conditions, significant improvement on walking function was observed in VRTCL and control groups (P < 0.05). In addition, in the dual task condition, greater improvement on walking function was observed in the VRTCL group, compared with the control group (P < 0.05). These findings demonstrated the efficacy of VRTCL on the walking function under the dual task condition. Therefore, we suggest that VRTCL may be an effective method for the achievement of independent walking in chronic stroke patients.

Parents Perceive Improvements in Socio-emotional Functioning in Adolescents with ASD Following Social Skills Treatment.

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N Lordo, Danielle; Bertolin, Madison; L Sudikoff, Eliana; Keith, Cierra; Braddock, Barbara; Kaufman, David A S

2017-01-01

The current study examined the effectiveness of a social skills treatment (PEERS) for improving socio-emotional competencies in a sample of high-functioning adolescents with ASD. Neuropsychological and self- and parent-report measures assessing social, emotional, and behavioral functioning were administered before and after treatment. Following social skills treatment, adolescents with ASD exhibited decreased aggression, anxiety, and withdrawal, as well as improvements in emotional responsiveness, adaptability, leadership, and participation in activities of daily living, though no change was found in affect recognition abilities. These findings suggest that PEERS social skills treatment improves particular aspects of emotional, behavioral, and social functioning that may be necessary for developing and maintaining quality peer relationships and remediating social isolation in adolescents with ASD.

Protein-protein interaction site prediction in Homo sapiens and E. coli using an interaction-affinity based membership function in fuzzy SVM.

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Sriwastava, Brijesh Kumar; Basu, Subhadip; Maulik, Ujjwal

2015-10-01

Protein-protein interaction (PPI) site prediction aids to ascertain the interface residues that participate in interaction processes. Fuzzy support vector machine (F-SVM) is proposed as an effective method to solve this problem, and we have shown that the performance of the classical SVM can be enhanced with the help of an interaction-affinity based fuzzy membership function. The performances of both SVM and F-SVM on the PPI databases of the Homo sapiens and E. coli organisms are evaluated and estimated the statistical significance of the developed method over classical SVM and other fuzzy membership-based SVM methods available in the literature. Our membership function uses the residue-level interaction affinity scores for each pair of positive and negative sequence fragments. The average AUC scores in the 10-fold cross-validation experiments are measured as 79.94% and 80.48% for the Homo sapiens and E. coli organisms respectively. On the independent test datasets, AUC scores are obtained as 76.59% and 80.17% respectively for the two organisms. In almost all cases, the developed F-SVM method improves the performances obtained by the corresponding classical SVM and the other classifiers, available in the literature.

Randomized clinical trial of cognitive behavioral social skills training for schizophrenia: improvement in functioning and experiential negative symptoms.

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Granholm, Eric; Holden, Jason; Link, Peter C; McQuaid, John R

2014-12-01

Identifying treatments to improve functioning and reduce negative symptoms in consumers with schizophrenia is of high public health significance. In this randomized clinical trial, participants with schizophrenia or schizoaffective disorder (N = 149) were randomly assigned to cognitive behavioral social skills training (CBSST) or an active goal-focused supportive contact (GFSC) control condition. CBSST combined cognitive behavior therapy with social skills training and problem-solving training to improve functioning and negative symptoms. GFSC was weekly supportive group therapy focused on setting and achieving functioning goals. Blind raters assessed functioning (primary outcome: Independent Living Skills Survey [ILSS]), CBSST skill knowledge, positive and negative symptoms, depression, and defeatist performance attitudes. In mixed-effects regression models in intent-to-treat analyses, CBSST skill knowledge, functioning, amotivation/asociality negative symptoms, and defeatist performance attitudes improved significantly more in CBSST relative to GFSC. In both treatment groups, comparable improvements were also found for positive symptoms and a performance-based measure of social competence. The results suggest CBSST is an effective treatment to improve functioning and experiential negative symptoms in consumers with schizophrenia, and both CBSST and supportive group therapy actively focused on setting and achieving functioning goals can improve social competence and reduce positive symptoms.

Grafting both acute wound site and adjacent donor site with the same graft: an easy and safe procedure to improve healing and minimize pain in elderly and bedridden patients.

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Keilani, C; Agard, D; Duhoux, A; Lakhel, A; Giraud, O; Brachet, M; Duhamel, P; Bey, E

2017-03-31

In harvesting skin to cover the defect caused by a burn, a second wound is created, the donor site wound. We propose an alternative method to manage the donor site: taking a split-thickness skin graft (STSG) from a donor site adjacent to the burn wound to be treated, and meshing at a 3:1 ratio to cover both sites at once. The main objective of this study is to evaluate the effectiveness of covering both burn wound and adjacent donor site with the same STSG in elderly and bedridden patients. We retrospectively reviewed the medical records of 6 patients over 60 years old or/and bedridden presenting with a small burn wound who underwent STSG of both burn wound and adjacent donor site between April 2016 and November 2016 in the Department of Plastic Surgery and Burn Treatment at Percy Military Hospital (France). Their data were compared with data of five patients who had undergone the usual STSG procedure during the same period. There was a statistically significant difference between patients who underwent adjacent STSG procedure and those who underwent usual STSG procedure in healing time (days) mean (SD) (7,33 ± 1,03 vs. 16,2 ± 0,83; p = 0,007) and Numeric Rating Scale pain mean (SD) at day 2 (0,33 ± 0,33 vs. 2,4 ± 1,35; p = 0,04). Grafting both acute burn wound and adjacent donor site with the same graft seems to be an easy method to improve healing and minimize pain in the STSG donor site in elderly and bedridden patients.

Features generated for computational splice-site prediction correspond to functional elements

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Wilbur W John

2007-10-01

Full Text Available Abstract Background Accurate selection of splice sites during the splicing of precursors to messenger RNA requires both relatively well-characterized signals at the splice sites and auxiliary signals in the adjacent exons and introns. We previously described a feature generation algorithm (FGA that is capable of achieving high classification accuracy on human 3' splice sites. In this paper, we extend the splice-site prediction to 5' splice sites and explore the generated features for biologically meaningful splicing signals. Results We present examples from the observed features that correspond to known signals, both core signals (including the branch site and pyrimidine tract and auxiliary signals (including GGG triplets and exon splicing enhancers. We present evidence that features identified by FGA include splicing signals not found by other methods. Conclusion Our generated features capture known biological signals in the expected sequence interval flanking splice sites. The method can be easily applied to other species and to similar classification problems, such as tissue-specific regulatory elements, polyadenylation sites, promoters, etc.

An Atlas of Peroxiredoxins Created Using an Active Site Profile-Based Approach to Functionally Relevant Clustering of Proteins.

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Angela F Harper

2017-02-01

Full Text Available Peroxiredoxins (Prxs or Prdxs are a large protein superfamily of antioxidant enzymes that rapidly detoxify damaging peroxides and/or affect signal transduction and, thus, have roles in proliferation, differentiation, and apoptosis. Prx superfamily members are widespread across phylogeny and multiple methods have been developed to classify them. Here we present an updated atlas of the Prx superfamily identified using a novel method called MISST (Multi-level Iterative Sequence Searching Technique. MISST is an iterative search process developed to be both agglomerative, to add sequences containing similar functional site features, and divisive, to split groups when functional site features suggest distinct functionally-relevant clusters. Superfamily members need not be identified initially-MISST begins with a minimal representative set of known structures and searches GenBank iteratively. Further, the method's novelty lies in the manner in which isofunctional groups are selected; rather than use a single or shifting threshold to identify clusters, the groups are deemed isofunctional when they pass a self-identification criterion, such that the group identifies itself and nothing else in a search of GenBank. The method was preliminarily validated on the Prxs, as the Prxs presented challenges of both agglomeration and division. For example, previous sequence analysis clustered the Prx functional families Prx1 and Prx6 into one group. Subsequent expert analysis clearly identified Prx6 as a distinct functionally relevant group. The MISST process distinguishes these two closely related, though functionally distinct, families. Through MISST search iterations, over 38,000 Prx sequences were identified, which the method divided into six isofunctional clusters, consistent with previous expert analysis. The results represent the most complete computational functional analysis of proteins comprising the Prx superfamily. The feasibility of this novel method is

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

KAUST Repository

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

2018-01-01

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

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

KAUST Repository

Khamis, Abdullah M.

2018-03-20

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

Relief of depression and pain improves daily functioning and quality of life in patients with major depressive disorder.

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Lin, Ching-Hua; Yen, Yung-Chieh; Chen, Ming-Chao; Chen, Cheng-Chung

2013-12-02

The objective of this study was to investigate the effects of depression relief and pain relief on the improvement in daily functioning and quality of life (QOL) for depressed patients receiving a 6-week treatment of fluoxetine. A total of 131 acutely ill inpatients with major depressive disorder (MDD) were enrolled to receive 20mg of fluoxetine daily for 6 weeks. Depression severity, pain severity, daily functioning, and health-related QOL were assessed at baseline and again at week 6. Depression severity, pain severity, and daily functioning were assessed using the 17-item Hamilton Depression Rating Scale, the Short-Form 36 (SF-36) Body Pain Index, and the Work and Social Adjustment Scale. Health-related QOL was assessed by three primary domains of the SF-36, including social functioning, vitality, and general health perceptions. Pearson's correlation and structural equation modeling were used to examine relationships among the study variables. Five models were proposed. In model 1, depression relief alone improved daily functioning and QOL. In model 2, pain relief alone improved daily functioning and QOL. In model 3, depression relief, mediated by pain relief, improved daily functioning and QOL. In model 4, pain relief, mediated by depression relief, improved daily functioning and QOL. In model 5, both depression relief and pain relief improved daily functioning and QOL. One hundred and six patients completed all the measures at baseline and at week 6. Model 5 was the most fitted structural equation model (χ(2) = 8.62, df = 8, p = 0.376, GFI = 0.975, AGFI = 0.935, TLI = 0.992, CFI = 0.996, RMSEA = 0.027). Interventions which relieve depression and pain improve daily functioning and QOL among patients with MDD. The proposed model can provide quantitative estimates of improvement in treating patients with MDD. © 2013 Elsevier Inc. All rights reserved.

Improving Survival and Promoting Respiratory Motor Function After Cervical Spinal Cord Injury

Science.gov (United States)

2017-09-01

AWARD NUMBER: W81XWH-15-1-0378 TITLE: Improving Survival and Promoting Respiratory Motor Function After Cervical Spinal Cord Injury PRINCIPAL...TITLE AND SUBTITLE CordCorInjury 5a. CONTRACT NUMBER Improvi g Survival and Promoting Respiratory Motor Function After Cervical Spinal Cord...care. However, despite these drastic interventions, the cervical injured patient is still susceptible to death due to respiratory complications

Functional-Strengthening: A Pilot Study on Balance Control Improvement in Community-Dwelling Older Adults

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Micah D. Josephson

2017-09-01

Full Text Available Adults over the age of 65 have a 1 in 3 chance of falling; in 2012, more than $30 billion was spent on medical costs due to these falls. The division of resistance training and neuromotor training balance improvement interventions has shown to yield low to moderate results. Athletes combine both resistance training and skill development (function training to improve skilled performance. Older adults may not be performing high-level sports activities, but still require strength, power, and functional fitness levels to perform relatively high-level skills. The purpose of this study was to determine the effects of combining resistance and functional training into functional-strength training on dynamic balance control in moderately active older adults. Eighteen healthy older adults were divided into three groups; functional resistance, standard resistance, and control. All groups met for their intervention twice a week for six weeks. Dynamic balance was assessed using the Fullerton Advanced Balance Scale (0-40. Results of individual paired T-tests showed a significant improvement in balance control in the functional resistance group (t(5 =-3.492, p=.017 and a very large effect size (d=1.33 whereas neither the standard resistance nor control group had a significant reduction in the risk of falls. Manipulating multidimensional, neuromotor function during resistance training exercises is an effective method of applying the overload principle in order to reduce falls risk in moderately active seniors.

How do probiotics and prebiotics function at distant sites?

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Reid, G; Abrahamsson, T; Bailey, M; Bindels, L B; Bubnov, R; Ganguli, K; Martoni, C; O'Neill, C; Savignac, H M; Stanton, C; Ship, N; Surette, M; Tuohy, K; van Hemert, S

2017-08-24

The realisation that microbes regarded as beneficial to the host can impart effects at sites distant from their habitat, has raised many possibilities for treatment of diseases. The objective of a workshop hosted in Turku, Finland, by the International Scientific Association for Probiotics and Prebiotics, was to assess the evidence for these effects and the extent to which early life microbiome programming influences how the gut microbiota communicates with distant sites. In addition, we examined how probiotics and prebiotics might affect the skin, airways, heart, brain and metabolism. The growing levels of scientific and clinical evidence showing how microbes influence the physiology of many body sites, leads us to call for more funding to advance a potentially exciting avenue for novel therapies for many chronic diseases.

Improving Multi-Functional Properties in Polymer Based Nano Composites by Interfacial

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Tajaddod, Navid

Polymer nanocomposites (PNCs) have become an area of increasing interest for study in the field of polymer science and technology since the rise of nanotechnology research. Despite the significant amount of progress being made towards producing high quality PNC materials, improvement in the mechanical, electrical, thermal and other functional properties still remain a challenge. To date, these properties are only a fraction of the expected theoretical values predicted for these materials. Development of interfacial regions between the filler and matrix within the composite has been found to be an important focus in terms of processing. Proper interfacial control and development may ensure excellent interaction and property transfer between the filler and polymer matrix in addition to improvement of multi-functional properties of PNCs. The property-structure importance for the existence of the interfacial and interphase region within PNCs is discussed in this thesis work. Two specific PNC systems are selected for study as part of this dissertation in order to understand the effect of interfacial region development on influencing multi-functional property trends. Polyethylene (PE)/boron nitride (BN) and polyacrylonitrile (PAN)/carbon nanotube (CNT) composites were selected to investigate their mechanical performance and thermal and electrical conductivity properties, respectively. For these systems it was found that the interfacial region structure is directly related to the enhancement of the subsequent multi-functional properties.

Improving the work function of the niobium surface of SRF cavities by plasma processing

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Tyagi, P. V.; Doleans, M.; Hannah, B.; Afanador, R.; McMahan, C.; Stewart, S.; Mammosser, J.; Howell, M.; Saunders, J.; Degraff, B.; Kim, S.-H.

2016-04-01

An in situ plasma processing technique using chemically reactive oxygen plasma to remove hydrocarbons from superconducting radio frequency cavity surfaces at room temperature has been developed at the spallation neutron source, at Oak Ridge National Laboratory. To understand better the interaction between the plasma and niobium surface, surface studies on small samples were performed. In this article, we report the results from those surface studies. The results show that plasma processing removes hydrocarbons from top surface and improves the surface work function by 0.5-1.0 eV. Improving the work function of RF surface of cavities can help to improve their operational performance.

Physical activity and enhanced fitness to improve cognitive function in older people without known cognitive impairment

NARCIS (Netherlands)

Angevaren, Maaike; Aufdemkampe, Geert; Verhaar, H. J. J.; Aleman, A.; Vanhees, Luc

2008-01-01

Background Physical activity is beneficial for healthy ageing. It may also help maintain good cognitive function in older age. Aerobic activity improves cardiovascular fitness, but it is not known whether this sort of fitness is necessary for improved cognitive function. Studies in which activity,

Covalent Surface Functionalization of Boron Nitride Nanotubes Fabricated with Diazonium Salt

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Zhujun Wang

2018-01-01

Full Text Available The chemical inertness and poor wetting properties of boron nitride nanotubes (BNNTs hindered their applications. In this work, BNNTs have been functionalized with aniline groups by reacting with diazonium salt and the graft content of aniline component was calculated as high as 71.4 wt.%. The chemical structure, composition, and morphology of functionalized BNNTs were carefully characterized to illustrate the modification. The anilinocarbocation generated by decomposition of diazonium salt reacted not only with NH2 sites, but also with B-OH sites on the surface of BNNTs. Meanwhile, the reaction applied a hot strong acid environment, which would help to open parts of B-N bonds to produce more reactive sites and enrich the functional groups grafted on the surface of BNNTs. Consequently, the functionalized BNNTs exhibited significantly improved dispersion stability in chloroform compared with pristine BNNTs. Amino surface functionalization of BNNTs offered more possibilities for surface chemical design of boron nitride and its practical application.

Exploring the composition of protein-ligand binding sites on a large scale.

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Nickolay A Khazanov

Full Text Available The residue composition of a ligand binding site determines the interactions available for diffusion-mediated ligand binding, and understanding general composition of these sites is of great importance if we are to gain insight into the functional diversity of the proteome. Many structure-based drug design methods utilize such heuristic information for improving prediction or characterization of ligand-binding sites in proteins of unknown function. The Binding MOAD database if one of the largest curated sets of protein-ligand complexes, and provides a source of diverse, high-quality data for establishing general trends of residue composition from currently available protein structures. We present an analysis of 3,295 non-redundant proteins with 9,114 non-redundant binding sites to identify residues over-represented in binding regions versus the rest of the protein surface. The Binding MOAD database delineates biologically-relevant "valid" ligands from "invalid" small-molecule ligands bound to the protein. Invalids are present in the crystallization medium and serve no known biological function. Contacts are found to differ between these classes of ligands, indicating that residue composition of biologically relevant binding sites is distinct not only from the rest of the protein surface, but also from surface regions capable of opportunistic binding of non-functional small molecules. To confirm these trends, we perform a rigorous analysis of the variation of residue propensity with respect to the size of the dataset and the content bias inherent in structure sets obtained from a large protein structure database. The optimal size of the dataset for establishing general trends of residue propensities, as well as strategies for assessing the significance of such trends, are suggested for future studies of binding-site composition.

Improving construction site safety through leader-based verbal safety communication.

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Kines, Pete; Andersen, Lars P S; Spangenberg, Soren; Mikkelsen, Kim L; Dyreborg, Johnny; Zohar, Dov

2010-10-01

The construction industry is one of the most injury-prone industries, in which production is usually prioritized over safety in daily on-site communication. Workers have an informal and oral culture of risk, in which safety is rarely openly expressed. This paper tests the effect of increasing leader-based on-site verbal safety communication on the level of safety and safety climate at construction sites. A pre-post intervention-control design with five construction work gangs is carried out. Foremen in two intervention groups are coached and given bi-weekly feedback about their daily verbal safety communications with their workers. Foremen-worker verbal safety exchanges (experience sampling method, n=1,693 interviews), construction site safety level (correct vs. incorrect, n=22,077 single observations), and safety climate (seven dimensions, n=105 questionnaires) are measured over a period of up to 42 weeks. Baseline measurements in the two intervention and three control groups reveal that foremen speak with their workers several times a day. Workers perceive safety as part of their verbal communication with their foremen in only 6-16% of exchanges, and the levels of safety at the sites range from 70-87% (correct observations). Measurements from baseline to follow-up in the two intervention groups reveal that safety communication between foremen and workers increases significantly in one of the groups (factor 7.1 increase), and a significant yet smaller increase is found when the two intervention groups are combined (factor 4.6). Significant increases in the level of safety are seen in both intervention groups (7% and 12% increases, respectively), particularly in regards to 'access ways' and 'railings and coverings' (39% and 84% increases, respectively). Increases in safety climate are seen in only one of the intervention groups with respect to their 'attention to safety.' No significant trend changes are seen in the three control groups on any of the three measures

Predictors of improved functioning in patients with psychosis: The role of amotivation and defeatist performance beliefs.

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Pillny, Matthias; Lincoln, Tania M

2016-10-30

Defeatist performance beliefs (DPBs) are associated with the severe impairments in functioning of patients with negative symptoms of schizophrenia. This association has been found to be mediated by amotivation, a core aspect of negative symptoms. Although causality is assumed, longitudinal evidence for this is lacking. The current study aimed to extend previous findings by investigating both cross-sectional and longitudinal associations between DPBs, motivational impairments and functioning in a sample of patients with psychotic disorders (N=58). We hypothesized, that DPBs would be related to functioning in cross-sectional and longitudinal analyses and that this link would be mediated by motivational impairments. Data was assessed at baseline and post-treatment in a trial on the effects of cognitive behavior therapy for psychosis. At baseline, amotivation mediated the association between DPBs and functioning. From baseline to post-treatment, reduction of amotivation was associated with improvement of functioning significantly, whereas reduction of DPBs was unrelated to improvements in functioning or amotivation. The findings suggest that improvement in amotivation accounts for favorable treatment outcomes in regard to functioning but question the causal role of DPBs in negative symptoms and functioning. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Improving regulatory effectiveness in federal/state siting actions: state regulatory activity involved in need for power

International Nuclear Information System (INIS)

Nassikas, J.

1977-04-01

The individual views are presented of the panel members relating to the basic issues and framework for improvements of the Federal/state process for licensing of nuclear power plants, associated facilities, transmission lines, reprocessing of fuel and uranium enrichment. The synopsis supplements the initial synopsis of the views presented to the National Governors Conference Workshop ''State Perspectives on Energy Facility Siting'' in Atlanta, Georgia on December 15--16, 1976. Both synopses constitute the report of this panel

A Quality Improvement Approach to Reducing the Caesarean section Surgical Site Infection Rate in a Regional Hospital

LENUS (Irish Health Repository)

O’ Hanlon, M

2016-09-01

Surgical site infection (SSI) rates are used extensively by hospitals as a basis for quality improvement. A 30-day post-discharge SSI programme for Caesarean section operations has been implemented in Our Lady of Lourdes Hospital since 2011. It has been shown that skin antisepsis and antibiotic prophylaxis are key factors in the prevention of SSI. Using quality improvement methodology, an infection prevention bundle was introduced to address these two factors. Skin antisepsis was changed from povidone-iodine to chlorhexidine-alcohol. Compliance with choice of antibiotic prophylaxis increased from 89.6% in 2014 to 98.5% in 2015. Compliance with timing also improved. The SSI rate of 7.5% was the lowest recorded to date, with the majority of SSIs (64%) diagnosed after hospital discharge. The level of variation was also reduced. However, the continued presence of variation and possibility of lower infection rates from the literature imply that further improvements are required.

Vagus nerve stimulation paired with tactile training improved sensory function in a chronic stroke patient.

Science.gov (United States)

Kilgard, Michael P; Rennaker, Robert L; Alexander, Jen; Dawson, Jesse

2018-01-01

Recent studies indicate that vagus nerve stimulation (VNS) paired with rehabilitation can enhance neural plasticity in the primary sensory and motor cortices, improve forelimb function after stroke in animal models and improve motor function in patients with arm weakness after stroke. To gain "first-in-man" experience of VNS paired with tactile training in a patient with severe sensory impairment after stroke. During the long-term follow-up phase of a clinical trial of VNS paired with motor rehabilitation, a 71-year-old man who had made good motor recovery had ongoing severe sensory loss in his left hand and arm. He received VNS paired with tactile therapy in an attempt to improve his sensory function. During twenty 2-hour sessions, each passive and active tactile event was paired with a 0.5 second burst of 0.8 mA VNS. Sensory function was measured before, halfway through, and after this therapy. The patient did not report any side effects during or following VNS+Tactile therapy. Quantitative measures revealed lasting and clinically meaningful improvements in tactile threshold, proprioception, and stereognosis. After VNS+Tactile therapy, the patient was able to detect tactile stimulation to his affected hand that was eight times less intense, identify the joint position of his fingers in the affected hand three times more often, and identify everyday objects using his affected hand seven times more often, compared to baseline. Sensory function significantly improved in this man following VNS paired with tactile stimulation. This approach merits further study in controlled clinical trials.

Vapor-Phase Hydrodeoxygenation of Guaiacol to Aromatics over Pt/HBeta: Identification of the Role of Acid Sites and Metal Sites on the Reaction Pathway

Energy Technology Data Exchange (ETDEWEB)

Nie, Lei [Collaborative Innovation Center of Chemical Science and Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 P.R. China; Institute for Integrated Catalysis, Pacific Northwest National Laboratory, P.O. Box 999 Richland WA 99352 USA; Peng, Bo [Institute for Integrated Catalysis, Pacific Northwest National Laboratory, P.O. Box 999 Richland WA 99352 USA; Zhu, Xinli [Collaborative Innovation Center of Chemical Science and Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 P.R. China

2018-02-05

Hydrodeoxygenation of guaiacol, a phenolic compound derived from lignin fraction of biomass, over a Pt/HBeta catalyst at 350 °C and atmospheric pressure produces benzene, toluene, xylenes, and C9+ aromatics with yield of 42%, 29%, 12%, and 5%, respectively. Reaction pathways for conversion of two functional groups (hydroxyl and methoxyl) over the bifunctional catalyst were studied. Both guaiacol and intermediate products (catechol and cyclopentanone) were fed onto zeolite HBeta and Pt/SiO2 to identify the individual role of acid site and metal site. Acid sites (mainly Brønsted acid site, BAS) catalyze transalkylation and dehydroxylation reactions in sequence, producing phenol, cresols and xylenols as the major products at high conversion. Pt sites catalyze demethylation reaction resulting in catechol as the primary product, which can either be deoxygenated to phenol followed by phenol to benzene, or decarbonylated to cyclopentanone and further to butane. The close proximity of Pt and BAS in bifunctional Pt/HBeta enables both transalkylation and deoxygenation reactions with inhibited demethylation and decarbonylation reactions, producing aromatics as major final products with a total yield > 85%. Both activity and stability of bifunctional Pt/HBeta during hydrodeoxygenation of guaiacol is improved compared to HBeta and Pt/SiO2. The addition of water to the feed further improves the activity and stability via hydrolysis of O-CH3 bond of guaiacol on BAS and removing coke around Pt.

Shifting the Paradigm for Long Term Monitoring at Legacy Sites to Improve Performance while Reducing Cost

International Nuclear Information System (INIS)

Eddy-Dilek, Carol A.; Looney, Brian B.; Seaman, John; Kmetz, Thomas

2013-01-01

A major issue facing many government and private industry sites that were previously contaminated with radioactive and chemical wastes is that often the sites cannot be cleaned up enough to permit unrestricted human access. These sites will require long-term management, in some cases indefinitely, leaving site owners with the challenge of protecting human health and environmental quality in a cost effective manner. Long-term monitoring of groundwater contamination is one of the largest projected costs in the life cycle of environmental management at the Savannah River Site (SRS), the larger DOE complex, and many large federal and private sites. Currently, most monitoring strategies are focused on laboratory measurements of contaminants measured in groundwater samples collected from wells. This approach is expensive, and provides limited and lagging information about the effectiveness of cleanup activities and the behavior of the residual contamination. Over the last twenty years, DOE and other federal agencies have made significant investments in the development of various types of sensors and strategies that would allow for remote analysis of contaminants in groundwater, but these approaches do not promise significant reductions in risk or cost. Scientists at SRS have developed a new paradigm to simultaneously improve the performance of long term monitoring systems while lowering the overall cost of monitoring. This alternative approach incorporates traditional point measurements of contaminant concentration with measurements of controlling variables including boundary conditions, master variables, and traditional plume/contaminant variables. Boundary conditions are the overall driving forces that control plume movement and therefore provide leading indication to changes in plume stability. These variables include metrics associated with meteorology, hydrology, hydrogeology, and land use. Master variables are the key variables that control the chemistry of the

Improving the effectiveness of ecological site descriptions: General state-and-transition models and the Ecosystem Dynamics Interpretive Tool (EDIT)

Science.gov (United States)

Bestelmeyer, Brandon T.; Williamson, Jeb C.; Talbot, Curtis J.; Cates, Greg W.; Duniway, Michael C.; Brown, Joel R.

2016-01-01

State-and-transition models (STMs) are useful tools for management, but they can be difficult to use and have limited content.STMs created for groups of related ecological sites could simplify and improve their utility. The amount of information linked to models can be increased using tables that communicate management interpretations and important within-group variability.We created a new web-based information system (the Ecosystem Dynamics Interpretive Tool) to house STMs, associated tabular information, and other ecological site data and descriptors.Fewer, more informative, better organized, and easily accessible STMs should increase the accessibility of science information.

Anti-tachycardia therapy can improve altered cardiac adrenergic function in tachycardia-induced cardiomyopathy

Energy Technology Data Exchange (ETDEWEB)

Ohkusu, Yasuo; Takahashi, Nobukazu; Ishikawa, Toshiyuki [Yokohama City Univ. (Japan). School of Medicine] [and others

2002-11-01

We investigated whether anti-tachycardia therapy might improve the altered cardiac adrenergic and systolic function in tachycardia-induced cardiomyopathy (TC) in contrast to dilated cardiomyopathy (DCM). The subjects were 23 patients with heart failure, consisting of 8 patients with TC (43.6{+-}10.0 yrs) and 15 with DCM (45.3{+-}8.2 yrs). TC was determined as impairment of left ventricular function secondary to chronic or very frequent arrhythmia during more than 10% of the day. All patients were receiving anti-tachycardia treatment. Cardiac {sup 123}I-MIBG uptake was assessed as the heart/mediastinum activity ratio (H/M) before and after treatment. Left ventricular ejection fraction (LVEF) was also assessed. In the baseline study, H/M and LVEF showed no difference between TC and DCM (2.21{+-}0.44 vs. 2.10{+-}0.42, 35.3{+-}13.1 vs. 36.0{+-}10.9%, respectively). After treatment, the degree of change in H/M and LVEF differed significantly (0.41{+-}0.34 vs. 0.08{+-}0.20, 20.5{+-}14.4 vs. -2.1{+-}9.6%, p<0.01). In TC, heart failure improved after a shorter duration of treatment (p<0.05). In conclusion, anti-tachycardia therapy can improve altered cardiac adrenergic function and systolic function in patients with TC over a shorter period than in those with DCM. (author)

An improved, bias-reduced probabilistic functional gene network of baker's yeast, Saccharomyces cerevisiae.

Directory of Open Access Journals (Sweden)

Insuk Lee

2007-10-01

Full Text Available Probabilistic functional gene networks are powerful theoretical frameworks for integrating heterogeneous functional genomics and proteomics data into objective models of cellular systems. Such networks provide syntheses of millions of discrete experimental observations, spanning DNA microarray experiments, physical protein interactions, genetic interactions, and comparative genomics; the resulting networks can then be easily applied to generate testable hypotheses regarding specific gene functions and associations.We report a significantly improved version (v. 2 of a probabilistic functional gene network of the baker's yeast, Saccharomyces cerevisiae. We describe our optimization methods and illustrate their effects in three major areas: the reduction of functional bias in network training reference sets, the application of a probabilistic model for calculating confidences in pair-wise protein physical or genetic interactions, and the introduction of simple thresholds that eliminate many false positive mRNA co-expression relationships. Using the network, we predict and experimentally verify the function of the yeast RNA binding protein Puf6 in 60S ribosomal subunit biogenesis.YeastNet v. 2, constructed using these optimizations together with additional data, shows significant reduction in bias and improvements in precision and recall, in total covering 102,803 linkages among 5,483 yeast proteins (95% of the validated proteome. YeastNet is available from http://www.yeastnet.org.

Empirical estimation of school siting parameter towards improving children's safety

International Nuclear Information System (INIS)

Aziz, I S; Yusoff, Z M; Rasam, A R A; Rahman, A N N A; Omar, D

2014-01-01

Distance from school to home is a key determination in ensuring the safety of hildren. School siting parameters are made to make sure that a particular school is located in a safe environment. School siting parameters are made by Department of Town and Country Planning Malaysia (DTCP) and latest review was on June 2012. These school siting parameters are crucially important as they can affect the safety, school reputation, and not to mention the perception of the pupil and parents of the school. There have been many studies to review school siting parameters since these change in conjunction with this ever-changing world. In this study, the focus is the impact of school siting parameter on people with low income that live in the urban area, specifically in Johor Bahru, Malaysia. In achieving that, this study will use two methods which are on site and off site. The on site method is to give questionnaires to people and off site is to use Geographic Information System (GIS) and Statistical Product and Service Solutions (SPSS), to analyse the results obtained from the questionnaire. The output is a maps of suitable safe distance from school to house. The results of this study will be useful to people with low income as their children tend to walk to school rather than use transportation

Neurologic music therapy improves executive function and emotional adjustment in traumatic brain injury rehabilitation.

Science.gov (United States)

Thaut, Michael H; Gardiner, James C; Holmberg, Dawn; Horwitz, Javan; Kent, Luanne; Andrews, Garrett; Donelan, Beth; McIntosh, Gerald R

2009-07-01

This study examined the immediate effects of neurologic music therapy (NMT) on cognitive functioning and emotional adjustment with brain-injured persons. Four treatment sessions were held, during which participants were given a pre-test, participated in 30 min of NMT that focused on one aspect of rehabilitation (attention, memory, executive function, or emotional adjustment), which was followed by post-testing. Control participants engaged in a pre-test, 30 min of rest, and then a post-test. Treatment participants showed improvement in executive function and overall emotional adjustment, and lessening of depression, sensation seeking, and anxiety. Control participants improved in emotional adjustment and lessening of hostility, but showed decreases in measures of memory, positive affect, and sensation seeking.

A new therapeutic effect of simvastatin revealed by functional improvement in muscular dystrophy.

Science.gov (United States)

Whitehead, Nicholas P; Kim, Min Jeong; Bible, Kenneth L; Adams, Marvin E; Froehner, Stanley C

2015-10-13

Duchenne muscular dystrophy (DMD) is a lethal, degenerative muscle disease with no effective treatment. DMD muscle pathogenesis is characterized by chronic inflammation, oxidative stress, and fibrosis. Statins, cholesterol-lowering drugs, inhibit these deleterious processes in ischemic diseases affecting skeletal muscle, and therefore have potential to improve DMD. However, statins have not been considered for DMD, or other muscular dystrophies, principally because skeletal-muscle-related symptoms are rare, but widely publicized, side effects of these drugs. Here we show positive effects of statins in dystrophic skeletal muscle. Simvastatin dramatically reduced damage and enhanced muscle function in dystrophic (mdx) mice. Long-term simvastatin treatment vastly improved overall muscle health in mdx mice, reducing plasma creatine kinase activity, an established measure of muscle damage, to near-normal levels. This reduction was accompanied by reduced inflammation, more oxidative muscle fibers, and improved strength of the weak diaphragm muscle. Shorter-term treatment protected against muscle fatigue and increased mdx hindlimb muscle force by 40%, a value comparable to current dystrophin gene-based therapies. Increased force correlated with reduced NADPH Oxidase 2 protein expression, the major source of oxidative stress in dystrophic muscle. Finally, in old mdx mice with severe muscle degeneration, simvastatin enhanced diaphragm force and halved fibrosis, a major cause of functional decline in DMD. These improvements were accompanied by autophagy activation, a recent therapeutic target for DMD, and less oxidative stress. Together, our findings highlight that simvastatin substantially improves the overall health and function of dystrophic skeletal muscles and may provide an unexpected, novel therapy for DMD and related neuromuscular diseases.

A ChIP-Seq benchmark shows that sequence conservation mainly improves detection of strong transcription factor binding sites.

Directory of Open Access Journals (Sweden)

Tony Håndstad

Full Text Available BACKGROUND: Transcription factors are important controllers of gene expression and mapping transcription factor binding sites (TFBS is key to inferring transcription factor regulatory networks. Several methods for predicting TFBS exist, but there are no standard genome-wide datasets on which to assess the performance of these prediction methods. Also, it is believed that information about sequence conservation across different genomes can generally improve accuracy of motif-based predictors, but it is not clear under what circumstances use of conservation is most beneficial. RESULTS: Here we use published ChIP-seq data and an improved peak detection method to create comprehensive benchmark datasets for prediction methods which use known descriptors or binding motifs to detect TFBS in genomic sequences. We use this benchmark to assess the performance of five different prediction methods and find that the methods that use information about sequence conservation generally perform better than simpler motif-scanning methods. The difference is greater on high-affinity peaks and when using short and information-poor motifs. However, if the motifs are specific and information-rich, we find that simple motif-scanning methods can perform better than conservation-based methods. CONCLUSIONS: Our benchmark provides a comprehensive test that can be used to rank the relative performance of transcription factor binding site prediction methods. Moreover, our results show that, contrary to previous reports, sequence conservation is better suited for predicting strong than weak transcription factor binding sites.

Traditional Chinese Medicine Tongxinluo Improves Cardiac Function of Rats with Dilated Cardiomyopathy

Directory of Open Access Journals (Sweden)

Fang-Fang Shen

2014-01-01

Full Text Available The study aimed at testing the hypothesis that tongxinluo capsule might exert its cardioprotective effect by preventing ventricular remodeling and improving coronary microvascular function in a rat model of doxorubicin-induced dilated cardiomyopathy (DCM. Rats that survived DCM induction were randomly divided into three groups to be given 1.5 g·kg−1·day−1 (TXL-H, n=9 or 0.15 g·kg−1·day−1 (TXL-L, n=10 of tongxinluo, or normal saline at the same volume (DCM-C, n=10 intragastrically. Age matched normal rats treated with normal saline were used as normal controls (NOR-C, n=9. After four weeks of treatment, the DCM-C, TXL-H, and TXL-L groups exhibited significant cardiac dysfunction, left ventricular remodeling, and coronary microvascular dysfunction, compared with the NOR-C rats. However, myocardial functional parameters were significantly improved and microvascular density (MVD increased in the TXL-H group compared with the DCM-C group (all P<0.01. Left ventricular remodeling was prevented. There were close linear relationships between CVF and LVEF (r=-0.683, P<0.05, MVD and LVEF (r=0.895, P<0.05, and MVD and CVF (r=-0.798, P<0.05. It was indicated that high-dose tongxinluo effectively improved cardiac function in rat model of DCM.

E-KIT: An Electronic-Knowledge Information Tool for Organizing Site Information and Improving Technical Communication with Stakeholders - 13082

International Nuclear Information System (INIS)

Kautsky, Mark; Findlay, Richard C.; Hodges, Rex A.

2013-01-01

Managing technical references for projects that have long histories is hampered by the large collection of documents, each of which might contain discrete pieces of information relevant to the site conceptual model. A database application has been designed to improve the efficiency of retrieving technical information for a project. Although many databases are currently used for accessing analytical and geo-referenced data, applications designed specifically to manage technical reference material for projects are scarce. Retrieving site data from the array of available references becomes an increasingly inefficient use of labor. The electronic-Knowledge Information Tool (e-KIT) is designed as a project-level resource to access and communicate technical information. The e-KIT is a living tool that grows as new information becomes available, and its value to the project increases as the volume of site information increases. Having all references assembled in one location with complete reference citations and links to elements of the site conceptual model offers a way to enhance communication with outside groups. The published and unpublished references are incorporated into the e-KIT, while the compendium of references serves as a complete bibliography for the project. (authors)

E-KIT: An Electronic-Knowledge Information Tool for Organizing Site Information and Improving Technical Communication with Stakeholders - 13082

Energy Technology Data Exchange (ETDEWEB)

Kautsky, Mark [U.S. Department of Energy Office of Legacy Management, 2597 Legacy Way, Grand Junction CO 81503 (United States); Findlay, Richard C.; Hodges, Rex A. [Stoller LMS Team, 2597 Legacy Way, Grand Junction CO 81503 (United States)

2013-07-01

Managing technical references for projects that have long histories is hampered by the large collection of documents, each of which might contain discrete pieces of information relevant to the site conceptual model. A database application has been designed to improve the efficiency of retrieving technical information for a project. Although many databases are currently used for accessing analytical and geo-referenced data, applications designed specifically to manage technical reference material for projects are scarce. Retrieving site data from the array of available references becomes an increasingly inefficient use of labor. The electronic-Knowledge Information Tool (e-KIT) is designed as a project-level resource to access and communicate technical information. The e-KIT is a living tool that grows as new information becomes available, and its value to the project increases as the volume of site information increases. Having all references assembled in one location with complete reference citations and links to elements of the site conceptual model offers a way to enhance communication with outside groups. The published and unpublished references are incorporated into the e-KIT, while the compendium of references serves as a complete bibliography for the project. (authors)

Improving Site Management Practices in the Nigerian Construction ...

African Journals Online (AJOL)

Site management involves a combination of activities, which turn basic resources into a finished product. The effectiveness of managing production process cannot be economically attained by force, but requires the creation of conditions that will encourage self-motivation and bring about team spirit that is important to an ...

Searching the protein structure database for ligand-binding site similarities using CPASS v.2

Directory of Open Access Journals (Sweden)

Caprez Adam

2011-01-01

Full Text Available Abstract Background A recent analysis of protein sequences deposited in the NCBI RefSeq database indicates that ~8.5 million protein sequences are encoded in prokaryotic and eukaryotic genomes, where ~30% are explicitly annotated as "hypothetical" or "uncharacterized" protein. Our Comparison of Protein Active-Site Structures (CPASS v.2 database and software compares the sequence and structural characteristics of experimentally determined ligand binding sites to infer a functional relationship in the absence of global sequence or structure similarity. CPASS is an important component of our Functional Annotation Screening Technology by NMR (FAST-NMR protocol and has been successfully applied to aid the annotation of a number of proteins of unknown function. Findings We report a major upgrade to our CPASS software and database that significantly improves its broad utility. CPASS v.2 is designed with a layered architecture to increase flexibility and portability that also enables job distribution over the Open Science Grid (OSG to increase speed. Similarly, the CPASS interface was enhanced to provide more user flexibility in submitting a CPASS query. CPASS v.2 now allows for both automatic and manual definition of ligand-binding sites and permits pair-wise, one versus all, one versus list, or list versus list comparisons. Solvent accessible surface area, ligand root-mean square difference, and Cβ distances have been incorporated into the CPASS similarity function to improve the quality of the results. The CPASS database has also been updated. Conclusions CPASS v.2 is more than an order of magnitude faster than the original implementation, and allows for multiple simultaneous job submissions. Similarly, the CPASS database of ligand-defined binding sites has increased in size by ~ 38%, dramatically increasing the likelihood of a positive search result. The modification to the CPASS similarity function is effective in reducing CPASS similarity scores

Virtual Reality Rehabilitation With Functional Electrical Stimulation Improves Upper Extremity Function in Patients With Chronic Stroke: A Pilot Randomized Controlled Study.

Science.gov (United States)

Lee, Stephanie Hyeyoung; Lee, Ji-Yeong; Kim, Mi-Young; Jeon, Yu-Jin; Kim, Suyoung; Shin, Joon-Ho

2018-03-02

To compare virtual reality (VR) combined with functional electrical stimulation (FES) with cyclic FES for improving upper extremity function and health-related quality of life in patients with chronic stroke. A pilot, randomized, single-blind, controlled trial. Stroke rehabilitation inpatient unit. Participants (N=48) with hemiplegia secondary to a unilateral stroke for >3 months and with a hemiplegic wrist extensor Medical Research Council scale score ranging from 1 to 3. FES was applied to the wrist extensors and finger extensors. A VR-based wearable rehabilitation device was used combined with FES and virtual activity-based training for the intervention group. The control group received cyclic FES only. Both groups completed 20 sessions over a 4-week period. Primary outcome measures were changes in Fugl-Meyer Assessment-Upper Extremity and Wolf Motor Function Test scores. Secondary outcome measures were changes in Box and Block Test, Jebsen-Taylor Hand Function Test, and Stroke Impact Scale scores. Assessments were performed at baseline (t0) and at 2 weeks (t1), 4 weeks (t4), and 8 weeks (t8). Between-group comparisons were evaluated using a repeated-measures analysis of variance. Forty-one participants were included in the analysis. Compared with FES alone, VR-FES produced a substantial increase in Fugl-Meyer Assessment-distal score (P=.011) and marginal improvement in Jebsen-Taylor Hand Function Test-gross score (P=.057). VR-FES produced greater, although nonsignificant, improvements in all other outcome measures, except in the Stroke Impact Scale-activities of daily living/instrumental activities of daily living score. FES with VR-based rehabilitation may be more effective than cyclic FES in improving distal upper extremity gross motor performance poststroke. Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

DAMBE7: New and Improved Tools for Data Analysis in Molecular Biology and Evolution.

Science.gov (United States)

Xia, Xuhua

2018-06-01

DAMBE is a comprehensive software package for genomic and phylogenetic data analysis on Windows, Linux, and Macintosh computers. New functions include imputing missing distances and phylogeny simultaneously (paving the way to build large phage and transposon trees), new bootstrapping/jackknifing methods for PhyPA (phylogenetics from pairwise alignments), and an improved function for fast and accurate estimation of the shape parameter of the gamma distribution for fitting rate heterogeneity over sites. Previous method corrects multiple hits for each site independently. DAMBE's new method uses all sites simultaneously for correction. DAMBE, featuring a user-friendly graphic interface, is freely available from http://dambe.bio.uottawa.ca (last accessed, April 17, 2018).

Application of Taguchi methodology to improve the functional quality of a mechanical device

International Nuclear Information System (INIS)

Regeai, Awatef Omar

2005-01-01

Manufacturing and quality control are recognized branches of engineering management. special attention has been made to improve thr tools and methods for the purpose of improving the products quality and finding solutions for any Obstacles and/or problems during the production process. Taguchi methodology is one of the most powerful techniques for improving product and manufacturing process quality at low cost. It is a strategical and practical method that aims to assist managers and industrial engineers to tackle manufacturing quality problems in a systematic and structured manner. The potential benefit of Taguchi methodology lies in its ease of use, its emphasis on reducing variability to give more economical products and hence the accessibility to the engineering fraternity for solving real life quality problems. This study applies Taguchi methodology to improve the functional quality of a local made chain gear by a purposed heat treatment process. The hardness of steel is generally a function not of its composition only, but rather of its heat treatment. The study investigates the effects of various heat treatment parameters, including ramp rate of heating, normalizing holding time, normalizing temperature, annealing holding time, annealing temperature, hardening holding time, hardening temperature, quenching media, tempering temperature and tempering holding time upon the hardness, which is a measure of resistance to plastic deformation. Both the analysis of means (ANOM) and Signal to Noise ratio (S/N) have been carried out for determining the optimal condition of the process. A significant improvement of the functional quality characteristic (hardness) by more than 32% was obtained. The Scanning Electron Microscopy technique was used in this study to obtain visual evidence of the quality and continuous improvement of the heat treated samples. (author)

Short term (14 days) consumption of insoluble wheat bran fibre-containing breakfast cereals improves subjective digestive feelings, general wellbeing and bowel function in a dose dependent manner.

Science.gov (United States)

Lawton, Clare L; Walton, Jenny; Hoyland, Alexa; Howarth, Elaine; Allan, Peter; Chesters, David; Dye, Louise

2013-04-22

This study investigated whether increasing insoluble (predominantly wheat bran) fibre over 14 days improves subjective digestive feelings, general wellbeing and bowel function. A single centre, multi-site, open, within subjects design with a 14 day non-intervention (baseline) monitoring period followed by a 14 day fibre consumption (intervention) period was performed. 153 low fibre consumers (breakfast cereal containing at least 5.4 g fibre (3.5 g from wheat bran) for 14 days and completed a daily symptom diary. Significant improvements were demonstrated in subjective perception of bowel function (e.g., ease of defecation) and digestive feelings (bloating, constipation, feeling sluggish and digestive discomfort). Significant improvements were also found in subjective perception of general wellbeing (feeling less fat, more mentally alert, slim, happy and energetic whilst experiencing less stress, mental and physical tiredness, difficulty concentrating and fewer headaches). In general, improvements in study outcomes increased with increasing cereal/fibre consumption. However, consuming an additional minimum 5.4 g of fibre (3.5 g wheat bran) per day was shown to deliver measurable and significant benefits for digestive health, comfort and wellbeing. Encouraging consumption of relatively small amounts of wheat bran could also provide an effective method of increasing overall fibre consumption.

Theoretical and Experimental Studies of Functionalized Carbon Nanotubes for Improved Thermal Conductivity

Science.gov (United States)

Kerr, Alexander; Burt, Timothy; Mullen, Kieran; Glatzhofer, Daniel; Houck, Matthew; Huang, Paul

The use of carbon nanotubes (CNTs) to improve the thermal conductivity of composite materials is thwarted by their large thermal boundary resistance. We study how to overcome this Kapitza resistance by functionalizing CNTs with mixed molecular chains. Certain configurations of chains improve the transmission of thermal vibrations through our systems by decreasing phonon mismatch between the CNTs and their surrounding matrix. Through the calculation of vibrational normal modes and Green's functions, we develop a variety of computational metrics to compare the thermal conductivity (κ) of our systems. We show how different configurations of attached chains affect the samples' κ values by varying chain identity, chain length, number of chains, and heat driver behavior. We vary the parameters to maximize κ. To validate and optimize these metrics, we perform molecular dynamics simulations for comparison. We also present experimental results of composites enhanced with CNTs and make comparisons to the theory. We observe that some composites are thermally improved with the inclusion of CNTs, while others are scarcely changed, in agreement with theoretical models. This work was supported by NSF Grant DMR-1310407.

Dynamic Sensor Management Algorithm Based on Improved Efficacy Function

Directory of Open Access Journals (Sweden)

TANG Shujuan

2016-01-01

Full Text Available A dynamic sensor management algorithm based on improved efficacy function is proposed to solve the multi-target and multi-sensory management problem. The tracking task precision requirements (TPR, target priority and sensor use cost were considered to establish the efficacy function by weighted sum the normalized value of the three factors. The dynamic sensor management algorithm was accomplished through control the diversities of the desired covariance matrix (DCM and the filtering covariance matrix (FCM. The DCM was preassigned in terms of TPR and the FCM was obtained by the centralized sequential Kalman filtering algorithm. The simulation results prove that the proposed method could meet the requirements of desired tracking precision and adjust sensor selection according to target priority and cost of sensor source usage. This makes sensor management scheme more reasonable and effective.

Active robotic training improves locomotor function in a stroke survivor

Directory of Open Access Journals (Sweden)

Krishnan Chandramouli

2012-08-01

Full Text Available Abstract Background Clinical outcomes after robotic training are often not superior to conventional therapy. One key factor responsible for this is the use of control strategies that provide substantial guidance. This strategy not only leads to a reduction in volitional physical effort, but also interferes with motor relearning. Methods We tested the feasibility of a novel training approach (active robotic training using a powered gait orthosis (Lokomat in mitigating post-stroke gait impairments of a 52-year-old male stroke survivor. This gait training paradigm combined patient-cooperative robot-aided walking with a target-tracking task. The training lasted for 4-weeks (12 visits, 3 × per week. The subject’s neuromotor performance and recovery were evaluated using biomechanical, neuromuscular and clinical measures recorded at various time-points (pre-training, post-training, and 6-weeks after training. Results Active robotic training resulted in considerable increase in target-tracking accuracy and reduction in the kinematic variability of ankle trajectory during robot-aided treadmill walking. These improvements also transferred to overground walking as characterized by larger propulsive forces and more symmetric ground reaction forces (GRFs. Training also resulted in improvements in muscle coordination, which resembled patterns observed in healthy controls. These changes were accompanied by a reduction in motor cortical excitability (MCE of the vastus medialis, medial hamstrings, and gluteus medius muscles during treadmill walking. Importantly, active robotic training resulted in substantial improvements in several standard clinical and functional parameters. These improvements persisted during the follow-up evaluation at 6 weeks. Conclusions The results indicate that active robotic training appears to be a promising way of facilitating gait and physical function in moderately impaired stroke survivors.

Promoter proximal polyadenylation sites reduce transcription activity

DEFF Research Database (Denmark)

Andersen, Pia Kjølhede; Lykke-Andersen, Søren; Jensen, Torben Heick

2012-01-01

Gene expression relies on the functional communication between mRNA processing and transcription. We previously described the negative impact of a point-mutated splice donor (SD) site on transcription. Here we demonstrate that this mutation activates an upstream cryptic polyadenylation (CpA) site......, which in turn causes reduced transcription. Functional depletion of U1 snRNP in the context of the wild-type SD triggers the same CpA event accompanied by decreased RNA levels. Thus, in accordance with recent findings, U1 snRNP can shield premature pA sites. The negative impact of unshielded pA sites...... on transcription requires promoter proximity, as demonstrated using artificial constructs and supported by a genome-wide data set. Importantly, transcription down-regulation can be recapitulated in a gene context devoid of splice sites by placing a functional bona fide pA site/transcription terminator within ∼500...

IBRD AND ITS INVOLVEMENT IN MODERNISING AND IMPROVING THE FUNCTIONALITY OF PENSION SYSTEMS

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Cristina Rosu

2014-12-01

Full Text Available In our research we review the International Bank for Reconstruction and Development’s (IBRD most important contributions to the functionality of the pension systems around the world. The pension systems design constitutes an important premise for the adequate functioning of these systems. In international practice, there is a wide variety of principles and mechanisms which can constitute the foundation of pension systems, the most common being materialized in the multi-pillar pension system, promoted by the IBRD. Its involvement in modernizing and improving the functionality of pension systems has reached also many other aspects such as evaluation of the national pension systems’ performance, financial assistance to governments with the aim of meeting the objectives corresponding to pension systems, scientific, technical and informational support. We conclude that IBRD’s involvement in modernizing and improving the functionality of pension systems has determined a significant transformation of the national pension systems, especially in Latin America and Eastern and Central Europe. However, its well-known multi-pillar model is not free of criticism as a result of the various analytical errors.

Improved laboratory resource utilization and patient care with the use of rapid on-site evaluation for endobronchial ultrasound fine-needle aspiration biopsy.

Science.gov (United States)

Collins, Brian T; Chen, Alexander C; Wang, Jeff F; Bernadt, Cory T; Sanati, Souzan

2013-10-01

Endobronchial ultrasound guided (EBUS) fine-needle aspiration (FNA) biopsy has become widely used to evaluate patients with thoracic abnormalities. Rapid on-site evaluation (ROSE) can provide the bronchoscopist with immediate evaluation findings during the procedure. This study examines EBUS FNA biopsy procedures with and without ROSE, and investigates the impact of ROSE service on the EBUS procedure and laboratory resource utilization. The cytopathology database at Washington University Medical Center, St. Louis, Missouri, was searched for EBUS FNA biopsy cases before and after introduction of ROSE service, and a matched cohort was collected. Reports were reviewed and pertinent data was collected, such as sites biopsied, ROSE performance, slide smears, cell blocks, and diagnostic categories. Statistical analysis of the results was performed. A matched case-controlled EBUS FNA cohort of 340 patients (680 total) for each category of non-ROSE and ROSE service were identified. There was a 33% reduction in the number of sites biopsied with ROSE. A total of 68% of patients with ROSE had just one biopsy site compared to only 36% of non-ROSE patients. There was a 30% decrease in total slides (mean, 5.27 slides) after the introduction of ROSE. All of these improvements were statistically significant. EBUS FNA biopsy ROSE service benefits patients by contributing to significantly fewer biopsies and improved utilization of health care resources. ROSE service results in substantially fewer total slides, which has a significant impact on the cytopathology laboratory work effort. The use of ROSE for EBUS FNA biopsy provides significant improvements in patient care and laboratory resource utilization. © 2013 American Cancer Society.

Activity-Based Probes for Isoenzyme- and Site-Specific Functional Characterization of Glutathione S -Transferases

Energy Technology Data Exchange (ETDEWEB)

Stoddard, Ethan G. [Chemical Biology and Exposure; Killinger, Bryan J. [Chemical Biology and Exposure; Nair, Reji N. [Chemical Biology and Exposure; Sadler, Natalie C. [Chemical Biology and Exposure; Volk, Regan F. [Chemical Biology and Exposure; Purvine, Samuel O. [Chemical Biology and Exposure; Shukla, Anil K. [Chemical Biology and Exposure; Smith, Jordan N. [Chemical Biology and Exposure; Wright, Aaron T. [Chemical Biology and Exposure

2017-11-01

Glutathione S-transferases (GSTs) comprise a highly diverse family of phase II drug metabolizing enzymes whose shared function is the conjugation of reduced glutathione to various endo- and xenobiotics. Although the conglomerate activity of these enzymes can be measured by colorimetric assays, measurement of the individual contribution from specific isoforms and their contribution to the detoxification of xenobiotics in complex biological samples has not been possible. For this reason, we have developed two activity-based probes that characterize active glutathione transferases in mammalian tissues. The GST active site is comprised of a glutathione binding “G site” and a distinct substrate binding “H site”. Therefore, we developed (1) a glutathione-based photoaffinity probe (GSH-ABP) to target the “G site”, and (2) a probe designed to mimic a substrate molecule and show “H site” activity (GST-ABP). The GSH-ABP features a photoreactive moiety for UV-induced covalent binding to GSTs and glutathione-binding enzymes. The GST-ABP is a derivative of a known mechanism-based GST inhibitor that binds within the active site and inhibits GST activity. Validation of probe targets and “G” and “H” site specificity was carried out using a series of competitors in liver homogenates. Herein, we present robust tools for the novel characterization of enzyme- and active site-specific GST activity in mammalian model systems.

Conversion of agonist site to metal-ion chelator site in the beta(2)-adrenergic receptor

DEFF Research Database (Denmark)

Elling, C E; Thirstrup, K; Holst, Birgitte

1999-01-01

Previously metal-ion sites have been used as structural and functional probes in seven transmembrane receptors (7TM), but as yet all the engineered sites have been inactivating. Based on presumed agonist interaction points in transmembrane III (TM-III) and -VII of the beta(2)-adrenergic receptor,...... as generic, pharmacologic tools to switch 7TM receptors with engineered metal-ion sites on or off at will.......Previously metal-ion sites have been used as structural and functional probes in seven transmembrane receptors (7TM), but as yet all the engineered sites have been inactivating. Based on presumed agonist interaction points in transmembrane III (TM-III) and -VII of the beta(2)-adrenergic receptor......, in this paper we construct an activating metal-ion site between the amine-binding Asp-113 in TM-III-or a His residue introduced at this position-and a Cys residue substituted for Asn-312 in TM-VII. No increase in constitutive activity was observed in the mutant receptors. Signal transduction was activated...

Assessment of candidate sites for disposal of treated effluents at the Hanford Site, Washington

International Nuclear Information System (INIS)

Davis, J.D.

1992-01-01

A rigidly defined evaluation process was used to recommend a preferred location to dispose of treated effluents from facilities in the 200 Areas of the US Department of Energy's Hanford Site in Washington State. First, siting constraints were defined based on functional design considerations and siting guidelines. Then, criteria for selecting a preferred site from among several candidates were identified and their relative importance defined. Finally, the weighted criteria were applied and a site was selected for detailed characterization by subsurface investigations

Site scientific mission plan for the southern Great Plains CART site, January--June 1998

Energy Technology Data Exchange (ETDEWEB)

Peppler, R.A.; Lamb, P.J. [Univ. of Oklahoma, Norman, OK (United States). Cooperative Inst. for Mesoscale Meteorological Studies; Sisterson, D.L. [Argonne National Lab., IL (United States). Environmental Research Div.

1998-01-01

The Southern Great Plains (SGP) Cloud and Radiation Testbed (CART) site is designed to help satisfy the data needs of the Atmospheric Radiation Measurement (ARM) Program Science Team. The primary purpose of this site scientific mission plan is to provide guidance for the development of plans for site operations. It also provides information on current plans to the ARM functional teams (Management Team, Data and Science Integration Team, Operations Team, and Instrument Team) and serves to disseminate the plans more generally within the ARM Program and among the members of the Science Team. This document includes a description of the operational status of the site and the primary site activities envisioned, together with information concerning approved and proposed intensive observation periods (IOPs). The primary users of this document are the Site operator, the Site Scientist Team (SST), the Science Team through the ARM Program science director, the ARM Program Experiment Center, and the aforementioned ARM Program functional teams. This plan is a living document that is updated and reissued every six months as the observational facilities are developed, tested, and augmented and as priorities are adjusted in response to developments in scientific planning and understanding.

Dodecylamine functionalization of carbon nanotubes to improve dispersion, thermal and mechanical properties of polyethylene based nanocomposites

Science.gov (United States)

Ferreira, F. V.; Franceschi, W.; Menezes, B. R. C.; Brito, F. S.; Lozano, K.; Coutinho, A. R.; Cividanes, L. S.; Thim, G. P.

2017-07-01

This study presents the effect of dodecylamine (DDA) functionalization of carbon nanotubes (CNTs) on the thermo-physical and mechanical properties of high-density polyethylene (HDPE) based composites. Here, we showed that the functionalization with DDA improved the dispersion of the CNTs as well as the interfacial adhesion with the HDPE matrix via non-covalent interactions. The better dispersion and interaction of CNT in the HDPE matrix as a function of the surface chemistry was correlated with the improved thermo-physical and mechanical properties.

Transplantation of motoneurons derived from MASH1-transfected mouse ES cells reconstitutes neural networks and improves motor function in hemiplegic mice.

Science.gov (United States)

Ikeda, Ritsuko; Kurokawa, Manae S; Chiba, Shunmei; Yoshikawa, Hideshi; Hashimoto, Takuo; Tadokoro, Mamoru; Suzuki, Noboru

2004-10-01

Mouse embryonic stem (ES) cells were transfected with a MASH1 expression vector and G418-resistant cells were selected. The MASH1-transfected cells became neuron-like appearance and expressed betaIIItubulin and panNCAM. Glial fibrillary acidic protein (GFAP) and galactocerebroside (GalC)-expressing cells were rarely detected. Half of the neural cells differentiated into the Islet1+ motoneuron lineage. Thus, we obtained motoneuron lineage-enriched neuronal cells by transfection of ES cells with MASH1. A hemiplegic model of mice was developed by cryogenic injury of the motor cortex, and motoneuron lineage-enriched neuronal cells were transplanted underneath the injured motor cortex neighboring the periventricular region. The motor function of the recipients was assessed by a beam walking and rotarod tests, whereby the results gradually improved, but little improvement was observed in vehicle injected control mice. We found that the grafted cells not only remained close to the implantation site, but also exhibited substantial migration, penetrating into the damaged lesion in a directed manner up to the cortical region. Grafted neuronal cells that had migrated into the cortex were elongated axon-positive for neurofilament middle chain (NFM). Synaptophysin immunostaining showed a positive staining pattern around the graft, suggesting that the transplanted neurons interacted with the recipient neurons to form a neural network. Our study suggests that the motoneuron lineage can be induced from ES cells, and grafted cells adapt to the host environment and can reconstitute a neural network to improve motor function of a paralyzed limb.

Interdisciplinary treatment of an adult patient with old extraction sites.

Science.gov (United States)

Taner, Tülin Ugur; Germec, Derya; Er, Nuray; Tulunoglu, Ibrahim

2006-11-01

This case report describes the interdisciplinary treatment of a 31-year-old female patient showing a protrusive profile, maxillary constriction, mandibular crowding, a Class III canine relationship complicated with multiple missing teeth, old atrophic extraction sites, and periodontal defects. The lower dental arch irregularity was eliminated by air-rotor stripping (ARS). The upper extraction site was opened for prosthetic rehabilitation, whereas closure of the lower extraction space was preferred. The narrow alveolar crest of the atrophic bone was augmented with the use of autogenous bone, beta-tricalcium phosphate (Cerasorb), and autogenous platelet-rich plasma. A functional and esthetic occlusion in an improved facial profile was established at the end of orthodontic treatment combined with ARS technique, surgery, and prosthodontics.

The N-terminal tropomyosin- and actin-binding sites are important for leiomodin 2's function.

Science.gov (United States)

Ly, Thu; Moroz, Natalia; Pappas, Christopher T; Novak, Stefanie M; Tolkatchev, Dmitri; Wooldridge, Dayton; Mayfield, Rachel M; Helms, Gregory; Gregorio, Carol C; Kostyukova, Alla S

2016-08-15

Leiomodin is a potent actin nucleator related to tropomodulin, a capping protein localized at the pointed end of the thin filaments. Mutations in leiomodin-3 are associated with lethal nemaline myopathy in humans, and leiomodin-2-knockout mice present with dilated cardiomyopathy. The arrangement of the N-terminal actin- and tropomyosin-binding sites in leiomodin is contradictory and functionally not well understood. Using one-dimensional nuclear magnetic resonance and the pointed-end actin polymerization assay, we find that leiomodin-2, a major cardiac isoform, has an N-terminal actin-binding site located within residues 43-90. Moreover, for the first time, we obtain evidence that there are additional interactions with actin within residues 124-201. Here we establish that leiomodin interacts with only one tropomyosin molecule, and this is the only site of interaction between leiomodin and tropomyosin. Introduction of mutations in both actin- and tropomyosin-binding sites of leiomodin affected its localization at the pointed ends of the thin filaments in cardiomyocytes. On the basis of our new findings, we propose a model in which leiomodin regulates actin poly-merization dynamics in myocytes by acting as a leaky cap at thin filament pointed ends. © 2016 Ly, Moroz, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

The application of passive sampler (DGT technology for improved understanding of metal behaviour at a marine disposal site

Directory of Open Access Journals (Sweden)

Parker R.

2013-04-01

Full Text Available Metal behaviour and availability at a contaminated dredge material disposal site within UK waters has been investigated using Diffusive Gradient in Thin films (DGT passive sampling technology. Three stations representing contrasting history and presence of maintenance dredge disposal, including a control station outside the disposal site, have been studied and depth profiles of fluxes of different metals (Fe, Mn, Pb, Cu, Cd, Cr, Ni, Zn to the binding gel (Chelex 100 have been derived. Higher flux rates and shallower mobilisation of metals (Mn and Fe to the binding gel were observed at the disposal stations compared to the control station. Here we describe metal mobilization at different depths, linking the remobilization of Fe2+ and Mn2+ to the sediment (resupply of other heavy metals of interest with a focus on Cd, Ni and Pb and as they are on the Water Framework Directive (WFD list of priority substances and OSPAR list of priority pollutants. Results showed that Cd, Pb and Ni exhibited signs of resupply at the sediment-water interface (SWI. There was a potential increased mobilisation and source to the water column of Pb and Ni at the disposal site stations, but there was no Cd source, despite higher total loadings. This information has the potential to improve our current understanding of metal cycles at disposal sites. This work can be used as an indication of likely metal bioavailability and also assist in determining whether the sites act as sources or sinks of heavy metals. This information could assist disposal site monitoring and dredge material licensing.

Repeated sessions of noninvasive brain DC stimulation is associated with motor function improvement in stroke patients.

Science.gov (United States)

Boggio, Paulo S; Nunes, Alice; Rigonatti, Sergio P; Nitsche, Michael A; Pascual-Leone, Alvaro; Fregni, Felipe

2007-01-01

Recent evidence has suggested that a simple technique of noninvasive brain stimulation - transcranial direct current stimulation (tDCS) - is associated with a significant motor function improvement in stroke patients. We tested the motor performance improvement in stroke patients following 4 weekly sessions of sham, anodal- and cathodal tDCS (experiment 1) and the effects of 5 consecutive daily sessions of cathodal tDCS (experiment 2). A blinded rater evaluated motor function using the Jebsen-Taylor Hand Function Test. There was a significant main effect of stimulation condition (p=0.009) in experiment 1. Furthermore there was a significant motor function improvement after either cathodal tDCS of the unaffected hemisphere (p=0.016) or anodal tDCS of the affected hemisphere (p=0.046) when compared to sham tDCS. There was no cumulative effect associated with weekly sessions of tDCS, however consecutive daily sessions of tDCS (experiment 2) were associated with a significant effect on time (pmotor function improvement in stroke patients; and support that consecutive daily sessions of tDCS might increase its behavioral effects. Because the technique of tDCS is simple, safe and non-expensive; our findings support further research on the use of this technique for the rehabilitation of patients with stroke.

Hepatocyte nuclear factor 4A improves hepatic differentiation of immortalized adult human hepatocytes and improves liver function and survival.

Science.gov (United States)

Hang, Hua-Lian; Liu, Xin-Yu; Wang, Hai-Tian; Xu, Ning; Bian, Jian-Min; Zhang, Jian-Jun; Xia, Lei; Xia, Qiang

2017-11-15

Immortalized human hepatocytes (IHH) could provide an unlimited supply of hepatocytes, but insufficient differentiation and phenotypic instability restrict their clinical application. This study aimed to determine the role of hepatocyte nuclear factor 4A (HNF4A) in hepatic differentiation of IHH, and whether encapsulation of IHH overexpressing HNF4A could improve liver function and survival in rats with acute liver failure (ALF). Primary human hepatocytes were transduced with lentivirus-mediated catalytic subunit of human telomerase reverse transcriptase (hTERT) to establish IHH. Cells were analyzed for telomerase activity, proliferative capacity, hepatocyte markers, and tumorigenicity (c-myc) expression. Hepatocyte markers, hepatocellular functions, and morphology were studied in the HNF4A-overexpressing IHH. Hepatocyte markers and karyotype analysis were completed in the primary hepatocytes using shRNA knockdown of HNF4A. Nuclear translocation of β-catenin was assessed. Rat models of ALF were treated with encapsulated IHH or HNF4A-overexpressing IHH. A HNF4A-positive IHH line was established, which was non-tumorigenic and conserved properties of primary hepatocytes. HNF4A overexpression significantly enhanced mRNA levels of genes related to hepatic differentiation in IHH. Urea levels were increased by the overexpression of HNF4A, as measured 24h after ammonium chloride addition, similar to that of primary hepatocytes. Chromosomal abnormalities were observed in primary hepatocytes transfected with HNF4A shRNA. HNF4α overexpression could significantly promote β-catenin activation. Transplantation of HNF4A overexpressing IHH resulted in better liver function and survival of rats with ALF compared with IHH. HNF4A improved hepatic differentiation of IHH. Transplantation of HNF4A-overexpressing IHH could improve the liver function and survival in a rat model of ALF. Copyright © 2017 Elsevier Inc. All rights reserved.

On Improving Reliability of SRAM-Based Physically Unclonable Functions

Directory of Open Access Journals (Sweden)

Arunkumar Vijayakumar

2017-01-01

Full Text Available Physically unclonable functions (PUFs have been touted for their inherent resistance to invasive attacks and low cost in providing a hardware root of trust for various security applications. SRAM PUFs in particular are popular in industry for key/ID generation. Due to intrinsic process variations, SRAM cells, ideally, tend to have the same start-up behavior. SRAM PUFs exploit this start-up behavior. Unfortunately, not all SRAM cells exhibit reliable start-up behavior due to noise susceptibility. Hence, design enhancements are needed for improving reliability. Some of the proposed enhancements in literature include fuzzy extraction, error-correcting codes and voting mechanisms. All enhancements involve a trade-off between area/power/performance overhead and PUF reliability. This paper presents a design enhancement technique for reliability that improves upon previous solutions. We present simulation results to quantify improvement in SRAM PUF reliability and efficiency. The proposed technique is shown to generate a 128-bit key in ≤0.2 μ s at an area estimate of 4538 μ m 2 with error rate as low as 10 − 6 for intrinsic error probability of 15%.

Improving Assessment of Work Related Mental Health Function Using the Work Disability Functional Assessment Battery (WD-FAB).

Science.gov (United States)

Marfeo, Elizabeth E; Ni, Pengsheng; McDonough, Christine; Peterik, Kara; Marino, Molly; Meterko, Mark; Rasch, Elizabeth K; Chan, Leighton; Brandt, Diane; Jette, Alan M

2018-03-01

Purpose To improve the mental health component of the Work Disability Functional Assessment Battery (WD-FAB), developed for the US Social Security Administration's (SSA) disability determination process. Specifically our goal was to expand the WD-FAB scales of mood & emotions, resilience, social interactions, and behavioral control to improve the depth and breadth of the current scales and expand the content coverage to include aspects of cognition & communication function. Methods Data were collected from a random, stratified sample of 1695 claimants applying for the SSA work disability benefits, and a general population sample of 2025 working age adults. 169 new items were developed to replenish the WD-FAB scales and analyzed using factor analysis and item response theory (IRT) analysis to construct unidimensional scales. We conducted computer adaptive test (CAT) simulations to examine the psychometric properties of the WD-FAB. Results Analyses supported the inclusion of four mental health subdomains: Cognition & Communication (68 items), Self-Regulation (34 items), Resilience & Sociability (29 items) and Mood & Emotions (34 items). All scales yielded acceptable psychometric properties. Conclusions IRT methods were effective in expanding the WD-FAB to assess mental health function. The WD-FAB has the potential to enhance work disability assessment both within the context of the SSA disability programs as well as other clinical and vocational rehabilitation settings.

Effect of neurofeedback and electromyographic-biofeedback therapy on improving hand function in stroke patients.

Science.gov (United States)

Rayegani, S M; Raeissadat, S A; Sedighipour, L; Rezazadeh, I Mohammad; Bahrami, M H; Eliaspour, D; Khosrawi, S

2014-01-01

The aim of the present study was to evaluate the effect of applying electroencephalogram (EEG) biofeedback (neurobiofeedback) or electromyographic (EMG) biofeedback to conventional occupational therapy (OT) on improving hand function in stroke patients. This study was designed as a preliminary clinical trial. Thirty patients with stroke were entered the study. Hand function was evaluated by Jebsen Hand Function Test pre and post intervention. Patients were allocated to 3 intervention cohorts: (1) OT, (2) OT plus EMG-biofeedback therapy, and (3) OT plus neurofeedback therapy. All patients received 10 sessions of conventional OT. Patients in cohorts 2 and 3 also received EMG-biofeedback and neurofeedback therapy, respectively. EMG-biofeedback therapy was performed to strengthen the abductor pollicis brevis (APB) muscle. Neurofeedback training was aimed at enhancing sensorimotor rhythm after mental motor imagery. Hand function was improved significantly in the 3 groups. The spectral power density of the sensorimotor rhythm band in the neurofeedback group increased after mental motor imagery. Maximum and mean contraction values of electrical activities of the APB muscle during voluntary contraction increased significantly after EMG-biofeedback training. Patients in the neurofeedback and EMG-biofeedback groups showed hand improvement similar to conventional OT. Further studies are suggested to assign the best protocol for neurofeedback and EMG-biofeedback therapy.

Field demonstration of improved shallow land burial practices for low-level radioactive solid wastes: preliminary site characterization and progress report

International Nuclear Information System (INIS)

Vaughan, N.D.; Haase, C.S.; Huff, D.D.; Lee, S.Y.; Walls, E.C.

1982-12-01

A 5-year field demonstration (ETF) of improved shallow land burial practices for low-level radioactive solid wastes in a humid environment evaluates the use of a trench liner and grout as alternate trench treatments for improving shallow land burial site performance in the humid East. The ETF is located within the Copper Creek thrust block of the Valley and Ridge Province of east Tennessee and is underlain by strata of the Middle to Late Cambrian Conasauga Group. The Maryville Limestone formation, which is composed of ribbon-bedded and interclastic limestones and dark grey shales and mudstones, comprises the bedrock immediately beneath the site. The bedrock and residuum structure are characterized by anticlinal folds with numerous joints and fractures, some of which are filled with calcite. Seismic and electrical resistivity geophysical methods were useful in characterizing the thickness of residuum and presence of structural features. Soils are illitic and range from podzolic to lithosols to alluvial in the vicinity of the ETF, but the original soil solum was removed in 1975 when the mixed hardwood forest was cleared and the site was planted in grasses. The remaining residuum consists of acidic soil aggregate and extensively weathered siltstone and sandstone which exhibit the original rock structure. Mean annual precipitation at the site is 1500 mm, although during the initial study period (10-1-80 to 9-30-81) the annual total was 939 mm. Runoff was estimated to be about 50% of the precipitation total, based on observations at two Parshall flumes installed at the site. Storm runoff is quite responsive to rainfall, and the lag time between peak rainfall and runoff is less than 15 min during winter storms. Tracer studies of the ground-water system, suggest that ground-water flow has two distinct components, one associated with fracture flow and the other with intergranular flow

Prediction of glycosylation sites using random forests

Directory of Open Access Journals (Sweden)

Hirst Jonathan D

2008-11-01

Full Text Available Abstract Background Post translational modifications (PTMs occur in the vast majority of proteins and are essential for function. Prediction of the sequence location of PTMs enhances the functional characterisation of proteins. Glycosylation is one type of PTM, and is implicated in protein folding, transport and function. Results We use the random forest algorithm and pairwise patterns to predict glycosylation sites. We identify pairwise patterns surrounding glycosylation sites and use an odds ratio to weight their propensity of association with modified residues. Our prediction program, GPP (glycosylation prediction program, predicts glycosylation sites with an accuracy of 90.8% for Ser sites, 92.0% for Thr sites and 92.8% for Asn sites. This is significantly better than current glycosylation predictors. We use the trepan algorithm to extract a set of comprehensible rules from GPP, which provide biological insight into all three major glycosylation types. Conclusion We have created an accurate predictor of glycosylation sites and used this to extract comprehensible rules about the glycosylation process. GPP is available online at http://comp.chem.nottingham.ac.uk/glyco/.

PASSPORT-seq: A Novel High-Throughput Bioassay to Functionally Test Polymorphisms in Micro-RNA Target Sites

Directory of Open Access Journals (Sweden)

Joseph Ipe

2018-06-01

Full Text Available Next-generation sequencing (NGS studies have identified large numbers of genetic variants that are predicted to alter miRNA–mRNA interactions. We developed a novel high-throughput bioassay, PASSPORT-seq, that can functionally test in parallel 100s of these variants in miRNA binding sites (mirSNPs. The results are highly reproducible across both technical and biological replicates. The utility of the bioassay was demonstrated by testing 100 mirSNPs in HEK293, HepG2, and HeLa cells. The results of several of the variants were validated in all three cell lines using traditional individual luciferase assays. Fifty-five mirSNPs were functional in at least one of three cell lines (FDR ≤ 0.05; 11, 36, and 27 of them were functional in HEK293, HepG2, and HeLa cells, respectively. Only four of the variants were functional in all three cell lines, which demonstrates the cell-type specific effects of mirSNPs and the importance of testing the mirSNPs in multiple cell lines. Using PASSPORT-seq, we functionally tested 111 variants in the 3′ UTR of 17 pharmacogenes that are predicted to alter miRNA regulation. Thirty-three of the variants tested were functional in at least one cell line.

Site scientific mission plan for the Southern Great Plains CART Site, January--June 1999

Energy Technology Data Exchange (ETDEWEB)

Peppler, R.A.; Sisterson, D.L.; Lamb, P.

1999-03-10

The Southern Great Plains (SGP) Cloud and Radiation Testbed (CART) site was designed to help satisfy the data needs of the Atmospheric Radiation Measurement (ARM) Program Science Team. This Site Scientific Mission Plan defines the scientific priorities for site activities during the six months beginning on January 1, 1999, and looks forward in lesser detail to subsequent six-month periods. The primary purpose of this document is to provide scientific guidance for the development of plans for site operations. It also provides information on current plans to the ARM functional teams (Management Team, Data and Science Integration Team [DSIT], Operations Team, and Instrument Team [IT]) and serves to disseminate the plans more generally within the ARM Program and among the members of the Science Team. This document includes a description of the operational status of the site and the primary site activities envisioned, together with information concerning approved and proposed intensive observation periods (IOPs). The primary users of this document are the site operator, the site program manager, the Site Scientist Team (SST), the Science Team through the ARM Program science director, the ARM Program Experiment Center, and the aforementioned ARM Program functional teams. This plan is a living document that is updated and reissued every six months as the observational facilities are developed, tested, and augmented and as priorities are adjusted in response to developments in scientific planning and understanding.

Site scientific mission plan for the Southern Great Plains CART site: July--December 1998

Energy Technology Data Exchange (ETDEWEB)

Peppler, R.A.; Lamb, P. [Univ. of Oklahoma, Norman, OK (United States). Cooperative Inst. for Mesoscale Meteorological Studies; Sisterson, D.L. [Argonne National Lab., IL (United States). Environmental Research Div.

1998-07-01

The Southern Great Plains (SGP) Cloud and Radiation Testbed (CART) site was designed to help satisfy the data needs of the Atmospheric Radiation Measurement (ARM) Program Science Team. This Site Scientific Mission Plan defines the scientific priorities for site activities during the six months beginning on July 1, 1998, and looks forward in lesser detail to subsequent six-month periods. The primary purpose of this document is to provide scientific guidance for the development of plans for site operations. It also provides information on current plans to the ARM functional teams (Management Team, Data and Science Integration Team [DSIT], Operations Team, and Instrument Team [IT]) and serves to disseminate the plans more generally within the ARM Program and among the members of the Science Team. This document includes a description of the operational status of the site and the primary site activities envisioned, together with information concerning approved and proposed intensive observation periods (IOPs). The primary users of this document are the site operator, the site program manager, the Site Scientist Team (SST), the Science Team through the ARM Program science director, the ARM program Experiment Center, and the aforementioned ARM Program functional teams. This plan is a living document that is updated and reissued every six months as the observational facilities are developed, tested, and augmented and as priorities are adjusted in response to developments in scientific planning and understanding.

Family history of Alzheimer’s disease limits improvement in cognitive function after bariatric surgery

Directory of Open Access Journals (Sweden)

Michael L Alosco

2014-06-01

Full Text Available Background/Objective: Bariatric surgery can reverse cognitive impairments associated with obesity. However, such benefits may be attenuated in individuals with a predisposing risk for cognitive impairment such as family history of Alzheimer’s disease. Methods: In all, 94 bariatric surgery participants completed a computerized cognitive test battery before and 12 weeks after surgery. Family history of Alzheimer’s disease was obtained through self-report. Results: In the overall sample, cognitive function improved in memory and attention/executive function 12 weeks post-surgery. Repeated measures showed similar rates of improvements in attention/executive function between patients with and without a family history of Alzheimer’s disease. In contrast, only individuals without a family history of Alzheimer’s disease exhibited post-operative improvements in memory. A family history of Alzheimer’s disease was associated with greater post-surgery rates of cognitive impairment. Conclusions: Family history of Alzheimer’s disease may limit post-surgery cognitive benefits. Future studies should examine whether weight loss can modify the course of cognitive decline in patients at-risk for Alzheimer’s disease.

Review of functional markers for improving cooking, eating, and the nutritional qualities of rice

Science.gov (United States)

Lau, Wendy C. P.; Rafii, Mohd Y.; Ismail, Mohd R.; Puteh, Adam; Latif, Mohammad A.; Ramli, Asfaliza

2015-01-01

After yield, quality is one of the most important aspects of rice breeding. Preference for rice quality varies among cultures and regions; therefore, rice breeders have to tailor the quality according to the preferences of local consumers. Rice quality assessment requires routine chemical analysis procedures. The advancement of molecular marker technology has revolutionized the strategy in breeding programs. The availability of rice genome sequences and the use of forward and reverse genetics approaches facilitate gene discovery and the deciphering of gene functions. A well-characterized gene is the basis for the development of functional markers, which play an important role in plant genotyping and, in particular, marker-assisted breeding. In addition, functional markers offer advantages that counteract the limitations of random DNA markers. Some functional markers have been applied in marker-assisted breeding programs and have successfully improved rice quality to meet local consumers’ preferences. Although functional markers offer a plethora of advantages over random genetic markers, the development and application of functional markers should be conducted with care. The decreasing cost of sequencing will enable more functional markers for rice quality improvement to be developed, and application of these markers in rice quality breeding programs is highly anticipated. PMID:26528304

Cardiac autonomic function in patients with diabetes improves with practice of comprehensive yogic breathing program

Directory of Open Access Journals (Sweden)

Viveka P Jyotsna

2013-01-01

Full Text Available Background: The aim of this study was to observe the effect comprehensive yogic breathing (Sudarshan Kriya Yoga [SKY] and Pranayam had on cardiac autonomic functions in patients with diabetes. Materials and Methods: This is a prospective randomized controlled intervention trial. Cardiac autonomic functions were assessed in 64 diabetics. Patients were randomized into two groups, one group receiving standard therapy for diabetes and the other group receiving standard therapy for diabetes and comprehensive yogic breathing program. Standard therapy included dietary advice, brisk walking for 45 min daily, and administration of oral antidiabetic drugs. Comprehensive yogic breathing program was introduced to the participants through a course of 12 h spread over 3 days. It was an interactive session in which SKY, a rhythmic cyclical breathing, preceded by Pranayam is taught under the guidance of a certified teacher. Cardiac autonomic function tests were done before and after 6 months of intervention. Results: In the intervention group, after practicing the breathing techniques for 6 months, the improvement in sympathetic functions was statistically significant (P 0.04. The change in sympathetic functions in the standard therapy group was not significant (P 0.75.Parasympathetic functions did not show any significant change in either group. When both parasympathetic and sympathetic cardiac autonomic functions were considered, there was a trend toward improvement in patients following comprehensive yogic breathing program (P 0.06. In the standard therapy group, no change in cardiac autonomic functions was noted (P 0.99. Conclusion: Cardiac autonomic functions improved in patients with diabetes on standard treatment who followed the comprehensive yogic breathing program compared to patients who were on standard therapy alone.

The Effectiveness of Transactional Analysis Group-counseling on the Improvement of Couples’ Family Functioning

Directory of Open Access Journals (Sweden)

Ghorban Ali Yahyaee

2015-06-01

Full Text Available Background & Aims of the Study: Family functioning is among the most important factors ensuring the mental health of family members. Disorder or disturbance in family functioning would cause many psychological problems for family members. Current study intended to examine the effectiveness of transactional analysis group counseling on the improvement of couple's family functioning. Materials & Methods: The design of the study is as semi experimental research with pretest and posttest with follow up and control group. Statistical population consists all couples referring to the psychological and counseling centers of Rasht city in 2012. Samples were selected at first by available sampling method and after completing family assessment  device, and obtaining score for enter to research, were placement using random sampling method in two experimental and control groups (N = 8 couples per group. The experimental group participated in 12 sessions of group counseling based on transactional analysis and control group received no intervention. The gathered data were analyzed using covariance analysis. Results: The results show that there are significant differences between the pre-test and post test scores of the experimental group. This difference is significant at the level of 0.05. Therefore it seems that transactional group therapy improved the dimensions of family functioning in couples. Conclusions: The results indicated that transactional analysis group counseling can improve the family functioning and use this approach to working with couples is recommended.

Improvement of the bio-functional properties of TiO{sub 2} nanotubes

Energy Technology Data Exchange (ETDEWEB)

Roguska, A. [Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw (Poland); Pisarek, M., E-mail: mpisarek@ichf.edu.pl [Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw (Poland); Belcarz, A. [Chair and Department of Biochemistry and Biotechnology, Medical University of Lublin, Chodźki 1, 20-093 Lublin (Poland); Marcon, L. [Interdisciplinary Research Institute, USR CNRS 3078 Parc de la Haute Borne, 50 av. de Halley 59658 Villeneuve d’Ascq (France); Holdynski, M. [Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw (Poland); Andrzejczuk, M. [Faculty of Materials Science and Engineering, Warsaw University of Technology, Wołoska 141, 02-507 Warsaw (Poland); Janik-Czachor, M. [Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw (Poland)

2016-12-01

Highlights: • The methods of biofunctional properties improvement of TiO{sub 2} nanotubes are proposed. • The increase of TiO{sub 2} nanotubes diameter promotes the U2OS cell proliferation. • Calcium phosphate coating deposited TiO{sub 2} nanotube layer promotes the cell growth. • Deposition of Ag nanoparticles inhibits the survivability of S. epidermidis cells. - Abstract: Titanium oxide nanotubes with diameters from ca. 40–120 nm fabricated by the anodic oxidation of Ti at a constant voltage (10–28 V) were investigated to identify factors improving their bio-functional properties. Prepared substrates were subsequently annealed at 450 °C and 650 °C to obtain nanotubes having a crystalline structure, and were then examined by SEM, XRD, XPS, BET and contact angle measurement techniques. The thermally stabilized surfaces were subjected to bidirectional functionalization: by deposition of a thin layer of Ca-P and by loading with silver nanoparticles. Three factors were found to promote the proliferation of osteoblast (U2OS) cells: a larger nanotube diameter, a higher annealing temperature, and the presence of a thin Ca-P layer. Differentiation of these cells (by ALP test) was stimulated by a higher (650 °C) nanotube annealing temperature, but not by a thin Ca-P layer. The TiO{sub 2} nanotubes-modified samples exhibited noticeable antibacterial properties. Moreover, the additional deposition of Ag nanoparticles almost completely inhibited the survivability of S. epidermidis cells beyond 3 h of contact. In conclusion, TiO{sub 2} nanotubes-modified surfaces exhibit distinct bone forming ability and significant antibacterial properties, and can be easily functionalized by a thin Ca-P layer or nano-Ag deposition for further improvement of the above functionalities.

CLIP-seq analysis of multi-mapped reads discovers novel functional RNA regulatory sites in the human transcriptome.

Science.gov (United States)

Zhang, Zijun; Xing, Yi

2017-09-19

Crosslinking or RNA immunoprecipitation followed by sequencing (CLIP-seq or RIP-seq) allows transcriptome-wide discovery of RNA regulatory sites. As CLIP-seq/RIP-seq reads are short, existing computational tools focus on uniquely mapped reads, while reads mapped to multiple loci are discarded. We present CLAM (CLIP-seq Analysis of Multi-mapped reads). CLAM uses an expectation-maximization algorithm to assign multi-mapped reads and calls peaks combining uniquely and multi-mapped reads. To demonstrate the utility of CLAM, we applied it to a wide range of public CLIP-seq/RIP-seq datasets involving numerous splicing factors, microRNAs and m6A RNA methylation. CLAM recovered a large number of novel RNA regulatory sites inaccessible by uniquely mapped reads. The functional significance of these sites was demonstrated by consensus motif patterns and association with alternative splicing (splicing factors), transcript abundance (AGO2) and mRNA half-life (m6A). CLAM provides a useful tool to discover novel protein-RNA interactions and RNA modification sites from CLIP-seq and RIP-seq data, and reveals the significant contribution of repetitive elements to the RNA regulatory landscape of the human transcriptome. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.